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Sample records for simulating early rheumatoid

  1. [Early rheumatoid arthritis].

    PubMed

    Babić-Naglić, Durdica

    2008-01-01

    Rheumatoid arthritis (RA) is chronic joint disease which if untreated leads to permanent structural damage and disability. Early diagnosis and therapy are the main requests for good clinical practice. Early diagnosis tools include specific clinical assesment, serological, immunogenetic and radiological evaluation. Disease activity score is cornerstone in clinical assesment, rheumatoid factor and anti-cyclic citrullinated peptide antibodies (anti-CCP) are very specific serological parameters. The shared epitope containing HLA-DRB1* alleles represent the most significant genetic risk for RA. Magnetic resonance and ultrasound imaging are very sensitive methods in early phase of disease. PMID:19024271

  2. New autoantibodies in early rheumatoid arthritis

    PubMed Central

    2013-01-01

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

  3. 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

  4. Treatment of early rheumatoid arthritis with rifampicin.

    PubMed Central

    Cox, N L; Prowse, M V; Maddison, M C; Maddison, P J

    1992-01-01

    Following a report that seven of 20 patients with rheumatoid arthritis (RA) had come into clinical and laboratory remission after treatment with rifampicin, and that six of the seven responders had a disease duration of less than three years, 21 patients with classical or definite RA of recent onset were treated with 600 mg rifampicin and 300 mg isoniazid daily for six months. Fourteen of 21 patients completed six months' treatment, but there was no significant improvement in the mean values of the clinical and laboratory parameters measured. The improvement suggested by preliminary studies in patients with early RA is not seen in this larger group. In patients with a disease duration of less than 18 months, however, there was a significant decrease in the erythrocyte sedimentation rate and the serum concentrations of C reactive protein after treatment for six months, although there was no significant clinical improvement. Future studies of this drug in patients with RA should concentrate on this group. PMID:1540033

  5. Generalised bone loss in patients with early rheumatoid arthritis.

    PubMed

    Gough, A K; Lilley, J; Eyre, S; Holder, R L; Emery, P

    1994-07-01

    Generalised osteoporosis is a feature of established rheumatoid arthritis but whether this is a consequence of treatment, immobility, or disease activity has been unclear. We estimated bone mineral density by dual energy x-ray absorptiometry on 148 patients with early rheumatoid arthritis before treatment with corticosteroids or disease-modifying drugs and 730 normal controls. Scans were done at 12-month intervals in patients and at 0 and 12 months on 50 of the controls matched for menopausal status. At presentation, bone mineral density of patients did not differ from controls. However, patients with disease for less than 6 months had significantly higher spinal bone mineral density than those of longer duration. Over the next 12 months, bone mineral density loss was greater in patients with rheumatoid arthritis compared with controls; significantly so for early disease (eg, -2.4 [0.8] vs -0.6 [0.4] g/cm2, p < 0.05 in the spine and -4.3 [0.8] vs -0.4 [0.5] g/cm2, p < 0.001 in the trochanter). For the lumbar spine, only disease activity was significantly associated with this bone mineral density loss. For patients with active disease over 2 years, mean bone mineral density loss at each site was between 5.5 and 10% (p < 0.01 compared to patients with inactive disease). Suppression of disease activity stabilised this bone loss. In patients with rheumatoid arthritis significant amounts of generalised skeletal bone were lost early in the disease and the loss was associated with disease activity. These findings have implications for the management of patients with rheumatoid arthritis and possibly other inflammatory diseases. PMID:7912297

  6. Treatment Strategies in Early Rheumatoid Arthritis and Prevention of Rheumatoid Arthritis

    PubMed Central

    Demoruelle, M. Kristen

    2013-01-01

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

  7. 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

  8. Evidence for early disease-modifying drugs in rheumatoid arthritis

    PubMed Central

    Scott, David L

    2004-01-01

    Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated. PMID:14979927

  9. Study: Smoking Hikes Chances of Early Death for Rheumatoid Arthritis Patients

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_158127.html Study: Smoking Hikes Chances of Early Death for Rheumatoid Arthritis ... 4, 2016 MONDAY, April 4, 2016 (HealthDay News) -- Smoking increases the chances of early death in people ...

  10. Early-onset pauciarticular juvenile rheumatoid arthritis. A histopathologic study.

    PubMed

    Merriam, J C; Chylack, L T; Albert, D M

    1983-07-01

    A young girl with early-onset pauciarticular juvenile rheumatoid arthritis suffered from recurrent severe bilateral iridocyclitis. Despite intensive medical therapy, she gradually lost all useful vision and ultimately required bilateral enucleation at the age of 10 years for control of pain and photophobia. Histopathologic study of the eyes revealed in the iris and ciliary body a dense inflammatory infiltrate composed principally of plasma cells, as well as angle closure, a dense cyclitic membrane, retinal detachment, cystoid macula, and optic atrophy. Immunoperoxidase stains showed little immunoglobulin within or around the plasma cells within the ciliary body, although strong reactions for IgG and kappa- and lambda-light chains were seen in other parts of the eyes. PMID:6347150

  11. 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

  12. Combination DMARD therapy including corticosteroids in early rheumatoid arthritis.

    PubMed

    Möttönen, T T; Hannonen, P J; Boers, M

    1999-01-01

    A number of reports indicating the growing acceptance of simultaneous therapy with multiple disease-modifying anti-rheumatic drugs (DMARDs), as well as the use of more aggressive treatment measures in the early phases of disease to combat rheumatoid arthritis (RA), have appeared during the last decade. However, only a few randomized controlled clinical trials have been conducted on the use of DMARD combinations in early RA. We review these trials in this article. In two separate one-year studies combination therapy with sulphasalazine (SSZ) and methotrexate (MTX) seemed to offer no benefits compared to either drug used as monotherapy. On the other hand, the DMARD combinations so far proven to be superior to single DMARDs have initially also included a corticosteroid component. In the COBRA study (Combinatietherapie Bij Reumatoide Artritis) the combination of SSZ (2 gm/day), MTX (7.5 mg/week for 40 weeks), and prednisolone (Prd) (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day and stopped after 28 weeks) compared to SSZ alone (2 gm/day) resulted in significantly better clinical outcomes at week 28. Although the difference in clinical response between the treatment arms was lost at week 58, the progression of joint damage remained statistically significantly slower at week 80 in the patients initially assigned to the combination therapy. Furthermore, in the FIN-RACo trial (Finnish Rheumatoid Arthritis Combination Therapy Trial), therapy using a "tailored-steps" strategy with SSZ (1-2 gm/day), MTX (7.5-1.5 mg/week), hydroxychloroquine (300 mg/day), and Prd (up to 10 mg/day) yielded a significantly increased remission rate and less peripheral joint damage at two years than the single DMARD treatment strategy (initially SSZ 2 gm/day), with or without Prd. Adverse effects in both study arms were comparable. Two additional preliminary reports (in abstract form) suggest that intensive local therapy in the form of intra-articular injections added to single or combination therapy improves both local and systemic disease control, with increased remissions and less damage. Although still preliminary, these results should encourage the rheumatological community to treat selected RA patients with DMARD combinations from the very start. PMID:10589359

  13. Could Early Rheumatoid Arthritis Resolve After Periodontitis Treatment Only?

    PubMed Central

    Salemi, Simonetta; Biondo, Michela I.; Fiorentino, Chiara; Argento, Giuseppe; Paolantonio, Michele; Di Murro, Carlo; Malagnino, Vito A.; Canzoni, Marco; Diamanti, Andrea Picchianti; D’Amelio, Raffaele

    2014-01-01

    Abstract Rheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge. A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy. It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management. PMID:25501069

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

    PubMed Central

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

    1996-01-01

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

  15. 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

  16. 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

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

    PubMed

    Herasymenko, S I; Huzhevs'kyĭ, 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

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

    PubMed Central

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

    2013-01-01

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

  19. Early intervention in the treatment of rheumatoid arthritis: focus on tocilizumab

    PubMed Central

    Yilmaz, Sedat; Simsek, Ismail

    2013-01-01

    Tocilizumab is a fully humanized monoclonal antibody against interleukin-6 receptors that was approved for the treatment of patients with rheumatoid arthritis (RA). Several lines of evidence, obtained both from conventional disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors, have supported the concept of “window of opportunity” as showing that these therapies consistently work better in early disease as compared to established RA. This review addresses the question of whether a window of opportunity gained with conventional DMARDs and TNF inhibitors can also be achieved with tocilizumab. To this end, data regarding the use of tocilizumab in early RA patients are summarized. Currently available data suggest that the earlier the treatment with tocilizumab, the better the clinical outcome can be, which may have implications for various aspects of RA treatment strategies. PMID:24179334

  20. 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

  1. Prognostic factors of 10-year radiographic outcome in early rheumatoid arthritis: a prospective study

    PubMed Central

    Courvoisier, Natacha; Dougados, Maxime; Cantagrel, Alain; Goupille, Philippe; Meyer, Olivier; Sibilia, Jean; Daures, Jean Pierre; Combe, Bernard

    2008-01-01

    Introduction The objectives of this study were to determine the predictive factors of long-term radiographic outcome of rheumatoid arthritis (RA) and to describe the relationship between joint damage and disability over the course of the disease. Methods A cohort of 191 patients with early RA referred from primary care physicians were prospectively followed for 10 years. To determine the predictive factors of radiographic outcome, univariate analysis of the relationship between baseline values and outcome measures was undertaken using a chi-squared or Fisher's exact test. Stepwise multiple logistic regression was also performed to select independent prognostic factors. Results From data available for 112 patients, univariate analysis revealed a total Sharp score at 10 years that was significantly correlated with erythrocyte sedimentation rate (ESR), presence and level of IgA rheumatoid factor, presence of an anti-citrullinated protein antibody (ACPA), serum level of matrix metalloproteinase-3 and radiographic score at baseline. Logistic regression identified the baseline erosion score to be the most important baseline parameter as an independent prognostic factor of total radiographic score at 10 years (odds ratio = 5.64; 95% confidence interval = 1.78 to 17.86). After excluding radiographic scores from the entry parameters, the presence of ACPA and ESR were also predictive of the final total Sharp score. The Health Assessment Questionnaire (HAQ) score was strongly correlated with disease activity parameters, such as disease activity score and pain, at baseline and at three, five and 10 years. No correlation was found between total radiographic Sharp score and HAQ score throughout the study. Conclusions In this prospective study, baseline radiographic score, ESR and ACPA were the best predictive factors of 10-year radiographic outcome in early RA. HAQ disability was associated with disease activity throughout the 10-year follow-up but not with joint damage. This discrepancy with previous reports may be due in part to the early start of therapy with disease-modifying anti-rheumatic drugs. PMID:18771585

  2. [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

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

    PubMed Central

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

    2014-01-01

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

  4. Determination of Specificity and Sensitivity of Anti-RA 33 in Diagnosis of Early Rheumatoid Arthritis

    PubMed Central

    Lashkari, Mahin; Noori, Akram; Hajiimanouchehri, Fatemeh; Oveisi, Sonia; Kazemifar, Amir Mohammad

    2014-01-01

    Background: Rheumatoid arthritis is a chronic inflammatory disease with uncertain etiology. It is characterized by symmetric polyarthritis in peripheral joints. Its diagnosis is based on clinical findings and serologic tests. However, its diagnosis is rarely conclusive in early course of the disease. So, its early diagnosis could be difficult. The present study was designed to evaluate the role of anti -RA33; an auto-antibody against RA33 in early diagnosis of the disease. Materials and Methods: forty three patients with RA who had been visited in a rheumatology clinic were randomly selected. Their disease has been diagnosed by a rheumatologist. They served as the case group. 55 persons were also chosen from healthy individuals who had attended in other clinic. They served as control. Their age and sex were matched with the case group. Anti-RA33 and RF titers were measured in their blood sample using standard methods. Findings: RF and anti-RA33 titers had significant correlation in the case group (p=0.015). Anti -RA33 test had 98% sensitivity, 20% specificity, 50% positive predictive value, and 90% negative predictive value. Conclusion: Anti -RA33 could have diagnostic and prognostic importance in diagnosis and evaluation of patients with RA, and its differentiation from other small joint disorders, particularly when the other serologic tests are negative. PMID:24999142

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Manrique-Arija, Sara; Ureña, Inmaculada; Valdivielso, Pedro; Rioja, José; Jiménez-Núñez, Francisco G; Irigoyen, María V; Fernández-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 <1 year, 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 6 months of treatment (visit 2). The main outcomes were homeostatic model assessment of IR (HOMA-IR) and β-cell function (HOMA-β) 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-β, 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-β, 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 6 months after treatment. However, symptom duration and fat mass appear to be related. PMID:26526677

  7. A systematic review of infliximab in the treatment of early rheumatoid arthritis

    PubMed Central

    Du Pan, Sophie Martin; Gabay, Cem; Finckh, Axel

    2007-01-01

    Background Several health authorities have recently revised the indication of infliximab (IFX) to include the treatment of early rheumatoid arthritis (RA). The aim of this systematic review of the literature was to appraise the efficacy, safety, and cost-effectiveness of early therapy with IFX. Methods We identified published clinical trials from 1966 to May 2006. We included randomized clinical trials (RCTs) in RA with disease duration of less than 3 years comparing the treatment of methotrexate-IFX (MTX-IFX) with methotrexate-placebo (MTX-placebo). Results A total of 8 studies met inclusion criteria. Three studies reported redundant data regarding the vdH Sharp Score. Out of the 5 remaining studies, 4 analyzed structural joint destruction (vdH Sharp Score) and demonstrated a significant reduction in radiographic damage progression in favor of the combination of MTX-IFX compared with MTX-placebo (−4.1 vdH Sharp Score units (95% CI: 3.5; 4.6). Three studies also displayed a benefit of MTX-IFX on functional outcomes of RA (HAQ score) and disease activity measures (DAS, ACR response criteria), although less markedly. Conclusions Although data might be skewed because of only 2 existing large studies with concordant data, results from RCTs demonstrate improved efficacy of the combination MTX-IFX compared with MTX-placebo in early RA. However, many early RA patients probably do not require the addition of IFX to achieve a satisfying clinical and radiological course. So far, no evidence has established the superiority of MTX-IFX over MTX-prednisone or other combinations of traditional disease-modifying anti-rheumatic agents. PMID:18473014

  8. [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

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

    PubMed Central

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

    2013-01-01

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

  10. A population model of early rheumatoid arthritis disease activity during treatment with methotrexate, sulfasalazine and hydroxychloroquine

    PubMed Central

    Wojciechowski, Jessica; Wiese, Michael D; Proudman, Susanna M; Foster, David J R; Upton, Richard N

    2015-01-01

    Aims To develop a population model describing the disease activity (DAS28) time course in patients with early rheumatoid arthritis (RA) treated with triple disease-modifying anti-rheumatic drug (DMARD) therapy (methotrexate, sulfasalazine and hydroxychloroquine). Methods DAS28 was obtained in 263 patients with early RA from initiation of therapy until 60 weeks. Using nonmem®, base models (DAS28 vs. time) and covariate influences were investigated for the population. Results The best model was an exponential model of DAS28 vs. time that was additive to baseline DAS28, with covariance between parameters, and a combined residual error model. Age and patient smoking history were covariates significantly affecting response to therapy. Population estimates were baseline DAS28 (5.7), extent of change in DAS28 (−2.8) and the half-life of disease activity (6.2 weeks; time to steady disease state achieved within approximately 30 weeks). Older individuals exhibited more severe baseline DAS28, described by a power function centred around 57 years (baseline DAS28 for 40- and 70-year-old patients were 5.4 vs. 5.8, respectively) and current smokers took longer to achieve a steady disease state (approximately 50 weeks). There was considerable within-patient random variability in DAS28 over time (empirical 90% CI for DAS28 in a population typical patient at 60 weeks: 1.8, 4.2 with median value of 2.8). Conclusions This is the first report of a disease activity model for early RA treated with triple DMARD therapy. Smoking and age were identified as covariates. PMID:25394211

  11. Why are Dutch rheumatologists reluctant to use the COBRA treatment strategy in early rheumatoid arthritis?

    PubMed Central

    van Tuyl, Lilian H D; Plass, Anne Marie C; Lems, Willem F; Voskuyl, Alexandre E; Dijkmans, Ben A C; Boers, Maarten

    2007-01-01

    Background The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow‐up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. Objective To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. Methods A short structured questionnaire based on social–psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). Results The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high‐dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. Conclusion The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient‐related consequences of the therapy. PMID:17392349

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. Characterization of histopathology and gene-expression profiles of synovitis in early rheumatoid arthritis using targeted biopsy specimens

    PubMed Central

    Tsubaki, Takahito; Arita, Norimasa; Kawakami, Takuma; Shiratsuchi, Takayuki; Yamamoto, Haruyasu; Takubo, Nobuo; Yamada, Kazuhito; Nakata, Sanpei; Yamamoto, Sumiki; Nose, Masato

    2005-01-01

    The disease category of early rheumatoid arthritis (RA) has been limited with respect to clinical criteria. Pathological manifestations of synovitis in patients whose disease is clinically classified as early RA seem to be heterogeneous, with regular variations. To clarify the relation between the molecular and histopathological features of the synovitis, we analyzed gene-expression profiles in the synovial lining tissues to correlate them with histopathological features. Synovial tissues were obtained from knee joints of 12 patients with early RA by targeted biopsy under arthroscopy. Surgical specimens of long-standing RA (from four patients) were examined as positive controls. Each histopathological parameter characteristic of rheumatoid synovitis in synovial tissues was scored under light microscopy. Total RNAs from synovial lining tissues were obtained from the specimens selected by laser capture microdissection and the mRNAs were amplified by bacteriophage T7 RNA polymerase. Their cDNAs were analyzed in a cDNA microarray with 23,040 cDNAs, and the levels of gene expression in multilayered lining tissues, compared with those of normal-like lining tissues in specimens from the same person, were determined to estimate gene-expression profiles characteristic of the synovial proliferative lesions in each case. Based on cluster analysis of all cases, gene-expression profiles in the lesions in early RA fell into two groups. The groups had different expression levels of genes critical for proliferative inflammation, including those encoding cytokines, adhesion molecules, and extracellular matrices. One group resembled synovitis in long-standing RA and had high scores for some histopathological features – involving accumulations of lymphocytes and plasma cells – but not for other features. Possible differences in the histopathogenesis and prognosis of synovitis between the two groups are discussed in relation to the candidate genes and histopathology. PMID:15987484

  15. 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

  16. Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis

    PubMed Central

    Yeo, L; Adlard, N; Juarez, M; Smallie, T; Snow, M; Buckley, C D; Raza, K; Filer, A; Scheel-Toellner, D

    2016-01-01

    Background and objectives For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Methods Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. Results A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68+ macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis Conclusions Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA. PMID:25858640

  17. 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 ...

  18. Clinical practice decision tree for the choice of the first disease modifying antirheumatic drug for very early rheumatoid arthritis: a 2004 proposal of the French Society of Rheumatology

    PubMed Central

    Loët, X Le; Berthelot, J M; Cantagrel, A; Combe, B; De Bandt, M; Fautrel, B; Flipo, R M; Lioté, F; Maillefert, J F; Meyer, O; Saraux, A; Wendling, D; Guillemin, F

    2006-01-01

    Objective To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months' duration. Methods Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) inventory of the information available to guide DMARD choice; (3) selection of the most pertinent information by 12 experts using a Delphi method; and (4) choice of DMARDs in 12 clinical situations defined by items selected in step 3 (28 joint disease activity score (DAS 28): ⩽3.2; >3.2 and ⩽5.1; >5.1; rheumatoid factor status (positive/negative); structural damage (with/without)—that is, 3×2×2). Thus, multiplied by all the possible treatment pairs, 180 scenarios were obtained and presented to 36 experts, who ranked treatment choices according to the Thurstone pairwise method. Results Among the 77 items identified, 41 were selected as pertinent to guide the DMARD choice. They were reorganised into five domains: rheumatoid arthritis activity, factors predictive of structural damage; patient characteristics; DMARD characteristics; physician characteristics. In the majority of situations, the two top ranking DMARD choices were methotrexate and leflunomide. Etanercept was an alternative for these agents when high disease activity was associated with poor structural prognosis and rheumatoid factor positivity. Conclusions Starting with simple scenarios and using the pairwise method, a clinical decision tree could be devised for the choice of the first DMARD to treat very early rheumatoid arthritis. PMID:15994280

  19. Excretion of pyridinium crosslinks correlates with disease activity and appendicular bone loss in early rheumatoid arthritis.

    PubMed Central

    Gough, A K; Peel, N F; Eastell, R; Holder, R L; Lilley, J; Emery, P

    1994-01-01

    OBJECTIVE--To establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (RA), are useful markers of bone loss in this disease. METHODS--Eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. Bone mineral density (BMD), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. RESULTS--The rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p < 0.001). Pyridinoline excretion was associated with increased disease activity (ESR/CRP) but not disability (HAQ score/Functional Grade), and correlated with BMD loss at the femoral neck (p < 0.01). CONCLUSION--The excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with RA. PMID:8311548

  20. Arthritis instantaneously causes collagen type I and type II degradation in patients with early rheumatoid arthritis: a longitudinal analysis

    PubMed Central

    Landewé, R B M; Geusens, P; van der Heijde, D M F M; Boers, M; van der Linden, S J; Garnero, P

    2006-01-01

    Background Markers of collagen type I (CTX‐1) and type II (CTX‐II) degradation, reflecting bone and cartilage breakdown, appear to predict long term radiographic progression in chronic persistent arthritis. Objective To analyse longitudinally whether changes in arthritis severity are linked to immediate changes in the level of CTX‐I and CTX‐II degradation. Methods CTX‐I and CTX‐II were measured in urine samples from 105 patients with early rheumatoid arthritis who had participated in the COBRA trial at baseline and at 3, 6, 9, and 12 months after the start of treatment. The course of the biomarkers over time was compared with the course of ESR, swollen and tender joint counts, and 28 joint disease activity score (DAS28), measured at the same time points, with adjustment for rheumatoid factor, treatment, and baseline radiographic damage, by generalised estimating equations (GEE) with first order autoregression. Results GEE showed that CTX‐I was longitudinally associated with DAS28, but not with ESR, swollen joint count, or tender joint count. CTX‐II, however, was longitudinally associated with ESR, swollen joint count and DAS28, but not with tender joint count. The longitudinal association implies that an increase in the extent of arthritis is immediately followed by an increase in collagen type II degradation, and to a lesser extent collagen type I degradation. Conclusions Cartilage degradation as measured by CTX‐II and to a lesser extent bone degradation as measured by CTX‐I closely follows indices of arthritis. Clinically perceptible arthritis is responsible for immediate damage, which will become visible on plain x rays only much later. PMID:16126801

  1. 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

  2. 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 ...

  3. The Role of Genetic Variants in CRP in Radiographic Severity in African Americans with Early and Established Rheumatoid Arthritis

    PubMed Central

    Danila, Maria I.; Westfall, Andrew O.; Raman, Krishnan; Chen, Lang; Reynolds, Richard J.; Hughes, Laura B.; Arnett, Donna K.; McGwin, Gerald; Szalai, Alexander J.; van der Heijde, Désirée M.; Conn, Doyt; Callahan, Leigh F.; Moreland, Larry W.; Bridges, S. Louis

    2015-01-01

    This study investigates the association of CRP 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 in 294 individuals from CLEAR 1 [median (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 (IRR) 0.37 (95% 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 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

  4. 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

  5. Rheumatoid Arthritis

    MedlinePlus

    ... with rheumatoid arthritis also experience issues related to depression, anxiety feelings of helplessness low self-esteem. Rheumatoid arthritis can affect virtually every area of a person’s life from work life to family life. It can also interfere with the joys ...

