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Sample records for simulating early rheumatoid

  1. Preclinical lung disease in early rheumatoid arthritis.

    PubMed

    Robles-Perez, Alejandro; Luburich, Patricio; Rodriguez-Sanchon, Benigno; Dorca, Jordi; Nolla, Joan Miquel; Molina-Molina, Maria; Narvaez-Garcia, Javier

    2016-02-01

    Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels. PMID:26846584

  2. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Hirata, Shintaro; Tanaka, Yoshiya

    2015-01-01

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

  5. Factors associated with time to diagnosis in early rheumatoid arthritis.

    PubMed

    Barnabe, Cheryl; Xiong, Juan; Pope, Janet E; Boire, Gilles; Hitchon, Carol; Haraoui, Boulos; Carter Thorne, J; Tin, Diane; Keystone, Edward C; Bykerk, Vivian P

    2014-01-01

    Early diagnosis and treatment yield optimal outcomes in rheumatoid arthritis (RA); thus, barriers to disease recognition must be identified and addressed. We determined the impact of sociodemographic factors, medical comorbidities, family history, and disease severity at onset on the time to diagnosis in early RA. The Canadian early ArThritis CoHort study data on 1,142 early RA patients were analyzed for predictors of time to diagnosis using regression analysis. Sociodemographic factors (age, sex, income strata, education, ethnicity), measures of disease activity (joint counts, DAS28 score, acute-phase reactants, patient global evaluation, function), family history, serology, chronic musculoskeletal and mental health conditions, and obesity at diagnosis were considered. In multivariate linear regression analysis, more swollen joints (β = -0.047 per joint, 95 % CI -0.085, -0.010, p = 0.014), higher erythrocyte sedimentation rate (ESR) (β = -0.012 per 1 mm/h, 95 % CI -0.022, -0.002, p = 0.0018), and worse patient global scores (β = -0.082 per 1 unit on a visual analogue scale, 95 % CI -0.158, -0.006, p = 0.034) at baseline predicted a shorter time to diagnosis. Anti-cyclic citrullinated peptide (anti-CCP) antibody positivity (β = 0.688, 95 % CI 0.261, 1.115, p = 0.002) and low income (annual <$20,000 β = 1.185, 95 % CI 0.227, 2.143, p = 0.015; annual $20,000-50,000 β = 0.933, 95 % CI 0.069, 1.798, p = 0.034) increased time to diagnosis. In the logistic regression models, the odds of being diagnosed within 6 months of symptom onset were increased for each swollen joint present [odds ratio (OR) 1.04, 95 % CI 1.02-1.06 per joint], each 1 mm/h elevation in the ESR (OR 1.01, 95 % CI 1.00-1.02), and decreased for patients who were either rheumatoid factor or anti-CCP positive compared to both factors being negative (OR 0.68, 95 % CI 0.51-0.91). Higher disease activity results in a more rapid diagnosis for Canadian patients with early RA, but those with lower income have delays in diagnosis. Strategies to identify patients with a less severe disease presentation and in lower socioeconomic strata are needed to ensure equal opportunity for optimal management. PMID:23989941

  6. Outcomes of early rheumatoid arthritis--the WHO ICF framework.

    PubMed

    Verstappen, Suzanne M M

    2013-08-01

    With the establishment of the new American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for rheumatoid arthritis (RA) to diagnose patients earlier and with the introduction of early and aggressive treatment, the current aim is remission resulting in less functional disability, halting of radiographic damage, less pain, less fatigue and no loss of employment. These outcomes can be related to the World Health Organization International Classification of Functioning, Disability and Health (the WHO ICF framework). This framework includes the component body functions, body structures, activities and participation related to the disease. These components are related to each other in a bidirectional way and can be influenced by contextual factors including environmental and personal factors. This framework can be used to describe trends in RA outcomes and the impact of contextual factors on these outcomes. Despite aggressive treatment strategies, patients with RA still experience loss of function, pain and fatigue, and a relatively high proportion of patients have to take sick leave or become work disabled within the first few years of the disease. There is evidence that more stringent definitions of remission lead to greater improvement of outcomes and that the aim should be sustained remission and not just remission. There is, however, a need for a better understanding of the relation between contextual factors and activity and participation outcomes to better guide therapy decisions by rheumatologists and provide information to patients, families and policymakers about the impact of RA on their lives and to the society. The overall aim of this overview is to highlight the important contextual factors and consequences that relate to outcomes typically measured in RA studies and to demonstrate the additional benefits that can be achieved with remission and sustained remission. PMID:24315054

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

    PubMed

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

    2014-02-01

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

  8. 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 36 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

  9. Isoprinosine in the early pre-erosive stage of rheumatoid arthritis: a pilot study.

    PubMed

    Sadowska-Wróblewska, M; Wróblewska-Graff, T; Weryńska-Przybylska, J; Rell-Bakalarska, M; Kurdybacha, J

    1988-01-01

    The etiology of rheumatoid arthritis is unknown. Virus infection is one of alleged factors initiating the disease process. In view of this, the authors undertook a trial of administration of an antiviral and immunostimulating preparation - isoprinosine, given in the early phase of the disease prior to the development of erosions. Isoprinosine was given to ten seropositive cases of rheumatoid arthritis (two males, eight females) aged 34-61 years, with disease duration from 6 months to 5 years treated previously only with non-steroidal anti-inflammatory drugs. Isoprinosine was administered for 4 weeks (2 weeks of 3.0 g daily and 2 weeks of 1.5 g daily). After the treatment, a statistically significant reduction was observed in the number of joints painful on pressure, the number of swollen joints, and the duration of morning stiffness. The grip strength of the left hand was increased. The ESR and serum uric acid level were not changed significantly. The titre of Waaler-Rose reaction in four patients was decreased, in two it was increased, and in four it remained unchanged. No side effects were observed during the treatment. In the light of these observations it seems worthwhile to continue further studies on the action of isoprinosine in early rheumatoid arthritis. PMID:2455393

  10. A prospective study of the radiological changes in the cervical spine in early rheumatoid disease.

    PubMed Central

    Winfield, J; Cooke, D; Brook, A S; Corbett, M

    1981-01-01

    The cervical spine radiographs of 100 patients with early rheumatoid disease were studied annually, on a prospective basis, for a mean follow-up period of 7 years 2 months. Atlantoaxial subluxation developed in 12 patients. The subluxation was more frequent in females, more severe in patients with progressive, seropositive, erosive rheumatoid disease, and more marked in patients treated with oral corticosteroids. Subaxial subluxation, affecting upper cervical disc levels, occurred in a further 20 patients. Three patients developed vertical subluxation. The mobility of the cervical spine affects the degree of subluxation achieved, and when assessing serial films for subluxation it may be necessary to measure the cervical spine flexion before deciding whether subluxation has progressed or not. Over 80% of the patients with subluxation developed the first evidence of subluxation within 2 years of disease onset. Subluxation in the cervical spine is not, therefore, a late complication of rheumatoid disease. During the follow-up period none of the patients developed neurological signs. PMID:7224682

  11. Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1β and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis. PMID:20961415

  12. [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

  13. 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 19.549%) of RA patients and ACR remission in 15.2% (range 8.520.6%). 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

  14. Induction therapy with combination TNF inhibitor and methotrexate in early rheumatoid arthritis.

    PubMed

    Hwang, Yong Gil; Moreland, Larry W

    2014-05-01

    With the introduction of more objective disease activity measures and the development of biological therapies, there were dramatic changes in the treatment of rheumatoid arthritis (RA). The combination therapy with tumor necrosis factor (TNF) inhibitor and methotrexate (MTX) has unprecedentedly improved prognosis and outcomes, and very low disease activity or remission has been achievable goal in RA. Although the concept of remission induction and maintenance was first discussed in longstanding RA patients, several clinical trials have demonstrated that there is a therapeutic window of opportunity, and early effective control of inflammation in early RA could lead to less joint damage and better long-term outcomes. Emerging evidence suggests that early combination therapy with TNF inhibitor and MTX leads to rapid clinical remission and thereby improved quality of life. Furthermore, remission status may be sustained in some patients even if a TNF inhibitor is discontinued after sustained remission in early RA patients. While there are many potential benefits of early remission induction therapy with the combination of a TNF inhibitor and MTX, the best therapeutic regimen and strategy for remission induction and maintenance in early RA remain controversial. There are no data to decide a priori when and in whom TNF blocker drugs are indicated in early disease-modifying anti-rheumatic drug (DMARD)-nave RA. PMID:24619653

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

    PubMed Central

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

    2012-01-01

    Objective To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA). Methods The Early Rheumatoid Arthritis Network (ERAN) database was used for analysis of baseline and 1-year pain data. The ERAN is a hospital-based inception cohort of 1,189 people. Short Form 36 questionnaire bodily pain scores were used to calculate change in pain at 1 year as the outcome. The proportion of the Disease Activity Score in 28 joints (DAS28) attributable to patient-reported components (joint tenderness and visual analog scale score; DAS28-P) at baseline was derived as a predictor. Predictors of less improvement in pain were investigated using adjusted odds ratios (ORadj) generated by logistic regression, adjusting for 14 additional clinical and demographic covariates. Results Greater pain at baseline was associated with sex, high DAS28, worse mental health, and smoking. Most patients with early RA reported incomplete improvement in bodily pain after 1 year. The DAS28-P index did not significantly change in the patients whose disease remained active. Less improvement in pain was predicted by female sex (ORadj 3.41, 95% confidence interval [95% CI] 1.358.64) and a high DAS28-P index at baseline (ORadj for tertiles 2.09, 95% CI 1.243.55). Other conventional RA risk factors did not predict pain changes. Conclusion The factors most likely to predict less improvement in pain in early RA are female sex and a high DAS28-P index. A high DAS28-P index may reflect greater contributions of noninflammatory factors, such as central sensitization, to pain. Strategies in addition to inflammatory disease suppression may be required to adequately treat pain. PMID:22556121

  16. [Early and advanced rheumatoid arthritis. Diagnosis and state of the art therapy strategy].

    PubMed

    Wollenhaupt, J; Krüger, K

    2012-01-01

    The diagnosis of rheumatoid arthritis (RA) is often based on classification criteria. In 2010 ACR and EULAR presented new classification criteria for RA which allow patients with a high risk for persistent, chronic and erosive arthritis and therefore fulfill the current definition of RA, to be defined. Therapy of RA should be initiated as early as possible. Methotrexate remains the first-line therapy of RA. In patients showing insufficient response of RA, biological agents have been demonstrated to be an effective second-line therapy. It is essential to define and follow an individual treatment target to obtain remission or low disease activity. This target should be reassessed regularly and treatment should be correspondingly adapted to achieve the target. PMID:22286356

  17. 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 99.600.07%. Our optimized matrix mini-tablets-filled-capsule formulation F30 released lornoxicam after a lag time of 5.020.92 hr, 95.480.65 % at the end of 8 hr and 99.900.83 % 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

  18. 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 (19972008) 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

  19. Insulin resistance and levels of adipokines in patients with untreated early rheumatoid arthritis.

    PubMed

    Manrique-Arija, Sara; Urea, Inmaculada; Valdivielso, Pedro; Rioja, Jos; Jimnez-Nez, Francisco G; Irigoyen, Mara V; Fernndez-Nebro, Antonio

    2016-01-01

    The aim of this study is to investigate the presence of insulin resistance (IR) in patients with untreated early rheumatoid arthritis (ERA) and its relationship with adipokines, inflammatory cytokines, and treatment. In this prospective study, we enrolled 46 ERA patients with a disease duration of <1year, and 45 sex-, age-, race-, and body mass index (BMI)-matched controls. Patients and controls with diabetes or a history of glucocorticoid (GC) or disease-modifying antirheumatic drugs (DMARDs) use were excluded. Patients were assessed at the time of diagnosis (visit 1) and after 6months of treatment (visit 2). The main outcomes were homeostatic model assessment of IR (HOMA-IR) and ?-cell function (HOMA-?) and quantitative insulin sensitivity check index (QUICKI). A multivariate regression analysis was performed to analyze IR adjusting according to lipids, body composition, physical activity, nutrition, and inflammatory cytokine and adipokine levels. The baseline HOMA-IR, HOMA-?, and QUICKI values were similar in both groups. However, patients showed lower levels of physical activity, total cholesterol, and high-density lipoprotein. Moreover, the inflammatory cytokines and resistin concentrations were higher in patients than controls. Multivariate analysis indicated that BMI and baseline rheumatoid factor levels were positively associated with HOMA-IR and HOMA-?, and negatively with QUICKI. After DMARD treatment, patients showed improvements in inflammatory parameters and lipids whereas IR remained stable. Furthermore, adiponectin and resistin concentrations decreased slightly. Our data suggest that IR is not present in ERA patients either at diagnosis or at 6months after treatment. However, symptom duration and fat mass appear to be related. PMID:26526677

  20. Magnetic resonance imaging in early rheumatoid arthritis: a multicenter, prospective study.

    PubMed

    Li, Ru; Liu, Xia; Ye, Hua; Yao, Hai-Hong; Guo, Jia-Long; Li, Guang-Tao; Li, Xing-Fu; Xue, Yu; Zhao, Jin-Xia; Gu, Fei; Zou, Qing-Hua; Chen, Li-Na; Bi, Li-Qi; Zhang, Zhuo-Li; Zou, He-Jian; Liu, Xiang-Yuan; Sun, Ling-Yun; Fang, Yong-Fei; Zhu, Ping; Su, Yin; Li, Zhan-Guo

    2016-02-01

    To identify the magnetic resonance imaging (MRI) features of hands and wrists in early rheumatoid arthritis (RA). A total of 129 early arthritis patients (?1year) were enrolled in the study. At presentation, MRI of the hands was performed, with clinical and laboratory analyses. After a 1-year follow-up, clinical diagnosis of early RA or non-RA was confirmed by two rheumatologists. The characteristics of MRI variables at baseline in RA patients not fulfilling ACR 1987 criteria [RA-87(-)] were compared with those fulfilling ACR1987 criteria [RA-87(+)] and non-RA. In the 129 early arthritis patients, 90 were diagnosed with RA in a 1-year follow-up. There were 47.8% (43/90) of the RA patients not fulfilling ACR 1987 criteria [RA-87(-)]. The scores of synovitis in RA-87(-) patients were similar with those in RA-87(+) [Synovitis score, 14.0 (IQR, 4.0-25.0) vs. 14.0 (IQR, 10.0-25.0), p?>?0.05]. Compared with those in non-RA, RA-87(-) patients had higher synovitis scores and occurrence of synovitis in proximal interphalangeal (PIP) joints [synovitis score, 14.0 (IQR, 4.0-25.0) vs. 6.0 (IQR, 2.0-14.5), p?=?0.046; occurrence of PIP synovitis: 53.5 vs. 27.3%, p?=?0.02]. There was no significant difference of bone marrow edema, bone erosion, and tenosynovitis between RA-87(-) and non-RA. Synovitis in PIP joints was independent predictor for RA-87(-) [OR, 3.1 (95%CI 1.2-8.1)]. High synovitis scores and synovitis in PIP joints on MRI were important in early RA, especially those not fulfilling ACR 1987 criteria. PMID:26781784

  1. [Combined step-by-step rehabilitation of the patients presenting with early-onset rheumatoid arthritis].

    PubMed

    Orlova, E V; Karateev, D E; Kochetkov, A V; Denisov, L N; Surnov, A V

    2013-01-01

    The objective of the present study was to develop the program for combined step-by-step rehabilitation of the patients presenting with early-onset rheumatoid arthritis (RA); the secondary objective was to estimate the effectiveness of this program. A total of 34 patients were recruited for the participation in the study. They received medicamental therapy in combination with the rehabilitative treatment during 6 months. The hospital-based treatment included therapeutic exercises for large joints under the supervision of a specialist (45 min), occupational therapy (45 min), local aerial cryotherapy of wrist, knee, and ankle joints (10 sessions 15 min each at a temperature of -60 degrees C), ortheses, and the educational program (4 daily studies 90 min each). The outpatient and home-based treatment included therapeutic exercises for large joints (45 min), wrist exercises (45 min) three times every week, ortheses. 26 patients received only medicamental therapy (control group). The following characteristics were measured: the average power of extension of knee joints and of flexion of ankle joints (by means of En-TreeM analysis of movements), wrist grip strength, articular pain (100 mm VAS, DAS28, HAQ, RAPID3 indices). The rehabilitative program ensured excellent compliance with basal therapy, reduced requirements for symptomatic medicines, and improved adherence to the methods for the formation of the correct movement patterns, orthesis wearing, and regular therapeutic exercises. The rehabilitative treatment resulted in the relief of articular pain by 70.4% (p < 0.01), decrease of DAS28 by 31.9% (p < 0.05), HAQ by 75.8% (p < 0.01), and RAPID3 by 60.1% (p < 0.01). The grip strength of the more seriously injured wrist increased by 44.9% (p < 0.05) and that of the less damaged one by 31.3% (p < 0.05). The average extension power of the weaker knee joint increased by 88.7% (p < 0.01) and that of the stronger joint by 67.7% (p < 0.01). The average flexion power of the more seriously injured ankle joint increased by 81.6% (p < 0.01) and that of the less damaged one by 70.2% (p < 0.01). The two groups were significantly different in terms of the majority of characteristics evaluated. It is concluded that the combined rehabilitative treatment helps to control the activity of the disease, enhances the functional abilities, improves the locomotor activity and quality of life of the patients with early-onset rheumatoid arthritis. PMID:23520927

  2. 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

  3. 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, Dsire; 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 1.94.6% 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 0.710.81 and 0.690.78 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

  4. 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

  5. Rheumatoid Arthritis

    MedlinePLUS

    MENU Return to Web version Rheumatoid Arthritis Overview What is rheumatoid arthritis? Rheumatoid (say: "roo-mah-toyd") arthritis (RA) is an autoimmune disease that causes inflammation and pain in ...

  6. Aggressive rheumatoid arthritis registry in Italy. Characteristics of the early rheumatoid arthritis subtype among patients classified according to the ACR criteria.

    PubMed

    2003-01-01

    The Italian Society of Rheumatology in the year 2000 decided to sponsor the creation of a data base (Registry) of consecutive patients who fulfilled the diagnosis of rheumatoid arthritis (RA) according to the American College of Rheumatology (ACR) criteria. The registry is designed to collect data on the "aggressive" type of RA all over the country in order to determine the percentage of patients who satisfy the established criteria among incident cases of RA and to define the therapeutic approach according to the characteristics of the enrolled patients. Predefined criteria set up by eight recognized opinion leaders on the disease were used by all the centers to create the database. The GIARA registry (Gruppo Italiano Artrite Reumatoide Aggressiva) has now enrolled 706 patients who will be followed up for 24 months. They have been divided into two major subsets--patients with early (< 4 months' disease duration) and late (> 4 months) RA--with the aim of establishing whether differences in clinical, serological, radiographic and therapeutic (DMARDs: disease modifying antirheumatic drugs) parameters may distinguish the two subsets. The major conclusion of this preliminary analysis is that an overall tendency to undertreatment is discernable. PMID:14969064

  7. Comparison of haplotyping methods using families and unrelated individuals on simulated rheumatoid arthritis data.

    PubMed

    Li, Xin; Li, Jing

    2007-01-01

    In this report, we compared haplotyping approaches using families and unrelated individuals on the simulated rheumatoid arthritis (RA) data in Problem 3 from Genetic Analysis Workshop (GAW) 15. To investigate these two approaches, we picked two representative programs: PedPhase and fastPHASE, respectively, for each approach. PedPhase is a rule-based method focusing on the haplotyping constraints within each pedigree and solving them using integer linear programming. fastPHASE is a statistical method based on the clustering property of haplotypes in a population over short regions. It is believed that with family information, one can obtain more accurate phasing results with considerably more cost for genotyping additional family members. Our results indicate that, though only relying on the constraints within each family (with four members) individually, PedPhase has better phasing accuracy than fastPHASE, even when the total numbers of genotyped individuals are the same. But for missing genotype imputation, fastPHASE performs better than PedPhase by taking population information into consideration. The relative influence of family constraints and population information on haplotyping accuracy as shown in this report provides some empirical bases on assessing the trade-off of genotyping family data under different settings. PMID:18466555

  8. Comparison of haplotyping methods using families and unrelated individuals on simulated rheumatoid arthritis data

    PubMed Central

    Li, Xin; Li, Jing

    2007-01-01

    In this report, we compared haplotyping approaches using families and unrelated individuals on the simulated rheumatoid arthritis (RA) data in Problem 3 from Genetic Analysis Workshop (GAW) 15. To investigate these two approaches, we picked two representative programs: PedPhase and fastPHASE, respectively, for each approach. PedPhase is a rule-based method focusing on the haplotyping constraints within each pedigree and solving them using integer linear programming. fastPHASE is a statistical method based on the clustering property of haplotypes in a population over short regions. It is believed that with family information, one can obtain more accurate phasing results with considerably more cost for genotyping additional family members. Our results indicate that, though only relying on the constraints within each family (with four members) individually, PedPhase has better phasing accuracy than fastPHASE, even when the total numbers of genotyped individuals are the same. But for missing genotype imputation, fastPHASE performs better than PedPhase by taking population information into consideration. The relative influence of family constraints and population information on haplotyping accuracy as shown in this report provides some empirical bases on assessing the trade-off of genotyping family data under different settings. PMID:18466555

  9. Rheumatoid Nodules.

    PubMed

    Tilstra, Jeremy S; Lienesch, Douglas W

    2015-07-01

    Rheumatoid nodules are a common manifestation of rheumatoid arthritis. These lesions are often easily identified based on typical diagnostic features and characteristic locations. When biopsied, nodules have a characteristic histologic appearance. Uncommonly, rheumatoid nodules can occur in systemic locations. There is no evidence that systemic therapy treats underlying rheumatoid nodules. Paradoxically, methotrexate and possibly tumor necrosis factor inhibitors can increase nodule development. Treatment of rheumatoid nodules is often not necessary, unless patients are experiencing pain or there is interference of mechanical function. This review outlines the available data on and associations of rheumatoid nodules. PMID:26143419

  10. 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 ...

  11. Rheumatoid Vasculitis

    MedlinePLUS

    ... Hypocomplementemia, anti-nuclear antibodies (ANA), and atypical anti-neutrophil cytoplasmic antibodies (ANCA) are common. Rheumatoid factor levels ... Hypocomplementemia, anti-nuclear antibodies (ANAs), and atypical anti-neutrophil cytoplasmic antibodies (atypical ANCAs) are common. Rheumatoid factor ...

  12. Radiographic Structural Damage Is Worse in the Dominant than the Non-Dominant Hand in Individuals with Early Rheumatoid Arthritis

    PubMed Central

    Koh, Jung Hee; Jung, Seung Min; Lee, Jennifer Jooha; Kang, Kwi Young; Kwok, Seung-Ki; Park, Sung-Hwan; Ju, Ji Hyeon

    2015-01-01

    Objective The relationship between mechanical stress and radiographic progression in rheumatoid arthritis (RA) is unclear. The assumption is that mechanical stress is greater in the dominant hand. Therefore, the aim of the present study was to compare the presence and progression of erosions and joint space narrowing (JSN) in the dominant and non-dominant hand. Methods Data from 194 patients recently diagnosed with seropositive RA, and with hand radiographs taken at the time of diagnosis and at 2-year follow-up, were analyzed retrospectively. Radiographs were scored using the van der Heijde-modified Sharp Score (HSS) method. Each joint group within each hand was rated separately by two independent examiners in a double-blinded manner. Results One hundred and ninety-four patients were enrolled (80% female, 88% positive rheumatoid factor, 92% positive anti-citrullinated protein antibody, and 95.4% right-handed). The baseline, follow-up erosion and JSN HSS were significantly higher in the dominant hand than in the non-dominant hand. The annual rate of radiographic progression was also higher in the dominant hand. The erosive progression in the wrist joints varied significantly according to handedness, but the erosion in the proximal interphalangeal joints and metacarpophalangeal joints was similar in both hands. The radiographic progression was associated with the dominant hand, an abnormal baseline C-reactive protein level, and joint damage at baseline. There was no significant difference in bone mineral density between the right and left hands. Conclusion Radiological damage was worse and progressed faster in the dominant hand, suggesting that mechanical stress is associated with radiographic joint damage in early and active RA. PMID:26247204

  13. From desk to bed: Computational simulations provide indication for rheumatoid arthritis clinical trials

    PubMed Central

    2013-01-01

    Background Rheumatoid arthritis (RA) is among the most common human systemic autoimmune diseases, affecting approximately 1% of the population worldwide. To date, there is no cure for the disease and current treatments show undesirable side effects. As the disease affects a growing number of individuals, and during their working age, the gathering of all information able to improve therapies -by understanding their and the disease mechanisms of action- represents an important area of research, benefiting not only patients but also societies. In this direction, network analysis methods have been used in previous work to further our understanding of this complex disease, leading to the identification of CRKL as a potential drug target for treatment of RA. Here, we use computational methods to expand on this work, testing the hypothesis in silico. Results Analysis of the CRKL network -available at http://www.picb.ac.cn/ClinicalGenomicNTW/software.html- allows for investigation of the potential effect of perturbing genes of interest. Within the group of genes that are significantly affected by simulated perturbation of CRKL, we are lead to further investigate the importance of PXN. Our results allow us to (1) refine the hypothesis on CRKL as a novel drug target (2) indicate potential causes of side effects in on-going trials and (3) importantly, provide recommendations with impact on on-going clinical studies. Conclusions Based on a virtual network that collects and connects a large number of the molecules known to be involved in a disease, one can simulate the effects of controlling molecules, allowing for the observation of how this affects the rest of the network. This is important to mimic the effect of a drug, but also to be aware of -and possibly control- its side effects. Using this approach in RA research we have been able to contribute to the field by suggesting molecules to be targeted in new therapies and more importantly, to warrant efficacy, to hypothesise novel recommendations on existing drugs currently under test. PMID:23339423

  14. 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) nave 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 1263% 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

  15. Rheumatoid lung disease

    MedlinePLUS

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

  16. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    2010-01-01

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

  19. 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, Ren; 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

  20. Motivations for inadequate persistence with disease modifying anti-rheumatic drugs in early rheumatoid arthritis: the patients perspective

    PubMed Central

    2013-01-01

    Background Knowledge of factors that contribute to non-persistence with disease modifying anti-rheumatic drugs (NP) is essential to improve rheumatoid arthritis (RA) outcomes. Aims of the study were to investigate patients motivations and risk factors for NP in a cohort of early RA patients. Methods Up to September 2012, data from 149 patients, who had at least 1year of follow-up, at least one drug indication, and at least 2 consecutive six-months-apart rheumatic evaluations that included assessment of compliance were reviewed. NP and patients motivations of NP were evaluated according to a questionnaire. NP was defined when patients referred that they had completely stop RA medication, Sometimes, Almost always or Always. Patients had to pay for their medication. Descriptive statistics and logistic regression models were used. Statistical significance was set at a p value of less than 0.05. The study was approved by the internal review board. Results Up to cut-off, 715 questionnaires were applied to 149 patients, who had follow-up of 58.7??27.9months and were indicated 2.4??0.7 DMARDs/patient/follow-up. Patients were most frequently female (88.6%), middle-aged ([mean??SD] age of 38.5??12.8years) with lower-middle/lower socio-economic status (87.9%) and scholarship of 11??3.9years. Ninety-nine (66.4%) patients were NP and filled 330 questionnaires. Multivariate analysis showed that years of formal education (OR: 1.12, 95% CI: 1.1-1.24, p?=?0.03), perception of at least some difficulty to find arthritis medication (OR: 5.68, 95% CI: 2.48-13, p?=?0.000) and perception that arthritis medication is expensive (OR: 5.27, 95% CI: 2.1-13.84, p?=?0.001) at the first evaluation of patients compliance were all predictors of NP. Among the 99 NP patients, 25 (25.3%) were recurrent-NP and accumulated more disease activity. The combination of both reasons of NP (Because it was not available at the drugstore and Because the medication is very expensive) when selected at the first evaluation of compliance was the only variable to predict recurrent NP, OR: 4.8, 95% CI: 1.1-20.8, p?=?0.04. Conclusions Health systems should provide (first line) treatment for RA as a strategy to improve compliance with therapy and clinical outcomes, particularly in vulnerable populations. PMID:24289729

  1. Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of Developing Rheumatoid Arthritis and in Early Arthritis Patients

    PubMed Central

    Newsum, Elize C.; Maijer, Karen I.; van de Sande, Marleen G. H.; Ramwadhdoebe, Tamara H.; van Schaardenburg, Dirkjan; van Baarsen, Lisa G. M.; Korotkova, Marina; Gerlag, Danielle M.; Tak, Paul-Peter; Jakobsson, Per-Johan

    2015-01-01

    Objective Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA). A major pathway involved in pain is the prostaglandin (PG) E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients. Methods Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) with arthralgia (n=15) and/or a positive family history of RA (n=8), who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug nave) who after 2 years follow up fulfilled classification criteria for RA (n=63), spondyloarthritis (SpA; n=14), or had unclassified arthritis (UA; n=27). In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH). Results In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals). However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients. Conclusion Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease. PMID:26225917

  2. Rheumatoid Arthritis

    MedlinePLUS

    ... and support programs. In recent years, research has led to a new understanding of rheumatoid arthritis and has increased the likelihood that, in time, researchers will find even better ways to treat the disease. home | health topics A-Z | videos A-Z | training | ...

  3. Rheumatoid arthritis

    MedlinePLUS

    ... that often help in the diagnosis are: Rheumatoid factor Anti-CCP antibody Other tests that may be done include: Complete blood count C-reactive protein Erythrocyte sedimentation rate Joint ultrasound or MRI Joint x-rays Synovial fluid analysis

  4. 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

  5. Emotions related to participation restrictions as experienced by patients with early rheumatoid arthritis: a qualitative interview study (the Swedish TIRA project).

    PubMed

    Östlund, Gunnel; Björk, Mathilda; Thyberg, Ingrid; Thyberg, Mikael; Valtersson, Eva; Stenström, Birgitta; Sverker, Annette

    2014-01-01

    Psychological distress is a well-known complication in rheumatoid arthritis (RA), but knowledge regarding emotions and their relationship to participation restrictions is scarce. The objective of the study was to explore emotions related to participation restrictions by patients with early RA. In this study, 48 patients with early RA, aged 20-63 years, were interviewed about participation restrictions using the critical incident technique. Information from transcribed interviews was converted into dilemmas and linked to International Classification of Functioning, Disability, and Health (ICF) participation codes. The emotions described were condensed and categorized. Hopelessness and sadness were described when trying to perform daily activities such as getting up in the mornings and getting dressed, or not being able to perform duties at work. Sadness was experienced in relation to not being able to continue leisure activities or care for children. Examples of fear descriptions were found in relation to deteriorating health and fumble fear, which made the individual withdraw from activities as a result of mistrusting the body. Anger and irritation were described in relation to domestic and employed work but also in social relations where the individual felt unable to continue valued activities. Shame or embarrassment was described when participation restrictions became visible in public. Feelings of grief, aggressiveness, fear, and shame are emotions closely related to participation restrictions in everyday life in early RA. Emotions related to disability need to be addressed both in clinical settings in order to optimize rehabilitative multi-professional interventions and in research to achieve further knowledge. PMID:24838364

  6. Changes in the anticitrullinated peptide antibody response in relation to therapeutic outcome in early rheumatoid arthritis: results from the SWEFOT trial

    PubMed Central

    Kastbom, Alf; Forslind, Kristina; Ernestam, Sofia; Geborek, Pierre; Petersson, Ingemar F; Saevarsdottir, Saedis; Klareskog, Lars; van Vollenhoven, Ronald F; Lundberg, Karin

    2016-01-01

    Objective To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA). Methods Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and ?-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24?months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression. Results During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three?months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression. Conclusions The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA. Trial registration number WHO database at the Karolinska institute: CT20080004; and clinicaltrials.gov: NCT00764725. PMID:25550338

  7. Current Therapy of Rheumatoid Arthritis

    PubMed Central

    Kamin, Edward J.; Multz, Carter V.

