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Sample records for simulating early rheumatoid

  1. [Early diagnosis of rheumatoid arthritis].

    PubMed

    Badot, V

    2014-09-01

    Rheumatoid arthritis is the most common chronic inflammatory rheumatic disorder, and is characterized by inflammation of the joint, which can lead to irreversible bone damage, joint deformity and disability, if not diagnosed timely or treated adequately. New classification criteria were developed in 2010 in order to identify patients at risk of developing persistent or erosive arthritis, and requiring early therapy. In order to detect early arthritis or bone erosions before their appearance on X-rays, ultrasound and magnetic resonance imaging are now routinely used by clinicians, and also seem to deliver prognostic information about the disease. Synovial biopsies are potentially interesting in case of early arthritis to identify markers of diagnosis, prognosis or therapeutic response. Genetic or environmental risk factors were described to play a role in the development or maintenance of the disease; they could also help to screen early RA. A rapid diagnosis is eventually based on the right information and a tight collaboration between the primary care physician and the rheumatology care specialist. PMID:25675622

  2. Radiographic changes in early rheumatoid disease.

    PubMed Central

    Brook, A; Corbett, M

    1977-01-01

    We have studied the radiological features in 94 patients with early rheumatoid disease followed prospectively for 5 years. The changes appeared very early and occurred in up to 71-3% of patients. Erosive changes occurred in the feet much more commonly than in the hands and considerably earlier. Erosive changes were present before there was joint-space loss. Frequent x-ray examination of feet and hands in the first 2 years after presentation is required if we are to identify patients at risk for serious joint damage. PMID:843114

  3. Pulmonary involvement in early rheumatoid arthritis patients.

    PubMed

    Habib, Hisham M; Eisa, Ashraf A; Arafat, Waleed R; Marie, Mohamed A

    2011-02-01

    Pulmonary involvement in rheumatoid arthritis (RA) is common and can be due to the disease itself as well as to the therapies used to treat it. The purpose of this study was to disclose the pulmonary involvement in early RA patients not more than 2 years disease duration using the computed tomography (CT) as well as the pulmonary function tests as ways of pulmonary involvement assessment. Forty patients aged 37.6 ± 10.3 with early rheumatoid arthritis not more than 2 years of disease duration were recruited for the study. All patients were assessed clinically for their RA with DAS28, which was utilized for disease activity determination. Ten percent of our patients were found to be clinically involved by interstitial lung disease (ILD), where 27% have abnormal HRCT finding and 32.5% with abnormal PFT. Predilection for clinically manifest ILD was evident in active RA patients with high DAS28 score, seropositive RA patients, and in patients receiving steroids and anti-TNFα therapy. ILD occurs early in the course of RA, with more predilection for clinically active RA disease.

  4. 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

  5. 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.

  6. Hip involvement in early rheumatoid arthritis.

    PubMed Central

    Eberhardt, K; Fex, E; Johnsson, K; Geborek, P

    1995-01-01

    OBJECTIVE--To study early hip involvement in rheumatoid arthritis (RA) and to evaluate the usefulness of ultrasonography in the detection of hip joint synovitis in RA. METHODS--Study I: The number of hip joint replacements was recorded in a cohort of 113 patients with RA of at least five years disease duration followed from an early stage. Study II: Ultrasonography was evaluated as a method to identify hip joint synovitis in 76 patients with RA of shorter disease duration, by relating it to radiograms and clinical findings. RESULTS--Study I: Twenty one hip joint replacements were performed in 15 of the 113 patients. The median disease duration at the time of first arthroplasty was 48 (range 10-76) months; the annual incidence was approximately constant between two and six years. High disease activity at the start of the study was predictive of requirement for hip prosthesis. Study II: Hip ultrasonography was pathological in 13 of the 76 patients studied, bilaterally in nine. Hip joint synovitis could not be confirmed on clinical grounds only as seven of the patients with positive ultrasonographic findings were asymptomatic, and the remaining six patients had only mild symptoms of hip involvement. Also, six of the 63 patients with normal ultrasonography had mild symptoms. There was no difference regarding demographic, clinical, and laboratory findings in patients with and without hip synovitis. CONCLUSIONS--Early hip joint destruction giving symptoms mostly at a very late stage is frequent in RA. Ultrasonography rather than signs or symptoms could identify patients with hip joint involvement and provide a rationale for early treatment. Images PMID:7880121

  7. Ultrasonography applications in diagnosis and management of early rheumatoid arthritis.

    PubMed

    Thiele, Ralf G

    2012-05-01

    Ultrasonography is an elegant tool for the detection of tenosynovitis, synovitis, and erosions very early in rheumatoid arthritis, and the presence of a power Doppler signal is one of the best predictors of joint damage. Although clinical scores remain the mainstay of disease activity assessment, ultrasonography has proved to be a remarkably robust tool for reliable assessment of changes in rheumatoid arthritis. There is no evidence to suggest that problems with operator dependence would be greater than with other imaging modalities or physical examination, if performed by trained providers.

  8. 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

  9. 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

  10. Non-drug therapies in early rheumatoid arthritis.

    PubMed

    Vliet Vlieland, Theodora P M; Pattison, Dorothy

    2009-02-01

    Non-pharmacological treatment modalities are often used as an adjunct to drug therapy in patients with rheumatoid arthritis (RA). The aim of this overview is to summarize the available evidence on the effectiveness of these modalities in early RA. The few available randomized controlled trials that have specifically investigated patients with early RA support the effectiveness of dynamic exercise and cognitive behavioural interventions, and to a lesser extent of joint protection programmes and foot orthoses. The effectiveness of multidisciplinary team-care programmes, specialist nurse care, electro-physical modalities (including passive hydrotherapy), wrist orthoses, and dietary interventions have not been studied in patients with early RA. Current recommendations on the usage of non-pharmacological treatment modalities in sets of guidelines on the management of early RA vary with respect to their scope, strength and level of detail. The results of this review indicate a need for further investigation into the most clinically effective and cost-effective strategies to deliver non-pharmacological treatment modalities as well as comprehensive arthritis care models in early RA.

  11. Managing early presentation of rheumatoid arthritis. Systematic overview.

    PubMed Central

    Glazier, R.

    1996-01-01

    OBJECTIVE: To describe evidence-based management of patients presenting to family physicians with typical signs and symptoms of recent onset of rheumatoid arthritis (RA). STUDY SELECTION: Articles for critical review were included if relevant to primary care management of early RA (less than 1 year duration). Sources included MEDLINE from 1966 to December 1995, the reference library of the Arthritis Community Research and Evaluation Unit, and conference abstracts. FINDINGS: Evidence from randomized, controlled trials supports the short-term benefit of nonsteroidal anti-inflammatory drugs, disease-modifying agents for rheumatic diseases, intravenous pulse corticosteroid therapy, intra-articular therapy, aerobic exercise, patient education, psychologic intervention, home physiotherapy, home occupational therapy, and rehabilitation programs. Some evidence favours acetaminophen for analgesia, low-dose oral corticosteroids for symptom control, and referral to a rheumatologist. Evidence for rest, ice, and heat for symptom control is conflicting and based on low-quality studies. CONCLUSION: Family physicians play an important role in establishing early and accurate diagnosis of RA, coordinating therapy, and providing ongoing support, education, and monitoring to patients and their families. PMID:8688694

  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

  13. Predictors of functional status in patients with early rheumatoid arthritis

    PubMed Central

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

    2000-01-01

    OBJECTIVE—To find disease parameters that can predict the functional capacity of patients with early rheumatoid arthritis (RA) at the first visit to the rheumatologist and one year after entry.
METHODS—Patients referred to the outpatients clinic between 1995 and 1996, with a symptom duration of less than three years and fulfilling the American Rheumatism Association 1987 revised criteria for RA within one year after entry were included. Assessments of the duration of morning stiffness, the Disease Activity Score (DAS: a composite score based on erythrocyte sedimentation rate (ESR), number of painful and swollen joints and patient global assessment), pain (Visual Analogue Scale), the Arthritis Impact Measurement Scale (AIMS) and the Health Assessment Questionnaire (HAQ) were performed every three months. Possible predictors of the HAQ at entry and after one year were analysed by logistic regression.
RESULTS—133 patients were included in the study. The median duration of complaints was three months (range 0-35) and the median HAQ score at entry was 1.12 (range 0-3). There was no correlation between duration of complaints and the HAQ at entry (r = 0.01). An HAQ score under the 50th percentile at entry could be predicted correctly for 74% of the patients by entry DAS and C reactive protein concentration, and at one year could be predicted correctly for 73% of the patients by entry HAQ and pain score.
CONCLUSION—Disease activity is strongly correlated with a lower functional capacity at entry, whereas disease duration is not. The functional status at entry is a good predictor for functional status at one year. Severity rather than duration of arthritis prompts referral in this cohort.

 PMID:10700432

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

    PubMed Central

    Orozco, Catalina; Olsen, Nancy J.

    2006-01-01

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

  15. Identification of patients with early rheumatoid arthritis: challenges and future directions.

    PubMed

    Orozco, Catalina; Olsen, Nancy J

    2006-01-01

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

  16. 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

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

    PubMed Central

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

    1981-01-01

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

  18. Remission-induction therapies for early rheumatoid arthritis: evidence to date and clinical implications

    PubMed Central

    Espinoza, Francisco; Fabre, Sylvie; Pers, Yves-Marie

    2016-01-01

    Recent guidelines on rheumatoid arthritis (RA) point to the importance of achieving remission as soon as possible during the course of the disease. The appropriate use of antirheumatic drugs is critical, particularly in early RA patients, before 24 weeks, since this is a ‘window of opportunity’ for treatment to modify disease progression. A treat-to-target strategy added to an aggressive therapeutic approach increases the chance of early remission, particularly in early RA patients. We conducted an overview of current therapeutic strategies leading to remission in early RA patients. We also provide interesting predictive factors that can guide the RA management strategy with regard to disease-modifying treatment and/or drug-free remission. PMID:27493689

  19. Remission-induction therapies for early rheumatoid arthritis: evidence to date and clinical implications.

    PubMed

    Espinoza, Francisco; Fabre, Sylvie; Pers, Yves-Marie

    2016-08-01

    Recent guidelines on rheumatoid arthritis (RA) point to the importance of achieving remission as soon as possible during the course of the disease. The appropriate use of antirheumatic drugs is critical, particularly in early RA patients, before 24 weeks, since this is a 'window of opportunity' for treatment to modify disease progression. A treat-to-target strategy added to an aggressive therapeutic approach increases the chance of early remission, particularly in early RA patients. We conducted an overview of current therapeutic strategies leading to remission in early RA patients. We also provide interesting predictive factors that can guide the RA management strategy with regard to disease-modifying treatment and/or drug-free remission. PMID:27493689

  20. Magnetic resonance imaging applications in early rheumatoid arthritis diagnosis and management.

    PubMed

    Troum, Orrin M; Pimienta, Olga; Olech, Ewa

    2012-05-01

    Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is a sensitive modality that can assess both inflammatory and structural lesions. MRI can assist in following the disease course in patients treated with traditional disease-modifying antirheumatic drugs and biological therapies both in the clinic and in research trials. Therefore, it is anticipated that MRI becomes the diagnostic imaging modality of choice in RA clinical trials while remaining a useful tool for clinicians evaluating patients with RA.

  1. Rheumatoid arthritis in Latin America: the importance of an early diagnosis.

    PubMed

    da Mota, Licia Maria Henrique; Brenol, Claiton Viegas; Palominos, Penelope; Pinheiro, Geraldo da Rocha Castelar

    2015-03-01

    The generalization of the early rheumatoid arthritis (ERA) concept and the existence of a window of therapeutic opportunity-a time span in which the institution of a proper therapeutic method for the disease would determine clinical improvement-have set the notion that early diagnosis and treatment may modify the course of the disease. Although in several regions of the world, especially in North America and Europe, since the year 2000, a significant reduction in diagnostic delay was observed in cohorts of patients with rheumatoid arthritis (RA), probably reflecting a stronger awareness of the importance of early diagnosis, this is not a reality in Latin America (LA). LA is a region of great economic inequality, with disparities in access to the public healthcare system and limited access to private medicine, being widely difficult to obtain a specialized medical evaluation in both scenarios. This paper aims to briefly review the main difficulties in the management of ERA in LA, based on the review of the literature, on the evaluation of a survey conducted among 214 rheumatologists of LA, members of Pan-American League of Associations for Rheumatology (PANLAR) and the experience of the authors. The paper also aims to propose solutions to the difficulties in managing ERA in LA.

  2. Serum levels of IL-17, IL-4, and INFγ in Serbian patients with early rheumatoid arthritis

    PubMed Central

    Pavlovic, Voja; Dimic, Aleksandar; Milenkovic, Sasa; Krtinic, Dane

    2014-01-01

    Background: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease with autoimmune etiology, characterized by synovial inflammation and destruction of joint cartilage and bone. There are controversial data about the profile of interleukin-17 (IL-17A), interleukin-4 (IL-4), and interferon-gamma (INFγ), indicating in some studies the key role of IL-17, while in others the Th1 cytokines. Materials and Methods: Serum samples of 31 early RA patients were evaluated for erythrocytes sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and for the tested cytokines (IL-17A, IL-4, and INFγ). Disease activity score (DAS28) calculation was done for all patients. Control serum samples were obtained from 29 healthy volunteers. Results: The levels of tested cytokines were significantly higher (IL-17A, p < 0.001; INFγ, p < 0.001; IL-4, p < 0.01) in patients with early RA, compared to the healthy controls. In early RA patients, a strong correlation of serum IL-17A was found with DAS28, ESR, and CRP. Also, significant negative correlation was found between serum INFγ levels and the DAS28 score, indicating that INFγ may play a key role in maintaining immune homeostasis in patients with RA. Conclusion: The mean serum IL-17A levels in patients with early RA, corresponded with the disease activity and severity. This might highlight the usefulness of the serum IL-17A level in defining the activity and predictive patterns, for aggressive disease therapy, and it might express specific therapeutically targets. PMID:24672560

  3. A historical perspective concerning population-based and clinical studies of early arthritis and early rheumatoid arthritis.

    PubMed

    Sokka, T; Pincus, T

    2003-01-01

    Research concerning early arthritis and early rheumatoid arthritis (RA) may be considered to have begun with population-based studies in the United Kingdom, the United States and Scandinavia, from the late 1950s to the late 1960s. These studies indicated that the majority of people with clinical findings of RA had no evidence of disease 3-5 years later, and that only about 25% to 30% of people in a population who met the criteria for RA had rheumatoid factor. These findings may have contributed to an underestimation of RA until the severity of long-term outcomes of clinical RA were recognized in the 1980s on the basis of clinical cohorts. The first major early RA clinical cohort was established in 1957-1963 in Bath, England. Although results at 3 and even 11 years were not overly unfavorable, by 15 and 20 years most patients had severe outcomes of functional declines and premature mortality. The Middle-sex (UK) early RA cohort established in 1966-1971 indicated that radiographic abnormalities were observed in about 70% of patients by 2 years of disease, and were seen in most patients initially in the feet. The Memphis (Tennessee, USA) early RA cohort established in 1967-1971 suggested that a progressive course of RA is predicted by a higher number of involved joints at baseline. The Lund (Sweden) early RA cohort established in 1985-1989 indicated rather severe long-term outcomes in patients treated according to traditional conservative approaches to use of disease modifying anti-rheumatic drugs (DMARDs). The early RA study (ERAS) involving nine National Health Service trusts in the UK was established in 1987-93, and showed associations of education level and socioeconomic status with clinical status. The movement towards early arthritis clinics was given great impetus following the work by Emery in the early 1990s. These studies and others described elsewhere in this supplement have contributed to the foundations for the clinical approach to early arthritis in the

  4. Only high disease activity and positive rheumatoid factor indicate poor prognosis in patients with early rheumatoid arthritis treated with "sawtooth" strategy

    PubMed Central

    Mottonen, T; Paimela, L; Leirisalo-Repo, M; Kautiainen, H; Ilonen, J; Hannonen, P

    1998-01-01

    OBJECTIVES—To investigate the prognostic significance of clinical and genetic markers on the outcome of patients with recent-onset rheumatoid arthritis (RA) treated actively with slow acting antirheumatic drugs (SAARDs).
METHODS—A total of 142 consecutive patients with early RA (median disease duration of 7 months) were treated according to the "sawtooth" strategy and prospectively followed up for an average of 6.2 years. Several clinical parameters at start as well as genetic markers were related to the functional outcome (ARA Functional class and HAQ disability score) and radiographic joint damage (Larsen's score) at the latest visit.
RESULTS—In logistic regression analysis only Mallya score (including morning stiffness, pain scale, grip strength, Ritchie's articular index, haemoglobin, and erythrocyte sedimentation rate) at baseline, and Mallya score and rheumatoid factor (RF) positivity at one year were found to be of significance with respect to the radiographic outcome of the patients. Furthermore, at the latest visit HAQ score was related to radiographic score. At baseline the mean ages of the DR4 positive patients and the patients with RA associated DR alleles were statistically significantly lower than those without the above mentioned risk factors (44 v 49, p=0.03 and 41 v 53, p=0.04, respectively). However, these genetic markers had no prognostic significance on the functional or radiographic outcome of the patients.
CONCLUSION—High clinical disease activity at baseline and RF positivity especially at one year after the institution of SAARD treatment are the best predictors of poor prognosis in early RA. However, from the clinical point of view, the disease outcome of an individual patient with early RA, cannot be predicted accurately enough by present means.

 Keywords: rheumatoid arthritis; prognosis; outcome; prediction PMID:9849312

  5. 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

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

    PubMed

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

    2015-01-01

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

  7. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    PubMed Central

    Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

    2016-01-01

    Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. Methods MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. Results Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. Conclusions Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. Trial registration number NCT01039688; Results. PMID:27493790

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

    PubMed Central

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

    2015-01-01

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

  9. 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

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

    PubMed

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

    2016-02-01

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

  11. Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease.

    PubMed

    Smolen, Josef S; Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J; Kvien, Tore K; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F; Abadie, Eric C; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves

    2016-07-01

    The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for the treatment of RA' released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria. PMID:27037326

  12. Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease

    PubMed Central

    Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J; Kvien, Tore K; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F; Abadie, Eric C; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves

    2016-01-01

    The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft ‘Guideline on clinical investigation of medicinal products for the treatment of RA’ released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria. PMID:27037326

  13. Prediction of Disease Severity in Patients with Early Rheumatoid Arthritis by Gene Expression Profiling

    PubMed Central

    Liu, Zheng; Sokka, Tuulikki; Maas, Kevin; Olsen, Nancy J.; Aune, Thomas M.

    2009-01-01

    In order to test the ability of peripheral blood gene expression profiles to predict future disease severity in patients with early rheumatoid arthritis (RA), a group of 17 patients (1 ± 0.2 years disease duration) was evaluated at baseline for gene expression profiles. Disease status was evaluated after a mean of 5 years using an index combining pain, global and recoded MHAQ scores. Unsupervised and supervised algorithms identified “predictor genes” whose combined expression levels correlated with follow-up disease severity scores. Unsupervised clustering algorithms separated patients into two branches. The only significant difference between these two groups was the disease severity score; demographic variables and medication usage were not different. Supervised T-Test analysis identified 19 “predictor genes” of future disease severity. Results were validated in an independent cohort of subjects of established RA with using Support Vector Machines and K-Nearest-Neighbor Classification. Our study demonstrates that peripheral blood gene expression profiles may be a useful tool to predict future disease severity in patients with early and established RA. PMID:20948566

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

    PubMed

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

    2015-11-01

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

  15. A prospective study of renal disease in patients with early rheumatoid arthritis

    PubMed Central

    Koseki, Y; Terai, C; Moriguchi, M; Uesato, M; Kamatani, N

    2001-01-01

    OBJECTIVES—This prospective study was designed to clarify the frequency, causes, and clinical course of renal disease in patients with early rheumatoid arthritis (RA).
METHODS—235 patients (185 women, mean age 49.4 years) with early RA of less than one year's duration were enrolled and assessed monthly. Proteinuria was defined as a positive dipstick result and microscopic haematuria was defined as the presence of ⩾5 red blood cells per high power field. Urinary abnormalities lasting three months or longer were defined as persistent abnormalities.
RESULTS—At entry, 40 patients exhibited haematuria, two had a raised serum creatinine concentration, and none had proteinuria. During the observation period (average 42 months), persistent haematuria was found in 43, persistent proteinuria in 17, and a raised serum creatinine concentration in 14 patients. Persistent proteinuria was caused by drugs in 14 of 17 patients and disappeared in most cases. Risk factors for drug induced proteinuria included a raised C reactive protein and erythrocyte sedimentation rate and age over 50 at entry. Drugs resulted in a raised serum creatinine concentration in eight of 14 patients. The incidence of haematuria at entry did not differ among patients who had been treated with non-steroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, or no drugs. In some patients with isolated haematuria, the haematuria appeared when the activity of RA was high and resolved when it was low.
CONCLUSIONS—This study suggests that a raised serum creatinine concentration or persistent proteinuria in patients with early RA is predominantly drug related whereas, in contrast, isolated haematuria is more directly associated with the activity of the disease process.

 PMID:11247860

  16. Rheumatoid Factors: Clinical Applications

    PubMed Central

    Castelli, Roberto

    2013-01-01

    Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy. PMID:24324289

  17. 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

  18. Responsiveness of the core set, response criteria, and utilities in early rheumatoid arthritis

    PubMed Central

    Verhoeven, A; Boers, M; van der Linden, S

    2000-01-01

    OBJECTIVE—Validation of responsiveness and discriminative power of the World Health Organisation/International League of Associations for Rheumatology (WHO/ILAR) core set, the American College of Rheumatology (ACR), and European League for Rheumatology (EULAR) criteria for improvement/response, and other single and combined measures (indices) in a trial in patients with early rheumatoid arthritis (RA).
METHODS—Ranking of measures by response (standardised response means and effect sizes) and between-group discrimination (unpaired t test and χ2 values) at two time points in the COBRA study. This study included 155 patients with early RA randomly allocated to two treatment groups with distinct levels of expected response: combined treatment, high response; sulfasalazine treatment, moderate response.
RESULTS—At week 16, standardised response means of core set measures ranged between 0.8 and 3.5 for combined treatment and between 0.4 and 1.2 for sulfasalazine treatment (95% confidence interval ±0.25). Performance of patient oriented measures (for example, pain, global assessment) was best when the questions were focused on the disease. The most responsive single measure was the patient's assessment of change in disease activity, at 3.5. Patient utility, a generic health status measure, was moderately (rating scale) to poorly (standard gamble) responsive. Response means of most indices (combined measures) exceeded 2.0, the simple count of core set measures improved by 20% was most responsive at 4.1. Discrimination performance yielded similar but not identical results: best discrimination between treatment groups was achieved by the EULAR response and ACR improvement criteria (at 20% and other percentage levels), the pooled index, and the disease activity score (DAS), but also by the Health Assessment Questionnaire (HAQ) and grip strength.
CONCLUSIONS—Responsiveness and discrimination between levels of response are not identical concepts, and

  19. Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial

    PubMed Central

    Burmester, Gerd R; Rigby, William F; van Vollenhoven, Ronald F; Rubbert-Roth, Andrea; Kelman, Ariella; Dimonaco, Sophie; Mitchell, Nina

    2016-01-01

    Objectives The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA). Methods In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28–erythrocyte sedimentation rate (ESR) <2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week 52. Results The intent-to-treat population included 1157 patients. Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX achieved DAS28-ESR remission at week 24 (45% and 39% vs 15%; p<0.0001). The 8 mg/kg TCZ+MTX group also achieved significantly greater improvement in radiographic disease progression and physical function at week 52 than did patients treated with placebo+MTX (mean change from baseline in van der Heijde–modified total Sharp score, 0.08 vs 1.14 (p=0.0001); mean reduction in Health Assessment Disability Index, −0.81 vs −0.64 (p=0.0024)). In addition, the 8 mg/kg TCZ+placebo and 4 mg/kg TCZ+MTX groups demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints. Serious adverse events were similar among treatment groups. Adverse events resulting in premature withdrawal occurred in 20% of patients in the 8 mg/kg TCZ+MTX group. Conclusions TCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA. Trial registration number ClinicalTrials.gov, number NCT01007435 PMID:26511996

  20. The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumatoid Arthritis.

    PubMed

    Siloşi, Isabela; Boldeanu, Mihail Virgil; Cojocaru, Manole; Biciuşcă, Viorel; Pădureanu, Vlad; Bogdan, Maria; Badea, Ramona Georgiana; Avramescu, Carmen; Petrescu, Ileana Octavia; Petrescu, Florin; Siloşi, Cristian A

    2016-01-01

    Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA), the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP. PMID:27579330

  1. The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumatoid Arthritis

    PubMed Central

    Siloşi, Isabela; Boldeanu, Mihail Virgil; Cojocaru, Manole; Badea, Ramona Georgiana

    2016-01-01

    Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA), the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP. PMID:27579330

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

    PubMed Central

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

    2011-01-01

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

  3. 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.

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

    PubMed

    2003-01-01

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

  5. Rheumatoid Vasculitis

    MedlinePlus

    ... RV) is an unusual complication of longstanding, severe rheumatoid arthritis. The active vasculitis associated with rheumatoid disease occurs ... a manifestation of “extra-articular” (beyond the joint)rheumatoid arthritis and involves the small and medium-sized arteries ...

  6. Timing the therapeutic window of opportunity in early rheumatoid arthritis: proposal for definitions of disease duration in clinical trials.

    PubMed

    Raza, Karim; Saber, Tajvur P; Kvien, Tore K; Tak, Paul P; Gerlag, Danielle M

    2012-12-01

    The effects of treatment in early rheumatoid arthritis (RA) and the consequences of delayed therapy represent important areas for research. The concept of a 'window of opportunity' is now well established and considerable attention has been paid to when it might close. However, in order to study how long the window of opportunity lasts, the timing of its opening must be precisely defined. An analysis of definitions of 'onset' in clinical studies reveals imprecision and heterogeneity, making accurate assessment of this important concept of the 'window of opportunity' very difficult. In this paper we propose that, in clinical trials in early RA, data on durations since onset of symptoms and onset of joint swelling as well as disease duration based on fulfilment of classification criteria should be routinely presented.

  7. Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis

    PubMed Central

    Peterfy, Charles; Burmester, Gerd R; Bykerk, Vivian P; Combe, Bernard G; DiCarlo, Julie C; Furst, Daniel E; Huizinga, Tom W J; Wong, Dennis A; Conaghan, Philip G; Emery, Paul

    2016-01-01

    Objectives To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity. Methods Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population. Results 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (−2.35 vs −0.68, −2.58 vs −0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (−1.34 vs −0.49 −2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX. Conclusions Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity. Trial registration number NCT01142726; Results. PMID:26865601

  8. [Rheumatoid arthritis].

    PubMed

    Strunk, J; Lange, U; Müller-Ladner, U

    2005-07-29

    The development of novel anti-rheumatic drugs revolutionizes currently therapeutic strategies and diagnostic management of patients with rheumatoid arthritis, facilitating the goal of true remission instead of only symptomatic treatment as in former years. Since early treatment is known to be crucial for the longterm outcome, imaging modalities such as magnetic resonance imaging and high-frequency ultrasonography including Doppler sonography, which allow direct visualization of very early pathologic alterations of synovitis, or even initial destruction, become increasingly important. Besides the established therapy with methotrexate, new drugs such as leflunomide or the use of various combination therapies have been successfully introduced into the therapeutic armamentarium. Especially the introduction of cytokine-antagonists such as TNF-a inhibitors target the aim of remission. In addition, the upcoming therapeutic agents, which influence very effectively the inflammatory and destructive process need also to be integrated into the concert of different therapeutic strategies in the management of patients with rheumatoid arthritis, which includes the mandatory complementary factors such as physiotherapy, ergotherapy and orthopedic surgery.

  9. 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

  10. 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

  11. 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 ...

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

    PubMed

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

    2015-11-01

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

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

    PubMed

    Combe, Bernard; Rincheval, Nathalie

    2015-01-01

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

  14. Could early rheumatoid arthritis resolve after periodontitis treatment only?: case report and review of the literature.

    PubMed

    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

    2014-12-01

    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

  15. Impact of intensive treatment and remission on health-related quality of life in early and established rheumatoid arthritis

    PubMed Central

    Scott, I C; Ibrahim, F; Lewis, C M; Scott, D L; Strand, V

    2016-01-01

    Objectives To establish if using intensive treatment to reduce synovitis and attain remission in active rheumatoid arthritis (RA) improves all aspects of health-related quality of life (HRQoL). Methods A secondary analysis of two randomised clinical trials (CARDERA and TACIT) was undertaken. CARDERA randomised 467 patients with early active RA to different disease-modifying antirheumatic drug (DMARD) regimens, including high-dose tapering corticosteroids. TACIT randomised 205 established patients with active RA to combination DMARDs (cDMARDs) or tumour necrosis factor-α inhibitors (TNFis). Short-Form 36 (SF-36) measured HRQoL across eight domains, generating physical (PCS) and mental (MCS) component summary scores. Linear regression evaluated 6-month intensive treatment impacts. Mean SF-36 scores, stratified by end point disease activity category, were compared with age/gender-matched population scores. Results In CARDERA, intensive corticosteroid treatment gave significantly greater improvements in PCS but not MCS scores relative to placebo. In TACIT, all eight SF-36 domains had improvements from baseline exceeding minimal clinically important differences with cDMARDs and TNFis. Significantly greater improvements with TNFi relative to cDMARDs were reported in PCS only (p=0.034), after adjusting for covariates. Remission provided the best SF-36 profiles, but scores in physical functioning, role physical and general health in both trials remained below normative values. Patient global assessment of disease activity had a greater association with HRQoL than other disease activity score (DAS28) components. Conclusions Intensive corticosteroid treatment in early RA improves physical but not mental health, relative to placebo. In established RA, cDMARDs and TNFi provide similar improvements in HRQoL. As remission optimises but fails to normalise HRQoL, a focus on treatment strategies targeting HRQoL is required. Trial registration numbers CARDERA was registered as

  16. Impact of intensive treatment and remission on health-related quality of life in early and established rheumatoid arthritis

    PubMed Central

    Scott, I C; Ibrahim, F; Lewis, C M; Scott, D L; Strand, V

    2016-01-01

    Objectives To establish if using intensive treatment to reduce synovitis and attain remission in active rheumatoid arthritis (RA) improves all aspects of health-related quality of life (HRQoL). Methods A secondary analysis of two randomised clinical trials (CARDERA and TACIT) was undertaken. CARDERA randomised 467 patients with early active RA to different disease-modifying antirheumatic drug (DMARD) regimens, including high-dose tapering corticosteroids. TACIT randomised 205 established patients with active RA to combination DMARDs (cDMARDs) or tumour necrosis factor-α inhibitors (TNFis). Short-Form 36 (SF-36) measured HRQoL across eight domains, generating physical (PCS) and mental (MCS) component summary scores. Linear regression evaluated 6-month intensive treatment impacts. Mean SF-36 scores, stratified by end point disease activity category, were compared with age/gender-matched population scores. Results In CARDERA, intensive corticosteroid treatment gave significantly greater improvements in PCS but not MCS scores relative to placebo. In TACIT, all eight SF-36 domains had improvements from baseline exceeding minimal clinically important differences with cDMARDs and TNFis. Significantly greater improvements with TNFi relative to cDMARDs were reported in PCS only (p=0.034), after adjusting for covariates. Remission provided the best SF-36 profiles, but scores in physical functioning, role physical and general health in both trials remained below normative values. Patient global assessment of disease activity had a greater association with HRQoL than other disease activity score (DAS28) components. Conclusions Intensive corticosteroid treatment in early RA improves physical but not mental health, relative to placebo. In established RA, cDMARDs and TNFi provide similar improvements in HRQoL. As remission optimises but fails to normalise HRQoL, a focus on treatment strategies targeting HRQoL is required. Trial registration numbers CARDERA was registered as

  17. MRI of the wrist in early rheumatoid arthritis can be used to predict functional outcome at 6 years

    PubMed Central

    Benton, N; Stewart, N; Crabbe, J; Robinson, E; Yeoman, S; McQueen, F

    2004-01-01

    Objectives: To determine whether magnetic resonance (MR) scans of the dominant wrist of patients with early rheumatoid arthritis (RA) can be used to predict functional outcome at 6 years' follow up. Methods: Dominant wrist MR scans were obtained in 42 patients with criteria for RA at first presentation. Patients were followed up prospectively for 6 years, and further scans obtained at 1 year (42 patients) and 6 years (31 patients). Two radiologists scored scans for synovitis, tendonitis, bone oedema, and erosions. The Stanford Health Assessment Questionnaire (HAQ) score, indicating functional outcome, and standard measures of disease activity were assessed at 0, 1, 2, and 6 years. The physical function component of the SF-36 score (PF-SF36) was also used as a functional outcome measure at 6 years. Results: Baseline MR parameters, including bone oedema score and the total baseline MR score, were predictive of the PF-SF36 at 6 years (R2 = 0.22, p = 0.005 and R2 = 0.16, p = 0.02, respectively). The PF-SF36 score correlated strongly with the HAQ score at 6 years (rs = –0.725, p<0.0001); none of the baseline MR parameters predicted the 6 year HAQ score. The total MR score obtained at 1 year was predictive of the 6 year HAQ (R2 = 0.04, p = 0.01). Standard clinical and radiographic measures at baseline were not predictive of the 6 year PF-SF36, but when combined in a model with baseline MR oedema score, prediction increased from 0.09 to 0.23, or 23% of the 6 year variance. Conclusion: MR imaging of the wrist in patients with early RA can help to predict function at 6 years and could be used to plan aggressive management at an earlier stage. PMID:15082487

  18. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals progression of erosions despite clinical improvement

    PubMed Central

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

    1999-01-01

    OBJECTIVES—To investigate the progression of joint damage in early rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of the wrist and determine whether this technique can be used to predict prognosis.
METHODS—An inception cohort of 42 early patients has been followed up prospectively for one year. Gadolinium enhanced MRI scans of the dominant wrist were obtained at baseline and one year and scored for synovitis, tendonitis, bone marrow oedema, and erosions. Plain radiographs were performed concurrently and scored for erosions. Patients were assessed clinically for disease activity and HLA-DRB1 genotyping was performed.
RESULTS—At one year, MRI erosions were found in 74% of patients (31 of 42) compared with 45% at baseline. Twelve patients (28.6%) had radiographic erosions at one year. The total MRI score and MRI erosion score increased significantly from baseline to one year despite falls in clinical measures of inflammation including erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and swollen joint count (p < 0.01 for all). Baseline findings that predicted carpal MRI erosions at one year included a total MRI score of 6 or greater (sensitivity: 93.3%, specificity 81.8%, positive predictive value 93.3%, p = 0.000007), MRI bone oedema (OR = 6.47, p < 0.001), MRI synovitis (OR = 2.14, p = 0.003), and pain score (p = 0.01). Radiological erosions at one year were predicted by a total MRI score at baseline of greater than 13 (OR = 12.4, p = 0.002), the presence of MRI erosions (OR = 11.6, p = 0.005), and the ESR (p = 0.02). If MRI erosions were absent at baseline and the total MRI score was low, radiological erosions were highly unlikely to develop by one year (negative predictive value 0.91 and 0.92 respectively). No association was found between the shared epitope and erosions on MRI (p = 0.4) or radiography (p = 1.0) at one year.
CONCLUSIONS—MRI scans of the dominant wrist are useful

  19. 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

  20. Rheumatoid arthritis: early treatment with corticosteroids and nonsteroidal anti-inflammatory drugs.

    PubMed

    Ruoff, Gary

    2014-02-01

    The family physician plays several important roles in the management of patients with RA by early diagnosis of RA, with initiation of synthetic DMARD therapy, and in long-term follow-up to minimize complications of DMARD therapy and its impact on patient comorbidities. Three recently approved products offer some benefit as adjunctive therapy. PMID:24527481

  1. 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

  2. [Familial form of rheumatoid nodulosis].

