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Sample records for simulating early rheumatoid

  1. 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

  2. The safety of biologic agents in early rheumatoid arthritis.

    PubMed

    Kavanaugh, A; Keystone, E C

    2003-01-01

    Accompanying the excitement surrounding the prominent efficacy of biologic agents in rheumatoid arthritis (RA) has been concern regarding potential adverse effects. Data from clinical trials and pharmacovigilance has provided an assessment of their safety in patients with established RA. As biologic agents are utilized in patients with earlier disease, optimal determination of the risk/benefit will depend on continued careful monitoring, collection, reporting and analysis of safety information. PMID:14969079

  3. Approaches to the treatment of early rheumatoid arthritis with disease-modifying antirheumatic drugs

    PubMed Central

    Sizova, Lyudmila

    2008-01-01

    This paper reviews recent approaches to treatment of early rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs). The literature on treatment the early RA published between 1995 and 2007 was accessed through the PubMed database from the National Library of Medicine. Keywords were ‘early rheumatoid arthritis’, ‘disease-modifying antirheumatic drugs’, ‘biologic agents’ and ‘combination therapy’. Only results of trials on human subjects that directly measured the effects of DMARDs or biological agents on clinical, laboratory parameters and radiological progression of early RA were selected. Combination therapy suppresses RA activity and radiological progression more effectively than monotherapy. If better control of RA is evident after 3–6 months of treatment with the combination of DMARDs, one must still decide whether to stop the first DMARD, stop the second, or continue with the combination. Combination therapy biological agents (infliximab, adalimumab) with methotrexate and etanercept therapy alone may induce remission in many patients with early RA. It is a method of choice in patients with an adverse prognosis. The main indications for combination therapy ‘standard’ DMARDs or combination 1 DMARDs with a biological agent are such variables as detection of a shared epitope, increase of concentration of anticyclic citrullinated peptide antibodies, rheumatoid factor, C-reactive protein, 28-joint disease activity score, Sharp score and presence of erosion in joints. The majority of rheumatologists believe that patients with RA should be treated with DMARDs earlier rather than later in the disease process. Further trials should establish the optimal approaches to early RA therapy. PMID:18537958

  4. [The ultrasonography of the capsular ligamentous apparatus of the knee joint in the early stages of rheumatoid arthritis].

    PubMed

    Herasymenko, S I; Huzhevs'ky?, I V; Vovchenko, H Ia; Babko, A N

    1999-07-01

    With the purpose of finding out informative value of the ultrasound investigation designed to study the capsular and ligamentous apparatus of the knee joint in its instability during the early stages of rheumatoid arthritis and correlating clinical symptoms with ultrasonographic findings an examination was done of twenty joints of patients in early stages of rheumatoid arthritis presenting with clinical signs of anterior-medial instability. Sonography confirmed the presence of instability and permitted the qualitative assessment of its degree to be done. The method allows us to disclose relative incompetence of the anterior-medial sector of the knee joint in those patients presenting with early stages of rheumatoid arthritis, which is one of causes of instability, with the cruciate and lateral ligaments remaining uninjured. Ultrasonography makes it possible to perform a quantitative assessment of the degree of instability of the joint irrespective of the clinical test used and experience of the orthopedist. PMID:10822686

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

    NASA Astrophysics Data System (ADS)

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

    2003-07-01

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

  6. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study

    PubMed Central

    Gremese, Elisa; Salaffi, Fausto; Bosello, Silvia Laura; Ciapetti, Alessandro; Bobbio-Pallavicini, Francesca; Caporali, Roberto; Ferraccioli, Gianfranco

    2013-01-01

    Background To assess whether, in the real world of three early arthritis clinics, early referral could allow the best outcome, ie, remission, to be reached, and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa. Methods 1795 patients with early arthritis (symptom duration ?12?months) were entered into a prospective follow-up study. 711 patients (39.6%) were diagnosed with rheumatoid arthritis (RA). Each RA patient was treated according to the local algorithm, in three tertiary referral centres (representing a small province, a medium sized province and a metropolitan area, respectively). Remission, defined using the disease activity score in 28 joints (DAS28 <2.6) and American College of Rheumatology (ACR) criteria, was the major outcome evaluated at the 12-month follow-up. Results DAS28 remission was achieved in 34.3% (range 19.5–49%) of RA patients and ACR remission in 15.2% (range 8.5–20.6%). At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome: being in very early rheumatoid arthritis (VERA; less than 12?weeks symptom duration at the time of first treatment) and being on disease-modifying antirheumatic drugs (DMARD) within 3?months from disease onset. Among RA patients in remission, only 10% of VERA subjects received an anti-TNF blocker compared with 32.2% of non-VERA patients (p=0.002, OR 0.23, 95% CI 0.09 to 0.64). Conclusions In a real-world setting, the 12?weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome, ie, remission of RA. Moreover, VERA represents a window of opportunity in terms of cost saving. PMID:22798566

  7. 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

  8. 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

  9. Structural and Functional Changes of the Invariant NKT Clonal Repertoire in Early Rheumatoid Arthritis.

    PubMed

    Mansour, Salah; Tocheva, Anna S; Sanderson, Joseph P; Goulston, Lyndsey M; Platten, Helen; Serhal, Lina; Parsons, Camille; Edwards, Mark H; Woelk, Christopher H; Elkington, Paul T; Elliott, Tim; Cooper, Cyrus; Edwards, Christopher J; Gadola, Stephan D

    2015-12-15

    Invariant NKT cells (iNKT) are potent immunoregulatory T cells that recognize CD1d via a semi-invariant TCR (iNKT-TCR). Despite the knowledge of a defective iNKT pool in several autoimmune conditions, including rheumatoid arthritis (RA), a clear understanding of the intrinsic mechanisms, including qualitative and structural changes of the human iNKT repertoire at the earlier stages of autoimmune disease, is lacking. In this study, we compared the structure and function of the iNKT repertoire in early RA patients with age- and gender-matched controls. We analyzed the phenotype and function of the ex vivo iNKT repertoire as well as CD1d Ag presentation, combined with analyses of a large panel of ex vivo sorted iNKT clones. We show that circulating iNKTs were reduced in early RA, and their frequency was inversely correlated to disease activity score 28. Proliferative iNKT responses were defective in early RA, independent of CD1d function. Functional iNKT alterations were associated with a skewed iNKT-TCR repertoire with a selective reduction of high-affinity iNKT clones in early RA. Furthermore, high-affinity iNKTs in early RA exhibited an altered functional Th profile with Th1- or Th2-like phenotype, in treatment-naive and treated patients, respectively, compared with Th0-like Th profiles exhibited by high-affinity iNKTs in controls. To our knowledge, this is the first study to provide a mechanism for the intrinsic qualitative defects of the circulating iNKT clonal repertoire in early RA, demonstrating defects of iNKTs bearing high-affinity TCRs. These defects may contribute to immune dysregulation, and our findings could be exploited for future therapeutic intervention. PMID:26553073

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

    PubMed Central

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

    2013-01-01

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

  11. A European chart review study on early rheumatoid arthritis treatment patterns, clinical outcomes, and healthcare utilization.

    PubMed

    Emery, Paul; Solem, Caitlyn; Majer, Istvan; Cappelleri, Joseph C; Tarallo, Miriam

    2015-11-01

    This retrospective medical chart review aimed to provide a current, real-world overview of biologic usage in patients with rheumatoid arthritis (RA) in Germany, Spain, and the UK, and estimate clinical and healthcare utilization outcomes associated with early versus late treatment. Adults (?18 years) with a confirmed RA diagnosis between January 2008 and December 2010, who received biologic treatment for ?3 months and had ?12 months of follow-up were included. Early treatment was receipt of biologic agent ?1 year after RA diagnosis. Outcomes included 28-joint disease activity score (DAS28) reduction of ?1.2 from biologic start and remission (DAS28 < 2.6). Time to outcome was evaluated using Kaplan-Meier curves and log-rank tests. Of 328 patients enrolled (Germany [n = 111], Spain [n = 106], UK [n = 111]), 58.2 % received early biologic (Germany: 55.0 %, UK: 55.9 %, Spain: 64.2 %; p = 0.321). First-line biologics were more frequent in Spain (26.4 %) and Germany (19.8 %) versus the UK (7.2 %; p < 0.001). Late-treated patients were hospitalized more often than early-treated patients (10.5 vs 2.9 % [p = 0.006] for 9.0 vs 5.4 mean inpatient days [p = 0.408]). DAS28 was 5.1 at biologic initiation (n = 310); 73.5 % of patients had a DAS28 decrease of ?1.2 and 44.5 % achieved remission. More patients had DAS28 decrease of ?1.2 (79.2 vs 65.9 %; p = 0.009) and remission (51.1 vs 35.6 %; p = 0.007) with early versus late treatment, with a significant difference in Kaplan-Meier curves when indexing on time since diagnosis (p < 0.001) and biologic start (p = 0.024). In RA patients receiving biologic therapy, over half received biologic therapy early. Early initiation was associated with improved clinical outcomes and reduced hospitalization rates versus late treatment. PMID:26164150

  12. 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

  13. Circulating soluble E-selectin in early rheumatoid arthritis: a prospective five year study

    PubMed Central

    Kuuliala, A; Eberhardt, K; Takala, A; Kautiainen, H; Repo, H; Leirisalo-Repo, M

    2002-01-01

    Background: Soluble E-selectin (sE-selectin) is a marker of activation of vascular endothelium. Objective: To examine serum levels of sE-selectin in a cohort of 85 patients with early rheumatoid arthritis (RA) followed up for five years. Methods: sE-selectin levels were assessed annually using an enzyme linked immunosorbent assay (ELISA) and related to simultaneously obtained clinical and laboratory measures. Joint inflammation was evaluated by active joint count, functional status by Health Assessment Questionnaire (HAQ), and radiographic findings in hands and feet by the Larsen method. Laboratory tests included serum C reactive protein (CRP) level, erythrocyte sedimentation rate, blood haemoglobin level, white blood cell count (WBC), and platelet count. Area under the curve (AUC) was calculated for each variable, and Jonckheere's test for ordered alternatives was applied to assess significance of association between sE-selectin AUC tertiles and other variables. Baseline sE-selectin tertiles were related to change in Larsen score and HAQ score at five years. Odds ratios (OR) with 95% confidence interval (CI) were calculated using univariate and multivariate logistic regression. Results: sE-selectin levels were associated with CRP level (p=0.012), WBC (p=0.037), active joint count (p=0.019), progression of joint destruction (p=0.038), and HAQ score at five years (p=0.021), but not with extra-articular symptoms or comorbidity. Baseline sE-selectin levels in the third tertile predicted the HAQ score at five years (OR 4.18, 95% CI 1.15 to 15.22). sE-selectin levels of patients did not differ significantly from those of healthy control subjects. Conclusion: The degree of activation of vascular endothelium is associated with activity and outcome of early RA. PMID:11830430

  14. Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study

    PubMed Central

    Hafström, Ingiäld; Engvall, Inga-Lill; Rönnelid, Johan; Boonen, Annelies; van der Heijde, Désirée; Svensson, Björn

    2014-01-01

    Objective To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change). Design Prospective, randomised study of patients with early RA. Setting Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. Participants In all, 225 patients, 64% women, with a diagnosis of RA according to the American College of Rheumatology criteria, were included if they were between 18 and 80?years of age and had a disease duration of less than 1?year. Intervention The patients were randomised to 7.5?mg prednisolone daily for 2?years (P-group; n=108) or no prednisolone (NoP-group; n=117) when they started with their first disease-modifying anti-rheumatic drug and were prospectively followed for 2?years. Results The frequency of patients with radiographic progression after 2?years was 26% in the P-group and 39% in the NoP-group (p=0.033). Relevant interactions between treatment and rheumatoid factor (RF) (p=0.061) and between treatment and anti-cyclic citrullinated peptide 2 (anti-CCP) (p=0.096) were found. RF and anti-CCP independently predicted radiographic progression only in the NoP-group, OR (95% CI) 9.4 (2.5 to 35.2), p=0.001 and OR (95% CI) 8.7 (2.5 to 31.3), p=0.001, respectively. Conclusions The presence of RF and anti-CCP predicted radiographic progression in patients not treated with prednisolone but failed to predict progression in patients treated with this drug. The data suggest that early treatment with prednisolone may modulate not only inflammation but also autoimmunity-associated pathogenetic mechanisms. Trial registration number ISRCTN20612367. PMID:25079933

  15. Computerised versus conventional methodology of radiographic joint destruction assessment in early rheumatoid arthritis

    PubMed Central

    Huo, Yinghe; De Hair, Maria J H; Shaib, Yasmin O; van der Heijde, Désirée; Kuchuk, Natalia O; Viergever, Max A; van Laar, Jacob M; Vincken, Koen L; Lafeber, Floris P

    2015-01-01

    Objectives To compare computerised and conventional methodology of radiographic joint destruction assessment in early rheumatoid arthritis (RA). Methods We investigated the contribution of the 3rd-to-5th carpometacarpal joints (CMC3-5, which are excluded in computerised assessment so far owing to bone overlapping) to total joint space narrowing (JSN) scores in two cohorts of patients with early RA (n=392). Next, we investigated agreement between JSN scoring using single time point individual joint-based method (individual joint of a single time point (IJSTP), reflecting computerised reading) and conventional JSN scoring using the Sharp-van der Heijde (SvdH) method in a cohort of patients with early RA (n=59). We used intraclass correlation coefficients (ICCs), Bland and Altman plots, and linear mixed modelling to analyse differences in progression between two methods. Radiographs were available at baseline, and at 1 and 2?years of follow-up. Results Of all joints affected by JSN at baseline or JSN progression during 2?years of follow-up, 3.9% and 6.6% concerned CMC3-5. Exclusion of CMC3-5 resulted in a decrease of 1.9–4.6% in JSN progression scores during 2?years of follow-up. The ICCs for JSN progression scores using IJSTP with or without CMC3-5 compared with SvdH were 0.71–0.81 and 0.69–0.78 at 1 and 2?years of follow-up. Signal-to-noise ratios for IJSTP-based and SvdH scoring were 0.51 and 0.58, respectively. The progression rate for each year was not statistically significantly different between two scoring methods (p=0.59 and 0.89). Conclusions This study showed that excluding CMC3-5 has limited influence on JSN (progression) scores and showed the feasibility of using IJSTP-based reading for computerised scoring of JSN (progression) in RA. PMID:26688750

  16. 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

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

    PubMed

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

    2015-07-01

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

  18. Initial high-dose prednisolone combination therapy using COBRA and COBRA-light in early rheumatoid arthritis.

    PubMed

    Rasch, Linda A; van Tuyl, Lilian H D; Lems, Willem F; Boers, Maarten

    2015-01-01

    Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low. PMID:25227967

  19. Rheumatoid Arthritis

    MedlinePLUS

    Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness and loss of function in ... wrist and fingers. More women than men get rheumatoid arthritis. It often starts in middle age and is ...

  20. Clinical validation of surface-enhanced Raman scattering-based immunoassays in the early diagnosis of rheumatoid arthritis.

    PubMed

    Chon, Hyangah; Wang, Rui; Lee, Sangyeop; Bang, So-Young; Lee, Hye-Soon; Bae, Sang-Cheol; Hong, Sung Hyun; Yoon, Young Ho; Lim, Dong Woo; deMello, Andrew J; Choo, Jaebum

    2015-11-01

    We assessed the clinical feasibility of conducting immunoassays based on surface-enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group (n?=?31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group (n?=?43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA. PMID:26362159

  1. Current smoking status is a strong predictor of radiographic progression in early rheumatoid arthritis: results from the SWEFOT trial

    PubMed Central

    Saevarsdottir, Saedis; Rezaei, Hamed; Geborek, Pierre; Petersson, Ingemar; Ernestam, Sofia; Albertsson, Kristina; Forslind, Kristina; van Vollenhoven, Ronald F

    2015-01-01

    Objectives To study clinical predictors for radiographic progression after 1?year in an early rheumatoid arthritis (RA) trial. Methods In the SWEFOT trial population, disease modifying antirheumatic drug (DMARD) naïve RA patients started methotrexate; 3-month responders (DAS28 <3.2) continued (n=147), while non-responders were randomised to addition of sulfasalazine+hydroxychloroquine (n=130) or infliximab (n=128). X-rays were scored by the Sharp-van der Hejde score (SHS) method and radiographic progression was defined as a ?5 increase after 1?year. Potential baseline predictors of radiographic progression were tested using multivariable logistic regression, adjusted for potential confounders. Results 79 of 311 patients with available radiographs at baseline and follow-up had radiographic progression. The following baseline parameters were independent predictors of radiographic progression at 1?year: baseline erosions (adjusted OR=2.29, 95% CI 1.24 to 4.24), erythrocyte sedimentation rate (adjusted OR per tertile increase=1.72, 95% CI 1.12 to 2.65) and C-reactive protein (adjusted OR per tertile increase=1.52, 95% CI 1.03 to 2.26). Current smoking was an independent predictor of radiographic progression (adjusted OR=2.17, 95% CI 1.06 to 4.45). These results remained after further adjustment for treatment strategy. Three-dimensional matrix including current smoking status, erosions and C-reactive protein tertiles showed a 12–63% risk gradient from patients carrying none compared with all predictors. Rheumatoid factor (RF)/anti-cyclic citrullinated peptide (anti-CCP) positivity did not significantly predict radiographic progression using SHS increase ?5 as cut-off. In a secondary exploratory analysis using cut-off >1, both RF and anti-CCP positivity were significant predictors in the unadjusted, but not the adjusted analyses. The other parameters also remained significant using this lower cut-off. Conclusions In addition to previously described predictors, we identified smoking as a strong independent risk factor for radiographic progression in early RA. Trial registration number NCT00764725. PMID:24706006

  2. The role of genetic variants in CRP in radiographic severity in African Americans with early and established rheumatoid arthritis.

    PubMed

    Danila, M I; Westfall, A O; Raman, K; Chen, L; Reynolds, R J; Hughes, L B; Arnett, D K; McGwin, G; Szalai, A J; van der Heijde, D M; Conn, D; Callahan, L F; Moreland, L W; Bridges, S L

    2015-10-01

    This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg?dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA. PMID:26226010

  3. Approaches to the management of rheumatoid arthritis: rationale for early combination therapy.

    PubMed

    Wilske, K R

    1993-03-01

    In evaluating current therapy of RA, it is becoming recognized that sequential single drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little and too late in patients with aggressive 'at risk' synovitis. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used. Until a major breakthrough occurs in this disease, it is recommended that patients with 'at risk' RA be treated aggressively to achieve early control of inflammation, and then 'bridge down' to a simplified maintenance programme. While currently available fast and slow acting drugs might be used in combination today for early induction therapy, newer drugs, cancer chemotherapeutic preparations, biologic agents, or novel therapies may prove more effective and superior tomorrow. Control trials will be necessary to establish the most effective and least toxic induction and maintenance programmes. PMID:8448633

  4. A maximum difference scaling survey of barriers to intensive combination treatment strategies with glucocorticoids in early rheumatoid arthritis.

    PubMed

    Meyfroidt, Sabrina; Hulscher, Marlies; De Cock, Diederik; Van der Elst, Kristien; Joly, Johan; Westhovens, René; Verschueren, Patrick

    2015-05-01

    The objectives of the study were to determine the relative importance of barriers related to the provision of intensive combination treatment strategies with glucocorticoids (ICTS-GCs) in early rheumatoid arthritis (ERA) from the rheumatologists' perspective and to explore the relation between rheumatologists' characteristics and importance scores. A maximum difference scaling (MDS) survey was administered to 66 rheumatologists in Flanders and the Brussels-Capital Region. The survey included 25 barriers, previously being discovered in a qualitative study. The survey included 25 choice sets, each of which contained a different set of four barriers. In each choice situation, respondents were asked to choose the most important barrier. The mean relative importance score (RIS) for each barrier was calculated using hierarchical Bayes modeling. The potential relation between rheumatologists' characteristics and the RIS was examined using Spearman's correlation coefficient, Mann-Whitney U test, and Kruskal-Wallis H test. The three highest ranked barriers included "contraindicated for some patients (e.g., patients with comorbidities, older patients)," "an increased risk of side effects and related complications," and "patients' resistance" with a mean?±?SD RIS of 9.76?±?0.82, 8.50?±?1.17, and 7.45?±?1.22, respectively. Comparing the RISs based on rheumatologists' characteristics, a different ranking was found for three barriers depending on the age, university location, and/or frequency of prescribing ICTS-GCs. The dominant barriers hindering ICTS-GCs prescription from a rheumatologists' perspective are patient-related barriers and barriers related to the complexity of prescribing a combination therapy including GCs. A tailored improvement intervention is needed to overcome these barriers and should focus on the familiarity of rheumatologists with ICTS-GC and patient education. PMID:25711874

  5. Rheumatoid lung disease

    MedlinePLUS

    Lung disease - rheumatoid arthritis; Rheumatoid nodules ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The causes of lung disease associated with rheumatoid arthritis are unknown. Sometimes the medicines used to ...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Clerici, A M; Bono, G; Delodovici, M L; Azan, G; Cafasso, G; Micieli, G

    2013-01-01

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

  8. Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients from the community treated with methotrexate or leflunomide: results from the ESPOIR cohort

    PubMed Central

    2012-01-01

    Introduction Early rheumatoid arthritis (RA) patients may show rapid radiographic progression (RRP) despite rapid initiation of synthetic disease-modifying anti-rheumatic drugs (DMARDs). The present study aimed to develop a matrix to predict risk of RRP despite early DMARD initiation in real life settings. Methods The ESPOIR cohort included 813 patients from the community with early arthritis for < 6 months; 370 patients had early RA and had received methotrexate or leflunomide during the first year of follow-up. RRP was defined as an increase in the van der Heijde-modified Sharp score (vSHS) ? 5 points at 1 year. Determinants of RRP were examined first by bivariate analysis, then multivariate stepwise logistic regression analysis. A visual matrix model was then developed to predict RRP in terms of patient baseline characteristics. Results We analyzed data for 370 patients. The mean Disease Activity Score in 28 joints was 5.4 ± 1.2, 18.1% of patients had typical RA erosion on radiographs and 86.4% satisfied the 2010 criteria of the American College of Rheumatology/European League Against Rheumatism. During the first year, mean change in vSHS was 1.6 ± 5.5, and 41 patients (11.1%) showed RRP. A multivariate logistic regression model enabled the development of a matrix predicting RRP in terms of baseline swollen joint count, C-reactive protein level, anti-citrullinated peptide antibodies status, and erosions seen on radiography for patients with early RA who received DMARDs. Conclusions The ESPOIR matrix may be a useful clinical practice tool to identify patients with early RA at high risk of RRP despite early DMARD initiation. PMID:23164197

  9. Effects of long-term corticosteroid usage on functional disability in patients with early rheumatoid arthritis, regardless of controlled disease activity.

    PubMed

    Tanaka, Eiichi; Mannalithara, Ajitha; Inoue, Eisuke; Iikuni, Noriko; Taniguchi, Atsuo; Momohara, Shigeki; Singh, Gurkirpal; Yamanaka, Hisashi

    2012-03-01

    We investigated the effect of long-term corticosteroid usage in suppressing the progression of functional disability in patients with early rheumatoid arthritis (RA). We studied 3,982 RA patients, who had continuous enrollment for at least 3 years, among 9,132 RA patients enrolled in an observational cohort study, IORRA, in Tokyo, Japan, from 2000 to 2007. The DAS28 and Japanese version of Health Assessment Questionnaire (J-HAQ) scores were collected at 6-month intervals (each phase). Among these patients, those with DAS28 values under 3.2 in all phases and RA disease duration under 2 years at study entry were selected as "early RA patients with well-controlled disease". These patients were further classified into 3 groups based on average months of steroid usage per year: Non-users, Medium-users, and Frequent-users. Multiple linear regression analysis was used to study the relationship between steroid usage and the final J-HAQ scores. Among the 3,982 patients, 109 had DAS28 values under 3.2 in all the phases and were selected as study cohort. The average Final J-HAQ in Non-user (N = 64), in Medium-user (N = 25), in Frequent-user group (N = 20) was 0.04, 0.06, and 0.33, respectively. Multiple linear regression analysis after adjusting for all potential covariates confirmed that frequent steroid usage was the most significant factor associated with higher final J-HAQ scores (P < 0.05). Frequent steroid usage was associated with significantly higher final J-HAQ scores in early RA patients, even though their disease was managed efficiently by maintaining the DAS28 values under 3.2 over a long-term period. PMID:21161535

  10. 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

  11. 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

  12. 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

  13. A CD4 T cell gene signature for early rheumatoid arthritis implicates interleukin 6-mediated STAT3 signalling, particularly in anti-citrullinated peptide antibody-negative disease

    PubMed Central

    Pratt, Arthur G; Swan, Daniel C; Richardson, Sarah; Wilson, Gillian; Hilkens, Catharien M U; Young, David A; Isaacs, John D

    2012-01-01

    Objective We sought clinically relevant predictive biomarkers present in CD4 T-cells, or in serum, that identified those patients with undifferentiated arthritis (UA) who subsequently develop rheumatoid arthritis (RA). Methods Total RNA was isolated from highly purified peripheral blood CD4 T cells of 173 early arthritis clinic patients. Paired serum samples were also stored. Microarray analysis of RNA samples was performed and differential transcript expression among 111 ‘training cohort’ patients confirmed using real-time quantitative PCR. Machine learning approaches tested the utility of a classification model among an independent validation cohort presenting with UA (62 patients). Cytokine measurements were performed using a highly sensitive electrochemiluminescence detection system. Results A 12-gene transcriptional ‘signature’ identified RA patients in the training cohort and predicted the subsequent development of RA among UA patients in the validation cohort (sensitivity 68%, specificity 70%). STAT3-inducible genes were over-represented in the signature, particularly in anti-citrullinated peptide antibody-negative disease, providing a risk metric of similar predictive value to the Leiden score in seronegative UA (sensitivity 85%, specificity 75%). Baseline levels of serum interleukin 6 (IL-6) (which signals via STAT3) were highest in anti-citrullinated peptide antibodies-negative RA and distinguished this subgroup from non-RA inflammatory synovitis (corrected p<0.05).Paired serum IL-6 measurements correlated strongly with STAT3-inducible gene expression. Conclusion The authors have identified IL-6-mediated STAT-3 signalling in CD4 T cells during the earliest clinical phase of RA, which is most prominent in seronegative disease. While highlighting potential biomarker(s) for early RA, the role of this pathway in disease pathogenesis awaits clarification. PMID:22532634

  14. Rheumatoid arthritis (image)

    MedlinePLUS

    Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints ... other joints and is worse in the morning. Rheumatoid arthritis is also a systemic disease, involving other body ...

  15. What Is Rheumatoid Arthritis?

    MedlinePLUS

    ... Information Arthritis Find a Clinical Trial Journal Articles Rheumatoid Arthritis PDF Version Size: 57 KB Audio Version Time: ... Size: 9.7 MB November 2014 What Is Rheumatoid Arthritis? Fast Facts: An Easy-to-Read Series of ...

  16. 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

  17. 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.

  18. Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial

    PubMed Central

    Ajeganova, Sofia; Svensson, Björn; Hafström, Ingiäld

    2014-01-01

    Objective To examine the long-term effects of early low-dose prednisolone use in patients with rheumatoid arthritis (RA) on cardiovascular (CV) morbidity and mortality. Design Retrieval of data from a 2-year open randomised trial comparing prednisolone 7.5?mg/day in addition to disease-modifying antirheumatic drugs (DMARDs) with DMARD therapy alone. Participants were followed for 10?years since inclusion into the original prednisolone trial or until occurrence of the studied outcomes. Setting Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. Participants Overall, 223 patients with early RA were included. The participants had no history of CV events at baseline and incident cases were identified via the Swedish Hospital Discharge and Cause of Death Registries. Outcomes Composite CV events, that is, ischaemic coronary and cerebrovascular events, components of the composite CV outcome, and death. Relative HRs from Cox proportional-hazards regression models were calculated. Results Within 2041 person-years, 17 incident composite CV events occurred in 112 patients (15%) randomised to prednisolone, and 15 events of 111 patients (14%) who were assigned not to receive prednisolone. There were nine deaths (8%) in each group. The age-adjusted relative hazards (HRs; 95% CI) for the first composite CV event, first coronary event and death in the prednisolone group versus the group not treated with prednisolone were 1.8 (0.9 to 3.6), 0.98 (0.4 to 2.6) and 1.6 (0.6 to 4.1), respectively. The risk for the first cerebrovascular event showed a 3.7-fold increased relative hazard (95% CI 1.2 to 11.4) among prednisolone treated patients. Conclusions In this inception cohort study of low-dose prednisolone use during the first 2?years of RA disease, the incidence of ischaemic coronary artery events was similar in the two treatment groups, whereas the long-term risk of ischaemic cerebrovascular events was higher in the prednisolone group. There was a trend towards reduced survival in the prednisolone group. Trial registration number ISRCTN20612367. PMID:24710131

  19. Rheumatoid Factor

    MedlinePLUS

    ... AIDS , hepatitis , infectious mononucleosis , cancers such as leukemia and multiple myeloma , parasitic infection, or disease of the liver , lung , ... months after the beginning of symptoms. Early detection and diagnosis of RA allows health practitioners to begin aggressive ...

  20. 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

  1. Treatment of rheumatoid arthritis using photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    1995-03-01

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

  2. [Rheumatoid arthritis and ankylosing spondylitis].

    PubMed

    Jaji?, Z; Jaji?, I; Dubravica, M

    1995-01-01

    A case of a patient having ankylosing spondylitis of 16 years duration is presented. Eight years ago developed a clinical picture with symptoms which completely fulfill criteria for diagnosing rheumatoid arthritis with exception of rheumatoid factor. As a conclusion we can say that in our patient there have been developed ankylosing spondylitis and rheumatoid arthritis as a coexistence of two diseases. PMID:8693201

  3. Glucocorticoids and Rheumatoid Arthritis.

    PubMed

    Ferreira, Joana Fonseca; Ahmed Mohamed, Alaa Abdelkhalik; Emery, Paul

    2016-02-01

    Glucocorticoids (GCs) were discovered in the 1940s and were administered for the first time to patients with rheumatoid arthritis in 1948. However, side effects were subsequently reported. In the last 7 decades, the mechanisms of action for both therapeutic properties and side effects have been elucidated. Mechanisms for minimizing side effects were also developed. GCs are the most frequently used class of drugs in the treatment of rheumatoid arthritis because of their efficacy in relieving symptoms and their low cost. A review of clinical applications, side effects, and drug interactions is presented. PMID:26611549

  4. Laryngeal Manifestations of Rheumatoid Arthritis

    PubMed Central

    Hamdan, A. L.; Sarieddine, D.

    2013-01-01

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

  5. 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

  6. Predictive value of autoantibodies from anti-CCP2, anti-MCV and anti-human citrullinated fibrinogen tests, in early rheumatoid arthritis patients with rapid radiographic progression at 1?year: results from the ESPOIR cohort

    PubMed Central

    Degboé, Yannick; Constantin, Arnaud; Nigon, Delphine; Tobon, Gabriel; Cornillet, Martin; Schaeverbeke, Thierry; Chiocchia, Gilles; Nicaise-Roland, Pascale; Nogueira, Leonor; Serre, Guy; Cantagrel, Alain; Ruyssen-Witrand, Adeline

    2015-01-01

    Objectives We compared the ability of antibodies against cyclic citrullinated peptides (anti-CCP2), against mutated citrullinated vimentin (anti-MCV) and against citrullinated fibrinogen (AhFibA) to predict 1?year rapid radiographic progression (RRP; total Sharp score variation ?5 points), in early rheumatoid arthritis (RA). Methods We analysed 566 patients from the ESPOIR cohort with early RA fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria at year 1. We assayed the 3 anticitrullinated peptide antibodies (ACPA) tests on baseline sera. We compared the performance of these 3 ACPA tests to predict first-year RRP, by comparing areas under the receiver operating characteristic curves (ROCs). We assessed the 1?year RRP risk by ACPA titres. We used a logistic multivariate regression to analyse RRP risk in terms either of ACPA positivity or titre: high (>3 times the N cut-off) and low (1 to 3N). Results 145 patients displayed RRP. Areas under the ROCs were similar (0.60) for the 3 tests. High ACPA titres were associated with 1?year RRP, whatever the test was, and with similar ORs. Low+ anti-MCV titres were not associated with 1-year RRP, whereas low+ anti-CCP2 titres (p=0.0226) and low+ AhFibA titres (p=0.0332) were significantly associated. In multivariate analysis, 1?year RRP was associated with anti-CCP2 positivity (p<0.0001), AhFibA positivity (p<0.0001) and high anti-MCV titres (p<0.0001). Conclusions Anti-CCP2 antibodies and AhFibA were predictive of 1?year RRP in early RA whatever their titre was, whereas only high anti-MCV antibody titres were predictive, potentially making them more discriminant to predict 1?year RRP risk. PMID:26635969

  7. 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 ...

  8. Biomarkers for rheumatoid arthritis: Making it personal

    PubMed Central

    Lindstrom, Tamsin M.; Robinson, William H.

    2012-01-01

    Effective treatment of rheumatoid arthritis (RA) has been hampered by the heterogeneity of the disease. Although early intervention can result in disease remission, it requires early diagnosis – and current diagnostic tests are not sufficiently accurate or sensitive in the early stages of RA. As a result, RA is typically diagnosed only once damage to the joints has already begun, a time at which the window for optimal treatment may have been missed. Furthermore, a significant proportion of RA patients do not respond to any given therapeutic. Research efforts are increasingly focused on discovery of biomarkers that enable early diagnosis and stratification of RA, and thus the implementation of timely, targeted therapy. Biomarkers have the potential to transform the management of RA by enabling not only early diagnosis, but also assessment and prediction of disease severity, selection of therapy, and monitoring of response to therapy. In this mini review, we discuss the development of molecular biomarkers for RA. PMID:20515283

  9. 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

  10. The clinical features of rheumatoid arthritis.

    PubMed

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

    1998-05-01

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

  11. Presence of Rheumatoid Factor during Chronic HCV Infection Is Associated with Expansion of Mature Activated Memory B-Cells that Are Hypo-Responsive to B-Cell Receptor Stimulation and Persist during the Early Stage of IFN Free Therapy

    PubMed Central

    Reyes-Avilés, Elane; Kostadinova, Lenche; Rusterholtz, Anne; Cruz-Lebrón, Angelica; Falck-Ytter, Yngve; Anthony, Donald D.

    2015-01-01

    Approximately half of those with chronic hepatitis C virus (HCV) infection have circulating rheumatoid factor (RF), and a portion of these individuals develop cryoglobulinemic vasculitis. B cell phenotype/function in relation to RF in serum has been unclear. We examined B cell subset distribution, activation state (CD86), cell cycle state (Ki67), and ex-vivo response to BCR, TLR9 and TLR7/8 stimulation, in chronic HCV-infected donors with or without RF, and uninfected donors. Mature-activated B-cells of HCV-infected donors had lower CD86 expression compared to uninfected donors, and in the presence of RF they also showed reduced CD86 expression in response to BCR and TLR9 stimulation. Additionally, mature activated memory B cells of HCV RF+ donors less commonly expressed Ki67+ than HCV RF- donors, and did not proliferate as well in response to BCR stimulation. Proportions of mature-activated B cells were enhanced, while naïve B-cells were lower in the peripheral blood of HCV-RF+ compared to RF- and uninfected donors. None of these parameters normalize by week 8 of IFN free direct acting antiviral (DAA) therapy in HCV RF+ donors, while in RF- donors, mature activated B cell proportions did normalize. These data indicate that while chronic HCV infection alone results in a lower state of activation in mature activated memory B cells, the presence of RF in serum is associated with a more pronounced state of unresponsiveness and an overrepresentation of these B cells in the blood. This phenotype persists at least during the early time window after removal of HCV from the host. PMID:26649443

  12. 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

  13. Elevated Membrane and Soluble CD64: A Novel Marker Reflecting Altered Fc?R Function and Disease in Early Rheumatoid Arthritis That Can Be Regulated by Anti-Rheumatic Treatment

    PubMed Central

    2015-01-01

    Objectives Fc receptors (FcR) interacting with immune complexes (ICs) is a central event in the immune pathogenesis of rheumatoid arthritis (RA). Here we asked if a specific FcR is linked to RA pathogenesis and if FcR activities relate to disease and treatment outcome in early RA. Material and Methods Twenty autoantibody-positive RA patients and 33 HC were included. The patients were evaluated before and after treatment with methotrexate and prednisolone. At follow-up, the EULAR response criteria were applied to determine the individual treatment outcomes. Serum immunoglobulin levels were measured and the expression of FcR for IgG (Fc?R) and IgA (Fc?R) on peripheral blood monocytes were determined by flow cytometry. The monocytic Fc?R function was evaluated by human IgG1 and IgG3 IC-binding and TNF? stimulated release. Plasma levels of soluble FcRs (sFcRs) were determined with ELISA. Results The IgG1 and IgG3 levels were elevated in the RA sera. The RA monocytes expressed more CD64 and cell surface-bound IgG than HC monocytes, and showed an impaired Fc?R function as reflected by changes in IC-binding and decreased IC-stimulated TNF? secretion. These findings correlated significantly with different disease activity markers. Furthermore, sFcRs were elevated in the patient plasma, and sCD64 was specific for RA (compared with a reference group of patients with active psoriatic arthritis). Following treatment, immunoglobulins and sFcR levels were reduced, whereas membrane CD64 was only decreased in patients with good response to treatment. Conclusions Early RA patients display increased membrane and soluble CD64 and an impaired Fc?R function correlating with joint disease activity. Beneficial responses of anti-rheumatic treatment in patients reduce CD64. These data suggest sCD64 as an important objective biomarker in RA. PMID:26406605

  14. Understanding IFN? in rheumatoid arthritis

    PubMed Central

    2014-01-01

    Unraveling the mechanisms underlying the inflammatory response in rheumatoid arthritis is crucial in order to better understand the disease and to develop novel therapeutic approaches. Although the effect of type I interferons on fibroblasts and in the context of rheumatoid arthritis has been described for some time, little is known on the effects of the type III interferons, also known as IFN?. In a previous issue, Xu and colleagues demonstrate that one of the members of the IFN? family, IFN?1, enhances Toll-like receptor expression and consequently promotes the production of proinflammatory cytokines known to be involved in initiating and maintaining the inflammatory responses in rheumatoid arthritis. PMID:24443794

  15. Radiolabelled lymphocyte migration in rheumatoid synovitis.

    PubMed Central

    Jorgensen, C; Couret, I; Bologna, C; Rossi, M; Sany, J

    1995-01-01

    OBJECTIVES--To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA). METHODS--After isolation of the lymphocytes, the cells were radiolabelled in vitro with 250 MBq 99mTc-HMPAO. The scans were performed 30 minutes, three hours and 20 hours after injection. RESULTS--An increase of the scintigram signal obtained at 20 hours was associated with a high joint swelling and joint pain score (F test = 3.07, p < 0.002), but not with the radiological score. A positive joint scintigram was predictive of active synovitis. Although the scintigram variation over time did not reach statistical significance, the kinetics of the scintigram signal tended to differ according to the disease duration: in early RA, active arthritis could be clearly imaged as early as 30 minutes, increased at three hours and the signal intensity persisted at 20 hours. In contrast, in long standing disease, the affected joints were imaged at 30 minutes, persisted unchanged at three hours, and the scintigram score decreased significantly at 20 hours. CONCLUSIONS--The study shows that 99mTc-HMPAO joint scintigraphy may be used to detect and to localise active rheumatoid arthritis. Images PMID:7880120

  16. Handout on Health: Rheumatoid Arthritis

    MedlinePLUS

    ... term side effects of methotrexate is liver damage. Climate: Some people notice that their arthritis gets worse ... However, there is no evidence that a specific climate can prevent or reduce the effects of rheumatoid ...

  17. Physiotherapy in Rheumatoid Arthritis

    PubMed Central

    Kavuncu, Vural; Evcik, Deniz

    2004-01-01

    Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented. PMID:15266230

  18. The effects of infant simulators on early adolescents.

    PubMed

    Divine, J H; Cobbs, G

    2001-01-01

    The researchers examined the effects of infant simulators (computerized dolls designed to simulate normal infants) on 236 eighth-grade students. As part of their health and sex education curriculum, students had to provide care--24 hours a day, over several days--to dolls that cried when they "were hungry," "needed a diaper change," or "needed attention." The dolls enabled teachers to evaluate the care given by students. Students kept daily charts and journals, and wrote essays about their experiences. One to two years later, the students were surveyed, along with 461 comparison students who did not have the infant simulator experience. The findings indicated that the doll experience had a significant impact on the students, especially the females. It helped them to learn about the challenges of infant care, and to think of the implications before engaging in sexual intercourse. The comparison group felt less knowledgeable about what it takes to care for an infant, and judged infant care as less time consuming, difficult, and expensive than did those who had the infant simulator experience. PMID:11817639

  19. The pathogenesis of rheumatoid arthritis in radiological studies. Part II: Imaging studies in rheumatoid arthritis

    PubMed Central

    Zaniewicz-Kaniewska, Katarzyna; Warczy?ska, Agnieszka; Matuszewska, Genowefa; Saied, Fadhil; Kunisz, Wojciech

    2012-01-01

    Early diagnosis of rheumatoid arthritis followed by early initiation of treatment, prevent the destruction of joints and progression to disability in the majority of patients. A traditional X-ray fails to capture early inflammatory changes, while late changes (e.g. erosions) appear after a significant delay, once 20–30% of bone mass has been lost. Sonography and magnetic resonance imaging studies have shown that erosions are seen in the first 3 months from the appearance of symptoms in 10–26% of patients, while in 75% they are seen in the first 2 years of the disease. Power Doppler ultrasound and dynamic magnetic resonance studies allow for qualitative, semiquantitative and quantitative monitoring of the vascularization of the synovium. In addition, magnetic resonance enables assessment of the bone marrow. The ultrasonographic examination using a state-of-the-art apparatus with a high-frequency probe allows for images with great spatial resolution and for the visualization of soft tissues and bone surfaces. However, the changes seen in ultrasonography (synovial pathologies, the presence of exudate, tendons changes, cartilage and bone lesions, pathologies of tendon attachments and ligaments – enthesopathies) are not only specific for rheumatoid arthritis and occur in other rheumatic diseases. Qualitative methods are sufficient for diagnosing the disease through ultrasound or magnetic resonance imaging. Whereas semiquantitative and quantitative scales serve to monitor the disease course – efficacy of conservative treatment and qualification for radioisotope synovectomy or surgical synovectomy – and to assess treatment efficacy.

  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. T Cell Migration in Rheumatoid Arthritis.

    PubMed

    Mellado, Mario; Martínez-Muñoz, Laura; Cascio, Graciela; Lucas, Pilar; Pablos, José L; Rodríguez-Frade, José Miguel

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. PMID:26284069

  2. T Cell Migration in Rheumatoid Arthritis

    PubMed Central

    Mellado, Mario; Martínez-Muñoz, Laura; Cascio, Graciela; Lucas, Pilar; Pablos, José L.; Rodríguez-Frade, José Miguel

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies. PMID:26284069

  3. Modelling Charge Coupled Device Readout: Simulation Overview and Early Results

    E-print Network

    P. Bristow; A. Alexov

    2002-11-29

    The Calibration enhancement effort for the Space Telescope Imaging Spectrograph (STIS) aims to improve data calibration via the application of physical modelling techniques. We describe here a model of the Charge Transfer process during read-out of modern Charge Coupled Devices, and its application to data from STIS. The model draws upon previous investigations of this process and, in particular, the trapping and emission model developed by Robert Philbrick of Ball Aerospace. Early comparison to calibration data is encouraging. Essentially, a physical description of the STIS CCD combined with the physics of known defects in the silicon lattice expected to arise in a hostile radiation environment, is enough to yield results which approximately match real data. Uncertainties remain, however, in the details of the model and the physical description of STIS.

  4. [Pathology of rheumatoid lung].

    PubMed

    Theile, A; Müller, K M

    1994-02-01

    In the framework of rheumatic illnesses, the lungs and pleura are often observed to be involved. Dependent on the basic illness in question, conditions of the bronchoalveolar system, vessels, lymphatic system, and pleura that have developed differently inter- and intra-individually can be diagnosed in topo-regionally variable forms and combinations. In the causal pathogenesis, the initial (auto-) immunological alteration of the alveolar septa plays a role. When the monocytes, macrophages, and fibroblasts are activated, as a result of a chronic inflammatory process there is increasing reparative proliferation, which finally leads to the non-specific end stage of irreversible interstitial fibrosis. The incidence and manifestation forms of lung changes show certain differences dependent on the underlying illness (e.g., rheumatoid arthritis, systemic lupus erythematosus, progressive systemic scleroderma, dermatomyositis and polymyositis, Sjögren syndrome, and mixed connective tissue disease). In addition to vasculitis and granulomatosis of the lung, therapy-induced lung changes must also be considered in the differential diagnosis since almost all basic therapeutic agents can cause this type of lung condition. Good knowledge of the parameters from the viewpoint of possible therapeutic measures is indispensable, as is close cooperation between the treating physician and the pathologist. PMID:8153077

  5. [Leishmaniasis in rheumatoid arthritis].

    PubMed

    Pizzorni, C; Secchi, M E; Cutolo, M

    2007-01-01

    Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis is of higher priority than cutaneous leishmaniasis as it is a fatal disease in the absence of treatment. The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. TNF-alpha has been implicated in cytokine-induced macrophage activation and tissue granuloma formation, two activities linked to control of intracellular visceral infection caused by Leishmania donovani. Anti-tumor necrosis factor-alpha (TNF-alpha) strategies have had a marked and substantial impact in the treatment of rheumatoid arthritis, however the clinical use of TNF-alpha antagonists has been accompanied by increased reporting of infections. Here we report the first case of visceral leishmaniasis in a patient treated for a long period of time with human anti TNF-alpha monoclonal antibody, adalimumab. Due to the low incidence rate of Mediterranean visceral leishmaniasis, a systematic screening for leishmaniasis in all patients treated with biologics may be not recommended. However, for those patients living at high risk of leishmaniasis exposure, a periodical serological monitoring should be performed during therapy with anti-TNF monoclonal antibodies. PMID:17898884

  6. 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.

  7. Prevention of Stroke in Rheumatoid Arthritis.

    PubMed

    Zha, Alicia M; Di Napoli, Mario; Behrouz, Réza

    2015-12-01

    The risk of cerebrovascular disease is increased among rheumatoid arthritis (RA) patients and remains an underserved area of medical need. Only a minor proportion of RA patients achieve suitable stroke prevention. Classical cardiovascular risk factors appear to be under-diagnosed and undertreated among patients with RA. Reducing the inflammatory burden is also necessary to lower the cardiovascular risk. An adequate control of disease activity and cerebrovascular risk assessment using national guidelines should be recommended for all patients with RA. For patients with a documented history of cerebrovascular or cardiovascular risk factors, smoking cessation and corticosteroids and non-steroidal anti-inflammatory drugs at the lowest dose possible are crucial. Risk score models should be adapted for patients with RA by introducing a 1.5 multiplication factor, and their results interpreted to appropriately direct clinical care. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers are preferred treatment options. Biologic and non-biologic disease-modifying anti-rheumatic drugs should be initiated early to mitigate the necessity of symptom control drugs and to achieve early alleviation of the inflammatory state. Early control can improve vascular compliance, decrease atherosclerosis, improve overall lipid and metabolic profiles, and reduce the incidence of heart disease that may lead to atrial fibrillation. In patients with significant cervical spine involvement, early intervention and improved disease control are necessary and may prevent further mechanical vascular injury. PMID:26486791

  8. Proposed Planning Procedures: Gaming-Simulation as a Method for Early Assessment.

    ERIC Educational Resources Information Center

    Smit, Peter H.

    1982-01-01

    Examines the use of simulation gaming as a research tool in the early assessment of proposed planning procedures in urban renewal projects. About one-half of the citations in the 36-item bibliography are in Dutch; the remainder are in English. (Author/JJD)

  9. Gage for evaluating rheumatoid hands

    NASA Technical Reports Server (NTRS)

    Houge, J. C.; Plautz, K. A.

    1981-01-01

    Two-axis goniometer accurately measures movements of fingers about knuckle joints, diagnosing hands structurally changed by rheumatoid arthritis. Instrument measures lateral movement which is small in normal knuckles but increased in diseased joints. Goniometer is two connected protractors that simultaneously measure angles in perpindicular planes. Dials are offset to clear bony protuberances; extension and offset adjustments span any hand size.

  10. Conceptual Design of Simulation Models in an Early Development Phase of Lunar Spacecraft Simulator Using SMP2 Standard

    NASA Astrophysics Data System (ADS)

    Lee, Hoon Hee; Koo, Cheol Hea; Moon, Sung Tae; Han, Sang Hyuck; Ju, Gwang Hyeok

    2013-08-01

    The conceptual study for Korean lunar orbiter/lander prototype has been performed in Korea Aerospace Research Institute (KARI). Across diverse space programs around European countries, a variety of simulation application has been developed using SMP2 (Simulation Modelling Platform) standard related to portability and reuse of simulation models by various model users. KARI has not only first-hand experience of a development of SMP compatible simulation environment but also an ongoing study to apply the SMP2 development process of simulation model to a simulator development project for lunar missions. KARI has tried to extend the coverage of the development domain based on SMP2 standard across the whole simulation model life-cycle from software design to its validation through a lunar exploration project. Figure. 1 shows a snapshot from a visualization tool for the simulation of lunar lander motion. In reality, a demonstrator prototype on the right-hand side of image was made and tested in 2012. In an early phase of simulator development prior to a kick-off start in the near future, targeted hardware to be modelled has been investigated and indentified at the end of 2012. The architectural breakdown of the lunar simulator at system level was performed and the architecture with a hierarchical tree of models from the system to parts at lower level has been established. Finally, SMP Documents such as Catalogue, Assembly, Schedule and so on were converted using a XML(eXtensible Mark-up Language) converter. To obtain benefits of the suggested approaches and design mechanisms in SMP2 standard as far as possible, the object-oriented and component-based design concepts were strictly chosen throughout a whole model development process.

  11. Treatment in juvenile rheumatoid arthritis and new treatment options

    PubMed Central

    Kasapçopur, Özgür; Barut, Kenan

    2015-01-01

    Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of the childhood with the highest risk of disability. Active disease persists in the adulthood in a significant portion of children with juvenile rheumatoid arthritis despite many developments in the diagnosis and treatment. Therefore, initiation of efficient treatment in the early period of the disease may provide faster control of the inflammation and prevention of long-term harms. In recent years, treatment options have also increased in children with juvenile idiopathic arthritis owing to biological medications. All biological medications used in children have been produced to target the etiopathogenesis leading to disease including anti-tumor necrosis factor, anti-interleukin 1 and anti-interleukin 6 drugs. In this review, scientific data about biological medications used in the treatment of rheumatoid arthritis and new treatment options will be discussed. PMID:26078691

  12. Role of ineffective erythropoiesis in the anaemia of rheumatoid arthritis.

    PubMed Central

    Samson, D; Halliday, D; Gumpel, J M

    1977-01-01

    The importance of inadequate haemoglobin synthesis and ineffective erythropoiesis in the anaemia of rheumatoid arthritis was studied by measuring the incorporation of 15N glycine into haemoglobin haem and early labelled bilirubin in a patient with severe anaemia before and after response to gold therapy. Initially, total erythroid haem turnover was decreased but haem turnover due to ineffective erythropoiesis was markedly increased, accounting for 29% of total erythroid haem turnover. Gold therapy resulted in marked clinical improvement, accompanied by a rise in haemoglobin to normal. Total erythroid haem turnover increased and the percentage ineffective erythropoiesis fell to normal. Ineffective erythropoiesis may thus be an important reversible factor in the production of the anaemia of rheumatoid arthritis. PMID:857744

  13. 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.