  6. Neo-Epitopes—Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis

    PubMed Central

    Karsdal, Morten Asser; Gerlag, Daniëlle M.; Tak, Paul Peter; Bay-Jensen, Anne Christine

    2016-01-01

    Objective Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis. Methods Ninety-two early arthritis patients (arthritis duration<1 year, DMARD naïve) were enrolled. Patients either fulfilled the ACR/EULAR2010 criteria for RA (n = 60) or had unclassified arthritis (UA) (n = 32). Patients fulfilling the RA criteria after 2 years follow-up were classified into non-erosive (n = 25), or erosive disease (n = 13). Concentrations of the biomarkers: C1M, C2M, C3M, VICM and CRPM were measured in baseline serum. Results C1M, C3M and CRPM were able to discriminate between the UA and RA baseline diagnosis in 92 patients with an AUROC of 0.64 (95%CI 0.517 to 0.762), 0.73 (95%CI 0.622 to 0.838) and 0.68 (95%CI 0.570 to 0.795). C2M showed a potential for discrimination between non-erosive and erosive disease in 38 patients with an AUROC of 0.75 (95%CI 0.597 to 0.910). All of the applied biomarkers correlated with one or more of the disease activity parameters: DAS28, ESR, CRP, SJC66, TJC68 and/or HAQ. Conclusion This is the first study evaluating the applied biomarkers at this early stage of arthritis. C1M, C3M, CRPM might be the best diagnostic marker, whereas high levels of C2M indicated progression of disease at follow-up in early RA patients. PMID:27019199

  7. Recurrence of cervical spine instability in rheumatoid arthritis following previous fusion: can disease progression be prevented by early surgery?

    PubMed

    Agarwal, A K; Peppelman, W C; Kraus, D R; Pollock, B H; Stolzer, B L; Eisenbeis, C H; Donaldson, W F

    1992-09-01

    In a retrospective study, 110 patients with rheumatoid arthritis who had cervical spine fusion were evaluated for recurrence of cervical spine instability and resultant need for further surgery. Recurrence of cervical instability was correlated with initial radiographic abnormality, primary surgical procedure and interval between the 2 surgeries. There were 55 patients who had atlantoaxial subluxation (AAS) and required C1-C2 fusion as primary surgery. Three of these patients (5.5%) developed subaxial subluxation (SAS) and had a second procedure after a mean interval of 9 years. Twenty-two patients had AAS with superior migration of the odontoid (AAS-SMO) and had initial surgery of occiput-C3 fusion. Eight of these patients (36%) developed SAS and had a second surgery after a mean interval of 2.6 years. Of the 19 patients with primary radiographic deformity of SAS, one required further surgery for subluxation of an adjacent superior vertebra after a period of 6 years. Fourteen patients had combined deformity of AAS-SMO-SAS, and one required further surgery for SAS after an interval of 22 months. Recurrence of cervical instability following a previous fusion occurred in 15% of these 110 patients. It was seen in 5.5% of patients with initial deformity of AAS vs 36% of patients with AAS-SMO. No patients with C1-C2 fusion for AAS progressed to develop superior migration of the odontoid. We conclude that early C1-C2 fusion for AAS before development of SMO decreases the risk of further progression of cervical spine instability. The pattern of progression of cervical spine involvement, as discussed in the literature, is reviewed. PMID:1433002

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2009-01-01

    Introduction Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort. Methods In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients. Results All markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA. Conclusions Markers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA. PMID:19627580

  10. Reduction in Serum Uric Acid May Be Related to Methotrexate Efficacy in Early Rheumatoid Arthritis: Data from the Canadian Early Arthritis Cohort (CATCH)

    PubMed Central

    Lee, Jason J.; Bykerk, Vivian P.; Dresser, George K.; Boire, Gilles; Haraoui, Boulos; Hitchon, Carol; Thorne, Carter; Tin, Diane; Jamal, Shahin; Keystone, Edward C.; Pope, Janet E.

    2016-01-01

    OBJECTIVES The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA). METHODS Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded. RESULTS In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 µmol/L and 273 µmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 µmol/L and a follow-up level of 282 µmol/L (P = 0.448); mean change in UA with methotrexate was −26.8 µmol/L vs. 2.3 µmol/L in the no methotrexate group (P = 0.042). Methotrexate users with a decrease in UA had a disease activity score of 2.37 for 28 joints when compared with the controls (3.26) at 18 months (P = 0.042). Methotrexate users with decreased UA had a lower swollen joint count (SJC) of 0.9 at 18 months, whereas methotrexate users without lowering of UA had an SJC of 4.5 (P = 0.035). Other analyses were not significant. CONCLUSIONS Methotrexate response is associated with lowering of serum UA in ERA compared to nonusers. This may be due to changes in adenosine levels. Methotrexate response is associated with lower UA and fewer swollen joints compared to nonresponders. PMID:27081318

  11. Multifactorial intervention to prevent cardiovascular disease in patients with early rheumatoid arthritis: protocol for a multicentre randomised controlled trial

    PubMed Central

    Svensson, Annemarie Lyng; Løgstrup, Brian Bridal; Giraldi, Annamaria; Graugaard, Christian; Blegvad, Jesper; Thygesen, Tina; Sheetal, Ekta; Svendsen, Lone; Emmertsen, Henrik

    2016-01-01

    Introduction Cardiovascular morbidity is a major burden in patients with rheumatoid arthritis (RA). In this study, we compare the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment of modifiable risk factors for cardiovascular disease (CVD) in patients with early RA fulfilling the 2010 American College of Rheumatology European League Against Rheumatism (ACR/EULAR) criteria. Methods and analysis The study is a prospective, randomised, open label trial with blinded end point assessment and balanced randomisation (1:1) conducted in 10 outpatient clinics in Denmark. The primary end point after 5 years of follow-up is a composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularisation. Secondary outcomes are: the proportion of patients achieving low-density lipoprotein cholesterol <2.5 mmol/L, glycated haemoglobin <48 mmol/mol, blood pressure <140/90 mm  Hg for patients without diabetes and <130/80 mm Hg for patients with diabetes and normoalbuminuria (urinary albumin creatinine ratio <30 mg/g) after 1 year of follow-up and the proportion of patients in each treatment group achieving low RA disease activity after 1 year, defined as a disease activity score C-reactive protein (DAS28-CRP) <3.2 and a DAS28-CRP score <2.6 after 12, 24 and 60 months. Furthermore, all hospitalisations for acute and elective reasons will be adjudicated by the event committee after 12, 24 and 60 months. Three hundred treatment-naive patients with early RA will be randomly assigned (1:1) to receive either conventional treatment administered and monitored by their general practitioner according to national guidelines (control group) or a stepwise implementation administered and monitored in a quarterly rheumatological nurse-administered set-up of behaviour modification and pharmacological therapy targeting (1) hyperlipidaemia, (2) hypertension, (3) hyperglycaemia and (4) microalbuminuria (intervention group). Ethics and dissemination This protocol is approved by the local ethics committee (DK-S-2014007) and The Danish Health and Medicines Authority. Dissemination will occur through presentations at National and International conferences and publications in international peer-reviewed journals. Trial registration number NCT02246257 PMID:27098820

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

    PubMed Central

    2013-01-01

    Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to CMV exposure. Conclusions A profile of T-cell immunity associated with CMV exposure influences the clinical response to DMARD therapy in patients with early RA. Because CMV latency is associated with greater joint destruction, our findings suggest that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly long-term outcomes of RA. PMID:24267267

  13. Profile and course of early rheumatoid arthritis in Morocco: a two-year follow-up study

    PubMed Central

    2011-01-01

    Background This study aimed to establish the profile and the evolution of an early Rheumatoid arthritis (RA) cohort in the Moroccan population and also to search possible predictor factors of structural progression. Methods Patients with early RA (< 12 months) were enrolled in a 2-year follow-up study. Clinical, biological, immunogenetic, and radiographical data were analyzed at study entry and at 24 months. Presence of radiographic progression was retained when the total score was superior to the smallest detectable difference (SDD) calculated to be 5.4 according the Sharp/van der Heijde (SVDH) method. Results Fifty one patients (88.8% women, mean age of 46.9 [ 24-72 ] ± 10.8 years, mean disease duration of 24 [ 6-48 ] ± 13.9 weeks) were enrolled in this study. 68.6% were illiterate and 19.6% reported at least one comorbid condition. The mean delay in referral for specialist care was 140 [ 7-420 ] ± 43 days. Thirteen patients (62.5%) were IgM or IgA RF positive. HLA-DRB1*01 and DRB1*04 alleles were present respectively in 11.8% and 45.1% of patients. At baseline, 35.3% patients were taking corticosteroids and 7.8% were under conventional DMARDs. At 24 months, 77.2% received a median dose of 5 mg/day of prednisone. Methotrexate (MTX) was the most frequently prescribed DMARD, being taken by 65.2% of patients. 13.6% of patients had stopped their DMARD because of socioeconomic difficulties. Comparison of clinical and biologic parameters between baseline and 24 months thereafter revealed a significant global improvement of the disease status including morning stiffness, pain score, swollen joint count, DAS 28 and HAQ scores, ESR and CRP. Sixteen patients (34.8%) were in remission at 2 years versus no patients at baseline; P < 0.001. Forteen patients (27.5%) had at least one erosion at baseline. Radiographic progression occurred in 33.3% of patients and was associated in univariate analysis to swollen joint count (p = 0.03), total SVDH score (P = 0.04) and joint space narrowing score (P = 0.03). No independent factors of radiographic progression were shown by logistic regression. Conclusions These study reports, provided for the first time in Morocco, a developing African country, a large amount of information concerning the profile and the course of early RA. Patients who were receiving, for most of them, Methotrexate in monotherapy and low doses of corticosteroids, showed an improvement of all clinic and biologic disease parameters. Moreover, DAS remission was obtained in one third of patients and two thirds of the cohort had no radiographic progression at 2 years. No predictor factors of radiographic progression were found out. These results should be confirmed or not by a large unbiased RA cohort which will give more relevant information about early RA characteristics and its course and will constitute a major keystone of its management. PMID:22111841

  14. Rheumatoid Factor

    MedlinePlus

    ... profit organization and does not endorse non-AACC products and services. Advertising & Sponsorship: Policy | Opportunities PLEASE NOTE: Your web browser does not have JavaScript enabled. Unless ... this page helpful? Also known as: RF Formal name: Rheumatoid Factor Related tests: Cyclic Citrullinated Peptide Antibody , ANA , ESR , C- ...

  15. The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis

    PubMed Central

    Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan; Boshnjaku, Shkumbin

    2016-01-01

    Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. Objective: The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). Materials and methods: This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2–4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. Conclusion: Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required. PMID:27147781

  16. Trends in disease modifying antirheumatic drug prescription in early rheumatoid arthritis are influenced more by hospital setting than patient or disease characteristics

    PubMed Central

    Carli, C; Ehlin, A G C; Klareskog, L; Lindblad, S; Montgomery, S M

    2006-01-01

    Objective To characterise temporal trends and factors associated with the prescription of disease modifying antirheumatic drugs (DMARDs) at the initial consultation in early rheumatoid arthritis (RA). Methods Data from 2584 patients with early RA at 19 hospitals were extracted from the Swedish Rheumatoid Arthritis Register for the period 1997–2001. Disease characteristics and DMARD prescription at first consultation with the rheumatologist were investigated using cross tabulation and logistic regression. Results DMARD prescriptions, particularly for methotrexate, increased from 1997 to 2001 independently of patient characteristics. Stratification by hospital type showed that patients in district hospitals were less likely to be prescribed DMARDs than those in university hospitals (adjusted odds ratio (OR) = 0.53 (95% confidence interval (CI) 0.40 to 0.69), p<0.001), independently of confounding factors. Association of the DAS28 with the likelihood of DMARD prescription was greater among patients attending district hospitals (OR = 1.65 (1.34 to 2.02), p<0.001) than those at university hospitals (OR = 1.23 (1.07 to 1.41), p = 0.003) and county hospitals (OR = 1.34 (1.01 to 1.63), p = 0.003). Interaction testing indicated that the difference was significant (p = 0.007). Conclusions Temporal trends in DMARD prescription indicate an increasingly aggressive approach to disease management among Swedish rheumatologists. However, the association of hospital type with DMARD prescription suggests that the adoption of research findings in clinical care varies considerably. PMID:16322085

  17. 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

  18. Simulation Training in Early Emergency Response (STEER).

    PubMed

    Generoso, Jose Roberto; Latoures, Renee Elizabeth; Acar, Yahya; Miller, Dean Scott; Ciano, Mark; Sandrei, Renan; Vieira, Marlon; Luong, Sean; Hirsch, Jan; Fidler, Richard Lee

    2016-06-01

    HOW TO OBTAIN CONTACT HOURS BY READING THIS ISSUE Instructions: 1.3 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded after you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. In order to obtain contact hours you must: 1. Read the article, "Simulation Training in Early Emergency Response (STEER)," found on pages 255-263, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website to register for contact hour credit. You will be asked to provide your name, contact information, and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until May 31, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. OBJECTIVES Define the purpose of the Simulation Training in Early Emergency Response (STEER) study. Review the outcome of the STEER study. DISCLOSURE STATEMENT Neither the planners nor the author have any conflicts of interest to disclose. Little has been published about nurses' responses in the first 5 minutes of in-hospital emergencies. This study aimed to test a simulation curriculum based on institutional priorities using high-intensity, short-duration, frequent in situ content delivery based on deliberate practice. The study design was a prospective, single-center, mixed-methods quasi-experimental study. Scenarios used in this study were ventricular fibrillation, opiate-related respiratory depression, syncopal fall, and hemorrhagic stroke. The convenience sample included 41 teams (147 participants). Improvements were noted in initiating chest compressions (p = .018), time to check blood glucose (p = .046), and identification of heparin as a contributor to stroke (p = .043). Establishing in situ simulation-based teaching program is feasible and well received. This approach appears effective in increasing confidence, initiating life-saving measures, and empowering nurses to manage emergencies. Future studies should evaluate and improve on the curriculum, on data collection tools quantitatively, and on overcoming barriers to high-quality emergency care. J Contin Educ Nurs. 2016;47(6):255-263. PMID:27232223

  19. Rheumatoid hindfoot.

    PubMed

    Kitaoka, H B

    1989-10-01

    Rheumatoid arthritis of the hindfoot is a relatively common problem and should be distinguished from other hindfoot and ankle disorders. Various nonoperative and operative treatments may be used effectively to relieve pain, functional restrictions, and footwear restrictions and, in some instances, to correct deformity. Management demands a multidisciplinary approach coordinated with a rheumatologist or other internist, a pedorthist, and a physiatrist or physical therapist. PMID:2677895

  20. Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts

    PubMed Central

    Tsubaki, T; Takegawa, S; Hanamoto, H; Arita, N; Kamogawa, J; Yamamoto, H; Takubo, N; Nakata, S; Yamada, K; Yamamoto, S; Yoshie, O; Nose, M

    2005-01-01

    Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks in the histopathological manifestations of rheumatoid arthritis (RA). This seems to be prominent even prior to significant B cell infiltration and/or formation of lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell accumulation, we examined in situ expression of chemokines and their receptors using synovial targeting biopsy specimens, which were obtained under arthroscopy from early RA patients. By immunohistochemical staining, plasma cells were found to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription-polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the synovial sublining regions were remarkably high and were likely to be associated with interferon (IFN)-γ expression. Furthermore, cultured synovial fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-γ. Our results indicate that in the early stage of RA, plasma cells expressing CXCR3 may be recruited directly from the circulation into the synovial sublining regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts. PMID:15996201

  1. 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

  2. Validation of Methotrexate-First Strategy in Patients with Early, Poor-Prognosis Rheumatoid Arthritis: Results From a Two-Year Randomized, Double-Blind Trial

    PubMed Central

    O'Dell, James R.; Curtis, Jeffrey R.; Mikuls, Ted R.; Cofield, Stacey S.; Bridges, S. Louis; Ranganath, Veena K.; Moreland, Larry

    2016-01-01

    Objective Methotrexate (MTX) taken as monotherapy is recommended as the initial disease-modifying antirheumatic drug for rheumatoid arthritis (RA). The purpose of this study was to examine outcomes of a blinded trial of initial MTX monotherapy with the option to step-up to combination therapy as compared to immediate combination therapy in patients with early, poor-prognosis RA. Methods In the Treatment of Early Rheumatoid Arthritis (TEAR) trial, 755 participants with early, poor-prognosis RA were randomized to receive MTX monotherapy or combination therapy (MTX + etanercept or MTX + sulfasalazine + hydroxychloroquine). Participants randomized to receive MTX monotherapy stepped up to combination therapy at 24 weeks if the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was ≥ 3.2. Results Attrition at 24 weeks was similar in the MTX monotherapy and combination groups. Of the 370 evaluable participants in the initial MTX group, 28% achieved low levels of disease activity and did not step-up to combination therapy (MTX monotherapy group). The mean ± SD DAS28-ESR in participants continuing to take MTX monotherapy at week 102 was 2.7 ± 1.2, which is similar to that in participants who were randomized to immediate combination therapy (2.9 ± 1.2). Participants who received MTX monotherapy had less radiographic progression at week 102 as compared to those who received immediate combination therapy (mean ± SD change in modified Sharp score 0.2 ± 1.1 versus 1.1 ± 6.4. Participants assigned to initial MTX who required step-up to combination therapy at 24 weeks (72%) demonstrated similar DAS28-ESR values (3.5 ± 1.3 vs 3.2 ± 1.3 at week 48) and radiographic progression (change in modified Sharp score 1.2 ± 4.1 vs 1.1 ± 6.4 at week 102) as those assigned to immediate combination therapy. The results for either of the immediate combination approaches, whether triple therapy or MTX + etanercept, were similar. Conclusion These results in patients with early, poor prognosis RA validate the strategy of starting with MTX monotherapy. This study is the first to demonstrate in a blinded trial that initial MTX monotherapy with the option to step-up to combination therapy results in similar outcomes to immediate combination therapy. Approximately 30% of patients will not need combination therapy, and the 70% who will need it are clinically and radiographically indistinguishable from those who were randomized to receive immediate combination therapy. PMID:23686414

  3. The gap between practice and guidelines in the choice of first-line disease modifying antirheumatic drug in early rheumatoid arthritis: results from the ESPOIR cohort

    PubMed Central

    Benhamou, Mathilde; Rincheval, Nathalie; Roy, Carine; Foltz, Violaine; Rozenberg, Sylvie; Sibilia, Jean; Schaeverbeke, Thierry; Bourgeois, Pierre; Ravaud, Philippe; Fautrel, Bruno

    2009-01-01

    Introduction To compare rheumatologists’ prescription for first disease-modifying anti-rheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with two clinical practice guidelines (CPG), STPR [1] and EULAR [2] and thus assess the gap between practices and guidelines. Methods ESPOIR is a French multicentre cohort study that included 813 early arthritis patients between 2002 and 2005. ‘Definite’ and ‘probable’ RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to: 1/assess conformity between the observed first-line DMARD prescribed for those patients and the guidelines’ recommended DMARD; and 2/conduct a mail survey of patients’ usual rheumatologists to explore the reasons for their non-conformity with guidelines. Results 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were: disease activity and presence of severity predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as soon as the first visits to the rheumatologist. Conclusion There is a substantial gap between CPG and rheumatologists’ daily practice concerning the first DMARD to prescribe in early RA. It is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA. PMID:19286850

  4. [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

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

    PubMed Central

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

    2015-01-01

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

  6. Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention

    PubMed Central

    2015-01-01

    OBJECTIVES: Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA). METHODS: Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group. RESULTS: The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6±13.2 years vs. 46.6±10.9 years), and disease duration (15.3±6.7 months vs. 14.5±6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits. CONCLUSIONS: Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities. PMID:26552423

  7. 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

  8. 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

  9. Simulation models of early visual processes

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  10. 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

  11. 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

  12. 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 ...

  13. 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.

  14. Predictors of remission, erosive disease and radiographic progression in a Colombian cohort of early onset rheumatoid arthritis: a 3-year follow-up study.

    PubMed

    Quintana-Duque, M A; Rondon-Herrera, F; Mantilla, R D; Calvo-Paramo, E; Yunis, J J; Varela-Nariño, A; Restrepo, J F; Iglesias-Gamarra, A

    2016-06-01

    The objective of the study is to find predictors of remission, radiographic progression (RP), and erosive disease in a cohort of patients with early onset rheumatoid arthritis (EORA) that followed a therapeutic protocol aiming at remission, in a real world tight-control setting. EORA patients were enrolled in a 3-year follow-up study. Clinical, biological, immunogenetic, and radiographical data were analyzed. Radiographs were scored according to Sharp-van der Heijde (SvdH) method. RP was defined by an increase of 3 units in 36 months. Remission was defined as DAS28 <2.6. A stepwise multiple logistic regression model was used to identify independent predictors of the three target outcomes. One hundred twenty-nine patients were included. Baseline disease activity was high. Significant overall improvement was observed, but only 33.3 % achieved remission. At 36 month, 50.4 % (65) of patients showed erosions. RP was observed in 62.7 % (81) of cases. Statistical analysis showed that baseline SvdH score was the only predictive factor associated with the three outcomes evaluated. Lower HAQ-DI and absence of autoantibodies were predictive of remission. Higher levels of ESR and presence of erosions at entry were predictive of RP. Independent baseline predictors of incident erosive disease were anti-CCP and RF positivity, symptom duration at baseline >3 months, and presence of HLA-DRB1 shared epitope. Radiographic damage at baseline was the main predictor of outcomes. Autoantibodies, HAQ and ESR at baseline, symptom duration before diagnosis, and HLA-DRB1 status had influence on clinical course and development of structural joint damage in Colombian RA patients. PMID:27041382

  15. 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-naïve 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

  16. Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort

    PubMed Central

    2013-01-01

    Introduction Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA. Methods In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ≥5 in total Sharp-van der Heijde Score (∆SHS) between inclusion and 1 year (∆SHS ≥1 or rapid radiographic progression: ∆SHS ≥5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion). Results Adiponectin level was independently associated with baseline total SHS (adjusted β = 0.12; P = 0.006). It was also associated with ∆SHS ≥1 (adjusted odds ratio (aOR) = 1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR = 1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ∆SHS ≥5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ∆SHS >0 (aOR = 1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 μg/ml for ∆SHS ≥1 and 6.04 μg/ml for ∆SHS ≥5, with a good specificity (58% and 75% for ∆SHS ≥1 and ∆SHS ≥5, respectively) and high negative predictive values (75% and 92% for ∆SHS ≥1 or ∆SHS ≥5, respectively). Conclusion Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status. PMID:24314299

  17. Disease modifying anti-rheumatic drug use and the risk of incident hyperlipidemia in patients with early rheumatoid arthritis: A retrospective cohort study

    PubMed Central

    Desai, Rishi J; Eddings, Wesley; Liao, Katherine P; Solomon, Daniel H; Kim, Seoyoung C

    2016-01-01

    Objective To compare the risk of incident hyperlipidemia in early rheumatoid arthritis (ERA) patients after initiation of various disease modifying anti-rheumatic drugs (DMARDs). Methods We conducted a cohort study using insurance claims data (2001–2012) in ERA patients. ERA was defined by the absence of any RA diagnosis or DMARD prescriptions for 12 months. Four mutually exclusive groups were defined based on DMARD initiation, TNF-α inhibitors ± non-biologic (nb) DMARDs, methotrexate ± non-hydroxycholorquine nbDMARDs, hydroxychloroquine ± non-methotrexate nbDMARDs, and other nbDMARDs only. The primary outcome was incident hyperlipidemia, defined by a diagnosis and a prescription for a lipid-lowering agent. For the subgroup of patients with laboratory results available, change in lipid levels was assessed. Multivariable Cox proportional hazard models and propensity score (PS) decile stratification with asymmetric trimming were used to control for confounding. Results Of the 17,145 ERA patients included in the study, 364 developed incident hyperlipidemia. The adjusted hazard ratios (95% CI) for hyperlipidemia were 1.41 (0.99–2.00) for TNF-α inhibitors, 0.81 (0.63–1.04) for hydroxychloroquine, and 1.33 (0.95–1.84) for other nbDMARDs compared with methotrexate in the full cohort, while 1.18 (0.80–1.73), 0.75 (0.58–0.98) and 1.41 (1.01–1.98), respectively in the PS trimmed cohort. In the subgroup analysis, hydroxychloroquine use showed significant reduction in low density lipoprotein (−8.9 mg/dl, 95% CI −15.8, −2.0), total cholesterol (−12.3 mg/dl, 95% CI −19.8, −4.8) and triglyceride (−19.5 mg/dl, 95% CI −38.7, −0.3) levels from baseline compared with methotrexate. Conclusion Use of hydroxychloroquine may be associated with a lower risk of hyperlipidemia among ERA patients. PMID:25302481

  18. 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.