    PubMed

    Bosser, H; Schubert, B; Grosshans, E

    1993-01-01

    We report a familial form of rheumatoid nodulosis where the early lesions appeared in the first years of life in a young man and his son. The numerous papular and nodular skin lesions disclosed an ulcerative evolution leaving atrophic scars mainly near the limbs' joints. In both patients the evolution was characterized by the late onset of polyarthralgias and of a non-destructive seronegative polyarthritis; intra-osseous lesions were present in the metatarsal bones in the father. Rheumatoid nodulosis is a rare disease, sometimes considered as a benign variant of rheumatoid arthritis without destructive joint involvement. A serum rheumatoid factor is inconstantly present and the intra-osseous geodes have been shown to be rheumatoid nodules exhibiting the same histological structures of palisading granulomas as the subcutaneous nodules. The main symptom of the disease is the occurrence of multiple nodules followed by the delayed onset of a polyarthritis with a benign course without systemic involvement.

  3. 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

  4. Rheumatoid lung disease

    MedlinePlus

    Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Elsevier Saunders; 2016:chap 65. Lake F, Proudman S. Rheumatoid arthritis and lung disease: from mechanisms to a practical approach. Semin Respir ...

  5. Rheumatoid arthritis

    MedlinePlus

    ... with rest, strengthening exercise, and anti-inflammatory drugs. Methotrexate is the most commonly used DMARD for rheumatoid ... is a drug that is often combined with methotrexate and hydroxychloroquine (triple therapy). It may be weeks ...

  6. 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

  7. Rheumatoid arthritis.

    PubMed

    Scott, David L; Wolfe, Frederick; Huizinga, Tom W J

    2010-09-25

    Rheumatoid arthritis is characterised by persistent synovitis, systemic inflammation, and autoantibodies (particularly to rheumatoid factor and citrullinated peptide). 50% of the risk for development of rheumatoid arthritis is attributable to genetic factors. Smoking is the main environmental risk. In industrialised countries, rheumatoid arthritis affects 0·5-1·0% of adults, with 5-50 per 100 000 new cases annually. The disorder is most typical in women and elderly people. Uncontrolled active rheumatoid arthritis causes joint damage, disability, decreased quality of life, and cardiovascular and other comorbidities. Disease-modifying antirheumatic drugs (DMARDs), the key therapeutic agents, reduce synovitis and systemic inflammation and improve function. The leading DMARD is methotrexate, which can be combined with other drugs of this type. Biological agents are used when arthritis is uncontrolled or toxic effects arise with DMARDs. Tumour necrosis factor inhibitors were the first biological agents, followed by abatacept, rituximab, and tocilizumab. Infections and high costs restrict prescription of biological agents. Long-term remission induced by intensive, short-term treatment selected by biomarker profiles is the ultimate goal.

  8. Early changes in bone mineral density measured by digital X-ray radiogrammetry predict up to 20 years radiological outcome in rheumatoid arthritis

    PubMed Central

    2011-01-01

    Introduction Changes in bone mineral density (BMD) in the hand as evaluated by digital X-ray radiogrammetry (DXR) of the second to fourth metacarpal bones has been suggested to predict future joint damage in patients with rheumatoid arthritis (RA). This study's objective was to investigate whether DXR-BMD loss early in the course of the disease predicts the development of joint damage in RA patients followed for up to 20 years. Methods A total of 183 patients (115 women and 68 men) with early RA (mean disease duration, 11 months) included from 1985 to 1989 were followed prospectively (the Lund early RA cohort). Clinical and functional measures were assessed yearly. Joint damage was evaluated according to the Larsen score on radiographs of the hands and feet obtained in years 0 to 5 and years 10, 15 and 20. These radiographs were digitized, and BMD of the second to fourth metacarpal bones was evaluated by DXR. Early DXR-BMD change rate (that is, bone loss) per year calculated from the first two radiographs obtained on average 9 months apart (SD ± 4.8) were available for 135 patients. Mean values of the right and left hand were used. Results Mean early DXR-BMD loss during the first year calculated was -0.023 g/cm2 (SD ± 0.025). Patients with marked bone loss, that is, early DXR-BMD loss above the median for the group, had significantly worse progression of joint damage at all examinations during the 20-year period. Conclusions Early DXR-BMD progression rate predicted the development of joint damage evaluated according to Larsen score at year 1 and for up to 20 years in this cohort of early RA patients. PMID:21345204

  9. 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.

  10. Looking through the 'window of opportunity': is there a new paradigm of podiatry care on the horizon in early rheumatoid arthritis?

    PubMed Central

    2010-01-01

    Over the past decade there have been significant advances in the clinical understanding and care of rheumatoid arthritis (RA). Major paradigm changes include earlier disease detection and introduction of therapy, and 'tight control' of follow-up driven by regular measurement of disease activity parameters. The advent of tumour necrosis factor (TNF) inhibitors and other biologic therapies have further revolutionised care. Low disease state and remission with prevention of joint damage and irreversible disability are achievable therapeutic goals. Consequently new opportunities exist for all health professionals to contribute towards these advances. For podiatrists relevant issues range from greater awareness of current concepts including early referral guidelines through to the application of specialist skills to manage localised, residual disease activity and associated functional impairments. Here we describe a new paradigm of podiatry care in early RA. This is driven by current evidence that indicates that even in low disease activity states destruction of foot joints may be progressive and associated with accumulating disability. The paradigm parallels the medical model comprising early detection, targeted therapy, a new concept of tight control of foot arthritis, and disease monitoring. 'Podiatrists are experts on foot disorders: both patients and rheumatologists can profit from the involvement of a podiatrist' - Korda and Balint, 2004 [1]. PMID:20478038

  11. 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

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

    PubMed Central

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

    1998-01-01

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

 Keywords: magnetic resonance imaging; carpus; rheumatoid arthritis PMID:9771209

  13. Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data

    PubMed Central

    Granger, Benjamin; Combe, Bernard; Le Loet, Xavier; Saraux, Alain; Guillemin, Francis; Fautrel, Bruno

    2016-01-01

    Introduction Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX). Methods We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for ≥3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS≥5 points during the first year. Results At 1 year, the mean vSHS score was 1.7±5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC) <0.7. The AUC for the BEST and SONORA matrices were 0.73 and 0.76. Presence of rheumatoid factor (RF)—or anti-citrullinated protein antibodies (ACPAs) and initial structural damage were always predictive of RRP at 1 year. Disease Activity Score in 28 joints (DAS28) and C reactive protein (ASPIRE threshold) were not associated with RRP. Conclusions Matrices to identify patients at risk of RRP tested in the ESPOIR cohort seem to perform moderately. There is no matrix that shows clearly superior performance. PMID:27252898

  14. 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.

  15. Cerebral rheumatoid vasculitis: a case report

    PubMed Central

    2012-01-01

    Introduction Central nervous system involvement in rheumatoid arthritis is infrequent. The most frequent neurological manifestations of rheumatoid arthritis are peripheral neuropathy and cervical spinal cord compression due to subluxation of the cervical vertebrae. Cerebral rheumatoid vasculitis is an uncommon and serious complication which can be life-threatening. Case presentation A 52-year-old North African Tunisian Caucasian woman presented with a six-week history of headache. She had suffered seropositive and destructive rheumatoid arthritis for nine years without any extra-articular complications. Magnetic resonance imaging of the brain with the T2 sequence showed high-intensity signal images at the frontal and parietal cortico-subcortical junction suggesting hemispheric vasculitis. Conclusions Cerebral vasculitis is an infrequent complication in rheumatoid arthritis which is associated with high morbidity and in some cases can be life-threatening. Early assessment and a high index of suspicion to recognize such complications are essential in managing these patients. PMID:22974191

  16. A proposal of simple calculation (ERI calculator) to predict the early response to TNF-α blockers therapy in rheumatoid arthritis.

    PubMed

    Bazzichi, Laura; Rossi, Paolo; Giacomelli, Camillo; De Feo, Francesca; Bobbio-Pallavicini, Francesca; Rossi, Alessandra; Baldini, Chiara; Consensi, Arianna; Doveri, Marica; Bonino, Claudia; Mazzantini, Maurizio; Della Rossa, Alessandra; Montecucco, Carlomaurizio; Bombardieri, Stefano

    2012-02-01

    Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-α blocking agents. The formulation and definition of an early indicator of patient's reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.

  17. 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

  18. My treatment approach to rheumatoid arthritis.

    PubMed

    Davis, John M; Matteson, Eric L

    2012-07-01

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

  19. Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility and Early Disease Activity in Rheumatoid Arthritis

    PubMed Central

    Sandoughi, Mahnaz; Fazeli, Seyed Amirhossein; Bahari, Gholamreza; Rezaei, Maryam

    2016-01-01

    Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects. The HLA-G rs1063320 (+3142G>C) and rs66554220 (14 bp ins/del) variants were genotype by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38–0.97, p = 0.038, GC versus GG; OR = 0.36, 95% CI = 0.14–0.92, p = 0.034, CC versus GG), dominant (OR = 0.56, 95% CI = 0.36–0.87, p = 0.011, GC + CC versus GG), and allele (OR = 0.58, 95% CI = 0.41–0.84, p = 0.004, C versus G) inheritance models tested. Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. In addition, no significant association was found between the polymorphism and early disease activity. Conclusion. In summary, our results showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of RA in a sample of the Iranian population. PMID:27610404

  20. Circadian rhythm and the influence of physical activity on circulating surfactant protein D in early and long-standing rheumatoid arthritis.

    PubMed

    Christensen, A F; Hoegh, S V; Lottenburger, T; Holmskov, U; Tornoe, I; Hørslev-Petersen, K; Sørensen, G L; Junker, P

    2011-12-01

    Surfactant protein D (SP-D) belongs to the collectin family and has pro-and anti-inflammatory capacities depending on its oligomerization. Previously, circulating SP-D was shown to be decreased in early rheumatoid arthritis (RA) and negatively correlated to disease activity. This study aimed at assessing the diurnal rhythmicity and the influence of physical activity on circulating SP-D in patients with RA at different stages compared with healthy individuals. Patients with early RA (ERA) with disease duration <6 months and with long-standing RA (LRA) with disease duration 5-15 years were included in two sub-studies. Healthy individuals served as controls. Diurnal variation: blood samples were collected every 3 h from 7 a.m to 10 p.m and the following morning. Physical activity: blood sampling was done before and after standardized physical challenge. SP-D was measured by ELISA. SP-D exhibited diurnal variation in healthy controls (n = 15) and in patients with ERA (n = 9) and LRA (n = 9) with peak values at 10 a.m. and nadir in the evening (controls: P < 0.001, ERA: P = 0.004 and LRA: P = 0.009). Three hours after cessation of physical activity, SP-D decreased below pre-exercise levels in both ERA (n = 10), LRA (n = 10) and controls (n = 13) (ERA: P < 0.001, LRA: P < 0.001 and controls: P = 0.005). In patients with RA, the decline was already observed 1 h post-exercise. Circulating SP-D exhibits diurnal variation both in patients with RA at different stages and in healthy controls. SP-D in serum decreases following physical activity in health and RA disease. This study underscores the need of standardized blood sampling conditions in future studies on SP-D.

  1. Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility and Early Disease Activity in Rheumatoid Arthritis

    PubMed Central

    Sandoughi, Mahnaz; Fazeli, Seyed Amirhossein; Bahari, Gholamreza; Rezaei, Maryam

    2016-01-01

    Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects. The HLA-G rs1063320 (+3142G>C) and rs66554220 (14 bp ins/del) variants were genotype by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38–0.97, p = 0.038, GC versus GG; OR = 0.36, 95% CI = 0.14–0.92, p = 0.034, CC versus GG), dominant (OR = 0.56, 95% CI = 0.36–0.87, p = 0.011, GC + CC versus GG), and allele (OR = 0.58, 95% CI = 0.41–0.84, p = 0.004, C versus G) inheritance models tested. Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. In addition, no significant association was found between the polymorphism and early disease activity. Conclusion. In summary, our results showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of RA in a sample of the Iranian population.

  2. Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility and Early Disease Activity in Rheumatoid Arthritis.

    PubMed

    Hashemi, Mohammad; Sandoughi, Mahnaz; Fazeli, Seyed Amirhossein; Bahari, Gholamreza; Rezaei, Maryam; Zakeri, Zahra

    2016-01-01

    Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects. The HLA-G rs1063320 (+3142G>C) and rs66554220 (14 bp ins/del) variants were genotype by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38-0.97, p = 0.038, GC versus GG; OR = 0.36, 95% CI = 0.14-0.92, p = 0.034, CC versus GG), dominant (OR = 0.56, 95% CI = 0.36-0.87, p = 0.011, GC + CC versus GG), and allele (OR = 0.58, 95% CI = 0.41-0.84, p = 0.004, C versus G) inheritance models tested. Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. In addition, no significant association was found between the polymorphism and early disease activity. Conclusion. In summary, our results showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of RA in a sample of the Iranian population. PMID:27610404

  3. Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals high expression of catabolic bone markers that is modulated by methotrexate

    PubMed Central

    2013-01-01

    Introduction We aimed to investigate the expression and therapeutic modulation of the receptor activator of the NF-κB ligand (RANKL) system in early-untreated rheumatoid arthritis (RA). Methods In this study, 15 patients with newly diagnosed RA (median symptom duration 7 months) were started on methotrexate (MTX) 20 mg weekly. Synovial biopsies were obtained by needle arthroscopy at baseline and 8 weeks after initiation of therapy. X-rays of the hands and feet were obtained at baseline and 1 year after diagnosis. Immunohistochemistry was performed to detect RANKL, receptor activator of nuclear factor-κB (RANK) and osteoprotegerin (OPG) in the synovial biopsies. The in vitro effect of MTX was tested on RA-derived primary fibroblasts and the osteoblasts-like osteosarcoma cell line (rtPCR, Western blot and ELISA) and in osteoclasts (tartrate-resistant acid phosphatase staining and dentine pit formation assay). Results MTX decreased synovial cellularity as well as RANK expression and the RANKL/OPG ratio. We confirmed this effect by a decrease of the mRNA and protein RANKL/OPG ratio in synovial-derived fibroblasts and osteoblasts-like tumoral cells exposed in vitro to methotrexate. Supernatants from MTX treated osteoblasts-like tumoral cells prevented pre-osteoclast formation in the absence of exogenous RANKL. Furthermore, MTX blocked osteoclastogenesis from peripheral blood mononuclear cells despite the presence of macrophage colony stimulating factor and RANKL, which indicates that MTX directly inhibits osteoclastogenesis. Conclusions The synovial membrane of early-untreated RA is characterized by a high RANKL/OPG ratio that can be reversed by methotrexate. PMID:24295447

  4. Early morphea simulating patch-stage mycosis fungoides.

    PubMed

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

    2015-05-01

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

  5. What Is Rheumatoid Arthritis?

    MedlinePlus

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

  6. 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 ...

  7. Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study

    PubMed Central

    D'Agostino, Maria-Antonietta; Wakefield, Richard J; Berner-Hammer, Hilde; Vittecoq, Olivier; Filippou, Georgios; Balint, Peter; Möller, Ingrid; Iagnocco, Annamaria; Naredo, Esperanza; Østergaard, Mikkel; Boers, Maarten; Gaillez, Corine; Van Holder, Karina; Le Bars, Manuela

    2016-01-01

    Objectives To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology–European League Against Rheumatism (OMERACT–EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT–EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2–5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2–5): −0.7 (95% CIs −1.2 to −0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number NCT00767325. PMID:26590174

  8. Sustained maintenance of exercise induced muscle strength gains and normal bone mineral density in patients with early rheumatoid arthritis: a 5 year follow up

    PubMed Central

    Hakkinen, A; Sokka, T; Kautiainen, H; Kotaniemi, A; Hannonen, P

    2004-01-01

    Objective: To investigate at 5 years whether an initial 2 year home based strength training period imposes sustained effects on muscle strength, bone mineral density (BMD), structural joint damage, and on disease activity in patients with early rheumatoid arthritis (RA). Methods: Seventy patients were randomised either to perform home based strength training with loads of 50–70% of repetition maximum (EG) or range of motion exercises (CG). Both groups were encouraged to take part in aerobic activities 2–3 times a week. Maximal muscle strength of different muscle groups was measured by dynamometers, and BMD at the femoral neck and lumbar spine by dual x ray densitometry. Disease activity was assessed by the 28 joint disease activity score, and joint damage by x ray findings. Results: 62 patients completed 2 years' training and 59 patients attended check up at 5 years. Mean (SD) maximum muscle strength indices increased from baseline to 2 years—in EG from 212 (78) kg by a mean (95% CI) of 68 (55 to 80) and in CG from 195 (72) kg by 35 (13 to 60) kg—and remained at that level for the next 3 years. Development of BMD in EG tended to be more favourable than that in CG. Muscle strength training was not detrimental to joint structures or disease activity. Conclusion: The patients' exercise induced muscle strength gains during a 2 year training period were maintained throughout a subsequent self monitored training period of 3 years. Despite substantial training effects in muscle strength, BMD values remained relatively constant. Radiographic damage remained low even at 5 years. PMID:15249317

  9. 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

  10. [The rheumatoid hand].

    PubMed

    Henry, Julien; Roulot, Eric; Gaujoux-Viala, Cécile

    2013-12-01

    Rheumatoid arthritis usually affects the hand (90%). Without treatment, joint damages and deformities lead to loss of the ability to grip, grasp, and pinch, often leaving the patient unable to perform the activities of daily living. Early treatment with DMARDs ± physical therapy is the best way to control the disease and prevent deformity, as well as disability, which often occurs when joints get damaged. Two decades later dramatic advances have been made in the medical therapy of RA with the expanded range of effective disease-modifying antirheumatic drugs. When a patient with RA develops joint damages in the hand or wrist that are unresponsive to medical management and injections therapy, surgical intervention may be necessary. Optimal care involves a team approach among the patient involving rheumatologists, physical therapists and hand surgeons. Patients with RA should be closely monitored in order to detect joint damages necessitating physical therapist or hand surgeon consultation.

  11. Rheumatoid Arthritis Educational Video Series

    MedlinePlus

    ... Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos was designed ... Activity Role of Body Weight in Osteoarthritis Educational Videos for Patients Rheumatoid Arthritis Educational Video Series Psoriatic ...

  12. Cyclosporin A monotherapy versus cyclosporin A and methotrexate combination therapy in patients with early rheumatoid arthritis: a double blind randomised placebo controlled trial

    PubMed Central

    Gerards, A; Landewe, R; Prins, A; Bruijn, G; Goei, T; Laan, R; Dijkmans, B

    2003-01-01

    Patients and methods: 120 patients with active RA, rheumatoid factor positive and/or erosive, were randomly allocated to receive CsA with MTX (n=60) or CsA with placebo (n=60). Treatment with CsA was started in all patients at 2.5 mg/kg/day and increased to a maximum of 5 mg/kg/day in 16 weeks. MTX was started at 7.5 mg/week and increased to a maximal dose of 15 mg/week at week 16. Primary outcomes were clinical remission (Pinals criteria) and radiological damage (Larsen score), at week 48. Results: Treatment was discontinued prematurely in 27 patients in the monotherapy group (21 because of inefficacy, and six because of toxicity) and in 26 patients in the combination therapy group (14 and 12, respectively). At week 48, clinical remission was achieved in four patients in the monotherapy group and in six patients in the combination therapy group (p=0.5). The median Larsen score increased to 10 (25th, 75th centiles: 3.5; 13.3) points in the monotherapy group and to 4 (1.0; 10.5) points in the combination therapy group (p=0.004). 28/60 (47%) of patients in the monotherapy group v 34/60 (57%) of patients in the combination therapy group had reached an American college of Rheumatology 20% (ACR20) response (p=0.36) at week 48; 15/60 (25%) v 29/60 (48%) of patients had reached an ACR50 response (p=0.013); and 7 (12%) v 12 (20%) of patients had reached an ACR70 response (p=0.11).Their was a tendency towards more toxicity in the combination therapy group. Conclusions: In patients with early RA, neither CsA plus MTX combination therapy nor CsA monotherapy is very effective in inducing clinical remission. Combination therapy is probably better at improving clinical disease activity, and definitely better at slowing radiological progression. Combination therapy should still be compared with methotrexate monotherapy. PMID:12634224

  13. 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

  14. Biomarkers for rheumatoid and psoriatic arthritis.

    PubMed

    Verheul, M K; Fearon, U; Trouw, L A; Veale, D J

    2015-11-01

    Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.

  15. Rheumatoid arthritis: vocational rehabilitation.

    PubMed

    Cochrane, G M

    1982-01-01

    The consequences of inflation and accelerating introduction of automation and microprocessors into industry are a shift from unskilled to skilled work, the lessening of opportunities for the unskilled worker, and growing unemployment. If disabled people are competing for employment they must take every opportunity to extend education and acquire skills. Juvenile chronic arthritis presents one set of problems in vocational rehabilitation at the beginning of a working career and adult rheumatoid arthritis another, commonly in those over 45 years old and previously established in work. The prevalence of severe disability in juvenile chronic arthritis is about 1 in 20 000 of the population, females are affected twice as often as males and 1 in 10 has defective vision or blindness due to chronic iridocyclitis. At school, besides education, there must be emphasis on encouraging independence, self-confidence, mobility and determination. A School Leavers' Conference early in the last year at school gives the adolescent the best chance of choosing a career. Rheumatoid arthritis is three times more common in women and increasingly, over the last 40 years, women are working besides home-making. Morning stiffness, fatigue, immobility and pain are the common symptoms of widespread involvement of joints and systemic disturbance. The principal determinant in the success of vocational rehabilitation is personality, and the social and environmental factors are more significant than the degree of disability. The Disablement Resettlement Officer can assure continuity of rehabilitation between the health and employment services: a favourable outcome is work, self-derived income independence and freedom of movement using whatever technical aids are required to achieve this.

  16. 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.

  17. 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. PMID:27123445

  18. What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease

    PubMed Central

    McQueen, F; Benton, N; Crabbe, J; Robinson, E; Yeoman, S; McLean, L; Stewart, N

    2001-01-01

    OBJECTIVES—To investigate the progression of erosions at sites within the carpus, in patients with early rheumatoid arthritis (RA), using magnetic resonance imaging (MRI) and plain radiology over a two year period.
METHODS—Gadolinium enhanced MRI scans of the dominant wrist were performed in 42 patients with RA at baseline (within six months of symptom onset) and one year. Plain wrist radiographs (x rays) and clinical data were obtained at baseline, one year, and two years. Erosions were scored by two musculoskeletal radiologists on MRI and x ray at 15 sites in the wrist. A patient centred analysis was used to evaluate the prognostic value of a baseline MRI scan. A lesion centred analysis was used to track the progression of individual erosions over two years.
RESULTS—The baseline MRI erosion score was predictive of x ray erosion score at two years (p=0.004). Patients with a "total MRI score" (erosion, bone oedema, synovitis, and tendonitis) ⩾13 at baseline were significantly more likely to develop erosions on x ray at two years (odds ratio 13.4, 95% CI 2.65 to 60.5, p=0.002). Baseline wrist MRI has a sensitivity of 80%, a specificity of 76%, a positive predictive value of 67%, and a high negative predictive value of 86% for the prediction of wrist x ray erosions at two years. A lesion centred analysis, which included erosions scored by one or both radiologists, showed that 84% of baseline MRI erosions were still present at one year. When a more stringent analysis was used which required complete concordance between radiologists, all baseline lesions persisted at one year. The number of MRI erosion sites in each patient increased from 2.1 (SD 2.7) to 5.0 (4.6) (p<0.0001) over the first year of disease. When MRI erosion sites were tracked, 21% and 26% were observed on x ray, one and two years later. A high baseline MRI synovitis score, Ritchie score, and erythrocyte sedimentation rate were predictive of progression of MRI erosions to x ray

  19. Rheumatoid vasculitis - Case report.

    PubMed

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

    2015-01-01

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

  20. [Current treatment of rheumatoid arthritis].

    PubMed

    Carli, P; Landais, C; Aletti, M; Cournac, J-M; Poisnel, E; Paris, J-F

    2009-12-01

    Over the past 10 years, the management of rheumatoid arthritis has been revolutionized. Early diagnosis is essential and should allow an early initiation of disease modifying anti-rheumatic drugs (DMARD), if possible within the first 3 three months after disease onset, aiming at disease remission and the best long-term prognosis. Recommendations for the prescription of synthetic and biologic DMARD (mainly anti-TNFalpha agents) are available since September 2007 [6] by HAS in France. The great efficacy of these drugs has been established from many clinical trials including tens of thousands of patients. However, severe adverse side effects may occur (allergy, tuberculosis, opportunistic infections, demyelination) and rheumatologists should remain vigilant. Global care of the patient includes prescription of pharmacologic and non-pharmacologic treatments (education, physical treatment, ergotherapy, psychotherapy, surgery). A good coordination between all specialists is required. Screening and treatment of extra-articular manifestations, prevention of infections, osteoporosis and cardiovascular complications are essential to allow a better long-term prognosis, and reduce disability and mortality of rheumatoid arthritis.

  1. 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

  2. Rheumatoid Arthritis Educational Video Series

    MedlinePlus

    ... Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos was designed to help you ... Educational Videos for Patients Rheumatoid Arthritis Educational Video Series Psoriatic Arthritis 101 2010 E.S.C.A.P. ...

  3. [Dry eye syndrome in rheumatoid arthritis patients].

    PubMed

    Polanská, V; Hlinomazová, Z; Fojtík, Z; Nemec, P

    2007-11-01

    between the dry eye syndrome presence and duration of the RA longer than 10 years; we did not find the dependence among the RF presence and stage of the rheumatoid arthritis and the appearance of the dry eye syndrome. The early diagnosis of the dry eye syndrome and the effective local therapy may prevent very serious corneal complications, which are difficult to treat.

  4. [Differential therapy for the rheumatoid shoulder].

    PubMed

    Schill, S; Thabe, H; Grifka, J

    2002-12-01

    Despite frequent involvement, the rheumatoid shoulder is neglected in operative treatment of the upper extremities. The slow course of omarthritis, the compensation mechanism of scapulothoracic motion and neighbouring joints as well as dominating disabilities of the lower extremities and the rheumatoid hand are possible explanations. The pattern of destruction of the rheumatoid shoulder is characterized by progressive joint and soft tissue deterioration. Soft tissue involvement determines the course of the shoulder joint. The subacromial space is a common and early site for rheumatoid involvement, often leading to bursitis, tenosynovitis of the biceps tendon and rotator cuff rupture. Sonography and MRI enable the early detection of subacromial and glenohumeral pathology before deterioration is visible radiologically. Surgical intervention in patients with rheumatoid arthritis of the shoulder is based on the degree of radiological destruction according to Larsen, the natural course of the shoulder joint and the soft-tissue condition. The goals of surgery are to relieve pain, increase motion and restore shoulder function. Surgery should be carried out early in the course of the disease, thus determining the long-term prognosis and the remaining surgical options. Depending on the pattern of destruction of the rheumatoid shoulder, the options for treatment can be divided into early and late procedures.Joint-preserving surgery is indicated in the early stages of radiological destruction according to Larsen classification O-III, whereas the late stages of destruction (Larsen IV-V) require reconstructive surgery. The introduction of arthroscopic and semiarthroscopic techniques has improved the acceptance of early synovectomy for the rheumatoid shoulder, but there is still a place for open synovectomy in patients with extensive soft-tissue repair and bone-remodelling procedures. Arthroscopic and open synovectomy are supplementary and noncompetitive surgical procedures for

  5. [Therapy of cervical rheumatoid arthritis].

    PubMed

    Kothe, R; Wiesner, L; Rüther, W

    2004-08-01

    The rheumatoid involvement of the cervical spine can be divided into three phases. In the early stage of the disease there is an isolated atlantoaxial subluxation (AAS), followed by vertical instability and subaxial instability. If patients show clear symptoms of cervical myelopathy, which can occur during any stage of the disease, the progression cannot be stopped by conservative treatment, which is of great importance at the beginning of the cervical manifestation. Patient education, physiotherapy and immobilization with a stiff collar can significantly reduce pain. Early and effective DMARD therapy can have a positive effect on the natural history of the disease. In case of progressive instability, cervical myelopathy or severe pain operative treatment is indicated. If there is an isolated AAS, fusion can be restricted to the C1/C2 segment. The Magerl transarticular screw fixation is the preferred technique for stabilization. If there is evidence for vertical instability or severe destruction of the C0/C1 joints, occipital cervical fusion has to be performed. Durin the preoperative planning it is necessary to look for signs of subaxial instability. If this is the case, fusion should include the entire cervical spine. Transoral decompression may be necessary when there is persistent anterior compression of the myelon, typically seen in fixed AAS. Non-ambulatory myelopathic patients are more likely to develop severe surgical complications. Therefore, it is important to avoid the development of severe cervical instability by early surgical intervention. The right timing for surgery is still a matter of controversy. Future prospective randomized trials should address this topic to improve the treatment concept for the rheumatoid patient.

  6. Dermatoglyphics in rheumatoid arthritis.

    PubMed

    Ravindranath, Roopa; Shubha, R; Nagesh, H V; Johnson, Job; Rajangam, Sayee

    2003-10-01

    Patients with rheumatoid arthritis have been referred to Division of Human Genetics for counselling. Qualitative dermatoglyphics comprising of finger print pattern, interdigital pattern, hypothenar pattern and palmar crease were studied on 26 female and 11 male rheumatoid arthritis patients. Comparison between patient male and control male; and patient female and control female has been done. 'Chi' square test was performed. In male patients, with hands together, arches were increased, loops/ whorls were decreased. Partial Simian crease was significantly increased. In the right hand, patterns were increased in the 3rd interdigital area. On the other hand, in female patients there was a significant increase in whorls and decrease in loops on the first finger on both the hands, increase in arches on the 3rd finger; both arches and whorls on the 4th finger of left hand. Present study has emphasized that dermatoglyphics could be applied as a diagnostic tool to patients with rheumatoid arthritis.

  7. Glucocorticoids and Rheumatoid Arthritis.

    PubMed

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

    2016-02-01

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

  8. Discovery 3: A Simulation of Early American Colonization.

    ERIC Educational Resources Information Center

    Wesley, John

    This simulation allows students to experience the mystery of exploration and the hazards and perils of colonial life. Students are divided into 4- to 6-person colonizing groups. After acquiring some background information they then become colonists. They spend the remainder of the simulation making decisions, working, coping, surviving, and…

  9. Rheumatoid arthritis in Saudi Arabia

    PubMed Central

    Almoallim, Hani M.; Alharbi, Laila A.

    2014-01-01

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

  10. Rheumatoid arthritis: MR imaging manifestations.

    PubMed

    Beltran, J; Caudill, J L; Herman, L A; Kantor, S M; Hudson, P N; Noto, A M; Baran, A S

    1987-10-01

    Radiologic assessment of the stage and treatment response of rheumatoid arthritis (RA) is based on the presence of bone erosions, joint-space narrowing, and osteoporosis. Most radiologic methods for staging RA lack interobserver correlation and are time consuming. Magnetic resonance (MR) imaging provides excellent depiction of soft-tissue abnormalities of the joints affected by RA, which allows detection of early changes. Nineteen joints of 17 patients with RA were studied with surface-coil MR imaging. Measurable abnormalities demonstrated by MR imaging but not clearly seen on plain radiographs included bone erosions, joint effusion, synovial sheath effusion, and cartilage irregularity and thinning. Seven patients of this group underwent MR imaging before and after 6 months of gold therapy. Four patients had significant interval changes on MR images that were not seen on plain radiographs. MR imaging may become a sensitive and objective method for quantitative assessment of the joint changes of RA. PMID:3628762

  11. Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter, double-blind, randomized controlled study.

    PubMed

    Ichikawa, Yoichi; Saito, Terunobu; Yamanaka, Hisashi; Akizuki, Masashi; Kondo, Hirobumi; Kobayashi, Shigeto; Oshima, Hisaji; Kawai, Shinichi; Hama, Nobuaki; Yamada, Hidehiro; Mimori, Tsuneyo; Amano, Koichi; Tanaka, Yasushi; Matsuoka, Yasuo; Yamamoto, Sumiki; Matsubara, Tsukasa; Murata, Norikazu; Asai, Tomiaki; Suzuki, Yasuo

    2005-01-01

    Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group), 200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 +/- 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 +/- 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.

  12. 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

  13. [Immunological markers of rheumatoid arthritis].

    PubMed

    Matuszewska, Agnieszka; Madej, Marta; Wiland, Piotr

    2016-03-25

    Rheumatoid arthritis (RA) is the most common connective tissue disease of autoimmune origin. The disease is characterized by chronic inflammation leading to bone erosions and organ involvement. RA is a progressive disease. It affects the quality of life, leading to disability and death mainly due to premature cardiovascular disease. Early diagnosis and appropriate treatment are essential for prognosis and quality of life improvement. In 2010 the American College of Rheumatology (ACR) and The European League Against Rheumatism (EULAR) established new RA classification criteria. Besides clinical symptoms it includes two immunologic criteria: rheumatoid factor (RF) and anti-citrullinated protein antibodies (anti-CCP antibodies). RF is the first well-known RA immunologic marker. It is observed in 80-85% of patients with RA. Elevated serum level of RF has been associated with increased disease activity, radiographic progression, and the presence of extraarticular manifestations. The sensitivity of RF is 50-90%, and specificity is 50-95%. Anti-CCP antibodies appear to be a more specific marker than RF. They are often present at the very beginning of the disease, or even years before the first symptoms. The prognostic value of anti-CCP antibodies is well established. High serum level of anti-CCP correlates with poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%. New immunologic markers include anti-carbamylated protein antibodies (anti-CarP) and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33). Scientists aim to identify a highly sensitive and specific biomarker of the disease that not only has diagnostic and prognostic value but also may predict the response to treatment.