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

    NASA Astrophysics Data System (ADS)

    Carmichael, M. J.; Lunt, D. J.; Huber, M.; Heinemann, M.; Kiehl, J.; LeGrande, A.; Loptson, C. A.; Roberts, C. D.; Sagoo, N.; Shields, C.; Valdes, P. J.; Winguth, A.; Winguth, C.; Pancost, R. D.

    2015-07-01

    Recent studies, utilising a range of proxies, indicate that a significant perturbation to global hydrology occurred at the Paleocene-Eocene Thermal Maximum (PETM; ~56 Ma). An enhanced hydrological cycle for the warm early Eocene is also suggested to have played a key role in maintaining high-latitude warmth during this interval. However, comparisons of proxy data to General Circulation Model (GCM) simulated hydrology are limited and inter-model variability remains poorly characterised, despite significant differences in simulated surface temperatures. In this work, we undertake an intercomparison of GCM-derived precipitation and P-E distributions within the EoMIP ensemble (Lunt et al., 2012), which includes previously-published early Eocene simulations performed using five GCMs differing in boundary conditions, model structure and precipitation relevant parameterisation schemes. We show that an intensified hydrological cycle, manifested in enhanced global precipitation and evaporation rates, is simulated for all Eocene simulations relative to preindustrial. This is primarily due to elevated atmospheric paleo-CO2, although the effects of differences in paleogeography/ice sheets are also of importance in some models. For a given CO2 level, globally-averaged precipitation rates vary widely between models, largely arising from different simulated surface air temperatures. Models with a similar global sensitivity of precipitation rate to temperature (dP/dT) display different regional precipitation responses for a given temperature change. Regions that are particularly sensitive to model choice include the South Pacific, tropical Africa and the Peri-Tethys, which may represent targets for future proxy acquisition. A comparison of early and middle Eocene leaf-fossil-derived precipitation estimates with the GCM output illustrates that a number of GCMs underestimate precipitation rates at high latitudes. Models which warm these regions, either via elevated CO2 or by varying poorly constrained model parameter values, are most successful in simulating a match with geologic data. Further data from low-latitude regions and better constraints on early Eocene CO2 are now required to discriminate between these model simulations given the large error bars on paleoprecipitation estimates. Given the clear differences apparent between simulated precipitation distributions within the ensemble, our results suggest that paleohydrological data offer an independent means by which to evaluate model skill for warm climates.

  15. 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

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

    NASA Astrophysics Data System (ADS)

    Carmichael, Matthew; Lunt, Daniel; Pancost, Richard

    2015-04-01

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

  17. Simulated Microgravity as a Probe for Understanding the Mechanisms of Early Pattern Specification

    NASA Technical Reports Server (NTRS)

    Neff, A. W.; Malacinski, G. M.

    1985-01-01

    Early pattern specification (e.g., axial structure morphogenesis, doreal ventral polarity, etc.) is monitored in amphibian eggs which were subjected to microgravity simulation by constant rotation on a horizontal clinostat. In contrast to previous clinostat experiments, rotation is initiated either prior to fertilization or immediately thereafter. Large proportions of clinostated eggs developed normal axial structures. A model which employs a multiple set of signals for specifying early pattern is discussed. Effects of microgravity simulation on the earliest post fertilization pattern specification event dorsal/ventral polarization is analyzed in detail. Other models are developed and they are discussed. As a general mechanism for explaining the manner in which regional developmental patterns emerge from the initial, radially symmetrial egg, the density compartment model is described. The identification of the various zones or compartments of egg cytoplasm using inverted eggs is explained.

  18. Numerical simulation of quench propagation at early phase by high-order methods

    NASA Astrophysics Data System (ADS)

    Mao, Shaolin; Luongo, Cesar A.; Kopriva, David A.

    2006-07-01

    In this paper a high-order discontinuous Galerkin (DG) spectral element method (SEM) is introduced to deal with thermo-hydraulic quench simulation in superconducting magnets, specifically in the case of cable-in-conduit conductors (CICC). We will focus on 1D quench propagation at early phase which is important to understand the mechanism of quench propagation and protect the superconducting magnets. A second-order polynomial interpolation to the helium heat capacity is introduced in this study, and boundary conditions are imposed along the characteristics to overcome the typical difficulties encountered in numerical studies. Explicit fourth order Runge-Kutta time integration is used to match the high accuracy in space. Numerical results demonstrate the advantages in accuracy of this method when used to simulate early quench development.

  19. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis.

    PubMed

    Stahl, Eli A; Wegmann, Daniel; Trynka, Gosia; Gutierrez-Achury, Javier; Do, Ron; Voight, Benjamin F; Kraft, Peter; Chen, Robert; Kallberg, Henrik J; Kurreeman, Fina A S; Kathiresan, Sekar; Wijmenga, Cisca; Gregersen, Peter K; Alfredsson, Lars; Siminovitch, Katherine A; Worthington, Jane; de Bakker, Paul I W; Raychaudhuri, Soumya; Plenge, Robert M

    2012-05-01

    The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases. PMID:22446960

  20. Constrictive pericarditis in rheumatoid arthritis.

    PubMed Central

    Thould, A K

    1986-01-01

    Constrictive pericarditis is an unusual complication of rheumatoid arthritis, and its development appears to be uninfluenced by second-line therapy. Five patients are described who developed the disease, with possibly two more. Medical treatment is ineffective: the treatment of choice is surgical, and the postoperative prognosis is good. The crude prevalence rate for the association is 0.64% for males and 0.06% for females. PMID:3947148

  1. [Bone structure in rheumatoid arthritis].

    PubMed

    Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

    2013-07-01

    In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA. PMID:23811586

  2. The Early Jurassic Climate: General Circulation Model Simulations and the Paleoclimate Record.

    NASA Astrophysics Data System (ADS)

    Chandler, Mark Arnold

    This thesis presents the results of several general circulation model simulations of the Early Jurassic climate. The simulations were designed so that meaningful model-data comparisons could be made. The general circulation model employed was developed at the Goddard Institute for Space Studies while most paleoclimate data were provided by the Paleogeographic 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^circC warmer, globally, than at present and a latitudinal temperature gradient dominated by high-latitude warming (+20^ circC) and little tropical change (+1 ^circC). Western Pangaea, in the low and mid-latitudes, is arid except along the Tethys coast, while eastern Pangaea, located in mid to high latitudes, experiences seasonal to year-round wet conditions. Comparisons show a good correlation between simulated results and paleoclimate data. Sensitivity experiments, which address regional exceptions, 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. Since hydrologic characteristics are not simulated as accurately as radiative properties, this chapter asks: to what extent can we use general circulation models to identify arid regions and what methods are most appropriate for use in paleoclimate studies? 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. Application of (1)H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis.

    PubMed

    Zabek, Adam; Swierkot, Jerzy; Malak, Anna; Zawadzka, Iga; Deja, Stanis?aw; Bogunia-Kubik, Katarzyna; Mlynarz, Piotr

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune-based inflammatory disease that leads to progressive joint degeneration, disability, and an increased risk of cardiovascular complications, which is the main cause of mortality in this population of patients. Although several biomarkers are routinely used in the management of rheumatoid arthritis, there is a high demand for novel biomarkers to further improve the early diagnosis of rheumatoid arthritis, stratification of patients, and the prediction of a better response to a specific therapy. In this study, the metabolomics approach was used to provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy. The results indicated that twelve metabolites were important for the discrimination of healthy control and rheumatoid arthritis. Notably, valine, isoleucine, lactate, alanine, creatinine, GPC??APC and histidine relative levels were lower in rheumatoid arthritis, whereas 3-hydroxyisobutyrate, acetate, NAC, acetoacetate and acetone relative levels were higher. Simultaneously, the analysis of the concentration of metabolites in rheumatoid arthritis and 3 months after induction treatment revealed that L1, 3-hydroxyisobutyrate, lysine, L5, acetoacetate, creatine, GPC+APC, histidine and phenylalanine were elevated in RA, whereas leucine, acetate, betaine and formate were lower. Additionally, metabolomics tools were employed to discriminate between patients with different IL-17A genotypes. Metabolomics may provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy in rheumatoid arthritis. PMID:26476882

  4. Simulating the climate of the early Eocene, a perturbed physics approach

    NASA Astrophysics Data System (ADS)

    Sagoo, N.; Valdes, P. J.; Gregoire, L. J.; Flecker, R.

    2012-12-01

    Modelling past climates that are very different to the modern provide an important test for the climate models used to predict future climates. The early Eocene was a period of global extreme warmth and simulating the extent of high latitude warmth in this period without overheating the tropics has been problematic, leading to a significant climate model geological data mismatch. There are several areas of uncertainty in climate models but parameter uncertainty is the largest component: sub-grid scale and temporally fast processes such as those that operate in the atmosphere are particularly difficult to measure in the environment and subsequently hard to parameterise in the climate models, resulting in a large range of possible values. Perturbed physics simulations are run by perturbing ten uncertain parameters within their plausible range in the model FAMOUS, an intermediate complexity general circulation model in order to see if the model is capable of generating the global warmth of the early Eocene. The uncertain parameters are perturbed both individually and in combination (single and multiple parameter perturbations). Latin hypercube sampling is used to create the parameter values for the multiple parameter perturbations in order to maximise the parameter space sampled. 2 x pre-industrial atmospheric CO2 is used for the early Eocene simulations. From over one hundred initial parameter sets three simulations have a temperature distribution that overlaps with the available early Eocene proxy data. These are referred to as the good Eocene simulations. In two simulations only a single parameter is varied and in the third parameter all the parameters are co-varied together. In the single parameter perturbations the critical relative humidity for cloud formation and the horizontal atmospheric diffusion parameters are reduced to 89% and 72% of the control value respectively. In the third good simulation all ten uncertain parameters are perturbed; two parameters involved in cloud liquid content and precipitation are increased to the upper end of their plausible range whilst the remaining parameters are only perturbed to within 8% of their original value. Present day and future simulations have also been run with the multiple parameter perturbation sets. Arcsin Mielke scores have been calculated for a number of climate variables for the present day simulations (e.g. surface air temperature, precipitation, sea ice and top of atmosphere energy balance. Our good Eocene simulation with perturbed cloud parameters outperforms the control parameter set for present day boundary conditions. It also has the highest score for present day precipitation out of all 100 parameter sets. These results increase confidence in this parameter set. The good early Eocene simulations are presented along with the reference geological dataset in this work. Present day and future simulations for both the control parameter set and the good multiple parameter perturbation set are also presented.

  5. The Paris Local Universe Simulation (PLUS): bridging the early and late Digital Universe

    NASA Astrophysics Data System (ADS)

    Lavaux, Guilhem

    2015-08-01

    The Paris Local Universe Simulation (PLUS) is an attempt to reproduce the full chronology of galaxies and Large Scale structure formation of our Local Universe using constrained N-body simulation and known baryon physics. To achieve this we produce initial conditions generated from a full Bayesian analysis of galaxy redshift surveys which include bias analysis, power spectrum sampling, boundary and incompleteness effects and evolutionary effects. These initial conditions are provided to N-body simulation code (like Ramses and Gadget) which provides detailed predictions on the formation of galaxies at all redshift. The result can then be matched one by one with the galaxies observed at low redshift. These simulations constitute an ideal laboratory to link the high and low redshift universe and confront the observations at different redshifts with the predictions of numerical models.I will show some early results of the PLUS collaboration on the formation of galaxies and galaxy clusters in the late universe and the prediction for how our own galaxies looked like in the early universe. This work is the basis of a more ambitious project aiming at reconstructing the initial conditions of the observable Universe from galaxy surveys, using SDSS (Main sample, LRG, LOWZ and CMASS, eBOSS) and Quasar surveys.

  6. Metabolic activity of erosions in rheumatoid arthritis.

    PubMed Central

    Pitt, P; Berry, H; Clarke, M; Foley, H; Barratt, J; Parsons, V

    1986-01-01

    The hands of 10 patients with rheumatoid arthritis were investigated with diphosphonate scanning and radiology. Increased uptake of isotope can be associated with some erosions but not all and also reflects other processes more linked to acute inflammatory areas unassociated with the development of erosions. If the latter are the hallmark of active rheumatoid arthritis then bone scans are not. PMID:3954472

  7. An Early Warning System for Loan Risk Assessment Based on Rare Event Simulation

    NASA Astrophysics Data System (ADS)

    Zhou, Hong; Qiu, Yue; Wu, Yueqin

    System simulation is one of important tool for risk assessment. In this paper, a new method is presented to deal with credit risk assessment problems for commercial banks based on rare event simulation. The failure probability of repaying loans of listed company is taken as the criterion to measure the level of credit risk. The rare-event concept is adopted to construct the model of credit risk identification in commercial banks, and cross-entropy scheme is designed to implement the rare event simulation, based on which the loss probability can be assessed. Numerical experiments have shown that the method has a strong capability to identify the credit risk for commercial banks and offers a good tool for early warning.

  8. 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.

  9. Involvement of the Circadian Rhythm and Inflammatory Cytokines in the Pathogenesis of Rheumatoid Arthritis

    PubMed Central

    Yoshida, Kohsuke; Hashimoto, Teppei; Sakai, Yoshitada; Hashiramoto, Akira

    2014-01-01

    Among the symptoms of patients with rheumatoid arthritis (RA), joint stiffness is influenced by diurnal rhythm and reaches peak in the morning, which is a common complaint and reflects the circadian nature of disease manifestation. In addition, inflammatory cytokines, which reach peak secretion early in the morning are major players causing the morning stiffness. In this review, we explore the link between the circadian clock and inflammation, focusing on the interactions of various clock genes with the immune-pathways underlying the pathology of rheumatoid arthritis. PMID:24901009

  10. [Orthopedic treatment of the shoulder joint impairment in patients with rheumatoid arthritis].

    PubMed

    Herasymenko, S I; Babko, A M; Poluliakh, M V; Huzhevs'ky?, I V; Herasymenko, A S

    2014-12-01

    Brachial joint affection in patients, suffering rheumatoid arthritis, occupies a third place after such of the elbow and the hand. Due to significant reduction of a freedom degree, caused by inflammation, the upper extremity looses function of active instrument for the items transposition. Volume of surgical treatment of such patients depends on stage of the process. On early stages arthroscopic synovectomy of brachial joint is performed and on the late--endoprosthesis. Late results of the treatment are mainly positive. Satisfactory results are based, predominantly, on raising of activity of general rheumatoid inflammation. PMID:25842886

  11. Fluorescence imaging of experimental rheumatoid arthritis in vivo using a fast flying-spot scanner

    NASA Astrophysics Data System (ADS)

    Berger, J.; Voigt, J.; Seifert, F.; Ebert, B.; Macdonald, R.; Gemeinhardt, I.; Gemeinhardt, O.; Schnorr, J.; Taupitz, M.; Vater, A.; Vollmer, S.; Licha, K.; Schirner, M.

    2007-07-01

    We have developed a flying-spot scanner for fluorescence imaging of rheumatoid arthritis in the near infrared (NIR) spectral range following intravenous administration of contrast agents. The new imaging system has been characterized with respect to linearity, dynamic range and spatial resolution with the help of fluorescent phantoms. In vivo experiments were performed on an animal model of rheumatoid arthritis. Finally, NIR-fluorescence images of early stages of joint inflammation have been compared with findings from contrast enhanced MR imaging and histology.

  12. A Solution to the Rheumatoid Factor Paradox Pathologic Rheumatoid Factors Can Be Tolerized by Competition with Natural

    E-print Network

    Beauchemin, Catherine A.A.

    and in patients with rheumatoid arthritis). The /ourna/ of Immunology, 1997, 159: 1728-1 738. There are two important being that pathologic RFs are associated with rheumatoid arthritis (RA) while natural RFs are notA Solution to the Rheumatoid Factor Paradox Pathologic Rheumatoid Factors Can Be Tolerized

  13. Circadian variation in disease activity in rheumatoid arthritis.

    PubMed Central

    Harkness, J A; Richter, M B; Panayi, G S; Van de Pette, K; Unger, A; Pownall, R; Geddawi, M

    1982-01-01

    Disease activity in rheumatoid arthritis as measured by repeated estimation of joint pain, stiffness, articular index, and grip strength was shown to have a circadian rythm, maximal activity being seen between 0200 and 0400 and minimal activity in the early afternoon. This variation in disease activity may be related to circadian alterations in immune and inflammatory responses (such as immune complexes and neutrophil function) dependent on alterations in circulating concentrations of steroids. The circadian variation in disease activity has important implications in assessment of patients, prescription of drugs, and performance of drug trials. PMID:6800538

  14. Pangaean climate during the Early Jurassic: GCM simulations and the sedimentary record of paleoclimate

    SciTech Connect

    Chandler, M.A.; Rind, D.; Ruedy, R.

    1992-05-01

    Results from new simulations of the Early Jurassic climate show that increased ocean heat transport may have been the primary force generating warmer climates during the past 180 m.y. The simulations, conducted using the general circulation model (GCM) at the Goddard Institute for Space Studies, include realistic representations of paleocontinental distribution, topography, epeiric seas, and vegetation, in order to facilitate comparisons between model results and paleoclimate data. three major features of the simulated Early Jurassic climate include the following. (1) A global warming, compared to the present, of 5 {degrees}C to 10 {degrees}C, with temperature increases at high latitudes five times this global average. Average summer temperatures exceed 35 {degrees}C in low-latitude regions of western Pangaea where eolian sandstones testify to the presence of vast deserts. (2) Simulated precipitation and evaporation patterns agree closely with the moisture distribution interpreted from evaporites, and coal deposits. High rainfall rates are associated primarily with monsoons that originate over the warm Tethys Ocean. Unlike the {open_quotes}megamonsoons{close_quotes} proposed in previous studies, these systems are found to be associated with localized pressure cells whose positions are controlled by topography and coastal geography. (3) Decreases in planetary albedo, occurring because of reductions in sea ice, snow cover, and low clouds, and increases in atmospheric water vapor are the positive climate feedbacks that amplify the global warming. Similar to other Mesozoic climate simulations, our model finds that large seasonal temperature fluctuations occurred over mid- and high-latitude continental interiors, refuting paleoclimate evidence that suggests more equable conditions. 101 refs., 9 figs., 3 tabs.

  15. Automated radiographic absorptiometry system for quantitative rheumatoid arthritis assessment

    NASA Astrophysics Data System (ADS)

    Swarnakar, Vivek; Fan, Bo; Genant, Harry K.

    2001-07-01

    Quantifying disease progression of patients with early stage Rheumatoid Arthritis (RA) presents special challenges. Establishing a robust and reliable method that combines the ACR criteria with bone and soft-tissue measurement techniques, would make possible the diagnosis of early RA and/or the monitoring of the progress of the disease. In this paper an automated, reliable and robust system that combines the ACR criteria with radiographic absorptiometry based bone and soft-tissue density measurement techniques is presented. The system is comprised of an image digitization component and an automated image analysis component. Radiographs of the hands and the calibration wedges are acquired and digitized following a standardized procedure. The image analysis system segments the relevant joints into soft-tissue and bone regions and computes density values of each of these regions relative to the density of the reference wedges. Each of the joints are also scored by trained radiologists using the well established ACR criteria. The results of this work indicate that use of standardized imaging procedures and robust image analysis techniques can significantly improve the reliability of quantitative measurements for rheumatoid arthritis assessment. Furthermore, the methodology has the potential to be clinically used in assessing disease condition of early stage RA subjects.

  16. Neuropsychiatric manifestations in rheumatoid arthritis.

    PubMed

    Joaquim, Andrei F; Appenzeller, Simone

    2015-12-01

    Rheumatoid arthritis (RA) is a chronic disease characterized by persistent synovitis, systemic inflammation, and the presence of autoantibodies. Neuropsychiatric manifestations are quite common in RA, including depression, cognitive dysfunction, behavior changes, spinal cord compression and peripheral nerve involvement. Potential causes include systemic inflammatory process, neural compression due to bone and joint destruction, side effects of medications and copying difficulties due to the chronicity of the disease. A high level of suspicious is required for an adequate diagnosis and treatment. In this review, we will discuss topographically the main neuropsychiatric manifestations described in RA patients, in an attempt to help in the management of these complex and multifaceted disease. PMID:26238502

  17. [Surgical treatment of the rheumatoid hand].

    PubMed

    Kénési, C

    1996-10-01

    In rheumatoid arthritis, involvement of the hand is serious, frequent and occurs early. It reaches synovial sheets, articular or tendinous, and causes painful and invalidating deformities. Our experience, based on 537 operations of the hand, indicates that reconstructive surgery can be practised at all levels. For the wrist, inferior radio ulnar arthrodesis strengthens the articulation and eradicates pain when performed in the early stage. Segmentar resection of ulnar diaphysis ensures the conservation of "prono- supination". In the case of destruction or luxation of the wrist, a choice has to be made between prosthesis and arthrodesis. We tend to prefer the latter which confers a strong, painless and definitive articulation. Ulnar deviation of metacarpo-phalangeal articulations of long fingers can be corrected by ligamentar or tendinous plasties. But the results are not always durable and they cannot be used when the articulations are destroyed. In that case prostheses have to be implanted. Swanson's silastic implants enable to straighten the fingers and to suppress pain but ensure a limited mobility. Likewise, interphalangeal deviations generally call for implants or arthrodeses. Trapezo-metacarpal or phalangeo-metacarpal deformities of the thumb are stabilised by arthrodeses, ensuring a strong and painless prehension. In conclusion, reconstructive surgery allows many possibilities but its results are often incomplete. It is therefore advisable to perform synovectomy as early as possible before the occurrence of deformities. Surgical synovectomy competes with isotopic, chemical or corticoid synoviosthesis. But at tendinous level, synovectomy alone should be used, since it gives excellent results. Even though rehabilitation after synovectomies is not always easy, we hope that it will prevent the occurrence of articular or tendinous destruction for many years. PMID:9102148

  18. Competition between nucleation and early growth of ferrite from austenite -- Studies using cellular automaton simulations

    SciTech Connect

    Kumar, M.; Sasikumar, R.; Nair, P.K.

    1998-11-02

    A model for the nucleation of ferrite on austenite grain boundaries and the growth of these nuclei along the grain boundary and into the grain, is developed. A cellular automaton algorithm, with transformation rules based on this model, is used to simulate the decomposition of austenite into ferrite. When performed under continuous cooling conditions, the simulations give an insight into the competition between nucleation and early growth, which determines the variation of ferrite grain size with the cooling rate and with austenite grain size. The number of ferrite grains per austenite grain, ferrite grain size and the kinetics of ferrite formation are obtained as a function of the cooling rate and austenite grain size. Contour plots of the volume fraction of ferrite in the cells at different times, enables visualization of the ferrite growth process.

  19. Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, and hidden rheumatoid factors.

    PubMed Central

    Bonagura, V R; Wedgwood, J F; Agostino, N; Hatam, L; Mendez, L; Jaffe, I; Pernis, B

    1989-01-01

    The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs. PMID:2662917

  20. 3D simulations of the early stages of AGN jets: geometry, thermodynamics and backflow

    E-print Network

    Cielo, S; Macciò, A V; Romeo, A D; Silk, J

    2013-01-01

    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 behavior. 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 order of a few percent 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 (ISM volume. Finally we demonstrate the relevance of backflows ...

  1. Testing early life connectivity using particle tracking simulations and otolith chemistry

    NASA Astrophysics Data System (ADS)

    Ashford, Julian; Fach, Bettina A.; La Mesa, Mario; Jones, Christopher; Everson, Inigo

    2010-05-01

    Large-scale circulation may structure populations of oceanic fish, and hence distributions of chemistry in their otoliths. We applied a combination of Lagrangian modelling and otolith chemistry of Scotia Sea icefish (Chaenocephalus aceratus), a species with a long pelagic larval phase found along the Antarctic Circumpolar Current, to test connectivity previously predicted between the Antarctic Peninsula and South Georgia. Material laid down in the otolith nucleus during early life showed evidence of heterogeneity between sampling areas on the northern Antarctic Peninsula, whereas similar nucleus chemistry at sampling areas off South Georgia suggested a discrete, locally-recruiting population, consistent with observed larval assemblages. Strong evidence of a population boundary discounted hypotheses of early life connectivity between the two regions. This was consistent with particle simulations of the large-scale circulation, which predicted that particles released deep on the Antarctic Peninsula shelf during late winter, corresponding to hatching of icefish larvae from benthic nests, are transported close to the ACC southern boundary, missing South Georgia but following trajectories along the south Scotia Ridge. Used together, the two techniques promise an innovative approach to generate and test predictions, and resolve early dispersal and connectivity related to the physical circulation of oceanic systems.

  2. Methods for Detecting Early Warnings of Critical Transitions in Time Series Illustrated Using Simulated Ecological Data

    PubMed Central

    Dakos, Vasilis; Carpenter, Stephen R.; Brock, William A.; Ellison, Aaron M.; Guttal, Vishwesha; Ives, Anthony R.; Kéfi, Sonia; Livina, Valerie; Seekell, David A.; van Nes, Egbert H.; Scheffer, Marten

    2012-01-01

    Many dynamical systems, including lakes, organisms, ocean circulation patterns, or financial markets, are now thought to have tipping points where critical transitions to a contrasting state can happen. Because critical transitions can occur unexpectedly and are difficult to manage, there is a need for methods that can be used to identify when a critical transition is approaching. Recent theory shows that we can identify the proximity of a system to a critical transition using a variety of so-called ‘early warning signals’, and successful empirical examples suggest a potential for practical applicability. However, while the range of proposed methods for predicting critical transitions is rapidly expanding, opinions on their practical use differ widely, and there is no comparative study that tests the limitations of the different methods to identify approaching critical transitions using time-series data. Here, we summarize a range of currently available early warning methods and apply them to two simulated time series that are typical of systems undergoing a critical transition. In addition to a methodological guide, our work offers a practical toolbox that may be used in a wide range of fields to help detect early warning signals of critical transitions in time series data. PMID:22815897

  3. 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.

  4. Vocational Rehabilitation for Persons with Rheumatoid Arthritis.

    ERIC Educational Resources Information Center

    Allaire, Saralynn H.

    1998-01-01

    Useful vocational rehabilitation strategies for persons with rheumatoid arthritis include (1) management of symptoms and reduction of energy demand; (2) reasonable job accommodations; (3) identification of suitable jobs and necessary training; and (4) enhancement of self-advocacy skills. (SK)

  5. Rheumatoid Arthritis - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... List of All Topics All Rheumatoid Arthritis - Multiple Languages To use the sharing features on this page, please enable JavaScript. Chinese - Simplified (????) Chinese - Traditional (????) Korean (???) Spanish (español) Vietnamese (Tiê?ng Viê?t) Chinese - Simplified ( ...

  6. ASTROMEDICINE IN THE TREATMENT OF RHEUMATOID ARTHRITIS

    PubMed Central

    Janai, Sudhakar; Biviji, A. T.; Naik, D. G.; Lakhe, R. T.; Rao, V. Bhaskar

    1991-01-01

    One patient of rheumatoid arthritis was treated according to astromedicine. Wearing of Coral beads had remarkable effect on the disease. The interesting finding are reported in this paper. PMID:22556538

  7. Rheumatoid myositis leading to acute lower extremity compartment syndrome: a case-based review.

    PubMed

    Jo, Daniel; Pompa, Tiffany; Khalil, Ambreen; Kong, Frank; Wetz, Robert; Goldstein, Mark

    2015-10-01

    Muscle pain and weakness in a rheumatoid arthritis (RA) patient has a broad differential, and myositis should be considered early in the disease course as serious limb and life-threatening sequelae may occur. A 55-year-old woman with a past medical history of methotrexate-controlled RA presented with right leg pain for 4 days. The patient suffered sensory loss in the right foot and decreased strength in the toes. Lab tests revealed elevated creatine kinase, ESR, and anti-rheumatoid factor antibody titers. CT scan revealed myositis of posterior compartment muscles. Progressive edema, pain, and neuromuscular deficits persisted despite steroid and antibiotic therapy, so the patient was taken for urgent fasciotomy for acute compartment syndrome. The muscle biopsy showed diffuse mononuclear cell infiltration as well as perivascular and perineural involvement consistent with rheumatoid myositis (RM). The patient did well post-op on a prednisone taper. This case underlines the systemic nature of RA and exemplifies the severity of inflammation that may lead to grave consequences such as compartment syndrome. The histopathology is diagnostic when there is evidence of mononuclear cell infiltration; however, this is not entirely specific. Early, aggressive therapy with immunosuppressives is warranted in such patients. RM has not, to our knowledge, been recorded to cause acute compartment syndrome. Clinicians should be aware of this uncommon manifestation of RA keeping the various presentations of rheumatoid disease in mind when faced with these patients. PMID:24810700

  8. New insight into the rheumatoid vasculitis.

    PubMed

    Cojocaru, M; Cohocaru, Inimioara Mihaela; Chico, B

    2015-01-01

    Vasculitis in rheumatoid arthritis (rheumatoid vasculitis, RV) has a heterogeneous clinical presentation that includes skin disorders, neuropathy, eye symptoms and systemic inflammation. Rheumatoid vasculitis is an unusual complication of longstanding, severe rheumatoid arthritis (RA). While RA affects the body's joints, vasculitis is a condition in which blood vessels become inflamed. Rheumatoid vasculitis occurs in approximately 2 to 5% of patients who have RA. The blood vessels most often involved are arteries that bring blood to the skin, nerves, and internal organs. Veins can also be involved. Rheumatoid vasculitis is skin condition that is a typical feature of RA, presenting as peripheral vascular lesions that are localized (purpura, cutaneous ulceration, and gangrene of the distal parts of the extremities). The cause of RV is unknown, but given the prominence of immune components and the pathologic changes in involved blood vessels, an autoimmune process is suggested. Compared to other forms of vasculitis, there has been relativejy little research in recent years on the specific entity of RV. There is some evidence that the incidence of RV has decreased over the past several decades, perhaps because of a better treatment of the underlying RA. In the present review, we discuss the clinical features, laboratory tests, the pathogenesis of RV. PMID:26402981

  9. Proteomics in Rheumatoid Arthritis Research

    PubMed Central

    Park, Yune-Jung; Chung, Min Kyung; Hwang, Daehee

    2015-01-01

    Although rheumatoid arthritis (RA) is the most common chronic inflammatory autoimmune disease, diagnosis of RA is currently based on clinical manifestations, and there is no simple, practical assessment tool in the clinical field to assess disease activity and severity. Recently, there has been increasing interest in the discovery of new diagnostic RA biomarkers that can assist in evaluating disease activity, severity, and treatment response. Proteomics, the large-scale study of the proteome, has emerged as a powerful technique for protein identification and characterization. For the past 10 years, proteomic techniques have been applied to different biological samples (synovial tissue/fluid, blood, and urine) from RA patients and experimental animal models. In this review, we summarize the current state of the application of proteomics in RA and its importance in identifying biomarkers and treatment targets. PMID:26330803

  10. Beyond the joints: neurological involvement in rheumatoid arthritis.

    PubMed

    Ramos-Remus, Cesar; Duran-Barragan, Sergio; Castillo-Ortiz, Jose Dionisio

    2012-01-01

    Although arthritis is the most notable component, rheumatoid arthritis (RA) is a systemic inflammatory disorder where extra-articular manifestations are common; among them, central and peripheral nervous system involvement is frequent and associated with significant morbidity and, in some cases, reduced life span. It may produce a myriad of symptoms and signs ranging from subtle numbness in a hand, to quadriparesis and sudden death. Central and peripheral neurologic manifestations may arise from structural damage produced by RA in diarthroidal joints, by the systemic inflammatory process of the disease itself or by the drugs used to treat it. Neurologic syndromes may appear suddenly or developed slowly through months, and emerge early or after years of having RA. Neurologic manifestations may be easily overlooked or incorrectly assigned to peripheral arthritis unless the attending physician is aware of these complications. In this article, we review neurologic involvement in RA patients with emphasis on clinical approach for early detection. PMID:21932019

  11. Assessment of early onset of driver fatigue using multimodal fatigue measures in a static simulator.

    PubMed

    Jagannath, M; Balasubramanian, Venkatesh

    2014-07-01

    Driver fatigue is an important contributor to road accidents. This paper reports a study that evaluated driver fatigue using multimodal fatigue measures, i.e., surface electromyography (sEMG), electroencephalography (EEG), seat interface pressure, blood pressure, heart rate and oxygen saturation level. Twenty male participants volunteered in this study by performing 60 min of driving on a static simulator. Results from sEMG showed significant physical fatigue (? < 0.05) in back and shoulder muscle groups. EEG showed significant (? < 0.05) increase of alpha and theta activities and a significant decrease of beta activity during monotonous driving. Results also showed significant change in bilateral pressure distribution on thigh and buttocks region during the study. These findings demonstrate the use of multimodal measures to assess early onset of fatigue. This will help us understand the influence of physical and mental fatigue on driver during monotonous driving. PMID:24581559

  12. Effect of simulated early weight bearing on micromotion and pullout strength of uncemented distal femoral stems.

    PubMed

    Barr, Jennifer S; White, Jedediah K; Punt, Stephanie E W; Conrad, Ernest U; Ching, Randal P

    2015-05-01

    The effect of simulated early weight bearing on both micromotion and pullout strength of uncemented distal femoral stems was evaluated in this study. The effect of stem endosteal contact and bone quality on implant pullout strength was also analyzed. A randomized matched-pair study was performed using 8 bilateral pairs of fresh human cadaveric femoral specimens. Each specimen pair was dual-energy x-ray absorptiometry scanned, uniformly implanted, fluoroscopically imaged, and randomly assigned to the cycled or uncycled group. The cycled group received 5000 cycles of axial compressive loading (to 700 N) and the contralateral side was not cycled. Micromotion was monitored during cycling and compared with a failure threshold (150 µm), and all implants underwent direct axial distraction (pullout) testing. During cycling, minimal micromotion was observed with an asymptotic decrease in differential motion between the first and last 50 cycles. Both cycled and uncycled groups demonstrated no statistical difference in average pullout force (4888±2124 N vs 4367±1154 N; P=.43). The percentage of cortical contact for each implant was determined from panoramic fluoroscopy images using digital image analysis software. Contact area for the distal third of the stem showed the highest correlation with pullout force and with predicting pullout force. Bone quality did not correlate with pullout force (r(2)=0.367) or stem contact area (r(2)=0.394). In sum, press-fit uncemented femoral stems did not loosen or demonstrate decreased pullout strength with early weight bearing simulated by cyclical axial compressive loading. PMID:25970370

  13. 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...

  14. 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.

  15. What People with Rheumatoid Arthritis Need to Know about Osteoporosis

    MedlinePLUS

    ... Osteoporosis Osteoporosis and Other Conditions What People With Rheumatoid Arthritis Need to Know About Osteoporosis Publication available in: ... Lupus Osteogenesis Imperfecta Prostate Cancer Smoking Partner Resources Rheumatoid Arthritis (NIAMS) ¿Qué es la artritis reumatoide? (NIAMS) What ...

  16. Cyclophilins in rheumatoid arthritis--stepping into an undiscovered country?

    E-print Network

    Lee, Won-Ha

    Cyclophilins in rheumatoid arthritis--stepping into an undiscovered country? Thomas Pap Division 2005 Recent years have seen enormous progress in under- standing the pathogenesis of rheumatoid arthritis (RA), an autoimmunological disorder that primarily affects the joints and leads

  17. Early MIMD experience with a plasma physics simulation program on the CRAY X-MP

    SciTech Connect

    Rhoades, C.E. Jr.

    1986-02-01

    This paper describes some early experience with converting a plasma physics simulation program to the CRAY X-MP, a current multiple instruction, multiple data (MIMD) computer consisting of two processors with architecture similar to that of the CRAY-1. The computer program used in this study is an all Fortran version of SELF, a two species, one space, two velocity, electromagnetic, Newtonian, particle in cell, plasma simulation code. The approach to converting SELF to use both processors of the CRAY X-MP is described in some detail. The resulting multiprocessor version of SELF is nearly a factor of two faster in real time than the single processor version. The multiprocessor version obtains 58.2+-.1 seconds of central processor time in 30+-.5 seconds of real time. For comparison, the CRAY-1 execution time if 74.5 seconds. For SELF, which is mostly scalar coding, the CRAY X-MP is about 2.5 times faster overall than the CRAY-1.

  18. 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

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

    NASA Astrophysics Data System (ADS)

    Meng, J. C.; Colonius, T.

    2015-07-01

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

  20. EXTENDED REPORT DNA methylome signature in rheumatoid arthritis

    E-print Network

    Wang, Wei

    EXTENDED REPORT DNA methylome signature in rheumatoid arthritis Kazuhisa Nakano,1 John W Whitaker,2 in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA epigenetic contributions to inflammatory arthritis. INTRODUCTION Rheumatoid arthritis (RA) is an immune

  1. Remission-inducing drugs in rheumatoid arthritis.

    PubMed Central

    Anastassiades, T. P.

    1980-01-01

    The administration of certain drugs to patients with established rheumatoid arthritis frequently results in improvement that is slow to appear but persists for long periods, even after the drug is discontinued. The three main drugs with this effect, whose efficacy and toxicity are reviewed in this paper, are gold salts, D-penicillamine and chloroquine. The cytotoxic agents used to treat rheumatoid arthritis, which likely have nonspecific anti-inflammatory actions and have serious long-term side effects, are also briefly reviewed. A new drug, levamisole, is currently being tested in patients with rheumatoid arthritis. It is suggested that the time for considering the introduction of a remission-inducing drug in patients with progressive rheumatoid arthritis is after an adequate trial of therapy with salicylates or other nonsteroidal anti-inflammatory agents, or both, and before the oral administration of steroids. It is difficult, however, on the basis of rigorous clinical comparisons, to recommend which of the three main remission-inducing drugs should be tried first, although gold salts have been used the most. Patients who have improved with 6 months of chrysotherapy may continue treatment for at least 3 years, during which time the frequency of mucocutaneous and renal toxic effects will steadily decrease. Some aspects of the medical economics of therapy with remission-inducing drugs for rheumatoid arthritis are discussed. PMID:6768438

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  3. Rheumatoid arthritis and work: The impact of rheumatoid arthritis on absenteeism and presenteeism.

    PubMed

    Verstappen, Suzanne M M

    2015-06-01

    For patients with rheumatoid arthritis (RA), being in paid work is very important, and it increases self-esteem and financial independence. Although the management of RA has changed in the last 15 years to early aggressive treatment and the introduction of biologic treatments, many patients still have to take sick leave or even stop working because of their RA (i.e., absenteeism). For those remaining in paid work, patients may experience problems due to RA resulting in productivity loss while at work (i.e., presenteeism). The costs attributed to absenteeism and presenteeism (i.e., indirect costs) have been estimated to be very high, and they even exceed direct costs. However, there is no consensus on how to calculate these costs. This manuscript examines the relationship between the use of biologic therapy and absenteeism, with a focus on sick leave, and on presenteeism, and it provides an overview of indirect costs of absenteeism and presenteeism in those treated with biologic therapies. PMID:26612244

  4. 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. )

    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.

  5. The microbiome and rheumatoid arthritis

    PubMed Central

    Scher, Jose U.; Abramson, Steven B.

    2012-01-01

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

  6. HLA-linked rheumatoid arthritis

    SciTech Connect

    Hasstedt, S.J.; Clegg, D.O.; Ingles, L.; Ward, R.H.

    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.

  7. 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.

  8. 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.

  9. 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

  10. [Occupational therapy after rheumatoid hand surgery].

    PubMed

    Holzer, K

    2005-02-01

    Occupational therapists face a number of challenges in the after-treatment of rheumatoid hand surgery. They have to take into account the specialties of the surgery and the remaining deformities of the rheumatoid hand. Edema prophylaxis and scar treatment are similar for all patients, while splinting and functional training depend greatly on the different kinds of surgery. Both splinting and mobilization have to be adjusted to patient and process of the therapy. The protracted treatment requires a high compliance of the patient. Instruction and information about operation and postoperative therapy support comprehension and cooperation of the patient. PMID:15744658

  11. Ensemble hydro-meteorological simulation for flash flood early detection in southern Switzerland

    NASA Astrophysics Data System (ADS)

    Alfieri, Lorenzo; Thielen, Jutta; Pappenberger, Florian

    2012-03-01

    SummaryOngoing changing climate has raised the attention towards weather driven natural hazards. Local floodings and debris flows following exceptional downpours often come without any adequate warning and cause heavy tolls to the human society. This work proposes a novel flood alert system for small catchments prone to flash flooding, capable of monitoring a large portion of the European domain. Operational streamflow simulations are produced through distributed hydrological modeling of ensemble weather forecasts. A long-term reforecast dataset is run through the same hydrological model to derive coherent warning thresholds. These are compared with operational discharge ensembles in a threshold exceedance analysis to produce early warnings. A case study in the southern Switzerland is tested over a 17-month period and system skills are evaluated by means of different quantitative and qualitative analyses. Results from three different predictors derived from the streamflow ensemble are shown and compared, also by accounting for the persistence of lagged forecasts. Significant improvements in predicting discharge thresholds exceedance are achieved by fitting gamma probability distributions to the raw ensemble. Further discussion underlines the limits of predictability of extreme events in small catchments due to the comparatively coarse space-time resolution of current weather forecasts.

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

    NASA Astrophysics Data System (ADS)

    van de Voort, Freeke; Davis, Timothy A.; Kereš, Dušan; Quataert, Eliot; Faucher-Giguère, Claude-André; Hopkins, Philip F.

    2015-08-01

    Massive early-type galaxies (ETGs) commonly have gas discs which are kinematically misaligned with the stellar component. These discs feel a torque from the stars and the angular momentum vectors are expected to align quickly. We present results on the evolution of a misaligned gas disc in a cosmological simulation of a massive ETG from the feedback in realistic environments project. This galaxy experiences a merger which, together with a strong galactic wind, removes most of the original gas disc. The galaxy subsequently reforms a gas disc through accretion of cold gas, but it is initially 120° misaligned with the stellar rotation axis. This misalignment persists for about 2 Gyr before the gas-star misalignment angle drops below 20°. The time it takes for the gaseous and stellar components to align is much longer than previously thought, because the gas disc is accreting a significant amount of mass for about 1.5 Gyr after the merger, during which the angular momentum change induced by accreted gas dominates over that induced by stellar torques. Once the gas accretion rate has decreased sufficiently, the gas disc decouples from the surrounding halo gas and realigns with the stellar component in about six dynamical times. During the late evolution of the misaligned gas disc, the centre aligns faster than the outskirts, resulting in a warped disc. We discuss the observational consequences of the long survival of our misaligned gas disc and how our results can be used to calibrate merger rate estimates from observed gas misalignments.

  13. 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.

  14. 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.

  15. 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

  16. CD44 in rheumatoid arthritis

    PubMed Central

    Naor, David; Nedvetzki, Shlomo

    2003-01-01

    CD44 is a multistructural cell-surface glycoprotein that can theoretically generate close to 800 isoforms by differential alternative splicing. At present, several dozen isoforms are known. The polymorphic nature of CD44 might explain its multifunctionality and its ability to interact with many cell-surface and extracellular ligands, the principal one being hyaluronic acid (HA). Of the many CD44 functions, our review focuses on its involvement in cell–cell and cell–matrix interactions, as well as on its implication in the support of cell migration and the presentation of growth factors to their cognate receptors. Cells involved in pathological activities such as cancer cells and destructive inflammatory cells, and also normal cells engaged in physiological functions, use cell-surface CD44 for their localization and expansion at extravascular sites. This article reviews the evidence that the joint synovium of patients with rheumatoid arthritis (RA) contains considerable amounts of various CD44 isoforms as well as the HA ligand. The review also shows that anti-CD44 monoclonal antibody (mAb) directed against constant epitopes, shared by all CD44 isoforms, can markedly reduce the inflammatory activity of arthritis induced by collagen or proteoglycans in mice. Anti-CD44 mAb also interferes with the migration of RA synovial-like fibroblasts in vitro and is able to disturb the destructive interaction between RA synovial-like fibroblasts and the cartilaginous matrix. However, the transition from the experimental model to the patient's bedside is dependent on the ability to target the CD44 of cells engaged in RA pathology, while skipping the CD44 of normal cells. PMID:12723975

  17. [Socioeconomic aspects of rheumatoid arthritis].

    PubMed

    Jaji?, I; Jaji?, Z; Ozi?-Bebek, M; Su?ur, A

    1991-01-01

    This study investigated the financial parameters of the hospital treatment and of the rehabilitation in the Centers for Rehabilitation for the patients with rheumatoid arthritis (RA). The control group consisted of patients who were ill or had been ill from some other diseases which were controlled at the physician of the primary health service. The average duration of the treatment of the patients with RA in hospital was 28 days (ranging from 21 to 35 days), while the average duration of the treatment of the patients from the control group was 18 days (ranging 7 to 45 days). 45 patients with RA were hospitalized and 22 from 65 patients from the control group (P greater than 0.05). The duration of the hospital treatment of 45 patients with RA was 2548 days and it was 1818 days for the patients from the control group (P = 0.039). The cost of one stay of 28 days in the hospital amounted 56.000 din per one patient with RA and it was 36.000 din per one patient from the control group (according to the price-list from 31. 7. 1991.). 49 patients with RA went for several times to the rehabilitation into the Centers for Rehabilitation and 11 from 65 patients from the control group (P less than 0.0001). The average duration of rehabilitation for the patients with RA was 23 days while it was 26 days for the patients from the control group (P greater than 0.06). The rehabilitation for the patients with RA lasted 4278 days and 832 days for the patients from the control group (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1809995

  18. Simulation Shows That Early Treatment of Chronic Hepatitis B Infection Can Cut Deaths and Be Cost-Effective

    PubMed Central

    Post, Sarah E.; Sodhi, Neetu Khurana; Peng, Chia-hui; Wan, Kejia; Pollack, Henry J.

    2014-01-01

    Chronic hepatitis B affects more than a million people in the U.S. and causes 4,000 deaths each year, yet the costs and benefits of treatment have not been fully evaluated. Using a model that simulates disease progression, we compare treatment programs for hepatitis B that start at an early versus late stage of disease. Early care is shown to improve health, reduce premature deaths, and prevent expensive complications, making it highly cost-effective. Our results demonstrate the importance of linking hepatitis B screening to treatment, and illustrate how predictive models can be used to evaluate strategies for improving access to care. PMID:21289356

  19. 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…

  20. Complement activation induced by rabbit rheumatoid factor.

    PubMed Central

    Meyer, R R; Brown, J C

    1980-01-01

    Rabbit rheumatoid factor produced in animals by hyperimmunized with group C streptococcal vaccine activated guinea pig complement. Anti-streptococcal serum was fractionated by Sephacryl S-200 chromatography into excluded (19S) and included (7S) material and examined for hemolytic activity in a sensitive homologous hemolytic assay system. In the presence of complement, both 19S and 7S antistreptococcal serum fractions induced lysis of bovine (ox) erythrocytes coated with mildly reduced and carboxymethylated rabbit anti-erythrocyte immunoglobulin G. That rabbit rheumatoid factor was responsible for the observed hemolytic activity was substantiated by hemolytic inhibition assays. Significant inhibition of hemolysis was effected when antistreptococcal serum fractions were incubated in the presence of human immunoglobulin G, rabbit immunoglobulin G, and Fc, whereas, no inhibition was detected when the same fractions were tested in the presence of rabbit Fab or F(ab')2 fragments. Deaggregation of inhibitor preparations revealed a preferential reactivity of rheumatoid factor for rabbit immunoglobulin G. In addition to the rheumatoid factor-dependent hemolytic activity observed in humoral preparations, immunoglobulin G-specific antibody-forming cells in spleen and peripheral blood lymphocyte isolates were enumerated by plaque-forming cell assay. PMID:7399707

  1. Stem Cell Therapy for Rheumatoid Arthritis

    E-print Network

    Brutlag, Doug

    Cells vs Gene TherapyStem Cells vs Gene Therapy For RA, not all genetic causes are known to kill oversecreted or transformed cells Gene therapy may have long term side effects #12;BibliographyStem Cell Therapy for Rheumatoid Arthritis By: Matt Ferry Biochem 118 Brutlag Winter 2012 #12

  2. Update on Treatment of Rheumatoid Arthritis

    PubMed Central

    Patterson, A. Caroline

    1987-01-01

    Treatment of rheumatoid arthritis consists of use of drugs, physical measures, social work interventions, education and reconstructive surgery. The physician plays a co-ordinating role, since most patients with significant rheumatoid arthritis will require treatment by more than one member of the health-care team. Our drug armamentarium, including anti-inflammatory agents, disease suppressants, analgesics, rarely steroids, and even more rarely immunosuppressants, can be used to good effect in suppressing the synovitis of rheumatoid arthritis and in relieving pain. Physiotherapy, occupational therapy, nursing and social work interventions will help the patient to maintain function and to maintain their optimal level of fitness, including exercise tolerance, joint range, muscle strength and psycho-social function. Coping abilities can be greatly enhanced by a positive approach from the physician, and this, together with the very real benefits of the foregoing treatments, can produce a highly rewarding result for physician and patient alike, in terms of improved quality of life for the rheumatoid arthritis patient. PMID:21263856

  3. Microarray analysis of the primate luteal transcriptome during chorionic gonadotrophin administration simulating early pregnancy

    PubMed Central

    Bishop, C.V.; Satterwhite, S.; Xu, L.; Hennebold, J.D.; Stouffer, R.L.

    2012-01-01

    To explore chorionic gonadotrophin (CG)-regulated gene expression in the primate corpus luteum (CL), adult female rhesus macaques were treated in a model of simulated early pregnancy (SEP). Total RNA was isolated from individual CL after specific intervals of exposure (1, 3, 6 and 9 days) to recombinant hCG in vivo and hybridized to Affymetrix™ GeneChip Rhesus Macaque Genome Arrays. The mRNA levels of 1192 transcripts changed ?2-fold [one-way ANOVA, false discovery rate (FDR) correction; P< 0.05] during SEP when compared with Day 10 untreated controls. Real-time PCR validation indicated that 15 of 17 genes matched in expression pattern between PCR and microarray. Protein levels of three genes identified as CG-sensitive, CYP19A1 (aromatase), PGRMC1 (progestin-binding protein) and STAR (steroidogenic acute regulatory protein) were quantified by western blot analysis. To further analyze global changes in gene expression induced by CG exposure, luteal gene expression was compared between SEP (rescued) and regressing CL, utilizing previously banked GeneChip data from the luteal phase of the menstrual cycle. Expression patterns and mRNA levels were analyzed between time-matched intervals. Transcripts for 7677 mRNAs differed in expression patterns ?2-fold (one-way ANOVA, FDR correction; P< 0.05) between the hCG-exposed (SEP) CL and regressing CL. Regressed CL (at menses) were most unlike all other CL. Pathway analysis of significantly affected transcripts was performed; the pathway most impacted by CG exposure was steroid biosynthesis. Further comparisons of the genome-wide changes in luteal gene expression during CG rescue and luteolysis in the natural menstrual cycle should identify additional key regulatory pathways promoting primate fertility. PMID:22072816

  4. Detection of rheumatoid arthritis using infrared imaging Monique Frizea,b

    E-print Network

    Payeur, Pierre

    Detection of rheumatoid arthritis using infrared imaging Monique Frizea,b , Cynthia Adéaa , Pierre Rheumatology, Ottawa Hospital, Riverside Dr., Ottawa, ON, Canada. ABSTRACT Rheumatoid arthritis (RA subjects and 13 patients diagnosed with Rheumatoid Arthritis (RA), thermal images were collected from

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  6. Treat-to-target: a tailored treatment approach to rheumatoid arthritis.