    1969-01-01

    The well informed and well motivated patient with rheumatoid arthritis today has an excellent chance of avoiding serious disability and deformity. No available pharmacologic agent can permanently alter the course of the disease, and no pharmacologic agent can preclude the need for a balanced program emphasizing moderation, rest and constant attention to physical therapy. Early synovectomy is enjoying increasing popularity although the long-term benefits have yet to be established. The several drugs now undergoing trial hold little promise of materially altering the management of rheumatoid arthritis in the near future. The skills of physician, surgeon, and physiatrist must be brought to bear to provide optimal care. PMID:4883503

  8. IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anticitrullinated peptide antibody-negative rheumatoid arthritis

    PubMed Central

    Anderson, Amy E; Pratt, Arthur G; Sedhom, Mamdouh A K; Doran, John Paul; Routledge, Christine; Hargreaves, Ben; Brown, Philip M; L Cao, Kim-Anh; Isaacs, John D; Thomas, Ranjeny

    2016-01-01

    Objectives A previously identified signal transduction and activator of transcription-3 (STAT3) target-enriched gene signature in circulating CD4+ T cells of patients with early rheumatoid arthritis (RA) was prominent in autoantibody-negative individuals. Here, interleukin (IL)-6-mediated STAT signalling was investigated in circulating lymphocytes of an independent early arthritis patient cohort, seeking further insight into RA pathogenesis and biomarkers of potential clinical utility. Methods Constitutive and IL-6-induced expression of phosphorylated STAT1 (pSTAT1) and pSTAT3 was determined in T and B cells using Phosflow cytometric analysis in patients with RA and controls. Contemporaneous levels of serum cytokines were measured by immunoassay. Induced gene expression was measured in cultured CD4+T cells by quantitative real-time PCR. Results Among circulating lymphocytes of 187 patients with early arthritis, constitutive pSTAT3 correlated with serum IL-6 levels maximally in CD4+ T cells. Increased constitutive pSTAT3, but not pSTAT1, was observed in circulating CD4+ T cells of patients with early anticitrullinated peptide autoantibody (ACPA)-negative RA compared with disease controls, and these levels decreased alongside markers of disease activity with IL-6R-targeted treatment. Among patients presenting with seronegative undifferentiated arthritis (UA) the ratio of constitutive pSTAT3:pSTAT1 in CD4+ T cells contributed substantially to an algorithm for predicting progression to classifiable RA during a median of 20 months follow-up (area under receiver operator characteristic curve=0.84; p<0.001). Conclusions Our findings support a particular role for IL-6-driven CD4+ T cell activation via STAT3 during the induction of RA, particularly as a feature of ACPA-negative disease. CD4+ T cell pSTAT measurements show promise as biomarkers of UARA progression and now require independent validation. PMID:25649145

  9. [Rheumatoid arthritis].

    PubMed

    Kameda, Hideto; Takeuchi, Tsutomu

    2009-03-01

    Pathogenesis of rheumatoid arthritis is likely to implicate anti-citrullinated protein/ peptide antibody(ACPA) and an immunodistortion including abnormal T cell subpopulation. Based on above and other recent findings, new biological agents targeted to inflammatory cytokines such as tocilizumab, activated T cells (abatacept) or B cells (ocrelizumab), as well as new small molecule drugs such as JAK3 inhibitor, are sure to further facilitate remission without impaired activity of daily life in patients with RA. The contribution of Japanese physician-scientists to the progress in rheumatology has been significant as described in this review, and it must be increasingly greater in the near future. PMID:19280922

  10. Macrophages in rheumatoid arthritis

    PubMed Central

    Kinne, Raimund W; Bruer, Rolf; Stuhlmller, Bruno; Palombo-Kinne, Ernesta; Burmester, Gerd-R

    2000-01-01

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

  11. Simulation models of early visual processes

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  12. 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 20.324.1?g/mL, compared with 8.812.0?g/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

  13. Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

    PubMed

    Krintel, S B; Dehlendorff, C; Hetland, M L; Hørslev-Petersen, K; Andersen, K K; Junker, P; Pødenphant, J; Ellingsen, T; Ahlquist, P; Lindegaard, H M; Linauskas, A; Schlemmer, A; Dam, M Y; Hansen, I; Horn, H C; Jørgensen, A; Raun, J; Ammitzbøll, C G; Østergaard, M; Stengaard-Pedersen, K; Johansen, J S

    2016-04-01

    At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed. PMID:25939484

  14. Tissue-derived macromolecules and markers of inflammation in serum in early rheumatoid arthritis: relationship to development of joint destruction in hands and feet.

    PubMed

    Fex, E; Eberhardt, K; Saxne, T

    1997-11-01

    We have previously shown that serum concentrations of cartilage oligomeric matrix protein (COMP) are increased early in rheumatoid arthritis (RA) patients who subsequently develop advanced large-joint destruction. A prognostic value for joint damage of serum concentrations of hyaluronan (HA) is also suggested by previous studies. In contrast, serum concentrations of bone sialoprotein (BSP) have not been useful for identifying patients with progressive large-joint destruction. In the present study, we have examined the hypothesis that serum concentrations of these tissue-derived markers are of prognostic value in RA for the development of radiographically detectable joint damage in hands and feet. Serum concentrations of COMP, HA and BSP were quantified in samples obtained from 62 patients within the first year after onset of RA and were related to the development of radiographically detectable damage in these joints after 5 yr. Neither the serum concentrations of COMP nor of BSP at inclusion predicted joint damage in hands and feet after 5 yr, and the concentration of these proteins did not change over the 5 yr period. However, the serum concentration of HA at inclusion correlated with the radiographic score at the 5 yr follow-up (r = 0.425, P < 0.01), but was not a better predictor in this respect than the erythrocyte sedimentation rate or C-reactive protein levels at inclusion. Thus, serum concentrations of the three studied tissue-derived macromolecules were in this study not useful for identifying patients prone to small-joint destruction. PMID:9402859

  15. 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.

  16. Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study

    PubMed Central

    Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Miyasaka, Nobuyuki; Mukai, Masaya; Matsubara, Tsukasa; Uchida, Shoji; Akama, Hideto; Kupper, Hartmut; Arora, Vipin; Tanaka, Yoshiya

    2014-01-01

    Objectives To evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics. Methods This randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26. Results A total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed. Conclusions Adalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity. PMID:23316080

  17. 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

  18. Estimating the monetary value of the annual productivity gained in patients with early rheumatoid arthritis receiving etanercept plus methotrexate: interim results from the PRIZE study

    PubMed Central

    Zhang, Wei; Bansback, Nick; Sun, Huiying; Pedersen, Ronald; Kotak, Sameer; Anis, Aslam H

    2015-01-01

    Objective To measure and value the impact of combined etanercept (ETN) and methotrexate (MTX) therapy on work productivity in patients with early rheumatoid arthritis (RA) over 52?weeks. Methods MTX- and biological-nave patients with RA (symptom onset ?12?months; Disease Activity Score based on a 28-joint count (DAS28) >3.2) received open-label ETN50/MTX for 52?weeks. The Valuation of Lost Productivity (VOLP) questionnaire, measuring paid and unpaid work productivity impacts, was completed approximately every 13?weeks. Bootstrapping methods were used to test changes in VOLP outcomes over time. One-year productivity impacts were compared between responders (DAS28 ?3.2) at week 13 and non-responders using zero-inflated models for time loss and two-part models for total costs of lost productivity. Results 196 patients were employed at baseline and had ?1 follow-up with VOLP. Compared with baseline, at week 52, patients gained 33.4?h per 3?months in paid work and 4.2?h per week in unpaid work. Total monetary productivity gains were 1322 per 3?months. Over the 1-year period, responders gained paid (231?h) and unpaid work loss (122?h) compared with non-responders, which amounted to a gain of 3670 for responders. Conclusions This is the first clinical trial to measure and value the impact of biological treatment on all the labour input components that affect overall productivity. Combination therapy with ETN50/MTX was associated with a significant productivity gain for patients with early RA who were still observed at week 52. Over the 1-year treatment period, responders at week 13 suffered significantly less productivity loss than non-responders suggesting this gain was related to treatment response. Trial registration number ClinicalTrials.gov number NCT00913458 PMID:26535135

  19. 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 ...

  20. What Is Rheumatoid Arthritis?

    MedlinePLUS

    ... 20 Size: 9.7 MB November 2014 What Is Rheumatoid Arthritis? Fast Facts: An Easy-to-Read ... passed from parent to child) Environment Hormones. How Is Rheumatoid Arthritis Diagnosed? People can go to a ...

  1. 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; Barr, 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

  2. Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy. Methods Forty patients with early RA who failed treatment with methotrexate up to 20 mg/week for 3 months were randomised to addition of sulphasalazine and hydroxychloroquine (treatment A) or addition of infliximab (treatment B). At 3, 12 and 24 months, body composition and BMD were assessed by total-body dual-energy X-ray absorptiometry. At the same time points, leptin, adiponectin, apolipoproteins, insulin-like growth factor-1 (IGF-1) and markers of bone remodelling were analysed. Compliance to treatment was considered in the analyses. Data were analysed with a mixed, linear model. Results Patients treated with anti-TNF had a significant increase in fat mass at 2 years, 3.8 (1.6 to 5.9) kg, in contrast to patients in treatment A, 0.4 (-1.5 to 2.2) kg (P = 0.040), despite similar reduction in disease activity. Both treatment strategies prevented loss of muscle mass and bone. Leptin concentrations increased significantly in both groups at 2 years and adiponectin increased significantly at 2 years in treatment A and at 1 year in treatment B. There were no significant changes in apolipoproteins or IGF-1. The markers of bone resorption decreased at 12 months in both treatment groups with no significant difference between the treatment groups. Conclusions Infliximab therapy increased body fat mass, an effect that was not achieved with the combination of DMARDs, despite a similar reduction in disease activity, and thus seemed to be drug specific. The increase of fat mass was not associated with an exacerbated atherogenic lipid profile. Leptin and adiponectin concentrations increased in both treatment groups. The increase of adiponectin may partially explain the reduced frequency of cardiovascular diseases found when disease activity is reduced in RA. Trial registration ISRCTN39045408. PMID:20964833

  3. Relationship between time-integrated disease activity estimated by DAS28-CRP and radiographic progression of anatomical damage in patients with early rheumatoid arthritis

    PubMed Central

    2011-01-01

    Background The main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA). Methods Forty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altman's 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model. Results After 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044). Conclusions These data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA. PMID:21624120

  4. 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.

  5. Rheumatoid arthritis affecting temporomandibular joint

    PubMed Central

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

    2015-01-01

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

  6. Localized striated muscle vasculitis in rheumatoid arthritis.

    PubMed

    Ali, Zarmeena; Ranganathan, Prabha; Perry, Arie; Gelbart, Michael

    2007-02-01

    Rheumatoid arthritis (RA) is one of the most prevalent connective tissue diseases and can be complicated by vasculitis with systemic manifestations. Rheumatoid vasculitis can range in severity from a widespread, life-threatening disease refractory to treatment to a more benign, localized disease responsive to treatment. We describe here a patient with RA who presented with bilateral calf muscle pain secondary to rheumatoid vasculitis. The patient had intractable calf muscle pain which did not respond to nonsteroidal anti-inflammatory drugs and muscle relaxants. He did not have any other manifestations of rheumatoid vasculitis such as skin ulcers, peripheral neuropathy, or gastrointestinal involvement. A thorough diagnostic work-up concluding with a muscle biopsy revealed a non-necrotizing small vessel vasculitis. The patient's symptoms responded very well to a course of steroids and he required no additional cytotoxic agents. This case illustrates that rheumatoid vasculitis can present as an isolated striated muscle vasculitis characterized by a relatively benign course and prompt resolution with the initiation of steroids. Clinicians need to be aware that such a phenomenon can exist to facilitate early recognition and appropriate treatment. PMID:17278948

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

    NASA Astrophysics Data System (ADS)

    Weber, Tobias; Thomas, Maik

    2014-05-01

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

  8. Rheumatoid vasculitis - Case report.

    PubMed

    Pecly, Inah Maria Drummond; Ocampo, Juan Felipe; Ramirez, Guillermo Pandales; de Oliveira, Hedi Marinho de Melo Guedes; Saud, Claudia Guerra Murad; Arantes, Milton Dos Reis

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease and its main manifestation is persistent synovitis affecting peripheral joints symmetrically, In spite of its destructive potential, the evolution of RA is highly variable. Some patients may have only a short-term process oligoarticular with minimum lesion, while others suffers a polyarthritis evolving with progressive and continuous involvement of other organ systems such as skin, heart, lungs, muscles and blood vessels rarely leading to rheumatoid vasculitis. The aim of this study was to describe a case of rheumatoid vasculitis a rare and severe condition. PMID:25772654

  9. 3D simulations of early blood vessel formation

    NASA Astrophysics Data System (ADS)

    Cavalli, F.; Gamba, A.; Naldi, G.; Semplice, M.; Valdembri, D.; Serini, G.

    2007-08-01

    Blood vessel networks form by spontaneous aggregation of individual cells migrating toward vascularization sites (vasculogenesis). A successful theoretical model of two-dimensional experimental vasculogenesis has been recently proposed, showing the relevance of percolation concepts and of cell cross-talk (chemotactic autocrine loop) to the understanding of this self-aggregation process. Here we study the natural 3D extension of the computational model proposed earlier, which is relevant for the investigation of the genuinely three-dimensional process of vasculogenesis in vertebrate embryos. The computational model is based on a multidimensional Burgers equation coupled with a reaction diffusion equation for a chemotactic factor and a mass conservation law. The numerical approximation of the computational model is obtained by high order relaxed schemes. Space and time discretization are performed by using TVD schemes and, respectively, IMEX schemes. Due to the computational costs of realistic simulations, we have implemented the numerical algorithm on a cluster for parallel computation. Starting from initial conditions mimicking the experimentally observed ones, numerical simulations produce network-like structures qualitatively similar to those observed in the early stages of in vivo vasculogenesis. We develop the computation of critical percolative indices as a robust measure of the network geometry as a first step towards the comparison of computational and experimental data.

  10. The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression

    PubMed Central

    Atsumi, Tatsuya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Yasuda, Shinsuke; Yamanishi, Yuji; Kita, Yasuhiko; Matsubara, Tsukasa; Iwamoto, Masahiro; Shoji, Toshiharu; Okada, Toshiyuki; Miyasaka, Nobuyuki; Koike, Takao

    2016-01-01

    Objectives To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. Methods MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. Results 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. Conclusions In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. Trial registration number (NCT01451203). PMID:26139005

  11. Genetics Home Reference: Rheumatoid arthritis

    MedlinePLUS

    ... the condition. Where can I find information about diagnosis or management of rheumatoid arthritis? These resources address the diagnosis or management of rheumatoid arthritis and may include treatment providers. ...

  12. RHEUMATOID ARTHRITIS AND ASTERCANTHA LONGIFOLIA

    PubMed Central

    Thankamma, A.

    1999-01-01

    Rheumatoid Arthritis is found to be very effective in alleviating the symptoms in the hapless victims of rheumatoid arthritis as stipulated in ashtanga hridaya. This paper deals with the role of asteracantha longifolia in the treatment of Rheumatoid arthritis. But in the initial stages the paneeya made out of kokilasha (Asteracantha longifolia) is found to be very effective in alleviating the symptoms in the hapless victims of rheumatoid arthritis as stipulated in ashtanga hridaya. This paper deals with the role of asteracantha longifolia in the treatment of Rheumatoid arthritis. PMID:22556897

  13. 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

  14. Rheumatoid arthritis pharmacotherapy and predictors of disease-modifying anti-rheumatic drug initiation in the early years of biologic use in Quebec, Canada.

    PubMed

    Roussy, Jean-Pascal; Bessette, Louis; Rahme, Elham; Bernatsky, Sasha; Lgar, Jean; Lachaine, Jean

    2013-08-20

    Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) pharmacotherapy and should be initiated promptly after RA diagnosis. We examined trends in use of traditional and biologic DMARDs, and non-DMARD treatments, among overall RA patients, and factors associated with DMARD initiation in the newly diagnosed RA. RA subjects identified with the Quebec administrative databases were followed between January 1, 2002, and December 31, 2008. DMARD use was characterized on November 1 of each year using cross-sectional analyses. For a subgroup of newly diagnosed subjects, we used multivariable logistic regressions to identify predictors of DMARD initiation within 12months of diagnosis and survival analyses to appraise time to DMARD initiation. A total of 37,399 subjects were included (65.8% ?65years; 70.5% female). The percentage of subjects using any DMARDs increased over the study period from 41.4% [95% confidence interval (CI) 40.8-42.0] to 43.3% (95% CI 42.7-43.9). Among newly diagnosed RA, being followed by a rheumatologist was the strongest predictor of DMARD initiation (odds ratio 4.31; 95% CI 3.73-4.97). Care by an internist, increasing calendar year, use of NSAIDs, corticosteroids, or opioids, and a history of hospitalization increased the likelihood of DMARD initiation. Older age, female, higher comorbidity score, number of medical visits pre-diagnosis, care by other specialists, and the use of acetaminophen were inversely associated with DMARD initiation. The probability of any DMARD initiation at 12months was 38.5%. Despite the clinical practice guideline recommendations for earlier aggressive RA management, DMARD use appears to be suboptimal in Quebec. PMID:23959574

  15. Adalimumab discontinuation in patients with early rheumatoid arthritis who were initially treated with methotrexate alone or in combination with adalimumab: 1 year outcomes of the HOPEFUL-2 study

    PubMed Central

    Tanaka, Yoshiya; Yamanaka, Hisashi; Ishiguro, Naoki; Miyasaka, Nobuyuki; Kawana, Katsuyoshi; Hiramatsu, Katsutoshi; Takeuchi, Tsutomu

    2016-01-01

    Objectives To evaluate the impact of discontinuation of adalimumab (ADA) for 1 year in Japanese patients with early rheumatoid arthritis (RA). Methods This 52-week postmarketing study, HOPEFUL-2, enrolled patients who had completed HOPEFUL-1 for early RA, in which patients received either ADA + methotrexate (MTX) or MTX alone in a 26-week randomised phase, followed by ADA+MTX in a 26-week open-label phase. Results A total of 220 patients (ADA discontinuation: 114 patients vs ADA continuation: 106 patients) were enrolled in this study. The proportion of patients with sustained low disease activity (LDA) in the ADA discontinuation group was significantly lower than that in the continuation group (80% (64/80 patients) vs 97% (71/73 patients); p=0.001); however, most patients sustained LDA in both groups. In patients with 28-joint disease activity score (DAS28)-C reactive protein ≤2.0 at week 52, the proportion of patients who achieved sustained LDA at week 104 was 93%, suggesting that DAS28 remission may be a predictor to indicate biological-free disease control in patients with early RA. The incidence of adverse events (AE) was significantly lower in the ADA discontinuation group than in the continuation group (34.2% (39/114 patients) vs 48.1% (51/106 patients); p=0.04), most notably for infection (14.9% vs 27.4%, p=0.031). Conclusions Although ADA discontinuation was associated with an increase in disease activity, a large proportion of patients maintained LDA with MTX monotherapy after ADA discontinuation. Since ADA discontinuation was associated with a lower AE incidence, physicians should weigh the risks and benefits of ADA discontinuation. Trial registration number NCT01163292. PMID:26925252

  16. 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

  17. Alcohol consumption is associated with lower self-reported disease activity and better health-related quality of life in female rheumatoid arthritis patients in Sweden: data from BARFOT, a multicenter study on early RA

    PubMed Central

    2013-01-01

    Background Earlier studies have found a positive effect of alcohol consumption, with a reduced disease activity in rheumatoid arthritis (RA). The aim of this study was to assess alcohol consumption and its association with disease activity and health related quality of life (HRQL) in Swedish RA patients. Methods Between 1992 and 2005, 2,800 adult patients were included in the BARFOT study of early RA in Sweden. In 2010 a self-completion postal questionnaire was sent to all 2,102 prevalent patients in the BARFOT study enquiring about disease severity, HRQL, and lifestyle factors. Alcohol consumption was assessed using the validated AUDIT-C questionnaire. Results A total of 1,238 out of 1,460 patients answering the questionnaire had data on alcohol consumption: 11% were non-drinkers, 67% had a non-hazardous drinking, and 21% were classified as hazardous drinkers. Women who drank alcohol reported lower disease activity and better HRQL, but there were no association between alcohol consumption and disease activity in men. For current smokers, alcohol use was only associated with fewer patient-reported swollen joints. The outcome was not affected by kind of alcohol consumed. Conclusions There was an association between alcohol consumption and both lower self-reported disease activity and higher HRQL in female, but not in male, RA patients. PMID:23879655

  18. Imaging in rheumatoid arthritis: options, uses and optimization.

    PubMed

    Grassi, Walter; Okano, Tadashi; Di Geso, Luca; Filippucci, Emilio

    2015-01-01

    Recent advances in imaging technology are dramatically changing the approach to patients with inflammatory arthritis. Conventional radiography is still the major imaging modality used to evaluate patients with rheumatoid arthritis in daily clinical practice. In the last decade, several investigations have shown the diagnostic ability of MRI and ultrasound to rectify the traditional approach to early diagnosis and disease activity monitoring. This review will summarize the options, uses and optimization of these imaging modalities with a special focus on ultrasound, which is currently the most promising tool to change the paradigms in both early diagnosis and therapy monitoring of rheumatoid arthritis. PMID:26389852

  19. Rheumatoid meningitis associated with infliximab

    PubMed Central

    Stroberg, Edana; Metting, Austin

    2016-01-01

    We present a patient who had rheumatoid meningitis while on infliximab, a tumor necrosis factor alpha (TNF-α) inhibitor, which initially presented as transient ischemic attacks. Although our patient had been stable on infliximab for several years, her neurologic symptoms improved when her infliximab was held due to active infection and then recurred after reinitiation of therapy. Rheumatoid meningitis is exceedingly rare; however, there have been several other reports of rheumatoid meningitis developing in patients on TNF-α inhibitor therapy.

  20. Oxidation in rheumatoid arthritis

    PubMed Central

    Hitchon, Carol A; El-Gabalawy, Hani S

    2004-01-01

    Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. They also serve as important intracellular signaling molecules that amplify the synovial inflammatoryproliferative response. Repetitive cycles of hypoxia and reoxygenation associated with changes in synovial perfusion are postulated to activate hypoxia-inducible factor-1? and nuclear factor-?B, two key transcription factors that are regulated by changes in cellular oxygenation and cytokine stimulation, and that in turn orchestrate the expression of a spectrum of genes critical to the persistence of synovitis. An understanding of the complex interactions involved in these pathways might allow the development of novel therapeutic strategies for rheumatoid arthritis. PMID:15535839

  1. [Rheumatoid arthritis: psychosomatic aspects].

    PubMed

    Grekhov, R A; Kharchenko, S A; Suleĭmanova, G P; Aleksandrov, A V; Zborovskiĭ, A B

    2012-01-01

    The review considers the results of studies of the psychosomatic aspects of rheumatoid arthritis (RA), which have been published in the past 5 years. In particular, there is evidence for the impact of chronic pain on the psychological status of patients with RA, for that of the disease on quality of life in the patients, their sociopsychological and interpersonal relationships; trials of the efficiency of additional treatment options for RA are given. PMID:23480004

  2. 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

  3. 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

  4. 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

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

    PubMed Central

    Fraser, Kevin J.

    1982-01-01

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

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

    ERIC Educational Resources Information Center

    van Ments, Morry

    2011-01-01

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

  7. Practicing Parenting? Effects of Computerized Infant Simulators on Teenage Attitudes toward Early Parenthood.

    ERIC Educational Resources Information Center

    Mallery, Janet G.

    2002-01-01

    Computerized infant simulators may deter early parenthood. A survey of 1,285 teenagers before and after simulation showed a significant change in some attitudes toward parenting. Males reported the strongest attitude change, while females began with more realistic understandings of parenting. Further study is needed to determine whether attitude

  8. Elevated Membrane and Soluble CD64: A Novel Marker Reflecting Altered FcγR 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 (FcγR) and IgA (FcαR) on peripheral blood monocytes were determined by flow cytometry. The monocytic FcγR function was evaluated by human IgG1 and IgG3 IC-binding and TNFα 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 FcγR function as reflected by changes in IC-binding and decreased IC-stimulated TNFα 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 FcγR 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

  9. Early genetic responses in rat vascular tissue after simulated diving.

    PubMed

    Eftedal, Ingrid; Jrgensen, Arve; Rsbjrgen, Ragnhild; Flatberg, Arnar; Brubakk, Alf O

    2012-12-18

    Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po(2)) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats (n = 8) and unexposed controls (n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 (Nr4a3), plasminogen activator inhibitor 1 (Serpine1), cytokine TWEAK receptor FN14 (Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 (Bhlhe40), and adrenomedullin (Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-? was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po(2) instigated the observed genetic reactions. PMID:23132759

  10. 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 ...

  11. Genetics Home Reference: Rheumatoid arthritis

    MedlinePLUS

    ... factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes, especially the HLA-DRB1 gene. ... HLA ; immune system ; inflammation ; inheritance ; inheritance pattern ; joint ; leukocyte ; population ; risk factors ; tissue You may find definitions ...

  12. Fatal sepsis in a patient with rheumatoid arthritis treated with etanercept.

    PubMed

    Baghai, M; Osmon, D R; Wolk, D M; Wold, L E; Haidukewych, G J; Matteson, E L

    2001-06-01

    Patients with long-standing, severe, erosive rheumatoid arthritis who have extra-articular manifestations and have undergone joint replacement surgery are at increased risk for serious infection and premature mortality. New therapies, including cytokine antagonists, hold great promise for improving the course of rheumatoid arthritis. However, they have powerful anti-inflammatory effects that may mask symptoms of serious infection. We report a case of fatal pneumococcal sepsis occurring in a 37-year-old woman with rheumatoid arthritis treated with the tumor necrosis factor antagonist etanercept and suggest management strategies for early detection and management of this complication. PMID:11393506

  13. [The comparative effectiveness of high-intensity dynamic training with the use of exercise machines and therapeutic gymnastics for the joints in the patients presenting with early rheumatoid arthritis].

    PubMed

    Orlova, E V; Karateev, D E; Kochetkov, A V; Mozhar, T E

    2013-01-01

    The objective of the present work was to compare the effectiveness of two therapeutic exercise programs for the patients presenting with early rheumatoid arthritis (RA). The study included 51 patients. Fifteen of them (group 1) were given conventional medicamental therapy in combination with high-intensity dynamic physical exercises with the use of the Enraf-Nonius training devices (45-60 min). Eighteen patients of group 2 were offered 10 sessions of remedial gymnastics for the joints (45 min each) under the guidance of an instructor that were continued under the domestic conditions (45 min each session thrice weekly for 3 months). Eighteen patients of group 3 were given medicamental therapy alone (control). The parameters estimated in the study included the mean strength of knee joint extension and ankle joint flexion measured with the use of En-TreeM devices, articular pain (100 mm BAHI), DAS28, HAQ, and RAPID3 indices. It was shown that both programs of therapeutic exercises reduced the severity of the disease, improved the functional and motor activity of the patients and their quality of life. The majority of these characteristics were significantly different from those documented in the control group (p<0.05). The clinical effectiveness of high-intensity training with the use of exercise machines was higher than without them (articular pain was reduced by 57.9% (p<0.01), DAS28 by 24.7% (p<0.05), HAQ by 60.7% (p<0.01). RAPID3 by 47.5% (p<0.01), mean strength of extension of the weak and strong knee joints increased by 87.9% (p<0.01) and 70.5% (p<0.01) respectively, the strength of flexion of the severely and less severely affected ankle joints increased by 84.6 (p<0.01) and 68.8% (p<0.01) respectively. Compliance with regular performance of therapeutic joint exercises during 3 months was higher (83.3%) than with high-intensity dynamic training with the use of exercise machines (60%). It is concluded that the latter modality should be recommended to the younger patients with RA (below 40 years), a short history of the disease, and its low activity. PMID:23718079

  14. [Citrullinated proteins in rheumatoid arthritis].

    PubMed

    Olivares Martínez, Elizabeth; Hernández Ramírez, Diego F; Núñez-Álvarez, Carlos A; Cabiedes, Javier

    2011-01-01

    Rheumatoid arthritis is an autoimmune disease of multifactorial etiology characterized by inflammation of the joints and presence of autoantibodies directed against multiple autoantigens. Recently the study of the anti-citrullinated protein antibodies (ACP) has acquired great interest due to its high specificity and sensitivity for diagnosis, in addition to which it has shown to be a predictor of severity in patients with rheumatoid arthritis, suggesting an important participation in the pathogenesis of the disease. PMID:21794783

  15. [Pathogenesis of rheumatoid arthritis].

    PubMed

    Branimir Ani?; Miroslav Mayer

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibro- blasts, chondrocytes and dendritic cells. Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components. In the initial disease stage there are qualitative and quantitative disturbances ofpeptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC's elicit specific humoral B cell re- sponse resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure. Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc. Accumulated complications and comorbidities finally result in handicap, social dysfunction and premature death. PMID:25427390

  16. [Pathogenesis of rheumatoid arthritis].

    PubMed

    Branimir Ani?; Miroslav Mayer

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibro- blasts, chondrocytes and dendritic cells. Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components. In the initial disease stage there are qualitative and quantitative disturbances ofpeptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC's elicit specific humoral B cell re- sponse resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure. Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc. Accumulated complications and comorbidities finally result in handicap, social dysfunction and premature death. PMID:25507640

  17. 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.

  18. 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)

  19. Risks and benefits of low-dosage cyclosporin in rheumatoid arthritis.

    PubMed

    Pasero, G; Ferraccioli, G F; Portioli, I

    1997-05-01

    The effects of cyclosporin on the activity of rheumatoid arthritis have mainly been investigated in patients with active, refractory, long-standing disease. The data obtained in these trials suggest that cyclosporin is not only a symptomatic treatment for rheumatoid arthritis but can also be considered a disease-modifying antirheumatic drug (DMARD), since it seems to be capable of slowing the progression of cartilage and bone damage due to rheumatoid arthritis. The trials conducted so far have led to a better understanding of cyclosporin toxicity and, therefore, to better monitoring of patients in order to avoid it. The reasons for studying the role of cyclosporin in patients with early, active and potentially severe rheumatoid arthritis are the poor prognosis of the disease despite the use of the presently available DMARDs, and the hypothesis that the drug is more efficacious and better tolerated in early rheumatoid arthritis. A new classification of antirheumatic drugs proposes that disease-controlling antirheumatic therapies decrease inflammatory synovitis and prevent structural joint damage or significantly reduce its rate of progression. However, few existing drugs meet these criteria. The 12-month results of a disease-controlling antirheumatic therapy clinical trial with a blinded radiological end-point, named GRISAR (Gruppo Reumatologi Italiani Studio Artrite Reumatoide) comparing cyclosporin with conventional DMARDs in patients with early rheumatoid arthritis provide strong evidence that cyclosporin offers better control of ongoing joint damage than do conventional DMARDs. PMID:18031101

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

    PubMed

    Slater, Graham J; Pennell, Matthew W

    2014-05-01

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

  1. Early Eocene perturbed parameter simulations: multiple methods of proxy-model comparison

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

    Geological proxy data for the early Eocene, ~55 million years ago, indicate widespread greenhouse conditions across the Earth. High latitude early Eocene temperature estimates inferred from a variety of proxy data are much warmer than their modern counterparts (~10-20C), whilst low latitude early Eocene temperature estimates where available (~30-35C) are only slightly warmer than their modern equivalent. This implies a reduced pole to equator temperature gradient during the early Eocene. Climate models are unable to simulate the low latitudinal temperature gradients seen in the early Eocene. The mechanisms for transporting and maintaining heat at high latitudes in order to achieve these reduced gradients are still uncertain although several hypotheses have been proposed. We are interested in reducing this model-data discrepancy by considering both climate model and proxy data uncertainty. A comprehensive study by Murphy et al. 20041 identified a subset of 29 parameters within the UK Hadley centre climate model (HadCM3) whose values cannot be accurately determined from observations. These 29 parameters were identified as being responsible for controlling key physical characteristics of sub-grid scale atmospheric and surface processes by modelling experts. Using a subset of 12 of the uncertain parameters identified by Murphy et al. 2004, we have run climate model experiments perturbing these parameters singly and jointly, within a realistic range, in order to understand the spectrum of climates that result. We use the model, FAMOUS (Fast Met Office/UK Universities Simulator), a low resolution emulator of HadCM3 for our experiments. The relatively low computing time of FAMOUS makes it ideal for long paleoclimate studies. We use an early Eocene paleogeography and run our simulations at 560 ppm, (2 x pre-industrial CO2.) The solar constant for the early Eocene is set to 1359.5 Wm-2. The climate proxy dataset (terrestrial and marine) available for the early Eocene is limited and there are many uncertainties associated with interpreting absolute climate values from it. In order to make best use of the data and its availability we have used several model-data approaches. First, rather than using the absolute values deduced from the proxy data we use them as a reference dataset against which changes in the parameter simulations can be compared. Secondly, in acknowledging the large uncertainties associated with temperature and precipitation values we target areas which have a large model anomaly signal. Finally we incorporate qualitative geological data to extend the spatial coverage of our comparison. 1. Murphy et al., 2004, Quantification of modelling uncertainties in a large ensemble of climate change simulations paper, Nature 430, 768-772

  2. 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 2030% 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 1026% 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.

  3. 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

  4. T Cell Migration in Rheumatoid Arthritis.

    PubMed

    Mellado, Mario; Martnez-Muoz, Laura; Cascio, Graciela; Lucas, Pilar; Pablos, Jos L; Rodrguez-Frade, Jos 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

  5. 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.

  6. Vaccinations for Rheumatoid Arthritis

    PubMed Central

    Perry, Lisa M.; Winthrop, Kevin L.; Curtis, Jeffrey R.