  14. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques

    PubMed Central

    Conaghan, Philip G; Østergaard, Mikkel; Bowes, Michael A; Wu, Chunying; Fuerst, Thomas; Irazoque-Palazuelos, Fedra; Soto-Raices, Oscar; Hrycaj, Pawel; Xie, Zhiyong; Zhang, Richard; Wyman, Bradley T; Bradley, John D; Soma, Koshika; Wilkinson, Bethanie

    2016-01-01

    Objectives To explore the effects of tofacitinib—an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)—with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. Methods In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant. Results In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were −1.55 (90% CI −2.52 to −0.58) for tofacitinib + MTX and −1.74 (−2.72 to −0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were −0.63 (−1.58 to 0.31) for tofacitinib + MTX and −0.52 (−1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy. Conclusions These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage. Trial registration number NCT01164579. PMID:27002108

  15. Induction maintenance with tumour necrosis factor-inhibitor combination therapy with discontinuation versus methotrexate monotherapy in early rheumatoid arthritis: a systematic review and meta-analysis of efficacy in randomised controlled trials

    PubMed Central

    Emamikia, Sharzad; Arkema, Elizabeth V; Györi, Noémi; Detert, Jacqueline; Chatzidionysiou, Katerina; Dougados, Maxime; Burmester, Gerd Rüdiger; van Vollenhoven, Ronald

    2016-01-01

    Objective To determine whether an induction-maintenance strategy of combined therapy (methotrexate (MTX)+tumour necrosis factor (TNF) inhibitor (TNFi)) followed by withdrawal of TNFi could yield better long-term results than a strategy with MTX monotherapy, since it is unclear if the benefits from an induction phase with combined therapy are sustained if TNFi is withdrawn. Methods We performed a meta-analysis of trials using the initial combination of MTX+TNFi in conventional synthetic disease-modifying antirheumatic drug-naïve patients with early rheumatoid arthritis (RA). A systematic literature search was performed for induction-maintenance randomised controlled trials (RCTs) where initial combination therapy was compared with MTX monotherapy in patients with clinically active early RA. Our primary outcome was the proportion of patients who achieved low disease activity (LDA; Disease Activity Score (DAS)28<3.2) and/or remission (DAS28<2.6) at 12–76 weeks of follow-up. A random-effects model was used to pool the risk ratio (RR) for LDA and remission and heterogeneity was explored by subgroup analyses. Results We identified 6 published RCTs, 4 of them where MTX+adalimumab was given as initial therapy and where adalimumab was withdrawn in a subset of patients after LDA/remission had been achieved. 2 additional trials used MTX+infliximab as combination therapy. The pooled RRs for achieving LDA and clinical remission at follow-up after withdrawal of TNFi were 1.41 (95% CI 1.05 to 1.89) and 1.34 (95% CI 0.95 to 1.89), respectively. There was significant heterogeneity between trials due to different treatment strategies, which was a limitation to this study. Conclusions Initial therapy with MTX+TNFi is associated with a higher chance of retaining LDA and/or remission even after discontinuation of TNFi. PMID:27651929

  16. Induction maintenance with tumour necrosis factor-inhibitor combination therapy with discontinuation versus methotrexate monotherapy in early rheumatoid arthritis: a systematic review and meta-analysis of efficacy in randomised controlled trials

    PubMed Central

    Emamikia, Sharzad; Arkema, Elizabeth V; Györi, Noémi; Detert, Jacqueline; Chatzidionysiou, Katerina; Dougados, Maxime; Burmester, Gerd Rüdiger; van Vollenhoven, Ronald

    2016-01-01

    Objective To determine whether an induction-maintenance strategy of combined therapy (methotrexate (MTX)+tumour necrosis factor (TNF) inhibitor (TNFi)) followed by withdrawal of TNFi could yield better long-term results than a strategy with MTX monotherapy, since it is unclear if the benefits from an induction phase with combined therapy are sustained if TNFi is withdrawn. Methods We performed a meta-analysis of trials using the initial combination of MTX+TNFi in conventional synthetic disease-modifying antirheumatic drug-naïve patients with early rheumatoid arthritis (RA). A systematic literature search was performed for induction-maintenance randomised controlled trials (RCTs) where initial combination therapy was compared with MTX monotherapy in patients with clinically active early RA. Our primary outcome was the proportion of patients who achieved low disease activity (LDA; Disease Activity Score (DAS)28<3.2) and/or remission (DAS28<2.6) at 12–76 weeks of follow-up. A random-effects model was used to pool the risk ratio (RR) for LDA and remission and heterogeneity was explored by subgroup analyses. Results We identified 6 published RCTs, 4 of them where MTX+adalimumab was given as initial therapy and where adalimumab was withdrawn in a subset of patients after LDA/remission had been achieved. 2 additional trials used MTX+infliximab as combination therapy. The pooled RRs for achieving LDA and clinical remission at follow-up after withdrawal of TNFi were 1.41 (95% CI 1.05 to 1.89) and 1.34 (95% CI 0.95 to 1.89), respectively. There was significant heterogeneity between trials due to different treatment strategies, which was a limitation to this study. Conclusions Initial therapy with MTX+TNFi is associated with a higher chance of retaining LDA and/or remission even after discontinuation of TNFi.

  17. 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…

  18. 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…

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

    SciTech Connect

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

    2011-03-07

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

  20. Overview of vasculitis and vasculopathy in rheumatoid arthritis--something to think about.

    PubMed

    Radic, Mislav; Martinovic Kaliterna, Dusanka; Radic, Josipa

    2013-07-01

    The vasculature plays a crucial role in inflammation and atherosclerosis associated with the pathogenesis of rheumatoid arthritis. Vasculitis in rheumatoid arthritis is associated with longstanding disease, has an important impact on a patient's quality of life and influences patient life expectancy. Seropositivity, specific human leukocyte antigen variations, antibodies to cyclic citrullinated peptides, and cigarette smoking are among the genetic and environmental predictors of rheumatoid vasculitis. Atherosclerosis is an early and common finding in rheumatoid arthritis and it correlates with disease duration, activity, and severity. Apart from conventional risk factors such as cigarette smoking, physical inactivity, obesity, arterial hypertension, dyslipidemia and diabetes mellitus, rheumatoid arthritis-related risk factors including disease duration, severity and activity, rheumatoid factor and antibodies to cyclic citrullinated peptides status, functional impairment, C-reactive protein, radiographic changes, presence of the shared epitope, and treatment modalities are all implicated in the development of accelerated atherosclerosis. Atherosclerosis is also considered an inflammatory disease; thus, it may share common pathogenic mechanisms with rheumatic diseases such as rheumatoid arthritis. Advances in treatment of rheumatoid arthritis with disease-modifying biologic and nonbiologic agents will probably continue to reduce the incidence of vasculitis. Since the goal of treatment for rheumatoid arthritis is to decrease inflammatory burden, successful treatment may theoretically reduce the risk of accelerated atherosclerosis.

  1. Simulation of early 20th century global warming

    PubMed

    Delworth; Knutson

    2000-03-24

    The observed global warming of the past century occurred primarily in two distinct 20-year periods, from 1925 to 1944 and from 1978 to the present. Although the latter warming is often attributed to a human-induced increase of greenhouse gases, causes of the earlier warming are less clear because this period precedes the time of strongest increases in human-induced greenhouse gas (radiative) forcing. Results from a set of six integrations of a coupled ocean-atmosphere climate model suggest that the warming of the early 20th century could have resulted from a combination of human-induced radiative forcing and an unusually large realization of internal multidecadal variability of the coupled ocean-atmosphere system. This conclusion is dependent on the model's climate sensitivity, internal variability, and the specification of the time-varying human-induced radiative forcing.

  2. [Rheumatoid arthritis: diagnostics and therapy 2012].

    PubMed

    Lorenz, H-M

    2012-07-01

    Rheumatoid Arthritis (RA) should be suspected if patients do not only complain of joint pain, but suffer from joint swelling, sensation of heat, hyperemia and warmth around the joints. An arthritic joint pain should be most prominent at night time or early in the morning and cause morning stiffness (> 30 min) of the joint, exercise will improve the symptoms. Diagnosis of RA will be even more likely if wrists, MCP- or PIP joints are affected. Serologic procedures will test for rheumatoid factor or anti-citrullinated antibodies (CCP Ab). One needs to keep in mind that positive results for rheumatoid factor or CCP Ab alone never proves the diagnosis of RA. After diagnosis therapy should be started immediately, recruiting physiotherapy, pain medication, corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), primarily methotrexate. At the latest after failure of two DMARDs biologics like TNF-α-blockers, an Interleukin-6-Receptor-antibody, a B-cell-specific antibody or a rather T-cell-specific biologic will be initiated. Aim of therapy is freedom of symptoms of an ongoing arthritis, low dosage of immunosuppressants (especially corticosteroids maximally 5 mg/day), stop of radiological progression and prevention of long term consequences of inflammation like myocardial infarction, stroke or lymphoma.

  3. 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

  4. [Personalized Medicine in Rheumatoid Arthritis].

    PubMed

    Kumagai, Shunichi

    2015-10-01

    Medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introductions of biologics and methotrexate as an anchor drug have made it possible to not only suppress pain and inflammation (clinical remission), but also to inhibit joint destruction (structural remission), leading to cure of the disease. In order to achieve this target, it is the most important to diagnose RA early and promote disease remission. However, since the condition and pathology are diverse among patients, optimal treatment for each patient is desired (personalized medicine). Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics (genetic polymorphism, etc.), are indispensable for personalized medicine. We have established a predictive model for methotrexate hepatotoxicity, consisting of 13 SNPs with a sensitivity of 100% and specificity of 89%, although the model should be validated with a larger-scale prospective study. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of anti-CCP antibodies (ACPA); thereafter, secondary stimuli of joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. Cure can be achieved through complete remission by early aggressive treatment and returning to the pre-clinical state of RA with environmental improvement.

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

    PubMed Central

    Fraser, Kevin J.

    1982-01-01

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

  6. The clinical features of rheumatoid arthritis.

    PubMed

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

    1998-05-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive damage of synovial-lined joints and variable extra-articular manifestations. Tendon and bursal involvement are frequent and often clinically dominant in early disease. RA can affect any joint, but it is usually found in metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints, as well as in the wrists and knee. Articular and periarticular manifestations include joint swelling and tenderness to palpation, with morning stiffness and severe motion impairment in the involved joints. The clinical presentation of RA varies, but an insidious onset of pain with symmetric swelling of small joints is the most frequent finding. RA onset is acute or subacute in about 25% of patients, but its patterns of presentation also include palindromic onset, monoarticular presentation (both slow and acute forms), extra-articular synovitis (tenosynovitis, bursitis), polymyalgic-like onset, and general symptoms (malaise, fatigue, weight loss, fever). The palindromic onset is characterized by recurrent episodes of oligoarthritis with no residual radiologic damage, while the polymyalgic-like onset may be clinically indistinguishable from polymyalgia rheumatica in elderly subjects. RA is characteristically a symmetric erosive disease. Although any joint, including the cricoarytenoid joint, can be affected, the distal interphalangeal, the sacroiliac, and the lumbar spine joints are rarely involved. The clinical features of synovitis are particularly apparent in the morning. Morning stiffness in and around the joints, lasting at least 1 h before maximal improvement is a typical sign of RA. It is a subjective sign and the patient needs to be carefully informed as to the difference between pain and stiffness. Morning stiffness duration is related to disease activity. Hand involvement is the typical early manifestation of rheumatoid arthritis. Synovitis involving the metacarpophalangeal

  7. 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

  8. Gold nephropathy in juvenile rheumatoid arthritis.

    PubMed

    Husserl, F E; Shuler, S E

    1979-01-01

    A 2-year-old girl was treated with gold salts for juvenile rheumatoid arthritis. Treatment had to be discontinued when persistent proteinuria was detected. As this case report indicates, close monitoring of the urine is mandatory during treatment with gold salts to detect early signs of toxicity: hematuria followed by casts and then proteinuria as therapy is continued. Histologic examination with electron microscopy will help to differentiate the different forms of gold toxicity. When the findings are consistent with gold-induced renal involvement, therapy should be discontinued. The gold nephropathy usually resolves in time, with no permanent renal damage.

  9. 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.

  10. 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.

  11. 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)

  12. Rheumatoid arthritis: Disease or syndrome?

    PubMed Central

    Stanich, Jessica A; Carter, John D; Whittum-Hudson, Judith; Hudson, Alan P

    2009-01-01

    Rheumatoid arthritis (RA) has been described in the medical literature for over two hundred years, but its etiology remains unknown. RA displays phenotypic heterogeneity, and it is a relatively prevalent clinical entity: it affects approximately 1% of the population, resulting in enormous pathologic sequelae. Earlier studies targeting the cause(s) of RA suggested potential infectious involvement, whereas more recent reports have focused on a genetic origin of the disease. However, neither infection nor genetics, nor any other single factor is currently accepted as causative of RA. In this article we review studies relating to the etiology of RA, and those of several related matters, and we conclude that the literature indeed does provide insight into the causes underlying the initiation of RA pathogenesis. Briefly, given the remarkable phenotypic variation of RA, especially in its early stages, as well as a number of other characteristics of the condition, we contend that RA is not a discrete clinical entity with a single etiological source. Rather, we argue that it represents a common clinical endpoint for various starting points, each of which is largely guided by as yet poorly understood aspects of the genetic background of the affected individual. Adoption of this alternative view of the origin of RA will have significant consequences for future research and for development of new therapeutic interventions for this burdensome condition.

  13. 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.

  14. [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

  15. [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

  16. Rheumatoid arthritis and ocular involvement.

    PubMed

    Shaw, Chittaranjan; Banik, Sujoy; Islam, Md Nazarul; Biswas, Mukul Chandra; Biswas, Gautam; Biswas, Sobhan

    2003-09-01

    To study the occurrence and incidence of different ocular manifestations in rheumatoid arthritis a random cross-sectional study was carried out among 54 patients with active rheumatoid arthritis. The patients were examined thoroughly to detect any ocular disease associated with rheumatoid arthritis. Complete ocular examination with special emphasis on anterior segment evaluation and tearfilm study was done. Two-thirds of the patients examined had some kind of visual problem at presentation. Three patients (5.55%) had marked dry eye with another 20 (37.03%) having borderline tear deficiency. Two cases ( 3.70% ) of episcleritis were also seen. No cases of scleritis or retinopathy were found. The most common ocular association with rheumatoid arthritis was secondary Sjogren's syndrome. Other conditions include episcleritis and marginal keratitis.

  17. 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.

  18. The first national clinical audit for rheumatoid arthritis.

    PubMed

    Firth, J; Snowden, N; Ledingham, J; Rivett, A; Galloway, J; Dennison, E M; MacPhie, E; Ide, Z; Rowe, I; Kandala, N; Jameson, K

    The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice.

  19. [Rheumatoid arthritis and cytokines].

    PubMed

    Kaneko, Shunta; Kondo, Yuya; Yokosawa, Masahiro; Sumida, Takayuki

    2016-06-01

    The cytokines are an important substance involved in the immune reaction and maintenance of homeostasis. An imbalance in the cytokine network may lead to inflammation and autoimmune diseases such as rheumatoid arthritis (RA). RA is an autoimmune and systemic inflammatory disorder characterized by synovial inflammation, destruction of cartilage and bone and systemic manifestations. The pro-inflammatory cytokines such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), IL-6 and IL-17 induce the inflammation of the joints and destruction of bone and cartilage via activation of macrophages, fibroblast like synoviocytes (FLS), helper T (Th) cells and osteoclasts. Recently, the available therapeutic agents that target these cytokines have excellent clinical effects in RA patients.

  20. Physiotherapy in rheumatoid arthritis.

    PubMed

    Kavuncu, Vural; Evcik, Deniz

    2004-01-01

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

  1. Physiotherapy in rheumatoid arthritis.

    PubMed

    Kavuncu, Vural; Evcik, Deniz

    2004-05-17

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

  2. [Pathogenesis of rheumatoid arthritis].

    PubMed

    Branimir Anić; Miroslav Mayer

    2014-01-01

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

  3. 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.

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

    PubMed

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

    1997-05-01

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

  5. Rheumatoid nodule presenting as Morton's neuroma.

    PubMed

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

    2013-09-01

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

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

    PubMed Central

    Zaniewicz-Kaniewska, Katarzyna; Warczyńska, Agnieszka; Matuszewska, Genowefa; Saied, Fadhil; Kunisz, Wojciech

    2012-01-01

    Early diagnosis of rheumatoid arthritis followed by early initiation of treatment, prevent the destruction of joints and progression to disability in the majority of patients. A traditional X-ray fails to capture early inflammatory changes, while late changes (e.g. erosions) appear after a significant delay, once 20–30% of bone mass has been lost. Sonography and magnetic resonance imaging studies have shown that erosions are seen in the first 3 months from the appearance of symptoms in 10–26% of patients, while in 75% they are seen in the first 2 years of the disease. Power Doppler ultrasound and dynamic magnetic resonance studies allow for qualitative, semiquantitative and quantitative monitoring of the vascularization of the synovium. In addition, magnetic resonance enables assessment of the bone marrow. The ultrasonographic examination using a state-of-the-art apparatus with a high-frequency probe allows for images with great spatial resolution and for the visualization of soft tissues and bone surfaces. However, the changes seen in ultrasonography (synovial pathologies, the presence of exudate, tendons changes, cartilage and bone lesions, pathologies of tendon attachments and ligaments – enthesopathies) are not only specific for rheumatoid arthritis and occur in other rheumatic diseases. Qualitative methods are sufficient for diagnosing the disease through ultrasound or magnetic resonance imaging. Whereas semiquantitative and quantitative scales serve to monitor the disease course – efficacy of conservative treatment and qualification for radioisotope synovectomy or surgical synovectomy – and to assess treatment efficacy. PMID:26673409

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

    NASA Astrophysics Data System (ADS)

    Zhou, Hong; Qiu, Yue; Wu, Yueqin

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

  8. Direct Monte Carlo Simulations of the Intermediate Experimental Vehicle at Early Stages of Reentry

    NASA Astrophysics Data System (ADS)

    Banyai, T.; Torres, E.; Kashkovsky, A. V.; Vashchenkov, P. V.; Ivanov, M. S.; Rambaud, P.

    2011-05-01

    Within the European Space Agency (ESA) framework program FLPP Next Generation Launcher (NGL) preparatory activities on System, In-Flight Experimentation and Aerothermodynamics Period 1, Step 2, von Karman Institute (VKI) has to perform ground testing and numerical simulations to contribute to the aerothermodynamic database of the Intermediate eXperimental Vehicle (IXV) along its trajectory during re-entry. The present article summarizes the part of these activities in relation with the evaluation of the aerodynamic properties in the early stages of reentry. Due to the rarefied nature of the higher atmosphere, the computations were carried out by means of Direct Simulation of Monte Carlo (DSMC) method. The aim of this work was to a., validate the methodology used at VKI, b., perform computations at several points along the trajectory and c., assess the feasibility of joint simulation of rarefied flow and thrusters.

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

    SciTech Connect

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

    1985-11-01

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

  10. Biomarkers in Rheumatoid Arthritis, what is new?

    PubMed Central

    Gavrilă, BI; Ciofu, C; Stoica, V

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease with autoimmune pathogenesis. It affects mainly small joints (of the hands and feet) and has many systemic manifestations. Studying biomarkers in rheumatology intensely appeared from the need to understand the mechanisms underlying some rheumatic diseases. Discovering new biomarkers with key roles in various stages of evolution, remains a subject of interest for RA. Currently, according to the EULAR 2010 criteria, the rheumatoid factor (RF) and the anti-cyclic citrullinated peptide (anti-CCP) are used for RA diagnosis. Since 2010, new biomarkers were discovered and proved useful in identifying RA in early stages. For a more rigorous management of these cases, one of the key steps in the evolution of patients with RA is to recognize and distinguish the more aggressive forms of the disease through prognostic biomarkers. “Treat to target” recommends the use of 3 composite scores to monitor the evolution of the disease: disease activity score (DAS 28), simple disease activity index (SDAI) and clinical disease activity index (CDAI), but, a new test was developed which better monitors the disease activity. The introduction of biological therapies has revolutionized the treatment of RA. Despite these advances, 20-40% of the patients are declared nonresponders to at least one of the therapies. The patient exposure to the potential side effects and high costs requires the discovery of a biomarker that could identify those who can benefit from the pretreatment of a certain therapy. Abbreviations: RA = rheumatoid arthritis, RF = rheumatoid factor, DAS 28 = disease activity score, SDAI = simple disease activity index, CDAI = clinical disease activity index, ACR = American College of Rheumatology, EULAR = European League against Rheumatism, anti-CCP = antibodies against cyclic citrullinated proteins, anti-MCV = mutated citrullinated vimentin antibodies, anti-CarP = antibodies against carbamylated proteins, MBDA

  11. T Cell Migration in Rheumatoid Arthritis.

    PubMed

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

    2015-01-01

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

  12. 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

  13. Ultrasound in rheumatoid arthritis.

    PubMed

    Rizzo, Chiara; Ceccarelli, Fulvia; Gattamelata, Angelica; Vavala, Caterina; Valesini, Guido; Iagnocco, Annamaria

    2013-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation that can lead to structural damage of cartilage, bone and tendons. Assessing the inflammatory activity and the severity is essential in RA to help rheumatologists in adopting proper therapeutic strategies and in evaluating disease outcome and response to treatment. In the last years musculoskeletal (MS) ultrasonography (US) underwent tremendous technological development of equipment with increased sensitivity in detecting a wide set of joint and soft tissues abnormalities. In RA MSUS with the use of Doppler modalities is a useful imaging tool to depict inflammatory abnormalities (i.e. synovitis, tenosynovitis and bursitis) and structural changes (i.e. bone erosions, cartilage damage and tendon lesions). In addition, MSUS has been demonstrated to be able to monitor the response to different therapies in RA to guide local diagnostic and therapeutic procedures such as biopsy, fluid aspirations and injections. Future applications based on the development of new tools may improve the role of MSUS in RA.

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

    SciTech Connect

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

    1992-05-01

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

  15. Ratio of Circulating IFNγ+ “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

    PubMed Central

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

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. 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. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146

  16. Simulating a Dynamic Antarctic Ice Sheet in the Early to Middle Miocene

    NASA Astrophysics Data System (ADS)

    Gasson, E.; DeConto, R.; Pollard, D.; Levy, R. H.

    2015-12-01

    There are a variety of sources of geological data that suggest major variations in the volume and extent of the Antarctic ice sheet during the early to middle Miocene. Simulating such variability using coupled climate-ice sheet models is problematic due to a strong hysteresis effect caused by height-mass balance feedback and albedo feedback. This results in limited retreat of the ice sheet once it has reached the continental size, as likely occurred prior to the Miocene. Proxy records suggest a relatively narrow range of atmospheric CO2 during the early to middle Miocene, which exacerbates this problem. We use a new climate forcing which accounts for ice sheet-climate feedbacks through an asynchronous GCM-RCM coupling, which is able to better resolve the narrow Antarctic ablation zone in warm climate simulations. When combined with recently suggested mechanisms for retreat into subglacial basins due to ice shelf hydrofracture and ice cliff failure, we are able to simulate large-scale variability of the Antarctic ice sheet in the Miocene. This variability is equivalent to a seawater oxygen isotope signal of ~0.5 ‰, or a sea level equivalent change of ~35 m, for a range of atmospheric CO2 between 280 - 500 ppm.

  17. 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.

  18. [Diagnosis and treatment of rheumatoid arthritis].

    PubMed

    Krüger, K

    2014-09-01

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

  19. 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.

  20. Prognostic laboratory markers of joint damage in rheumatoid arthritis

    PubMed Central

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

    2005-01-01

    Objective: To investigate whether determination of a set of laboratory markers at baseline provides prognostic information on joint damage in hands and feet in rheumatoid arthritis. Methods: 183 patients with early rheumatoid arthritis included in a prospective study were examined. Radiographic changes in hands and feet at 5 and 10 years after inclusion were evaluated (Larsen). The markers analysed were: erythrocyte sedimentation rate (ESR); HLA-DRB alleles typed by restriction fragment length polymorphism; and C reactive protein, cartilage oligomeric matrix protein (COMP), rheumatoid factor (RF) (IgG, IgA, and IgM subtypes), antibodies against cyclic citrullinated peptide (anti-CCP), and antibodies against interleukin 1α (anti-IL1α), analysed by immunoassays. Multiple linear regression with backward elimination was used to determine the prognostic value of the variables. Results: 117/176 patients were positive for IgG RF, 138/176 for IgA RF, 139/176 for IgM RF, 140/176 for anti-CCP, and 40/182 for anti-IL1α. After five years, ESR, the presence of IgA RF, serum COMP, and the presence of anti-CCP were significantly associated with more severe joint damage, and the presence of anti-IL1α with less severe joint damage. Baseline C reactive protein and anti-CCP predicted radiographic outcome after 10 years. A stronger prediction was obtained by combining the prognostic factors. Conclusions: Early determination of anti-CCP, IgA RF, anti-IL-1α, ESR, C reactive protein, and COMP predicted the development of joint damage in hands and feet in this cohort. A combination of these measures reflecting different aspects of the disease process should be useful for evaluating prognosis in individual patients with early rheumatoid arthritis. PMID:15458956

  1. Genetics Home Reference: rheumatoid arthritis

    MedlinePlus

    ... risk factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes , especially the HLA-DRB1 gene. The proteins produced from HLA genes help the immune system distinguish the body's own proteins from proteins made by foreign invaders ( ...

  2. Medicines to Treat Rheumatoid Arthritis

    MedlinePlus

    ... and 55, but it can happen at any age. Rheumatoid arthritis affects women more than men. Visit your doctor to talk about your health and the medicines you may need. This factsheet will give you information about a type of medicine. You will learn ...

  3. 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.

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

    PubMed

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

    2015-05-01

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

  5. 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

  6. Computer simulation on the cooperation of functional molecules during the early stages of evolution.

    PubMed

    Ma, Wentao; Hu, Jiming

    2012-01-01

    It is very likely that life began with some RNA (or RNA-like) molecules, self-replicating by base-pairing and exhibiting enzyme-like functions that favored the self-replication. Different functional molecules may have emerged by favoring their own self-replication at different aspects. Then, a direct route towards complexity/efficiency may have been through the coexistence/cooperation of these molecules. However, the likelihood of this route remains quite unclear, especially because the molecules would be competing for limited common resources. By computer simulation using a Monte-Carlo model (with "micro-resolution" at the level of nucleotides and membrane components), we show that the coexistence/cooperation of these molecules can occur naturally, both in a naked form and in a protocell form. The results of the computer simulation also lead to quite a few deductions concerning the environment and history in the scenario. First, a naked stage (with functional molecules catalyzing template-replication and metabolism) may have occurred early in evolution but required high concentration and limited dispersal of the system (e.g., on some mineral surface); the emergence of protocells enabled a "habitat-shift" into bulk water. Second, the protocell stage started with a substage of "pseudo-protocells", with functional molecules catalyzing template-replication and metabolism, but still missing the function involved in the synthesis of membrane components, the emergence of which would lead to a subsequent "true-protocell" substage. Third, the initial unstable membrane, composed of prebiotically available fatty acids, should have been superseded quite early by a more stable membrane (e.g., composed of phospholipids, like modern cells). Additionally, the membrane-takeover probably occurred at the transition of the two substages of the protocells. The scenario described in the present study should correspond to an episode in early evolution, after the emergence of single

  7. 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 ...

  8. [The usefulness of the latest diagnostic and therapeutic criteria ACR/EULAR in the treatment of rheumatoid arthritis].

    PubMed

    Pytel, Aleksandra; Wrzosek, Zdzisława; Demczyszak, Iwona; Brzyski, Jakub

    2012-01-01

    In Poland nearly 400 thousand people are treated for rheumatoid arthritis and each year there are about 8 to 16 thousand new patients with this disease. Rheumatoid diseases constitute and enormous health problem which statistically encounters every the third person of the population. The condition for effective treatment of rheumatoid arthritis is early diagnosis and aggressive treatment of disease. So it became necessary to develop in 2010, the new ACR/ EULAR, much simpler than the ACR criteria of 1987, intended to enable the rapid implementation of appropriate intensive treatment, both conventional disease modifying drugs and biologicals.

  9. Treatment in juvenile rheumatoid arthritis and new treatment options

    PubMed Central

    Kasapçopur, Özgür; Barut, Kenan

    2015-01-01

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

  10. 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

  11. Simulating a dynamic Antarctic ice sheet in the early to middle Miocene

    NASA Astrophysics Data System (ADS)

    Gasson, Edward; DeConto, Robert; Pollard, David; Levy, Richard

    2016-04-01

    A variety of sources of geological data suggest that there were major variations in Antarctic ice sheet volume and extent during the early to middle Miocene. Simulating such large-scale changes is problematic due to a strong hysteresis effect, which results in limited retreat of the terrestrial ice sheet once it has reached continental size. A relatively narrow range of atmospheric CO2 concentrations shown by proxy records exacerbates this problem. Here we use a new asynchronous climate-ice sheet coupling method, using a high-resolution atmospheric component, to account for ice sheet-climate feedbacks. Accounting for these processes results in increased retreat when compared with standard offline simulations. Combined with recently proposed mechanisms for ice retreat into deep subglacial basins, we are able to simulate large-scale variability of the Miocene Antarctic ice sheet. This variability is equivalent to a seawater oxygen isotope signal of 0.52 - 0.66 ‰, or a sea level equivalent change of 30 - 36 m, for a range of atmospheric CO2 between 280 - 500 ppm and a changing astronomical configuration. This result represents a substantial advance in resolving the long-standing model-data conflict of Miocene Antarctic ice sheet and sea level variability, and provides a mechanistic explanation for new ice-proximal records emerging from sedimentological drill cores.

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  13. Extra-articular Manifestations in Rheumatoid Arthritis

    PubMed Central

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

    2010-01-01

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

  14. Epidemiology of Rheumatoid Arthritis in Tirana, Albania

    PubMed Central

    Duraj, Valbona; Tafaj, Argjent; Backa, Teuta

    2013-01-01

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

  15. 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

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

    PubMed

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

    2012-05-01

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

  17. 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.

  18. Pulmonary involvement in rheumatoid arthritis.

    PubMed

    Bilgici, Ayhan; Ulusoy, H; Kuru, O; Celenk, C; Unsal, M; Danaci, M

    2005-08-01

    The primary objective of this investigation was to assess the relationships between clinical characteristics, lung involvement, and frequency of pulmonary involvement in rheumatoid arthritis (RA). Using high-resolution computed tomography (HRCT) and pulmonary function tests (PFT), we prospectively evaluated 52 patients with RA (eight males and 44 females, mean age 53.6 years). The HRCT was abnormal in 35 patients (67.3%), the most frequent abnormalities being reticulonodular patterns, which were found in 22 patients (62.9%), ground-glass attenuation (20%), and bronchiectasis (17%). In this group of patients, PFT results were normal in 13 patients (37%). Titers of rheumatoid factor and erythrocyte sedimentation rate were significantly higher in abnormal HRCT presence. Higher Larsen's score, advanced age, and severe disease were significant risk factors for lung involvement (p<0.001, p<0.01, and p<0.01, respectively) and are suggested by our data to be statistically significant predictors of lung involvement in RA.

  19. [Pulmonary manifestations in rheumatoid arthritis].

    PubMed

    Morawska, Justyna; Domysławska, Izabela; Bagrowska, Magdalena; Sierakowski, Stanislaw

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destructive cartilages, bones and other structures formed joints. RA belongs to connective tissue diseases represented by systemic nature, internal illness, extra-articular features and rapidly progress of atherosceirosis. The extra-articular complications cause the reduction of patient longevity. The frequency of symptoms in patient with RA and respiratory disorders occur in 10-20% of cases. Pulmonary complications are the second most common cause of premature of patient deaths. Respiratory disorders associated with RA are devided into 3 groups: infection, lung disease caused by drugs and pulmonary manifestation connected by RA. These last affect interstitial tissue, bronchioli, pulmonary vessels, pleura, also are presented by pulmonary rheumatoid nodules and pulmonary hypertension.

  20. RADIATION MAGNETOHYDRODYNAMIC SIMULATIONS OF PROTOSTELLAR COLLAPSE: NONIDEAL MAGNETOHYDRODYNAMIC EFFECTS AND EARLY FORMATION OF CIRCUMSTELLAR DISKS

    SciTech Connect

    Tomida, Kengo; Okuzumi, Satoshi; Machida, Masahiro N. E-mail: okuzumi@geo.titech.ac.jp

    2015-03-10

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

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

    PubMed Central

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

    2012-01-01

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

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

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

  4. 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.

  5. Application of (1)H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis.

    PubMed

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

    2016-01-01

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

  6. [Rheumatoid arthritis in Morocco. Apropos of 404 observations].

    PubMed

    Benamour, S; Zeroual, B; Fares, L; el Kabli, H; Bettal, S

    1992-12-01

    A retrospective study of 404 cases of rheumatoid arthritis seen in a department of internal medicine in Casablanca highlights a number of specific features of the disease in Morocco. Onset occurred early and mean age of patients was 34.4 years. Analysis of joint manifestations showed that the disease tended to be mild in the hips and perhaps in the cervical spine. Thirty-five percent of patients were Steinbrocker's class II and 25.5% had carpal bone fusion. Only 20 patients had severely erosive disease, which manifested as giant geodes in 8 cases and as main en lorgnette deformity in one case. Subcutaneous nodules (7.9%) and systemic visceral disorders were fairly infrequent. Only three cases of malignant rheumatoid arthritis were found. Gougerot-Sjögren syndrome was present in 13.6% of patients. Among comorbid conditions, thyroid gland diseases and tuberculosis were fairly common. Serologic tests were positive in 61.14% of cases, often in low titres. Gold salt therapy was well tolerated. No patients in this group had surgical treatment. These data suggest that in Morocco rheumatoid arthritis may be less aggressive than in Europe.

  7. [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.

  8. Therapeutic exercise for rheumatoid arthritis and osteoarthritis.

    PubMed

    Semble, E L; Loeser, R F; Wise, C M

    1990-08-01

    Therapeutic exercise in rheumatoid arthritis and osteoarthritis may be useful in improving aerobic capacity, strengthening muscles, improving endurance and increasing flexibility. This article reviews the major studies of exercise in these conditions and summarizes the authors recommendations regarding the use of therapeutic exercise in the treatment of rheumatoid arthritis osteoarthritis.

  9. 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.

  10. [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.

  11. Molecular Simulation Study of the Early Stages of Formation of Bioinspired Mesoporous Silica Materials.

    PubMed

    Centi, Alessia; Jorge, Miguel

    2016-07-19

    The use of bioinspired templates, such as polyamines and polypeptides, could lead to significant improvements in the synthesis conditions under which mesoporous materials are traditionally produced, removing the need for strong pH as well as high temperature or pressure. In this work, we perform atomistic molecular dynamics simulations of 1,12-diaminododecane surfactants, in water and in the presence of silica monomers, to investigate the early stages of synthesis of one of the first examples of bioinspired silica materials. Different surfactant concentrations and pH were considered, clarifying the influence of the charge state of the molecules on the self-assembly process. We show that the amphiphilic amines form stable lamellar structures at equilibrium in the range from intermediate to high pH values. In a later stage, when silica species are added to the system, our results reveal that, in the same range of pH, silicates strongly adsorb around these aggregates at the interface with water. This causes a considerable modification of the curvature of the layer, which suggests a tendency for the system to evolve from a lamellar phase to the formation of vesicle structures. Furthermore, we show that silica monomers are able to penetrate the layer spontaneously when defects are created as a result of surfactants' head-to-head repulsion. These findings are in agreement with experimental observations and support the pillaring mechanism postulated for this class of materials. However, our simulations indicate that the aggregation process is driven by charge matching between surfactant heads and silica monomers rather than by hydrogen bond interactions between neutral species, as had been previously hypothesized. PMID:27340948

  12. 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

  13. The socio-economical burden of schizophrenia: a simulation of cost-offset of early intervention program in Italy.

    PubMed

    Serretti, Alessandro; Mandelli, Laura; Bajo, Emanuele; Cevenini, Nadia; Papili, Pietro; Mori, Elisa; Bigelli, Marco; Berardi, Domenico

    2009-01-01

    Schizophrenia is associated with a high familiar, social and economic burden. During the recent years early and specific intervention for first psychotic episodes has been suggested to improve the long term outcome of the disease. Despite the promising results obtained so far, early intervention is still scarcely applied. One major problem arises from the translation of research findings into stakeholder policies. In fact very few analyses of cost reductions obtained with early intervention have been reported. In the present paper we present a simulation of direct cost reduction that can be obtained with early intervention programmes. We based our analysis on available data about schizophrenia care costs in Italy and the expected cost reduction with the use of early intervention. We observed that the increase in costs due to the more intensive early intervention is largely compensated by the reduction of inpatient admissions with a reduction of direct costs of 6.01%. Despite the apparently small economic gain, early intervention offers more clinical and social benefits as it seems to be effective also in decreasing relapse rates, in improving the patients' quality of life and disability associated with psychosis and in increasing employment rates. Those indirect costs however are difficult to estimate and were not included in our model. In conclusion, our study supports the use of early intervention in schizophrenia, which could allow an outcome improvement with lower direct and indirect costs.

