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1

[Early diagnosis of rheumatoid arthritis].  

PubMed

On the basis of own observations of courses the author adopts a definite attitude to the early symptomatology of the rheumatoid arthritis. During the first weeks of the rheumatoid arthritis the following symptoms are found: articular syndromes, more frequently in form of obstinate polyarthralgias, mono-oligoarthritis, accompanied by morning rigidity and accelerated BSR as well as impairment of the general condition. In the majority of the patients only the tentative diagnosis rheumatoid arthritis may be made. After a one to three months' course of the disease the diagnosis becomes more probable. It is above all based on constancy and symmetry, characteristic localisation of the articular process, morning rigidity, radiologically paraarticular loosening of the structure and morphological symptoms of an acute and subacute synovialitis. 6 to 12 months after the beginning of the disease a clinical picture forms which allows to make the diagnosis of a certain or classical rheumatoid arthritis in accordance with the criteria of the ARA. The occurrence of a high activity of multiple affection of the joints (permanent symmetrical polyarthritis including the small joints of the hands and feet), distinctive morning rigidity, high fever and much accelerated BSR, beginning with the first weeks of the disease, speaks for the possibility of the development of an arthrovisceral form of the course of rheumatoid arthritis. PMID:997658

Astapenko, M G; Otto, W; Trofimowa, T M; Häntzschel, H; Tautenhahn, B; Reinelt, D; Treutler, H; Speranskij, A I; Mylow, N M; Duljapin, W A; Tarasenkowa, T A

1976-08-15

2

Pathogenesis of rheumatoid arthritis: how early is early?  

Microsoft Academic Search

Studies of cytokine expression in rheumatoid arthritis have provided key insights into the pathogenesis of disease and have offered clues for effective therapy. Patterns of T-cell products in chronic rheumatoid synovitis suggest that T helper type 1 cells contribute to the perpetuation of disease. However, there is no guarantee that the mechanisms of late disease are identical to very early

Gary S Firestein

2005-01-01

3

Early environmental factors and rheumatoid arthritis  

PubMed Central

The precise cause of autoimmune diseases such as rheumatoid arthritis (RA) remains uncertain. In recent years there has been extensive investment in pursuing genes important in RA. However, estimates suggest that the risk of developing RA is at most 50% determined by genes. There has been limited success defining the environmental factors important in developing RA. We hypothesize that this lack of success may be due to a concentration on the time around disease onset. There is evidence of production of the autoantibodies rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) and increased levels of C-reactive protein (CRP) years before RA becomes clinically apparent. In addition, early life events including intrauterine growth retardation (IUGR) may have long lasting effects on immune function. We review the evidence that the early environment through effects on growth and infectious exposure may influence the likelihood of developing autoimmune diseases such as RA.

Edwards, C J; Cooper, C

2006-01-01

4

Infliximab in active early rheumatoid arthritis  

PubMed Central

Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA). Methods: Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy (ATTRACT) study, in which 428 patients with active RA despite MTX therapy received placebo with MTX (MTX-only) or infliximab 3 mg/kg or 10 mg/kg every (q) 4 or 8 weeks with MTX (infliximab plus MTX) for 102 weeks. Early RA was defined as disease duration of 3 years or less; 82 of the 428 patients (19%) met this definition. Structural damage was assessed with the modified van der Heijde-Sharp score. The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group. Results: The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen. Consistent benefit was seen in the joints of both hands and feet. Conclusions: Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment. Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity.

Breedveld, F; Emery, P; Keystone, E; Patel, K; Furst, D; Kalden, J; St, C; Weisman, M; Smolen, J; Lipsky, P; Maini, R

2004-01-01

5

Early rheumatoid arthritis —onset, course, and outcome over 2 years  

Microsoft Academic Search

Summary  Eighty-nine patients, 33 men and 56 women, with early definite rheumatoid arthritis were followed for 2 years. Two-thirds were seropositive. About 1\\/3 were eventually treated with second line drugs. The disease mostly had an insidious onset initially involving the finger joints. Early remission occurred in 16%. Patient relevant measures such as pain, patient's overall assessment of disease activity and anxiety

K. B. Eberhardt; L. C. Rydgren; H. Pettersson; F. A. Wollheim

1990-01-01

6

Prognostic value of early features in rheumatoid disease.  

PubMed

Extensive data on 102 patients who presented with rheumatoid disease within a year of onset were gathered by a prospective study to assess the prognostic value of early features. Outcome was evaluated at a mean 4-5 years from onset on the basis of functional grade, extent of joint disease, early morning stiffness, and grip strength. Twenty-six patients improved, 14 pursued a mild steady course, and 62 had a persistently severe or deteriorating condition. The features recorded at the first visit were correlated with outcome. Those indicating a poor prognosis were: older age at onset, being underweight, poor grip strength, many affected joints, involvement of wrist or metatarsophalangeal joints, poor functional status, fulfilment of many of the American Rheumatism Association criteria for rheumatoid disease, raised erythrocyte sedimentation rate, seropositivity on sheep cell agglutination or latex tests, low haemoglobin level, raised blood urea level, and early erosions on x-ray films. PMID:1083760

Fleming, A; Crown, J M; Corbett, M

1976-05-22

7

How early is the atherosclerotic risk in rheumatoid arthritis?  

PubMed

Rheumatoid arthritis is a systemic disease characterized by a reduced life expectancy mainly due to cardiovascular disease. In long-standing disease, it has been widely demonstrated that both traditional cardiovascular risk factors than chronic inflammation and immune-mediated mechanisms play a relevant role in atherosclerosis. Recently, it has been shown that the increased cardiovascular risk appears to precede rheumatoid arthritis onset and that particular immune and inflammatory factors, predating disease presentation, in association with a well-defined genetic background, may be associated with increased risk of accelerated atherosclerosis in patients with early disease. However, the effect of early immunosuppressive treatment on cardiovascular disease outcome remains uncertain. A multidisciplinary cardiovascular risk management is required to provide the better care of patients with RA at disease onset. PMID:20542146

Bartoloni, Elena; Alunno, Alessia; Bistoni, Onelia; Gerli, Roberto

2010-08-01

8

Clinical and Morphological Aspects of Sinovitis in Early Rheumatoid Arthritis  

PubMed Central

The earliest joint changes in rheumatoid arthritis occur in the synovial membrane, leading to development of an unsuppurated proliferative synovitis. This study is based on 33 cases of early rheumatoid arthritis for which we have investigated a series of clinical and morphological parameters. For the examined cases we found that the disease incidence reached its maximum in fifth and sixth decades of life, predominantly in females, over half of cases being diagnosed in the first six months from the onset of the disease. Histopathological study of synovial membrane samples showed characteristic morphological changes but unspecific for the disease, represented by the synoviocytes proliferation, inflammatory infiltrates, fibrinoid necrosis, fibroblasts proliferation and vascular changes. Reaching composite histological score may be useful by providing some information on the severity of the disease.

Capitanescu, B.; Simionescu, Cristiana; Margaritescu, C.; Stepan, Al.; Ciurea, Raluca

2011-01-01

9

Factors associated with time to diagnosis in early rheumatoid arthritis.  

PubMed

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

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

2014-01-01

10

Are glucocorticoids harmful to bone in early rheumatoid arthritis?  

PubMed

In the past, patients with rheumatoid arthritis (RA) were treated with monotherapy with conventional drugs, such as sulfasalazine, methotrexate, and intramuscular gold, which often leads to persistent arthritis, loss of functional capacity, and decreased quality of life. Both active RA and the use of high-dose glucocorticoids (GCs) are associated with generalized bone loss and fractures, but it is well known that GCs have a strong immunosuppressive effect. With the introduction of tumor necrosis factor (TNF-?)-blockers and other biologics, clinical remission is a realistic target in approximately half of the early RA patients; the same seems to be true for the use of methotrexate with chronic low-dose or initially high-dose GCs. With the use of a treat-to-target strategy focusing on clinical remission or low disease activity in early RA patients, the negative effects of systemic inflammation on bone can be arrested, and both local bone loss (in the joints) and generalized bone loss at the spine and hips can be prevented. PMID:24739059

Lems, Willem F

2014-05-01

11

Managing early presentation of rheumatoid arthritis. Systematic overview.  

PubMed Central

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.

Glazier, R.

1996-01-01

12

Rheumatoid arthritis and primary care: the case for early diagnosis and treatment.  

PubMed

Rheumatoid arthritis is a chronic inflammatory disease that can cause severe pain and disability. Disease management historically was based on a "therapeutic pyramid" in which treatment escalated as symptoms worsened. However, the demonstration of early joint damage in patients with rheumatoid arthritis has emphasized the importance of early identification and treatment. Key features in establishing a diagnosis include joint examinations, assessments of extra-articular manifestations, laboratory tests, and radiologic examinations. Care must be taken to rule out other disorders with symptoms that overlap those of rheumatoid arthritis. Treatment of rheumatoid arthritis typically involves disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and low-dose corticosteroids--often used in combination. A new class of therapeutic agents designed to neutralize inflammatory cytokines has added a new dimension to the therapeutic armamentarium against rheumatoid arthritis. Etanercept, a bioengineered soluble receptor fusion protein that blocks tumor necrosis factor activity, is the first compound in this class to be approved for treatment of patients with refractory rheumatoid arthritis. Therapeutic trials indicate that etanercept can reduce disease activity with relatively few drug-related adverse effects, thus helping persons with rheumatoid arthritis return to more normal, healthy lives. PMID:10405518

Calabrese, L H

1999-06-01

13

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

PubMed

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

Verstappen, Suzanne M M

2013-08-01

14

Left ventricular function in treatment-naive early rheumatoid arthritis  

PubMed Central

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

L?gstrup, Brian B; Deibjerg, Lone K; Hedemann-Andersen, Agnete; Ellingsen, Torkell

2014-01-01

15

Correlation between upper limb functional ability and structural hand impairment in an early rheumatoid population  

Microsoft Academic Search

Objective: To explore the relationship in individuals with early rheumatoid arthritis (RA) between self-report upper limb function, therapist-assessed upper limb function and therapist-assessed measures of structural impairment (handgrip, active hand motion and metacarpophalangeal (MCP) joint ulnar deviation).Design: Thirty-six patients with early RA were recruited across seven outpatient occupational therapy departments.Outcome measures: Upper limb functional activity and ability was measured using

J Adams; J Burridge; M Mullee; A Hammond; C Cooper

2004-01-01

16

Early results of the Universal total wrist arthroplasty in rheumatoid arthritis  

Microsoft Academic Search

Early results of 2 surgeons involved in a prospective study of the Universal total wrist prosthesis (KMI, San Diego, CA) are reported. Twenty-two prostheses were implanted in 19 patients for the treatment of severe rheumatoid arthritis. Two-year follow-up results of 8 wrists and 1-year follow-up results of 14 wrists were reviewed. Total arcs of motion (flexion[ndash ]extension, radial[ndash ]ulnar deviation,

Brian J. Divelbiss; Christer Sollerman; Brian D. Adams

2002-01-01

17

How accurately does a simulation glove reflect function compared to rheumatoid arthritis sufferers?  

PubMed Central

INTRODUCTION This study assessed the ability of gloves to simulate rheumatoid arthritis of the hand. SUBJECTS AND METHODS Assessments were made in the dominant hand of 24 healthy volunteers with no glove, glove A (simulating stiffness only) and glove B (simulating stiffness and pain). Results were compared to data held on 23 rheumatoid arthritis patients. Sollerman score was used as a standardised measure of hand function and time taken to complete testing was recorded. Grip strength was also measured in volunteers. RESULTS Both gloves simulate a reduction in power and prolong time taken to complete Sollerman hand-function testing. The gloves are less able to simulate a matched reduction in function when compared to rheumatoid arthritis sufferers. Sollerman score is 9.7% less in rheumatoid arthritis hands than a healthy volunteer using the glove. CONCLUSIONS The glove could, therefore, be used to guide future design of tools and aides that accommodate for hand disorders. More work on the usefulness of such disease simulation in the design of tools for such patients is needed.

Hall, TC; Nixon, MF; Dias, JJ; Graham, T; Cook, S

2010-01-01

18

Women with early rheumatoid arthritis are referred later than men  

PubMed Central

Methods: All referred patients with early RA over a 1 year period were prospectively registered. The lag time between disease onset and the first encounter with a physician was recorded as the "patient's delay". The time between this encounter and the referral to our department was recorded as the "physician's delay". The lag time between referral and rheumatological encounter was recorded as the "hospital's delay". Results: The median total lag time between onset of RA and rheumatological encounter was 16 weeks, with no difference between men and women. Women were referred significantly later than men ("physician's delay" median 10 weeks v 3 weeks). The "patient's delay" and the "hospital's delay" were a median of 4 weeks each. Conclusion: Women with early RA were referred later than men and the total lag time between disease onset and rheumatological encounter was quite long for both sexes.

Palm, O; Purinszky, E

2005-01-01

19

Tailored cognitive-behavioral therapy in early rheumatoid arthritis for patients at risk: a randomized controlled trial  

Microsoft Academic Search

Recent developments in chronic pain research suggest that effectiveness of cognitive-behavioral therapy (CBT) may be optimized when applying early, customized treatments to patients at risk. For this purpose, a randomized, controlled trial with tailor-made treatment modules was conducted among patients with relatively early rheumatoid arthritis (RA disease duration of

Andrea W. M Evers; Floris W Kraaimaat; Piet L. C. M van Riel; Alphons J. L de Jong

2002-01-01

20

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

Microsoft Academic Search

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

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

2005-01-01

21

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

Microsoft Academic Search

INTRODUCTION: The present study was carried out to assess whether IgA-class antibodies against cyclic citrullinated peptides (IgA anti-CCP) in recent-onset rheumatoid arthritis add diagnostic and\\/or prognostic information to IgG anti-CCP analysis. METHODS: Serum samples were obtained from 228 patients with recent-onset (<12 months) rheumatoid arthritis at the time of inclusion in the Swedish TIRA cohort (Swedish Early Intervention in Rheumatoid

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

2008-01-01

22

Diagnostic performance of the Forced Oscillation Technique in the detection of early respiratory changes in Rheumatoid Arthritis  

Microsoft Academic Search

The objective of this study was to evaluate the clinical potential of the Forced Oscillation Technique (FOT) in the detection of the early alterations in respiratory mechanics of Rheumatoid Arthritis (RA) patients. A total of 36 individuals were analyzed, 18 healthy and 18 with RA. The clinical usefulness of the parameters was evaluated investigating sensibility (Se), specificity (Sp) and the

A. C. D. Faria; A. J. Lopes; J. M. Jansen; G. R. C. Pinheiro; P. L. Melo

2010-01-01

23

FACTORS PREDICTING DEATH, SURVIVAL AND FUNCTIONAL OUTCOME IN A PROSPECTIVE STUDY OF EARLY RHEUMATOID DISEASE OVER FIFTEEN YEARS  

Microsoft Academic Search

SUMMARY Sixty-four survivors from a prospective study of early rheumatoid disease were assessed again at a mean of 15.2 years from presentation and their status compared with 29 patients who had died. Eleven of the dead and only two of the survivors had been treated with steroids. There was a small increase in mortality due to the disease itself but

M. CORBETT; S. DALTON; A. YOUNG; A. SILMAN; M. SHIPLEY

1993-01-01

24

Soluble CD30 in early rheumatoid arthritis as a predictor of good response to second-line therapy  

Microsoft Academic Search

Objective. To evaluate whether serum levels of the soluble form of CD30 (sCD30) correlate with disease activity in early rheumatoid arthritis (RA) and may have prognostic value in predicting the response to disease-modifying anti-rheumatic drugs (DMARDs). Methods. The levels of sCD30 and C-reactive protein (CRP) were measured in the serum of 14 untreated subjects with early RA, before and during

R. Gerli; O. Bistoni; C. Lunardi; R. Giacomelli; C. Tomassini; P. Biagini; C. Pitzalis

1999-01-01

25

Increased frequency of metabolic syndrome among Vietnamese women with early rheumatoid arthritis: a cross-sectional study  

Microsoft Academic Search

INTRODUCTION: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease, and this occurs early in the disease process. The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in RA; however, little information is available regarding MetS in early RA. We aimed to identify the prevalence of MetS and to determine the potential

Hanh-Hung Dao; Quan-Trung Do; Junichi Sakamoto

2010-01-01

26

Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis  

PubMed Central

Objective: To evaluate a contribution of selected laboratory parameters for a prediction of progressive and erosive development in patients with early rheumatoid arthritis (RA). Methods: In a prospective study baseline levels of antibodies to cyclic citrullinated peptide (anti-CCP), IgM, IgA, and IgG rheumatoid factors (RFs) were measured by enzyme linked immunosorbent assay (ELISA) in 104 patients with RA with disease duration <2 years. Antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence. Patients were divided into two groups based either on the presence or absence of erosions or according to progression of Larsen score at the end of the 24 months' follow up. Results: Sixty seven (64%) patients developed radiographic erosions, 49 (47%) had progression in Larsen score, and 36 (35%) progressed by more than 10 Larsen units. Significant differences in erosions and progression between the two groups were detected for anti-CCP, AKA, APF, IgM RF, IgA RF, and IgG RF. Baseline Larsen score correlated significantly with anti-CCP, IgM RF, and IgA RF levels, and all measured antibodies correlated with the progression >10 units. The combination of anti-CCP and IgM RF increased the ability to predict erosive and progressive disease. Conclusion: The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course. Combined analysis of anti-CCP and IgM RF provides the most accurate prediction.

Vencovsky, J; Machacek, S; Sedova, L; Kafkova, J; Gatterova, J; Pesakova, V; Ruzickova, S

2003-01-01

27

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

PubMed Central

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.

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

2014-01-01

28

Clinical correlations with Porphyromonas gingivalis antibody responses in patients with early rheumatoid arthritis  

PubMed Central

Introduction Prior studies have demonstrated an increased frequency of antibodies to Porphyromonas gingivalis (Pg), a leading agent of periodontal disease, in rheumatoid arthritis (RA) patients. However, these patients generally had long-standing disease, and clinical associations with these antibodies were inconsistent. Our goal was to examine Pg antibody responses and their clinical associations in patients with early RA prior to and after disease-modifying antirheumatic drug (DMARD) therapy. Methods Serum samples from 50 DMARD-naïve RA patients were tested using an enzyme-linked immunosorbent assay with whole-Pg sonicate. For comparison, serum samples were tested from patients with late RA, patients with other connective tissue diseases (CTDs), age-similar healthy hospital personnel and blood bank donors. Pg antibody responses in early RA patients were correlated with standard RA biomarkers, measures of disease activity and function. Results At the time of enrollment, 17 (34%) of the 50 patients with early RA had positive immunoglobulin G (IgG) antibody responses to Pg, as did 13 (30%) of the 43 patients with late RA. RA patients had significantly higher Pg antibody responses than healthy hospital personnel and blood bank donors (P < 0.0001). Additionally, RA patients tended to have higher Pg antibody reactivity than patients with other CTDs (P = 0.1), and CTD patients tended to have higher Pg responses than healthy participants (P = 0.07). Compared with Pg antibody-negative patients, early RA patients with positive Pg responses more often had anti-cyclic citrullinated peptide (anti-CCP) antibody reactivity, their anti-CCP levels were significantly higher (P = 0.03) and the levels of anti-Pg antibodies correlated directly with anti-CCP levels (P < 0.01). Furthermore, at the time of study entry, the Pg-positive antibody group had greater rheumatoid factor values (P = 0.04) and higher inflammatory markers (erythrocyte sedimentation rate, or ESR) (P = 0.05), and they tended to have higher disease activity scores (Disease Activity Score based on 28-joint count (DAS28)-ESR and Clinical Disease Activity Index) and more functional impairment (Health Assessment Questionnaire). In Pg-positive patients, greater disease activity was still apparent after 12 months of DMARD therapy. Conclusions A subset of early RA patients had positive Pg antibody responses. The responses correlated with anti-CCP antibody reactivity and to a lesser degree with ESR values. There was a trend toward greater disease activity in Pg-positive patients, and this trend remained after 12 months of DMARD therapy. These findings are consistent with a role for Pg in disease pathogenesis in a subset of RA patients.

2013-01-01

29

The performance of a point of care test for detection of anti-mutated citrullinated vimentin and rheumatoid factor in early rheumatoid arthritis.  

PubMed

The purpose of this study was to determine the diagnostic performance of a point-of-care test (POCT) for detection of anti-mutated citrullinated vimentin (anti-MCV) and rheumatoid factor (RF) in early rheumatoid arthritis (RA) with 2 years of disease duration or less. Additionally, we evaluated the agreement of these tests when using EDTA whole blood and capillary blood. Patients with RA and other rheumatic disorders were consecutively recruited from the rheumatology outpatient clinic. The POCT for detection of anti-MCV and RF using capillary blood and EDTA whole blood was performed in 78 patients with early RA, 55 patients with other rheumatic disorders, and 55 healthy blood donors. The sensitivity and specificity of anti-MCV POCT in patients with early RA were 64 and 97 %, respectively, while the sensitivity and specificity of RF POCT were 51 and 95 %, respectively. The positive likelihood ratio of the POCT for anti-MCV was higher than those for RF (23.5 vs 9.4). The negative likelihood was 0.37 for anti-MCV and 0.52 for RF. There were three cases with false positive for anti-MCV including a patient with psoriatic arthritis and the other two with systemic sclerosis. The agreement between capillary blood and EDTA whole blood testing for anti-MCV and RF was low to moderate with Cohen's kappa of 0.58 and 0.49, respectively. This POCT for detection of anti-MCV and RF yielded high specificity and may be a valuable tool for the diagnosis of early RA. Using this POCT with EDTA whole blood instead of capillary blood is not recommended. PMID:24577818

Rojanasantikul, Preeda; Pattrapornpisut, Prapa; Anuruckparadorn, Kulvara; Katchamart, Wanruchada

2014-07-01

30

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

PubMed Central

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

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

2013-01-01

31

Synovial mast cell responses during clinical improvement in early rheumatoid arthritis  

PubMed Central

OBJECTIVES—To determine the synovial mast cell response in early rheumatoid arthritis (RA) during clinical improvement, and to examine for relations with clinical and histological parameters of disease activity.?METHODS—Twenty two synovial samples were obtained from six patients with RA using needle arthroscopy. The mean disease duration at baseline was eight months, and two to three further samples were obtained over a mean follow up period of 15 months during which treatment initiated clinical improvement occurred. Sections were immunostained to detect MCT and MCTC mast cells and correlations were sought between clinical and histological data.?RESULTS—The overall mean synovial mast cell density was 40.3 cells/mm2, with regional densities of 60.6 and 34.2 mast cells/mm2 in the superficial and deeper synovial layers respectively. The MCT subset predominated, outnumbering MCTC by 3:1. There was a significant correlation between the histological inflammation index and the MCT density, (r = 0.4, p < 0.05) but not the MCTC subset. The regional distribution and predominant subset of mast cells varied in individual patient's synovia over time, with a trend towards restriction of the mast cell response to the superficial synovium during clinical improvement.?CONCLUSIONS—The mast cell response in early RA is characterised by substantial expansion of predominantly MCT mast cells that correlates with histological indices of inflammation. During clinical improvement, this expansion tended to become more superficial. Taken together with previous studies of long duration RA, which implicate MCTC cells in synovial damage and disease progression, these results suggest that MCT and MCTC mast cells may possess distinct functions in the spectrum of inflammatory events occurring during RA.??

Gotis-Graham, I.; Smith, M.; Parker, A.; McNeil, H

1998-01-01

32

Relationship between pulse wave velocity and serum YKL-40 level in patients with early rheumatoid arthritis.  

PubMed

Subclinical atherosclerosis has been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs of cardiovascular disease (CVD). The aim of this study was to investigate the relationship between serum YKL-40 level and arterial stiffness in patients with ERA. Forty two patients with ERA and 35 healthy controls with no history or current sign of CVD were included in the study. ERA patients with active disease, defined as DAS28 ? 3.2, and symptoms onset <12 months were recruited. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (CF-PWV), and the intima-media thickness carotid (IMT-C) was measured by carotid ultrasonography. Serum YKL-40 levels were measured by an enzyme-linked immunoassay method. The mean age was 43.1 ± 5.8 years in ERA patients and 41.0 ± 5.9 years in control group. The CFPWV and IMT-C of the ERA patients were determined significantly higher than the control group (P = .001, P < .001, respectively). YKL-40 levels were significantly elevated in ERA patients than controls (P = .008). The serum levels of YKL-40 in the ERA patients showed a strong correlation with CF-PWV (r = .711, P < .001) and IMT-C (r = .733, P < .001). Multiple linear regression analysis revealed that CF-PWV could be explained by serum YKL-40 levels (adjusted R² = .493, P < .001). We have shown that patients with ERA had increased CF-PWV and serum YKL-40 levels. In addition, there was an association between CF-PWV values and serum YKL-40 levels in patients with ERA. As a result, we believe that serum YKL-40 level and CF-PWV might reflect early atherosclerosis in patients with ERA. PMID:23797781

Turkyilmaz, Aysegul Kucukali; Devrimsel, Gul; Kirbas, Aynur; Cicek, Yuksel; Karkucak, Murat; Capkin, Erhan; Gokmen, Ferhat

2013-11-01

33

Relationship between inflammation and joint destruction in early rheumatoid arthritis: a mathematical description  

PubMed Central

Background: The relationship between inflammation and joint destruction in rheumatoid arthritis (RA) has not been unequivocally characterised. Joint destruction may result from the cumulative inflammatory burden over time, modified by an individual constant factor. Objective: To test the hypothesis that the relationship between radiological progression and inflammation can mathematically be expressed as: ? where ? is a factor that varies from person to person. Methods: Clinical data and radiographs of 76 patients with early RA receiving different disease modifying antirheumatic drugs were analysed. Radiographs were quantified using the modified Larsen score and the "X-Ray RheumaCoach" software. The cumulative inflammatory burden was estimated by the time integrated 28 joint Disease Activity Score (DAS28), calculated as the area under the curve. Results: 76 patients with early RA who started treatment with methotrexate (n = 20), sulfasalazine (n = 37), or oral gold (n = 19) monotherapy were evaluated. The mean (SEM) DAS28 decreased from 4.6 (0.1) at baseline to 2.3 (0.1) after 2 years. The mean (SEM) ?Larsen score from baseline to year 2 was 10.3 (1.5). Correlation between cumulative inflammation and radiographic change was poor. In contrast, when calculating a person's factor ? in year 1 (?1) and year 2 (?2), a strong and significant correlation (r = 0.58, p<0.000001) was seen between ?1 and ?2. Conclusions: Joint destruction is the result of the cumulative burden of inflammation over time, modified by an individual factor ? that remains relatively constant over the first 2 years of observation. The data support a mathematical model that expresses the interrelationship between inflammation and joint destruction.

Wick, M; Lindblad, S; Klareskog, L; van Vollenhoven, R F

2004-01-01

34

Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study  

PubMed Central

Introduction Disease activity, severity and comorbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in patients with early disease. Methods In this study, 950 RA patients were followed regularly from the time of inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or swollen joints, Visual Analogue Scale pain and global scores, and Disease Activity Score in 28 joints (DAS28)) and function (Health Assessment Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of the hands and feet (erosions based on Larsen score), extraarticular disease, nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs) were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid factor, antinuclear antibodies and antibodies against cyclic citrullinated peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analysed at the time of inclusion. Data were stratified as young-onset RA (YORA) and late-onset RA (LORA), which were defined as being below or above the median age at the time of onset of RA (58 years). Results LORA was associated with lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01), but with greater disease activity at the time of inclusion measured on the basis of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24 months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA patients. At baseline and 24 months, LORA was more often associated with erosions (P < 0.01 for both) and higher Larsen scores (P < 0.001 for both). LORA was more often treated with corticosteroids (P < 0.01) and less often with methotrexate (P < 0.001) and biologics (P < 0.001). YORA was more often associated with early DMARD treatment (P < 0.001). The results of multiple regression analyses supported our findings regarding the impact of age on chosen treatment. Conclusion YORA patients were more frequently ACPA-positive than LORA patients. LORA was more often associated with erosions, higher Larsen scores, higher disease activity and higher HAQ scores at baseline. Nevertheless, YORA was treated earlier with DMARDs, whilst LORA was more often treated with corticosteroids and less often with DMARDs in early-stage disease. These findings could have implications for the development of comorbidities.

2014-01-01

35

Spontaneous expression of immediately-early response genes c-fos and egr-1 in collagenase-producing rheumatoid synovial fibroblasts  

Microsoft Academic Search

In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could

A. Trabandt; W. K. Aicher; R. E. Gay; V. P. Sukhatme; H.-G. Fassbender; S. Gay

1992-01-01

36

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

PubMed Central

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.