  19. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161+Th1 Cells) to CD161+Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients

    PubMed Central

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161+Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161+Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

  20. 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

  1. [Tocilizumab in rheumatoid arthritis].

    PubMed

    Rueda Gotor, Javier; Blanco Alonso, Ricardo

    2011-03-01

    Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the receptor for IL-6, approved for the treatment of rheumatoid arthritis (RA) in Japan, Europe and the US. Wide clinical development has shown the efficacy of TCZ in most of the possible situations of RA: RA without prior failure to MTX (AMBITION), RA unresponsive to MTX (SATORI, OPTION, LITHE) or any DMARD (TOWARD, ROSE) as well as RA refractory to anti-TNFa agents (RADIATE). In addition to its early onset, efficacy was constant and even increased as time passed (GROWTH95, GROWTH96). TCZ has shown great efficacy in correcting laboratory alterations in RA, both in acute phase reactants as well as anemia of inflammatory disease. Although in RA TCZ us initially indicated in combination with MTX, it has also shown its efficacy as monotherapy (AMBITION). TCZ is equally effective in the prevention of structural damage (SAMURAI, LITHE). In addition, it has shown to be a safe and well-tolerated drug, similar to other biologic therapies. All of these aspects make TCZ an adequate therapeutic alternative to be considered in any RA scenario. PMID:21794769

  2. Surgery of the rheumatoid elbow.

    PubMed Central

    Souter, W A

    1990-01-01

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

  3. Simulation Study Of Early Afterglows Observed With Swift

    NASA Astrophysics Data System (ADS)

    Nishikawa, Ken-Ichi; Hededal, C.; Hardee, P.; Mizuno, Y.; Fishman, G. J.

    2006-09-01

    A 3-D relativistic particle-in-cell code has been used to simulate the dynamics of forward and reverse shocks with thin and thick shells within the parameter constraints provided by present Swift observations and the present models of GRB emission. Our 3-D RPIC simulations have provided the dynamics of collisionless shocks in electron-ion and electron-positron plasmas with and without initial ambient magnetic fields and revealed the importance of ``jitter radiation'' with prompt and afterglow spectra due to the inhomogeneous magnetic fields generated by the Weibel instability. It is different from synchrotron radiation, which is usually assumed to be the dominant radiation process. We have investigated gamma-ray burst emissions from prompt, early, and late afterglows considering microscopic processes. Based on our previous investigation of the Weibel instability for each stage of evolution of ejecta propagating in the ISM, we have incorporated the plasma conditions (relativistic jets) with the density and composition of the plasmas, the magnetic field strength ($\\sigma$-values (the ratio of the electromagnetic energy flux to the particle energy flux)) and its direction, and the Lorentz factor for the different stages in prompt and afterglows. Systematic simulation studies of the relativistic collisionless shocks, associated particle acceleration, magnetic field generation and self-consistent radiation provide insight into undetermined issues in prompt and afterglows observed by Swift. Self-consistently calculated lightcurves, spectra, spectral evolutions, and polarization as function of viewing angle will be done to light a shed on recent new observations by Swift, in particular, X-ray flares, early steep decay, and shallow decay.

  4. Rheumatoid Arthritis Educational Video Series

    MedlinePlus Videos and Cool Tools

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

  5. 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

  6. 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.

  7. Rheumatoid arthritis in a military aviator.

    PubMed

    Moszyk, Danielle J; Sulit, Daryl J

    2007-01-01

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

  8. [Treatment strategy for rheumatoid arthritis in Croatia].

    PubMed

    Curković, Bozidar

    2008-01-01

    The main objectives of the current treatment of rheumatoid arthritis are disease control, inhibition of radiographic progression and finally remission. Presumptions to achieving these goals are early diagnosis of rheumatoid arthritis and early administered therapy with disease modifying drugs as monotherapy or combination of drugs. The optimal therapeutic response is influenced by tight control of the patients, evaluation of efficacy and tolerability and change of therapeutic strategy as needed. For the patients refractory to standard disease modifying drugs anti-TNFa drugs can be added. The choice of anti-TNFalpha drug should be done regarding efficacy, tolerability and method of drug administration. In a patient who is failing to respond after 3 months to one anti-TNFalpha we can try other one or rituximab. PMID:19024273

  9. 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

  10. Laryngeal Manifestations of Rheumatoid Arthritis

    PubMed Central

    Hamdan, A. L.; Sarieddine, D.

    2013-01-01

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

  11. Simulations of nucleation and early growth stages of protein crystals.

    PubMed Central

    Kierzek, A M; Wolf, W M; Zielenkiewicz, P

    1997-01-01

    Analysis of known protein crystal structures reveals that interaction energies between monomer pairs alone are not sufficient to overcome entropy loss related to fixing monomers in the crystal lattice. Interactions with several neighbors in the crystal are required for stabilization of monomers in the lattice. A microscopic model of nucleation and early growth stages of protein crystals, based on the above observations, is presented. Anisotropy of protein molecules is taken into account by assigning free energies of association (proportional to the buried surface area) to individual monomer-monomer contacts in the lattice. Lattice simulations of the tetragonal lysozyme crystal based on the model correctly reproduce structural features of the movement of dislocation on the (110) crystal face. The dislocation shifts with the speed equal to the one determined experimentally if the geometric probability of correct orientation is set to 10(-5), in agreement with previously published estimates. At this value of orientational probability, the first nuclei, the critical size of which for lysozyme is four monomers, appear in 1 ml of supersaturated solution on a time scale of microseconds. Formation of the ordered phase proceeds through the growth of nuclei (rather then their association) and requires nucleations on the surface at certain stages. Images FIGURE 2 PMID:9251778

  12. 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

  13. 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

  14. 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

  15. Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression

    PubMed Central

    Ronnelid, J; Wick, M; Lampa, J; Lindblad, S; Nordmark, B; Klareskog, L; van Vollenhoven, R F

    2005-01-01

    Objective: To study serum levels of citrullinated protein/peptide antibodies (anti-CP) during up to 5 years' follow up of patients with early rheumatoid arthritis (RA), and to relate serum levels to disease course and to treatments in clinical practice. Methods: 279 patients with early RA were followed up with clinical investigations, radiographs, and measurement of anti-CP at baseline and after 3 months, 1, 2, 3, and 5 years. Results: 160/279 (57.3%) patients were anti-CP positive at the first visit (mean 5 months after first symptoms). During follow up only 11/279 (3.9%) of the patients changed their anti-CP status. Anti-CP levels fell significantly during the first year, and this drop correlated with the extent of sulfasalazine treatment but not with other drugs or clinical indices. Anti-CP positive and negative patients had similar disease activities at baseline, but during follow up the anti-CP positive patients had worse clinical disease and greater radiological progression, despite at least equally intensive antirheumatic treatment. Conclusions: Anti-CP are stable during the first 5 years of RA, suggesting that events before rather than after onset of clinical manifestations of disease determine this phenotype. The presence of anti-CP at diagnosis predicts a less favourable disease course and greater radiological progression despite antirheumatic treatment, but subsequent changes in antibody levels do not reflect changes in disease activity. Taken together, these observations suggest that anti-CP positive RA is a distinct clinical and pathophysiological entity. PMID:15843452

  16. [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

  17. [The pulmonological manifestations of rheumatoid arthritis].

    PubMed

    Bernscherer, György; Karabélyos, Csaba; Tarján, Zsolt

    2008-07-20

    In their review article the authors overview the primary and secondary pulmonary complications of rheumatoid arthritis with the help of bibliographic data. They emphasize the pulmonological complications of disease modifying antirheumatic drugs used for the pharmaceutical therapy of rheumatoid arthritis, of which they discuss the methotrexate induced pulmonary diseases. Methotrexate participates nearly in all of additive double and triple--O'Dell-scheme--combined disease modifying antirheumatic drugs therapy. Because of that, the early detection of drug-induced pulmonological complications is important. For rheumatologists the treatment of methotrexate resistant rheumatoid arthritis is always getting a higher and higher challenge. Biological therapeutical drugs act as cytokine antagonists, by blocking TNF-alpha and, compared to disease modifying antirheumatic drugs, they can more effectively inhibit the progression of the disease. These are the biological response modifiers. Their main representatives are infliximab, adalimumab, and etanercept. At the end, the authors discuss secondary pulmonary complications caused by biological response modifiers, e.g. the biological response modifiers associated pulmonary tuberculosis, bacterial tracheobronchitis, bacterial pneumonia, bronchiectasia, pulmonary oedema, rapid fibrosing alveolitis, and coccidioidomycosis. At 3% of patients with rheumatoid arthritis, treated with biological response modifiers, who live in Arizona, California, Nevada, pulmonary and systemic mycosis--coccidioidomycosis can appear with a 15% of mortality. As a consequence of frequent earthquakes, the spores getting into the air from the ground infect immunosuppressed patients treated with biological response modifiers. The authors draw attention to the fact that patients who receive biological therapy and travel to the above-mentioned endemic or earthquake-active regions, have a potential high risk, so it is indispensable that they are informed by the doctor. Testing and use of newer and newer groups of biological response modifiers are expected in the near future in the therapy of rheumatoid arthritis. Nowadays--in patients, who are non-reactive for TNF-alpha inhibitor treatment--the use of B-lymphocyte inhibitor rituximab, characteristic in non-Hodgkin lymphoma therapy is possible. The pulmonary complications of rheumatoid arthritis therapy of that cytokine are not known yet. Today, antirheumatic therapy results in a significant improvement of patients' life-quality, whilst the more and more modern therapeutical methods cause more complications. PMID:18617467

  18. The Effects of Infant Simulators on Early Adolescents.

    ERIC Educational Resources Information Center

    Divine, James H.; Cobbs, Gene

    2001-01-01

    Examined the effects of infant simulators (computerized dolls designed to simulate normal infants) on 236 8th-grade students. Findings indicated that the doll experience had a significant impact on the students, especially females. It helped them to learn about the challenges of infant care, and to think of the implications before engaging in…

  19. 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

  20. 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

  1. [Biomarkers in rheumatoid arthritis].

    PubMed

    Sanmartí, Raimon; Gómez-Puerta, José A

    2011-03-01

    The search for biomarkers in rheumatoid arthritis (RA) has been the object of interesting research in the past few years, although results have not always been relevant. Several biomarkers, from several different locations (blood, urine, synovial fluid, synovial tissue) and of different nature (autoantibodies, genetic markers, joint remodeling markers), and related to different outcomes, diagnostic and prognostic markers (joint destruction, disability, lack of remission, mortality, response to anti-rheumatic treatment, etc.) have been studied. The present article reviews research only on soluble biomarkers, mainly those in serum, related to the diagnosis and joint destruction in RA. PMID:21794768

  2. Computational Simulations of the Early Steps of Protein Aggregation

    PubMed Central

    Wei, Guanghong; Mousseau, Normand

    2007-01-01

    There is strong evidence that the oligomers of key proteins, formed during the early steps of aggregation, could be the primary toxic species associated with human neurodegenerative diseases, such as Alzheimer's and prion diseases. Here, we review recent progress in the development of computational approaches in order to understand the structures, dynamics and free energy surfaces of oligomers. We also discuss possible research directions for the coming years. PMID:19164927

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

    PubMed Central

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

    2014-01-01

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

  4. 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

  5. Rheumatoid factor and glomerulonephritis

    PubMed Central

    Miyazaki, M.; Endoh, M.; Suga, T.; Yano, N.; Kuramoto, T.; Matsumoto, Y.; Eguchi, K.; Yagame, M.; Miura, M.; Nomoto, Y.; Sakai, H.

    1990-01-01

    It is presently unknown whether rheumatoid factors have a pathogenic role in the development of various types of glomerulonephritis with immune deposits. Three isotypes of rheumatoid factors (RFs), which are autoantibodies to IgG, were measured using the solid-phase fluorescence immunoassay in sera from patients with diffuse proliferative lupus nephritis (DPLN), membranous lupus nephritis (MLN), IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN). RF activity of immunoglobulins deposited in the glomeruli from these patients was also studied by examining the binding of the FITC-conjugated human IgG and Fc portion of IgG to the glomeruli of renal biopsy specimens. IgG, IgA and IgM RFs were significantly increased in sera from patients with DPLN, and the increase was significantly lower in patients with MLN, IgAN and MN. Human IgG bound to immunoglobulin on the glomeruli only in DPLN, but not in MLN, IgAN or MN. The Fc portion of IgG was demonstrated to be involved in this reaction. It was suggested that RFs and IgG may play a major role in immune deposits on the glomeruli in DPLN and may be involved in the development of DPLN; however, this is not likely in MLN, IgAN or MN. PMID:2201469

  6. 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

  7. 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. PMID:27034572

  8. 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

  9. 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

  10. 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…

  11. GUEPARD treat-to-target strategy is significantly more efficacious than ESPOIR routine care in early rheumatoid arthritis according to patient-reported outcomes and physician global estimate

    PubMed Central

    Castrejón, Isabel; Soubrier, Martin; Lin, Yih Chang; Rat, Anne-Christine; Combe, Bernard; Dougados, Maxime

    2013-01-01

    Objective. To analyse seven RA Core Data Set measures and three indices for their capacity to distinguish treatment results in early RA in the GUEPARD treat-to-target clinical trial vs ESPOIR routine care. Methods. Post hoc analyses compared 65 GUEPARD and 130 matched control ESPOIR patients over 6 and 12 months for mean changes in measures, relative efficiencies and standardized response means (SRM). Three indices—28-joint disease activity score (DAS28), clinical disease activity index (CDAI) and routine assessment of patient index data (RAPID3)—were compared for mean changes and numbers of patients with high, moderate or low activity or remission using κ values. Results. Greater improvement was seen for GUEPARD vs ESPOIR, statistically significant for physician and patient global estimates and pain and health assessment questionnaire physical function (HAQ-FN), but not joint counts and laboratory tests. Relative efficiencies with tender joint count as the referent measure indicated that pain (2.57) and global estimates by patient (3.13) and physician (2.31) were most efficient in distinguishing GUEPARD from ESPOIR. Mean improvements in GUEPARD vs ESPOIR were −3.4 vs −2.6 for DAS28 (0–10) (24%), −29.8 vs −23.1 for CDAI (0–76) (23%) and −13.0 vs −7.8 for RAPID3 (0–30) (40%) (all P < 0.01); agreement was moderate between CDAI vs DAS28 (κ = 0.56) and vs RAPID3 (κ = 0.48), and fair between DAS28 vs RAPID3 (κ = 0.26). Conclusion. Patient and global measures indicate greater efficacy than joint counts or laboratory measures in detecting difference between GUEPARD treat-to-target and ESPOIR routine care. A RAPID3 of only patient measures may help guide treat-to-target in busy clinical settings. PMID:23864169

  12. Rheumatoid disease resembling lung neoplasia.

    PubMed

    García-Vicuña, R; Díaz-González, F; Castañeda, S; Arranz, M; López-Bote, J P

    1990-12-01

    We describe a 67-year-old man with severe rheumatoid arthritis of long duration. He developed a peculiar extraarticular rheumatoid complication consisting of localized lung consolidation with a pathological costal fracture, together with an abrupt systemic reaction that occurred in the course of immunosuppressive treatment. The diagnosis first proposed was lung cancer with costal metastases. However exhaustive studies performed in the search of malignancy were systematically negative and pathologic studies finally demonstrated bronchiolitis obliterans with organizing pneumonia (BOOP) as responsible for parenchymal lung consolidation with a rheumatoid nodule eroding bone at the level of the rib fracture. These findings, after long followup of the patient, attest to the rheumatoid origin of his bizarre manifestations and definitely rule out a neoplastic etiology. PMID:2084246

  13. Handout on Health: Rheumatoid Arthritis

    MedlinePlus

    ... or changes in certain hormones, may promote the development of rheumatoid arthritis in a genetically susceptible person who has been exposed to a triggering agent from the environment. Even though all the answers are not known, ...

  14. 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

  15. [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

  16. Smoking and Rheumatoid Arthritis

    PubMed Central

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

    2014-01-01

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

  17. [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

  18. Early postmortem electrical stimulation simulates PSE pork development.

    PubMed

    Hammelman, J E; Bowker, B C; Grant, A L; Forrest, J C; Schinckel, A P; Gerrard, D E

    2003-01-01

    Carcasses from 64 gilts were subjected to electrical stimulation (ES) at 3, 15, 25, 35, 45, and 55 min postmortem or were untreated (NS). Temperature and pH of longissimus muscles were recorded at 1, 7, 14, 20, 30, 40, 50, and 60 min, and 24 h postmortem. Muscle samples were collected at 1, 30 and 60 min, and 24 h for determining glycolytic metabolite concentrations. ES at 3, 15, and 25 min resulted in lower (P<0.05) muscle pH, but stimulation after 25 min had no effect on muscle pH. Likewise, ES prior to 25 min resulted in greater (P<0.05) muscle temperatures. Muscle lactate concentrations were greater (P<0.05) in carcasses stimulated before 45 min postmortem. Glucose 6-phosphate concentration decreased (P<0.05) during the first hr postmortem and increased (P<0.05) thereafter. ES of carcasses at 45 and 55 min resulted in higher (P<0.05) concentrations of muscle glucose 6-phosphate at 24 h compared with NS and early-stimulated carcasses. Muscle glycogen concentrations at 30 min in carcasses stimulated at 3, 15 and 25 min were lower (P<0.05) than NS carcasses. Carcasses stimulated at 3 and 15 min exhibited lower (P<0.05) concentrations of muscle glycogen at 60 min than NS carcasses. Carcasses stimulated at 3 and 15 min postmortem exhibited lower (P<0.05) color and firmness scores, while ES at 3 and 25 min postmortem resulted in lower (P<0.05) water holding capacity. ES had no significant effect on CIE L(∗), a(∗), b(∗), or 24 h muscle pH. These data show that ES of pork carcasses during the first 25 min postmortem creates PSE-like quality characteristics and suggest that ES is a potential model for studying pork quality development. PMID:22061988

  19. Gut Microbes Linked to Rheumatoid Arthritis

    MedlinePlus

    ... Arthritis The presence of a specific type of gut bacteria correlates with rheumatoid arthritis in newly diagnosed, untreated ... had rheumatoid or psoriatic arthritis. The team identified gut bacteria by extracting DNA from the samples and then ...

  20. Experimental Drug for Rheumatoid Arthritis Shows Promise

    MedlinePlus

    ... medlineplus/news/fullstory_158076.html Experimental Drug for Rheumatoid Arthritis Shows Promise Baricitinib helped patients who failed other ... 2016 (HealthDay News) -- An experimental drug to treat rheumatoid arthritis showed promise in a new six-month trial. ...

  1. Can Rheumatoid Arthritis Be Prevented?

    PubMed Central

    Deane, Kevin

    2013-01-01

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

  2. Model simulations of early westward flow across the Tasman Gateway during the early Eocene

    NASA Astrophysics Data System (ADS)

    Sijp, Willem P.; von der Heydt, Anna S.; Bijl, Peter K.

    2016-04-01

    The timing and role in ocean circulation and climate of the opening of Southern Ocean gateways is as yet elusive. Recent micropalaeontological studies suggest the onset of westward throughflow of surface waters from the SW Pacific into the Australo-Antarctic Gulf through a southern shallow opening of the Tasman Gateway from 49-50 Ma onwards, a direction that is counter to the present-day eastward-flowing Antarctic Circumpolar Current. Here, we present the first model results specific to the early-to-middle Eocene where, in agreement with the field evidence, southerly shallow opening of the Tasman Gateway indeed causes a westward flow across the Tasman Gateway. As a result, modelled estimates of dinoflagellate biogeography are in agreement with the recent findings. Crucially, in this situation where Australia is still situated far south and almost attached to Antarctica, the Drake Passage must be sufficiently restricted to allow the prevailing easterly wind pattern to set up this southerly restricted westward flow. In contrast, an open Drake Passage, up to 517 m deep, leads to an eastward flow, even when the Tasman Gateway and the Australo-Antarctic gulf are entirely contained within the latitudes of easterly wind.

  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. 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.

  5. [Pathophysiology of rheumatoid arthritis].

    PubMed

    Lequerré, Thierry; Richez, Christophe

    2012-10-01

    These last years were especially marked by the best understanding of the physiopathological mechanisms at the onset of rheumatoid arthritis (RA) and in the processes of joint inflammation and joint destruction. RA is more and more considered as a syndrome with at least two clinical entities with different phenotype and profiles: seronegative RA and seropositive RA. In RA with ACPA, it is the process of immunization, that is the immunological reaction against citrullinated peptides, that leads to the disease. The peptide citrullination is directly favored by environmental factors such as tobacco, infection to Porphyromonas gingivalis and alcohol. The immunization supposes a genetic predisposition including approximately 22 genetic factors including the molecules of the major histocompatibility complex (MHC) and PTPN22. Finally, joint damage result at the same time from an excess of destruction (RANK/RANKL, TNFalpha) and from a defect of bone reparation by the way Wnt/Frizzled. It is thanks to the best understanding of RA physiopathology that leads to development of targeted treatments and specially processing for this disease. PMID:23227604

  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. Meloxicam in rheumatoid arthritis.

    PubMed

    Ahmed, Mansoor; Khanna, Dinesh; Furst, Daniel E

    2005-12-01

    Rheumatoid arthritis (RA), a chronic inflammatory multisystem disorder marked by joint pain, stiffness, swelling and multiple systemic involvements, requires a multifaceted approach for its management. It includes symptomatic treatment with analgesics as well as disease-modifying medications to alter the course of RA over time. NSAIDS have been widely used for their symptomatic effects, but their use is not free from adverse effects, which may include life-threatening adverse events such as gastrointestinal (GI) bleeding and perforation. Meloxicam, an oxicam derivative that is a member of the enolic acid group of NSAIDs, has recently been approved by the US FDA for use in RA and osteoarthritis. At the FDA-recommended doses meloxicam is COX-2 preferential. By virtue of this COX-2 preferential activity it is expected to have lower GI toxicity as compared with COX-2 nonselective NSAIDs. Clinical trials have shown that meloxicam at 7.5 - 15 mg/day is as effective as diclofenac, piroxicam and naproxen as an anti-inflammatory and analgesic, and was associated with fewer GI adverse effects. PMID:16863437

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

    ERIC Educational Resources Information Center

    Smit, Peter H.