  14. 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

  15. 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

  16. 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

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

    PubMed

    Boonen, Annelies; Lems, Willem F

    2015-01-01

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

  18. [Magnetic resonance imaging of the hand in rheumatoid arthritis. New scientific insights and practical application].

    PubMed

    Hermann, K-G A

    2006-05-01

    Magnetic resonance imaging (MRI) is a sensitive diagnostic modality for the detection of inflammatory changes in peripheral joints. Nevertheless, the widespread clinical use of MRI in assessing patients with early rheumatoid arthritis is still hampered by the technical complexity and higher cost of MRI compared with conventional radiography. This overview summarizes the results of recent research and gives practical tips on how to perform MRI of the hands. The authors present an MR protocol for hand imaging, discuss the pros and cons of low-field MR scanners, and outline pitfalls and artifacts. The MRI changes associated with rheumatoid arthritis such as synovitis, tenosynovitis, erosions, and bone marrow edema are described including their prognostic significance. The proven facts on the validation and grading of MR changes in rheumatoid arthritis are summarized. Finally, the role of MRI in the differential diagnosis of arthritis is critically discussed. PMID:16612602

  19. [Cardiovascular diseases in rheumatoid arthritis].

    PubMed

    Nakajima, Ayako

    2016-06-01

    Cardiovascular diseases (CVD) are serious complications in patients with rheumatoid arthritis (RA) in its high morbidity and mortality. The risk of coronary artery disease (CAD)has been reported to relate to RA disease activity. By improvement of treatment agents and treatment strategy aiming remission or low disease activity of RA, the incidence of CAD can be decreasing. The cardiovascular morbidity may be attributed to other types of CVD such as large vessel diseases, microvascular myocardial dysfunction or arrhythmia in addition to CAD. To improve quality of life and mortality of RA patients, physicians should treat patients to prevent cardiovascular morbidity through RA disease control. PMID:27311194

  20. Lung disease in rheumatoid arthritis.

    PubMed

    Yunt, Zulma X; Solomon, Joshua J

    2015-05-01

    Rheumatoid arthritis (RA) affects approximately 1% of the US population frequently has extra-articular manifestations. Most compartments of the lung are susceptible to disease. Interstitial lung disease (ILD) and airways disease are the most common forms of RA-related lung disease. RA-ILD carries the worst prognosis and most often manifests in a histologic pattern of usual interstitial pneumonia or nonspecific interstitial pneumonia. There have been no large, well-controlled prospective studies investigating therapies for RA-ILD. Treatment usually entails immunomodulatory agents. Further studies are needed to better understand pathogenic mechanisms of disease that lead to lung involvement in these patients.

  1. 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.

  2. Virtual Quake and Tsunami Squares: Scenario Earthquake and Tsunami Simulations for a Pacific Rim GNSS Tsunami Early Warning System

    NASA Astrophysics Data System (ADS)

    Schultz, K.; Yoder, M. R.; Sachs, M. K.; Heien, E. M.; Donnellan, A.; Rundle, J. B.; Turcotte, D. L.

    2015-12-01

    Plans for the first operational prototype for a Pacific Rim Tsunami Early Warning (TEW) system utilizing real-time data from the Global Navigational Satellite System (GNSS) are now gaining momentum. The proposed Pacific Rim TEW prototype may resemble the Japanese Meteorological Society's early warning algorithms and use earthquake parameters rapidly determined from GPS data to select the most similar earthquake and tsunami scenario from a database of precomputed scenarios to guide alerts and disaster response. To facilitate the development of this Pacific Rim TEW system, we have integrated tsunami modeling capabilities into the earthquake simulator Virtual Quake (formerly Virtual California). We will present the first results from coupling the earthquake simulator output (seafloor displacements) with the tsunami modeling method called Tsunami Squares. Combining Virtual Quake and Tsunami Squares provides a highly scalable and flexible platform for producing catalogs of tsunami scenarios for a wide range of simulated subduction zone earthquakes.

  3. 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

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

    PubMed

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

    1989-06-01

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

  5. 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.

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

    PubMed Central

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

    2014-01-01

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

  7. ASTROMEDICINE IN THE TREATMENT OF RHEUMATOID ARTHRITIS

    PubMed Central

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

    1991-01-01

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

  8. Rheumatoid lymphadenopathy: a morphological and immunohistochemical study.

    PubMed Central

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

    1990-01-01

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

  9. 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)

  10. Psychosocial problems among newly diagnosed rheumatoid arthritis patients.

    PubMed

    Gåfvels, C; Hägerström, M; Nordmark, B; Wändell, P E

    2012-03-01

    We identified patients with newly diagnosed rheumatoid arthritis (RA) in the ages 18-65 years who needed psychosocial interventions. A total of 123 patients (90 women) were asked to participate, but 19 declined and 4 dropped out early in the study, leaving a total of 100 patients (75 women) in the sample. Questionnaires used were the Epidemiological Investigation on Rheumatoid Arthritis study questionnaire, the Hospital Anxiety and Depression Scale, the Sense of Coherence (SOC) scale, and the General Coping Questionnaire. Interviews showed that 46% of the included 100 patients had psychosocial problems (PSP). One third of them had problems directly related to RA. The rest had problems with their life situation in general, without or reinforced by RA. Compared to patients without psychosocial problems, PSP patients lived in more strained social situations, especially regarding personal finances and social support. More of the PSP patients were anxious, showed lower SOC scores, and also used more emotion-based coping strategies (resignation, protest, isolation and intrusion) and less problem-oriented (minimization). They also had higher scores on depression and more frequently expected that RA would negatively affect their future. PSP patients also experienced a more negative impact of the disease, a finding not confirmed by the sickness activity score judged by the rheumatologist. Thus, early in the course of RA, screening instruments should be used to identify PSP patients. Psychosocial treatment and support by medical social workers skilled in RA care should be offered. PMID:22089162

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

    PubMed

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

    2015-10-01

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

  12. Diagnosis and management of rheumatoid arthritis.

    PubMed

    Wasserman, Amy M

    2011-12-01

    Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management.

  13. Diagnosis and management of rheumatoid arthritis.

    PubMed

    Wasserman, Amy M

    2011-12-01

    Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management. PMID:22150658

  14. 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.

  15. 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

  16. [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.

  17. Hypercalcaemia in rheumatoid arthritis revisited.

    PubMed Central

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

    1990-01-01

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

  18. [Team management of rheumatoid arthritis].

    PubMed

    Le Loët, X; Vittecoq, O

    2001-12-01

    The main objectives of team management of rheumatoid arthritis are to stop structural damage of joints and to reduce functional, psychological, socioprofessional and economic consequences. Team management requires the collaboration, around the patient, of a rheumatologist, a nurse, a psychologist, a physiotherapist, an occupational therapist, an orthopaedic surgeon at the same time, in the same place. More and more patients wish to manage their disease by themselves. Team care should not be proposed to every patient; it must be reserved to patients whose condition required such an approach because of the severity of the disease, comorbidity, psychological or socioprofessionnal difficulties. Team management should be personalized. Utility of team management is now accepted; out-patient administration is as effective as in-patient one. A good educational program is very important. However, search is still needed to define optimal modalities of team management and tools to measure the efficiency of this approach.

  19. 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

  20. 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.

  1. Complement fixation by rheumatoid factor.

    PubMed Central

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

    1975-01-01

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

  2. 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.

  3. Bringing skin assessments to life using human patient simulation: an emphasis on cancer prevention and early detection.

    PubMed

    Kuhrik, Marilee; Seckman, Christy; Kuhrik, Nancy; Ahearn, Tina; Ercole, Patrick

    2011-12-01

    Skin cancer is the most common cancer in the United States, with about 1,000,000 people developing the disease each year. The incidence of melanoma has rapidly increased in young white women between the ages of 15-34 over the last three decades. While melanoma accounts for approximately 3% of skin cancers, it causes more than 75% of skin cancer deaths. Thorough skin assessments and awareness of new or changing appearance of skin lesions are critical to early detection and treatment of skin cancer, as well as teaching sun-protective behaviors. Educators created a novel approach to "bring to life" skin cancer assessment skills to promote awareness of prevention and early detection of skin cancer using moulage in a human patient simulation lab. Through the use of moulage-like lesions, simulated patients were evaluated and taught skin cancer prevention and early detection principles by baccalaureate nursing students. The average age of study participants (n = 104) was 26.50 years. The majority of responders were female. At the end of the lab, students' average responses to an evaluation based on program goals were very positive. Anecdotal comments affirmed positive student perceptions of their simulation experience. Data analyses indicated item means were consistently higher for upper-division students. The age and gender of students who participated in this study align with the NCI statistics on age and gender of the population with increased incidence of melanoma.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  5. Significance of bone marrow edema in pathogenesis of rheumatoid arthritis

    PubMed Central

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Warczyńska, Agnieszka; Kwiatkowska, Brygida

    2013-01-01

    Summary Assessing the pathology of the synovium, its thickening and increased vascularity through ultrasound and magnetic resonance examinations (more often an ultrasound study alone) is still considered a sensitive parameter in the diagnosis of rheumatoid arthritis and in monitoring of treatment efficacy. Magnetic resonance studies showed that, aside from the joint pannus, the subchondral bone tissue constitutes an essential element in the development of rheumatoid arthritis. Bone marrow edema correlates with inflammation severity, joint destruction, clinical signs and symptoms of rheumatoid arthritis, and thus is considered a predictor of rapid radiological progression of the disease. The newest studies reveal that bone marrow edema may be a more sensitive indicator of the response to therapy than appearance of the synovium. Bone marrow edema presents with increased signal in T2-weighted images, being most visible in fat saturation or IR sequences (STIR, TIRM). On the other hand, it is hypointense and less evident in T1-weighted images. It becomes enhanced (hyperintense) after contrast administration. Histopathological studies confirmed that it is a result of bone inflammation (osteitis/osteomyelitis), i.e. replacememt of bone marrow fat by inflammatory infiltrates containing macrophages, T lymphocytes, B lymphocytes, plasma cells and osteoclasts. Bone marrow edema appears after a few weeks from occurrence of symptoms and therefore is considered an early marker of inflammation. It correlates with clinical assessment of disease activity and elevated markers of acute inflammatory phase, i.e. ESR and CRP. It is a reversible phenomenon and may become attenuated due to biological treatment. It is considered a “herald” of erosions, as the risk of their formation is 6-fold higher in sites where BME was previously noted PMID:23493495

  6. Nerve Zap Eased Rheumatoid Arthritis in Small Study

    MedlinePlus

    ... news/fullstory_159838.html Nerve Zap Eased Rheumatoid Arthritis in Small Study Treatment worked some for patients ... gut may help ease stubborn symptoms of rheumatoid arthritis, preliminary research suggests. The study, of 17 adults ...

  7. Total ankle prostheses in rheumatoid arthropathy

    PubMed Central

    Schutte, Bernard; Louwerens, Jan Willem K; van den Hoogen, Frank H J; de Waal Malefijt, Maarten C

    2009-01-01

    Background and purpose The first generations of total ankle replacements (TARs) showed a high rate of early failure. In the last decades, much progress has been made in the development of TARs, with the newer generation showing better results. We evaluated TARs implanted with rheumatoid arthritis (RA) or juvenile inflammatory arthritis (JIA) as indication. Patients and methods 58 total ankle prostheses (Buechel-Pappas and STAR type) were implanted in patients with RA (n = 53) or JIA (n = 5) in 54 patients (4 bilateral). After a mean follow-up of 2.7 (1–9) years, all patients were reviewed by two orthopedic surgeons who were not the surgeons who performed the operation. Standard AP and lateral radiographs were taken and a Kofoed ankle score was obtained; this is a clinical score ranging from 0–100 and consists of sub-scores for pain, disability, and range of motion. Results 2 patients died of unrelated causes. Of the 52 patients who were alive (56 prostheses), 51 implants were still in place and showed no signs of loosening on the most recent radiographs. The mean Kofoed score at follow-up was 73 points (SD 16, range 21–92). 4 patients showed a poor result (score < 50) with persistent pain for which no obvious reason could be found. 5 implants were removed, 4 because of infection and 1 because of aseptic loosening. Interpretation Medium-term results of the STAR and BP types of TAR in RA were satisfactory. The main reason for failure of the implant was infection. PMID:19634020

  8. [Presurgical and postsurgical orthotic management of the rheumatoid foot].

    PubMed

    Carl, H D; Swoboda, B

    2012-10-01

    Foot complaints remain frequent in patients with rheumatoid arthritis (RA) even in the era of biological anti-rheumatic drugs. Orthotic management of rheumatoid foot disorders is able to improve mobility and thus the quality of life in RA patients. This article highlights the preoperative and postoperative orthotic management of the rheumatoid arthritic foot.

  9. Juvenile rheumatoid arthritis: therapeutic perspectives.

    PubMed

    Chikanza, Ian C

    2002-01-01

    Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic systemic autoimmune inflammatory disease. The therapeutic approach to JRA has, to date, been casual and based on extensions of clinical experiences gained in the management of adult rheumatoid arthritis (RA). The physiology of inflammation has been systemically studied and this has led to the identification of specific therapeutic targets and the development of novel approaches to the management of JRA. The classical treatments of the disease such as methotrexate, sodium aurothiomalate and sulfasalazine, are not always effective in controlling RA and JRA. This has necessitated the development of novel agents for treating RA, most of which are biological in nature and are targeted at specific sites of the inflammatory cascades. These biological therapeutic strategies in RA have proved successful and are being applied in the management of JRA. These developments have been facilitated by the advances in molecular biology which have heralded the advent of biodrugs (recombinant proteins) and gene therapy, in which specific genes can be introduced locally to enhance in vivo gene expression or suppress gene(s) of interest with a view to down-regulating inflammation. Some of these biodrugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), monoclonal antibodies (infliximab, adalimumab), TNF soluble receptor constructs (etanercept) and interleukin-1 receptor antagonist (IL-1Ra) have been tested and shown to be effective in RA. Etanercept has now been licensed for JRA. Clinical trials of infliximab in JRA are planned. Studies show that the clinical effects are transient, necessitating repeated treatments and the risk of vaccination effects. Anti-inflammatory cytokines such as IL-4, IL-10, transforming growth factor-beta and interferon-beta (IFN-beta) are undergoing clinical trials. Many of these agents have to be administered parenterally and production costs are very high; thus, there is a need

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

    PubMed Central

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

    2013-01-01

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

  11. The multifaceted aspects of interstitial lung disease in rheumatoid arthritis.

    PubMed

    Cavagna, Lorenzo; Monti, Sara; Grosso, Vittorio; Boffini, Nicola; Scorletti, Eva; Crepaldi, Gloria; Caporali, Roberto

    2013-01-01

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

  12. Autologous stem cell transplantation in the treatment of refractory rheumatoid arthritis.

    PubMed Central

    Kim, Ki Chan; Lee, In Hong; Choi, Jung Hye; Oh, Mee Ran; Ahn, Myung Ju; Kim, Seong Yoon

    2002-01-01

    The concept of using high-dose immunosuppressive treatment (HDIT) with autologous stem cell transplantation (ASCT) to treat patients with refractory rheumatoid arthritis has been provided by animal studies and anecdotal case reports. Over the past five years, an increasing number of patients with refractory rheumatoid arthritis have received HDIT with ASCT as an adjunct to intense immunosuppression. Here, we present a case of refractory rheumatoid arthritis in a 54-yr-old woman using HDIT with ASCT. Peripheral blood stem cells were mobilized with cyclophosphamide (4 g/m(2)) followed by G-CSF (5 microg/kg/day). Leukapheresis continued daily until the number of harvested progenitor cells reached 2 x 10(6) CD34+ cells/kg after CliniMax CD34+ positive selection. For HDIT, high-dose cyclophosphamide (total dose 200 mg/kg) and antithymocyte globulin (total dose 90 mg/kg) were administered and CD34+ cells were infused 24 hr after HDIT. The patient tolerated the treatment well but experienced an episode of neutropenic fever. She achieved an early dramatic improvement of joint symptoms during therapy. Fifty percent of improvement of rheumatoid arthritis by the American College of Rheumatology (ACR 50) preliminary definition was fulfilled during the 6 months following ASCT. Although further long-term follow-up is required, the patient's activity of arthritis has been stable since receiving HDIT with ASCT. PMID:11850603

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

    PubMed Central

    2010-01-01

    Background Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics. Methods HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future. Results Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone. Conclusions HYDREMATS can be used to make reasonable predictions of mosquito populations and vectorial capacity, and provide early warnings of the potential for malaria epidemics in Africa. PMID:21073726

  14. 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.

  15. Mouse Models of Rheumatoid Arthritis.

    PubMed

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.

  16. 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

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

    PubMed

    Verstappen, Suzanne M M

    2015-06-01

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

  18. 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.

  19. International Reference Preparation of Rheumatoid Arthritis Serum

    PubMed Central

    Anderson, S. G.; Bentzon, M. W.; Houba, V.; Krag, P.

    1970-01-01

    The National Institute for Medical Research, London, England, was requested by the WHO Expert Committee on Biological Standardization to arrange a collaborative study of the serum pool they had obtained, to determine its suitability to serve as an international reference preparation of rheumatoid arthritis serum. A batch of this serum was assayed by 11 laboratories in 7 countries against 30 test preparations. On the basis of the results obtained, the serum has been established as the International Reference Preparation of Rheumatoid Arthritis Serum and the International Unit of Rheumatoid Arthritis Serum has been defined as the activity contained in 0.171 mg of the international reference preparation. A description is also given of the British reference preparation of rabbit antibody to sheep red blood cells (amboceptor) and this material was also tested in the collaborative study. PMID:5310143

  20. [Scleromalacia perforans. Rheumatoid arthritis--case report].

    PubMed

    Gheorghe, Anghel; Pandelescu, Monica; Muraru, Cristina

    2009-01-01

    The authors present the case of a 73-year-old patient who comes in our clinic because of the existence of a tumoral formation pigmented and elevated, situated in the temporal side of the right eye and because of decreasing of her visual acuity at both eyes, as well as foreign body eye sensation, tearing, light sensitivity redness of the eye. The ophthalmological examination establishes the diagnosis of the right eye: Scleromalacia perforans, scleral temporal nodule considering the chronic, systemic inflammatory invalidated disorder, rheumatoid arthritis fourth stage. The purpose of this case presentation is represented by the rarity of this type of ocular manifestation presented in late stages of rheumatoid arthritis.

  1. [Guidelines for the management of rheumatoid arthritis].

    PubMed

    Kawahito, Yutaka

    2016-06-01

    In 2014, guidelines for the management of rheumatoid arthritis, was announced from Japan College of Rheumatology. This guideline was made by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method with a concept of "treat to target" led for European and American recommendation of rheumatoid arthritis. It assesses not only evidences but also the balance of desirable and undesirable consequences, values and preferences of the patient, and resource use. It is constructed by evidence summary of 88 clinical questions and 37 recommendations about medication, orthopaedic surgery and rehabilitation. PMID:27311182

  2. Psychological care of adults with rheumatoid arthritis.

    PubMed

    Rogers, M P; Liang, M H; Partridge, A J

    1982-03-01

    Physicians treating patients with chronic rheumatoid arthritis spend a considerable amount of time dealing with the psychological and social aspects of the disease. The patients' reaction to the disease can be related to age, experience, personality, and environment at work and at home. Common problems include loss of independence and self esteem, relations with family and friends, employment, and management of pain. Physicians should be attentive to the psychosocial aspects of rheumatoid arthritis and recognize their dynamic interactions to minimize their impact. PMID:7059100

  3. Rheumatoid arthritis and cryptogenic organising pneumonitis.

    PubMed

    Rees, J H; Woodhead, M A; Sheppard, M N; du Bois, R M

    1991-05-01

    We describe three patients with rheumatoid arthritis who presented with non-specific pulmonary symptoms, a restrictive defect in lung function and bilateral changes on chest radiograph. Lung histology showed characteristic features of cryptogenic organising pneumonitis and treatment with steroids produced significant improvement. The clinical and laboratory features of cryptogenic organising pneumonitis (otherwise known as bronchiolitis obliterans organising pneumonia, 'BOOP') are discussed and compared with those of bronchiolitis obliterans with which the condition should not be confused. Cryptogenic organising pneumonitis should be considered as one of the pulmonary manifestations of rheumatoid arthritis, but lung biopsy is essential to make the diagnosis.

  4. [HLA antigens in juvenile rheumatoid arthritis].

    PubMed

    Rumba, I V; Sochnev, A M; Kukaĭne, E M; Burshteĭn, A M; Benevolenskaia, L I

    1990-01-01

    Antigens of I class HLA system (locus A and B) were investigated in 67 patients of Latvian nationality suffering from juvenile rheumatoid arthritis (JRA). Associations of HLA antigens with juvenile rheumatoid arthritis partially coincided with the ones revealed earlier. Typing established an increased incidence of antigen B27 (p less than 0.01) and gaplotype A2, B40 (p less than 0.01). Antigen B15 possessed a protective action with respect to JRA. Interlocus combinations demonstrated a closer association with the disease than a single antigen. The authors also revealed markers of various clinico-anatomical variants of JRA.

  5. Monte Carlo simulation of early molecular evolution in the RNA World.

    PubMed

    Ma, Wentao; Yu, Chunwu; Zhang, Wentao

    2007-01-01

    The origin of life remains a highly speculative field, mainly due to the shortage of our knowledge on prebiotic chemistry and basic understanding on the essence of life. In this context, computer simulation is expected to play an important role. For instance, the scenario concerning the genesis of the widely accepted RNA World remains blurry, though we have gathered some circumstantial evidence and fragmented knowledge on several supposed stages, including formation of polynucleotides from a prebiotic nucleotide pool, emergence of RNA replicases (RNA molecules catalyzing their own replication), and evolution of RNA replicases. It is highly valuable to simulate the stages as a continuous process to evaluate the plausibility of the supposition and study the rules involved. Here we construct a computer simulation on the process using Monte Carlo method. It demonstrates that primordial RNA replicases may appear and spread in a nucleotide pool provided they could recognize their own sequence and their complements as catalytic targets, and then may evolve to more efficient RNA replicases. Apart from its indication on the genesis of the RNA World, the vivid simulation of emergence of the "first replicative molecules" and their subsequent evolution is impressive and may help to get insight into "how could self-replication and Darwinian evolution, two key features of life, emerge in a non-life background?" thus improve our understanding of "what is life" when studying origins of life. PMID:17014951

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid...

  8. 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.

  9. Postoperative inflammation after cataract surgery in patients with rheumatoid arthritis.

    PubMed

    Pahor, D; Pahor, A; Gracner, B

    2001-01-01

    The purpose of the present study was to assess the influence of preoperative activity of rheumatoid arthritis (RA) on early postoperative anterior chamber inflammation after phacoemulsification and intraocular lens implantation. Twenty-three eyes in 18 patients were included in our study. On the first postoperative day, anterior chamber inflammation was observed in 11 eyes (47.8%). Five days after surgery, we found postoperative inflammation only in 1 eye (4.3%). Keratic precipitates were observed in 1 eye (4.3%) on the second postoperative day. We found no correlation between the extent of anterior chamber inflammation and the preoperative activity of RA. Postoperative anterior chamber inflammation was also not associated with the medical management of RA.

  10. 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.

  11. The rheumatoid shoulder: current consensus on diagnosis and treatment.

    PubMed

    Thomas, Thierry; Noël, Eric; Goupille, Philippe; Duquesnoy, Bernard; Combe, Bernard

    2006-03-01

    Shoulder involvement is usually inconspicuous in patients with rheumatoid arthritis, and the clinical manifestations are nonspecific. Nevertheless, shoulder involvement should be sought routinely and detected early. Range of motion at the shoulder should be evaluated. Although normal radiographic findings do not rule out shoulder involvement, radiographs are crucial for detecting micro- and macro-geodes during follow-up. The development of glenohumeral joint space narrowing is a turning point that indicates a risk of rapid joint destruction. Magnetic resonance imaging is useful for assessing the lesions and guiding the treatment strategy. Stepwise use of local interventions as indicated by imaging findings is recommended. Joint replacement should not be left too late, and surgical procedures on the shoulder should be built into the overall treatment plan.

  12. Transcript profiling towards personalised medicine in rheumatoid arthritis.

    PubMed

    Verweij, C L

    2009-12-01

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

  13. Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A Synopsis.

    PubMed

    Gibofsky, Allan

    2014-05-01

    Rheumatoid arthritis (RA) is one of the more common autoimmune disorders, affecting approximately 1% of the population worldwide. The exact cause of RA is not known; however, initiation of disease seems to result from an interaction among genetic susceptibility, environmental triggers, and chance. RA is characterized by dysregulated inflammatory processes in the synovium of the joint that eventually leads to the destruction of both cartilaginous and bony elements of the joint, with resulting pain and disability. Systemic inflammation associated with RA is associated with a variety of extra-articular comorbidities, including cardiovascular disease, resulting in increased mortality in patients with RA. RA is also associated with several psychosocial disorders. Classification criteria for RA that were promulgated jointly by the American College of Rheumatology and the European League Against Rheumatism in 2010 emphasize early detection of RA so that effective management can be initiated before pathological changes become irreversible.

  14. 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).

  15. 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.

  16. 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.

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

    PubMed

    Skagen, E B; Iversen, T H

    2000-01-01

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

  18. Post-impact climate conditions on early Mars: preliminary results from GCM simulations

    NASA Astrophysics Data System (ADS)

    Steakley, Kathryn; Murphy, Jim; Kahre, Melinda A.; Haberle, Robert

    2016-10-01

    Observations imply that liquid water was stable on Mars' surface during the late Noachian/early Hesperian era, with valley networks forming roughly 3.5-3.75 billion years ago, possibly from precipitation and runoff (Fassett & Head 2008, Icarus 195, 61; Hynek et al., 2010, JGR Planets, 115, E09008). Climate models, however, struggle to reproduce such warm conditions (Forget et al., 2013, Icarus 21, 81). Volcanism and impacts have been suggested as mechanisms of either inducing a warm and wet environment or causing local melting in a cold and wet environment. Comets and asteroids are capable of injecting into the atmosphere both kinetic energy from the impact and water from the object itself and from vaporized surface and subsurface ice. Segura et al. (2008, JGR Planets 113, E11007) find using a 1-D atmospheric model that significant rainfall and periods of above-freezing temperatures lasting months to years can follow impacts of objects between 30 and 100 km in diameter. We revisit this work utilizing a 3-D global climate model (GCM) to consider the effects of dynamics, topography, global surface ice variations, etc. We present preliminary results from the NASA ARC Mars GCM investigating global temperature and precipitation behavior in a post-impact, early Mars environment.

  19. 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.

  20. [Osteoporosis and fracture in rheumatoid arthritis].

    PubMed

    Norimatsu, H

    2001-05-01

    Patients with rheumatoid arthritis often have periarticular and generalized osteoporosis. Bone resorption develops through increased productions of cytokines and prostaglandines by synovium and bone. Important risk factors of osteoporosis are functional impairment, postmenopausal state, and corticosteroids usage. Osteoporotic fracture occurs at the spinal body, femoral neck, distal radius, and periprosthetic bone.

  1. 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…

  2. [Regaining quality of life despite rheumatoid arthritis].

    PubMed

    A, Madame

    2016-01-01

    A patient aged 32 who had been living with her partner for a few years, is diagnosed with rheumatoid arthritis. They both needed to understand and adapt. The caregivers had a frontline role in the multidisciplinary care but addressing the impact on the patient's sexual quality of life remains difficult. The patient describes her experience and how harmony and desire were re-established.

  3. [Cystic Rheumatoid Arthritis--case report].

    PubMed

    Mourão, Ana Filipa; Santos, Fernando Pimentel; Falcão, Sandra; Pinto, Teresa Laura; Barros, Rita; de Matos, António Alves; Branco, Jaime Cunha

    2007-01-01

    Among the many radiological findings seen in Rheumatoid Arthritis RA small subchondral geodes and erosions are typical. Large geodes are far less common abnormalities and their presence may indicate diagnostic and therapeutic difficulties. We present a case report of a 55-year old woman with seronegative RA that developed a large geode in the knee with extensive joint destruction.

  4. Isolated pulmonary hypertension secondary to rheumatoid arthritis.

    PubMed

    Castro, Glaucio W R; Appenzeller, Simone; Bertolo, Manoel B; Costallat, Lilian T L

    2006-11-01

    The authors report a case of a woman with pulmonary hypertension secondary to rheumatoid arthritis, whose treatment with azathioprine resulted in normalization of pulmonary artery pressure and resolution of clinical symptoms. Different etiologies for pulmonary hypertension are discussed and literature review is presented.

  5. [The golden age of rheumatoid arthritis treatment].

    PubMed

    Mercado, Ulises

    2014-01-01

    Today, we enjoy the golden age of rheumatology. In the 1970s, the paradigm for treating rheumatoid arthritis consisted in a pyramid. In the decade of the 1980s, and shortly after began a revolution in the understanding and treatment of rheumatic diseases. Methotrexate and tumor necrosis factor-blockers came on the scene.

  6. Rheumatoid Meningitis: Diagnostic and Therapeutic Observations.

    PubMed

    Stretz, Christoph; Song, Xianyuan; Killory, Brendan D; Ollenschleger, Martin D; Nouh, Amre M

    2016-03-01

    A 75-year-old female with untreated rheumatoid arthritis presented with two weeks of behavioral changes and cognitive decline. A neurologic examination showed severe encephalopathy, brisk reflexes, and bilateral Babinski sign. A contrast-enhanced brain MRI demonstrated right meningeal enhancement and periventricular white matter disease. A computed tomographic angiogram (CTA) of the head and neck was negative for vasculitis. The cerebrospinal fluid (CSF) demonstrated lymphocytic pleocytosis. The patient's serum rheumatoid factor levels were elevated. A biopsy of the leptomeninges and cortex showed lymphocytic vasculitis of the cortical tissue and patchy lymphoplasmacytic infiltrates of dural small vessels consistent with rheumatoid meningitis. The patient received pulse-dose steroids followed by cyclophosphamide infusions. At her three month follow-up appointment, the patient's mental status had improved mildly. A follow-up brain MRI showed resolution of enhancement, but progression of subcortical bihemispheric white matter disease. Subsequently, the patient developed a respiratory infection and passed away. In rheumatoid arthritis, symptoms of encephalopathy, headaches, seizures, or focal neurologic deficits should raise suspicion for CNS involvement. This potentially treatable disease warrants prompt diagnosis.

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

    NASA Astrophysics Data System (ADS)

    Naoz, Smadar; Yoshida, Naoki; Barkana, Rennan

    2011-09-01

    We run very large cosmological N-body hydrodynamical simulations in order to study statistically the baryon fractions in early dark matter haloes. We critically examine how differences in the initial conditions affect the gas fraction in the redshift range z= 11-21. We test three different linear power spectra for the initial conditions. (1) A complete heating model, which is our fiducial model; this model follows the evolution of overdensities correctly, according to Naoz & Barkana (2005), in particular including the spatial variation of the speed of sound of the gas due to Compton heating from the CMB. (2) An equal-δ model, which assumes that the initial baryon fluctuations are equal to those of the dark matter, while conserving σ8 of the total matter. (3) A mean cs model, which assumes a uniform speed of sound of the gas. The latter two models are often used in the literature. We calculate the baryon fractions for a large sample of haloes in our simulations. Our fiducial model implies that before reionization and significant stellar heating took place, the minimum mass needed for a minihalo to keep most of its baryons throughout its formation was ˜3 × 104 M⊙. However, the alternative models yield a wrong (higher by about 50 per cent) minimum mass, since the system retains a memory of the initial conditions. We also demonstrate this using the 'filtering mass' from linear theory, which accurately describes the evolution of the baryon fraction throughout the simulated redshift range.

  8. The early stage of folding of villin headpiece subdomain observed in a 200-nanosecond fully solvated molecular dynamics simulation

    PubMed Central

    Duan, Yong; Wang, Lu; Kollman, Peter A.

    1998-01-01

    A new approach in implementing classical molecular dynamics simulation for parallel computers has enabled a simulation to be carried out on a protein with explicit representation of water an order of magnitude longer than previously reported and will soon enable such simulations to be carried into the microsecond time range. We have used this approach to study the folding of the villin headpiece subdomain, a 36-residue small protein consisting of three helices, from an unfolded structure to a molten globule state, which has a number of features of the native structure. The time development of the solvation free energy, the radius of gyration, and the mainchain rms difference from the native NMR structure showed that the process can be seen as a 60-nsec “burst” phase followed by a slow “conformational readjustment” phase. We found that the burial of the hydrophobic surface dominated the early phase of the folding process and appeared to be the primary driving force of the reduction in the radius of gyration in that phase. PMID:9707572

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

    NASA Astrophysics Data System (ADS)

    Duan, Yong; Wang, Lu; Kollman, Peter A.

    1998-08-01

    A new approach in implementing classical molecular dynamics simulation for parallel computers has enabled a simulation to be carried out on a protein with explicit representation of water an order of magnitude longer than previously reported and will soon enable such simulations to be carried into the microsecond time range. We have used this approach to study the folding of the villin headpiece subdomain, a 36-residue small protein consisting of three helices, from an unfolded structure to a molten globule state, which has a number of features of the native structure. The time development of the solvation free energy, the radius of gyration, and the mainchain rms difference from the native NMR structure showed that the process can be seen as a 60-nsec ``burst'' phase followed by a slow ``conformational readjustment'' phase. We found that the burial of the hydrophobic surface dominated the early phase of the folding process and appeared to be the primary driving force of the reduction in the radius of gyration in that phase.

  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

  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. Early and transient stages of Cu oxidation: Atomistic insights from theoretical simulations and in situ experiments

    NASA Astrophysics Data System (ADS)

    Zhu, Qing; Zou, Lianfeng; Zhou, Guangwen; Saidi, Wissam A.; Yang, Judith C.

    2016-10-01

    Understanding of metal oxidation is critical to corrosion control, catalysis synthesis, and advanced materials engineering. Although, metal oxidation process is rather complicated, different processes, many of them coupled, are involved from the onset of reaction. Since first introduced, there has been great success in applying heteroepitaxial theory to the oxide growth on a metal surface as demonstrated in the Cu oxidation experiments. In this paper, we review the recent progress in experimental findings on Cu oxidation as well as the advances in the theoretical simulations of the Cu oxidation process. We focus on the effects of defects such as step edges, present on realistic metal surfaces, on the oxide growth dynamics. We show that the surface steps can change the mass transport of both Cu and O atoms during oxide growth, and ultimately lead to the formation of different oxide morphology. We also review the oxidation of Cu alloys and explore the effect of a secondary element to the oxide growth on a Cu surface. From the review of the work on Cu oxidation, we demonstrate the correlation of theoretical simulations at multiple scales with various experimental techniques.