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

37

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

Microsoft Academic Search

OBJECTIVESTo evaluate the role of magnetic resonance imaging (MRI) of the wrist in detecting early joint damage in patients with rheumatoid arthritis (RA).METHODSMRI was performed on 42 patients with early RA (median symptom duration of four months). Scans were scored separately by two musculoskeletal radiologists using a newly devised scoring system, which was validated. MRI findings were compared with plain

Fiona M McQueen; Neal Stewart; Jeff Crabbe; Elizabeth Robinson; Sue Yeoman; Paul L J Tan; Lachy McLean

1998-01-01

38

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

PubMed Central

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

2014-01-01

39

Prediction of erosiveness and rate of development of new erosions in early rheumatoid arthritis  

Microsoft Academic Search

Fifty eight patients suffering from a recent onset of rheumatoid arthritis (RA) were studied. Fifty six patients were followed up for 24 months and two for 18 months. Erosions were detected in 17 patients at the onset and at the end of the follow up period the number of patients with erosions was 44. The erosiveness in the joint groups

T T Möttönen

1988-01-01

40

Seroreactivity to Borrelia burgdorferi antigens in early rheumatoid arthritis: a case-control study  

Microsoft Academic Search

SUMMARY This study investigates the seroreactivity to Borrelia burgdorferi antigens of patients suÄering from rheumatoid arthritis (RA) for <5 yr. Subjects were matched with controls for age, sex and area of residence in order to minimize the risk of diÄerential exposure to B. burgdorferi. A total of 57 pairs were tested by immunofluorescence assay (IFA) and Western blotting. Only two

I. CHARY-VALCKENAERE; F. GUILLEMIN; J. POUREL; F. SCHIELE

1997-01-01

41

Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis  

Microsoft Academic Search

Rheumatoid arthritis (RA) is a chronic disease requiring potential nephrotoxic therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs). The rationale of our study was to examine the renal status of patients suffering from prolonged RA by means of plasma cystatin C, a new parameter of renal function. Fifty-six patients affected with RA for more than 5

Harald Mangge; Peter Liebmann; Hinazant Tanil; Josef Herrmann; Carola Wagner; Siegfried Gallistl; Konrad Schauenstein; Wolfgang Erwa

2000-01-01

42

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

PubMed Central

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

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

2005-01-01

43

Inter-observer agreement of standard joint counts in early rheumatoid arthritis: a comparison with grey scale ultrasonography a preliminary study  

Microsoft Academic Search

Objectives. The aims of the present study were to assess the inter-observer agreement of standard joint count and to compare clinical examination with grey scale ultrasonography (US) findings in patients with early rheumatoid arthritis (RA). Methods. The study was conducted on 44 RA patients with a disease duration of <2yrs. Clinical evaluation was performed independently by two rheumatologists for detection

F. Salaffi; E. Filippucci; M. Carotti; E. Naredo; G. Meenagh; A. Ciapetti; V. Savic; W. Grassi

2008-01-01

44

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

Microsoft Academic Search

The relationships between two personality characteristics (neuroticism, extraversion), three types of supportive transactions (emotional support, social companionship, instrumental support) and satisfaction with these transactions, and two aspects of mental health (feelings of anxiety and depressive mood) were studied among 280 patients with early rheumatoid arthritis. Structural equation modeling of the relevant variables showed that people with a more neurotic personality

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

2005-01-01

45

Changes in Lipoproteins Associated with Treatment with Methotrexate or Combination Therapy in Early Rheumatoid Arthritis: Results from the TEAR Trial  

PubMed Central

Objective To study changes in lipid profiles at 24 weeks among early rheumatoid arthritis (RA) patients participating in the Treatment of Early Rheumatoid Arthritis (TEAR) Trial randomized to initiate methotrexate plus etanercept (MTX+ETA), triple therapy (TT) [MTX plus sulfasalazine plus hydroxychloroquine] or aggressively-titrated MTX monotherapy. Methods The TEAR biorepository study had 459 participating patients. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured in serum plasma at 0 and 24 weeks. Results At 24 weeks, there were statistically significant mean increases in cholesterol levels in the MTX + ETA, TT, and MTX monotherapy arms, the observed increases were 31.4, 28.7 and 30 mg/dL in LDL-C; 19.3, 22.3 and 20.6 mg/dL in HDL-C and 56.8, 53 and 57.3 mg/dL values in TC (p < 0.001 all compared to baseline). There was a statistically significant decrease in TC/HDL-C ratio at 24 weeks in all 3 treatment groups from baseline. There was no difference in any lipid changes between the 3 treatment arms. After multivariable adjustment, change in C-reactive protein was associated with change in LDL-C (p=0.03), HDL-C (p=0.09), and TC (p=0.01), but disease activity score in 28-joints was not. Baseline glucocorticoid use was associated with changes in HDL-C (p=0.03) and TC (p=0.02). Conclusion Levels of TC, LDL-C, and HDL-C increased equivalently shortly after initiation of MTX + ETA, TT and MTX monotherapy among early RA patients with active disease participating in a clinical trial. The clinical relevance of short term changes in traditional lipids on cardiovascular outcomes remains to be determined.

Navarro-Millan, Iris; Charles-Schoeman, Christina; Yang, Shuo; Bathon, Joan M.; Bridges, S. Louis; Chen, Lang; Cofield, Stacey S.; Dell'Italia, Louis J.; Moreland, Larry W.; O'Dell, James R.; Paulus, Harold E.; Curtis, Jeffrey R.

2013-01-01

46

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

Microsoft Academic Search

INTRODUCTION: Rheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy. METHODS: Forty patients with early RA who

Inga-Lill Engvall; Birgitta Tengstrand; Kerstin Brismar; Ingiäld Hafström

2010-01-01

47

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

PubMed Central

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

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

2009-01-01

48

Serum cotinine as a biomarker of tobacco exposure is not associated with treatment response in early rheumatoid arthritis  

PubMed Central

Objective Cigarette smoking has emerged as a risk factor for development of rheumatoid arthritis (RA). Recent studies have suggested that cigarette smoking may lead to lower treatment response rates with methotrexate (MTX) and some biologic agents in RA. Knowledge of whether tobacco exposure reduces treatment efficacy is important as smoking could represent a modifiable factor in optimizing RA treatment. Methods Study participants included patients with early RA (<3 years duration) enrolled in the Treatment of Early Aggressive RA (TEAR) trial, a randomized, blinded, placebo-controlled clinical trial (RCT) comparing early intensive therapy (MTX + etanercept or MTX + hydroxychloroquine + sulfasalazine [triple therapy]) versus initial treatment with MTX with step-up to MTX + etanercept or to triple therapy if still active at 24 weeks. Serum cotinine was measured using a commercially available ELISA at baseline and 48 weeks with detectable concentrations at both visits serving as indicator of smoking status. Mean Disease Activity Score (DAS-28) was compared by smoking status, adjusting for baseline disease activity. Results Of 412 subjects included in the analysis, 293 (71%) were categorized as ‘non-smokers’ and 119 (29%) as ‘current smokers’. There were no differences in the mean DAS-28 between 48 and 102 weeks based on smoking status for the overall group (p=0.881) or by specific treatment assignment. Conclusion Among patients enrolled in a large RCT of early RA with poor prognostic factors, smoking status did not impact treatment responses for those receiving early combination or initial MTX with step-up therapy at 24 weeks if still active.

Maska, Leann B.; Sayles, Harlan R.; O'Dell, James R.; Curtis, Jeffrey R.; Bridges, S. Louis; Moreland, Larry W.; Cofield, Stacey S.; Mikuls, Ted R.

2012-01-01

49

The impact of rheumatoid arthritis on foot function in the early stages of disease: a clinical case series  

PubMed Central

Background Foot involvement occurs early in rheumatoid arthritis but the extent to which this impacts on the structure and function leading to impairment and foot related disability is unknown. The purpose of this study was to compare clinical disease activity, impairment, disability, and foot function in normal and early rheumatoid arthritis (RA) feet using standardised clinical measures and 3D gait analysis. Methods Twelve RA patients with disease duration ?2 years and 12 able-bodied adults matched for age and sex underwent 3D gait analysis to measure foot function. Disease impact was measured using the Leeds Foot impact Scale (LFIS) along with standard clinical measures of disease activity, pain and foot deformity. For this small sample, the mean differences between the groups and associated confidence intervals were calculated using the t distribution Results Moderate-to-high foot impairment and related disability were detected amongst the RA patients. In comparison with age- and sex-matched controls, the patients with early RA walked slower (1.05 m/s Vs 1.30 m/s) and had a longer double-support phase (19.3% Vs 15.8%). In terminal stance, the heel rise angle was reduced in the patients in comparison with normal (-78.9° Vs -85.7°). Medial arch height was lower and peak eversion in stance greater in the RA patients. The peak ankle plantarflexion power profile was lower in the patients in comparison with the controls (3.4 W/kg Vs 4.6 W/kg). Pressure analysis indicated that the RA patients had a reduced lesser toe contact area (7.6 cm2 Vs 8.1 cm2), elevated peak forefoot pressure (672 kPa Vs 553 kPa) and a larger mid-foot contact area (24.6 cm2 Vs 19.4 cm2). Conclusion Analysis detected small but clinically important changes in foot function in a small cohort of RA patients with disease duration <2 years. These were accompanied by active joint disease and impairment and disability.

Turner, Deborah E; Helliwell, Philip S; Emery, Paul; Woodburn, James

2006-01-01

50

Disease activity and the course of wrist joint deterioration over 10 years in the patients with early rheumatoid arthritis.  

PubMed

The objectives of this study were to evaluate the course of radiographic deterioration of the wrist joint with rheumatoid arthritis (RA), and to determine the influence of disease activity on its deterioration. A retrospective study was performed on 122 wrists in 66 patients, who started treatment using disease-modifying antirheumatic drugs within the first year of the disease and followed for more than 10 years without surgical intervention. The mean disease activity score (DAS28-CRP[3]) was high during the first 2 years, followed by a decrease and a flattening of the curve of disease activity. Generally, carpal collapse progressed more in the early stage and decreased linearly over 10 years. Individually, continuous high disease activity and progression in radiographic damage were observed in carpal collapsed groups from early stage of the disease. The cut-off values of the mean DAS28-CRP(3) during year 0-2, which indicated progression to Larsen grade III or more and Schulthess type I (ankylosis) or III (disintegration) at year 10 were 3.34 (sensitivity: 70.9% and specificity: 72.1%) and 3.63 (sensitivity: 74.3% and specificity: 77.0%), respectively. In patients with RA, deterioration of the wrist joint was influenced by disease activity. Identifying this activity and the course of wrist progression may be useful in predicting wrist deterioration. PMID:18758892

Toyohara, Issaku; Ishikawa, Hajime; Abe, Asami; Nakazono, Kiyoshi; Murasawa, Akira

2009-01-01

51

Early disease control by low-dose prednisone comedication may affect the quality of remission in patients with early rheumatoid arthritis.  

PubMed

In order to identify rate and stability of remission induced by low-dose prednisone comedication in early rheumatoid arthritis (RA), we evaluated patients with early RA (<1 year) who were randomized to receive (P) or not (non-P) low-dose prednisone in association with step-up disease-modifying antirheumatic drug therapy over 2 years. Prevalence and duration of clinical remission were evaluated in the first and second year. Each treatment group included 105 patients; no significant differences were found at baseline. During the first year, P patients achieved higher rates of clinical remission with a time-averaged odds ratio (OR) of 1.965 (CI 95% 1.214-3.182, P= 0.006). Moreover, they showed a higher probability of sustained remission during the second year (OR 4.480, CI 95% 1.354-14.817, P= 0.014). In conclusion, we found as in early RA low-dose prednisone comedication is associated with higher rate of clinical remission, earlier disease activity control and more stable remission over time. PMID:20398020

Todoerti, Monica; Scirè, Carlo Alberto; Boffini, Nicola; Bugatti, Serena; Montecucco, Carlomaurizio; Caporali, Roberto

2010-04-01

52

Efficacy of initial methotrexate monotherapy versus combination therapy with a biological agent in early rheumatoid arthritis: a meta-analysis of clinical and radiographic remission  

Microsoft Academic Search

ObjectiveThe target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure.MethodsA systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model

B. Kuriya; E. V. Arkema; V. P. Bykerk; E. C. Keystone

2010-01-01

53

Usefulness of ultrasonography-proven tenosynovitis to monitor disease activity of a patient with very early rheumatoid arthritis treated by abatacept.  

PubMed

We introduced abatacept (ABT) in a very early rheumatoid arthritis (RA) patient with active tenosynovitis of hands defined by musculoskeletal ultrasonography (MSKUS). MSKUS-proven tenosynovitis remarkably improved at 2 months in spite of clinical exacerbation, followed by clinical remission at 5 months. MSKUS abnormalities also disappeared. Although ABT was discontinued due to an adverse event after the sixth infusion, she remained in clinical remission as well as imaging remission by MSKUS at 13 months. PMID:22772459

Kawashiri, Shin-ya; Fujikawa, Keita; Nishino, Ayako; Suzuki, Takahisa; Okada, Akitomo; Nakamura, Hideki; Kawakami, Atsushi

2013-05-01

54

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

Microsoft Academic Search

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

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

2007-01-01

55

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

PubMed Central

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

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

2010-01-01

56

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

PubMed

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

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

2011-01-01

57

Polyarticular pseudosepsis in rheumatoid arthritis.  

PubMed

Three patients with longstanding seropositive rheumatoid arthritis had fever and marked synovial fluid leukocytosis in multiple joints. No infectious agents were found in synovial fluid or blood, and the patients recovered uneventfully without prolonged antibiotic therapy. Acute, severe exacerbations of synovitis in patients with rheumatoid arthritis may simulate a septic process and involve multiple joints. PMID:1566139

Fuchs, H A

1992-04-01

58

Early cardiovascular adaptation to simulated zero gravity  

NASA Technical Reports Server (NTRS)

A study was conducted on five normal male volunteers (23-29 yr), under controlled conditions, to evaluate early adaptive responses to zero gravity. Specific objectives are (1) to characterize the hemodynamic, renal and hormonal responses to a central fluid shift, and (2) to compare data obtained during and after head-down tilt with corresponding data from actual space flight to validate tilt as a physiological model for simulation of zero gravity. Zero gravity is simulated by a 24-hr period of head-down tilt at 5 deg. The results suggest that hemodynamic adaptation occurs rapidly and is essentially accomplished by 6 hr, and that adaptation includes diuresis and reduction in blood volume. The validity of head-down tilt at 5 deg as an experimental model is established by comparing the results obtained with data from Apollo and Skylab astronauts on body fluid distributions and postflight responses to orthostatic and exercise stress.

Nixon, J. V.; Murray, R. G.; Bryant, C.; Johnson, R. L., Jr.; Mitchell, J. H.; Holland, O. B.; Gomez-Sanchez, C.; Vergne-Marini, P.; Blomqvist, C. G.

1979-01-01

59

Further Optimization of the Reliability of the 28-Joint Disease Activity Score in Patients with Early Rheumatoid Arthritis  

PubMed Central

Background The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint count (TJC28 and SJC28), a patient-reported measure for general health (GH), and an inflammatory marker (either the erythrocyte sedimentation rate [ESR] or the C-reactive protein [CRP]) into a composite measure of disease activity in rheumatoid arthritis (RA). This study examined the reliability of the DAS28 in patients with early RA using principles from generalizability theory and evaluated whether it could be increased by adjusting individual DAS28 component weights. Methods Patients were drawn from the DREAM registry and classified into a “fast response” group (N?=?466) and “slow response” group (N?=?80), depending on their pace of reaching remission. Composite reliabilities of the DAS28-ESR and DAS28-CRP were determined with the individual components' reliability, weights, variances, error variances, correlations and covariances. Weight optimization was performed by minimizing the error variance of the index. Results Composite reliabilities of 0.85 and 0.86 were found for the DAS28-ESR and DAS28-CRP, respectively, and were approximately equal across patients groups. Component reliabilities, however, varied widely both within and between sub-groups, ranging from 0.614 for GH (“slow response” group) to 0.912 for ESR (“fast response” group). Weight optimization increased composite reliability even further. In the total and “fast response” groups, this was achieved mostly by decreasing the weight of the TJC28 and GH. In the “slow response” group, though, the weights of the TJC28 and SJC28 were increased, while those of the inflammatory markers and GH were substantially decreased. Conclusions The DAS28-ESR and the DAS28-CRP are reliable instruments for assessing disease activity in early RA and reliability can be increased even further by adjusting component weights. Given the low reliability and weightings of the general health component across subgroups it is recommended to explore alternative patient-reported outcome measures for inclusion in the DAS28.

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

2014-01-01

60

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

PubMed Central

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

2013-01-01

61

COBRA combination therapy in patients with early rheumatoid arthritis: Long-term structural benefits of a brief intervention  

Microsoft Academic Search

Objective. The Combinatietherapie Bij Reuma- toide Artritis (COBRA) trial demonstrated that step- down combination therapy with prednisolone, metho- trexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radio- logic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which

Maarten Boers; Arco C. Verhoeven; Rene Westhovens; Mart A. F. J. van de Laar; Harry M. Markusse; J. Christiaan van Denderen; Marie Louise Westedt; Andre J. Peeters; Ben A. C. Dijkmans; Piet Jacobs; Annelies Boonen; Sjef van der Linden

2002-01-01

62

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components  

PubMed Central

OBJECTIVES—To investigate the potential clinical benefit of a combination therapy.?METHODS—205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying anti-rheumatoid drugs previously, with an early (?1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68).?RESULTS—The mean changes in the DAS during the one year follow up of the study was ?1.15, ?0.87, ?1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007).?CONCLUSION—This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.?? Keywords: rheumatoid arthritis; combination therapy; sulphasalazine; methotrexate

Dougados, M.; Combe, B.; Cantagrel, A.; Goupille, P.; Olive, P.; Schattenkirchner, M.; Meusser, S; Paimela, L; Rau, R.; Zeidler, H.; Leirisalo-Repo, M.; Peldan, K.

1999-01-01

63

Cervical Myelopathy in Rheumatoid Arthritis  

PubMed Central

Involvement of the cervical spine is common in rheumatoid arthritis. Clinical presentation can be variable, and symptoms may be due to neck pain or compressive myeloradiculopathy. We discuss the pathology, grading systems, clinical presentation, indications for surgery and surgical management of cervical myelopathy related to rheumatoid arthritis in this paper. We describe our surgical technique and results. We recommend early consultation for surgical management when involvement of the cervical spine is suspected in rheumatoid arthritis. Even patients with advanced cervical myelopathy should be discussed for surgical treatment, since in our experience improvement in function after surgery is common.

Mukerji, N.; Todd, N. V.

2011-01-01

64

Rheumatoid Arthritis  

MedlinePLUS Videos and Cool Tools

... vertebrae to prevent slippage of the vertebrae. Self-Care Rheumatoid arthritis cannot be cured but it can be managed through medications and self-care. The following are important self-care tips: Exercise ...

65

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

PubMed Central

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

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

2013-01-01

66

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

Microsoft Academic Search

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

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

2004-01-01

67

Clinical and radiological dissociation of anti-TNF plus methotrexate treatment in early rheumatoid arthritis in routine care: Results from the ABRAB study  

PubMed Central

Background Rheumatoid arthritis (RA) is a chronic autoinflammatory joint disease which leads to the destruction of joints and disability of the patients. Anti-tumour necrosis factor (anti-TNF) drugs can halt radiological progression better than conventional DMARDs even in clinical non-responders. Methods The efficacy of anti-TNF plus methotrexate (MTX) treatment versus MTX monotherapy on clinical and radiological outcomes were compared in early rheumatoid arthritis (RA) patients in clinical practice by retrospective analysis of an observational cohort. 49 early RA patients (group A) on first-line MTX monotherapy and 35 early RA patients (group B) on anti-TNF plus MTX treatment were selected from an observational cohort and evaluated retrospectively focusing on their first twelve months of treatment. Data on disease activity (DAS28) and functional status (HAQ-DI) were collected three monthly. One-yearly radiological progression was calculated according to the van der Heijde modified Sharp method (vdHS). Clinical non-responder patients in both groups were selectively investigated from a radiological point of view. Results Disease activity was decreased and functional status was improved significantly in both groups. One-yearly radiological progression was significantly lower in group B than in group A. The percentage of patients showing radiological non-progression or rapid radiological progression demonstrated a significant advantage for group B patients. In addition non-responder patients in group B showed similar radiological results as responders, while a similar phenomenon was not observed in patients in group A. Conclusions Clinical efficacy within our study was similar for tight-controlled MTX monotherapy as well as for combination treatment with anti-TNF and MTX. However MTX monotherapy was accompanied by more rapid radiological progression and less radiological non-progression. Anti-TNF plus MTX decreased radiological progression even in clinical non-responders supporting the advantage of anti-TNF plus MTX combination in dissociating clinical and radiological effects.

2014-01-01

68

Apoptosis in rheumatoid arthritis  

Microsoft Academic Search

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

Paul P. Tak; Gary S. Firestein

69

Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis.  

PubMed

This study was performed to estimate the population pharmacokinetic (PK) parameters of etanercept in pediatric juvenile rheumatoid arthritis (JRA) patients and to compare the steady-state time-concentration profiles between etanercept 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly subcutaneous (SC) regimens by clinical trial simulation. To this end, mixed-effect analysis (NONMEM, Version 5.1) was performed using the etanercept PK database consisting of 69 JRA patients (4-17 years). Based on the population PK parameters obtained herein, a Monte Carlo clinical trial simulation experiment was conducted to compare the PK profiles in 200 virtual JRA patients who randomly received either etanercept 0.4 mg/kg SC twice weekly or 0.8 mg/kg once weekly for 12 weeks. The following population PK model could adequately describe etanercept PK profiles for twice-weekly SC dosing of 0.4 mg/kg: CL/F (L/h)=0.0576 (female) or 0.0772 (male) x (body surface area in m2/1.071)1.41, V/F(L)=7.88 x (body weight in kg/30.8). The means +/- standard deviations of simulated trough concentrations for 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly dosing regimens were 1.58 +/- 1.07 mg/L and 1.92 +/- 1.09 mg/L, respectively. Peaks during 0.8-mg/kg once-weekly dosing (2.92 +/- 1.41 mg/L) were only 11% higher than during 0.4 mg/kg twice-weekly dosing (2.62 +/- 1.23 mg/L). In conclusion, the clinical trial simulation confirmed that 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly SC regimens of etanercept are expected to yield overlapping steady-state time-concentration profiles, leading to equivalent clinical outcomes. This has been the basis of the recent Food and Drug Administration approval of the 0.8-mg/kg once-weekly regimen in pediatric patients with JRA. PMID:15703360

Yim, Dong-Seok; Zhou, Honghui; Buckwalter, Mary; Nestorov, Ivan; Peck, Carl C; Lee, Howard

2005-03-01

70

Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis  

PubMed Central

Background Currently available biomarkers for the early tissue process leading to joint damage in rheumatoid arthritis are insufficient and lack prognostic accuracy, possibly a result of variable activity of the disease over time. This study represents a novel approach to detect an altered activity of the disease process detected as increasing serum-COMP levels over a short time and whether this would correlate with joint damage progression over the first 5 years of disease. Methods In all, 349 patients from the Swedish BARFOT early RA study were examined. Serum-COMP was analysed by ELISA at diagnosis and after 3 months. Based on changes in serum-COMP levels, three subgroups of patients were defined: those with unchanged levels (change ? 20%) (N=142), decreasing levels (> 20%) (N=173) and increasing levels (> 20%) (N=34). Radiographs of hands and feet were obtained at inclusion, after 1, 2 and 5 years and scored according to Sharp van der Heijde (SHS). Radiographic progression was defined as increase in SHS by ?5.8. Results The group of patients with increasing COMP levels showed higher median change in total SHS and erosion scores at 1, 2 and 5 year follow-up compared with the groups with stable or decreasing COMP levels. Furthermore, the odds ratio of radiographic progression was 2.8 (95% CI 1.26-6.38) for patients with increasing COMP levels vs. patients with unchanged levels. The group of patients with increasing COMP levels had higher ESR at inclusion but there were no baseline differences between the groups for age, gender, disease duration, disease activity (DAS28), function (HAQ), CRP, nor presence of rheumatoid factor or anti-CCP. Importantly, neither did changes over the 3-month period in DAS28, HAQ, ESR nor CRP differ between the groups and these variables did not correlate to joint damage progression. Conclusion Increasing serum-COMP levels between diagnosis and the subsequent 3 months in patients with early RA represents a novel indicator of an activated destructive process in the joint and is a promising tool to identify patients with significant joint damage progression during a 5-year period.

2013-01-01

71

Pharmacogenomics of NAT2 and ABCG2 influence the toxicity and efficacy of sulphasalazine containing DMARD regimens in early rheumatoid arthritis.  

PubMed

Sulphasalazine (SSA) is a disease modifying anti-rheumatic drug (DMARD) that is commonly used to treat rheumatoid arthritis (RA). Plasma levels of SSA and its metabolite sulphapyridine are influenced by common polymorphisms in genes that encode N-acetyl transferase 2 (NAT2) and ATP-binding cassette protein G2 (ABCG2). Study participants had early RA that was treated with a combination DMARD regimen that included SSA. Toxicity was defined by cessation of SSA due to adverse effects and response as remission after 12 months of treatment. The effect of variables on toxicity was assessed by a Cox-proportional Hazard model and response by logistic regression. After correction for conventional variables, toxicity in 229 participants was influenced by NAT2 phenotype (hazard ratio=1.74 (95% confidence interval (CI) 1.01-3.21), P=0.044) and remission in 141 participants was associated with ABCG2 genotype (odds ratio=3.34 (95% CI 1.18-9.50), P=0.024). In our sample of early RA patients who were primarily treated with a combination of DMARDs, common variants in genes that encode NAT2 and ABCG2 were associated respectively with toxicity and response to SSA. PMID:24394199

Wiese, M D; Alotaibi, N; O'Doherty, C; Sorich, M J; Suppiah, V; Cleland, L G; Proudman, S M

2014-08-01

72

1H NMR-based metabolomic analysis for identifying serum biomarkers to evaluate methotrexate treatment in patients with early rheumatoid arthritis  

PubMed Central

To identify the major serum biomarkers predicting the response to methotrexate (MTX) treatment in patients with early rheumatoid arthritis (RA), we evaluated the relationships between the individual response to MTX and various associated factors utilizing the 1H nuclear magnetic resonance (1H NMR)-based metabolomic method. Thirty-eight early RA patients were enrolled in this cohort study, and they received MTX (10 mg/week) orally as monotherapy for 24 weeks. According to the American College of Rheumatology criteria for improvement, clinical evaluation following MTX treatment was carried out at baseline and at the end of 24 weeks. Furthermore, collected serum samples were analyzed using 600 M 1H NMR for spectral binning. The obtained data were processed by both the unsupervised principal component analysis (PCA) and the supervised partial least squares discriminant analysis (PLS-DA). Lastly, multivariate analyses were performed to recognize the spectral pattern of endogenous metabolites related to MTX treatment. Differential clustering of 1H NMR spectra identified by PCA was found between the effective (n=25) and non-effective (n=13) group of RA patients receiving MTX treatment. Multivariate statistical analysis showed a difference in metabolic profiles between the two groups using PLS-DA (R2=0.802, Q2=0.643). In targeted profiling, 11 endogenous metabolites of the effective group showed a significant difference when compared with those of the non-effective group (p<0.05). Serum metabolites correlated with MTX treatment in patients with early RA were identified, which may be the major predictive factors for evaluating the response to MTX treatment in patients with early RA. Furthermore, our results highlight the usefulness of 1H NMR-based metabolomics as a feasible and efficient prognostic tool for predicting therapeutic efficacy to MTX treatment.

WANG, ZHIGANG; CHEN, ZHE; YANG, SISI; WANG, YU; YU, LIFANG; ZHANG, BICHENG; RAO, ZHIGUO; GAO, JIANFEI; TU, SHENGHAO

2012-01-01

73

Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12-month open-label randomised study  

PubMed Central

Introduction In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients. Methods Two hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome. Results Each group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group. Conclusion In early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control. Trial registration number Current Controlled Trials ISRCTN2486111

2012-01-01

74

(1)H NMR-based metabolomic analysis for identifying serum biomarkers to evaluate methotrexate treatment in patients with early rheumatoid arthritis.  

PubMed

To identify the major serum biomarkers predicting the response to methotrexate (MTX) treatment in patients with early rheumatoid arthritis (RA), we evaluated the relationships between the individual response to MTX and various associated factors utilizing the (1)H nuclear magnetic resonance ((1)H NMR)-based metabolomic method. Thirty-eight early RA patients were enrolled in this cohort study, and they received MTX (10 mg/week) orally as monotherapy for 24 weeks. According to the American College of Rheumatology criteria for improvement, clinical evaluation following MTX treatment was carried out at baseline and at the end of 24 weeks. Furthermore, collected serum samples were analyzed using 600 M (1)H NMR for spectral binning. The obtained data were processed by both the unsupervised principal component analysis (PCA) and the supervised partial least squares discriminant analysis (PLS-DA). Lastly, multivariate analyses were performed to recognize the spectral pattern of endogenous metabolites related to MTX treatment. Differential clustering of (1)H NMR spectra identified by PCA was found between the effective (n=25) and non-effective (n=13) group of RA patients receiving MTX treatment. Multivariate statistical analysis showed a difference in metabolic profiles between the two groups using PLS-DA (R(2)=0.802, Q(2)=0.643). In targeted profiling, 11 endogenous metabolites of the effective group showed a significant difference when compared with those of the non-effective group (p<0.05). Serum metabolites correlated with MTX treatment in patients with early RA were identified, which may be the major predictive factors for evaluating the response to MTX treatment in patients with early RA. Furthermore, our results highlight the usefulness of (1)H NMR-based metabolomics as a feasible and efficient prognostic tool for predicting therapeutic efficacy to MTX treatment. PMID:23060942

Wang, Zhigang; Chen, Zhe; Yang, Sisi; Wang, Yu; Yu, Lifang; Zhang, Bicheng; Rao, Zhiguo; Gao, Jianfei; Tu, Shenghao

2012-07-01

75

Early development of Xenopus embryos is affected by simulated gravity  

NASA Technical Reports Server (NTRS)

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.

Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

1994-01-01

76

Rheumatoid Arthritis  

Microsoft Academic Search

\\u000a Rheumatoid arthritis (RA) affects all ethnic groups. Women are nearly three times more likely than men to develop the disease.\\u000a The pattern of arthritis typically favors distal and symmetrical involvement. The most commonly involved joints are the wrists,\\u000a metacarpophalangeal, proximal interphalangeal, and metatarsophalangeal joints. However, many other joints can also be involved.\\u000a Shoulder, elbow, hip, knee, or neck disease (particularly

James R. O'Dell; Josef S. Smolen; Daniel Aletaha; Dwight R. Robinson; E. William St. Clair

77

Does digital X-ray radiogrammetry have a role in identifying patients at increased risk for joint destruction in early rheumatoid arthritis?  

PubMed Central

Introduction The aim of this study was to investigate the role of hand bone mineral density (BMD) loss analyzed with digital X-ray radiogrammetry (DXR) in early rheumatoid arthritis (RA) as a predictor for progression of joint damage. Methods In 379 patients with early RA, baseline and one-year hand BMD was measured with DXR and the hand bone loss (HBL) was analyzed using the smallest detectable change (HBLsdc) and tertiles (HBLtertiles). Joint damage in hands and feet were scored according to the Sharp van der Heijde (SHS) method at baseline and at one, two, five and eight years. At the same time-points Disease Activity Score (DAS28) was calculated and functional disability assessed. Rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed at baseline. Results Sixty-six percent of the patients had hand BMD loss in the first year of RA determined by HBLsdc and 65% by HBLtertiles. Radiographic progression after two, five and eight years was associated with hand bone loss defined by HBLsdc. By HBLtertiles there were significant associations at all time-points except at eight years. The change in DXR at one year (ChDXR1yr) correlated significantly and inversely with the change in SHS (ChSHS) at two, five and eight years. Multivariate analysis showed that only change in SHS during the first year and the presence of anti-CCP were independent predictors of long-term progressive joint damage. If radiographic scores were not included, DXR-BMD loss was an independent predictor. Patients with great bone loss by HBLtertiles had significantly more often high disease activity after two years. However, neither bone loss by HBLsdc or HBLtertiles nor by ChDXR1yr was an independent predictor of remission after two, five and eight years. Conclusions This study confirms previous reports of an association of decrease in DXR-BMD during the first disease year with progression of radiographic joint damage over an extended period of time. This association was independent in a regression model only when radiological findings were excluded suggesting a possible predictive role of DXR-BMD in clinical practice when radiographic evaluation is not available. However, further studies are required before this can be established.

2012-01-01

78

Cerebral rheumatoid vasculitis: a case report  

PubMed Central

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.

2012-01-01

79

Macrophages in rheumatoid arthritis  

PubMed Central

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

Kinne, Raimund W; Brauer, Rolf; Stuhlmuller, Bruno; Palombo-Kinne, Ernesta; Burmester, Gerd-R

2000-01-01

80

[Rheumatoid arthritis].  

PubMed

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

Kameda, Hideto; Takeuchi, Tsutomu

2009-03-01

81

Early rheumatoid arthritis 6 years after diagnosis is still associated with high direct costs and increasing loss of productivity: the Swedish TIRA project.  

PubMed

Objectives: To calculate total costs over 6 years after diagnosis of early rheumatoid arthritis (RA). Method: In the longitudinal prospective multicentre TIRA study, 239 patients from seven units, diagnosed in 1996-98, reported regularly on health-care utilization and the number of days lost from work. Costs were obtained from official databases and calculated using unit costs (Swedish kronor, SEK) from 2001. Indirect costs were calculated using the human capital approach (HCA). Costs were inflation adjusted to Euro June 2012, using the Swedish Consumer Price Index and the exchange rate of June 2012. Statistical analyses were based on linear mixed models (LMMs) for changes over time. Results: The mean total cost per patient was EUR 14 768 in year 1, increasing to EUR 18 438 in year 6. Outpatient visits and hospitalization decreased but costs for surgery increased from EUR 92/patient in year 1 to EUR 444/patient in year 6. Drug costs increased from EUR 429/patient to EUR 2214/patient, mainly because of the introduction of biologics. In year 1, drugs made up for 10% of direct costs, and increased to 49% in year 6. Sick leave decreased during the first years but disability pensions increased, resulting in unchanged indirect costs. Over the following years, disability pensions increased further and indirect costs increased from EUR 10 284 in year 1 to EUR 13 874 in year 6. LMM analyses showed that indirect costs were unchanged whereas direct costs, after an initial fall, increased over the following years, leading to increasing total costs. Conclusions: In the 6 years after diagnosis of early RA, drug costs were partially offset by decreasing outpatient visits but indirect costs remained unchanged and total costs increased. PMID:24354438

Hallert, E; Husberg, M; Kalkan, A; Skogh, T; Bernfort, L

2014-01-01

82

Evidence of linkage to chromosome 1 for early age of onset of rheumatoid arthritis and HLA marker DRB1 genotype in NARAC data  

PubMed Central

Focusing on chromosome 1, a recursive partitioning linkage algorithm (RP) was applied to perform linkage analysis on the rheumatoid arthritis NARAC data, incorporating covariates such as HLA-DRB1 genotype, age at onset, severity, anti-cyclic citrullinated peptide (anti-CCP), and life time smoking. All 617 affected sib pairs from the ascertained families were used, and an RP linkage model was used to identify linkage possibly influenced by covariates. This algorithm includes a likelihood ratio (LR)-based splitting rule, a pruning algorithm to identify optimal tree size, and a bootstrap method for final tree selection. The strength of the linkage signals was evaluated by empirical p-values, obtained by simulating marker data under null hypothesis of no linkage. Two suggestive linkage regions on chromosome 1 were detected by the RP linkage model, with identified associated covariates HLA-DRB1 genotype and age at onset. These results suggest possible gene × gene and gene × environment interactions at chromosome 1 loci and provide directions for further gene mapping.

Xu, Wei; Lan, Hui; Hu, Pingzhao; Bull, Shelley B; Greenwood, Celia MT

2007-01-01

83

Radiological outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis  

PubMed Central

Objective: To determine the effect of different treatment strategies (early versus delayed) on the radiological progression of joint damage during 4 years. Additionally, to determine the effect of treatment strategy on the association of HLA class II alleles and joint damage. Methods: Progression of radiographic damage and association of radiographic damage and genetic predisposition were compared in two cohorts, one treated according to the delayed treatment strategy (initial treatment with analgesics), the other treated according to the early treatment strategy (treatment with disease modifying antirheumatic drugs (DMARDs) chloroquine or sulfasalazine). Radiographic damage was measured by the modified Sharp-van der Heijde method. Genetic predisposition was determined by high resolution HLA-DR and DQ typing. Results: A completers-only analysis of 153 patients (originally 206 patients) in a non-randomised design showed less radiographic progression from 0 to 4 years in the early treatment group (median Sharp progression rate 1.3 points/year, n = 75) than in the delayed treatment group (2.5 points/year, n = 78) (p = 0.03). The progression from 1 to 4 years did not differ significantly between the groups. At 4 years, joint destruction in both groups was positively correlated with the presence of the shared epitope. Conclusions: The beneficial effect of early DMARD treatment on the radiological progression of joint damage is still present at 4 years. However, the rate of joint destruction from 1 to 4 years did not differ between the delayed and early treatment group. Neither the radiographic nor the immunogenetic data suggest that longlasting disease modification has been induced by early treatment.

van Aken, J; Lard, L; le Cessie, S; Hazes, J; Breedveld, F; Huizinga, T

2004-01-01

84

Trajectory of intensive treat-to-target disease modifying drug regimen in an observational study of an early rheumatoid arthritis cohort  

PubMed Central

Objectives Studies of early rheumatoid arthritis (RA) cohorts have analysed treatment response and prognostic factors at fixed time points. However, in treat-to-target protocols, therapeutic decision-making is dynamic and responsive to disease activity over time. To determine when a minimal residual disease response target should be expected, our primary objective was to identify the time-dependent therapeutic response to combination disease modifying antirheumatic drugs (DMARDs) for 12?months. Our secondary objective determined factors affecting this response trajectory. Design Observational cohort. Setting Treat-to-target early RA clinic in Australian tertiary referral hospital. Participants We enrolled consecutive patients attending an early arthritis clinic with symptom duration less than 12?months, who were diagnosed with RA for the first time between 2004 and 2008. 101 met these eligibility criteria and data were available at baseline through 12?months. Interventions intensive DMARDs according to a treat-to-target protocol. Primary and secondary outcome measures We measured disease activity scores (DAS) at each visit, then analysed therapeutic response and associated factors in a time-dependent fashion over 12?months. Results The median DAS4vESR of 4.46 at baseline decreased 12?weeks later by 24%, while the proportion with DAS4v???2.6 increased (p<0.01). DAS4v continued to decrease over 52?weeks. DAS4v reduction of at least ?0.45 at 4?weeks was predictive of DAS4v at 28 and 52?weeks. Female gender, current smoking, primary education and an interaction between baseline weight and C reactive protein (CRP) negatively impacted DAS4v reduction over 4 and 52?weeks. Time-varying effects of blood pressure, neutrophils, erythrocyte sedimentation rate and CRP also significantly influenced DAS4v over 52?weeks. Conclusions Time-dependent data suggest that the largest reduction of DAS4v to combination DMARDs occurs in the first month of therapy, and this predicts subsequent response. Variables known to impact long-term treatment response in RA also impacted early DAS4v response to combination DMARDs.

White, Douglas; Pahau, Helen; Duggan, Emily; Paul, Sanjoy; Thomas, Ranjeny

2013-01-01

85

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

PubMed Central

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

2013-01-01

86

Local Rheumatoid Arthritis and Radiation Synovectomy  

Microsoft Academic Search

The approach to treatment of rheumatoid arthritis is undergoing fundamental change, and the concept that early and aggressive\\u000a suppression of inflammation and control of disease activity may slow the rate of disease progression is increasingly accepted\\u000a [22]. Nonsteroidal anti-inflammatory and slow-acting antirheumatic drugs are indisputably the primary treatment modalities in\\u000a rheumatoid arthritis (RA). However, persistent synovitis in one or a

Georg M. Kacl; Gerold Stucki

87

Which patients stop working because of rheumatoid arthritis? Results of five years' follow up in 732 patients from the Early RA Study (ERAS)  

PubMed Central

Objectives: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). Setting: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. Patients: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. Methods: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. Outcome measures: Changes in, and loss of paid work by five years' follow up. Results: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. Conclusions: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs.

Young, A; Dixey, J; Kulinskaya, E; Cox, N; Davies, P; Devlin, J; Emery, P; Gough, A; James, D; Prouse, P; Williams, P; Winfield, J

2002-01-01

88

Rheumatoid factor (RF)  

MedlinePLUS

Rheumatoid factor (RF) is a blood test that measures the amount of the RF antibody in the blood. ... still have a "normal" or low rheumatoid factor (RF). Normal value ranges may vary slightly among different ...

89

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

PubMed Central

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

Ajeganova, Sofia; Svensson, Bjorn; Hafstrom, Ingiald

2014-01-01

90

The rheumatoid forefoot.  

PubMed

Rheumatoid arthritis (RA) manifests itself in a variety of ways, with its effect being seen in around 90 % of sufferers' feet. The foot has been found to be the most common reason for incapacity in patients with RA, with the forefoot the most common area. The foot is second, behind only the hand, as the most common place for manifestation of RA. Pain in the foot is commonly the most debilitating condition, which causes the patient to seek specialist help. As well as pain, foot deformities such as hallux valgus and claw toes are common complaints. These symptoms often arise as a result of continued walking on an unstable foot, leading to painful callosities and dislocation of the metatarsophalangeal joints. Other conditions, such as pannus formation and Morton's neuroma, can be related to RA. This review sets out what we believe to be a successful approach to the rheumatoid forefoot, which aims at the relief of pain and the preservation of ambulation. Key to a successful outcome is appropriate medical control with a multidisciplinary approach that enables close liaison between orthopaedic surgeons, orthotists, and rheumatologists. Combined clinics provide this multidisciplinary care. Those treating RA need to be aware of the high incidence of foot involvement and how early intervention may benefit the patient. The aim of this article is to present current evidence to enable people to develop a treatment algorithm for this condition. PMID:23943297

Brooks, Francis; Hariharan, Kartik

2013-12-01

91

A Randomized Comparative Effectiveness Study of Oral Triple Therapy versus Etanercept plus Methotrexate in Early, Aggressive Rheumatoid Arthritis  

PubMed Central

Objective To assess if it is better to intensively treat all early RA patients with drug combinations or reserve this for those who do not appropriately respond to methotrexate monotherapy and assess if the combination therapy of methotrexate plus etanercept is superior to the combination of methotrexate plus sulfasalazine plus hydroxychloroquine. Methods The TEAR study is a 2-year, randomized, double-blind trial. Using a 2×2 factorial design, participants were randomized to one of four treatment arms: immediate combination therapy of methotrexate plus etanercept; or oral triple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine); or initial methotrexate monotherapy with a step-up to one of the combination therapies (all arms included matching placebos). The primary outcome was an observed-group analysis of DAS28-ESR scores from weeks 48 to 102. Results At the week 24 step-up period, those receiving immediate combination therapy (etanercept plus methotrexate; or triple therapy) demonstrated greater reduction in DAS28-ESR compared to those on initial methotrexate monotherapy (DAS28-ESR: 3.6 vs. 4.6, p<0.0001), with no differences between regimens of combination therapy. For weeks 48 through 102, participants randomized to step-up arms had a DAS28-ESR clinical response that was not different than those who received initial combination therapy, regardless of the treatment arm (3.2 vs. 3.2, p=0.75). There was no significant difference in DAS28-ESR between participants receiving oral triple therapy versus combination methotrexate plus etanercept (3.1 vs. 3.2, p=0.42). By week 102, there was a small, statistically significant difference in change in radiographic measurements from baseline between methotrexate plus etanercept compared to oral triple therapy (0.64 vs. 1.69, p= 0.047). The absolute difference at week 102 was small. Conclusions There were no differences in the mean DAS28-ESR during weeks 48-102 between participants randomized to methotrexate plus etanercept or triple therapy, regardless of whether they received immediate combination treatment or step-up from methotrexate monotherapy. At 24 months, immediate combination treatment with either strategy was more effective than methotrexate monotherapy prior to step-up. Initial use of methotrexate monotherapy with the addition of sulfasalazine plus hydroxychloroquine; or etanercept, if necessary after 6 months, is a reasonable therapeutic strategy for early RA. The combination of etanercept plus methotrexate resulted in a statistically significant, but clinically small, radiographic benefit over oral triple therapy.

Moreland, Larry W.; O'Dell, James R.; Paulus, Harold E.; Curtis, Jeffrey R.; Bathon, Joan M.; Clair, E. William St.; Bridges, S. Louis; Zhang, Jie; McVie, Theresa; Howard, George; van der Heijde, Desiree; Cofield, Stacey S.

2014-01-01

92

Rheumatoid Factor Secretion from Human Leu1+ B Cells  

Microsoft Academic Search

A human B cell subpopulation identifiable by the expression of the cell surface antigen Leu-1 (CD5) is responsible for most of the immunoglobulin M rheumatoid factor secreted in vitro after the cells are stimulated with Staphylococcus aureus. The ability of B cells bearing the Leu-1 marker (Leu-1+) to secrete rheumatoid factor is present early in development and extends to adulthood,

Richard R. Hardy; Kyoko Hayakawa; Masatoshi Shimizu; Katsuhiko Yamasaki; Tadamitsu Kishimoto

1987-01-01

93

Genotyping for disease associated HLA DR ?1 alleles and the need for early joint surgery in rheumatoid arthritis: a quantitative evaluation  

Microsoft Academic Search

OBJECTIVETo determine the value of HLA DR ?1 disease associated epitope (DAE) and erythrocyte sedimentation (ESR) in predicting the need for major joint replacement in rheumatoid arthritis (RA).METHODSSixty five RA patients who had undergone hip, knee or shoulder arthroplasty within 15 years of disease onset and 65 who had not. HLA DR ?1 genotype was determined by polymerase chain reaction.

Anne Crilly; Nicola Maiden; Hilary A Capell; Rajan Madhok

1999-01-01

94

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

Microsoft Academic Search

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

James Woodburn; Kym Hennessy; Martijn PM Steultjens; Iain B McInnes; Deborah E Turner

2010-01-01

95

Optical imaging of rheumatoid arthritis  

PubMed Central

Optical Imaging (OI) for rheumatoid arthritis is a novel imaging modality. With the high number of people affected by this disease, especially in western countries, the availability of OI as an early diagnostic imaging method is clinically highly relevant. In this article we describe the current techniques of OI and discuss potential future applications of this promising technology. Overall, we demonstrate that OI is a fast, inexpensive, noninvasive, nonionizing and accurate imaging modality. Furthermore, OI is a clinically applicable tool allowing for the early detection of inflammation and potentially facilitating the monitoring of therapy.

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

2011-01-01

96

Single-factor scoring validation for the Health Assessment Questionnaire-Disability Index (HAQ-DI) in patients with systemic sclerosis and comparison with early rheumatoid arthritis patients  

Microsoft Academic Search

Objective  Structural validity for the Health Assessment Questionnaire-Disability Index (HAQ-DI) has recently been provided for patients with rheumatoid arthritis (RA). The goal of the current study was to examine the structural validity of the HAQ-DI in patients with systemic sclerosis (SSc, scleroderma) and to compare its performance with that in patients with RA.Methods  The HAQ-DI structural validity was first assessed in a

Jason C. Cole; Dinesh Khanna; Philip J. Clements; James R. Seibold; Donald P. Tashkin; Harold E. Paulus; Michael R. Irwin; Sarosh J. Motivala; Daniel E. Furst

2006-01-01

97

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

Microsoft Academic Search

Rheumatoid arthritis is a chronic inflammatory disease, associated with an excess of cardiovascular morbidity and mortality due to accelerated atherosclerosis. Oxidized low-density lipoprotein (oxLDL), the antibodies against oxLDL and the lipoprotein-associated phospholipase A2 (Lp-PLA2) may play important roles in inflammation and atherosclerosis. We investigated the plasma levels of oxLDL and Lp-PLA2 activity as well as the autoantibody titers against mildly

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

2007-01-01

98

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

NASA Astrophysics Data System (ADS)

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

Weber, Tobias; Thomas, Maik

2014-05-01

99

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

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 erosions over one year (p=0.005, 0.01, and 0.03 respectively), but there was no association with the shared epitope. Progression of MRI erosions to x ray erosions was not seen in those with transient polyarthritis.?CONCLUSIONS—MRI scans of the wrist, taken when patients first present with RA, can predict radiographic erosions at two years. MRI may have a role in the assessment of disease prognosis and selection of patients for more or less aggressive treatment. However, only one in four MRI erosions progresses to an x ray erosion over one year, possibly owing to healing, observer error, or technical limitations of radiography at the carpus. Progression of MRI erosions to x ray erosions is greatest in those with high baseline disease activity.??

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

2001-01-01

100

Rejuvenating the immune system in rheumatoid arthritis  

Microsoft Academic Search

In rheumatoid arthritis (RA), the aging process of the immune system is accelerated. Formerly, this phenomenon was suspected to be a consequence of chronic inflammatory activity. However, newer data strongly suggest that deficiencies in maintaining telomeres and overall DNA stability cause excessive apoptosis of RA T cells, imposing proliferative pressure and premature aging on the system. Already during the early

Hiroshi Fujii; Lan Shao; Jörg J. Goronzy; Cornelia M. Weyand

2009-01-01

101

Organizing Pneumonia Preceding Rheumatoid Arthritis  

PubMed Central

Rheumatoid arthritis patients are susceptible to interstitial lung disease, and joint manifestations of rheumatoid arthritis usually precede lung involvements by several years. Organizing pneumonia, as the first manifestation of rheumatoid arthritis, is extremely rare, and its clinical features remain currently unknown. We present a case and a literature review of patients who were pathologically diagnosed with organizing pneumonia first and met the diagnostic criteria of rheumatoid arthritis later. In this review, we observed the following: (1) patients with organizing pneumonia preceding rheumatoid arthritis have a high prevalence of rheumatoid factor or anticyclic citrullinated peptide antibodies; (2) almost all patients developed rheumatoid arthritis within one year after the diagnosis of organizing pneumonia. We suggest that patients with organizing pneumonia and positive for either rheumatoid factor or anticyclic citrullinated peptide antibody should be cautiously followed up regarding the development of rheumatoid arthritis, particularly during the first year after the diagnosis of organizing pneumonia.

Kinoshita, Yoshiaki; Sakamoto, Atsuhiko; Hidaka, Kouko

2014-01-01

102

The likelihood of persistent arthritis increases with the level of anti-citrullinated peptide antibody and immunoglobulin M rheumatoid factor: a longitudinal study of 376 patients with very early undifferentiated arthritis  

PubMed Central

Introduction We wanted to assess the importance of the levels of anti-citrullinated peptide antibody (anti-CCP) and immunoglobulin M (IgM) rheumatoid factor (RF) in predicting development of persistent arthritis from undifferentiated arthritis (UA), and to investigate whether there is an added predictive value for persistent arthritis in testing for both anti-CCP and IgM RF. Methods Patients with UA (exclusion of definite non-rheumatoid arthritis (RA) diagnoses) included in the Norwegian very early arthritis clinic were assessed for development of persistent arthritic disease. The effect of antibody level on the likelihood of persistent arthritis was investigated, and the sensitivity and specificity for persistent arthritis for anti-CCP and IgM RF, separately and combined, was determined. Results A total of 376 UA patients were included (median arthritis duration 32 days). 59 (15.7%) patients were IgM RF positive, and 62 (16.5%) anti-CCP positive. One hundred, seventy-four (46.3%) had persistent disease after one year. Overlap of anti-CCP and IgM RF positivity was 58%. Sensitivity/specificity for persistent arthritis was 28/95% for IgM RF alone, 30/95% for anti-CCP alone, and 37/92% for positivity of both anti-CCP and IgM RF. The likelihood for persistent disease increased with increasing levels of both anti-CCP and IgM RF. Conclusions The likelihood of developing persistent arthritis in UA patients increases with the level of anti-CCP and IgM RF. Testing both anti-CCP and IgM RF has added predictive value in UA patients. This study suggests that antibody level should be taken into account when making risk assessments in patients with UA.

2010-01-01

103

Rheumatoid arthritis and fatigue.  

PubMed

Essential facts There are nearly 690,000 people in the UK with rheumatoid arthritis, a chronic autoimmune disease. Many of these people experience pain, inflammation, stiffness, reduced mobility and joint function, and fatigue. PMID:25005390

2014-07-01

104

Epigenetics in Rheumatoid Arthritis  

Microsoft Academic Search

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

Michelle Trenkmann; Matthias Brock; Caroline Ospelt; Steffen Gay

2010-01-01

105

Juvenile Rheumatoid Arthritis  

Microsoft Academic Search

\\u000a Juvenile rheumatoid arthritis (JRA) is the most common type of childhood and adolescent chronic arthritis and a major cause\\u000a of short- and long-term disability among the pediatric age group with chronic pediatric diseases (Cassidy & Petty, 2005) The\\u000a term juvenile rheumatoid arthritis is used here because the criteria for this diagnosis (Cassidy et al., 1986) were the inclusion\\u000a criteria for

Michael A. Rapoff; Carol B. Lindsley

106

Rheumatoid Arthritis Educational Video Series  

MedlinePLUS Videos and Cool Tools

... Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid ... intended for educational purposes only. Physicians and other health care professionals are encouraged to consult other sources ...

107

BAGGING OPTIMAL ROC CURVE METHOD FOR PREDICTIVE GENETIC TESTS, WITH AN APPLICATION FOR RHEUMATOID ARTHRITIS  

PubMed Central

Translation studies have been initiated to assess the combined effect of genetic loci from recently accomplished genome-wide association studies and the existing risk factors for early disease prediction. We propose a bagging optimal receiver operating characteristic (ROC) curve method to facilitate this research. Through simulation and real data application, we compared the new method with the commonly used allele counting method and logistic regression, and found that the new method yields a better performance. The new method was applied on the Wellcome Trust data set to form a predictive genetic test for rheumatoid arthritis. The formed test reached an area under the curve (AUC) value of 0.7.

Lu, Qing; Cui, Yuehua; Ye, Chengyin; Wei, Changshuai; Elston, Robert C.

2013-01-01

108

Discovery 3: A Simulation of Early American Colonization.  

ERIC Educational Resources Information Center

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…

Wesley, John

109

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

PubMed Central

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

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

2005-01-01

110

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

Microsoft Academic Search

This thesis presents the results of several general circulation model simulations of the Early Jurassic climate. The simulations were designed so that meaningful model-data comparisons could be made. The general circulation model employed was developed at the Goddard Institute for Space Studies while most paleoclimate data were provided by the Paleogeographic Atlas Project of the University of Chicago. The first

Mark Arnold Chandler

1992-01-01

111

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

Microsoft Academic Search

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

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

1992-01-01

112

Can we simulate issues of diversity in early childhood education? Teacher preparation in interpersonal skills  

Microsoft Academic Search

This article describes the effectiveness of the Structured Simulation Training Method (SSTM) as a pedagogical too] to prepare student teachers for work in inclusive early childhood settings. Simulations are a performance?based methodology designed to allow student teachers to directly experience issues in diversity and practice interpersonal communication, consultation and decision?making skills. Qualitative methodologies were employed to analyze data collected from

Elaine B. Frankel; Patricia Corson

2003-01-01

113

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

ERIC Educational Resources Information Center

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…

Mallery, Janet G.

2002-01-01

114

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

ERIC Educational Resources Information Center

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…

van Ments, Morry

2011-01-01

115

Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset  

Microsoft Academic Search

Objective: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression.Methods: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients)

E Berglin; T Johansson; U Sundin; E Jidell; G Wadell; G Hallmans; S Rantapa?a?-Dahlqvist

2006-01-01

116

What Is Rheumatoid Arthritis?  

MedlinePLUS

... publication. To order Rheumatoid Arthritis Handout on Health full-text version, please contact NIAMS using the contact information above. To view the complete text or to order online, visit ... updates and for any questions about any medications you are taking, please ...

117

Rheumatoid arthritis: sequences  

Microsoft Academic Search

Objective: Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology characterized by symmetric, erosive synovitis and sometimes multisystem involvement. It affects 1% of the adult population and exhibits a chronic fluctuating course which may result in progressive joint destruction, deformity, disability and premature death. We review the literature data relative to the peculiar pathologic features of the disease shown

Pier Nuccio Scutellari; Carlo Orzincolo

1998-01-01

118

Oxidation in rheumatoid arthritis  

Microsoft Academic Search

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. They also serve as

Carol A Hitchon; Hani S El-Gabalawy

2004-01-01

119

Clinical features, diagnosis, and prognosis in rheumatoid arthritis.  

PubMed

The past year has witnessed a modest expansion in our understanding of the clinical, diagnostic, and prognostic features of rheumatoid arthritis. Almost every continent has reported prevalence, phenotype, and clinical features of rheumatoid arthritis subpopulations. Reviews of the natural history and therapy of cervical spine disease, Felty's disease, and lung involvement dominate the clinical literature. Rheumatoid arthritis-like syndromes have been reported to occur after immunotherapy with interferon alfa and interleukin-2. There have been case studies on human immunodeficiency virus, cachexia, pregnancy, "pseudosepsis," bone loss, and malignancy in rheumatoid arthritis. Diagnostic criteria and new classifications for functional and global impairment have been published, and new health impairment questionnaires have been evaluated. Novel isotopes and the role of magnetic resonance imaging in damaged joints were discussed. Rheumatoid factor was reaffirmed as a significant prognostic variable, and the roles of immunogenetic loci, sulfur oxidation, and serum matrix proteins were evaluated in early rheumatoid arthritis. Functional status was again verified as a strong prognostic marker. PMID:8452769

Morgan, G J; Chow, W S

1993-03-01

120

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

ERIC Educational Resources Information Center

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

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

2005-01-01

121

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

SciTech Connect

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.

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

2011-03-07

122

Early Evolution of Vertical Vorticity in a Numerically Simulated Idealized Convective Line.  