    PubMed

    Palmer, Deborah; El Mledany, Yasser

    In contrast to articles and books written about rheumatoid arthritis (RA) two or more decades ago that largely focused on 'coping' with the disease, there have been significant developments in the treatment of RA over the past 10 years. Patients can now be diagnosed and treated and expect to live functional lives, with less likelihood of experiencing the associated joint damage and disability. An important goal of RA therapy has shifted to initiate treatment early and aggressively, with frequent assessment and a target to achieve remission as quickly as possible. This 'treat-to-target' concept has been endorsed to maximise long-term health-related quality of life through control of symptoms, prevention of structural damage, normalisation of function and social participation. This article will look at therapies and strategies for the treatment of RA. It will also discuss a treatment algorithm for rheumatoid arthritis tailored to the individual patient's disease activity status. PMID:23901448

  7. Optical monitoring of rheumatoid arthritis: Monte Carlo generated reconstruction kernels

    NASA Astrophysics Data System (ADS)

    Minet, O.; Beuthan, J.; Hielscher, A. H.; Zabarylo, U.

    2008-06-01

    Optical imaging in biomedicine is governed by the light absorption and scattering interaction on microscopic and macroscopic constituents in the medium. Therefore, light scattering characteristics of human tissue correlate with the stage of some diseases. In the near infrared range the scattering event with the coefficient approximately two orders of magnitude greater than absorption plays a dominant role. When measuring the optical parameters variations were discovered that correlate with the rheumatoid arthritis of a small joint. The potential of an experimental setup for transillumination the finger joint with a laser diode and the pattern of the stray light detection are demonstrated. The scattering caused by skin contains no useful information and it can be removed by a deconvolution technique to enhance the diagnostic value of this non-invasive optical method. Monte Carlo simulations ensure both the construction of the corresponding point spread function and both the theoretical verification of the stray light picture in rather complex geometry.

  8. Current Concepts in the Management of the Rheumatoid Hand

    PubMed Central

    Chung, Kevin C; Pushman, Allison G

    2011-01-01

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

  9. The pathogenesis of rheumatoid arthritis in radiological studies. Part I: Formation of inflammatory infiltrates within the synovial membrane

    PubMed Central

    Kontny, Ewa; Ma?li?ski, W?odzimierz; Prochorec-Sobieszek, Monika; Kwiatkowska, Brygida; Zaniewicz-Kaniewska, Katarzyna; Warczy?ska, Agnieszka

    2012-01-01

    Rheumatoid arthritis is a chronic inflammatory disease with a multifactorial etiology and varied course, which in the majority of patients leads to partial disability or to permanent handicap. Its characteristic trait is a persistent inflammation of the synovial membrane and the formation of an invasive synovial tissue, called the pannus, which in time leads to destruction of the cartilage, subchondral bone tissue, and the soft tissue of the affected joint(s). The pathogenesis of rheumatoid arthritis is complex and involves cells of both innate and adaptive immunity, a network of various cytokines and an immunoregulatory dysfunction. An important role in the discovery of rheumatoid arthritis pathogenesis was played by magnetic resonance imaging, which showed the disease process to extend beyond the synovium into the bone marrow. Many studies have shown a strict correlation between the vascularity of the synovium (assessed through the power Doppler ultrasound and magnetic resonance examinations), bone marrow edema and the clinical, laboratory and histopathological parameters of rheumatoid arthritis. From the current understanding of rheumatoid arthritis, bone erosions could occur from two directions: from the joint cavity and from the bone marrow. With power Doppler ultrasound, as well as in magnetic resonance imaging, it is possible to visualize the well-vascularized pannus and its destructive effects on joint structures and ligaments. In addition, the magnetic resonance study shows inflammatory and destructive changes within the bone marrow (bone marrow edema, inflammatory cysts, and erosions). Bone marrow edema occurs in 68–75% of patients with early rheumatoid arthritis and is considered to be a predictor of rapid disease progression.

  10. Molecular events during the early stages of aggregation of GNNQQNY: An all atom MD simulation study of randomly dispersed peptides.

    PubMed

    Srivastava, Alka; Balaji, Petety V

    2015-12-01

    This study probes the early events during lag phase of aggregation of GNNQQNY using all atom MD simulations in explicit solvent. Simulations were performed by varying system size, temperature and starting configuration. Peptides dispersed randomly in the simulation box come together early on in the simulation and form aggregates. These aggregates are dynamic implying the absence of stabilizing interactions. This facilitates the exploration of alternate arrangements. The constituent peptides sample a variety of conformations, frequently re-orient and re-arrange with respect to each other and dissociate from/re-associate with the aggregate. The size and lifetime of aggregates vary depending upon the number of inter-peptide backbone H-bonds. Most of the aggregates formed are amorphous but crystalline aggregates of smaller size (mainly 2-mers) do appear and sustain for varying durations of time. The peptides in crystalline 2-mers are mostly anti-parallel. The largest crystalline aggregate that appears is a 4-mer in a single sheet and a 4-, 5-, or 6-mer in double layered arrangement. Crystalline aggregates grow either by the sequential addition of peptides, or by the head-on or lateral collision-adhesion of 2-mers. The formation of various smaller aggregates suggests the polymorphic nature of oligomers and heterogeneity in the lag phase. PMID:26433030

  11. 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".

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

    PubMed Central

    Deane, Kevin D.

    2014-01-01

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

  13. Tocilizumab for the treatment of rheumatoid arthritis.

    PubMed

    Tanaka, Toshio; Ogata, Atsushi; Narazaki, Masashi

    2010-11-01

    Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody, which binds to circulating soluble IL-6 receptor and membrane-expressed IL-6 receptor, inhibiting IL-6 binding to both forms of IL-6 receptor. Several Phase III clinical trials demonstrate the clinical efficacy of tocilizumab as monotherapy or with disease-modifying anti-rheumatic drugs for adult patients with moderately to severely active rheumatoid arthritis. Tocilizumab in combination with methotrexate after 24 weeks of treatment could induce disease remission in 30% of patients with rheumatoid arthritis refractory to anti-TNF antagonist therapy. The most common adverse reactions reported in clinical studies are upper respiratory tract infection, nasopharyngitis, headache, hypertension and mild, reversible increases in alanine aminotransferase enzymes. Serious adverse reactions include infections, gastrointestinal perforations and hypersensitivity reactions, including anaphylaxis. The clinical efficacy and safety of tocilizumab has led to the approval of this innovative drug for the treatment of rheumatoid arthritis in more than 70 countries worldwide. PMID:20979549

  14. 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

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

    PubMed Central

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

    2013-01-01

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

  16. Studying the Early Stages of Protein Aggregation Using Replica Exchange Molecular Dynamics Simulations.

    PubMed

    Shea, Joan-Emma; Levine, Zachary A

    2016-01-01

    The simulation of protein aggregation poses several computational challenges due to the disparate time and lengths scales that are involved. This chapter focuses on the use of atomistically detailed simulations to probe the initial steps of aggregation, with an emphasis on the Tau peptide as a model system, run under a replica exchange molecular dynamics protocol. PMID:26453216

  17. Classification of Rheumatoid Joint Inflammation Based on Laser Imaging

    E-print Network

    Tresp, Volker

    1 Classification of Rheumatoid Joint Inflammation Based on Laser Imaging Anton Schwaighofer, Volker of patients suffering from rheumatoid arthritis. Basis of this system is a laser imaging technique which is sensitive to the optical characteristics of finger joint tissue. From the laser images acquired at baseline

  18. Is rheumatoid arthritis a disease that starts in the intestine? A pilot study comparing an elemental diet with oral prednisolone

    PubMed Central

    Podas, Thrasyvoulos; Nightingale, Jeremy M D; Oldham, Roger; Roy, S; Sheehan, Nicholas J; Mayberry, John F

    2007-01-01

    Objectives This pilot study aimed to determine if an elemental diet could be used to treat patients with active rheumatoid arthritis and to compare its effect to that of oral prednisolone. Methods Thirty patients with active rheumatoid arthritis were randomly allocated to 2?weeks of treatment with an elemental diet (n?=?21) or oral prednisolone 15?mg/day (n?=?9). Assessments of duration of early morning stiffness (EMS), pain on a 10?cm visual analog scale (VAS), the Ritchie articular index (RAI), swollen joint score, the Stanford Health Assessment Questionnaire, global patient and physician assessment, body weight, erythrocyte sedimentation rate (ESR), C?reactive protein (CRP) and haemoglobin, were made at 0, 2, 4 and 6?weeks. Results All clinical parameters improved in both groups (p<0.05) except the swollen joint score in the elemental diet group. An improvement of greater than 20% in EMS, VAS and RAI occurred in 72% of the elemental diet group and 78% of the prednisolone group. ESR, CRP and haemoglobin improved in the steroid group only (p<0.05). Conclusions An elemental diet for 2?weeks resulted in a clinical improvement in patients with active rheumatoid arthritis, and was as effective as a course of oral prednisolone 15?mg daily in improving subjective clinical parameters. This study supports the concept that rheumatoid arthritis may be a reaction to a food antigen(s) and that the disease process starts within the intestine. PMID:17308218

  19. Case Studies of Systems Integration through Energy Simulation During Early Design Phase 

    E-print Network

    Upadhyaya, K.; McLean, D.

    2008-01-01

    The paper presents two case studies, a commercial & a community project, in Houston Texas, where energy simulation and a decision matrix were used to solve budget conflicts and meet LEED EA-1 requirements. The first case study consists...

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  1. 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.; Johns, H.; Joshi, T.; Mayes, D.; Mancini, R. C.; Nagayama, T.

    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.

  2. 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

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

    E-print Network

    Liao, Katherine P.

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

  4. [A case of Churg-Strauss syndrome in which positive rheumatoid factor and MPO-ANCA preceded the development of clinical symptoms of vasculitis].

    PubMed

    Furuiye, M; Konno, K; Sumi, Y; Ohtani, Y; Sawada, M; Umino, T; Inase, N; Miyake, S; Yoshizawa, Y

    2001-06-01

    A 52-year-old man in whom bronchial asthma had been diagnosed in 1995 was admitted for the treatment of Churg-Strauss syndrome in June 1997. Positive tests MPO-ANCA and rheumatoid factor preceded the symptoms of vasculitis for several months. A skin biopsy revealed infiltration of eosinophils in the vessel walls, and the diagnosis of Churg-Strauss syndrome was confirmed. After systemic administration of corticosteroids, the symptoms other than mononeuritis improved markedly, and his MPO-ANCA and rheumatoid factor became negative. Rheumatoid factor and MPO-ANCA may be useful for the early diagnosis of Churg-Strauss syndrome in patients with bronchial asthma in which a well-controlled disease develops into an intractable condition. PMID:11530389

  5. 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

  6. Evaluation of aqua crop simulation of early season evaporation and water flux in a semiarid environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The AquaCrop model of crop growth, water use, yield and water use efficiency (WUE) is intended for use by extension personnel, farm and irrigation managers, planners and other less advanced users of simulation models in irrigation planning and scheduling. It could be useful in estimating changes in ...

  7. Effects of steroid ablation and progestin replacement on the transcriptome of the primate corpus luteum during simulated early pregnancy.

    PubMed

    Bishop, C V; Aazzerah, R A; Quennoz, L M; Hennebold, J D; Stouffer, R L

    2014-03-01

    Previous microarray analyses indicated that a portion of the transcriptome in the macaque corpus luteum (CL) of the menstrual cycle was regulated indirectly by luteinizing hormone via the local actions of steroid hormones, notably progesterone (P). The current study was designed to investigate this concept in the CL of early pregnancy by analyzing chorionic gonadotrophin (CG)-regulated genes that are dependent versus independent of local steroid action. Exogenous human chorionic gonadotropin treatment simulating early pregnancy (SEP) began on Day 9 of the luteal phase in female rhesus monkeys with and without concurrent administration of the 3-?-hydroxysteroid dehydrogenase inhibitor trilostane (TRL) with or without the synthetic progestin R5020. Compared with SEP treatment alone, TRL altered 50 mRNA transcripts on Day 10, rising to 95 on Day 15 (P<0.05, ?2-fold change in gene expression). Steroid-sensitive genes were validated; notably effects of steroid ablation and P replacement varied by day. Expression of some genes previously identified as P-regulated in the macaque CL during the menstrual cycle were not significantly altered by steroid ablation and P replacement during CG exposure in SEP. These data indicate that the majority of CG-regulated luteal transcripts are differentially expressed independently of local steroid actions. However, the steroid-regulated genes in the macaque CL may be essential during early pregnancy, based on previous reports that TRL treatment initiates premature structural regression of the CL during SEP. These data reinforce the concept that the structure, function and regulation of the rescued CL in early pregnancy differs from the CL of the menstrual cycle in primates. PMID:24219889

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  9. 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).

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

    SciTech Connect

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

  11. The non-linear evolution of baryonic overdensities in the early universe: initial conditions of numerical simulations

    NASA Astrophysics Data System (ADS)

    Naoz, Smadar; Yoshida, Naoki; Barkana, Rennan

    2011-09-01

    We run very large cosmological N-body hydrodynamical simulations in order to study statistically the baryon fractions in early dark matter haloes. We critically examine how differences in the initial conditions affect the gas fraction in the redshift range z= 11-21. We test three different linear power spectra for the initial conditions. (1) A complete heating model, which is our fiducial model; this model follows the evolution of overdensities correctly, according to Naoz & Barkana (2005), in particular including the spatial variation of the speed of sound of the gas due to Compton heating from the CMB. (2) An equal-? model, which assumes that the initial baryon fluctuations are equal to those of the dark matter, while conserving ?8 of the total matter. (3) A mean cs model, which assumes a uniform speed of sound of the gas. The latter two models are often used in the literature. We calculate the baryon fractions for a large sample of haloes in our simulations. Our fiducial model implies that before reionization and significant stellar heating took place, the minimum mass needed for a minihalo to keep most of its baryons throughout its formation was ˜3 × 104 M?. However, the alternative models yield a wrong (higher by about 50 per cent) minimum mass, since the system retains a memory of the initial conditions. We also demonstrate this using the 'filtering mass' from linear theory, which accurately describes the evolution of the baryon fraction throughout the simulated redshift range.

  12. Is air pollution a risk factor for rheumatoid arthritis?

    PubMed

    Essouma, Mickael; Noubiap, Jean Jacques N

    2015-01-01

    Rheumatoid arthritis is a chronic inflammatory debilitating disease triggered by a complex interaction involving genetic and environmental factors. Active smoking and occupational exposures such as silica increase its risk, suggesting that initial inflammation and generation of rheumatoid arthritis-related autoantibodies in the lungs may precede the clinical disease. This hypothesis paved the way to epidemiological studies investigating air pollution as a potential determinant of rheumatoid arthritis. Studies designed for epidemiology of rheumatoid arthritis found a link between traffic, a surrogate of air pollution, and this disease. Furthermore, a small case-control study recently found an association between wood smoke exposure and anticyclic citrullinated protein/peptide antibody in sera of patients presenting wood-smoke-related chronic obstructive pulmonary disease. However, reports addressing impact of specific pollutants on rheumatoid arthritis incidence and severity across populations are somewhat conflicting. In addition to the link reported between other systemic autoimmune rheumatic diseases and particulate matters/gaseous pollutants, experimental observation of exacerbated rheumatoid arthritis incidence and severity in mice models of collagen-induced arthritis after diesel exhaust particles exposure as well as hypovitaminosis D-related autoimmunity can help understand the role of air pollution in rheumatoid arthritis. All these considerations highlight the necessity to extend high quality epidemiological researches investigating different sources of atmospheric pollution across populations and particularly in low-and-middle countries, in order to further explore the biological plausibility of air pollution's effect in the pathogenesis of rheumatoid arthritis. This should be attempted to better inform policies aiming to reduce the burden of rheumatoid arthritis. PMID:26225124

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  14. The interplay between inflammation and metabolism in rheumatoid arthritis

    PubMed Central

    Chimenti, M S; Triggianese, P; Conigliaro, P; Candi, E; Melino, G; Perricone, R

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response. PMID:26379192

  15. Screening Optimization of Latent Tuberculosis Infection in Rheumatoid Arthritis Patients

    PubMed Central

    Mehta, Bella; Zapantis, Ekaterini; Petryna, Olga; Efthimiou, Petros

    2015-01-01

    Objective. Rheumatoid arthritis (RA) patients are at increased risk of latent tuberculosis infection (LTBI) but there are no clear guidelines for LTBI screening with Tuberculin Skin Test (TST) or Quantiferon TB Gold testing (QFT-G). Methods. A retrospective study was conducted in a high risk, largely foreign-born, inner city, RA population. After screening 280 RA patients, 134 patients who had both TST and QFT-G testing performed during their initial evaluation were included. Results. Out of 132 RA patients included in our analysis, 50 (37.8%) patients were diagnosed with LTBI with either positive TST 42 (31.8%) or QFT-G 23 (17.4%). 15 (11.4%) were positive and 82 (62.1%) were negative for both tests. The agreement between TST and QFT-G was 73.5% (Kappa 0.305, CI = 95% 0.147–0.463, p = 0.081).? Conclusions. There was low-moderate agreement (? = 0.305) between TST and QFT-G. In the absence of clearly defined gold standard and limitations associated with both tests, we propose early screening with both tests for patients who need prompt treatment with BRMs. Patients who are not immediate candidates for BRM treatment may be safely and cost effectively screened with a two-step process: initial screening with TST and if negative, IGRA testing. Patients positive for either test should be promptly treated. PMID:26294972

  16. Reverse Shoulder Arthroplasty in Rheumatoid Arthritis: A Systematic Review

    PubMed Central

    Gee, Edward C.A.; Hanson, Emma K.; Saithna, Adnan

    2015-01-01

    Background: Anatomical shoulder replacement for rheumatoid arthritis (RA) is complicated by a high incidence of rotator cuff tears and glenoid erosion. This can lead to poor function and early failure. Reverse shoulder arthroplasty (RSA) has gained popularity as an alternative. This systematic review attempts to further define the role of RSA in RA. Methods: A systematic review identified seven studies reporting outcomes of RSA in RA patients. Studies were critically appraised, and data on outcomes, complications and technical considerations were extracted and analysed. Results: One hundred and twenty one shoulders were included (mean follow up 46.9 months). Consistent improvements in the main outcome measures were noted between studies. Ninety five percent of patients described excellent to satisfactory outcomes. The minimum mean forward elevation reported in each study was 115 degrees. Symptomatic glenoid loosening (1.7%), deep infection (3.3%) and revision surgery (5%) rates were no higher than for a population of mixed aetiologies. Discussion: Previous concerns regarding high pre- and peri-operative complication and revision rates in RA patients were not shown to be valid by the results of this review. Although associated cuff tears are common and glenoid bone loss can increase the technical complexity of surgery, RSA provides consistent and predictable improvements in key outcome measures and the revision and complication rates do not appear to be higher than reported in a large population of mixed aetiologies. Conclusion: The contemporary literature shows that RSA is a safe, effective and reliable treatment option in RA patients. PMID:26448802

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

    PubMed Central

    2014-01-01

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

  18. The interplay between inflammation and metabolism in rheumatoid arthritis.

    PubMed

    Chimenti, M S; Triggianese, P; Conigliaro, P; Candi, E; Melino, G; Perricone, R

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response. PMID:26379192

  19. Screening Optimization of Latent Tuberculosis Infection in Rheumatoid Arthritis Patients.

    PubMed

    Mehta, Bella; Zapantis, Ekaterini; Petryna, Olga; Efthimiou, Petros

    2015-01-01

    Objective. Rheumatoid arthritis (RA) patients are at increased risk of latent tuberculosis infection (LTBI) but there are no clear guidelines for LTBI screening with Tuberculin Skin Test (TST) or Quantiferon TB Gold testing (QFT-G). Methods. A retrospective study was conducted in a high risk, largely foreign-born, inner city, RA population. After screening 280 RA patients, 134 patients who had both TST and QFT-G testing performed during their initial evaluation were included. Results. Out of 132 RA patients included in our analysis, 50 (37.8%) patients were diagnosed with LTBI with either positive TST 42 (31.8%) or QFT-G 23 (17.4%). 15 (11.4%) were positive and 82 (62.1%) were negative for both tests. The agreement between TST and QFT-G was 73.5% (Kappa 0.305, CI = 95% 0.147-0.463, p = 0.081).? Conclusions. There was low-moderate agreement (? = 0.305) between TST and QFT-G. In the absence of clearly defined gold standard and limitations associated with both tests, we propose early screening with both tests for patients who need prompt treatment with BRMs. Patients who are not immediate candidates for BRM treatment may be safely and cost effectively screened with a two-step process: initial screening with TST and if negative, IGRA testing. Patients positive for either test should be promptly treated. PMID:26294972

  20. 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.

  1. Preliminary numerical simulations of the 27 February 2010 Chile tsunami: first results and hints in a tsunami early warning perspective

    NASA Astrophysics Data System (ADS)

    Tinti, S.; Tonini, R.; Armigliato, A.; Zaniboni, F.; Pagnoni, G.; Gallazzi, Sara; Bressan, Lidia

    2010-05-01

    The tsunamigenic earthquake (M 8.8) that occurred offshore central Chile on 27 February 2010 can be classified as a typical subduction-zone earthquake. The effects of the ensuing tsunami have been devastating along the Chile coasts, and especially between the cities of Valparaiso and Talcahuano, and in the Juan Fernandez islands. The tsunami propagated across the entire Pacific Ocean, hitting with variable intensity almost all the coasts facing the basin. While the far-field propagation was quite well tracked almost in real-time by the warning centres and reasonably well reproduced by the forecast models, the toll of lives and the severity of the damage caused by the tsunami in the near-field occurred with no local alert nor warning and sadly confirms that the protection of the communities placed close to the tsunami sources is still an unresolved problem in the tsunami early warning field. The purpose of this study is two-fold. On one side we perform numerical simulations of the tsunami starting from different earthquake models which we built on the basis of the preliminary seismic parameters (location, magnitude and focal mechanism) made available by the seismological agencies immediately after the event, or retrieved from more detailed and refined studies published online in the following days and weeks. The comparison with the available records of both offshore DART buoys and coastal tide-gauges is used to put some preliminary constraints on the best-fitting fault model. The numerical simulations are performed by means of the finite-difference code UBO-TSUFD, developed and maintained by the Tsunami Research Team of the University of Bologna, Italy, which can solve both the linear and non-linear versions of the shallow-water equations on nested grids. The second purpose of this study is to use the conclusions drawn in the previous part in a tsunami early warning perspective. In the framework of the EU-funded project DEWS (Distant Early Warning System), we will try to give some clues for discussion on the deficiencies of the existing tsunami early warning concepts as regards the warning to the areas which are found close to the tsunami source, and on the strategies that should be followed in the near future in order to make significant progress in the protection and safeguarding of local communities.

  2. Observations on Drug Prescribing in Rheumatoid Arthritis

    PubMed Central

    Lee, P.; Ahola, S. J.; Grennan, D.; Brooks, P.; Buchanan, W. Watson

    1974-01-01

    A total of 125 patients with rheumatoid arthritis were investigated about their drug therapy before referral to a specialist centre. Most referrals were from general practitioners. Only 47 of the patients had received salicylates as the first drug and 18 had never had them at all. Soluble aspirin was the preparation of salicylates most frequently prescribed (for 63 patients). Only 60 patients had been given an adequate dose and only 62 an adequate course of treatment with salicylates. In 28 patients salicylates had been stopped on account of side effects. About one-third of the patients had been prescribed oral corticosteroids. The referral letters were poor in giving details of past and present drug therapy, and there were serious omissions in reporting of previous side effects. Seventy-five general practitioners were asked to rate several currently marketed antirheumatic drugs in terms of effectiveness. Though prednisolone 15 mg daily ranked higher than aspirin 4 g daily the difference was not significant. The study shows the inadequacies of drug prescribing for rheumatoid arthritis in the Glasgow area. PMID:4544646

  3. Laser transillumination for diagnosis of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Boerner, E.; Podbielska, H.; Bauer, J.; Dmochowska, L.; Dziewi?cka, M.

    2006-02-01

    In this work, the special portable apparatus was constructed for performing the transillumination examination on interphalangeal joints of patients suffering from rheumatoid arthritis. It consisted of He-Ne laser with optics for collimated illumination, special holder for placing the finger (perpendicular to optical axis, dorsal site towards camera), and CCD camera with memory stick. The captured images in JPEG format with 1152x864 resolution were converted into the gray level pictures and analyzed by means of image processing program from OPTIMAS. 35 ill patients and 11 healthy volunteers were examined. The histograms and 35 luminances were calculated. The average function was applied in order to calculate the mean gray level values in images of corresponding fingers of healthy subjects. These values were compared with values calculated for ill persons. We proved that that transillumination images may have a diagnostic value. For RA suffering patients the corresponding transillumination images represented the lower gray level values than the average value of finger of health volunteers. For II finger of left hand 96% images of ill persons have lower gray level and in case of right hand it was 93%. This proves that basing in transillumination one can diagnose with high probability the patient with rheumatoid arthritis.

  4. 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

  5. Trace element analysis in rheumatoid arthritis under chrysotheraphy

    NASA Astrophysics Data System (ADS)

    Lecomte, R.; Paradis, P.; Monaro, S.; Barrette, M.; Lamoureux, G.; Menard, H.-A.

    1981-03-01

    Proton induced X-ray emission (PIXE) analysis is used to measure trace element concentrations in blood serum from patients with rheumatoid arthritis. Initially trace element contaminations in blood-collecting and storing devices are determined. Then mean values and nyctemeral cycles are measured both in normal subjects and patients with rheumatoid arthritis and other similar pathologies. Abnormal concentrations of Cu and Zn and anomalies in the nyctemeral cycle are found in the patients. In the second phase of the project, the special case of chrysotherapeutically treated (gold salt treatment) rheumatoid arthritis patients is studied for extended periods of time (up to 53 weeks).

  6. Simulation of Prebiotic Processing by Comet and Meteoroid Impact: Implications for Life on Early Earth and Other Planets

    NASA Technical Reports Server (NTRS)

    Dateo, Christopher E.

    2003-01-01

    We develop a reacting flow model to simulate the shock induced chemistry of comets and meteoroids entering planetary atmospheres. Various atmospheric compositions comprising of simpler molecules (i.e., CH4, CO2, H2O, etc.) are investigated to determine the production efficiency of more complex prebiotic molecules as a function of composition, pressure, and entry velocity. The possible role of comets and meteoroids in creating the inventory of prebiotic material necessary for life on Early Earth is considered. Comets and meteoroids can also introduce new materials from the Interstellar Medium (ISM) to planetary atmospheres. The ablation of water from comets, introducing the element oxygen into Titan's atmosphere will also be considered and its implications for the formation of organic and prebiotic material.

  7. 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.

  8. 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.

  9. 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. Pareige, C.; Lardé, R.; Blavette, D.

    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.

  10. 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

  11. Rheumatoid serumfactor in populations in the U.K. I. Lung disease and rheumatoid serum factor

    PubMed Central

    Lawrence, J. S.; Locke, G. B.; Ball, J.

    1971-01-01

    In population samples in England and Wales a greater frequency of positive sheep cell agglutination tests has been found in Leigh and the Rhondda than in Wensleydale, the Vale of Glamorgan or Watford. The urban population of Leigh had more X-ray evidence of lung pathology than the rural population of Wensleydale. Seropositive persons in both the urban populations of Leigh and the Rhondda and the rural populations of Wensleydale and Glamorgan had more X-ray evidence of lung pathology than seronegative individuals, the difference being significant for healed tuberculosis of the lungs, thickened basal pleura and increased basal vascular markings. The association between the first two and rheumatoid factor was equally present in those with and without arthritis but in the third it was limited to those with arthritis. A history of bronchitis was no more common in persons with a positive sheep cell test than in those with a negative test and the indirect maximum breathing capacity showed no significant relationship to rheumatoid factor titre. No association was found between cigarette smoking and the sheep cell titre. It is concluded that parenchymal lung and pleural disease may act as a stimulus to the production of rheumatoid serum factor and that this stimulus is independent of the presence or absence of arthritis. ImagesFIG. 1FIG. 2 PMID:5104047

  12. Spectral-Domain Optical Coherence Tomography of Preclinical Chloroquine Maculopathy in Egyptian Rheumatoid Arthritis Patients

    PubMed Central

    Allam, Riham S. H. M.; Abd-Elmohsen, Mai N.; Khafagy, Mohamed M.; Raafat, Karim A.; Sheta, Sherif M.

    2015-01-01

    Purpose. To evaluate the role of spectral-domain optical coherence tomography (SD-OCT) in early detection of Chloroquine maculopathy in rheumatoid arthritis (RA) patients. Methods. 40 left eyes of 40 female rheumatoid arthritis patients who received treatment chloroquine for more than one year were recruited in the study. All patients had no symptoms or signs of Chloroquine retinopathy. They were evaluated using SD-OCT, where the Central Foveal Thickness (CFT), parafoveal thickness and perifoveal thickness, average Retinal Nerve Fiber Layer (RNFL) thickness, and Ganglion Cell Complex (GCC) measurements were measured and compared to 40 left eyes of 40 normal females. Results. The mean CFT was found to be thinner in the Chloroquine group (238.15?µm ± 22.49) than the normal controls (248.2?µm ± 19.04), which was statistically significant (p value = 0.034). The mean parafoveal thickness was lesser in the Chloroquine group than the control group in all quadrants (p value <0.05). The perifoveal thickness in both groups showed no statistically significant difference (p value >0.05) in all quadrants. No significant difference was detected between the two groups regarding RNFL, GCC, or IS/OS junction. Conclusions. Preclinical Chloroquine toxicity can lead to early thinning in the central fovea as well as the parafoveal regions that is detected by SD-OCT. PMID:26301102

  13. Pixel value analysis for detection of simulated early external root resorption.

    PubMed

    Poleti, Marcelo Lupion; Fernandes, Thais Maria Freire; Paiz, Camila Cristina; Rubira-Bullen, Izabel Regina Fischer; Capelozza, Ana Lúcia Alvares

    2014-01-01

    The aim of this study was to determine the efficacy of pixel value analysis using images generated by the Digora™ and Visualix™ systems for the early detection of external root resorption (ERR). Thirty extracted human lower incisors were radiographed using the Digora and Visualix systems; then, ERR was induced by immersing the teeth in 6 mol L-1 of hydrochloric acid for different periods of time (10, 30 and 60 minutes). ERR was confirmed by calcium quantification with an atomic absorption spectrophotometer. One digital image was acquired per time period at 70 kVp, 7 mA, 2.2 mm filtration, focus-film distance of 30 cm, and with exposure times of 0.09 s in the Digora system and 0.05 s in Visualix system. The region of interest was defined using ImageJ software. Statistical analysis was performed using ANOVA and Pearson's correlation (p < 0.05). There was no statistically significant difference between the time for ERR induction and the pixel values with either system. A positive correlation between the time of ERR induction and the calcium concentration was observed (r = 0.8892; p < 0.001). In conclusion, independent of the site of ERR induction and the digital system, pixel value analysis was not effective for ERR detection. PMID:25229785

  14. Parallel Detection of Autoantibodies with Microarrays in Rheumatoid Diseases

    E-print Network

    Tian, Weidong

    patterns were seen in patients with clinical diagnoses of rheumatoid arthri- tis (n 83), systemic lupus diseases affect an estimated 3­5% of the total population (1), with the highest prevalence in the elderly

  15. 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 ...

  16. 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.

  17. Observations on the treatment of rheumatoid disease with penicillamine

    PubMed Central

    Golding, John R.; Wilson, J. V.; Day, Albert T.

    1970-01-01

    Forty-five patients with severe rheumatoid arthritis were given D-penicillamine hydrochloride according to a fixed regimen for up to 2 years. The effects of treatment were observed both clinically and by the use of laboratory parameters. The results show that about 75% of patients exhibited objective improvement. Those with rheumatoid arthritis were found to do particularly well. The incidence, type and severity of side-effects are discussed. PMID:5488219

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

    PubMed

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

    2015-01-01

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

  19. Emerging role of leptin in rheumatoid arthritis

    PubMed Central

    Tian, G; Liang, J-N; Wang, Z-Y; Zhou, D

    2014-01-01

    Numerous studies have suggested the importance of leptin against autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and psoriasis. To summarize our current understanding of the role of leptin in inflammatory responses and rheumatoid arthritis (RA), a systematic review was conducted to assess the discrepancy of leptin in RA and its effect on immunity according to different studies. Recently, emerging data have indicated that leptin is involved in the pathological function of RA, which is common in autoimmune disorders. This review discusses the possible consequences of leptin levels in RA. Blocking the key signal pathways of leptin and inhibiting the leptin activity-like leptin antagonist may be a promising way for potential therapeutic treatment of RA at risk of detrimental effects. However, leptin was increased in patients with RA and may also regulate joint damage. Thus, more understanding of the mechanism of leptin in RA would be advantageous in the future. PMID:24802245

  20. Galectins in the Pathogenesis of Rheumatoid Arthritis

    PubMed Central

    Li, Song; Yu, Yangsheng; Koehn, Christopher D; Zhang, Zhixin; Su, Kaihong

    2013-01-01

    Rheumatoid arthritis (RA) is a complex and common systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Multiple proteins, cells, and pathways have been identified to contribute to the pathogenesis of RA. Galectins are a group of lectins that bind to ?-galactoside carbohydrates on the cell surface and in the extracellular matrix. They are expressed in a wide variety of tissues and organs with the highest expression in the immune system. Galectins are potent immune regulators and modulate a range of pathological processes, such as inflammation, autoimmunity, and cancer. Accumulated evidence shows that several family members of galectins play positive or negative roles in the disease development of RA, through their effects on T and B lymphocytes, myeloid lineage cells, and fibroblast-like synoviocytes. In this review, we will summarize the function of different galectins in immune modulation and their distinct roles in RA pathogenesis. PMID:24416634

  1. Effect of yogic package on rheumatoid arthritis.

    PubMed

    Singh, Vijay Kumar; Bhandari, R B; Rana, Budhi Bal

    2011-01-01

    This study aimed at studying the effect of yogic package (YP) with some selected pranayama, cleansing practices and meditation on pain intensity, inflammation, stiffness, pulse rate (PR), blood pressure (BP), lymphocyte count (LC), C-reactive protein (CRP) and serum uric acid (UA) level among subjects of rheumatoid arthritis (RA). Randomized control group design was employed to generate pre and post data on participants and controls. Repealed Measure ANOVAs with Bonferroni adjustment were applied to check significant overall difference among pre and post means of participants and controls by using PASW (SPSS Inc. 18th Version). Observed result favored statistically significant positive effect of YP on selected RA parameters and symptoms under study at P<0.05, 0.01 and 0.001 respectively that showed remarkable improvement in RA severity after 40-day practice of YP. It concluded that YP is a significant means to reduce intensity of RA. PMID:23362725

  2. Light scattering study of rheumatoid arthritis

    SciTech Connect

    Beuthan, J; Netz, U; Minet, O; Mueller, G; Scheel, A; Henniger, J

    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)

  3. The Wnt signaling pathway and rheumatoid arthritis.

    PubMed

    Rabelo, Francieli de Sousa; da Mota, Licia Maria Henrique; Lima, Rodrigo Aires Corrêa; Lima, Francisco Aires Corrêa; Barra, Gustavo Barcelos; de Carvalho, Jozélio Freire; Amato, Angélica Amorim

    2010-02-01

    The Wnt signaling pathways play a key role in cell renewal, and there are two such pathways. In patients with rheumatoid arthritis (RA), the synovial membrane expresses genes such as Wnt and Fz at higher levels than those observed in patients without RA. The Wnt proteins are glycoproteins that bind to receptors of the Fz family on the cell surface. The Wnt/Fz complex controls tissue formation during embryogenesis, as well as throughout the process of limb development and joint formation. Recent studies have suggested that this signaling pathway plays a role in the pathophysiology of RA. Greater knowledge of the role of the Wnt signaling pathway in RA could improve understanding of the differences in RA clinical presentation and prognosis. Further studies should also focus on Wnt family members as molecular targets in the treatment of RA. PMID:19683077

  4. Rheumatoid arthritis: recommendations for treat to target.

    PubMed

    Palmer, Deborah; El Miedany, Yasser

    Integrating the rheumatoid arthritis (RA) treat-to-target concept into standard clinical practice represents a challenge to health professionals. So far, this practice-changing approach has not been widely implemented, in spite of linking its outcome to payment, which was adopted in the best practice tariffs. The recently published revisions in classification criteria and updated recommendations for optimising the use of disease-modifying anti-rheumatic and biologic agents in the treatment of RA paved the way for re-evaluating the standard clinical care models in order to improve patient outcomes, prevent joint damage, and maintain patients' functional ability as well as their quality of life. This article discusses the recent advances in the management of RA and provides a set of recommendations to provide comprehensive guidance for treatment to target with the aim of improving the quality of care for RA patients. PMID:24690926

  5. 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.

  6. 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.

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

    NASA Technical Reports Server (NTRS)

    Herant, Marc; Benz, Willy; Colgate, Stirling

    1992-01-01

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

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

    SciTech Connect

    Herant, M.; Benz, W.; Colgate, S. Steward Observatory, Tucson, AZ Los Alamos National Laboratory, NM )

    1992-08-01

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

  9. Dynamics of the sleep EEG after an early evening nap: experimental data and simulations.

    PubMed

    Werth, E; Dijk, D J; Achermann, P; Borbély, A A

    1996-09-01

    Increasing sleep pressure is associated with highly predictable changes in the dynamics of the sleep electroencephalogram (EEG). To investigate whether the effects of reduced sleep pressure also can be accounted for by homeostatic mechanisms, nighttime sleep following an evening nap was recorded in healthy young men. In comparison with the baseline night, sleep latency in the postnap night was prolonged, rapid eye movement sleep (REMS) latency was reduced, and EEG power density in non-REMS was decreased in the delta and theta band. The buildup of both EEG slow-wave activity (SWA; power density in the 0.75-to 4.5-Hz range) and spindle frequency activity (SFA; power density in the 12.25-to 15.0-Hz range) in non-REMS episodes was diminished (SWA: episodes 1-3; SFA: episode 1). The typical declining trend of SWA over consecutive non-REM sleep episodes was attenuated. The time course of SWA could be closely simulated with a homeostatic model of sleep regulation, although some discrepancies in level and buildup of SWA were apparent. We conclude that homeostatic mechanisms can largely account for the dynamics of the sleep EEG under conditions of reduced sleep pressure. PMID:8853369

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

    SciTech Connect

    Naoz, Smadar; Yoshida, Naoki; Gnedin, Nickolay Y.

    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.

  11. Stem cell transplantation in rheumatoid arthritis.

    PubMed

    Snowden, J A; Kapoor, S; Wilson, A G

    2008-12-01

    The therapeutic potential of high dose cytotoxic therapy and stem cell transplantation (SCT) in severe rheumatoid arthritis (RA) was originally supported by animal studies and serendipitous clinical cases where allogeneic and autologous procedures were shown to ameliorate and potentially cure the disease. Phase I and Phase II clinical studies established the feasibility, safety and efficacy of autologous stem cell mobilisation and transplantation. Although it was clear that the effects of high dose chemotherapy and autologous SCT could safely achieve profound responses, sustained control of disease usually required the reintroduction of disease modifying agents. Responses were improved with dose escalation of the conditioning regimen, and also with post-SCT therapy, such as rituximab, but were not observed with graft manipulation. Phase III studies were attempted, but recruitment was compromised by the increasingly widespread use of biological anti-rheumatic agents. Autologous SCT is now only reasonably considered in relatively rare patients whose disease has resisted conventional and biological treatments, and small numbers of cases continue to be registered with the EBMT. Occasional patients treated with allogeneic and syngeneic SCT continue to stimulate academic interest, particularly as some appear to be cured, but significant logistical and toxicity issues mean that routine and widespread application is unrealistic. In summary, SCT continues to have a limited therapeutic potential in rare patients with RA refractory to modern therapy and sufficient fitness for the procedure. From a scientific perspective, ablation of the dysfunctional rheumatoid immune system and its reconstruction with SCT has provided useful insights into the pathophysiology of RA. PMID:18958746

  12. 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

  13. Simulation of Birch and Pine Litter Influence on Early Stage of Reclaimed Soil Formation Process under Controlled Conditions.

    PubMed

    Wo?, Bart?omiej; Pietrzykowski, Marcin

    2015-07-01

    The impact of litter decomposition on chemical substrate properties and element leaching during early soil formation in afforested post-mine sites and the influence of different tree species are key issues in new ecosystem development. Scots pine ( L.) and common birch ( Roth) are important pioneering species used in afforestation of post-mine sites in central and eastern Europe. The aim of this study was to assess the impact of litter decomposition of these species on the chemical properties of mine soil substrates. The impact of litter decomposition on soil properties was tested on quaternary and neogene substrates with different textures (sands, loams, and mixtures of clays and sands) in a controlled incubation experiment using PVC columns. Simulation of precipitation and leaching was undertaken for 10 wk at a temperature of 16°C with distilled water (200 mL wk) through cylinders with litter, substrate + litter, and control substrate (no litter). Filtrated water solution was collected once a week for laboratory analysis, and the concentrations of dissolved organic C, total N, K, Ca, Mg, and P were determined. The study results indicate a stronger impact of the common birch on the chemical properties of reclaimed mine soils compared with pine. After the experiment, birch litter caused significant changes in pH in quaternary sands, concentration of P in quaternary loams (Ql) and mixtures of neogene clays and quaternary sands (QsNc), exchangeable Ca in QsNc, and Mg in Ql and QsNc compared with pine litter. Birch, in comparison to pine, may affect the intensity of early-stage soil-forming processes by increasing nutrient availability and transport into the soil profile, which may affect the development of soil microbial communities. This process results in different soil properties under the two tree species. PMID:26437090

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

    MedlinePLUS

    ... Among Rheumatoid Arthritis Patients People with rheumatoid arthritis (RA) have lower thresholds for pain and may have deficits in a central nervous system (CNS) mechanism that helps to modulate how the ...

  15. 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 ...

  16. 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 ...

  17. 78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ...industry entitled ``Rheumatoid Arthritis: Developing Drug...the treatment of patients with rheumatoid arthritis (RA). It also...and Radiological Health, Food and Drug Administration...reflect the current status of the RA...

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

    SciTech Connect

    Ford, Corey C.; 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. 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

  20. 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.; Xiao, B.

    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.

  1. Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part

    E-print Network

    Hielscher, Andreas

    Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 2: image H. Hielscher #12;Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 2) for diagnosing rheumatoid arthritis (RA). A comprehensive analysis of techniques for the classification of DOT

  2. Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part

    E-print Network

    Shepard, Kenneth

    Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 1: feature H. Hielscher #12;Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 1 to diagnose rheumatoid arthritis (RA) are presented. Feature extraction is the focus of Part 1, while

  3. Combinatorial Analysis of Disease Association and Susceptibility for Rheumatoid Arthritis SNP Data

    E-print Network

    Zelikovsky, Alexander

    Combinatorial Analysis of Disease Association and Susceptibility for Rheumatoid Arthritis SNP Data Problem Set 2) for rheumatoid arthritis (RA) trying to check if it is caused by combinations of several Problem 2 (Rheumatoid Arthritis). 2 Combinatorial Methods for Disease Association Search Here we follow

  4. Evaluation of Fourier Transform Coefficients for The Diagnosis of Rheumatoid Arthritis From Diffuse Optical Tomography Images

    E-print Network

    Hielscher, Andreas

    Evaluation of Fourier Transform Coefficients for The Diagnosis of Rheumatoid Arthritis From Diffuse: Diffuse Optical Tomography, Computer-Aided Diagnosis, Rheumatoid Arthritis 1. INTRODUCTION Rheumatoid arthritis (RA) is an autoimmune disorder that affects 0.5-1.0% of adults in industrialized countries

  5. Preliminary Results of Severity of Illness Measures of Rheumatoid Arthritis Using Infrared Imaging

    E-print Network

    Payeur, Pierre

    Preliminary Results of Severity of Illness Measures of Rheumatoid Arthritis Using Infrared Imaging with rheumatoid arthritis (RA) by a rheumatologist. The ultimate goal is to create a low cost effective method- infrared imaging; measuring temperatures; rheumatoid arthritis patients; normal subjects. I. INTRODUCTION

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

    PubMed Central

    2010-01-01

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

  7. [Assessment of functional capacity in patients with rheumatoid arthritis: implications for recommending exercise].

    PubMed

    de Santana, Frederico Santos; Nascimento, Dahan da Cunha; de Freitas, João Paulo Marques; Miranda, Raphaela Franco; Muniz, Luciana Feitosa; Santos Neto, Leopoldo; da Mota, Licia Maria Henrique; Balsamo, Sandor

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic symmetric polyarthritis of large and small joints and by morning stiffness that may lead to musculoskeletal impairment, with functional impotence. The concept of functionality relates to the ability of an individual to perform effectively and independently daily activities and tasks of everyday life. The aim of this review is to familiarize the rheumatologist with the concept of functional capacity evaluation and with the tests that can be applied in this population, as these are important steps for a proper exercise prescription. From functional tests already used in the elderly population, the Physical Fitness and Rheumatology Laboratory - LAR - Brasilia, which is accompanying patients from Brasilia Cohort of Early Rheumatoid Arthritis, describes in this article a protocol of tests to assess functional capacity for application in patients with RA, including the description of tests: 1) Sit and Reach; 2) Agility/Dynamic Balance; 3) Manual Dynamometry; 4) Sit Back and Lift; 5) Biceps Curl and 6) Six-minute Walk Test. PMID:25627302

  8. Migration of the Charnley stem in rheumatoid arthritis and osteoarthritis. A roentgen stereophotogrammetric study.

    PubMed

    Onsten, I; Akesson, K; Besjakov, J; Obrant, K J

    1995-01-01

    Migration of 65 Charnley stems implanted with modern cementing techniques was studied by roentgen stereophotogrammetry. There were 25 patients with rheumatoid arthritis (RA) and 40 with osteoarthritis (OA) followed up for two years. In 43 cases a bone sample for histomorphometric analysis was obtained from the femur during the operation. In 22 cases the mean subsidence of the prosthetic head was 0.40 mm and in 20 the mean posterior migration was 1.25 mm. There was no difference in migration between the two diagnostic groups (p = 0.8) after adjusting for variations in gender, age and weight. Male gender was associated with increased subsidence (p = 0.006). Histological examination showed that the RA series had more osteoid surface (p = 0.04), but neither this, nor any of the other histomorphometric variables, influenced migration. These results suggest that, unlike the acetabular socket, the cemented Charnley femoral component is equally secure in osteoarthritis and in rheumatoid arthritis, and that its initial fixation is not influenced by the quality of the local cancellous bone. Our results provide data with which the early performance of new prosthetic designs and fixation methods can be compared. PMID:7822389

  9. 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.

  10. Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors.

    PubMed Central

    Hanly, J G; Hassan, J; Moriarty, M; Whelan, A; Feighery, C; Bresnihan, B

    1985-01-01

    Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The invitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. PMID:4085151

  11. Epidemiology of Rheumatoid Arthritis in Southern Albania

    PubMed Central

    Koko, Vjollca; Ndrepepa, Ana; Skenderaj, Skender

    2015-01-01

    Objectives: The aim of this study was to assess the prevalence, incidence and the burden of rheumatoid arthritis (RA) in the Southern Albania. Material and Methods: This is an epidemiologic observational study with cross-sectional analyses of all patients with RA who lived in Southern Albania during the 1995-2011 years. The RA prevalence, incidence and disability-adjusted life years (DALY) were assessed. Results: During the 1995-2011 years, 194 patients (154 females and 40 males) with RA living in Southern Albania were identified. The prevalence of RA in 2011 was 0.25% in general population and 0.34% in adult (>14 years) population. The incidence of RA in 2011 was 0.012% (12 new cases per 100000 inhabitants) and 0.016% (16 new cases per 100000 adults). The prevalence increased (from 0.036% in 1996 to 0.25% in 2011) and the incidence did not change over the study period. The mortality was 3.2% (n=7 deaths). The DALY due to RA was 823 years per 100000 inhabitants during 1995-2011 years. Conclusion: RA in Southern Albania has a prevalence of 0.25 % and an annual incidence of 0.012% in the general population in 2011. RA was responsible for a considerable burden on the health of population during the 1995-2011 years. PMID:26236163

  12. Rheumatoid Arthritis and Periodontal Disease. An Update.

    PubMed

    Venkataraman, Archana; Almas, Khalid

    2015-01-01

    A review of the epidemiological, pathological and immunological relationships between two chronic inflammatory diseases: rheumatoid arthritis (RA) and periodontal disease (PD). RA is a chronic inflammatory disease of the joints, characterized by loss of connective tissue and mineralized structures, the so-called "synovial membrane." Periodontitis is the inflammatory destruction of the periodontal attachment and alveolar bone. While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are similar. And it is possible that individuals manifesting both PD and RA may suffer from a unifying underlying systemic deregulation of the inflammatory response. There is an overproduction of a variety of cytokines and MMPs that appears to be common in both diseases. Oral health parameters should be more closely monitored in patients with RA, an autoimmune disease. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Interventions to prevent, minimize or treat periodontitis in arthritis patients will definitely promise a better quality of life for these patients. PMID:26521325

  13. [Management of rheumatoid arthritis medications and pregnancy].