  13. Rheumatoid factor (RF) distribution in periodontal disease.

    PubMed

    Thé, J; Ebersole, J L

    1991-05-01

    This study investigated the occurrence of an autoantibody, IgM rheumatoid factor, that may result from the chronic inflammation noted in periodontal disease and rheumatoid arthritis. In order to detect IgM-RF, a biotin-avidin ELISA was developed. This assay was found to be sensitive and accurate by testing a rheumatoid arthritis population. The characteristics of this rheumatoid arthritis group were further determined, such that the total serum immunoglobulin concentrations were slightly elevated although within the normal range for IgM, IgG, and IgA; IgG antibody levels were elevated against oral microorganisms of the genus Capnocytophaga, while elevated IgM antibody levels were noted to Bacteroides species. In a population of 260 subjects of which 171 were periodontal disease patients, 16 of 171 (9.4%) were seropositive for IgM-RF, of which the predominant disease types were advanced destructive periodontitis and adult periodontitis. For comparison, a random population of seronegative periodontal disease patients was constructed that was matched for sex and approximate age to the seropositive group. The total immunoglobulin levels of the two groups were not significantly different and the means of both were slightly lower than the rheumatoid arthritis group. When the antibody profiles of the two periodontal disease populations were compared it became evident that the RF-positive group showed IgM and IgG antibody that was significantly elevated to Capnocytophaga species and F. nucleatum. Therefore, the chronic inflammation associated with periodontitis appears to increase significantly the formation of IgM-RF; however, there does appear to be a relationship between IgM-RF and elevated antibody to selected oral microorganisms. PMID:1890163

  14. 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.

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

    PubMed

    Bharate, Sonali S; Vishwakarma, Ram A

    2015-04-01

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

  16. 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.

  17. Current concepts in the management of the rheumatoid hand.

    PubMed

    Chung, Kevin C; Pushman, Allison G

    2011-04-01

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

  18. 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.

  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. Serum melatonin in juvenile rheumatoid arthritis: correlation with disease activity.

    PubMed

    El-Awady, Hanaa Mahmoud; El-Wakkad, Amany Salah El-Dien; Saleh, Maysa Tawheed; Muhammad, Saadia Ibraheem; Ghaniema, Eiman Mahmoud

    2007-05-01

    The study was conducted to investigate the abnormalities in early morning serum melatonin among patients with Juvenile Rheumatoid Arthritis (JRA) and to outline its relation to disease activity and severity. Twenty one patients with JRA and twenty healthy age and sex matched controls were enrolled in the study. Fifteen patients had polyarticular JRA, 3 had oligoarticular and 3 had systemic onset JRA. Evaluation was carried out clinically, functionally and radiologically by using disease activity score, Juvenile Arthritis Functional Assessment Report for Children (JAFAR-C score) and modified Larsen score, respectively. Laboratory investigations included Complete Blood Picture (CBC), The Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), classic IgM Rheumatoid Factor (RF), Anti-nuclear Antibodies (ANA) and melatonin estimation in serum. The serum levels of melatonin were significantly increased in JRA patients (mean +/- SD = 13.9 +/- 8 pg mL(-1)) as compared to healthy controls (mean +/- SD = 8.1 +/- 2.7 pg mL(-1), p < 0.01). A significant positive correlation could link serum melatonin levels to disease activity scores and ESR (r = 0.91, p < 0.001 and r = 0.55, p < 0.01, respectively). No significant correlation was found between melatonin and either Larsen or JAFAR scores (r = 0.19, r = 0.15, respectively). According to melatonin levels, there were 2 groups of patients: Group I with elevated melatonin level (more than 11 pg mL(-1)) (n = 15) and group II with normal melatonin level (less than 11 pg mL(-1)) (n = 6). Patients with elevated melatonin levels had higher ESR (p < 0.05), higher disease activity scores (p < 0.01) and Larsen scores (p < 0.05), than the group of patients with normal serum melatonin. The results of GAFAR scores were comparable between the two groups (p > 0.05). Hence the study conclude that the elevated melatonin levels among JRA patients with active synovitis and its close relation to disease activity rather than disease severity

  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 Astrophysics Data System (ADS)

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

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

    NASA Astrophysics Data System (ADS)

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

    1992-08-01

    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.

  4. 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.

  5. Monsters in the dark: predictions for luminous galaxies in the early Universe from the BLUETIDES simulation

    NASA Astrophysics Data System (ADS)

    Waters, Dacen; Wilkins, Stephen M.; Di Matteo, Tiziana; Feng, Yu; Croft, Rupert; Nagai, Daisuke

    2016-09-01

    Using deep Hubble and Spitzer observations Oesch et al. have identified a bright (MUV ≈ -22) star-forming galaxy candidate at z ≈ 11. The presence of GN-z11 implies a number density ˜10-6 Mpc-3, roughly an order of magnitude higher than the expected value based on extrapolations from lower redshift. Using the unprecedented volume and high resolution of the BLUETIDES cosmological hydrodynamical simulation, we study the population of luminous rare objects at z > 10. The luminosity function in BLUETIDES implies an enhanced number of massive galaxies, consistent with the observation of GN-z11. We find about 30 galaxies at MUV ≈ -22 at z = 11 in the BLUETIDES volume, including a few objects about 1.5 mag brighter. The probability of observing GN-z11 in the volume probed by Oesch et al. is ˜13 per cent. The predicted properties of the rare bright galaxies at z = 11 in BLUETIDES closely match those inferred from the observations of GN-z11. BLUETIDES predicts a negligible contribution from faint AGN in the observed SED. The enormous increase in volume surveyed by WFIRST will provide observations of ˜1000 galaxies with MUV < -22 beyond z = 11 out to z = 13.5.

  6. 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.

  7. Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.

    PubMed

    Boers, M; Croonen, A M; Dijkmans, B A; Breedveld, F C; Eulderink, F; Cats, A; Weening, J J

    1987-09-01

    Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and non-rheumatoid disease may play a part in the cause of these abnormalities. PMID:3675007

  8. Rheumatoid arthritis associated interstitial lung disease: a review.

    PubMed

    Assayag, Deborah; Lee, Joyce S; King, Talmadge E

    2014-01-01

    Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

  9. Morbidity impact of rheumatoid arthritis on society.

    PubMed

    McDuffie, F C

    1985-01-21

    Classic and definite rheumatoid arthritis affects from 0.5 to 1 percent of the United States' population between the ages of 20 and 80. In the age group of 55 to 75 years, this figure increases to 4.5 percent. In addition to the pain and suffering produced by this disease, family structure is dramatically affected--the divorce rate for patients with rheumatoid arthritis is 70 percent above that for the general population. Rheumatoid arthritis also results in serious economic loss to society. In 1983, the direct cost (out-of-pocket expense for medical care) was $777 million, and the indirect cost (loss of productivity) was $215 million, with a total of approximately $1 billion. The average person with stage III rheumatoid arthritis suffers a 60 percent decline in earnings during the first six years after onset of the disease. Recent studies have indicated that the ability to remain employed depends at least as much on job-related factors as on the extent of disease or success of medical treatment. Job autonomy or the ability to control one's working conditions is the most important factor. Other important variables are education, seniority, and work that is not excessively physically demanding. Good transportation between home and job is also an essential requirement for remaining employed. There are few data available on the cost/benefit ratio of the treatment of rheumatoid arthritis. An 18-month study showed a trend toward greater improvement in patients given optimal care by a team of experts in a medical center as compared with average treatment provided in the community. A study in Scotland on cost of hospitalization of 366 patients (about one half underwent surgery) showed cost benefits of xi 14,000 to xi 131,000 over a five- to 10-year period for those who returned to work. Patients who did not return to work incurred medical costs of xi 100,000. There is little question that more effective medical treatment and better rehabilitation strategies for people

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

    PubMed Central

    Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Kwiatkowska, Brygida; Zaniewicz-Kaniewska, Katarzyna; Warczyńska, Agnieszka

    2012-01-01

    Rheumatoid arthritis is a chronic inflammatory disease with a multifactorial etiology and varied course, which in the majority of patients leads to partial disability or to permanent handicap. Its characteristic trait is a persistent inflammation of the synovial membrane and the formation of an invasive synovial tissue, called the pannus, which in time leads to destruction of the cartilage, subchondral bone tissue, and the soft tissue of the affected joint(s). The pathogenesis of rheumatoid arthritis is complex and involves cells of both innate and adaptive immunity, a network of various cytokines and an immunoregulatory dysfunction. An important role in the discovery of rheumatoid arthritis pathogenesis was played by magnetic resonance imaging, which showed the disease process to extend beyond the synovium into the bone marrow. Many studies have shown a strict correlation between the vascularity of the synovium (assessed through the power Doppler ultrasound and magnetic resonance examinations), bone marrow edema and the clinical, laboratory and histopathological parameters of rheumatoid arthritis. From the current understanding of rheumatoid arthritis, bone erosions could occur from two directions: from the joint cavity and from the bone marrow. With power Doppler ultrasound, as well as in magnetic resonance imaging, it is possible to visualize the well-vascularized pannus and its destructive effects on joint structures and ligaments. In addition, the magnetic resonance study shows inflammatory and destructive changes within the bone marrow (bone marrow edema, inflammatory cysts, and erosions). Bone marrow edema occurs in 68–75% of patients with early rheumatoid arthritis and is considered to be a predictor of rapid disease progression. PMID:26673660

  11. 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.

  12. Pachymeningitis and optic neuritis in rheumatoid arthritis: MRI findings.

    PubMed

    Ağildere, A M; Tutar, N U; Yücel, E; Coşkun, M; Benli, S; Aydin, P

    1999-04-01

    Rheumatoid arthritis is a systemic disease in which cerebral and eye involvement is neither common nor fully understood. Although it is rarely the cause of pachymeningitis and optic neuritis, rheumatoid arthritis should always be kept in mind in these two conditions. We present a 52-year-old male with an 8 month history of rheumatoid arthritis who was referred to the neurology department with headache and decreasing vision and was diagnosed as having rheumatoid pachymeningitis and optic neuritis on the basis of MRI findings.

  13. Rat Bite Fever Resembling Rheumatoid Arthritis.

    PubMed

    Akter, Ripa; Boland, Paul; Daley, Peter; Rahman, Proton; Al Ghanim, Nayef

    2016-01-01

    Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID:27366177

  14. Rat Bite Fever Resembling Rheumatoid Arthritis

    PubMed Central

    Akter, Ripa; Boland, Paul; Daley, Peter; Rahman, Proton; Al Ghanim, Nayef

    2016-01-01

    Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID:27366177

  15. 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

  16. Dual diagnosis: rheumatoid arthritis and multiple sclerosis.

    PubMed

    Ozsahin, Mustafa; Dikici, Suber; Kocaman, Gülsen; Besir, Fahri Halit; Baltaci, Davut; Ataoglu, Safinaz

    2014-01-01

    Juvenile rheumatoid arthritis (JRA) is the most common rheumatologic disease in children. Moreover, multiple sclerosis (MS) is the most frequent demyelinating disease and has been associated with various chronic inflammatory diseases. However, its association with JRA has not been frequently described. Autoimmunity in both JRA and MS has been documented in the scientific literature, although there has been no definitive finding that patients with JRA are prone to the development of MS. An increasing frequency of MS resulting from an increased use of antitumor necrosis factor agents in the treatment of rheumatoid arthritis and other chronic inflammatory diseases has been reported recently. In this study, we report on the development of MS in a patient with JRA who did not have a history of antitumor necrosis factor use.

  17. Cytokines in juvenile rheumatoid arthritis (JRA).

    PubMed

    Mangge, H; Schauenstein, K

    1998-06-01

    Juvenile rheumatoid arthritis (JRA), unlike rheumatoid arthritis of adulthood (RA), is a heterogenous disease comprising at least five subtypes that differ in clinical course and prognosis, and require different therapeutical approaches. As compared to RA, the production of local and systemic cytokines in JRA have not yet been as extensively investigated. In this article we review the available literature on cytokine expression in serum and synovial fluid in all five different subtypes of JRA. Even though the data are still fragmentary, the evidence so far suggests that the determination of serum cytokines yields relevant information as to clinical subtype and inflammatory activity of the disease. Furthermore, the cytokine data suggest that the pathogenesis of JRA may even by more heterogenous than defined by the clinical subtypes. Finally, future directions of research in this area are proposed, and-based on the latest results-arguments for (anti)cytokine therapies in JRA are critically discussed.

  18. Osteoporosis diagnostics in patients with rheumatoid arthritis.

    PubMed

    Węgierska, Małgorzata; Dura, Marta; Blumfield, Einat; Żuchowski, Paweł; Waszczak, Marzena; Jeka, Sławomir

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease. The development of comorbidities often occurs in the course of RA. One of them is osteoporosis, which has serious social and economic effects and may contribute to the increase in the degree of disability and premature death of the patient. Due to the young age in which RA disease occurs, densitometry (DXA) of the lumbar spine is the basic examination in osteoporosis diagnostics. In the course of RA, much more frequently than in healthy persons of the same age, osteoporotic fractures of vertebral bodies occur, which hinder a correct assessment in the DXA test. Rheumatoid arthritis patients often undergo computed tomography (CT) examination of the abdominal cavity for other medical indications than suspected spinal injury. Then, CT examination may also serve for the assessment of bone density, especially in patients with osteoporotic fractures. PMID:27407274

  19. 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

  20. Nanomedicine delivers promising treatments for rheumatoid arthritis

    PubMed Central

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

    2015-01-01

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

  1. Benefits of Exercise in Rheumatoid Arthritis

    PubMed Central

    Cooney, Jennifer K.; Law, Rebecca-Jane; Matschke, Verena; Lemmey, Andrew B.; Moore, Jonathan P.; Ahmad, Yasmeen; Jones, Jeremy G.; Maddison, Peter; Thom, Jeanette M.

    2011-01-01

    This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA) and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, “rheumatoid cachexia”. These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training. PMID:21403833

  2. [Basic research overview in rheumatoid arthritis].

    PubMed

    Iwasaki, Yukiko; Yamamoto, Kazuhiko

    2016-06-01

    Rheumatoid arthritis (RA) is a common autoimmune disease with a prevalence of 0.5-1.0% worldwide. Although advances in understanding the pathogenesis of RA have led to new therapeutics with good outcomes, the real cause of the disease is still unknown. RA is characterized by synovial inflammation and hyperplasia, which erodes cartilage and bone, and autoantibody production (rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)). There are many critical questions on the mechanism of the disease onset and progression: How genetic and environmental factors interact with each other? Why does the inflammatory response localize in joints? What are the key players to perpetuate synovial inflammation? In this review, we summarize pathogenetic advances in these issues especially from the point of view of basic research.

  3. Naproxen in rheumatoid arthritis. Extended trial.

    PubMed Central

    Mowat, A G; Ansell, B M; Gumpel, J M; Hill, H F; Hill, A G; Stoppard, M

    1976-01-01

    121 patients with active rheumatoid arthritis, 91 of whom had proved intolerant of other nonsteroidal anti-inflammatory agents, were treated for a mean of 10 months with naproxen. A dosage of 250 mg twice daily produced sustained improvement in most of the standard clinical measurements. 28 patients complained of side effects, with a lower than expected incidence of gastrointestinal complaints and no drug-induced rash being recorded. 19 patients withdrew from the trial because of side effects, while a further 22 withdrew because the drug was ineffective. Naproxen is a useful drug for long-term use in patients with rheumatoid arthritis, including those who have proved intolerant of or experienced inadequate symptomatic relief from other nonsteriodal anti-inflammatory agents. PMID:795386

  4. Rheumatoid factors, B cells and immunoglobulin genes.

    PubMed

    Jefferis, R

    1995-04-01

    The paradigm of self, non-self discrimination in the immune system is under review as autoreactive B or T cells are increasingly delineated within normal individuals. The products of autoreactive B cells are, mostly, polyspecific IgM antibodies of low affinity. These 'natural' antibodies include rheumatoid factors (RF) encoded by unmutated germline immunoglobulin genes. In rheumatoid arthritis (RA) the RF may be of the IgM, IgG or IgA isotype, show evidence of somatic mutation and have increased affinity; consistent with maturation of an antigen driven immune response. This response could be initiated or driven by an auto-immunogenic form of IgG or an exogenous cross-reactive antigen. Changes in galactosylation of IgG have been reported to be a valuable diagnostic and prognostic indicator in RA. Speculation that these changes may precipitate some of the disease processes is critically reviewed.

  5. Rheumatoid arthritis and pseudo-vesicular skin plaques: rheumatoid neutrophilic dermatosis*

    PubMed Central

    Manriquez, Juan; Giesen, Laura; del Puerto, Constanza; Gonzalez, Sergio

    2016-01-01

    A 54 year-old woman with a 3-year history of rheumatoid arthritis (RA) consulted us because of weight loss, fever and skin eruption. On physical examination, erythematous plaques with a pseudo-vesicular appearance were seen on the back of both shoulders. Histological examination was consistent with rheumatoid neutrophilic dermatosis (RND). After 3 days of prednisone treatment, the skin eruption resolved. RND is a rare cutaneous manifestation of seropositive RA, characterized by asymptomatic, symmetrical erythematous plaques with a pseudo-vesicular appearance. Histology characteristically reveals a dense, neutrophilic infiltrate with leucocitoclasis but without other signs of vasculitis. Lesions may resolve spontaneously or with RA treatment. This case illustrates an uncommon skin manifestation of active rheumatoid arthritis. PMID:27579747

  6. Rheumatoid arthritis and pseudo-vesicular skin plaques: rheumatoid neutrophilic dermatosis.

    PubMed

    Manriquez, Juan; Giesen, Laura; Puerto, Constanza Del; Gonzalez, Sergio

    2016-01-01

    A 54 year-old woman with a 3-year history of rheumatoid arthritis (RA) consulted us because of weight loss, fever and skin eruption. On physical examination, erythematous plaques with a pseudo-vesicular appearance were seen on the back of both shoulders. Histological examination was consistent with rheumatoid neutrophilic dermatosis (RND). After 3 days of prednisone treatment, the skin eruption resolved. RND is a rare cutaneous manifestation of seropositive RA, characterized by asymptomatic, symmetrical erythematous plaques with a pseudo-vesicular appearance. Histology characteristically reveals a dense, neutrophilic infiltrate with leucocitoclasis but without other signs of vasculitis. Lesions may resolve spontaneously or with RA treatment. This case illustrates an uncommon skin manifestation of active rheumatoid arthritis. PMID:27579747

  7. B Cell Lymphoma mimicking Rheumatoid Arthritis.

    PubMed

    Cosatti, M A; Pisoni, C N; Altuve, J L; Lorente, C

    2016-01-01

    Non Hodking´s lymphoma (NHL) may involve bones but synovial involvement is uncommon. We describe a patient who presented with polyarthritis, sicca symptoms and rash suggestive of rheumatoid arthritis. An atypical skin rash prompted skin and synovial biopsies. A diagnosis of synovial and skin malignant large B-cell lymphoma anaplastic subtype was performed. Chemotherapy with dexamethasone, vincristine and rituximab was started. Following treatment the patient had complete resolution of cutaneous and articular lymphoma manifestations. PMID:27419896

  8. [Regaining quality of life despite rheumatoid arthritis].

    PubMed

    A, Madame

    2016-01-01

    A patient aged 32 who had been living with her partner for a few years, is diagnosed with rheumatoid arthritis. They both needed to understand and adapt. The caregivers had a frontline role in the multidisciplinary care but addressing the impact on the patient's sexual quality of life remains difficult. The patient describes her experience and how harmony and desire were re-established. PMID:27317820

  9. Lower limb arterial incompressibility and obstruction in rheumatoid arthritis

    PubMed Central

    del Rincon, I; Haas, R; Pogosian, S; Escalante, A

    2005-01-01

    Background: Despite increased cardiovascular morbidity and mortality in rheumatoid arthritis, the peripheral arteries remain understudied. Objective: To examine the lower limb arteries in age and sex matched, non-smoking subjects with and without rheumatoid arthritis. Methods: The ankle-brachial index (ABI) was measured at the posterior tibial and dorsal pedal arteries. Arteries were classified as obstructed with ABI ⩽0.9, normal with ABI >0.9 but ⩽1.3, and incompressible with ABI >1.3. Multinomial logistic regression was used to estimate differences in ABI between patients and controls, adjusting for cardiovascular risk factors, rheumatoid arthritis manifestations, inflammation markers, and glucocorticoid dose. Results: 234 patients with rheumatoid arthritis and 102 controls were studied. Among the rheumatoid patients, 66 of 931 arteries (7%) were incompressible and 30 (3%) were obstructed. Among the controls, three of 408 arteries (0.7%) were incompressible (p = 0.002) and four (1%) were obstructed (p = 0.06). At the person level, one or more abnormal arteries occurred among 45 rheumatoid patients (19%), v five controls (5%, p = 0.001). The greater frequency of arterial incompressibility and obstruction in rheumatoid arthritis was independent of age, sex, and cardiovascular risk factors. Adjustment for inflammation markers, joint damage, rheumatoid factor, and glucocorticoid use reduced rheumatoid arthritis v control differences. Most arterial impairments occurred in rheumatoid patients with 20 or more deformed joints. This subgroup had more incompressible (15%, p⩽0.001) and obstructed arteries (6%, p = 0.005) than the controls, independent of covariates. Conclusions: Peripheral arterial incompressibility and obstruction are increased in rheumatoid arthritis. Their propensity for patients with advanced joint damage suggests shared pathogenic mechanisms. PMID:15271772

  10. Early warning of freshwater salinization due to upward brine displacement by species transport simulations combined with a hydrochemical genesis model

    NASA Astrophysics Data System (ADS)

    Langer, Maria; Kühn, Michael

    2016-04-01

    Shallow groundwater resources could be possibly affected by intruding brines, which are displaced along hydraulically conductive faults as result of subsurface activities like CO2 injection. To avoid salinization of potable freshwater aquifers an early detection of intruding saline water is necessary, especially in regions where an initial geogenic salinization already exists. Our study is based on work of Tillner et al. [1] and Langer et al. [2] who investigated the influence of permeable fault systems on brine displacement for the prospective storage site Beeskow-Birkholz in the Northeast German Basin. With a 3D regional scale model considering the deep groundwater system, they demonstrated that the existence of hydraulically conductive faults is not necessarily an exclusion criterion for potential injection sites, because salinization of shallower aquifers strongly depends on the effective damage zone volume, the initial salinity distribution and overlying reservoirs [2], while permeability of fault zones does not influence salinization of shallower aquifers significantly [1]. Here we extracted a 2D cross section regarding the upper 220 m of the study area mainly represented by shallow freshwater aquifers, but also considering an initial geogenic salinization [3]. We took flow rates of the intruding brines from the previous studies [2] and implemented species transport simulations with the program code SHEMAT [4]. Results are investigated and interpreted with the hydrochemical genesis model GEBAH [5] which has been already applied as early warning of saltwater intrusions into freshwater aquifers and surface water [6]. GEBAH allows a categorization of groundwater by the ion ratios of the dissolved components and offers a first indicative determination for an existence and the intensity of saline water intrusion in shallow groundwater aquifer, independent of the concentration of the solution. With our model we investigated the migration of saline water through a

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

    PubMed

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

    2015-03-15

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. PMID:25568077

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

    PubMed Central

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

    2015-01-01

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. PMID:25568077

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

    PubMed Central

    Al-Mughales, Jamil A.

    2015-01-01

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

  14. 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.

  15. Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arthritis.

    PubMed

    Prahalad, S; Bohnsack, J F; Jorde, L B; Whiting, A; Clifford, B; Dunn, D; Weiss, R; Moroldo, M; Thompson, S D; Glass, D N; Bamshad, M J

    2006-09-01

    Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T cells express high levels of the Th1-chemokine receptor CC chemokine receptor 5 (CCR5), which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA-affected sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly undertransmitted to children with early-onset JRA (P<0.01). C-1835T was genotyped in 424 additional simplex and multiplex families. CCR5-1835T allele was undertransmitted in the cohort of all probands with JRA (P<0.02), as well as in those with early-onset (P<0.01) or pauciarticular JRA (P<0.05). Another variant, a 32-bp deletion in the open reading frame of CCR5 (CCR5-Delta32) was also tested in approximately 700 simplex and multiplex families. CCR5-Delta32 was also significantly undertransmitted to probands with early-onset JRA (P<0.05). Both variants are in regions under natural selection, and result in functional consequences. Our results suggest these CCR5 variants are protective against early-onset JRA.

  16. Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arthritis

    PubMed Central

    Prahalad, Sampath; Bohnsack, John F.; Jorde, Lynn B.; Whiting, April; Clifford, Bronte; Dunn, Diane; Weiss, Robert; Moroldo, Marta; Thompson, Susan D.; Glass, David N.; Bamshad, Michael J.

    2010-01-01

    Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T-cells express high levels of the Th1-chemokine receptor CCR5, which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA affected-sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly under-transmitted to children with early-onset JRA (p<0.01). C-1835T was genotyped in 424 additional simplex and multiplex families. CCR5-1835T allele was under-transmitted in the cohort of all probands with JRA (p<0.02), as well as in those with early-onset (p<0.01) or pauciarticular JRA (p<0.05). Another variant, a 32-bp deletion in the open reading frame of CCR5, (CCR5-Δ32), was also tested in ~700 simplex and multiplex families. CCR5-Δ32 was also significantly under-transmitted to probands with early-onset JRA (p<0.05). Both variants are in regions under natural selection, and result in functional consequences. Our results suggest these CCR5 variants are protective against early-onset JRA. PMID:16775617

  17. Chloroquine-induced bull's eye maculopathy in rheumatoid arthritis: related to disease duration?

    PubMed

    Shinjo, Samuel K; Maia, Otacílio O; Tizziani, Vivian A P; Morita, Celso; Kochen, Jussara A L; Takahashi, Walter Y; Laurindo, Ieda M M

    2007-08-01

    Chloroquine diphosphate has been used in the treatment of various rheumatic diseases, including rheumatoid arthritis. The most important of its side effects is retinopathy. If not diagnosed early, this lesion can evolve into irreversible bull's eye maculopathy and visual loss. The aim of this study was to define the outcome of chloroquine-induced maculopathy after cessation of chloroquine therapy and also to identify the risk factors involved in case of retinopathy evolution. The design of this cohort study was longitudinal and retrospective. Over the period spanning 2000 to 2005, out of 607 medical records of patients with rheumatoid arthritis followed in our Division of Rheumatology, 27 had been diagnosed with chloroquine-induced maculopathy through clinical funduscopy with pupil dilation. In all cases, there was immediate chloroquine intake cessation. After a mean time of 5 years, 16 of these patients were available for follow-up and underwent a new ophthalmologic evaluation by funduscopy, using biomicroscopy and angiofluorescein when necessary. Sequelae maculopathy were reconfirmed in all 16 cases, but progression to advanced stage (bull's eye maculopathy) was found in half of the cohort, even though chloroquine had been suspended. All patients complained of visual alterations, but without progression. Comparison between patient groups with and without bull's eye maculopathy revealed a statistically significant longer rheumatoid arthritis disease history in the former group. Also, the bull's eye group had higher dose intakes of chloroquine and over a longer period compared to the other group, but not statistically significant. This study corroborates the progression of maculopathy even after cessation of chloroquine intake, pointing out the need for careful screening in the high-risk patients. Furthermore, it indicates that duration of rheumatoid arthritis disease could be a possible factor linked to worse prognosis of chloroquine-induced maculopathy.

  18. Chorioretinitis as a complication of pauciarticular juvenile rheumatoid arthritis.

    PubMed

    Thacker, Neepa M; Demer, Joseph L

    2005-01-01

    A girl with pauciarticular juvenile rheumatoid arthritis developed bilateral uveitis complicated by cataract and glaucoma. Sequential fundus photography documented development of extensive choroidal scarring and retinal pigment epithelial atrophy in the left macula. Vision was not impaired. This case suggests uveitis in juvenile rheumatoid arthritis can be associated with chorioretinitis.

  19. Rheumatoid synovial cells from intact joints. Morphology, growth, and polykaryocytosis.

    PubMed

    Clarris, B J; Fraser, J R; Moran, C J; Muirden, K D

    1977-08-01

    Synovial cell lines were isolated by instillation of trypsin or chymotrypsin into intact knee joints of patients with persistent rheumatoid effusions resistant to conventional therapy. Morphology and growth in the primary phase were compared with rheumatoid cells isolated from excised synovium and nonrheumatoid synovial cells obtained from intact joints of cadavers or amputated limbs. Cell populations from all sources included varying proportions of macrophage-like and fibroblast-like cells, with only 1-3% multinucleated cells. In medium supplemented with calf serum alone, rheumatoid cells from intact joints showed negligible changes in morphology. However, in the presence of nonrheumatoid, autologous rheumatoid or homologous rheumatoid serum a rapid increase occurred in size of the macrophage-like cells and numbers of polykaryocytes, including some giant syncytial cells. These effects were directly proportional to serum concentration and were identical in fresh or heat-inactivated serum. In most of these rheumatoid cell lines no multiplication occurred, regardless of serum type or concentration. In rheumatoid synovial cells from excised synovium, human serum induced both polykaryocytosis and rapid growth of fibroblasts. Nonrheumatoid synovial cells grew rapidly but few polykaryocytes developed, mostly with less than 6 nuclei. Evidence of viral infection in rheumatoid synovial cells was sought by electron microscopy after stimulation of polykaryocytosis by human serum. In one of the cultures many cells were found with intranuclear particles possessing characteristics of the adenovirus group. PMID:901027

  20. Evaluating and mitigating fracture risk in established rheumatoid arthritis.

    PubMed

    Mullen, Matthew B; Saag, Kenneth G

    2015-01-01

    Patients with rheumatoid arthritis are predisposed to systemic bone loss, and they are at an increased risk of fractures. Although there are similarities in the patient demographics between rheumatoid arthritis patients and the general population of osteoporosis patients, there are factors, particularly the use of glucocorticoids, which are specific to rheumatoid arthritis. These factors can lead to an increased risk of bone loss and fracture. Given that fractures are often very debilitating, especially in elderly patients, it is of paramount importance for the practicing rheumatologist to be aware of ways to reduce the risk of fracture in patients with rheumatoid arthritis. This review discusses currently available modalities for fracture risk assessment as well as pharmacologic and lifestyle interventions available to treat and prevent bone loss in rheumatoid arthritis patients.

  1. Rheumatoid arthritis and tabetic arthropathy: physiopathological link or simple association?

    PubMed Central

    Aradoini, Nassira; Talbi, Sofia; Angala, Romaric; Es-Souiri, Jamila; Abourazzak, Fatima Ezzahra; Harzy, Taoufik

    2016-01-01

    To the best of our knowledge, the association of rheumatoid arthritis and tabetic arthropathy has never been described before in the literature. We report here a first observation. We report the case of a 50-year-old man, treated for syphilitic arthritis evolving for 4 years, who presented with a table of rheumatoid arthritis. The diagnosis of rheumatoid arthritis was established according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria (ACR/EULAR). The treatment was based on weekly injection of methotrexate and a symptomatic treatment by corticosteroid. The association of rheumatoid arthritis and tabetic arthropathy is rare, to our knowledge this is the first case reported. This case reminds us that a neuropathic arthropathy as tabetic arthropathy, although it is rare, can be associated in a sporadic or exceptional way with other rheumatic disease like rheumatoid arthritis. A physiopathological link between the both diseases remains to be proved.

  2. 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.

  3. In-office magnetic resonance imaging to monitor responses to therapy in rheumatoid arthritis.

    PubMed

    Gaylis, Norman B; Needell, Steven D

    2009-12-01

    Low-field extremity magnetic resonance imaging (MRI) has been developed as an alternative method for detecting inflammatory changes and structural damage associated with rheumatoid arthritis (RA). Studies have shown that extremity MRI is able to predict future joint damage in patients with early RA and is more sensitive than conventional radiography at detecting joint erosions. This report uses four different cases to illustrate how extremity MRI can be used to monitor disease activity and inform treatment decisions during the management of RA in the routine clinical practice setting. PMID:19387648

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

    PubMed Central

    Envalds, Minja; Pincus, Theodore

    2008-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. HIV/AIDS and rheumatoid arthritis.

    PubMed

    Cunha, Bernardo M; Mota, Licia Maria H; Pileggi, Gecilmara S; Safe, Izabella P; Lacerda, Marcus V G

    2015-05-01

    The acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). It was first recognized in the United States in 1981, and the HIV/AIDS epidemic has since spread to affect all countries. The interface of HIV/AIDS with opportunistic infectious diseases is well characterized, but further research is required into the concurrence of other chronic diseases. The objective of this review was to identify possible interferences of HIV infection in the diagnosis and management of rheumatoid arthritis (RA). A review of the available evidence was conducted using the GRADE approach. Overall, the quality of evidence was low. Our main conclusions were: (1) the occurrence of rheumatoid-like arthritis in patients with HIV/AIDS is quite rare; therefore, it is not recommended that HIV infection be considered routinely as a differential diagnosis in this condition (C2); (2) HIV infection may lead to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity, but usually at low titers (C1); (3) RA might cause false-positive HIV serology and ELISA seems to be a more specific test for HIV in patients with RA (C2); (4) RA and AIDS may coexist, even in cases of severe immunosuppression (C1); (5) RA emergence may seldom occur during or after immune reconstitution (C1); and (6) there is insufficient safety data to recommend use of specific disease-modifying antirheumatic drugs (DMARDs) in RA patients with HIV/AIDS. Therefore, these drugs should be used cautiously (C1).

  7. Antimalarial drugs for rheumatoid disease during pregnancy.

    PubMed Central

    Koren, G.

    1999-01-01

    QUESTION: One of my patients, who has rheumatoid arthritis, has just found out she is pregnant. She is being treated with hydroxychloroquine. I could not find anything about the safety of this drug during pregnancy. ANSWER: Most of the literature on this drug relates to prophylaxis for malaria. Much lower doses than those used for rheumatic diseases are given with no adverse fetal effects. Several studies on use of the drug for rheumatic diseases during pregnancy also failed to show adverse fetal effects, although, in most cases, only first-trimester exposure was reported. PMID:10626050

  8. [Interstitial lung disease in rheumatoid arthritis].

    PubMed

    Froidevaux-Janin, Sylvie; Dudler, Jean; Nicod, Laurent P; Lazor, Romain

    2011-11-23

    Interstitial lung disease (ILD) is found in up to 30% of patients with rheumatoid arthritis (RA) and is clinically manifest in 5 to 10%, resulting in significant morbidity and mortality. The most frequent histopathological forms are usual interstitial pneumonia and nonspecific interstitial pneumonia. Another recently described presentation is combined pulmonary fibrosis and emphysema. Similarly to idiopathic pulmonary fibrosis, acute exacerbation of ILD may occur in RA and is associated with severe prognosis. Smoking is a known risk factor of RA and may also play a role in the pathogenesis of RA-associated ILD, in combination with genetic and immunologic mechanisms. Several treatments of RA may also lead to drug-induced ILD.