    1982-01-01

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

  9. 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

  10. Rheumatoid factor in syphilis.

    PubMed Central

    Cerny, E H; Farshy, C E; Hunter, E F; Larsen, S A

    1985-01-01

    Immunoglobulin M (IgM) antibodies directed against IgG antibodies (rheumatoid factor [RF]) are known to occur often in patients with syphilis and to interfere with serological tests measuring specific antibodies of the IgM class. In this study we examined the occurrence and specificity of the RF and demonstrated a simple method to detect and eliminate the RF for a specific Treponema pallidum IgM enzyme-linked immunosorbent assay. We measured the occurrence of the RF with a sensitive enzyme-linked immunosorbent assay and found that it increased with the duration of syphilitic disease: 1 of 13 primary syphilis serum specimens, 3 of 13 secondary syphilis serum specimens, and 10 of 27 latent syphilis serum specimens were reactive in this RF test. Those sera containing IgM RF were immunoprecipitated with anti-human gamma chain antibodies and 2% polyethylene glycol until the RF was removed. One serum specimen from a patient in the secondary stage of syphilis and eight serum specimens from patients with latent disease still presented the RF after immunoprecipitation. Removal of the IgG antibodies also improved the sensitivity of the treponemal IgM test, indicating competition of these antibodies for binding sites of the antigen. The enzyme-linked immunosorbent assays for detection of RF and antitreponemal IgM antibodies are performed on the same plate. Theoretically, only sera positive for both tests have to be immunoprecipitated. But our findings indicated an increase in sensitivity of the IgM enzyme-linked immunosorbent assay after removal of IgG antibodies responsible for competition at the binding sites. PMID:3894413

  11. 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.

  12. 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.

  13. Detection of rheumatoid arthritis using infrared imaging

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  14. 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.

  15. Prevention of Stroke in Rheumatoid Arthritis.

    PubMed

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

    2015-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Carmichael, Matthew; Lunt, Daniel; Pancost, Richard

    2015-04-01

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

  17. Treating Rheumatoid Arthritis: Are Biologic Drugs Right for You?

    MedlinePlus

    Treating Rheumatoid Arthritis: Are Biologic Drugs Right for You? What is rheumatoid arthritis (RA)? Rheumatoid arthritis (RA) is a serious condition. The body’s immune system attacks the lining of ...

  18. 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.

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

    PubMed Central

    Kim, Sharon; Parker, Wendy L.

    2008-01-01

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

  20. Unstable pelvic insufficiency fracture in a patient with rheumatoid arthritis.

    PubMed

    Hoshino, Yuichi; Doita, Minoru; Yoshikawa, Masaho; Hirayama, Kenichi; Sha, Norihide; Kurosaka, Masahiro

    2004-01-01

    The occurrence of pelvic insufficiency fractures in patients with rheumatoid arthritis has not previously been well emphasized. These fractures are difficult to detect clinically, and appropriate radiological investigation is necessary for diagnosis. A 72-year-old woman with rheumatoid arthritis presented with severe left groin pain. Pelvic radiographs showed parasymphyseal fractures, and marked instability of these fractures was observed at the follow-up 2 weeks later. Computed tomographic scan of the sacrum showed a widened linear fracture gap in the left sacral ala. Because the patient's pain was so severe that she could not change position, external fixation was performed to achieve rapid pain relief and early mobilization. Although most patients with these fractures respond well to simple conservative treatments, parasymphyseal fractures combined with sacral fractures may cause disruption of the pelvic ring and occasionally need operative management. PMID:12748811

  1. 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

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

    PubMed Central

    2006-01-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. Virtually simulated social pressure influences early visual processing more in low compared to high autonomous participants.

    PubMed

    Trautmann-Lengsfeld, Sina Alexa; Herrmann, Christoph Siegfried

    2014-02-01

    In a previous study, we showed that virtually simulated social group pressure could influence early stages of perception after only 100  ms. In the present EEG study, we investigated the influence of social pressure on visual perception in participants with high (HA) and low (LA) levels of autonomy. Ten HA and ten LA individuals were asked to accomplish a visual discrimination task in an adapted paradigm of Solomon Asch. Results indicate that LA participants adapted to the incorrect group opinion more often than HA participants (42% vs. 30% of the trials, respectively). LA participants showed a larger posterior P1 component contralateral to targets presented in the right visual field when conforming to the correct compared to conforming to the incorrect group decision. In conclusion, our ERP data suggest that the group context can have early effects on our perception rather than on conscious decision processes in LA, but not HA participants. PMID:24313603

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

    PubMed

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

    2014-01-01

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

  12. [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

  13. Ectopic lesion of schistosomiasis of the penis simulating an early carcinoma.

    PubMed

    Badejo, O A; Soyinka, F; Laja, A O

    1978-09-01

    A case of ectopic lesion of Schistosoma haematobium of the penis with extensive tissue destruction, simulating an early carcinoma of the penis and almost resulting in an autoamputation of the crown of the penis, is presented. The penis was surgically repaired and the patient treated with ambilhar. In schistosoma endemic area, it is important to think of ectopic schistosoma lesion by such a presentation. Existing theories to explain the presence of schistosoma eggs in locations outside the portal-caval system were reviewed and another one was advanced: its being sexually transmitted. PMID:31780

  14. 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.

  15. [Non-pharmacologic treatment of rheumatoid arthritis].

    PubMed

    Curković, Bozidar

    2010-01-01

    Non-pharmacologic interventions are the part of comprehensive therapy of rheumatoid arthritis, proposed by all guidelines and recommendations. Patients with rheumatoid arthritis have pain, limited joint mobility, and impaired quality of life. Physical modalities are prescribed exactly with idea to diminish pain, iprove joint mobility and quality of life. Physical procedures are generally safe and well tolerated. PMID:21875001

  16. Adenosine deaminase activity in rheumatoid pleural effusion.

    PubMed Central

    Ocaña, I; Ribera, E; Martinez-Vázquez, J M; Ruiz, I; Bejarano, E; Pigrau, C; Pahissa, A

    1988-01-01

    The activity of adenosine deaminase was studied in nine cases of rheumatoid pleural effusion, showing an increase in enzyme activity in all. Rheumatoid arthritis seems unique, however, as it cannot be differentiated from pleural tuberculosis on the basis of this test. Selective increase of adenosine deaminase in both conditions is attributed to stimulation of T lymphocytes in the pleural fluid. PMID:3389927

  17. Role of basophils in rheumatoid arthritis (Review)

    PubMed Central

    TANG, PEI; CHEN, QIUHUA; LAN, QIAOFEN; CHEN, YANWEN; YANG, HAIJUAN; AN, NING; XIAO, HAIYAN; LIU, HUAFENG; WU, PING; XIE, TONG; PAN, QINGJUN

    2015-01-01

    The T helper (Th)1/Th2 imbalance plays a crucial role in the development of rheumatoid arthritis (RA). It is well known that basophils can affect the Th1/Th2 balance by enhancing the Th2 response, while impairing the Th1 response, which is known to be involved in the development of a number of diseases. However, limited information is available with regard to the role of basophils in RA. Decreased levels of circulating basophils and a dominant Th1 response have been reported in adult patients with RA, while children with juvenile RA have been largely found to have increased levels of circulating basophils and a dominant Th2 response. Furthermore, the circulating basophils in the two conditions have an activated phenotype and are associated with disease activity. In addition, a longitudinal study found the Th2 response was dominant in the early stages of RA, while the Th1 response was dominant in long-term chronic RA. These observations indicate that basophils may be involved in the development of RA by affecting the Th1/Th2 balance, particularly in the early stages of RA. Therefore, targeting basophils may be a novel therapeutic strategy for the treatment of RA; however, further investigation is required. PMID:26136859

  18. [Anticitrullin antibodies--modern markers of rheumatoid arthritis].

    PubMed

    Shilkina, N P; Luzinova, M S; Vinogradov, A A

    2011-01-01

    Modern diagnosis of rheumatoid arthritis (RA) is based on the ARA criteria with seropositivity detection by the rheumatoid factor (RF). In a clinically evident stage of the disease this factor is highly sensitive and specific (about 90%), but in early RA efficacy of this diagnosis is considerably less. RF-IgM phenotype has limitation: frequent detection of this factor in the absence of RA and unstability of RF-IgM phenotype. Therefore, it is necessary to search for new serological criteria of RA diagnosis at early stage of the disease. Proteins containing citrullin appear only in the course of posttranslation modification of arginin residues. This fact gave rise to an original, available for clinical practice method of enzyme immunoassay for detection of antibodies to cyclic citrullinized (ACCP)--filaggrin derivative with synthetic cyclic citrullinized peptide serves as antigenic substance. According to the results of different studies, ACCP specificity in early RA diagnosis is more than 80%, combination of ACCP with ESR, RF-IgM, CRP, morning stiffness--more than 90%. As specificity of combination of these autoantibodies is almost 100%, their simultaneous determination is indicated in patients with undifferentiated arthritis for specification of the diagnosis. ACCP and antibodies to modified citrullinized vimentin (AMCV) significantly correlate with RA activity, are prognostic factors of rapidly progressive course and can be used for the disease prognosis at its early stage. Present-day data on comparative specificity and sensitivity of ACCP and AMCV are not certain and need further study. PMID:21446207

  19. 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

  20. 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

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

    NASA Astrophysics Data System (ADS)

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

    2010-05-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  4. 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

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

    PubMed

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

  6. 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.

  7. Metabolic Syndrome in Rheumatoid Arthritis

    PubMed Central

    Ferraz-Amaro, Iván; González-Juanatey, Carlos; López-Mejias, Raquel; Riancho-Zarrabeitia, Leyre; González-Gay, Miguel A.

    2013-01-01

    Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-α antagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA. PMID:23431244

  8. Genetic studies of rheumatoid arthritis

    PubMed Central

    YAMAMOTO, Kazuhiko; OKADA, Yukinori; SUZUKI, Akari; KOCHI, Yuta

    2015-01-01

    Rheumatoid arthritis (RA) is a common autoimmune disease that results in significant morbidity. As with other complex disorders, genome-wide association studies (GWASs) have greatly contributed to the current understanding of RA etiology. In this review, we describe the genetic configuration of RA as revealed primarily through GWASs and their meta-analyses. In addition, we discuss the pathologic mechanisms of RA as suggested by the findings of genetic and functional studies of individual RA-associated genes, including HLA-DRB1, PADI4, PTPN22, CCR6 and FCRL3, and the potential use of genetic information for RA treatment in clinical practice. PMID:26460319

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

    PubMed Central

    Strand, Vibeke; Sokolove, Jeremy

    2009-01-01

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

  10. 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

  11. 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.

  12. [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

  13. 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

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

    PubMed

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

    2012-07-01

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

  15. 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.

  16. [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

  17. 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.

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

    PubMed Central

    2013-01-01

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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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)

  4. Laminin and vascular proliferation in rheumatoid arthritis.

    PubMed Central

    Scott, D L; Salmon, M; Morris, C J; Wainwright, A C; Walton, K W

    1984-01-01

    Laminin is a high molecular weight basement membrane structural glycoprotein. In rheumatoid arthritis and other arthropathies immunoreactive laminin was prominent in synovial blood vessel basement membranes and acted as a marker for them. It codistributed with collagen type IV. Immunohistological reactivity to laminin showed extensive vascular proliferation in rheumatoid arthritis together with basement membrane reduplication, which was confirmed ultrastructurally. Parallel histological studies showed vascular proliferation was predominantly in the subintimal rheumatoid synovium, where it was related to connective tissue proliferation but not to the inflammatory cell infiltrate. Vascular proliferation was also seen in relation to connective tissue changes in biopsies from cases of haemophilic arthritis, osteoarthritis, and meniscal tears. We suggest connective tissue activation is non-specific reaction associated with vascular proliferation. This involves laminin and other structural proteins. It occurs in rheumatoid arthritis and other arthropathies but is distinct from inflammatory cell infiltration. Images PMID:6383233

  5. Towards a flash flood early warning system through hydrological simulation of probabilistic ensemble forecasts

    NASA Astrophysics Data System (ADS)

    Alfieri, Lorenzo; Thielen Del Pozo, Jutta

    2010-05-01

    In this work we test a flash flood early warning system based on state-of-the-art probabilistic weather forecasting input data. We make use of the Limited area Ensemble Prediction System (LEPS) provided by the Consortium for Small scale Modeling (COSMO). COSMO-LEPS ensembles are fed into a distributed hydrological model, to obtain discharge estimates. Likewise, discharge climatology is created from a continuous meteorological dataset based on 30-year COSMO-LEPS hindcasts, and used as reference to detect threshold exceedance in the operational ensemble hydrographs. Coherent reference climatology is particularly useful for flash flood events, as they often take place in small watersheds, where no gauge measurements are available. The concept of persistence of meteorological forecasts is also tested as a method to improve the detection of severe events. Starting from the operational 5-km simulation at the European scale, when a signal for possible flash flooding is detected a regional catchment-scale simulation is activated on a finer spatial scale (1 km grid). Two targeted analyses are carried out to investigate: a) an automatic rule to activate the fine-scale analysis, and b) the influence of initial conditions on the estimated hydrographs, and in turn on threshold exceedances. The Gardon d'Anduze catchment, in the south of France, is chosen as a case study. A number of simulations are performed and results are analyzed and discussed. Our findings show that flash floods can sometimes be detected with a considerable lead time, especially if compared to the response time of the catchments where these phenomena take place. However, the amount of uncertainty related to the forecast is considerable, therefore the choice of appropriate thresholds for flash flood detection is of crucial importance and should account for the maximum acceptable number of either false alarms and undetected events.

  6. 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

  7. The Biology of the Rheumatoid Synovial Cell

    PubMed Central

    Haselwood, Douglas M.; Castles, James J.

    1977-01-01

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

  8. New insight into the rheumatoid vasculitis.

    PubMed

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

    2015-01-01

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

  9. Proteomics in Rheumatoid Arthritis Research

    PubMed Central

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

    2015-01-01

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

  10. The Rheumatoid Arthritic At Home

    PubMed Central

    Hunt, T. E.

    1977-01-01

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

  11. [New therapies for rheumatoid arthritis].

    PubMed

    Salgado, Eva; Maneiro, José Ramón

    2014-11-18

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage and bone. Advances in the knowledge of disease pathogenesis allowed the identification of novel therapeutic targets such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT phosphorylation. At present there are 5 TNF antagonists approved for RA. Tocilizumab blocks the pathway of IL-6 and is the only biological with proven efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is the first kinase inhibitor approved for this disease. Biologic drugs have proven efficacy, almost always in combination with methotrexate, and even halt radiographic progression. Monitoring infection is the main precaution in handling these patients. PMID:24461738

  12. Microbial Infection and Rheumatoid Arthritis

    PubMed Central

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

    2014-01-01

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

  13. 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

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

    PubMed Central

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

    2014-01-01

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

  15. 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.

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

    NASA Astrophysics Data System (ADS)

    Mori, Masao; Ferrara, Andrea; Madau, Piero

    2002-05-01

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

  17. 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 12.6±11.1 and 31.2±14.7 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: 0.12±0.14 and 0.08±0.08, for the Snellen and ETDRS charts, respectively. Reproducibility, expressed as test-retest variability, was superior in the ETDRS charts: 0.23±0.17 and 0.11±0.09 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. PMID:26949621

  18. 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

  19. 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 ...

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Rheumatoid arthritis: an evolutionary force in biologics.

    PubMed

    Brown, Philip M; Isaacs, John D

    2015-01-01

    The advent of biologic therapy has transformed the outcomes of patients with Rheumatoid Arthritis (RA), but has also highlighted important issues for their development. Early attempts at T-cell driven therapies gave mixed results with difficulties extrapolating from non-human models to first in man trials. There is currently one T-cell modulating therapy - abatacept - licenced for use in RA. Cytokine inhibition has proven to be more fruitful with a number of anti-TNF and IL6 agents either licenced for use in RA or in development. The B-cell depleting therapy rituximab has also shown good efficacy as a chemotherapy agent repurposed for RA treatment. Overall the biologics show good efficacy in RA and have been shown to retard progression of radiographic joint damage. However, this benefit comes with a burden of increased infection risk and a financial cost significantly higher than conventional disease modifying therapies. As a result current UK licencing holds the biologics in reserve following failure of a conventional therapy and the presence of moderate to severely active disease. The long term use of the biologics in RA has highlighted the risk of immunogenicity, with significant proportions of patients developing anti-drug antibodies and losing therapeutic effect. The side effect profile and cost also raise the question around duration of therapy and trials of drug tapering following disease remission are now taking place with several biologic agents. Our inability to stratify patients to the most appropriate biologic drug (stratified or precision medicine) has also catalysed a large and critically important research agenda. Beyond identifying new biologic targets, the development of biosimilar agents will likely drive the future shape of the RA biologics market as lower cost alternatives are developed, thereby improving access to these therapies. PMID:25760301

  5. 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

  6. Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis.

    PubMed

    Sangueza, Omar P; Caudell, Misty D; Mengesha, Yebabe M; Davis, Loretta S; Barnes, Cheryl J; Griffin, Julia E; Fleischer, Alan B; Jorizzo, Joseph L

    2002-08-01

    Palisaded neutrophilic granulomatous dermatitis (PNGD) is an entity that has not been clearly defined either clinically or histopathologically. It is seen in patients with rheumatoid arthritis and other connective tissue diseases. In the past, many cases of PNGD have been described under several different names including palisaded neutrophilic and granulomatous dermatitis, linear subcutaneous bands, interstitial granulomatous dermatitis with cutaneous cords and arthritis, rheumatoid papules, and Churg-Strauss granuloma. We report 7 additional cases of PNGD. Clinically, 6 patients presented with erythematous to violaceous plaques, papules, and nodules on multiple body sites; one presented with subcutaneous linear bands on the shoulder. Five had rheumatoid arthritis; one had adult-onset Still's disease; and one showed clinical signs of rheumatoid arthritis, although serologically the rheumatoid factor was negative. On histologic examination, a spectrum of changes was observed ranging from urticaria-like infiltrates to leukocytoclastic vasculitis and granuloma annulare with neutrophils. We report these cases to expand the histologic spectrum of this entity and to further delineate the different forms of clinical presentation. PMID:12140472

  7. 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

  8. 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

  9. 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

  10. Interleukin 6 and Rheumatoid Arthritis

    PubMed Central

    Yoshida, Yuji

    2014-01-01

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

  11. 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.

  12. 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

  13. 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.

  14. Isolated Rheumatoid Nodules: A Diagnostic Dilemma

    PubMed Central

    Gale, Michael; Gilbert, Erin; Blumenthal, David

    2015-01-01

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

  15. [Seronegative hashitoxicosis in patient with rheumatoid arthritis].

    PubMed

    Spina, M P; Cerri, A; Piacentini, V; Stringa, A; Visca, U

    1990-01-01

    Hashimoto's thyroiditis is known to occur in conjunction with other autoimmune disorders including rheumatoid arthritis. We describe herein a patient with long before-onset seronegative rheumatoid arthritis who developed Hashimoto's thyroiditis and hyperthyroidism without serologic evidence of thyroglobulin, microsomal and/or anti-TSH receptor antibodies. The occurrence of these autoimmune diseases in individual patients suggests an imbalance in immune function which effects more than one organ system. The predisposition to this spectrum of autoimmune diseases may be genetically determined, with specific HLA haplotypes associated with a variety of autoimmune diseases. The case of this patient provides the demonstration that intrathyroidal lymphocytes in autoimmune thyroid disorders and T-lymphocytes in the synovium are responsible for mediating the glandular destruction in Hashimoto disease and intraarticular lesions in rheumatoid arthritis, since the disorders can exist without evidence of a systemic immune response. PMID:2101432

  16. 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

  17. 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.

  18. 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

  19. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid...

  20. 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

  1. [Therapeutic update in rheumatoid arthritis].

    PubMed

    Lequerré, T; Avenel, G; Vittecoq, O

    2013-12-01

    The treatment of rheumatoid arthritis (RA) was revolutionized by the introduction of the biologics. Their power and their good safety profile have allowed to define new objectives and procedures to reach them; it is the "treat to target" concept. New recommendations were published by EULAR or ACR to obtain the remission as soon as possible. Disease-modifying antirheumatic drugs, in particular the methotrexate (MTX), remain the cornerstone of RA treatment in association with symptomatic treatments. The use of corticosteroids can be necessary to control the disease activity in the waiting time of the DMARDs efficiency or to control a flare. The absence of remission after 3months after initiation of MTX should prompt the rheumatologist to intensify the treatment with biologics. The increasing number of biologics targeting different mechanisms (5 anti-tumor necrosis factor-α, antagonist of interleukine-1 [IL-1] receptor, antagonist of IL-6 receptor, anti-CD20, anti-cytotoxic T-lymphocyte antigen 4) asks the question of the strategy in their prescription. Besides, all the registers or meta-analysis plead in favor of a good safety subject to a moderate prescription and to a greater vigilance. Except the opportunist infections, it is more the comorbidities or the associated treatments such as corticoids or MTX, which would favor the infections than anti-TNFα. There is no indication that biologics may increase the risk of solid cancer compared with a population of RA patients not exposed to anti-TNFα. However, biologics could increase the risk of cutaneous cancers, including melanoma. PMID:24200099

  2. Acute periostitis in early acquired syphilis simulating shin splints in a jogger.

    PubMed

    Meier, J L; Mollet, E

    1986-01-01

    Acute periostitis affecting the long bones is a characteristic but uncommon manifestation of syphilis in the adult with an early acquired infection. This report describes the history of a jogger who developed acute localized periostitis of the shaft of both tibiae during the early stage of acquired syphilis. Symptomatology was initially attributed to the medial tibial stress syndrome. PMID:3728786

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Endothelial Dysfunction and Inflammation: Immunity in Rheumatoid Arthritis

    PubMed Central

    Yang, XueZhi; Chang, Yan; Wei, Wei

    2016-01-01

    Inflammation, as a feature of rheumatoid arthritis (RA), leads to the activation of endothelial cells (ECs). Activated ECs induce atherosclerosis through an increased expression of leukocyte adhesion molecules. Endothelial dysfunction (ED) is recognized as a failure of endothelial repair mechanisms. It is also an early preclinical marker of atherosclerosis and is commonly found in RA patients. RA is now established as an independent cardiovascular risk factor, while mechanistic determinants of ED in RA are still poorly understood. An expanding body of study has shown that EC at a site of RA is both active participant and regulator of inflammatory process. Over the last decade, a role for endothelial dysfunction in RA associated with cardiovascular disease (CVD) has been hypothesized. At the same time, several maintenance drugs targeting this phenomenon have been tested, which has promising results. Assessment of endothelial function may be a useful tool to identify and monitor RA patients. PMID:27122657

  8. A rheumatoid arthritis study by Fourier transform infrared spectroscopy

    NASA Astrophysics Data System (ADS)

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

    2012-01-01

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

  9. Lungs, joints and immunity against citrullinated proteins in rheumatoid arthritis.

    PubMed

    Catrina, Anca I; Ytterberg, A Jimmy; Reynisdottir, Gudrun; Malmström, Vivianne; Klareskog, Lars

    2014-11-01

    Rheumatoid arthritis (RA) is a prototype for a criterion-defined inflammatory disease, for which the aetiology and initial molecular pathogenesis has been elusive for a long time. We describe in this Review how studies on the interplay between specific immunity, alongside genetic and environmental predisposing factors, provide new tools to understand the molecular basis of distinct subsets of the disease. A particular emphasis is on the possibility that pathogenic immune reactions might be initiated at other sites than the joints, and that the lungs could harbour such sites. New data strengthen this concept, showing that local immunity towards citrullinated proteins and accompanying inflammation might be present in the lungs early during disease development. This progress makes RA an interesting case for the future development of therapies that might be directed against disease-inducing immunity even before inflammation and destruction of joints has begun. PMID:25072264

  10. 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.