NASA Astrophysics Data System (ADS)

The generation and organization of mesoscale convective vortices (MCVs) is a recurring theme in midlatitude and tropical meteorology during the warm season. In this work a simulation of a finite-length idealized convective line in a westerly shear environment is investigated in the absence of ambient vertical vorticity. An asymmetry in average vertical vorticity forms rapidly at early times in the present simulation. This study focuses on the formation and organization of vertical vorticity at these early simulation times. Previous simulations suggest that tilting of either ambient or storm-generated horizontal vorticity is the primary mechanism responsible for the formation, organization, and maintenance of MCVs. This study confirms recent work regarding the generation of vertical vorticity at early times in the simulation. A Lagrangian budget analysis of the vertical vorticity equation, however, shows that vorticity convergence becomes a comparable, and at times dominant, mechanism for the enhancement and long-term organization of vertical vorticity early in the simulation. Despite differences in the initial ambient horizontal vorticity, hodograph, and convective available potential energy, the Lagrangian budget analysis in the present midlatitude case is consistent with the Lagrangian budget results of a previous tropical squall line simulation. The study of idealized convective lines in midlatitude environmental conditions therefore provide valuable insight into understanding vertical vorticity production in tropical squall lines and their potential relevance to tropical cyclogenesis.

Cram, Thomas A.; Montgomery, Michael T.; Hertenstein, Rolf F. A.

2002-07-01

123

The NOAR Damaged Joint Count (NOAR-DJC): a clinical measure for assessing articular damage in patients with early inflammatory polyarthritis including rheumatoid arthritis  

Microsoft Academic Search

Objectives. To evaluate the reliability and validity of the Norfolk Arthritis Register Damaged Joint Count (NOAR-DJC) in patients with early inflammatory polyarthritis (IP). Methods. The NOAR-DJC examines deformity in 51 joints. Deformity is defined as inability to adopt the anatomical position, reduction in range of movement by at least one-third, and\\/or surgical alteration of the joint. Reliability was investigated by

D. K. Bunn; L. Shepstone; L. M. Galpin; N. J. Wiles; D. P. M. Symmons

2004-01-01

124

Molecular dynamics simulation suggests possible interaction patterns at early steps of beta2-microglobulin aggregation.  

PubMed

Early events in aggregation of proteins are not easily accessible by experiments. In this work, we perform a 5-ns molecular dynamics simulation of an ensemble of 27 copies of beta(2)-microglobulin in explicit solvent. During the simulation, the formation of intermolecular contacts is observed. The simulation highlights the importance of apical residues and, in particular, of those at the N-terminus end of the molecule. The most frequently found pattern of interaction involves a head-to-head contact arrangement of molecules. Hydrophobic contacts appear to be important for the establishment of long-lived (on the simulation timescale) contacts. Although early events on the pathway to aggregation and fibril formation are not directly related to the end-state of the process, which is reached on a much longer timescale, simulation results are consistent with experimental data and in general with a parallel arrangement of intermolecular beta-strand pairs. PMID:17158575

Fogolari, Federico; Corazza, Alessandra; Viglino, Paolo; Zuccato, Pierfrancesco; Pieri, Lidia; Faccioli, Pietro; Bellotti, Vittorio; Esposito, Gennaro

2007-03-01

125

Molecular Dynamics Simulation Suggests Possible Interaction Patterns at Early Steps of ?2-Microglobulin Aggregation  

PubMed Central

Early events in aggregation of proteins are not easily accessible by experiments. In this work, we perform a 5-ns molecular dynamics simulation of an ensemble of 27 copies of ?2-microglobulin in explicit solvent. During the simulation, the formation of intermolecular contacts is observed. The simulation highlights the importance of apical residues and, in particular, of those at the N-terminus end of the molecule. The most frequently found pattern of interaction involves a head-to-head contact arrangement of molecules. Hydrophobic contacts appear to be important for the establishment of long-lived (on the simulation timescale) contacts. Although early events on the pathway to aggregation and fibril formation are not directly related to the end-state of the process, which is reached on a much longer timescale, simulation results are consistent with experimental data and in general with a parallel arrangement of intermolecular ?-strand pairs.

Fogolari, Federico; Corazza, Alessandra; Viglino, Paolo; Zuccato, Pierfrancesco; Pieri, Lidia; Faccioli, Pietro; Bellotti, Vittorio; Esposito, Gennaro

2007-01-01

126

Oxidation in rheumatoid arthritis  

PubMed Central

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

Hitchon, Carol A; El-Gabalawy, Hani S

2004-01-01

127

[Elderly onset rheumatoid arthritis].  

PubMed

Elderly-onset rheumatoid arthritis (EORA), defined as rheumatoid arthritis (RA) with the onset at the age > or =60 differs sligthy at presentation from younger-onset RA (YORA) by a more equal sex distribution, a higher frequency of an acute onset, more frequent involvement of large joints, especially of the shoulder, and higher disease activity. Longitudinal studies have shown greater disease activity, more severe radiographic damage and functional decline in patients with EORA than in those with YORA. These differences were only found in seropositive patients. In seronegative EORA patients a less severe course of the disease and a better outcome have been observed, with the clinical manifestations of polymyalgia rheumatica or remitting seronegative symmetrical synovitis with pitting edema. This article is a review of available data concerning differences between EORA and YORA. PMID:19562968

Filipowicz-Sosnowska, Anna; Rupi?ski, Robert

2008-01-01

128

Myositis bei rheumatoider Arthritis?  

Microsoft Academic Search

Summary Myositis in rheumatoid arthritis? Cholesterol-lowering therapy using 3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has been shown to reduce cardiovascular risk in both primary and secondary prevention studies. Although statins are generally well tolerated, they also have potentially serious adverse effects on skeletal muscles. We describe the case of a patient presenting with regional muscle pain of the shoulder and

Beat Flückiger; Mario Picozzi; Robert Theiler

129

Elderly Onset Rheumatoid Arthritis  

Microsoft Academic Search

\\u000a As the number of people who are over the age of 60 years is growing in the general population, the prevalence of disability\\u000a from rheumatoid arthritis (RA) is also on the rise. This is an important health concern for patients, their families, and\\u000a society. This review highlights various aspects of elderly onset RA (EORA), including differences from younger onset RA

Venkata Sri Cherukumilli; Arthur Kavanaugh

130

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

PubMed

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. [Adaptive Radiations, Early Burst, Posterior Predictive Simulations, Quantitative Characters]. PMID:24149077

Slater, Graham J; Pennell, Matthew W

2014-05-01

131

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

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.

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

132

Early genetic responses in rat vascular tissue after simulated diving.  

PubMed

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

Eftedal, Ingrid; Jørgensen, Arve; Røsbjørgen, Ragnhild; Flatberg, Arnar; Brubakk, Alf O

2012-12-18

133

Anglo-French contributions to the recognition of rheumatoid arthritis  

PubMed Central

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

Fraser, Kevin J.

1982-01-01

134

Randomized controlled trial design in rheumatoid arthritis: the past decade  

Microsoft Academic Search

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

Vibeke Strand; Jeremy Sokolove

2009-01-01

135

Patients with rheumatoid arthritis have an altered circulatory aggrecan profile  

Microsoft Academic Search

BACKGROUND: Rheumatoid arthritis (RA) is a chronic auto-immune disease with extensive articular cartilage destruction. Aggrecan depletion, mediated by aggrecanases is one of the first signs of early cartilage erosion. We investigated, whether measurement of aggrecan and fragments thereof in serum, could be used as biomarkers for joint-disease in RA patients and furthermore characterized the fragments found in the circulation. METHODS:

Jean C Rousseau; Eren U Sumer; Gert Hein; Bodil C Sondergaard; Suzi H Madsen; Christian Pedersen; Thomas Neumann; Andreas Mueller; Per Qvist; Pierre Delmas; Morten A Karsdal

2008-01-01

136

Functional Ability, Social Support, and Depression in Rheumatoid Arthritis  

Microsoft Academic Search

Objective: First, to investigate the patterns of functional ability, depressive feelings, and social support in early stage rheumatoid arthritis (RA) patients. Second, to demonstrate the stress buffering effect of social support. Social support is thought to reduce the impact of chronic stress on psychological well-being; for patients without social support the impact of functional ability on depressive feelings will be

D. M. Doeglas; Th. P. B. M. Suurmeijer; B. Krol; M. H. van Rijswijk; M. A. van Leeuwen; R. Sanderman

2004-01-01

137

Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs  

PubMed Central

Introduction Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA. Methods The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ? 1) at 12 months. Results Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ? 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01). Conclusions CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.

2012-01-01

138

B cells in rheumatoid arthritis  

Microsoft Academic Search

Though its etiology remains unknown thus far, the role that autoimmune processes play in rheumatoid arthritis (RA) pathogenesis has been widely proven. Given the easier accessibility of humoral components, the first feature of this contribution to be recognized has been the occurrence of the so-called rheumatoid factor in a large proportion of RA patients. This antibody recognizes the Fc portion

Serena Bugatti; Veronica Codullo; Roberto Caporali; Carlomaurizio Montecucco

2007-01-01

139

Rheumatoid Arthritis May Harm Kidneys  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Rheumatoid Arthritis May Harm Kidneys Study found patients may be ... 11, 2014 Related MedlinePlus Pages Chronic Kidney Disease Rheumatoid Arthritis FRIDAY, April 11, 2014 (HealthDay News) -- People with ...

140

Hidden 19S IgM rheumatoid factor in adults with juvenile rheumatoid arthritis onset.  

PubMed Central

Forty-eight adult patients with juvenile rheumatoid arthritis (JRA) (onset before age 16 years) were evaluated at the age of 17 years or more for the presence of hidden 19S IgM rheumatoid factors (RF), i.e., 19S IgM RF that can be detected by the complement-dependent haemolytic assay in the IgM-containing fraction after separation of the serum by acid gel filtration. The average age of the patients was 25.3 years. The mean duration of disease was 16.5 years. Thirty-two of 48 patients (67%) showed the presence of hidden 19S IgM RF in their serum. Disease activity correlated with hidden RF titres in 62% (55/88) of the evaluations. The results indicate that patients with seronegative JRA onset continue to have significant titres of hidden 19S IgM RF in their sera into early adulthood.

Speiser, J C; Moore, T L; Weiss, T D; Baldassare, A R; Ross, S C; Osborn, T G; Dorner, R W; Zuckner, J

1985-01-01

141

Arthroscopic Synovectomy in Rheumatoid Arthritis of Wrist  

PubMed Central

The wrist is the most commonly involved region of the upper extremity in rheumatoid arthritis (RA). Because the wrist joint becomes involved early during the disease course and its involvement rapidly progresses, and because the disabilities associated with progressive RA are significant, early and adequate treatment must be introduced to prevent disease progression. Various treatment methods can be employed to treat RA wrists based on radiological and clinical findings. Arthroscopic synovectomy is recommended for pain relief and functional recovery in early stage RA, and is also helpful in advanced staged RA with Larsen stage III. However, arthroscopic synovectomy is not recommended as an effective method of treatment for all patients with advanced radiographic changes. Nevertheless, arthroscopic synovectomy may delay the need for complex surgery, such as wrist arthrodesis or total wrist arthroplasty in selective cases. Although arthroscopic synovectomy of the wrist cannot improve grip strength or range of motion, it can reduce wrist pain and improve function, and thus facilitate return to work.

Kim, Sung-Jae; Jung, Kwang-Am

2007-01-01

142

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

NASA Astrophysics Data System (ADS)

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

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

2012-04-01

143

Understanding IFN? in rheumatoid arthritis  

PubMed Central

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

2014-01-01

144

Rheumatoid Arthritis Educational Video Series  

MedlinePLUS Videos and Cool Tools

... Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ... Sheets Benefits and Risks of Opioids in Arthritis Management How to Give a Subcutaneous Injection All information ...

145

[Endoprosthetic procedures in rheumatoid patients].  

PubMed

Rheumatoid diseases are generalized chronic inflammatory diseases of the musculoskeletal system. Although the different structures and different joints are affected, all cause a very uniform type of pathology and joint destruction. The main indication for implantation of the endoprosthesis are severe pain and walking disability with poor quality of life. On the X-ray involvement includes periarticular osteopenia, cystic changes, and destruction's affected joints. Endoprosthetic replacement has been successful in the treatment of severe rheumatoid disease of almost all joints of all ages, but predominantly replacement of the hip, knee, shoulder, elbow and MCP joints. Arthroplasty has proved to be an excellent addition to the therapeutic armamentarium for the rehabilitation of handicapped patients with rheumatoid disease. Advancements in endoprosthetic technology and surgical techniques, allow us to perform alloarthroplasty in most of the patients with severe rheumatoid disease of all different joints. PMID:15098366

Orli?, Dubravko

2003-01-01

146

Simulated microgravity as a probe for understanding the mechanisms of early pattern specification  

NASA Technical Reports Server (NTRS)

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.

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

1985-01-01

147

Support for early verification of embedded real-time systems through UML models simulation  

Microsoft Academic Search

Identifying errors in early design phases leads to a decrease in the repairing cost compared to the situation in which such problems are discovered only in advanced design phases. This work is a first step toward an automatic verification approach for embedded and real-time systems' high-level specifications, such as UML models. This paper presents a model-driven framework to simulate system's

Marco A. Wehrmeister; Joao G. Packer; Luis M. Ceron

2012-01-01

148

[Electrocardiographic changes in rheumatoid arthritis].  

PubMed

The clinical course of 50 patients with rheumatoid arthritis has been reviewed with special emphasis on the electrocardiographic changes. Thirty two of 50 of these patients presented electrocardiographic abnormalities and two cases had myocardial infarction. Electrocardiographic changes were associated with activity of the sickness. It is possible that the electrocardiovasculars manifestations represent the first manifestation of the rheumatoid arthritis therefore it is convenient to check them the whole time, even in case the patient does not present clinical abnormalities. PMID:748909

Cetina Manzanilla, J A; Patrón Amador, E

1978-01-01

149

Rheumatoid nodule presenting as Morton's neuroma.  

PubMed

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. PMID:23135058

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

2013-09-01

150

Does parvovirus B19 have a role in rheumatoid arthritis?  

PubMed Central

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

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

1994-01-01

151

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

SciTech Connect

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.

Chandler, M.A. [Columbia Univ., Palisades, NY (United States)] [Columbia Univ., Palisades, NY (United States); Rind, D.; Ruedy, R. [Goddard Institute for Space Studies, New York, NY (United States)] [Goddard Institute for Space Studies, New York, NY (United States)

1992-05-01

152

Early human-plant interactions based on palaeovegetation simulations of Africa over glacial-interglacial cycles  

NASA Astrophysics Data System (ADS)

A greater understanding of African palaeovegetation environments over the Pleistocene (1.6 Mya) is important for evaluating potential catalysts underlying the anatomical, social and demographic changes observed in early human populations. We used a state-of-the-art fully-coupled earth system model (HADLEY-GCM3) to simulate typical glacial and interglacial environments likely encountered by late-Pleistocene humans. Our simulations indicate that tropical broadleaf forests of central Africa were not severely restricted by expanding grasslands during the last glacial maximum, although the carbon content of stem and density of leaf components were substantially reduced. We interpret a natural eastern migration corridor between southern Africa and the Rift Valley based on simulations of a no-analogue vegetation assemblage characterised by a unique combination of grass and low density forest. We postulate that early human populations in southern Africa were isolated from northern groups during warm interglacials, and that trans-African migration was facilitated during glacial cycles via a more openly forested eastern corridor.

Cowling, S. A.; Cox, P. M.; Jones, C. D.; Maslin, M. A.; Spall, S. A.

2003-04-01

153

Decision-Making Through Performance Simulation and Code Compliance from the Early, Schematic Phases of Building Design.  

National Technical Information Service (NTIS)

This paper is about the merging of two software applications that allows building decision makers to consider code compliance and to use performance simulation tools from the early, schematic phases of building design. By making the capabilities of a code...

G. Reichard K. Papamichael

2005-01-01

154

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

PubMed

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

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

2014-08-01

155

New Directions for Biological Therapy in Rheumatoid Arthritis  

Microsoft Academic Search

Advances in our understanding of the pathogenesis of rheumatoid arthritis (RA), together with developments in hybridoma and molecular technology have opened the way for more directed therapy in this disease. In reviewing the experience so far with T-cell-directed biological agents, we show that the early promise displayed by anti-CD4 monoclonal antibodies in open clinical trials has not been sustained in

Michael J. Elliott; Ravinder N. Maini

1994-01-01

156

Combination Therapy for Rheumatoid Arthritis in the Era of Biologicals  

Microsoft Academic Search

Early, aggressive disease management is critical for halting disease progression and joint destruction in patients with rheumatoid\\u000a arthritis. Combination therapy with at least two disease-modifying antirheumatic drugs, such as methotrexate (MTX), sulfasalazine,\\u000a or hydroxychloroquine, is often more effective than monotherapy in reducing disease activity. Biologic therapies represent\\u000a more effective and tolerable treatment options that, when combined with MTX, have been

Allan Gibofsky

2006-01-01

157

Does parvovirus B19 have a role in rheumatoid arthritis?  

Microsoft Academic Search

OBJECTIVES--To determine whether parvovirus B19 (B19) infection is associated with rheumatoid arthritis (RA). METHODS--The polymerase chain reaction was applied to serum, cells isolated from synovial fluid, and synovial fluid. Enzyme immunoassay technique was used to detect antibodies against B19. RESULTS--Of 142 patients with early RA (onset of disease under one year) and 67 control patients, serological evidence of recent parvoviral

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

1994-01-01

158

Rheumatoid pneumoconiosis (Caplan's syndrome).  

PubMed

In 1953, Caplan described a characteristic radiographic pattern in coal miners with rheumatoid arthritis (RA) that was distinct from the typical progressive massive fibrosis pattern of coalworkers' pneumoconiosis. It consists of multiple well-defined rounded nodules on chest X-ray, from about 0.5 to about several centimetres in diameter, distributed throughout the lungs but predominantly at the lung periphery. Lesions appear often in crops, may coalesce and form a larger confluent nodule. Nodules often cavitate or calcify. They typically occur in the setting of pre-existing mild pneumoconiosis, but pneumoconiosis is not a prerequisite. The onset of the nodules is typically sudden, and their course varies thereafter, ranging from regression to progression. Histologically, the nodules have a characteristic appearance and are distinguishable from silicotic nodules or progressive massive fibrosis. Individual susceptibility is considered to play a role in the development of the disease. However, the pathogenetic link between exposure to silica, pneumoconiosis and RA has not been clarified conclusively. This review summarizes history, definition and current knowledge on epidemiology, pathology, pathophysiology, clinical presentation and treatment of Caplan's syndrome. PMID:20493416

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

2010-06-01

159

Ultrasound in rheumatoid arthritis.  

PubMed

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. PMID:23979615

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

2013-09-01

160

Vaccinations for rheumatoid arthritis.  

PubMed

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

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

2014-08-01

161

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

NASA Technical Reports Server (NTRS)

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

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

1979-01-01

162

Simulation of multiple ion channel block provides improved early prediction of compounds' clinical torsadogenic risk  

PubMed Central

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

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

2011-01-01

163

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

PubMed Central

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.

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

2012-01-01

164

Comparing stochastic differential equations and agent-based modelling and simulation for early-stage cancer.  

PubMed

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

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

2014-01-01

165

Recent advances in rheumatoid arthritis  

Microsoft Academic Search

Management of rheumatoid arthritis (RA) has radically changed over the last decade. Diagnostic methods have improved with availability of highly specific tests such as antibody to cyclic citrullinated peptide (specificity ?96%), and introduction of advanced imaging modalities such as ultrasound and magnetic resonance imaging to facilitate earlier diagnosis. The current aim of management is to achieve remission and prevent joint

Ernest Suresh

2010-01-01

166

Therapeutic strategies for rheumatoid arthritis  

Microsoft Academic Search

Recent years have seen considerable advances in our understanding of both the clinical and basic-research aspects of rheumatoid arthritis. Clinical progress has come from a better recognition of the natural history of the disease, the development and validation of outcome measures for clinical trials and, consequently, innovative trial designs. In parallel, basic research has provided clues to the pathogenic events

Günter Steiner; Josef S. Smolen

2003-01-01

167

Conjunctival nodule in rheumatoid arthritis.  

PubMed

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

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

2012-02-01

168

Epigenetic modifications in rheumatoid arthritis  

Microsoft Academic Search

Over the last decades, genetic factors for rheumatoid diseases like the HLA haplotypes have been studied extensively. However, during the past years of research, it has become more and more evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic background of a patient. Epigenetic processes are heritable changes in

Simon Strietholt; Britta Maurer; Marvin A Peters; Thomas Pap; Steffen Gay

2008-01-01

169

Somatostatin Involvement in Rheumatoid Arthritis  

Microsoft Academic Search

Somatostatin (somatotropin release inhibitory factor; SRIF) peptides are widely distributed in the mammalian body and, acting through a family of genetically homologous cell surface receptors (sst1-5), regulate cellular secretion and proliferation. Compelling evidence implicates SRIF peptides and peptidyl analogues in chronic inflammatory diseases such as rheumatoid arthritis (RA). SRIF membrane receptors exist on immune and synovial cells, thereby providing mo-

Allan D. Blake; Frances Mae West; Sadia Ghafoor; Petros Efthimiou

2007-01-01

170

Organising pneumonia as the first manifestation of rheumatoid arthritis  

PubMed Central

Organising pneumonia (OP) is an inflammatory lung disease with distinctive clinicopathological features. OP can be evident during the course of rheumatoid arthritis (RA) with increased disease activity. The authors report an OP associated with RA case in which pulmonary symptoms preceded the onset of joint symptoms. An OP patient with elevated serum anticyclic citrullinated peptide antibody is likely to manifest RA in the near future, reflecting its high disease activity. Thus, an early rheumatologic consultation should be taken into consideration to make an early decision to initiate disease-modifying antirheumatic drugs therapy.

Hoshino, Chisho; Satoh, Noriyuki; Narita, Masashi; Kikuchi, Akio; Inoue, Minoru

2011-01-01

171

Interest of modelling in rheumatoid arthritis.  

PubMed

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

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

2012-01-01

172

Rheumatoid Factor in Liver Shown by Immunofluorescence Method.  

National Technical Information Service (NTIS)

In liver diseases and in chronic bronchitis the appearance of sera testing positive for rheumatoid factor is quite frequently noted. The presence of rheumatoid factor was demonstrated in the livers of patients with rheumatoid arthritis and in patients wit...

L. Bonomo

1966-01-01

173

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

SciTech Connect

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

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

2012-08-01

174

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

NASA Astrophysics Data System (ADS)

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

D'Alessio, M. A.

2010-12-01

175

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

NASA Technical Reports Server (NTRS)

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

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

1993-01-01

176

Class-specific rheumatoid factors, DR antigens, and amyloidosis in patients with rheumatoid arthritis  

Microsoft Academic Search

Class-specific rheumatoid factors (RFs) were measured by enzyme immunoassay in 59 patients with rheumatoid arthritis complicated by systemic amyloidosis (RA+A), 47 patients with rheumatoid arthritis without amyloid (RA), 106 patients with other rheumatic diseases (juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome), and 55 blood donors. The patients with RA+A were characterised by a high prevalence of RF negativity; the

C P Maury; A M Teppo; F Wafin; O Wegelius; C Friman; S Koskimies

1988-01-01

177

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

NASA Astrophysics Data System (ADS)

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.

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

2014-04-01

178

Simulation of planetary UV radiation climate on the example of the early earth  

NASA Astrophysics Data System (ADS)

Solar UV radiation is a dynamic driving force of organic chemical evolution. However, it may have severe constraints in biological evolution, for instance in the early history of life on Earth, before atmospheric evolution of a protective ozone layer. Today, the full spectrum of solar UV radiation is experienced only in space. In the experiment RD-UVRAD on D-2 the biological response to solar UV as a function of ozone concentrations down to very low values was investigated. Biofilms, biological UV dosimeters, were exposed to the extraterrestrial solar radiation on one of the two exposure trays mounted on the User Support Structure (USS) with free access to space. Different cut-off filters, which exclude UV of short wavelengths, and neutral density filters were used. After the flight the biofilms were developed and analyzed on ground. As a result a strong correlation between the increase in biologically effective UV radiation with decreasing (simulated) ozone concentrations was observed. Without any ozone the solar UV radiation is about three orders of magnitude more effective than today on Earth. This space experiment resulted in new insights in the environmental conditions of life on the early Earth and in the deleterious biological consequences of future stratospheric ozone depletion.

Rettberg, P.; Horneck, G.; Strauch, W.; Facius, R.; Seckmeyer, G.

179

Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies  

PubMed Central

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease, characterized by chronic, erosive polyarthritis and by the presence of various autoantibodies in serum and synovial fluid. Since rheumatoid factor (RF) was first described, a number of other autoantibodies have been discovered in RA patients. The autoantigens recognized by these autoantibodies include cartilage components, chaperones, enzymes, nuclear proteins and citrullinated proteins. However, the clinical significances and pathogenic roles of these antibodies are largely unknown except for RF and anticitrullinated protein antibodies (ACPAs), whose clinical usefulness has been acknowledged due to their acceptable sensitivities and specificities, and prognostic values. This review presents and discusses the current state of the art regarding RF and ACPA in RA.

Kang, E.H.

2010-01-01

180

Coexistence of ochronosis and rheumatoid arthritis  

Microsoft Academic Search

We describe a 64-year-old female patient with ochronosis and rheumatoid arthritis. Magnetic resonance imaging of the spinal column disclosed the destruction of vertebral disks, and a bony bridging in Th12 to L2. In addition, we observed joint space narrowing in the wrists as well as among the carpal bones, positive rheumatoid factor and the presence of rheumatoid nodules, in which

T. Kihara; M. Yasuda; H. Watanabe; Y. Suenaga; S. Shiokawa; T. Wada; S. Nonaka; T. Suzuki; M. Nobunaga

1994-01-01

181

SIMULATIONS OF EARLY BARYONIC STRUCTURE FORMATION WITH STREAM VELOCITY. I. HALO ABUNDANCE  

SciTech Connect

It has been recently shown that the relative velocity between the dark matter and the baryons (v{sub bc}) at the time of recombination can affect the structure formation in the early universe. We statistically quantify this effect using large cosmological simulations. We use three different high-resolution sets of simulations (with separate transfer functions for baryons and dark matter) that vary in box size, particle number, and the value of the relative velocity between dark matter and baryons. We show that the total number density of halos is suppressed by {approx}20% at z = 25 for v{sub bc} = 1{sigma}{sub vbc}, where {sigma}{sub vbc} is the variance of the relative velocity, while for v{sub bc} = 3.4{sigma}{sub vbc} the relative suppression at the same redshift reaches 50%, remaining at or above the 30% level all the way to z = 11. We also find a high abundance of 'empty halos', i.e., halos that have gas fraction below half of the cosmic mean baryonic fraction f-bar{sub b}. Specifically, we find that for v{sub bc} = 1{sigma}{sub vbc} all halos below 10{sup 5} M{sub Sun} are empty at z {>=} 19. The high abundance of empty halos results in significant delay in the formation of gas-rich minihalos and the first galaxies.

Naoz, Smadar [CIERA, Northwestern University, Evanston, IL 60208 (United States); Yoshida, Naoki [IPMU, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583 (Japan); Gnedin, Nickolay Y., E-mail: snaoz@northwestern.edu [Particle Astrophysics Center, Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States)

2012-03-10

182

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

NASA Astrophysics Data System (ADS)

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.

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

183

Modelling of 3D Early Blood Vessel Formation: Simulations and Morphological Analysis  

NASA Astrophysics Data System (ADS)

Vascular networks form by a self-aggregation process of individual endothelial cells that differentiate at seemingly random sites in the embryo and collectively migrate toward each other forming a preliminary vascular plexus (vasculogenesis), followed by functional remodelling that gives rise to the final hierarchical system (angiogenesis). The study of this phenomenon is performed by biologists using in vitro and in vivo assays, both in two and three dimensional settings. The lack of direct biological evidence of the chemotactic autocrine loop that is thought to be the main responsible for the early aggregation, called for the development of mathematical models of this process, in order to study the possible effects of such a loop. After successful two-dimensional studies, the model was recently extended to a three dimensional setting and a suitably efficient approximation scheme for the numerical simulations has been developed, while three-dimensional images of embryo vascular networks are becoming available through confocal microscopy. This paper is concerned with the comparison of experimental and simulated data on embryo vascular plexi. Critical exponents of percolation, Euler-Poincaré characteristic, fractal dimension, power spectrum decay and maximum distance from a vessel are considered and compared.

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

2008-07-01

184

Immunological and immunohistochemical analysis of rheumatoid nodules.  

PubMed Central

An attempt was made to examine the pathophysiology of the rheumatoid nodule. Significant amounts of interleukin 1-like activity and prostaglandin E2 were detected in the supernatants from in vitro organ cultures of rheumatoid nodule tissue. When fresh (but not old) rheumatoid nodules were minced and cultured in vitro prominent outgrowths of cells were observed. These cells expressed both HLA-DR and CD14 antigens but lacked conventional differentiation antigens for T cells and B cells, suggesting that they are of monocyte-macrophage origin. These data suggest that interleukin 1 and prostaglandin E2 may be deeply involved in the formation of rheumatoid nodules. Images

Miyasaka, N; Sato, K; Yamamoto, K; Goto, M; Nishioka, K

1989-01-01

185

Ayurvedic medicine for rheumatoid arthritis.  