  9. [Physiotherapy in rheumatoid arthritis and ankylosing spondylitis].

    PubMed

    Mariacher-Gehler, S; Wyss-Näther, A; Aeschlimann, A G

    2001-08-01

    Both Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) are chronic, inflammatory systemic diseases. RA predominantly manifests itself in the peripheral joints, whereas AS most prominently in the spine. As time progresses the roles of active and physical therapy become increasingly important. The aims of intensive and dynamic exercise for patients with RA and AS are formulated following the ICIDH-2. Thus, the aims are a direct equation of body function, activities and participation. The benefits of exercise therapy are increased joint mobility, increased muscle strength, improved functional ability and better cardiorespiratory function without incurring a flare of the disease.

  10. Hepatic hemorrhage in malignant rheumatoid arthritis.

    PubMed

    Mizuno, K; Ikeda, K; Saida, Y; Takenaka, R; Shibata, M; Takeuchi, T

    1996-12-01

    Intrahepatic hemorrhage is a serious and life-threatening complication in liver disease. We describe a patient who had two episodes of intrahepatic hemorrhage after having malignant rheumatoid arthritis for 8 yr. Abdominal CT scans revealed a large intrahepatic, subcapsular hematoma. Arteriography demonstrated irregularity, caliber change, and pseudoaneurysms of the right hepatic artery, suggesting vasculitis as a cause of the bleeding. The hemorrhage was first treated with transcatheter arterial embolization, which failed to exert long term control, but arterial infusion of a large dose of prednisolone when the hemorrhage appeared was successful in managing it.

  11. Risk factors for asymptomatic ventricular dysfunction in rheumatoid arthritis patients.

    PubMed

    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.

  12. 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

  13. 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.

  14. Rheumatoid Arthritis: The Stride from Research to Clinical Practice

    PubMed Central

    Chung, Ill-Min; Ketharnathan, Sarada; Thiruvengadam, Muthu; Rajakumar, Govindasamy

    2016-01-01

    Over 70 different genetic variants with a significant association with rheumatoid arthritis (RA) have been discovered. Anti-citrullination protein antibodies (ACPA)-positive RA variants are more well-defined than their ACPA-negative counterparts. The human leukocyte antigen, HLA-DRB1 locus remains the prime suspect in anti-citrullination protein antibodies (ACPA)—positive RA. Different HLA-DRB1 alleles are linked to RA susceptibility across different ethnicities. With evolving techniques, like genome-wide association studies (GWAS) and single nucleotide polymorphism (SNP) arrays, more non-HLA susceptibility loci have been identified for both types of RA. However, the functional significance of only a handful of these variants is known. Their roles include increasing susceptibility to RA or in determining the speed at which the disease progresses. Additionally, a couple of variations are associated with protection from RA. Defining such clear-cut biological functions can aid in the clinical diagnosis and treatment of RA. Recent research has focused on the implication of microRNAs, with miR-146a widely studied. In addition to disease susceptibility, genetic variations that influence the efficacy and toxicity of anti-RA agents have also been identified. Polymorphisms in the MTHFR gene influence the effectiveness of methotrexate, the first line of therapy in RA. Larger studies are, however, needed to identify potential biomarkers for early disease identification and monitoring disease progression. PMID:27338350

  15. 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

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

    PubMed

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

    2015-01-01

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

  17. [Clinical approach to a patient with rheumatoid arthritis].

    PubMed

    Perković, Dijana; Kaliterna, DuSanka Martinović; Krstulović, Daniela Marasović; Bozić, Ivona; Borić, Katarina; Radić, Mislav

    2014-01-01

    Rheumatoid arthritis (RA) is chronic inflammatory rheumatic disease which leads to joint damage, functional im- pairment and reduced quality of life. The disease should be recognized early when there is a "window of oppor- tunity" to apply adequate treatment which may prevent structural damage. As clinical presentation of RA is not always typical, great knowledge and clinical experience, including collaboration of rheumatologist, general practi- tioner and patient, are required. The treatment should be started immediately upon the diagnosis, while the choice of modality of treatment depends on the rheumatologist in accordance with the patient. The RA patients with the higher risk of aggressive disease need to be recognized because they require more aggressive treatment from the start. The goal of the treatment is remission or at least low disease activity. Current treatment of RA includes disease modifying antirheumatic drugs (DMARDs) synthetics and biologics, nonsteroidal antirheumatic drugs (NSAIDs), glucocorticoids, analgesics, and rarely cytostatics. The course of disease is usually fluctuating with the exchange of relapses and remissions. Recognition of the relapsing patient on time enables treatment intensification or modifications in treatment scheme. Special issue in RA represents glucocorticoid-induced osteoporosis (GIO) which should be prevented by usage of calcium and vitamin D supplements and treated by antiresorptive or osteoanabolic agents. Besides the treatment of the primary disease, the care of RA patients should consider comorbidities, side effects of treatment, complications of disease, and psychosocial aspects of chronic disease. PMID:25427391

  18. [Clinical approach to a patient with rheumatoid arthritis].

    PubMed

    Perković, Dijana; Kaliterna, DuSanka Martinović; Krstulović, Daniela Marasović; Bozić, Ivona; Borić, Katarina; Radić, Mislav

    2014-01-01

    Rheumatoid arthritis (RA) is chronic inflammatory rheumatic disease which leads to joint damage, functional im- pairment and reduced quality of life. The disease should be recognized early when there is a "window of oppor- tunity" to apply adequate treatment which may prevent structural damage. As clinical presentation of RA is not always typical, great knowledge and clinical experience, including collaboration of rheumatologist, general practi- tioner and patient, are required. The treatment should be started immediately upon the diagnosis, while the choice of modality of treatment depends on the rheumatologist in accordance with the patient. The RA patients with the higher risk of aggressive disease need to be recognized because they require more aggressive treatment from the start. The goal of the treatment is remission or at least low disease activity. Current treatment of RA includes disease modifying antirheumatic drugs (DMARDs) synthetics and biologics, nonsteroidal antirheumatic drugs (NSAIDs), glucocorticoids, analgesics, and rarely cytostatics. The course of disease is usually fluctuating with the exchange of relapses and remissions. Recognition of the relapsing patient on time enables treatment intensification or modifications in treatment scheme. Special issue in RA represents glucocorticoid-induced osteoporosis (GIO) which should be prevented by usage of calcium and vitamin D supplements and treated by antiresorptive or osteoanabolic agents. Besides the treatment of the primary disease, the care of RA patients should consider comorbidities, side effects of treatment, complications of disease, and psychosocial aspects of chronic disease. PMID:25507641

  19. Optimal dose of etanercept in the treatment of rheumatoid arthritis

    PubMed Central

    Curtis, Elizabeth Mary; Marks, Jonathan Lewis

    2014-01-01

    Etanercept (ETN) is one of a number of biological therapies targeting the proinflammatory cytokine tumor necrosis factor-alpha that have demonstrated efficacy in the management of rheumatoid arthritis (RA). As experience has grown, a number of different treatment strategies have been investigated to ascertain the optimal conditions for use of ETN in RA and maximize the clinical gains from therapy. These have included the use of higher- and lower-dose treatment regimens, ETN as a monotherapy or in combination with other nonbiologic disease-modifying antirheumatic drugs, the use of ETN in very early clinical disease, and intraarticular ETN administration for resistant synovitis. Recent trials have focused on phased dose reduction or withdrawal of ETN in patients achieving low disease activity states or clinical remission. This review summarizes existing data regarding the optimal timing of ETN initiation and dosing regimens and also evaluates more recent evidence regarding dose-reduction strategies that offer the possibility of biologic-free remission in RA.

  20. Macrophage heterogeneity in the context of rheumatoid arthritis.

    PubMed

    Udalova, Irina A; Mantovani, Alberto; Feldmann, Marc

    2016-08-01

    Macrophages are very important in the pathogenesis of rheumatoid arthritis (RA). The increase in the number of sublining macrophages in the synovium is an early hallmark of active rheumatic disease, and high numbers of macrophages are a prominent feature of inflammatory lesions. The degree of synovial macrophage infiltration correlates with the degree of joint erosion, and depletion of these macrophages from inflamed tissue has a profound therapeutic benefit. Research has now uncovered an unexpectedly high level of heterogeneity in macrophage origin and function, and has emphasized the role of environmental factors in their functional specialization. Although the heterogeneous populations of macrophages in RA have not been fully characterized, preliminary results in mouse models of arthritis have contributed to our understanding of the phenotype and ontogeny of synovial macrophages, and to deciphering the properties of monocyte-derived infiltrating and tissue-resident macrophages. Elucidating the molecular mechanisms that drive polarization of macrophages towards proinflammatory or anti-inflammatory phenotypes could lead to identification of signalling pathways that inform future therapeutic strategies. PMID:27383913

  1. IL-17 contributes to angiogenesis in rheumatoid arthritis.

    PubMed

    Pickens, Sarah R; Volin, Michael V; Mandelin, Arthur M; Kolls, Jay K; Pope, Richard M; Shahrara, Shiva

    2010-03-15

    Angiogenesis is an early and a critical event in the pathogenesis of rheumatoid arthritis (RA). Neovascularization is dependent on endothelial cell activation, migration and proliferation, and inhibition of angiogenesis may provide a novel therapeutic approach in RA. In this study, we document a novel role of IL-17 in mediating angiogenesis. Local expression of IL-17 in mouse ankles increases vascularity. We further demonstrate that IL-17 is angiogenic by showing its ability to promote blood vessel growth in Matrigel plugs in vivo. Additionally, IL-17, in concentrations present in the RA joint, induces human lung microvascular endothelial cell (HMVEC) migration mediated through the PI3K/AKT1 pathway. Furthermore, suppression of the PI3K pathway markedly reduces IL-17-induced tube formation. We also show that both IL-17-induced HMVEC chemotaxis and tube formation are mediated primarily through IL-17 receptor C. Neutralization of either IL-17 in RA synovial fluids or IL-17 receptor C on HMVECs significantly reduces the induction of HMVEC migration by RA synovial fluid. Finally, RA synovial fluid immunoneutralized with anti-IL-17 and antivascular endothelial growth factor does not reduce HMVEC migration beyond the effect detected by immunodepleting each factor alone. These observations identify a novel function for IL-17 as an angiogenic mediator in RA, supporting IL-17 as a therapeutic target in RA.

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

    PubMed

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

    2013-10-01

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

  3. [Optimal Treatment for Rheumatoid Arthritis with Companion Diagnostics].

    PubMed

    Kumagai, Shunichi

    2015-11-01

    The medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introduction of biologics in addition to methotrexate, an anchor drug, has made it possible to not only suppress pain and inflammation (clinical remission), but also inhibit joint destruction (structural remission), leading to cure from the disease. Since the condition and pathology are heterogeneous among individual patients, optimal treatment for each patient based on the use of companion diagnostics is desired (precision medicine). ACPA is important to diagnose RA, but also to assess the prognosis. ACPA is also a part of companion diagnostics for preclinical RA because it has been found to be positive before the onset. Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics, have been reported as companion diagnostics for optimal treatment of RA. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of ACPA, and then secondary stimuli to joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. It is possible to cure RA, achieving complete remission, by early aggressive treatment and returning to the pre-clinical state with environmental improvement. [Review

  4. 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

  5. Tendon Transfers in the Rheumatoid Hand for Reconstruction.

    PubMed

    O'Sullivan, Michael Brody; Singh, Hardeep; Wolf, Jennifer Moriatis

    2016-08-01

    Long-standing rheumatoid arthritis can result in spontaneous tendon rupture caused by attrition of the tendons. Ruptures of the ulnar-sided extensor tendons, flexor pollicis longus, and the flexor digitorum profundus can be seen. Primary repair of these tendon ruptures is frequently not possible because of delayed presentation and tendon damage by the disease process. Tendon transfers are the preferred method of treatment in patients with rheumatoid arthritis. At surgery, it is critical to address the underlying cause of rupture to prevent future tendon ruptures. Rates of tendon rupture may decrease due to improved medications for rheumatoid arthritis. PMID:27387084

  6. [Intrathoracic lymphadenopathy: an unusual manifestation of rheumatoid arthritis].

    PubMed

    Khammassi, N; Bayouth, A; Abdelhedi, H; Balhouane, I; Hergli, I; Cherif, O

    2012-02-01

    Lung disease is the most frequent extra-articular manifestation of rheumatoid arthritis. It is detected in nearly 50% of patients with this multisystem affection, his knowledge has benefited from advances in computed tomography (CT). The inflammation can affect the pleura, the airways and the lung parenchyma. Intrathoracic lymphadenopathy complicating rheumatoid lung are not usual, and then pose the problem of differential diagnosis. We report a 51-year-old man, with a history of tobacco intoxication, suffering from rheumatoid arthritis who developed an interstitial lung disease at stage of fibrosis with mediastinal and hilar adenopathy. We will discuss the clinical, paraclinical, evolutionary and therapeutic particularities case.

  7. Contribution of rheumatoid arthritis disease activity and disability to rheumatoid cachexia.

    PubMed

    Fukuda, Wataru; Omoto, Atsushi; Oku, Saori; Tanaka, Toru; Tsubouchi, Yasunori; Kohno, Masataka; Kawahito, Yutaka

    2010-10-01

    This cross-sectional study was done to show how nutritional indices influence each other and the contributions made by inflammation to the development of rheumatoid cachexia. We studied 295 female patients with rheumatoid arthritis (RA). We chose five nutritional indices: body mass index (BMI), arm muscle area (AMA), triceps skinfold thickness (TSF), which were obtained via anthropometric measurements, and serum albumin and cholesterol. Clinical indicators of RA included disease duration, C-reactive protein (CRP) and Disease Activity Score 28 (DAS28). We performed a bivariate correlation test between the nutritional indices and multiple regression analysis for each nutritional index. Mean AMA was low, 87.3% of the normal value, whereas TSF was not different. Muscle protein expressed by AMA decreased according to RA duration, whereas visceral protein indicated by serum albumin decreased with an increase in RA activity. The continuation of inflammation appears to be essential for a decrease in muscle protein in rheumatoid cachexia. DAS28 showed a positive contribution to BMI in the regression model, and the increase in RA disease activity causes an increase in BMI via an accumulation of tissue fat. PMID:20508962

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

    MedlinePlus

    ... increased risk for osteoporosis, are two to three times more likely than men to have rheumatoid arthritis as well. Osteoporosis Management Strategies Strategies for preventing and treating osteoporosis in ...

  9. Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course.

    PubMed

    Llamas-Covarrubias, Mara Anaís; Valle, Yeminia; Navarro-Hernández, Rosa Elena; Guzmán-Guzmán, Iris Paola; Ramírez-Dueñas, María Guadalupe; Rangel-Villalobos, Héctor; Estrada-Chávez, Ciro; Muñoz-Valle, José Francisco

    2012-08-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology. Many cytokines have been found to be associated with RA pathogenesis and among them is macrophage migration inhibitory factor (MIF). The aim of this study was to determine whether MIF serum levels are associated with RA course, clinical activity, and clinical biomarkers of the disease. MIF levels were determined in serum samples of 54 RA patients and 78 healthy subjects (HS) by enzyme-linked immunosorbent assay (ELISA). Disease activity was evaluated using the DAS28 score. Patients were subgrouped according to disease activity and years of evolution of disease. Statistical analysis was carried out by SPSS 10.0 and GraphPad Prism 5 software. RA patients presented increased levels of MIF as compared to HS. MIF levels were raised on early stages of RA and tend to decrease according to years of evolution. Moreover, MIF levels positively correlated with rheumatoid factor in RA patients and with C reactive protein in all individuals studied. Our findings suggest that MIF plays a role in early stages of RA.

  10. [Strategies for improved healthcare of people with the endemic disease rheumatism exemplified by rheumatoid arthritis].

    PubMed

    Kalden, J R; Burkhardt, H; Buss, B; Donhauser-Gruber, U; Erstling, U; Gromnica-Ihle, E; Karberg, K; Karger, T; Kneitz, C H; Krause, A; Krüger, K; Lorenz, H-M; Müller-Ladner, U; Rubbert-Roth, A; Steffens-Korbanka, P; Tony, H-P; Wendler, J; Wollenhaupt, J; Burmester, G

    2011-10-01

    New therapeutic principles and considerable diagnostic advances have made it possible to define different rheumatic diseases and especially rheumatoid arthritis (RA) at an early stage and by starting an early and aggressive medication a considerable proportion of patients with RA will reach the status of low disease activity or even remission. With the additional development of composite measures to estimate the disease activity of RA, it was the goal of an international working group consisting of rheumatologists and patients to develop recommendations for treating rheumatoid arthritis in a similar way as for patients with hypertension or diabetes, with the aim to achieve remission as often as possible. This treat-to-target initiative has taken off in quite a number of different countries including Germany leading to discussions on how this initiative can be integrated into the specific national healthcare systems and what possibilities would exist for its implementation. To develop strategies for an improved healthcare of people suffering from rheumatic diseases and using RA as an example, action elements and postulates were developed which will be discussed in more detail in the present manuscript. PMID:21979315

  11. Pain in rheumatoid arthritis: a critical review.

    PubMed

    Sarzi-Puttini, P; Salaffi, F; Di Franco, M; Bazzichi, L; Cassisi, G; Casale, R; Cazzola, M; Stisi, S; Battellino, M; Atzeni, F

    2014-06-06

    Patients with rheumatoid arthritis (RA) are frequently afflicted by pain, which may be caused by joint inflammation (leading to structural joint damage) or secondary osteoarthritis, and may be increased by central sensitisation. Non-inflammatory pain may also confuse the assessment of disease activity, and so the aim of treatment is not only to combat inflammatory disease, but also relieve painful symptoms. In order to ensure effective treatment stratification, it is necessary to record a patients medical history in detail, perform a physical examination, and objectively assess synovitis and joint damage. The management of pain requires various approaches that include pharmacological analgesia and biological and non-biological treatments. Although joint replacement surgery can significantly improve RA-related pain, it may only be available to patients with the most severe advanced disease.

  12. 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)

  13. Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis

    PubMed Central

    Rego-Pérez, Ignacio; Fernández-Moreno, Mercedes; Blanco, Francisco J

    2008-01-01

    Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient’s genetic profile. PMID:19506728

  14. Rheumatoid arthritis susceptibility genes: An overview

    PubMed Central

    Korczowska, Izabela

    2014-01-01

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

  15. Hypoxia and its implications in rheumatoid arthritis.

    PubMed

    Quiñonez-Flores, Celia María; González-Chávez, Susana Aideé; Pacheco-Tena, César

    2016-08-22

    Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as hypoxia, is a relevant feature in RA since it is involved in angiogenesis, inflammation, apoptosis, cartilage degradation, energy metabolism, and oxidative damage. Therefore, alterations in hypoxia-related signaling pathways are considered potential mechanisms of disease pathogenesis. The objective of this review is to highlight and update our current knowledge of the role of hypoxia in the pathogenesis of RA. We describe the experimental evidence that RA synovial tissue exists in a hypoxic state, as well as the origin and involvement of synovial hypoxia in different aspects of the pathogenic process.

  16. 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

  17. [Genetic risk factors for rheumatoid arthritis].

    PubMed

    Ikari, Katsunori

    2016-06-01

    Rheumatoid arthritis (RA), the most common autoimmune diseases, is a systemic, chronic inflammatory disease, which is primarily involves the joints affecting up to 1% of the population. RA is believed to be a complex, multifarious disease that is influenced by both genetic and environmental factors. Disease susceptibility has been estimated to have a genetic component of 60% by data from twin studies. To date, more than 100 RA susceptibility loci, including HLA-DRB1, have been identified by genome-wide association studies (GWAS) and GWAS meta-analyses. Through a big data approach using large amounts of comprehensive biologic data included GWAS, we identified important information, such as susceptible genes, pathways and cell types that contribute to RA pathogenesis. PMID:27311175

  18. Hypoxia and its implications in rheumatoid arthritis.

    PubMed

    Quiñonez-Flores, Celia María; González-Chávez, Susana Aideé; Pacheco-Tena, César

    2016-01-01

    Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as hypoxia, is a relevant feature in RA since it is involved in angiogenesis, inflammation, apoptosis, cartilage degradation, energy metabolism, and oxidative damage. Therefore, alterations in hypoxia-related signaling pathways are considered potential mechanisms of disease pathogenesis. The objective of this review is to highlight and update our current knowledge of the role of hypoxia in the pathogenesis of RA. We describe the experimental evidence that RA synovial tissue exists in a hypoxic state, as well as the origin and involvement of synovial hypoxia in different aspects of the pathogenic process. PMID:27549205

  19. 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

  20. 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.

  1. Cardiovascular risk score in Rheumatoid Arthritis

    PubMed Central

    Wagan, Abrar Ahmed; Mahmud, Tafazzul E Haque; Rasheed, Aflak; Zafar, Zafar Ali; Rehman, Ata ur; Ali, Amjad

    2016-01-01

    Objective: To determine the 10-year Cardiovascular risk score with QRISK-2 and Framingham risk calculators in Rheumatoid Arthritis and Non Rheumatoid Arthritis subjects and asses the usefulness of QRISK-2 and Framingham calculators in both groups. Methods: During the study 106 RA and 106 Non RA patients age and sex matched participants were enrolled from outpatient department. Demographic data and questions regarding other study parameters were noted. After 14 hours of fasting 5 ml of venous blood was drawn for Cholesterol and HDL levels, laboratory tests were performed on COBAS c III (ROCHE). QRISK-2 and Framingham risk calculators were used to get individual 10-year CVD risk score. Results: In this study the mean age of RA group was (45.1±9.5) for Non RA group (43.7±8.2), with female gender as common. The mean predicted 10-year score with QRISK-2 calculator in RA group (14.2±17.1%) and Non RA group was (13.2±19.0%) with (p-value 0.122). The 10-year score with Framingham risk score in RA group was (12.9±10.4%) and Non RA group was (8.9±8.7%) with (p-value 0.001). In RA group QRISK-2 (24.5%) and FRS (31.1%) cases with predicted score were in higher risk category. The maximum agreement scores between both calculators was observed in both groups (Kappa = 0.618 RA Group; Kappa = 0.671 Non RA Group). Conclusion: QRISK-2 calculator is more appropriate as it takes RA, ethnicity, CKD, and Atrial fibrillation as factors in risk assessment score. PMID:27375684

  2. 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. PMID:27182251

  3. 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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2013-03-27

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

  6. 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 ...

  7. 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 ...

  8. 78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Rheumatoid Arthritis... guidance for industry entitled ``Rheumatoid Arthritis: Developing Drug Products for Treatment.''...

  9. Postoperative Surgical Infection After Spinal Surgery in Rheumatoid Arthritis.

    PubMed

    Koyama, Kensuke; Ohba, Tetsuro; Ebata, Shigeto; Haro, Hirotaka

    2016-05-01

    Individuals with rheumatoid arthritis are at higher risk for infection than the general population, and surgical site infection after spinal surgery in this population can result in clinically significant complications. The goal of this study was to identify risk factors for acute surgical site infection after spinal surgery in patients with rheumatoid arthritis who were treated with nonbiologic (conventional) disease-modifying antirheumatic drugs (DMARDs) alone or with biologic DMARDs. All patients treated with biologic agents were treated with nonbiologic agents as well. The authors performed a retrospective, single-center review of 47 consecutive patients with rheumatoid arthritis who underwent spinal surgery and had follow-up of 3 months or longer. The incidence of surgical site infection was examined, and multivariate logistic regression analysis was performed to test the association of surgical site infection with putative risk factors, including the use of biologic agents, methotrexate, and prednisolone, as well as the duration of rheumatoid arthritis, the presence of diabetes, patient age, length of surgery, and number of operative levels. After spinal surgery, 14.89% (7 of 47) of patients had surgical site infection. Use of methotrexate and/or prednisolone, patient age, diabetes, duration of rheumatoid arthritis, length of surgery, number of operative levels, and use of biologic DMARDs did not significantly increase the risk of infection associated with spinal surgery. All patients who had surgical site infection had undergone spinal surgery with instrumentation. The findings show that greater attention to preventing surgical site infection may be needed in patients with rheumatoid arthritis who undergo spinal surgery with instrumentation. To the authors' knowledge, this is the first study to show that the use of biologic agents did not increase the incidence of surgical site infection after spinal surgery in patients with rheumatoid arthritis

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

    NASA Technical Reports Server (NTRS)

    Estep, Leland; Spruce, Joseph P.

    2007-01-01

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

  11. Leflunomide: mode of action in the treatment of rheumatoid arthritis

    PubMed Central

    Breedveld, F; Dayer, J

    2000-01-01

    Leflunomide is a selective inhibitor of de novo pyrimidine synthesis. In phase II and III clinical trials of active rheumatoid arthritis, leflunomide was shown to improve primary and secondary outcome measures with a satisfactory safety profile. The active metabolite of leflunomide, A77 1726, at low, therapeutically applicable doses, reversibly inhibits dihydroorotate dehydrogenase (DHODH), the rate limiting step in the de novo synthesis of pyrimidines. Unlike other cells, activated lymphocytes expand their pyrimidine pool by approximately eightfold during proliferation; purine pools are increased only twofold. To meet this demand, lymphocytes must use both salvage and de novo synthesis pathways. Thus the inhibition of DHODH by A77 1726 prevents lymphocytes from accumulating sufficient pyrimidines to support DNA synthesis. At higher doses, A77 1726 inhibits tyrosine kinases responsible for early T cell and B cell signalling in the G0/G1 phase of the cell cycle. Because the immunoregulatory effects of A77 1726 occur at doses that inhibit DHODH but not tyrosine kinases, the interruption of de novo pyrimidine synthesis may be the primary mode of action. Recent evidence suggests that the observed anti-inflammatory effects of A77 1726 may relate to its ability to suppress interleukin 1 and tumour necrosis factor α selectively over their inhibitors in T lymphocyte/monocyte contact activation. A77 1726 has also been shown to suppress the activation of nuclear factor κB, a potent mediator of inflammation when stimulated by inflammatory agents. Continuing research indicates that A77 1726 may downregulate the glycosylation of adhesion molecules, effectively reducing cell-cell contact activation during inflammation.

 PMID:11053058

  12. Epidemiology and burden of illness of rheumatoid arthritis.

    PubMed

    Kvien, Tore K

    2004-01-01

    Rheumatoid arthritis (RA) is a chronic, generally progressive autoimmune disease that causes functional disability, significant pain and joint destruction, and leads to premature mortality. It is estimated to affect between 0.5 and 1.0% of the adult population worldwide, increases in prevalence with age and affects more women than men. The magnitude of the severe long-term economic consequences of RA has been underestimated in the past. Most patients with the disease require continuous treatment to retard or stop progression and to control disease flares. Many also require surgery, such as total hip or knee replacement. In addition to these direct costs, work disability leads to reduced productivity and early retirement, and as a result, substantial indirect costs. The individual and his or her family must cope with the feeling of loss of contribution to society combined with redefined social roles, and the effects of pain, fatigue, low self-esteem, mental distress and depression. A number of countries in North America and Europe have reported a decline in the incidence of RA in recent years, although geographical differences remain that may be associated with genetic, environmental or cultural factors. Nevertheless, patients with RA have not shared the improvements in survival rates seen with other diseases over the last 40 years, and have a mean reduction in life expectancy of between 5 and 10 years. Disease severity, activity and disability are strongly linked to premature mortality in patients with RA. The high direct and indirect costs associated with RA, together with the substantial morbidity and mortality affecting millions of people worldwide, underline the potential benefits of improved treatments for this chronic disease to patients, their families and society. PMID:15157000

  13. 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

  14. Sleep Loss Exacerbates Fatigue, Depression, and Pain in Rheumatoid Arthritis

    PubMed Central

    Irwin, Michael R.; Olmstead, Richard; Carrillo, Carmen; Sadeghi, Nina; FitzGerald, John D.; Ranganath, Veena K.; Nicassio, Perry M.

    2012-01-01

    Study Objectives: Disturbances of sleep are hypothesized to contribute to pain. However, experimental data are limited to healthy pain-free individuals. This study evaluated the effect of sleep loss during part of the night on daytime mood symptoms and pain perceptions in patients with rheumatoid arthritis in comparison with control subjects. Design: A between-groups laboratory study with assessment of mood symptoms and pain perception before and after partial night sleep deprivation (PSD; awake 23:00 hr to 03:00 hr). Setting: General clinical research center. Participants: Patients with rheumatoid arthritis (n = 27) and volunteer comparison control subjects (n = 27). Measurements: Subjective reports of sleep, mood symptoms and pain, polysomnographic assessment of sleep continuity, and subjective and objective assessment of rheumatoid arthritis-specific joint pain. Results: PSD induced differential increases in self-reported fatigue (P < 0.09), depression (P < 0.04), anxiety (P < 0.04), and pain (P < 0.01) in patients with rheumatoid arthritis compared with responses in control subjects, in whom differential increases of self-reported pain were independent of changes in mood symptoms, subjective sleep quality, and objective measures of sleep fragmentation. In the patients with rheumatoid arthritis, PSD also induced increases in disease-specific activity as indexed by self-reported pain severity (P < 0.01) and number of painful joints (P < 0.02) as well as clinician-rated joint counts (P < 0.03). Conclusion: This study provides the first evidence of an exaggerated increase in symptoms of mood and pain in patients with rheumatoid arthritis after sleep loss, along with an activation of rheumatoid arthritis-related joint pain. Given the reciprocal relationship between sleep disturbances and pain, clinical management of pain in patients with rheumatoid arthritis should include an increased focus on the prevention and treatment of sleep disturbance in this clinical

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

    PubMed

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

    2014-01-01

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

  16. 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.

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

    PubMed

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

    2015-07-01

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

  18. Circadian rhythm of C-reactive protein in patients with rheumatoid arthritis.

    PubMed

    Herold, M; Günther, R

    1987-01-01

    Ten men with classic rheumatoid arthritis were studied for 23 days in Badgastein, Austria, in August, 1980. One man (patient 07) showed a marked increase of disease activity after a few days. C-reactive protein (CRP) concentrations increased from 8.7 mg/dl on day 2 to 13.0 mg/dl on day 16. CRP values expressed as percent mean of a day showed a significant circadian rhythm with the acrophase at -30 degrees. For the same patient we also found significant circadian rhythms in grip strength and pearl stringing with acrophases in the evening and a circadian rhythm in walking time with the acrophase in the early morning. Seven of the ten men in the study had elevated CRP concentrations during the 3 weeks of observation. Population-mean cosinor results of CRP, grip strength, pearl stringing, and walking time revealed acrophases similar to the single cosinor results of patient 07. Our results suggest that inflammation in rheumatoid arthritis is a circadian rhythmic process with lowest disease activity in the evening.

  19. Rheumatoid symptoms following breast cancer treatment: a controlled comparison.

    PubMed

    Andrykowski, M A; Curran, S L; Carpenter, J S; Studts, J L; Cunningham, L; McGrath, P C; Sloan, D A; Kenady, D E

    1999-08-01

    The prevalence of rheumatoid symptoms following breast cancer (BC) treatment was examined. Breast cancer patients (n = 111) who were a mean of 27.6 months postcompletion of BC treatment and 99 otherwise healthy women with benign breast problems (BBP) completed a self-report measure that assessed current joint pain, swelling, and stiffness, as well as measures of quality of life. Results supported a hypothesized link between BC and rheumatoid symptoms: (1) the BC group was more likely to report joint stiffness lasting more than 60 min following morning waking; (2) the prevalence of unilateral or bilateral joint point or swelling was greater (P < 0.10) in the BC group for four of 10 joint-symptom combinations examined, with differences between the BC and BBP groups in upper extremity joint swelling particularly pronounced; and (3) 41% of the BC group reported that current rheumatoid symptoms exceeded those experienced prior to diagnosis. Within the BC group, the data did not support postchemotherapy rheumatism as an explanation for rheumatoid symptoms. Rather, data suggested that symptoms were associated with surgical management of BC. Finally, among women in the BC group with the most severe joint pain, only a minority were receiving medication for these symptoms. Given the relationship between rheumatoid symptoms and quality of life, more systematic research examining potential contributing factors such as menopausal status, concurrent lymphedema, and weight gain is warranted.

  20. 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.

  1. Neurophysiology study of early visual processing of face and non-face recognition under simulated prosthetic vision.

    PubMed

    Yang, Yuan; Guo, Hong; Tong, Shanbao; Zhu, Yisheng; Qiu, Yihong

    2009-01-01

    Behavioral researches have shown that the visual function can be partly restored by phosphene-based prosthetic vision for the non-congenital blinds. However, the early visual processing mechanisms of phosphene object recognition is still unclear. This paper aimed to investigate the electro-neurophysiology underlying the phosphene face and non-face recognition. The modulations of latency and amplitude of N170 component in the event-related potential (ERP) were analyzed. Our preliminary results showed that (1) both normal and phosphene face stimuli could elicit prominent N170; nevertheless, phosphene stimuli caused notable latency delay and amplitude suppression on N170 compared with normal stimuli and (2) under phosphene non-face stimuli, a slight but significant latency delay occurred compared with normal stimuli, while amplitude suppression was not observed. Therefore, it was suggested that (1) phosphene perception caused a disruption of the early visual processing for non-canonical images of objects, which was more profound in phosphene face processing; (2) the face-specific processing was reserved under prosthetic vision and (3) holistic processing was the major stage in early visual processing of phosphene face recognition, while part-based processing was attenuated due to the loss of the details.

  2. Historical observations contributing insights on etiopathogenesis of rheumatoid arthritis and role of rheumatoid factor.

    PubMed

    Tan, Eng M; Smolen, Josef S

    2016-09-19

    When studies on rheumatoid arthritis (RA) that were made many decades ago and could be considered "historical" in nature are analyzed in the context of recent observations, important insights on RA and on the function of rheumatoid factor (RF) become apparent. RF in the role of antibody to immune complexes (ICs) appears to be involved in activation of the complement system and in the production of chemotactic and inflammatory mediators, creating a condition that can be sustained and reinitiated. In the synovial cavity, a state of nonresolving inflammation is produced with the formation of citrullinated protein antigen-antibody complexes or other forms of ICs. This is followed by a second wave of IC production in the form of RF acting as antibody reactive with the initial ICs. Both of these processes are associated with complement consumption and production of inflammatory mediators. We present a model of an initiation phase of RA that might represent an example of repetitive formation of ICs and complement-mediated inflammation. Targeting therapy at this phase of RA to break the cycles of recurrent inflammation might be a novel approach to aid in further control of the disease. PMID:27621417

  3. Salicylate pharmacokinetics in patients with rheumatoid arthritis.

    PubMed Central

    Owen, S G; Roberts, M S; Friesen, W T; Francis, H W

    1989-01-01

    1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations. PMID:2590603

  4. TNF inhibitor therapy for rheumatoid arthritis

    PubMed Central

    MA, XIXI; XU, SHENGQIAN

    2013-01-01

    Immunotherapy has markedly improved treatment outcomes in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-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

  5. Sarcopenia in women with rheumatoid arthritis

    PubMed Central

    Doğan, Sevil Ceyhan; Hizmetli, Sami; Hayta, Emrullah; Kaptanoğlu, Ece; Erselcan, Taner; Güler, Emel

    2015-01-01

    Objective To assess sarcopenia status in women with rheumatoid arthritis (RA). Material and Methods Thirty female patients with RA and 30 female controls without RA were enrolled in this study. Sarcopenia status in patients with RA was evaluated by assessing body composition using dual X-ray absorptiometry (DXA). C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were measured, and body mass index (BMI) and Disease Activity Score (DAS28) were calculated. Because sarcopenia differs between men and women, the study groups comprised only females. Results It was found that skeletal muscle index (SMI) was lower in patients with RA (5.83±0.807) than in controls (7.30±1.640). Sarcopenia (in females with an SMI of ≤5.75 kg/m2) was more common in the RA group and the difference was statistically significant (p=0.004). Sarcopenia was more common in patients with RA who were normal or overweight than in those who were obese according to their BMI. There was no relationship between sarcopenia and DAS28 in the RA group (p=0.530), whereas CRP levels were significantly higher in patients with sarcopenia (p=0.230). No relationship was found between drug use and sarcopenia in the RA group. Conclusion It was found that SMI was decreased and sarcopenia risk was elevated in patients with RA and the risk was higher in non-obese patients. PMID:27708927

  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. [GWAS of Rheumatoid Arthritis and Drug Discovery].