    2014-01-01

    Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious disease-related morbidity and mortality and have twice the risk of acquiring a severe infection compared to the general population. This increased risk is not only a result of the autoimmune disease but is also attributed to the immunosuppressive therapies that are commonly used in this patient population. Given the increase in infection-related risks in RA, there is great interest in mitigating such risk. A number of vaccines are available to the rheumatologist, with a handful that are of importance for RA patients in the United States. The goal of this paper is to highlight the most recent literature on the key vaccines and the specific considerations for the rheumatologist and their RA patients, with a particular focus on influenza, pneumococcal, and herpes zoster vaccines. It is important for rheumatologist to understand and be aware of which vaccines are live and what potential contraindications exist for giving vaccines to RA patients. PMID:24925587

  7. Does parvovirus B19 have a role in rheumatoid arthritis?

    PubMed Central

    Nikkari, S; Luukkainen, R; Mttnen, T; Meurman, O; Hannonen, P; Skurnik, M; Toivanen, P

    1994-01-01

    OBJECTIVES--To determine whether parvovirus B19 (B19) infection is associated with rheumatoid arthritis (RA). METHODS--The polymerase chain reaction was applied to serum, cells isolated from synovial fluid, and synovial fluid. Enzyme immunoassay technique was used to detect antibodies against B19. RESULTS--Of 142 patients with early RA (onset of disease under one year) and 67 control patients, serological evidence of recent parvoviral infection was found in 4/135 and 2/62, respectively. However, no evidence for the presence of parvoviral DNA was observed in 18 synovial fluids, 21 samples of synovial fluid granulocytes or 40 sera, all obtained from 65 patients diagnosed with early RA. CONCLUSION--Although there is published evidence of chronic rheumatoid-like arthropathy following acute parvovirus infection, our findings do not support the involvement of B19 in the aetiopathogenesis of RA. Images PMID:8129454

  8. 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.

  9. 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.

  10. Radiation Changes in GCM Simulations in the Late 19th and Early 20th Century

    NASA Astrophysics Data System (ADS)

    Folini, D.; Wild, M.

    2009-04-01

    We use the latest version of the ECHAM5-HAM model to perform transient climate simulations covering the late 19th and early 20th century. The aim is to estimate the impact of different aerosol forcings, such as SO2 and black carbon from fossil fuel combustion or volcanic aerosol, on the radiation balance of the earth. Aerosol emissions are taken from the National Institute for Environmental Studies (NIES). Besides a control run, simulations were carried out in which emissions of individual aerosols categories were frozen at their 1870 values (geographical distribution and total amount). The results from the different experiments are analyzed on the global and regional scale.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Detection of rheumatoid arthritis using infrared imaging

    NASA Astrophysics Data System (ADS)

    Frize, Monique; Ada, 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.

  16. 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.

  17. 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.

  18. Prevention of Stroke in Rheumatoid Arthritis.

    PubMed

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

    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

  19. 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.

  20. Interest of modelling in rheumatoid arthritis.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

    Kim, Sharon; Parker, Wendy L.

    2008-01-01

    Subcutaneous nodules occur in approximately 2025% of rheumatoid factor (RF)-positive rheumatoid patients. In this paper, we present a unique case of a 47-year-old healthy RF-negative woman with a 3-year history of necrobiotic nodules over the dorsum of her hands, extensor forearms, and lower extremities. This may represent an atypical presentation or a new rheumatoid variant. PMID:19048351

  2. Experimental Synthesis of Organic Compounds From Inorganic Materials by the Simulated Impact on the Early Earth

    NASA Astrophysics Data System (ADS)

    Furukawa, Y.; Sekine, T.; Oba, M.; Kakegawa, T.; Nakazawa, H.

    2008-12-01

    How to prepare prebiotic organic molecules on the early Earth has been debated vigorously. One of points of debates is how to overcome the difficulty to produce prebiotic organic molecules under moderately oxidizing CO2 and N2-rich early atmosphere. Previous investigators suggested the existence of early oceans well before 4.0 Ga, late heavy bombardments at around 4.0 Ga, and the earliest life at 3.8 Ga. In order to connect these geological evidences, we hypothesized that meteorite impacts, which brought many reductants, on the early oceans followed by interaction with the atmosphere were responsible for production of prebiotic organic molecules. In order to simulate the impact reaction, we performed shock-recovery experiments with single-stage propellant gun. The shocked materials are composed of mixture of iron, nickel, carbon, water and gaseous nitrogen or dissolved ammonia. The carbon in the starting materials is enriched in 99% of 13C so that the C-bearing products can be distinguished from contaminants. These mixtures were encapsulated in metal containers and then shocked with impact velocities of 1 km/s. Analyses of the experimental products were performed using the state-of-the-art LC/MS and GC/MS. Various organic molecules including bio molecules composed only of 13C are detected, verifying syntheses of those organic molecules during the shock experiments. This result further suggests that the late heavy bombardment on the early oceans, dynamic high-pressure conditions, triggered to form a large mass and variety of prebiotic organic molecules on the early Earth.

  3. 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.

  4. 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

  5. Treatment in juvenile rheumatoid arthritis and new treatment options

    PubMed Central

    Kasapopur, zgr; 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

  6. Tryptase is a candidate autoantigen in rheumatoid arthritis

    PubMed Central

    Guo, Yanyan; Wu, Qiao; Ni, Bing; Mou, Zhirong; Jiang, Qiong; Cao, Yi; Dong, Hui; Wu, Yuzhang

    2014-01-01

    Autoimmune processes have been implicated in the development of rheumatoid arthritis (RA); however, specific autoantigens that play a role in the aetiology of RA have been lacking. In this study, we found that sera from RA patients were particularly immunoreactive against the protein tryptase. Compared with osteoarthritis (OA) patients and healthy controls, RA patients had relatively higher levels of tryptase and concomitant anti-tryptase antibodies in their synovial tissues and sera. Similarly, synovial fluid from RA patients, but not from OA patients, contained antibodies that recognized tryptase in vitro. In addition, serum tryptase levels in both early and late RA patients significantly correlated with clinical indices usually used to diagnose RA, such as rheumatoid factor, Disease Activity Score using 28 joint counts and autoantibodies against cyclic citrullinated peptide. Our results identify tryptase as a candidate autoantigen involved in the pathogenesis of RA and monitoring its levels may have diagnostic and prognostic value. PMID:24433328

  7. Epigenetics in the pathogenesis of rheumatoid arthritis

    PubMed Central

    2014-01-01

    An increasing number of studies show that besides the inherited genetic architecture (that is, genomic DNA), various environmental factors significantly contribute to the etiology of rheumatoid arthritis. Epigenetic factors react to external stimuli and form bridges between the environment and the genetic information-harboring DNA. Epigenetic mechanisms are implicated in the final interpretation of the encoded genetic information by regulating gene expression, and alterations in their profile influence the activity of the immune system. Overall, epigenetic mechanisms further increase the well-known complexity of rheumatoid arthritis by providing additional subtle contributions to rheumatoid arthritis susceptibility. Although there are controversies regarding the involvement of epigenetic and genetic factors in rheumatoid arthritis etiology, it is becoming obvious that the two systems (genetic and epigenetic) interact with each other and are ultimately responsible for rheumatoid arthritis development. Here, epigenetic factors and mechanisms involved in rheumatoid arthritis are reviewed and new, potential therapeutic targets are discussed. PMID:24568138

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

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  9. 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.

  10. Epidemiology of Rheumatoid Arthritis in Tirana, Albania

    PubMed Central

    Duraj, Valbona; Tafaj, Argjent; Backa, Teuta

    2013-01-01

    Conflict of interest: none declared. Aim Rheumatoid arthritis is considered a clinical syndrome across several disease subsets characterized by systemic inflammation, persistent synovitis, and autoantibodies. Our aim was to assess the distribution of risk factors among people diagnosed with rheumatoid arthritis in the adult population of Tirana, the capital city of Albania. Methods All individuals diagnosed with rheumatoid arthritis in primary health care services of Tirana city during the period 2009-2012 were included in this study. The diagnosis of rheumatoid arthritis was based on the clinical signs and symptoms and laboratory tests including measurement of the rheumatoid factor. Results Overall, there were identified 817 cases with rheumatoid arthritis in all primary health care centers of Tirana for the period 2009-2012. Of these, 529 (65%) were women and 288 (35%) were men. Genetic factors accounted for 60% of the diseases in women and 45% in men (P<0.001). In both sexes, the proportion of older individuals was higher compared with younger adults. Most of the individuals with rheumatoid were from urban areas of Tirana. Conclusion Our study provides new evidence about the distribution of risk factors of rheumatoid arthritis in transitional Albania where valid and reliable data about this disease were scarce. Future studies in Albania should assess the prevalence of rheumatoid arthritis in population-based samples. PMID:24082831

  11. Extra-articular Manifestations in Rheumatoid Arthritis

    PubMed Central

    Cojocaru, Manole; Cojocaru, Inimioara Mihaela; Silosi, Isabela; Vrabie, Camelia Doina; Tanasescu, R

    2010-01-01

    ABSTRACT Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main characteristic is persistent joint inflammation that results in joint damage and loss of function. Although RA is more common in females, extra-articular manifestations of the disease are more common in males. The extra-articular manifestations of RA can occur at any age after onset. It is characterised by destructive polyarthritis and extra-articular organ involvement, including the skin, eye, heart, lung, renal, nervous and gastrointestinal systems. The frequence of extra-articular manifestations in RA differs from one country to another. Extra-articular organ involvement in RA is more frequently seen in patients with severe, active disease and is associated with increased mortality. Incidence and frequence figures for extra-articular RA vary according to study design. Extra-articular involvement is more likely in those who have RF and/or are HLA-DR4 positive. Occasionally, there are also systemic manifestations such as vasculitis, visceral nodules, Sjgren's syndrome, or pulmonary fibrosis present. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjgren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common in 6-10%, are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease in particular functional impairment and mortality. The occurrence of these systemic manifestations is a major predictor of mortality in patients with RA. This paper focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system. PMID:21977172

  12. Simulation of the Caribbean Climate during the early and mid-Holocene with GCM

    NASA Astrophysics Data System (ADS)

    Wei, Wei; Lohmann, Gerrit

    2010-05-01

    Although a set of coupled ocean-atmosphere simulations using state-of-the-art climate models is available for the mid-Holocene since PMIP2 (Paleoclimate Modeling Intercomparison Project Phase II), little research has been directed towards climate variability in the early Holocene when the Laurentide ice sheet presented. The Holocene thermal maximum between 11,000 and 5,000 years ago is mostly recorded in the middle and high latitudes; however, the subtropical and tropical regions play a quite important role in modulating the global climate, and more debates exist concerning the consistence of simulation and proxy reconstructions in these regions. Long-term Simulations with a coupled atmosphere-ocean-vegetation general circulation model (ECHAM5/JSBACH/MPI-OM ) configured for the present, mid-Holocene (6 ka B.P.) and early Holocene (9 ka B.P. with/without Laurentide ice sheet) are performed in this study by specifying the appropriate change of forcing, i.e., orbital parameter, greenhouse gases and topography. Prescribed changes in insolation due to orbital variations are considered to be the major external forcing, which leads to increased seasonality in the Caribbean as indicated by the surface temperature, with a cooling in the winter and a warming in the summer. The magnitude of the seasonality variation is approximately 1-2C, comparably much smaller than that in the extratropics, whereas, it is consistent with coral-based ?18O and Sr/Ca seasonality analysis. Compared to the mid-Holocene, the early Holocene seasonality increase is more dramatic due to more incoming radiation in summer and less in winter. The sea surface temperature (SST) is similar, showing the expansion of the Atlantic warm pool in summer during the Holocene. Weakening of the thermohaline circulation during the Holocene results in less northwards heat transport at 30N and thus partly contributes to the warming in the summer. Comparison of the two simulations for the early Holocene shows that the topography change in high latitudes which is associated with change in glacial distribution and the corresponding albedo does not only influence the local climate but also have a cooling effect in the tropics. The simulated hydrological cycle reflects the wetter conditions of the Holocene (especially for the early Holocene) in the south Caribbean, which have been proved by marine and lake sediment records. The annual precipitation anomaly during the Holocene can be more than 500mm/a, similar to that for Africa over the same period. This long-term change can be attributed to orbitally forced variations in solar insolation, which led to a more northwards shift of the mean latitude of the Atlantic Intertropical Convergence Zone (ITCZ). Meanwhile, the prevailing easterly trade wind gets weakened during the Holocene, which may reduce the water vapor transported from the tropical Atlantic to the western Pacific via the Caribbean. This provides another explanation of the wetter conditions in the Caribbean. The teleconnection pattern, which refers to the interannual variability of the Caribbean climate, ENSO and the Atlantic, does not have much change during the Holocene compared to the present. The Caribbean rainfall is positively correlated to the tropical Atlantic SST, while it shows a La Nia-like pattern with the western Pacific, as deciphered in research related to the modern Caribbean climate. Nevertheless, some proxy studies demonstrate the ENSO only became as active as it is at present after the mid-Holocene. From this point of view, more proxy and simulation comparisons are required as well as comparisons between different GCM results.

  13. Immune modulation of rheumatoid arthritis.

    PubMed

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

    2011-12-01

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

  14. Tyrosine kinases in rheumatoid arthritis

    PubMed Central

    2011-01-01

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

  15. ROENTGEN THERAPY OF RHEUMATOID SPONDYLITIS

    PubMed Central

    Spishakoff, Nathan M.; Low-Beer, B. V. A.

    1949-01-01

    Based on the pathological processes involved in rheumatoid spondylitis, comparison is made between the physical qualities of certain techniques of roentgen therapy. Graphic representation of the isodose curves and the homogeneous distribution of radiation pertaining to the method herein advocated is shown. Results obtained in the treatment of 125 cases illustrative of the evolution of technique experienced at the University of California Hospital are tabulated. The indications, contraindications, and complications of the method are discussed. Practically every patient with rheumatoid spondylitis, regardless of the stage of the disease, was benefited, with the best results having been obtained when the radiation was given in three courses, separated by rest periods, and homogeneously distributed along the spine. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:18123526

  16. 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

  17. Contrasting diagnosis performance of forced oscillation and spirometry in patients with rheumatoid arthritis and respiratory symptoms

    PubMed Central

    Faria, Alvaro Camilo Dias; Barbosa, Wellington Ribeiro; Lopes, Agnaldo Jos; da Rocha Castelar Pinheiro, Geraldo; de Melo, Pedro Lopes

    2012-01-01

    OBJECTIVES: Pulmonary involvement in rheumatoid arthritis is directly responsible for 10% to 20% of all mortality. The best way to improve the prognosis is early detection and treatment. The forced oscillation technique is easy to perform and offers a detailed exam, which may be helpful in the early detection of respiratory changes. This study was undertaken to (1) evaluate the clinical potential of the forced oscillation technique in the detection of early respiratory alterations in rheumatoid arthritis patients with respiratory complaints and (2) to compare the sensitivity of forced oscillation technique and spirometric parameters. METHODS: A total of 40 individuals were analyzed: 20 healthy and 20 with rheumatoid arthritis (90% with respiratory complaints). The clinical usefulness of the parameters was evaluated by investigating the sensibility, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01641705. RESULTS: The early adverse respiratory effects of rheumatoid arthritis were adequately detected by the forced oscillation technique parameters, and a high accuracy for clinical use was obtained (AUC>0.9, Se?=?80%, Sp?=?95%). The use of spirometric parameters did not obtain an appropriate accuracy for clinical use. The diagnostic performance of the forced oscillation technique parameters was significantly higher than that of spirometry. CONCLUSIONS: The results of the present study provide substantial evidence that the forced oscillation technique can contribute to the easy identification of initial respiratory abnormalities in rheumatoid arthritis patients that are not detectable by spirometric exams. Therefore, we believe that the forced oscillation technique can be used as a complementary exam that may help to improve the treatment of breathing disorders in rheumatoid arthritis patients. PMID:23018292

  18. Two cases of rheumatoid meningitis.

    PubMed

    Magaki, Shino; Chang, Edward; Hammond, Robert R; Yang, Isaac; Mackenzie, Ian R A; Chou, Benedict T; Choi, Soo I; Jen, Joanna C; Pope, Whitney B; Bell, David A; Vinters, Harry V

    2016-02-01

    Central nervous system (CNS) involvement by rheumatoid arthritis (RA) in the form of rheumatoid meningitis (RM) is rare and most commonly occurs in the setting of longstanding severe RA. Due to a wide range of clinical presentations and nonspecific laboratory findings, it presents a diagnostic challenge often requiring brain biopsy. Only a few histopathologically confirmed cases have been described in the literature. Our aim is to describe two cases of RM and review the literature. The first case is of a previously healthy 37-year-old man who presented with severe headaches and focal neurologic deficits. Magnetic resonance imaging demonstrated abnormal leptomeningeal enhancement in the left frontal and parietal sulci. The second case is of a 62-year-old woman with a history of mild chronic joint pain who presented with confusion, personality changes and seizures. Both patients ultimately underwent brain biopsy which demonstrated RM on pathologic examination. Administration of corticosteroids resulted in significant clinical improvement in both cases. To our knowledge, our unusual case of RM in the young man is the fifth reported case of rheumatoid meningitis in a patient with no prior history of RA. Such an atypical presentation makes diagnosis even more difficult and highlights the need for awareness of this entity in the diagnostic consideration of a patient presenting with unexplained neurologic symptoms. Our literature review underscores the clinical and pathologic heterogeneity of CNS involvement in RA. PMID:26350538

  19. A mathematical model for simulation of early decelerations in the cardiotocogram during labor.

    PubMed

    van der Hout-van der Jagt, M Beatrijs; Oei, S Guid; Bovendeerd, Peter H M

    2012-06-01

    Fetal welfare during labor and delivery is commonly monitored through the cardiotocogram (CTG), the combined registration of uterus contractions and fetal heart rate (FHR). The CTG gives an indication of the main determinant of the acute fetal condition, namely its oxygen state. However, interpretation is complicated by the complex relationship between the two. Mathematical models can be used to assist with the interpretation of the CTG, since they enable quantitative modeling of the cascade of events through which uterine contractions affect fetal oxygenation and FHR. We developed a mathematical model to simulate 'early decelerations', i.e. variations in FHR originating from caput compression during uterine contractions, as mediated by cerebral flow reduction, cerebral hypoxia and a vagal nerve response to hypoxia. Simulation results show a realistic response, both for fetal and maternal hemodynamics at term, as for FHR variation during early decelerations. The model is intended to be used as a training tool for gynaecologists. Therefore 6 clinical experts were asked to rate 5 real and 5 model-generated CTG tracings on overall realism and realism of selected aspects. Results show no significant differences between real and computer-generated CTG tracings. PMID:22041128

  20. Methods for detecting early warnings of critical transitions in time series illustrated using simulated ecological data.

    PubMed

    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

  1. 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.; Kfi, 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

  2. 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

  3. [Surgical procedures for treatment of the rheumatoid knee].

    PubMed

    Judas, Fernando; da Costa, Portela; Teixeira, Luís; Saavedra, Maria João

    2007-01-01

    In the last decade considerable modifications in the surgical procedures recommended for the treatment of rheumatoid knee have been observed. This was due to all the medical developments achieved in pharmacology and therapeutic as well as a significant quality improvement of the rheumatologist s intervention. The synovectomy and namely the total knee arthroplasty represent the most commonly procedures used in the surgical treatment of the rheumatoid knee. An arthroscopic followed by a radionuclide synovectomy can be an appropriate treatment in a knee with an inflammatory arthritis Larsen radiograph grade I II . The ideal patient for synovectomy must present an early disease absence of deformity or instability good range of motion and preserved articular cartilage. On the other hand a total knee arthroplasty represents the only possible operation to treat a rheumatoid knee with a severe bone and cartilage damage Larsen radiograph grade IV V including younger patients. Total knee arthroplasty is actually a successful operation providing pain relief and the restoration of the function. Nevertheless the excellent good short and medium-term results achieved do not resist over time. Similarly to what happens with every other arthoplasty joint replacements the particules that come from the wear of the biomaterials included in its composition are the cause of biological intolerance reactions which can lead to the need of a new implant. The replacement prosthesis raises technical issues related to the reconstruction of bone mass losses where the cryopreserved bone allografts can be recommended. PMID:18159199

  4. 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.

  5. 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

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

    PubMed Central

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

    2011-01-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification....

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

    SciTech Connect

    Johansson, Peter H.; Naab, Thorsten; Ostriker, Jeremiah P.

    2012-08-01

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

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

    NASA Astrophysics Data System (ADS)

    D'Alessio, M. A.

    2010-12-01

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

  10. 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

  11. [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

  12. What is MRI bone oedema in rheumatoid arthritis and why does it matter?

    PubMed Central

    McQueen, Fiona M; Ostendorf, Benedikt

    2006-01-01

    MRI bone oedema occurs in various forms of inflammatory and non-inflammatory arthritis and probably represents a cellular infiltrate within bone. It is common in early rheumatoid arthritis and is associated with erosive progression and poor functional outcome. Histopathological studies suggest that a cellular infiltrate comprising lymphocytes and osteoclasts may be detected in subchondral bone and could mediate the development of erosions from the marrow towards the joint surface. There is emerging evidence from animal models that such an infiltrate corresponds with MRI bone oedema, pointing towards the bone marrow as a site for important pathology driving joint damage in rheumatoid arthritis. PMID:17169137

  13. 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.

  14. 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

  15. 3D simulations of the early stages of AGN jets: geometry, thermodynamics and backflow

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  16. 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.

  17. Alternative treatments for rheumatoid arthritis.

    PubMed

    Gaby, A R

    1999-12-01

    Conventional treatments for rheumatoid arthritis (RA) present a number of problems, in terms of both safety and efficacy. A number of different alternative therapies have been studied, including dietary modifications, nutritional supplements, botanicals, and antibiotics. While the response to these treatments is variable and often unpredictable, some patients have shown dramatic improvement or even complete and long-lasting remission. Moreover, alternative therapies, with the exception of antibiotics, have a low incidence of adverse effects. Consideration of these treatment options has the potential to benefit many patients with RA. PMID:10608912

  18. 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

  19. 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

  20. Rheumatoid arthritis: from palliation to remission in two decades.

    PubMed

    Brown, Philip M; Isaacs, John D

    2014-12-01

    The last 20years have seen a transformation in the landscape of rheumatoid arthritis, which has changed from being a life limiting condition to a chronic but often remitting illness. The importance of early disease control, the better use of existing therapies, and the development of new therapies have all been key to this success. The future of therapy now lies in the identification of stratifying biomarkers, to allow more rational delivery of treatment. The ultimate goal remains the reintroduction of immune tolerance to potentially achieve a 'cure.' PMID:25468920

  1. Management of pregnancy in women with rheumatoid arthritis.

    PubMed

    Ngian, Gene-Siew; Briggs, Andrew M; Ackerman, Ilana N; Van Doornum, Sharon

    2016-02-01

    Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease-modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal-fetal medicine specialist for risk assessment and advice. PMID:26821101

  2. Cardiovascular disease risk scores in the current practice: which to use in rheumatoid arthritis?

    PubMed

    Purcarea, A; Sovaila, S; Gheorghe, A; Udrea, G; Stoica, V

    2014-01-01

    Cardiovascular disease (CVD) is the highest prevalence disease in the general population (GP) and it accounts for 20 million deaths worldwide each year. Its prevalence is even higher in rheumatoid arthritis. Early detection of subclinical disease is critical and the use of cardiovascular risk prediction models and calculators is widely spread. The impact of such techniques in the GP was previously studied. Despite their common background and similarities, some disagreement exists between most scores and their importance in special high-risk populations like rheumatoid arthritis (RA), having a low level of evidence. The current article aims to single out those predictive models (models) that could be most useful in the care of rheumatoid arthritis patients. PMID:25713603

  3. [Worker participation as a treatment goal: new guideline "Rheumatoid Arthritis and Participation in Work"].

    PubMed

    Boonen, A; Lems, W F

    2015-01-01

    Participation in work is important for every individual and for society as a whole. Despite large improvements in the outcomes of rheumatoid arthritis as a consequence of earlier diagnosis and more effective drug strategies, the disease continues to lead to restrictions in work participation in a substantial proportion of patients. The Dutch Rheumatology Association (NVR) has therefore developed a multidisciplinary guideline, "Rheumatoid Arthritis and Participation in Work". The main aim of this guideline is to improve early recognition by healthcare providers of disease related problems in work participation and to guide the development of a work-directed individual treatment plan. The ultimate goal is to prevent long-term sickness absences and work disability in patients with rheumatoid arthritis. PMID:26732216

  4. Diagnosis of periarticular osteoporosis in rheumatoid arthritis using digital X-ray radiogrammetry.

    PubMed

    Bttcher, Joachim; Pfeil, Alexander

    2008-01-01

    Osteoporosis can manifest in two ways in rheumatoid arthritis: generalized bone loss, which may result from immobility, the inflammatory process per se and/or treatments such as steroids; and periarticular demineralization, which is probably due to local release of inflammatory agents. Digital X-ray radiogrammetry (DXR) is an effective and sensitive modality for monitoring periarticular osteoporosis, which is among the earliest features of rheumatoid arthritis, preceding bone erosions. DXR is a promising technique, which can provide quantitative data that allow early diagnosis. During the course of rheumatoid arthritis it can be deployed in combination with established X-ray scoring methods to inform decisions regarding the optimal therapy to prevent joint destruction. PMID:18254923

  5. 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

  6. 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.

  7. 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.

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

    PubMed

    Galesić, Kresimir; Prkacin, Ingrid; Tisljar, Miroslav; Vergles, Jadranka Morović

    2009-01-01

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

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

    PubMed

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

    2012-07-01

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

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

    PubMed Central

    2013-01-01

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

  11. Wnt signalling in rheumatoid arthritis.

    PubMed

    Sen, M

    2005-06-01

    Rheumatoid arthritis (RA) is a symmetrical polyarticular disease of unknown aetiology that affects primarily the diarthrodial joints. Characteristic features of RA pathogenesis are synovial hyperplasia and inflammation accompanied by cartilage loss and joint destruction. Synovial hyperplasia and inflammation are a consequence of an increase in the macrophage-like and fibroblast-like synoviocytes of the synovial intimal lining associated with infiltration of leucocytes into the subintimal space. Although therapeutic interventions are available, the disease persists despite therapy in a significant fraction of patients. Several lines of evidence have substantiated a crucial role of activated fibroblast-like synoviocytes (FLS) during RA pathogenesis. The hyperplastic FLS population potentially promotes leucocyte infiltration and retention. The rheumatoid synovium eventually transforms into a pannus that destroys articular cartilage and bone. There are no approved drugs that are known to target the FLS in RA, and the underlying mechanisms driving FLS activation remain unresolved. In this review, the importance of Wnt-frizzled (Fz)-mediated signalling in the autonomous activation of FLS is discussed. Anti-Wnt/anti-Fz antibodies, Fz receptor antagonists or small-molecule inhibitors of Wnt-Fz signalling might be useful for therapeutic interventions in refractory RA. PMID:15705634

  12. [Therapy of rheumatoid arthritis (chronic polyarthritis)].

    PubMed

    Villiger, P M; Stucki, G

    1996-09-10

    A continuous and systematic monitoring of disease activity provides the basis for the therapeutic management of rheumatoid arthritis patients. This helps to individually tailor medication and to correctly time physiotherapy, ergotherapy, surgery, and rehabilitative measures. NSAID are the drugs of choice for symptomatic therapy. The dosage is adjusted to the circadian rhythm of the patient's complaints. Systemic glucocorticoids are very efficacious to control inflammation; however, caution is required in their long-term usage. Preventive measures to limit bone loss are mandatory. Disease-modifying antirheumatic drugs (DMARD) are prescribed early, at the time of diagnosis. The choice of sulfasalazine, antimalaric drugs, methotrexate or parenteral gold is based on the clinical presentation, the degree of systemic inflammation and on prognostic parameters. Treatment with DMARD has to be continued for years. If complete remission is achieved, lasting for at least six months, the dosage can be gradually reduced and finally stopped. At late stages of disease, residual joint pain is often due to secondary osteoarthritis. PMID:8927885

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

    PubMed Central

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

    2009-01-01

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

  14. 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.

  15. Simulation of blast-induced early-time intracranial wave physics leading to traumatic brain injury.

    PubMed

    Taylor, Paul A; Ford, Corey C

    2009-06-01

    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 mm3 voxels) five material model of the human head was created by segmentation of color cryosections from the Visible Human Female data set. 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 stress within the first 2 ms 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 ms 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. PMID:19449961

  16. Comparison of Snellen and Early Treatment Diabetic Retinopathy Study charts using a computer simulation

    PubMed Central

    Shamir, Reuben R.; Friedman, Yael; Joskowicz, Leo; Mimouni, Michael; Blumenthal, Eytan Z.

    2016-01-01

    AIM To compare accuracy, reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study (ETDRS) charts, two main tools used to measure visual acuity (VA). METHODS A computer simulation was programmed to run multiple virtual patients, each with a unique set of assigned parameters, including VA, false-positive and false-negative error values. For each virtual patient, assigned VA was randomly chosen along a continuous scale spanning the range between 1.0 to 0.0 logMAR units (equivalent to 20/200 to 20/20). Each of 30 000 virtual patients were run ten times on each of the two VA charts. RESULTS Average test duration (expressed as the total number of characters presented during the test SD) was 12.611.1 and 31.214.7 characters, for the Snellen and ETDRS, respectively. Accuracy, defined as the absolute difference ( SD) between the assigned VA and the measured VA, expressed in logMAR units, was superior in the ETDRS charts: 0.120.14 and 0.080.08, for the Snellen and ETDRS charts, respectively. Reproducibility, expressed as test-retest variability, was superior in the ETDRS charts: 0.230.17 and 0.110.09 logMAR units, for the Snellen and ETDRS charts, respectively. CONCLUSION A comparison of true (assigned) VA to measured VA, demonstrated, on average, better accuracy and reproducibility of the ETDRS chart, but at the penalty of significantly longer test duration. These differences were most pronounced in the low VA range. The reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies.

  17. 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)

  18. 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

  19. 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 (espaol) Vietnamese (Ti?ng Vi?t) Chinese - Simplified ( ...

  20. A rheumatoid nodule in an unusual location: mediastinal lymph node

    PubMed Central

    Yachoui, Ralph; Ward, Celine; Kreidy, Mazen

    2013-01-01

    Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterised by destructive synovitis and varied extra-articular involvement. Rheumatoid lung nodules are the most common pulmonary manifestations of RA. Rheumatoid nodules in mediastinal lymph nodes are extremely uncommon. We describe a male patient with long-standing RA and subcutaneous rheumatoid nodules presenting with multiple lung nodules and mediastinal lymphadenopathies. Definite histopathology of a lymph node was consistent with necrobiotic granuloma due to RA. Clinicians should be aware of rheumatoid nodules as a potential cause of mediastinal lymphadenopathies, mainly in advanced rheumatoid arthritis. PMID:23645652

  1. 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.; Kere, Duan; Quataert, Eliot; Faucher-Gigure, Claude-Andr; 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.

  2. Observing System Simulation Experiments for Hurricanes: Early results and plans for the future

    NASA Astrophysics Data System (ADS)

    Atlas, R. M.; Pu, Z.

    2010-12-01

    Observing System Simulation Experiments (OSSEs) are an important tool for evaluating the potential impact of proposed new observing systems, as well as for evaluating trade-offs in observing system design, and in developing and assessing improved methodology for assimilating new observations. Extensive OSSEs have been conducted at NASA/GSFC and NOAA/AOML in collaboration with Simpson Weather Associates, operational data assimilation centers, and academic partners over the last 25 years. These OSSEs determined correctly the quantitative potential for several proposed satellite observing systems to improve weather analysis and prediction prior to their launch, evaluated trade-offs in orbits, coverage and accuracy for space-based wind lidars, and were used in the development of the methodology that led to the first beneficial impacts of satellite surface winds on numerical weather prediction. In this paper, we will summarize early applications of global OSSEs to hurricane track forecasting, current experiments using both global and regional models aimed at both track and intensity forecasting, and plans for future experiments.

  3. Predicting early dolomitization: outcrop-based numerical simulations of carbonate diagenesis by free-convecting brines

    NASA Astrophysics Data System (ADS)

    Garcia-Fresca, B.; Lucia, F. J.; Sharp, J. M.; Kerans, C.; Jones, G. D.

    2008-12-01

    Free-convection of brines, or reflux, can be an efficient hydrologic mechanism to deliver sufficient magnesium for dolomitization. The replacement of calcite by dolomite, dolomite cementation, and sulfate precipitation and dissolution affect the porosity and permeability of carbonates reservoirs and aquifers. We evaluate hydrologic and geochemical controls on reflux dolomitization using outcrop data to constrain numerical models. First we built a hydrogeologic model of brine circulation during the accumulation of the Permian San Andres Formation (west Texas and southeast New Mexico), where we hypothesize that high-salinity fluids were present in restricted parts of the platform as inferred by the presence of evaporite-rich peritidal deposits. These fluids circulated through the platform in response to density and hydraulic gradients and caused early dolomitization. This model simulates the source of dolomitizing fluids as it migrates across the platform top in response to relative sea-level fluctuations. Brine plumes develop, migrate, grow, and shrink over time in the underlying sediments. We predict that dolomitization is most likely to occur in areas of high- salinity and high fluid flow rate. Mass-balance analysis indicates that this process is capable of delivering enough magnesium to completely dolomitize the San Andres platform. Reactive transport simulations using provide insight on the dissolution and precipitation reactions taking place along flow paths in the reflux system. A model based on Cretaceous Glen Rose Formation in central Texas indicates that concentrated seawater is capable of dolomitizing the top 1.5 m of a high-frequency cycle within 450 years. Reaction kinetics, brine concentration, and brine residence time are critical factors that control the timing, extent, and distribution of dolomitization. A model of episodic high-frequency cycle deposition and brine reflux simulated both complete and partially dolomitized cycles. These experiments illustrate how a single refluxing brine may result in the advance of separate dolomitization fronts and result in separate dolomite bodies. This reveals the importance of the "seed effect", whereby the amount of dolomite in the system is a key control on the dolomitization rate. In general, replacement of calcite by dolomite increases porosity, however, the more saline fluids precipitate sulfates, which tend to reduce porosity.