PubMed

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

Basnyat, Shristi; Kolasinski, Sharon L

2014-08-01

186

Infliximab in the treatment of rheumatoid arthritis  

PubMed Central

Infliximab was the first monoclonal antibody to human necrosis factor alpha (TNF?) developed for treating rheumatoid arthritis (RA). This chimeric antibody binds with high affinity to both soluble and trans-membrane TNF and is able to reduce synovial inflammation, bone resorption and cartilage degradation. The efficacy of infliximab has been observed in active RA despite treatment with multiple disease modifying anti-rheumatic drugs (DMARDs), and in early disease with no prior treatment by methotrexate (MTX). Infliximab has been shown to reduce joint inflammation and to slow radiographic progression, in both clinical and non-clinical responders. Recent data suggest that using infliximab early in RA treatment increases the percentage of clinical remission and allows infliximab discontinuation. The recommended dosage of 3 mg/kg could be increased up to 10 mg/kg with partial efficacy of the dose escalation. Antibodies to infliximab have been observed in 7% to 61% of patients and are associated with a low trough level of infliximab and secondary response failure. Their occurrence could be prevented by co-medication with MTX. The combination of DMARDs other than MTX with infliximab was found to be safe and efficacious. Infections, principally tuberculosis, are increased in treated patients, and the risk is greater at higher dose. Even if the treatment is generally safe and well tolerated, patients treated with infliximab should be closely monitored.

Perdriger, A

2009-01-01

187

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

PubMed Central

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

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

1970-01-01

188

Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis  

PubMed Central

Introduction To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations.

2010-01-01

189

Family-level coping in juvenile rheumatoid arthritis: Assessing the utility of a quantitative family interview  

Microsoft Academic Search

Objective. To explore the viability of a quantita- tive family interview to describe family-level coping strategies used to deal with juvenile rheumatoid ar- thritis (JRA)-related stressors for early and late ado- lescents. Method. A structured interview protocol with 30 adolescents with JRA and family members assessed ways JRA disrupts or changes family functioning. Emotional reactions, sequential phases of family re-

Pamela J. Degotardi; Tracey A. Revenson; Norman T. Ilowite

1999-01-01

190

Release of cartilage and bone macromolecules into synovial fluid: differences between psoriatic arthritis and rheumatoid arthritis  

Microsoft Academic Search

OBJECTIVETo elucidate whether differences in the destructive tissue process in cartilage and bone in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) can be recognised by different release patterns of molecular fragments derived from joint tissue.METHODSAggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) were quantified by immunoassays in knee joint synovial fluid samples. These were obtained early in the

B Månsson; A Gülfe; P Geborek; D Heinegård; T Saxne

2001-01-01

191

Study on the early stage of thin film growth in pulsed beam deposition by kinetic Monte Carlo simulation  

Microsoft Academic Search

In this study a pulse beam (PB) deposition model based on a square lattice is proposed and is used to simulate the process of thin film growth with the kinetic Monte Carlo method. The influence of frequency and duration of pulse on the nucleation, aggregation, and morphology of thin film growth in the early stage is investigated and discussed. The

Q. Y Zhang; P. K Chu

2002-01-01

192

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

PubMed

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

Taylor, Paul A; Ford, Corey C

2009-06-01

193

Simulating the early Holocene eastern Mediterranean sapropel formation using an ocean biogeochemical model  

NASA Astrophysics Data System (ADS)

The early Holocene sapropel S1 is an organic-rich sediment layer deposited under oxygen depleted conditions below 1800 m between 10 to 6.5 kyr BP in the eastern Mediterranean Sea. Whereas this silled ocean basin is well-ventilated and has a low biological productivity today, the S1 formation indicates drastic changes in the deep water circulation and/or productivity. Commonly, both of these processes are attributed to an enhanced humidity over the broader Mediterranean area. In particular, an increase in the strength of the African monsoon during the African humid period (AHP) is thought to have provided enhanced Nile runoff and nutrient load. However, the exact mechanisms leading to S1 formation are still being debated. Here we apply a regional ocean general circulation model coupled to a marine biogeochemical model covering the entire Mediterranean Sea to explore some of the many published hypotheses on sapropel formation. With a set of simulations we show that S1 formation cannot be explained by either enhanced biological productivity fueled by increased riverine nutrient input, or by an AHP climatic induced stagnating deep water circulation combined with enhanced biological productivity. The main reasons are: (i) Enhanced biological productivity cannot overcome the effect of a continuous deep ventilation, so that a stagnating deep water circulation is a prerequisite for S1 formation. (ii) The pre-sapropel period is characterized by low particulate organic carbon (POC) sediment burial fluxes, implying that river induced eutrophication is not a viable scenario. (iii) The time span required for complete oxygen depletion within the stagnating deep water circulation exceeds the time span between the beginning of the AHP and the onset of the S1 oxygen deficiency, so that the enhanced Nile runoff fueled by the AHP climate is an unlikely trigger for deep water isolation that caused S1 formation. Available data suggest substantial freshening and warming of the Mediterranean upper ocean during the last glacial-interglacial transition that stabilized stratification and prevented deep water ventilation. Imposing the climatic signals of the last glacial-interglacial transition triggers a persistent (> 4 kyr) deep water stagnation in this simulation. The productivity regime in this simulation was assumed similar to the present-day oligotrophic regime, and the simulated POC burial fluxes agree with observed pre-sapropel burial fluxes in sediments. No deep water anoxia evolves in the short time frame of this simulation (4 kyr) relative to the temporal extent of the deglaciation period, which started at ~17.5 kyr BP. The trend of the modeled oxygen consumption suggests that it takes at least 6.5 kyr until deep water anoxia is established. The simulation also suggests that addition of freshwater is required to maintain the stratification in order to meet the reconstructed spatial extent and duration of the S1 deposition. An examination of records of epibenthic deep-sea foraminifera ?18O supports our findings, and indicates that the stagnation of the deep circulation started ~6 kyr before the onset of the S1 deposition.

Grimm, Rosina; Maier-Reimer, Ernst; Mikolajewicz, Uwe; Schmiedl, Gerhard; Adloff, Fanny; Emeis, Kay

2013-04-01

194

Cytokines in the pathogenesis of rheumatoid arthritis  

Microsoft Academic Search

Cytokines regulate a broad range of inflammatory processes that are implicated in the pathogenesis of rheumatoid arthritis. In rheumatoid joints, it is well known that an imbalance between pro- and anti-inflammatory cytokine activities favours the induction of autoimmunity, chronic inflammation and thereby joint damage. However, it remains less clear how cytokines are organized within a hierarchical regulatory network, and therefore

Georg Schett; Iain B. McInnes

2007-01-01

195

Septic arthritis in patients with rheumatoid arthritis  

Microsoft Academic Search

There is an increasing number of rheumatoid patients who get septic arthritis. Chronic use of steroids is one of the important predisposing factors. The clinical picture of septic arthritis is different in immunocompromised patients like patients with rheumatoid arthritis. The diagnosis and management are discussed in this review article.

Abdulaziz Al-Ahaideb

2008-01-01

196

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

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

197

Strategies to control disease in rheumatoid arthritis with tumor necrosis factor antagonists—an opportunity to improve outcomes  

Microsoft Academic Search

Recent data have shown that disability and joint destruction in rheumatoid arthritis (RA) occur early on in the course of the disease and progress rapidly. It has been shown that in the early stages of RA, disability is attributed to increased disease activity, whereas later in the course of the disease, disability results from irreversible joint damage. These findings support

Edward C Keystone

2006-01-01

198

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

PubMed Central

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

McQueen, Fiona M; Ostendorf, Benedikt

2006-01-01

199

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

PubMed Central

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

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

2014-01-01

200

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

Federal Register 2010, 2011, 2012, 2013

...Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products...for industry entitled ``Rheumatoid Arthritis: Developing Drug Products...treatment of patients with rheumatoid arthritis (RA). It also...

2013-05-31

201

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

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

202

Treatment of Rheumatoid Arthritis with Traditional Chinese Medicine  

PubMed Central

Rheumatoid arthritis (RA) is a chronic inflammatory disease that will affect quality of life and, working efficiency, and produce negative thoughts for patients. Current therapy of RA is treated with disease-modifying antirheumatic drugs (DMARDs). Although most of these treatment methods are effective, most patients still have a pleasant experience either due to poor efficacy or side effects or both. Interleukin-6 receptor (IL6R) is important in the pathogenesis of RA. In this study, we would like to detect the potential candidates which inhibit IL6R against RA from traditional Chinese medicine (TCM). We use TCM compounds from the TCM Database@Taiwan for virtually screening the potential IL6R inhibitors. The TCM candidate compound, calycosin, has potent binding affinity with IL6R protein. The molecular dynamics simulation was employed to validate the stability of interaction in the protein complex with calycosin. The analysis indicates that protein complex with calycosin is more stable. In addition, calycosin is known to be one of the components of Angelica sinensis, which has been indicated to have an important role in the treatment of rheumatoid arthritis. Therefore, calycosin is a potential candidate as lead compounds for further study in drug development process with IL6R protein against rheumatoid arthritis.

Lee, Wen-Yuan; Chen, Hsin-Yi

2014-01-01

203

Cost-effectiveness of Adding Magnetic Resonance Imaging to Rheumatoid Arthritis Management  

PubMed Central

Background Early, aggressive treatment of rheumatoid arthritis (RA) improves outcomes but confers increased risk. Risk stratification to target aggressive treatment of high-risk individuals with early RA is considered important to optimize outcomes while minimizing clinical and monetary costs. Some advocate the addition of magnetic resonance imaging (MRI) to standard RA risk stratification with clinical markers for patients early in the disease course. Our objective was to determine the incremental cost-effectiveness of adding MRI to standard risk stratification in early RA. Methods Using a decision analysis model of standard risk stratification with or without MRI, followed by escalated standard treatment protocols based on treatment response, we estimated 1-year and lifetime quality-adjusted life-years, RA-related costs, and incremental cost-effectiveness ratios (with MRI vs without MRI) for RA patients with fewer than 12 months of disease and no baseline radiographic erosions. Inputs were derived from the published literature. We assumed a societal perspective with 3.0% discounting. Results One-year and lifetime incremental cost-effectiveness ratios for adding MRI to standard testing were $204 103 and $167 783 per quality-adjusted life-year gained, respectively. In 1-way sensitivity analyses, model results were insensitive to plausible ranges for every variable except MRI specificity, which published data suggest is below the threshold for MRI cost-effectiveness. In probabilistic sensitivity analyses, most simulations produced lifetime incremental cost-effectiveness ratios in excess of $100 000 per quality-adjusted life-year gained, a commonly cited threshold. Conclusion Under plausible clinical conditions, adding MRI is not cost-effective compared with standard risk stratification in early-RA patients.

Suter, Lisa G.; Fraenkel, Liana; Braithwaite, R. Scott

2014-01-01

204

Randomized controlled trial design in rheumatoid arthritis: the past decade  

PubMed Central

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.

Strand, Vibeke; Sokolove, Jeremy

2009-01-01

205

Rheumatoid arthritis in paintings: a tale of two origins.  

PubMed

Rheumatoid arthritis (RA) is thought to be a 'recent' disease in that descriptions of it were only noted in the 17th century. However, a study of paintings would suggest that RA could have been present as early as the 15th century, when artists started to paint the human body accurately rather than figuratively. Thus, it was possible to deduce from their paintings the occurrence of various medical conditions. If present, RA with its typical finger deformities should be apparent. This review discusses the known occurrences of RA-type deformities in paintings and places this in the context of the origins of the disease. PMID:20374373

Yeap, Swan Sim

2009-12-01

206

Metabolic Syndrome in Rheumatoid Arthritis  

PubMed Central

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

Ferraz-Amaro, Ivan; Gonzalez-Juanatey, Carlos; Lopez-Mejias, Raquel; Riancho-Zarrabeitia, Leyre; Gonzalez-Gay, Miguel A.

2013-01-01

207

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

NASA Astrophysics Data System (ADS)

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.

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

2012-12-01

208

Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study.  

PubMed

Early afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs may also occur at rapid heart rates if repolarization reserve is sufficiently reduced. In this setting, spontaneous diastolic sarcoplasmic reticulum (SR) Ca release can facilitate cellular EAD formation by augmenting inward currents during the action potential plateau, allowing reactivation of the window L-type Ca current to reverse repolarization. Here, we investigated the effects of spontaneous SR Ca release-induced EADs on reentrant wave propagation in simulated one-, two-, and three-dimensional homogeneous cardiac tissue using a version of the Luo-Rudy dynamic ventricular action potential model modified to increase the likelihood of these EADs. We found: 1) during reentry, nonuniformity in spontaneous SR Ca release related to subtle differences in excitation history throughout the tissue created adjacent regions with and without EADs. This allowed EADs to initiate new wavefronts propagating into repolarized tissue; 2) EAD-generated wavefronts could propagate in either the original or opposite direction, as a single new wave or two new waves, depending on the refractoriness of tissue bordering the EAD region; 3) by suddenly prolonging local refractoriness, EADs caused rapid rotor displacement, shifting the electrical axis; and 4) rapid rotor displacement promoted self-termination by collision with tissue borders, but persistent EADs could regenerate single or multiple focal excitations that reinitiated reentry. These findings may explain many features of Torsades des pointes, such as perpetuation by focal excitations, rapidly changing electrical axis, frequent self-termination, and occasional degeneration to fibrillation. PMID:17307992

Huffaker, Ray B; Weiss, James N; Kogan, Boris

2007-06-01

209

Microvascular abnormalities in patients with rheumatoid arthritis.  

PubMed

Microvascular involvement represents one of the first apparent steps in many autoimmune diseases such as rheumatoid arthritis (RA). Early in the disease, peripheral microangiopathy may be easily recognized and studied by videocapillaroscopy. The aim of this study has been to observe the differences in labial microcirculation between healthy patients and patients suffering from RA. A total of 30 healthy patients and 30 patients suffering from RA were examined. The patients with conditions known to compromise microcirculation, such as diabetes, hypertension, or some pharmacological treatments were not included in the study. All the patients were non-smokers. Labial capillaroscopy was used to investigate the characteristics of microcirculation. Visibility, course, tortuosity, as well as the possible presence of microhemorrhages, the average caliber of the capillary loops and the number of visible capillary loops per square millimeter were evaluated for each patient. The investigation was simple, non-invasive, and repeatable for each patient. In patients suffering from RA, it was possible to observe a reduced caliber of capillaries, as well as greater elongated capillaries, in comparison to controls. This study shows that capillary alterations in patients suffering from RA occur in labial mucosa microcirculation; such evidence could be extremely important in the diagnosis of suspected RA. PMID:16999205

Scardina, Giuseppe A; Messina, Pietro

2006-09-01

210

B cells in rheumatoid arthritis.  

PubMed

Though its etiology remains unknown thus far, the role that autoimmune processes play in rheumatoid arthritis (RA) pathogenesis has been widely proven. Given the easier accessibility of humoral components, the first feature of this contribution to be recognized has been the occurrence of the so-called rheumatoid factor in a large proportion of RA patients. This antibody recognizes the Fc portion of human IgG. By investigating RA pathologic processes and also through experimental models where immune complexes play a fundamental role, many other autoantibodies have then come to our knowledge to be associated with the disease. Their presence and persistence implies that clones of autoreactive B cells survive and proliferate in RA patients under a continuous stimulation. Whether this is a mechanism of disease initiation or just an epiphenomenon is still unclear but no doubt exists that autoantibodies represent a very useful tool in both diagnostic and prognostic terms. Being much more than simple autoantibody producers, B cells are able to secrete many important cytokines and to efficiently present antigens to T lymphocytes in the synovial environment. All of these functions are essential in the development of RA, and lately have claimed attention as B cell depletion has become a common and effective strategy of treatment in RA. PMID:18035324

Bugatti, Serena; Codullo, Veronica; Caporali, Roberto; Montecucco, Carlomaurizio

2007-12-01

211

Epigenetic modifications in rheumatoid arthritis.  

PubMed

Over the last decades, genetic factors for rheumatoid diseases like the HLA haplotypes have been studied extensively. However, during the past years of research, it has become more and more evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic background of a patient. Epigenetic processes are heritable changes in gene expression without alteration of the nucleotide sequence. Such modifications include chromatin methylation and post-translational modification of histones or other chromatin-associated proteins. The latter comprise the addition of methyl, acetyl, and phosphoryl groups or even larger moieties such as binding of ubiquitin or small ubiquitin-like modifier. The combinatory nature of these processes forms a complex network of epigenetic modifications that regulate gene expression through activation or silencing of genes. This review provides insight into the role of epigenetic alterations in the pathogenesis of rheumatoid arthritis and points out how a better understanding of such mechanisms may lead to novel therapeutic strategies. PMID:18947370

Strietholt, Simon; Maurer, Britta; Peters, Marvin A; Pap, Thomas; Gay, Steffen

2008-01-01

212

STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus  

PubMed Central

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

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

2009-01-01

213

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)

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.

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

2010-12-01

214

Differential Reactivity of Rheumatoid Synovial Cells and Serum Rheumatoid Factors to Human Immunoglobulin G Subclasses 1 and 3 and Their CH3 Domains in Rheumatoid Arthritis.  

National Technical Information Service (NTIS)

Nineteen S Immunoglobulin M rheumatoid factors (RF) are polyclonal autoantibodies that may play an important pathogenic role in sustaining inflammatory synovitis in rheumatoid arthritis (RA). RF in RA have reactivity for as-yet-uncharacterized antigenic d...

D. L. Robbins W. F. Benisek E. Benjamini R. Wistar

1987-01-01

215

The Simulated Effects of Iron Dust and Acidity During the Early Stages of Establishment of Two Coastal Plant Species  

Microsoft Academic Search

In Brazil’s littoral, many iron ore industries are located in areas of restinga, a type of coastal ecosystem; such industries represent stationary sources of iron and acid particulates. The industrial\\u000a sector is under expansion, threatening the already fragile ecosystem. In the present study, the simulated impact of these\\u000a emissions was studied on the early establishment stages of two native plant

K. N. Kuki; M. A. Oliva; A. C. Costa

2009-01-01

216

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

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

217

Psychosocial problems among newly diagnosed rheumatoid arthritis patients.  

PubMed

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

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

2012-03-01

218

The role of the circadian clock in rheumatoid arthritis  

PubMed Central

Rheumatoid arthritis exhibits diurnal variation in symptoms, with patients suffering with increased painful joint stiffness in the early morning. This correlates with an early morning rise in circulating levels of pro-inflammatory cytokines, such as interleukin-6. This temporal variation in disease pathology is directed by the circadian clock, both at a systemic level, through signalling pathways derived in the central clock, and at a local level by autonomous clocks found within inflammatory organs and cells. Indeed, many cellular components of the immune system, which are involved in the pathogenesis of rheumatoid arthritis, possess independent clocks that facilitate temporal gating of their functions. Furthermore, the circadian clock regulates the expression and activity of several genes and proteins that have demonstrated roles in progression of this autoimmune disease. These include a number of nuclear receptors and also fat-derived adipokines. Employing the knowledge we have about how the inflammatory response is regulated by the clock will facilitate the development of chronotherapy regimens to improve the efficacy of current treatment strategies. Furthermore, a full understanding of the mechanisms by which the clock couples to the immune system may provide novel therapeutic targets for the treatment of this debilitating disease.

2013-01-01

219

Astromedicine in the treatment of rheumatoid arthritis.  

PubMed

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

Janai, S; Biviji, A T; Naik, D G; Lakhe, R T; Rao, V B

1991-04-01

220

Vocational Rehabilitation for Persons with Rheumatoid Arthritis.  

ERIC Educational Resources Information Center

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)

Allaire, Saralynn H.

1998-01-01

221

A Rheumatoid arthritis study using Raman spectroscopy  

Microsoft Academic Search

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the joints and can lead to a progressive destruction\\u000a of articular cartilage and bone. In this study, the specificity and sensitivity of the RA diagnostic methods based on the\\u000a receiver-operating characteristic curves for monitoring C-reactive protein (CRP) and rheumatoid factor (RF) were compared\\u000a with the Raman spectroscopic diagnostic method developed in

C. S. Carvalho; A. A. Martin; A. M. E. Santo; L. E. C. Andrade; M. M. Pinheiro; M. A. G. Cardoso; L. Raniero

222

Prospective new biological therapies for rheumatoid arthritis  

Microsoft Academic Search

Advances in the current knowledge of pathogenetic mechanisms of rheumatoid arthritis have contributed to the development of biological therapy, and translated research findings into clinical practice. TNF-? (infliximab, etanercept, adalimumab), IL-1 (anakinra) and IL-6 (tocilizumab) inhibitors, a B-cell depleting agent (rituximab) and a drug blocking T-cell costimulation (abatacept) have been approved for rheumatoid arthritis. The progress in manufacturing biotechnology has

Ladislav Šenolt; Ji?í Vencovský; Karel Pavelka; Caroline Ospelt; Steffen Gay

2009-01-01

223

Rheumatoid arthritis, corticosteroid therapy and hip fracture  

Microsoft Academic Search

OBJECTIVE--To identify the risk of hip fracture in patients with rheumatoid arthritis and those taking corticosteroids. METHODS--In a population based case-control study, we compared 300 consecutive patients with hip fracture aged 50 years and over from a defined district and 600 age and sex matched community controls. RESULTS--The risk of hip fracture was increased in patients with rheumatoid arthritis (odds

C Cooper; C Coupland; M Mitchell

1995-01-01

224

Update on autoantibodies in rheumatoid arthritis  

Microsoft Academic Search

Detection of rheumatoid factor (RF) in the serum of patients with rheumatoid arthritis (RA) was one of the first indications\\u000a of autoimmunity in RA. The role of RF in the diagnosis of RA has been well-documented, but it has suboptimal sensitivity and\\u000a specificity. Although patients with RF-positive RA generally have more severe disease than those with RF-negative RA, RF is

S. Louis Bridges

2004-01-01

225

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

PubMed Central

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

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

2014-01-01

226

Metalloproteinases, inflammation, and rheumatoid arthritis  

PubMed Central

Ideally, the inflammatory response occurs rapidly to terminate infection. It also must halt in a timely manner to stop this reaction from inflicting self damage. Such a highly regulated process results from altering balances in pro- and anti-inflammatory signals orchestrated by multiple cell types and factors within the tissue microenvironment. The discovery of new substrates of metalloproteinases within this microenvironment has disclosed a new function in inflammation. The role of these proteases now extends beyond extracellular matrix remodelling enzymes to that of mediators of inflammatory signals involving various chemokines and cytokines. As natural inhibitors of these metalloproteinases, TIMPs have the potential of regulating the inflammatory response and affecting diseases such as rheumatoid arthritis. TIMP-3, in particular, stands out as an important regulator of inflammation with its ability to specifically inhibit proinflammatory cytokines and tissue destruction in the joint.

Mohammed, F; Smookler, D; Khokha, R

2003-01-01

227

Rheumatoid arthritis in elderly patients.  

PubMed

Rheumatoid arthritis (RA) in the geriatric population presents a unique challenge to treating clinicians. It can present as preexisting disease that may have been present for years or as a de novo onset of the illness. Diagnosis and management requires a detailed knowledge of the disease, its differential diagnoses, and the therapeutic options. A number of other diseases can mimic the illness and must be thoroughly evaluated to avoid serious consequences. New agents to treat RA are available that have shown promise in clinical trials and practice. Aggressive RA treatment should not be withheld in the geriatric population just because of advanced age, rather, treatment should be individualized, especially considering comorbidities and other factors that can specifically affect a patient's quality of life. Coordination of care among geriatricians and rheumatologists is the key to achieving optimal outcome. PMID:20722245

Majithia, Vikas; Peel, Chere; Geraci, Stephen A

2009-09-01

228

The Rheumatoid Arthritic At Home  

PubMed Central

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

Hunt, T. E.

1977-01-01

229

Rheumatoid arthritis is caused by a Proteus urinary tract infection.  

PubMed

Genetic, molecular and biological studies indicate that rheumatoid arthritis (RA), a severe arthritic disorder affecting approximately 1% of the population in developed countries, is caused by an upper urinary tract infection by the microbe, Proteus mirabilis. Elevated levels of specific antibodies against Proteus bacteria have been reported from 16 different countries. The pathogenetic mechanism involves six stages triggered by cross-reactive autoantibodies evoked by Proteus infection. The causative amino acid sequences of Proteus namely, ESRRAL and IRRET, contain arginine doublets which can be acted upon by peptidyl arginine deiminase thereby explaining the early appearance of anti-citrullinated protein antibodies in patients with RA. Consequently, RA patients should be treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages. PMID:23992372

Ebringer, Alan; Rashid, Taha

2014-05-01

230

Magnetic resonance imaging of the axial skeleton in rheumatoid disease.  

PubMed

The axial skeleton is a target for both spondyloarthritis and rheumatoid arthritis. While conventional radiography allows the clear documentation of the late stages of inflammatory changes, magnetic resonance imaging (MRI) is sensitive enough to depict early inflammatory lesions. It is, therefore, of particular importance for radiologists and clinicians to know the MRI appearances of inflammatory changes of the axial skeleton in rheumatoid diseases. Typical lesions in ankylosing spondylitis and related conditions comprise spondylitis (Romanus lesion), spondylodiscitis (Andersson lesion), arthritis of the apophyseal joints, the costovertebral and costotransverse joints, and insufficiency fractures of the ankylosed vertebral spine (non-inflammatory type of Andersson lesion). Sacroiliitis is associated with chronic changes such as sclerosis, erosions, transarticular bone bridges, periarticular accumulation of fatty tissue and ankylosis. In addition, acute findings include capsulitis, juxta-articular osteitis and the enhancement of the joint space after contrast medium administration. Another important sign of spondyloarthritis is enthesitis, which affects the interspinal and supraspinal ligaments of the vertebral spine and the interosseous ligaments in the retroarticular space of the sacroiliac joints. The main site of manifestation of spinal involvement in rheumatoid arthritis is the cervical spine. Typical changes are the destruction of the atlantoaxial complex by pannus tissue with subsequent atlantoaxial subluxation, basilar impression and erosion of the dens axis. Changes in the lower segments of the cervical spine are destruction of the apophyseal joints resulting in the so-called stepladder phenomenon. Because of the uniform response of the discovertebral complex to different noxae, a number of different conditions must be distinguished on the basis of the patient's clinical findings and history in combination with their imaging appearance. These conditions comprise degenerative disc disease, septic spondylodiscitis, Scheuermann's disease, Paget's disease and diffuse idiopathic skeletal hyperostosis (DISH). PMID:15501188

Hermann, Kay-Geert A; Bollow, Matthias

2004-12-01

231

Common Therapy for Rheumatoid Arthritis Reduces Risk of Death  

MedlinePLUS

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

232

Constrictive Pericarditis and Rheumatoid Nodules with Severe Aortic Incompetence  

PubMed Central

The case of a female patient presenting with constrictive rheumatoid pericarditis and aortic incompetence secondary to valvular rheumatoid nodules is described along with a review of the literature with the aim to highlight this rare cause of aortic insufficiency.

Booth, Karen; Herron, Brian; Sheppard, Mary N.; Parissis, Haralambos

2014-01-01

233

New paradigm of predictive MOSFET and interconnect modeling for early circuit simulation  

Microsoft Academic Search

A new paradigm of predictive MOSFET and interconnect modeling is introduced. This approach is developed to specifically address SPICE compatible parameters for future technology generations. For a given technology node, designers can use default values or directly input L eff, Tok, Vt, Rdsw and interconnect dimensions to instantly obtain a BSIM3v3 customized model for early stages of circuit design and

Yu Cao; Takashi Sato; Michael Orshansky; Dennis Sylvester; Chenming Hu

2000-01-01

234

Laboratory biomarkers or imaging in the diagnostics of rheumatoid arthritis?  

PubMed

Rheumatoid arthritis (RA) is a common autoimmune disease in which a heterogeneous course and different pathogenic mechanisms are implicated in chronic inflammation and joint destruction. Despite the diagnostic contribution of anti-citrullinated protein/peptide antibodies (ACPAs) and rheumatoid factors, about one-third of RA patients remain seronegative. ACPAs belong to a heterogeneous family of autoantibodies targeting citrullinated proteins, including myelin-basic protein, several histone proteins, filaggrin and fibrin, fibrinogen or vimentin. In addition to ACPAs, antibodies directed against other post-translationally modified-carbamylated proteins (anti-CarP) were detected in up to 30% of ACPA-negative patients. Using phage display technology, further autoantibodies were recently discovered as candidate biomarkers for seronegative RA patients. Furthermore, in clinical practice, ultrasound may reveal subclinical synovitis and radiographically undetected bone erosions. To improve diagnostic certainty in undifferentiated arthritis and seronegative patients, ultrasound imaging and several new biomarkers may help to identify at risk patients and those with early disease. In this commentary we summarize recent advances in joint ultrasound and future potential of serological biomarkers to improve diagnosis of RA. PMID:24642071

Šenolt, Ladislav; Grassi, Walter; Szodoray, Peter

2014-01-01

235

The multifaceted aspects of interstitial lung disease in rheumatoid arthritis.  

PubMed

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

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

2013-01-01

236

The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis  

PubMed Central

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.