    PubMed

    Ohmura, Koichiro

    2015-04-01

    We have conducted genome-wide association studies (GWAS) for rheumatoid arthritis (RA). We previously found that myelin basic protein (MBP) is associated with RA. One of the MBP isoforms (Golli-MBP) is expressed not only in nerve cells, but also in hematopoietic cells, and may negatively regulate T-cell receptor signaling. We expanded the GWAS level by collaborating with laboratories in Japan and then throughout the world. Meta-analysis of GWAS data resulted in the identification of -100 genomic loci associated with RA development. The -100 genomic loci contain -400 candidate genes, and it is not easy to find out which genes actually play important roles in RA. By incorporating available public databases, we succeeded in narrowing down the susceptibility genes from 377 to 98. We also showed that regulatory T cells are associated with RA based on the combination of the histone methylation database and our mega-GWAS results. Protein-protein interaction and drug discovery databases gave us information that some of the drugs have already been developed as therapeutic medicines for RA, and some of them were used for diseases other than RA. These drugs may be used for RA in the near future (drug repurposing). The combination of biological databases and GWAS results may be a novel method to identify new therapeutic targets.

  8. Epidemiology of Rheumatoid Arthritis in Southern Albania

    PubMed Central

    Koko, Vjollca; Ndrepepa, Ana; Skenderaj, Skender

    2015-01-01

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

  9. 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

  10. Interstitial lung disease in rheumatoid arthritis.

    PubMed

    Ascherman, Dana P

    2010-10-01

    Rheumatoid arthritis (RA) is the most common systemic autoimmune disease in the United States, affecting 1% to 2% of the adult population. Although joints and synovium are the primary targets in this disorder, extra-articular manifestations involving the lungs can lead to significant morbidity and excess mortality. Among the various pulmonary complications that occur in RA, interstitial lung disease (ILD) is the most damaging, with effects ranging from subclinical inflammation/scarring to end-stage pulmonary fibrosis. New insights during the past several years have underscored the epidemiologic impact of clinically/functionally significant RA-associated ILD (RA-ILD) and have begun to identify factors contributing to the pathogenesis of this potentially devastating complication of RA. Despite these advancements, the complexity of RA-ILD and the lack of reliable predictors for disease progression highlight the need for improved biomarker development. Establishing such detailed molecular signatures will ultimately guide the application and timing of therapeutic agents that include immunomodulators as well as newly studied antifibrotic agents.

  11. 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.

  12. [Colonic microbial biocenosis in rheumatoid arthritis].

    PubMed

    Gul'neva, M Iu; Noskov, S M

    2011-01-01

    The aim of the work was to study colonic microbial biocenosis and colonizing ability of opportunistic bacteria in 32 patients with rheumatoid arthritis (RA) and 30 healthy subjects. RA was diagnosed based on the American Rheumatism Association criteria (1987). Qualitative and quantitative composition of the microflora was detected by a bacteriological method. StatSoft Statistics 6.0 was used to treat the data obtained. RA was associated with significant modification of the intestinal flora, viz. decrease in lactobacteria and significant increase of enterococci, clostridia, colibacteria showing reduced enzymatic activity, and opportunistic species. Also, symbiotic relationships between microorganisms altered. The fraction of bifidobacteria, bacteroids, and lactopositive colibacteria reduced while the abundance of opportunistic enterobacteria and staphylococci was elevated. Opportunistic Enterobacteriaceae were present in urine and nasal mucosa which suggested their translocation from the intestines. It is concluded that changes in intestinal microflora and colonization by opportunistic bacteria enhance the risk of development of co-morbid conditions in patients with RA. PMID:21932563

  13. Mesenchymal stem cells, autoimmunity and rheumatoid arthritis

    PubMed Central

    El-Jawhari, J.J.; El-Sherbiny, Y.M.; Jones, E.A.

    2014-01-01

    The vast majority of literature pertaining to mesenchymal stem cells (MSC) immunomodulation has focussed on bone marrow-derived MSC that are systemically infused to alleviate inflammatory conditions. Rheumatoid arthritis (RA) is the commonest autoimmune joint disease that has witnessed significant therapeutic advances in the past decade, but remains stubbornly difficult to treat in a subset of cases. Pre-clinical research has demonstrated that bone marrow, adipose, synovial and umbilical cord-derived MSC all suppress the functions of different immune cells thus raising the possibility of new therapies for autoimmune diseases including RA. Indeed, preliminary evidence for MSC efficacy has been reported in some cases of RA and systemic lupus erythromatosis. The potential use of bone marrow-MSC (BM-MSC) for RA therapy is emerging but the use of synovial MSC (S-MSC) to suppress the exaggerated immune response within the inflamed joints remains rudimentary. Synovial fibroblasts that are likely derived from S-MSCs, also give rise to a cell-cultured progeny termed fibroblast-like synoviocytes (FLS), which are key players in the perpetuation of joint inflammation and destruction. A better understanding of the link between these cells and their biology could be a key to developing novel MSC-based strategies for therapy. The review briefly focuses on BM-MSC and gives particular attention to joint niche synovial MSC and FLS with respect to immunoregulatory potential therapy roles. PMID:24518000

  14. Rheumatoid arthritis-associated interstitial lung disease

    PubMed Central

    Solomon, Joshua J; Brown, Kevin K

    2012-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting 1% of the US population. Patients can have extra-articular manifestations of their disease and the lungs are commonly involved. RA can affect any compartment of the respiratory system and high resolution computed tomography (HRCT) of the lung is abnormal in over half of these patients. Interstitial lung disease is a dreaded complication of RA. It is more prevalent in smokers, males, and those with high antibody titers. The pathogenesis is unknown but data suggest an environmental insult in the setting of a genetic predisposition. Smoking may play a role in the pathogenesis of disease through citrullination of protein in the lung leading to the development of autoimmunity. Patients usually present in middle age with cough and dyspnea. Pulmonary function testing most commonly shows reduced diffusion capacity for carbon monoxide and HRCT reveals a combination of reticulation and ground glass abnormalities. The most common pattern on HRCT and histopathology is usual interstitial pneumonia (UIP), with nonspecific interstitial pneumonia seen less frequently. There are no large-scale well-controlled treatment trials. In severe or progressive cases, treatment usually consists of corticosteroids with or without a cytotoxic agent for 6 months or longer. RA interstitial lung disease is progressive; over half of patients show radiographic progression within 2 years. Patients with a UIP pattern on biopsy have a survival similar to idiopathic pulmonary fibrosis.

  15. Periodontitis and rheumatoid arthritis: a review.

    PubMed

    Bartold, P M; Marshall, R I; Haynes, D R

    2005-11-01

    Periodontitis and rheumatoid arthritis (RA) appear to share many pathologic features. In this review, the common pathologic mechanisms of these two common chronic conditions are explored. Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and RA. While this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to experience more significant periodontal problems compared to their non-RA counterparts, and vice versa. A case is made that these two diseases could be very closely related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of such dysfunction is still unknown. Nonetheless, there is accruing evidence to support the notion that both conditions manifest as a result of an imbalance between proinflammatory and anti-inflammatory cytokines. As a result, new treatment strategies are expected to emerge for both diseases that may target the inhibition of proinflammatory cytokines and destructive proteases. The clinical implications of the current data dictate that patients with RA should be carefully screened for their periodontal status. PMID:16277578

  16. Rheumatoid arthritis treated with vegetarian diets.

    PubMed

    Kjeldsen-Kragh, J

    1999-09-01

    The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.

  17. Genetics of rheumatoid arthritis: GWAS and beyond

    PubMed Central

    McAllister, Kate; Eyre, Stephen; Orozco, Gisela

    2011-01-01

    The study of complex genetics in autoimmune diseases has progressed at a tremendous pace over the last 4 years, as a direct result of the enormous gains made by genome wide association studies (GWAS). Novel genetic findings are continuously being reported alongside the rapid development of genetic technologies, sophisticated statistical analysis, and larger sample collections. It is now becoming clear that multiple genes contribute to disease risk in many complex genetic disorders including rheumatoid arthritis (RA) and that there are common genetic risk factors that underlie a spectrum of autoimmune diseases. This review details the current genetic landscape of RA, and describes what GWAS has taught us in terms of missing heritability, subsets of disease, existence of genetic heterogeneity, and shared autoimmune risk loci. Finally, this review addresses the initial challenges faced in translating the wealth of genetic findings into determining the biological mechanisms that contribute to the relationship between genotype and phenotype. Unraveling the mechanism of how genes directly influence the cause of RA will lead to a better understanding of the disease and will ultimately have a direct clinical impact, informing the development of new therapies that can be utilized in the treatment of RA. PMID:27790002

  18. Sarilumab for the treatment of rheumatoid arthritis.

    PubMed

    Cooper, Simon

    2016-01-01

    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.

  19. Targeting GM-CSF in rheumatoid arthritis.

    PubMed

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

    2016-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well-known as a haemopoietic growth factor. However, it is also essential in regulating functions of mature myeloid cells such as macrophages. Preclinical studies and observations of flares of arthritis in patients following GM-CSF treatment supported its important contribution to the pathogenesis of rheumatoid arthritis (RA). As the most advanced compound, mavrilimumab, a monoclonal antibody against GM-CSF receptor, has already completed phase II trials with a long term of follow-up period of 74 weeks. During this exposure period, an acceptable sustained safety and tolerability profile has been observed addressing the concerns of development of cytopenias or pulmonary alveolar proteinosis. Of note, a rapid and sustained efficacy and normalisation of acute phase reactants were consistently shown in studies both targeting GM-CSF and its receptor. Its tumour necrosis factor (TNF) independent mode of action with concurrent blockade of GM-CSF as well as IL-17 signalling reported from preclinical studies supports the assumption that it can be a useful biologic and an alternative agent in TNF inhibitor resistant patients with RA. Therefore, subsequent studies are warranted to investigate the safety and efficacy of GM-CSF blocking agents in different subgroups of RA. PMID:27586802

  20. A specific HLA-DP beta allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis.

    PubMed Central

    Begovich, A B; Bugawan, T L; Nepom, B S; Klitz, W; Nepom, G T; Erlich, H A

    1989-01-01

    Nonradioactive sequence-specific oligonucleotide probes specific for the HLA-DP beta locus have been used in a simple dot-blot format to type samples amplified by the polymerase chain reaction from 44 patients with pauciarticular juvenile rheumatoid arthritis, 32 patients with adult rheumatoid arthritis, and 50 random controls. The sequences of four new DP beta alleles derived from these patients and controls are reported, bringing the total number of alleles identified thus far to 19. The DPB2.1 allele is significantly increased in juvenile rheumatoid arthritis patients over controls; this allele is not increased in patients with adult rheumatoid arthritis. The association of juvenile rheumatoid arthritis with the DPB2.1 allele is independent of linkage with previously defined HLA-D region markers of disease. Analysis of the DPB2.1 sequence shows that it differs from the nonsusceptible DPB4.2 allele by only 1 amino acid at position 69 in the beta 1 domain. PMID:2512583

  1. Juvenile rheumatoid arthritis in children with diabetes mellitus.

    PubMed

    Rudolf, M C; Genel, M; Tamborlane, W V; Dwyer, J M

    1981-10-01

    Seven children with insulin-dependent diabetes mellitus were found to have juvenile rheumatoid arthritis; six of these children had the polyarticular form of the disease. All six had positive serology (rheumatoid factor and/or antinuclear antibody) and clinical or serologic evidence of autoimmune diseases usually ascribed to the thyrogastric cluster. Five expressed HLA antigens associated with increased risk for both diabetes and rheumatoid arthritis in adults. Evidence of B cell hyperactivity and impaired T cell response was found in some, but immunoregulatory function was normal in all. The association of these two diseases may be the result of factors other than chance alone, and may be more common than previously suspected. PMID:6974234

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

    PubMed

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

    2015-06-08

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  4. Concurrent validation of activity monitors in patients with rheumatoid arthritis☆

    PubMed Central

    Backhouse, Michael R.; Hensor, Elizabeth M.A.; White, Derrick; Keenan, Anne-Maree; Helliwell, Philip S.; Redmond, Anthony C.

    2013-01-01

    Background Physical activity is frequently reported in rheumatology but it is difficult to measure objectively outside the gait laboratory. A new generation of activity monitors offers this potential but it has not yet been evaluated in patients with rheumatoid arthritis. This study aimed to evaluate three types of activity monitors in patients with rheumatoid arthritis. Methods The Step-N-Tune, Activ4Life Pro V3.8, and the Intelligent Device for Energy Expenditure and Activity activity monitors were tested concurrently in 12 patients with rheumatoid arthritis as well as in a healthy control group of 12 volunteers. Participants walked at a self selected speed for two minutes and were filmed for later review. Temporal and spatial gait parameters were also validated against the GAITRite walkway and the total number of steps recorded by each activity monitor was compared to a gold standard derived from half speed video replays. Findings Activity monitor performance varied between devices but all showed poorer performance when used in the group with rheumatoid arthritis. Bland–Altman plots demonstrated wider 95% limits of agreement in the group with rheumatoid arthritis and a systematic decrease in agreement between activity monitors and the gold standard with decreasing functional ability. Interpretation Despite some variation between devices, all the activity monitors tested performed reasonably well in healthy young volunteers. All except the Activ4Life showed a marked decrease in performance in patients with rheumatoid arthritis, suggesting Activ4Life could be the most suitable for use in this patient group. The marked between group difference in functional ability, and systematic decrease in device performance with deteriorating gait, indicate that activity monitors require specific validation in target clinical populations. PMID:23522723

  5. Certolizumab in the long-term treatment of rheumatoid arthritis

    PubMed Central

    Khan, Abdul; Scott, David L

    2011-01-01

    Rheumatoid arthritis is the most common inflammatory arthritis and continues to have major long-term effects on quality of life. Early and intensive treatment has now become the norm in clinical practice with changes of medication dictated by measuring the presence of continued disease activity. Biologics, particular tumor necrosis factor inhibitors, have a crucial role in the management of very severe disease. Certolizumab is a relatively new tumor necrosis factor inhibitor which uses a novel strategy to neutralize TNF-alpha – the conjugation of tumor necrosis factor specific Fab antibody fragments to polyethylene glycol. Two Phase II and three Phase III randomized controlled trials have evaluated the efficacy and toxicity of certolizumab. More than 2000 patients were enrolled, and followed from 12–52 weeks. The number of patients achieving significant improvements with certolizumab, was indicated by the American College of Rheumatology with a 50% response rate. The risk ratios of achieving this response at 24 weeks was 6.01 (95% confidence interval [CI]: 3.84–9.40). At 52 weeks the risk ratio was 5.27 (95% CI: 3.19–8.71). The number of patients needed to treat, to obtain this benefit at 24 weeks was 4 (95% CI: 3–5). Certolizumab also had important clinical benefits in reducing erosive damage to joints, limiting disability, and enhancing other outcomes of importance to patients such as fatigue. The patient-related benefits were present from the early weeks of treatment. The clinical trials showed serious adverse events, including infections, which were more frequent for certolizumab. The most common adverse events comprised upper respiratory tract infections, hypertension, and nasopharyngitis. The balance of evidence suggests that certolizumab is equivalent to other tumor necrosis factor inhibitors, though no head-to-head trials have been undertaken. Having several effective treatments available, benefits patient choice, because the frequency and route

  6. 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.

  7. 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.

  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. 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.

  10. Coeliac Disease With Rheumatoid Arthritis: An Unusual Association

    PubMed Central

    Warjri, Synrang Batngen; Ete, Tony; Beyong, Taso; Barman, Bhupen; Lynrah, Kyrshanlang G.; Nobin, Hage; Perme, Obang

    2015-01-01

    Coeliac disease has a significant association with many autoimmune disorders. It shares many common genetic and immunological features with other autoimmune diseases. Gluten, a gut-derived antigen, is the driver of the autoimmunity seen in coeliac disease. The altered intestinal permeability found in coeliac patients, coupled with a genetic predisposition and altered immunological response, may result in a systemic immune response that is directed against sites other than the gut. Gut-derived antigens may have a role in the pathogenesis of other autoimmune disorders including rheumatoid arthritis. Here we report a case of adult coeliac disease associated with rheumatoid arthritis.

  11. 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

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

    PubMed

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

    2014-06-05

    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.

  13. 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.

  14. Silica exposure and rheumatoid arthritis: a follow up study of granite workers 1940-81.

    PubMed

    Klockars, M; Koskela, R S; Järvinen, E; Kolari, P J; Rossi, A

    1987-04-18

    The incidence and prevalence of subjects awarded disability pensions and the prevalence of subjects receiving free medicines because of rheumatoid arthritis were studied in a Finnish cohort of 1026 granite workers hired between 1940 and 1971 and followed up until 31 December 1981. The incidence of awards of disability pensions because of rheumatoid arthritis during 1969-81, the prevalence of rheumatoid arthritis on 31 December 1981, and the prevalence of subjects receiving free medicines for rheumatoid arthritis at the end of 1981 were significantly higher among the granite workers than in the general male population of the same age. Retrospective analysis of the records of all patients with rheumatoid arthritis in the cohort showed a predominance of a severe, serologically positive and erosive form of rheumatoid arthritis, usually with an age at onset of 50 or over. The possible aetiological or pathophysiological role of granite dust in rheumatoid arthritis may be based on the effects of quartz on the immune system.

  15. CTLA-4 Ig as an effective treatment in a patient with type I diabetes mellitus and seropositive rheumatoid arthritis.

    PubMed

    Fedele, Anna Laura; Alivernini, Stefano; Gremese, Elisa; Ferraccioli, Gianfranco

    2016-01-01

    We describe a patient suffering from seropositive rheumatoid arthritis (RA) and type I diabetes mellitus (T1DM), who achieved a good EULAR response together with an improvement of the glycemic profile under treatment with CTLA-4 Ig. A close association is known to exist between T1DM and RA, and CTLA-4 exon 1 polymorphism has been associated to RA with coexisting autoimmune endocrinopathies. The possible common genetic background and the potential role of CTLA-4 Ig in the early phases of T1DM, could be considered in the therapeutic interventions in RA patients with type 1 diabetes. PMID:26575162

  16. [Immunologic diagnosis of rheumatoid polyarthritis using a new micromethod of quantitative hemagglutination of the rheumatoid factor: the polyartiter].

    PubMed

    Marcelli-Barge, A; Prévost, P; Chapuis, E; Simard, M C

    1983-03-01

    A new micromethod of quantitative haemagglutination of the rheumatoid factor (class IgM) "polyartitre" was studied and compared with the classical Waaler-Rose reaction to the polyartest and to the rheumalatex using sera from 40 patients with rheumatoid arthritis, confirmed both radiologically and clinically. Thirty controls were selected from among the blood donors and 29 subjects with viral infections, hepatic or systematic illnesses or metabolic troubles. This method presents an excellent concordance with other methods. It is quantitatively more sensitive as the rheumatoid factor titres are higher than those obtained with the classical Waaler-Rose reaction. The polyartitre is simple to perform, easy to read, specific and reproducible, and the results are expressed in international units.

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

    NASA Astrophysics Data System (ADS)

    Gsponer, Jörg; Haberthür, Urs; Caflisch, Amedeo

    2003-04-01

    Understanding the early steps of aggregation at atomic detail might be crucial for the rational design of therapeutics preventing diseases associated with amyloid deposits. In this paper, aggregation of the heptapeptide GNNQQNY, from the N-terminal prion-determining domain of the yeast protein Sup35, was studied by 20 molecular dynamics runs for a total simulation time of 20 μs. 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.

  18. 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

  19. Prevention of cardiovascular disease in rheumatoid arthritis.

    PubMed

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

    2015-10-01

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

  20. [Evaluation of radiologic criteria in rheumatoid arthritis].

    PubMed

    Henrard, J C; Schoen, E; Verret, J M

    1977-02-01

    The authors compared the hand Xrays of 53 patients with rheumatoid arthritis (AR) with those of 53 control subjects matched for age and s. x. Each AR patient conformed to the New York clinical criteria. Assesment was carried out on Xrays of both hands, search being made for erosions, geodes, and joint narrowing, the severity being graduated from 0 to 4, according to data from the international Atlas of Radiology. The sensitivity, sepcificity and severity of each of these abnormalities was studied joint by joint (18 for the hand). Analysis of the results shows that study of all 18 joints in the hand is not useful; account may be taken only of the first three metacarpo-phalangeal joints, the carpo-metacarpal joints and the radio-carpal joint. The proximal interphalangeal joints, contrary to the most commonly held opinion, are more a source of errors than of diagnosis. Erosion is the most specific sign, especially if one is only considering the characteristic sites. With a specificity of the order of 98 per cent, this abnormality has sufficient weight to counteract the very low incidence of the disease in a population in comparison with degenerative disorders. Geodes should be studied more by their severity than by their frequency; this is high in the controls, which diminishes their specificity (45 for the wrist, 62 for the first carpo-metacarpal, and 75 for the first metacarpo-phalangeal joint). Joint narrowing is a difficult sign to read and its value is all at the radiocarpal and carpal joints.

  1. Co-morbidities in established rheumatoid arthritis.

    PubMed

    Gullick, Nicola J; Scott, David L

    2011-08-01

    Co-morbid conditions are common in patients with rheumatoid arthritis (RA). Although the presence of co-morbid conditions can be assessed using standardised indexes such as the Charlson index, most clinicians prefer to simply record their presence. Some co-morbidities are causally associated with RA and many others are related to its treatment. Irrespective of their underlying pathogenesis, co-morbidities increase disability and shorten life expectancy, thereby increasing both the impact and mortality of RA. Cardiac co-morbidities are the most crucial, because of their frequency and their negative impacts on health. Treatment of cardiac risk factors and reducing RA inflammation are both critical in reducing cardiac co-morbidities. Gastrointestinal and chest co-morbidities are both also common. They are often associated with drug treatment, including non-steroidal anti-inflammatory drug and disease-modifying drugs. Osteoporosis and its associated fracture risk are equally important and are often linked to long-term glucocorticoid treatment. The range of co-morbidities associated with RA is increasing with the recognition of new problems such as periodontal disease. Optimal medical care for RA should include an assessment of associated co-morbidities and their appropriate management. This includes risk factor modification where possible. This approach is essential to improve quality of life and reduce RA mortality. An area of genuine concern is the impact of treatment on co-morbidities. A substantial proportion is iatrogenic. As immunosuppression with conventional disease-modifying drugs and biologics has many associated risks, ranging from liver disease to chest and other infections, it is essential to balance the risks of co-morbidities against the anticipated benefits of treatment.

  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. 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

  4. 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

  5. Genetics of rheumatoid arthritis - a comprehensive review.

    PubMed

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

    2013-10-01

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

  6. Exercise and fatigue in rheumatoid arthritis.

    PubMed

    Balsamo, Sandor; Diniz, Leonardo R; dos Santos-Neto, Leopoldo L; da Mota, Licia M H

    2014-01-01

    Fatigue, the enduring sensation of weakness, lack of energy, tiredness or exhaustion, is described by 40%-80% of patients with rheumatoid arthritis as their most disabling symptom with wide-ranging consequences for quality of life. Little attention has been paid to its multidimensional nature or to its reliability as a measure to evaluate progression of the disease. Low impact aerobic exercise affects the level of fatigue, and this same level of fatigue influences the exercise itself. We searched Medline, Cochrane Collaboration Register of Controlled Trials (CCRCT), Lilacs, PubMed and Scopus databases for randomized controlled trials (with appropriate description of methods, materials and results) on the assessment of fatigue and exercise. Review articles, case reports, letters to the editor and editorials were excluded. Of 121 references initially identified, 4 randomized controlled trials met the inclusion criteria. Two studies used the MAF scale (Multidimensional Assessment of Fatigue), one used the MAC (Mental Adjustment to Cancer) fatigue scale, and all trials used POMS (Profile of Mood States) to assess fatigue. All four trials conducted a 12 week program of two to three times/ week and different periods of follow-up. Two studies used low impact aerobic exercise, one used dance-based exercise, and another study followed a home cardiopulmonary conditioning program using a stationary bicycle. While fatigue appears to be a reliable outcome measure in the clinical management of RA, especially when related to exercise prescription, further research is needed to evaluate the correlation between exercise, fatigue and quality of life, using fatigue scales validated to explore the different components of fatigue and its wide-ranging consequences.

  7. Genetics of rheumatoid arthritis - a comprehensive review.

    PubMed

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

    2013-10-01

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

  8. Methotrexate: Optimizing the Efficacy in Rheumatoid Arthritis

    PubMed Central

    Braun, Jürgen

    2011-01-01

    Methotrexate (MTX) is currently the most frequently used drugs in the treatment of rheumatoid arthritis (RA). The drug had been synthesized in 1948 and first tests to treat patients with psoriasis and RA were published in 1951. However, until the 1980s there was only limited use of MTX in the treatment of RA. Since the 1990s MTX is the disease-modifying antirheumatic drug (DMARD) of first choice for the treatment of RA in most countries worldwide. By definition, DMARDs in RA are those compounds for which an inhibiting effect on radiographic progression has been demonstrated. Several combinations of DMARDs have been tested, most commonly with MTX as the anchor drug. Regarding the route of administration of MTX there is some evidence that the parenteral route, most often performed subcutaneously, has some additional benefits over the oral route. In MTX monotherapy, dosages up to 30 mg/week are now used. There are now three main combinations that are playing an important role: MTX + sulfasalazine (SSZ) + hydroxychloroquine, MTX + leflunomide (LEF), and MTX + biologics such as antitumour necrosis factor (anti-TNF) and other new compounds which block the interleukin 6 (IL6) receptor or T-cell activation and delete B cells. Regarding clinical efficacy, MTX monotherapy has performed almost similarly well in comparison with biologic mono-therapy, both usually combined with glucocorticoids. However, structural damage is usually inhibited to a significantly greater degree with the biologics. The combination of MTX with biologics has proven superior to either agent alone in all aspects. Current strategic regimens which concentrate on systematic ways to bring patients into remission all include MTX as first choice. PMID:22870474

  9. Prevention of cardiovascular disease in rheumatoid arthritis.

    PubMed

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

    2015-10-01

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

  10. The past versus the present, 1980-2004: reduction of mean initial low-dose, long-term glucocorticoid therapy in rheumatoid arthritis from 10.3 to 3.6 mg/day, concomitant with early methotrexate, with long-term effectiveness and safety of less than 5 mg/day.

    PubMed

    Pincus, Theodore; Sokka, Tuulikki; Cutolo, Maurizio

    2015-01-01

    Quantitative observations are presented concerning treatment with glucocorticoids of 308 patients with rheumatoid arthritis (RA) at a weekly academic rheumatology setting over 25 years from 1980 to 2004. A database of all visits included medications and multidimensional health assessment questionnaire scores for physical function, pain and routine assessment of patient index data (RAPID3; and a surrogate RAPID3-EST), completed by each patient at each visit in routine care. Over the 5-year periods of 1980-1984, 1985-1989, 1990-1994, 1995-1999 and 2000-2004, the mean initial prednisone daily dose declined from 10.3 to 6.5, 5.1, 4.1 and 3.6 mg/day, as initial doses were >5 mg/day in 49, 16, 7, 7 and 3% of patients, 5 mg/day in 51, 80, 70, 26 and 10%, and <5 mg/day in 0, 4, 23, 67 and 86%. Reduction of prednisone doses in the respective five-year periods was accompanied by increased and earlier use of methotrexate as the first disease-modifying antirheumatic drug (DMARD) in 10, 26, 57, 71 and 78%, and methotrexate treatment in 10, 26, 74, 82 and 92% of patients within the first year of disease. Higher methotrexate doses in the respective five-year periods were used after 1990, along with lower prednisone doses. Most patients were treated indefinitely with both low-dose prednisone and methotrexate; 80% continued both medications for more than 5 years. The primary adverse events were skin-thinning and bruising. New hypertension, diabetes and cataracts were seen in fewer than 10% of patients. While efficacy and safety cannot be analyzed definitively from observational data, the data suggest that many patients with RA might be treated effectively with weekly low-dose methotrexate along with initial and long-term, low-dose prednisone of <5 mg/day. PMID:25228430

  11. The clinical efficacy and safety of certolizumab pegol (CZP) in the treatment of rheumatoid arthritis: focus on long-term use, patient considerations and the impact on quality of life

    PubMed Central

    Fleischmann, Roy

    2009-01-01

    Rheumatoid arthritis can cause chronic pain, disability, fatigue and loss of productivity both in the workplace and at home. Fatigue, not joint pain, swelling or that there may be radiographic damage, is frequently mentioned by patients as their most debilitating problem. In the era prior to biologic therapy in rheumatoid arthritis, it was reported that 40% to 50% of individuals reported work loss within 10 years of the onset of their disease. Rheumatoid arthritis is not just associated with chronic pain and inability to function normally; there is a significant economic burden caused by the disease which affects society as well the individual. Work disability in individuals with rheumatoid arthritis occurs early and increases over time. Early, aggressive treatment has now become the norm in clinical practice with changes of medication dictated by measuring the presence of continued disease activity. The combination of adequately dosed methotrexate and a biologic agent, especially a TNFα inhibitor, has been shown to be far more effective than traditional disease modifying anti-rheumatic drugs in early and long-standing disease, with respect to clinical, radiologic and functional outcomes. Unfortunately, not all patients respond to all medications equally; indeed a patient may fail a number of medications, either alone or in combination, and then respond to another medication. For this reason, there is room in our therapeutic armamentarium for additional effective agents such as certolizumab pegol. The results of up to 100 weeks of treatment with certolizumab pegol with an emphasis on functional outcomes, is the focus of this review.

  12. Olecranon Bursitis Caused by Candida parapsilosis in a Patient with Rheumatoid Arthritis.

    PubMed

    Gamarra-Hilburn, Carla F; Rios, Grissel; Vilá, Luis M

    2016-01-01

    Septic bursitis is usually caused by bacterial organisms. However, infectious bursitis caused by fungi is very rare. Herein, we present a 68-year-old woman with long-standing rheumatoid arthritis who developed pain, erythema, and swelling of the right olecranon bursa. Aspiration of the olecranon bursa showed a white blood cell count of 3.1 × 10(3)/μL (41% neutrophils, 30% lymphocytes, and 29% monocytes). Fluid culture was positive for Candida parapsilosis. She was treated with caspofungin 50 mg intravenously daily for 13 days followed by fluconazole 200 mg orally daily for one week. She responded well to this treatment but had recurrent swelling of the bursa. Bursectomy was recommended but she declined this option. This case, together with other reports, suggests that the awareness of uncommon pathogens, their presentation, and predisposing risk factors are important to establish an early diagnosis and prevent long-term complications. PMID:27595032

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

    PubMed Central

    Hampel, Constanze; Anastasiadis, Panos Z.; Kallakury, Bhaskar; Uren, Aykut; Foley, David W; Brown, Milton L.; Shapiro, Lawrence; Brenner, Michael; Haigh, David; Byers, Stephen W.

    2014-01-01

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

  14. Olecranon Bursitis Caused by Candida parapsilosis in a Patient with Rheumatoid Arthritis

    PubMed Central

    Rios, Grissel

    2016-01-01

    Septic bursitis is usually caused by bacterial organisms. However, infectious bursitis caused by fungi is very rare. Herein, we present a 68-year-old woman with long-standing rheumatoid arthritis who developed pain, erythema, and swelling of the right olecranon bursa. Aspiration of the olecranon bursa showed a white blood cell count of 3.1 × 103/μL (41% neutrophils, 30% lymphocytes, and 29% monocytes). Fluid culture was positive for Candida parapsilosis. She was treated with caspofungin 50 mg intravenously daily for 13 days followed by fluconazole 200 mg orally daily for one week. She responded well to this treatment but had recurrent swelling of the bursa. Bursectomy was recommended but she declined this option. This case, together with other reports, suggests that the awareness of uncommon pathogens, their presentation, and predisposing risk factors are important to establish an early diagnosis and prevent long-term complications. PMID:27595032

  15. Vascular calcification in rheumatoid arthritis: prevalence, pathophysiological aspects and potential targets.

    PubMed

    Paccou, J; Brazier, M; Mentaverri, R; Kamel, S; Fardellone, P; Massy, Z A

    2012-10-01

    Individuals with rheumatoid arthritis (RA) are at increased risk for morbidity and mortality from cardiovascular disease. Excess cardiovascular mortality in RA patients cannot be fully explained by conventional cardiovascular risk factors. The purpose of this review is to discuss recent progress concerning the prevalence and pathophysiological aspects of vascular calcification in RA. RA patients have early-onset diffuse calcification involving multiple vascular beds compared to age and sex-matched controls. Pathogenesis of vascular calcification in RA patients is not fully understood, but specific mediators such as proinflammatory cytokines and not global inflammation could be involved. The possible link between osteoporosis and vascular calcification in RA will not be discussed. Finally, potential targets to reduce vascular calcification in RA will be discussed.

  16. Efficacy, safety, and tolerability of abatacept in the management of rheumatoid arthritis

    PubMed Central

    Lutt, Joseph R

    2009-01-01

    The management of rheumatoid arthritis (RA) has undergone an impressive transformation over the past few decades. Further understanding of the pathophysiology of the disease process has resulted in the development of biologic agents that target proinflammatory cytokines and both B and T lymphocytes. By blocking an important costimulatory pathway, abatacept leads to a dramatic reduction in T cell stimulation and proliferation. Multiple clinical trials have revealed consistent benefit with regards to clinical and radiographic efficacy, quality of life, and disability in patients suffering from RA who have had inadequate responses to methotrexate or tumor necrosis factor inhibitors. The possibility of remission when used early in the disease course has also been demonstrated. Importantly, abatacept has been very well tolerated with a low rate of serious infections and no apparent increase in malignancies to date. Continued surveillance of the benefits and risks will help to better define its place amongst the other biologic agents in the treatment of RA.

  17. 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.

  18. 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

  19. 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

  20. 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

  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. Infliximab treatment in a case of rheumatoid scleromalacia perforans.