  4. 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.

  5. 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.

  6. T cells in rheumatoid arthritis

    PubMed Central

    Cope, Andrew P

    2008-01-01

    Over the past decade and a half, advances in our understanding of the pathogenesis of immune-mediated diseases such as rheumatoid arthritis (RA) have translated directly into benefit for patients. Much of this benefit has arisen through the introduction of targeted biological therapies. At the same time, technological advances have made it possible to define, at the cellular and molecular levels, the key pathways that influence the initiation and persistence of chronic inflammatory autoimmune reactions. As our understanding grows, it is likely that this knowledge will be translated into a second generation of biological therapies that are tailor-made for the patient. This review summarizes current perspectives on RA disease pathogenesis, with particular emphasis on what RA T cells look like, what they are likely to see, and how they contribute to persistence of the chronic inflammatory response. PMID:19007421

  7. Hypercalcaemia in rheumatoid arthritis revisited.

    PubMed Central

    Ralston, S H; Fraser, W D; Jankowski, J; Richards, I M; Cowan, R A; Capell, H A; Sturrock, R D

    1990-01-01

    The prevalence and mechanisms of hypercalcaemia were studied in a series of patients attending a regional referral centre for rheumatic diseases. In a prospective study one case of hypercalcaemia due to primary hyperparathyroidism was found in 251 consecutive patients who were screened over a three month period. In a retrospective study of 39 patients who had been discovered to be hypercalcaemic during the preceding 12 months known cases of hypercalcaemia were found in 38 (97%) cases. Primary hyperparathyroidism was the most common cause (n = 24; 62%), followed by thiazide treatment in five (13%), cancer in three (8%), immobility in three (8%), vitamin D toxicity in two (5%), and chronic liver disease in one (3%). In one case the diagnosis remained unclear after full investigation. This study shows that the causes of hypercalcaemia in rheumatological patients are similar to those in the general population. These observations contrast with previous reports, which suggested that hypercalcaemia may be a complication of rheumatoid arthritis itself. PMID:2310223

  8. 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

  9. 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.

  10. Complement fixation by rheumatoid factor.

    PubMed Central

    Tanimoto, K; Cooper, N R; Johnson, J S; Vaughan, J H

    1975-01-01

    The capacity for fixation and activation of hemolytic complement by polyclonal IgM rheumatoid factors (RF) isolated from sera of patients with rheumatoid arthritis and monoclonal IgM-RF isolated from the cryoprecipitates of patients with IgM-IgG mixed cryoglobulinemia was examined. RF mixed with aggregated, reduced, and alkylated human IgG (Agg-R/A-IgG) in the fluid phase failed to significantly reduce the level of total hemolytic complement, CH50, or of individual complement components, C1, C2, C3, and C5. However, sheep erythrocytes (SRC) coated with Agg-R/A-IgG or with reduced and alkylated rabbit IgG anti-SRC antibody were hemolyzed by complement in the presence of polyclonal IgM-RF. Human and guinea pig complement worked equally well. The degree of hemolysis was in direct proportion to the hemagglutination titer of the RF against the same coated cells. Monoclonal IgM-RF, normal human IgM, and purified Waldenstrm macroglobulins without antiglobulin activity were all inert. Hemolysis of coated SRC by RF and complement was inhibited by prior treatment of the complement source with chelating agents, hydrazine, cobra venom factor, specific antisera to C1q, CR, C5, C6, or C8, or by heating at 56 degrees C for 30 min. Purified radiolabeled C4, C3, and C8 included in the complement source were bound to hemolysed SRC in direct proportion to the degree of hemolysis. These data indicate that polyclonal IgM-RF fix and activate complement via the classic pathway. The system described for assessing complement fixation by isolated RF is readily adaptable to use with whole human serum. PMID:1078825

  11. Common Therapy for Rheumatoid Arthritis Reduces Risk of Death

    MedlinePLUS

    ... Common Therapy for Rheumatoid Arthritis Reduces Risk of Death Taking methotrexate—a commonly prescribed anti-inflammatory medication—may reduce the risk of death among patients with rheumatoid arthritis (RA), according to ...

  12. Antibodies Act Jointly to Promote Inflammation in Rheumatoid Arthritis

    MedlinePLUS

    ... historical) Antibodies Act Jointly to Promote Inflammation in Rheumatoid Arthritis Two types of antibody molecules act in concert to stimulate inflammation in people with rheumatoid arthritis, according to research funded in part by the ...

  13. [Classification of hip joint involvement in rheumatoid polyarthritis].

    PubMed

    Thabe, H

    1983-10-01

    The involvement of hip joint in rheumatoid arthritis is regarded. According to the onset, clinical picture, progress and macroscopic shape of the synovial membrane a classification of rheumatoid attack is tried. PMID:6642375

  14. Chiral changes of simple amino acids in early Earth's ocean by meteorite impacts: Experimental simulations

    NASA Astrophysics Data System (ADS)

    Takase, A.; Sekine, T.; Furukawa, Y.; Kakegawa, T.

    2012-12-01

    It has been recognized that meteorite impacts on early Earth ocean may have contributed significantly for molecules related to the origin of life to originate and evolve. We have already established the formation of simple biomolecules from inorganic materials through oceanic impacts that may have occurred at late heavy bombardment. These simple molecules including amino acids need to be subjected to further developments to initiate life on the Earth. The chirality of terrestrial amino acids constructing proteins is only L-type. In order to make clear the the point that biomolecules are formed by oceanic impacts of meteorites, it wll be crucial to determine how they select the chirality. In order to investigate the basic chemistry on chirality of simple amino acids, we tried to simulate experimentally the chiral change of some amino acids present in ocean at that time under shock loading. Each aqueous solution (0.1 M) of L- and D-valine was prepared and used as mixtures of olivine powders and solutions in sealed steel containers. We performed shock recovery experiments at an impact condition where samples were compressed at ~5 GPa. The analytical results of shock recovered solutions indicate that valine survives significantly (~10%) and that L- and D-valines transform partially to D- and L-valine, respectively. The transformation rate varied with the chemical species present in solutions. These results imply that meteorite impacts as well as the surrounding conditions play important roles to control the chirality of simple amino acids that may have been formed at that time.

  15. Circadian use of glucocorticoids in rheumatoid arthritis.

    PubMed

    Cutolo, Maurizio; Sulli, Alberto; Pincus, Theodore

    2015-01-01

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

  16. Spatiotemporal analysis for indocyanine green-aided imaging of rheumatoid arthritis in hand joints.

    PubMed

    Mohajerani, Pouyan; Meier, Reinhard; Noël, Peter B; Rummeny, Ernst J; Ntziachristos, Vasilis

    2013-09-01

    Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease, with a prevalence of 0.5 to 1% in the general population. Imaging can possibly aid in early diagnosis, crucial to effective personalized therapeutic strategies and treatment follow-up. The intravenous administration of indocyanine green (ICG) has been considered for identifying synovial hyperperfusion as an RA physiological biomarker. However, while the distribution of ICG in the human hand is a time-dependent process, the particular biodistribution dynamic patterns established following intravenous administration have not yet been studied. For this reason, the dynamic relationships of ICG distribution in the human hand in RA patients using a method based on principal component analysis are analyzed. In vivo analyses were corroborated by simulations of clinical scenarios using a finite element method. Observations of spatiotemporal characteristics are contrasted to fluorescence intensity images and magnetic resonance images of the hand joints, employed as the anatomical and diagnostic reference. Processing results for 450 joints from 5 healthy volunteers and 10 patients show that image features obtained from the spatiotemporal analysis offer good congruence with synovitis and reveal better detection performance compared to observations of raw fluorescence intensity images. PMID:24045692

  17. 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

  18. Effects of fish oil supplementation in rheumatoid arthritis.

    PubMed Central

    van der Tempel, H; Tulleken, J E; Limburg, P C; Muskiet, F A; van Rijswijk, M H

    1990-01-01

    Sixteen patients with rheumatoid arthritis entered a trial to determine the clinical and biochemical effects of dietary supplementation with fractionated fish oil fatty acids. A randomised, double blind, placebo controlled crossover design with 12 week treatment periods was used. Treatment with non-steroidal anti-inflammatory drugs and with disease modifying drugs was continued throughout the study. Placebo consisted of fractionated coconut oil. The following results favoured fish oil rather than placebo: joint swelling index and duration of early morning stiffness. Other clinical indices improved but did not reach statistical significance. During fish oil supplementation relative amounts of eicosapentaenoic acid and docosahexaenoic acid in the plasma cholesterol ester and neutrophil membrane phospholipid fractions increased, mainly at the expense of the omega-6 fatty acids. The mean neutrophil leucotriene B4 production in vitro showed a reduction after 12 weeks of fish oil supplementation. Leucotriene B5 production, which could not be detected either in the control or in the placebo period, rose to substantial quantities during fish oil treatment. This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis. PMID:2138449

  19. The pathogenic potential of autoreactive antibodies in rheumatoid arthritis.

    PubMed

    Bax, Marieke; Huizinga, Tom W J; Toes, René E M

    2014-05-01

    Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1 % of the population. Although major advances have been made in the treatment of RA, relatively little is known about disease pathogenesis. Autoantibodies, present in approximately 60 % of the patients with early disease, might provide indications for immunological mechanisms underlying RA. Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade. The discovery of ACPAs resulted into novel insight in RA pathogenesis and allowed division of the heterogeneous entity of RA into an ACPA-positive and ACPA-negative subset of disease. Other autoantibodies discovered in the serum of RA patients, including rheumatoid factors (RFs) targeting human IgG and anti-peptidylarginine deiminase (PAD)3/4 antibodies reactive against and activating the enzyme involved in citrullination, might contribute in collaboration with ACPAs to a feed-forward loop to aggravate erosive outcome of disease. Recently, a novel autoantibody system associated with RA was identified. These autoantibodies recognize carbamylated proteins (anti-CarP antibodies) and are detected in approximately 20 % of ACPA-negative patients, suggesting another parameter to sub-classify RA. In this review, the implication of autoantibodies in RA pathogenesis, diagnosis, prognosis and as biomarker for personalized medicine is discussed. PMID:24763532

  20. ANTHEM simulations of the early time magnetic field penetration of the plasma surrounding a high density Z-pinch

    SciTech Connect

    Mason, R.J. )

    1989-12-01

    The early time penetration of magnetic field into the low density coronal plasma of a Z-pinch fiber is studied with the implict plasma simulation code ANTHEM. Calculations show the emission of electrons from the cathode, pinching of the electron flow, magnetic insulation of the electrons near the anode, and low density ion blow off. PIC-particle ion calculations show a late time clumping of the ion density not seen with a fluid ion treatment.

  1. ANTHEM simulation of the early time magnetic field penetration of the plasma surrounding a high density Z-pinch

    SciTech Connect

    Mason, R.J.

    1989-01-01

    The early time penetration of magnetic field into the low density coronal plasma of a Z-pinch fiber is studied with the implicit plasma simulation code ANTHEM. Calculations show the emission of electrons from the cathode, pinching of the electron flow, magnetic insulation of the electrons near the anode, and low density ion blow off. PIC-particle ion calculations show a late time clumping of the ion density not seen with a fluid ion treatment. 4 refs., 4 figs.

  2. 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.

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

    PubMed Central

    Rakieh, Chadi; Conaghan, Philip G

    2014-01-01

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

  4. Study of early stages of amyloid Aβ13-23 formation using molecular dynamics simulation in implicit environments.

    PubMed

    Bajda, Marek; Filipek, Slawomir

    2015-06-01

    β-amyloid aggregation and formation of senile plaques is one of the hallmarks of Alzheimer's disease (AD). It leads to degeneration of neurons and decline of cognitive functions. The most aggregative and toxic form of β-amyloid is Aβ1-42 but in experiments, the shorter forms able to form aggregates are also used. The early stages of amyloid formation are of special interest due to the influence of this peptide on progression of AD. Here, we employed nine helices of undecapeptide Aβ13-23 and studied progress of amyloid formation using 500ns molecular dynamics simulation and implicit membrane environment. The small β-sheets emerged very early during simulation as separated two-strand structures and a presence of the membrane facilitated this process. Later, the larger β-sheets were formed. However, the ninth helix which did not form paired structure stayed unchanged till the end of MD simulation. Paired helix-helix interactions seemed to be a driving force of β-sheet formation at early stages of amyloid formation. Contrary, the specific interactions between α-helix and β-sheet can be very stable and be stabilized by the membrane. PMID:25749181

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  7. 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.

  8. 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

  9. Diet therapy for rheumatoid arthritis.

    PubMed

    Panush, R S; Carter, R L; Katz, P; Kowsari, B; Longley, S; Finnie, S

    1983-04-01

    Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10-week, controlled, double-blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty-six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a "placebo" diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overall clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease. PMID:6838671

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  11. Performance of a new digital flat-panel detector system in the detection of simulated rheumatoid erosions: a comparison with a speed-class 200 screen-film system, a mammography screen-film system, and a storage-phosphor system at different levels of exposure.

    NASA Astrophysics Data System (ADS)

    Ludwig, Karl; Henschel, Andreas; Bernhardt, Thomas; Lenzen, Horst; Wormanns, Dag; Diederich, Stefan; Heindel, Walter

    2002-05-01

    The purpose of this study was to compare a large-area direct read-out flat-panel detector system with a speed class 200 screen-film system, a storage-phosphor system and a mammography screen-film system with regard to the detection of simulated rheumatoid erosions and to assess its diagnostic performance with decreasing exposure dose. The performance of a flat-panel system in such small lesions was considered especially interesting, as the spatial resolution of this system, limited by its pixel size, is considerably lower than that of conventional screen-film systems. An animal model with 160 joint specimens from 20 monkey paws was used. 640 regions were defined in these 160 meta- carpophalangeal and proximal interphalangeal joint specimens. Simulated rheumatoid erosions were created in 320 of these 640 regions. Specimens were enclosed in containers filed with water to obtain absorption and scatter radiation conditions similar to a human hand. Imaging was performed using a flat-panel system, a sped class 200 screen-film system, a mammography screen-film system and a storage- phosphor system under exactly matched conditions. Different exposure doses equivalent to speed classes of S equals 100, 200, 400, 800, 1600 and 3200 were used. Presence or absence of a lesion was assessed by three radiologists using a five level confidence scale. Receiver operating characteristic analysis was performed for a total of 21,120 observations and diagnostic performance estimated by the area under the ROC curve. The significance of differences between Az values was tested with analysis of variance. ROC-analysis showed Az values of 0.809, 0.768, 0.737, 0.710 and 0.685 for the flat-panel system, 0.770 for the screen-film system, 0.781, 0.739, 0.724 and 0.680 for the storage-phosphor system, and 0.798 for the mammography screen-film system. Analysis of variance showed significant differences for certain combinations of imaging modalities and exposure doses. The diagnostic performance of the flat-panel detector system is superior to that of a screen-film system and a storage-phosphor system for the detection of erosive lesions at clinical exposure settings. Using the flat-panel system the exposure does can be reduced by 50 percent to obtain a diagnostic performance comparable to a speed class 200 screen-film system.

  12. Isotypes of Epstein-Barr Virus Antibodies in Rheumatoid Arthritis: Association with Rheumatoid Factors and Citrulline-Dependent Antibodies

    PubMed Central

    Westergaard, Marie Wulff; Draborg, Anette Holck; Troelsen, Lone; Jacobsen, Sren; Houen, Gunnar

    2015-01-01

    In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were investigated by enzyme-linked immunosorbent assays (ELISA). Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs, IgG) and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection). Notably, for IgM and IgA (but not IgG), these were associated with the presence of characteristic RA autoantibodies. PMID:26000294

  13. Rheumatoid arthritis, the contraceptive pill, and androgens.

    PubMed Central

    James, W H

    1993-01-01

    Evidence is accumulating that low androgen concentrations are a cause of rheumatoid arthritis. This would explain a number of established features of the epidemiology of the disease. These include: (a) the variation of disease activity with pregnancy; (b) the variation of age at onset by sex; (c) the variation by sex with HLA-B15; (d) the association with bone mineral density; and (e) the differing time trends in incidence rates by sex. It is argued, moreover, that if one makes a plausible assumption--namely, that women who choose oral contraceptives have high androgen concentrations at the time they first make this choice--then an explanation becomes available for the confusion about the relation between rheumatoid arthritis and oral contraception. Grounds are adduced for that assumption. If this line of reasoning is substantially correct it also has implications for the relations between rheumatoid arthritis and smoking and consumption of alcohol. PMID:8323402

  14. Rheumatoid arthritis, the contraceptive pill, and androgens.

    PubMed

    James, W H

    1993-06-01

    Evidence is accumulating that low androgen concentrations are a cause of rheumatoid arthritis. This would explain a number of established features of the epidemiology of the disease. These include: (a) the variation of disease activity with pregnancy; (b) the variation of age at onset by sex; (c) the variation by sex with HLA-B15; (d) the association with bone mineral density; and (e) the differing time trends in incidence rates by sex. It is argued, moreover, that if one makes a plausible assumption--namely, that women who choose oral contraceptives have high androgen concentrations at the time they first make this choice--then an explanation becomes available for the confusion about the relation between rheumatoid arthritis and oral contraception. Grounds are adduced for that assumption. If this line of reasoning is substantially correct it also has implications for the relations between rheumatoid arthritis and smoking and consumption of alcohol. PMID:8323402

  15. 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.

  16. 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".

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

    PubMed Central

    Masuko, Kayo

    2014-01-01

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

  18. 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

  19. I have mastered the challenge of living with a chronic disease: life stories of people with rheumatoid arthritis.

    PubMed

    Stamm, Tanja; Lovelock, Linda; Stew, Graham; Nell, Valerie; Smolen, Josef; Jonsson, Hans; Sadlo, Gaynor; Machold, Klaus

    2008-05-01

    Our aim with this study was to explore the narrative life story of individuals diagnosed with rheumatoid arthritis. An open qualitative approach, namely narrative biographic methodology, was applied to include the life context of the participants and to deliberately exclude predefinitions of concepts. Ten people with rheumatoid arthritis who retired early because of the disease participated and were interviewed three times according to a narrative biographic interview style. The biographical data and the interview texts were analyzed both individually and in comparison to each other. Some participants regarded rheumatoid arthritis as a challenge for mastery in their lives, whereas others adapted to the disease and "made the best out of a bad situation." Especially in countries where the medical model predominates in health care, our findings can be used to broaden the current view that some health professionals have toward patients, and stress the importance of patients being self-responsible. PMID:18420538

  20. Rheumatoid arthritis and periodontal disease.

    PubMed

    Berthelot, Jean-Marie; Le Goff, Benot

    2010-12-01

    The prevalence of periodontal disease has increased two-fold among patients with rheumatoid arthritis (RA) compared to the general population. This increased prevalence is unrelated to secondary Sjgren's syndrome but instead reflects shared pathogenic mechanisms, including an increased prevalence of the shared epitope HLA-DRB1-04; exacerbated T-cell responsiveness with high tissue levels of IL-17; exaggerated B-cell responses, with plasma cells being the predominant cell type found within gingival tissue affected with periodontitis and B cells being twice as numerous as T cells; RANK overexpression; and an increase in the ratio of RANK-L over osteoprotegerin with a high level of RANK-L expression on gingival B cells, most notably those capable of recognizing Porphyromonas gingivalis. Other factors conducive to periodontitis include smoking and infection with the Epstein-Barr virus or cytomegalovirus, which act by promoting the growth of organisms such as P. gingivalis, whose DNA is often found in synovial tissue from RA patients. P. gingivalis produces the enzyme peptidylarginine deiminase that induces citrullination of various autoantigens, and levels of anti-CCP antibodies are considerably higher in RA patients with than without periodontal disease, suggesting that periodontitis may contribute to the pathogenesis of RA. Further support for this hypothesis comes from evidence that other antigens involved in RA, such as HC-gp39, are also present in gingival tissue. TNF? antagonists slow alveolar resorption but may perpetuate infection of periodontal pockets. Therefore, rheumatology patients, including those taking biotherapies, are likely to benefit from increased referral to dental care (e.g., scaling, root planing and, if needed, dental surgery), particularly as periodontitis is also associated with an increased risk of premature atheroma. PMID:20646949

  1. 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 cellcell and cellmatrix 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

  2. 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 Clia; Andrade, Lus 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.

  3. Rheumatoid cachexia and other nutritional alterations in rheumatologic diseases.

    PubMed

    Hurtado-Torres, Gilberto Fabián; González-Baranda, Lourdes Larisa; Abud-Mendoza, Carlos

    2015-01-01

    The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations. PMID:26094123

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

    PubMed

    Duprez, D; De Buyzere, M; Trouerbach, J; Ranschaert, W; Clement, D L

    2000-03-01

    This study examined the integrative changes of blood pressure (BP) and stroke volume (SV) leading to the initial biphasic heart rate (fc) response (first 15 s) in simulated diving manoeuvres with and without breathholding (BH). Simulated diving was studied in ten young healthy volunteers by application of a gel-filled pack at 0 degree C and 18 degrees C on the forehead with and without BH. Beat-by-beat and second-to-second fc, BP, SV, and total peripheral vascular resistance (TPR) were followed by continuous non-invasive monitoring. In all conditions (BH with forehead cooling at 0 degree and 18 degrees C) there was an early rise in BP triggering the first tachycardial response (fc acceleration) which was immediately counteracted by the concurrent further increase of SV leading to the second phase of early bradycardic response (fc deceleration). Furthermore, the continuous beat-by-beat and second-to-second monitoring allowed the documentation of a highly significant increase of TPR within the first few seconds of the manoeuvres. Our data further indicated that the differences in haemodynamics observed during the stimuli at different temperatures was overruled by BH. Detailed comparisons of the beat-by-beat and second-to-second analyses were unable to show that one method was better than the other. Using continuous non-invasive monitoring of haemodynamic variables during simulated diving manoeuvres it was possible to provide better insights into the physiological principles and meaning of the diving reflex in humans. PMID:10751103

  5. 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

  6. 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…

  7. Prospective new biological therapies for rheumatoid arthritis.

    PubMed

    Senolt, Ladislav; Vencovský, Jirí; Pavelka, Karel; Ospelt, Caroline; Gay, Steffen

    2009-12-01

    Advances in the current knowledge of pathogenetic mechanisms of rheumatoid arthritis have contributed to the development of biological therapy, and translated research findings into clinical practice. TNF-alpha (infliximab, etanercept, adalimumab), IL-1 (anakinra) and IL-6 (tocilizumab) inhibitors, a B-cell depleting agent (rituximab) and a drug blocking T-cell costimulation (abatacept) have been approved for rheumatoid arthritis. The progress in manufacturing biotechnology has contributed to the development of several other prospective agents that may form the basis for the therapy of rheumatoid arthritis in the near future. New or modified TNF-alpha inhibitors (golimumab, certolizumab pegol), new monoclonal antibodies against other cytokines (e.g. IL-1, IL-6, IL-12, IL-15, IL-17, IL-23), and other agents targeting B-cell depletion (e.g. ocrelizumab, ofatumumab) are in various stages of development. Many pharmaceutical companies have focused on developing small molecule inhibitors with possible peroral administration, which are considered promising drugs for rheumatoid arthritis. In most cases, these small molecules inhibit cellular kinases (e.g. p38, JAK or Syk) that mediate the signaling and transcription of proinflammatory genes. In this review, we describe the cytokine inhibitors and modulators of the immune response currently in ongoing clinical trials, the results of which may further expand the spectrum of efficient therapies for chronic autoimmune diseases. PMID:19328245

  8. Altered T lymphocyte signaling in rheumatoid arthritis.

    PubMed

    Allen, M E; Young, S P; Michell, R H; Bacon, P A

    1995-06-01

    Synovial and peripheral blood T cells from patients with rheumatoid arthritis are functionally deficient. This may be secondary to their reduced cytokine (e.g. interleukin-2) synthesis. We have investigated the possibility of an alteration in pathways common to interleukin-2 production and proliferation in peripheral blood T cells from patients with active rheumatoid arthritis. Intracellular calcium levels ([Ca2+]i) were analyzed by flow cytometric methods in Indo1-loaded T cells. These were purified by negative selection from patients or age/sex-matched controls, and stimulated with phytohemagglutinin-P or anti-CD3. Rheumatoid [Ca2+]i responses to both stimuli were reduced (p < 0.005). Patient cell samples included a larger proportion of non-responding cells, but even in the responsive population the magnitude of the response in rheumatoid cells was impaired compared with those in normal cell samples (p < 0.0001) for both stimuli. Proliferation responses were also impaired (p < 0.005), and there was a positive correlation between the paired [Ca2+]i elevation and proliferative responses for both stimuli. CD2 and CD3 expression were normal, and the proportions of CD4, CD8 and CD45RO and CD45RA subsets were also unaffected by disease. Thus a signaling defect downstream of CD2 or CD3 surface molecules may contribute to functional deficiencies in rheumatoid T lymphocytes. This effect is not due to non-steroidal anti-inflammatory drugs which some patients were taking. We have demonstrated similar alterations in [Ca2+]i responses and proliferation in a smaller study of patients with inflammatory bowel disease, indicating that such changes might be present in other chronic inflammatory states. PMID:7614981

  9. Quality in rheumatoid arthritis care.

    PubMed

    Mahmood, Sehrash; Lesuis, Nienke; van Tuyl, Lilian H D; van Riel, Piet; Landew, Robert

    2015-01-01

    While most rheumatology practices are characterized by strong commitment to quality of care and continuous improvement to limit disability and optimize quality of life for patients and their families, the actual step toward improvement is often difficult. This is because there are still barriers to be addressed and facilitators to be captured before a satisfying and cost-effective practice management is installed. Therefore, this review aims to assist practicing rheumatologists with quality improvement of their daily practice, focusing on care for rheumatoid arthritis (RA) patients. First we define quality of care as "the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge". Often quality is determined by the interplay between structure, processes, and outcomes of care, which is also reflected in the corresponding indicators to measure quality of care. Next, a brief overview is given of the current treatment strategies used in RA, focusing on the tight control strategy, since this strategy forms the basis of international treatment guidelines. Adherence to tight control strategies leads, also in daily practice, to better outcomes in patients with regard to disease control, functional status, and work productivity. Despite evidence in favor of tight control strategies, adherence in daily practice is often challenging. Therefore, the next part of the review focuses on possible barriers and facilitators of adherence, and potential interventions to improve quality of care. Many different barriers and facilitators are known and targeting these can be effective in changing care, but these effects are rather small to moderate. With regard to RA, few studies have tried to improve care, such as a study aiming to increase the number of disease activity measures done by a combination of education and feedback. Two out of the three studies showed markedly positive effects of their interventions, suggesting that change is possible. Finally, a simple step-by-step plan is described, which could be used by rheumatologists in daily practice wanting to improve their RA patient care. PMID:26697773

  10. [Diet, nutrition and rheumatoid arthritis].

    PubMed

    Miggiano, G A D; Gagliardi, L

    2005-01-01

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

  11. SMBH growth parameters in the early Universe of Millennium and Millennium-II simulations

    NASA Astrophysics Data System (ADS)

    Smole, Majda; Micic, Miroslav; Martinovi?, Nemanja

    2015-08-01

    We make black hole (BH) merger trees from Millennium and Millennium-II simulations to find under what conditions 109 M? SMBH can form by redshift z = 7. In order to exploit both: large box size in the Millennium simulation; and large mass resolution in the Millennium-II simulation, we develop a method to combine these two simulations together, and use the Millennium-II merger trees to predict the BH seeds to be used in the Millennium merger trees. We run multiple semi-analytical simulations where SMBHs grow through mergers and episodes of gas accretion triggered by major mergers. As a constraint, we use observed BH mass function at redshift z = 6. We find that in the light of the recent observations of moderate super-Eddington accretion, low-mass seeds (100 M?) could be the progenitors of high-redshift SMBHs (z 7), as long as the accretion during the accretion episodes is moderately super-Eddington, where fEdd = 3.7 is the effective Eddington ratio averaged over 50 Myr.

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. 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.

  15. [Diagnostic and prognostic value of antibodies to cyclic citrullinated peptide (Anti-CCP) in rheumatoid arthritis].

    PubMed

    Erre, G L; Tocco, A; Faedda, R; Cossu, A; Carcassi, A

    2004-01-01

    There is strong evidence that the determination of autoantibodies against filaggrine is a very useful tool for the diagnosis of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide antibodies (Anti-CCP)-ELISA appear to be the most efficient test among those available for the detection of antifilaggrine autoantibodies, as it has the best diagnostic accuracy for the diagnosis of RA. Furthermore, the anti-CCP-ELISA determination in early arthritis is a good predictor of disease persistence and radiographic joint damage. The positivity of Anti-CCP some years before the onset of the RA and the high concentration of autoantibodies in synovial fluid suggest a possible pathogenetic role of citrullination. However, at present, it is unclear whether anti-CCP antibodies have a better diagnostic performance than rheumatoid factor in recent onset synovitis and if they confer any additional value to the prognostic evaluation obtained with validated predictors of outcome (FR, joint count, duration of disease). PMID:15309221

  16. 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 ...

  17. Skills of novices early trained or traditionaly trained versus experienced drivers confronted to simulated urban accidents' scenarios.

    PubMed

    Berthelon, Catherine; Damm, Loc

    2012-01-01

    In order to prevent the over-representation of young drivers in car crashes, France instated an early driver training from the age of 16, but the positive effects of this opportunity have not yet been proven. Three groups of male drivers (12 subjects each) were confronted with some prototypical accident scenarios introduced in a simulated urban circuit. The first and second groups were composed of young drivers having less than one month of driving licence; twelve have had a traditional learning course, and twelve had followed, in addition to the initial course, an early driver training under the supervision of an adult. The third group was composed of experienced drivers. Strategies of the three groups were analyzed through their response time, speed and maneuvers. No difference appeared across groups regarding obstacle detection. But traditionally-trained drivers' position control was more conservative than the two others groups, which were more likely to involve efficient evasive action. The exposure gained during early training could thus increase the development of visuo-motor coordination and involve better skills in case of difficult situations. Others accidents' scenarios could be used to confront young drivers with difficult situations not commonly encountered in natural driving. PMID:22317478

  18. 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).

  19. 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.

  20. 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 6875% of patients with early rheumatoid arthritis and is considered to be a predictor of rapid disease progression.

  1. 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.

  2. 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

  3. Recognizing Rheumatoid Arthritis: Oncoprotein Survivin Opens New Possibilities

    PubMed Central

    Chun-Lai, Too; Murad, Shahnaz; Erlandsson, Malin C.; Hussein, Heselynn; Sulaiman, Wahinuddin; Dhaliwal, Jasbir S.; Bokarewa, Maria I.

    2015-01-01

    Abstract Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n?=?1233) and controls (n?=?1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR?=?5.40, 95% CI 3.817.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR?=?16.21, 95% CI 5.7046.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA. PMID:25634192

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

    SciTech Connect

    Kruger, A.A.; Olson, R.A.; Tennis, P.D.

    1995-04-01

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

  5. Follicular helper T cells in rheumatoid arthritis.

    PubMed

    Yu, Meixing; Cavero, Vanesssa; Lu, Qiao; Li, Hong

    2015-09-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in the joints and other tissues. Rheumatoid factor (RF) and anticyclic citrullinated peptides (anti-CCP) are biomarkers for the evaluation of RA although their functions in the pathogenesis of RA are poorly understood. CXC-chemokine receptor 5 (CXCR5)(+) T follicular helper (TFH) cells are essential for B cell maturation and antibody production. Recent studies have showed that dysregulated TFH cells are associated with the development of autoimmune diseases. This article reviews the characters and functions of TFH cells, such as their differentiation, expression, transcription factor, and B cell maturation. Meanwhile, we also discuss the possible mechanisms underlying the role of these cells in RA and potential treatments, including antibody-blocking agents, gene therapies, T cell vaccines, and T follicular regulatory (TFR) cells. Overall, we discuss the roles of TFH cells in the pathogenesis of RA and potential therapies for RA. PMID:26227164

  6. 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

  7. Autoantibodies to posttranslational modifications in rheumatoid arthritis.

    PubMed

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

    2014-01-01

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

  8. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

    PubMed Central

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

    2014-01-01

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

  9. Discriminating early stage A?42 monomer structures using chirality-induced 2DIR spectroscopy in a simulation study

    PubMed Central

    Zhuang, Wei; Sgourakis, Nikolaos G.; Li, Zhenyu; Garcia, Angel E.; Mukamel, Shaul

    2010-01-01

    Elucidating the structural features of the A? monomer, the peptide constituent of amyloid fibrils found in Alzheimers disease, can enable a direct characterization of aggregation pathways. Recent studies support the view that the ensemble of A?42 monomers is a mixture of diverse ordered and disordered conformational species, which can be classified according to the formation of a characteristic ?-hairpin conformation in a certain region. Despite the disparity in the structural features of these species, commonly used spectroscopic techniques such as NMR may not directly trace the conformational dynamics in the ensemble due to the limited time resolution and the lack of well-resolved spectral features for different comformers. Here we use molecular dynamics simulations combined with simulations of two-dimensional IR (2DIR) spectra to investigate the structure of these species, their interchange kinetics, and their spectral features. We show that while the discrimination efficiency of the ordinary, nonchiral 2DIR signal is limited due to its intrinsic dependence on common order parameters that are dominated by the generally unstructured part of the sequence, signals with carefully designed chirality-sensitive pulse configurations have the high resolution required for differentiating the various monomer structures. Our combined simulation studies indicate the power of the chirality-induced (CI) 2DIR technique in investigating early events in A?42 aggregation and open the possibility for their use as a novel experimental tool. PMID:20798063

  10. 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.