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

2013-01-01

237

B cells in the pathogenesis and treatment of rheumatoid arthritis  

PubMed Central

Purpose of review Our understanding of the multiple physiological and pathogenic functions of B cells in rheumatoid arthritis continues to expand. In turn, the availability of effective agents targeting the B cell compartment increases. In this review, we discuss novel insights into the roles of B cells in RA and recent evidence regarding the efficacy of B cell depletion and biomarkers of treatment response. Recent findings Recent data has further elucidated the requirements for the generation of ectopic lymphoid structures in the rheumatoid synovium, their frequency, and role in pathogenesis. Additional studies have described the phenotype of infiltrating B cells in the synovium and the unexpected role for B cells in bone homeostasis. In addition to pathogenic roles for B cells, there is also mounting evidence for regulatory B cell subsets that may play a protective role. New data on radiographic progression, efficacy in early disease, the role of re-treatment, and biomarkers of treatment response continue to refine the role of B cell depletion in the treatment armamentarium. Summary The past few years have seen new advances in immunology applied to the study of RA with surprising observations and interesting new insights into etiology and pathogenesis.

Marston, Bethany; Palanichamy, Arumugam; Anolik, Jennifer H.

2010-01-01

238

Effects of fish oil supplementation in rheumatoid arthritis.  

PubMed Central

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

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

1990-01-01

239

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

PubMed

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. PMID:23052558

Carl, H D; Swoboda, B

2012-10-01

240

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

PubMed Central

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

Rakieh, Chadi; Conaghan, Philip G

2014-01-01

241

Remission-inducing drugs in rheumatoid arthritis.  

PubMed Central

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

Anastassiades, T. P.

1980-01-01

242

Emerging optical and nuclear medicine imaging methods in rheumatoid arthritis.  

PubMed

Molecular and multimodal imaging procedures that complement the use of existing anatomical modalities for the diagnosis and monitoring of rheumatoid arthritis (RA) have undergone substantial developmental advances. These techniques have the potential to greatly improve the management of patients with RA through early diagnosis and maximization of the newly available opportunities for early therapeutic intervention. Quantitative, noninvasive monitoring of biomarkers of the molecular events induced during the onset of RA could be used to guide the initial selection of therapy and for assessment of early therapeutic responses. Biomolecular imaging techniques that can reveal the pathophysiological features of RA--including infrared thermography, near-infrared molecular imaging, and PET--are being used to investigate the earliest cellular and biochemical inflammatory events in the development of the disease. Noninvasive imaging of abnormal specific molecular events in early RA could enable early targeted intervention that could be tailored to optimize patient responses before destructive anatomical changes occur. In this Review, we summarize new advances in biomolecular imaging techniques, with an emphasis on their current state of development in terms of the management of RA. PMID:23007740

Mountz, James M; Alavi, Abass; Mountz, John D

2012-12-01

243

Serum interleukin 18 and interleukin 18 binding protein in rheumatoid arthritis  

Microsoft Academic Search

Objective: To measure serum interleukin 18 (IL18) and IL18 binding protein (IL18BP) levels in patients with inflammatory arthropathies, and to identify associations with disease status and the response to treatment.Methods: Serum samples were obtained before and after methotrexate treatment from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) attending an early arthritis clinic. IL18 and IL18BP were measured by

B Bresnihan; P Roux-Lombard; E Murphy; D Kane; O FitzGerald; J-M Dayer

2002-01-01

244

Observation of early shell-dopant mix in OMEGA direct-drive implosions and comparisons with radiation-hydrodynamic simulations  

NASA Astrophysics Data System (ADS)

Temporally, spatially, and spectrally resolved x-ray image data from direct-drive implosions on OMEGA were interpreted with the aid of radiation-hydrodynamic simulations. Neither clean calculations nor those using a turbulent mix model can explain fully the observed migration of shell-dopant material (titanium) into the core. Shell-dopant migration was observed via time-dependent, spatially integrated spectra, and spatially and spectrally resolved x-ray images of capsule implosions and resultant dopant emissions. The titanium emission was centrally peaked in narrowband x-ray images. In post-processed clean simulations, the peak titanium emission forms in a ring in self-emission images as the capsule implodes. Post-processed simulations with mix reproduce trends in time-dependent, spatially integrated spectra, as well having centrally peaked Ti emission in synthetic multiple monochromatic imager. However, mix simulations still do not transport Ti to the core as is observed in the experiment. This suggests that phenomena in addition to the turbulent mix must be responsible for the transport of Ti. Simple diffusion estimates are unable to explain the early Ti mix into the core. Mechanisms suggested for further study are capsule surface roughness, illumination non-uniformity, and shock entrainment.

Baumgaertel, J. A.; Bradley, P. A.; Hsu, S. C.; Cobble, J. A.; Hakel, P.; Tregillis, I. L.; Krasheninnikova, N. S.; Murphy, T. J.; Schmitt, M. J.; Shah, R. C.; Obrey, K. D.; Batha, S.; Johns, H.; Joshi, T.; Mayes, D.; Mancini, R. C.; Nagayama, T.

2014-05-01

245

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

PubMed Central

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

Ng, Eddie Y-K; Sudharsan, NM

2004-01-01

246

Laboratory simulation of cosmic string formation in the early Universe using superfluid 3He  

Microsoft Academic Search

TOPOLOGICAL defects in the geometry of space-time (such as cosmic strings) may have played an important role in the evolution of the early Universe, by supplying initial density fluctuations which seeded the clusters of galaxies that we see today1. The formation of cosmic strings during a symmetry-breaking phase transition shortly after the Big Bang is analogous to vortex creation in

C. Bäuerle; Yu. M. Bunkov; S. N. Fisher; H. Godfrin; G. R. Pickett

1996-01-01

247

Glucocorticoid treatment in rheumatoid arthritis.  

PubMed

Introduction: In spite of its broad use since 1950 the role of low-dose glucocorticoids (GCs) (up to 7.5 mg/day prednisone) in the treatment of rheumatoid arthritis is still controversial. Areas covered: Publications comparing disease-modifying anti-rheumatic drugs (DMARD) plus prednisolone with DMARD monotherapy were reviewed. Most studies reported greater clinical improvement and greater inhibition of damage progression in the prednisone group. These advantages had vanished after 6 - 12 months in most studies. Expert opinion: Several limitations of the studies are discussed. Often the advantage of GC treatment was not clinically important. Long-term data are needed to evaluate the real benefit of GC treatment in relation to its toxicity. Knowing the potential toxicity 'bridging' GC treatment should be reserved for patients at high risk of damage progression; a reliable method to identify these patients is needed. The toxicity of low-dose GC treatment is often played down. The reporting is incomplete. The increased mortality ratio with GC treatment is rarely mentioned. High cumulative doses are a risk factor. A more comprehensive set of toxicity items is urgently needed. Problems of GC treatment are the 'drug addiction' of the patient and the difficulty to reduce or withdraw prednisone. PMID:24856989

Rau, Rolf

2014-08-01

248

Vitamin D in rheumatoid arthritis.  

PubMed

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

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

2007-11-01

249

The microbiome and rheumatoid arthritis  

PubMed Central

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.

Scher, Jose U.; Abramson, Steven B.

2012-01-01

250

Emerging therapeutics for rheumatoid arthritis.  

PubMed

Therapeutics options for rheumatoid arthritis (RA) have increased tremendously in the past decade with the introduction of biological agents in 1999. Several different cellular and cytokine targets have been identified, with specific inhibitors now approved to treat RA, including the tumor necrosis factor (TNF) antagonists (adalimumab, etanercept, infliximab), an interleukin 1 (IL1) antagonist (anakinra), an inhibitor of T cell co-stimulation (abatacept), and a selective depleter of B cells (rituximab). As research has progressed, additional promising targets have been identified. Results from RA studies using several new agents have been reported in the last year. Some of these compounds are similar to agents already available, with additional TNF inhibitors (certolizumab pegol, golimumab) and agents targeting CD20 (ocrelizumab, ofatumumab, TRU-015) in development. Other agents are directed toward new cytokine targets, including IL-6 (tocilizumab), and lymphotoxin pathways (briobacept), as well as other B-cell targets, to include BLyS and APRIL (belimumab, atacicept). Additional small molecule therapies have been studied that are directed against intracellular kinases, including JAK-3 and Syk. This article provides a brief update of data from selected clinical trials in RA, highlighting efficacy, and mechanism-based safety concerns. PMID:18937634

Bingham, Clifton O

2008-01-01

251

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

PubMed Central

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

Baumketner, Andrij; Nesmelov, Yuri

2011-01-01

252

Hallux metatarsophalangeal arthroplasty in the rheumatoid forefoot.  

PubMed

Surgical options for treatment of the hallux valgus deformity in the rheumatoid forefoot are numerous, but long-term results of many of these procedures have been less than satisfactory. Controversy exists as to whether excision or fusion is preferred for the treatment of the hallux metatarsophalangeal (MTP) joint. The role of replacement arthroplasty needs to be evaluated. The available surgical options for treatment of the arthritic first MTP joint in rheumatoid arthritis include arthrodesis, excision of the metatarsal head with or without interposition of the soft tissues, excision of the proximal phalanx, and silicone hinge replacement. This article discusses the various types of arthroplasty of the first MTP joint and the reported outcomes in the rheumatoid forefoot. PMID:17765836

Kumar, C Senthil; Holt, G

2007-09-01

253

Numerical Simulation Of The Segregation Process Of Metal In Early Magma Ocean  

NASA Astrophysics Data System (ADS)

Earth's core is considered to have been formed by separation of iron from the silicate magma ocean. This metal- silicate separation is important because it controls the initial states of the core and mantle, in particular concerning the distribution of heat and chemical species between them. In this process, the size of metal droplet is critical, which is estimated as an order of 1 cm by a simple balance of the surface tension and the shear stress (Rubie et al., 2003). Here we report quantitative estimate how the metal size evolves during the metal-silicate separation based on numerical simulation of two-phase flow under gravity. The gravitational energy that is gained, is transformed in heat by viscous heating and we want to quantify the resulting thermal structure. In the numerical method that simulates the process, tracking of the metal-silicate boundary is crucial. In this study, we adopt the moving particle semi-implicit (MPS) method based on the Lagrangian particle method. This method avoids numerical diffusion in the surface tracking of metal-silicate phase boundary because of its Lagrangian nature. Incorporation of the surface tension between metal and silicate phase is another critical factor in this simulation. In the 2-D simulation, we adopted the model by Nomura et al., 2001 implemented in MPS. In 3-D, we employed a new model that we invented. In the simulations, several interesting features have been clarified: irrespective of the initial size, size of the metal droplets evolve to a stable size of the order of 1 cm, which is mainly controlled by the surface tension and the viscosity of silicate melt. We discuss the size and shape of droplets, their falling speed, the interaction between droplets, and the resulting temperature distribution.

Ichikawa, H.; Labrosse, S.; Kurita, K.

2007-12-01

254

Apoptosis regulator proteins: basis for the development of innovation strategies for the treatment of rheumatoid arthritis in patients of different age.  

PubMed

Apoptosis markers (p53, PUMA, p21, and Mdm2) were studied in patients with rheumatoid arthritis at the early and late stages of disease on bone marrow smears and frozen sections of the articular synovial membrane. The target molecules were found in all patients. The early stage was characterized by maximum expression of antiapoptotic (Mdm2) molecule and the minimum expression of proapoptotic molecules (p53, PUMA, and p21). The proapoptotic proteins predominated in patients with the late stage of rheumatoid arthritis, while the antiapoptotic factor (Mdm2) was depressed significantly. These data suggested total suppression of apoptosis at the early stage of rheumatoid arthritis and recommended the Mdm2 molecule as a prospective target for the development of new drugs. PMID:24771380

Doroshevskaya, A Yu; Kondratovskii, P M; Dubikov, A I; Eliseikina, M G

2014-01-01

255

[Renal leiomyosarcoma, rheumatoid arthritis and methotrexate].  

PubMed

Leiomyosarcoma of the renal vein is a rare and malignant tumor difficult to diagnose. No standard treatment has been defined and prognosis is poor. We described the case of a 68-year-old woman with rheumatoid arthritis treated by methotrexate who developed a leiomyosarcoma of the left renal vein with a fatal outcome in less than 1 year. Association of a leiomyosarcoma and rheumatoid arthritis raises the question of a casual association or of a predisposing factor since studies have shown increased risk of cancer with this rheumatism. PMID:20347241

Houitte, R; Jousset, Y; Delori, M; Abgueguen, P; Tanguy, M; Fanello, S

2010-06-01

256

Soft-laser therapy of rheumatoid arthritis.  

PubMed

The effect of soft-laser therapy on rheumatoid arthritis was evaluated in 17 patients with symmetrical involvement of the metacarpophalangeal joint of the index. Nine treatments with a He-Ne laser, 6 J/cm2, were given on the one hand with a sham irradiation of the other. The study was double-blind. The laser therapy gave some pain relief, but no difference in morning stiffness or joint performance was obtained. It is concluded that the laser therapy is of limited value in rheumatoid arthritis. PMID:3629205

Bliddal, H; Hellesen, C; Ditlevsen, P; Asselberghs, J; Lyager, L

1987-01-01

257

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

SciTech Connect

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.

Kruger, A.A. [Westinghouse Hanford Co., Richland, WA (United States); Olson, R.A.; Tennis, P.D. [Northwestern Univ., Evanston, IL (United States). Center for Advanced Cement-Based Materials] [and others

1995-04-01

258

Early containment of high-alkaline solution simulating low-level radioactive waste in blended cement  

Microsoft Academic Search

Portland cement blended with fly ash and attapulgite clay was mixed with high-alkaline solution simulating low-level radioactive waste at a one-to-one weight ratio. The pastes 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.The total alkalinity is characterized by two main drops. The

R. A. Olson; P. D. Tennis; D. Bonen; H. M. Jennings; T. O. Mason; B. J. Christensen; A. R. Brough; G. K. Sun; J. F. Young

1997-01-01

259

[Repair of bone and articular destruction in rheumatoid arthritis].  

PubMed

Repair of bone and articular destruction in rheumatoid arthritis (RA) is major problem to treat RA patients recently. However bone destruction starts in early phase of disease duration in RA. Histological meta-analysis of synovium is one of a key to solve the problem in RA. We investigated synovial histology about five factors including synovial proliferation, pillonodular synovium, vascular proliferation, and fibrin deposit and lymphocyte infiltration. Disease duration and pilonodular synovium has significant correlation by multiple regression analysis (p = 0.018). Therefore pillonodular synovium is important to decrease bone destruction in RA. It is possible that biological treatment for RA is effective to bone and cartilage metabolism, however some cases do not improve bone metabolism. Further investigation needs to analyze the factors of efficacy of bone and cartilage metabolism. PMID:17404483

Kanbe, Katsuaki

2007-04-01

260

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

NASA Astrophysics Data System (ADS)

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.

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

261

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

PubMed Central

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

2013-01-01

262

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

NASA Astrophysics Data System (ADS)

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

Naoz, Smadar; Yoshida, Naoki; Barkana, Rennan

2011-09-01

263

CD44 in rheumatoid arthritis  

PubMed Central

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

Naor, David; Nedvetzki, Shlomo

2003-01-01

264

One year treatment with low dose methotrexate in rheumatoid arthritis: Effect on class specific rheumatoid factors  

Microsoft Academic Search

We evaluated the effect of a one-year treatment of low dose methotrexate (MTX) on class specific rheumatoid factors in 27 patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assay (ELISA) showed after 6 and 12 months a significant reduction of IgM-RF, IgA-RF and IgF-RF levels from the baseline values. During MTX treatment, changes of each RF isotype were not correlated with

A. Spadaro; V. Riccieri; A. Sili Scavalli; E. Taccari; A. Zoppini

1993-01-01

265

Clinical relevance of IgA rheumatoid factor (RF) in children with juvenile rheumatoid arthritis  

Microsoft Academic Search

This study proposed to investigate the prevalence and clinical relevance of serum immunoglobulin A (IgA) rheumatoid factor\\u000a (RF) in juvenile rheumatoid arthritis (JRA) as published reports vary in their conclusion. Sera of 82 children with JRA and\\u000a 25-age and sex-matched healthy children were measured for IgA RF by an enzyme linked immunoassay using human IgG as the antigen.\\u000a Forty-three percent

A. Bharadwaj; A. Aggarwal; R. Misra

1999-01-01

266

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

NASA Astrophysics Data System (ADS)

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

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

2012-04-01

267

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

NASA Astrophysics Data System (ADS)

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

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

2010-05-01

268

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

NASA Technical Reports Server (NTRS)

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

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

2008-01-01

269

Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis  

Microsoft Academic Search

Palisaded neutrophilic granulomatous dermatitis (PNGD) is an entity that has not been clearly defined either clinically or histopathologically. It is seen in patients with rheumatoid arthritis and other connective tissue diseases. In the past, many cases of PNGD have been described under several different names including palisaded neutrophilic and granulomatous dermatitis, linear subcutaneous bands, interstitial granulomatous dermatitis with cutaneous cords

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

2002-01-01

270

Aerobic Exercise Prescription for Rheumatoid Arthritics.  

ERIC Educational Resources Information Center

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…

Evans, Blanche W.; Williams, Hilda L.

271

[The golden age of rheumatoid arthritis treatment].  

PubMed

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. PMID:24758843

Mercado, Ulises

2014-01-01

272

Intracellular Signaling Pathways in Rheumatoid Arthritis  

PubMed Central

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

Malemud, Charles J

2013-01-01

273

Carnitine homeostasis in patients with rheumatoid arthritis  

Microsoft Academic Search

Myopathy is a frequent finding in patients with rheumatoid arthritis (RA). Since carnitine is important for skeletal muscle energy metabolism, carnitine metabolism was investigated in patients with RA and myopathy. Muscle strength was estimated by determination of a muscle strength index (MSI) which is derived from isometric measurements of muscle strength at knees and elbows. Carnitine was determined by a

Stephan Krähenbühl; Barbara Willer; Pius Brühlmann; Hans Hoppeler; Gerold Stucki

1999-01-01

274

[Monitoring of patients with rheumatoid arthritis].  

PubMed

Monitoring of patients with rheumatoid arthritis must include the monitoring of the effectiveness of the treatments with a goal of remission or of low disease activity, the tolerance follow-up of the different treatments and the monitoring of cardiovascular risk factors. This follow-up is collaboration between the rheumatologist and the general practitioner for optimal outcomes. PMID:23227612

Pham, Thao

2012-10-01

275

Outcome of Penetrating Keratoplasty in Rheumatoid Arthritis  

Microsoft Academic Search

Background: Keratolysis in rheumatoid arthritis is a well-known disorder that may rapidly destroy the entire corneal stroma, resulting in descemetocele formation and eventually corneal perforation. The purpose of this study was to determine the anatomical and functional results of therapeutic penetrating keratoplasty (PK) in these patients. Patients and Methods: We reviewed the charts of patients having undergone PK over a

Uwe Pleyer; Eckart Bertelmann; Peter Rieck; Christian Hartmann

2002-01-01

276

Prospective new biological therapies for rheumatoid arthritis.  

PubMed

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

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

2009-12-01

277

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

NASA Technical Reports Server (NTRS)

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.

Dateo, Christopher E.

2003-01-01

278

Early stages of carbonate mineralization revealed from molecular simulations: Implications for biomineral formation  

NASA Astrophysics Data System (ADS)

The carbonate mineral constituents of many biomineralized products, formed both in and ex vivo, grow by a multi-stage crystallization process that involves the nucleation and structural reorganization of transient amorphous phases. The existence of transient phases and cluster species has significant implications for carbonate nucleation and growth in natural and engineered environments, both modern and ancient. The structure of these intermediate phases remains elusive, as does the nature of the disorder to order transition, however, these process details may strongly influence the interpretation of elemental and isotopic climate proxy data obtained from authigenic and biogenic carbonates. While molecular simulations have been applied to certain aspects of crystal growth, studies of metal carbonate nucleation are strongly inhibited by the presence of kinetic traps that prevent adequate sampling of the potential landscape upon which the growing clusters reside within timescales accessible by simulation. This research addresses this challenge by marrying the recent Kawska-Zahn (KZ) approach to simulation of crystal nucleation and growth from solution with replica-exchange molecular dynamics (REMD) techniques. REMD has been used previously to enhance sampling of protein conformations that occupy energy wells that are separated by sizable thermodynamic and kinetic barriers, and is used here to probe the initial formation and onset of order within hydrated calcium and iron carbonate cluster species during nucleation. Results to date suggest that growing clusters initiate as short linear ion chains that evolve into two- and three-dimensional structures with continued growth. The planar structures exhibit an obvious 2d lattice, while establishment of a 3d lattice is hindered by incomplete ion desolvation. The formation of a dehydrated core consisting of a single carbonate ion is observed when the clusters are ~0.75 nm. At the same size a distorted, but discernible calcite-type lattice is also apparent. Continued growth results in expansion of the dehydrated core, however, complete desolvation and incorporation of cations into the growing carbonate phase is not achieved until the cluster grows to ~1.2 nm. Exploration of the system free energy along the crystallization path reveals "special" cluster sizes that correlate with ion desolvation milestones. The formation of these species comprise critical bottlenecks on the energy landscape and for the establishment of order within the growing clusters.

Wallace, A. F.; DeYoreo, J.; Banfield, J. F.

2011-12-01

279

Vitamin D and rheumatoid arthritis  

PubMed Central

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

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

2012-01-01

280

Hepatotoxicity due to tocilizumab and anakinra in rheumatoid arthritis: two case reports  

PubMed Central

Elevation of liver enzymes in patients with rheumatoid arthritis treated with the biological agents, tocilizumab and anakinra, is now well documented. However, histological characterization of these effects and outcomes has not been defined. Here we report toxic liver effects in two women with rheumatoid arthritis, refractory to all nonbiological therapies, following treatment with anakinra and tocilizumab. Liver biopsy in both cases showed focal necrosis of hepatocytes as a hallmark of drug toxicity, along with steatosis and early fibrosis. In addition, the patient treated with anakinra demonstrated inflammatory changes. Tocilizumab was continued with no further deterioration in liver function. Withdrawal of anakinra led to rapid normalization of liver function. The biological agents, tocilizumab and anakinra, may result in significant histological hepatic changes, including necrosis, but despite this, the outcome appears to be good.

Mahamid, Mahmud; Paz, Kalman; Reuven, Mader; Safadi, Rifaat

2011-01-01

281

[The patella and the femoro-patellar joint during rheumatoid polyarthritis].  

PubMed

The authors report 2 series of cases of rheumatoid arthritis, one prospective of 115 cases, the other retrospective of 72 cases, and note the frequency of clinical and radiological patellar and femoro-patellar involvement during this disease. Signs of active rheumatoid disease in the patella were present in 31 cases. The most common lesions of the femoro-patellar joint space are narrowing and lateral dislocation of the patella. The femoro-patellar lesions evolve in parallel to the femoro-tibial lesions, but dissociation is possible. The early detection of a femoro-patellar syndrome permits effective treatment by isometric rehabilitation of the quadriceps. On the most advanced lesions, and when pain is limited to the femur and patella, an operation of reaxation of the patella may provide remarkable functional improvement. PMID:504947

Amor, B; Heuleu, J N; Pariente, J; Ghozlan, R

1979-01-01

282

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

Code of Federal Regulations, 2010 CFR

...measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins...body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class...

2009-04-01

283

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

Code of Federal Regulations, 2010 CFR

...measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins...body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class...

2010-04-01

284

Marine methane cycle simulations for the period of early global warming  

SciTech Connect

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.

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

2011-01-02

285

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

NASA Technical Reports Server (NTRS)

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

Herant, Marc; Benz, Willy; Colgate, Stirling

1992-01-01

286

Discontinuation of biologics in patients with rheumatoid arthritis.  

PubMed

The use of early aggressive treatment combined with the availability of biological agents targeting pro-inflammatory cytokines such TNF and IL-6 has greatly advanced the treatment of rheumatoid arthritis (RA). Clinical remission is a realistic primary goal and its maintenance leads to stabilisation of structural deterioration and functional remission. With the achievement of sustained remission, discontinuation of biological agents has emerged as an important consideration, with subsequent reductions in medication-induced side effects and health costs. Evidence from studies suggests that MTX-naïve, early RA patients can achieve sustained biologic-free remission with no functional or radiographic progression, after treatment with combination TNF inhibitors and MTX. For patients with long-standing RA and who have previous inadequate responses to MTX, the evidence for sustained biologic-free remission is less convincing. The discontinuation of TNF-inhibitors after sustained remission has been shown to be possible in some long-standing RA patients with inadequate response to MTX, particularly in Japanese patients. However, high flare rates and adverse long-term outcomes have been documented in other studies. For these patients a biologic dose-reduction regimen may be preferable. The combination of early treatment with TNF inhibitors and MTX plus tight control of inflammation provide the best chance of a biologic-free remission or at least the possibility of 'biologic treatment holidays'. PMID:24129132

Tanaka, Yoshiya; Hirata, Shintaro; Saleem, Benazir; Emery, Paul

2013-01-01

287

Abatacept treatment for rheumatoid arthritis  

PubMed Central

Significant advances in our understanding of RA and its management have been made in the past decade, resulting in earlier intervention with biologic DMARDs, particularly in patients with evidence of aggressive, erosive disease. Here, one such biologic therapy, the T-cell co-stimulation modulator abatacept, is discussed, exploring clinical evidence published to date on its use in patients with very early arthritis/early RA who are MTX naïve, and in patients with established RA and an inadequate response to MTX or TNF antagonists. Data from relevant clinical trials are overviewed, discussing the clinical efficacy of abatacept in early disease, the clinical outcomes over long-term treatment in different patient populations and the effects of abatacept on structural damage. Findings from integrated safety analyses of abatacept clinical trial data, representing 10?366 patient-years of exposure are described, and clinically important safety events, including serious infections, malignancies and autoimmune events, are highlighted. It is concluded that abatacept represents an effective treatment option with an established safety profile across different patient populations, including patients with both early and erosive RA and those with established disease. Furthermore, efficacy data from studies in patients with early disease suggest that the risk–benefit profile of abatacept may be more favourable when introduced earlier in the treatment paradigm.

2011-01-01

288

Reoperation rate after elbow synovectomy in rheumatoid arthritis  

Microsoft Academic Search

The purpose of this study was to evaluate the reoperation rate of elbow synovectomy in patients with rheumatoid arthritis. A total of 103 synovectomies were performed in 88 patients (61 women) with rheumatoid factor–positive rheumatoid arthritis with a mean follow-up of 5.2 years (range, 1-8 years). The survival rate after elbow synovectomy (free from reoperation) was 77% (95% confidence interval,

Heikki M Mäenpää; Pekko P Kuusela; Kalevi Kaarela; Hannu J Kautiainen; Janne T Lehtinen; Eero A Belt

2003-01-01

289

Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients  

Microsoft Academic Search

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

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

2007-01-01

290

Serum selenium concentrations in rheumatoid arthritis.  

PubMed Central

Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis.

O'Dell, J R; Lemley-Gillespie, S; Palmer, W R; Weaver, A L; Moore, G F; Klassen, L W

1991-01-01

291

Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis  

PubMed Central

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.

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

2014-01-01

292

Benefits of Exercise in Rheumatoid Arthritis  

PubMed Central

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.

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

293

Bronchiectasis and rheumatoid arthritis: a clinical study.  

PubMed Central

OBJECTIVES--To examine the relation between rheumatoid arthritis (RA) and bronchiectasis (BR). METHODS--Disease activity, outcome, extra-articular manifestations, and laboratory features were compared in 32 patients with BR and RA (RA-BR group), 32 matched patients with RA without BR (RA group), and 31 patients with BR but without arthritis (BR group). RESULTS--In 30 of the 32 (94%) patients with RA-BR, BR preceded RA. There was no functional or radiological difference between the RA-BR and RA groups, and except for xerophthalmia, which was more common in patients with RA-BR than patients with RA, there was no difference in extra-articular or laboratory features. CONCLUSIONS--Bronchiectasis does not lead to a more aggressive disease course in RA and, despite the recognised association, BR is not an extra-articular manifestation of rheumatoid disease.

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

1993-01-01

294

[Protein binding of salicylates in rheumatoid arthritis].  

PubMed

Protein binding of salicylates was determined in 16 control subjects and 27 patients suffering from rheumatoid arthritis. Results obtained after separation of the free and bound fractions by dialysis to equilibrium and measured by spectrofluorometry were analyzed using a new mathematical model. In correlation with the decrease in plasma albumin concentrations, a decrease was found in the protein binding of salicylates in patients with rheumatoid arthritis. This phenomenon was less marked in therapeutic zones and was related to the degree of severity of the inflammatory syndrome. The binding capacity per albumin molecule at saturation was decreased in patients suffering from advanced forms, suggesting that the changes seen were not due solely to quantitative variations in serum albumin levels. This study confirms the value of the determination of free salicylate levels in patients suffering from inflammatory rheumatic disorders. PMID:7112023

Netter, P; Monot, C; Stalars, M C; Mur, J M; Royer, R J; Pourel, J; Faure, G; Martin, J; Gaucher, A

1982-05-01

295

Benefits of exercise in rheumatoid arthritis.  

PubMed

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

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

296

Anticardiolipin antibodies in rheumatoid arthritis: their relation to rheumatoid nodules and cutaneous vascular manifestations.  