  11. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  13. Rheumatoid Arthritis - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Arthritis and Musculoskeletal and Skin Diseases Spanish (español) Artritis reumatoide Vietnamese (Tiếng Việt) What Is Rheumatoid Arthritis? English Bệnh Thấp Khớp Là Gì? - Tiếng ...

  14. Rheumatoid Arthritis and Complementary Health Approaches

    MedlinePlus

    ... Griner E, McFann K, Nahin RL. Complementary and alternative medicine use among adults: United States, 2002. CDC Advance ... rheumatoid arthritis: a review. Evidence-Based Complementary and Alternative Medicine: e-CAM . 2005;2(3):301–308. Cameron ...

  15. 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

  16. 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…

  17. 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".

  18. 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

  19. Vitamin D and rheumatoid arthritis

    PubMed Central

    Athanassiou, Panagiotis; Lyraki, Aikaterini; Raftakis, Ioannis; Antoniadis, Christodoulos

    2012-01-01

    Objectives: Vitamin D deficiency has been implicated in the pathogenesis of autoimmune diseases, such as diabetes mellitus type 1 and multiple sclerosis. Reduced vitamin D intake has been linked to increased susceptibility to the development of rheumatoid arthritis (RA) and vitamin D deficiency has been found to be associated with disease activity in patients with RA. The objective was to evaluate vitamin D status in patients with RA and to assess the relationship between vitamin D levels and disease activity. Methods: In a cohort of 44 patients with RA, 25-hydroxyvitamin D3 [25(OH)D3] levels, parathyroid hormone levels, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured. Disease activity was evaluated by calculating the 28-joint Disease Activity Score (DAS28). A control group (n = 44), matched for age and sex, was evaluated as well. Results: In the cohort of 44 patients with RA 25(OH)D3 levels were found to be low compared with the control group, 25(OH)D3 being 15.26 ± 1.07 ng/ml [mean ± standard error of the mean (SEM)] and 25.8 ± 1.6 ng/ml in the patient and control group respectively (Student’s t test, p < 0.001). Parathyroid hormone levels were 71.08 ± 7.02 pg/ml (mean ± SEM) (normal values 10.0–65.0 pg/ml), CRP 7.6 ± 1.57 mg/litre (mean ± SEM) (normal values < 3 mg/litre) and ESR was 38.0 ± 4.6 mm/h (mean ± SEM) in the group of patients with RA. Levels of 25(OH)D3 were found to be negatively correlated to the DAS28, the correlation coefficient being −0.084. Levels of 25(OH)D3 were also found to be negatively correlated to CRP and ESR, the correlation coefficient being –0.115 and −0.18, respectively. Conclusion: It appears that vitamin D deficiency is highly prevalent in patients with RA, and that vitamin D deficiency may be linked to disease severity in RA. As vitamin D deficiency has been linked to diffuse musculoskeletal pain, these results have therapeutic implications. Vitamin D supplementation may be needed both for the prevention of osteoporosis as well as for pain relief in patients with RA. PMID:23323190

  20. 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

  1. 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.

  2. 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

  3. Recurrent Stenosis of the Ileum Caused by Rheumatoid Vasculitis.

    PubMed

    Tago, Masaki; Naito, Yuka; Aihara, Hiroki; Furukawa, Naoko E; Yamashita, Shu-Ichi

    2016-01-01

    A 65-year-old man with a 20-year history of rheumatoid arthritis was transferred to our hospital due to a second episode of intestinal obstruction, a fever, and joint pain within the previous 6 months. He had an extremely high rheumatoid factor level and decreased complement levels. Abdominal computed tomography, a small bowel series, and small intestinal endoscopy revealed severe ileal stenosis. Resection of the stenotic lesion was performed, and a histopathological examination revealed vasculitis. Rheumatoid vasculitis was diagnosed, and the patient began treatment with prednisolone and methotrexate, which improved his condition. Rheumatoid vasculitis is a rare, but possible cause of recurrent bowel obstruction. PMID:27041172

  4. Fistulization of rheumatoid joints. Spectrum of identifiable syndromes.

    PubMed Central

    Shapiro, R F; Resnick, D; Castles, J J; D'Ambrosia, R D; Lipscomb, P R

    1975-01-01

    Eight patients with rheumatoid arthritis developed cutaneous fistulae adjacent to affected joints. Rheumatoid factor was positive in eight patients; subcutaneous nodules were noted in seven. Two patients had features of rheumatoid vasculitis. A spectrum of syndrome characterized by cutaneous fistulae was observed. Three patients showed classical fistulous rheumatism. Four patients developed septic arthritis which subsequently fistulized; in two, infection was associated with total joint replacement. One patient showed a cutaneous sinus accompanying a large calf cyst. A variety of diagnoses must be considered when cutaneous fistulae appear near joints in patients with rheumatoid arthritis. Images PMID:1221937

  5. 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

  6. Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations.

    PubMed

    Lei, Hongxing; Wang, Xiaofeng; Wu, Chun

    2012-09-01

    The intercalation mode between doxorubicin (an anticancer drug) and two 6-base-pair DNA model fragments (d(CGATCG)₂ and d(CGTACG)₂) has been well studied by X-ray crystallography and NMR experimental methods. Yet, the detailed intercalation pathway at molecular level remains elusive. In this study, we conducted molecular dynamics binding simulations of these two systems using AMBER DNA (parmbsc0) and drug (GAFF) force fields starting from the unbound state. We observed outside binding (minor groove binding or end-binding) in all six independent binding simulations (three for each DNA fragment), followed by the complete intercalation of a drug molecule in two simulations (one for each DNA fragment). First, our data directly supported that the minor groove binding is the dominant pre-intercalation step. Second, we observed that the opening and flipping of a local base pair (A3-T10 for d(CGATCG)₂ and C1-G12 for d(CGTACG)₂) in the two intercalation trajectories. This locally cooperative flipping-intercalation mechanism was different from the previously proposed rise-insertion mechanism by which the distance between two neighboring intact base pairs increases to create a space for the drug insertion. Third, our simulations provided the first set of data to support the applicability of the AMBER DNA and drug force fields in drug-DNA atomistic binding simulations. Implications on the kinetics pathway and drug action are also discussed. PMID:23079648

  7. Infectious arthritis in patients with rheumatoid arthritis.

    PubMed Central

    Mateo Soria, L; Miquel Nolla Solé, J; Rozadilla Sacanell, A; Valverde García, J; Roig Escofet, D

    1992-01-01

    Eleven cases of infectious arthritis occurring in patients with rheumatoid arthritis are reported. Staphylococcus aureus was the causative organism in eight patients. Streptococcus anginosus and Streptococcus agalactiae in one patient each, and Mycobacterium tuberculosis in two patients. The mean duration of symptoms before diagnosis was 16 days in patients with pyogenic arthritis. The diagnosis of joint infection caused by Mycobacterium tuberculosis was especially delayed (57 days). Four patients died; they were found to have a longer time to diagnosis and two of them had multiple joint infection. Although Staphylococcus aureus is the microorganism most often affecting patients with rheumatoid arthritis, infection caused by Mycobacterium tuberculosis must also be considered in such patients. PMID:1575593

  8. 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

  9. 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

  10. 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

  11. [Endoprosthetic replacement of the rheumatoid wrist].

    PubMed

    Thabe, H

    2011-07-01

    For patients with rheumatoid arthritis preventive and reconstructive surgery of the hand provide better functional results and higher patient satisfaction when surgery is done adequately before the inflammatory stage, especially when multiple joints are affected. Synovectomy, arthrodesis and prosthetic reconstruction are able to guarantee maintenance of function even in late stages and severe destruction, when modern drug therapy cannot prevent further inflammatory attacks and increasing destruction. PMID:21691913

  12. [Endoprosthetic replacement of rheumatoid finger joints].

    PubMed

    Thabe, H

    2011-07-01

    Resection arthroplasty, arthrodesis and prosthetic reconstruction are able to guarantee the maintenance of good functional ability of finger joints even in late stages and with severe destruction. Destruction of soft tissues of the finger joints cannot be corrected by prosthetic measures alone. A stabile situation of the wrist joint is one of the most important prerequisites for a normal performance of daily life activities. Silastic endoprostheses are still the gold standard for finger replacement in rheumatoid arthritis. PMID:21695554

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

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  14. Computer simulation in conjunction with medical thermography as an adjunct tool for early detection of breast cancer

    PubMed Central

    Ng, Eddie Y-K; Sudharsan, NM

    2004-01-01

    Background Mathematical modelling and analysis is now accepted in the engineering design on par with experimental approaches. Computer simulations enable one to perform several 'what-if' analyses cost effectively. High speed computers and low cost of memory has helped in simulating large-scale models in a relatively shorter time frame. The possibility of extending numerical modelling in the area of breast cancer detection in conjunction with medical thermography is considered in this work. Methods Thermography enables one to see the temperature pattern and look for abnormality. In a thermogram there is no radiation risk as it only captures the infrared radiation from the skin and is totally painless. But, a thermogram is only a test of physiology, whereas a mammogram is a test of anatomy. It is hoped that a thermogram along with numerical modelling will serve as an adjunct tool. Presently mammogram is the 'gold-standard' in breast cancer detection. But the interpretation of a mammogram is largely dependent on the radiologist. Therefore, a thermogram that looks into the physiological changes in combination with numerical simulation performing 'what-if' analysis could act as an adjunct tool to mammography. Results The proposed framework suggested that it could reduce the occurrence of false-negative/positive cases. Conclusion A numerical bioheat model of a female breast is developed and simulated. The results are compared with experimental results. The possibility of this method as an early detection tool is discussed. PMID:15113442

  15. 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.

  16. 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

  17. 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 ...

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  1. Early stage oxynitridation process of Si(001) surface by NO gas: Reactive molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Cao, Haining; Srivastava, Pooja; Choi, Keunsu; Kim, Seungchul; Lee, Kwang-Ryeol

    2016-03-01

    Initial stage of oxynitridation process of Si substrate is of crucial importance in fabricating the ultrathin gate dielectric layer of high quality in advanced MOSFET devices. The oxynitridation reaction on a relaxed Si(001) surface is investigated via reactive molecular dynamics (MD) simulation. A total of 1120 events of a single nitric oxide (NO) molecule reaction at temperatures ranging from 300 to 1000 K are statistically analyzed. The observed reaction kinetics are consistent with the previous experimental or calculation results, which show the viability of the reactive MD technique to study the NO dissociation reaction on Si. We suggest the reaction pathway for NO dissociation that is characterized by the inter-dimer bridge of a NO molecule as the intermediate state prior to NO dissociation. Although the energy of the inter-dimer bridge is higher than that of the intra-dimer one, our suggestion is supported by the ab initio nudged elastic band calculations showing that the energy barrier for the inter-dimer bridge formation is much lower. The growth mechanism of an ultrathin Si oxynitride layer is also investigated via consecutive NO reactions simulation. The simulation reveals the mechanism of self-limiting reaction at low temperature and the time evolution of the depth profile of N and O atoms depending on the process temperature, which would guide to optimize the oxynitridation process condition.

  2. Demonstration of a cross-reactive idiotype (IdRQ) in rheumatoid factors from patients with rheumatoid arthritis but not in rheumatoid factors from healthy, aged subjects.

    PubMed

    Ruiz-Arguelles, A; Presno-Bernal, M

    1989-02-01

    A human monoclonal IgM kappa paraprotein with rheumatoid factor (RF) activity was used to elicit antiidiotypic antibodies in rabbits. The antiidiotypic antiserum thus obtained reacted with samples from 40% of 72 rheumatoid arthritis patients, but not with any of the samples from 22 aged control subjects having serum RF. Our findings suggest that, despite the similarities between RF from rheumatoid arthritis patients and that from healthy individuals, the expression of V region genes may be different in healthy subjects and those with the disease. PMID:2920049

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

    PubMed

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

    2013-01-01

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

  4. Heparan Sulfate Differences in Rheumatoid Arthritis versus Healthy Sera

    PubMed Central

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

    2015-01-01

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

  5. 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.

  6. Bone marrow edema and osteitis in rheumatoid arthritis: the imaging perspective

    PubMed Central

    2012-01-01

    Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and widespread lesion that is often apparent at the hands and wrists but has also been described elsewhere, including the feet. It may occur in early or late disease and has been shown in several large cohort studies to have major negative implications for prognosis. It is the strongest predictor of erosive progression yet to be identified and characteristically occurs in those patients with the most aggressive and potentially disabling disease. In patients with undifferentiated arthritis, bone edema also predicts progression to criteria-positive RA, both independently and to a greater extent when combined with anti-cyclic citrullinated peptide status or rheumatoid factor positivity. Its histological correlate in the late stages of RA has been shown to be osteitis, in which the bone marrow beneath the joint is invaded by an inflammatory and vascular lymphoplasmacytic infiltrate. This lies adjacent to trabecular bone, where increased numbers of osteoclasts have been observed within resorption lacunae, suggesting a mechanistic link between inflammation and erosive bone damage. This could lead to erosion both of the overlying cortex, leading to classic radiographic rheumatoid erosions, and of local trabecular bone, possibly contributing to periarticular osteopenia and cyst formation. In addition to synovitis, osteitis is now regarded as a major rheumatoid lesion that is responsive to therapeutic intervention. PMID:23043770

  7. 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

  8. Serum protein fractions in rheumatoid pneumoconiosis without arthritis

    PubMed Central

    Payne, R. B.

    1962-01-01

    Fractionation of the serum proteins by filter-paper electrophoresis in 14 coal-miners who had the characteristic radiological opacities of rheumatoid pneumoconiosis but no evidence of rheumatoid arthritis showed a reduction in the mean level of albumin and increases in the alpha-2 and gamma-globulins compared with the values in non-arthritic miners with simple coal-workers' pneumoconiosis and in normal subjects. The changes were smaller than those found in miners with both rheumatoid arthritis and the radiological appearances of rheumatoid pneumoconiosis (Caplan's syndrome) and the mean levels did not differ significantly from those found in non-arthritic miners with progressive massive fibrosis. It is concluded that estimation of the serum protein fractions, unlike tests for rheumatoid factors, is unlikely to help in the differential diagnosis of unusual opacities seen on chest radiographs of miners without arthritis. PMID:13942168

  9. 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.

  10. 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.

  11. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-05-01

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

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

    PubMed

    Kilic, Gamze; Ozgocmen, Salih

    2015-01-18

    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

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

    PubMed Central

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

    2015-01-01

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

  15. Cryoimmunoglobulinemia in rheumatoid arthritis. Significance in serum of patients with rheumatoid vasculitis.

    PubMed Central

    Weisman, M; Zvaifler, N

    1975-01-01

    Cryogloculins were examined in a standardized manner in an unselected group of 35 patients with rheumatoid arthritis (RA) and 8 patients with RA complicated by cutaneous vasuclitis and neuropathy. Optimum conditions for detection and characterization of cryoglobulins were established; the proportion of resolubilized to total precipitable protein remained constant in an individual patient under these conditions. All 8 vascultis patients and 9 of 35 other patients with RA exhibited cryoglobulins; total protein and immunoglobin content were significantly higher in the cryoglobulins of patients with vasculitis. Immunoglobulins G and M constituted two-thirds and three-quarters of the total protein in the cryoglobulins from uncomplicated rheumatoid and vasculitis patients, respectively. Serum antiglobulin titers were higher, and serum C3 levels were lower, in vasculitis patients compared to rheumatoid patients without vasclitis. Anti-gamma globulin activity was detected in all cryoglobulins from vasculitis patients. Cryoglobulin IgG and IgM were polyclonal. Density gradient analyses demonstrated the majority of the cryoglobulin activity to reside in the 19S IgM fraction. There was no evidence of a light weight (8S) IgM. A monoclonal rheumatoid factor did not detect 7S-ANTI-7S complexes in the cryoprecipitates, but acid eluates from some cryoglobulins absorbed with insoluble IgG revealed an antiglobulin of the IgG class. Serial studies performed on vasculitis patients treated with cyclophosphamide disclosed a relationship between clinical evidence of vasculitis and the presence of cryoglobulins. The antigen (IgG) and antibody (largely IgM rheumatoid factor) nature of these cryglobulins is presented as evidence that the widespread vascular complications of RA are mediated, at least in part, by circulating immune complexes. PMID:169295

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

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

    NASA Astrophysics Data System (ADS)

    Elliott, Scott; Maltrud, Mathew; Reagan, Matthew; Moridis, George; Cameron-Smith, Philip

    2011-03-01

    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 CH4 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.

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

    SciTech Connect

    Mouton, I.; Talbot, E. Pareige, C.; Lardé, R.; Blavette, D.

    2014-02-07

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

  4. Gestational and Early Postnatal Exposure to Simulated High Altitude Does Not Modify Postnatal Body Mass Growth Trajectory in the Rat

    PubMed Central

    Champin, Graciela M.; Bozzini, Clarisa; Alippi, Rosa M.

    2014-01-01

    Abstract Bozzini, Carlos E, Graciela M. Champin, Clarisa Bozzini, and Rosa M. Alippi. Gestational and Early Postnatal Exposure to Simulated High Altitude Does Not Modify Postnatal Body Mass Growth Trajectory in the Rat. High Alt Med Biol 15:418–421, 2014.—Postnatal hypoxia blunts body mass growth. It is also known that the quality of the fetal environment can influence the subsequent adult phenotype. The main purpose of the study was to determine whether gestational hypoxia and early postnatal hypoxia are able to blunt growth when the offspring is raised under normoxia. Hypobaric hypoxia was induced in simulated high altitude (SHA) chambers in which air was maintained at 380 mmHg (5450 m). Mature Sprague-Dawley rats of both sexes were divided in normoxic (NX) and hypoxic (HX) groups and, in the case of the HX group, maintained for 1 month at 5450 m. Mating was then allowed under NX or HX conditions. Offspring were NX-NX, NX-HX, HX-HX, or HX-NX: the first term indicates NX or HX during both gestation and the first 30 days of life; the second term indicates NX or HX during postnatal life between days 30 and 133. Body mass (g) was measured periodically and body mass growth rate (BMGR, g/d) was estimated between days 33 and 65 of postnatal life. Results can be summarized as follows: 1) BM was significantly higher in NX than in HX rats at weaning; 2) BMGR was not significantly different between NX-NX and HX-NX rats, and between HX-HX and NX-HX animals; and 3) BMGR was significantly higher in rats living under NX conditions than in those living under HX conditions during postnatal life. Data suggest that that hypobaric hypoxia during gestational and early postnatal development of rats does not alter the regulation of body mass growth in rats when compared to that seen under sea-level conditions. PMID:25184739

  5. 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.

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

    PubMed Central

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

    2013-01-01

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

  7. Formation and evolution of early-type galaxies: spectro-photometry from cosmo-chemo-dynamical simulations

    NASA Astrophysics Data System (ADS)

    Tantalo, R.; Chinellato, S.; Merlin, E.; Piovan, L.; Chiosi, C.

    2010-07-01

    Context. One of the major challenges in modern astrophysics is to understand the origin and the evolution of galaxies, the bright, massive early type galaxies (ETGs) in particular. There is strong observational evidence that massive ETGs are already in place at redshift z ~ 2-3 and that they formed most of their stars well before z = 1. Therefore, these galaxies are likely to be good probes of galaxy evolution, star formation and, metal enrichment in the early Universe. Aims: In this context it is very important to set up a diagnostic tool able to combine results from chemo-dynamical N-Body-TSPH (NB-TSPH) simulations of ETGs with those of spectro-photometric population synthesis and evolution so that all key properties of galaxies can be investigated. These go from the integrated spectrum and magnitudes in any photometry, both in the rest-frame and as a function of the redshift, to present-day structural properties. The main goal of this paper is to provide a preliminary validation of the software package before applying it to the analysis of observational data. Methods: The galaxy models in use where calculated by the Padova group in two different cosmological scenarios: the standard cold dark matter cosmology (SCDM), and the so-called Concordance cosmology (Λ CDM, with Ω_Λ = 0.762). For these template galaxies, we recover their spectro-photometric evolution through the entire history of the Universe. This is done in particular for two important photometric systems, the Bessell-Brett and the Sloan Digital Sky Survey (SDSS) passbands. Results: We computed magnitudes and colors and their evolution with the redshift along with the evolutionary and cosmological corrections for the model galaxies at our disposal, and compared them with data for ETGs taken from the COSMOS and the GOODS databases. Finally, starting from the dynamical simulations and photometric models at our disposal, we created synthetic images in a given photometric system, from which we derived the structural and morphological parameters. In addition to this, we address the question of the scaling relations, and in particular we examine the one by Kormendy. The theoretical results are compared with observational data of ETGs selected form the SDSS database. Conclusions: The simulated colors for the different cosmological scenarios follow the general trend shown by galaxies of the COSMOS and GOODS surveys at lower redshifts and are in good agreement with the data up to z ~ 1, where the number of early-type galaxies observed falls abruptly. In conclusion, within the redshift range considered, all the simulated colors reproduce the observational data quite well. Looking at the structural parameters derived from the surface imaging, the luminosities and effective radii (Kormendy relation) measured for our model galaxies are consistent with the archival data from the SDSS.

  8. Laser transillumination for diagnosis of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Boerner, E.; Podbielska, H.; Bauer, J.; Dmochowska, L.; Dziewięcka, 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.

  9. Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis

    PubMed Central

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

    2014-01-01

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

  10. Developments in the clinical understanding of rheumatoid arthritis

    PubMed Central

    Smolen, Josef S; Aletaha, Daniel

    2009-01-01

    The changes occurring in the field of rheumatoid arthritis (RA) over the past decade or two have encompassed new therapies and, in particular, a new look at the clinical characteristics of the disease in the context of therapeutic improvements. It has been shown that composite disease activity indices have special merits in following patients, that disease activity governs the evolution of joint damage, and that disability can be dissected into several components – among them disease activity and joint damage. It has also been revealed that aiming at any disease activity state other than remission (or, at worst, low disease activity) is associated with significant progression of joint destruction, that early recognition and appropriate therapy of RA are important facets of the overall strategy of optimal clinical control of the disease, and that tight control employing composite scores supports the optimization of the therapeutic approaches. Finally, with the advent of novel therapies, remission has become a reality and the treatment algorithms encompassing all of the above-mentioned aspects will allow us to achieve the rigorous aspirations of today and tomorrow. PMID:19232060

  11. 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

  12. [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

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

    PubMed Central

    2014-01-01

    Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ3 integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein. PMID:25099015

  14. 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

  15. 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

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

    PubMed Central

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

    2015-01-01

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

  17. 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

  18. 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

  19. 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

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

    PubMed

    Woś, Bartłomiej; Pietrzykowski, Marcin

    2015-07-01

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

  1. [Occurrence of subcutaneous rheumatoid nodules in patients with rheumatoid arthritis in Croatia].