  11. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  13. 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.

  14. 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.

  15. 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.

  16. Efficacy of radiosynovectomy in rheumatoid arthritis.

    PubMed

    Liepe, Knut

    2012-10-01

    In this retrospective study, we evaluated the effect of radiosynovectomy of patients with rheumatoid arthritis. Radiosynovectomy was performed in 577 joints of 137 rheumatoid patients. We applied 185 MBq yttrium-90 in knees (n = 58), 74-111 MBq rhenium-186 colloids in ankle (n = 50), wrists (n = 43) and shoulders (n = 35), and 15 to 37 MBq in finger (n = 298) and toe joints (n = 46). The effect of radiosynovectomy was scored in 4 subjective categories: excellent response (no symptoms); good response (significant reduction of symptoms); moderate response (slight decrease); and bad response (no change or worsening), of pain and/or swelling in treated joint 3 months after the procedure. Excellent or good response was observed in 57% of treated knees, 63% of shoulders, 60% of wrists, 64% of ankles, 54% of thumb bases, 55% of MCP's, 54% of PIP's, 53% of DIP's, and 54% of MTP's. Side effects associated to the RSO, i.e., swelling or transient increase of pain, were recorded in 7% of the patients that resolved within 1 month. No patient had any non-reversible skin alteration after treatment, only slight erythema was observed in 5 patients. Radiosynovectomy is effective and safe in the treatment of rheumatoid arthritis. PMID:21964982

  17. 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

  18. Advances in the treatment of rheumatoid arthritis

    PubMed Central

    Vivar, Nancy

    2014-01-01

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

  19. 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.

  20. 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

  1. 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.

  2. 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.

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

    SciTech Connect

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

    2011-01-02

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

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

    PubMed

    Werth, E; Dijk, D J; Achermann, P; Borbly, 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

  5. Management of the foot and ankle in rheumatoid arthritis.

    PubMed

    Mann, R A; Horton, G A

    1996-08-01

    Rheumatoid arthritis frequently involves the foot and ankle, resulting in pain, deformity, and difficulty with ambulation. This article outlines clinical, radiographic, and gait evaluation in the management of foot and ankle problems in rheumatoid arthritis. Conservative nonsurgical management of foot deformities is presented including available shoewear and orthotic options. Surgical considerations including indications, biomechanic implications, and specific operative procedures are discussed. PMID:8844908

  6. Modern treatment strategies in rheumatoid arthritis.

    PubMed

    Hetland, Merete Lund

    2011-11-01

    The main aim of the thesis was to evaluate the impact of modern treatment strategies on disease activity and disease course in patients with rheumatoid arthritis (RA), and to identify predictors for treatment response. Two different treatment strategies were investigated: (A) Aggressive, conventional treatment aiming at achieving inflammatory control in patients with recent-onset RA and (B) Treatment with tumour necrosis factor alpha (TNF?) inhibitors in patients with RA, who had an incomplete response to conventional treatment. (A) was studied in a randomized, placebo-controlled clinical trial (CIMESTRA), whereas (B) was investigated in an observational, nationwide cohort study (the DANBIO database). The main findings were: 1. Treatment strategy (A) with methotrexate (MTX) and injections of glucocorticoids into swollen joints had rapid and sustained effect and reduced disease activity and halted joint damage. Addition of cyclosporine during the first 2 years reduced disease activity for as long as it was given, but had no effect on the development of joint damage. After 5 years, the majority of the patients was in remission and had no progression of structural joint damage. 2. Bone marrow oedema by Magnetic resonance imaging (MRI) scans of the wrists predicted the development of structural joint damage 2 to 5 years later (based on x-rays). Anti-CCP antibodies and structural joint damage at the start of treatment were also independent predictors for joint damage after 5 years. 3. Routine registration of adverse events observed in patients who received treatment with etanercept or infliximab (TNF? inhibitors) in the DANBIO database picked up twice as many serious adverse events than the spontaneous, mandatory reports to the Danish Medicines Agency. 4. Despite changes in prescription practice for the treatment with TNF? inhibitors in clinical practice from year 2000 to year 2005 towards less stringent treatment criteria, DANBIO data showed an improved treatment response. 5. High age, low functional status and concomitant treatment with prednisolone were negative predictors of a EULAR good response and remission after 6 months of treatment with TNF? inhibitors in clinical practice. 6. In patients, who were nave to treatment with TNF? inhibitors, significant differences between drugs were observed regarding treatment responses and adherence to therapies. Infliximab had the lowest treatment response, remission rates and adherence to therapy. Adalimumab had the highest treatment response and remission rates, whereas etanercept had the highest adherence. In conclusion, the results from the CIMESTRA trial and the DANBIO database showed that an aggressive treatment strategy with conventional drugs and intra-articular injections with betamethasone effectively controlled disease activity and prevent structural joint damage in patients with early RA. TNF? inhibitors were efficacious in clinical practice in the treatment of RA patients that had failed conventional treatment. Differences between the TNF? inhibitors regarding efficacy and drug adherence were found. Predictors of disease course and treatment response were identified. PMID:22047935

  7. 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.

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

    PubMed Central

    Kilic, Gamze; Ozgocmen, Salih

    2015-01-01

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

  9. 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.

  10. Cardiovascular Disease and Rheumatoid Arthritis: An Update

    PubMed Central

    Charles-Schoeman, Christina

    2012-01-01

    Patients with rheumatoid arthritis (RA) suffer significantly increased cardiovascular (CV) morbidity and mortality when compared to the general population. Both traditional CV risk factors and high levels of systemic inflammation have been linked to the increased CV risk in RA patients, but significant uncertainty remains regarding the mechanisms through which these factors contribute to CVD. In addition, ongoing questions remain regarding how best to identify RA patients at high risk for CVD, and what primary and secondary prevention strategies are effective at influencing CV outcome. The current review summarizes recent research in this field. PMID:22791398

  11. 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 (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 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 μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg 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, Il2rα, Ifnγ, 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 sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg 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

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

    PubMed Central

    Martinez, Emily M.; Yoshida, Miya C.; Candelario, Tara Lynne T.

    2015-01-01

    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 (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 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 μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg 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, Il2rα, Ifnγ, 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 sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg 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. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. [Topics of glucocorticoids--centered on therapy for rheumatoid arthritis].

    PubMed

    Akama, Hideto

    2011-01-01

    Glucocorticoids (steroids) have been widely used for the treatment of patients with rheumatoid arthritis (RA) since Hench had attempted to administer cortisone (Kendall's compound E) to an active RA patient in 1948. Rheumatologists even in the 21st century can learn a lot from the history of steroid. In this feature article on steroid, a brief outline of 11β-hydroxysteroid dehydrogenase type 1, a tissue-specific regulator of steroid response, is presented. The isozyme re-activates inactive cortisone (compound E) to active cortisol (compound F), and seems to play an important role particularly in adipose tissue. In addition, I give an account of non-genomic mechanisms of steroid, which might be relevant to early and rapid effects during methylprednisolone pulse therapy. As for the field of practical rheumatology, rates and dosages of steroid administration for RA in Japan are shown, by looking into 3 large observational cohort researches and post-marketing surveillance programs for several biologics. The definition or an appropriate interpretation of medical/technical terms such as 'effectiveness' in the clinical setting and 'low-dose' steroid is also described. PMID:22214807

  20. 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 (κ = 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

  1. 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

  2. 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

  3. Genetic markers of cardiovascular disease in rheumatoid arthritis.

    PubMed

    Rodrguez-Rodrguez, Luis; Lpez-Mejas, Raquel; Garca-Bermdez, Mercedes; Gonzlez-Juanatey, Carlos; Gonzlez-Gay, Miguel A; Martn, Javier

    2012-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    2013-01-01

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

  6. 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 (κ = 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

  7. 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

  8. The lung in rheumatoid arthritis, cause or consequence? Erratum.

    PubMed

    2016-03-01

    The name of the one of the first authors is spelt incorrectly in the article, 'The lung in rheumatoid arthritis, cause or consequence? The correct spelling is Aikaterini Chatzidionysiou. PMID:26855334

  9. 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

  10. 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

  11. Perna canaliculus in the treatment of rheumatoid arthritis.

    PubMed

    Caughey, D E; Grigor, R R; Caughey, E B; Young, P; Gow, P J; Stewart, A W

    1983-01-01

    Freeze-dried extracts of the New Zealand green lipped mussel, Perna canaliculus, have been promoted extensively as a treatment for rheumatoid arthritis for some years though there have been few published trials of its effectiveness. Our study was designed to test the ability of the mussel extract to relieve the symptoms of rheumatoid arthritis as both a supplement and an alternative to orthodox anti-inflammatory medication. PMID:6673984

  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?m 22.49) than the normal controls (248.2?m 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. Quality of life in rheumatoid arthritis.

    PubMed

    Whalley, D; McKenna, S P; de Jong, Z; van der Heijde, D

    1997-08-01

    Patient-completed health status instruments currently available for use with rheumatoid arthritis (RA) patients lack adequate reliability and responsiveness, making them unsuitable for use as outcome measures in clinical trials. A search of the literature failed to identify a quality of life (QoL) instrument specific to RA. The present study was designed to be the first stage in the development of such a measure. Qualitative interviews were held with 50 RA patients, 25 in the UK and 25 in The Netherlands. The interviews indicated that RA has a detrimental effect on many areas of life, including moods and emotions, social life, hobbies, everyday tasks, personal and social relationships, and physical contact. Transcripts of the interviews formed the source of items for the RAQoL, the first RA-specific QoL instrument. PMID:9291858

  14. Prolactin/cortisol ratio in rheumatoid arthritis.

    PubMed

    Zoli, Angelo; Ferlisi, Ester Maria; Lizzio, Marco; Altomonte, Lorenzo; Mirone, Luisa; Barini, Angela; Scuderi, Flavia; Bartolozzi, F; Magaro, Mario

    2002-06-01

    Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. PRL/cortisol ratio, and IL-1beta and TNF-alpha levels were determined in patients with RA and in control subjects at 0600, 1000, 1400, 1800, 2200, and 0200 hours. In patients with RA we observed higher PRL/cortisol ratio at 0200 hours, whereas IL-1beta and TNF-alpha reached their highest serum levels at 0200 and 0600 hours. In patients with RA we observed an imbalance in favor of proinflammatory hormones as opposed to levels of antiinflammatory hormones during nocturnal hours together with increased levels of IL-1beta and TNF-alpha of the diurnal rhythm of disease activity. PMID:12114312

  15. 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

  16. 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)

  17. Galectins in the Pathogenesis of Rheumatoid Arthritis.

    PubMed

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

    2013-09-30

    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

  18. Rheumatoid Arthritis: A Role for Immunosenescence?

    PubMed Central

    Lindstrom, Tamsin M.; Robinson, William H.

    2010-01-01

    Aging is accompanied by a progressive decline in the integrity of the immune system, a process known as immunosenescence. Rheumatoid arthritis (RA), an autoimmune disease whose incidence increases with age, is characterized by pathological features typical of immune dysfunction in the elderly, encompassing dysregulation of both innate and adaptive immune responses. Recent evidence suggests that certain features of immunosenescence, such as the decrease in T-cell generation and diversity, may contribute to the development of RA. Thus, physiological immunosenescence may render the elderly susceptible to RA, while premature immunosenescence may contribute to the development of RA in young adults. In addition, other features of immunosenescence may result from the chronic immune stimulation that occurs in RA and lead to worsening of the disease. Here we review the immunopathological features common to aging and RA, and discuss the mechanisms by which immunosenescence may contribute to the development or progression of RA. PMID:20942872

  19. [Update rheumatism focusing on rheumatoid arthritis].

    PubMed

    Duhme, H

    2015-09-01

    Rheumatic diseases do not only represent a challenge in day to day clinical medicine but also during underwriting and claims handling in insurance medicine. New diagnostic laboratory tests and therapeutic options constantly improve diagnostic quality and treatment outcomes. Using rheumatoid arthritis (RA) as an example this article explains how this new aspects found their way into international diagnostic criteria and treatment guidelines. The introduction of diagnostic ACPAs (Anti-Citrullinated Protein Antibodies) and the therapeutic use of currently still relatively expensive biologicals have to be highlighted in this respect. Backed by modern therapeutic options recent RA morbidity figures of employed persons indicate a shift to less severe morbidity spectra. For individual case evaluation it is of importance to understand the most relevant aspects of such innovations for adequate and sound case assessment in underwriting and claims. PMID:26548003

  20. 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

  1. Adipokines as Potential Biomarkers in Rheumatoid Arthritis

    PubMed Central

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

    2014-01-01

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

  2. 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

  3. 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

  4. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

    Weller, R. O.; Bruckner, F. E.; Chamberlain, M. Anne

    1970-01-01

    Peripheral nerves in five patients with rheumatoid neuropathy were examined electrophysiologically and by sural nerve biopsy. There was close correlation between the clinical severity of the disease and the degree of nerve damage found histologically and by EMG. Group 1 patients with a mild distal sensory neuropathy showed varying degrees of axonal degeneration in the large myelinated fibres and some segmental demyelination. Group 2 patients with a severe, rapidly progressive sensori-motor neuropathy had extensive loss of myelinated fibres. In one case all the large fibres had degenerated. The second case had lost both large and small myelinated fibres together with many of the non-myelinated axons. The major nerve damage in both groups appeared to be axonal degeneration but some segmental demyelination was detected. Occlusive vascular disease in the vasa nervorum was considered to be the major cause of the nerve damage. Images PMID:4320255

  5. Role of ultrasound in managing rheumatoid arthritis.

    PubMed

    Hammer, Hilde Berner; Terslev, Lene

    2012-10-01

    Ultrasound (US) is a valid and reliable imaging tool for evaluation of joint and tendon inflammation as well as cartilage and erosions in patients with rheumatoid arthritis (RA). Synovitis is usually scored semiquantitatively for both gray scale synovitis and power Doppler activity, and use of an atlas for US scoring has shown excellent reliability. Several scores are shown to be responsive to medical treatment, but the optimal joint/tendon score is to be explored. Doppler activity may be quantified by use of pixel counts and flow may be examined by use of resistive index. US-guided injections are better tolerated and have increased efficacy, as compared with palpation guidance, and should thus be included in rheumatologic practice. Different methods such as three-dimensional US, contrast-enhanced US and fusion imaging methods are all possible US approaches that may be used in treatment of RA patients in the future. PMID:22763856

  6. Rheumatoid arthritis in the United Arab Emirates.

    PubMed

    Badsha, Humeira; Kong, Kok Ooi; Tak, Paul P

    2008-06-01

    Studies have shown that patients with rheumatoid arthritis (RA) in the Middle East have delayed diagnosis and low disease-modifying anti-rheumatic drug (DMARD) utilization. We describe the characteristics and treatments of consecutive RA patients presenting to a new musculoskeletal clinic in Dubai, United Arab Emirates (UAE). Demographic and clinical data were collected over a 10-month period at the first visit to our clinic for patients meeting the American College of Rheumatology (ACR) criteria for RA. A total of 100 patients were seen: (average +/- SD) age 42.2 +/- 12.3 years; female 87%; Arabs 38%, Indian 36%, Caucasian and others 26%; 73% rheumatoid-factor positive; years since diagnosis: 3.9 +/- 5.7; lag time between symptom onset to diagnosis 1.2 +/- 1.3 years and lag time to first DMARD was 1.6 +/- 2.0 years. Mean tender joint count was 8.9 +/- 7.9, mean swollen joint count 9.0 +/- 7.6, mean patient's global assessment of disease activity 57.4 +/- 25.0 mm, mean ESR 33 +/- 25 mm/h, mean DAS28 5.2 +/- 1.6, physician global assessment 55.0 +/- 23.8. Only 43% were on DMARDs (25% MTX, 5% TNF blockers). Among the patients who were not on DMARD, only 28.1% had disease duration less than 1 year (p = <0.01). Erosions were present in 55.2% of patients with available X-rays, and deformities in 26% of patients. There were no racial differences in disease characteristics. The UAE has a unique population with many races residing in the country. Among the first 100 consecutive patients seen at our clinic, there were no significant differences in disease characteristics with the majority of the patients having very active disease, delayed diagnosis, and not being treated with DMARDs. PMID:17973153

  7. Radiological picture of juvenile rheumatoid arthritis.

    PubMed

    Streda, A; Trnavsk, K; Pazderka, V; Bardfeld, R

    1989-01-01

    Basing on the results of radiological, clinical and laboratory examinations of 200 children with juvenile rheumatoid arthritis, we tried to obtain a comprehensive picture of radiological changes in the joints, the spine and the remaining skeleton caused by JRA. The bulk of data was obtained in the period between 1954 and 1972, but for some of the patients, our follow-up continued until 1987. Our main interest were differences in morphological changes caused by JRA and adult RA. We described initial changes and their progress in childhood, adolescence and adulthood, drawing attention to fundamental differences in radiological changes and their progress in patients with an onset of disease in the first half of childhood (up to the age of 8) and in those with an onset in the second half of childhood, where these changes were similar already to those caused by adult RA. Juvenile rheumatoid arthritis affects mainly skeletal growth by either retarding or accelerating various ossification processes. The skeleton of children has a great regenerative capacity, but this, on the other hand, supports various disturbances of growth brought forth by disease. This, apparently, account for differences of changes in the skeleton of the joints observed in JRA patients during childhood and adulthood. Whenever a case is suspected of JRA, a radiological examination of the joints involved ought to be complemented by a radiological examination of the hands because most of our radiographs showed structural changes in the hands. Particular attention should also be given to the knees and hips of children with active disease over a period of 3-6 years. Synostosis of arches and joints of the cervical spine, a typical feature of JRA, was observed in 20-25% of former JRA patients. Synostoses occurred either in the individual segments or in the whole cervical spine, but were never absent at the level of vertebral bodies C2-C3. There were neither objective nor subjective complaints. PMID:2486228

  8. 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

  9. Mixed lymphocyte cultures in rheumatoid arthritis.

    PubMed Central

    Stastny, P

    1976-01-01

    Random one-way microtiter mixed lymphocyte cultures between 43 rheumatoid arthritis (RA) patients and 45 controls consisting of 26 normal subjects and 19 miscellaneous non-RA patients were performed and results were evaluated as relative responses. Low responses (consisting of relative response less than 38%) were found in 31 out of 43 RA patients in cultures against eight of the RA stimulators. The remaining 35 RA stimulators tested yielded only normal mixed lymphocyte culture reactions. The same RA patients used as responders never produced low responses when stimulated by non-RA lymphocytes. But six of the control subjects gave low responses to two RA stimulators. The low responses did not appear to correlate with intake of aspirin, prednisolone, or gold salts, nor could they be reproduced by addition of RA serum of 7S or 19S fractions thereof containing either polyclonal or monoclonal rheumatoid factors. Short-term culture and washing before mixing with the allogeneic cells did not change the low responses suggesting that in vivo bound autoantibodies against lymphocyte receptors were not involved. Study of the inheritance of HLA and mixed lymphocyte culture determinants in the family of patient A. C. who most frequently elicited low responses indicated she was homozygous for a lymphocyte-defined determinant which has been called R. The low responses to A. C. could be interpreted as typing responses based on sharing of the same or of a similar lymphocyte-defined determinant. This gene appears to be increased in patients with RA with respect to non-RA controls and may reflect an association of genes within the HLA chromosomal region leading to predisposition for the development of RA. Images PMID:1262462

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

    NASA Technical Reports Server (NTRS)

    Cao, Y.; Faghri, A.

    1993-01-01

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

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

    PubMed

    Clarke, Lynsey; Kirwan, John

    2012-06-01

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

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

    MedlinePLUS

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

  13. 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 ...

  14. 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 ...

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

    MedlinePLUS

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  16. Site-specific Ground-Motion Predictions for Earthquake Early Warning in the LA Basin using CyberShake Simulations

    NASA Astrophysics Data System (ADS)

    Boese, M.; Graves, R. W.; Callaghan, S.; Maechling, P. J.

    2012-12-01

    Predicting site-specific ground-motion intensity measures for large earthquakes (M>6.5) in real-time is a major challenge in earthquake early warning (EEW). Commonly, ground-motion parameters are predicted indirectly from magnitude and distance using empirical ground-motion attenuation relations. This approach though bears two major problems: (1) the extent of fault ruptures is usually unknown in real-time and the earthquake has to be approximated by a simple point-source; (2) directivity and basin effects are generally neglected. This can lead to a serious under estimation of ground-motions and result in warnings not being issued. To overcome these shortcomings, we have developed a novel approach for site-specific ground-motion prediction based on physics-based statistical models. Our models were derived from the SCEC CyberShake dataset that consists of around 400,000 full 3D wave-propagation simulations (6.5≤M≤8.5) at around 200 locations in and around the Los Angeles (LA) basin. The original purpose of this dataset was to develop a physics-based computational approach to probabilistic seismic hazard analysis (PSHA) based on southern California ruptures defined in Unified California Earthquake Rupture Forecast 2.0 (UCERF2.0). Here we extend the application of the CyberShake dataset to improve ground-motion predictions in the LA area for EEW and other purposes. The aim of our study is to provide fast and realistic site-specific ground-motion estimates for any large earthquake (M>6.5) in southern California. For this purpose we developed statistical models based on Support Vector Machines (SVMs) which were trained with source and ground-motion parameters from the CyberShake dataset to predict the expected long-period spectral acceleration (3 to 10 seconds) in the LA basin. SVMs are supervised learning models for classification and regression. Once trained, our SVM models are able to predict the spectral acceleration (SA) for any given earthquake magnitude and location in southern California. The results from our study show that due to the combined effects of fault geometries, wave propagation, and rupture directivity, it is not necessarily the closest fault ruptures that cause strongest shaking in the LA basin in the long-period range, but can be those that are considerably far away (such as those on the southern San Andreas Fault). This observation suggests that warnings could be provided some tens of seconds to around one minute before long-period shaking in the LA basin starts. Our approach does not only give a qualitative, but quantitative description of this shaking in terms of SA levels. Long-period shaking as analyzed in this study is most critical for high-rise buildings; the ground-motion predictions from our models can thus find possible application in structural control systems. However, as wave propagation simulations covering a broader frequency band become available, our ground-motion prediction models can be easily extended to shorter periods.

  17. 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

  18. Current concepts in the management of rheumatoid arthritis.

    PubMed

    Tanaka, Yoshiya

    2016-03-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaïve, inadequately responsive to methotrexate or tumor necrosis factor (TNF)-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and "deep remission" at the discontinuation was a key factor to keep the treatment holiday of biological DMARD. PMID:26932398

  19. Current concepts in the management of rheumatoid arthritis

    PubMed Central

    Tanaka, Yoshiya

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaïve, inadequately responsive to methotrexate or tumor necrosis factor (TNF)-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and “deep remission” at the discontinuation was a key factor to keep the treatment holiday of biological DMARD. PMID:26932398

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

    PubMed Central

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

    2015-01-01

    Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disorder and anti-cyclic citrullinated peptide antibody (anti-CCP Ab) is regarded as a serological marker for diagnosing early and late RA. In the present study, we aimed to determine the levels of anti-CCP Ab in serum, synovial tissue (ST) and synovial fluid (SF) in RA patients undergoing total knee arthroplasty (TKA). 23 patients were included. Rheumatoid factor (RF) and anti-CCP Ab in serum were detected prior to surgery and then at 1, 3, 6 and 12 months after TKA. Synovial samples were obtained by knee arthroscopy and used for anti-CCP detection. One month after TKA, anti-CCP levels were significantly reduced (P < 0.01) in RA patients. However, their levels were not significantly different between pre-surgery and 1 year post-surgery (P > 0.05). Furthermore, anti-CCP levels in ST were much higher than in serum. These findings suggest that RA patients should continue antirheumatic therapy after TKA. ST is the preferred place for the synthesis of anti-CCP Ab. PMID:26064362

  1. The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis.

    PubMed

    Paulissen, Sandra M J; van Hamburg, Jan Piet; Dankers, Wendy; Lubberts, Erik

    2015-07-01

    The IL-17A producing T-helper-17 (Th17) cell population plays a major role in rheumatoid arthritis (RA) pathogenesis and has gained wide interest as treatment target. IL-17A expressing Th cells are characterized by the expression of the chemokine receptor CCR6 and the transcription factor RORC. In RA, CCR6+ Th cells were identified in peripheral blood, synovial fluid and inflamed synovial tissue. CCR6+ Th cells might drive the progression of an early inflammation towards a persistent arthritis. The CCR6+ Th cell population is heterogeneous and several subpopulations can be distinguished, including Th17, Th22, Th17.1 (also called non-classic Th1 cells), and unclassified or intermediate populations. Interestingly, some of these populations produce low levels of IL-17A but are still very pathogenic. Furthermore, the CCR6+ Th cells phenotype is unstable and plasticity exists between CCR6+ Th cells and T-regulatory (Treg) cells and within the CCR6+ Th cell subpopulations. In this review, characteristics of the different CCR6+ Th cell populations, their plasticity, and their potential impact on rheumatoid arthritis are discussed. Moreover, current approaches to target CCR6+ Th cells and future directions of research to find specific CCR6+ Th cell targets in the treatment of patients with RA and other CCR6+ Th cell mediated autoimmune diseases are highlighted. PMID:25828206

  2. 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

  3. 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.

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

    PubMed

    de Santana, Frederico Santos; Nascimento, Dahan da Cunha; de Freitas, Joo 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

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

    PubMed Central

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

    1993-01-01

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

  6. 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

  7. Steroids reduce complement activation in rheumatoid arthritis.

    PubMed

    Brandslund, I; Peters, N D; Ejstrup, L

    1985-01-01

    Patients with seropositive, classical rheumatoid arthritis (RA) with severe active disease have raised plasma concentrations of the complement C3 split product C3d. These values display little diurnal or circadian variation in the individual patient. During a 3-month period the variation was within 10 mU/l in 45 patients (ref. range 20-52 mU/l, RA patients up to 120 mU/l.) Six RA patients were treated with steroids on clinical indication, and the plasma C3d, Ritchie index and pain score before and during the treatment (30 mg prednisolone per day) were measured. The variables showed a steady decrease during the next 14 days. Plasma C3d fell 2/3 of the total fall within the first 48 hours, while the serum total haemolytic complement activity, complement C3 and C4 did not change significantly. This shows that the anti-inflammatory effect of steroids is accompanied by a reduction of complement activation. PMID:3875589

  8. [The aetiology of rheumatoid arthritis (author's transl)].

    PubMed

    Denman, A M

    1976-04-01

    An ineffective aetiology for rheumatoid arthritis and other connective tissue diseases has been frequently postulated but never proven. Despite the failure to obtain firm evidence of viral infection in most patients with these disorders for several reasons this theory should not be discarded. Firstly several mechanisms have been discovered by which virus infections can persist in lymphocytes and other tissue thereby provoking inflammation without the production of complete readily detectable virus particles. Secondly there are numerous ways in which host resistance to virus can be subverted with the perpetuation of an ineffective or inappropriate immune response. Thirdly the immunopathological features of these diseases are entirely compatible with an infective aetiology. The main problem is likely to prove the difficulty in attributing a primary pathogenetic role to any isolated virus rather than regarding it as a passenger virus which has been non-specifically activated by the disease process. However preoccupation with a viral aetiology should not blind one to other possibilities since many environmental allergens can produce immunopathological disease of highly protean nature. PMID:1085744

  9. Mechanisms involved in triggering rheumatoid arthritis.

    PubMed

    Catrina, Anca I; Joshua, Vijay; Klareskog, Lars; Malmstrm, 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

  10. Osteoporosis and osteoarthritis, rheumatoid arthritis and spondylarthropathies.

    PubMed

    Clayton, Elizabeth Smelter; Hochberg, Marc C

    2013-12-01

    Osteoporosis (OP) commonly occurs in the setting of inflammatory arthritis, whereas there is an inverse relationship with osteoarthritis (OA). We review the recent updates in epidemiology and pathophysiology of OP relating to several arthridities. In ankylosing spondylitis, lateral lumbar spine dual x-ray absorptiometry is better at detecting osteoporosis compared with the AP view and patients receiving treatment with anti- tumor necrosis factor medications had lower levels of bone turnover markers. With regard to rheumatoid arthritis, anticitrullinated peptide positivity without clinical arthritis as well as higher levels of interleukin-6 is associated with decreased bone mineral density and polymorphisms in the vitamin D receptor in RA patients may predispose to OP. With regard to OA, results from the Global Longitudinal Study of Osteoporosis in Women study and several radiological studies suggest that differences in the distribution of bone mass at the femoral neck may account for the inverse relationship of OA and OP, and several studies suggest that OA and OP have opposing cytokine and bone metabolism marker profiles. PMID:24085651

  11. T Cell Aging in Rheumatoid Arthritis

    PubMed Central

    Weyand, Cornelia M.; Yang, Zhen; Goronzy, Jörg J.

    2014-01-01

    Purpose of review With progressive age, the immune system and the propensity for abnormal immunity change fundamentally. Individuals >50 years of age are more susceptible to infection and cancer, but also at higher risk for chronic inflammation and immune-mediated tissue damage. The process of immunosenescence is accelerated in rheumatoid arthritis. Recent findings Premature T cell senescence occurs not only in RA, it has also been involved in morbidity and mortality of chronic HIV infection. Senescent cells acquire the “senescence associated secretory phenotype (SASP)”, which promotes and sustains tissue inflammation. Molecular mechanisms underlying T cell aging are beginning to be understood. Besides the contraction of T cell diversity due to uneven clonal expansion, senescent T cells have defects in balancing cytoplasmic kinase and phosphatase activities, changing their activation thresholds. Also, leakiness in repairing DNA lesions and uncapped telomeres imposes genomic stress. Age-induced changes in the tissue microenvironment may alter T cell responses. Summary Gain- and loss-of-function in senescent T cells undermine protective immunity and create the conditions for chronic tissue inflammation, a combination typically encountered in RA. Genetic programs involved in T cell signaling and DNA repair are of high interest in the search for underlying molecular defects. PMID:24296720

  12. Targeting interleukin-21 in rheumatoid arthritis.

    PubMed

    Yuan, Feng-Lai; Hu, Wei; Lu, Wei-Guo; Li, Xia; Li, Jian-Ping; Xu, Rui-Sheng; Li, Cheng-Wan; Chen, Fei-Hu; Jin, Cheng

    2011-03-01

    Interleukin-21 (IL-21) is a new member of the type I cytokine superfamily, which binds to a composite receptor that consists of a private receptor (IL-21R) and the common cytokine receptor γ chain. Recently, increasing evidence has shown that IL-21 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases because of its pro-inflammatory and immune-mediated properties. IL-21 induced T-cell activation and pro-inflammatory cytokine secretion in rheumatoid arthritis (RA). IL-21R RNA transcripts were found in synovial tissue samples of patients with RA. In addition, blockade of the IL-21/IL-21R pathway ameliorated disease in animal models of RA and significantly inhibited inflammatory cytokine production in vitro. Moreover, IL-21R deficiency in the K/BxN mouse model of inflammatory arthritis was sufficient to block arthritis initiation completely. All theses findings suggest that IL-21 has important biological effects in autoimmunity that might be a promising therapeutic target for RA. In this review, we discuss the biological features of IL-21 and summarize recent advances in the role of IL-21 in the pathogenesis and treatment of RA. PMID:20848219

  13. Genetics and epigenetics of rheumatoid arthritis

    PubMed Central

    Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

    2013-01-01

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

  14. Bone remodelling markers in rheumatoid arthritis.

    PubMed

    Fardellone, Patrice; Sjourn, Alice; Paccou, Julien; Gob, 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. TNF inhibitor therapy for rheumatoid arthritis

    PubMed Central

    MA, XIXI; XU, SHENGQIAN

    2013-01-01

    Immunotherapy has markedly improved treatment outcomes in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-? antagonists, such as infliximab (IFX), etanercept (ETN), adalimumab (ADA), golimumab (GOLI) and certolizumab pegol (CZP) have been widely used for the treatment of RA. IFX provides significant, clinically relevant improvement in physical function and the quality of life, inhibits progressive joint damage and sustains improvement in the signs and symptoms of patients with RA. ETN is effective and safe for patients with RA. Combination therapy with ETN plus methotrexate (MTX) reduces disease activity, decreases total joint score progression, slows the pace of joint destruction and improves function more effectively compared to any of the monotherapies. ADA with or without MTX also relieves the signs and symptoms of RA. CZP and GOLI expand the therapeutic schedule for patients with RA. The TNF-? inhibitors have similar efficacy, but distinct clinical pharmacokinetic and -dynamic properties. The common adverse events of these TNF-? antagonists include adverse reactions, infections and injection-site reaction. Additionally, these adverse events are mostly mild or moderate and their incidence is low. Certain patients exhibit a lack of response to anti-TNF-? therapies. Some patients may discontinue the initial drug and switch to a second anti-TNF-? agent. The shortage of clinical response to one agent may not predict deficiency of response to another. This review mainly addresses the latest developments of these biological agents in the treatment of RA. PMID:24648915

  16. Sarilumab for the treatment of rheumatoid arthritis.

    PubMed

    Cooper, Simon

    2016-03-01

    Simon Cooper is interviewed by Ellen Clarke, Commissioning Editor Simon Cooper has >18 years of global experience in the pharmaceutical industry. He joined Sanofi in July 2014 as the Vice President, Global Project Head. In his current position at Sanofi, Dr Cooper is responsible for the clinical development of sarilumab and the worldwide submission in rheumatoid arthritis. He joined Sanofi after serving as the Global Program Medical Director at Novartis since 2012. In this role, Dr Cooper acted as the clinical lead for secukinumab psoriasis submission. Prior to Novartis, Dr Cooper held various posts at Human Genome Sciences, USA, including Executive Director of Clinical Research, Senior Director of Clinical Research and Director of Clinical Research. During his tenure at Human Genome Sciences, USA, Dr Cooper was involved in the submission of belimumab leading to its approval for SLE, and was responsible for its subsequent clinical development program. Dr Cooper has also previously held positions at MedImmune Ltd, UK, Roche, Napp Pharmaceutical Research Ltd, Wyeth Research and Medeval Ltd. In these roles, his responsibilities ranged from medical oversight of clinical trials to medical support for commercial, medical affairs and business development. He received a Bachelor of Medicine and Bachelor of Surgery from University of Newcastle upon Tyne Medical School. PMID:26860742

  17. The pill, parity, and rheumatoid arthritis.

    PubMed

    Spector, T D; Roman, E; Silman, A J

    1990-06-01

    We report on a case-control study investigating the relationship of oral contraceptive pill (OCP) use and parity to the development of rheumatoid arthritis (RA). Women with RA were compared with 2 separate control groups, women with osteoarthritis (OA) and women randomly selected from a population-based electoral register. Nulliparity was found to be a risk factor for the development of RA, with age-adjusted odds ratios of 1.82 (95% confidence interval [CI] 1.09-3.03) versus the OA control group and 1.83 (95% CI 1.03-3.06) versus the population control group. Use of OCPs before the age of 35 was negatively associated with RA (odds ratio 0.56, 95% CI 0.29-1.12 versus the OA control group; odds ratio 0.6, 95% CI 0.30-1.17 versus the population control group). Some evidence of a duration-response effect was seen, although the numbers were small. The 2 variables were also multiplicative, with nulliparous non-OCP users having a 4-fold risk of RA compared with parous OCP users. These findings suggest that pregnancy and OCP use have a "protective effect" on the development of RA, although the mechanism remains unclear. PMID:2363734

  18. Utilizing Regulatory T Cells Against Rheumatoid Arthritis

    PubMed Central

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

    2014-01-01

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

  19. 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

  20. 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

  1. 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

  2. [Economic evaluation of a new treatment for rheumatoid arthritis].