    PubMed

    Funakubo Asanuma, Yu

    2015-01-01

    Rheumatoid arthritis (RA) affects mainly women during their childbearing years. As aging of childbirth advances in Japan, women who plan pregnancy would increase after they developed RA. Recent findings showed that high disease activity of RA might impair fertility. Planning pregnancy is preferable after female patients achive and maintain low disease activity or remission of RA. Women on methotrexate, which is the anchor drug for RA, need to discontinue the medication with a high risk of causing birth defects during conception and pregnancy. Data of RA patients exposed TNF inhibitors during pregnancy has been accumulating in recent years. These data suggest that increased risk of spontaneous abortion and congenital abnomalies has not been observed. Although there is insufficient data about safety of breastfeeding while using TNF inhibitors, the secretion of the drugs in breast milk is very little and fetal toxicity has not been observed. Since long term safety of children exposed TNF inhibitors in uterus has not been established, we should discontinue the drugs as soon as pregnancy is recognized. TNF inhibitors may be an useful tools for management of active RA resistant to conventional DMARDs in women who desire to bear children. PMID:25765688

  14. Bone remodelling markers in rheumatoid arthritis.

    PubMed

    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

  15. Biologicals in rheumatoid arthritis: current and future

    PubMed Central

    Avci, Ali Berkant; Feist, Eugen; Burmester, Gerd-R

    2015-01-01

    The aim of the review is to highlight the current knowledge about established and new biologicals and to summarise recent advances by focusing on comparative efficacy, safety and possible discontinuation of treatment in patients with rheumatoid arthritis (RA). Up to now, comparative analyses showed only minor differences with respect to efficacy and safety among the established biologicals. Studies confirmed the excellent drug retention rate as well as efficacy and safety of approved biologicals including their use in monotherapy. Tapering and in some instances discontinuation of biologicals is possible in disease remission. In case of relapse, patients usually show full response after reintroduction of the same compound. The development of biologicals continues fast with several new biologicals targeting different or established cytokines or cellular subsets of the immune system. With several new biologicals in the pipeline and different formulations for established compounds, treatment options for RA will become even more versatile and sophisticated. Although we get closer to the aim of decreasing the proportion of refractory patients, many questions have to be addressed in the near future regarding emerging biosimilars and biologicals with new modes of action. PMID:26535144

  16. Mechanisms involved in triggering rheumatoid arthritis.

    PubMed

    Catrina, Anca I; Joshua, Vijay; Klareskog, Lars; Malmström, Vivianne

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory syndrome with a strong autoimmune component. The autoantigens in RA are neither tissue nor organ-specific, but comprise a broad collection of post-translational modified proteins, such as citrullinated proteins. These modifications are likely to be triggered by innate stimuli. In genetically susceptible hosts, they can lead to a more substantiated secondary autoimmune reaction targeting the joints and precipitating the clinical onset of RA. Both innate and adaptive mechanisms will then closely interplay to promote chronic joint inflammation in the several absence of appropriate treatment. This scenario, is shared with other autoimmune diseases where potentially pathogenic immune responses are present already before disease onset. Better understanding of these processes will allow both earlier diagnosis of RA and identification of those healthy individuals that are at risk of developing disease, opening possibilities for disease prevention. In this review, we discuss the iterative processes of innate and adaptive immunity responsible for the (longitudinal) development of immune reactions that may contribute to the development of RA. PMID:26683152

  17. Is yoga a suitable treatment for rheumatoid arthritis: current opinion.

    PubMed

    Telles, Shirley; Singh, Nilkamal

    2012-01-01

    We reviewed published literature regarding the use of yoga for managing rheumatoid arthritis to determine whether adequate evidence exists to suggest its usefulness as a therapy. A search for previous studies involving yoga and rheumatoid arthritis in PubMed yielded eight reports. These studies reported the benefits of yoga in the physical and mental health of patients with rheumatoid arthritis (RA), suggesting that yoga is a useful add-on therapy for RA patients. However, all studies showed limitations with respect to sample size, study design, description and duration of yoga intervention, and assessment tools and statistical methods used. Additionally, the studies did not attempt to understand the mechanisms underlying observed benefits. Hence, evidence suggests a definite role of yoga in RA improvement, reducing pain, improving function, and creating a positive mental state. However, detailed analysis and additional studies are necessary to verify these observations. PMID:24198591

  18. Symmetrical primary cutaneous marginal zone lymphoma associated with rheumatoid arthritis.

    PubMed

    Yildirim, Fatma Elif; Karaduman, Ay?en; Hürmüz, Pervin; Ozyar, Enis; Bari?ta, Ibrahim; Sa?lam, Arzu

    2010-05-01

    Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is an indolent low grade B cell lymphoma of the skin, with lack of extracutaneous involvement at the time of diagnosis. Herein we report the case of a patient with rheumatoid arthritis (RA) who developed symmetrical PCMZL lesions on both ear lobes. Lesions occurring symmetrically on ear lobes are more specific for cutaneous lymphoid hyperplasia (CLH) and this kind of symmetrical localization hasn't been reported for PCMZL before. PCMZL is considered to arise from a background of reactive lymphoid hyperplasia and this case point out the concept of CLH and PCMZL spectrum. Association of marginal zone lymphoma with rheumatoid arthritis and resolution of lesions together with the resolution of symptoms due to rheumatoid arthritis after rituximab therapy is another interesting point for this case. To the best of our knowledge PCMZL associated with RA has not been reported previously. PMID:19674036

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

    SciTech Connect

    Kitahara, Kanako; Kusunoki, Natsuko; Kakiuchi, Terutaka; Suguro, Toru; Kawai, Shinichi

    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.

  20. Pathogenesis of rheumatoid arthritis and the immune response

    SciTech Connect

    Scheinberg, M.A.

    1983-08-01

    The interrelationship among lymphocytes, macrophages, and neutrophils appears to be an important aspect of the synovial inflammation that is characteristic of rheumatoid arthritis. In a study comparing gold sodium aurothiomalate (GST) with auranofin (Au), an orally absorbed compound, both appeared to inhibit the disease process and no difference between parenteral and oral administration was observed. Another study involved two groups of nine patients with severe rheumatoid arthritis. One group underwent plasmapheresis. The second group underwent total lymphoid irradiation. Both agents appeared to inhibit the disease process. Plasmapheresis was better tolerated that irradiation.

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

    PubMed

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

    2012-03-01

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

  2. Development and Evaluation of Dual Cross-Linked Pulsatile Beads for Chronotherapy of Rheumatoid Arthritis.

    PubMed

    Bansal, Abanesh Kumar; Pande, Vishal

    2013-01-01

    In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Lornoxicam dual cross-linked beads were prepared by dropping dispersed phase of lornoxicam, pectin, and sodium alginate into the dispersion phase of different concentrations of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1?:?2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 5-8?h before release of lornoxicam from the formulated beads. Thus, formulated dual cross-linked beads when administered at bed time may release lornoxicam when needed most for chronotherapeutics of early morning rheumatoid arthritis attacks in chronic patients. PMID:26556001

  3. [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

  4. [Systemic corticosteroids in rheumatoid arthritis: to use or not to use?].

    PubMed

    Amano, Koichi

    2002-12-01

    Systemic corticosteroids(steroids) were initially introduced after the dramatic efficacy in individual patients with rheumatoid arthritis(RA). Since the outcome of steroid therapy in RA turned to be awesome, steroids had been put at the apex of the therapeutic pyramid for a long time. However, most rheumatologists have subscribed steroids for the treatment of early active RA because they can provide rapid and significant clinical response. Moreover, recent several studies have shown that low dose(5 to 10 mg/day) of prednisolone retard joint destruction in a few years. However, the demonstrated negatives(opportunistic infections, osteoporosis, metabolic disorders, atherosclerotic vascular events etc.) of steroids may outweigh these advantages in the longterm clinical course of RA. PMID:12510363

  5. Treatment of rheumatoid arthritis: Unraveling the conundrum.

    PubMed

    Zampeli, Evangelia; Vlachoyiannopoulos, Panayiotis G; Tzioufas, Athanasios G

    2015-12-01

    Rheumatoid arthritis (RA) is a heterogeneous disease with a complex and yet not fully understood pathophysiology, where numerous different cell-types contribute to a destructive process of the joints. This complexity results into a considerable interpatient variability in clinical course and severity, which may additionally involve genetics and/or environmental factors. After three decades of focused efforts scientists have now achieved to apply in clinical practice, for patients with RA, the "treat to target" approach with initiation of aggressive therapy soon after diagnosis and escalation of the therapy in pursuit of clinical remission. In addition to the conventional synthetic disease modifying anti-rheumatic drugs, biologics have greatly improved the management of RA, demonstrating efficacy and safety in alleviating symptoms, inhibiting bone erosion, and preventing loss of function. Nonetheless, despite the plethora of therapeutic options and their combinations, unmet therapeutic needs in RA remain, as current therapies sometimes fail or produce only partial responses and/or develop unwanted side-effects. Unfortunately the mechanisms of 'nonresponse' remain unknown and most probable lie in the unrevealed heterogeneity of the RA pathophysiology. In this review, through the effort of unraveling the complex pathophysiological pathways, we will depict drugs used throughout the years for the treatment of RA, the current and future biological therapies and their molecular or cellular targets and finally will suggest therapeutic algorithms for RA management. With multiple biologic options, there is still a need for strong predictive biomarkers to determine which drug is most likely to be effective, safe, and durable in a given individual. The fact that available biologics are not effective in all patients attests to the heterogeneity of RA, yet over the long term, as research and treatment become more aggressive, efficacy, toxicity, and costs must be balanced within the therapeutic equation to enhance the quality of life in patients with RA. PMID:26515757

  6. Prevention of cardiovascular disease in rheumatoid arthritis.

    PubMed

    Hollan, I; Dessein, P H; Ronda, N; Wasko, M C; Svenungsson, E; Agewall, S; Cohen-Tervaert, J W; Maki-Petaja, K; Grundtvig, M; Karpouzas, G A; Meroni, P L

    2015-10-01

    The increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been recognized for many years. However, although the characteristics of CVD and its burden resemble those in diabetes, the focus on cardiovascular (CV) prevention in RA has lagged behind, both in the clinical and research settings. Similar to diabetes, the clinical picture of CVD in RA may be atypical, even asymptomatic. Therefore, a proactive screening for subclinical CVD in RA is warranted. Because of the lack of clinical trials, the ideal CVD prevention (CVP) in RA has not yet been defined. In this article, we focus on challenges and controversies in the CVP in RA (such as thresholds for statin therapy), and propose recommendations based on the current evidence. Due to the significant contribution of non-traditional, RA-related CV risk factors, the CV risk calculators developed for the general population underestimate the true risk in RA. Thus, there is an enormous need to develop adequate CV risk stratification tools and to identify the optimal CVP strategies in RA. While awaiting results from randomized controlled trials in RA, clinicians are largely dependent on the use of common sense, and extrapolation of data from studies on other patient populations. The CVP in RA should be based on an individualized evaluation of a broad spectrum of risk factors, and include: 1) reduction of inflammation, preferably with drugs decreasing CV risk, 2) management of factors associated with increased CV risk (e.g., smoking, hypertension, hyperglycemia, dyslipidemia, kidney disease, depression, periodontitis, hypothyroidism, vitamin D deficiency and sleep apnea), and promotion of healthy life style (smoking cessation, healthy diet, adjusted physical activity, stress management, weight control), 3) aspirin and influenza and pneumococcus vaccines according to current guidelines, and 4) limiting use of drugs that increase CV risk. Rheumatologists should take responsibility for the education of health care providers and RA patients regarding CVP in RA. It is immensely important to incorporate CV outcomes in testing of anti-rheumatic drugs. PMID:26117596

  7. Immunogenetics of rheumatoid arthritis: Understanding functional implications.

    PubMed

    Messemaker, Tobias C; Huizinga, Tom W; Kurreeman, Fina

    2015-11-01

    The last decade has seen a dramatic technological revolution. The characterisation of the majority of the common variations in our genetic code in 2003 precipitated the discovery of the genetic risk factors predisposing to Rheumatoid Arthritis development and progression. Prior to 2007, only a handful of genetic risk factors had been identified, HLA, PTPN22 and CTLA4. Since then, over 100 genetic risk loci have been described, with the prediction that an ever-increasing number of risk alleles with consistently decreasing effect sizes will be discovered in the years to come. Each risk locus harbours multiple candidate genes and the proof of causality of each of these candidates is as yet unknown. An enrichment of these RA-associated genes is found in three pathways: T-cell receptor signalling, JAK-STAT signalling and the NF-?B signalling cascade, and currently drugs targeting these pathways are available for the treatment of RA. However, the role that RA-associated genes have in these pathways and how they contribute to disease is not always clear. Major efforts in understanding the contribution of genetic risk factors are currently under way with studies querying the role of genetic variation in gene expression of coding and non-coding genes, epigenetic marks and other regulatory mechanisms yielding ever more valuable insights into mechanisms of disease. Recent work has suggested a possible enrichment of non-coding RNAs as well as super-enhancers in RA genetic loci indicating possible new insights into disease mechanism. This review brings together these emerging genetic data with an emphasis on the immunogenetic links these findings have provided and what we expect the future will bring. PMID:26215034

  8. Rheumatoid arthritis patients’ experience of climate care

    PubMed Central

    Vaks, Katrin; Sjöström, Rita

    2015-01-01

    The purpose of this qualitative study was to understand and examine how patients with rheumatoid arthritis (RA) experience climate care and its effects. A qualitative approach was chosen for the study. Two men and six women were interviewed according to a semistructured interview guide. The text was analyzed using a manifest content analysis. The analysis resulted in four categories and 10 subcategories. The interviewees experienced climate care positively. The training was perceived increasing gradually. The patients felt that they performed to a maximum capacity during training and were impressed by the staff’s enthusiasm and encouragement. The patients felt that they were involved in the goal setting and the choice of treatment, and the staff noticed individual needs. There was a feeling among the patients of being acknowledged by the staff. Information about the disease was perceived as individualized. The climate and beautiful surroundings were viewed as encouraging physical activity and a feeling of well-being. Patients made new friends, had fun together and also shared experiences about their disease. Furthermore, the patients described a sense of belonging to a group as well as a feeling of not being the only one that was sick among the healthy. Not having to do everyday tasks and having time to themselves were perceived positively. Several factors contributed to the positive experiences of climate care; climate, environment, physical activity, social context, staff involvement, and information about the disease were described as interacting together and resulting in a sense of well-being. A proposal for future research would be to examine if/how the various factors might interact and affect the RA patients’ illness and quality of life.

  9. Cognitive Impairment in Persons With Rheumatoid Arthritis

    PubMed Central

    Shin, So Young; Katz, Patricia; Wallhagen, Margaret; Julian, Laura

    2013-01-01

    Objective To explore the prevalence and possible predictors of cognitive impairment in persons with rheumatoid arthritis (RA). Methods Individuals from a longitudinal cohort study of RA participated in a study visit that included a range of physical, psychosocial, and biologic metrics. Cognitive function was assessed using a battery of 12 standardized neuropsychological measures yielding 16 indices. Subjects were classified as “impaired” if they performed 1 SD below age-based population norms on at least 4 of 16 indices. Logistic regression analyses were conducted to identify which of the following were significant predictors of cognitive impairment: sex, race, income, education, depression, disease duration, disease severity, C-reactive protein (CRP) level, glucocorticoid use, and cardiovascular disease (CVD) risk factors. Results A total of 115 subjects with a mean ± SD age of 58.6 ± 10.8 years were included; 64% were women and 81% were white. The proportion of persons who were classified as cognitively impaired was 31%. Education, income, glucocorticoid use, and CVD risk factors independently predicted cognitive impairment, controlling for sex, race, disease duration, disease severity, CRP level, and depression. Individuals with cognitive impairment were more likely to have low education (odds ratio [OR] 6.18, 95% confidence interval [95% CI] 1.6 –23.87), have low income (OR 7.12, 95% CI 1.35–37.51), use oral glucocorticoids (OR 2.92, 95% CI 1.05–8.12), and have increased CVD risk factors (OR 1.61, 95% CI 1.19–2.17 per risk factor). Conclusion The findings of this study suggest that the burden of cognitive impairment in RA is significant, and future studies identifying specific etiologic contributors to cognitive impairment are warranted. PMID:23322467

  10. Isolated talonavicular arthrodesis in patients with rheumatoid arthritis of the foot and tibialis posterior tendon dysfunction

    PubMed Central

    2010-01-01

    Background The foot is often affected in patients with rheumatoid arthritis. Subtalar joints are involved more frequently than ankle joints. Deformities of subtalar joints often lead to painful flatfoot and valgus deformity of the heel. Major contributors to the early development of foot deformities include talonavicular joint destruction and tibialis posterior tendon dysfunction, mainly due to its rupture. Methods Between 2002 and 2005 we performed isolated talonavicular arthrodesis in 26 patients; twenty women and six men. Tibialis posterior tendon dysfunction was diagnosed preoperatively by physical examination and by MRI. Talonavicular fusion was achieved via screws in eight patients, memory staples in twelve patients and a combination of screws and memory staples in six cases. The average duration of immobilization after the surgery was four weeks, followed by rehabilitation. Full weight bearing was allowed two to three months after surgery. Results The mean age of the group at the time of the surgery was 43.6 years. MRI examination revealed a torn tendon in nine cases with no significant destruction of the talonavicular joint seen on X-rays. Mean of postoperative followup was 4.5 years (3 to 7 years). The mean of AOFAS Hindfoot score improved from 48.2 preoperatively to 88.6 points at the last postoperative followup. Eighteen patients had excellent results (none, mild occasional pain), six patients had moderate pain of the foot and two patients had severe pain in evaluation with the score. Complications included superficial wound infections in two patients and a nonunion developed in one case. Conclusions Early isolated talonavicular arthrodesis provides excellent pain relief and prevents further progression of the foot deformities in patients with rheumatoid arthritis and tibialis posterior tendon dysfunction. PMID:20187969

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  13. 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.-

  14. 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,…

  15. Pain Coping Strategies and Depression in Rheumatoid Arthritis.

    ERIC Educational Resources Information Center

    Brown, Gregory K.; And Others

    1989-01-01

    Examined role of pain episodes and active and passive pain coping strategies in predicting depression in 287 patients with rheumatoid arthritis (RA). Findings revealed pain, passive coping, and interaction between the 2 accounted for higher depression. Results also indicated that frequent use of passive pain coping strategies in face of high pain…

  16. Cognitive Distortion in Rheumatoid Arthritis: Relation to Depression and Disability.

    ERIC Educational Resources Information Center

    Smith, Timothy W.; And Others

    1988-01-01

    Examined the relation between cognitive distortion, as measured by the Cognitive Error Questionnaire, and both self-reported and interview-rated depression and disability in 92 rheumatoid arthritis (RA) patients. Found cognitive distortion significantly associated with depression, and also related to physical disability. Discusses the results,…

  17. Anti-perinuclear Factor as Diagnostic Marker in Rheumatoid Arthritis

    PubMed Central

    Abedian, Zeinab; Sagafi, Masoud; Kenari, Saeid Abedian

    2015-01-01

    Introduction Rheumatoid Arthritis (RA) is a systemic autoimmune disease. It is associated with several auto antibodies which can serve as diagnostic and prognostic markers. Aim In this study, Anti perinuclear Factor (APF) was evaluated as a biomarker in comparison with Rheumatoid Factor (RF) in Rheumatoid Arthritis. Materials and Methods Fifty two sera of patients with RA (mean age 48±15.8), 23 sera of Patient control group (mean age 32.5 ± 16.9) and 30 sera of Healthy control group (mean age 32.1± 16.9) were analysed. The method is based on the binding of APF to perinuclear keratohyalin granules of buccal mucosal cell and its detection using a fluorescently labeled anti human total antiserum. Results: APF were found in 71.2 %(37/52) of patients with RA. The sensitivity and specificity for APF from 1/5 serum dilution was 71.2% and 94.3% respectively. RF test had higher sensitivity (88.5%) compare to the APF test (71.2%), but its specificity was (86.8%) less than APF (94.3%). There was no significant relationship between the onset of APF and severity of disease but there was significant relationship between the APF titer and severity of disease (p<0.05). Conclusion It is concluded that APF test is a valuable serological tool for the diagnosis of the disease and a useful serological marker to differentiate from the other inflammatory rheumatoid diseases. PMID:26500935

  18. Effect of Rheumatoid Factor on Complement-Mediated Phagocytosis

    PubMed Central

    McDuffie, F. C.; Brumfield, H. W.

    1972-01-01

    The frequency and amount of IgM rheumatoid factor (RF) in the blood of patients with rheumatoid arthritis (RA) correlate with the severity of the disease and the number of complications. Though previous studies of RF in subacute bacterial endocarditis have shown that RF inhibits phagocytosis of microorganisms by granulocytes, the presence of low levels of complement (C) in blood and synovial fluid of patients with the highest titers of RF suggests that an interaction between RF and C may contribute to the inflammatory process in RA. We thus employed a quantitative methodology to examine the effect of RF on complement-dependent phagocytosis of sheep erythrocytes by rabbit granulocytes. Addition of 2500 molecules of IgM RF to sheep cells heavily coated with IgG antibody (195,000 molecules per cell) resulted in virtually complete inhibition of uptake of C3 (?1c) and prevention of phagocytosis, an effect resulting from inhibition of uptake of C1 by the cells. When erythrocytes coated with only 34,000 molecules of IgG antibody were employed, phagocytosis was similarly inhibited. However the effect of RF on such cells was shown to be primarily mediated through inhibition of C4 rather than C1 uptake. Although the results do not exclude the participation of an IgM RF of higher avidity, present only in the tissues in rheumatoid inflammation, circulating IgM RF probably does not play a potentiating role in rheumatoid inflammation. PMID:4640945

  19. Aalborg Universitet Adherence to methotrexate in rheumatoid arthritis

    E-print Network

    Schwefel, Hans-Peter

    Aalborg Universitet Adherence to methotrexate in rheumatoid arthritis Bliddal, Henning; Eriksen from Aalborg University Citation for published version (APA): Bliddal, H., Eriksen, S. A., Christensen: A Danish Nationwide Cohort Study Henning Bliddal,1,2 Stine A. Eriksen,1,3 Robin Christensen,1 Tove Lorenzen

  20. Detection of rheumatoid arthritis in humans by fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Ebert, Bernd; Dziekan, Thomas; Weissbach, Carmen; Mahler, Marianne; Schirner, Michael; Berliner, Birgitt; Bauer, Daniel; Voigt, Jan; Berliner, Michael; Bahner, Malte L.; Macdonald, Rainer

    2010-02-01

    The blood pool agent indo-cyanine green (ICG) has been investigated in a prospective clinical study for detection of rheumatoid arthritis using fluorescence imaging. Temporal behavior as well as spatial distribution of fluorescence intensity are suited to differentiate healthy and inflamed finger joints after i.v. injection of an ICG bolus.

  1. Sputum Autoantibodies in Patients With Established Rheumatoid Arthritis and Subjects at Risk of Future Clinically Apparent Disease

    PubMed Central

    Willis, Van C.; Demoruelle, M. Kristen; Derber, Lezlie A.; Chartier-Logan, Catherine J.; Parish, Mark C.; Pedraza, Isabel F.; Weisman, Michael H.; Norris, Jill M.; Holers, V. Michael; Deane, Kevin D.

    2014-01-01

    Objective To evaluate the generation of rheumatoid arthritis (RA)–related autoantibodies in the lung. Methods Simultaneous collection of serum and induced sputum was performed in 21 healthy controls, 49 at-risk subjects without inflammatory arthritis but at risk of RA due to family history or seropositivity for anti–citrullinated protein antibodies, and 14 subjects with early RA. Samples were tested for anti–cyclic citrullinated peptide 2 (anti-CCP2), anti-CCP3, anti-CCP3.1, rheumatoid factor isotypes IgM, IgG, and IgA, and total IgM, IgG, and IgA. Results One or more autoantibodies were present in sputum of 39% of at-risk seronegative subjects, 65% of at-risk seropositive subjects, and 86% of subjects with early RA. In at-risk seronegative subjects, the rate of anti-CCP3.1 positivity and the median number of autoantibodies were elevated in sputum versus serum. In subjects with early RA, the rate of positivity for several individual autoantibodies and the median number of autoantibodies were higher in serum than in sputum. Results in at-risk seropositive subjects were intermediate between these groups. In at-risk subjects with autoantibody positivity in sputum, the ratios of autoantibody to total Ig were higher in sputum than in serum, suggesting that these autoantibodies are generated or sequestered in the lung. Conclusion RA-related autoantibodies are detectable in sputum in subjects at risk of RA and in subjects with early RA. In a subset of at-risk subjects, the presence of sputum autoantibodies in the absence of seropositivity, and the increased autoantibody-to–total Ig ratios in sputum, suggest that the lung may be a site of autoantibody generation in the early development of RA. These findings suggest an important role of the lung in the pathogenesis of RA. PMID:23817979

  2. Power-Aware Multi-Core Simulation for Early Design Stage Hardware/Software Co-Optimization

    E-print Network

    Eeckhout, Lieven

    infrastruc- ture by combining high-abstraction performance simulation using Sniper with power modeling using McPAT and cus- tom DRAM power models. Sniper/McPAT is fast -- sim- ulation speed is around 2 MIPS multi-core simulation. We demonstrate Sniper/McPAT's accuracy through validation against real hardware

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

    PubMed Central

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

    2012-01-01

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

  4. Effectiveness of early cardiology undergraduate learning using simulation on retention, application of learning and level of confidence during clinical clerkships

    PubMed Central

    Lin, Weiqin; Lee, Glenn K; Loh, Joshua P; Tay, Edgar L; Sia, Winnie; Lau, Tang-Ching; Hooi, Shing-Chuan; Poh, Kian-Keong

    2015-01-01

    INTRODUCTION This study aimed to assess the effectiveness of the use of a cardiopulmonary patient simulator in the teaching of second-year medical students. Effectiveness was measured in terms of the extent of knowledge retention and students’ ability to apply the skills learned in subsequent real-life patient contact. METHODS In this study, ten third-year medical students who had previously undergone simulator training as part of their second-year curriculum underwent an objective structured clinical examination (OSCE) and a multiple-choice question (MCQ) test to assess their ability to apply the knowledge gained during the simulator training when dealing with real patients. The performance of this group of students was compared with that of a group of ten fourth-year medical students who did not undergo simulation training. RESULTS Although the third-year medical students performed well in the OSCE, they were outperformed by the group of fourth-year medical students, who had an extra year of clinical exposure. The MCQ scores of the two groups of students were similar. Post-simulation training survey revealed that students were generally in favour of incorporating cardiopulmonary simulator training in the preclinical curriculum. CONCLUSION Cardiopulmonary simulator training is a useful tool for the education of preclinical medical students. It aids the translation of preclinical knowledge into real-life clinical skills. PMID:25715855

  5. Radiographic changes in the temporomandibular joint of patients with rheumatoid arthritis, psoriatic, arthritis, and ankylosing spondylitis.

    PubMed

    Wenneberg, B; Könönen, M; Kallenberg, A

    1990-01-01

    Sixty-one subjects with rheumatoid arthritis, 61 with psoriatic arthritis, 61 with ankylosing spondylitis, and 77 healthy controls were examined using orthopantomography to determine the frequency of radiographic changes in the condyle of the temporomandibular joint. Radiographic changes were found significantly more often in subjects with rheumatoid arthritis (66%), psoriatic arthritis (38%), and ankylosing spondylitis (30%) than in controls (12%). Subjects with rheumatoid arthritis also had significantly more radiographic changes, especially cortical erosions and subcortical cysts, than subjects with psoriatic arthritis or ankylosing spondylitis. It may be concluded that rheumatoid arthritis is a more severe disease than psoriatic arthritis or ankylosing arthritis regarding temporomandibular joint involvement. PMID:2098385

  6. 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.

  7. The molecular mechanism of osteoclastogenesis in rheumatoid arthritis

    PubMed Central

    Udagawa, Nobuyuki; Kotake, Shigeru; Kamatani, Naoyuki; Takahashi, Naoyuki; Suda, Tatsuo

    2002-01-01

    Bone-resorbing osteoclasts are formed from hemopoietic cells of the monocyte–macrophage lineage under the control of bone-forming osteoblasts. We have cloned an osteoblast-derived factor essential for osteoclastogenesis, the receptor activator of NF-?B ligand (RANKL). Synovial fibroblasts and activated T lymphocytes from patients with rheumatoid arthritis also express RANKL, which appears to trigger bone destruction in rheumatoid arthritis as well. Recent studies have shown that T lymphocytes produce cytokines other than RANKL such as IL-17, granulocyte–macrophage colony-stimulating factor and IFN-?, which have powerful regulatory effects on osteoclastogenesis. The possible roles of RANKL and other cytokines produced by T lymphocytes in bone destruction are described. PMID:12223101

  8. Conditional analysis of the major histocompatibility complex in rheumatoid arthritis.

    PubMed

    Taylor, Kimberly E; Criswell, Lindsey A

    2009-01-01

    We performed a whole-genome association study of rheumatoid arthritis susceptibility using Illumina 550k single-nucleotide polymorphism (SNP) genotypes of 868 cases and 1194 controls from the North American Rheumatoid Arthritis Consortium (NARAC). Structured association analysis with adjustment for potential population stratification yielded 200 SNPs with p < 1 x 10-8 for association with RA, all of which were on chromosome 6 in a 2.7-Mb region of the major histocompatibility complex (MHC). Given the extensive linkage equilibrium in the region and known risk of HLA-DRB1 alleles, we then applied conditional analyses to ascertain independent signals for RA susceptibility among these 200 candidate SNPs. Conditional analyses incorporating risk categories of the HLA-DRB1 "shared epitope" revealed three SNPs having independent associations with RA (conditional p < 0.001). This supports the presence of significant effects on RA susceptibility in the MHC in addition to the shared epitope. PMID:20018027

  9. Indium-111 leukocyte imaging in patients with rheumatoid arthritis

    SciTech Connect

    Uno, K.; Matsui, N.; Nohira, K.; Suguro, T.; Kitakata, Y.; Uchiyama, G.; Miyoshi, T.; Uematsu, S.; Inoue, S.; Arimizu, N.

    1986-03-01

    This study evaluates the usefulness of labeled leukocyte imaging in patients with rheumatoid arthritis. In 33 patients, the incidence of pain and swelling in 66 wrist joints and 66 knee joints was compared with the accumulation of (/sup 111/In)leukocytes. No accumulation of (/sup 111/In)leukocytes was seen in any of the patients' wrists (0/12) or knee joints (0/14) when both pain and swelling were absent. In contrast, 93% (25/27) of wrist joints and 80% (24/30) of knee joints with both pain and swelling were positive by (/sup 111/In)leukocyte scintigraphy. There was little correlation between the stage of the disease, as determined by radiography, and (/sup 111/In)leukocyte accumulation. This study suggests that (/sup 111/In)leukocyte imaging may be a reliable procedure for monitoring the activity of rheumatoid arthritis, especially for confirming the lack of an ongoing inflammatory response.

  10. Treatment of intractable rheumatoid arthritis with lymphoid irradiation

    SciTech Connect

    Strober, S.; Kotzin, B.L.; Hoppe, R.T.; Slavin, S.; Gottlieb, M.; Calin, A.; Fuks, Z.; Kaplan, H.S.

    1981-01-01

    Subdiaphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdiaphragmatic lymphoid tissues in fractionated doses of 150 to 250 rad each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.

  11. [Aims of hand therapy in treatment of rheumatoid hand].

    PubMed

    Bureck, W

    2005-02-01

    When dealing with rheumatoid arthritis, the main issues of hand therapy are the treatment of hand and finger joints. We emphasize mobilisation of joints, muscle strengthening, correcting deformities by low temperature splints and joint protection. Further tasks of occupational therapy are: Informing patients about adaptive devices and training their use as well as educational programs for patients with reduced mobility of the upper limb. The most common surgery on the rheumatoid hand, that need postoperative treatment by a hand therapist are complete and limited arthrodesis of the wrist, surgical reconstruction of tendons, arthroplasty and arthrodeses of and for finger joints, and so on. At the Nordwestdeutsches Rheumazentrum St. Josef-Stift Sendenhorst we have designed a standard postoperative management for treating arthroplasty with a "Silikonspacer" in the metacarpophalangeal joints. PMID:15744657

  12. Usefulness of sonography in the diagnosis of rheumatoid hand

    PubMed Central

    Sudo?-Szopi?ska, Iwona

    2013-01-01

    Ultrasound examination is becoming more and more common in patients with rheumatoid diseases. Above all, it enables the assessment of articular soft tissues and constitutes a non-invasive examination. In a rheumatologist's everyday practice, it is conducted at the stage of initial diagnosis as well as to monitor the treatment and to confirm the remission if the clinical picture is ambiguous. The first sign of arthritis (including rheumatoid arthritis) that is visible on ultrasound examination is the thickening of the synovial membrane of the joint cavities, tendon sheaths or bursae. It is frequently accompanied by the exudate in the joint, sheath or bursa. In a subsequent stage, in Doppler examination, enhanced vascularization of the synovial membrane is observed. Sometimes, the inflammatory process of the tendon sheaths also affects the tendons, which might lead to their damage. Moreover, ultrasound examination also reveals erosions and inflammatory cysts (geodes) which attest to the advancement of the disease. A dynamic ultrasound examination enables to diagnose the capsule-ligamentous contracture of the interphalangeal joints, which occurs due to the lack of rehabilitation that should begin at the moment of the commencement of the inflammation. The ultrasound image does not allow for the differentiation between various rheumatoid entities, including those encompassing the joints in the hand, wrist. The observed changes, i.e. thickening of the synovial membrane, hyperemia, effusions, erosions or tendon damage, may accompany various rheumatoid entities. The purpose of the ultrasound examination is to recognize these irregularities, determine their localization and advancement and, finally, to monitor the course of treatment. Furthermore, ultrasound scan enables to assess the joints and tendons in a dynamic examination in relation to local ailments of the patient as well as to monitor the biopsy, aspiration and medicine administration. Sonography is used for a US-guided administration of radioisotope substances for synoviorthesis. PMID:26673521

  13. Studies on collagenase from rheumatoid synovium in tissue culture

    PubMed Central

    Evanson, John M.; Jeffrey, John J.; Krane, Stephen M.

    1968-01-01

    Fragments of synovium from patients with rheumatoid arthritis survive in defined tissue culture medium in the absence of added serum and, after 3-4 days, release into the medium enzyme capable of degrading undenatured collagen. Maximal activity is observed at pH 7-9 but the enzyme is inactive at pH 5. At temperatures of 20° and 27°C, collagen molecules in solution are cleaved into 3/4 and 1/4 length fragments with minimal loss of negative optical rotation, but with loss in specific viscosity of approximately 60%. Above 30°C the fragments begin to denature and denaturation is complete at 37°C. If the enzyme is not inhibited at this stage the large fragments are broken down further to polypeptides of low molecular weight. Reconstituted collagen fibrils and native fibers at 37°C are cleaved to the low molecular weight fragments, although the fibrils are resistant to breakdown at lower temperatures (20°-27°C). It is proposed that the production of such an enzyme by inflamed and proliferating rheumatoid synovium may be responsible for some of the destruction of collagenous structures that accompanies rheumatoid arthritis. Images PMID:4302179

  14. Relationship between Periodontitis and Rheumatoid Arthritis: Review of the Literature

    PubMed Central

    Araújo, Vilana Maria Adriano; Melo, Iracema Matos; Lima, Vilma

    2015-01-01

    Periodontitis (PD) and rheumatoid arthritis (RA) are immunoinflammatory diseases where leukocyte infiltration and inflammatory mediators induce alveolar bone loss, synovitis, and joint destruction, respectively. Thus, we reviewed the relationship between both diseases considering epidemiological aspects, mechanical periodontal treatment, inflammatory mediators, oral microbiota, and antibodies, using the keywords “periodontitis” and “rheumatoid arthritis” in PubMed database between January 2012 and March 2015, resulting in 162 articles. After critical reading based on titles and abstracts and following the inclusion and exclusion criteria, 26 articles were included. In the articles, women over 40 years old, smokers and nonsmokers, mainly constituted the analyzed groups. Eight studies broached the epidemiological relationship with PD and RA. Four trials demonstrated that the periodontal treatment influenced the severity of RA and periodontal clinical parameters. Nine studies were related with bacteria influence in the pathogenesis of RA and the presence of citrullinated proteins, autoantibodies, or rheumatoid factor in patients with PD and RA. Five studies investigated the presence of mediators of inflammation in PD and RA. In summary, the majority of the articles have confirmed that there is a correlation between PD and RA, since both disorders have characteristics in common and result from an imbalance in the immunoinflammatory response. PMID:26347200

  15. Non-Biologic Nanodelivery Therapies for Rheumatoid Arthritis.

    PubMed

    Gouveia, Virgínia M; Lima, Sofia A Costa; Nunes, Cláudia; Reis, Salette

    2015-10-01

    Rheumatoid arthritis is a common chronic inflammatory disease characterized by progressive bone and cartilage destruction causing severe functional limitations, increased morbidity and mortality rate, which results in a strong negative socioeconomic impact. Current therapies only slow the progression of the disease and try to enhance quality of life. Furthermore, such therapies present several drawbacks due to the adverse effects caused by the lack of selectively of the drugs and frequent and long-term dosing that lead to patient non-compliance. Drug delivery systems based on nanocarriers represent a promising approach to overcome the current therapeutic limitations because they can selectively carry drugs to inflamed synovium allowing for improved drug efficacy, thereby reducing the biodistribution of anti-rheumatic drugs. Additionally, controlled drug release can lead to the reduction of drug dosages. The increasing interest and confidence that nanocarriers can revolutionize the treatment of rheumatoid arthritis has led to an increased number of investigations in this field. In this context, the present review focuses on drug delivery system strategies for non-biological drugs developed for the treatment of rheumatoid arthritis. PMID:26502635

  16. 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.

  17. On some additional recollections, and the absence thereof, about the early history of computer simulations in statistical mechanics

    SciTech Connect

    Wood, W.W.

    1995-09-01

    This lecture is an extension and correction of a previous lecture given by the author ten years ago at ``Corso 97`` in Varenna. Here again he emphasizes that his early work was exclusively with applications of the Metropolis Monte Carlo method. His only connection with the early work on the molecular dynamics method was in collaboration with Alder and Wainwright in their joint effort to reconcile the results of the Monte Carlo and molecular dynamics methods for hard spheres. Here he amplifies a point suggested by a question asked by Professor Ciccotti: Namely, when was it discovered that the Metropolis method consists in the generation of a realization of a Markov chain, for which there was a large body of mathematical theory that made the justification of the method quite a simple matter?

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

    PubMed

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

    2015-06-01

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

  19. Two- and three-dimensional optical tomography of finger joints for diagnostics of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Klose, Alexander D.; Hielscher, Andreas H.; Hanson, Kenneth M.; Beuthan, Juergen

    1998-12-01

    Rheumatoid arthritis (RA) is one of the most common diseases of human joints. This progressive disease is characterized by an inflammation process that originates in the inner membrane (synovalis) of the capsule and spreads to other parts of the joint. In early stages the synovalis thickness and the permeability of this membrane changes. This leads to changes in the optical parameters of the synovalis and the synovial fluid (synovia), which occupies the space between the bones. The synovia changes from a clear yellowish fluid to a turbid grayish substance. In this work we present 2 and 3-dimensional reconstruction schemes for optical tomography of the finger joints. Our reconstruction algorithm is based on the diffusion approximation and employs adjoint differentiation techniques for the gradient calculation of the objective function with respect to the spatial distribution of optical properties. In this way, the spatial distribution of optical properties within the joints is reconstructed with high efficiency and precision. Volume information concerning the synovial space and the capsula are provided. Furthermore, it is shown that small changes of the scattering coefficients can be monitored. Therefore, optical tomography has the potential of becoming a useful tool for the early diagnosis and monitoring of disease progression in RA.

  20. Impact of morning stiffness on working behaviour and performance in people with rheumatoid arthritis.

    PubMed

    Mattila, Kalle; Buttgereit, Frank; Tuominen, Risto

    2014-12-01

    Work disability remains a considerable problem for many patients with rheumatoid arthritis (RA). Morning stiffness is a symptom of RA associated with early retirement from work and with impaired functional ability. We aimed to explore the patient's perception of the impact of morning stiffness on the working life of patients with RA. A survey was conducted in 11 European countries. Patients of working age, with RA for ?6 months and morning stiffness ?3 mornings a week, were interviewed by telephone using a structured questionnaire. Responses were assessed in the total sample and in subgroups defined by severity and duration of morning stiffness and by country. A total of 1,061 respondents completed the survey, 534 were working, 224 were retired and the rest were, i.e. homemakers and unemployed. Among the 534 working respondents, RA-related morning stiffness affected work performance (47 %), resulted in late arrival at work (33 %) and required sick leave in the past month (15 %). Of the 224 retired respondents, 159 (71 %) stopped working earlier than their expected retirement age, with 64 % giving RA-related morning stiffness as a reason. There was a differential impact of increasing severity and increasing duration of morning stiffness on the various parameters studied. There were notable inter-country differences in the impact of RA-related morning stiffness on ability to work and on retirement. This large survey showed that from the patient's perspective, morning stiffness reduces the ability to work in patients with RA and contributes to early retirement. PMID:24871158

  1. Access To Success: The Second Annual UCBeyond Scholarship Program -Fulfilling Dreams for Students Living With Crohn's Disease and Rheumatoid Arthritis -

    E-print Network

    Lotze, Heike K.

    for Students Living With Crohn's Disease and Rheumatoid Arthritis - February 27, 2008 (Burlington, ON) -- UCB Pharma Canada is pleased to announce the return of the UCBeyond Crohn's Disease and Rheumatoid Arthritis education an achievable goal for students living with Crohn's Disease and Rheumatoid Arthritis, UCB Pharma

  2. British Journal of Rheumatology 1988;27(suppl 11)162-169 RHEUMATOID ARTHRITIS AS A GLYCOSYLATION

    E-print Network

    British Journal of Rheumatology 1988;27(suppl 11)162-169 RHEUMATOID ARTHRITIS AS A GLYCOSYLATION in the pathology of rheumatoid arthritis is reviewed. KEYWORDS: Galactose. Immunoglobulin, Immune complexes) of serum IgG in rheumatoid arthritis may be an important marker of the disease or contribute directly

  3. Genetic Epidemiology 31 (Supplement 1):S12S21 (2007) Genetic Association with Rheumatoid Arthritis--Genetic Analysis

    E-print Network

    Yu, Zhaoxia

    2007-01-01

    Genetic Epidemiology 31 (Supplement 1):S12­S21 (2007) Genetic Association with Rheumatoid Arthritis Analysis Workshop 15 (GAW15) conducted association analyses of rheumatoid arthritis data. The analyses were carried out primarily in the data provided by the North American Rheumatoid Arthritis Consortium (NARAC

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

    PubMed Central

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

    2009-01-01

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

  5. Systems biology for battling rheumatoid arthritis: application of the Entelos PhysioLab platform.

    PubMed

    Rullmann, J A C; Struemper, H; Defranoux, N A; Ramanujan, S; Meeuwisse, C M L; van Elsas, A

    2005-12-01

    A large-scale mathematical model, the Entelos Rheumatoid Arthritis (RA) PhysioLab platform, has been developed to describe the inflammatory and erosive processes in afflicted joints of people suffering from RA. The platform represents the life cycle of inflammatory cells, endothelium, synovial fibroblasts, and chondrocytes, as well as their products and interactions. The interplay between these processes culminates in clinically relevant measures for inflammation and erosion. The simulation model is deterministic, which allows tracing back the mechanism of action for a particular simulation result. Different patient phenotypes are represented by different virtual patients. The RA PhysioLab platform has been used to systematically and quantitatively study the predicted therapeutic effect of modulating several molecular targets, which resulted in a ranking of putative drug targets and a workflow to confirm the simulations experimentally. In addition, critical pathways were identified that drive the predicted disease outcome. Within these pathways, targets were identified from public literature that were not previously associated with arthritis. The model provides insights into the biology of RA and can be used as a platform for hypothesis-driven research. Case studies of therapies directed against IL-12 and IL-15 illustrate the approach, with emphasis on the analysis of system dynamics. PMID:16986268

  6. Optimizing Rheumatoid Arthritis Therapy: Using Objective Measures of Disease Activity to Guide Treatment

    PubMed Central

    Owens, Gary M.

    2015-01-01

    Background Rheumatoid arthritis (RA) affects approximately 1.5 million individuals in the United States, or approximately 1% of the US adult population. In women, RA most often begins between age 30 and 60 years; in men, it often starts later in life. Patients with RA may have rapid declines in physical function that can begin early in the disease course. Disability increases most rapidly during the early years of the disease course, and if patients are not accurately diagnosed and do not receive appropriate care early, substantial functional declines may result. Objective To review strategies and clinical assessment tools that may optimize patient outcomes by using objective measures of disease activity. Discussion The goal of treatment for patients newly diagnosed with RA should be preventing joint damage from developing by employing early and aggressive approaches to therapy that minimize disease activity. Likewise, for established disease, treatment should be aimed at limiting the progression of existing joint damage. Substantial advances have been made in the treatment of RA over the past 2 decades, in large part as a result of better understanding of the biology of RA and the resultant introduction of biologic therapies. In 2010, an international task force published recommendations for a treat-to-target management approach to RA, much of which was based on the use of biologic drugs. This treatment strategy emphasized that the primary target in the treatment of patients with RA should be clinical remission or low disease activity. The tools necessary to measure RA disease activity are often incomplete, imprecise, or rely on a combination of physician and patient subjective evaluations. There is no one symptom, laboratory measure, or clinical tool that provides a truly accurate assessment of disease activity in patients with RA. Conclusion Thus, there is a large gap between what is recommended in clinical guidelines and the actual practice of rheumatologists. Better methods of assessing RA disease activity are still needed to enable widespread adoption of guidelines in the clinical community. PMID:26557229

  7. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rheumatoid factor immuno-logical test system. 866.5775 Section 866.5775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and...

  8. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rheumatoid factor immuno-logical test system. 866.5775 Section 866.5775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and...

  9. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rheumatoid factor immuno-logical test system. 866.5775 Section 866.5775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and...

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rheumatoid factor immuno-logical test system. 866.5775 Section 866.5775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rheumatoid factor immuno-logical test system. 866.5775 Section 866.5775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and...

  12. The Rheumatoid Arthritis Risk Gene, LBH, Regulates Growth in Fibroblast-like Synoviocytes

    E-print Network

    Wang, Wei

    The Rheumatoid Arthritis Risk Gene, LBH, Regulates Growth in Fibroblast-like Synoviocytes Anna pathology in rheumatoid arthritis (RA). Currently, no treatment specifically targets these aggressive cells@ucsd.edu) Conflict of interest: The authors have declared that no conflict of interest exists. Full Length Arthritis

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

    NASA Astrophysics Data System (ADS)

    Gsponer, Jörg; Haberthür, Urs; Caflisch, Amedeo

    2003-04-01

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

  14. 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

  15. 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.

  16. 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

  17. Early breast cancer detection method based on a simulation study of single-channel passive microwave radiometry imaging

    NASA Astrophysics Data System (ADS)

    Kostopoulos, Spiros A.; Savva, Andonis D.; Asvestas, Pantelis A.; Nikolopoulos, Christos D.; Capsalis, Christos N.; Cavouras, Dionisis A.

    2015-09-01

    The aim of the present study is to provide a methodology for detecting temperature alterations in human breast, based on single channel microwave radiometer imaging. Radiometer measurements were simulated by modelling the human breast, the temperature distribution, and the antenna characteristics. Moreover, a simulated lesion of variable size and position in the breast was employed to provide for slight temperature changes in the breast. To detect the presence of a lesion, the temperature distribution in the breast was reconstructed. This was accomplished by assuming that temperature distribution is the mixture of distributions with unknown parameters, which were determined by means of the least squares and the singular value decomposition methods. The proposed method was validated in a variety of scenarios by altering the lesion size and location and radiometer position. The method proved capable in identifying temperature alterations caused by lesions, at different locations in the breast.

  18. 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.

  19. Bio-imaging and Photodynamic Therapy with Tetra Sulphonatophenyl Porphyrin (TSPP)-TiO2 Nanowhiskers: New Approaches in Rheumatoid Arthritis Theranostics

    PubMed Central

    Zhao, Chunqiu; Ur Rehman, Fawad; Yang, Yanlong; Li, Xiaoqi; Zhang, Dong; Jiang, Hui; Selke, Matthias; Wang, Xuemei; Liu, Chongyang

    2015-01-01

    Since Rheumatoid arthritis (RA) is one of the major human joint diseases with unknown etiology, the early diagnosis and treatment of RA remains a challenge. In this contribution we have explored the possibility to utilize novel nanocomposites of tetera suplhonatophenyl porphyrin (TSPP) with titanium dioxide (TiO2) nanowhiskers (TP) as effective bio-imaging and photodynamic therapeutic (PDT) agent for RA theranostics. Our observations demonstrate that TP solution PDT have an ameliorating effect on the RA by decreasing significantly the IL-17 and TNF-? level in blood serum and fluorescent imaging could enable us to diagnose the disease in subclinical stages and bio-mark the RA insulted joint. PMID:26153895

  20. Bio-imaging and Photodynamic Therapy with Tetra Sulphonatophenyl Porphyrin (TSPP)-TiO2 Nanowhiskers: New Approaches in Rheumatoid Arthritis Theranostics.

    PubMed

    Zhao, Chunqiu; Ur Rehman, Fawad; Yang, Yanlong; Li, Xiaoqi; Zhang, Dong; Jiang, Hui; Selke, Matthias; Wang, Xuemei; Liu, Chongyang

    2015-01-01

    Since Rheumatoid arthritis (RA) is one of the major human joint diseases with unknown etiology, the early diagnosis and treatment of RA remains a challenge. In this contribution we have explored the possibility to utilize novel nanocomposites of tetera suplhonatophenyl porphyrin (TSPP) with titanium dioxide (TiO2) nanowhiskers (TP) as effective bio-imaging and photodynamic therapeutic (PDT) agent for RA theranostics. Our observations demonstrate that TP solution PDT have an ameliorating effect on the RA by decreasing significantly the IL-17 and TNF-? level in blood serum and fluorescent imaging could enable us to diagnose the disease in subclinical stages and bio-mark the RA insulted joint. PMID:26153895

  1. An extreme value theory approach for the early detection of time clusters. A simulation-based assessment and an illustration to the surveillance of Salmonella.

    PubMed

    Guillou, A; Kratz, M; Le Strat, Y

    2014-12-10

    We propose a new method that could be part of a warning system for the early detection of time clusters applied to public health surveillance data. This method is based on the extreme value theory (EVT). To any new count of a particular infection reported to a surveillance system, we associate a return period that corresponds to the time that we expect to be able to see again such a level. If such a level is reached, an alarm is generated. Although standard EVT is only defined in the context of continuous observations, our approach allows to handle the case of discrete observations occurring in the public health surveillance framework. Moreover, it applies without any assumption on the underlying unknown distribution function. The performance of our method is assessed on an extensive simulation study and is illustrated on real data from Salmonella surveillance in France. PMID:25060768

  2. Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis.

    PubMed

    Lyseng-Williamson, Katherine A; Foster, Rachel H

    2004-01-01

    Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD), binds to and inhibits the activity of tumour necrosis factor-alpha, which is thought to play an important role in the pathophysiology of rheumatoid arthritis. Intravenous infliximab plus methotrexate is recommended in patients with rheumatoid arthritis who have not achieved satisfactory disease control with adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks plus methotrexate demonstrated rapid and sustainable improvements in clinical response, delayed radiographic progression, and/or improved functional status and health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and 102. In cost-utility analyses of infliximab plus methotrexate conducted from a healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios relative to methotrexate alone in patients with active, refractory rheumatoid arthritis. When only direct costs were considered, the lifetime incremental cost per discounted QALY gained with infliximab plus methotrexate relative to methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported; treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses, and euro39 500 (year of costing not reported; lifelong treatment) in the Portuguese analysis. The cost-utility ratios were more favourable when lost productivity costs or the additional benefit of infliximab on radiographic stabilisation were considered. In the Swedish and UK analyses with a 10-year time horizon, infliximab plus methotrexate for 1 or 2 years was associated with cost-utility ratios of euro28 600-56 100 (year of costing not reported) when direct costs were considered, and euro3440-48 200 when direct costs plus loss-of-productivity costs were considered. In conclusion, cost-utility analyses, which were based on modelling of data from the pivotal clinical trial of infliximab plus methotrexate, indicate that infliximab plus methotrexate is associated with acceptable cost-effectiveness ratios (<$US50,000 per discounted QALY gained) relative to methotrexate monotherapy in patients with active rheumatoid arthritis who have not responded to previous methotrexate or other DMARD therapy. The cost effectiveness of infliximab versus other DMARDs is at present unclear, but will be clarified when appropriate data from directly comparative clinical and/or pharmacoeconomic studies become available. In patients in whom adequate courses of other DMARDs have failed to achieve satisfactory disease control, infliximab plus methotrexate may prevent or delay disability, which may produce reductions in nondrug costs that can help offset its acquisition cost. PMID:14731052

  3. Serum level of oxidative stress marker is dramatically low in patients with rheumatoid arthritis treated with tocilizumab.