    PubMed

    Vlak, T; Grazio, S; Jajić, Z

    1998-01-01

    The subcutaneous rheumatoid nodules (RN) have been recognized by the American Rheumatism Association, both in 1958 and in 1987, as one of the diagnostic criteria (ARA criteria) among other rheumatoid arthritis (RA) symptoms. The aim of this research has been both to provide the incidence of occurrence of RN in patients with RA in Croatia and to determine its significance in making the RA diagnose. The test group comprised 233 patients (182 women and 51 men) with RA, their average age being 48.3 years in the range of 18 to 77. Both the anamnesis and the clinical examination have determined the occurrence of RN in 54 (23.2%) of 233 patients. The range of occurrences was more evident in men (31.4%) than in women (20.8%), though this difference was statistically irrelevant. The most common localization of benign rheumatoid nodules was the exterior side of elbow and PIP hand joints. The obtained results prove that the incidence of RN in our tested patients with RA can be compared with those of the earlier researches done in Croatia (18.1% Jajić, Vlak; 20-25% Jajić), as well as with those obtained in the western European countries (20% Doherty, George; 25% Ziff; 20-25% Miehle; 21% Wolf et al.). PMID:9921005

  2. 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

  3. A 15-year exercise program for rheumatoid vasculitis.

    PubMed

    Marley, W P; Santilli, T F

    1998-01-01

    A rare case of rheumatoid vasculitis and responses to a 15-year supervised exercise program. This patient presented with significant impairment in mobility and physical work capacity. His exercise tolerance improved considerably and he benefited emotionally. PMID:9572643

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

    MedlinePlus

    ... Effective Health Care Program EHC Component EPC Project Topic Title Drug Therapy for Rheumatoid Arthritis in Adults: ... Review Jun. 1, 2012 Related Products for this Topic Research Protocol Dec. 6, 2010 Executive Summary Apr. ...

  5. Antibodies Act Jointly to Promote Inflammation in Rheumatoid Arthritis

    MedlinePlus

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

  6. 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.

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

    PubMed

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

    1976-01-01

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

  8. 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

  9. [New drugs and treatment strategies for rheumatoid arthritis].

    PubMed

    Fantini, Flavio

    2003-09-01

    The management of rheumatoid arthritis (RA) has changed considerably during the past 15 years. Current strategies emphasize the need for early diagnosis and therapeutic intervention based on the use of disease modifying antirheumatic drugs (DMARDs). More than a dozen drugs or drug classes of DMARDs are currently in common use in RA. After a long hiatus, drug development for RA resumed a few years ago with the introduction of Leflunomide and the biologic agents. Unlike the older DMARDs (apart from the cytotoxics) the newer drugs were designed with strict reference to RA pathophysiology and the intended action of these agents is highly likely the explanation for the observed efficacy. Proinflammatory cytokines, such as interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF), play an important role in maintaining the chronicity of RA and mediating tissue damage. TNF antagonists have rapidly emerged as a valuable class of antirheumatic agents. Etanercept, a dimerized version of the soluble TNF receptor II, and infliximab, a chimeric anti-TNF monoclonal antibody, are currently approved in our country for the treatment of refractory RA in the frame of ANTARES Project. Other two biologic agents, adalimumab, a fully humanized anti-TNF monoclonal antibody, and anakinra, a recombinant human IL-1 receptor antagonist, will be also soon available. It is recommended to initiate pharmacological treatment with an effective DMARD early in the course of the disease. Biological therapies have the potential to revolutionize the treatment of RA; however the use of TNF blocking agents as the first DMARD for the treatment of RA should, at present, be limited, because these compounds are expensive and one needs to include cost considerations along with those of efficacy, effectiveness and long-term safety. PMID:12942798

  10. News and Views: Sculptor image shows VST potential; Eccentric dust ring signals planets; Simulations show early black holes were fast eaters

    NASA Astrophysics Data System (ADS)

    2012-02-01

    Planets form around stars in dusty discs; the process remains uncertain. Now adaptive optics on the Subaru Telescope has revealed disruptions to a debris disc that indicate large planetary bodies - and their sizes and orbits. The largest cosmological simulation yet throws light on the formation of the first galaxies, suggesting that early supermassive black holes gained their mass from thin streams of cold gas.

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

    PubMed Central

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

    2015-01-01

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

  12. Parasympathetic dysfunction in rheumatoid arthritis patients with ocular dryness.

    PubMed Central

    Barendregt, P J; van der Heijde, G L; Breedveld, F C; Markusse, H M

    1996-01-01

    OBJECTIVE: To determine whether abnormalities in the function of the autonomic nervous system are associated with oral and ocular dryness in rheumatoid arthritis. METHODS: Pupillography was done using an infrared light reflection method (IRIS) to measure both parasympathetic function (constriction latency and the latency of maximum constriction velocity (MCV)) and sympathetic function (dilatation latency) in rheumatoid arthritis patients with and without ocular dryness. The Schirmer and Saxon tests were used to measure the tear and saliva production respectively. RESULTS: The Schirmer and Saxon test results in rheumatoid arthritis patients with ocular dryness were reduced (P < 0.05) compared with rheumatoid arthritis patients without ocular dryness and healthy controls. Constriction latency and MCV latency were prolonged in rheumatoid arthritis patients with ocular dryness compared to the other two groups (P < 0.05). A negative correlation was found between the degree of ocular dryness and both constriction latency and MCV latency. No correlation was found between the results of pupillography and saliva production. CONCLUSIONS: Parasympathetic dysfunction may play a role in ocular dryness in patients with rheumatoid arthritis. PMID:8882130

  13. Multidimensional Simulations for Early-Phase Spectra of Aspherical Hypernovae: SN 1998bw and Off-Axis Hypernovae

    NASA Astrophysics Data System (ADS)

    Tanaka, Masaomi; Maeda, Keiichi; Mazzali, Paolo A.; Nomoto, Ken'ichi

    2007-10-01

    Early-phase optical spectra of aspherical jet-like supernovae (SNe) are presented. We focus on energetic core-collapse SNe, or hypernovae. Based on hydrodynamic and nucleosynthetic models, radiative transfer in the SN atmosphere is solved with a multidimensional Monte Carlo radiative transfer code, SAMURAI. Since the luminosity is boosted in the jet direction, the temperature there is higher than in the equatorial plane by ~2000 K. This causes anisotropic ionization in the ejecta. Emergent spectra are different depending on viewing angle, reflecting both aspherical abundance distribution and anisotropic ionization. Spectra computed with an aspherical explosion model with kinetic energy 20×1051 ergs are compatible with those of the Type Ic SN 1998bw if ~10%-20% of the synthesized metals are mixed out to higher velocities. The simulations enable us to predict the properties of off-axis hypernovae. Even if an aspherical hypernova explosion is observed from the side, it should show hypernova-like spectra but with some differences in the line velocity, the width of the Fe absorptions, and the strength of the Na I line.

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

    SciTech Connect

    Barnes, P.W.; Flint, S.D.; Caldwell, M.M. )

    1994-06-01

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

  15. 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.

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

    PubMed Central

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

    2013-01-01

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

  17. 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

  18. How does infliximab work in rheumatoid arthritis?

    PubMed Central

    2002-01-01

    Since the initial characterization of tumor necrosis factor alpha (TNFα), it has become clear that TNFα has diverse biologic activity. The realization that TNFα plays a role in rheumatoid arthritis (RA) has led to the development of anti-TNF agents for the treatment of RA. Infliximab, a chimeric monoclonal antibody that specifically, and with high affinity, binds to TNFα and neutralizes the cytokine, is currently approved for the treatment of RA and Crohn's disease, another immune-inflammatory disorder. In addition to establishing the safety and efficacy of infliximab, clinical research has also provided insights into the complex cellular and cytokine-dependent pathways involved in the pathophysiology of RA, including evidence that supports TNFα involvement in cytokine regulation, cell recruitment, angiogenesis, and tissue destruction. PMID:12110154

  19. 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

  20. 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)

  1. Effect of yogic package on rheumatoid arthritis.

    PubMed

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

    2011-01-01

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

  2. 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

  3. [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

  4. Impact of rheumatoid arthritis on sexual function

    PubMed Central

    Tristano, Antonio G

    2014-01-01

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

  5. 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

  6. 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

  7. Adherence to Methotrexate therapy in Rheumatoid Arthritis

    PubMed Central

    Arshad, Nasim; Ahmad, Nighat Mir; Saeed, Muhammad Ahmed; Khan, Saira; Batool, Shabnam; Farman, Sumaira

    2016-01-01

    Objective: To determine adherence to methotrexate (MTX) therapy in patients with Rheumatoid Arthritis (RA) and to identify factors that promote either adherence or non adherence. Methods: One hundred Rheumatoid Arthritis patients on MTX for at least two months were enrolled. Questionnaire was completed by direct interview. Details recorded were, demographics (age, sex, education, monthly income), disease duration, duration on MTX and current dose. Disease Activity Score on 28 joint counts (DAS 28) at the current visit, concomitant drugs taken and number of doses of MTX missed in the previous 8 weeks were noted. Non adherence was defined as omission of any three or more prescribed doses of MTX in previous 8 week. Patients were asked for the factors that motivated their adherence to MTX as well as factors for non adherence. Presence of side effects due to MTX was also recorded. Result: Non adherence was found among 23% of cases. Patients of low socioeconomic group (p <0.0001) and on MTX for longer duration (p <0.001) had higher non adherence. Non adherent patients had significantly higher disease activity as measured by DAS 28 (p<0.001). Good counseling and education by the doctor was a strong predictor of adherence (p <0.001). Lack of affordability (p <0.001); lack of availability at local pharmacy (p <0.001); lack of family support (p <0.001) and lack of awareness regarding need and importance of MTX (p < 0.001were found as significant factors for non adherence. Conclusion: MTX non adherence in RA is noted in about one fourth of study group. Various economical and social issues lead to non adherence but good patient education and counseling by doctor could promote adherence in this study group.

  8. 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

  9. 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, ...

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. Cost Effectiveness Analysis of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. A Systematic Review Literature

    PubMed Central

    Benucci, Maurizio; Saviola, Gianantonio; Manfredi, Mariangela; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola

    2011-01-01

    The cost effectiveness of treatments that have changed the “natural history” of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA. PMID:22162693

  14. 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

  15. Differences in early contrail evolution of two-engine versus four-engine aircraft: Lidar measurements and numerical simulations

    NASA Astrophysics Data System (ADS)

    Sussmann, Ralf; Gierens, Klaus M.

    2001-03-01

    Jet- and vortex-regime evolution of contrails behind cruising aircraft is investigated by focusing on the role of aircraft type. Cross-section measurements by ground-based lidar and observational analysis are combined with numerical simulations of fluid dynamics and microphysics in the wake of a two-engine aircraft. Depending on ambient humidity levels, contrail evolution behind short-/medium-range twin-turbofan airliners is classified into two scenarios, which is in contrast to the three scenarios observed for a wide-body four-turbofan aircraft. In the case of ice-subsaturated ambient air, a short visible contrail is formed behind a two-engine aircraft that disappears before the ice is fully entrained into the wingtip vortices (in most cases ≈4 s behind aircraft). The early evaporation of the ice is mainly due to the fast initial jet expansion, mixing the exhaust with the ambient air. Contrails behind a wide-body four-engine aircraft always survive at least until vortex breakdown (i.e., typically 2 min behind aircraft). This is simply due to the larger ice mass in the contrail because of the higher fuel flow rate. Generally, in the case of ice supersaturation, a diffuse secondary wake evolves above the primary vortex wake. For a two-engine aircraft, always the whole contrail persists, while for a four-engine aircraft, the ice inside the primary wake disappears in most cases after vortex breakdown, when the relative humidity is only slightly above ice saturation. In the more rare cases of higher ice-supersaturation the ice in the primary wake survives vortex breakdown and becomes part of the persistent contrail.

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

    PubMed Central

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

    1998-01-01

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

  17. Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis.

    PubMed Central

    Weyand, C M; McCarthy, T G; Goronzy, J J

    1995-01-01

    RA is a heterogeneous group of disorders characterized by variations in clinical manifestations, disease course, and probably response to therapeutic interventions. We have addressed the question whether genetically and potentially etiologically more homogeneous subgroups of RA patients can be defined based upon the expression of the RA-linked sequence motif in the third hypervariable region of the HLA-DRB1 gene. Genetic comparison of patients classified upon clinical manifestation and disease course demonstrated that patients with mild disease were genetically distinct from those progressing to severe and destructive disease. Specifically, rheumatoid factor (RF) negative patients preferentially expressed RA-linked HLA-DRB1 alleles with an arginine substitution in position 71, whereas the alleles with a lysine substitution in position 71 accumulated in RF+ patients. RF- patients were further subdivided based on clinical markers (time of onset of erosive disease and requirement for aggressive therapy). Clinical heterogeneity correlated with genetic heterogeneity. Patients with early erosive disease and patients requiring aggressive therapy frequently typed HLA-DRB1*04+. Patients with late erosive/nonerosive disease or a benign disease course manageable with nonaggressive treatment preferentially expressed HLA-DRB1*01 or lacked an RA-linked haplotype. These data indicate that the heterogeneity of RA reflects genetic differences. Sequence variations within the disease-linked sequence motif, as well as polymorphisms surrounding the candidate genetic element, affect pattern, course, and treatment response of RA. Amino acid position 71 in the HLA-DRB1 gene has a unique role, the understanding of which may provide important clues to disease etiology. PMID:7738179

  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. 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.

  1. 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

  2. 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.

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

    PubMed Central

    Bogoch, Earl R.

    2008-01-01

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

  4. Bone Remodelling Markers in Rheumatoid Arthritis

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Mutated citrullinated vimentin antibodies in rheumatoid arthritis.

    PubMed

    Kuna, Andrea Tesija

    2012-01-18

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

  10. TNF inhibitor therapy for rheumatoid arthritis.

    PubMed

    Ma, Xixi; Xu, Shengqian

    2013-03-01

    Immunotherapy has markedly improved treatment outcomes in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α 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-α inhibitors have similar efficacy, but distinct clinical pharmacokinetic and -dynamic properties. The common adverse events of these TNF-α 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-α therapies. Some patients may discontinue the initial drug and switch to a second anti-TNF-α 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

  11. 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

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

    PubMed

    Funakubo Asanuma, Yu

    2015-01-01

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

  13. Biologicals in rheumatoid arthritis: current and future.

    PubMed

    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

  14. [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

  15. Neutrophil gene expression in rheumatoid arthritis.

    PubMed

    Cross, Andrew; Bakstad, Denise; Allen, John C; Thomas, Luke; Moots, Robert J; Edwards, Steven W

    2005-10-01

    There is now a growing awareness that infiltrating neutrophils play an important role in the molecular pathology of rheumatoid arthritis. In part, this arises from the fact that neutrophils have potent cytotoxic activity, but additionally from the fact that inflammatory neutrophils can generate a number of cytokines and chemokines that can have a direct influence on the progress of an inflammatory episode. Furthermore, the molecular properties of inflammatory neutrophils are quite different from those normally found in the circulation. For example, inflammatory neutrophils, but not blood neutrophils, can express cell surface receptors (such as MHC Class II molecules and FcgammaRI) that dramatically alter the way in which these cells can interact with ligands to modulate immune function. Cytokine/chemokine expression and surface expression of these novel cell surface receptors is dependent upon the neutrophil responding to local environmental factors to selectively up-regulate the expression of key cellular components via signalling pathways coupled to transcriptional activation. However, major changes in the expression levels of some proteins are also regulated by post-translational modifications that alter rates of proteolysis, and hence changes in the steady-state levels of these molecules. PMID:16112850

  16. 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

  17. Serum Trace Element Concentrations in Rheumatoid Arthritis.

    PubMed

    Sahebari, Maryam; Ayati, Razie; Mirzaei, Hamed; Sahebkar, Amirhossein; Hejazi, Sepideh; Saghafi, Massoud; Saadati, Nayyereh; Ferns, Gordon A; Ghayour-Mobarhan, Majid

    2016-06-01

    Rheumatoid arthritis (RA) is a condition that is associated with oxidative stress. Serum trace elements and their related transport proteins, e.g., albumin and ceruloplasmin, play an important role in the antioxidant defense. Trace element status may therefore be involved in the pathogenesis of RA or be affected by the disease activity of this chronic inflammatory condition. The study participants were 110 patients with RA and 100 sex- and age-matched healthy volunteers. Serum concentrations of albumin, ceruloplasmin, selenium, zinc, copper, and zinc/copper ratio were measured in all subjects. The relationship between these parameters and disease activity score was also assessed. Lower concentrations of serum Alb, Zn, and Se were independently related to disease activity index. High concentrations of serum copper were associated with the presence of RA. Serum Cu concentrations were positively related to disease activity as assessed by the disease activity score. Low serum concentrations of Zn and Se, and high serum Cu concentrations may be associated with the presence of RA or be a consequence of this condition. Of the trace elements that were investigated in the present study, only serum Cu was positively correlated with disease activity. PMID:26450515

  18. 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

  19. Clocking in: chronobiology in rheumatoid arthritis.

    PubMed

    Buttgereit, Frank; Smolen, Josef S; Coogan, Andrew N; Cajochen, Christian

    2015-06-01

    Circadian rhythms are of crucial importance for cellular and physiological functions of the brain and body. Chronobiology has a prominent role in rheumatoid arthritis (RA), with major symptoms such as joint pain and stiffness being most pronounced in the morning, possibly mediated by circadian rhythms of cytokine and hormone levels. Chronobiological principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients (chronotherapy) could optimize results. Trials of NSAID or methotrexate chronotherapy for patients with RA suggest such an approach can improve outcomes and reduce adverse effects. The most compelling evidence for RA chronotherapy, however, is that coordinating the timing of glucocorticoid therapy to coincide with the nocturnal increase in blood IL-6 levels results in reduced morning stiffness and pain compared with the same glucocorticoid dose taken in the morning. Aside from optimizing relief of the core symptoms of RA, chronotherapy might also relieve important comorbid conditions such as depression and sleep disturbances. Surprisingly, chronobiology is not mentioned in official guidelines for conducting RA drug registration trials. Given the imperative to achieve the best value with approved drugs and health budgets, the time is ripe to translate the 'circadian concept' in rheumatology from bench to bedside. PMID:25800214

  20. 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.

  1. Molecular discrimination of responders and nonresponders to anti-TNFalpha therapy in rheumatoid arthritis by etanercept

    PubMed Central

    Koczan, Dirk; Drynda, Susanne; Hecker, Michael; Drynda, Andreas; Guthke, Reinhard; Kekow, Joern; Thiesen, Hans-Juergen

    2008-01-01

    Introduction About 30% of rheumatoid arthritis patients fail to respond adequately to TNFα-blocking therapy. There is a medical and socioeconomic need to identify molecular markers for an early prediction of responders and nonresponders. Methods RNA was extracted from peripheral blood mononuclear cells of 19 rheumatoid arthritis patients before the first application of the TNFα blocker etanercept as well as after 72 hours. Clinical response was assessed over 3 months using the 28-joint-count Disease Activity Score and X-ray scans. Supervised learning methods were applied to Affymetrix Human Genome U133 microarray data analysis to determine highly selective discriminatory gene pairs or triplets with prognostic relevance for the clinical outcome evinced by a decline of the 28-joint-count Disease Activity Score by 1.2. Results Early downregulation of expression levels secondary to TNFα neutralization was associated with good clinical responses, as shown by a decline in overall disease activity 3 months after the start of treatment. Informative gene sets include genes (for example, NFKBIA, CCL4, IL8, IL1B, TNFAIP3, PDE4B, PPP1R15A and ADM) involved in different pathways and cellular processes such as TNFα signalling via NFκB, NFκB-independent signalling via cAMP, and the regulation of cellular and oxidative stress response. Pairs and triplets within these genes were found to have a high prognostic value, reflected by prediction accuracies of over 89% for seven selected gene pairs and of 95% for 10 specific gene triplets. Conclusion Our data underline that early gene expression profiling is instrumental in identifying candidate biomarkers to predict therapeutic outcomes of anti-TNFα treatment regimes. PMID:18454843

  2. [The B cell in the pathogenesis of rheumatoid arthritis].

    PubMed

    Díaz-González, José Federico; Ferraz Amaro, Iván

    2007-07-01

    Classically, B-cells have been considered to play a secondary role in the pathogenesis of rheumatoid artritis, restricted to the production of auto-antibodies. Nevertheless, the unexpected good clinical response that the systemic depletion of B-cells has demonstrated in a well-controlled clinical trial in patients with rheumatoid artritis has revitalized the interest in this cell type in the pathogenesis of this autoimmune disease. Several evidences suggest that B-cells can regulate the course of the immune response through antibody productionindependent mechanisms. These mechanisms include antigen presentation and the release of soluble factors such as proinflammatory cytokines, metalloproteinases, and chemokines. This article reviews experimental data supporting that the participation of B-cells in the pathogenesis of rheumatoid arthritis occurs through multiple mechanisms. PMID:21794424

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Telles, Shirley; Singh, Nilkamal

    2012-01-01

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

  5. [Possible involvement of the auditory system in rheumatoid arthritis].

    PubMed

    Walek, H; Fritze, W; Kolarz, G

    1980-01-01

    32 patients with definite or classical rheumatoid artritis, aged between 22 and 60 years, were checked with respect to clinical aspects, laboratory data and pure-tone audiometry. None of them had received salicylates in former times or at the time of this study. The audiometric results in the arthritis patients did not differ from those in comparison with the results of a random sample study of clinically normal ears. Ototoxic salicylate therapy may have influenced earlier results about hearing loss in rheumatoid arthritis. PMID:7424204

  6. 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

  7. 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.

  8. 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.