    PubMed

    Suka, Machi; Yoshida, Katsumi

    2007-07-01

    In recent years, new biologic agents have been approved for the treatment of rheumatoid arthritis. These agents may yield clear clinical benefits but impose greater costs than standard treatment. Economic evaluations have been used to provide evidence for the cost-effectiveness of treatment. We described two approaches to the cost-effectiveness analysis of the treatment of rheumatoid arthritis-micro-level economic evaluation based on quality-adjusted life years (QALYs) and macro-level economic evaluation based on disability-adjusted life years (DALYs). PMID:17642251

  3. Outcome of orthoses intervention in the rheumatoid foot.

    PubMed

    Kavlak, Yasemin; Uygur, Fatma; Korkmaz, Cengiz; Bek, Nilgn

    2003-06-01

    This study was carried out to determine the effect of foot orthoses on pain, gait, and energy expenditure in patients with rheumatoid arthritis. Eighteen patients were evaluated for these parameters. Each patient was given a foot insert or shoe modification suitable for his or her foot deformity. Following 3 months of orthosis use, a significant difference was found in regards to pain (p < .05), step length and stride length (p < .05), and physiological cost index (p < .05). The results suggest that foot orthoses are an important feature in the rehabilitation of the rheumatoid foot. PMID:12854671

  4. Intestinal Amyloidosis in Common Variable Immunodeficiency and Rheumatoid Arthritis

    PubMed Central

    Meira, T.; Sousa, R.; Cordeiro, A.; Ilgenfritz, R.; Borralho, P.

    2015-01-01

    We present a case of reactive amyloidosis that developed secondary to common variable immunodeficiency and rheumatoid arthritis. A 66-year-old woman, with prior history of common variable immunodeficiency and rheumatoid arthritis, was referred to our clinic for chronic diarrhea investigation. The patient was submitted to colonoscopy with ileoscopy, which did not show relevant endoscopic alterations. However, undertaken biopsies revealed amyloid deposition. Since amyloidosis with GI involvement is a rare cause of chronic diarrhea, this pathology should be considered in etiologic investigation, especially when associated with chronic inflammatory diseases. PMID:26351592

  5. Tocilizumab-induced psoriasiform rash in rheumatoid arthritis.

    PubMed

    Palmou-Fontana, Natalia; Snchez Gavio, Juan Antonio; McGonagle, Dennis; Garca-Martinez, Eva; Iiguez de Onzoo Martn, Luis

    2014-01-01

    Tocilizumab (TCZ) is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and has been approved for the treatment of rheumatoid arthritis (RA) patients who have had an inadequate response to previous biological therapies. Psoriasiform skin lesions, especially palmoplantar pustulosis lesions, are well described following anti-tumour necrosis factor therapy. We describe a 79-year-old woman with rheumatoid factor-positive, anti-citrullinated protein antibody-positive erosive RA, who developed a psoriasiform palmoplantar pustulosis reaction following treatment with TCZ therapy (IL-6 receptor). The rash showed histological features compatible with psoriasis and disappeared following discontinuation of TCZ. PMID:24942661

  6. Intestinal Amyloidosis in Common Variable Immunodeficiency and Rheumatoid Arthritis.

    PubMed

    Meira, T; Sousa, R; Cordeiro, A; Ilgenfritz, R; Borralho, P

    2015-01-01

    We present a case of reactive amyloidosis that developed secondary to common variable immunodeficiency and rheumatoid arthritis. A 66-year-old woman, with prior history of common variable immunodeficiency and rheumatoid arthritis, was referred to our clinic for chronic diarrhea investigation. The patient was submitted to colonoscopy with ileoscopy, which did not show relevant endoscopic alterations. However, undertaken biopsies revealed amyloid deposition. Since amyloidosis with GI involvement is a rare cause of chronic diarrhea, this pathology should be considered in etiologic investigation, especially when associated with chronic inflammatory diseases. PMID:26351592

  7. 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.

  8. 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.

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

    PubMed Central

    Dustin, Michael L

    2003-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Estep, Leland; Spruce, Joseph P.

    2007-01-01

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

  11. Rheumatoid arthritis patients' experience of climate care.

    PubMed

    Vaks, Katrin; Sjöström, Rita

    2015-12-01

    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. PMID:26730385

  12. Trends in Serious Infections in Rheumatoid Arthritis

    PubMed Central

    Mhuircheartaigh, Orla Ni; Matteson, Eric L.; Green, Abigail B.; Crowson, Cynthia S.

    2013-01-01

    Objective To examine trends in the rates of serious infections among patients diagnosed with rheumatoid arthritis (RA) in 1995-2007 compared to rates previously reported from the same geographical area diagnosed in 1955-1994. Methods A population-based inception cohort of patients with RA in 1995-2007 was assembled and followed through their complete medical records until death, migration, or December 31, 2008. All serious infections (requiring hospitalization or IV antibiotics) were recorded. Person-year (py) methods were used to compare rates of infection. Results Among 464 patients with incident RA in 1995-2007, 54 had ?1 serious infection (178 total). These were compared to609 patients with incident RA in 1955-1994 (290 experienced ?1 serious infection; 740 total). The rate of serious infections declined from 9.6 per 100py in the 1955-1994 cohort to 6.6 per 100py in the 1995-2007 cohort. However, serious gastrointestinal infection rates increased from 0.5 per 100py in the 1955-1994 cohort to 1.25 per 100py in the 1995-2007 cohort. Among patients with a history of serious infection, the rate of subsequent infection increased from 16.5 per 100py in 1955-1994 to 37.4 per 100py in 1995-2007. There was an increase in the rate of serious infections in patients who received biologic agents, but this did not reach significance. Conclusions Aside from gastrointestinal infections, the rate of serious infections in patients with RA has declined in recent years. However, the rate of subsequent infections was higher in recent years than previously reported. PMID:23547208

  13. 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-κB 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

  14. 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. PMID:26730385

  15. Relationship between Metabolic Syndrome and Rheumatoid Arthritis

    PubMed Central

    Lee, Sang-Hyun; Cho, Be-Long; An, Ah-Reum; Seo, Young-Gyun; Jin, Ho-Seong; Oh, Seung-Min; Jang, Soo Hyun

    2016-01-01

    Background Rheumatoid arthritis (RA) and metabolic syndrome (Mets) are considered to be diseases with common traits that can increase the risk of cardiovascular disease incidence; studies in other countries examined the relationship between these diseases. However, existing studies did not show consistent results. In the present study, the relationship between RA and Mets in Koreans was examined using the data of the 4th and 5th Korea National Health and Nutrition Examination Survey (KNHANES). Methods The present study used the data of the 4th and 5th KNHANES, conducted between 2007 and 2012. Among 25,812 adults aged over 40, 19,893 were selected as study subjects, excluding 5,919 who did not have variable information needed for the analysis. T-test and chi-square test were used for the analysis of related variables. To determine the relationship between diagnostic status of RA and Mets, multivariate logistic regression analysis was performed by controlling confounding variables, which were selected through literature review and statistical analysis. Results Multivariate logistic regression analysis was conducted to examine the relationship between diagnostic status of RA and Mets. When age, education level, average monthly household income, smoking, alcohol consumption, and level of physical activity were adjusted, the prevalence of Mets was lower in RA patients (adjusted odds ratio [aOR], 0.79; 95% confidence interval [CI], 0.65 to 0.96). Multivariate logistic regression analysis was performed to examine the relationship between treatment status of RA and Mets. When age, education level, average monthly household income, smoking, alcohol consumption, and level of physical activity were adjusted, there was a significant negative correlation in women (aOR, 0.65; 95% CI, 0.44 to 0.96). Conclusion The relationship between RA and Mets showed a significantly negative correlation in Korean women. The group that received RA treatment showed significantly lower prevalence of the Mets as compared to the untreated group in Korean RA women. PMID:26885322

  16. Development of macromolecular prodrug for rheumatoid arthritis?

    PubMed Central

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

    2012-01-01

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

  17. Genetics of rheumatoid arthritis - a comprehensive review.

    PubMed

    Kurk, Jlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T; Mikecz, Katalin; Szekanecz, Zoltn

    2013-10-01

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

  18. Genetics of Rheumatoid Arthritis A Comprehensive Review

    PubMed Central

    Kurk, Jlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T.; Mikecz, Katalin

    2013-01-01

    The Bermuda triangle of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 1137 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics. PMID:23288628

  19. 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

  20. 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

  1. Targeting interleukin-6 in rheumatoid arthritis.

    PubMed

    Md Yusof, Md Yuzaiful; Emery, Paul

    2013-03-01

    Interleukin (IL)-6 is a potent pro-inflammatory agent that plays a crucial role in the pathogenesis of systemic inflammatory disease. Targeting this pathway in rheumatoid arthritis (RA) seems an attractive option as IL-6 is important for both joint destruction and systemic manifestations. Currently, tocilizumab, which binds the IL-6 receptor, is licensed for treatment in active, moderate to severe disease in RA and systemic juvenile idiopathic arthritis (JIA). Several other promising IL-6 blocking agents as well as a subcutaneous form of tocilizumab are currently undergoing phase III clinical trials. The aim of this article is to provide an up-to-date analysis of clinical efficacy and tolerability data concerning the use of IL-6 inhibitors. Data from clinical trials demonstrated that clinical efficacy for tocilizumab, which included improvement in physical function and halting radiographic progression, were comparable to other biologics licensed for use in RA. Patients who should gain most are RA patients with systemic features such as high inflammatory markers and anaemia. Perhaps, the strongest selling point lies in its effectiveness as a monotherapy. This is particularly useful in those who are not tolerating combination treatment with methotrexate. Tocilizumab is one of a few biologics that have been shown to be superior to methotrexate in head-to-head studies. The safety profile of tocilizumab also is comparable to other currently available biologics. There is a small but significant increase in adverse events including infections in patients treated with tocilizumab compared to placebo, particularly in patients who are elderly and those with multiple comorbidities. Elevated lipid profiles are frequent but have not been associated with major cardiovascular events. IL-6 blockade is a major advancement in the treatment of RA as it targets a unique molecule. Over the next few years, evidence will be available on the long-term cardiovascular safety and efficacy of subcutaneous IL-6 blocking agents. PMID:23456676

  2. Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection.

    PubMed

    Ebringer, Alan; Rashid, Taha

    2006-03-01

    Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age. Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies. Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments. PMID:16603443

  3. Chronotherapy with modified-release prednisone in patients with rheumatoid arthritis.

    PubMed

    Alten, Rieke

    2012-02-01

    Glucocorticoids are indispensable for the treatment of systemic inflammatory diseases such as rheumatoid arthritis (RA), though their beneficial effects have to be balanced with potential complications arising from high doses, prolonged use or dose splitting. A glucocorticoid formulation (modified-release prednisone) has been developed to be taken in accordance with biological rhythms (chronotherapy). Morning symptoms of RA are caused by elevated nocturnal levels of proinflammatory cytokines, particularly IL-6. Endogenous cortisol levels may be insufficient to counter the inflammatory effects of IL-6. The early morning rise in cortisol can be supplemented with exogenous glucocorticoid replacement therapy if this is given as the recently developed chronotherapy formulation. There is no adverse impact of modified-release prednisone on the hypothalamic-pituitary-adrenal (HPA) axis; indeed, there might be evidence of a beneficial effect on HPA axis function. This review summarizes the development of modified-release prednisone, pharmacokinetic characteristics and clinical experience in patients with RA. PMID:22288450

  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. 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?

  6. 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.

  7. 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

  8. Molecular Dynamics Simulation Study of the Early Stages of Nucleation of Iron Oxyhydroxide Nanoparticles in Aqueous Solutions.

    PubMed

    Zhang, Hengzhong; Waychunas, Glenn A; Banfield, Jillian F

    2015-08-20

    Nucleation is a fundamental step in crystal growth. Of environmental and materials relevance are reactions that lead to nucleation of iron oxyhydroxides in aqueous solutions. These reactions are difficult to study experimentally due to their rapid kinetics. Here, we used classical molecular dynamics simulations to investigate nucleation of iron hydroxide/oxyhydroxide nanoparticles in aqueous solutions. Results show that in a solution containing ferric ions and hydroxyl groups, iron-hydroxyl molecular clusters form by merging ferric monomers, dimers, and other oligomers, driven by strong affinity of ferric ions to hydroxyls. When deprotonation reactions are not considered in the simulations, these clusters aggregate to form small iron hydroxide nanocrystals with a six-membered ring-like layered structure allomeric to gibbsite. By comparison, in a solution containing iron chloride and sodium hydroxide, the presence of chlorine drives cluster assembly along a different direction to form long molecular chains (rather than rings) composed of Fe-O octahedra linked by edge sharing. Further, in chlorine-free solutions, when deprotonation reactions are considered, the simulations predict ultimate formation of amorphous iron oxyhydroxide nanoparticles with local atomic structure similar to that of ferrihydrite nanoparticles. Overall, our simulation results reveal that nucleation of iron oxyhydroxide nanoparticles proceeds via a cluster aggregation-based nonclassical pathway. PMID:26222332

  9. Adrenal suppression following herbal remedy for rheumatoid arthritis

    PubMed Central

    Premkumar, Balasekar; Murthy, Muppavarapu Srinivasa; Rajagopal, Karuppasamy; Nagaprabu, Vadivelmurugan Nagasubramani; Ponugupati, Sree Madhuri

    2015-01-01

    A patient suffering from rheumatoid arthritis who had extreme adrenal suppression as a result of chronic use of herbal medicines presented with complications of adrenal suppression such as muscle weakness. He also had psychiatric disturbances such as confusion and suicidal tendency. Steroids in the herbal medication were found and hence there exists a need for investigation into their safety and efficacy. PMID:25969663

  10. Kinase inhibitors for the treatment of rheumatoid arthritis.

    PubMed

    Yazici, Yusuf; Steiger, Benjamin

    2012-01-01

    Kinase inhibitors have now been shown to work in various types of patients and have potential to be additional weapons in our armamentarium in rheumatoid arthritis treatment. This review will go over the currently available data and discuss potential uses for these new agents. PMID:23259630

  11. 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.

  12. 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

  13. 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,

  14. 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,

  15. [Indometacin glucosamide in the therapy of rheumatoid arthritis (author's transl)].

    PubMed

    Chlud, K; Kaik, B; Pangerl, S

    1978-01-01

    40 patients with classical or definite rheumatoid arthritis were included in a double blind trial to assess efficacy and side effects of indometacin (n = 20) versus glucametacin (n = 20). In a daily dose of 420 mg glucametacin proved to be equally potent to 150 mg indometacin daily in its anti-inflammatory activity but showed fewer side effects. PMID:582710

  16. 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

  17. 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,…

  18. Correlation between clotting and collagen metabolism markers in rheumatoid arthritis.

    PubMed

    Gabazza, E C; Osamu, T; Yamakami, T; Ibata, H; Sato, T; Sato, Y; Shima, T

    1994-02-01

    Rheumatoid arthritis is a chronic inflammatory disease caused essentially by an immune-mediated mechanism. However, abnormalities of the clotting system have also been incriminated as having an important role in the pathogenesis of this disease. This study aims at assessing the clotting system and collagen metabolism alterations and the relationship between perturbances of the hemostatic pathway and the destructive and fibroproliferative processes in patients with rheumatoid arthritis. The coagulation system was evaluated by measuring thrombin-antithrombin III complex (TAT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antithrombin III (AT-III). The fibrinolysis system was assessed by measuring fibrin degradation products (FDP), fibrinogen (FBG), alpha 2-antiplasmin (alpha 2-PI), D-dimer (DD) and plasmin-alpha 2-antiplasmin complex (PAP). As markers of collagen metabolism, the type III procollagen peptide (PIIIP) and the 7S domain of type IV collagen (7S-collagen) were determined. Blood concentrations of DD, PAP, TAT, PIIIP, and 7S-collagen were significantly higher in rheumatoid arthritis patients compared to controls. Serum levels of PIIIP were significantly correlated with PT, APTT, AT-III, FDP, and DD. 7S-collagen levels were inversely related to AT-III and FBG values. This study demonstrated the occurrence of a subclinical intravascular coagulation in rheumatoid arthritis and suggested the important role of blood coagulation in the alteration of the extracellular matrix metabolism in this disease. PMID:7514817

  19. [Genetic and environmental contribution to rheumatoid arthritis: a family study].

    PubMed

    Iebba, Filippo; Di Sora, Fiorella; Leti, Wilma; Montella, Tatiana; Montella, Francesco

    2012-01-01

    We report on the HLA typing of three brothers (A, B, C) with rheumatoid arthritis (RA) and their six sons. This family is interesting for the full concordance for RA between parents. The aim of this study was the discovery of genetic and/or enviromental cofactors determining this absolute concordance. PMID:22825383

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

    PubMed Central

    enolt, Ladislav; umov, Barbora; Jandov, Romana; Hulejov, Hana; Mann, He?man; Pavelka, Karel; Vencovsk, Ji?; Filkov, Mria

    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 nave 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 nave 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 nave 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 nave 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

  1. Detection and measurement of rheumatoid bone and joint lesions of fingers by tomosynthesis: a phantom study for reconstruction filter setting optimization.

    PubMed

    Ono, Yohei; Kamishima, Tamotsu; Yasojima, Nobutoshi; Tamura, Kenichi; Tsutsumi, Kaori

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic disease that is caused by autoimmunity. RA causes synovial proliferation, which may result in bone erosion and joint space narrowing in the affected joint. Tomosynthesis is a promising modality which may detect early bone lesions such as small bone erosion and slight joint space narrowing. Nevertheless, so far, the optimal reconstruction filter for detection of early bone lesions of fingers on tomosynthesis has not yet been known. Our purpose in this study was to determine an optimal reconstruction filter setting by using a bone phantom. We obtained images of a cylindrical phantom with holes simulating bone erosions (diameters of 0.6, 0.8, 1.0, 1.2, and 1.4 mm) and joint spaces by aligning two phantoms (space widths from 0.5 to 5.0 mm with 0.5 mm intervals), examining six reconstruction filters by using tomosynthesis. We carried out an accuracy test of the bone erosion size and joint space width, done by one radiological technologist, and a test to assess the visibility of bone erosion, done by five radiological technologists. No statistically significant difference was observed in the measured bone erosion size and joint space width among all of the reconstruction filters. In the visibility assessment test, reconstruction filters of Thickness+- and Thickness-- were among the best statistically in all characteristics except the signal-to-noise ratio. The Thickness+- and Thickness-- reconstruction filter may be optimal for evaluation of RA bone lesions of small joints in tomosynthesis. PMID:26092218

  2. 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.-

  3. 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.

  4. Macrophage migration inhibitory factor in rheumatoid arthritis.

    PubMed

    Morand, Eric F; Leech, Michelle

    2005-01-01

    Rheumatoid arthritis is characterised by the interaction of multiple mediators, among the most important of which are cytokines. In recent years, extensive data demonstrates a pivotal role for one cytokine, macrophage migration inhibitory factor (MIF), in fundamental events in innate and adaptive immunity. MIF has now been demonstrated to be involved in the pathogenesis of many diseases, but in the case of RA the evidence for a role of MIF is very strong. MIF is abundantly expressed in the serum of RA patients, and in RA synovial tissue where it correlates with disease activity. MIF induces synoviocyte expression of key proinflammatory genes including TNF, IL-1, IL-6, IL-8, cPLA2, COX2 and MMPs. MIF also regulates the function of endothelial cells and B cells. Moreover, MIF is implicated in the control of synoviocyte proliferation and apoptosis via direct effects on the expression of the tumor suppressor protein p53. In multiple rat and mouse models of RA, anti-MIF antibodies or genetic MIF deficiency are associated with significant inhibition of disease. MIF -/- mice further demonstrate increases in synovial apoptosis. That the human Mif gene is encoded by different functional alleles in subjects with inflammatory disease also provides evidence for the role of MIF in RA. The mechanism of action of MIF is becoming better understood. MIF appears to interact with cell surface CD74, with consequent activation of MAP kinases but possibly not NFkappaB intracellular signal transduction. This apparent selectivity may be implicated in the ability of MIF to antagonise the effects of glucocorticoids. As MIF expression is induced by glucocorticoids, inhibition of its antagonistic effects may permit enhanced therapeutic effect of glucocorticoids, or "steroid sparing". To date there are no clinical trials of MIF antagonism in any disease, but exploitation of antibody, soluble receptor, or small molecule approaches enabled by the unique crystal structure of MIF, may soon lead to the ability to test in the clinic the importance of this cytokine in human RA. PMID:15576336

  5. 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

  6. 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.

  7. 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, Jrg; Haberthr, 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.

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

    PubMed Central

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

    2009-01-01

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

  9. Safety of low- to medium-dose glucocorticoid treatment in rheumatoid arthritis: myths and reality over the years.

    PubMed

    Santiago, Tânia; da Silva, José António P

    2014-05-01

    Low- to medium-dose glucocorticoids have been shown to have not only anti-inflammatory but also disease-modifying properties in rheumatoid arthritis. The evidence for the benefit of its early use in combination with disease-modifying antirheumatic drugs underlines the need for a close evaluation of their risk-benefit ratio. Over time, numerous myths and fears about glucocorticoid toxicity in rheumatoid arthritis have arisen from observational studies, and many concerns have been unduly extrapolated from observations with higher-dose treatment. Furthermore, we cannot exclude the possibility of a powerful effect of bias by indication in these studies. Low- to medium-dose glucocorticoid regimens continued to be evaluated in randomized clinical trials, particularly in early disease, but these studies also have relevant methodological limitations in assessing safety, particularly due to small size and/or short duration. At present, the evidence on which to support clear recommendations about glucocorticoid toxicity remains remarkably weak. A large prospective pragmatic trial dedicated to the toxicity of low-dose glucocorticoids is dearly needed. Meanwhile, adherence to recommendations on standardized methodologies for registration and report of glucocorticoid adverse events is essential for improving our knowledge and competence in the best management of these important medications. PMID:24814757

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  11. 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.

  12. Ulcerative colitis complicating seronegative HLA-A2-B27 rheumatoid arthritis with sacroiliitis.

    PubMed Central

    Klausen, T; Amris, K; Helin, P

    1992-01-01

    The case is reported of a 50 year old man with longstanding seronegative rheumatoid arthritis who developed ulcerative colitis. The patient also had sacroiliitis and his tissue was typed as HLA-A2-B27 several years before the bowel disease began. A possible overlap between primary inflammatory bowel disease, complications to the treatment of rheumatoid arthritis with drugs, and gastrointestinal rheumatoid vasculitis is discussed. Images PMID:1417108

  13. 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.

  14. Monitoring the Remineralization of Early Simulated Lesions using a pH Cycling Model with CP-OCT

    PubMed Central

    Kang, Hobin; Chan, Kenneth; Darling, Cynthia L.; Fried, Daniel

    2013-01-01

    If caries lesions are detected early enough they can be arrested by chemical intervention and dietary changes without the need for chemical intervention. Optical coherence tomography is ideally suited to monitor the changes that occur in caries lesions as a result of nonsurgical intervention, since OCT can nondestructively image the internal structure of the lesion. One of the most important changes that occurs in a lesion is preferential deposition of mineral in the outer surface zone. The deposition creates a highly mineralized and weakly scattering surface zone that is clearly visible in OCT images. Since this zone is near the highly reflective surface it is necessary to use cross-polarization OCT imaging to resolve this zone. Several CP-OCT studies have been conducted employing different remineralization models that produce lesions with varying mineral gradients. Previous studies have also demonstrated that automated algorithms can be used to assess the lesion depth and severity even with the presence of the weakly reflective surface zone. In this study we investigated the remineralization of lesions of varying severity using a pH cycling remineralization model and the change of the lesion was monitored using CP-OCT. Although the lesion depth and severity decreased after remineralization, there was still incomplete remineralization of the body of the lesion. PMID:24353383

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

    PubMed

    Wenneberg, B; Knnen, 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

  16. 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

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

    PubMed Central

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

    2005-01-01

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

  18. MDR-ABC transporters: biomarkers in rheumatoid arthritis.

    PubMed

    Mrki-Zay, Jnos; Taubern Jakab, Katalin; Szermy, Pter; Krajcsi, Peter

    2013-01-01

    MDR-ABC transporters are widely expressed in cell types relevant to pathogenesis of rheumatoid arthritis. Many reports demonstrate the interaction of small molecule drugs with MDR-ABC transporters. Cell-based assays for disease relevant cell types can be easily gated and could reveal specific drug targets and may increase significance and utilisation of data in clinical practice. Many commonly used DMARDs (e.g. methotrexate, sulfasalazine, leflunomide/teriflunomide, hydroxychloroquine) are ABCG2 substrates. Consequently, the activity of this transporter in patients should be determined to understand the disposition and pharmacokinetics of the therapy. In addition, MDR-ABC transporters transport a variety of endobiotics that play important roles in cell proliferation, cell migration, angiogenesis and inflammation. Therefore, MDR-ABC transporters are important biomarkers in rheumatoid arthritis. PMID:23711386

  19. Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications.

    PubMed Central

    Colville-Nash, P R; Scott, D L

    1992-01-01

    Rheumatoid arthritis can be considered as one of the family of 'angiogenesis dependent diseases'. Angiogenesis in rheumatoid arthritis is controlled by a variety of factors found in the synovial fluid and pannus tissue. Modulation of the angiogenic component of the disease may alter the pathogenesis of the condition, and subsequent cartilage and joint destruction, by reducing the area of the endothelium in the pannus and restricting pannus growth. Current therapeutic strategies exert, to varying extents, an inhibitory effect on the angiogenic process. In particular, the mode of action of the slow acting antirheumatic drugs may be due to their effect on the angiogenic response. The development of novel angiostatic treatments for chronic inflammatory joint disease may lead to a new therapeutic approach in controlling disease progression. PMID:1378718

  20. The current relevance and use of prednisone in rheumatoid arthritis.

    PubMed

    Krasselt, Marco; Baerwald, Christoph

    2014-05-01

    Prednisone is an old and very valuable drug in clinical use for over 60 years by now. It is well known by physicians and widely used for different kinds of inflammatory states including rheumatoid arthritis (RA). Clinical trials during the last 20 years have changed its clinical use, particularly with regards to dosage. Today, rheumatologists are treating their patients much more likely over a long period of time using a low-dose scheme. The effectiveness and safety of this low-dose use is the objective of the current clinical research and shall be enlightened in this drug profile. It is also featuring current knowledge about the value of modified-release prednisone with regards to the just published results of the 2nd Circadian Administration of Prednisone in Rheumatoid Arthritis trial. Moreover, the mechanisms of action of prednisone and its relatives will be summed up. PMID:24717015

  1. Genetic influences modulating the radiological severity of rheumatoid arthritis.

    PubMed

    Marinou, I; Maxwell, J R; Wilson, A G

    2010-03-01

    This review focuses on the contribution of genetic markers to the severity of radiological damage in rheumatoid arthritis (RA). Currently available biomarkers of more severe disease include elevated erythrocyte sedimentation rates or C-reactive protein levels and rheumatoid factor (RF) or anticyclic citrullinated protein antibodies positivity; however, these biomarkers explain a relatively modest proportion of the variance in radiological damage. An important role of genetic factors on RA severity has recently emerged but studies to date have generally been of low statistical power and many have not been replicated. Genetic markers have a number of advantages over conventional biomarkers; genotypes are stable, measurable at disease onset, remain unchanged by treatment and are amenable to high-throughput assays. The recent advances in genome-wide genetic analysis should lead to a more comprehensive understanding of RA severity genes. This knowledge could be used, along with existing biomarkers, to therapeutically target subjects at risk of poor radiological outcome. PMID:20124360

  2. Autonomic (sympathetic) nervous system involvement in rheumatoid arthiritis patients.

    PubMed

    Bidikar, Mukta P; Ichaporia, Rati B

    2010-01-01

    Fifty Rheumatoid arthritis (RA) patients between the age group of 20 to 60 years were investigated for sympathetic autonomic functions using standard tests. All the patients liable to develop dysautonomia or having a treatment interfering with autonomic nervous system were excluded. Previous studies to evalute sympathetic nervous system involvement used only a single test like sweating response, orthostatic test. In the present study 3 tests of sympathetic nervous system evaluation have been used. The evaluation was done by cardiovascular tests like orthostatic test, sustained hand grip and cold pressor test. A control series of 50 healthy subjects was tested to determine abnormal threshold for each one of the 3 tests. The reference value of Ewing and Clark were used to interpret the results of the tests. Sympathetic dysfuction was found in 26% of rheumatoid arthritis patients. PMID:21046924

  3. Power Doppler ultrasound of rheumatoid synovitis: quantification of therapeutic response.

    PubMed

    Teh, J; Stevens, K; Williamson, L; Leung, J; McNally, E G

    2003-12-01

    The aim of this study is to quantify power Doppler assessment of therapeutic response in rheumatoid synovitis. 13 patients (6 male, 7 female) with rheumatoid arthritis, who had an acute exacerbation of small joint synovitis in the hands, were examined with quantitative power Doppler, before and after intravenous corticosteroid treatment. All patients were examined by a single radiologist, using an ATL HDI 5000 ultrasound machine (ATL, Boswell). The images were analysed using a specially developed software package (HDI Lab), which quantifies power Doppler signal. All patients improved clinically following treatment, which was reflected in functional disability scores, and in the C-reactive protein levels and erythrocyte sedimentation rate. In all cases, there was a significant decrease in synovial vascularity as measured by the mean amplitude of signal on quantitative power Doppler. Quantitative power Doppler may allow objective assessment of treatment in small joint synovitis. PMID:14711774

  4. Ulnar drift in rheumatoid arthritis: a review of biomechanical etiology.

    PubMed

    Morco, Stephanie; Bowden, Anton

    2015-02-26

    The objective of this article is to summarize current understanding of biomechanical factors that cause ulnar drift in the hands of patients with rheumatoid arthritis. This was done through literature review of published articles on the mechanical etiology of ulnar drift. There are several theories regarding the cause of ulnar drift, however conclusive evidence is still lacking. Current mechanical factors that are postulated to play a role include: failure of the collateral ligaments, intra-articular pressure changes, degenerative changes in the carpal and metacarpal anatomy, muscle hypoxia induced changes in wrist tension, and exacerbating activities of daily living. Although current theories regarding ulnar drift almost universally include an at least partially mechanical rationale, the causes may be multifactorial. Significantly more research is needed to elucidate the relative importance of mechanical factors leading to significant ulnar drift concurrent with advanced rheumatoid arthritis. PMID:25614089

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

    PubMed Central

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

    2014-01-01

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

  6. 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.