    PubMed

    Hirao, Makoto; Yamasaki, Naomi; Oze, Hiroki; Ebina, Kosuke; Nampei, Akihide; Kawato, Yoshitaka; Shi, Kenrin; Yoshikawa, Hideki; Nishimoto, Norihiro; Hashimoto, Jun

    2012-12-01

    Regarding the pathobiology of rheumatoid arthritis, oxidative stress induced by reactive oxygen species is an important mechanism that underlies destructive and proliferative synovitis. Abundant amounts of reactive oxygen species have been detected in the synovial fluid of inflamed rheumatoid joints. It is reported that drugs that block tumor necrosis factor-? reduce the oxidative stress marker levels in patients with rheumatoid arthritis. In this study, we measured reactive oxygen species using a free radical analytical system in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, tumor necrosis factor-?-blocking drugs (infliximab, etanercept), and an interleukin-6-blocking drug (tocilizumab). The serum level of oxidative stress was drastically low in patients with rheumatoid arthritis treated with tocilizumab, suggesting that interleukin-6 blocking therapy reduces not only joint damage, but also vascular degeneration in patients with rheumatoid arthritis. We believe that such a drastic effect would reduce the incidence of cardiovascular events and mortality in patients with rheumatoid arthritis. PMID:21909945

  4. Recurrent spontaneous subcutaneous emphysema in a patient with rheumatoid arthritis.

    PubMed

    Adelowo, Olufemi; Akintayo, Richard Oluyinka; Olaosebikan, Hakeem; Oba, Rasheedat

    2015-01-01

    Pulmonary air leak syndromes are extremely rare complications of systemic autoimmune connective tissue diseases and the occurrence of spontaneous subcutaneous emphysema (SSE) from pulmonary leak in the absence of pneumothorax or pneumomediastinum is even rarer. We report a case of recurrent SSE in a patient with rheumatoid arthritis and interstitial lung disease. The SSE was managed conservatively each time and it resorbed over several days. There has been no previous documented report of SSE in the absence of pneumomediastinum, pneumothorax or pulmonary nodules in a patient with RA. PMID:26472288

  5. Ultrastructural changes produced in rheumatoid synovial membrane by chrysotherapy.

    PubMed Central

    Ghadially, F N; Oryschak, A F; Mitchell, D M

    1976-01-01

    Biopsies of rheumatoid synovial membrane before and after chrysotherapy were examined with the light and electron microscopes, and subjected to electronprobe x-ray analysis. The main change noted was the occurrence of electron-dense deposits of characteristic morphology within pre-existing lysosomes. Such deposits were also seen in other varieties of lysosomal bodies. X-ray analysis showed the presence of gold, phosphorus, osmium, and calcium in these deposits. The present study shows that gold enters the pre-existing lysosomes, supporting the concept that the beneficial effects of chrysotherapy are due to its action on the lysosome. Images PMID:818965

  6. Assessment of phalangeal bone loss in patients with rheumatoid arthritis by quantitative ultrasound

    PubMed Central

    Roben, P; Barkmann, R; Ullrich, S; Gause, A; Heller, M; Gluer, C

    2001-01-01

    OBJECTIVE—Periarticular osteopenia is an early radiological sign of rheumatoid arthritis (RA). Quantitative ultrasound (QUS) devices have recently been shown to be useful for assessing osteoporosis. In this study the capability of a transportable and easy to use QUS device to detect skeletal impairment of the finger phalanges in patients with RA was investigated.?METHODS—In a cross sectional study 83 women (30 controls, 29 with glucocorticosteroid (GC) treated RA, and 24 with GC treated vasculitis) were examined. QUS measurements were obtained at the metaphyses of the proximal phalanges II-V and directly at the proximal interphalangeal joints II-IV with a DBM Sonic 1200 (IGEA, Italy) QUS device. Amplitude dependent speed of sound (AD-SoS) was evaluated. In 23 of the patients with RA, hand radiographs were evaluated.?RESULTS—Significant differences between patients with RA and the other groups were found for AD-SoS at both measurement sites. Compared with age matched controls, the AD-SoS of patients with RA was lowered by two and three standard deviations at the metaphysis and joint, respectively. Fingers of patients with RA without erosions (Larsen score 0-I) already had significantly decreased QUS values, which deteriorated further with the development of erosions (Larsen II-V).?CONCLUSION—This study indicates that QUS is sensitive to phalangeal periarticular bone loss in RA. QUS is a quick, simple, and inexpensive method free of ionising radiation that appears to be suited to detection of early stages of periarticular bone loss. Its clinical use in the assessment of early RA should be further evaluated in prospective studies.?? PMID:11406521

  7. Fatigue in rheumatoid arthritis; a persistent problem: a large longitudinal study

    PubMed Central

    van Steenbergen, Hanna W; Tsonaka, Roula; Huizinga, Tom W J; Boonen, Annelies; van der Helm-van Mil, Annette H M

    2015-01-01

    Objective Fatigue is prevalent and disabling in rheumatoid arthritis (RA). Surprisingly, the long-term course of fatigue is studied seldom and it is unclear to what extent it is influenced by inflammation. This study aimed to determine the course of fatigue during 8?years follow-up, its association with the severity of inflammation and the effect of improved treatment strategies. Methods 626 patients with RA included in the Leiden Early Arthritis Clinic cohort were studied during 8?years. Fatigue severity, measured on a 0–100?mm scale, and other clinical variables were assessed yearly. Patients included in 1993–1995, 1996–1998 and 1999–2007 were treated with delayed treatment with disease-modifying antirheumatic drugs (DMARDs), early treatment with mild DMARDs and early treatment with methotrexate respectively. After multiple imputation, the serial measurements were analysed using linear quantile mixed models. Results Median fatigue severity at baseline was 45?mm and remained, despite treatment, rather stable thereafter. Female gender (effect size=4.4?mm), younger age (0.2?mm less fatigue/year), higher swollen and tender joint counts (0.3?mm and 1.0?mm more fatigue/swollen or tender joint) and C reactive protein-levels (0.1?mm more fatigue per mg/L) were independently and significantly (p<0.05) associated with fatigue severity over 8?years. Although improved treatment strategies associated with less severe radiographic progression, there was no effect on fatigue severity (p=0.96). Conclusions This largest longitudinal study on fatigue so far demonstrated that the association between inflammation and fatigue is statistically significant but effect sizes are small, suggesting that non-inflammatory pathways mediate fatigue as well. Improved treatment strategies did not result in less severe fatigue. Therefore, fatigue in RA remains an ‘unmet need’. PMID:26509063

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

    NASA Astrophysics Data System (ADS)

    Glover, Simon C. O.

    2015-08-01

    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 ˜ 6 by assuming that they grow from seeds with masses M > 104 M? that form by the direct collapse of metal-free gas in atomic cooling haloes 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, Jcrit: if this is too large, then too few seeds will form to explain the observed number density of SMBHs. In order to determine Jcrit 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 analyse the chemistry of H2 in these conditions, allowing us to identify the key chemical reactions that are responsible for determining the value of Jcrit. We construct a reduced network of 26 reactions that allows us to determine Jcrit accurately, and compare it with previous treatments in the literature. We show that previous studies have often omitted one or more important chemical reactions, and that these omissions introduce an uncertainty of up to a factor of 3 into previous determinations of Jcrit.

  9. Upconversion nanoprobes for efficiently in vitro imaging reactive oxygen species and in vivo diagnosing rheumatoid arthritis.

    PubMed

    Chen, Zhaowei; Liu, Zhen; Li, Zhenhua; Ju, Enguo; Gao, Nan; Zhou, Li; Ren, Jinsong; Qu, Xiaogang

    2015-01-01

    Over-generation of reactive oxygen species (ROS) is closely associated with the biological processes of rheumatoid arthritis (RA). Thus, efficient monitoring ROS in inflammatory joints would be essential for better understanding the pathogenesis and optimizing therapeutic interventions. Herein, we designed a ratiometric nanoprobe utilizing upconversion nanoparticles (UCNPs) conjugated with chromophore labeled hyaluronic acid (HA) for high sensitively sensing ROS in the aqueous solution, bioimaging ROS in inflammatory mimic cells and diagnosing RA in vivo. In this approach, the conjugation of HA conferred UCNPs not only water solubility but also biocompatibility and ROS recognizing properties. Particularly, the HA backbone cleavage and detachment of chromophore labeled HA fragments from UCNPs induced by ROS inhibited the luminescent energy transfer (LRET) and allowed rational metric upconversion luminescence (UCL) emission as the detection signal. Importantly, the upconversion nanoprobe showed high effectiveness for early assessing the treatment response of arthritic animals to an antiarthritic drug-methotrexate (MTX). PMID:25477167

  10. 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

  11. Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)

    PubMed Central

    Hughes-Austin, Jan M; Deane, Kevin D; Derber, Lezlie A; Kolfenbach, Jason R; Zerbe, Gary O; Sokolove, Jeremy; Lahey, Lauren J; Weisman, Michael H; Buckner, Jane H; Mikuls, Ted R; O’Dell, James R; Keating, Richard M; Gregersen, Peter K; Robinson, William H; Holers, V Michael; Norris, Jill M

    2013-01-01

    Objective We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development. Methods We studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum. As a comprehensive measure of inflammation, we calculated a Cytokine Score by summing all cytokine/chemokine levels, weighted by their regression coefficients for RA-autoantibody association. We compared C-reactive protein, individual cytokines/chemokines and Cytokine Score to the outcomes: positivity for RF and for the HRP using logistic regression. Results Adjusting for age, sex, ethnicity and ever smoking, the Cytokine Score and levels of IL-6 and IL-9 were associated with both RF and HRP. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN)-? were associated with HRP only. Associations between the Cytokine Score and RF and HRP positivity were replicated in an independent military personnel cohort. Conclusions In first-degree relatives of patients with RA, RA-related autoimmunity is associated with inflammation, as evidenced by associations with multiple cytokines and chemokines. PMID:22915618

  12. Cell culture and passaging alters gene expression pattern and proliferation rate in rheumatoid arthritis synovial fibroblasts

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis synovial fibroblasts (RASF) are key players in synovial pathophysiology and are therefore examined extensively in various experimental approaches. We evaluated, whether passaging during culture and freezing has effects on gene expression and cell proliferation. Methods RASF were passaged for up to 8 passages. RNA was isolated after each passage and cDNA arrays were performed to evaluate the RNA expression pattern during passaging. In addition, doubling time of the cells was also measured. Results From passages 2-4, mRNA expression did not change significantly. Gene expression in RASF started to change in passages 5-6 with 7-10% differentially expressed genes. After passages 7-8, more than 10% of the genes were differentially expressed. The doubling rate was constant for up to 5 passages and decreased after passages 6-8. After freezing, gene expression of the second passage is comparable to gene expression prior to freezing. Conclusions The results of this study show, that experiments, which examine gene expression of RASF and shall reflect or imitate an in vivo situation, should be limited to early culture passages to avoid cell culture effects. It is not necessary to stop culturing SF after a few passages, but to keep the problems of cell culture in mind to avoid false positive results. Especially, when large-scale screening methods on mRNA level are used. Of note, freezing does not affect gene expression substantially. PMID:20462438

  13. 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.

  14. 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

  15. 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

  16. The association between rheumatoid arthritis and periodontal disease

    PubMed Central

    2010-01-01

    Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. Nevertheless, many mechanisms in the pathogenesis have not yet been examined sufficiently, so that a final explanatory model is still under discussion, and we hereby present arguments in favor of this. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that support the hypothesis that oral infections play a role in RA pathogenesis. Of special importance are the impact of periodontal pathogens, such as Porphyromonas gingivalis on citrullination, and the association of PD in RA patients with seropositivity toward rheumatoid factor and the anti-cyclic citrullinated peptide antibody. PMID:21062513

  17. MUTYH Gene Polymorphisms as Risk Factors for Rheumatoid Arthritis

    PubMed Central

    Kung, Yung-Jen; Tsai, Kun Shi; Huang, Chung-Ming; Lin, Hui-Ju; Chen, Ter-Hsin; Hsu, Yu-An; Chang, Ching-Yao; Huang, Yong-San; Wan, Lei

    2015-01-01

    Objectives. MUTYH glycosylase involved in DNA repair pathways may be associated with the risk of autoimmune diseases such as rheumatoid arthritis (RA). Therefore, the association between polymorphisms in the MUTYH gene and RA was evaluated. Methods. We recruited 192 RA patients and 192 healthy subjects in Taiwan. The 4 MUTYH polymorphisms (rs3219463, rs3219476, rs3219489, and rs3219493) were detected and haplotype analysis was performed using the Bayesian method. The genotype and allelic frequency distributions of the polymorphisms in both RA patients and healthy patients were compared by the chi-square test. Results. Comparison of the genotype/allele frequencies between individuals with RA and the control groups revealed significant differences in 2 MUTYH gene polymorphisms, rs3219463 and rs3219476. After we performed a haplotype-specific analysis, the haplotypes Ht6-GTGC and Ht8-GGCG had lower presenting rates in RA patients than in the control groups. Furthermore, the genotype frequency of rs3219463 G/? was significantly increased among patients with immunoglobulin M rheumatoid factors, whereas that of rs3219476 was not. Conclusion. We demonstrated that the rs3219463 and rs3219476 polymorphisms in RA patients from a Taiwan Chinese population were associated with disease susceptibility. These data indicate that the MUTYH gene may play a role in the progression of RA. PMID:26273655

  18. 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

  19. Lysosomal ?-glucuronidase regulates Lyme and rheumatoid arthritis severity

    PubMed Central

    Bramwell, Kenneth K.C.; Ma, Ying; Weis, John H.; Chen, Xinjian; Zachary, James F.; Teuscher, Cory; Weis, Janis J.

    2013-01-01

    Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most prevalent arthropod-borne illness in the United States and remains a clinical and social challenge. The spectrum of disease severity among infected patients suggests that host genetics contribute to pathogenic outcomes, particularly in patients who develop arthritis. Using a forward genetics approach, we identified the lysosomal enzyme ?-glucuronidase (GUSB), a member of a large family of coregulated lysosomal enzymes, as a key regulator of Lyme-associated arthritis severity. Severely arthritic C3H mice possessed a naturally occurring hypomorphic allele, Gusbh. C57BL/6 mice congenic for the C3H Gusb allele were prone to increased Lyme-associated arthritis severity. Radiation chimera experiments revealed that resident joint cells drive arthritis susceptibility. C3H mice expressing WT Gusb as a transgene were protected from severe Lyme arthritis. Importantly, the Gusbh allele also exacerbated disease in a serum transfer model of rheumatoid arthritis. A known GUSB function is the prevention of lysosomal accumulation of glycosaminoglycans (GAGs). Development of Lyme and rheumatoid arthritis in Gusbh-expressing mice was associated with heightened accumulation of GAGs in joint tissue. We propose that GUSB modulates arthritis pathogenesis by preventing accumulation of proinflammatory GAGs within inflamed joint tissue, a trait that may be shared by other lysosomal exoglycosidases. PMID:24334460

  20. An approach to complex rheumatoid hand and wrist problems.

    PubMed

    Blair, W F

    1996-08-01

    Successful surgical reconstruction of the hands in patients with rheumatoid arthritis depends upon knowledge of the pathophysiology of the deformities and available surgical options, the use of appropriate operative and rehabilitative techniques, and, perhaps most importantly, a well-considered strategy for indicating and performing surgical procedures. In the case of complex hand deformities, two general approaches have guided the development of operative strategies. The first and most widely used strategy generally has involved sequential procedures. A less widely used but highly effective strategy uses multiple, concurrent procedures. Although it can be argued that both strategies are comprehensive, they are distinctly different. This article explores and defines the multiple, concurrent operations strategy and presents indications for and examples of its application. In contrast to sequential operations, in comprehensive reconstruction, all operations are done concurrently, providing that specific criteria are satisfied. When appropriately indicated by a hand surgeon experienced in all the technical components, a comprehensive strategy of rheumatoid hand reconstruction using multiple, concurrent operations can be highly effective. The strategy can provide restoration of patients' function and improve the quality of their life without compromising the results of any one component of the operation. PMID:8842724

  1. 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.

  2. [The treatment experience of rheumatoid arthritis patients in an industrial region of the Donets Basin].

    PubMed

    Kolchin, Iu M; Horobins'ka, S M; Matiukhin, P V; Maliuha, V A; Zenin, N F; Zenina, L V; Korniienko, V V

    2000-01-01

    The data submitted suggest that the most effective option in the treatment of rheumatoid arthritis is simultaneous employment of a nonsteroidal anti-inflammatory agent and metatrexate for 1.5 yr and courses of hormonotherapy, exercise therapy, and topical application to the joints of compresses with dimexide, heparin, and analginum as required and ultrasound with hydrocortisone as well. There was no increase in disability rates among patients with rheumatoid arthritis placed on the above combined treatment, which fact is also related to improvement of diagnosis rheumatoid arthritis, well-timed case follow-up, and prescription of courses of prophylactic treatment. PMID:11031440

  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. Standard instruction versus simulation: Educating registered nurses in the early recognition of patient deterioration in paediatric critical care.

    PubMed

    O'Leary, Jessica; Nash, Robyn; Lewis, Peter

    2016-01-01

    Identifying and stabilising deterioration in a child with significant clinical compromise is both a challenging and necessary role of the paediatric critical care nurse. Within adult critical care research, high fidelity patient simulation (HFPS) has been shown to positively impact learner outcomes regarding identification and management of a deteriorating patient; however, there is a paucity of evidence examining the use of HFPS in paediatric nursing education. The aim of this study was to investigate the effect of HFPS on nurses' self-efficacy and knowledge for recognising and managing paediatric deterioration. Further, participants' perceptions of the learning experiences specific to the identification and management of a deteriorating child were also explored. Registered nurses working in a tertiary-referral paediatric critical care unit were recruited for this quasi-experimental study. Using a pre-test/post-test control-group design, participants were assigned to one of two learning experiences: HFPS or standard instruction. Following the learning experience, nurses were also invited to participate in semi-structured interviews. 30 nurses participated in the study (control n=15, experiment n=15). Participants in the HFPS intervention were most likely to demonstrate an increase in both perceived self-efficacy (p=<0.01) and knowledge (p=<0.01). No statistically significant change was observed in control group scores. The mean difference in self-efficacy gain score between the two groups was 5.67 score units higher for the experiment group compared to the control. HFPS also yielded higher follow-up knowledge scores (p=0.01) compared to standard instruction. Ten nurses participated in semi-structured interviews. Thematic analysis of the interview data identified four themes: self-awareness, hands-on learning, teamwork, and maximising learning. The results of this study suggest that HFPS can positively influence nurses' self-efficacy and knowledge test scores specific to the recognition and management of paediatric deterioration. PMID:26249644

  5. Contributions of Familial Rheumatoid Arthritis or Lupus and Environmental Factors to Risk of Rheumatoid Arthritis in Women: a Prospective Cohort Study

    PubMed Central

    Sparks, Jeffrey A.; Chen, Chia-Yen; Hiraki, Linda T.; Malspeis, Susan; Costenbader, Karen H.; Karlson, Elizabeth W.

    2014-01-01

    Objective We assessed the contributions of familial rheumatoid arthritis (RA) or lupus and environmental factors to risk of RA. Methods Among 121,700 women in the Nurses’ Health Study, 65,457 provided data on familial RA/lupus. Among these, 493 RA cases (301 seropositive and 192 seronegative) were validated. We estimated hazard ratios (HR) for RA comparing those with and without familial RA/lupus, adjusting for environmental factors (smoking, alcohol, body mass index [BMI], parity, breastfeeding, menopause, hormone use, early menarche, and menstrual regularity) using Cox proportional hazards models. Population attributable risks (PAR) for RA within this cohort were calculated for familial RA/lupus, smoking, alcohol, BMI, parity, and breastfeeding. Results Familial RA/lupus was significantly associated with RA (HR 3.67), seropositive RA (HR 3.90) and seronegative RA (HR 3.95). After adjusting for environmental factors, familial RA/lupus was significantly associated with RA (HR 3.59, 95% confidence interval 2.94–4.37). Smoking >10 pack-years, alcohol intake 5–10 g/day, overweight, breastfeeding ?12 months, and pre-menopausal status remained significantly associated with RA after adjusting for familial RA/lupus. For RA in this cohort, the PAR for smoking, BMI, alcohol, parity, or breastfeeding collectively was 41%; the PAR due to heredity from familial RA/lupus was 21%. Conclusion In this large, prospective cohort, women with familial RA/lupus had a four-fold increased risk for RA that remained significant after adjusting for environmental factors. A large proportion of RA risk was attributable to environmental factors even among those with familial RA/lupus. PMID:25103278

  6. Time-resolved Study of Early-stage Formation of Iron Oxyhydroxide Nanoparticles in Simulated Acid Mine Drainage (AMD) Solutions

    NASA Astrophysics Data System (ADS)

    Zhu, M.; Legg, B.; Zhang, H.; Waychunas, G. A.; Banfield, J. F.

    2011-12-01

    Early stage development of ferric iron oxyhydroxide (FeOOH) nanoparticles from bicarbonate-neutralized Fe2(SO4)3 solutions was investigated using time-resolved UV-Vis spectroscopy and quick extended X-ray absorption fine structure (Q-EXAFS) spectroscopy. Two neutralization ratio ( h =[HCO3-]/[Fe3+]) of 1 and 2 were used. The neutralized systems changed visually from transparent solutions after the base addition to blurry and then opaque suspensions at extended reaction time. For the h=1 solution, its absorbance measured at 600 nm (due to scattering because of no absorption bands at this wavelength) increased quickly within initial 10 min, slightly between 10 - 26 min, and explosively afterwards. These three stages have been previously ascribed to hydrolysis and initial condensation, condensation, and aggregation processes, respectively. For the h=2 solution, only the two later evolution stages were recorded. UV-Vis spectra of the h=1 solution show that three absorption bands, likely resulting from Fe3+-sulfate species, gradually disappeared with the increase of reaction time and were not visible at about 10 min. Meanwhile, an electron pair transition (EPT) band centered at 485 nm emerged and gradually grew in its amplitude, indicating particles of a FeOOH phase being formed. For h=2, the three bands were not observed, but the EPT band at 485 nm was pronounced in the first collected spectrum and also grew with time, indicating that FeOOH particles were already formed from the very beginning. In addition, in both of the h=1 and 2 solutions the bands around 370 - 400 nm shifted to higher wavelength, suggesting that FeOOH particle size increased with time. Time-resolved Q-EXAFS spectra were collected every 2 s and were averaged over 15 consecutive scans, resulting in a time resolution of 30 s. For the h=1 solution, the EXAFS radial structural functions (RSF) initially had no or very weak peaks at positions corresponding to edge- and corner-sharing Fe shells. After 10 min of reaction time, the two Fe shells became obvious. This corroborates with the UV-Vis analysis that Fe-sulfate clusters were present at the beginning and FeOOH particles emerged later. For the h=2 solution, RSF shows high amplitudes of the two Fe shells in the first EXAFS spectrum. The amplitudes significantly grew with time, consistent with increasing Fe coordination numbers obtained by EXAFS shell-by-shell fitting. The EXAFS fitting also shows that the second Fe-Fe distance decreased from 3.41 to 3.36 Å with time while the first Fe-Fe distance was almost constant at 3.03 Å. X-ray diffraction identified the final precipitates as schwertmannite, a FeOOH phase containing structural sulfate.

  7. Poncet's disease with high titers of rheumatoid factor and anti-citrullinated peptide antibodies mimicking rheumatoid arthritis.

    PubMed

    Sasaki, Hirokazu; Inagaki, Masako; Shioda, Mikio; Nagasaka, Kenji

    2015-01-01

    Reactive arthritis accompanying tuberculosis (TB), also known as Poncet's disease, is a rare condition. In the present report, we describe the case of a patient with Poncet's disease, who presented with high titers of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), which mimicked rheumatoid arthritis (RA). A 69-year-old man with a childhood history of chronic left gonitis suffered from right knee arthritis for 3 years. Chronic monoarthritis in his right knee and positive results obtained on interferon-gamma release assay were suggestive of tuberculous arthritis. However, there was no evidence of TB infection. Moreover, the high titers of RF and ACPA suggested a diagnosis of RA. Surprisingly, the culture of a small sample from his bony ankylosed left knee that had no focal signs of infection, exhibited a positive result for TB infection. Thus, based on these findings, the patient was diagnosed with Poncet's disease. His symptoms improved after initiation of anti-TB therapy, which supported the accuracy of the diagnosis. In addition, we analyzed the characteristics of Poncet's disease by conducting a literature review, and identified that the presence of extra-articular manifestation and negative results for RF and ACPA tests were the features that facilitated distinguishing between typical Poncet's disease and RA; however, since tuberculous patients occasionally exhibit positive results for ACPA tests, the differential diagnosis is essential in ACPA-positive arthritic patients. PMID:25150438

  8. Insights from Populations At-Risk for the Future Development of Classified Rheumatoid Arthritis

    PubMed Central

    Holers, V. Michael

    2014-01-01

    SYNOPSIS Rheumatoid arthritis (RA) is characterized by the development of disease through a progressive series of stages. In the seropositive subset of patients with classified RA, a preclinical stage is present for a substantial number of years prior to the onset of clinically apparent inflammatory arthritis. Multiple environmental, hormonal and lifestyle factors likely play important roles in the initiation of RA-related autoimmunity during this very early period and the transition to clinically apparent arthritis. This preclinical period is characterized by the presence of autoimmune and inflammatory processes that can be assessed and quantitatively measured using biomarkers. In conjunction with qualitative phenotypes, these data can be used to develop algorithms designed to provide highly predictive estimates for the future onset of classifiable disease. Relevant biomarkers and measures for this period include autoantibodies, alterations of antigen-specific and innate lymphoid populations, elevated cytokines/chemokines, genetic/genomic factors, imaging study results, associated clinical findings, dietary and environmental biomarkers, assessments of cardiovascular disease and other comorbidity risks, microbiome analyses, and metabolomic changes. Most prior studies have used retrospective analyses of serum bank samples to study this period of disease evolution. A major challenge, however, has been how to identify from the contemporary population of asymptomatic subjects who are at sufficiently high risk for future disease to be informative and representative of “preclinical patients”. To find such subjects, studies have been performed using first-degree relatives of patients with RA as well as other populations who present to physicians in health care settings. This chapter will review the results of analyses that have been undertaken in these “at-risk” subjects, summarize the evidence which suggests that such populations are relevant to understand disease pathogenesis, and illustrate how the results of these studies have informed our current views of the initiation and early evolution of RA prior to the onset of clinically apparent disease. PMID:25437280

  9. Functional capacity in rheumatoid arthritis patients: comparison between Spanish and Brazilian sample.

    PubMed

    Ide, Maiza Ritomy; Gonzalez-Gay, Miguel A; Yano, Kelly Cristina; Imai, Marcelo Jun; de Andrade, Mario Chueire; Llorca, Javier

    2011-02-01

    The main objective of this study is to compare Spanish and Brazilian self-reported health-related functional capacity in patients with rheumatoid arthritis (RA). 197 patients diagnosed with RA were studied in Spain (n = 127) and Brazil (n = 70). Pain (Visual analog scale) and functional capacity (Health Assessment Questionnaire/HAQ) were assessed. Patients were questioned about regular exercise practice. Comparisons between groups were performed with Chi-square tests and Student t test. Pearson's correlation coefficient and linear regression models were used to analyze the associations. Brazilian patients were younger (p = 0.013), had worse levels of pain (p = 0.001) and a trend to experience worse functional capacity (p = 0.057) than Spanish ones. Spanish RA patients had higher body mass index (BMI) (p = 0.019) and longer disease duration (p = 0.001). Also, a higher percentage of subjects with RA from the Spanish cohort had been elected to take early retirement when compared with Brazilian patients (p = 0.010). Spanish RA patients had received more drugs than Brazilians (oral corticosteroids p = 0.010, Leflunomide p = 0.023, Methotrexate p = 0.072, non-steroidal anti-inflammatory drugs p = 0.064, biologic therapies p = 0.001). The functional capacity (HAQ) was correlated with age (p = 0.001), disease duration (p = 0.001), age at diagnosis (p = 0.001), pain (p = 0.001) and BMI (p = 0.001) in Spanish patients. In Brazilian, these correlations were only found with disease duration (p = 0.004) and pain (p = 0.001). In conclusion, our data suggest a better management of RA in Spanish when compared with Brazilians. Even with less pain and functional capacity, they receive more drug treatment and a higher percentage of them are retired early. PMID:20012868

  10. 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

  11. 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...

  12. 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.

  13. Pharmacology Update on Chronic Obstructive Pulmonary Disease, Rheumatoid Arthritis, and Major Depression.

    PubMed

    Weatherspoon, Deborah; Weatherspoon, Christopher A; Abbott, Brianna

    2015-12-01

    This article presents a brief review and summarizes current therapies for the treatment of chronic obstructive pulmonary disease, major depression, and rheumatoid arthritis. One new pharmaceutical agent is highlighted for each of the topics. PMID:26596663

  14. Rheumatoid Arthritis Treatment and Causes | NIH MedlinePlus the Magazine

    MedlinePLUS

    ... also enjoy a better quality of life. Self-management programs teach about rheumatoid arthritis and its treatments, exercise and relaxation approaches, communication between patients and health care providers, and problem solving. Research on these programs ...

  15. Interstitial Lung Disease of the UIP Variant as the Only Presenting Symptom of Rheumatoid Arthritis

    PubMed Central

    Agrawal, Abhinav; Thyagarajan, Braghadheeswar; Ceniza, Sidney; Hasan Yusuf, Syed

    2015-01-01

    Rheumatoid arthritis is a chronic inflammatory disease primarily manifesting with symptoms of joint pain. It also involves multiple organ systems in the body, including the lungs. Interstitial lung disease (ILD) is the most common form of pulmonary involvement in rheumatoid arthritis (RA). Without the typical symptoms such as chronic joint pain, establishing the diagnosis of RA could be quite challenging and a high index of suspicion is thereby required to diagnose ILD in patients with RA, thereby delaying treatment and increasing morbidity and mortality. We report a case of a 67-year-old Hispanic male with no previous history of rheumatoid arthritis or symptoms of typical joint pain who comes to the hospital only with the chief complaints of progressive worsening of shortness of breath for a duration of 6 months and was eventually diagnosed with ILD of the usual interstitial pneumonia variant with serologies positive for rheumatoid arthritis. PMID:26137341

  16. Two-dimensional electrophoretic analysis of human leukocyte proteins from patients with rheumatoid arthritis

    SciTech Connect

    Willard, K.E.; Thorsrud, A.K.; Munthe, E.; Jellum, E.

    1982-04-01

    Human leukocyte proteins from more than 150 patients with rheumatoid arthritis, together with age- and sex-matched controls, were analyzed by use of the ISO-DALT technique of two-dimensional polyacrylamide gel electrophoresis. Patients with ankylosing spondylitis, polymyalgia rheumatica, psoriatic arthritis, calcium tendinitis, post-infectious arthritis, and asymmetrical seronegative arthritis were also included as positive controls. Synthesis of several proteins, referred to by number as members of the Rheuma set, is shown to increase in the leukocyte preparations from patients with classical rheumatoid arthritis. Several of these proteins are specific to monocytes or granulocytes; others are of unknown cellular origin, but appear to be unique to rheumatoid arthritis. The Rheuma proteins appear to be indicators of disease activity, because their increased synthesis can be correlated with sedimentation rate and other clinical indices of rheumatoid disease activity.

  17. Development and Application of a Computer Simulation Program to Enhance the Clinical Problem-Solving Skills of Students.

    ERIC Educational Resources Information Center

    Boh, Larry E.; And Others

    1987-01-01

    A project to (1) develop and apply a microcomputer simulation program to enhance clinical medication problem solving in preclerkship and clerkship students and (2) perform an initial formative evaluation of the simulation is described. A systematic instructional design approach was used in applying the simulation to the disease state of rheumatoid

  18. A study of the early-stage evolution of relativistic electron-ion shock using three-dimensional particle-in-cell simulations

    SciTech Connect

    Choi, E. J.; Min, K.; Choi, C. R.; Nishikawa, K.-I.

    2014-07-15

    We report the results of a 3D particle-in-cell simulation carried out to study the early-stage evolution of the shock formed when an unmagnetized relativistic jet interacts with an ambient electron-ion plasma. Full-shock structures associated with the interaction are observed in the ambient frame. When open boundaries are employed in the direction of the jet, the forward shock is seen as a hybrid structure consisting of an electrostatic shock combined with a double layer, while the reverse shock is seen as a double layer. The ambient ions show two distinct features across the forward shock: a population penetrating into the shocked region from the precursor region and an accelerated population escaping from the shocked region into the precursor region. This behavior is a signature of a combination of an electrostatic shock and a double layer. Jet electrons are seen to be electrostatically trapped between the forward and reverse shock structures showing a ring-like distribution in a phase-space plot, while ambient electrons are thermalized and become essentially isotropic in the shocked region. The magnetic energy density grows to a few percent of the jet kinetic energy density at both the forward and the reverse shock transition layers in a rather short time scale. We see little disturbance of the jet ions over this time scale.

  19. Cluster evolution during the early stages of heating explosives and its relationship to sensitivity: a comparative study of TATB, ?-HMX and PETN by molecular reactive force field simulations.

    PubMed

    Wen, Yushi; Zhang, Chaoyang; Xue, Xianggui; Long, Xinping

    2015-05-14

    Clustering is experimentally and theoretically verified during the complicated processes involved in heating high explosives, and has been thought to influence their detonation properties. However, a detailed description of the clustering that occurs has not been fully elucidated. We used molecular dynamic simulations with an improved reactive force field, ReaxFF_lg, to carry out a comparative study of cluster evolution during the early stages of heating for three representative explosives: 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), ?-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and pentaerythritol tetranitrate (PETN). These representatives vary greatly in their oxygen balance (OB), molecular structure, stability and experimental sensitivity. We found that when heated, TATB, HMX and PETN differ in the size, amount, proportion and lifetime of their clusters. We also found that the clustering tendency of explosives decreases as their OB becomes less negative. We propose that the relationship between OB and clustering can be attributed to the role of clustering in detonation. That is, clusters can form more readily in a high explosive with a more negative OB, which retard its energy release, secondary decomposition, further decomposition to final small molecule products and widen its detonation reaction zone. Moreover, we found that the carbon content of the clusters increases during clustering, in accordance with the observed soot, which is mainly composed of carbon as the final product of detonation or deflagration. PMID:25872486

  20. Molecular-level insights of early-stage prion protein aggregation on mica and gold surface determined by AFM imaging and molecular simulation.

    PubMed

    Lou, Zhichao; Wang, Bin; Guo, Cunlan; Wang, Kun; Zhang, Haiqian; Xu, Bingqian

    2015-11-01

    By in situ time-lapse AFM, we investigated early-stage aggregates of PrP formed at low concentration (100ng/mL) on mica and Au(111) surfaces in acetate buffer (pH 4.5). Remarkably different PrP assemblies were observed. Oligomeric structures of PrP aggregates were observed on mica surface, which was in sharp contrast to the multi-layer PrP aggregates yielding parallel linear patterns observed Au(111) surface. Combining molecular dynamics and docking simulations, PrP monomers, dimers and trimers were revealed as the basic units of the observed aggregates. Besides, the mechanisms of the observed PrP aggregations and the corresponding molecular-substrate and intermolecular interactions were suggested. These interactions involved gold-sulfur interaction, electrostatic interaction, hydrophobic interaction, and hydrogen binding interaction. In contrast, the PrP aggregates observed in pH 7.2 PBS buffer demonstrated similar large ball-like structures on both mica and Au(111) surfaces. The results indicate that the pH of a solution and the surface of the system can have strong effects on supramolecular assemblies of prion proteins. This study provides in-depth understanding on the structural and mechanistic nature of PrP aggregation, and can be used to study the aggregation mechanisms of other proteins with similar misfolding properties. PMID:26275839

  1. 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.

  2. LASER BIOLOGY AND MEDICINE: Light scattering study of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Beuthan, J.; Netz, U.; Minet, O.; Klose, Annerose D.; Hielscher, A. H.; Scheel, A.; Henniger, J.; Müller, G.

    2002-11-01

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

  3. The role of BAFF in the progression of rheumatoid arthritis.

    PubMed

    Wei, Fang; Chang, Yan; Wei, Wei

    2015-12-01

    Rheumatoid arthritis (RA) is a common autoimmune disease that is marked by a systemic inflammatory reaction and joint erosions. Elevated levels of B cell activating factor (BAFF) have been detected in the serum and synovial fluid of RA patients. Moreover, the levels of BAFF increase in cases of autoimmune disease and are correlated with the level of disease activity. As an innate cytokine mediator, BAFF affects the immune response of the synovial microenvironment. In this review, we consider recent observations of BAFF and its receptors in RA progression, as well as the effects of BAFF on the cell-cell interactions network. We also summarize the clinical development of BAFF antagonists for the treatment of RA. PMID:26198030

  4. Rheumatoid arthritis, cardiovascular disease and physical exercise: a systematic review.

    PubMed

    Metsios, G S; Stavropoulos-Kalinoglou, A; Veldhuijzen van Zanten, J J C S; Treharne, G J; Panoulas, V F; Douglas, K M J; Koutedakis, Y; Kitas, G D

    2008-03-01

    This systematic review investigates the effectiveness of exercise interventions in improving disease-related characteristics in patients with rheumatoid arthritis (RA). It also provides suggestions for exercise programmes suitable for improving the cardiovascular profile of RA patients and proposes areas for future research in the field. Six databases (Medline, Cochrane Library, CINAHL, Google Scholar, EMBASE and PEDro) were searched to identify publications from 1974 to December 2006 regarding RA and exercise interventions. The quality of the studies included was determined by using the Jadad scale. Initial searches identified 1342 articles from which 40 met the inclusion criteria. No studies were found investigating exercise interventions in relation to cardiovascular disease in RA. There is strong evidence suggesting that exercise from low to high intensity of various modes is effective in improving disease-related characteristics and functional ability in RA patients. Future studies are required to investigate the effects of exercise in improving the cardiovascular status of this patient population. PMID:18045810

  5. Management of rheumatoid arthritis (Aamavata) using symbiohealth healthcare system

    PubMed Central

    Basisht, Gopal K.; Singh, Ram Harsh; Chandola, Harimohan

    2012-01-01

    Rheumatoid Arthritis (RA), according to modern medicine, and Aamavata according to Ayurveda, has an etiological and clinical relationship. Aamavata is a disease complex of which RA is a part. A comparative study of the pathophysiology of this disease by both systems reveals that modern medicine has investigated the mechanism of inflammation and has developed an offense strategy to control it. Ayurveda follows a defense strategy and it focuses its search on the etiological process, where disequilibrium at a higher level of physiology affects the gastrointestinal tract, causing an immune response that results in inflammation. Understanding the pathophysiology of both systems will help the treating physician to institute a dual treatment plan of modern medicine's offense strategy and Ayurvedic medicine's defense strategy at appropriate stages of the disease. Studying the pathophsiology of the two systems also gives insight into the genetic and epigenetic phenomenon in the treatment of disease and opens the doors for groundbreaking research. PMID:23723661

  6. Cytokines in rheumatoid arthritis - shaping the immunological landscape.

    PubMed

    McInnes, Iain B; Buckley, Christopher D; Isaacs, John D

    2016-01-01

    Cytokine-mediated pathways are central to the pathogenesis of rheumatoid arthritis (RA). The purpose of this short Opinion article is to briefly overview the roles of cytokine families in the various phases and tissue compartments of this disease. In particular, we consider the combinatorial role played by cytokines in mediating the overlapping innate and adaptive immune responses associated with disease onset and persistence, and also those cytokine pathways that, in turn, drive the stromal response that is critical for tissue localization and associated articular damage. The success of cytokine inhibition in the clinic is also considerable, not only in offering remarkable therapeutic advances, but also in defining the hierarchical position of distinct cytokines in RA pathogenesis, especially IL-6 and TNF. This hierarchy, in turn, promises to lead to the description of meaningful clinical endotypes and the consequent possibility of therapeutic stratification in future. PMID:26656659

  7. Sagittal laser optical tomography for imaging of rheumatoid finger joints

    NASA Astrophysics Data System (ADS)

    Hielscher, Andreas H.; Klose, Alexander D.; Scheel, Alexander K.; Moa-Anderson, Bryte; Backhaus, Marina; Netz, Uwe; Beuthan, Jürgen

    2004-04-01

    We present a novel optical tomographic imaging system that was designed to determine two-dimensional spatial distribution of optical properties in a sagittal plane through finger joints. The system incorporates a single laser diode and a single silicon photodetector into a scanning device that records spatially resolved light intensities as they are transmitted through a finger. These data are input to a model-based iterative image reconstruction (MOBIIR) scheme, which uses the equation of radiative transfer (ERT) as a forward model for light propagation through tissue. We have used this system to obtain tomographic images of six proximal interphalangeal finger joints from two patients with rheumatoid arthritis. The optical images were compared to clinical symptoms and ultrasound images.

  8. Pattern recognition of transillumination images for diagnosis of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Bauer, Joanna; Boerner, Ewa; Podbielska, Halina; Suchwalko, Artur

    2005-09-01

    In this work the statistical pattern recognition methods were applied for evaluation of transillumination images of interphalangeal joints of patients suffering from rheumatoid arthritis. Special portable apparatus was constructed for performing the transillumination examination. It consisted of He-Ne laser with optics for collimated illumination, special holder for placing the finger (perpendicular to optical axis, dorsal site towards camera), and CCD camera with memory stick. 20 ill patients and 20 healthy volunteers were examined. The captured images with 1152x864 resolution were converted into the gray level pictures and analyzed by means of statistical pattern recognition method. Principal Component Analysis (PCA) and cluster analysis by use of 1-NN method (1 Nearest Neighbour) were applied for classification. The recognition system was able to differentiate correctly between healthy and ill subjects with 72.35% accuracy in case the data base composed of 40 persons.

  9. Zingiber officinale: A Potential Plant against Rheumatoid Arthritis.

    PubMed

    Al-Nahain, Abdullah; Jahan, Rownak; Rahmatullah, Mohammed

    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

  10. 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

  11. Tongue diagnosis of traditional Chinese medicine for rheumatoid arthritis.

    PubMed

    Lo, Lun-Chien; Chen, Chia-Yun; Chiang, John Y; Cheng, Tsung-Lin; Lin, Hong-Jen; Chang, Hen-Hong

    2013-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with unknown aetiology that causes the immune system to attack the joints (synoviums), leading to chronic inflammation. According to the traditional Chinese medicine (TCM), RA falls into the category of Impediment disease ("Bi" syndrome), that is, poor circulation of qi and blood (stasis). Tongue diagnosis is an important method of TCM to detect blood stasis. In this study, 74 RA patients, meeting the pre-set criteria, were recruited via rheumatology outpatient clinic and examined by experienced rheumatology physicians. Two images-one of the tongue and the other, sublingual vessels-of the same patient were taken by a Canon digital camera in a darkroom with uniform lighting conditions. Relevant features of the tongue were extracted by utilising image processing techniques. Every tongue was classified into corresponding patterns based on the features identified. The subjects included 62 females and 12 males with an average age of 49.86 ± 13.81 years old, an average morbidity period of 4.56 ± 3.92 years, an average rheumatoid factor (RF) of 225.3 ± 373.8 IU/mL and an average erythrocyte sedimentation rate of (ESR) 40.9 ± 31.9 m/hr. According to our study, 86% of the patients with RA have tongues with sublingual vessels with a width of more than 2.7 mm, a length of more than 3/5 from tongue tipto sublingual caruncle, or a count of sublingual vessels more than 2. Moreover, since RA index is highly correlated with blood stasis in TCM, a logistic regression is conducted to predict the probability of presence of RA using RF and ESR as explanatory variables. Also, the logistic regression analysis of RA with respect to the conventional tongue diagnosis criteria was performed. Based on the aforementioned studies, we concluded that tongue diagnosis is helpful in detecting blood stasis of RA. PMID:24311851

  12. 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

  13. 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

  14. Differential expression of Ia antigens by rheumatoid synovial lining cells.

    PubMed Central

    Burmester, G R; Jahn, B; Rohwer, P; Zacher, J; Winchester, R J; Kalden, J R

    1987-01-01

    The differential expression of Ia antigens was studied in freshly isolated rheumatoid nonlymphoid synovial lining cells (SLC) and rheumatoid synovial fibroblast cell lines cultured in the presence of Interferon-gamma, using a large panel of anti-Ia reagents with monomorphic or polymorphic specificities. All the HLA-DR or -DQ specificities detectable on the corresponding peripheral blood B cells were also expressed in freshly isolated SLC. However, in all instances, the number of DR-positive SLC exceeded the percentage of cells expressing DQ antigens. In addition, the epitope expression of Ia antigens varied within the DR or DQ populations of Ia molecules as revealed by polymorphic reagents. Double-label experiments or using the ingestion of Latex particles as a marker demonstrated that the synovial macrophages (type I SLC) primarily bear the DR+DQ+ phenotype, while there is an additional population of nonphagocytic SLC (previously termed type II SLC) that has a DR+ and monocyte marker negative phenotype but did not have detectable levels of DQ antigens as analyzed by both fluorescence microscopy and cell sorter analysis. This latter population frequently had a morphology showing dendritic processes and rapidly lost the expression of Ia antigens upon culture. Cells with a similar, primarily DR+ phenotype were readily obtained in synovial fibroblast cultures after treatment with Interferon-gamma. These data suggest that there are two populations of Ia+ synovial lining cells: the synovial macrophages (type I cells) with the DR+DQ+ phenotype, and cells probably related to fibroblasts with a DR+ phenotype without detectable DQ antigens (type II cells). The fact that the latter phenotype could be induced by Interferon-gamma treatment of cultured synovial fibroblasts suggests that this mediator may have a similar role in vivo in the activation of certain synovial cell populations. Images PMID:2442194

  15. Prevalence of antiphospholipid antibodies in Chilean patients with rheumatoid arthritis.

    PubMed

    Palomo, Iván; Pinochet, Carmen; Alarcón, Marcelo; Sandoval, Rodrigo; Gonzalez, Jaime; Monsalves, Francisco; Forastiero, Ricardo

    2006-01-01

    Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are also detected in those with inflammatory diseases. The purpose of this study was to examine the prevalence of these antibodies in patients with rheumatoid arthritis (RA), and to evaluate the association of these antibodies with thrombosis and/or other clinical characteristics of this inflammatory disorder. Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies and the lupus anticoagulant (LA) activity were determined. Seven out of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti-beta(2)GPI, and six out of 84 (7.2%) for aPT, while in controls the overall prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls were LA negative. There was no correlation between the presence of aPL with thrombosis and/or other clinical features of the antiphospholipid syndrome. We found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid arthritis and this prevalence was statistically higher than in normal controls (P<0.003). In this study, the presence of aPL antibodies was not associated with the development of thrombosis and/or thrombocytopenia. Whether the presence of aPL antibodies implies an increased risk for thrombosis and atherosclerosis in these patients should be studied further. PMID:16960897

  16. Rheumatoid arthritis synovial fluid phospholipase A2 activating protein (PLAP) stimulates human neutrophil degranulation and superoxide ion production.

    PubMed

    Bomalaski, J S; Baker, D; Resurreccion, N V; Clark, M A

    1989-06-01

    Rheumatoid arthritis is characterized by excessive eicosanoid production, and phospholipase enzymes are the rate limiting step in eicosanoid synthesis. We have shown previously that cells from patients with rheumatoid arthritis express enhanced phospholipase A2 enzyme activities. Recently, we have isolated a phospholipase A2 activating protein termed PLAP from rheumatoid synovial fluid. This novel human protein shares biochemical and antigenic similarities with melittin, a bee venom phospholipase activating protein. Because melittin has been shown to induce neutrophil degranulation and superoxide formation, and because exuberent release of lysosomal enzymes and superoxide have been implicated in the pathogenesis of rheumatoid arthritis, we examined the role of PLAP on inducing these neutrophil functions. PMID:2552770

  17. Optimising the use of electronic health records to estimate the incidence of rheumatoid arthritis in primary care: what information is hidden in free text?