  9. Cells of the synovium in rheumatoid arthritis. B cells

    PubMed Central

    Mauri, Claudia; Ehrenstein, Michael R

    2007-01-01

    There is significant evidence arising from experimental models that autoantibodies play a key role in the pathogenesis of inflammatory arthritis. In addition to autoantibody production, B cells efficiently present antigen to T cells, produce soluble factors, including cytokines and chemokines, and form B cell aggregates in the target organ of rheumatoid arthritis. In this review we analyze the multifaceted role that B cells play in the pathogenesis of rheumatoid arthritis and discuss how this information can be used to guide more specific targeting of B cells for the therapy of this disease. PMID:17349064

  10. Synovial fluid osmolality in osteoarthritis and rheumatoid arthritis.

    PubMed

    Shanfield, S; Campbell, P; Baumgarten, M; Bloebaum, R; Sarmiento, A

    1988-10-01

    The osmolality of synovial fluid aspirated from the knees of 15 rheumatoid and 15 osteoarthritic patients was observed concurrently with the same measurement on blood serum. The group averages were compared to a group of 13 with identical apparati. Synovial fluid osmolality in rheumatoid arthritics (280 +/- 7.7 mmol/kg) was significantly different from that in osteoarthritics (297 +/- 16.9 mmol/kg), and both group averages were significantly different from normal (404 +/- 57 mmol/kg). Blood serum osmolality also differed between the normal and the two arthritic groups. The potential application of vapor pressure osmometry techniques in the diagnosis and management of joint disease is discussed. PMID:3416536

  11. Spleen and liver enlargement in a patient with rheumatoid arthritis.

    PubMed

    Bedoya, María Eugenia; Ceccato, Federico; Paira, Sergio

    2015-01-01

    We describe the case of a 51-year-old woman with a seropositive, erosive, and non-nodular rheumatoid arthritis of 15 year of evolution. The patient had poor compliance with medical visits and treatment. She came to the clinic with persistent pancytopenia and spleen and liver enlargement. Liver and bone marrow biopsies were carried out and amyloidosis, neoplasias and infections were ruled out. We discuss the differential diagnosis of pancytopenia and spleen and liver enlargement in a long-standing rheumatoid arthritis patient. PMID:25453596

  12. The role of exercise in the management of rheumatoid arthritis.

    PubMed

    Metsios, George S; Stavropoulos-Kalinoglou, Antonis; Kitas, George D

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with significant functional impairment and increased risk for cardiovascular disease. Along with pharmacological therapy, exercise seems to be a very promising intervention to improve disease-related outcomes, including functional ability and systemic manifestations, such as the increased cardiovascular risk. In this review, we discuss the physiological mechanisms by which exercise improves inflammation, cardiovascular risk and psychological health in patients with rheumatoid arthritis (RA) and describe in detail how exercise can be incorporated in the management of this disease using real examples from our clinical practice. PMID:26178249

  13. Rheumatoid-like arthritis in a lion tailed macaque.

    PubMed

    Anderson, S T; Schiller, C A

    1991-08-01

    Very few satisfactory models of rheumatoid arthritis (RA) exist in nonhuman species. It is particularly striking that nonhuman primates have only rarely been described to have disease processes resembling classic RA seen in humans. We describe the case of a lion tailed macaque (Macaca silenus), housed at the National Zoological Park in Washington DC, that had a polyarticular inflammatory arthropathy resembling RA. Gross and histopathologic examination of necropsy tissues and radiographic findings strongly suggest a rheumatoid-like disease, never before described in this species. PMID:1941834

  14. Retinoic acid attenuates rheumatoid inflammation in mice.

    PubMed

    Kwok, Seung-Ki; Park, Mi-Kyung; Cho, Mi-La; Oh, Hye-Jwa; Park, Eun-Mi; Lee, Dong-Gun; Lee, Jennifer; Kim, Ho-Youn; Park, Sung-Hwan

    2012-07-15

    Retinoic acid is the active vitamin A derivative and is well-known to have diverse immunomodulatory actions. In this study, we investigated the impact of all-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, on the development of arthritis and the pathophysiologic mechanisms by which ATRA might have antiarthritic effects in animal model of rheumatoid arthritis (RA; collagen-induced arthritis [CIA] in DBA/1J mice). We showed that treatment with ATRA markedly suppressed the clinical and histologic signs of arthritis in the CIA mice. It reduced the expression of IL-17 in the arthritic joints. Interestingly, Foxp3(+) regulatory T cells were markedly increased and IL-17-producing CD4(+) T cells (Th17 cells) were decreased in the spleens of ATRA-treated mice. In vitro treatment with ATRA induced the expression of Foxp3 and repressed the IL-17 expression in the CD4(+) T cells in mice. ATRA suppressed the production of total IgG and IgG2a in splenocytes that were stimulated by LPS. It also reduced serum levels of total IgG and IgG2 anti-collagen Abs and germinal center formation in CIA mice. In addition, the ATRA-treated mice showed decreased osteoclast formation in arthritic joints. Moreover, ATRA downregulated the expression of receptor activator of NF-κB ligand, the leading player of osteoclastogenesis, in the CD4(+) T cells and fibroblast-like synoviocytes from patients with RA. Furthermore, ATRA prevented both human monocytes and mice bone marrow-derived monocytes/macrophage cells from differentiating into osteoclasts. These data suggest ATRA might be an effective treatment modality for RA patients. PMID:22696440

  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. Glucocorticoids and chronotherapy in rheumatoid arthritis.

    PubMed

    Cutolo, Maurizio

    2016-01-01

    It is evident that the morning symptoms of rheumatoid arthritis (RA) are linked to the circadian abnormal increase in night inflammation, favoured by inadequate cortisol secretion under conditions of active disease. Therefore, exogenous glucocorticoid treatment is recommended in RA at low doses since it may partially act like a 'replacement therapy'. The prevention/treatment of the night upregulation of the immune/inflammatory reaction (and related flare of cytokine synthesis) has been shown to be more effective when exogenous glucocorticoid administration is obtained with a night-time-release formulation. Large-scale trials documented that modified-release prednisone has greater efficacy then morning prednisone for long-term low-dose glucocorticoid treatment in patients with RA, showing at least a more significant reduction in morning joint stiffness. Interestingly, despite a considerably higher cost than conventional prednisone, chronotherapy with night-time-release prednisone was recognised as a cost-effective option for patients with RA not on glucocorticoids who are eligible for therapy with biological disease-modifying antirheumatic drugs (DMARDs). Moreover, since different cell populations involved in the inflammatory process are particularly activated during the night, other therapeutical approaches used in RA, for example, conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs), should follow the same concepts of glucocorticoid chronotherapy. Indeed, bedtime methotrexate chronotherapy was found to improve RA symptoms compared to the current standard dosing methods, and several available NSAIDs (ie, indomethacin, aceclofenac, ketoprofen, flurbiporfen, lornoxicam) have been very recently modified in their formulation, in order to obtain chronotherapeutical effects in RA. PMID:27042335

  17. 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

  18. 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

  19. 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

  20. Choline kinase inhibition in rheumatoid arthritis

    PubMed Central

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

    2014-01-01

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

  1. Glucocorticoids and chronotherapy in rheumatoid arthritis

    PubMed Central

    Cutolo, Maurizio

    2016-01-01

    It is evident that the morning symptoms of rheumatoid arthritis (RA) are linked to the circadian abnormal increase in night inflammation, favoured by inadequate cortisol secretion under conditions of active disease. Therefore, exogenous glucocorticoid treatment is recommended in RA at low doses since it may partially act like a ‘replacement therapy’. The prevention/treatment of the night upregulation of the immune/inflammatory reaction (and related flare of cytokine synthesis) has been shown to be more effective when exogenous glucocorticoid administration is obtained with a night-time-release formulation. Large-scale trials documented that modified-release prednisone has greater efficacy then morning prednisone for long-term low-dose glucocorticoid treatment in patients with RA, showing at least a more significant reduction in morning joint stiffness. Interestingly, despite a considerably higher cost than conventional prednisone, chronotherapy with night-time-release prednisone was recognised as a cost-effective option for patients with RA not on glucocorticoids who are eligible for therapy with biological disease-modifying antirheumatic drugs (DMARDs). Moreover, since different cell populations involved in the inflammatory process are particularly activated during the night, other therapeutical approaches used in RA, for example, conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs), should follow the same concepts of glucocorticoid chronotherapy. Indeed, bedtime methotrexate chronotherapy was found to improve RA symptoms compared to the current standard dosing methods, and several available NSAIDs (ie, indomethacin, aceclofenac, ketoprofen, flurbiporfen, lornoxicam) have been very recently modified in their formulation, in order to obtain chronotherapeutical effects in RA. PMID:27042335

  2. 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

  3. Fucosyltransferase 1 mediates angiogenesis in rheumatoid arthritis

    PubMed Central

    Isozaki, Takeo; Amin, Mohammad A.; Ruth, Jeffrey H.; Campbell, Phillip L.; Tsou, Pei-Suen; Ha, Christine M.; Stinson, W. Alex; Domino, Steven E.; Koch, Alisa E.

    2015-01-01

    Objective The aim of this study was to determine the role of α(1,2)-linked fucosylation of proteins by fucosyltransferase1 (fut1) in rheumatoid arthritis (RA) angiogenesis. Methods Analysis of α(1,2)-linked fucosylated proteins in synovial tissues (STs) was performed by immunohistological staining. α(1,2)-linked fucosylated angiogenic chemokine expression in synovial fluids (SFs) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)-linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using nondepleted and α(1,2)-linked fucosylated protein depleted RA SFs. To examine the production of proangiogenic chemokines by fucosyltransferase 1 (fut1) in HMVECs, cells were transfected with fut1 sense or antisense oligonucleotides, and enzyme-linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (MLEC) chemotaxis using wild type and fut1 gene deficient MLECs. Results α(1,2)-linked fucosylated proteins on RA ST endothelial cells (ECs) were highly expressed compared to normal ST. α(1,2)-linked fucosylated monocyte chemoattract protein-1 (MCP-1)/CCL2 was present in RA SFs, and was significantly elevated compared to osteoarthritis SFs. Depletion of α(1,2)-linked fucosylated proteins in RA SFs induced less HMVEC migration and tube formation compared to nondepleted RA SFs. We found that blocking fut1 expression in ECs resulted in decreased MCP-1/CCL2 and regulated upon activation and normal T cell expressed and secreted (RANTES)/CCL5 production. Finally, we showed that fut1 regulates EC migration in response to vascular endothelial cell growth factor. Conclusions α(1,2)-linked fucosylation by fut1 may be an important new target for angiogenic diseases like RA. PMID:24692243

  4. 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

  5. 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

  6. 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

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

    PubMed Central

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

    2004-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

  9. Patient Preferences Regarding Rheumatoid Arthritis Therapies: A Conjoint Analysis

    PubMed Central

    Louder, Anthony M.; Singh, Amitabh; Saverno, Kim; Cappelleri, Joseph C.; Aten, Aaron J.; Koenig, Andrew S.; Pasquale, Margaret K.

    2016-01-01

    Background Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. Objective To investigate patient preferences for attributes associated with RA treatments. Methods A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21–80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to perform daily tasks; and medication burden. Mean attribute importance scores were calculated after adjusting for patient demographics (eg, age, sex, years since diagnosis) using a hierarchical Bayes model. Patient preferences for each treatment attribute were ranked by the importance score. Part-worth utilities (ie, preference scores) were used to perform a conjoint market simulation. Results A total of 380 patients (response rate, 27.1%) returned the survey. Their mean age (± standard deviation) was 54.9 (± 9.3) years. Nonrespondents were 2 years younger (mean, 52.9 years; P = .002) but did not differ significantly from respondents in known clinical characteristics. After adjustment for demographic characteristics, mean patients' ranking of treatment attribute importance, in decreasing order, was route of administration, 34.1 (± 15.5); frequency of administration, 16.4 (± 6.8); serious adverse events, 12.0 (± 9.3); cost, 10.1 (± 6.2); medication burden, 9.8 (± 8.2); joint pain reduction, 8.9 (± 3.8); and daily tasks improvement, 8.8 (± 4.7). For the route of administration attribute, the part-worth utility was highest for the oral route. Conjoint simulation results showed that 56.4% of respondents would prefer an oral route of administration. Conclusion Based on this survey completed by 380 patients with RA, commercially insured patients with RA consider the route of administration to be the most important attribute of their RA treatment. In this study, the majority (56.4%) of patients preferred the oral route of administration over other routes. Understanding patient preferences may help to inform provider and payer decisions in treatment selection that may enhance patient adherence to therapy. PMID:27182427

  10. [Rheumatoid shoulder: does minimally invasive therapy make sense?].

    PubMed

    Kiekenbeck, A; Preis, M; Salzmann, G

    2008-10-01

    Surgical treatment of patients with rheumatoid arthritis of the shoulder should be one part of a concept of conservative and surgical treatment. In addition to disease-modifying agents, local minimally invasive surgery can avoid structural damage to the shoulder and furthermore achieve a restitution of shoulder function. According to Larsen Stage 0-III, an arthroscopic synovectomy and bursectomy can achieve a good prognosis and help to avoid further structural damage to the rheumatoid shoulder. Minimally invasive procedures in the surgery of the rheumatoid shoulder lead to less immobilisation and faster rehabilitation, to the benefit of the joints in the operated limb, much like therapy of the knee. It is also possible to treat associated pathologies with minimally invasive surgery, such as bursitis, small rotator cuff defects, and synovitis of the acromioclavicular joint, as well as synovectomy of the glenohumeral joint Good results can be achieved in these cases using minimally invasive surgery. However, minimally invasive reconstructive procedures are limited in the rheumatoid shoulder. PMID:18781313

  11. 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

  12. 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,

  13. Adrenal suppression following herbal remedy for rheumatoid arthritis.

    PubMed

    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

  14. 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

  15. The Rehabilitation Unit in the Treatment of Rheumatoid Arthritis

    PubMed Central

    Harris, R.

    1963-01-01

    The Devonshire Royal Hospital, Buxton, England, was developed from a spa hospital into the Manchester Regional Centre for Rheumatism and Rehabilitation. Patients with active rheumatoid disease are admitted to the hospital's Rheumatism Service, not to the Rehabilitation Unit. Fifty per cent of patients admitted to the Rehabilitation Unit have rheumatoid arthritis, with reablement or resettlement as their main problem. Nine hundred and eighty-eight rheumatoid patients admitted in a period of five years had chronic disease but recent disability (633 off work under one year). Their average hospital stay was 10 weeks. Five hundred and forty-four were admitted severely disabled; 247 were discharged so graded. One hundred and thirty-eight were fit for some work on admission and 498 on discharge. Sixty-five per cent of housewives could run their homes. In a sample of 100 male rheumatoid patients, 39 men were fit for their own jobs and were easily placed; 43 needed lighter work and over 20 of these were adequately resettled when checked at three and 36 months. The earnings of these men exceeded the cost of rehabilitation for the whole group. PMID:13952954

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

    ERIC Educational Resources Information Center

    Smith, Timothy W.; And Others

    1988-01-01

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

  17. 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…

  18. 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,…

  19. 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.

  20. Sustainability of Forefoot Reconstruction for the Rheumatoid Foot.

    PubMed

    Whitt, Kathie J; Rincker, Sarah A; Hyer, Christopher F

    2016-01-01

    Ninety percent of patients with rheumatoid arthritis will display foot and ankle pathologic features, including hallux valgus, lesser metatarsophalangeal (MTP) joint subluxation/dislocation, and hammertoe deformity. Recently, a trend has ensued toward joint preservation with distal metatarsal osteotomies and various bunion corrective procedures. However, the reference standard remains first MTP joint fusion, lesser metatarsal head resection, and lesser proximal interphalangeal joint fusion. The present retrospective study followed the results of 4 different surgeons who had performed the reference standard rheumatoid forefoot reconstruction from August 2008 to August 2012 on patients with rheumatoid arthritis. Radiographic and statistical analysis of the data from 20 patients determined an overall first MTP joint fusion rate of 90%, often occurring by 108 (range 64 to 202) days postoperatively. Radiographic nonunion occurred in 2 of the 20 patients (10%), although both were asymptomatic, with no revision necessary. Lesser digit deformity revision occurred in 1 patient (5%), and mild to moderate infection developed in 4 patients (20%). The radiographic and clinical follow-up period was 12 months. Our study found that this technique provides exceptional radiographic improvement, an acceptable time to fusion, a low reoperation rate, and minimal complications. In addition, correction of the deformity was maintained at 1 year postoperatively. In conclusion, first MTP joint fusion with lesser metatarsal head resection should remain the reference standard for surgical intervention of the rheumatoid foot. PMID:26970909

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

    PubMed Central

    Šenolt, Ladislav; Šumová, Barbora; Jandová, Romana; Hulejová, Hana; Mann, Heřman; Pavelka, Karel; Vencovský, Jiří; Filková, Mária

    2015-01-01

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

  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. 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.

  4. 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

  5. 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

  6. Small Airways Involvement in Patients with Rheumatoid Arthritis

    PubMed Central

    Zohal, Mohammad Ali; Yazdi, Zohreh; Ghaemi, Ali Rassi; Abbasi, Mahnaz

    2013-01-01

    Objectives: One of the common causes of morbidity in patients with RA is pulmonary involvement. Some studies have shown that the possible abnormal results of pulmonary function tests in rheumatoid disease are higher than usual. We aimed to evaluate the prevalence of spirometric abnormalities in patients with RA. Materials & Methods: This case-control study was conducted on 99 patients with RA who referred to a rheumatology clinic in Qazvin, northwest Iran. Sixty five age- and sex-matched healthy controls were recruited as well. History taking, physical examination, laboratory tests and spirometry were performed for the participants. RA severity was assessed according to Disease Activity Score 28 (DAS28). The data were processed using SPSS software version 16. Chi square and student's t test and multiple logistic regressions were used as appropriated. Results: The mean (±SD) age of the patients was 46 (±10.5) years. The mean (±SD) duration of disease was 4.8 (±5.4) years, and the mean (±SD) DAS28 was 2.5 (±1.1). Dyspnea was the most common respiratory complaint (6.1%). Three (3%) patients had mild restrictive, 2 (2%) patients mild obstructive, and one (1%) patient moderate obstructive diseases. In the control group, only one participant had mild restrictive pulmonary disease (P<0.05). A significant decrease of FEF25 [OR=3.2; 95%CI (1.9-4.5)], FEF50 [OR=2.5; 95% CI (1.7-3.1)], FEF75 [OR=2.3; 95% CI (1.4-2.7)] and FEF25-75 [OR=2.7; 95% CI (1.7-3.5)] was observed in patients compared with the control group. We found no correlation between the patients’ age, duration and severity of the disease, and laboratory tests with spirometric indices. Conclusion: It is recommended that patients with RA be visited on a regular basis and PFT be done for them for the early diagnosis of pulmonary involvement. PMID:23445704

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

    PubMed

    Ebringer, Alan; Rashid, Taha; Wilson, Clyde

    2010-02-01

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

  8. A 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.

  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. 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

  11. Synovial fluid copper and related variables in rheumatoid and degenerative arthritis.

    PubMed Central

    Scudder, P R; McMurray, W; White, A G; Dormandy, T L

    1978-01-01

    Copper, caeruloplasmin, transferrin, albumin, and total protein were measured in the serum and synovial fluid of 40 patients with rheumatoid arthritis and 40 patients with osteoarthrosis. A raised synovial fluid copper and caeruloplasmin have been found to be characteristic of rheumatoid effusions. The relation between copper and caeruloplasmin in synovial fluid differs from that in serum. Synovial fluid caeruloplasmin was increased disproportionately in relation to other plasma proteins present in rheumatoid effusions. PMID:629608

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Panniculitis: an unusual presenting manifestation of rheumatoid arthritis.

    PubMed

    Fragoulis, George E; Stamopoulos, Paraskevas; Barbatis, Calypso; Tzioufas, Athanasios G

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting primarily the joints but also other organs including skin. Panniculitis is an extremely rare manifestation of the disease manifesting mainly as reddish, ulcerative painful nodules and papules, usually in the legs. Histopathologically, it is characterised by liponecrobiosis, granulocytic and histiocytic infiltrates and vasculopathy. Herein, we describe a middle-aged woman with past medical history of hypertension and diabetes mellitus, and unremarkable family history, who presented with symmetrical polyarthritis, low grade fever and painful subcutaneous nodules in the abdomen. Her laboratory tests showed high acute phase reactants, positive rheumatoid factor and anti-Ro autoantibodies and negative anti-CCP. Surgical resection and histological examination of the nodules revealed neutrophilic lobular panniculitis associated with RA. She was treated with low doses of glucocorticosteroids and methotrexate. The latter was substituted with leflunomide due to toxicity. The patient had significant clinical and laboratory improvement. PMID:26742648

  1. Structural damage in rheumatoid arthritis as visualized through radiographs

    PubMed Central

    2002-01-01

    Several agents show an effect on reducing radiographic progression in rheumatoid arthritis. It is tempting to retrospectively compare the effects of these agents on radiographic progression across clinical trials. However, there are several limitations in interpreting and comparing radiographic results across clinical trials. These limitations, including study designs, patient characteristics, durations of follow-up, scoring methodologies, reader reliability, radiograph sequence, handling of missing data, and data presentation, will be discussed. The consequences are illustrated with several examples of recent clinical trials that show an effect on radiographic progression. A guide in the interpretation and clinical relevance of radiographic results is presented, with the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy used as an example. PMID:12110155

  2. 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.

  3. Redox signalling and the inflammatory response in rheumatoid arthritis

    PubMed Central

    Filippin, L I; Vercelino, R; Marroni, N P; Xavier, R M

    2008-01-01

    Reactive oxygen species (ROS) are produced mainly during oxidative phosphorylation and by activated phagocytic cells during oxidative burst. The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signalling that enhances the inflammatory response. Many studies have demonstrated a role of ROS in the pathogenesis of inflammatory chronic arthropathies, such as rheumatoid arthritis. It is known that ROS can function as a second messenger to activate nuclear factor kappa-B, which orchestrates the expression of a spectrum of genes involved in the inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutic strategies for rheumatoid arthritis. PMID:18422737

  4. 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

  5. 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

  6. 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

  7. 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

  8. Acute atraumatic hip dislocation in an adult with rheumatoid arthritis.

    PubMed

    Kohan, Kevin J; Thomas, Mark A

    2012-04-01

    There are no reports of atraumatic hip subluxation and dislocation in the adult patient with rheumatoid arthritis (RA). This rare phenomenon is most prevalent in patients with congenital hip dislocation, von Recklinghausen disease, tumor infiltration, connective tissue disorders, and juvenile rheumatoid arthritis. We report an acute atraumatic dislocation of the hip in an adult patient with RA. We believe that two factors contributed to the patient's atraumatic dislocation: a shallow but appropriately positioned acetabulum and erosive RA with substantiate panus formation. Similar to previous reports, there was a rent or capsular defect that may have contributed to the mechanism of dislocation. Physicians should be aware that, although rare, a de novo atraumatic hip dislocation is a possibility in a patient with a long-standing history of RA and hip pain. Distinguishing features of this case include the acuteness of the dislocation, the absence of previous symptoms, and adult-onset RA. PMID:22411018

  9. Serum copper and erythrocyte superoxide dismutase in rheumatoid arthritis.

    PubMed Central

    Banford, J C; Brown, D H; Hazelton, R A; McNeil, C J; Sturrock, R D; Smith, W E

    1982-01-01

    Serum copper and thiol levels an caeruloplasmin activity were determined and compared with measurements of articular index, erythrocyte sedimentation rate, and zinc and haemoglobin levels in patients with rheumatoid arthritis. Superoxide dismutase activity, thiol, zinc, and copper levels of haemolysate were measured and compared with each other and to the above parameters. In serum, caeruloplasmin activity increased and thiol levels decreased, whereas in the haemolysate superoxide dismutase activity decreased and thiol levels increased. It is suggested that the changes in copper levels and in the activities of process which may be copper-dependent between plasma and cytosol in patients with rheumatoid arthritis reflect a change in oxidative status of the blood which may have implications in the pathogenesis of the disease. PMID:7125714

  10. 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

  11. [Leishmaniasis and rheumatoid nodulosis in a patient with HIV infection].

    PubMed

    García-Río, I; Daudén, E; Ballestero-Díez, M; Fraga, J; García-Díez, A

    2010-03-01

    We describe the case of a 44-year-old homosexual man diagnosed with HIV infection and visceral leishmaniasis. He presented nodules on the dorsum of the hands. Histological study of one of the nodules revealed necrobiotic palisading granulomas with abundant Leishmania amastigotes within the histiocytes and in the adjacent extracellular space. Tissue and peripheral blood cultures were positive for Leishmania infantum, zymodeme MON-24. A biopsy of healthy skin did not reveal the presence of Leishmania. A diagnosis of rheumatoid nodulosis with Leishmania was made and treatment was started with intravenous liposomal amphotericin, leading to slight improvement. We believe that the presence of the parasite within the nodules was the result of its dissemination during visceral leishmaniasis in an immunocompromised patient with HIV infection, and that the Leishmania did not have an etiological role in the appearance of the nodules. We present the first case of the association between Leishmania and rheumatoid nodulosis. PMID:20223159

  12. 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

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

    NASA Astrophysics Data System (ADS)

    Gsponer, 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.

  14. Alternative medicine: cost and subjective benefit in rheumatoid arthritis.

    PubMed Central

    Pullar, T; Capell, H A; Millar, A; Brooks, R G

    1982-01-01

    Seventy-eight patients with seropositive rheumatoid arthritis were asked about money spent in an attempt to help their arthritis. This included expenditure on alternative medicine, aids for the home, and conventional medicine. Most money was spent on, and most benefit was derived from, aids for the home. Sixty per cent of the patients had tried alternative medicine, but expenditure on this was relatively low and only a small proportion found it helpful. PMID:6814682

  15. A method for the production of rheumatoid factor in rabbits

    PubMed Central

    Biro, C. E.