  7. 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.

  8. Depression and level of functioning in patients with rheumatoid arthritis.

    PubMed

    Beckham, J C; D'Amico, C J; Rice, J R; Jordan, J S; Divine, G W; Brook, W B

    1992-10-01

    This study examined the degree to which depression is related to physical and psychosocial dysfunction. The Beck Depression Inventory and the Sickness Impact Profile were administered to 34 patients with rheumatoid arthritis. Information on the demographic variables (age and employment status) and medical status variables (duration of disease and functional classification) were collected for each patient. Regression analyses revealed that depression was an important predictor of total, physical and psychosocial sickness-related behavioural dysfunction. The proportion of variance attributed to depression was moderate to large and was significant even after controlling for important demographic and medical status variables. These results suggest that depression is an important factor to be considered when evaluating the clinical significance of physical and psychosocial dysfunction in patients with rheumatoid arthritis. PMID:1423154

  9. Food intolerance in rheumatoid arthritis. II. Clinical and histological aspects.

    PubMed Central

    van de Laar, M A; Aalbers, M; Bruins, F G; van Dinther-Janssen, A C; van der Korst, J K; Meijer, C J

    1992-01-01

    Six patients with rheumatoid factor positive rheumatoid arthritis who had shown a marked symptomatic improvement during four weeks of hypoallergic, artificial diet were studied in greater detail. Placebo controlled rechallenges showed intolerance for specific foodstuffs in four patients. In three of these patients biopsies of both the synovial membrane and of the proximal small intestine were carried out before and during allergen free feeding. In two patients, both with raised serum IgE concentrations and specific IgE antibodies to certain foods, a marked reduction of mast cells in the synovial membrane and proximal small intestine was demonstrated. Although the number of food intolerant patients with RA remains limited and markers of allergic activity are scanty, our observations suggest an underlying immunoallergological mechanism. PMID:1575572

  10. Gold Therapy in the Treatment of Rheumatoid Arthritis

    PubMed Central

    Davis, Paul

    1988-01-01

    For many years, gold therapy has been the mainstay in the management of patients with progressive rheumatoid disease. At the present time two forms of gold therapy are available: one by injection and the other by the oral route. A significant number of patients will achieve clinical benefit from treatment with one of these two compounds. Both compounds have a high prevalence of side-effects and should be regarded as toxic, although the oral preparation appears to have a somewhat better safety profile than has the injectable compound. While resort to these medications should be considered for the treatment of patients who have progressive rheumatoid disease, their use should not be taken lightly. The prescribing physician has an obligation to ensure constant monitoring of patients who are receiving either of these therapies.

  11. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis

    PubMed Central

    Bartok, Beatrix; Firestein, Gary S.

    2010-01-01

    Summary Rheumatoid arthritis (RA) remains a significant unmet medical need despite significant therapeutic advances. The pathogenesis of RA is complex and includes many cell types, including T cells, B cells, and macrophages. Fibroblast-like synoviocytes (FLS) in the synovial intimal lining also play a key role by producing cytokines that perpetuate inflammation and proteases that contribute to cartilage destruction. Rheumatoid FLS develop a unique aggressive phenotype that increases invasiveness into the extracellular matrix and further exacerbates joint damage. Recent advances in understanding the biology of FLS, including their regulation regulate innate immune responses and activation of intracellular signaling mechanisms that control their behavior, provide novel insights into disease mechanisms. New agents that target FLS could potentially complement the current therapies without major deleterious effect on adaptive immune responses. PMID:20193003

  12. 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-κB 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-γ, 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

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

    PubMed

    Tanaka, Keiichi; Yamaguchi, Tomonobu; Hara, Masako

    2015-05-01

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

  14. 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.

  15. Fatigue in rheumatoid arthritis. Conditions, strategies, and consequences.

    PubMed

    Tack, B B

    1990-06-01

    Fatigue is a frequent and debilitating problem for people with rheumatoid arthritis (RA). In this descriptive study a Fatigue Interview Schedule was administered to 20 patients with RA to elicit symptom-specific information. Qualitative analyses resulted in the identification of descriptors of fatigue, conditions under which fatigue occurs, an intricate repertoire of strategies used to prevent and manage fatigue, and the consequences of chronic fatigue. PMID:2285744

  16. Production of angiotensin converting enzyme by rheumatoid synovial membrane.

    PubMed Central

    Veale, D; Yanni, G; Bresnihan, B; FitzGerald, O

    1992-01-01

    Vascular proliferation and mononuclear cell infiltration are prominent changes observed in synovium from actively inflamed joints of patients with rheumatoid arthritis. Angiotensin converting enzyme (ACE) is a halide activated peptidase produced mainly by endothelial cells and by activated monocytes. It has been proposed that levels of ACE activity in synovial fluid might reflect changes in membrane vascularity, the degree of monocyte infiltration, or the thickness of the lining layer. In this study, ACE activity in serum and synovial fluid samples from 18 patients with inflammatory arthritis was measured and compared with levels in 12 control subjects with non-inflammatory arthritis. Although serum levels were similar in the two groups, ACE activity in synovial fluid was significantly increased in the group with inflammatory arthritis compared with controls (mean (SE) 37 (5) v 19 (3)). Staining of synovial membranes from patients with rheumatoid arthritis with a monoclonal antibody to ACE localised ACE to the endothelium and to mononuclear cells of macrophage origin. ACE activity was then measured in supernatants of synovial membrane from patients with rheumatoid arthritis after one and seven days of culture. A significant increase in ACE activity was observed after seven days of culture (mean (SE) day 1, 17 (5) v day 7, 25 (3)). Levels of ACE activity, however, did not correlate with the lining layer thickness, with the number of macrophages per square millimetre, nor with the number of blood vessels per square millimetre of synovial tissue. No correlation was observed either between levels of ACE in the supernatant of synovial membrane and levels of interleukin 1 or interleukin 6. In conclusion, ACE is produced by the synovial membrane of patients with rheumatoid arthritis and is localised to monocytes and endothelial cells. Levels of activity do not directly reflect membrane vascularity, monocyte or macrophage number, or the thickness of the lining layer. Images PMID:1316742

  17. Modified-release prednisone: in patients with rheumatoid arthritis.

    PubMed

    Henness, Sheridan; Yang, Lily P H

    2013-12-01

    Prednisone is a well-established treatment option in rheumatoid arthritis. Low-dose glucocorticoid therapy alleviates disease signs and symptoms, is better tolerated than high-dose therapy, and its addition to disease-modifying anti-rheumatic drugs (DMARDs) inhibits radiographic disease progression. A low-dose, modified-release (MR) formulation of prednisone, administered in the evening, was developed to counter the circadian rise in pro-inflammatory cytokine levels that contributes to disease activity. In a 12-week, randomized trial (CAPRA-2) in adult patients with rheumatoid arthritis who were receiving stable DMARD therapy, the addition of MR prednisone reduced disease signs and symptoms by ≥20 % according to the American College of Rheumatology criteria (in 48 % of patients vs. 29 % with placebo; p < 0.002 [primary endpoint]). In another 12-week trial (CAPRA-1), addition of evening MR prednisone to stable DMARD therapy reduced the mean duration of morning stiffness to a greater extent than addition of morning immediate-release (IR) prednisone (22.7 vs. 0.4 %; p = 0.045 [primary endpoint]). The improvement in morning stiffness with MR prednisone was maintained for 9-12 months during the open-label extension of CAPRA-1. These findings were supported by data from observational studies in various adult populations with rheumatoid arthritis. Treatment with evening MR prednisone for up to 12 months was generally well tolerated, with an overall similar tolerability profile compared with evening placebo or morning IR prednisone, and no new safety concerns. MR prednisone was estimated to be cost effective relative to IR prednisone in patients with rheumatoid arthritis in a UK pharmacoeconomic model. PMID:24249648

  18. 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

  19. Course and prognosis in seropositive and seronegative rheumatoid arthritis.

    PubMed

    Sahatiu-Meka, Vjollca; Rexhepi, Sylejman; Kukeli, Anton; Manxhuka-Krliu, Suzana; Pallaskas, Kelmend; Murtezani, Ardiana; Rexhepi, Mjellma; Rexhepi, Blerta

    2013-01-01

    Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis (RA), diagnosed with negative rheumatoid factor (RF) tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis. The aim of the study was to establish a scientific comparative analysis between RA seronegative and seropositive, regarding course and prognoses of the disease. Two hundred fifty patients with rheumatoid arthritis according to the (American College of Rheumatology) criteria were retrospectively studied by analysis the course and prognoses of disease. All examinees were between 25-60 years of age (Xb=49.9, SD=10.3) with disease duration between 1-27 years (Xbox=6.41, SD=6.47). Course of the disease with "remissions and exacerbations", progressive continual course and bad prognoses, were more presented in seropositive group ofpatients. Partial remission was more common in seronegative patients but according to serostatus and gender has not shown statistically significant difference. Duration of the disease was a specific prognostic sign for both subsets [(r=0.32, p<0.01) seronegative, (r=0.22, p<0.05) seropositive], while age was only a specific prognostic sign for the seropositive subset [(r=0.01, p>0.05) seronegative, (r=0.18, p<0.05) seropositive]. Seropositive and seronegative RA distinguish in course and prognostic feature, but not enough to differentiate them in two different forms of the disease. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. PMID:24003679

  20. [Pyoderma gangrenosum associated with rheumatoid arthritis: a case report].

    PubMed

    Beber, Andr Avelino Costa; Knob, Cristiane Faccin; Shons, Karen Regina Rosso; Neumaier, Walter; da Silva, Joo Carlos Nunes; Monticielo, Odirlei Andr

    2014-01-01

    Pyoderma gangrenosum is a chronic inflammatory dermatosis, which is associated with non-infectious systemic diseases such as rheumatoid arthritis and inflammatory bowel disease. It is more common in adults and may present with four distinct clinical forms, all leading to ulceration of the skin affected. Its diagnosis is clinical and demands exclusion of other causes. Treatment should be performed with local care and systemic therapy. PMID:25627229

  1. Interstitial granulomatous dermatitis: rare cutaneous manifestation of rheumatoid arthritis*

    PubMed Central

    Veronez, Isis Suga; Dantas, Fernando Luiz; Valente, Neusa Yuriko; Kakizaki, Priscila; Yasuda, Thas Helena; Cunha, Thas do Amaral

    2015-01-01

    Besides being an uncommon clinicopathological entity, interstitial granulomatous dermatitis, also described as interstitial granulomatous dermatitis with arthritis (IGDA), has shown a wide spectrum of clinical manifestations, such as linear and erythematous lesions, papules, plaques and nodules. Histological features include dense dermal histiocytic infiltrate, usually in a palisade configuration, and scattered neutrophils and eosinophils. We describe a middle aged woman with rheumatoid arthritis of difficult management and cutaneous lesions compatible with IGDA. PMID:26131871

  2. Tocilizumab improves systemic rheumatoid vasculitis with necrotizing crescentic glomerulonephritis.

    PubMed

    Iijima, Takashi; Suwabe, Tatsuya; Sumida, Keiichi; Hayami, Noriko; Hiramatsu, Rikako; Hasegawa, Eiko; Yamanouchi, Masayuki; Hoshino, Junichi; Sawa, Naoki; Takaichi, Kenmei; Oohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2015-01-01

    We report a Japanese woman with systemic rheumatoid vasculitis (SRV) complicated by necrotizing crescentic glomerulonephritis (NCGN). Rheumatoid arthritis first occurred at the age of 19 years, followed by interstitial pneumonia, hepatitis, rheumatoid nodules, mononeuritis multiplex, and hypocomplementemia in chronological order. At the age of 51 years, rapidly progressive renal failure occurred with nephrotic proteinuria, and NCGN with subepithelial deposits was revealed by renal biopsy. Severe destructive changes of multiple joints and scleritis were detected, but anti-neutrophil cytoplasmic antibody was negative on enzyme-linked immunosorbent assays and indirect immunofluorescence. SRV was diagnosed due to involvement of multiple extra-articular organs. An anti-interleukin (IL)-6 receptor antibody (tocilizumab) was started at dosage of 280 mg (8 mg/kg) monthly. After 18 months, her serum creatinine decreased from 1.7 to 1.3 mg/dL, and urinary protein excretion declined from 5.2 to 1.2 g daily. Tocilizumab may be a therapeutic option for SRV associated with NCGN. PMID:24533557

  3. Occurrence of pulmonary rheumatoid nodules following biological therapies.

    PubMed

    Kovcs, Attila; Baksay, Beta; Cserenyecz, Anita; Molnr, Klra; Takcs, Mria; Szekanecz, Zoltn

    2015-09-01

    In rheumatoid arthritis (RA), disease activity is generally determined by the joint involvement, but the treatment outcome is often influenced by extra-articular manifestations. Authors present a 74-year-old female patient's case history, who was treated with seropositive RA. Marked disease activity was observed even following combined traditional disease-modifying antirheumatic drug (DMARD) treatment (disease activity score in 28 joints (DAS28)?=?6.6). Therefore, the patient received TNF-? antagonist therapy. Golimumab was administered subcutaneous (SC) once monthly which resulted in significant improvement in both clinical and laboratory signs (DAS28?=?3:43). However, the follow-up chest x-ray indicated multiple intrapulmonary foci and enlarged lymph nodes. Biopsies and histology excluded malignancy; rheumatoid nodules were confirmed. Anti-TNF therapy was discontinued and tocilizumab treatment was initiated. The IL-6 receptor inhibitor suppressed arthritic activity, and 2 months later, the follow-up chest x-ray showed a regression of chest nodules. Our cases, as well as reports from other centers, suggest that TNF blockade may induce rheumatoid nodulosis and the use of alternative biologics may be feasible as further treatment of RA. PMID:25267563

  4. Radiocarpal and Midcarpal Instability in Rheumatoid Patients: A Systematic Review

    PubMed Central

    Raven, Eric E.J.; van den Bekerom, Michel P.J.; Beumer, Annechien; van Dijk, C. Niek

    2015-01-01

    Background: This study was aimed at identifying the criteria for the diagnosis of Radiocarpal instability in rheumatoid arthritis RA). Methods: The main databases were searched to identify studies describing the pathophysiology of Radiocarpal instability in patients with RA. We focussed on the epidemiology, radiographic parameters, criteria for instability and on treatment options. Results. In the search 108 articles were found, of these 12 studies were included for this review. Instability occurs in at an average of 35.2% of the rheumatoid wrists. The instability was found between 8 and 13 years after onset of rheumatoid arthritis. A strong correlation was found between instability, duration of RA and Larsen score. Several radiographic methods were described to evaluate Radiocarpal instability in RA. Several treatment options for instability in patients with RA are described. All with their own indications and limitations. Conclusion: On a standard AP radiograph deformity can be measured using the carpal height and the ulnar translation index of Chamay. This gives an indication for instability. For describing the deterioration of the joints the Larsen score is most used. If there are more radiographs in time the Simmen classification can be used. For real assessment of instability dynamic radiographs are needed. Level of Evidence: Level IV. PMID:26448803

  5. 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 27C, 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 30C the fragments begin to denature and denaturation is complete at 37C. 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 37C are cleaved to the low molecular weight fragments, although the fibrils are resistant to breakdown at lower temperatures (20-27C). 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

  6. 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

  7. Effect of rheumatoid arthritis on periodontitis: a historical cohort study

    PubMed Central

    Torkzaban, Parviz; Hjiabadi, Tayebeh; Basiri, Zahra

    2012-01-01

    Purpose Rheumatoid arthritis (RA) is a chronic multi-systemic disease that causes damage to the bone and connective tissues. This study was conducted in order to accurately measure the correlation between RA and periodontitis, and to obtain an unbiased estimate of the effect of RA on periodontal indices. Methods In this historical cohort study, which was conducted from February to May 2011 in Hamadan city, Iran, 53 exposed people (with RA) were compared with 53 unexposed people (without RA) in terms of clinical periodontal indices (the outcomes of interest) including 1) plaque index (PI), 2) bleeding on probing (BOP), and 3) clinical attachment loss (CAL). Results A sample of 106 volunteers were evaluated, 53 rheumatoid versus 53 non-rheumatoid subjects. There was a statistically significant correlation between RA and BOP (P<0.001) and between RA and CAL (P<0.001). However, there was no statistically significant correlation between RA and any of the periodontal indices. No correlation was seen between gender and any of the indices either. There was a strong positive correlation between age and all three periodontal indices (P<0.001). Conclusions The present study indicated a potential effect of RA on periodontal indices. However, much more evidence based on a prospective cohort study is needed to support the cause and effect relationship between RA and periodontal indices. PMID:22803007

  8. Circulating Antinuclear Antibody and Rheumatoid Factor in Coal Pneumoconiosis

    PubMed Central

    Soutar, C. A.; Turner-Warwick, Margaret; Parkes, W. Raymond

    1974-01-01

    Circulating antinuclear antibody and rheumatoid factor have been measured in 109 coal miners with pneumoconiosis whose chest radiograph showed a range of abnormalities varying from simple pneumoconiosis of mild degree to advanced progressive massive fibrosis. At a screening dilution of 1/10 the overall incidence of antinuclear antibody was 17%. In almost half of the positive cases the titre was 1/40 or greater. The prevalence of antinuclear antibody was lowest in those with simple pneumoconiosis (9%) and highest in those with category C progressive massive fibrosis (27%). A similar but less striking trend was seen with rheumatoid factor, ranging from 6% in simple pneumoconiosis to 18% in category C progressive massive fibrosis. The trend of increasing frequency of autoantibodies with advancing radiographic category was most marked when the frequencies of antinuclear antibody and rheumatoid factor were combined. These autoantibodies were found in 13% of the miners with simple pneumoconiosis and 45% of those with category C progressive massive fibrosis (P for the trend=0·01). PMID:4602134

  9. Non-Biologic Nanodelivery Therapies for Rheumatoid Arthritis.

    PubMed

    Gouveia, Virgnia M; Lima, Sofia A Costa; Nunes, Cludia; 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  11. 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.

  12. 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

  13. 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

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

    PubMed Central

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

    2016-01-01

    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

  15. 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, 1.2830.96; 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

  16. Cellular Response to Prosthetic Wear Debris Differs in Rheumatoid Versus Non-Rheumatoid Arthritis Patients

    PubMed Central

    Vasudevan, Anant; DiCarlo, Edward F.; Wright, Timothy; Chen, Dan; Figgie, Mark P.; Goldring, Steven R.; Mandl, Lisa A.

    2011-01-01

    Objective This study examined whether patients with rheumatoid arthritis (RA) demonstrate different patterns of prosthetic wear or cellular responses to implant wear debris compared to patients without inflammatory joint disease. Methods Thirty-eight patients who had a primary revision of a total elbow arthroplasty (TEA) for aseptic loosening between 1996 and 2008 were identified. Twenty-five had RA and 13 had no inflammatory arthritis. Clinical data, gross wear patterns of the removed prostheses, and histopathological analyses of peri-implant tissue were compared between RA and non-RA patients. Results Evaluation of the retrieved prostheses showed that conformational change of the humeral polyethylene bushing was associated with the generation of polyethylene and metal particles. The amount and type of wear debris in peri-prosthetic tissues was similar in RA and non-RA patients. RA patients not on anti-tumor necrosis factor (TNF) therapy exhibited a histologic pattern of interstitial and sheet-like lymphocytic infiltrates associated with a high plasma cell composition, which was different from the predominantly perivascular infiltrates with few plasma cells seen in non-RA patients (p-value = 0.04). RA patients on anti-TNF therapy fell in between these two groups. Conclusion RA patients exhibit a distinct cellular response to implant wear debris compared with non-RA patients. This reaction was unrelated to differences in the type or amount of wear debris and was mitigated by anti-TNF therapy. These results suggest an intrinsic alteration in immunoregulation in RA and have implications for potential immunologic treatment of osteolysis in these patients. PMID:22127818

  17. Biomechanical analysis of the wrist arthroplasty in rheumatoid arthritis: a finite element analysis.

    PubMed

    Bajuri, M N; Abdul Kadir, Mohammed Rafiq; Murali, Malliga Raman; Kamarul, T

    2013-02-01

    The total replacement of wrists affected by rheumatoid arthritis (RA) has had mixed outcomes in terms of failure rates. This study was therefore conducted to analyse the biomechanics of wrist arthroplasty using recently reported implants that have shown encouraging results with the aim of providing some insights for the future development of wrist implants. A model of a healthy wrist was developed using computed tomography images from a healthy volunteer. An RA model was simulated based on all ten general characteristics of the disease. The ReMotion total wrist system was then modelled to simulate total wrist arthroplasty (TWA). Finite element analysis was performed with loads simulating the static hand grip action. The results show that the RA model produced distorted patterns of stress distribution with tenfold higher contact pressure than the healthy model. For the TWA model, contact pressure was found to be approximately fivefold lower than the RA model. Compared to the healthy model, significant improvements were observed for the TWA model with minor variations in the stress distribution. In conclusion, the modelled TWA reduced contact pressure between bones but did not restore the stress distribution to the normal healthy condition. PMID:23124814

  18. Intensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritis.

    PubMed

    Tanaka, Yoshiya; Hirata, Shintaro

    2014-12-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate (MTX), a synthetic disease-modifying anti-rheumatic drug (sDMARD) and biological DMARDs (bDMARDs) has revolutionized treatment of RA and clinical remission or low disease activity (LDA) are now realistic targets, achieved by a large proportion of RA patients. We are now in a position to evaluate if it is possible to maintain remission or LDA while at the same time reducing the burden of treatment on the patient and healthcare system. Data are emerging from large, well-conducted studies designed to answer this question, shedding light on which patient populations and treatment algorithms can survive treatment discontinuation or tapering with low risk of disease flare. For early RA, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining clinical remission by bDMARDs with MTX. In contrast, for established RA, fewer patients sustained remission or LDA after the discontinuation of bDMARDs and "deep remission" at the discontinuation was a key factor to maintain the treatment holiday of bDMARDs. Thus, this article provides a brief outline on withdrawing or tapering bDMARDs once patients have achieved remission or LDA in RA. PMID:25389048

  19. Sociodemographic factors associated with functional disability in outpatients with rheumatoid arthritis in Southwest China.

    PubMed

    Zhao, Shangping; Chen, Yanling; Chen, Hong

    2015-05-01

    With the rising number of patients with rheumatoid arthritis (RA), there is a limited understanding about sociodemographic factors that influence functional disability in Chinese patients. In order to provide more targeted interventions to improve health-related quality of life (HRQoL) for patients with RA, we conducted a cross-sectional study to investigate the level and influencing factors of functional disability. Convenient samples were collected in outpatients with RA from a rheumatological center in southwest China from September to December 2013. Data were collected by printed questionnaires, and functional disability was measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). The results showed that 58.48 % of 607 outpatients had functional disability. Patients from rural residents, with lower household income and lower education level, were significantly associated with worse functional disability. Multivariate regression findings showed that pain, age, disease duration, total cost for treatment, and frequency of hospitalization were positively associated with functional disability. Meanwhile, subjective and available social support was the protective predictors for functional disability. The results suggested that systematic intervention and therapies should be provided as early as possible. Patients and health care providers should promote the awareness of the importance of accessible health education in early intervention of RA. Besides, pain management and social support are encouraged to postpone the process of disability of patients and improve the HRQoL. Lastly, but not least, prevention and intervention of RA should be incorporated into public health education. PMID:25687985

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. Computer simulation model for early post-capture phase of lunar orbital evolution: implications for thermal history of Earth and Moon

    SciTech Connect

    Malcuit, R.J.; Winters, R.R.

    1985-01-01

    Gravitational capture of a lunar-sized body entails dissipation of about 2 x 10/sup 35/ ergs within the bodies of Earth and Moon by body tides during a close gravitational encounter. For capture to occur, the deformation constants (Love numbers) must be sufficiently high and Q (specific energy dissipation factor) must be sufficiently low. Initial conditions for the two-body orbital simulation are perigee = 20 R/sub e/ (Earth radii), apogee = 270 R/sub e/, and semi-minor axis = 73 R/sub e/. This early post-capture orbit has angular momentum equivalent to a circular lunar orbit of 40 R/sub e/. For simplification, the effects of Earth rotation are neglected and Love numbers are held constant during each calculation. The main variable controlling orbital evolution is Q. Since about 7 x 10/sup 35/ ergs must be dissipated for capture and subsequent orbital circularization, the bodies of both Earth and Moon are heated considerably. Using the Love numbers given above, about 10% of the energy goes to Earth and about 90% goes to Moon. Although the 10% allocated to Earth would be sufficient to melt only a thin zone of mantle material, the combination of energy dissipation and tidal action during such as orbital circularization scenario could lead to enhanced rates of crustal spreading and subduction on an already warm Earth. The authors think that this thermal episode may be sufficient to cause widespread destruction and/or metamorphism of the ancient crust of Earth. They suggest that lunar capture and subsequent early geocentric orbital evolution occurred about 3.9 billion years ago.

  5. Transient thyrotoxicosis as an initial presentation of rheumatoid arthritis: a case report

    PubMed Central

    Brit, Michael

    2009-01-01

    Introduction Few reports in the literature describe the association of rheumatoid arthritis and transient thyrotoxicosis. We report a case of rheumatoid arthritis and painless thyroiditis presenting simultaneously and acutely with a cluster of symptoms that initially made the diagnosis of rheumatoid arthritis very challenging. Case presentation A 41-year-old Caucasian male presented with complaints of malaise and decreased range of motion in the left elbow. Physical examination and laboratory evaluation established the diagnosis of rheumatoid arthritis and painless thyroiditis. Conclusions When patients with rheumatoid arthritis present with numerous extra articular and constitutional symptoms, evaluation of thyroid disorder with thyroid function test should be considered to help establish the correct diagnosis. PMID:19829943

  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. Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response

    PubMed Central

    Kragstrup, Tue Wenzel; Jalilian, Babak; Keller, Kresten Krarup; Zhang, Xianwei; Laustsen, Julie Kristine; Stengaard-Pedersen, Kristian; Hetland, Merete Lund; Hørslev-Petersen, Kim; Junker, Peter; Østergaard, Mikkel; Hauge, Ellen-Margrethe; Hvid, Malene; Vorup-Jensen, Thomas; Deleuran, Bent

    2016-01-01

    Introduction In rheumatoid arthritis (RA) immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18) in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis. Methods The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1) plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice following arthritis induction, and 4) supernatants from synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from 6 RA patients cultured with TNFα or adalimumab. Results Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFα and decreased by adalimumab. Conclusions The plasma sCD18 levels were altered in patients with RA, in mice with autoimmune arthritis and in cell cultures treated with TNFα and adalimumab. Decreased levels of plasma sCD18 could reflect autoimmunity in transition from early to chronic disease and normalization in response to treatment could reflect autoimmunity in remission. PMID:26849368

  8. 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

  9. 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.

  10. The 29 September 2009 Samoa Islands Tsunami: Simulations Based on the First Focal Mechanism Solutions and Implications on Tsunami Early Warning Strategies

    NASA Astrophysics Data System (ADS)

    Tonini, Roberto; Armigliato, Alberto; Tinti, Stefano

    2011-06-01

    The tsunamigenic earthquake (Mw = 8.1) that occurred on 29 September 2009 at 17:48 UTC offshore of the Samoa archipelago east of the Tonga trench represents an example of the so-called "outer-rise" earthquakes. The areas most affected were the south coasts of Western and American Samoa, where almost 200 people were killed and run-up heights were measured in excess of 5 m at several locations along the coast. Moreover, tide gauge records showed a maximum peak-to-peak height of about 3.5 m near Pago Pago (American Samoa) and of 1.5 m offshore of Apia (Western Samoa). In this work, different fault models based on the focal mechanism solutions proposed by Global CMT and by USGS immediately after the 2009 Samoan earthquake are tested by comparing the near-field recorded signals (three offshore DART buoys and two coastal tide gauges) and the synthetic signals provided by the numerical simulations. The analysis points out that there are lights and shadows, in the sense that none of the computed tsunamis agrees satisfactorily with all the considered signals, although some of them reproduce some of the records quite well. This "partial agreement" and "partial disagreement" are analysed in the perspective of tsunami forecast and of Tsunami Early Warning System strategy.

  11. 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.

  12. Tsunami early warning in the Mediterranean: role, structure and tricks of pre-computed tsunami simulation databases and matching/forecasting algorithms

    NASA Astrophysics Data System (ADS)

    Armigliato, Alberto; Pagnoni, Gianluca; Tinti, Stefano

    2014-05-01

    The general idea that pre-computed simulated scenario databases can play a key role in conceiving tsunami early warning systems is commonly accepted by now. But it was only in the last decade that it started to be applied to the Mediterranean region, taking special impulse from initiatives like the GDACS and from recently concluded EU-funded projects such as TRIDEC and NearToWarn. With reference to these two projects and with the possibility of further developing this research line in the frame of the FP7 ASTARTE project, we discuss some results we obtained regarding two major topics, namely the strategies applicable to the tsunami scenario database building and the design and performance assessment of a timely and "reliable" elementary-scenario combination algorithm to be run in real-time. As for the first theme, we take advantage of the experience gained in the test areas of Western Iberia, Rhodes (Greece) and Cyprus to illustrate the criteria with which a "Matching Scenario Database" (MSDB) can be built. These involve 1) the choice of the main tectonic tsunamigenic sources (or areas), 2) their tessellation with matrices of elementary faults whose dimension heavily depend on the particular studied area and must be a compromise between the needs to represent the tsunamigenic area in sufficient detail and of limiting the number of scenarios to be simulated, 3) the computation of the scenarios themselves, 4) the choice of the relevant simulation outputs and the standardisation of their formats. Regarding the matching/forecast algorithm, we want it to select and combine the MSDB elements based on the initial earthquake magnitude and location estimate, and to produce a forecast of (at least) the tsunami arrival time, amplitude and period at the closest tide-level sensors and in all needed forecast points. We discuss the performance of the algorithm in terms of the time needed to produce the forecast after the earthquake is detected. In particular, we analyse the different contributions of a number of factors such as the efficient code development and availability of cutting-edge hardware to run the code itself, the wise selection of the MSDB outputs to be combined, the choice of the forecast points where water elevation time series must be taken into account, and few others.

  13. Treatment of rheumatoid arthritis: unknown long-term effects.

    PubMed

    2001-04-01

    (1) Rheumatoid arthritis, a chronic disease, is defined by a set of clinical, radiological and biochemical criteria. The diagnosis is initially uncertain. (2) Many patients have functional disability 10 years after onset, while others may have little or none. (3) The symptomatic and long-term efficacy of physical (nondrug, nonsurgical) therapies is poorly documented. (4) Various surgical approaches may restore a degree of functional capacity. (5) The use of paracetamol, possibly combined with codeine, can avoid recourse to nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are the best-assessed analgesics in this setting but carry a risk of severe adverse effects. (6) All long term treatments for rheumatoid arthritis carry a risk of severe adverse effects, and their chronic effects are poorly documented. There is no firm evidence that long term treatments reduce the risk of serious disability or death. (7) Methotrexate is the best-tolerated slow-acting antirheumatic in the medium term, despite a risk of hepatic cirrhosis, pulmonary fibrosis and haematological disorders. (8) Hydroxychloroquine and sulfasalazine are less effective. Hydroxychloroquine carries a risk of retinal damage, while sulfasalazine can cause haematological disorders and skin problems. Chloroquine seems to be slightly more effective than hydroxychloroquine, but at the cost of more adverse effects. (9) The adverse effects of D-penicillamine and injectable gold salts often require treatment withdrawal. (10) The risks associated with immunosuppressants such as ciclosporin mean that these agents should not be used for first-line treatment. (11) The place of various combinations of slow-acting antirheumatics remains to be established. (12) Recourse to systemic steroids must be minimised but is sometimes unavoidable. Low doses are usually adequate. (13) Treatment risks in elderly subjects and patients with comorbidity must be taken into account. (14) Women and men of child-bearing potential who have rheumatoid arthritis must be warned about the toxicity of antirheumatic drugs for the fetus and the effects on fertility. PMID:11718162

  14. Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa.