    PubMed Central

    2013-01-01

    Background Primary care databases are a major source of data for epidemiological and health services research. However, most studies are based on coded information, ignoring information stored in free text. Using the early presentation of rheumatoid arthritis (RA) as an exemplar, our objective was to estimate the extent of data hidden within free text, using a keyword search. Methods We examined the electronic health records (EHRs) of 6,387 patients from the UK, aged 30 years and older, with a first coded diagnosis of RA between 2005 and 2008. We listed indicators for RA which were present in coded format and ran keyword searches for similar information held in free text. The frequency of indicator code groups and keywords from one year before to 14 days after RA diagnosis were compared, and temporal relationships examined. Results One or more keyword for RA was found in the free text in 29% of patients prior to the RA diagnostic code. Keywords for inflammatory arthritis diagnoses were present for 14% of patients whereas only 11% had a diagnostic code. Codes for synovitis were found in 3% of patients, but keywords were identified in an additional 17%. In 13% of patients there was evidence of a positive rheumatoid factor test in text only, uncoded. No gender differences were found. Keywords generally occurred close in time to the coded diagnosis of rheumatoid arthritis. They were often found under codes indicating letters and communications. Conclusions Potential cases may be missed or wrongly dated when coded data alone are used to identify patients with RA, as diagnostic suspicions are frequently confined to text. The use of EHRs to create disease registers or assess quality of care will be misleading if free text information is not taken into account. Methods to facilitate the automated processing of text need to be developed and implemented. PMID:23964710

  18. Design Support of an Above Cap-rock Early Detection Monitoring System using Simulated Leakage Scenarios at the FutureGen2.0 Site

    DOE PAGESBeta

    Williams, Mark D.; USA, Richland Washington; Vermuel, Vince R.; USA, Richland Washington; Oostrom, Mart; USA, Richland Washington; Porse, Sean L.; USA, Richland Washington; Thorne, Paul D.; USA, Richland Washington; et al

    2014-12-31

    The FutureGen 2.0 Project will design and build a first-of-its-kind, near-zero emissions coal-fueled power plant with carbon capture and storage (CCS). To assess storage site performance and meet the regulatory requirements of the Class VI Underground Injection Control (UIC) Program for CO2 Geologic Sequestration, the FutureGen 2.0 project will implement a suite of monitoring technologies designed to evaluate CO2 mass balance and detect any unforeseen loss in CO2 containment. The monitoring program will include direct monitoring of the reservoir, and early-leak-detection monitoring directly above the primary confining zone. This preliminary modeling study described here focuses on hypothetical leakage scenarios intomore »the first permeable unit above the primary confining zone (Ironton Sandstone) and is used to support assessment of early-leak detection capabilities. Future updates of the model will be used to assess potential impacts on the lowermost underground source of drinking water (Saint Peter Sandstone) for a range of theoretical leakage scenarios. This preliminary modeling evaluation considers both pressure response and geochemical signals in the overlying Ironton Sandstone. This model is independent of the FutureGen 2.0 reservoir model in that it does not simulate caprock discontinuities, faults, or failure scenarios. Instead this modeling effort is based on theoretical, volumetric-rate based leakage scenarios. The scenarios include leakage of 1% of the total injected CO2 mass, but spread out over different time periods (20, 100, and 500 years) with each case yielding a different mass flux (i.e., smaller mass fluxes for longer duration leakage cases]. A brine leakage scenario using a volumetric leakage similar to the 20 year 1% CO2 case was also considered. A framework for the comparison of the various cases was developed based on the exceedance of selected pressure and geochemical thresholds at different distances from the point of leakage and at different vertical positions within the Ironton Sandstone. These preliminary results, and results from an updated models that incorporate additional site-specific characterization data, support development/refinement of the monitoring system design.« less

  19. Design Support of an Above Cap-rock Early Detection Monitoring System using Simulated Leakage Scenarios at the FutureGen2.0 Site

    SciTech Connect

    Williams, Mark D.; USA, Richland Washington; Vermuel, Vince R.; USA, Richland Washington; Oostrom, Mart; USA, Richland Washington; Porse, Sean L.; USA, Richland Washington; Thorne, Paul D.; USA, Richland Washington; Szecsody, Jim E.; USA, Richland Washington; Horner, Jake A.; USA, Richland Washington; Gilmore, Tyler J.; USA, Richland Washington

    2014-12-31

    The FutureGen 2.0 Project will design and build a first-of-its-kind, near-zero emissions coal-fueled power plant with carbon capture and storage (CCS). To assess storage site performance and meet the regulatory requirements of the Class VI Underground Injection Control (UIC) Program for CO2 Geologic Sequestration, the FutureGen 2.0 project will implement a suite of monitoring technologies designed to evaluate CO2 mass balance and detect any unforeseen loss in CO2 containment. The monitoring program will include direct monitoring of the reservoir, and early-leak-detection monitoring directly above the primary confining zone. This preliminary modeling study described here focuses on hypothetical leakage scenarios into the first permeable unit above the primary confining zone (Ironton Sandstone) and is used to support assessment of early-leak detection capabilities. Future updates of the model will be used to assess potential impacts on the lowermost underground source of drinking water (Saint Peter Sandstone) for a range of theoretical leakage scenarios. This preliminary modeling evaluation considers both pressure response and geochemical signals in the overlying Ironton Sandstone. This model is independent of the FutureGen 2.0 reservoir model in that it does not simulate caprock discontinuities, faults, or failure scenarios. Instead this modeling effort is based on theoretical, volumetric-rate based leakage scenarios. The scenarios include leakage of 1% of the total injected CO2 mass, but spread out over different time periods (20, 100, and 500 years) with each case yielding a different mass flux (i.e., smaller mass fluxes for longer duration leakage cases]. A brine leakage scenario using a volumetric leakage similar to the 20 year 1% CO2 case was also considered. A framework for the comparison of the various cases was developed based on the exceedance of selected pressure and geochemical thresholds at different distances from the point of leakage and at different vertical positions within the Ironton Sandstone. These preliminary results, and results from an updated models that incorporate additional site-specific characterization data, support development/refinement of the monitoring system design.

  20. Population Pharmacokinetics and Monte Carlo Dosing Simulations of Meropenem during the Early Phase of Severe Sepsis and Septic Shock in Critically Ill Patients in Intensive Care Units

    PubMed Central

    Thengyai, Suriyan; Wongpoowarak, Wibul; Wattanavijitkul, Thitima; Tangkitwanitjaroen, Kanyawisa; Sukarnjanaset, Waroonrat; Jullangkoon, Monchana; Samaeng, Maseetoh

    2015-01-01

    Pathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT>MIC) and 80% fT>MIC. The volume of distribution (V) and total clearance (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h, respectively. For pathogens with MICs of 4 ?g/ml, the PTAs of 40% fT>MIC following administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4-h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens with MICs of 2 ?g/ml in immunocompromised hosts, the PTAs of 80% fT>MIC following administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h were 84.32% and 94.72%, respectively. These findings indicated that the V of meropenem was greater and the CL of meropenem was lower than the values obtained in a previous study with healthy subjects. The maximum recommended dose, i.e., 2 g of meropenem every 8 h, may be required for treatment of life-threatening infections in this patient population. PMID:25753628

  1. Spinsterhood and its impact on disease features in women with rheumatoid arthritis

    PubMed Central

    2011-01-01

    Objective To evaluate the impact of spinsterhood on disease characteristics and quality of life (QoL) in Moroccan women with rheumatoid arthritis (RA). Methods 185 women with RA were recruited in this study. Marital status was specified as follow: 1. Spinsterhood (never-married woman aged 38 or over), 2. Distressed marriage; 3. Nondistressed marriage and 4. Divorced or widowed. Marital distress was assessed by a self-report concerning coping efficacy and burden caring of husbands. Assessment criteria included the evaluation of: age at onset (years), diagnosis delay (months), disease duration (years), disease activity (evaluated by physical examination, biological inflammatory tests; and disease activity score (DAS 28)), pain intensity (measured with a visual analogue scale (VAS)); and radiographic damage (evaluated by the Sharp's method as modified by van der Heijde). Treatments (doses and duration) were specified. The Health Assessment Questionnaire (HAQ) was used to evaluate functional disability. QoL was measured using the Arabic version of the generic instrument SF-36. Results In our data, spinsterhood was detected in 42 (22.7%) patients vs. 88 (47.5%) with distressed marriage, 28 (15.1%) with nondistressed marriage and 27 (14.6%) divorced or widowed. Comparing the 4 groups, we found that QoL in never-married women was damaged in a significant way comparing to the other groups. Mental as well as physical aspects were affected. Also, we found that spinsterhood was associated to an early age at onset (p = 0.009), pain intensity (p < 0.001); clinical (p < 0.001) and biological disease activity (C-reactive protein; p = 0.02) and functional disability (p < 0.001). Logistic regression analysis revealed a significant relationship between spinsterhood and early age at onset and severe functional disability (for all p ? 0.01). Conclusion This study suggests that spinsterhood in our RA patients was associated with an altered QoL even compared with distressed married women. Also, we state that spinsterhood was associated with an early age at onset, severe joint pain; higher disease activity and with altered functional ability. It seems important to consider not only disease-related parameters but also social status as a determinant factor of poor course in RA. PMID:21806812

  2. Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species

    PubMed Central

    Liebisch, Gerhard; Zhang, Ruiyan; Siebert, Hans-Christian; Wilhelm, Jochen; Kaesser, Ulrich; Dettmeyer, Reinhard B.; Klein, Heiko; Ishaque, Bernd; Rickert, Markus; Schmitz, Gerd; Schmidt, Tannin A.; Steinmeyer, Juergen

    2015-01-01

    Background Hyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA). Methods We used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis. Results Compared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs. Conclusions The levels, composition, and MW distribution of all currently known lubricants in SF—HA, lubricin, PLs—vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction. PMID:25933137

  3. An assessment of histopathological criteria for infection in joint arthroplasty in rheumatoid synovium.

    PubMed

    Kataoka, M; Torisu, T; Tsumura, H; Yoshida, S; Takashita, M

    2002-05-01

    Intraoperative frozen section is reported to be a reliable means of identifying occult infection for preoperative evaluation of arthroplasty. The aim of this study was to determine whether the reported histopathological criteria--the existence of more than 10 polymorphonuclear cells (PMN) per high-power field--is valuable for determination of infection during the arthroplasty of patients with rheumatoid arthritis (RA). The permanent histological sections of RA synovium were analysed to study the degree of infiltration of PMNs. Furthermore, in order to examine the penetrative distribution of PMNs within the synovial tissues, immunohistochemical staining of PMNs was performed. In addition, the clinical history, from the postoperative period to the present, was investigated in 46 patients (60 joints). The presence of early- and/or late-stage postoperative infection, the development of postoperative fever, the progression of erythrocyte sedimentation rate (ESR) (more than 30 mm per hour) and the changes in CRP (more than 10 mg per litre) were further examined and compared with the histopathological tissue analyses and findings. The results demonstrated the presence of more than five PMNs per high-power field, excluding surface fibrin and inflammatory exudate in at least five separate microscopic fields in 10 joints (16.7%) of nine patients, out of 60 joints of 46 patients, in which no postoperative infection was evident. As to the magnitude of penetrative distribution of PMNs in 10 joints, there was a trend of deepening infiltration among the patients with intensive PMN infiltration. In addition, no development of postoperative fever, CRP or continuous indications of high ESR values were evident in this group. As the existence of more than 10 PMN per high-power field was not absolutely indicative of occult infection, investigation of frozen section during arthroplasty should be carefully managed. PMID:12086168

  4. Socioeconomic disparities in the health of African-Americans with rheumatoid arthritis from the Southeastern USA

    PubMed Central

    Baldassari, Antoine R.; Cleveland, Rebecca J.; Jonas, Beth L.; Conn, Doyt L.; Moreland, Larry W.; Bridges, S. Louis; Callahan, Leigh F.

    2014-01-01

    Objective To examine cross-sectional baseline data from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis Registry (CLEAR) for the association between socioeconomic status (SES) with clinical and self-report health outcomes. Methods We analyzed data on 937 African Americans (AA) who provided comprehensive sociodemographic data in addition to self-reported health outcomes. SES measures included educational attainment, homeownership, household income and occupation. Outcomes included measures of disease activity, joint damage, autoantibody status, and self-reported measures. Multivariable linear, logistic and zero-inflated Poisson regression models were used to estimate associations of each SES measure with RA outcomes, controlling for gender, age, disease duration, comorbid conditions, BMI, smoking, methotrexate/leflunomide use and biologic agent use. Results The mean age was 54 years, 86% were female, and average RA disease duration was 7.8 years. Approximately 24% had less than a high-school degree, 56% a non-professional occupation, 75% a household income ?$30K, and 55% were non-homeowners. In multivariable regression models, significantly increased associations of disease activity measures and self-reported health outcomes were observed with low household income (?$30K/year) and non-homeownership. Education was primarily associated with self-reported health outcomes. Among participants with disease duration <2 years, associations of SES were confined to self-reported measures. Conclusion Our results indicate significant socioeconomic disparities in self-reported physical and mental health, clinical disease activity measures and autoantibody status among African-Americans with RA not explained by differences in demographics, medication use and health behaviors. PMID:24757034

  5. Vitamin D Status in Rheumatoid Arthritis: Inflammation, Arterial Stiffness and Circulating Progenitor Cell Number

    PubMed Central

    Bagnato, Gianluca; Aragona, Caterina Oriana; Imbalzano, Egidio; D’Ascola, Angela; Rotondo, Francesco; Cinquegrani, Antonella; Mormina, Enricomaria; Saitta, Carlo; Versace, Antonio Giovanni; Sardo, Maria Adriana; Lo Gullo, Renato; Loddo, Saverio; Saitta, Antonino

    2015-01-01

    Background and Aims Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA. Methods and Results CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen. Conclusions RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA. PMID:26241902

  6. Tumour necrosis factor ? antagonists in the treatment of rheumatoid arthritis: an immunological perspective.

    PubMed

    Meroni, Pier-Luigi; Valesini, Guido

    2014-04-01

    Rheumatoid arthritis (RA) is one of the most prevalent autoimmune conditions, affecting approximately 1% of the adult population. It is associated with decreased quality of life and considerable morbidity and mortality. Various inflammatory cells, including macrophages, neutrophils, mast cells, natural killer cells, B and T cells and stromal cells play key pathophysiological roles in joint inflammation and RA progression. Several cytokines, including interleukin (IL)-1? and/or IL-1?, and tumour necrosis factor (TNF)-?, are involved at each stage of RA pathogenesis; namely, by augmenting autoimmunity, sustaining long-term inflammatory synovitis and promoting joint damage. Different cell types are involved in RA pathogenesis through upregulation of several cytokine and soluble pro-inflammatory mediators. As early as the late 1980s, TNF had been identified as a potential target in RA. Five anti-TNF drugs, infliximab, adalimumab, certolizumab pegol, etanercept and golimumab, are now approved for the treatment of RA in various countries. All are bivalent monoclonal antibodies, with the exception of the monovalent certolizumab and etanercept, which is an engineered dimeric receptor. Although all react with and neutralise soluble TNF in vitro, structural differences in the molecules may contribute to differences in their therapeutic effects and the occurrence of side effects. Pegylated certolizumab permits once-monthly dosing. Other mechanisms of action proposed to be important for the efficacy of anti-TNF agents are as follows: induction of apoptosis of both monocytes and T cells; neutralization of membrane TNF; antibody-dependent cell-mediated and complement-dependent cytotoxicity; and reverse signaling via membrane TNF. PMID:24687234

  7. Is Lipoprotein-Associated Phospholipase A2 a Link between Inflammation and Subclinical Atherosclerosis in Rheumatoid Arthritis?

    PubMed Central

    Södergren, Anna; Karp, Kjell; Bengtsson, Christine; Möller, Bozena; Rantapää-Dahlqvist, Solbritt; Wållberg-Jonsson, Solveig

    2015-01-01

    Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation, is associated with cardiovascular disease. This prospective study of an inception cohort aimed to investigate whether the level of Lp-PLA2 is associated with subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Methods. Patients from northern Sweden diagnosed with early RA were consecutively recruited into an ongoing prospective study. From these, all patients ?60 years (n = 71) were included for measurements of subclinical atherosclerosis at inclusion (T0) and five years later (T5). Forty age- and sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score, and Larsen score were calculated, and blood samples were drawn from all individuals at T0 and T5. Results. There was no significant difference in the level of Lp-PLA2 between patients with RA and controls (p > 0.05). In simple linear regression models among patients with RA, Lp-PLA2 at T0 was significantly associated with intima media thickness (IMT) at T0 and T5, flow mediated dilation (FMD) at T0 and T5, ever smoking, male sex, HDL-cholesterol (inversely), non-HDL-cholesterol, SCORE, Reynolds Risk Score, and Larsen score (p < 0.05). Conclusion. In this cohort of patients with early RA, the concentration of Lp-PLA2 was associated with both subclinical atherosclerosis and disease severity. PMID:26504820

  8. Light scattering study of rheumatoid arthritis This article has been downloaded from IOPscience. Please scroll down to see the full text article.

    E-print Network

    Hielscher, Andreas

    Light scattering study of rheumatoid arthritis This article has been downloaded from IOPscience.62.Be DOI:10.1070/QE2002v032nllABEH002326 Light scattering study of rheumatoid arthritis J. Beuthan, U factor g) depend on the presence of the rheumatoid arthritis (RA). At the first stage, the distribution

  9. Abatacept for the treatment of rheumatoid arthritis: A review

    PubMed Central

    Kaine, Jeffrey L.

    2007-01-01

    Abstract Background: Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies—rituximab and abatacept—are currently available for TNF-antagonist inadequate responders. Abatacept is also indicated for inadequate responders to traditional DMARDs. Objectives: The aims of this review was to provide an overview of the issues surrounding the treatment of RA patients experiencing inadequate responses to current treatment and to discuss the current and future impact of abatacept on the RA treatment armamentarium. Methods: The MEDLINE, EMBASE, and BIOSIS databases were searched (search dates: January 1, 2000–September 19, 2007) using the terms abatacept or CTLA-4 or Orencia with rheumatoid arthritis. Full text articles in English were selected for relevance, and only articles presenting primary clinical trial data from randomized, placebo-controlled, clinical trials of abatacept were included. This review focused on the Phase III trials of abatacept in methotrexate and/or TNF-antagonist inadequate responders, as these trials had the largest number of patients and the longest study durations. Results:The literature search initially yielded 848 papers. A total of 12 articles fulfilled the inclusion criteria. Abatacept is a novel agent that has been reported to reduce the signs and symptoms of RA in patients with active RA with an inadequate response to DMARDs and/or TNF-antagonist treatment. In both of these patient populations, treatment with abatacept was found to provide clinically meaningful health-related quality-of-life benefits, such as improvements in physical function, activity limitation, sleep, and fatigue. Abatacept was reported to have a consistent safety and tolerability profile, with a low rate (3.5%–4.2%) of discontinuation due to adverse events. Conclusion: The efficacy and tolerability data from Phase III clinical trials suggest that abatacept is an effective and generally well tolerated treatment option for RA patients with an inadequate response to methotrexate and/or TNF antagonists. PMID:24692770

  10. Surgery in the Treatment of Rheumatoid Arthritis and Ankylosing Spondylitis

    PubMed Central

    Law, W. Alexander

    1948-01-01

    The pain, deformities and disabilities resulting from rheumatoid arthritis and ankylosing spondylitis must be treated by a team composed of physician, physical medicine expert, orthopædic surgeon, and, in certain cases, deep X-ray therapist working simultaneously. The principle of “rest” in order to relieve pain has to be combined with methods designed to preserve and restore function. The multiple joint deformities in these cases may necessitate a long programme of reconstructive or functional treatment, which entails whole-hearted co-operation on the part of the patient in intensive post-operative exercise regime. Procedures advocated for the upper limb include excision of the acromion process together with the subacromial bursa to allow free movement between the central tendon of the deltoid and the tendinous shoulder cuff: arthrodesis of the shoulder in cases where there is more severe joint destruction: in certain cases of elbow-joint arthritis, excision of the radial head and sub-total synovectomy may preserve joint function and avoid or delay the necessity for arthroplasty which can be carried out in two ways: (a) similar to the formal joint excision, or (b) re-shaping the lower end of the humerus and upper end of the ulna lining these surfaces with fascia. The former method is preferable in cases of rheumatoid arthritis. To overcome wrist-joint deformity and restore pronation and supination excision of the lower end of the ulna together with radiocarpal fusion in position for optimum function is advocated. Finger and toe joints may be corrected by resection of the bone ends and capsulectomy. In the lower limbs bilateral involvement of the hip-joint is best treated by vitallium mould arthroplasty which may be carried out in four ways: (1) Routine arthroplasty; (2) Modified Whitman procedure; (3) Modified Colonna operation; and (4) The proximal shaft or intertrochanteric arthroplasty. It is essential in these operations to have knowledge of the operative technique, the use of special hip gouges and reamers, and detailed post-operative supervision. For dorsal kyphosis of the spine, spinal osteotomy at the lumbar level provides excellent correction but is an operation demanding care and skill in its execution. The author's remarks are based on experience gained when working with Dr. M. N. Smith-Petersen at the Massachusetts General Hospital, Boston, U.S.A. PMID:18914877

  11. Clinical and serological features of severe vasculitis in rheumatoid arthritis: prognostic implications.

    PubMed Central

    Geirsson, A J; Sturfelt, G; Truedsson, L

    1987-01-01

    Sixteen patients with classic rheumatoid arthritis (RA) complicated by severe vasculitis were studied and compared with a matched control group of 16 RA patients without vasculitis. Seven of the patients with vasculitis died within 4 to 120 months (median 32 months) after developing vasculitic symptoms. Gangrene of digits and extremities, bowel ulcers or bowel perforation, or both, and cardiac involvement were more common among the patients who died than among those with a more favourable course. The present data suggest that large vessel vasculitis in RA is associated with high frequency of arteriosclerotic vascular disease. The serum concentrations of complement components C3 and C4 were lower, and concentrations of IgM rheumatoid factor, complement activating rheumatoid factor, and C1q binding immune complexes (C1q solid and C1q fluid phase assay) were significantly higher among vasculitic patients than in the control group. Laboratory data provided little prognostic information with regard to rheumatoid vasculitis, with the exception that IgM and IgG rheumatoid factors were significantly higher among patients with fatal course of disease than in those who achieved remission. PMID:3689000

  12. 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...

  13. Exploring the Impact of TeachME™ Lab Virtual Classroom Teaching Simulation on Early Childhood Education Majors' Self-Efficacy Beliefs

    ERIC Educational Resources Information Center

    Bautista, Nazan Uludag; Boone, William J.

    2015-01-01

    The purpose of this study was to investigate the impact of a mixed-reality teaching environment, called TeachME™ Lab (TML), on early childhood education majors' science teaching self-efficacy beliefs. Sixty-two preservice early childhood teachers participated in the study. Analysis of the quantitative (STEBI-b) and qualitative (journal entries)…

  14. Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part I: Rheumatoid adipose tissue

    PubMed Central

    Kontny, Ewa; Zaniewicz-Kaniewska, Katarzyna; Prohorec-Sobieszek, Monika; Saied, Fadhil; Ma?li?ski, W?odzimierz

    2013-01-01

    For many years, it was thought that synovial cells and chondrocytes are the only sources of proinflammatory cytokines and growth factors found in the synovial fluid in patients suffering from osteoarthritis and rheumatoid arthritis. Currently, it is more and more frequently indicated that adipose tissue plays a significant role in the pathogenesis of these diseases as well as that a range of pathological processes that take place in the adipose tissue, synovial membrane and cartilage are interconnected. The adipose tissue is considered a specialized form of the connective tissue containing various types of cells which produce numerous biologically active factors. The latest studies reveal that, similarly to the synovial membrane, articular adipose tissue may take part in the local inflammatory response and affect the metabolism of the cartilage and subchondral osseous tissue. In in vitro conditions, the explants of this tissue obtained from patients suffering from osteoarthritis and rheumatoid arthritis produce similar pro- and anti-inflammatory cytokines to the explants of the synovial membrane. At this stage already, knowledge translates into imaging diagnostics. In radiological images, the shadowing of the periarticular soft tissues may not only reflect synovial membrane pathologies or joint effusion, but may also suggest inflammatory edema of the adipose tissue. On ultrasound examinations, abnormal presentation of the adipose tissue, i.e. increased echogenicity and hyperemia, may indicate its inflammation. Such images have frequently been obtained during ultrasound scanning and have been interpreted as inflammation, edema, hypertrophy or fibrosis of the adipose tissue. At present, when the knowledge concerning pathogenic mechanisms is taken into account, abnormal echogenicity and hyperemia of the adipose tissue may be considered as a proof of its inflammation. In the authors’ own practice, the inflammation of the adipose tissue usually accompanies synovitis. However, we also diagnose cases in which the inflammatory process in the joint is no longer active, but abnormal vascularity still persists in the adipose tissue. There are also cases where abnormal adipose tissue is the only sign of inflammation. Therefore, ultrasound examination confirms the existence of the additional site of inflammation, i.e. the adipose tissue which should be evaluated at the stage of initial diagnosis and during follow-up, also in terms of remission. PMID:26674614

  15. Response to Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis for Function and Pain is Affected by Rheumatoid Factor

    PubMed Central

    Aberumand, Babak; Barra, Lillian; Cao, Yang; Riche, Nicole Le; Thompson, Andrew E; Rohekar, Gina; Rohekar, Sherry; Bonner, Ashley; Pope, Janet E

    2014-01-01

    Objectives : To investigate differences in response to tumor necrosis factor inhibitor treatment (TNFi) in seropositive (rheumatoid factor positive; RF+) versus seronegative (RF-) patients with established RA as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain. Methods : RA patients from an established RA cohort were studied according to rheumatoid factor (RF) status for change in HAQ-DI and pain (0-3 VAS) one year after starting treatment with a TNFi. Results : There were 238 patients treated with TNFi who had follow-up data (178 RF+ and 60 RF-). Disease duration was longer in RF+ vs RF- (12+8 vs 8+8 years) but the proportion of females (82% vs 72%, P=0.7), baseline HAQ-DI (1.44+0.63 vs 1.41+0.63, P=0.8) and pain (1.92+0.67 vs 1.93+0.67, P=0.9) were not different. The mean duration of treatment of first TNFi was 2.8 vs 2.3 years, P=0.1 and 68% of RF+ vs 62% of RF- were still receiving first TNFi at last visit (P=0.5). For patients with data at baseline and one year, the one-year HAQ-DI change was significantly greater in 90 RF+ patients (-0.356) versus 38 RF- patients (-0.126; P=0.04). The mean pain improvement was also greater in 77 RF+ vs 32 RF- patients (-0.725 vs -0.332 respectively; P=0.03). Numbers are small, data are missing and comorbidities, DAS28 and anti-CCP were not collected. Conclusion : Despite limitations in the data, in established RA after failure of DMARDs, RF+ patients may be more responsive to TNFi therapy as measured by changes in HAQ-DI and pain. Innovation : There may be a better response to TNFi in RA if RF positive for function and pain. PMID:25352925

  16. What makes psoriatic and rheumatoid arthritis so different?

    PubMed Central

    Veale, Douglas James; Fearon, Ursula

    2015-01-01

    In many ways, it may be easier to highlight what rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have in common. They are both common conditions characterised by a spectrum of features or clinical manifestations in different organ systems that have led many to conclude that they are actually ‘disease syndromes’. Furthermore, many of the organ systems that are affected in both conditions are the same: skin, joints, eyes, vasculature and even the immune system. Indeed, some clinicians fail to recognise these two common arthritides as distinct. And yet, while the manifestations may have a superficial similarity, there are significant differences at a number of levels including clinical, anatomical, microscopic and molecular levels. However, these differences may explain certain clinical manifestations of the two diseases, and more importantly, they may explain different responses to specific therapies and potentially different disease outcomes and prognoses. This may be especially relevant as new therapeutic targets are examined that may be specific for RA or PsA. PMID:26509055

  17. Current Concepts in the Management of Rheumatoid Hand

    PubMed Central

    Longo, Umile Giuseppe; Petrillo, Stefano; Denaro, Vincenzo

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a T cell-driven autoimmune process, which majorly involves the diarthrodial joints. It affects 1% of the US population, and approximately 70% of patients with RA develop pathologies of the hand, especially of the metacarpophalangeal joints (MCP). Furthermore, also the extensor and flexor tendons of the fingers are frequently involved. The first line of treatment should be conservative. Three general classes of drugs are currently available for RA: nonsteroidal anti-inflammatory agents (NSAIDs), corticosteroids, and disease modifying antirheumatic drugs (DMARDs). Encouraging results have been obtained using DMARDs. However, when severe deformities occur or when patients are unresponsive to medical management and injections therapy, surgical intervention should be performed to relieve pain and restore function. Several surgical options have been described for the management of MCP joint deformities, including soft tissue procedures, arthrodesis, and prosthetic replacement. Tendons ruptures are generally managed with tendon transfer surgery, while different surgical procedures are available to treat fingers deformities. The aim of the present review is to report the current knowledge in the management of MCP joint deformities, as well as tendons damage and fingers deformities, in patients with RA. PMID:26236341

  18. Sedentary behaviour in patients with rheumatoid arthritis: A qualitative study

    PubMed Central

    Thomsen, Tanja; Beyer, Nina; Aadahl, Mette; Hetland, Merete L.; Løppenthin, Katrine; Midtgaard, Julie; Esbensen, Bente A.

    2015-01-01

    Background Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA describe their daily SB. Methods Fifteen patients with RA (10 women and 5 men) from 23 to 73 years of age and with a disease duration ranging from 4 to 27 years were interviewed following a semi-structured interview guide. Data were analysed using the content analysis method described by Graneheim. Results SB appeared in three categories covering: 1) A constant battle between good and bad days; SB could be a consequence of RA in terms of days with pronounced pain and fatigue resulting in many hours of SB. 2) Adaptation to everyday life; living with the unpredictability of RA included constant modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way of living independent of the disease. Conclusions SB is perceived, motivated, and performed differently in patients with RA. An individually tailored approach may be essential in understanding and encouraging patients’ motivation towards sustainable change in SB and activity patterns. PMID:26462971

  19. Proteus mirabilis and rheumatoid arthritis: no association with the disease.

    PubMed

    Chandrashekara, S; Ramesh, M N; Shobha, A; Saravanan, Y; Vadiraja, H S; Navaneeth, B V; Sandhya Belwadi, M R

    2003-09-01

    Proteus mirabilis(PM) is implicated in different studies in the pathogenesis of rheumatoid arthritis (RA) because of the structural homogeneity of its haemolysin B precursor with EQRRAA sequences in DRB 1 haplotype. The aim of the study was to compare the levels of antibodies specific to PM in the sera of patients with RA and healthy controls in our population. Serum samples from 78 consecutive RA patients and 75 healthy controls were analysed for the presence of IgG isotype and total immunoglobulins (IgG+IgA+IgM) against PM using enzyme-linked immunosorbent assay (ELISA) with two kinds of antigen preparation, whole bacteria and SDS-lysed bacterial extract. There was no significant increase in the concentrations of anti- Proteus antibodies (APA) in patients with RA compared to healthy controls in our population, when SDS-lysed bacterial extract or whole bacteria were used as antigen. The APA levels did not correlate with serum CRP levels. Infection with P. mirabilis is found to have no pathological or aggravating role in RA. PMID:14505214

  20. Proteus mirabilis and rheumatoid arthritis: no association with the disease.

    PubMed

    Chandrashekara, S; Ramesh, M N; Shobha, A; Saravanan, Y; Vadiraja, H S; Navaneeth, B V; Sandhya Belwadi, M R

    2003-10-01

    Proteus mirabilis (PM) is implicated in different studies in the pathogenesis of rheumatoid arthritis (RA) because of the structural homogeneity of its haemolysin B precursor with EQRRAA sequences in DRB 1 haplotype. The aim of the study was to compare the levels of antibodies specific to PM in the sera of patients with RA and healthy controls in our population. Serum samples from 78 consecutive RA patients and 75 healthy controls were analysed for the presence of IgG isotype and total immunoglobulins (IgG + IgA + IgM) against PM using enzyme-linked immunosorbent assay (ELISA) with two kinds of antigen preparations, whole bacteria and SDS-lysed bacterial extract. There was no significant increase in the concentrations of anti- Proteus antibodies (APA) in patients with RA compared to healthy controls in our population, when SDS-lysed bacterial extract or whole bacteria were used as antigen. The APA levels did not correlate with serum CRP levels. We conclude that P. mirabilis has no pathological or aggravating role in RA. PMID:14576988

  1. Circadian Timekeeping Is Disturbed in Rheumatoid Arthritis at Molecular Level

    PubMed Central

    Kaivosoja, Emilia; Ainola, Mari; Juhila, Juuso; Hovatta, Iiris; Konttinen, Yrjö T.; Mandelin, Jami

    2013-01-01

    Introduction Patients with rheumatoid arthritis (RA) have disturbances in the hypothalamic-pituitary-adrenal (HPA) axis. These are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and IL-6 levels and in chronic fatigue. We hypothesized that the molecular machinery responsible for the circadian timekeeping is perturbed in RA. The aim of this study was to investigate the expression of circadian clock in RA. Methods Gene expression of thirteen clock genes was analyzed in the synovial membrane of RA and control osteoarthritis (OA) patients. BMAL1 protein was detected using immunohistochemistry. Cell autonomous clock oscillation was started in RA and OA synovial fibroblasts using serum shock. The effect of pro-inflammatory stimulus on clock gene expression in synovial fibroblasts was studied using IL-6 and TNF-?. Results Gene expression analysis disclosed disconcerted circadian timekeeping and immunohistochemistry revealed strong cytoplasmic localization of BMAL1 in RA patients. Perturbed circadian timekeeping is at least in part inflammation independent and cell autonomous, because RA synovial fibroblasts display altered circadian expression of several clock components, and perturbed circadian production of IL-6 and IL-1? after clock resetting. However, inflammatory stimulus disturbs the rhythm in cultured fibroblasts. Throughout the experiments ARNTL2 and NPAS2 appeared to be the most affected clock genes in human immune-inflammatory conditions. Conclusion We conclude that the molecular machinery controlling the circadian rhythm is disturbed in RA patients. PMID:23335987

  2. Genetics of rheumatoid arthritis contributes to biology and drug discovery.

    PubMed

    Okada, Yukinori; Wu, Di; Trynka, Gosia; Raj, Towfique; Terao, Chikashi; Ikari, Katsunori; Kochi, Yuta; Ohmura, Koichiro; Suzuki, Akari; Yoshida, Shinji; Graham, Robert R; Manoharan, Arun; Ortmann, Ward; Bhangale, Tushar; Denny, Joshua C; Carroll, Robert J; Eyler, Anne E; Greenberg, Jeffrey D; Kremer, Joel M; Pappas, Dimitrios A; Jiang, Lei; Yin, Jian; Ye, Lingying; Su, Ding-Feng; Yang, Jian; Xie, Gang; Keystone, Ed; Westra, Harm-Jan; Esko, Tõnu; Metspalu, Andres; Zhou, Xuezhong; Gupta, Namrata; Mirel, Daniel; Stahl, Eli A; Diogo, Dorothée; Cui, Jing; Liao, Katherine; Guo, Michael H; Myouzen, Keiko; Kawaguchi, Takahisa; Coenen, Marieke J H; van Riel, Piet L C M; van de Laar, Mart A F J; Guchelaar, Henk-Jan; Huizinga, Tom W J; Dieudé, Philippe; Mariette, Xavier; Bridges, S Louis; Zhernakova, Alexandra; Toes, Rene E M; Tak, Paul P; Miceli-Richard, Corinne; Bang, So-Young; Lee, Hye-Soon; Martin, Javier; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Rantapää-Dahlqvist, Solbritt; Arlestig, Lisbeth; Choi, Hyon K; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Eyre, Steve; Bowes, John; Barton, Anne; de Vries, Niek; Moreland, Larry W; Criswell, Lindsey A; Karlson, Elizabeth W; Taniguchi, Atsuo; Yamada, Ryo; Kubo, Michiaki; Liu, Jun S; Bae, Sang-Cheol; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Gregersen, Peter K; Raychaudhuri, Soumya; Stranger, Barbara E; De Jager, Philip L; Franke, Lude; Visscher, Peter M; Brown, Matthew A; Yamanaka, Hisashi; Mimori, Tsuneyo; Takahashi, Atsushi; Xu, Huji; Behrens, Timothy W; Siminovitch, Katherine A; Momohara, Shigeki; Matsuda, Fumihiko; Yamamoto, Kazuhiko; Plenge, Robert M

    2014-02-20

    A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ?10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery. PMID:24390342

  3. 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

  4. Identifying genes related with rheumatoid arthritis via system biology analysis.

    PubMed

    Liu, Tao; Lin, Xinmei; Yu, Hongjian

    2015-10-15

    Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease that mainly attacks synovial joints. However, the underlying systematic relationship among different genes and biological processes involved in the pathogenesis are still unclear. By analyzing and comparing the transcriptional profiles from RA, OA (osteoarthritis) patients as well as ND (normal donors) with bioinformatics methods, we tend to uncover the potential molecular networks and critical genes which play important roles in RA and OA development. Initially, hierarchical clustering was performed to classify the overall transcriptional profiles. Differentially expressed genes (DEGs) between ND and RA and OA patients were identified. Furthermore, PPI networks were constructed, functional modules were extracted, and functional annotation was also applied. Our functional analysis identifies 22 biological processes and 2 KEGG pathways enriched in the commonly-regulated gene set. However, we found that number of set of genes differentially expressed genes only between RA and ND reaches up to 244, indicating this gene set may specifically accounts for processing to disease of RA. Additionally, 142 biological processes and 19 KEGG pathways are over-represented by these 244 genes. Meanwhile, although another 21 genes were differentially expressed only in OA and ND, no biological process nor pathway is over-represented by them. PMID:26117171

  5. Peptide motif analysis predicts alphaviruses as triggers for rheumatoid arthritis.

    PubMed

    Hogeboom, Charissa

    2015-12-01

    Rheumatoid arthritis (RA) develops in response to both genetic and environmental factors. The strongest genetic determinant is HLA-DR, where polymorphisms within the P4 and P6 binding pockets confer elevated risk. However, low disease concordance across monozygotic twin pairs underscores the importance of an environmental factor, probably infectious. The goal of this investigation was to predict the microorganism most likely to interact with HLA-DR to trigger RA under the molecular mimicry hypothesis. A set of 185 structural proteins from viruses or intracellular bacteria was scanned for regions of sequence homology with a collagen peptide that binds preferentially to DR4; candidates were then evaluated against a motif required for T cell cross-reactivity. The plausibility of the predicted agent was evaluated by comparison of microbial prevalence patterns to epidemiological characteristics of RA. Peptides from alphavirus capsid proteins provided the closest fit. Variations in the P6 position suggest that the HLA binding preference may vary by species, with Ross River virus, Chikungunya virus, and Mayaro virus peptides binding preferentially to DR4, and peptides from Sindbis/Ockelbo virus showing stronger affinity to DR1. The predicted HLA preference is supported by epidemiological studies of post-infection chronic arthralgia. Parallels between the cytokine profiles of RA and chronic alphavirus infection are discussed. PMID:26476978

  6. Association between Serum 25-Hydroxyvitamin D Level and Rheumatoid Arthritis

    PubMed Central

    Cen, Xiaomin; Liu, Yuan; Yin, Geng; Xie, Qibing

    2015-01-01

    The objective of this study is to examine and evaluate whether serum 25(OH)D is associated with disease activity in patients with rheumatoid arthritis (RA). Our results suggested that serum 25(OH)D in RA groups has significant lower level (35.99 ± 12.59?nmol/L) than that in the normal groups (54.35 ± 8.20?nmol/L, P < 0.05). Based on the DAS28, patients with RA were divided into four subgroups, and no differences were found in the four groups (P > 0.05). The 25(OH)D levels in complete remission, low disease activity, middle disease activity, and high disease activity group were 32.86 ± 12.26, 33.97 ± 13.28, 38.41 ± 10.64, and 38.94 ± 13.35?nmol/L, respectively. Based on the serum 25(OH)D levels, patients with RA were divided into inadequate group and normal group, and there were no significant differences in baseline characteristics and disease activity in the two groups. Our results showed that serum 25(OH)D levels in the inadequate group are significantly lower than those in the normal group. However, no correlations were found between 25(OH)D levels and disease activity among 116 patients with RA. The present findings will help to understand the association between 25(OH)D and disease activity of RA. PMID:26064964

  7. A Multidimensional Model of Fatigue in Patients with Rheumatoid Arthritis

    PubMed Central

    Nicassio, Perry M.; Ormseth, Sarah R.; Custodio, Mara K.; Irwin, Michael R.; Olmstead, Richard; Weisman, Michael H.

    2013-01-01

    Objective To evaluate a multidimensional model testing disease activity, mood disturbance, and poor sleep quality as determinants of fatigue in patients with rheumatoid arthritis (RA). Method The data of 106 participants were drawn from baseline of a randomized comparative efficacy trial of psychosocial interventions for RA. Sets of reliable and valid measures were used to represent model constructs. Structural equation modeling was used to test the direct effects of disease activity, mood disturbance, and poor sleep quality on fatigue, as well as the indirect effects of disease activity as mediated by mood disturbance and poor sleep quality. Results The final model fit the data well, and the specified predictors explained 62% of the variance in fatigue. Higher levels of disease activity, mood disturbance, and poor sleep quality had direct effects on fatigue. Further, disease activity was indirectly related to fatigue through its effects on mood disturbance, which, in turn, was related to poor sleep quality. Mood disturbance also indirectly influenced fatigue through poor sleep quality. Conclusion The findings from this study confirmed the importance of a multidimensional framework in evaluating the contribution of disease activity, mood disturbance, and sleep quality to fatigue in RA using a structural equation approach. Mood disturbance and poor sleep quality played major roles in explaining fatigue along with patient-reported disease activity. PMID:22660801

  8. Histone deacetylase 1 regulates tissue destruction in rheumatoid arthritis.

    PubMed

    Hawtree, Sarah; Muthana, Munitta; Wilkinson, J Mark; Akil, Mohammed; Wilson, Anthony G

    2015-10-01

    Emerging evidence implicates epigenetic mechanisms in the pathogenesis of rheumatoid arthritis (RA). In this study, we have investigated the role of histone deacetylase (HDAC) enzymes in RA synovial fibroblasts (RASFs), a key cellular mediator of cartilage and bone destruction and determined effects of HDAC1 inhibition on both RASF phenotype in vitro, and joint inflammation and damage in the collagen-induced arthritis (CIA) model. Expression of HDACs 1-11 messenger ribonucleic acid (mRNA) was compared between RASFs and osteoarthritic synovial fibroblast (OASFs) using quantitative polymerase chain reaction. HDAC1 expression in RASFs was inhibited using small interfering RNA (siRNA) technology to assess effects on invasiveness, migration, proliferation and apoptosis. Effects of HDAC1 knockdown (KD) on the transcriptome were assessed using gene microarrays. The effects of siRNA-mediated HDAC(KD) on clinical scores, tissue inflammation and damage were assessed on CIA up to 47 days following immunization. Expression of HDAC1 was significantly higher in RASFs than OASFs. HDAC1(KD) resulted in reduced proliferation, invasion and migration in vitro and transcriptome profiling revealed effects on expression of genes regulating proliferation migration and inflammation. Furthermore, inhibition of HDAC1 in CIA resulted in reduced joint swelling, cartilage and bone damage and lower tumor necrosis factor in joint tissue. These results implicate HDAC1 as an important mediator of tissue damage in RA and support the potential therapeutic utility of inhibitors of this enzyme. PMID:26152200

  9. Clinical features of rheumatoid arthritis-associated interstitial lung disease

    PubMed Central

    Wang, Ting; Zheng, Xing-Ju; Liang, Bin-Miao; Liang, Zong-An

    2015-01-01

    Interstitial lung disease (ILD) is the most common extra-articular manifestations of rheumatoid arthritis (RA) in the lung. This study aimed to identify clinical features of RA-associated ILD (RA-ILD). Patients with RA were retrospectively enrolled and sub-classified as RA-ILD or RA without ILD based on high-resolution computed tomography imaging. Pulmonary function testing parameters and levels of RA-related biomarkers, tumour markers, and acute-phase proteins were compared between the two groups. Logistic regression model was used to assess the strength of association between RA-ILD and clinical features of interest. Receiver operating characteristic analysis was performed to assess potential predictive value of clinical features for detecting RA-ILD. Comparison analysis indicated that the percentage of predicted value of total lung capacity, inspiratory capacity, and diffusion capacity of the lung for carbon monoxide (DLCO) were reduced in patients with RA-ILD. Tumour markers CA15–3 and CA125 were increased in patients with RA-ILD. Logistic regression analysis revealed that decreased DLCO was related to the increased likelihood of RA-ILD (OR?=?0.94, 95%CI?=?[0.91, 0.98]). The cut-off point at 52.95 percent of predicted value could sensitively discriminate RA patients with or without ILD. Our study suggested that DLCO value could be a useful tool for detecting ILD in patients with RA. PMID:26443305

  10. Subclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus.

    PubMed

    Salmon, Jane E; Roman, Mary J

    2008-10-01

    Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased mortality, largely as a consequence of cardiovascular disease. Increased cardiovascular morbidity and mortality in patients with RA and SLE cannot be entirely explained by traditional risk factors, suggesting that the systemic inflammation that characterizes these diseases may accelerate atherosclerosis. We used carotid ultrasonography to investigate the prevalence and correlates to preclinical atherosclerosis in patients with RA and SLE. Because atherosclerosis is a systemic disease, assessment of carotid plaque by ultrasonography provides a robust, direct measure of systemic atherosclerosis. We observed a substantially increased prevalence of carotid plaque in RA and SLE patients compared with age- and sex-matched controls, which remained after adjustment for traditional risk factors. The presence of carotid atherosclerosis was associated with disease duration in both RA and SLE and damage in SLE. These data support the hypothesis that inflammation associated with RA and SLE contributes to accelerated atherosclerosis and argue that RA and SLE disease activity should be more aggressively managed. PMID:18926167

  11. Developments in the scientific understanding of rheumatoid arthritis

    PubMed Central

    2009-01-01

    Rheumatoid arthritis (RA) is recognized to be an autoimmune disease that causes preclinical systemic abnormalities and eventually leads to synovial inflammation and destruction of the joint architecture. Recently identified genetic risk factors and novel insights from animal models of spontaneous arthritis have lent support to the concept that thymic selection of an autoreactive T-cell repertoire is an important risk factor for this disease. With advancing age, defects in the homeostatic control of the T-cell pool and in the setting of signaling thresholds lead to the accumulation of pro-inflammatory T-effector cell populations and loss of tolerance to neo-antigens, such as citrullinated peptides. As the breakdown of tolerance to modified self-antigens can precede synovitis by decades, repair of homeostatic defects may open a unique window of opportunity for preventive interventions in RA. The end result of RA, destruction of cartilage and bone, appears to be driven by cytokine- and cell contact-induced activation of synoviocytes and monocytic cells, some of which differentiate into tissue-destructive osteoclasts. Targeting mediators involved in this process has greatly improved the management of this chronic inflammatory syndrome. PMID:19835638

  12. Time of day of prednisolone administration in rheumatoid arthritis.

    PubMed Central

    Kowanko, I C; Pownall, R; Knapp, M S; Swannell, A J; Mahoney, P G

    1982-01-01

    Twelve patients with rheumatoid arthritis took low dosage prednisolone, mean 5.6 mg daily, at either 0800 h, 1300 h or 2300 h in a double-blind within-patient controlled trial. Each patient was studied on each of the 3 regimens to assess control of symptoms and side effects and also to examine circadian rhythms in signs and symptoms. For several days during each drug regimen patients collected urine at each micturition and self-assessed their signs and symptoms. Circadian rhythms of finger joint swelling and of grip strength were determined, and were similar on all regimens, with morning peaks of symptoms and signs. Subjective and objective assessments showed no differences in effectiveness between the 3 times of administration of prednisolone. Urinary excretion patterns were similar to those observed in untreated people. The quantity and circadian pattern of 11-hydroxycorticosteroids excreted were similar to those in healthy patients, providing no evidence of adrenal cortical suppression at the dose levels studied, even when this dose was taken in the evening. A single morning dose of prednisolone appears in many patients to be as effective as a single evening dose or divided doses. It is therefore reasonable to initiate therapy with a morning-only regimen, because adrenopituitary suppression should be minimised. PMID:6751242

  13. Vestibular evoked myogenic potentials in patients with rheumatoid arthritis

    PubMed Central

    Heydari, Nahid; Hajiabolhassani, Fahimeh; Fatahi, Jamileh; Movaseghi, Shafieh; Jalaie, Shohreh

    2015-01-01

    Background: Rheumatoid arthritis (RA) is an autoimmune systemic disease. Most common autoimmune diseases are multisystem disorders that may also present with otological manifestations, and autoimmune inner ear disease accompanied by vestibular dysfunction. This study aimed to compare the vestibular function between RA patients and normal subjects using cervical vestibular evoked myogenic potentials (cVEMPs). Methods: In this cross- sectional study, 25patients with RA (19 female and 6 male: mean (±SD) age, 40.00 (±7.92) years) and 20 healthy subjects (15 female and 5 male: mean (±SD) age, 35.35 (±10.48) years) underwent cVEMPs, using 500 Hz-tone bursts at 95 dB nHL intensity level. Data were analyzed using independent sample t-test through SPSS software v. 16. Results: The mean peak latency of p13 was significantly higher in RA patients (p<0.001). The mean peak latency of n23 was significantly higher in patients in the left ear (p=0.03). Vestibular evoked myogenic potential (VEMP) responses were present in all (100%) of the participants. There were no significant differences in mean peak to peak amplitude and amplitude ratio between the two groups. Conclusion: According to the prolonged latency of VEMP responses in RA patients, lesions in the retrolabyrinthine, especially in the vestibulospinal tract are suspected. PMID:26478874

  14. Autoimmune Thyroid Disease in Rheumatoid Arthritis: A Global Perspective

    PubMed Central

    Cárdenas Roldán, Jorge; Amaya-Amaya, Jenny; Castellanos-de la Hoz, Juan; Giraldo-Villamil, Juliana; Montoya-Ortiz, Gladys; Cruz-Tapias, Paola; Rojas-Villarraga, Adriana; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    Objective. To determine the prevalence and impact of autoimmune thyroid disease (AITD) in patients with rheumatoid arthritis (RA). Methods. Eight-hundred patients were included. The association between AITD and RA was analyzed was analyzed by bivariate and multivariate analysis. In addition, a literature review was done focusing on geographical variations. Results. In our cohort the prevalence of AITD was 9.8% while the presence of antibodies was 37.8% for antithyroperoxidase enzyme (TPOAb) and 20.8% for antithyroglobulin protein (TgAb). The presence of type 2 diabetes, thrombosis, abnormal body mass index, and a high educational level was positively associated with AITD. The literature review disclosed a geographical variation of AITD in RA ranging from 0.5% to 27%. Autoantibody prevalence ranges from 6% to 31% for TgAb, 5% to 37% for TPOAb, and from 11.4% to 32% for the presence of either of the two. Conclusion. AITD is not uncommon in RA and should be systematically assessed since it is a risk factor for developing diabetes and cardiovascular disease. These results may help to further study the common mechanisms of autoimmune diseases, to improve patients' outcome, and to define public health policies. An international consensus to accurately diagnose AITD is warranted. PMID:23209899

  15. Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis

    PubMed Central

    Ternant, David; Ducourau, Emilie; Perdriger, Aleth; Corondan, Anca; Le Goff, Benoît; Devauchelle-Pensec, Valérie; Solau-Gervais, Elisabeth; Watier, Hervé; Goupille, Philippe; Paintaud, Gilles; Mulleman, Denis

    2014-01-01

    Aims Infliximab, an anti-tumour necrosis factor-? monoclonal antibody, is indicated in rheumatoid arthritis (RA). Our objective was to evaluate the influence of the sources of infliximab pharmacokinetic variability in RA. Methods Eighty-four patients treated with infliximab for RA were included in a prospective noncomparative study. They were analysed between two consecutive infliximab infusions. Infliximab concentrations were measured before the infusion, 2 h, 1 and 4 weeks after the infusion and immediately before the next infusion. Infliximab concentrations were described using a two-compartment population pharmacokinetic model. Results The mean (interindividual standard deviation) estimated central volume of distribution was 2.3 l (36%) and systemic clearance was 0.019 l h?1 (37%). The central volume of distribution increased with bodyweight; it was doubled between 50 and 90 kg. Systemic clearance increased with pre-infusion C-reactive protein concentration by 20%, varying from 3 to 14 mg l?1, and was decreased by 30% when methotrexate was coadministered. Conclusions The influence of methotrexate and inflammation on infliximab clearance suggests that individual adjustment of infliximab doses according to disease activity may be useful in RA. PMID:24354889

  16. Atlanto-odontoid osteoarthritis in rheumatoid arthritis: dynamic CT findings.

    PubMed

    Baysal, Ozlem; Baysal, Tamer; Sigirci, Ahmet; Ersoy, Yuksel; Altay, Zuhal

    2004-10-01

    We analyzed the CT appearances of degenerative change in the atlanto-odontoid joint (AOJ) in patients with rheumatoid arthritis (RA) and evaluated the effect of these changes on atlanto-axial joint (AAJ) rotation by dynamic CT. This revealed that 9 patients (24%) treated with methotrexate had degenerative features in the AOJ. The ratio of AAJ rotation to the total rotation of the cervical spine was significantly higher in normal subjects (54 +/- 3%) than in patients (38 +/- 12%). The degree of AAJ rotation was significantly lower in the patient group with degenerative features in the AOJ (20.9 +/- 8.4 degrees ) than in patients without degenerative features (28.5 +/- 7.4 degrees ). RA patients with a history of longstanding disease and treatment with antirheumatic drugs may develop AO OA. Although secondary OA was described as healing phenomena in the joints of RA patients, it can limit rotation in the AAJ and cause suboccipital neck pain. A regular check-up of the AAJ and AOJ by means of dynamic CT in all RA patients is proposed to avoid possible antirheumatic drug complications. PMID:15459811

  17. Genetics of rheumatoid arthritis contributes to biology and drug discovery

    PubMed Central

    Okada, Yukinori; Wu, Di; Trynka, Gosia; Raj, Towfique; Terao, Chikashi; Ikari, Katsunori; Kochi, Yuta; Ohmura, Koichiro; Suzuki, Akari; Yoshida, Shinji; Graham, Robert R.; Manoharan, Arun; Ortmann, Ward; Bhangale, Tushar; Denny, Joshua C.; Carroll, Robert J.; Eyler, Anne E.; Greenberg, Jeffrey D.; Kremer, Joel M.; Pappas, Dimitrios A.; Jiang, Lei; Yin, Jian; Ye, Lingying; Su, Ding-Feng; Yang, Jian; Xie, Gang; Keystone, Ed; Westra, Harm-Jan; Esko, Tõnu; Metspalu, Andres; Zhou, Xuezhong; Gupta, Namrata; Mirel, Daniel; Stahl, Eli A.; Diogo, Dorothée; Cui, Jing; Liao, Katherine; Guo, Michael H.; Myouzen, Keiko; Kawaguchi, Takahisa; Coenen, Marieke J.H.; van Riel, Piet L.C.M.; van de Laar, Mart A.F.J.; Guchelaar, Henk-Jan; Huizinga, Tom W.J.; Dieudé, Philippe; Mariette, Xavier; Bridges, S. Louis; Zhernakova, Alexandra; Toes, Rene E.M.; Tak, Paul P.; Miceli-Richard, Corinne; Bang, So-Young; Lee, Hye-Soon; Martin, Javier; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Rantapää-Dahlqvist, Solbritt; Ärlestig, Lisbeth; Choi, Hyon K.; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Eyre, Steve; Bowes, John; Barton, Anne; de Vries, Niek; Moreland, Larry W.; Criswell, Lindsey A.; Karlson, Elizabeth W.; Taniguchi, Atsuo; Yamada, Ryo; Kubo, Michiaki; Liu, Jun S.; Bae, Sang-Cheol; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Gregersen, Peter K.; Raychaudhuri, Soumya; Stranger, Barbara E.; De Jager, Philip L.; Franke, Lude; Visscher, Peter M.; Brown, Matthew A.; Yamanaka, Hisashi; Mimori, Tsuneyo; Takahashi, Atsushi; Xu, Huji; Behrens, Timothy W.; Siminovitch, Katherine A.; Momohara, Shigeki; Matsuda, Fumihiko; Yamamoto, Kazuhiko; Plenge, Robert M.