    PubMed

    Herrera-Esparza, R; Avalos-Díaz, E

    2009-01-01

    Ocular rheumatoid disease manifests as hyperemia of the conjunctiva and episclera, and in severe cases, episcleritis can result in nodular sclerotic and scleromalacia perforans. A clinical case of scleromalacia perforans in a 56-year-old woman with 20 years of seropositive rheumatoid arthritis of functional class IV is presented here. During that period, she received exclusively non-steroidal anti-inflammatory drugs (NSAIDs). She developed acute episcleritis of the left ocular globe, which rapidly progressed to scleromalacia perforans. Since the left eye became perforated, it was surgically enucleated, and the patient was maintained with steroidal therapy. Nevertheless, two months later she developed new-onset episcleritis of the right eye followed by scleromalacia. She was first evaluated by a rheumatologist and treated with 200 mg/dose of infliximab, which was administered monthly for the following four months. The biological treatment was accompanied by methotrexate and prednisone. With this therapy, the ocular lesion dramatically improved, and complete remission of rheumatoid arthritis and scleritis was archived four months later. In conclusion, tumour necrosis factor (TNF) blockers are effective therapeutic agents in ocular complications of rheumatoid arthritis.

  3. Skeletal surgery in the treatment of the rheumatoid hand.

    PubMed

    Harrison, S H

    1983-04-01

    Surgery of the rheumatoid hand is complex. It is important to understand the pathophysiology of deformity at the several linkaged joints of convexity of the wrist, metacarpophalangeal and interphalangeal joints. Pegging offers one of the best and reliable techniques of stabilising the joints. However, arthroplasty and soft tissue reconstruction play equally important roles in restoring hand function.

  4. A dancer with rheumatoid arthritis: a role for biologics.

    PubMed

    Bird, H A; Bergstrom, A

    2013-04-01

    A case study is presented in which a student dancer who developed rheumatoid arthritis during her degree course was able to complete her course with meticulous treatment including the use of biologics. She describes her own reactions to the disease occurring at this crucial phase in her career.

  5. 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.

  6. Co-morbidity index in rheumatoid arthritis: time to think.

    PubMed

    El Miedany, Yasser

    2015-12-01

    Rheumatoid arthritis patients are clinically complex, and the interplay of their disease activity together with the other associated conditions may lead to increased morbidity and mortality. The recent advances in the disease management attracted the attention to its associated co-morbidities and highlighted the need for a tool to provide clinicians and potential payers with a clinically powerful measure of the disease burden and prognosis. Predicting outcome or co-morbidity probability has been previously implemented successfully for calculating 10-year fracture probability (FRAX) as well as for predicting 1-year patient mortality using co-morbidity data obtained (Charlson index). Developing a specific rheumatoid arthritis-independent tool able to predict morbidity, mortality, cost and hospitalization would be a step forward on the way to achieve full disease remission. The co-morbidity index should be used both at baseline as well as a continuous variable in analyses. It should be implemented regularly in the clinical assessment as a confounder of outcomes. This article will review the redefined health outcomes in rheumatoid arthritis and the concept of co-morbidity index for patients with inflammatory arthritis. It will also present a proposed co-morbidity index for rheumatoid arthritis patients. PMID:26497664

  7. Geode development and multiple fractures in rheumatoid arthritis.

    PubMed

    Lowthian, P J; Calin, A

    1985-02-01

    The radiological development from normal bone of geodes and subsequent fractures in phalanges of two adjacent fingers is described in a patient with classical rheumatoid arthritis. Presentation was as a septic, discharging focus, but infection was excluded; the pathology is described.

  8. Parasitic infection as a potential therapeutic tool against rheumatoid arthritis

    PubMed Central

    Apaer, Shadike; Tuxun, Tuerhongjiang; Ma, Hai-Zhang; Zhang, Heng; Aierken, Amina; Aini, Abudusalamu; Li, Yu-Peng; Lin, Ren-Yong; Wen, Hao

    2016-01-01

    Parasites, which are a recently discovered yet ancient dweller in human hosts, remain a great public health burden in underdeveloped countries, despite preventative efforts. Rheumatoid arthritis is a predominantly cosmopolitan health problem with drastic morbidity rates, although encouraging progress has been achieved regarding treatment. However, although various types of methods and agents have been applied clinically, their broad usage has been limited by their adverse effects and/or high costs. Sustained efforts have been exerted on the ‘hygiene hypothesis’ since the 1870s. The immunosuppressive nature of parasitic infections may offer potential insight into therapeutic strategies for rheumatoid arthritis, in which the immune system is overactivated. An increasing number of published papers are focusing on the preventive and/or curative effect of various parasitic infection on rheumatoid arthritis from experimental studies to large-scale epidemiological studies and clinical trials. Therefore, the present review aimed to provide a general literature review on the possible beneficial role of parasitic infection on rheumatoid arthritis. PMID:27698735

  9. Parasitic infection as a potential therapeutic tool against rheumatoid arthritis

    PubMed Central

    Apaer, Shadike; Tuxun, Tuerhongjiang; Ma, Hai-Zhang; Zhang, Heng; Aierken, Amina; Aini, Abudusalamu; Li, Yu-Peng; Lin, Ren-Yong; Wen, Hao

    2016-01-01

    Parasites, which are a recently discovered yet ancient dweller in human hosts, remain a great public health burden in underdeveloped countries, despite preventative efforts. Rheumatoid arthritis is a predominantly cosmopolitan health problem with drastic morbidity rates, although encouraging progress has been achieved regarding treatment. However, although various types of methods and agents have been applied clinically, their broad usage has been limited by their adverse effects and/or high costs. Sustained efforts have been exerted on the ‘hygiene hypothesis’ since the 1870s. The immunosuppressive nature of parasitic infections may offer potential insight into therapeutic strategies for rheumatoid arthritis, in which the immune system is overactivated. An increasing number of published papers are focusing on the preventive and/or curative effect of various parasitic infection on rheumatoid arthritis from experimental studies to large-scale epidemiological studies and clinical trials. Therefore, the present review aimed to provide a general literature review on the possible beneficial role of parasitic infection on rheumatoid arthritis.

  10. Increased incidence of rheumatoid arthritis in multiple sclerosis

    PubMed Central

    Tseng, Chia-Chun; Chang, Shun-Jen; Tsai, Wen-Chan; Ou, Tsan-Teng; Wu, Cheng-Chin; Sung, Wan-Yu; Hsieh, Ming-Chia; Yen, Jeng-Hsien

    2016-01-01

    Abstract Past studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness. A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01–2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24–2.56, P = 0.002). In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history. PMID:27368008

  11. Periodontal disease and rheumatoid arthritis: a systematic review.

    PubMed

    Kaur, S; White, S; Bartold, P M

    2013-05-01

    This systematic review considers the evidence available for a relationship between periodontal disease and rheumatoid arthritis. MEDLINE/PubMed, CINAHL, DOSS, Embase, Scopus, Web of Knowledge, MedNar, and ProQuest Theses and Dissertations were searched from the inception of the database until June 2012 for any quantitative studies that examined the association between periodontal disease and rheumatoid arthritis. Nineteen studies met our inclusion criteria. Good evidence was found to support an association between these conditions with regard to tooth loss, clinical attachment levels, and erythrocyte sedimentation rates. Moderate evidence was noted for C-reactive protein and interleukin-1β. Some evidence for a positive outcome of periodontal treatment on the clinical features of rheumatoid arthritis was noted. These results provide moderate evidence based on biochemical markers and stronger evidence with regard to clinical parameters that common risk factors or common pathologic processes may be responsible for an association between rheumatoid arthritis and periodontal disease. Further studies are required to fully explore both the biochemical processes and clinical relationships between these 2 chronic inflammatory conditions. There is a need to move from case-control studies to more rigorous studies using well-defined populations and well-defined biochemical and clinical outcomes as the primary outcome measures with consideration of potential confounding factors. PMID:23525531

  12. Costovertebral and costotransverse joint involvement in rheumatoid arthritis.

    PubMed Central

    Cohen, M J; Ezekiel, J; Persellin, R H

    1978-01-01

    Lesions of the costovertebral (CV) and costotransverse (CT) joints are distinctly unusual in rheumatoid arthritis. The patient presented had dramatic changes in these joints with destruction, ankylosis, and bony overgrowth. This led to a moderate respiratory impairment and a distinctive radiological presentation. Images PMID:718281

  13. [Severe disseminated constrictive polyserositis in a patient with rheumatoid arthritis].

    PubMed

    Blagova, O V; Tsaregorodtsev, D A; Nedostup, A V; Maevskaia, I V; Petukhova, N V; Troitskaia, M P; Shadaniia, Ia R

    2010-01-01

    Constrictive polyserositis (pleuritis, pericarditis) is a syndrome within the underlying disease (tuberculosis, periodic disease, rheumatoid arthritis, systemic lupus erythematosus, asbestos, silicosis, uremia, some genetic diseases), a complication due to chest surgery or radiation or drug therapy, is occasionally idiopathic (fibrosing mediastinitis). There are frequently great difficulties in making its nosological diagnosis. The paper describes a patient in whom the onset of disease was exudative pleurisy with the signs of constriction, arthralgias; pleural punctures provided serous exudates with 80% lymphocytes. A year later there was ascitis and shin and foot edemas, which concurrent with hepatomegaly and cholestasis was regarded as cryptogenic liver cirrhosis. The signs of constrictive pericarditis were further revealed. The disease was complicated by the development of pulmonary artery thromboembolism (PATE) (which required the use of warfarin) and hemorrhagic vasculitis. Therapy with metipred in combination with isoniazid yielded a slight effect. The diagnoses of tuberculosis, liver cirrhosis, and autoimmune hepatitis, systemic vasculitis were consecutively rejected; the diagnosis of rheumatoid polyarthritis with systemic manifestations was made, by taking into account persistent arthalgias with the minimum signs of arthritis, noticeably increased C-reactive protein, rheumatoid factor, and cyclic citrullinated peptide antibodies (CCPA); plasmapheresis, therapy with metipred and methotrexate, and subtotal pericardectomy were performed. Constrictive polyserositis concurrent with PATE, hemorrhagic vasculitis (probably, drug-induced one), and hepatic lesion has been first described in a CCPA-positive patient with rheumatoid arthritis in the presence of moderate true arthritis (during steroid therapy).

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

    ERIC Educational Resources Information Center

    Smith, Timothy W.; And Others

    1988-01-01

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

  15. Pain Coping Strategies and Depression in Rheumatoid Arthritis.

    ERIC Educational Resources Information Center

    Brown, Gregory K.; And Others

    1989-01-01

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

  16. Co-morbidity index in rheumatoid arthritis: time to think.

    PubMed

    El Miedany, Yasser

    2015-12-01

    Rheumatoid arthritis patients are clinically complex, and the interplay of their disease activity together with the other associated conditions may lead to increased morbidity and mortality. The recent advances in the disease management attracted the attention to its associated co-morbidities and highlighted the need for a tool to provide clinicians and potential payers with a clinically powerful measure of the disease burden and prognosis. Predicting outcome or co-morbidity probability has been previously implemented successfully for calculating 10-year fracture probability (FRAX) as well as for predicting 1-year patient mortality using co-morbidity data obtained (Charlson index). Developing a specific rheumatoid arthritis-independent tool able to predict morbidity, mortality, cost and hospitalization would be a step forward on the way to achieve full disease remission. The co-morbidity index should be used both at baseline as well as a continuous variable in analyses. It should be implemented regularly in the clinical assessment as a confounder of outcomes. This article will review the redefined health outcomes in rheumatoid arthritis and the concept of co-morbidity index for patients with inflammatory arthritis. It will also present a proposed co-morbidity index for rheumatoid arthritis patients.

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

    PubMed

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

    2013-01-01

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

  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. Treating growth and TMJ abnormalities in juvenile rheumatoid arthritis.

    PubMed

    Tanchyk, A

    1994-12-01

    Two case reports illustrate the orofacial aspects of juvenile rheumatoid arthritis. The disease can affect facial growth and cause TMJ abnormalities. Children may vary in the degree to which they are affected by JRA, and dentists should investigate JRA as a cause of these abnormalities or deformities.

  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. Monitoring the remineralization of early simulated lesions using a pH cycling model with CP-OCT

    NASA Astrophysics Data System (ADS)

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

    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.

  2. 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.

  3. 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.-

  4. 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

  5. Numerical simulation of formation of cyclone vortex flows in the intratropical zone of convergence and their early detection

    NASA Astrophysics Data System (ADS)

    Mingalev, I. V.; Astaf'eva, N. M.; Orlov, K. G.; Chechetkin, V. M.; Mingalev, V. S.; Mingalev, O. V.

    2012-05-01

    Mechanisms of formation of cyclonic vortices in the tropical atmosphere of the Earth are investigated in the intratropical zone of convergence using numerical simulation made with the complete system of equations of gas dynamics taking into account transport of infrared radiation, phase transitions of water vapor into microdrops of water and ice particles, and sedimentation of these drops and ice particles in the field of gravity force. Observational data on the structure of dominant air streams, which are formed in the intratropical zone of convergence over the North Atlantic in the periods of its highest thermodynamic intensity and instability, are used in the initial and boundary conditions of the model. Formation of cyclonic vortex flows is obtained numerically at sufficiently strong bending of the intratropical zone of convergence. The results of numerical modeling are compared with the data of satellite microwave monitoring: global radio thermal fields of the Earth from the electronic collection GLOBAL-Field allowing one to study the structure of atmospheric motions in a wide range of space-time scales.

  6. 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.

  7. Circulating interleukin-6 and rheumatoid arthritis

    PubMed Central

    Li, Bing; Xiao, Yu; Xing, Dan; Ma, Xin-long; Liu, Jun

    2016-01-01

    Abstract Interleukin-6 (IL-6), as a pleiotropic cytokine, has been demonstrated to be closely associated with the pathogenisis of rheumatoid arthritis (RA). However, whether this association is causal or not remains unclear, because of the multifactorial role of IL-6 and related confounding factors. We aimed to evaluate the causal relevance between circulating IL-6 levels and the risk of RA through meta-analytical Mendelian randomization approach. IL-6 gene -174G/C variant was selected as an instrument in this Mendelian randomization meta-analysis. Article identification and data collection were conducted in duplicate and independently by 2 authors. The STATA software was used for data analysis. In total, 15 and 5 articles on the association of the -174G/C variant with RA risk and circulating IL-6 level, respectively, were included. The overall analysis showed that C allelic and GC+CC genotype were significantly with 1.59-fold (95% CI: 1.19–2.14) and 1.63-fold (95% CI: 1.17–2.26) increased risk of developing RA, respectively. Asian populations showed stronger association with 4.55-fold (95% CI: 1.62–12.75), 1.84-fold (95% CI: 1.13–2.99), and 4.69-fold (95% CI: 1.68–13.14) increased RA risk in carriers of -174C allelic, CC, and GC+CC genotype, respectively. Carriers of GC+CC genotype showed significant reduction in the circulating IL-6 level compared with GG carriers (WMD = −0.77; 95% CI: −1.16 to −0.38; P = 0.000) in overall populations. Mendelian randomization presented 6% and 22% increased risk of RA with 0.1 pg/mL reduction of circulating IL-6 level in overall and Asian populations, respectively. This Mendelian randomization meta-analysis demonstrated that the long-term genetically reduced circulating IL-6 level might be causally related to a higher risk of RA, especially in Asian populations. PMID:27281095

  8. 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

  9. 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.

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

    PubMed

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

    2015-06-01

    The aim of this study was to assess the impact of tocilizumab on bone oedema in rheumatoid arthritis (RA) as shown by magnetic resonance imaging (MRI). In this longitudinal study, patients with rheumatoid arthritis according to the American College of Rheumatology (ACR) 2009 criteria with inadequate response or intolerance to disease-modifying anti-rheumatic drugs (DMARDs), treated with tocilizumab, were included. Sociodemographic characteristics and clinical and laboratory data for the disease were collected at baseline (M0) and 06 months (M6) of treatment. Disease activity was assessed using disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI). MRI of the dominant hand was performed at baseline and M6 of treatment. The primary outcome measure was the assessment of bone oedema by rheumatoid arthritis MRI scoring system (RAMRIS) bone oedema. Secondary outcomes included RAMRIS synovitis, DAS28, C-reactive protein (CRP) and SDAI at baseline and M6. Twenty-two patients with RA were included, 19 females (86.4 %), with a mean of age 42 ± 13.7. The mean disease duration was 8 ± 5.2 years. The mean DAS28 was 5.78 ± 0.87. The median CRP was 16 mg/l (6.7 to 36.3). The average SDAI was 90 ± 34. Three patients were excluded from the study for serious side effects. At baseline, bone oedema was present in 41 % of patients (N = 9), with a median bone oedema RAMRIS 0 (0 to 7.2). At M6, bone oedema decreased or disappeared in 32 % (N = 7) with a significant improvement in the RAMRIS bone oedema score (p = 0.04). Moreover, there is a significant improvement in RAMRIS synovitis (p < 0.0001) as well as in activity parameters: DAS28 (p < 0.0001), CRP (p < 0.0001) and SDAI (p < 0.0001). This study suggests that tocilizumab is associated with a significant improvement on MRI-determined bone oedema in the short term. This improvement in bone oedema is correlated

  11. Patient initiated outpatient follow up in rheumatoid arthritis: six year randomised controlled trial

    PubMed Central

    Hewlett, Sarah; Kirwan, John; Pollock, Jon; Mitchell, Kathryn; Hehir, Maggie; Blair, Peter S; Memel, David; Perry, Mark G

    2005-01-01

    Objectives To determine whether direct access to hospital review initiated by patients with rheumatoid arthritis would result in improved clinical and psychological outcome, reduced overall use of healthcare resources, and greater satisfaction with care than seen in patients receiving regular review initiated by a rheumatologist. Design Two year randomised controlled trial extended to six years. Setting Rheumatology outpatient department in teaching hospital. Participants 209 consecutive patients with rheumatoid arthritis for over two years; 68 (65%) in the direct access group and 52 (50%) in the control group completed the study (P = 0.04). Main outcome measures Clinical outcome: pain, disease activity, early morning stiffness, inflammatory indices, disability, grip strength, range of movement in joints, and bone erosion. Psychological status: anxiety, depression, helplessness, self efficacy, satisfaction, and confidence in the system. Number of visits to hospital physician and general practitioner for arthritis. Results Participants were well matched at baseline. After six years there was only one significant difference between the two groups for the 14 clinical outcomes measured (deterioration in range of movement in elbow was less in direct access patients). There were no significant differences between groups for median change in psychological status. Satisfaction and confidence in the system were significantly higher in the direct access group at two, four, and six years: confidence 9.8 v 8.4, 9.4 v 8.0, 8.7 v 6.9; satisfaction 9.3 v 8.3, 9.3 v 7.7, 8.9 v 7.1 (all P < 0.02). Patients in the direct access group had 38% fewer hospital appointments (median 8 v 13, P < 0.0001). Conclusions Over six years, patients with rheumatoid arthritis who initiated their reviews through direct access were clinically and psychologically at least as well as patients having traditional reviews initiated by a physician. They requested fewer appointments, found direct access more

  12. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

    PubMed Central

    Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

    2016-01-01

    clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology. Trial registration Clinical trials NCT01205854. PMID:27530741

  13. Cutaneous abnormalities in rheumatoid arthritis compared with non‐inflammatory rheumatic conditions

    PubMed Central

    Douglas, K M J; Ladoyanni, E; Treharne, G J; Hale, E D; Erb, N; Kitas, G D

    2006-01-01

    Background Cutaneous abnormalities are common in rheumatoid arthritis, but exact prevalence estimates are yet to be established. Some abnormalities may be independent and coincidental, whereas others may relate to rheumatoid arthritis or its treatment. Objectives To determine the exact nature and point prevalence of cutaneous abnormalities in patients with rheumatoid arthritis compared with those in patients with non‐inflammatory rheumatic disease. Methods 349 consecutive outpatients for rheumatology (205 with rheumatoid arthritis and 144 with non‐inflammatory rheumatic conditions) were examined for skin and nail signs by a dermatologist. Histories of rheumatology, dermatology, drugs and allergy were noted in detail. Results Skin abnormalities were reported by more patients with rheumatoid arthritis (61%) than non‐inflammatory controls (47%). More patients with rheumatoid arthritis (39%) than controls (10%) attributed their skin abnormality to drugs. Cutaneous abnormalities observed by the dermatologist were also more common in patients with rheumatoid arthritis (76%) than in the group with non‐inflammatory disease (60%). Specifically, bruising, athlete's foot, scars, rheumatoid nodules and vasculitic lesions were more common in patients with rheumatoid arthritis than in controls. The presence of bruising was predicted only by current steroid use. The presence of any other specific cutaneous abnormalities was not predicted by any of the variables assessed. In the whole group, current steroid use and having rheumatoid arthritis were the only important predictors of having any cutaneous abnormality. Conclusions Self‐reported and observed cutaneous abnormalities are more common in patients with rheumatoid arthritis than in controls with non‐inflammatory disease. These include cutaneous abnormalities related to side effects of drugs or to rheumatoid arthritis itself and other abnormalities previously believed to be independent but which may be of clinical

  14. A population-based study on the association between rheumatoid arthritis and voice problems.

    PubMed

    Hah, J Hun; An, Soo-Youn; Sim, Songyong; Kim, So Young; Oh, Dong Jun; Park, Bumjung; Kim, Sung-Gyun; Choi, Hyo Geun

    2016-07-01

    The objective of this study was to investigate whether rheumatoid arthritis increases the frequency of organic laryngeal lesions and the subjective voice complaint rate in those with no organic laryngeal lesion. We performed a cross-sectional study using the data from 19,368 participants (418 rheumatoid arthritis patients and 18,950 controls) of the 2008-2011 Korea National Health and Nutrition Examination Survey. The associations between rheumatoid arthritis and organic laryngeal lesions/subjective voice complaints were analyzed using simple/multiple logistic regression analysis with complex sample adjusting for confounding factors, including age, sex, smoking status, stress level, and body mass index, which could provoke voice problems. Vocal nodules, vocal polyp, and vocal palsy were not associated with rheumatoid arthritis in a multiple regression analysis, and only laryngitis showed a positive association (adjusted odds ratio, 1.59; 95 % confidence interval, 1.01-2.52; P = 0.047). Rheumatoid arthritis was associated with subjective voice discomfort in a simple regression analysis, but not in a multiple regression analysis. Participants with rheumatoid arthritis were older, more often female, and had higher stress levels than those without rheumatoid arthritis. These factors were associated with subjective voice complaints in both simple and multiple regression analyses. Rheumatoid arthritis was not associated with organic laryngeal diseases except laryngitis. Rheumatoid arthritis did not increase the odds ratio for subjective voice complaints. Voice problems in participants with rheumatoid arthritis originated from the characteristics of the rheumatoid arthritis group (higher mean age, female sex, and stress level) rather than rheumatoid arthritis itself.

  15. Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis

    PubMed Central

    Machado, Marina Amaral de Ávila; de Moura, Cristiano Soares; Ferré, Felipe; Bernatsky, Sasha; Rahme, Elham; Acurcio, Francisco de Assis

    2016-01-01

    ABSTRACT OBJECTIVE To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients’ chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS The study included 11,642 patients with rheumatoid arthritis – 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD – and 1,251 patients with ankylosing spondylitis – 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing

  16. Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis.

    PubMed

    Kremer, Joel M

    2005-06-01

    T cells have a central role in the orchestration of the immune pathways that contribute to the inflammation and joint destruction characteristic of rheumatoid arthritis (RA). The requirement for a dual signal for T-cell activation and the construction of a fusion protein that prevents engagement of the costimulatory molecules required for this activation has led to a new approach to RA therapy. This approach is mechanistically distinct from other currently used therapies; it targets events early rather than late in the immune cascade, and it results in immunomodulation rather than complete immunosuppression. The fusion protein abatacept is a selective costimulation modulator that avidly binds to the CD80/CD86 ligands on an antigen-presenting cell, resulting in the inability of these ligands to engage the CD28 receptor on the T cell. Abatacept dose-dependently reduces T-cell proliferation, serum concentrations of acute-phase reactants, and other markers of inflammation, including the production of rheumatoid factor by B cells. Recent studies have provided consistent evidence that treatment with abatacept results in a rapid onset of efficacy that is maintained over the course of treatment in patients with inadequate response to methotrexate and anti-tumor necrosis factor therapies. This efficacy includes patient-centered outcomes and radiographic measurement of disease progression. Abatacept has also demonstrated a very favorable safety profile to date. This article reviews the rationale for this therapeutic approach and highlights some of the recent studies that demonstrate the benefits obtained by using abatacept. This clinical experience indicates that abatacept is a significant addition to the therapeutic armamentarium for the management of patients with RA. PMID:16357751

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

    PubMed Central

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

    2012-01-01

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

  18. Subacromial bursitis with giant rice bodies as initial presentation of rheumatoid arthritis.

    PubMed

    Subramaniam, Ramesh; Tan, Justina Wei Lyn; Chau, Cora Yuk Ping; Lee, Keng Thiam

    2012-10-01

    Rice body formation is a nonspecific response to chronic synovial inflammation associated with tuberculous arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, seronegative inflammatory arthritis, and even osteoarthritis. Such bodies were termed rice bodies because of their close resemblance to grains of polished white rice. We present a case report of a middle-aged woman with right shoulder subacromial/subdeltoid bursitis with giant rice body formation as her initial presentation of rheumatoid arthritis. Her right shoulder symptoms resolved after subacromial and subdeltoid bursectomy and removal of the rice bodies. She subsequently developed inflammatory arthritis of other joints, met the criteria for rheumatoid arthritis, and has been treated medically. PMID:23013846

  19. Synthesis of some CC chemokines and their receptors in the synovium in rheumatoid arthritis.

    PubMed

    Zhebrun, D A; Totolyan, Areg A; Maslyanskii, A L; Titov, A G; Patrukhin, A P; Kostareva, A A; Gol'tseva, I S

    2014-12-01

    We studied the expression of some CC chemokines and their receptors in the synovium of patients with rheumatoid arthritis, osteoarthrosis, and a history of joint injury. In patients with rheumatoid arthritis, the levels mRNA for some angiogenic and proinflammatory chemokines (CCL5/RANTES, CCL11/eotaxin, CCL24/eotaxin-2, and CCL26/eotaxin-3) and their receptors (CCR1, CCR2, CCR3, CCR4, and CCR5) was elevated. mRNA expression correlated with activity, stage, and serological status of rheumatoid arthritis. Obtained data confirm the importance of CC chemokines as mediators of angiogenesis and inflammation in the synovium in rheumatoid arthritis.

  20. Palindromic rheumatism with rheumatoid nodules: a case report with ultrastructural studies.

    PubMed Central

    Schreiber, S; Schumacher, H R; Cherian, P V

    1986-01-01

    Rheumatoid nodules developed on the finger tips of a patient with palindromic rheumatism. The patient had no bone cysts or erosions and had no rheumatoid factor. A light microscopic and ultrastructural study of a nodule showed a necrotic centre with fibrin, collagen, and granular material surrounded by large histiocytes, fibrocytes, lymphocytes, and vessels with adjacent mast cells as has been seen with nodules in classical rheumatoid arthritis (RA). We describe the first immunoperoxidase studies on a rheumatoid nodule and have identified reaction products for immunoglobulins and C3 in perivascular and endothelial cell vacuoles and in the necrotic centre. Images PMID:3954461

  1. Should rheumatoid factor in rheumatoid arthritis be sent to Davy Jones's Locker?

    PubMed

    Besada, E; Nikolaissen, C; Nossent, H

    2012-03-01

    This article reviews the characteristics and weaknesses of the rheumatoid factor (RF) assay compared with anti-citrullinated peptide antibody (ACPA) testing in the work-up of patients with synovitis. This should lead physicians to change their ordering habits and replace RF by ACPA. For RA diagnosis, good clinical judgement based on clinical history, physical examination and routine laboratory work exceeds the value of RF and ACPA assays. In settings of both low and high pretest probability, the added value of each of these assays is low. In cases with intermediate probability, ACPA assays are superior to immunoglobulin (Ig)M-RF because of their higher specificity, and they should be the first choice in a RA diagnostic work-up. Dual testing brings few additional advantages and increases costs significantly. ACPA and IgM-RF are both imperfect tests; around 30% of patients with manifest RA will test negative in both assays and therefore caution needs to be exercised when interpreting negative results. Since 2009, the anti-cyclic citrullinated peptide (anti-CCP) antibody assay has been the only assay available at our institution for RA work-up, with IgM-RF available on a case-by-case basis for non-RA diseases. This has led to a 70% reduction in RF assays performed annually. PMID:22211313

  2. Established rheumatoid arthritis: rationale for best practice: physicians' perspective of how to realise tight control in clinical practice.

    PubMed

    Horton, S C; Walsh, C A E; Emery, P

    2011-08-01

    Developments in the understanding of the pathogenesis of rheumatoid arthritis (RA) and the introduction of targeted biologic therapies have greatly advanced the management of RA in clinical practice. The management of RA is now aimed at achieving remission, to prevent joint damage and disability. In particular, a critical period early in disease is recognised, in which early aggressive treatment with disease-modifying therapy is advocated. Although a state of remission is the ideal, this chapter discusses the difficulties which may arise in achieving this goal in patients with established disease. The evidence for best management, aimed at achieving clinical remission in established disease, is reviewed. The consequences of incomplete control of chronic inflammation in established disease, including pain, disability and co-morbidities (such as cardiovascular disease and osteoporosis), also pose a significant clinical challenge. The rationale for a multidisciplinary team approach in reducing the associated morbidity and mortality of the disease are examined.

  3. 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

  4. [Hepatic haemangioma as sistemic manifestation of rheumatoid arthritis].

    PubMed

    Babaeva, A R; Kalinina, E V; Solodenkova, K S

    2015-01-01

    This article presents the clinical data regarding to the incidence of hepatic haemangioma in rheumatoid arthritis (RA) patients. Haemangioma of the liver has been diagnosed by ultrasonography dramatically oftener in RA than in OA: in 8 from 37 RA pts and neither in 120 osteoarthritis pts. Hepatic haemangioma was associated with long standing erosive RA, extra-articular RA manifestations, high levels of rheumatoid factor and ACCP. Moreover in RA pts with hepatic haemangioma we revealed significantly raised levels of pro-inflammatory cytokines, which can impact on the angiogenesis in RA. Obtained clinical data may contribute in the understanding of liver vessels involvement in RA and pose the role of systemic connective tissue lesion and immune inflammation in this process.

  5. 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.

  6. Treatment of intractable rheumatoid arthritis with lymphoid irradiation

    SciTech Connect

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

    1981-01-01

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

  7. 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

  8. 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.

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

    PubMed

    Márki-Zay, János; Tauberné Jakab, Katalin; Szerémy, Péter; 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

  10. Eye disease in a patient with rheumatoid arthritis.

    PubMed

    Shinzato, M; Yamamoto, J; Hirata, C E; Goldberg, A C; Yoshinari, N H; Bonfá, E

    1999-11-01

    We report the case of a 40-year-old woman with diffuse uveitis, sensorineural hearing loss and cerebrospinal fluid pleocytosis as features of Vogt-Koyanagi-Harada syndrome who developed symmetric polyarthritis and stiffness of small and large joints, in addition to rheumatoid arthritis. Although their target tissues are distinct, both diseases have a possible autoimmune origin strongly associated with HLA-DRB4.

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

    PubMed

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

    2014-01-01

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

  12. 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

  13. 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

  14. Usefulness of sonography in the diagnosis of rheumatoid hand.

    PubMed

    Zaniewicz-Kaniewska, Katarzyna; Sudoł-Szopińska, Iwona

    2013-09-01

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

  15. Usefulness of sonography in the diagnosis of rheumatoid hand

    PubMed Central

    Sudoł-Szopińska, Iwona

    2013-01-01

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

  16. Pain and functional limitations in individuals with rheumatoid arthritis.

    PubMed

    MacKinnon, J R; Avison, W R; McCain, G A

    1994-03-01

    The focus of this investigation was to determine if health status variables such as pain and functional limitations are correlated with an individual's occupational profile (work, activities of daily living and leisure), and psychological adjustment (depression, anxiety and dissatisfaction with life). This study reports our findings for 143 individuals with rheumatoid arthritis (RA). It would appear from the results of this study that functional limitations have an even greater impact on individuals with RA than pain. This findings and its implications are discussed.

  17. [Rheumatoid factor or antinuclear antibodies as incidental finding].

    PubMed

    Biesen, R; Burmester, G-R; Hiepe, F

    2014-10-01

    Rheumatoid factor and antinuclear antibodies are detectable in many different conditions and are ordered by various specialities. The interpretation of results, however, is quite complex.The objective of this article is to help apply these tests correctly and enable an accurate interpretation of the test results. Furthermore, we describe the steps in the differential diagnostics for selecting those patients who need to be referred to a rheumatologist.

  18. Conservative treatments for rheumatoid arthritis in the foot and ankle.

    PubMed

    Anain, Joseph M; Bojrab, Angela R; Rhinehart, Francine C

    2010-04-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease that attacks peripheral joints, causing their destruction. Several pharmacologic therapies and physical modalities are available for its treatment. Because of the progressive nature of RA, complementary and alternative medicine therapy in conjunction with conventional medicine is administered to patients with RA. This article discusses the presence of undiagnosed RA in the foot and ankle and reviews the concurrent nonoperative measures in treatment, including pharmacologic and physical modalities.

  19. Rheumatoid Arthritis and Salivary Biomarkers of Periodontal Disease

    PubMed Central

    Mirrielees, Jeffrey; Crofford, Leslie J.; Lin, Yushun; Kryscio, Richard J.; Dawson, Dolphus R.; Ebersole, Jeffrey L.; Miller, Craig S.

    2010-01-01

    Aim To test the hypothesis that rheumatoid arthritis influenced levels of salivary biomarkers of periodontal disease. Methods Medical assessments, periodontal examinations, and pain ratings were obtained from 35 rheumatoid arthritis, 35 chronic periodontitis and 35 age and gender-matched healthy controls in a cross-sectional, case-controlled study. Unstimulated whole saliva samples were analyzed for interleukin-1β (IL-1β), matrix-metalloproteinase-8 (MMP-8) and tumor necrosis factor-α (TNF)-α concentrations. Results The arthritis and healthy groups had significantly less oral disease than the periodontitis group (p<0.0001), with the arthritis group having significantly more sites bleeding on probing (BOP) than matched controls (p=0.012). Salivary levels of MMP-8 and IL-1β were significantly elevated in the periodontal disease group (p≤0.002), and IL-1β was the only biomarker with significantly higher levels in the arthritis group compared with controls (p=0.002). Arthritis patients receiving anti-TNF-α antibody therapy had significantly lower IL-1β and TNF-α levels compared with arthritis patients not on anti-TNF-α therapy (p=0.016, p=0.024) and healthy controls (p<0.001, p=0.011), respectively. Conclusion Rheumatoid arthritis patients have higher levels of periodontal inflammation than healthy controls, ie. increased BOP. Systemic inflammation appears to influence levels of select salivary biomarkers of periodontal disease, and anti-TNF-α antibody-based disease modifying therapy significantly lowers salivary IL-1β and TNF-α levels in rheumatoid arthritis. PMID:20880053

  20. New and emerging therapies for the treatment of rheumatoid arthritis

    PubMed Central

    Feely, Michael G

    2010-01-01

    The introduction of tumor necrosis factor (TNF) inhibitors in the late 1990s significantly changed the therapeutic approach for rheumatoid arthritis (RA). With the approval of subsequent TNF inhibitors as well as other biologic agents effective in the management of RA, the treatment paradigm has become increasingly complex. This review examines the current literature regarding the efficacy and toxicity of these and other new anti-rheumatic therapies and discusses effective therapeutic strategies for their use.