PubMed

One hundred and seventy-three consecutive patients with rheumatoid arthritis were examined for the presence of anticardiolipin antibodies (ACA), and for the clinical relevance and the relation of these antibodies to skin manifestations. Abnormally elevated IgG- and/or IgM-ACA levels were detected by an enzyme-linked immunosorbent assay in the sera of 55 (32%) patients. There was no statistical evidence of an association between ACA and a history of thrombosis in these patients. However, ACA were statistically significantly linked to the presence of rheumatoid nodules, which were found in 36 (21%) patients. In three patients, ACA were associated with vascular manifestations, including livedo reticularis, thrombophlebitis, and leucocytoclastic vasculitis. Our findings suggest that, although a subset of ACA may be linked to cutaneous vascular conditions, the major fraction of ACA in rheumatoid arthritis may have a different specificity than in other diseases, in which ACA are often linked to thrombotic events. PMID:8043421

Wolf, P; Gretler, J; Aglas, F; Auer-Grumbach, P; Rainer, F

1994-07-01

297

Serum antioxidants and risk of rheumatoid arthritis  

Microsoft Academic Search

OBJECTIVES--Oxygen free radicals have been implicated as mediators of tissue damage in patients with rheumatoid arthritis (RA). Thus it is possible that several micronutrients acting as antioxidants and free radical scavengers provide protection against RA. Serum alpha-tocopherol, beta-carotene, and selenium were studied for their associations with the risk of RA. METHODS--A case control study was nested within a Finnish cohort

M Heliövaara; P Knekt; K Aho; R K Aaran; G Alfthan; A Aromaa

1994-01-01

298

The remission of rheumatoid arthritis during pregnancy  

Microsoft Academic Search

Rheumatoid arthritis (RA) is an autoimmune disease that is favorably influenced by pregnancy but relapses after delivery.\\u000a A variety of circulating factors has been considered as candidates for inducing gestational improvement of RA; however, the\\u000a factors\\/pathways responsible remain still elusive. This review discusses recent research on the effect of pregnancy on RA\\u000a with a focus on immunregulation, cytokine secretion, HLA

Monika Østensen; Peter M. Villiger

2007-01-01

299

Osteoarthritis and rheumatoid arthritis: conservative therapeutic management.  

PubMed

Hand therapists need to understand the basic science behind the therapy they carry out and the current evidence to make the best treatment decisions. The purpose of this article was to review current conservative therapeutic management of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) of the hand. Treatment interventions such as orthotics, exercise, joint protection, modalities, and adaptive equipment are discussed from a basic science and evidence-based practice perspective. PMID:22326361

Beasley, Jeanine

2012-01-01

300

Pathogenesis of bone lesions in rheumatoid arthritis  

Microsoft Academic Search

Histopathologic characterization of bone erosions from patients with rheumatoid arthritis (RA) and studies performed in animal\\u000a models of inflammatory arthritis provide strong evidence that osteoclasts play an important role in focal marginal and subchondral\\u000a bone loss in inflammatory arthritis. Much has been learned concerning the factors responsible for the induction and activation\\u000a of osteoclasts associated with the bone erosions in

Steven R. Goldring; Ellen M. Gravallese

2002-01-01

301

Vaccine responses in patients with rheumatoid arthritis  

Microsoft Academic Search

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is associated with immunologic alterations in T cells and\\u000a B cells. Moreover, many of the agents used in RA patients are potentially immunosuppressive. Thus, the underlying disease\\u000a and treatment may both increase the susceptibility to infections and decrease vaccine responses. With the growing use of aggressive\\u000a therapies for RA, including anti-tumor

Rajan Ravikumar; Jennifer Anolik; R. John Looney

2007-01-01

302

Rheumatoid arthritis in blacks in South Africa  

Microsoft Academic Search

The spectrum of rheumatoid arthritis (RA) was studied in a group of 52 blacks who attended a rheumatology unit in Cape Town, South Africa. The mean age of the patients was 44.6 years, and the female to male ratio was 3.7:1. Significant radiographic changes were frequently noted, and the mean Larsen scores were 34.9 for the hands, 19.6 for the

G M Mody; O L Meyers

1989-01-01

303

B cell targets in rheumatoid arthritis  

Microsoft Academic Search

B cells are critical to the pathogenesis of rheumatoid arthritis (RA). There is substantial evidence of the efficacy of depletion\\u000a of B cells in many patients with RA using the first licensed agent, rituximab. Recent research has focused on enhancing efficacy\\u000a using other targets to inhibit B cell function, including other B cell-depleting antibodies and cytokines critical to B cell

Edward M. Vital; Shouvik Dass; Paul Emery

304

Serum cytokines in patients with rheumatoid arthritis  

Microsoft Academic Search

Serum cytokines such as interleukin 1ß (IL-1ß), interferon ? (IFN-?), and tumor necrosis factor a (TNFa) were measured in 40 patients with rheumatoid arthritis (RA). In the 40 patients studied, serum IL-1ß was detected in 5 patients, IFN-? in 10 patients, and TNFa in 20 patients. The IL-1ß-positive group showed increased values of activity indices compared to the IL-1ß-negative group.

S. Sakito; Y. Ueki; K. Eguchi; Y. Kawabe; S. Nagataki

1995-01-01

305

Circulating human leucocyte elastase in rheumatoid arthritis  

Microsoft Academic Search

Elastase-inhibitor complex (EIC) levels were determined in EDTA-plasma samples of 40 patients with connective tissue disease by a double antibody immunoassay technique. In active rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), EIC levels were significantly higher than in the normal controls (P-8) and fell on remission. The mean EIC level in active RA was significantly greater than in inactive

E. O. Adeyemi; R. G. Hull; V. S. Chadwick; G. R. V. Hughes; H. J. F. Hodgson

1986-01-01

306

Advances in the treatment of rheumatoid arthritis  

PubMed Central

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

Vivar, Nancy

2014-01-01

307

Fibromyalgia complicating disease management in rheumatoid arthritis.  

PubMed

Objective: To evaluate frequency of fibromyalgia in rheumatoid arthritis and its effect on disease activity score. Study Design: Cross-sectional study. Place and Duration of Study: The Indus Hospital, Karachi, from December 2010 to May 2011. Methodology: All adult patients of either gender diagnosed as rheumatoid arthritis on the basis of clinical, laboratory and X-ray criteria were included in the study. The sample data was separated into two groups depending on presence or absence of fibromyalgia and 28 joint disease activity score (DAS-28) value was evaluated. Results: There were 31 (25.83%) patients with rheumatoid arthritis and fibromyalgia (RAFM) out of the total 120. The median (IQR) age of patients was 40 (32 - 51) years. All were females. The overall female frequency was 79 (88.8%). The median (IQR) DAS-28 score in RA group was 4.9 (3.66 - 5.71), while the median (IQR) DAS-28 score in RAFM was 7.04 (6.62 - 7.64) [p < 0.0001]. The number of patient getting combination therapy of DMARD in RAFM group was 61.3% while in RA group was 42.7%. Conclusion: DAS-28 was found to be significantly higher in RAFM patients probably because of higher perception of pain. PMID:24953918

Abbasi, Lubna; Haidri, Fakhir Raza

2014-06-01

308

Angiogenesis and its targeting in rheumatoid arthritis?  

PubMed Central

Angiogenesis, the development of new capillaries, is involved in leukocyte ingress into the synovium during the development and progression of rheumatoid arthritis. Several soluble and cell surface-bound mediators including growth factors, cytokines, chemokines, proteolytic matrix-degrading enzymes, cell adhesion molecules and others may promote synovial neovascularization. On the other hand, endogenous angiostatic factors, such as angiostatin, endostatin, interleukin-4 (IL-4), IL-13, interferons and some angiostatic chemokines are also produced within the rheumatoid synovium, however, their effects are insufficient to control synovial angiogenesis and inflammation. Several specific and non-specific strategies have been developed to block the action of angiogenic mediators. The first line of angiostatic agents include vascular endothelial growth factor (VEGF), angiopoietin, ?V?3 integrin antagonist, as well as non-specific angiogenesis inhibitors including traditional disease-modifying agents (DMARDs), anti-tumor necrosis factor biologics, angiostatin, endostatin, fumagillin analogues or thalidomide. Potentially any angiostatic compound could be introduced to studies using animal models of arthritis or even to human rheumatoid arthritis trials.

Szekanecz, Zoltan; Koch, Alisa E.

2010-01-01

309

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

PubMed Central

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

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

2013-01-01

310

Current therapies in rheumatoid arthritis: a Latin American perspective.  

PubMed

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

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

2013-01-01

311

Molecular dynamical simulation of the behavior of early precipitated stage in aging process in dilute Cu-Cr alloy  

NASA Astrophysics Data System (ADS)

The aging behaviors of Cu-Cr alloys in the early stage at different temperatures are investigated by molecular dynamics simulations. First principles potentials are used for the interactions between Cu and Cr atoms. The initial behavior of precipitation is characterized by transmission electron microscope and electron energy disperse spectroscopy. The results showed that Cu-Cr supersaturated solid solution is thermodynamically unstable. The mean-square displacements of the atoms are used to describe the diffusivity. At room temperature, the atoms only show harmonic vibrations near the equilibrium positions. The mutual diffusion at 873 K is different from the unidirectional diffusion in low temperatures. The calculation shows that aging process is accelerated with increasing temperature, which is not only due to the lower diffusion activation energy of Cr at higher temperature, but also because Cu atoms are also participated in the aging process. When ``aging'' at 1073 K, the precipitation of Cr element is dissolved again into Cu matrix, which is an ``over-aging'' state of Cu-Cr alloy at high temperature.

Feng, J.; Xiao, B.; Liu, L.; Chen, J.; Du, Y.; Zhou, R.

2010-06-01

312

A tumor endoprosthesis is useful in elderly rheumatoid arthritis patient with acute intercondylar fracture of the distal femur.  

PubMed

The purpose of this paper is to report the use of total knee arthroplasty using a tumor prosthesis in the treatment of elderly patients with an intercondylar fracture of the distal femur. Supracondylar fractures of the femur in patients with rheumatoid arthritis are difficult to treat due to joint deformity. We present outcomes for treating intercondylar fractures of the distal femur in rheumatoid arthritis patient using a tumor endoprosthesis. This technique allows early mobilization of the patient, with restoration of a good range of knee motion. A tumor prosthesis appears to be a viable treatment option for intercondylar femoral fractures in elderly patients. It is well tolerated and permits early ambulation and return to activities of daily living. PMID:21442168

Wakabayashi, Hiroki; Naito, Yohei; Hasegawa, Masahiro; Nakamura, Tomoki; Sudo, Akihiro

2012-05-01

313

[Diagnostic and prognostic significance of so-called rheumatoid vasculitis--2].  

PubMed

51 patients with rheumatoid arthritis and high rheumatoid factors (mean titres 928) underwent examination for the demonstration of an extraarticular organ manifestation within the scope of the cooperation between the Department of Medicine of the Karl-Marx-University Leipzig and the Institute for Rheumatology of the Academy of Medical Sciences of the USSR in Moscow. The frequency of nodous rheumatism (about 60%) is comparable with the frequency of polyneuropathy. In 20% of the patients a systemic muscle atrophy, a hepatomegaly as well as a Raynaud-syndrome were stated. By means of skin biopsy in 28% perivascular infiltrates were found. Altogether in 6 patients (12%) a participation of the lungs and the pleura, respectively, could be proved. Only rarely a clinically manifest heart disease caused by the rheu-we we found an pericardial effusions in 3 cases. In systemic manifestation, such as myositis, participation of the eyes or vasculitis of the digital arteries with necrosis, were only sporadically to be established. Among 22 patients we found an pericardial effusions in 3 cases. In systemic manifestation in most cases increased parameters of activity were found. From the practical point of view apart from increased titers of the rheumatoid titres and circulating immune complexes (C1q-BT) increased concentrations of the C-reactive protein are prognostically significant. The presence of high rheumatoid factor titres alone as well as the isolated presence of rheumatic nodes must not always be connected with an unfavourable prognosis. When severe extraarticular manifestations are present a possibly early, intensive occasionally extracorporeal treatment is indicated. PMID:3716509

Häntzschel, H; Seidel, W; Otto, W; Arnold, S; Fischer, H; Krüger, W; Gruber, G; Treutler, H; Lasek, G; Sack, G

1986-03-15

314

Immunopathological changes in rheumatoid arthritis and other joint diseases.  

PubMed Central

A comparative study of the distribution of immunoglobulins G, M, and A and C3 in the synovium and inside synovial fluid leucocytes and of the relative levels of IgG, IgM, AND C3 in paired samples of serum and synovial fluid from both seropositive and seronegative patients with rheumatoid arthritis and other types of non-infective synovitis shows that although there is no distinctive immunopathological feature of rheumatoid arthritis, the incidence of immune complexes containing IgG and IgM with and without detectable C3 in the affected synovium or inside synovial fluid granulocytes is higher in rheumatoid arthritis and especially so in seropositive cases. The mean level of C3 in synovial fluid from patients with rheumatoid arthritis is lower than that from the group without rheumatoid arthritis. In contrast to previous reports, extracellular clumps of IgA could be detected in the affected synovium of a number of affected patients. Aggretated human IgG could be bound by some of the synovial biopsies and synovial fluid leucocytes from both seropositive and seronegative rheumatoid arthritis patients. Antinuclear factor and rheumatoid factor could be detected in the synovial fluid but not in the serum of several patients suggesting either selective sequestration or local synthesis of antinuclear and rheumatoid factors in the affected joints. Images

Ghose, T; Woodbury, J F; Ahmad, S; Stevenson, B

1975-01-01

315

Synovial fibroblasts spread rheumatoid arthritis to unaffected joints  

Microsoft Academic Search

Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to

Stephanie Lefèvre; Anette Knedla; Christoph Tennie; Andreas Kampmann; Christina Wunrau; Robert Dinser; Adelheid Korb; Eva-Maria Schnäker; Ingo H Tarner; Paul D Robbins; Christopher H Evans; Henning Stürz; Jürgen Steinmeyer; Steffen Gay; Jürgen Schölmerich; Thomas Pap; Ulf Müller-Ladner; Elena Neumann

2009-01-01

316

Rheumatoid meningitis: an autopsy report and review of the literature  

Microsoft Academic Search

We report the clinical and autopsy findings of a 71-year-old Japanese woman with rheumatoid meningitis. This patient developed subacute meningitis during an inactive stage of rheumatoid arthritis (RA), and despite intensive examinations no causative agents or underlying disease could be identified except for RA. Based on persistent hypocomplementaemia and increased serum levels of immune complexes she was suspected of having

Takashi Kato; Ken-ichi Hoshi; Yoshiki Sekijima; Masayuki Matsuda; Takao Hashimoto; Masako Otani; Akio Suzuki; Shu-ichi Ikeda

2003-01-01

317

Cyclosporin a in rheumatoid arthritis: A critical review  

Microsoft Academic Search

Khawar K, Buchanan WW. Cyclosporin A in rheumatoid arthritis: a critical review. Inflammopharmacology. 1993;2:141–157. This\\u000a paper reviews the current position of cyclosporin A in the therapeutic armamentarium of rheumatoid arthritis. The pharmacokinetic\\u000a disposition, results of open and controlled trials, and toxicity will be reviewed.

K. Khawar; K. Al-jarallah; W. W. Buchanan

1993-01-01

318

Rheumatoid Arthritis - Hiroshima and Nagasaki: Prevalence, Incidence, and Clinical Characteristics.  

National Technical Information Service (NTIS)

Rheumatoid arthritis occurring between 1958 to 1964 in a fixed population of about 16,000 in Hiroshima and Nagasaki, Japan is reported. The prevalence of definite rheumatoid arthritis was 0.35% and the estimate of incidence was 45 per 100,000 per year. Su...

J. W. Wood H. Kato K. G. Johnson Y. Uda W. J. Russell

1966-01-01

319

[Lysis of the odontoid process in rheumatoid polyarthritis].  

PubMed

The authors report 9 cases of partial or total lysis of the odontoid peg in rheumatoid arthritis. Retrospective study of 100 cases of rheumatoid arthritis and the data from the literature demonstrate the rarity of these lesions, the last stage of the odontoid erosions which are much commoner. The therapeutic approach is usually nuero-surgical. PMID:675112

Rosenberg, F; Bataille, R; Sany, J; Rau, D; Serre, H

1978-04-01

320

Early treatment in early undifferentiated arthritis.  

PubMed

The early diagnosis of new-onset rheumatoid arthritis (RA) has become a major objective for rheumatologists in order to identify a management strategy able to change the natural history of the disease and to prevent joint damage and functional impairment. Emergent evidence emphasizes the benefits of early aggressive therapy of RA. By the nineties, early arthritis cohorts have been collected throughout the world with the aim to increase the early referral of patients with early onset disease by the general practitioners and to collect data on the development of full-blown RA. The frequency of undifferentiated arthritis (UA) ranged from 23% to 81% in these early cohorts with most of them reporting a rate of 30%. The transition rate from UA to RA was between 13% and 54%. A percentage of 20-60% of patients with UA had a self-limiting disease. Our article deals with the controversy existing in the management of UA. Should every patient with UA be treated? Could patients with a favorable disease course be exposed to unnecessary risk with initiation of aggressive therapy with synthetic disease-modifying anti-rheumatic drugs (DMARDs) or biologic agents? The pros and cons of treating patients with UA are examined. PMID:22037115

Olivieri, Ignazio; Sarzi-Puttini, Piercarlo; Bugatti, Serena; Atzeni, Fabiola; d'Angelo, Salvatore; Caporali, Roberto

2012-06-01

321

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\\/European League Against Rheumatism collaborative initiative  

Microsoft Academic Search

ObjectiveThe 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA.MethodsA joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to

Daniel Aletaha; Tuhina Neogi; Alan J. Silman; Julia Funovits; David T. Felson; Clifton O Bingham III; Neal S. Birnbaum; Gerd R. Burmester; Vivian P. Bykerk; Marc D. Cohen; Bernard Combe; Karen H. Costenbader; Maxime Dougados; Paul Emery; Gianfranco Ferraccioli; Johanna M. W. Hazes; Kathryn Hobbs; Tom W. J. Huizinga; Arthur Kavanaugh; Jonathan Kay; Tore K Kvien; Timothy Laing; Philip Mease; Henri A Ménard; Larry W. Moreland; Raymond L. Naden; Theodore Pincus; Josef S Smolen; Ewa Stanislawska-Biernat; Deborah Symmons; Paul P. Tak; Katherine S. Upchurch; Ji?í Vencovský; Frederick Wolfe; Gillian Hawker

2010-01-01

322

Relative sialylation and fucosylation of synovial and plasma fibronectins in relation to the progression and activity of rheumatoid arthritis  

Microsoft Academic Search

The expressions of terminal sugars in synovial and plasma fibronectins were studied in relation to rheumatoid arthritis (RA)\\u000a progression defined according to the early, established and late radiological changes in the patients’ hands. The relative\\u000a amounts of sialic acid and fucose were analyzed by lectin-ELISA using appropriate sialic acid-linked ?2-3 (Maackia amurensis) and ?2-6 (Sambucus nigra) lectins as well as

Magdalena Przybysz; Dorota Maszczak; Krzysztof Borysewicz; Jacek Szechi?ski; Iwona K?tnik-Prastowska

2007-01-01

323

Early identification of drug-induced impairment of gastric emptying through physiologically based pharmacokinetic (PBPK) simulation of plasma concentration-time profiles in rat.  

PubMed

Inhibition of gastric emptying rate can have adverse effects on the absorption of food and nutrients. The absorption phase of the plasma concentration-time profile of a compound administered orally to pre-clinical species reflects among others, the gastric and intestinal transit kinetics, and can thus assist in the early identification of delayed gastric emptying. The purpose of this article is to demonstrate the value of Physiologically Based Pharmacokinetic (PBPK) modelling in the early identification of drug induced impairment of gastric emptying from pharmacokinetic profiles. To our knowledge, this is first time that the value of a generic PBPK model for hypothesis testing has been demonstrated with examples. A PBPK model built in-house using MATLAB package and incorporating absorption, metabolism, distribution, biliary and renal elimination models has been employed for the simulation of concentration-time profiles. PBPK simulations of a few compounds that are currently in drug discovery projects show that the observed initial absorption phase of their concentration-time profiles in rat were consistent with reduced gastric emptying rates. The slow uptake of these compounds into the systemic circulation is reflected in their pharmacokinetic profiles but it is not obvious until PBPK simulations are done. Delayed gastric emptying rates of these compounds in rats were also independently observed in x-ray imaging. PBPK simulations can provide early alerts to drug discovery projects, besides aiding the understanding of complex mechanisms that determine the lineshapes of pharmacokinetic profiles. The application of PBPK simulations in the early detection of gastric emptying problems with existing data and without the need to resort to additional animal studies, is appealing both from an economic and ethical standpoint. PMID:17963025

Peters, Sheila Annie; Hultin, Leif

2008-02-01

324

Comparative Specificities of Serum and Synovial Cell 19S IgM Rheumatoid Factors in Rheumatoid Arthritis.  

National Technical Information Service (NTIS)

Rheumatoid factor (RF) may play a key role in sustaining the inflammatory events and tissue damage in rheumatoid arthritis (RA). However, many serum RF have greater specificity for rabbit IgG than for human IgG, thus raising questions about RF pathogenici...

D. L. Robbins R. Wistar

1985-01-01

325

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

PubMed Central

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.

Envalds, Minja; Pincus, Theodore

2008-01-01

326

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

NASA Astrophysics Data System (ADS)

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

Sussmann, Ralf; Gierens, Klaus M.

2001-03-01

327

RHEUMATOID (MARIE-STRUMPELL) SPONDYLITIS, Technique of Examination and Importance of the Costal Joints  

PubMed Central

Rheumatoid spondylitis in the early prodromal stage may present a complex and obscure clinical picture making diagnosis difficult. It is in this early stage that roentgen examination of the small joints of the spine will often aid in or lead to the correct diagnosis of the disease in which the classical clinical symptoms and roentenographic findings in the sacroiliac fissure have not appeared and may never appear. The changes in these small joints, particularly in the costovertebral and costotransverse joints, are less obvious and require experienced and careful interpretation, but it is to these that the roentgenologist must direct his attention if he is to be of assistance in early diagnosis. A technical procedure for this examination is presented, along with a discussion of the clinical importance of changes at this site. Demonstration of involvement of the sacroiliac joints is of diagnostic importance, but this finding is no more necessary to the diagnosis of rheumatoid spondylitis than is involvement of any other single joint of the spine. Insistence on sacroiliac involvement will often result in missed diagnosis, and has led in part to erroneous conclusions as to sex incidence of the disease. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.

Williams, A. Justin

1949-01-01

328

Rheumatoid (Marie-Strumpell) spondylitis; technique of examination and importance of the costal joints.  

PubMed

Rheumatoid spondylitis in the early prodromal stage may present a complex and obscure clinical picture making diagnosis difficult. It is in this early stage that roentgen examination of the small joints of the spine will often aid in or lead to the correct diagnosis of the disease in which the classical clinical symptoms and roentenographic findings in the sacroiliac fissure have not appeared and may never appear. The changes in these small joints, particularly in the costovertebral and costotransverse joints, are less obvious and require experienced and careful interpretation, but it is to these that the roentgenologist must direct his attention if he is to be of assistance in early diagnosis. A technical procedure for this examination is presented, along with a discussion of the clinical importance of changes at this site. Demonstration of involvement of the sacroiliac joints is of diagnostic importance, but this finding is no more necessary to the diagnosis of rheumatoid spondylitis than is involvement of any other single joint of the spine. Insistence on sacroiliac involvement will often result in missed diagnosis, and has led in part to erroneous conclusions as to sex incidence of the disease. PMID:18116229

WILLIAMS, A J

1949-04-01

329

Antibiotics for the treatment of rheumatoid arthritis.  

PubMed

Antibiotic treatment for rheumatoid arthritis (RA) commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin) were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment. PMID:24403843

Ogrendik, Mesut

2013-01-01

330

Total Knee Arthroplasty Considerations in Rheumatoid Arthritis  

PubMed Central

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

Danoff, Jonathan R.; Geller, Jeffrey A.

2013-01-01

331

Bilateral TMJ Involvement in Rheumatoid Arthritis  

PubMed Central

Rheumatoid arthritis (RA) is a systemic inflammatory, slowly progressive disease that results in cartilage and bone destruction. Temporomandibular joint (TMJ) involvement is not uncommon in RA, and it is present in about more than 50% of patients; however, TMJ is usually among the last joints to be involved and is associated with many varied clinical signs and symptoms. Hence, RA of TMJ presents to the dentist with great diagnostic challenges. This report presents a case of RA with bilateral TMJ involvement with its classical radiographic findings and review literature.

Ruparelia, Pritesh B.; Shah, Deep S.; Ruparelia, Kosha; Sutaria, Shreyansh P.; Pathak, Deep

2014-01-01

332

Antibiotics for the treatment of rheumatoid arthritis  

PubMed Central

Antibiotic treatment for rheumatoid arthritis (RA) commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin) were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment.

Ogrendik, Mesut

2014-01-01

333

Muehrcke lines associated to active rheumatoid arthritis.  

PubMed

Careful examination of the fingernails and toenails can help to detect underlying systemic diseases. Physicians should look for shape, growth, or color changes in the nails; the transverse nail discolorations include different diagnostic possibilities such as Muehrcke lines and Mees lines. Leukonychia striata or Muehrcke lines are transverse nail bands of discoloration that are unspecific, and there are around 70 different causes that include cancer treatment and less commonly rheumatic diseases. In this case, we report the unusual presentation of Muehrcke lines associated with active rheumatoid arthritis. PMID:23319020

Chávez-López, Mario Alfredo; Arce-Martínez, Francisco Javier; Tello-Esparza, Adolfo

2013-01-01

334

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

Microsoft Academic Search

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

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

2005-01-01

335

Risk Factors for Asymptomatic Ventricular Dysfunction in Rheumatoid Arthritis Patients  

PubMed Central

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.

Garza-Garcia, Carlos; Rocio, Sanchez-Santillan; Orea-Tejeda, Arturo; Castillo-Martinez, Lilia; Eduardo, Canseco; Lopez-Campos, Jose Luis; Keirns-Davis, Candace

2013-01-01

336

Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis  

PubMed Central

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

2013-01-01

337

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

PubMed

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

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

2013-10-01

338

Assessment of synovitis to predict bone erosions in rheumatoid arthritis  

PubMed Central

Although rheumatoid arthritis (RA) is traditionally considered as the prototype of destructive arthritis, the course of the disease varies considerably, with some patients experiencing more rapid progression of joint damage and disability than others. Given the increasing availability of treatment targets and options, timely recognition of individual’s outcomes could allow therapeutic allocation according to personalized benefit–risk profiles. Research efforts are thus increasingly focused at discovering predictive markers that could identify patients with aggressive, rapidly progressive disease and poor prognosis. As joint destruction in RA is the result of the cumulative burden of inflammation, variables reflecting the severity of synovitis and its persistence over time might refine our ability to build early prognostic algorithms. The goal of this article is to review the clinical implications of the assessment of synovitis in relation to radiographic outcomes. Traditional and novel assessment tools will be discussed, including clinical measures, imaging techniques and tissue biomarkers. Achievements in the field of synovial tissue analysis and peripheral blood biomarkers of synovitis represent only the first steps of ongoing progress, which still need to be integrated into the phenotypic heterogeneity of RA.

Manzo, Antonio; Caporali, Roberto; Montecucco, Carlomaurizio

2012-01-01

339

Assessment of synovitis to predict bone erosions in rheumatoid arthritis.  

PubMed

Although rheumatoid arthritis (RA) is traditionally considered as the prototype of destructive arthritis, the course of the disease varies considerably, with some patients experiencing more rapid progression of joint damage and disability than others. Given the increasing availability of treatment targets and options, timely recognition of individual's outcomes could allow therapeutic allocation according to personalized benefit-risk profiles. Research efforts are thus increasingly focused at discovering predictive markers that could identify patients with aggressive, rapidly progressive disease and poor prognosis. As joint destruction in RA is the result of the cumulative burden of inflammation, variables reflecting the severity of synovitis and its persistence over time might refine our ability to build early prognostic algorithms. The goal of this article is to review the clinical implications of the assessment of synovitis in relation to radiographic outcomes. Traditional and novel assessment tools will be discussed, including clinical measures, imaging techniques and tissue biomarkers. Achievements in the field of synovial tissue analysis and peripheral blood biomarkers of synovitis represent only the first steps of ongoing progress, which still need to be integrated into the phenotypic heterogeneity of RA. PMID:22859922

Bugatti, Serena; Manzo, Antonio; Caporali, Roberto; Montecucco, Carlomaurizio

2012-08-01

340

The role of adenosine receptors in rheumatoid arthritis.  