    2013-01-01

    A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery. PMID:24390342

  18. Infliximab treatment reduces complement activation in patients with rheumatoid arthritis

    PubMed Central

    Familian, A; Voskuyl, A; van Mierlo, G J; Heijst, H; Twisk, J; Dijkmans, B; Hack, C

    2005-01-01

    Background: Tumour necrosis factor (TNF) blocking agents decrease C reactive protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may contribute to complement activation in RA. Objective: To assess the effect of intravenous infliximab treatment on complement activation, especially that mediated by CRP, in RA. Methods: 35 patients with active RA (28 joint count Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma levels of complement activation products, of CRP and of CRP-complement complexes, which are specific markers for CRP mediated complement activation, were assessed at the indicated time points up to 22 weeks. The relationship between CRP and CRP-complement complexes was analysed by paired t test between two time points and by generalised estimated equation, to test differences of variables over time. Results: At 2 weeks after the first dose, infliximab significantly reduced overall C3 and C4 activation and plasma levels of CRP and CRP-complement complexes were also significantly reduced at this time point. The effects of infliximab on CRP and complement continued throughout the observation period and were more pronounced in patients with a good response to infliximab treatment. Conclusion: Treatment with infliximab decreases plasma levels of CRP and CRP dependent complement activation products and concomitantly may reduce complement activation in RA. Complement activation may be among the effector mechanisms of TNF in RA. PMID:15958758

  19. Rheumatoid Arthritis is Associated with Less Optimal Hip Structural Geometry

    PubMed Central

    Wright, Nicole C.; Lisse, Jeffrey R.; Beck, Thomas J.; Sherrill, Duane L.; Mohler, M. Jane; Bassford, Tamsen; Cauley, Jane A.; LaCroix, Andrea Z.; Lewis, Cora E.; Chen, Zhao

    2011-01-01

    The overall goal of this study was to assess the longitudinal changes in bone strength in women reporting rheumatoid arthritis (RA) (n=78) compared to non-arthritic control participants (n=4,779) of the Women's Health Initiative Bone Mineral Density sub-cohort. Hip structural analysis program was applied to archived dual energy X-ray absorptiometry scans (baseline, years 3, 6, and 9) to estimate bone mineral density (BMD) and hip structural geometry parameters in three femoral regions: narrow neck, intertrochanteric and shaft. The association between RA and hip structural geometry was tested using linear regression and random coefficient models (RCM). Compared to the non-arthritic control the RA group had a lower BMD (p=0.061) and significantly lower outer diameter (p=0.017), cross-sectional area (p=0.004), and section modulus (p=0.035) at the narrow neck region in the longitudinal models. No significant associations were seen at the intertrochanteric or shaft regions, and the association was not modified by age, ethnicity, glucocorticoid use, or time. Within the WHI-BMD, women with RA group had reduced BMD and structural geometry at baseline, and this reduction was seen at a fixed rate throughout the nine years of study. PMID:21852170

  20. Vertebral fractures affect functional status in postmenopausal rheumatoid arthritis patients.

    PubMed

    Omata, Yasunori; Hagiwara, Futoshi; Nishino, Jinju; Matsudaira, Ko; Kadono, Yuho; Juji, Takuo; Mori, Toshihito; Nakayama, Hisanori; Nagase, Yuichi; Hirose, Jun; Yasui, Tetsuro; Matsumoto, Takumi; Matsui, Toshihiro; Tohma, Shigeto; Tanaka, Sakae

    2014-11-01

    Functional disability is a major concern in patients with rheumatoid arthritis (RA). This retrospective study investigated the risk factors for vertebral fractures (VFs) in postmenopausal RA patients and determined the impact of VFs on functional status. Data from a cohort of 200 postmenopausal RA patients in a single hospital registry were analyzed. Demographic and clinical data, imaging data from spine radiographs, and bone mineral density (BMD) data were collected from the patients at baseline and at the final visit (a mean of 2.9 years after the first visit). Risk factors for incident VFs and their impact on the modified health assessment questionnaire (mHAQ) were analyzed. Twenty-eight patients (14%) developed new VFs (NVFs). Logistic regression analysis adjusted for age, BMI, and disease duration revealed that daily dose of prednisolone, femoral neck BMD, use of active vitamin D3, and use of a bisphosphonate at baseline were factors associated with NVF, with odds ratios (95% confidence interval) of 1.27 (1.05-1.54), 0.94 (0.91-0.97), 0.34 (0.13-0.89), and 0.31 (0.12-0.82), respectively. Patients with NVF exhibited worse mHAQ scores and a greater increase in mHAQ scores from baseline compared with those without NVF. In conclusion, incident VFs were associated with reduced functional status in postmenopausal patients with RA. It is important to prevent VFs to maintain the functional status of RA patients. PMID:24362454

  1. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    SciTech Connect

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

    1981-10-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

  2. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    SciTech Connect

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

    1981-10-22

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

  3. HLA heterozygosity contributes to susceptibility to rheumatoid arthritis

    SciTech Connect

    Wordsworth, P.; Pile, K.D.; Bell, J.I. ); Buckely, J.D. ); Lanchbury, J.S.S. ); Ollier, B. ); Lathrop, M. )

    1992-09-01

    The authors have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present-Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P < .02) and in those with Felty syndrome (RR 4.2; P < 0.2). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dw14 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. They also found four cases with the rare Dw4/Dw15 genotype (expected [<=]0.5; P [<=] .02). Since the Dw4, Dw14, Dw15, and DR1 molecules have similar antigen-binding sites and since combinations of these alleles particularly predispose to severe RA, the authors suggest that synergistic mechanisms are involved. These could include an effect on T-cell repertoire selection. 32 refs., 3 tabs.

  4. The role of leptin in the pathophysiology of rheumatoid arthritis.

    PubMed

    Toussirot, Éric; Michel, Fabrice; Binda, Delphine; Dumoulin, Gilles

    2015-11-01

    The past 20years of research on leptin has provided important insights into its role in rheumatoid arthritis (RA). Leptin is one of the different adipokines produced by the adipose tissue that influences the endocrine system, energy homeostasis and the immune response in several ways. Leptin is known to have predominantly pro-inflammatory effects, especially in the setting of chronic inflammation. Animal models of arthritis have illustrated well the participation of leptin in the inflammatory response within the joints. In patients with RA, numerous studies have evaluated the concentrations of leptin in the bloodstream and/or the joint cavity, showing higher levels compared to control populations. Leptin has also been found to correlate with clinical or biological measurements of disease activity of RA. Conversely, the relationship between serum leptin and joint structural damage is less evident. Leptin may also promote the development of atherosclerosis in RA and may contribute to the cardiovascular consequences of the metabolic syndrome that coexists with RA. Indeed, leptin could be a link between inflammation, metabolic risk factors and cardiovascular diseases in RA. Finally, due to abnormal body composition phenotypes with an increased prevalence of obesity in RA, the therapeutic response to traditional DMARDs and/or biological agents may be attenuated. This review discusses the multiple interplays that have been described between leptin and the clinical, radiographic and therapeutic aspects of RA. PMID:26025594

  5. The interaction of rheumatoid factor with hepatitis B surface antigen-antibody complexes.

    PubMed Central

    Markenson, J A; Daniels, C A; Notkins, A L; Hoofnagle, J H; Gerety, J; Barker, L F

    1975-01-01

    A solid phase radioimmunoassay was developed in which the hepatitis B surface antigen was adsorbed to the surface of plastic beads. When the antigen-coated beads were incubated with human IgG antibody against hepatitis B surface antigen, immune complexes were formed on the solid phase surface. IgM rheumatoid factor was found to bind to the hepatitis B surface antigen-antibody complexes but not to the antigen or the IgG antibody alone. Since both hepatitis B surface antigen-antibody complexes and rheumatoid factor are commonly present in type B viral hepatitis, it is suggested that rheumatoid factor may play a role in the pathogenesis of this viral disease in man. PMID:1212797

  6. A Case of REM Sleep Behavior Disorder, Narcolepsy-Cataplexy, Parkinsonism, and Rheumatoid Arthritis

    PubMed Central

    Cosentino, Filomena I. I.; Distefano, Angela; Plazzi, Giuseppe; Schenck, Carlos H.

    2014-01-01

    A patient is reported in whom signs and symptoms of REM sleep behavior disorder (RBD) and narcolepsy have been associated for almost two decades with a late development of parkinsonism and rheumatoid arthritis. A 78-year-old male patient in whom RBD was first diagnosed was followed-up by clinical examination, video-polysomnography, multiple sleep latency test, cerebral magnetic resonance imaging, and dopamine transporter imaging by single-photon emission computerized tomography. The patient was found to present for almost two decades, in addition to RBD, also narcolepsy. Moreover, a late development of parkinsonism and the occurrence of rheumatoid arthritis were detected and clinically and instrumentally characterized. Patients predisposed to RBD and later parkinsonism might be susceptible to a variety of triggers that, in our patient, might have been represented by a possible latent autoimmune process leading to the development of narcolepsy with cataplexy and rheumatoid arthritis, later. PMID:24825961

  7. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    SciTech Connect

    Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-10-22

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

  8. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    SciTech Connect

    Trentham, D.E.; Belli, J.A.Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-10-01

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

  9. Effect of bioresonance therapy on antioxidant system in lymphocytes in patients with rheumatoid arthritis.

    PubMed

    Islamov, B I; Balabanova, R M; Funtikov, V A; Gotovskii, Yu V; Meizerov, E E

    2002-09-01

    We measured activities of superoxide dismutase, catalase, and glutathione peroxidase and content of nonprotein thiol groups (reduced glutathione) in blood lymphocytes from patients with rheumatoid arthritis before and during bioresonance therapy. The state of the antioxidant system in lymphocyte from patients receiving standard pharmacotherapy was characterized by activation of the key antioxidant enzymes and decreased content of thiol groups. Bioresonance therapy increased the content of thiol groups and normalized activities of superoxide dismutase and glutathione peroxidase. However, catalase activity remained above the control. Changes in the lymphocyte antioxidant system indicate that bioresonance therapy activates nonspecific protective mechanisms in patients with rheumatoid arthritis. PMID:12511993

  10. Rheumatoid arthritis susceptibility loci at chromosomes 10p15, 12q13 and 22q13.

    PubMed

    Barton, Anne; Thomson, Wendy; Ke, Xiayi; Eyre, Steve; Hinks, Anne; Bowes, John; Plant, Darren; Gibbons, Laura J; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Worthington, Jane

    2008-10-01

    The WTCCC study identified 49 SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-4) - 1 x 10(-5) (tier 3). Here we show that three of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend P = 4 x 10(-5), P = 4 x 10(-4) and P = 4 x 10(-4), respectively) in a validation study of 4,106 individuals with rheumatoid arthritis and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in individuals of European ancestry. PMID:18794857

  11. An Insight into Methods and Practices in Hip Arthroplasty in Patients with Rheumatoid Arthritis

    PubMed Central

    Mosleh-shirazi, Mohammad Saeed; Ibrahim, Mazin; Pastides, Philip; Khan, Wasim; Rahman, Habib

    2015-01-01

    Total hip arthroplasty (THA) has improved the quality of life of patients with hip arthritis. Orthopedic community is striving for excellence to improve surgical techniques and postoperative care. Despite these efforts, patients continue facing postoperative complications. In particular, patients with rheumatoid arthritis display a higher risk of certain complications such as dislocation, periprosthetic infection, and shorter prosthesis durability. In this review we present the current knowledge of hip arthroplasty in patients with rheumatoid arthritis with more insight into common practices and interventions directed at enhancing recovery of these patients and current shortfalls. PMID:26236339

  12. MRI of cerebral rheumatoid pachymeningitis: report of two cases with follow-up.

    PubMed

    Cellerini, M; Gabbrielli, S; Maddali Bongi, S; Cammelli, D

    2001-02-01

    We report the clinical and neuroradiological features of cerebral rheumatoid pachymeningitis with 1 year follow-up in two patients. MRI of the head enabled noninvasive diagnosis of both the meningeal abnormality and its complications, consisting of hypertensive hydrocephalus and superior sagittal sinus thrombosis, respectively. Dural sinus thrombosis, very uncommon in rheumatoid arthritis, was confirmed by phase-contrast MRA. Worsening of the pachymeningitis at follow-up was observed in both patients despite regression or stability of the clinical picture and long-term therapy. PMID:11326561

  13. Changes of lymphocyte membrane fluidity in rheumatoid arthritis: a fluorescence polarisation study.

    PubMed Central

    Beccerica, E; Piergiacomi, G; Curatola, G; Ferretti, G

    1988-01-01

    Fluorescence polarisation of 1,6-diphenyl-1,3,5-hexatriene was used to study the lymphocyte membrane in rheumatoid arthritis. The increase of polarisation value in the patients (n = 27) compared with healthy controls (n = 32) suggests a decrease of membrane fluidity. Moreover, erythrocyte sedimentation rate (ESR) and plasma fibrinogen concentrations were positively correlated with lymphocyte fluorescence polarisation values (r = 0.66 and r = 0.76 respectively). The results suggest that the changes in lymphocyte membrane fluidity could be involved in the pathogenetic mechanism of rheumatoid arthritis. PMID:3382266

  14. DAS28: a useful instrument to monitor infliximab treatment in patients with rheumatoid arthritis.

    PubMed

    van Riel, Piet L C M; Fransen, Jaap

    2005-01-01

    The Disease Activity Score using 28 joint counts (DAS28) has been developed in a cohort of patients with rheumatoid arthritis in which only conventional anti-rheumatic treatments were used. It has extensively been validated to monitor disease activity in daily clinical practice as well as in clinical trials. The study of Vander Cruyssen and colleagues showed that the DAS28 correlated best with the decisions of rheumatologists to increase the infliximab dose because of insufficient response. This result once more confirms the validity of the DAS28 to monitor disease activity in patients with rheumatoid arthritis and to titrate treatment with biologicals. PMID:16207346

  15. Surgical Management of the Forefoot in Patients with Rheumatoid Arthritis - A Review Article

    PubMed Central

    Nash, W.J.; Al-Nammari, S.; Khan, W.S.; Pengas, I.P.

    2015-01-01

    Foot and ankle pathologies cause a significant disease burden on rheumatoid patients. Forefoot pathologies causes pain, callosities and possibly ulceration, and can cause problems with footwear. Forefoot correction in rheumatoid patients has historically comprised of excision of diseased joints. While satisfaction was high with this procedure, complications, changing expectations and improvement in medical therapy have raised expectation of patients, physicians and surgeons alike. This review assesses the role of joint preserving osteotomies and arthrodesis, as well as associated complications. It also describes the role of the multidisciplinary team in the management of these patients. PMID:25861409

  16. Detection of rheumatoid arthritis by evaluation of normalized variances of fluorescence time correlation functions

    NASA Astrophysics Data System (ADS)

    Dziekan, Thomas; Weissbach, Carmen; Voigt, Jan; Ebert, Bernd; MacDonald, Rainer; Bahner, Malte L.; Mahler, Marianne; Schirner, Michael; Berliner, Michael; Berliner, Birgitt; Osel, Jens; Osel, Ilka

    2011-07-01

    Fluorescence imaging using the dye indocyanine green as a contrast agent was investigated in a prospective clinical study for the detection of rheumatoid arthritis. Normalized variances of correlated time series of fluorescence intensities describing the bolus kinetics of the contrast agent in certain regions of interest were analyzed to differentiate healthy from inflamed finger joints. These values are determined using a robust, parameter-free algorithm. We found that the normalized variance of correlation functions improves the differentiation between healthy joints of volunteers and joints with rheumatoid arthritis of patients by about 10% compared to, e.g., ratios of areas under the curves of raw data.

  17. The effect of zinc on alkaline phosphatase activity in rheumatoid synovial tissue.

    PubMed Central

    Johnstone, J J; Bitensky, L; Cashman, B; Chayen, J

    1978-01-01

    To examine the reported beneficial effect of zinc in rheumatoid arthritis, rheumatoid synovial tissue has been maintained in vitro in non-proliferative culture with or without zinc sulphate in the culture medium. Alkaline phosphatase activity was measured by microdensitometry of the cytochemical reaction in cryostat sections; the activity in blood vessels was measured separately from that in the supporting tissue below the synovial surface. Zinc enhanced this activity optimally at concentrations of between 10(-5) and 10(-4) mol/l. Images PMID:749701

  18. Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation

    SciTech Connect

    Tanay, A.; Field, E.H.; Hoppe, R.T.; Strober, S.

    1987-01-01

    Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty-four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells.

  19. [Comparison of patients with rheumatoid arthritis and chronic backache from the aspect of psychological factors].

    PubMed

    Serbo, B; Jaji?, I

    1991-01-01

    36 patients with rheumatoid arthritis and 44 patients with chronic low back pain were psychologically tested by the MMPI-201, Self-concept of Invalidism Scale, Impact of Pain on the Patients' Lives Scale, and "Pain Games" Scale. Patients with rheumatoid arthritis show significantly higher values at the depression and hypomania scale, while those with chronic low back pain manifest significantly higher values at the hysteria scale of the MMPI-201. This latter group also manifests significantly higher values at the Self-concept of Invalidism Scale and at the "Pain-Game" Scale. PMID:1839749

  20. Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation

    SciTech Connect

    Gaston, J.S.; Strober, S.; Solovera, J.J.; Gandour, D.; Lane, N.; Schurman, D.; Hoppe, R.T.; Chin, R.C.; Eugui, E.M.; Vaughan, J.H.

    1988-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.

  1. The role of cytokines in the pathogenesis of rheumatoid arthritis - Practical and potential application of cytokines as biomarkers and targets of personalized therapy.

    PubMed

    Brzustewicz, Edyta; Bryl, Ewa

    2015-12-01

    Rheumatoid arthritis (RA), as a common chronic disease leading to severe disability, requires early diagnosis and introduction of proper treatment. Deregulation in the cytokine network plays an undoubtedly crucial role in the pathogenesis of RA. The understanding of the role of cytokines in RA can be used for patients' benefit. Technological advances had already allowed introduction of the tailor-made cytokine-targeted therapies (so far anti-TNF, anti-IL-1 and anti-IL-6) into clinical practice. This type of treatment is currently developing very fast. Moreover, cytokines are considered to be potential powerful biomarkers of RA with roles predicted to grow in the future. Detailed understanding of the cytokine balance in RA may assist both the diagnostic process and therapy. PMID:26321413

  2. Use of the Stoke Index to differentiate between disease-modifying agents and non-steroidal anti-inflammatory drugs in rheumatoid arthritis.

    PubMed

    Borg, A A; Fowler, P D; Shadforth, M F; Dawes, P T

    1993-01-01

    The Stoke Index is a validated composite algorithm that has been designed to give a global measure of disease activity in rheumatoid arthritis (RA). The use of this single measure of disease activity in RA simplifies the critical evaluation of drug therapy. 368 patients with RA of varying duration and severity, entered into comparative drug trials between 1980 and 1987, had the algorithm calculated four weeks prior to therapy, at the start of treatment, and bi-monthly to six months. The index score was significantly improved by drugs with known slow acting anti-rheumatic drug (SAARD) activity and improvement could be seen as early as two months after the beginning of treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) did not improve the score. The index differentiates between treatments in patients with minor or major disease activity. We conclude that this composite index of disease activity provides a sensitive, meaningful measure for the evaluation of therapy in RA. PMID:8275581

  3. [HLA-DRB1 alleles and rheumatoid arthritis in northern Italy: lack of correlation with disease severity and extra-articular manifestations].

    PubMed

    Beri, Ruggero; Peterlana, Dimitri; Puccetti, Antonio; Simeoni, Sara; Garzotti, Paolo; Biasi, Domenico; Caramaschi, Paola; Tinazzi, Elisa; Lunardi, Claudio

    2005-03-01

    We studied HLA-DRB1 alleles in 101 patients with rheumatoid arthritis (RA) and 229 normal subjects by polymerase chain reaction and sequence-specific oligonuclotide hybridization. We observed a statistically significant association between HLA-DR4 and RA (p = 0,0088). This association was not observed for the DR1 status. No particular DR4 suballeles were preferentially expressed in patients. Allele *0102 was more frequent in RA patients (p = 0.0084), while *0103 in controls (p = 0.000047). No difference was observed for the presence of early erosions and extra-articular features in patients with no, one or two RA associated alleles and among share epitope positive and negative patients. PMID:15929613

  4. Lymphoid irradiation in intractable rheumatoid arthritis. Long-term followup of patients treated with 750 rads or 2,000 rads

    SciTech Connect

    Soden, M.; Hassan, J.; Scott, D.L.; Hanly, J.G.; Moriarty, M.; Whelan, A.; Feighery, C.; Bresnihan, B.

    1989-05-01

    Twenty patients with intractable rheumatoid arthritis were randomized to receive 750 or 2,000 rads of lymphoid irradiation (LI) in a double-blind comparative study, and were followed for a maximum of 48 months (mean 40 months) after treatment. During followup, sustained immunomodulation (including lymphopenia, particularly of the T helper cell subset; reduced ratio of helper cells to suppressor cells; and impaired in vitro lymphocyte proliferation in response to phytohemagglutinin and pokeweed mitogen) was observed. Significant improvements in early morning stiffness, Ritchie articular index, pain score, grip strength, and 15-meter walk time were observed in both treatment groups, but these were not sustained through the followup period. Progressive joint damage was observed radiologically in both groups during followup. Thus, LI induced sustained immunosuppression, but resulted in only short-lived clinical improvement and was associated with progressive joint erosion in these patients.

  5. Pulmonary involvement in rheumatoid arthritis: evaluation by radiography and spirometry *

    PubMed Central

    Kawassaki, Alexandre Melo; Pereira, Daniel Antunes Silva; Uliana Kay, Fernando; Laurindo, Ieda Maria Magalhães; Carvalho, Carlos Roberto Ribeiro; Kairalla, Ronaldo Adib

    2015-01-01

    Abstract Objective: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA). Methods: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry. Results: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure. Conclusions: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms. PMID:26398753

  6. Biomarkers of Rheumatoid Arthritis–Associated Interstitial Lung Disease

    PubMed Central

    Chen, Juan; Doyle, Tracy J.; Liu, Yongliang; Aggarwal, Rohit; Wang, Xiaoping; Shi, Yonghong; Ge, Sheng Xiang; Huang, Heqing; Lin, Qingyan; Liu, Wen; Cai, Yongjin; Koontz, Diane; Fuhrman, Carl R.; Golzarri, Maria F.; Liu, Yushi; Hatabu, Hiroto; Nishino, Mizuki; Araki, Tetsuro; Dellaripa, Paul F.; Oddis, Chester V.; Rosas, Ivan O.; Ascherman, Dana P.

    2015-01-01

    Objective Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication. Methods Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA–no ILD, RA–mild ILD, or RA–advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest. Results MMP-7 and interferon-?–inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA–no ILD, 41 RA-ILD, 42 RA–indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA–no ILD, 49 RA-ILD, 15 RA–indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses. Conclusion Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication. PMID:25302945

  7. Periodontitis and Porphyromonas gingivalis in Patients with Rheumatoid Arthritis

    PubMed Central

    Mikuls, Ted R.; Payne, Jeffrey B.; Yu, Fang; Thiele, Geoffrey M.; Reynolds, Richard J.; Cannon, Grant W.; Markt, Jeffrey; McGowan, David; Kerr, Gail S.; Redman, Robert S.; Reimold, Andreas; Griffiths, Garth; Beatty, Mark; Gonzalez, Shawneen; Bergman, Debra A.; Hamilton, Bartlett C.; Erickson, Alan R.; Sokolove, Jeremy; Robinson, William; Walker, Clay; Chandad, Fatiha; O’Dell, James R.

    2014-01-01

    Purpose To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) with rheumatoid arthritis (RA) and to examine associations of PD and Porphyomonas gingivalis (Pg) with disease features. Methods RA cases (N=287) and controls (N=330) underwent a standardized periodontal examination. HLA-DRB1 status was imputed using SNPs from the extended MHC. Circulating anti-Pg antibody was measured using ELISA and subgingival plaque was assessed for the presence of Pg using PCR. Associations of PD with RA were examined using multivariable regression. Results PD was more common in RA (35%, p = 0.022) and aCCP positive RA (n=240; 37%; p = 0.006) vs. controls (26%). There were no RA-control differences in anti-Pg or the frequency of Pg positivity by PCR. Anti-Pg antibody showed weak but statistically significant associations with both anti-CCP (r=0.14, p=0.022) and RF (r=0.19, p=0.001). PD was associated with increased swollen joint counts (p=0.004), DAS-28-CRP (p=0.045), total Sharp scores (p=0.015), aCCP (p=0.011), and RF (p<0.001). Select anti-citrullinated peptide antibody (ACPA; including antibody to citrullinated filaggrin) were higher in patients with subgingival Pg and higher anti-Pg antibody levels irrespective of smoking. Associations of PD with established seropositive RA were independent of all covariates examined including evidence of Pg infection. Conclusions Both PD and Pg appear to shape RA-related autoreactivity in RA. In addition, PD demonstrates an independent relationship with established seropositive RA. PMID:24782175

  8. The impact of rheumatoid arthritis and treatment on patients' lives.

    PubMed

    Strand, Vibeke; Khanna, Dinesh

    2010-01-01

    Rheumatoid arthritis (RA) is a chronic, debilitating disease that significantly impacts patients' quality of life and socioeconomic productivity. On a personal level, RA has a significant socioeconomic impact on patients' lives, being ranked among the highest of all chronic diseases for its effect on health-related quality of life (HRQoL), and limitations in physical function as well as increased pain and fatigue affect patients' attendance at paid work, their work performance within and outside the home, and their participation in family, social, and leisure activities. Additional paid or unpaid support, as well as increased flexibility and job modifications from employers, are often required so that patients can meet their role obligations. Disease-related reductions in work and household productivity are not just due to the physical limitations posed by RA; mental/emotional limitations also play a key role in reducing patients' HRQoL and productivity. Newer, effective treatments, such as tumor necrosis factor (TNF) inhibitors, improve the signs and symptoms of disease, inhibit progression of joint damage, and improve physical function and HRQoL. A recently available TNF inhibitor for RA, certolizumab pegol, has been shown to increase productivity outside and within the home and participation in family, social, and leisure activities as well as rapidly improve physical function, fatigue, and pain. Due to the importance of these parameters to patients, new therapies are increasingly assessed based on their ability to improve HRQoL, productivity, and participation. These extend the more traditional measures of efficacy into outcomes that are more central to patients' daily lives. PMID:20576223

  9. Tocilizumab in the treatment of rheumatoid arthritis and beyond

    PubMed Central

    Shetty, Anjali; Hanson, Rebekah; Korsten, Peter; Shawagfeh, Munir; Arami, Shiva; Volkov, Suncica; Vila, Olga; Swedler, William; Shunaigat, Abdel Naser; Smadi, Sameer; Sawaqed, Ray; Perkins, David; Shahrara, Shiva; Sweiss, Nadera J

    2014-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1?, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases. PMID:24729685

  10. Cigarette smoking and radiographic progression in rheumatoid arthritis

    PubMed Central

    Finckh, A; Dehler, S; Costenbader, K H; Gabay, C

    2007-01-01

    Background Smoking is a well?established environmental risk factor for the development of rheumatoid arthritis (RA). However, it remains unclear whether smoking influences RA disease progression and whether smokers have more radiographic damage progression than non?smokers over time. Objective To compare the rates of radiographic damage progression in current smokers and non?smokers in a large prospective RA cohort. Methods The SCQM?RA is a population?based registry monitoring disease activity, radiographic damage and symptoms at regular intervals. All patients in the SCQM?RA database with sequential plain radiographs were included. Joint erosions were assessed in 38 hand and foot joints with a validated scoring method. The rate of erosion progression was analysed using multivariate longitudinal regression models and adjusted for potential confounders. Results 2004 RA patients with a mean of 3.6 sequential radiographs and 3.1 years of follow?up were included. The 545 (27%) current smokers smoked on average 16 cigarettes per day and had a mean past smoking exposure of 20.6 pack?years. Radiographic joint damage progressed at a similar rate in current smokers and non?smokers (p?=?0.26). However, smoking intensity was associated with a significant inverse dose–response; heavy smokers (>1 pack?day) progressed significantly less than non?smokers or moderate smokers (p<0.001). Conclusion Radiographic joint damage progressed at an equivalent rate in smokers and non?smokers. Furthermore, a significant trend was observed for reduced radiographic progression and generally more favourable functional scores among heavy smokers, suggesting that cigarette smoke does not accelerate RA disease progression. PMID:17237117

  11. Body awareness in persons diagnosed with rheumatoid arthritis

    PubMed Central

    Lööf, Helena; Johansson, Unn-Britt; Henriksson, Elisabet W.; Lindblad, Staffan; Bullington, Jennifer

    2014-01-01

    Living with rheumatoid arthritis (RA) poses physiological and psychological demands on a person. RA is a autoimmune disease that can cause pain, disability, and suffering. The ability to notice bodily inner sensations and stimuli (body awareness, BA) is described in the literature in ways that could have either a positive or a negative impact on a person’s health. The concept of BA is complex and a thorough understanding is needed about what BA means from the patient’s perspective. This study was therefore conducted to acquire greater insight into this phenomenon. The study is grounded in a phenomenological life-world perspective. Eighteen narrative interviews were conducted in patients (age range 23–78 years) with RA. The interviews were analyzed using the Empirical Phenomenological Psychological method. General characteristics were found running through all 18 interviews, indicating that the disease resulted in a higher degree of negatively toned BA. BA was either a reactive process of searching or controlling after disease-related symptoms or a reactive process triggered by emotions. BA was an active process of taking an inventory of abilities. All participants had the ability to shift focus from BA to the outside world. Four typologies were identified: “A reactive process on symptoms,” “A reactive process on emotional triggers,” “An active process of taking an inventory of abilities,” and “A shifting from BA to the outside world.” In conclusion, because BA can be both positively and negatively toned, health care professionals must have a good understanding of when BA is positive and when it is negative in relation to the patient. RA had caused a higher degree of negatively toned BA. Thus, the ability to shift attention from BA to activity in the outside world could sometimes be beneficial for the patient’s general health. PMID:25363521

  12. Early Earth

    NASA Astrophysics Data System (ADS)

    Brown, M.

    2015-05-01

    Earth has continents, subduction and mobile lid plate tectonics, but details of the early evolution are poorly understood. Here I summarize the Hadean-Archean record, review evidence for a hotter Earth and consider geodynamic models for early Earth.

  13. Space Station - early concept

    NASA Technical Reports Server (NTRS)

    1966-01-01

    'Langley's Otto Trout suggested as early as 1963 that zero-gravity activities could be simulated by immersing astronauts in a large tank of water. Years later, Marshall Space Flight Center turned Trout's abortive idea into a major component of NASA's astronaut training program.' Published in James R. Hansen, Spaceflight Revolution: NASA Langley Research Center From Sputnik to Apollo, (Washington: NASA, 1995), p. 303.

  14. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know

    PubMed Central

    Krause, Megan L.; Amin, Shreyasee

    2014-01-01

    Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease of synovial joints, can lead to chronic pain and structural joint damage, as well as other organ involvement, especially if not adequately controlled. Because it can affect women in their reproductive years, care of pregnant women with RA requires a delicate balance of maintaining disease control while limiting potential toxicity to the fetus and neonate. While most women experience a substantial improvement in disease activity during pregnancy, for some women their RA remains active. It can even manifest itself for the first time during pregnancy or early in the post-partum period. Optimizing disease control prior to conception is key, but utilizing disease-modifying treatments effectively and safely throughout pregnancy and lactation requires open dialogue and shared decision making. This review provides evidence-based recommendations for use of disease-modifying antirheumatic drugs (DMARDs) and biologic response modifiers to guide rheumatologists in their care of pregnant and lactating women with RA and serves as a guide to counsel male patients with RA on family planning decisions. PMID:25342996

  15. Fractured rheumatoid elbow: treatment with Souter elbow arthroplasty--a clinical and radiologic midterm follow-up study.

    PubMed

    Ikävalko, M; Lehto, M U

    2001-01-01

    We report the results in 26 patients who had 32 preoperative fractures treated with Souter elbow arthroplasty. All were rheumatoid patients with a mean disease duration of 29.7 years (range, 10 to 43). Six of the fractures were of the olecranon and 26 of the distal humerus. The time interval between fracture and arthroplasty was 9 months (mean; range, 0 to 48). Fragments were not excised, and osteosynthesis was performed. The follow-up was 2.6 years (mean; range, 0.5 to 8), when 20 of the fractures had united and 12 had not. K-wire fixation, either alone or in combination with cerclage or PDS suture, and bone grafting led to satisfactory results. Union was verified in 14 of 17 cases treated with this technique. There were no severe early complications. Six patients had late complications. In 3 cases, loosening of the humeral component was observed radiologically. One patient had a hematogenous deep infection 4 years after the operation, and 2 patients had avulsion rupture of the triceps tendon. Fracture in the badly destroyed elbow can be more reasonably treated with an arthroplasty than with an attempt of osteosynthesis before arthroplasty. If excision of the fragments is avoided, original, or near original, anatomy of the elbow joint can be better restored and acceptable outcome obtained with elbow arthroplasty. PMID:11408908

  16. Contribution of ethnic group and socioeconomic status to degree of disability in rheumatoid arthritis in Chilean patients.

    PubMed

    Alarcón, Ana M; Muñoz, Sergio; Kaufman, Jay S; Martínez, Carlos; Riedemann, Pablo; Kaliski, Sonia

    2015-04-01

    The aim of this study was to estimate the contributions of ethnic group and socioeconomic status as social determinants related to disability and disease activity in Chilean Mapuche and non-Mapuche patients with rheumatoid arthritis (RA). Descriptive cross-sectional study with a stratified hospital-based sample of 189 patients in treatment with disease-modifying anti-rheumatic drugs. We assessed disability as categorical variable with the Health Assessment Questionnaire, disease activity with the Disease Activity Score instrument, and socioeconomic status with a standard questionnaire used by the Chilean government. Measures of association, stratified analyses and a multiple logistic regression model were used to analyze the data using the Stata 12.1 software package. Low socioeconomic status (annual income below US$ 7,200) is associated with disability (OR 3.87 CI 1.68-9.20) and Mapuche ethnic identity also contributes to disability (OR 2.48, CI 1.09-5.89). Relevant but not statistically significant in multivariable models were variables such as age, gender and place of residence. RA patients with a low socioeconomic status have almost three times the odds of having a moderate to high disability, independent of their ethnic group, gender or place of residence. Therefore, healthcare efforts should be aimed at promoting early diagnosis and prompt treatment among populations with high levels of poverty, which in the region of the Araucanía means primarily indigenous rural areas. PMID:25178741

  17. Do You Have a Child with Juvenile Rheumatoid Arthritis in Your Class?

    ERIC Educational Resources Information Center

    Ferris, Jean; Fujishige, Carole

    The booklet provides information to help teachers understand juvenile rheumatoid arthritis (JRA). JRA is a chronic disease involving one or more joint(s); its cause is unknown. The five types of JRA are monarticular, pauciarticular of young girls, pauciarticular of boys, polyarticular, and systemic. Aspirin is the main treatment medication and…

  18. Gene hunting of the Genetic Analysis Workshop 16 rheumatoid arthritis data using rough set theory.

    PubMed

    Aporntewan, Chatchawit; Ballard, David H; Lee, Ji Young; Lee, Joon Sang; Wu, Zheyang; Zhao, Hongyu

    2009-01-01

    We propose to use the rough set theory to identify genes affecting rheumatoid arthritis risk from the data collected by the North American Rheumatoid Arthritis Consortium. For each gene, we employ generalized dynamic reducts in the rough set theory to select a subset of single-nucleotide polymorphisms (SNPs) to represent the genetic information from this gene. We then group the study subjects into different clusters based on their genotype similarity at the selected markers. Statistical association between disease status and cluster membership is then studied to identify genes associated with rheumatoid arthritis. Based on our proposed approach, we are able to identify a number of statistically significant genes associated with rheumatoid arthritis. Aside from genes on chromosome 6, our identified genes include known disease-associated genes such as PTPN22 and TRAF1. In addition, our list contains other biologically plausible genes, such as ADAM15 and AGPAT2. Our findings suggest that ADAM15 and AGPAT2 may contribute to a genetic predisposition through abnormal angiogenesis and adipose tissue. PMID:20017992

  19. Disability and Coping as Predictors of Psychological Adjustment to Rheumatoid Arthritis.

    ERIC Educational Resources Information Center

    Revenson, Tracey A.; Felton, Barbara J.

    1989-01-01

    Examined degree to which self-reported functional disability and coping efforts contributed to psychological adjustment among 45 rheumatoid arthritis patients over six months. Hierarchical multiple regression analyses indicated that increases in disability were related to decreased acceptance of illness and increased negative affect, while coping…

  20. Effects of Libby amphibole asbestos exposure on two rat models of rheumatoid arthritis

    EPA Science Inventory

    Epidemiological data suggests that occupational exposure to the amphibole-containing vermiculite in Libby, MT was associated with increased risk for developing autoimmune diseases and had an odds ratio of 3.23 for developing rheumatoid arthritis (RA). Our goal was to determine wh...

  1. How to use biologic agents in patients with rheumatoid arthritis who have comorbid disease.

    PubMed

    Richards, John S; Dowell, Sharon M; Quinones, Mercedes E; Kerr, Gail S

    2015-01-01

    Although biologic disease modifying anti-rheumatic drugs (bDMARDs) have improved the quality of life of patients with rheumatoid arthritis, side effects remain a problem, especially for patients with pre-existing comorbidities. Randomized controlled trials of such drugs in rheumatoid arthritis typically exclude patients with comorbidities and are of short duration, so they do not provide data on adverse events in these people. Other data sources such as national bDMARD registries are limited by the preselection of patients for both conventional synthetic chemical compound disease modifying anti-rheumatic drugs (csDMARDs) and bDMARDs, and although these databases document comorbidity, they rarely report its severity. This too limits definitive statements on the progression or resolution of pre-existing disease. Although bDMARDs may not be contraindicated in patients with rheumatoid arthritis and certain comorbid diseases, additional assessments or precautions are recommended. This review summarizes current data on the use of bDMARDs in people with rheumatoid arthritis and common comorbid diseases. It provides an evidence base for doctors and their patients when discussing and selecting the appropriate bDMARDs. PMID:26282936

  2. Fears and Beliefs in Rheumatoid Arthritis and Spondyloarthritis: A Qualitative Study

    PubMed Central

    Berenbaum, Francis; Chauvin, Pierre; Hudry, Christophe; Mathoret-Philibert, Florence; Poussiere, Maud; De Chalus, Thibault; Dreuillet, Caroline; Russo-Marie, Françoise; Joubert, Jean-Michel; Saraux, Alain

    2014-01-01

    Objectives To explore beliefs and apprehensions about disease and its treatment in patients with rheumatoid arthritis and spondyloarthritis. Methods 25 patients with rheumatoid arthritis and 25 with spondyloarthritis participated in semi-structured interviews about their disease and its treatment. The interviews were performed by trained interviewers in participants' homes. The interviews were recorded and the main themes identified by content analysis. Results Patients differentiated between the underlying cause of the disease, which was most frequently identified as a hereditary or individual predisposition. In patients with rheumatoid arthritis, the most frequently cited triggering factor for disease onset was a psychological factor or life-event, whereas patients with spondyloarthritis tended to focus more on an intrinsic vulnerability to disease. Stress and overexertion were considered important triggering factors for exacerbations, and relaxation techniques were frequently cited strategies to manage exacerbations. The unpredictability of the disease course was a common source of anxiety. Beliefs about the disease and apprehensions about the future tended to evolve over the course of the disease, as did treatment expectations. Conclusions Patients with rheumatoid arthritis and spondyloarthritis hold a core set of beliefs and apprehensions that reflect their level of information about their disease and are not necessarily appropriate. The physician can initiate discussion of these beliefs in order to dispel misconceptions, align treatment expectations, provide reassurance to the patient and readjust disease management. Such a dialogue would help improve standards of care in these chronic and incapacitating diseases. PMID:25474157

  3. False-Positive Results for Rapid Diagnostic Tests for Malaria in Patients with Rheumatoid Factor

    PubMed Central

    Lee, Jong-Han; Jang, Jin Woo; Cho, Chi Hun; Kim, Ju Yeon; Han, Eun Taek; Yun, Seung Gyu

    2014-01-01

    Four different rapid diagnostic tests (RDTs) for malaria were evaluated by testing 82 healthy control patients, 89 Plasmodium vivax-infected patients, and 92 rheumatoid factor (RF)-positive nonmalaria patients. The false-positive rate ranged from 2.2% to 13% in RF-positive patients. High RF levels are associated with malaria RDT false positivity. PMID:25056333

  4. A Crossover Trial Evaluating an Educational-Behavioral Joint Protection Programme for People with Rheumatoid Arthritis.

    ERIC Educational Resources Information Center

    Hammond, A.; Lincoln, N.; Sutcliffe, L.

    1999-01-01

    Joint protection, a self-management technique taught to people with rheumatoid arthritis, was used in a group education program. A crossover trial (N=35) was conducted. No significant changes in measures of pain, functional disability, grip strength, self-efficacy or helplessness occurred post-education, although this may have been due to the…

  5. The RA Scanner: Prediction of Rheumatoid Joint Inflammation Based on Laser Imaging

    E-print Network

    Tresp, Volker

    The RA Scanner: Prediction of Rheumatoid Joint Inflammation Based on Laser Imaging Anton. The RA scanner is based on a novel laser-based imaging technique which is sensitive to the optical characteristics of finger joint tissue. Based on the laser images, finger joints are classified according

  6. Acral vesicles and bullae in a patient with severe rheumatoid arthritis

    PubMed Central

    Soza, Gabriela M.

    2015-01-01

    We present the case of a 56-year-old black woman with rheumatoid arthritis who developed worsening fatigue, fever, weight loss, and a vesiculobullous skin eruption while being treated with certolizumab pegol for her arthritis. Microscopic findings confirmed the diagnosis of a neutrophilic dermatosis. PMID:26424941

  7. Hepatotoxicity associated with use of D-penicillamine in rheumatoid arthritis.

    PubMed Central

    Rosenbaum, J; Katz, W A; Schumacher, H R

    1980-01-01

    Two patients with rheumatoid arthritis developed evidence of hepatotoxicity while receiving D-penicillamine. Both recovered after withdrawal of the drug. These cases and a review of the literature suggested that hepatotoxicity, though rare, should be added to the list of adverse reactions to D-penicillamine. PMID:7387219

  8. Comparison of benorylate and ibuprofen in the treatment of established rheumatoid arthritis.

    PubMed

    Darlington, L G; Coomes, E N

    1975-05-01

    Benorylate and ibuprofen appear to be useful drugs for pain relief in rheumatoid arthritis but benorylate would appear to have a slightly better effect on the pain score and it improved the grip strength more than the moderate doses of ibuprofen. It could be a most useful drug when gastric problems limit the dose of aspirin or of other analgesics. PMID:238275

  9. Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis.

    PubMed

    Santella, Joseph B; Gardner, Daniel S; Duncia, John V; Wu, Hong; Dhar, Murali; Cavallaro, Cullen; Tebben, Andrew J; Carter, Percy H; Barrish, Joel C; Yarde, Melissa; Briceno, Stephanie W; Cvijic, Mary Ellen; Grafstrom, R Robert; Liu, Richard; Patel, Sima R; Watson, Andrew J; Yang, Guchen; Rose, Anne V; Vickery, Rodney D; Caceres-Cortes, Janet; Caporuscio, Christian; Camac, Daniel M; Khan, Javed A; An, Yongmi; Foster, William R; Davies, Paul; Hynes, John

    2014-09-25

    High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis. PMID:25101488

  10. Increased muscle activity to stabilise mobile bearing knees in patients with rheumatoid arthritis

    E-print Network

    van Vliet, Lucas J.

    with a PS total knee prosthesis and three patients with a MB total knee prosthesis were selected based. D 2004 Elsevier B.V. All rights reserved. Keywords: Mobile bearing; Knee prosthesis; EMGIncreased muscle activity to stabilise mobile bearing knees in patients with rheumatoid arthritis

  11. Improvement in hand grip strength in normal volunteers and rheumatoid arthritis patients following yoga training.

    PubMed

    Dash, M; Telles, S

    2001-07-01

    The present study aimed at assessing the effects of a set of yoga practices on normal adults (n = 37), children (n = 86), and patients with rheumatoid arthritis (n = 20). An equal number of normal adults, children, and patients with rheumatoid arthritis who did not practice yoga were studied under each category, forming respective control groups. Yoga and control group subjects were assessed at baseline and after varying intervals, as follows, adults after 30 days, children after 10 days and patients after 15 days, based on the duration of the yoga program, which they attended, which was already fixed. Hand grip strength of both hands, measured with a grip dynamometer, increased in normal adults and children, and in rheumatoid arthritis patients, following yoga, but not in the corresponding control groups, showing no re-test effect. Adult female volunteers and patients showed a greater percentage improvement than corresponding adult males. This gender-based difference was not observed in children. Hence yoga practice improves hand grip strength in normal persons and in patients with rheumatoid arthritis, though the magnitude of improvement varies with factors such as gender and age. PMID:11881576

  12. A rare case report of tumoral calcinosis syndrome in an adult with rheumatoid arthritis

    PubMed Central

    Patel, Hiren; Shaaban, Hamid; Benn, Howard

    2015-01-01

    Summary Tumoral calcinosis is a rare benign disease entity that mimics a neoplasm and is manifested by calcium deposition in the soft tissues around the large joints. It can be primary or secondary to renal failure and hyperparathyroidism. This is, to our knowledge, the first reported case of tumoral calcinosis in a Hispanic male with rheumatoid arthritis. PMID:26136800

  13. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...immuno-logical test system. 866.5775 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5775 Rheumatoid...factor immunological test system is a device that consists...immunoglobulins) in serum, other body fluids, and...

  14. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...immuno-logical test system. 866.5775 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5775 Rheumatoid...factor immunological test system is a device that consists...immunoglobulins) in serum, other body fluids, and...

  15. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...immuno-logical test system. 866.5775 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5775 Rheumatoid...factor immunological test system is a device that consists...immunoglobulins) in serum, other body fluids, and...

  16. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...immuno-logical test system. 866.5775 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5775 Rheumatoid...factor immunological test system is a device that consists...immunoglobulins) in serum, other body fluids, and...

  17. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...immuno-logical test system. 866.5775 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5775 Rheumatoid...factor immunological test system is a device that consists...immunoglobulins) in serum, other body fluids, and...

  18. Scabies in a Patient with Rheumatoid Arthritis Treated with Adalimumab - A Case Report.

    PubMed

    Markovi?, Ivan; Pukši?, Silva; Gudelj Gra?anin, Ana; ?ulo, Melanie Ivana; Mitrovi?, Joško; Morovi?-Vergles, Jadranka

    2015-09-01

    Rheumatoid arthritis is a chronic systemic inflammatory disease characterized by synovitis, erosions, and destruction of affected joints. If untreated, it leads to severe disability and premature mortality. Tumor necrosis factor alpha (TNF-?) inhibitors are biological drugs used in treatment of rheumatoid arthritis. Possible side effects include skin allergic reactions, which, if generalized, are the reason for discontinuation of the drug. We report the case of a 46-year-old female patient with rheumatoid arthritis who presented with pruritus and erythematous papular exanthema after administration of the second dose of adalimumab. At first, we suspected a drug hypersensitivity reaction. As the signs and symptoms persisted for 2 months after discontinuation of adalimumab and despite continuous administration of antihistamines and glucocorticoids, further work-up was performed, and scabies was diagnosed. The patient was treated with topical 10% crotamiton. The symptoms were persistent and additional applications of the preparation were needed. After clinical remission of scabies, treatment of active rheumatoid arthritis with adalimumab was restarted without any complications. PMID:26476903

  19. Disseminated histoplasmosis partially mimicking a dermatomyositis in a patient with rheumatoid arthritis.

    PubMed

    Dussouil, A S; Allardet-Servent, J; Dunogeant, L; Grauer, J L; Ranque, S; Nasser, V

    2015-09-01

    Histoplasma capsulatum var. capsulatum is a dimorphic fungus endemic to America and subtropical regions. Several cases of this opportunist mycosis have been reported in immunocompromised patients. We report the case of a patient treated with methotrexate and corticosteroid therapy for rheumatoid arthritis and who presented with disseminated histoplasmosis that partially mimicked a dermatomyositis. PMID:26197989

  20. Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model

    SciTech Connect

    Choi, Chang-Hyuk; Kim, Hong-Tae; Choe, Jung-Yoon; Kim, Jong Ki; Youn, Hwa Shik

    2007-01-19

    This study was performed to observe microstructures of the rheumatoid arthritis induced mouse feet using a synchrotron radiation beam and to compare findings with histological observations. X-ray refraction images from ex-vivo rheumatoid arthritis induced mouse feet were obtained with an 8KeV white (unmonochromatic) beam and 20 micron thick CsI(Tl) scintillation crystal. The visual image was magnified using a x 10 microscope objective and captured using digital CCD camera. Experiments were performed at 1B2 bending magnet beamline of the Pohang Accelerator Laboratory (PAL) in Korea. Obtained images were compared with histopathologic findings from same sample. Cartilage destruction and thickened joint capsule with joint space narrowing were clearly identified at each grade of rheumatoid model with spatial resolution of as much as 1.2 micron and these findings were directly correlated with histopathologic findings. The results suggest that x-ray microscopy study of the rheumatoid arthritis model using synchrotron radiation demonstrates the potential for clinically relevant micro structure of mouse feet without sectioning and fixation.