    1968-01-01

    Rabbits rendered immunologically unresponsive to native human IgG and then injected with a single large dose of heat-aggregated human IgG produce an antibody which resembles rheumatoid factor in all its properties that were tested. It is an exclusively IgM antibody which reacts with both human and rabbit (autologous) aggregated IgG, but not with either protein in the native state. PMID:5303049

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

    PubMed Central

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

  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. Measurement of rheumatoid factor isotypes in the clinical laboratory.

    PubMed

    Carpenter, A B; Smailer, S

    1989-07-01

    In this study we assessed the clinical utility of measuring all major rheumatoid factor (RF) isotypes (IgG, IgA, and IgM) in the diagnostic immunology laboratory using an enzyme-linked immunoassay (ELISA). An improved method for IgG-RF was tested which employed a commercially available monoclonal anti-human IgG Fd antibody and did not require pepsin digestion of samples. We detected elevated levels of all three RF isotypes in a population of hospitalized rheumatoid arthritis patients (n = 109). We demonstrated a significant association between IgM and IgA RF which occurred in 36% of our subjects, while less than 6% had IgM + IgG RF or IgG + IgA RF. A comparison of the IgM ELISA with the Rheumaton revealed a statistically significant correlation (r = 0.65, p = 0.001). In addition, the two methodologies were equivalent in sensitivity (ELISA: 76%, Rheumaton: 78%). However, the ELISA procedure was more time consuming, costly, and required greater technical expertise. The following clinical and laboratory findings were significantly associated with RF isotypes: IgG RF and the presence of rheumatoid nodules (p = 0.03), elevated erythrocyte sedimentation rate (ESR) and IgG RF (p = 0.007), and elevated ESR and IgM RF (p = 0.0009). Our ELISA methodology did not provide significant advantages over existing techniques to justify its use as part of the routine laboratory assessment of rheumatoid factor. PMID:2767737

  19. HLA-DRB1 genes and extraarticular rheumatoid arthritis

    PubMed Central

    Roudier, Jean

    2006-01-01

    The factors that trigger the development of extraarticular features of rheumatoid arthritis (RA) are still unknown. HLA-DR alleles such as HLA-DR4 and HLA-DR1 are associated with the risk to develop RA. A large scale study from Sweden and the Mayo Clinic suggests that HLA-DR4, but not HLA-DR1, is associated with the risk to develop extraarticular RA. PMID:16542468

  20. 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

  1. Polyamine oxidase activity in rheumatoid arthritis synovial fluid.

    PubMed Central

    Ferrante, A; Storer, R J; Cleland, L J

    1990-01-01

    Oxidation of polyamides by polyamine oxidases (PAO) leads to the generation of highly reactive aminoaldehydes which have been shown to have a variety of effects, including killing of pathogenic microorganisms and regulation of leucocyte functions. Data presented here show that PAO are present in synovial fluid from patients with rheumatoid arthritis. This finding may have important implications in the various properties attributed to synovial fluid which includes anti-inflammatory activity. PMID:2372986

  2. Clonality of T lymphocytes expanded with IL-2 from rheumatoid arthritis peripheral blood, synovial fluid and synovial membrane.

    PubMed Central

    Cantagrel, A; Alam, A; Coppin, H L; Mazieres, B; De Preval, C

    1993-01-01

    The association of rheumatoid arthritis (RA) with particular MHC class II genes suggests that autoantigen-specific T cell clones present in joints could be central to the pathogenesis of the disease. Previous investigations on the clonal diversity of T cells infiltrating the rheumatoid synovial membrane have yielded conflicting results. With the use of Southern blot analysis, we investigated the clonality of rheumatoid T cell lines expanded from peripheral blood, synovial fluid and synovial tissue. From peripheral blood lymphocyte (PBL) of RA patients and healthy normal controls, we also checked the consequences of two different culture conditions on the clonality of these cell lines. From control PBL, we found that in vitro non-specific expansion of non-clonal T cell populations does not create artefactual clonal selection. However, growing T cells in vitro with IL-2 seems to be able to lead to preferential expansion of cells bearing IL-2 receptor (IL-2R). We identified such in vivo activated IL-2-sensitive T cell clones frequently in RA synovial tissue (8/13) and more rarely in synovial fluid and peripheral blood (3/12). One patient presents the same T cell receptor gene rearrangements in synovial membrane of two affected joints. In RA synovial tissue, the frequency of these IL-2-responsive T cells is most prevalent among actively inflamed membranes removed early in the disease process. The role and the relevance to the disease of these IL-2-responsive T cells remain to be elucidated. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8380369

  3. A new thermography-based approach to early detection of cancer utilizing magnetic nanoparticles theory simulation and in vitro validation.

    PubMed

    Levy, Arie; Dayan, Abraham; Ben-David, Moshe; Gannot, Israel

    2010-12-01

    This work describes the utilization of tumor-specific magnetic nanoparticles together with an alternating magnetic field as a means to thermally mark a tumor so as to detect it using a thermal imaging system. Experiments were conducted using an in vitro tissue model, an inductive heating system, and an infrared camera. The thermal images, recorded by the infrared camera during the experiments, were analyzed using an algorithm that was developed as part of this work. The results show that small tumor phantoms (diameter of 0.5 mm) that were embedded under the surface of the tissue phantom (up to 14 mm below the surface) can be detected and located, indicating that the proposed method could potentially offer considerable advantages over conventional thermography and other methods for cancer early detection. Nevertheless, several issues should be clarified in future studies before the method can be offered for clinical use. PMID:20620238

  4. Clinical research on postoperative efficacy and related factors of early simulation hyperbaric oxygen therapy for severe craniocerebral injury.

    PubMed

    Xu, Lanjuan; Li, Baolin; Yang, Caifu; Li, Chengjian; Peng, Yueli

    2016-01-01

    In order to discuss the clinical efficacy of simulation hyperbaric oxygen therapy (HBOT) for severe craniocerebral injury and analyze the related factors of it, 108 patients who transferred to our department during December 2010 - December 2014 for ventilator treatment after operation of severe craniocerebral injury were taken as the subjects of the study. These patients were divided into conventional treatment group and simulation hyperbaric oxygen therapy group to contrast the curative effects. At the meantime, GOS score and length of stay in intensive care unit (ICU) of two groups 6 months after treatment, as well as changes in the indexes of the HBO group during treatment were performed statistical analysis. Then factors affecting prognosis of simulation HBOT were performed regression analysis and principal component analysis. The results showed that when compared to the control group, differences in cases with four GOS score and one GOS score in the treatment group were significant (p<0.05). Jugular venous oxygen saturation (SjvO2), jugular bulb oxygen partial pressure (PjO2), arterial partial pressure of oxygen (PaO2) and arterial oxygen saturation (SaO2) of the simulation HBO group before the first time treatment on the first day and after the first time treatment on the third day were significantly increased, with statistical significance (p<0.05); serum lactic acid (Lac) and blood glucose (Glu) decreased significantly (p<0.05). Prior to and during the first treatment on the first day, jugular bulb pressure (Pj) and central venous pressure (CVP) had no significant difference (p>0.05). Regression analysis indicated that factors affecting prognosis included cerebral contusion, coronary heart disease, hydrocephalus and tracheotomy. Principal component analysis found the factors were hydrocephalus, coronary heart disease, tracheotomy, cerebral contusion, cerebral infarction and glasgow coma scale (GCS) before treatment. Therefore, stimulation HBOT can significantly improve the prognosis of patients with severe craniocerebral injury. Paying attention to risk factors in clinics and giving timely interventional treatment can reduce morbidity and mortality in patients. PMID:27005496

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

    PubMed Central

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

    2009-01-01

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

  6. [Primary total hip arthroplasty in patients with rheumatoid arthritis].

    PubMed

    Gluscević, B M; Kraljević, B D; Jovanović, V A; Stosić, P B; Milosavljević, D M; Radivojević, R M

    2006-01-01

    Total hip arthroplasty has become a successful way of treating the painful and destroyed hip joint in the patient with rheumatoid arthritis (RA). Two hundred twenty (135 cemented and 85 noncemented) total hip arthroplasties were performed in 180 patients with rheumatoid arthritis. The average age was 48.61 years and the average follow-up was 8.4 years. Clinical evaluation was based on a Harris hip score that showed significant improvement in pain and function preoperatively compared with pain and function at followup. There were two deep infections requiring removal of the prosthesis. Four cemented acetabular cups and one cemented femoral component were revised due to aseptic loosening. Three acetabular rings were revised due to aseptic loosening. The relatively inferior results of total hip arthroplasty among RA patients is due not only to fixation method, but also to the poorer bone quality and weakening musculature. The results in these patients suggest that cementless total hip arthroplasty might become a successful way of treating the destroyed hip joint in the patient with rheumatoid artritis. PMID:17688046

  7. 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

  8. 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

  9. Non-Biologic Nanodelivery Therapies for Rheumatoid Arthritis.

    PubMed

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

    2015-10-01

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

  10. Thyroid dysfunction in rheumatoid arthritis: a controlled prospective survey.

    PubMed Central

    Shiroky, J B; Cohen, M; Ballachey, M L; Neville, C

    1993-01-01

    OBJECTIVES--To determine whether thyroid dysfunction is found with increased frequency in patients with rheumatoid arthritis (RA). METHODS--A controlled prospective survey was conducted on a cohort of patients with RA derived from a hospital clinic and a private surburban rheumatology practice. A control group with similar demographic features was generated from the same sources and included subjects with either osteoarthritis or fibromyalgia. Consecutive patients were evaluated over a six month period. The evaluation included a complete history and physical examination, and determination of serum thyroxine, free thyroxine, triiodothyronine, thyroid stimulating hormone (IRMA), antinuclear antibodies, and rheumatoid factor. RESULTS--Of the 91 women with RA evaluated, 29 (30%) had evidence of thyroid dysfunction compared with 10 (11%) of 93 controls. The excess thyroid dysfunction is due to either hypothyroidism or Hashimoto's thyroiditis and was independent of age, increasing duration of disease, rheumatoid factor, and antinuclear antibodies. CONCLUSIONS--Thyroid dysfunction is seen at least three times more often in women with RA than in women with similar demographic features with non-inflammatory rheumatic diseases such as osteoarthritis and fibromyalgia. PMID:8323398

  11. 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

  12. 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

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

    PubMed

    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

  14. 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.

  15. 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.

  16. 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

  17. Multispectral near-IR reflectance imaging of simulated early occlusal lesions: Variation of lesion contrast with lesion depth and severity

    PubMed Central

    Simon, Jacob C.; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-01-01

    Background and Objectives Early demineralization appears with high contrast at near-IR wavelengths due to a ten to twenty fold difference in the magnitude of light scattering between sound and demineralized enamel. Water absorption in the near-IR has a significant effect on the lesion contrast and the highest contrast has been measured in spectral regions with higher water absorption. The purpose of this study was to determine how the lesion contrast changes with lesion severity and depth for different spectral regions in the near-IR and compare that range of contrast with visible reflectance and fluorescence. Materials and Methods Forty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4×4 mm window on the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the unprotected windows after 12–48 hr exposure to a demineralizing solution at pH-4.5. Near-IR reflectance images were acquired over several near-IR spectral distributions, visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Cross polarization optical coherence tomography (CP-OCT) was used to non-destructively assess the depth and severity of demineralization in each sample window. Matching two dimensional CP-OCT images of the lesion depth and integrated reflectivity were compared with the reflectance and fluorescence images to determine how accurately the variation in the lesion contrast represents the variation in the lesion severity. Results Artificial lesions appear more uniform on tooth surfaces exposed to an acid challenge at visible wavelengths than they do in the near-IR. Measurements of the lesion depth and severity using CP-OCT show that the lesion severity varies markedly across the sample windows and that the lesion contrast in the visible does not accurately reflect the large variation in the lesion severity. Reflectance measurements at certain near-IR wavelengths more accurately reflect variation in the depth and severity of the lesions. Conclusion The results of the study suggest that near-IR reflectance measurements at longer wavelengths coincident with higher water absorption are better suited for imaging early caries lesions. PMID:24375543

  18. 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.

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

    PubMed

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

    2013-03-25

    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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  2. 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...

  3. 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...

  4. 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...

  5. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rheumatoid factor immuno-logical test system. 866.5775 Section 866.5775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5775 Rheumatoid factor immuno-logical...

  6. Psychosocial management of chronic pain in patients with rheumatoid arthritis: challenges and solutions.

    PubMed

    Sharpe, Louise

    2016-01-01

    There are numerous reviews and meta-analyses that confirm that psychological therapy is efficacious for patients with rheumatoid arthritis (RA) in terms of managing pain. Therefore, the literature has moved on to answer additional questions: 1) What types of interventions are most strongly supported by the current evidence? 2) Do different patients benefit from different approaches? 3) When is it best to intervene? 4) What modalities are best for administering the intervention? 5) What model of care should we be proposing that will result in widespread implementation and will ensure access for patients with RA? This review concludes that cognitive behavioral therapy (CBT) is the most efficacious treatment for pain management in RA; however, there are indications that mindfulness may have particular benefits for patients with a history of depression. CBT is most effective when administered early in the course of the disease. However, there is at present little evidence to confirm whether or not psychosocial interventions are effective for patients with comorbid psychological disorders. One of the major challenges is ensuring access to effective interventions for patients, particularly early on in the course of the disease, with a view to preventing physical and psychological morbidity. A stepped-care model is proposed; however, we urgently need more, better-quality trials of minimal interventions, particularly in Internet-delivered CBT, which appears promising and may form the cornerstone of future stepped-care models for providing psychosocial care to patients with RA. PMID:27042139

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

    NASA Astrophysics Data System (ADS)

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

    1998-12-01

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

  8. Psychosocial management of chronic pain in patients with rheumatoid arthritis: challenges and solutions

    PubMed Central

    Sharpe, Louise

    2016-01-01

    There are numerous reviews and meta-analyses that confirm that psychological therapy is efficacious for patients with rheumatoid arthritis (RA) in terms of managing pain. Therefore, the literature has moved on to answer additional questions: 1) What types of interventions are most strongly supported by the current evidence? 2) Do different patients benefit from different approaches? 3) When is it best to intervene? 4) What modalities are best for administering the intervention? 5) What model of care should we be proposing that will result in widespread implementation and will ensure access for patients with RA? This review concludes that cognitive behavioral therapy (CBT) is the most efficacious treatment for pain management in RA; however, there are indications that mindfulness may have particular benefits for patients with a history of depression. CBT is most effective when administered early in the course of the disease. However, there is at present little evidence to confirm whether or not psychosocial interventions are effective for patients with comorbid psychological disorders. One of the major challenges is ensuring access to effective interventions for patients, particularly early on in the course of the disease, with a view to preventing physical and psychological morbidity. A stepped-care model is proposed; however, we urgently need more, better-quality trials of minimal interventions, particularly in Internet-delivered CBT, which appears promising and may form the cornerstone of future stepped-care models for providing psychosocial care to patients with RA. PMID:27042139

  9. The kappa immunoglobulin light chain repertoire of peripheral blood B cells in patients with juvenile rheumatoid arthritis.

    PubMed

    Morbach, Henner; Richl, Petra; Faber, Claudius; Singh, Sunit K; Girschick, Hermann J

    2008-08-01

    The frequent appearance of antinuclear antibodies in patients with juvenile rheumatoid arthritis (JRA) indicates a loss of tolerance in B cell differentiation and/or activation. In this analysis, we were interested whether particular changes in the immunoglobulin light chain repertoire might exist in early-onset pauciarticular arthritis (EOPA) patients thereby potentially revealing distinct molecular patterns, which characterize defects in central tolerance mechanisms as well as an autoreactive peripheral B cell repertoire. Using single cell sorting and single cell PCR the distribution of Vkappa Jkappa rearrangements has been analyzed in individual naïve B cells of patients with EOPA-JRA and healthy individuals. The immunoglobulin kappa light chain repertoire of peripheral blood B cells in EOPA patients seems to be skewed to a decreased use of downstream Vkappa gene segments indicating increased events of secondary V(D)J-recombination. Another prominent molecular pattern in JRA B cells seem to be a restricted combination of Vkappa Jkappa rearrangements based on the predominant utilization of the Jkappa 1 and 2 gene segment. The current study indicates disturbances in the peripheral B cell pool in juvenile rheumatoid arthritis. The peripheral blood B cell pool of JRA patients did show molecular changes in the kappa light chain repertoire which, in part, could be a sequel of secondary V(D)J-recombination and of a molecular bias during immunoglobulin rearrangement in the bone marrow. Thus, B cell tolerance might be broken by more than one pathogenic mechanism. PMID:18614233

  10. Production of nitrogen oxides by lightning and coronae discharges in simulated early Earth, Venus and Mars environments.

    PubMed

    Nna Mvondo, D; Navarro-Gonzalez, R; McKay, C P; Coll, P; Raulin, F

    2001-01-01

    We present measurements for the production of nitrogen oxides (NO and N2O) in CO2-N2 mixtures that simulate different stages of the evolution of the atmospheres of the Earth, Venus and Mars. The nitrogen fixation rates by two different types of electrical discharges, namely lightning and coronae, were studied over a wide range in CO2 and N2 mixing ratios. Nitric oxide (NO) is formed with a maximum energy yield estimated to be ~1.3 x 10(16) molecule J-1 at 80% CO2 and ~1.3 x 10(14) molecule J-1 at 50% CO2 for lightning and coronae discharges, respectively. Nitrous oxide (N2O) is only formed by coronae discharge with a maximum energy yield estimated to be ~1.2 x 10(13) molecule J-1 at 50% CO2. The pronounced difference in NO production in lightning and coronae discharges and the lack of formation of N2O in lightning indicate that the physics and chemistry involved in nitrogen fixation differs substantially in these two forms of electric energy. PMID:11605635

  11. 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.

  12. IgG rheumatoid factor, complement and immune complexes in rheumatoid synovitis and vasculitis: comparative and serial studies during cytotoxic therapy.

    PubMed Central

    Scott, D G; Bacon, P A; Allen, C; Elson, C J; Wallington, T

    1981-01-01

    IgG and IgM rheumatoid factors (IgG-RF and IgM-RF), complement and three assays for immune complexes were measured in 22 patients with rheumatoid arthritis (RA) complicated by either chronic active synovitis or vasculitis. Patients with vasculitis had relatively inactive arthritis but had higher titres of rheumatoid factors, especially IgG-RF, anticomplementary activity (ACA) and lower levels of C4 than those with synovitis. Clq-binding and platelet aggregation (PA) levels were similar in both groups. Serial measurements during cytotoxic therapy showed a close temporal relationship between the clinical features of vasculitis and levels of IgG-RF, ACA and C4 both with remission and with relapse. We suggest that immune complexes containing IgG-RF which activate complement and are detected by ACA are useful markers of rheumatoid vasculitis and may be important in its pathogenesis. PMID:7249394

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Molecular characterization of rheumatoid arthritis with magnetic resonance imaging.

    PubMed

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

    2011-04-01

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

  1. [Trends in orthopaedic surgery for patients with rheumatoid arthritis].

    PubMed

    Matsumoto, Takumi; Tanaka, Sakae

    2015-12-01

    Significant advancement in pharmacological treatment including biological agents has gradually changed the role and content of surgical treatments for patients with rheumatoid arthritis. The number of joint replacements in the large joints of lower limbs has decreased, while the number of surgeries in the small joints of hand and feet has increased. Favorable disease control by pharmacological treatment has changed the needs of patients for surgeries and expanded the options of operative procedures for surgeons. The changing needs of patients demanding the higher level of quality of life may seek a change in the surgical treatments. PMID:26608856

  2. Role of immunity to mycobacterial stress proteins in rheumatoid arthritis.

    PubMed Central

    McLean, L.; Winrow, V.; Blake, D.

    1990-01-01

    'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis. PMID:2184873

  3. Rheumatoid arthritis: the role of the kinder and gentler therapies.

    PubMed

    Swezey, R L

    1990-11-01

    Rehabilitative therapies, as adjuncts to pharmacological and surgical therapies in rheumatoid arthritis (RA), help minimize pain and inflammation, improve functional capabilities, and, above all, enhance quality of life. The effects of heat, cold, and electrical stimulation on neurohumoral, inflammatory, and immunological mechanisms has been noted, although knowledge about their mode of action is lacking. There is, however, much that these modalities, in addition to splints, bracing, exercise, activities-of-daily-living training, and psychological, social, and vocational counseling can offer to reduce suffering and disability in patients with RA. Far more, however, needs to be learned to provide precise prescriptions and more effective applications. PMID:1703234

  4. 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

  5. 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

  6. 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

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

    PubMed Central

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

    2013-01-01

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

  8. 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

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

    PubMed

    Saleem, B; Nizam, S; Emery, P

    2006-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Treatment of Rheumatoid Arthritis with Fenoprofen: Comparison with Aspirin

    PubMed Central

    Huskisson, E. C.; Wojtulewski, J. A.; Berry, H.; Scott, Jane; Hart, F. Dudley; Balme, H. W.

    1974-01-01

    Fenoprofen, a compound with analgesic, anti-inflammatory, and antipyretic properties in animals, has been compared with placebo in a double-blind cross-over trial in 60 patients with rheumatoid arthritis. There was a statistically highly significant reduction in pain, duration of morning stiffness, analgesic requirements, and articular index, with increase in grip strength. There was no significant reduction in joint size or temperature. In a subsequent double-blind group-comparative study fenoprofen proved to be as effective as aspirin in relieving the symptoms of rheumatoid arthritis, with strikingly fewer side effects. Almost half of the patients taking aspirin were unable to tolerate the drug in adequate dosage for six months. The remainder were able to take on average only 4 g daily, and at this dose almost half still complained of tinnitus and deafness. Fenoprofen is likely to be useful for patients who cannot tolerate aspirin and other more toxic anti-inflammatory drugs or whose disease is not of sufficient severity to justify their use. PMID:4590669

  16. 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

  17. 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.

  18. 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

  19. Amyloid Goiter Associated with Amyloidosis Secondary to Rheumatoid Arthritis

    PubMed Central

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

    2013-01-01

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

  20. Successful treatment with tocilizumab of pericarditis associated with rheumatoid arthritis.

    PubMed

    Yoshida, Shuzo; Takeuchi, Tohru; Sawaki, Hideaki; Imai, Tamaki; Makino, Shigeki; Hanafusa, Toshiaki

    2014-07-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease often complicated by vasculitis. Pericarditis is a serious complication caused by vasculitis, resulting in retention of pericardial effusion that sometimes induces cardiac tamponade. We report a patient with RA in whom pericarditis improved after tocilizumab administration. A male patient was diagnosed with RA and chronic renal failure in 1980 and was treated with salazosulfapyridine, but disease activity remained high. In January 2012, at the age of 73 years, he developed organizing pneumonia as a complication and was admitted to our hospital. Treatment with prednisolone 30 mg/day was initiated. However, 20 days after initiation of treatment, chest pain and palpitation developed, and chest computed tomography (CT) and echocardiography (ECG) revealed retention of pericardial effusion without cardiac tamponade. Rheumatoid nodules and interstitial pneumonia were also observed, and serum C3 level was decreased. A diagnosis of pericarditis caused by vasculitis was made based on these findings, and tocilizumab 8 mg/kg was administered. His symptoms improved gradually, and chest CT and ECG showed no pericardial effusion after about 3 weeks. No adverse effects of tocilizumab were observed during the clinical course. Although there are only a few reports of the effects of tocilizumab on vasculitis associated with RA, tocilizumab administration appears worthwhile in RA patients with vasculitis who do not respond to conventional treatment. PMID:24517555