    PubMed

    Jiang, Cui-Ping; He, Xin; Yang, Xiao-Lin; Zhang, Su-Li; Li, Hui; Song, Zi-Jing; Zhang, Chun-Feng; Yang, Zhong-Lin; Li, Ping; Wang, Chong-Zhi; Yuan, Chun-Su

    2014-05-15

    The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20?g/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis. PMID:24561028

  15. Multiple Intracerebral Hemorrhages in an Old Patient with Rheumatoid Arthritis.

    PubMed

    Cojocaru, Inimioara Mihaela; Ştefănescu, V; Traşcă, Daniela; Şerban-Pereţeanu, Adelina; Chicoş, B; Cojocaru, M

    2015-01-01

    A 78-year-old Caucasian man was admitted in the Department of Neurology for visual disturbances, started two days before. The next day the patient experienced headache, fever and gait disturbances. He had hypertension, diabetes mellitus, an ischemic stroke 13 years ago, longstanding seronegative rheumatoid arthritis (17 years), polynodular goiter, right ischio-pubian fracture and right femoral vein thrombosis a year ago due to a car accident, since he is treated with oral anticoagulants associated to antiaggregant, hypotensors, statin and oral antidiabetics. The neurologic examination had evidenced nuchal rigidity, left homonymous hemianopsia, left central facial palsy, ataxia of the inferior limbs with wide-based gait, achilean reflexes abolished bilaterally, bilaterally abolished plantar reflexes, ideomotor apraxia, dysarthria, hypoprosexia, and preserved consciousness patient. A non-contrast cerebral CT scan had shown right temporal and parieto-occipital intraparenchymatous hemorrhages, a right frontal sequelar lesion, multiple old lacunar infarets, cortical atrophy. Laboratory findings included an inflammatory syndrome, absence of rheumatoid arthritis positive serology, normal coagulogram, an elevated proteinuria. The cerebral IRM performed on the seventh day of hospitalisation was suggestive for subacute right parietal hemorrhage, old cerebral infarction in the right anterior cerebral artery area, old lacunar infarcts and cerebral atrophy. The anticoagulant and antiaggregant treatment was stopped after a generalized tonic-clonic seizure occurred. Antiedematous, hypotensor, anticonvulsivant, beta-blocker, and symptomatic treatment was started, while the antidiabetic treatment was continued. All symptoms remitted. Arguments for amyloid angiopathy in our patient are previous non-cardioembolic ischemic stroke and a chronic inflammatory disease- rheumatoid arthritis in his personal medical history. PMID:26939215

  16. Spontaneous "spaghetti" flexor tendon ruptures in the rheumatoid wrist.

    PubMed

    Hashizume, Hiroyuki; Nishida, Keiichiro; Fujiwara, Kazuo; Inoue, Hajime

    2004-01-01

    A 54-year-old woman who had been treated for rheumatoid arthritis for 12 years developed spontaneous multiple flexor tendon ruptures during a 5-month period. Radiography revealed volar subluxation of the lunate bone. Surgery was performed 5 months after the first onset of tendon rupture. All eight flexors, except the flexor pollicis longus tendons, had ruptured, and the damage resembled spaghetti. Four flexor digitorum profundus tendons were reconstructed by bridge graft using their respective sublimis tendons. Wrist joint fusion and tenolysis were performed 3 months after the first operation. Each finger achieved a good range of motion 2 years and 6 months after the second operation. PMID:17143686

  17. Bone and TNF in rheumatoid arthritis: clinical implications

    PubMed Central

    Manara, Maria; Sinigaglia, Luigi

    2015-01-01

    Experimental data have demonstrated that tumour necrosis factor (TNF) plays a significant role in systemic and local bone loss related to rheumatoid arthritis (RA). In clinical studies on patients with RA, treatment with TNF inhibitors was able to arrest systemic bone loss assessed by bone mineral density and bone turnover markers, but there is scarce evidence of a clinically meaningful effect of TNF inhibition in preventing fractures. TNF inhibitors showed a higher efficacy in reducing radiographic progression related to the disease compared to methotrexate in randomised clinical trials. Data from observational studies seem to confirm the effectiveness of anti-TNF therapy in reducing joint damage evolution. PMID:26557382

  18. Are rheumatoid arthritis and systemic lupus erythematosus inversely related diseases?

    PubMed

    Mawson, A R

    1985-12-01

    Although rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have certain features in common, the literature suggests that the two diseases are inversely related to each other in at least eight major respects, viz., age of onset in relation to reproductive fertility; psychosis; kidney disease; nutritional status; and the differential effects of pregnancy, oral contraceptive use, jaundice, and penicillamine. It is suggested that associated with RA and SLE are differing blood and/or tissue levels of a common but as yet undetermined factor: deficient levels in RA, toxic levels in SLE. PMID:3854165

  19. Effect of dietary restrictions on disease activity in rheumatoid arthritis.

    PubMed Central

    Beri, D; Malaviya, A N; Shandilya, R; Singh, R R

    1988-01-01

    Additions in five steps were made, as a possible therapeutic measure, to the diet of 27 patients with rheumatoid arthritis (RA) after a period of two weeks of a basal isocaloric diet free from pulses, cereals, milk, and non-vegetarian protein foods. Fourteen patients finally took part in the trial, 10 (71%) of whom showed significant clinical improvement. Only three patients (11%) adhered to the diet for a period of 10 months. The others discontinued the diet and were then treated with conventional disease modifying drugs. The study indicates that dietary factors may influence inflammatory response in RA. PMID:3278696

  20. 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

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

    PubMed Central

    Kaplan, Mariana J.

    2010-01-01

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

  2. Biologic agents for rheumatoid arthritis: 2008 and beyond.

    PubMed

    Sweiss, Nadera J; Hushaw, Linda L

    2009-01-01

    Rheumatoid arthritis (RA) is a chronic disease with a complex underlying pathology and varied presentation in patients. Several novel biologic disease-modifying antirheumatic drugs have become available for the treatment of RA. Agents in late-stage clinical trials include golimumab and certolizumab, which are anti-tumor necrosis factor (TNF)-alpha agents; ocrelizumab, an anti-CD20 agent; and tocilizumab, an inhibitor of interleukin-6. As treatment options for RA expand, nursing care will play an increasingly important role in empowering patients through interventions such as patient education and adverse effect management. PMID:19142153

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

    PubMed

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

    2013-02-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology. Treatment of RA is very complex, and in the past years, some studies have investigated the use of low-level laser therapy (LLLT) in treatment of RA. However, it remains unknown if LLLT can modulate early and late stages of RA. With this perspective in mind, we evaluated histological aspects of LLLT effects in different RA progression stages in the knee. It was performed a collagen-induced RA model, and 20 male Wistar rats were divided into 4 experimental groups: a non-injured and non-treated control group, a RA non-treated group, a group treated with LLLT (780 nm, 22 mW, 0.10 W/cm(2), spot area of 0.214 cm(2), 7.7 J/cm(2), 75 s, 1.65 J per point, continuous mode) from 12th hour after collagen-induced RA, and a group treated with LLLT from 7th day after RA induction with same LLLT parameters. LLLT treatments were performed once per day. All animals were sacrificed at the 14th day from RA induction and articular tissue was collected in order to perform histological analyses related to inflammatory process. We observed that LLLT both at early and late RA progression stages significantly improved mononuclear inflammatory cells, exudate protein, medullary hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts and osteoblasts compared to RA group (p < 0.05). We can conclude that LLLT is able to modulate inflammatory response both in early as well as in late progression stages of RA. PMID:22538842

  4. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study

    PubMed Central

    2012-01-01

    Objective To analyse the association between alcohol intake and incidence of rheumatoid arthritis in women. Design Prospective cohort study with repeated measurements. Setting The Swedish Mammography Cohort, a population based cohort from central Sweden. Participants 34?141 women born between 1914 and 1948, followed up from 1 January 2003 to 31 December 2009. Main outcome measures Newly diagnosed cases of rheumatoid arthritis identified by linkage with two Swedish national registers. Data on alcohol consumption were collected in 1987 and 1997. Results During the follow-up period (226?032 person years), 197 incident cases of rheumatoid arthritis were identified. There was a statistically significant 37% decrease in risk of rheumatoid arthritis among women who drank >4 glasses of alcohol (1 glass = 15 g of ethanol) per week compared with women who drank <1 glass per week or who never drank alcohol (relative risk 0.63 (95% confidence interval 0.42 to 0.96), P=0.04). Drinking of all types of alcohol (beer, wine, and liquor) was non-significantly inversely associated with the risk of rheumatoid arthritis. Analysis of long term alcohol consumption showed that women who reported drinking >3 glasses of alcohol per week in both 1987 and 1997 had a 52% decreased risk of rheumatoid arthritis compared with those who never drank (relative risk 0.48 (0.24 to 0.98)). Conclusion Moderate consumption of alcohol is associated with reduced risk of rheumatoid arthritis. PMID:22782847

  5. Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis.

    PubMed

    Saad, Mohamed N; Mabrouk, Mai S; Eldeib, Ayman M; Shaker, Olfat G

    2016-01-01

    Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field. PMID:26843965

  6. Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis

    PubMed Central

    Saad, Mohamed N.; Mabrouk, Mai S.; Eldeib, Ayman M.; Shaker, Olfat G.

    2015-01-01

    Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field. PMID:26843965

  7. 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

  8. 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.

  9. Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity.

    PubMed

    Gerber, D A

    1975-06-01

    A study of sera from 285 patients with definite or classical rheumatoid arthritis (including 37 patients receiving no anti-inflammatory drugs) and sera from 67 healthy subjects has confirmed 10 published reports of a statistically significant decreased blood histidine concentration in patients with rheumatoid arthritis. Contrastingly, in sera from 231 patients with a variety of acute and chronic illnesses other than rheumatoid arthritis, no statistically significant hypohistidinemia was observed either in the group as a whole or in association with the administration of aspirin, prednisone, indomethacin, phenylbutazone, or dextropropoxyphene. In the patients with rheumatoid arthritis there was a statistically significant correlation between the serum histidine concentration and the following: Westergren sedimentation rate (r=-0.33, P smaller than 10- minus 9), grip strength (r=0.26, P smaller than 10- minus 9), hematocrit (r=0.23, P smaller than 10- minus 9), duration of morning stiffness (r=-0.14, P=10- minus 5), walking time (r=-0.13, P=10- minus 4), latex titer of rheumatoid factor (r=-0.11, P=0.001), and the duration of arthritis (r=-0.06, P=0.05). There was no statistically significant association between the serum histidine concentration and the duration of rheumatoid arthritis in the 151 patients with disease of 0-10-yr duration (r=0.02, P=0.5), the sex of the patient, or the presence of antinuclear antibody (R=0.007, P=0.9). The serum histidine concentration was less in rheumatoid patients receiving steroids (P=0.00001), gold (P=0.009), and aspirin (P=0.15) than in rheumatoid patients not receiving these drugs. This study indicates that histidine determinations on properly preserved casual serum samples can be helpful in the diagnosis of rheumatoid arthritis and in the evaluation of the activity of the disease. PMID:1079527

  10. Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients

    PubMed Central

    2014-01-01

    Background Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis. Results We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ≥3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis. Conclusions We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis. Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article. PMID:24393543

  11. 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

  12. Neutropenia in rheumatoid arthritis: studies on possible contributing factors.

    PubMed Central

    Bucknall, R C; Davis, P; Bacon, P A; Jones, J V

    1982-01-01

    Twenty-five patients with rheumatoid arthritis (RA) and neutropenia, of whom 19 had a palpable spleen, were compared with 24 patients with uncomplicated RA, and 16 patients with RA and associated splenomegaly without neutropenia. Clinically patients with neutropenia had evidence of a more systemic disease as assessed by prevalence of rheumatoid nodules, weight loss, and recurrent infections. However, there was less evidence of active synovitis than in the other 2 groups. Marrow neutrophil reserve was studied by means of a hydrocortisone stimulation test and was found to be lower in all 3 groups than in normal persons but with most marked depletion in the neutropenic group. Removal of the spleen in some patients with neutropenia resulted in a significant increase in marrow neutrophil reserve. Circulating immune complexes as detected by anticomplementary activity and platelet aggregation tests were detected in 68% of the RA neutropenia group, 31% of the RA splenomegaly group, and 8% of the uncomplicated RA group. Our results show that, assessed both clinically and by the above tests, patients with neutropenia have a greater prevalence of abnormalities which may be directly related to their neutropenia. Patients with splenomegaly alone closely resemble patients with uncomplicated RA. PMID:6979979

  13. ACTH, cortisol and prolactin in active rheumatoid arthritis.

    PubMed

    Zoli, A; Lizzio, M M; Ferlisi, E M; Massafra, V; Mirone, L; Barini, A; Scuderi, F; Bartolozzi, F; Magaró, M

    2002-08-01

    Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1 beta and TNF-alpha circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1 beta and TNF-alpha levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1 beta and TNF-alpha reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients. PMID:12189455

  14. 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

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

    PubMed

    Matuszewska, Agnieszka; Szechi?ski, Jacek

    2014-01-01

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

  16. Citrullination and Carbamylation in the Pathophysiology of Rheumatoid Arthritis

    PubMed Central

    Pruijn, Ger J. M.

    2015-01-01

    The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis (RA) had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalog of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially RA. PMID:25964785

  17. 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

  18. 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.

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

    PubMed

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

    2014-12-01

    Rheumatoid arthritis is a chronic inflammatory disease that causes pain, joint stiffness and swelling leading to impaired hand function and difficulty with daily activities. Wearing therapy gloves has been recommended by occupational therapists as one of the alternative treatment methods for rheumatoid arthritis. This study aims to review the available literature on the effects of wearing therapy gloves on patients' hand function and symptoms as well as to discuss the attributes of gloves that might influence the glove performance. An electronic databases search of MEDLINE, Physiotherapy Evidence Database, Occupational Therapy Systematic Evaluation of Evidence, Wiley Online Library, ScienceDirect and Cochrane Central Register of Controlled Trial was performed. Eight articles met the inclusion criteria, and covered seven clinical trials and one case study. Seven outcome measures were identified from the included studies and were then classified into two categories: hand function and hand symptoms. The hand symptoms such as pain, stiffness and swelling improve substantially when the therapy gloves are used. However, marginal or no improvement in hand function (with the exception of grip strength) linked to the use of therapy gloves is being reported. Further research is needed to quantify the effectiveness of therapy gloves, especially in improvement of hand function and in patients' interest in wearing therapy gloves. Furthermore, future studies should include parameters which might influence therapy gloves' performance, such as duration of trials, interface pressure generated by the gloves on the underlying skin and tissue, glove fit and construction, as well as thermophysiological comfort. PMID:25435925

  20. Immunological evaluation of rheumatoid arthritis patients treated with itolizumab.

    PubMed

    Aira, Lazaro E; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima

    2016-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:26466969

  1. Posterior subtalar joint synoviography and corticosteroid injection in rheumatoid arthritis.

    PubMed Central

    Beaudet, F; Dixon, A S

    1981-01-01

    Ten posterior subtalar joints of 8 patients with rheumatoid arthritis and 12 posterior subtalar joints of 6 cadavers were studied by contrast synoviography. In the rheumatoid group the abnormalities included posterior capsule distension, filling defects caused by hypertrophic synovitis, limited or irregular filling of the anterior recess of the joint in 5 out of 10, and communication with the ankle joint in 3 out of 10. None of the cadaveric joints showed posterior capsule distension or limited or irregular filling of the anterior recess of the joint, but communication with the ankle was present in 2 joints. The joints of the patients were injected with a 1:1 mixture of sodium iothalamate 70% (Conray 420) and triamcinolone hexacetonide (Lederspan) 20 mg/ml. All patients noticed a decrease in and an improvement in walking beginning 24-48 hours after the examination. Quantitative thermography was done immediately before and 1 after injection in 2 patients who showed an improvement in thermographic index. We conclude that hindfoot inflammatory pain arising from the posterior subtalar joint is caused by distension with hypertrophic synovitis which can be difficult to detect clinically. Images PMID:7224686

  2. 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

  3. The 29th September Samoa Islands tsunami: preliminary simulations based on the first focal mechanisms hypotheses and implications of uncertainties in tsunami early warning strategies

    NASA Astrophysics Data System (ADS)

    Tonini, R.; Pagnoni, G.; Armigliato, A.; Tinti, S.

    2009-12-01

    At 6:48 AM local time (17:48 UTC time) a strong earthquake of magnitude Mw=8.0 occurred less than 200 km south of the Samoa Islands (Western Samoa and American Samoa), triggering a tsunami that was detected by several tide gauges located all around the source area. The areas most affected were the south coasts of Western and American Samoa, where almost 200 persons were killed and run-up heights were measured in excess of 5 meters on several locations along the coast and and the tide gauges reached a maximum peak-to-peak height of about 3 meters near Pago-Pago (American Samoa) and 1.5 meters in front of Apia (Western Samoa) The existence of many tide gauge records is important to support the investigation of the source mechanism. The epicenter of this earthquake is located very close to the point where the Tonga trench turns its direction from northward to westward. Here the Pacific plate moves westward beneath the Australia plate, determining a subduction zone along the north-oriented segment of the trench and a transform zone along the west-oriented segment. The epicenter location in this complex tectonic context makes identifying the fault mechanism responsible for the tsunami generation a non-trivial task. The goal of this preliminary work is testing different fault models based on the focal mechanism solution proposed by USGS, CMT and EMSC for this earthquake, through the comparison between the tide gauge records and the synthetic signals provided by the numerical simulations, and possibly suggesting new source solutions trying to reproduce as better as possible the tsunami recordings. The numerical simulations are computed by means of the UBO-TSUFD code, developed and maintained by the Tsunami Research Team of the University of Bologna, Italy. The code solves the linear and non-linear shallow water equations and can compute inundation inland. Furthermore the computational domain can be split in grids of different space resolution in order to have more detailed results in specific areas. The objective difficulties in the identification of the tsunami source, due to the quite complex tectonic setting of the Tonga region in the epicentral area introduce uncertainties in the fault determination that maybe relevant a posteriori, and are a fortiori much more relevant in the real-time data processing practice. This reflects in uncertainties in the possibility of accurately forecasting tsunami propagation and arrival, which poses problems concerning the best strategy to adopt for tsunami early warning.

  4. Effects of rehabilitation for pain relief in patients with rheumatoid arthritis: a systematic review

    PubMed Central

    Park, Youngju; Chang, Moonyoung

    2016-01-01

    [Purpose] The purpose of this study was to find evidence for the effectiveness of rehabilitation for pain relief in patients with rheumatoid arthritis. [Subjects and Methods] A systematic review was conducted of MEDLINE, The Cochrane Central Register of Controlled Trials (CENTRAL), and OVID, for studies published from July 2005 to July 2015. We extracted data regarding patients, intervention, comparison, and outcomes, and assessed the methodological quality of the data. [Results] Nine randomized controlled trials comparing the effects of pain relief in patients with rheumatoid arthritis were found. [Conclusion] Physical therapy and occupational therapy can reduce pain in rheumatoid arthritis. PMID:26957779

  5. Azathioprine-induced accelerated cutaneous and pulmonary nodulosis in a patient with rheumatoid arthritis.

    PubMed

    Kellet, Cristian Vera; Navarrete, Romina Andino; Bombardieri, Sergio Gonzlez; Manriquez, Juan

    2015-01-01

    We report the case of a 42-year-old female with a 5-year history of rheumatoid arthritis treated with Rituximab and Azathioprine. Three months after the initiation of Azathioprine, the patient started with dry cough and noted the rapid development of multiple subcutaneous nodules on her right leg. CT scan of the chest demonstrates pulmonary nodulosis. Skin biopsy was compatible with rheumatoid nodule. A diagnosis of "accelerated cutaneous and pulmonary nodulosis" was considered. Azathioprine was discontinued and Rituximab was restarted. Two months later, most of the subcutaneous nodules had disappeared. This is the second case report of accelerated rheumatoid nodulosis in association with Azathioprine treatment. PMID:26312704

  6. Azathioprine-induced accelerated cutaneous and pulmonary nodulosis in a patient with rheumatoid arthritis*

    PubMed Central

    Kellet, Cristian Vera; Navarrete, Romina Andino; Bombardieri, Sergio Gonzlez; Manriquez, Juan

    2015-01-01

    We report the case of a 42-year-old female with a 5-year history of rheumatoid arthritis treated with Rituximab and Azathioprine. Three months after the initiation of Azathioprine, the patient started with dry cough and noted the rapid development of multiple subcutaneous nodules on her right leg. CT scan of the chest demonstrates pulmonary nodulosis. Skin biopsy was compatible with rheumatoid nodule. A diagnosis of "accelerated cutaneous and pulmonary nodulosis" was considered. Azathioprine was discontinued and Rituximab was restarted. Two months later, most of the subcutaneous nodules had disappeared. This is the second case report of accelerated rheumatoid nodulosis in association with Azathioprine treatment. PMID:26312704

  7. Does food intolerance have any role in the aetiology and management of rheumatoid disease?

    PubMed Central

    Darlington, L G

    1985-01-01

    Dietary therapy for rheumatoid disease has been used by patients for decades. Until recently, orthodox medical opinion has tended to ignore the subject, but interesting results from recent studies suggest that further investigation would now be appropriate. It is possible that food (which consists of many antigens regularly entering the body) could be responsible for altering immunological function. Be that as it may, it would seem logical, particularly in view of recent uncertainty about the efficacy and/or safety of various drugs used in the management of rheumatoid disease, to determine scientifically whether dietary manipulation has any value in the management of these rheumatoid patients. PMID:3904646

  8. Thrombokinetics in patients with rheumatoid arthritis treated with D-penicillamine.

    PubMed Central

    Thomas, D; Gallus, A S; Brooks, P M; Tampi, R; Geddes, R; Hill, W

    1984-01-01

    The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression. PMID:6742902

  9. Efficacy, tolerability and safety of biologic therapy in rheumatoid disease: patient considerations

    PubMed Central

    Horton, Sarah; Buch, Maya H; Emery, Paul

    2010-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease in which chronic inflammation leads to joint destruction and extra-articular complications. Early and effective inhibition of inflammation is critical in order to prevent the progressive joint damage that occurs rapidly after onset of the disease. In the past, treatment for this purpose was limited to conventional disease-modifying antirheumatic drugs (DMARDs), which were often suboptimal. Within the last decade however, the development of biologic therapies, targeted against cytokines and cells involved in the inflammatory process, has revolutionized the management of RA. Disease remission is now an achievable goal in newly diagnosed patients. Since the advent of the first tumor necrosis factor-α inhibitor in 1999, other biologics have proved necessary as individuals respond to varying degrees with different therapies. Several are now available for the treatment of patients with RA that remains active despite DMARD treatment. This article reviews the evidence, over the last decade, of the efficacy and safety of biologic therapies used in this context, and the recent clinical data supporting the use of biologic therapy earlier in the disease process as first-line therapy. PMID:21701623

  10. Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis.

    PubMed

    Kirwan, John R; Clarke, Lynsey; Hunt, Linda P; Perry, Mark G; Straub, Rainer H; Jessop, David S

    2010-04-01

    The morning stiffness and pain of rheumatoid arthritis (RA) is accompanied by a rise in serum interleukin-6 (IL-6) from 2 am to 7 am. Using a formulation that releases prednisone at 2 am (after ingestion at 10 pm), we studied the circadian dynamics of serum IL-6, other cytokines, and cortisol in 9 patients before and after 2 weeks, therapy. Significant improvements occurred in morning stiffness, pain, disease activity, and the acute-phase response. Only IL-6 showed measurable cytokine circadian variation, its high pretreatment peak was abolished, and changes in IL-6 correlated with the changes in morning stiffness. Following treatment, afternoon and evening serum cortisol was reduced, but in the early morning cortisol peak concentration increased. Thus the severity of morning symptoms is related to nocturnal serum IL-6 concentration. The specific timing of the medication, linked to the interaction between IL-6 and the hypothalamic-pituitary-adrenal (HPA) axis, may correct a postulated deficiency in HPA control in RA. PMID:20398018

  11. Septic arthiritis due to Prevotella bivia in a patient with rheumatoid arthritis.

    PubMed

    Alegre-Sancho, J J; Juanola, X; Narvaez, F J; Roig-Escofet, D

    2000-01-01

    Prevotella bivia is a gram-negative anaerobic bacteria traditionally classified in the genus Bacteroides, and usually reported in obstetric and gynecologic infections. To date, there has been only one description of infectious arthritis secondary to this germ. We report the first case of septic arthritis due to Prevotella bivia in a patient with severe, long-lasting rheumatoid arthritis (RA) treated with low doses of corticosteroids. RA is a well-known predisposing factor to septic arthritis, whose causes are multifactorial (general immunosuppression induced by the disease and its therapy, presence of prosthetic joints, etc.). However, infectious arthritis due to anaerobic bacteria is rarely observed. In general, clinical presentation varies widely: insidious onset, apyrexia, and lack of inflammatory signs or systemic disturbance are frequent features. Joint infection is generally secondary to hematogenous spread, the Bacteroides fragilis group being the most commonly isolated pathogens. Early diagnosis and prompt treatment, with drainage and debridement of the affected joint and specific antimicrobial treatment with Metronidazole are essential for a successful outcome. PMID:10875323

  12. MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential.

    PubMed

    Churov, Alexey V; Oleinik, Eugenia K; Knip, Mikael

    2015-11-01

    Rheumatoid arthritis (RA) is a polygenic disease characterized by autoimmunity and systemic inflammation with progressive impairment of joints that results in lifelong disability and increased mortality. Early diagnosis and therapeutic intervention or treatment can prevent severe disease manifestations in patients suffering from RA. The use of appropriate predictive biomarkers may improve the efficiency of RA therapy. The general aim of this review is to highlight the most recent findings on miRNAs expression profiles in RA patients and to discuss their potential as new biomarkers for diagnostic purposes. The current literature demonstrates that a variety of miRNAs is frequently dysregulated in RA patients. To date, the majority of miRNAs have been found to be overexpressed during the natural course of RA. MiR-16, miR-146a/b, miR-150, miR-155, and miR-223 described here were shown to be overexpressed at the systemic level: in both the periphery and RA joints. Circulating peripheral blood miRNAs, especially miR-16, miR-21, miR-24, miR-26a, miR-125a-5p, miR-125b, miR-126-3p, miR-223, and miR-451, which are elevated in the plasma or serum, are considered to be the most promising non-invasive biomarkers for the detection of RA. PMID:26164649

  13. The Role of Power Doppler Ultrasonography as Disease Activity Marker in Rheumatoid Arthritis

    PubMed Central

    Bhasin, Shaloo; Cheung, Peter P.

    2015-01-01

    Structural damage in rheumatoid arthritis (RA) occurs early if inflammation is not treated promptly. Treatment targeted to reduce inflammation, in particular, that of synovial inflammation in the joints (synovitis), has been recommended as standard treat-to-target recommendations by rheumatologists. The goal is to achieve disease remission (i.e., no disease activity). Several accepted remission criteria have not always equated to the complete absence of true inflammation. Over the last decade, musculoskeletal ultrasonography has been demonstrated to detect subclinical synovitis not appreciated by routine clinical or laboratory assessments, with the Power Doppler modality allowing clinicians to more readily appreciate true inflammation. Thus, targeting therapy to Power Doppler activity may provide superior outcomes compared with treating to clinical targets alone, making it an attractive marker of disease activity in RA. However, more validation on its true benefits such as its benefits to patients in regard to patient related outcomes and issues with standardized training in acquisition and interpretation of power Doppler findings are required. PMID:26063952

  14. Development of myeloid sarcoma after long-term methotrexate use for rheumatoid arthritis.

    PubMed

    Sakai, Tomomi; Tamura, Shinobu; Miyoshi, Takashi; Nesumi, Naofumi; Nagai, Kenichi; Oshima, Koichi

    2014-04-01

    Myeloid sarcoma (MS) in the complete absence of bone marrow disease is an extremely rare phenomenon. We report the case of a 78-year-old woman with multiple subcutaneous lung and liver nodules, including mediastinal and peritoneal lymph node swelling, who had been receiving methotrexate (MTX) for 10 years for rheumatoid arthritis (RA). She was initially diagnosed with ALK-negative anaplastic large cell lymphoma. After one course of an anthracycline-containing regimen, pathologic cells were identified as CD68 (Kp-1)-positive with myeloid-lineage tumor cells and abnormal karyotypes with 8q21 and 21q22. Subsequent treatment was changed to acute myelogenous leukemia (AML) induction chemotherapy. Although the lesions were partially reduced in size following treatment for lymphoma, complete response (CR) was obtained only after AML chemotherapy. The patient remained in CR over 3 years after the last chemotherapy. This case may indicate an association between long-term MTX use and MS. An early diagnosis and adequate therapy may be important for improving survival outcomes in MS. This report demonstrates that CD68 staining is important for the differential diagnosis of MS and lymphoma. Careful follow-up is necessary for this patient, who may be the first case of MS after methotrexate use for RA. PMID:24504437

  15. Lessons for the use of non-biologic anchor treatments for rheumatoid arthritis in the era of biologic therapies.

    PubMed

    Jacobs, Johannes W G

    2012-06-01

    Optimizing the use of key non-biologic drugs (MTX, prednisone) may prolong disease control, thereby delaying the need for costly biologic therapies. A number of lessons about the optimal use of therapy emerge from clinical studies. Clinical outcomes with non-biologic treatments, given early in the course of the disease, are as good as with biologic treatments. Combinations of treatments are usually required to achieve rapid and sustained remission. MTX remains an important anchor drug for RA therapy and should be given as soon as the diagnosis is made. As early disease control is important, the dose of MTX should be escalated rapidly to adequate levels. Tolerability of MTX is generally good relative to that of other alternative treatments. MTX (s.c.) may be considered if the response to oral MTX is inadequate or MTX is poorly tolerated. In addition to suppressing signs and symptoms of RA, glucocorticoids appear to have disease-modifying effects, at least in early RA. The disease-modifying effects of glucocorticoids probably persist after discontinuation of therapy. The risk of adverse effects of low-dose glucocorticoids is often overestimated. Administration of low-dose glucocorticoids in accordance with physiological circadian rhythms may bring efficacy and safety benefits. As a case in point, the CAMERA (Computer Assisted Management in Early Rheumatoid Arthritis) II study applied these lessons and has clearly shown the benefits of optimizing MTX and prednisone therapy. PMID:22685273

  16. Population pharmacokinetics and Monte Carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units.

    PubMed

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

    2015-01-01

    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 μg/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 μg/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

  17. Determining Thermal Inactivation of Escherichia coli O157:H7 in Fresh Compost by Simulating Early Phases of the Composting Process ▿

    PubMed Central

    Singh, Randhir; Kim, Jinkyung; Shepherd, Marion W.; Luo, Feng; Jiang, Xiuping

    2011-01-01

    A three-strain mixture of Escherichia coli O157:H7 was inoculated into fresh dairy compost (ca. 107 CFU/g) with 40 or 50% moisture and was placed in an environmental chamber (ca. 70% humidity) that was programmed to ramp from room temperature to selected composting temperatures in 2 and 5 days to simulate the early composting phase. The surviving E. coli O157:H7 population was analyzed by direct plating and enrichment. Optimal and suboptimal compost mixes, with carbon/nitrogen (C/N) ratios of 25:1 and 16:1, respectively, were compared in this study. In the optimal compost mix, E. coli O157:H7 survived for 72, 48, and 24 h in compost with 40% moisture and for 72, 24, and 24 h with 50% moisture at 50, 55, and 60°C, respectively, following 2 days of come-up time (rate of heating up). However, in the suboptimal compost mix, the pathogen survived for 288, 72, and 48 h in compost with 40% moisture and for 240, 72, 24 h in compost with 50% moisture at the same temperatures, respectively. Pathogen survival was longer, with 5 days of come-up time compared with 2 days of come-up. Overall, E. coli O157:H7 was inactivated faster in the compost with 50% moisture than in the compost with 40% at 55 and 60°C. Both moisture and come-up time were significant factors affecting Weibull model parameters. Our results suggest that slow come-up time at the beginning of composting can extend pathogen survival during composting. Additionally, both the C/N ratio and the initial moisture level in the compost mix affect the rate of pathogen inactivation as well. PMID:21498743

  18. 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 2.944.37). Smoking >10 pack-years, alcohol intake 510 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

  19. High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor α inhibitors in rheumatoid arthritis

    PubMed Central

    Bobbio‐Pallavicini, Francesca; Caporali, Roberto; Alpini, Claudia; Avalle, Stefano; Epis, Oscar M; Klersy, Catherine; Montecucco, Carlomaurizio

    2007-01-01

    Objective To investigate whether rheumatoid factor isotypes and anti‐cyclic citrullinated peptide (anti‐CCP) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor α (TNFα) inhibitors. Methods The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease‐modifying antirheumatic drugs. Patients were treated with infliximab (n = 63), etanercept (n = 35) or adalimumab (n = 34). All patients completed 1 year of follow‐up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM, IgA and IgG rheumatoid factors and anti‐CCP antibodies were assessed by ELISA both before anti‐TNFα treatment and 1 year later. Results The DAS response was reached in 66% of evaluable patients (61% infliximab, 65% etanercept and 76% adalimumab; p = 0.354). A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year. The frequency of positive tests for the different antibodies did not differ between responders and non‐responders at baseline; however, significantly higher IgA rheumatoid factor levels were reported by the non‐responder group (130.4 U/ml (interquartile range 13.8–276.7) v 24.8 U/ml (10.2–90.8); p = 0.003). A significant decrease (p<0.001) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment, whereas anti‐CCP antibody levels were not significantly affected. Conclusions According to the clinical response, anti‐TNFα agents seem to reduce IgM, IgG and IgA rheumatoid factor levels. More interestingly, high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFα inhibitors. PMID:17079248

  20. Craniomandibular disorders in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A clinical study.

    PubMed

    Knnen, M; Wenneberg, B; Kallenberg, A

    1992-10-01

    Sixty-one subjects with rheumatoid arthritis, 61 with psoriatic arthritis, 61 with ankylosing spondylitis, and 61 healthy controls were examined with regard to subjective symptoms and clinical signs of craniomandibular disorders (CMD). The frequencies of most subjective and clinical variables were higher in all three disease groups than in the control group. Subjects with rheumatoid arthritis and psoriatic arthritis showed more frequent and severe signs and symptoms than subjects with ankylosing spondylitis. It is concluded that subjective symptoms and clinical signs of CMD are common in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and are mainly caused by the respective general joint disease. None of the signs and symptoms is pathognomonic for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. PMID:1441932