  1. Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model

    NASA Astrophysics Data System (ADS)

    Choi, Chang-Hyuk; Kim, Hong-Tae; Choe, Jung-Yoon; Kim, Jong Ki; Youn, Hwa Shik

    2007-01-01

    This study was performed to observe microstructures of the rheumatoid arthritis induced mouse feet using a synchrotron radiation beam and to compare findings with histological observations. X-ray refraction images from ex-vivo rheumatoid arthritis induced mouse feet were obtained with an 8KeV white (unmonochromatic) beam and 20 micron thick CsI(Tl) scintillation crystal. The visual image was magnified using a × 10 microscope objective and captured using digital CCD camera. Experiments were performed at 1B2 bending magnet beamline of the Pohang Accelerator Laboratory (PAL) in Korea. Obtained images were compared with histopathologic findings from same sample. Cartilage destruction and thickened joint capsule with joint space narrowing were clearly identified at each grade of rheumatoid model with spatial resolution of as much as 1.2 micron and these findings were directly correlated with histopathologic findings. The results suggest that x-ray microscopy study of the rheumatoid arthritis model using synchrotron radiation demonstrates the potential for clinically relevant micro structure of mouse feet without sectioning and fixation.

  2. Genome-wide association study meta-analysis identifies 7 novel rheumatoid arthritis risk loci

    E-print Network

    de Bakker, Paul

    ! "! Genome-wide association study meta-analysis identifies 7 novel rheumatoid arthritis risk loci. Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA. 5. Arthritis Research Campaign (arc

  3. Social, Health, and Age Differences Associated with Depressive Disorders in Women with Rheumatoid Arthritis

    ERIC Educational Resources Information Center

    Plach, Sandra K.; Napholz, Linda; Kelber, Sheryl T.

    2005-01-01

    Depression in women with rheumatoid arthritis (RA) may be related to social role experiences, physical health, and age. The purpose of this study was to examine the social and health factors contributing to depression in two age groups of women with RA. One-hundred and thirty-eight midlife and late-life women with a diagnosis of RA participated in…

  4. Reliability of in-Shoe Plantar Pressure Measurements in Rheumatoid Arthritis Patients

    ERIC Educational Resources Information Center

    Vidmar, Gaj; Novak, Primoz

    2009-01-01

    Plantar pressures measurement is a frequently used method in rehabilitation and related research. Metric characteristics of the F-Scan system have been assessed from different standpoints and in different patients, but not its reliability in rheumatoid arthritis patients. Therefore, our objective was to assess reliability of the F-Scan plantar…

  5. Calciphylaxis in a patient affected by rheumatoid arthritis, chronic renal failure, and hyperparathyroidism: a case report

    PubMed Central

    Lurati, Alfredomaria; Laria, Antonella; Paolotti, Donatella; Scarpellini, Magda

    2015-01-01

    Calciphylaxis, or calcific uremic arteriolopathy, is the tissue and vascular calcification that occurs mainly in chronic kidney disease. However, it can be secondary to parathyroid dysfunction and it has been described in rheumatic patients. We present a case of calciphylaxis in a woman with inactive rheumatoid arthritis, acute renal failure, and hyperparathyroidism. PMID:26064073

  6. Family Health and Characteristics in Chronic Fatigue Syndrome, Juvenile Rheumatoid Arthritis, and Emotional Disorders of Childhood.

    ERIC Educational Resources Information Center

    Rangel, Luiza; Garralda, M. Elena; Jeffs, Jim; Rose, Gillian

    2005-01-01

    Objective: To compare family health and characteristics in children with chronic fatigue syndrome (CFS), in juvenile rheumatoid arthritis (JRA), and emotional disorders. Method: Parents of 28 children and adolescents aged 11 to 18 years with CFS, 30 with JRA, and 27 with emotional disorders (i.e., anxiety and/or depressive disorders) were…

  7. Innovative treatment approaches for rheumatoid arthritis. Cyclosporin, leflunomide and nitrogen mustard.

    PubMed

    Furst, D E

    1995-11-01

    Cyclosporin A (CSA) Cyclosporin inhibits IL-2 release and T-cell activation and, secondarily, affects B-cell function. It also inhibits bone resorption, at least in vitro. This drug's bio-availability averages 25-35% but is highly variable. Food and grapefruit juice enhance bio-availability and newer formulations may make its absorption more reliable. It is highly concentrated in fatty tissues and red blood cells but does not cross the blood-brain barrier. CSA is metabolized to numerous metabolites by the liver and its elimination half-life is 6-12 hours in the absence of severe liver disease. Biliary excretion accounts for 94% of CSAs elimination. Because it is highly metabolized, its metabolism can be inhibited by other drugs (e.g. ketoconazole and erythromycin) or its metabolism can be induced (e.g. anticonvulsants). Cyclosporin is more effective than placebo for the treatment of rheumatoid arthritis and as effective as other antirheumatics. There is potential for the use of CSAs in DMARD combinations. The principal toxicities of cyclosporin are gastro-intestinal and renal, with the latter being of more concern. Leflunomide (LF). Leflunomide may be a pyrimidine synthesis inhibitor, although tyrosine kinase inhibitor may also be part of its mechanism of action. Its active metabolite is excreted renally to a large degree, with a prolonged elimination half-life of about 11 days. Since LF is activated by liver metabolism, renal failure may have less effect on kinetics than severe liver disease. Early data on efficacy indicate efficacy at 10-25 mg/day, although more well-controlled data is necessary. Toxicity relates to the skin, liver and GI tract, although some degree of weight loss was also found. Nitrogen mustard (NM). Nitrogen mustard is an alkylating agent whose pharmacokinetics are poorly understood. Small, open studies in RA indicate that NM has a potential for relatively rapid response (1-2 weeks) but, clearly, much work remains to be done. As an alkylating agent, GI and hematological toxicities are of greatest concern. PMID:8591650

  8. Hypermobility of the first metatarsal bone in patients with Rheumatoid arthritis treated by lapidus procedure

    PubMed Central

    2012-01-01

    Background Foot deformities and related problems of the forefoot are very common in patients with rheumatoid arthritis. The laxity of the medial cuneometatarsal joint and its synovitis are important factors in the development of forefoot deformity. The impaired joint causes the first metatarsal bone to become unstable in the frontal and sagittal planes. In this retrospective study we evaluated data of patients with rheumatoid arthritis who underwent Lapidus procedure. We evaluated the role of the instability in a group of patients, focusing mainly on the clinical symptoms and X-ray signs of the instability. Methods The study group included 125 patients with rheumatoid arthritis. The indications of the Lapidus procedure were a hallux valgus deformity greater than 15 degrees and varus deformity of the first metatarsal bone with the intermetatarsal angle greater than 15 degrees on anterio-posterior weight-bearing X-ray. Results Data of 143 Lapidus procedures of 125 patients with rheumatoid arthritis, who underwent surgery between 2004 and 2010 was evaluated. Signs and symptoms of the first metatarsal bone instability was found in 92 feet (64.3%) in our group. The AOFAS score was 48.6 before and 87.6 six months after the foot reconstruction. Nonunion of the medial cuneometatarsal joint arthrodesis on X-rays occurred in seven feet (4.9%). Conclusion The Lapidus procedure provides the possibility to correct the first metatarsal bone varus position and its instability, as well as providing the possibility to achieve a painless foot for walking. We recommend using the procedure as a preventive surgery in poorly symptomatic patients with rheumatoid arthritis in case of the first metatarsal bone hypermobility. PMID:22906022

  9. Relationship between Sleep Disorders, Pain and Quality of Life in Patients with Rheumatoid Arthritis

    PubMed Central

    Purabdollah, Majid; Lakdizaji, Sima; Rahmani, Azad; Hajalilu, Mehrzad; Ansarin, Khalil

    2015-01-01

    Introduction: Rheumatoid arthritis as one of the most common autoimmune diseases is known to be one of the leading causes of disability. Sleep disorders have direct influence on patient’s life. According to studies, sleep problems are known to have negative impact on well-being and functioning, but the exact nature of relationship between sleep disorders and Rheumatoid arthritis is not completely understood. This study aimed to investigate the relationship between sleep disorders, pain and quality of life in patients with rheumatoid arthritis patients. Methods: In a descriptive -correlative study, 210 patients with rheumatoid arthritis referred to Tabriz medical university clinics selected by convenience sampling and were assessed by Sleep Disorders Questionnaire (SDQ), Epworth Sleepiness Scale (ESS), SF-36 Quality of Life Questionnaire and Visual Analog Scale (VAS). Data were analyzed using SPSS-13 by descriptive statistics such as frequency, mean (SD) and inferential statistics including Spearman correlation analysis, linear regression, ?2,t-test and ANOVA. Results: The mean age of participants was 48.41(12.92) years in which most of them (74%) were female. The mean (SD) quality of life was 40.51(22.94), sleepiness 13.14 (5.6) and pain 6.09 (2.14). There was significant negative relationship between some sleep disorders such as (naps, apnea, asphyxia,…) and pain with quality of life but pain severity had more effect on QOL compared to sleep problems. Furthermore, participants had low quality of life with more restriction in physical (mean=34.71) and general health (mean=34.42). Conclusion: Sleep problems and pain were associated with poor quality of life in Rheumatoid Arthritis patients. PMID:26464840

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

    PubMed Central

    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 randomized into either the 6-week Iyengar yoga program (12 - 1.5 hour sessions twice weekly) or the 6-week wait-list control condition. A 20% attrition rate is anticipated. The wait-list group will receive the yoga program following completion of the first arm of the study. We will collect data quantitatively, using questionnaires and markers of disease activity, and qualitatively using semi-structured interviews. Assessments include standardized measures of general and arthritis-specific function, pain, mood, and health-related quality of life, as well as qualitative interviews, blood pressure/resting heart rate measurements, a medical exam and the assessment of pro-inflammatory cytokines. Data will be collected three times: before treatment, post-treatment, and two months following the treatment. Discussion Results from this study will provide critical data on non-pharmacologic methods for enhancing function in rheumatoid arthritis patients. In particular, results will shed light on the feasibility and potential efficacy of a novel intervention for rheumatoid arthritis symptoms, paving the way for a larger clinical trial. Trial Registration ClinicalTrials.gov NCT01096823 PMID:21255431

  11. Elucidation of Cross-Talk and Specificity of Early Response Mechanisms to Salt and PEG-Simulated Drought Stresses in Brassica napus Using Comparative Proteomic Analysis

    PubMed Central

    Luo, Junling; Tang, Shaohua; Peng, Xiaojue; Yan, Xiaohong; Zeng, Xinhua; Li, Jun; Li, Xiaofei; Wu, Gang

    2015-01-01

    To understand the cross-talk and specificity of the early responses of plants to salt and drought, we performed physiological and proteome analyses of Brassica napus seedlings pretreated with 245 mM NaCl or 25% polyethylene glycol (PEG) 6000 under identical osmotic pressure (-1.0 MPa). Significant decreases in water content and photosynthetic rate and excessive accumulation of compatible osmolytes and oxidative damage were observed in response to both stresses. Unexpectedly, the drought response was more severe than the salt response. We further identified 45 common differentially expressed proteins (DEPs), 143 salt-specific DEPs and 160 drought-specific DEPs by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. The proteome quantitative data were then confirmed by multiple reaction monitoring (MRM). The differences in the proteomic profiles between drought-treated and salt-treated seedlings exceeded the similarities in the early stress responses. Signal perception and transduction, transport and membrane trafficking, and photosynthesis-related proteins were enriched as part of the molecular cross-talk and specificity mechanism in the early responses to the two abiotic stresses. The Ca2+ signaling, G protein-related signaling, 14-3-3 signaling pathway and phosphorylation cascades were the common signal transduction pathways shared by both salt and drought stress responses; however, the proteins with executive functions varied. These results indicate functional specialization of family proteins in response to different stresses, i.e., CDPK21, TPR, and CTR1 specific to phosphorylation cascades under early salt stress, whereas STN7 and BSL were specific to phosphorylation cascades under early drought stress. Only the calcium-binding EF-hand family protein and ZKT were clearly identified as signaling proteins that acted as cross-talk nodes for salt and drought signaling pathways. Our study provides new clues and insights for developing strategies to improve the tolerance of crops to complex, multiple environmental stresses. PMID:26448643

  12. Serum Adenosine Deaminase as Inflammatory Marker in Rheumatoid Arthritis

    PubMed Central

    Vinapamula, Kiranmayi S.; Bhattaram, Siddartha Kumar; Bitla, Aparna R.; Manohar, Suchitra M.

    2015-01-01

    Background Rheumatoid arthritis (RA) is a prototypical inflammatory joint disease. The degree of inflammation is reflected in the extent of joint damage, which further has influence on the quality of life of patients with RA, including risk of atherosclerosis. Hence, besides clinical indices, estimation of degree of inflammation using biochemical markers helps in effecting optimum treatment strategies. C-reactive protein (CRP) is established as an inflammatory marker in patients with RA. Adenosine deaminase (ADA), an enzyme of purine metabolism is considered as a marker of cell mediated immunity and has also been suggested as a marker of inflammatory process in RA. The present study attempts to study the efficacy of serum ADA activity as an inflammatory marker in RA. Materials and Methods Forty six RA patients and forty six age and sex matched healthy controls were included in the study. ADA activity and high sensitivity C-reactive protein (hsCRP) levels in serum were measured in all the subjects. Statistical analyses were done using Medcalc statistical software version 12.2.2. Results ADA activity and hsCRP levels were increased in RA patients compared to controls (p<0.0001 and 0.0001 respectively). Significant positive correlation was obtained between hsCRP and ADA in patients (r=0.316, p=0.033). Receiver operating characteristic (ROC) curve analysis revealed statistically significant area under curve (AUC) for ADA that is comparable to that obtained for hsCRP (0.776, p<0.0001 for ADA, 0.726, p<0.0001 for hsCRP). Similar diagnostic utility was obtained with ROC generated cut-off value of 25.3 IU/L (82.6% sensitivity and 65.2% specificity) and with control mean value of 23.48 IU/L (86.96% sensitivity and 54.35% specificity) for ADA. Conclusion Findings of the present study indicate the importance of ADA as a marker of inflammation. Considering the higher sensitivity obtained, we propose control mean (23.48 IU/L) as a cut-off for serum ADA activity as an inflammatory marker. Owing to the simplicity and also the cost effectiveness of ADA assay, ADA may be recommended as a marker of inflammation in patients with RA. However, further larger and well controlled studies are needed to establish its role as inflammatory marker. PMID:26500897

  13. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis

    PubMed Central

    Burmester, Gerd R; Weinblatt, Michael E; McInnes, Iain B; Porter, Duncan; Barbarash, Olga; Vatutin, Mykola; Szombati, Istvan; Esfandiari, Ehsanollah; Sleeman, Matthew A; Kane, Christopher D; Cavet, Guy; Wang, Bing; Godwood, Alex; Magrini, Fabio

    2013-01-01

    Objectives Mavrilimumab, a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, was evaluated in a phase 2 randomised, double-blind, placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis (RA). Methods Subcutaneous mavrilimumab (10?mg, 30?mg, 50?mg, or 100?mg) or placebo was administered every other week for 12?weeks in subjects on stable background methotrexate therapy. The primary endpoint was the proportion of subjects achieving a ?1.2 decrease from baseline in Disease Activity Score (DAS28-CRP) at week 12. Results 55.7% of mavrilimumab-treated subjects met the primary endpoint versus 34.7% placebo (p=0.003) at week 12; for the 10?mg, 30?mg, 50?mg, and 100?mg groups, responses were 41.0% (p=0.543), 61.0% (p=0.011), 53.8% (p=0.071), and 66.7% (p=0.001) respectively. Response rate differences from placebo were observed at week 2 and increased throughout the treatment period. The 100?mg dose demonstrated a significant effect versus placebo on DAS28-CRP<2.6 (23.1% vs 6.7%, p=0.016), all categories of the American College of Rheumatology (ACR) criteria (ACR20: 69.2% vs 40.0%, p=0.005; ACR50: 30.8% vs 12.0%, p=0.021; ACR70: 17.9% vs 4.0%, p=0.030), and the Health Assessment Questionnaire Disability Index (?0.48 vs ?0.25, p=0.005). A biomarker-based disease activity score showed a dose-dependent decrease at week 12, indicating suppression of disease-related biological pathways. Adverse events were generally mild or moderate in intensity. No significant hypersensitivity reactions, serious or opportunistic infections, or changes in pulmonary parameters were observed. Conclusions Mavrilimumab induced rapid clinically significant responses in RA subjects, suggesting that inhibiting the mononuclear phagocyte pathway may provide a novel therapeutic approach for RA. PMID:23234647

  14. Outcome of rheumatoid arthritis following adjunct statin therapy

    PubMed Central

    Das, Subham; Mohanty, Manjushree; Padhan, Prasanta

    2015-01-01

    Objective: Rheumatoid arthritis (RA) is characterized by symmetric peripheral polyarthritis, inflammatory synovitis, and articular destruction. Statins, 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors, mediate significant vascular risk reduction in patients with coronary artery disease by promoting reduction in plasma levels of low-density-lipoprotein cholesterol. Extensive in vitro data, experimental studies and more recently few clinical trials have strongly suggested statins to possess an important role in RA mainly mediated by their anti-inflammatory and immunomodulatory properties. The objective of this study was to evaluate the effect of adjunct statin therapy in comparison to standard disease modifying antirheumatic drugs (DMARD) therapy in patients with RA. Materials and Methods: In this observational study, diagnosed RA patients of age group between 40 and 60 years were selected as per the inclusion criteria from the rheumatology outdoor. From the selected patients, we identified two separate groups of patients. Group 1 included 30 patients of RA currently under DMARD therapy with adjunct statin medication. Group 2 included 30 patients of RA currently under DMARD therapy. Patients were followed up over 6 months. Standard parameters such as disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were recorded for comparing the outcome of RA in both groups. Results: Out of a total of 60 patients who took part in the study, significant beneficial role of adjunct statin medication was found in this study when prescribed along with conventional DMARDs in active RA patients. The mean DAS28, considered by far as the most important index of clinical disease activity in RA, was found to be significantly lower (P < 0.05) in the adjunct statin-treated group (group 1) than that of the conventional DMARD treated group (group 2) after 6 months of continuous therapy. Other two important biochemical markers of RA disease activity, that is, ESR and CRP were also found to be significantly lower (P < 0.05) in RA patients who were on adjunct statin medication (group 1) than in group 2 comprising RA patients only under conventional DMARDs therapy without statin medication. Conclusion: The results suggest an adjunct and potentially beneficial role of statin therapy in active cases of RA, producing significant clinical and biochemical improvement.

  15. Fatigue and severity of rheumatoid arthritis in Moroccan patients.

    PubMed

    Ibn Yacoub, Yousra; Amine, Bouchra; Laatiris, Assia; Wafki, Fahd; Znat, Fatima; Hajjaj-Hassouni, Najia

    2012-07-01

    The aim of this study was to assess fatigue aspects in Moroccan patients with rheumatoid arthritis (RA) and its relationships with disease-specific variables especially parameters of functional and structural severity. A total of 248 patients with RA were included. Patients' and disease characteristics were identified. Disease activity was measured clinically using physical examination, biologically and by the disease activity scores (DAS28). Radiographs were evaluated by using Sharp's method as modified by van der Heijde. Functional disability was measured by using the Moroccan version of Health Assessment Questionnaire (HAQ). Immunological abnormalities and treatment (doses and duration) were identified. Fatigue was evaluated by using a 0-100 visual analogue scale (VAS fatigue) and the multidimensional assessment of fatigue (MAF). Quality of life (QoL) was assessed using the Arabic version of the generic instrument SF-36. The mean age of patients was 47.5 ± 11.7 years [25-72]; 37.5% of patients had a high activity of disease and 11.3% were in remission. The mean Sharp score was 107.13 ± 91, and the mean score of HAQ was 1.40 ± 0.63. All domains of QoL were deteriorated; 89.51% of our patients experienced fatigue. The mean total score of MAF was 30.21 ± 11.32. A low level of education, low socioeconomic status, atlantoaxial subluxation, hip involvement, the presence of a Sjögren syndrome, and cigarette smoking had a negative impact on fatigue scores. The severity of fatigue was correlated with the duration of RA, the intensity of joint pain, the activity of disease, the importance of structural damage, the degree of functional impairment, and the rate of anti-cyclic citrullinated protein (CCP) antibodies (P < 0.05). Patients receiving methotrexate had better scores of fatigue. Also, severity of fatigue was correlated with the deterioration of all domains of QoL. Fatigue is a major issue for our patients with RA and must be included in the routine assessment of patients. In our sample, fatigue appears to be related to disease activity, functional disability, structural damage, and immunological status and had a negative impact on QoL. PMID:21448644

  16. Monitoring rheumatoid arthritis using an algorithm based on patient-reported outcome measures: a first step towards personalised healthcare

    PubMed Central

    Hendrikx, Jos; Fransen, Jaap; van Riel, Piet L C M

    2015-01-01

    Objectives The objective of this proof of concept study was to evaluate alerts generated by a patient-reported outcome measure (PROM)-based algorithm for monitoring patients with rheumatoid arthritis (RA). Methods The algorithm was constructed using an example PROM score of an equally weighted mean of visual analogue scale (VAS) general health, VAS disease activity and VAS pain. Based on the PROM score, red flags are generated in 2 instances: the target level of disease activity is not met; change in disease activity surpasses an early alert threshold. To reduce false alarms, 3 consecutive red flags are needed to trigger an alert to the physician. Time series data from patients included consecutively in the practice-based Nijmegen Early RA cohort were analysed to select an appropriate autoregressive integrated moving average (ARIMA) model. This allowed for advanced interpolation of PROM scores and weekly data evaluation. Alerts were evaluated against disease-modifying antirheumatic drug (DMARD)/biologic medication intensification registered in the cohort. Results Data of 165 patients followed in their second year postdiagnosis were analysed. In 89.8% of 716 visits, the algorithm did not generate an alert and medication was not escalated. Positive predictive value, sensitivity and specificity were 24.6%, 55.6% and 69.7%, respectively. Comparable performance was found when analyses were stratified for baseline Disease Activity Score 28-joint count (DAS28) level. Conclusions When using the algorithm to screen scheduled visits, the overall chance of missing patients in need of medication intensification is low. These findings provide evidence that an off-site monitoring system could aid in optimising the number and timing of face-to-face consultations of patients with their rheumatologists. PMID:26629364

  17. Tetrahydrobiopterin (BH?) supplementation improves endothelial function, but does not alter aortic stiffness in patients with rheumatoid arthritis

    E-print Network

    Mäki-Petäjä, Kaisa M.; Day, Lisa; Cheriyan, Joseph; Hall, Frances C.; Östör, Andrew J. K.; Shenker, Nicholas; Wilkinson, Ian B.

    2015-01-01

    Background: Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk, which may be due to underlying endothelial dysfunction, and subsequent aortic stiffening. We hypothesised that supplementation...

  18. A case of rheumatoid meningitis presented with generalized seizure in whom MRI images were helpful for the diagnosis.

    PubMed

    Yamashita, Kazuya; Terasaki, Yasukazu; Sakaguchi, Manabu; Nakatsuji, Yuji; Yoshizaki, Kazuyuki; Mochizuki, Hideki

    2015-12-23

    We report a 65-years-old woman with rheumatoid meningitis presented with a generalized seizure. She has a 18-year history of rheumatoid arthritis, which has been successfully treated. She developed a generalized seizure. She was diagnosed as having subarachnoid hemorrhage, because the brain magnetic resonance imaging (MRI) showed increased fluid attenuated inversion recovery (FLAIR) signals in her left frontoparietal subarachnoid space. After one month of clinical stabilization, she developed numbness and weakness in her right lower extremity that spread to her right upper extremity and face. Brain MRI showed progression of subarachnoid lesion on FLAIR image and leptomeningeal enhancement on gadolinium-enhanced T1 weighted image. She was diagnosed as having rheumatoid meningitis, and methylprednisolone pulse therapy was started. Then, her symptoms and MRI findings were rapidly improved. Though rheumatoid meningitis is rare and presents a difficulty in the diagnosis, MRI features may support the diagnosis. PMID:26511030

  19. Synthesis of arachidonate cyclo-oxygenase products by rheumatoid and nonrheumatoid synovial lining in nonproliferative organ culture

    PubMed Central

    Salmon, J. A.; Higgs, G. A.; Vane, J. R.; Bitensky, Lucille; Chayen, J.; Henderson, B.; Cashman, B.

    1983-01-01

    Specimens of human rheumatoid and nonrheumatoid synovial lining were maintained in nonproliferative organ culture for 20 hours. The culture fluids were then assayed for prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1? (6-keto-PGF1?) by specific radioimmunoassay. The presence of each of these substances was confirmed by gas chromatography and mass spectrometry. Rheumatoid tissue produced significantly more of each cyclo-oxygenase product than nonrheumatoid tissue. PMID:6402992

  20. Comparative study of the synovial histology in rheumatoid arthritis, spondyloarthropathy, and osteoarthritis: influence of disease duration and activity

    PubMed Central

    Baeten, D; Demetter, P; Cuvelier, C; Van den Bosch, F; Kruithof, E; Van Damme, N; Verbruggen, G; Mielants, H; Veys, E; De Keyser, F

    2000-01-01

    OBJECTIVES—To compare the macroscopic and microscopic characteristics of synovial tissue in rheumatoid arthritis (RA), spondyloarthropathy (SpA), and osteoarthritis (OA) after exclusion of possible biases induced by disease duration or activity, or both.?METHODS—Synovial biopsy specimens were obtained by needle arthroscopy in patients with early RA (n=16), late RA (n=14), early SpA (n=23), and OA (n=12). Macroscopic and microscopic features were scored on a four point scale and analysed as a function of disease duration (early versus late RA), local and systemic disease activity, and diagnosis.?RESULTS—Except for the maximal synovial lining thickness, no significant differences were seen between early and late RA. For disease activity, synovial histology was only weakly correlated with C reactive protein in RA, but seemed to be strongly dependent on effusion of the biopsied joint in all disease groups. After stratification for local disease activity, no disease related differences were found in patients without joint effusion. In contrast, important differences were found between patients with RA and SpA with active joint effusion. Synovial vascularity was macroscopically increased in SpA versus RA (p=0.017). A straight vessel pattern was only seen in RA, while tortuous vessels were preferentially seen in SpA. Vascularity was also microscopically increased in SpA compared with RA (p=0.031), and correlated with the macroscopic vascularity (rs=0.36, p=0.036). CD3+ (p=0.008), CD4+ (p=0.008), and CD20+ (p=0.024) lymphocytes were overrepresented in RA compared with SpA. The integrin expression in RA was characterised by a decrease of ?V?3 in the synovial lining (p=0.006) and an increase of ?V?5 in the sublining (p<0.001).?CONCLUSIONS—The immune architecture of the synovial membrane is more dependent on local disease activity than on disease duration. Synovium obtained from clinically affected joints shows important histological differences between RA and SpA.?? PMID:11087697

  1. Factors that influence fatigue status in patients with severe rheumatoid arthritis (RA) and good disease outcome following 6 months of TNF inhibitor therapy: a comparative analysis.

    PubMed

    Minnock, Patricia; Veale, Douglas J; Bresnihan, Barry; FitzGerald, Oliver; McKee, Gabrielle

    2015-11-01

    The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood/depression differed between groups. Patients with PF (PF; NF) (n?=?28; 28) reported significantly more overall pain (11.3?±?9.4 (0-33); 6.9?±?8.9 (0-33)), more recent and current pain intensity (41.4?±?26.6 (0-80) 24.4?±?26.6 (0-100) and depression (11.8?±?7.5 (1-35); 8.2?±?6.6 (0-26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an on-going state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue. PMID:26453249

  2. Exploring the Impact of TeachME™ Lab Virtual Classroom Teaching Simulation on Early Childhood Education Majors' Self-Efficacy Beliefs

    NASA Astrophysics Data System (ADS)

    Bautista, Nazan Uludag; Boone, William J.

    2015-04-01

    The purpose of this study was to investigate the impact of a mixed-reality teaching environment, called TeachME™ Lab (TML), on early childhood education majors' science teaching self-efficacy beliefs. Sixty-two preservice early childhood teachers participated in the study. Analysis of the quantitative (STEBI-b) and qualitative (journal entries) data revealed that personal science teaching efficacy and science teaching outcome expectancy beliefs increased significantly after one semester of participation in TML. Three key factors impacted preservice teachers' (PST) self-efficacy beliefs in the context of participation in TML: PSTs' perceptions of their science content knowledge, their familiarity with TML technology and avatars, and being observed by peers. Cognitive pedagogical mastery (TML practices), effective/actual modeling, cognitive self-modeling, and emotional arousal were the primary sources that increased the PSTs' perceived self-efficacy beliefs. Overall, the results of this study suggest that the TML is a worthwhile technology for learning to teach in teacher education. It provides a way for PSTs to have a highly personalized learning experience that enables them to improve their understanding and confidence related to teaching science, so that ideally someday they may translate such an experience into their classroom practices.

  3. Oxygen Transport in a Three-Dimensional Microvascular Network Incorporated with Early Tumour Growth and Preexisting Vessel Cooption: Numerical Simulation Study

    PubMed Central

    Cai, Yan; Zhang, Jie; Wu, Jie; Li, Zhi-yong

    2015-01-01

    We propose a dynamic mathematical model of tissue oxygen transport by a preexisting three-dimensional microvascular network which provides nutrients for an in situ cancer at the very early stage of primary microtumour growth. The expanding tumour consumes oxygen during its invasion to the surrounding tissues and cooption of host vessels. The preexisting vessel cooption, remodelling and collapse are modelled by the changes of haemodynamic conditions due to the growing tumour. A detailed computational model of oxygen transport in tumour tissue is developed by considering (a) the time-varying oxygen advection diffusion equation within the microvessel segments, (b) the oxygen flux across the vessel walls, and (c) the oxygen diffusion and consumption within the tumour and surrounding healthy tissue. The results show the oxygen concentration distribution at different time points of early tumour growth. In addition, the influence of preexisting vessel density on the oxygen transport has been discussed. The proposed model not only provides a quantitative approach for investigating the interactions between tumour growth and oxygen delivery, but also is extendable to model other molecules or chemotherapeutic drug transport in the future study. PMID:25695084

  4. Oxygen transport in a three-dimensional microvascular network incorporated with early tumour growth and preexisting vessel cooption: numerical simulation study.

    PubMed

    Cai, Yan; Zhang, Jie; Wu, Jie; Li, Zhi-yong

    2015-01-01

    We propose a dynamic mathematical model of tissue oxygen transport by a preexisting three-dimensional microvascular network which provides nutrients for an in situ cancer at the very early stage of primary microtumour growth. The expanding tumour consumes oxygen during its invasion to the surrounding tissues and cooption of host vessels. The preexisting vessel cooption, remodelling and collapse are modelled by the changes of haemodynamic conditions due to the growing tumour. A detailed computational model of oxygen transport in tumour tissue is developed by considering (a) the time-varying oxygen advection diffusion equation within the microvessel segments, (b) the oxygen flux across the vessel walls, and (c) the oxygen diffusion and consumption within the tumour and surrounding healthy tissue. The results show the oxygen concentration distribution at different time points of early tumour growth. In addition, the influence of preexisting vessel density on the oxygen transport has been discussed. The proposed model not only provides a quantitative approach for investigating the interactions between tumour growth and oxygen delivery, but also is extendable to model other molecules or chemotherapeutic drug transport in the future study. PMID:25695084

  5. Hand handicap and rheumatoid arthritis in a fish-eating society (the Faroe Islands).

    PubMed

    Recht, L; Helin, P; Rasmussen, J O; Jacobsen, J; Lithman, T; Scherstén, B

    1990-01-01

    In the county of Klaksvik, the Faroes, a simple hand test was used for screening all inhabitants between the ages of 40 and 74 years. With its high sensitivity and specificity it revealed a diagnostic panorama entirely different from that seen in previous investigations in other nordic countries. In Klaksvik the prevalence of hand handicap was about 40%, which is due to the high incidence of osteoarthrosis. The prevalence of rheumatoid arthritis was 1.1%. The high functional capacity and the lower occurrence of rheumatic nodules and erosions found in the patients with rheumatoid arthritis as compared with previous studies suggest that the disease takes a milder course in Klaksvik. This should support the hypothesis that RA patients benefit from a diet rich in fish. PMID:2137159

  6. The temporomandibular joint in a rheumatoid arthritis patient after orthodontic treatment.

    PubMed

    Sasaguri, Kenichi; Ishizaki-Takeuchi, Rika; Kuramae, Sakurako; Tanaka, Eliana Midori; Sakurai, Takashi; Sato, Sadao

    2009-07-01

    A 32-year-old Japanese female patient consulted the authors' dental clinic with a 4.5-year history of rheumatoid arthritis (RA). She complained of pain during mouth opening and difficulty in eating due to masticatory dysfunction caused by an anterior open bite. Imaging showed severe erosion and flattening of both condyles. RA stabilized after pharmacological therapy and became inactive during the orthodontic therapy aimed at reconstructing an optimal occlusion capable of promoting functional repositioning of the mandible. At present, 4 years and 2 months postretention, the reconstructed occlusion remains stable, and both condyles continue to be remodeled. The distance from reference position to intercuspal position has gradually decreased throughout the 4-year posttreatment and postretention periods. Orthodontic therapy that comprehensively reconstructs occlusion and enhances the functioning of the mandible can induce remodeling of eroded condyles, even those with a history of rheumatoid arthritis. PMID:19537854

  7. Mastocytic enterocolitis as a rare cause of chronic diarrhea in a patient with rheumatoid arthritis.

    PubMed

    Thonhofer, Rene; Siegel, Cornelia; Trummer, Markus; Langner, Cord

    2011-05-01

    The prevalence of chronic diarrhea within the U.S. population has been reported to be as high as five per cent, and numerous causes have been identified. Especially in patients suffering from rheumatoid arthritis drug therapy should be considered as possible cause. We report a case of chronic diarrhea triggered by mastocytic enterocolitis in a patient suffering from rheumatoid arthritis. Systemic mastocytosis and other causes of chronic diarrhea, especially therapy with methotrexate, were carefully ruled out. Treatment with desloratadin and ranitidine was initiated and led to a rapid and persistent amelioration of clinical symptoms. The diagnosis of mastocytic enterocolitis should be considered in patients with chronic diarrhea and normal clinical, laboratory, as well as endoscopical work-up. PMID:21499916

  8. Towards an understanding of the role of DNA methylation in rheumatoid arthritis: therapeutic and diagnostic implications.

    PubMed

    Cribbs, Adam; Feldmann, Marc; Oppermann, Udo

    2015-10-01

    The term 'epigenetics' loosely describes DNA-templated processes leading to heritable changes in gene activity and expression, which are independent of the underlying DNA sequence. Epigenetic mechanisms comprise of post-translational modifications of chromatin, methylation of DNA, nucleosome positioning as well as expression of noncoding RNAs. Major advances in understanding the role of DNA methylation in regulating chromatin functions have been made over the past decade, and point to a role of this epigenetic mechanism in human disease. Rheumatoid arthritis (RA) is an autoimmune disorder where altered DNA methylation patterns have been identified in a number of different disease-relevant cell types. However, the contribution of DNA methylation changes to RA disease pathogenesis is at present poorly understood and in need of further investigation. Here we review the current knowledge regarding the role of DNA methylation in rheumatoid arthritis and indicate its potential therapeutic implications. PMID:26425149

  9. Towards an understanding of the role of DNA methylation in rheumatoid arthritis: therapeutic and diagnostic implications

    PubMed Central

    Cribbs, Adam; Feldmann, Marc; Oppermann, Udo

    2015-01-01

    The term ‘epigenetics’ loosely describes DNA-templated processes leading to heritable changes in gene activity and expression, which are independent of the underlying DNA sequence. Epigenetic mechanisms comprise of post-translational modifications of chromatin, methylation of DNA, nucleosome positioning as well as expression of noncoding RNAs. Major advances in understanding the role of DNA methylation in regulating chromatin functions have been made over the past decade, and point to a role of this epigenetic mechanism in human disease. Rheumatoid arthritis (RA) is an autoimmune disorder where altered DNA methylation patterns have been identified in a number of different disease-relevant cell types. However, the contribution of DNA methylation changes to RA disease pathogenesis is at present poorly understood and in need of further investigation. Here we review the current knowledge regarding the role of DNA methylation in rheumatoid arthritis and indicate its potential therapeutic implications. PMID:26425149

  10. Anti-intermediate filament antibodies, antikeratin antibody, and antiperinuclear factor in rheumatoid arthritis and infectious mononucleosis.

    PubMed Central

    Kataaha, P K; Mortazavi-Milani, S M; Russell, G; Holborow, E J

    1985-01-01

    Sera from patients with rheumatoid arthritis (RA), patients with infectious mononucleosis (IM), and blood donors were tested by indirect immunofluorescence for the presence of antikeratin antibody (AKA), antibody to cytoskeletal intermediate filaments of prekeratin or vimentin type (AIFA) and antiperinuclear factor (APF). In 81.9% of the RA sera and 92.5% of the IM sera AIFA of IgM class was found at titres up to and in some cases exceeding 1/160. In blood donors the incidence of AIFA was 26%, at titres not exceeding 1/20. AKA and APF, always of IgG class, were found in 54.2% and 73.6% of rheumatoid sera. A weak correlation was found in RA between the incidence of AIFA and APF. AKA was not present in either IM or blood donor sera, and APF was found in only 2.5% and 3.2% of IM or blood donors respectively. PMID:2411230

  11. Developing the next generation of monoclonal antibodies for the treatment of rheumatoid arthritis

    PubMed Central

    Campbell, Jamie; Lowe, David; Sleeman, Matthew A

    2011-01-01

    Rheumatoid arthritis is one of the commonest autoimmune diseases affecting 0.8% of the population. Over the last decade the treatment of this chronic disease has been revolutionized by the use of monoclonal antibodies and fusion proteins, targeting molecules like tumour necrosis factor alpha. Nevertheless, approximately one-third of subjects fail to respond to these therapies and therefore significant unmet medical need remains. Following a decade of use, clinical, government and regulatory agency expectations have changed for new antibodies therapies entering this highly competitive area. In this review, we discuss the current advances being made in antibody engineering and how they are being considered and used in the development of the next generation of antibodies to meet future expectations of healthcare providers, physicians and patients. Moreover, we discuss how pattern recognition receptors may provide new antibody tractable targets that may break the cycle of autoimmunity in rheumatoid arthritis. PMID:21182494

  12. Treatment of rheumatoid arthritis with levamisole: long-term results and immune changes.

    PubMed Central

    Runge, L A; Pinals, R S; Tomar, R H

    1979-01-01

    We treated 29 rheumatoid arthritis patients with levamisole. on the basis of a 25% improvement in any 3 of 6 measurements 95% of the patients had a favourable response within 20 weeks. However, 64% of the patients discontinued levamisole by 40 to 60 weeks because of rash or secondary treatment failures. Delayed skin reactivity to streptokinase-streptodornase increased significantly in the entire treatment group, but there was in inverse correlation between skin test enhancement and clinical response. There was no overall change in lymphocytes response to phytohaemagglutinin (PHA) after 4 and 16 weeks of treatment, but seven patients with enhanced lymphocyte responsiveness to PHA experienced an earlier clinical response to levamisole. Treatment with levamisole frequently results in clinical improvement in rheumatoid arthritis, but this is not clearly related to a stimulatory effect on cell-mediated immunity. Its long-term usefulness may be limited by a high incidence of relapse and rash. PMID:375847

  13. Total lymphoid irradiation therapy in refractory rheumatoid arthritis. Fifteen- to forty-month followup

    SciTech Connect

    Brahn, E.; Helfgott, S.M.; Belli, J.A.; Anderson, R.J.; Reinherz, E.L.; Schlossman, S.F.; Austen, K.F.; Trentham, D.E.

    1984-05-01

    Twelve patients with refractory rheumatoid arthritis were treated with total lymphoid irradiation (TLI) to a total cumulative dose of 3,000 rads. Post-TLI morbidity/mortality included 8 patients with xerostomia, 4 with weight loss of greater than 10 kg, 3 with loss of 4 or more teeth, 3 with herpes zoster, 4 with bacterial infection that was fatal in 2, 3 with hypothyroidism, 1 with cutaneous vasculitis, and death from myocardial infarction in 1 patient and cardiorespiratory arrest in another. Ten of the patients were reevaluated 15-40 months (mean +/- SE, 30 +/- 2) after completion of TLI, and significant improvement was noted in several disease parameters including number of swollen joints, duration of morning stiffness, and 50-foot walking time. Blood lymphopenia and a decrease in helper T cells (T4) were also noted. These data suggest that changes in immunoregulation induced by TLI can produce longlasting alterations in rheumatoid arthritis, although adverse effects may limit its efficacy.

  14. The Relationship of Cardiovascular Risk in Rheumatoid Arthritis Comparing TNF? Blockade with Non-Biologic DMARDs

    PubMed Central

    Solomon, Daniel H.; Curtis, Jeffrey R.; Saag, Kenneth G.; Lii, Joyce; Chen, Lang; Harrold, Leslie R.; Herrinton, Lisa J; Graham, David J; Kowal, Mary K.; Kuriya, Bindee; Liu, Liyan; Griffin, Marie R.; Lewis, James D.; Rassen, Jeremy A.

    2015-01-01

    Background Elevated TNF? likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF? blocking agent versus a non-biologic disease-modifying anti-rheumatic drug (nbDMARD). Methods Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998-2007 who received methotrexate were eligible. Those who added a TNF? blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular endpoint of myocardial infarction, stroke, or coronary re-vascularization after six months. Results We compared 8,656 new users of a nbDMARD with 11,587 new users of a TNF? blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular endpoint were 3.05 (95% CI 2.54 – 3.65) for nbDMARDs and 2.52 (95% CI 2.12-2.98) for TNF? blocking agents. The hazard ratio (HR) for the TNF? blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95% CI 0.62 - 1.04), while the HR for the as-treated analysis was 0.71 (95% CI 0.52 - 0.97). The potential cardiovascular benefit of TNF? blocking agents was strongest among persons ? 65 years of age (HR 0.52, 95% CI 0.34 – 0.77; p for interaction = 0.075). Conclusion Among subjects with rheumatoid arthritis, TNF? blocking agents may be associated with a reduced risk of cardiovascular events compared to a nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis. PMID:23885678

  15. Repeat radiation synovectomy with dysprosium 165-ferric hydroxide macroaggregates in rheumatoid knees unresponsive to initial injection

    SciTech Connect

    Vella, M.; Zuckerman, J.D.; Shortkroff, S.; Venkatesan, P.; Sledge, C.B.

    1988-06-01

    Because of failure to fully respond to an initial intraarticular injection of dysprosium 165-ferric hydroxide macroaggregates, 17 patients with seropositive rheumatoid arthritis underwent repeat radiation synovectomy using this agent. Of the 13 patients who were evaluated 1 year later, 54% (7 knees) had good results, 31% (4 knees) had fair results, and 15% (2 knees) had poor results. The initial lack of significant benefit from radiation synovectomy did not appear to preclude a favorable response to a second injection.

  16. The role of opioid analgesics in rheumatoid disease in the elderly population.

    PubMed

    Griessinger, Norbert; Sittl, Reinhard; Jost, Robert; Schaefer, Michael; Likar, Rudolf

    2003-01-01

    Adequate pain therapy is an important aspect in the treatment of the elderly patient with rheumatoid disease. Problems with traditional NSAIDs include potentially serious gastrointestinal, cardiovascular and renal adverse effects, especially in the elderly. In addition, the selective cyclo-oxygenase-2 inhibitors have been associated with renal and cardiovascular adverse effects which may limit their use in the elderly with renal or cardiovascular disease. Opioids provide a treatment option for the management of pain in elderly patients with rheumatoid disease in whom pain control under standard management is poor; however, various therapeutic difficulties are encountered in the heterogeneous elderly population (increased risk of adverse effects, multimorbidity, and polypharmacy). Lower initial opioid dosage, prolonged dosage intervals and slower dosage titrations are advisable because of altered pharmacokinetics and pharmacodynamics. Kidney function should be tightly monitored and a timely use of laxatives is to be encouraged. Randomised clinical studies of opioids in musculoskeletal pain (e.g. osteoarthritis) have increasingly extended the scientific basis for their use. However, no randomised controlled clinical trials have examined the efficacy and the benefit/risk ratio of opioids in rheumatoid arthritis. Opioids also demonstrate an analgesic effect following local peripheral application. This opens the way to new therapeutic options in the future through the development of systemic peripherally selective opioids without CNS adverse effects. PMID:12795625

  17. Use of spinal manipulation in a rheumatoid patient presenting with acute thoracic pain: a case report

    PubMed Central

    Chung, Chadwick L. R.; Mior, Silvano A.

    2015-01-01

    Background: There is limited research related to spinal manipulation of uncomplicated thoracic spine pain and even less when pain is associated with comorbid conditions such as rheumatoid arthritis. In the absence of trial evidence, clinical experience and appropriate selection of the type of intervention is important to informing the appropriate management of these cases. Case presentation: We present a case of a patient with long standing rheumatoid arthritis who presented with acute thoracic pain. The patient was diagnosed with costovertebral joint dysfunction and a myofascial strain of the surrounding musculature. The patient was unresponsive to treatment involving a generalized manipulative technique; however, improved following the administration of a specific applied manipulation with modified forces. The patient was deemed recovered and discharged with ergonomic and home care recommendations. Discussion: This case demonstrates a clinical situation where there is a paucity of research to guide management, thus clinicians must rely on experience and patient preferences in the selection of an appropriate and safe therapeutic intervention. The case highlights the need to contextualize the apparent contraindication of manipulation in patients with rheumatoid arthritis and calls for further research. Finally the paper advances evidence based decision making that balances the available research, clinical experience, as well as patient preferences. PMID:26136606

  18. The recently identified hexosaminidase D enzyme substantially contributes to the elevated hexosaminidase activity in rheumatoid arthritis.

    PubMed

    Pásztói, Mária; Sódar, Barbara; Misják, Petra; Pálóczi, Krisztina; Kittel, Ágnes; Tóth, Kálmán; Wellinger, Károly; Géher, Pál; Nagy, György; Lakatos, Tamás; Falus, András; Buzás, Edit Irén

    2013-01-01

    Since the 1970s, numerous reports have described elevated hexosaminidase activities in rheumatoid arthritis. However, due to the overlapping substrate specificities of different hexosaminidases, identification of the exact enzyme(s) responsible for the elevated activity remains incomplete. In this work we tested if the recently described enzyme, hexosaminidase D was expressed in human arthritic joints, and could contribute to the elevated hexosaminidase activity in rheumatoid arthritis. Thermostable ?-d-N-acetyl-galactosaminidase (hexosaminidase D) activities were determined in synovial fluid samples, synovial membranes, synovial fibroblast cell strains and synovial fibroblast-derived extracellular vesicles of patients with rheumatoid arthritis and osteoarthritis using chromogenic substrates. Expression of the HEXDC gene was detected both in steady state and in TGF-? treated synovial fibroblasts by real time PCR. Strikingly, hexosaminidase D accounted for approximately 50% of the total ?-N-acetyl-galactosaminidase activity in synovial membranes and synovial fibroblasts, and it was responsible for the vast majority of the ?-d-N-acetyl-galactosaminidase activity in synovial fluid samples. TGF-? downregulated the expression of hexosaminidase D in synovial fibroblasts dose-dependently. Of note, significant activity of hexosaminidase D was also found in association with extracellular vesicles released by synovial fibroblasts. This first study that describes the expression and disease relevance of the HEXDC gene in humans demonstrates the expression of this novel enzyme within the joints, and suggests that its activity may significantly contribute to the overall local exoglycosidase activity. PMID:23099419

  19. Sexual function in Moroccan women with rheumatoid arthritis and its relationship with disease activity.

    PubMed

    Hari, Asmae; Rostom, Samira; Lahlou, Racha; Bahiri, Rachid; Hajjaj-Hassouni, Najia

    2015-06-01

    The objective of this study was to evaluate sexual function in women with rheumatoid arthritis (RA) using an auto-questionnaire Female Sexual Function Index (FSFI) and study its correlation with disease activity. Sixty patients with RA and 40 healthy controls were included in this exploratory study. Sociodemographic, clinical, and laboratory characteristics were assessed. The disease activity was assessed by auto-questionnaires Routine Assessment of Patient Index Data 3 (RAPID3) and Rheumatoid Arthritis Disease Activity Index 5 (RADAI5) judged by 28 DAS ESR. Sexual function was assessed by an auto-questionnaire specific for female sexuality: FSFI during the last 4 weeks. The definition of sexual dysfunction was considered by FSFI score less than or equal to 26.5. The mean age of RA patients and controls was 45.95?±?9.3 and 45.01?±?9.2, respectively. According to FSFI, the percentage of FSD in women with RA was significantly higher than that in the control group. All dimensions of sexuality were affected (desire, arousal, lubrication, orgasm, and satisfaction) except pain. The multivariate linear regression analysis indicated that the swollen joints and the RADAI5 were the independent variables of disease activity associated with sexual dysfunction in women with RA. This study suggests that sexual dysfunction among women suffering from rheumatoid arthritis is found when a targeted questionnaire is used to identify it and that the increased disease activity has a negative effect of sexual function. PMID:25677567

  20. Bacteriological and Molecular Assessment of Staphylococcal Enterotoxin E in the Blood of Patients With Rheumatoid Arthritis

    PubMed Central

    Zahiri Yeganeh, Samaneh; Ataee, Ramezan Ali; Alishiri, Gholam Hossein; Movahedi, Monireh

    2015-01-01

    Background: Rheumatoid arthritis (RA) is the most common chronic inflammatory disease of unknown etiology. In this regard, the role of bacterial superantigens (as an effective agent) were considered. Objectives: This study aimed to assess staphylococcal enterotoxin E in the blood of patients with rheumatoid arthritis. Patients and Methods: A total of 83 blood samples of patients with RA were studied. All of patient’s blood samples have been cultured. Polymerase chain reaction (PCR) and ELISA methods have been used to assess the existence of staphylococcal enterotoxin E (entE). The data were analyzed through descriptive statistics. Results: During this study and after sequential sub cultures, only 5 bacterial strains were isolated. Based on the results of biochemical tests, just one case was detected as Staphylococcus aureus. The result of molecular diagnosis of enterotoxin E gene was 13.25%. The results of ELISA were 40.96% positive for staphylococcal enterotoxin E. Conclusions: In this study, staphylococcal enterotoxin E (superantigen E) was detected in the blood of patients with RA, but its origin is unknown, because no staphylococcus enterotoxin E producer was isolated. This finding could provide a good model for the diagnosis and treatment of RA. However, the results of this study have shown some evidence regarding endogenous origin of involved superantigens in patients with rheumatoid arthritis. PMID:25793096