PubMed

Rheumatoid arthritis (RA), is the most common inflammatory musculoskeletal disease inducing diminished quality-of-life in the affected individuals and having major impact on society due to decrease work ability. Early diagnosis and immediate, effective therapy are crucial in order to prevent unfavorable outcome. Treatment of RA has progressed during the past two decades thanks to the advent of a large number of new agents targeting different specific molecules and pathways involved in the modulation of the inflammation. In this scenario an important role is covered by adenosine, a purine nucleoside released from a variety of cells in response to metabolic and inflammatory stress, which is considered to be a potent endogenous regulator acting through its interaction with 4 cell surface receptors named as A(1), A(2A), A(2B) and A(3). Adenosine receptor stimulation has complex effects on the release of pro-inflammatory cytokines depending on selective receptor engagement. Recent data show the involvement of adenosine pathways in RA and its potential therapeutic implications. PMID:20691813

Varani, Katia; Padovan, Melissa; Govoni, Marcello; Vincenzi, Fabrizio; Trotta, Francesco; Borea, Pier Andrea

2010-12-01

341

Genetic Markers of Cardiovascular Disease in Rheumatoid Arthritis  

PubMed Central

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

Rodriguez-Rodriguez, Luis; Lopez-Mejias, Raquel; Garcia-Bermudez, Mercedes; Gonzalez-Juanatey, Carlos; Gonzalez-Gay, Miguel A.; Martin, Javier

2012-01-01

342

Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years  

PubMed Central

Objective: To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence. Methods: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955–94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1–42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews. Results: ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmö, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity. Conclusion: There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA.

Turesson, C; O'Fallon, W; Crowson, C; Gabriel, S; Matteson, E

2003-01-01

343

TNF-? Antagonist and Infection in Rheumatoid Arthritis  

PubMed Central

Background Anti-TNF treatment may increase infection risk, although this has been difficult to study because the timing of anti-TNF treatment is driven by disease activity, which may influence infection susceptibility leading to confounding that varies over time. We evaluated the association between anti-TNF initiation in rheumatoid arthritis (RA) patients on disease modifying anti-rheumatic drugs (DMARD) and infection using multiple approaches adjusting for time-varying confounding. Methods 383 anti-TNF-naïve RA patients on ?1 non-biologic-DMARD at enrollment from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) were followed up to two years. Pooled logistic regressions estimated the association between anti-TNF and infection by including time-varying covariates in the adjusted models and inverse probability treatment weighting (IPTW). Results Adjustment for time-varying disease activity and other suspected confounders yielded non-statistically significant positive associations between anti-TNF start and infection regardless of analytic approach (RRmvar_adj = 2.1, 95% CI: 0.8 – 5.8). Conclusions Incorporating changing clinical status, and treatment indications and consequences, yielded consistently (though not significantly) elevated relative risks of infection associated with anti-TNF initiation. Due to limited statistical power, we cannot draw firm conclusions. However, we have illustrated multiple approaches adjusting for potential time-varying confounding in longitudinal studies and hope to replicate the approaches in larger studies.

Simard, Julia F.; Mittleman, Murray A.; Shadick, Nancy A.; Karlson, Elizabeth W.

2013-01-01

344

Targets of immune regeneration in rheumatoid arthritis.  

PubMed

Many of the aging-related morbidities, including cancer, cardiovascular disease, neurodegenerative disease, and infectious susceptibility, are linked to a decline in immune competence with a concomitant rise in proinflammatory immunity, placing the process of immune aging at the center of aging biology. Immune aging affects individuals older than 50 years and is accelerated in patients with the autoimmune disease rheumatoid arthritis. Immune aging results in a marked decline in protective immune responses and a parallel increase in tissue inflammatory responses. By studying immune cells in patients with rheumatoid arthritis, several of the molecular underpinnings of the immune aging process have been delineated, such as the loss of telomeres and inefficiencies in the repair of damaged DNA. Aging T cells display a series of abnormalities, including the unopposed up-regulation of cytoplasmic phosphatases and the loss of glycolytic competence, that alter their response to stimulating signals and undermine their longevity. Understanding the connection between accelerated immune aging and autoimmunity remains an area of active research. With increasing knowledge of the molecular pathways that cause immunosenescence, therapeutic interventions can be designed to slow or halt the seemingly inevitable deterioration of protective immunity with aging. PMID:24684878

Hohensinner, Philipp J; Goronzy, Jörg J; Weyand, Cornelia M

2014-04-01

345

Annexin V autoantibodies in rheumatoid arthritis.  

PubMed Central

OBJECTIVE: To investigate the occurrence of anti-annexin V autoantibodies in sera of patients with rheumatoid arthritis to assess involvement with the disease and any relation to glucocorticoid treatment. METHODS: Anti-annexin V antibodies were measured by an enzyme linked immunosorbent assay (ELISA) which used the purified human recombinant protein as antigen. RESULTS: Concentrations of anti-annexin V autoantibodies, predominantly of the IgG class, were significantly raised in sera from patients with rheumatoid arthritis compared to normal controls. This was not correlated with other indices of disease activity such as erythrocyte sedimentation rate or C reactive protein and was unrelated to glucocorticoid treatment. CONCLUSIONS: Extracellular annexin V provides an antigenic stimulus for autoantibody production and its in vivo expression is independent of glucocorticoid control. Such autoantibodies may have a detrimental role in the arthritic condition by interfering with putative functions of annexin V, including collagen type II binding, inhibition of phospholipase A2 activity, and Fc receptor activity. Images

Rodriguez-Garcia, M I; Fernandez, J A; Rodriguez, A; Fernandez, M P; Gutierrez, C; Torre-Alonso, J C

1996-01-01

346

Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis  

PubMed Central

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

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

2014-01-01

347

Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis.  

PubMed

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

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

2014-07-18

348

The diagnostic value of anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis.  

PubMed

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. The aim of this study was to evaluate the diagnostic value of anti CCP antibodies in patients with RA. This study included three groups; group I: 60 early diagnosed RA patients selected according to the ACR, group II: 30 patients of arthritis other than RA, group III: 10 healthy age and sex matched volunteer. Sera from all participants were tested for rheumatoid factor (IgM RF) and anti-CCP IgG antibodies using ELISA. Of 60 patients in group I, 52 subjects (86.7%) were RF positive, whereas all participants in groups II and III were negative. Similarly 56 patients (93.3%) of group I were anti-CCP antibody positive, but all subjects in groups II and III were negative. Thus detection of anti-CCP antibodies can be used as a diagnostic indicator for patients with early RA (P < 0.0001). PMID:23885402

Hashem, Shabaan; Mahmoud, Adel; Fahmy, Hossam; Habeib, Reem; Eltigani, Sara

2012-01-01

349

Recent Paradigm Shifts in the Diagnosis and Treatment of Rheumatoid Arthritis  

PubMed Central

Rheumatoid arthritis (RA) is a progressive inflammatory disease with severe symptoms of pain and stiffness. Chronic persistent inflammation of RA often leads to joint destruction, deformity and limitation of function, which ultimately results in significant deterioration of quality of life (QoL). RA is characterized pathogenetically by immunologically driven, chronic synovitis, and production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Although the cause of RA is yet unknown, advances in the molecular biology led to in-depth understanding of its pathogenesis, and have fostered the recent development of novel treatments. The last decade has seen the dramatic change in the landscape of RA treatment with more aggressive therapy early in the disease course and with treatment guided by a structured assessment of disease activity, with the ultimate goal of reaching remission. In addition, prevention and control of joint damage and improvement in QoL are important goals. To achieve these goals, a multidisciplinary approach to reduce disease activity with disease modifying antirheumatic drugs and biological therapy is needed. We also need to find ways to identify those patients who are at risk for more rapid disease progression who would benefit from intensive therapy early in the course of disease.

Jung, Young Ok

2012-01-01

350

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

PubMed Central

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

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

1983-01-01

351

Tissue factor expression in rheumatoid synovium: a potential role in pannus invasion of rheumatoid arthritis.  

PubMed

Angiogenesis, as well as pannus formation within the joint, plays an important role in the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). Tissue factor (TF), an essential initiator of the extrinsic pathway of blood coagulation, is also involved in the angiogenesis and the pannus formation of RA progression. In the present study, we used immunofluorescence and confocal scanning methods to characterize TF immunolocalization in RA synovium. We showed that positive staining of TF could be immunolocalized in synoviocytes, CD19(+) B cells and CD68(+) macrophages, whereas weak or negative staining of tissue factor could be found in CD34(+) endothelial cells of neo-vessels, CD3(+) T cells and CD14(+) monocytes in RA synovium tissues. Our study demonstrates a detailed local expression of TF in the rheumatoid synovium, and supports the notion that TF, expressed not only by the synoviocytes themselves, but also the infiltrating CD19(+) B cells and CD68(+) macrophages, is involved in the pannus invasion in the progression of rheumatoid arthritis. PMID:23490466

Chen, Lujun; Lu, Yahua; Chu, Yang; Xie, Jun; Ding, Wen'ge; Wang, Fengming

2013-09-01

352

Humoral Immune Function in Severe, Active Rheumatoid Arthritis.  

National Technical Information Service (NTIS)

Peripheral blood mononuclear cells (PBMC) from 30 patients with definite or classic active rheumatoid arthritis who were on no remittive drugs were studied for spontaneous and pokeweed mitogen (PWM)-stimulated immunoglobulin plaque-forming cell frequency ...

E. P. Boling T. Ohishi S. M. Wahl J. Misiti R. Wistar

1987-01-01

353

Prognostic Factors in Arthroplasty in the Rheumatoid Shoulder  

Microsoft Academic Search

Total shoulder arthroplasty is commonly considered a good option for treatment of the rheumatoid shoulder. However, when the\\u000a rotator cuff and glenoid bone stock are not preserved, the clinical outcome of arthroplasty in the rheumatoid patients remains\\u000a unclear. Aim of the study is to explore the prognostic value of multiple preoperative and peroperative variables in total\\u000a shoulder arthroplasty and shoulder

Piet M. Rozing; Jochem Nagels; Maarten P. Rozing

2011-01-01

354

T cells as Secondary Players in Rheumatoid Arthritis  

Microsoft Academic Search

\\u000a Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects about 1% of the general population worldwide [1]. The pathogenesis of RA remains a subject of debate, and many paradigms have been proposed and disputed over the years.\\u000a The concept of autoimmunity in RA appeared in the 1940’s when it was first appreciated that self-reacting antibodies (rheumatoid\\u000a factors) are present

Katherine H. Y. Nguyen; Gary S. Firestein

355

Blood cell gene expression profiling in rheumatoid arthritis  

Microsoft Academic Search

To study the pathogenic importance of the rheumatoid factor (RF) in rheumatoid arthritis (RA) and to identify genes differentially expressed in patients and healthy individuals, total RNA was isolated from peripheral blood mononuclear cells (PBMC) from eight RF-positive and six RF-negative RA patients, and seven healthy controls. Gene expression of about 10,000 genes were examined using oligonucleotide-based DNA chip microarrays.The

Lone Frier Bovin; Klaus Rieneck; Christopher Workman; Henrik Nielsen; Søren Freiesleben Sørensen; Henrik Skjødt; Adrian Florescu; Søren Brunak; Klaus Bendtzen

2004-01-01

356

Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications  

Microsoft Academic Search

Patients with rheumatoid arthritis (RA) are at high risk of cardiovascular events. Platelet biomarkers are involved in inflammation,\\u000a atherosclerosis and thrombosis. Cardiovascular and RA-associated factors can alter the structure and function of platelets,\\u000a starting from megakaryocytopoiesis. Reactive megakaryocytopoiesis increases circulating platelets count and triggers hyperactivity.\\u000a Hyperactive platelets target synovial membranes with subsequent local rheumatoid inflammation. Hyperactive platelets interact\\u000a with other

Armen Yuri Gasparyan; Antonios Stavropoulos-Kalinoglou; Dimitri P. Mikhailidis; Karen M. J. Douglas; George D. Kitas

2011-01-01

357

B Effector Cells in Rheumatoid Arthritis and Experimental Arthritis  

PubMed Central

Rheumatoid arthritis is a chronic autoimmune immune disease affecting approximately 1% of the population. There has been a renewed interest in the role of B cells in rheumatoid arthritis based on the evidence that B cell depletion therapy is effective in the treatment of disease. This review summarizes the current knowledge of the mechanisms by which B cells contribute to autoimmune arthritis including roles as autoantibody producing cells, antigen-presenting cells, cytokine producing cells, and regulatory cells.

Finnegan, Alison; Ashaye, Susan; Hamel, Keith M.

2013-01-01

358

A randomized controlled trial of homeopathy in rheumatoid arthritis  

Microsoft Academic Search

Objective. To test the hypothesis that homeopathy is effective in reducing the symptoms of joint inflammation in rheumatoid arthritis (RA). Method. This was a 6-month randomized, cross-over, double-blind, placebo-controlled, single-centre study set in a teaching hospital rheumatology out-patient clinic. The participants of the study were 112 patients who had definite or classical RA, were seropositive for rheumatoid factor and were

P. Fisher; D. L. Scott

2001-01-01

359

Prognostic Factors in Arthroplasty in the Rheumatoid Shoulder  

PubMed Central

Total shoulder arthroplasty is commonly considered a good option for treatment of the rheumatoid shoulder. However, when the rotator cuff and glenoid bone stock are not preserved, the clinical outcome of arthroplasty in the rheumatoid patients remains unclear. Aim of the study is to explore the prognostic value of multiple preoperative and peroperative variables in total shoulder arthroplasty and shoulder hemiarthroplasty in rheumatoid patients. Clinical Hospital for Special Surgery Shoulder score was determined at different time points over a mean period of 6.5 years in 66 rheumatoid patients with total shoulder arthroplasty and 75 rheumatoid patients with shoulder hemiarthroplasty. Moreover, radiographic analysis was performed to assess the progression of humeral head migration and glenoid loosening. Advanced age and erosions or cysts at the AC joint at time of surgery were associated with a lower postoperative Clinical Hospital for Special Surgery Shoulder score. In total shoulder arthroplasty, status of the rotator cuff and its repair at surgery were predictive of postoperative improvement. Progression of proximal migration during the period after surgery was associated with a lower clinical score over time. However, in hemiarthroplasty, no relation was observed between the progression of proximal or medial migration during follow-up and the clinical score over time. Status of the AC joint and age at the time of surgery should be taken into account when considering shoulder arthroplasty in rheumatoid patients. Total shoulder arthroplasty in combination with good cuff repair yields comparable clinical results as total shoulder arthroplasty when the cuff is intact.

Nagels, Jochem; Rozing, Maarten P.

2010-01-01

360

Regulatory T cells (Treg) in rheumatoid arthritis.  

PubMed

Modulation of the T-cell response depends chiefly on regulatory T cells (Treg), which express CD4 and CD25. Some Treg cells are present naturally, whereas others are induced in response to antigens. The immunomodulating effects of Treg cells are mediated by membrane molecules (e.g., CTLA4, GITR, and OX40) and cytokines. IL-35 seems to be a crucial mediator, although IL-10 and TGFbeta are also important. The role for Treg cells in rheumatoid arthritis (RA) has been established in both patients and animal models. Treg function is deficient in RA, whereas Treg counts vary. Treg counts increase in patients who are responding to TNFalpha antagonist therapy. Among current hypotheses, Treg expansion or transfer may hold promise for the treatment of RA. PMID:19028128

Boissier, Marie-Christophe; Assier, Eric; Biton, Jérome; Denys, Anne; Falgarone, Géraldine; Bessis, Natacha

2009-01-01

361

Impact of rheumatoid arthritis on sexual function  

PubMed Central

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.

Tristano, Antonio G

2014-01-01

362

Hemophagocytic syndrome associated with rheumatoid arthritis.  

PubMed

We report a patient with rheumatoid arthritis (RA) who showed bicytopenia with hyperferritinemia and hepatic dysfunction ascribable to hemophagocytic syndrome (HPS) 2 weeks after commencement of bucillamine. Pathology of the bone marrow showing infiltration of macrophages confirmed the diagnosis of HPS. On the basis of renal dysfunction with an increase in fibrin degradation products, disseminated intravascular coagulation was considered to be concurrent with HPS. Oral prednisolone and cyclosporine A were started right after cessation of bucillamine, and yielded complete normalization of hepatic and renal function and hematology. As there was neither disease activity of RA nor associated infection throughout the clinical course, bucillamine was suspected of being the cause of HPS in our patient. HPS is a very rare complication in RA, but should be actively considered when abnormalities in laboratory data, especially pancytopenia and hepatic dysfunction, quickly worsen. PMID:17978540

Katoh, Nagaaki; Gono, Takahisa; Mitsuhashi, Shigeaki; Fukushima, Kazuhiro; Takei, Yo-ichi; Matsuda, Masayuki; Ikeda, Shu-ichi

2007-01-01

363

Moving towards personalized medicine in rheumatoid arthritis  

PubMed Central

To develop personalized medicine strategies for improvement of patient management in rheumatoid arthritis, the clinical and molecular properties of the individual patients need to be well characterized. A crucial step in this approach is to discover subgroups of patients that are characterized by a good or poor treatment outcome. Dennis and colleagues have identified distinct pretreatment gene expression profiles in affected synovial tissue specimens and a tissue type-related systemic protein pattern which are associated with a positive or negative clinical outcome to monotherapy with adalumimab (anti-TNF?) and tocilizumab (anti-IL-6 receptor). These observations assign biological pathways associated with response outcome and provide evidence for the existence of systemic, easy-to-measure predictive biomarkers for clinical benefit of these biologics.

2014-01-01

364

Adipokines as Potential Biomarkers in Rheumatoid Arthritis  

PubMed Central

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

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

2014-01-01

365

Light scattering study of rheumatoid arthritis  

SciTech Connect

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)

Beuthan, J; Netz, U; Minet, O; Mueller, G [Institut fur Medizinische Physik/Laser-medizin, Freie Universitat Berlin, Universitaetsklinikum Benjamin Franklin, Berlin (Germany); Klose, Annerose D; Hielscher, A H [Columbia University, New York (United States); Scheel, A [Department of Medicine, Nephrology and Rheumatology, Georg-August-University, Goettingen (Germany); Henniger, J [Department of Physics, Technical University Dresden (Germany)

2002-11-30

366

Emerging role of leptin in rheumatoid arthritis.  

PubMed

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

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

2014-09-01

367

[Complex functional test in juvenile rheumatoid arthritis].  

PubMed

The Juvenile rheumatoid arthritis is a special form of rheumatoid arthritis which occurs in childhood and adolescence (before the age of sixteen). The disease primarily affects the joints, but can also cause heavy damages to organs and systems such as the heart, blood vessels, skin, epidermis, eyes, peripheral nerves etc. The disease occurs more often with girls. In the therapeutic sense, viewed from the physical medicine and rehabilitation aspect, lying in bed is needed during the acute phase of the disease, and when the inflammation ceases, normal body activities should be encouraged. Rehabilitation with standard methods of physical therapy includes enhancement of daily activities and quality of life, adaptation of patient to the new conditions and prevention of complications. At the Physical medicine and rehabilitation department of the Pediatric clinic CCU Sarajevo, during year 2001 and 2002, fourteen children were observed. All children were treated with kinezitherapy, after which everyday life activities were observed as well as the mobility. In these everyday life activities we were observing whether child can use spoon, fork and knife, whether or not a child can dress his/her upper or lower part of the body with or without buttoning, whether or not it can bathe without someone's help. While observing mobility we evaluated general mobility with changing the body's position from lying to sitting and also from sitting to standing position, climbing onto and getting of a bed, ascending and descending stairs, ability to crouch down or not. These methods are used to prevent inability or decrease it as much as possible. It is accomplished by preventing the forming of muscular atrophies, preventing the development of contractions of joints, as well as preventing the development of osteoporosis and bone destruction due to the inactivity. The imperative of a good rehabilitation is "active movement". PMID:16268068

Meholji?-Fetahovi?, Ajsa

2005-01-01

368

Vascular Function and Inflammation in Rheumatoid Arthritis: the Role of Physical Activity  

PubMed Central

Inflammation disturbs biochemical pathways involved in homeostasis of the endothelium. Research has established clear links between inflammatory mediators, particularly C-reactive protein and tumour necrosis factor alpha, endothelial dysfunction, and atherosclerosis. Endothelial dysfunction and atherosclerosis may be subclinical at early stages, and thus the ability to detect them with non-invasive techniques is crucially important, particularly in populations at increased risk for cardiovascular disease, such as those with rheumatoid arthritis. This may allow the identification of interventions that may reverse these processes early on. One of the best non-pharmacological interventions that may achieve this is physical activity. This review explores the associations between inflammation, endothelial dysfunction, and atherosclerosis and discusses the role of exercise in blocking specific pathways in the inflammation, endothelial dysfunction - atherosclerosis network.

Metsios, George S; Stavropoulos-Kalinoglou, Antonios; Sandoo, Aamer; van Zanten, Jet J.C.S. Veldhuijzen; Toms, Tracey E; John, Holly; Kitas, George D

2010-01-01

369

Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective.  

PubMed

ABSTRACT: The synovial tissue stands at the epicenter of joint pathology in rheumatoid arthritis (RA). As a primary target of the disease, studies on the synovium have provided invaluable insights into the mechanisms involved in disease pathogenesis. Recent work has, however, revealed the importance of a previously unseen anatomic compartment in direct contact with the joint space, namely the subchondral bone marrow. Bone marrow edema (BME) visible on magnetic resonance imaging (MRI) is clinically meaningful in both early and late RA as it associates with future development of bone erosions and poor functional outcomes. Although the histopathologic correlates of MRI-based BME in early RA remain obscure, studies in advanced disease are consistent in describing lymphocytic inflammatory infiltrates within the subchondral marrow cavity of affected joints. In this review, we discuss the nature of bone marrow lesions in patients with RA, analyze their relationship with synovitis, and explore their potential contribution to the pathological processes of the disease. PMID:23270711

Bugatti, Serena; Manzo, Antonio; Caporali, Roberto; Montecucco, Carlomaurizio

2012-12-27

370

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

PubMed Central

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

Clarke, Lynsey

2012-01-01

371

Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective  

PubMed Central

The synovial tissue stands at the epicenter of joint pathology in rheumatoid arthritis (RA). As a primary target of the disease, studies on the synovium have provided invaluable insights into the mechanisms involved in disease pathogenesis. Recent work has, however, revealed the importance of a previously unseen anatomic compartment in direct contact with the joint space, namely the subchondral bone marrow. Bone marrow edema (BME) visible on magnetic resonance imaging (MRI) is clinically meaningful in both early and late RA as it associates with future development of bone erosions and poor functional outcomes. Although the histopathologic correlates of MRI-based BME in early RA remain obscure, studies in advanced disease are consistent in describing lymphocytic inflammatory infiltrates within the subchondral marrow cavity of affected joints. In this review, we discuss the nature of bone marrow lesions in patients with RA, analyze their relationship with synovitis, and explore their potential contribution to the pathological processes of the disease.

2012-01-01

372

Development and validation of handy rheumatoid activity score with 38 joints (HRAS38) in rheumatoid arthritis patients receiving infliximab  

Microsoft Academic Search

The parameters involved in the Disease Activity Score of 28 joints (DAS28) are not mutually independent, and the evaluation\\u000a excludes ankle and foot joints. We developed a new quantitative and comprehensive assessment of the activity of rheumatoid\\u000a arthritis (RA), called the handy rheumatoid activity score, with 38 joints (HRAS38), to overcome these disadvantages of DAS28.\\u000a Forty-six RA patients who recently

Hideto Kameda; Naoya Sekiguchi; Hayato Nagasawa; Koichi Amano; Hirofumi Takei; Katsuya Suzuki; Eiko Nishi; Hiroe Ogawa; Tsutomu Takeuchi

2006-01-01

373

Airway obstruction in rheumatoid arthritis: CT manifestations, correlated with pulmonary function testing.  

PubMed

In the present study, the signs of airflow obstruction on inspiratory and expiratory CT scans in 45 patients with rheumatoid arthritis were investigated. Radiologic findings were evaluated and correlated with the clinical data, which included rheumatoid factors and pulmonary function tests results. A lung biopsy was performed in five patients. The pattern of CT findings was as follows: infiltrative (n=15), obstructive (n=12), mixed (infiltrative and obstructive; n=10), other complicating diseases (n=7), and normal (n=1). The rheumatologic factor between patients with bronchial wall thickenings and patients without thickenings was significantly different (p=0.009). The forced expiratory flow rate between 25% and 75% of the vital capacity (FEF(25-75%)) was significantly more reduced in patients with interlobular septal thickenings than in patients without these thickenings. The patients with mosaic attenuation had significantly lower mean values of FEF(25-75% ) (p=0.001) and a lower peak expiratory flow (p=0.003) than patients without mosaic attenuation. On expiratory scans, the mean air-trapping score was 21%. These air-trapping scores were found to be well correlated with FEV1/FVC (r=0.230, p=0.0452), and FEF25-75% (r=-0.63, p= 0.05). It is widely known that a relatively higher percentage of mosaic attenuation with air-trapping and a good correlation between these and functional values contribute to the detection of early airway obstruction in patients with rheumatoid arthritis, and even in patients with infiltrative lung disease only. PMID:15227731

Chung, Myung Hee; Lee, Hae Giu; Kwon, Soon Suck; Park, Seog Hee; Kim, Ki Joon; Jung, Jung Im; Sung, Mi Sook; Yoo, Won Jong

2004-06-30

374

Elderly onset rheumatoid arthritis: differential diagnosis and choice of first-line and subsequent therapy.  

PubMed

Elderly onset rheumatoid arthritis (EORA) has been considered a benign form of rheumatoid arthritis (RA). However, it most probably encompasses different subsets of patients with distinct outcomes. According to data reported in the most recent studies directly comparing older and younger RA patients, it seems that, overall, the prognosis of EORA patients is not very different from that of other patients with this disease. However, some cases with negative rheumatoid factor and polymyalgia-like symptoms appear to be a distinct subset with a different genetic basis and a more benign course. The differential diagnosis of EORA from other rheumatological disorders that are prevalent in this stratum of the population, such as polymyalgia rheumatica, crystal-induced arthritis or osteoarthritis, may be complicated because these disorders can present with signs and symptoms similar to those of RA in some circumstances. A prompt diagnosis of true RA is important because early treatment should be implemented. It is recommended that therapy of EORA be tailored according to disease activity, with the aim of achieving clinical remission or the lowest possible level of disease activity in order to minimize potential functional sequelae. Co-morbidities and drug toxicity profiles are major considerations when choosing the most suitable therapy for EORA patients. Prudent use and careful follow-up of all treatments are also required because of the increased risk of adverse events in elderly patients. However, no special contraindications to the use of disease-modifying antirheumatic drugs in this age group apply, and use of biological therapies currently used in younger RA patients has also been described in these patients. Therefore, a therapeutic strategy for first-line and subsequent treatment that is in accordance with the disease activity of patients with EORA is suggested. PMID:19728748

Villa-Blanco, Juan Ignacio; Calvo-Alén, Jaime

2009-01-01

375

An integrated approach to early process hazard identification of continuous and batch plants with statechart modelling and simulation  

Microsoft Academic Search

Safety is an important task in chemical plants and plays a significant role throughout the whole design process. To ensure the safety and environmental demands and to minimise later plant changes, safety analyses are performed in early design phases. Due to still manifold drawbacks of applied methods, e.g. Hazop studies, computer-based approaches are subject to research. This paper introduces a

Holger Graf; Henner Schmidt-Traub

2001-01-01

376

Simulating The 8 Kyr Bp Time Period: A Better Representation of Early To Mid-holocene Climate  

Microsoft Academic Search

Paleo proxy data show that in the northern hemisphere the early to middle Holocene (8 to 6 kyr BP) was warmer than the pre-industrial period. A special focus concern- ing the Mid-Holocene lies on the north African region as proxy data reveal that in this region a rather dramatic change in surface conditions (from a green Sahara to a desert)

M. Scholze; K.-G. Schnitzler; W. Knorr; U. Mikolajewicz

2002-01-01

377

Ab Initio Computer Simulation of the Early Stages of Crystallization: Application to Ge2Sb2Te5 Phase-Change Materials  

NASA Astrophysics Data System (ADS)

By virtue of the ultrashort phase-transition time of phase-change memory materials, e.g., Ge2Sb2Te5, we successfully reproduce the early stages of crystallization in such a material using ab initio molecular-dynamics simulations. A stochastic distribution in the crystallization onset time is found, as generally assumed in classical nucleation theory. The critical crystal nucleus is estimated to comprise 5-10 (Ge,Sb)4Te4 cubes. Simulated growth rates of crystalline clusters in amorphous Ge2Sb2Te5 are consistent with extrapolated experimental measurements. The formation of ordered planar structures in the amorphous phase plays a critical role in lowering the interfacial energy between crystalline clusters and the amorphous phase, which explains why Ge-Sb-Te materials exhibit ultrafast crystallization.

Lee, T. H.; Elliott, S. R.

2011-09-01

378

The early phase of psoriatic arthritis  

Microsoft Academic Search

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

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

2011-01-01

379

Rheumatoid Arthritis Treatment and Causes | NIH MedlinePlus the Magazine  

MedlinePLUS

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

380

Rheumatoid Arthritis When Your Immune System Attacks Your Body | NIH MedlinePlus the Magazine  

MedlinePLUS

... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Research Summer 2014 Table of Contents Accelerating ... a project plan to address relevant challenges for rheumatoid arthritis. Read Part 1 on Lupus in MedlinePlus magazine, ...

381

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

MedlinePLUS

... 2013 New Insights Found in Pain Processing and Sleep Disturbance Among Rheumatoid Arthritis Patients People with rheumatoid ... in the journal Arthritis and Rheumatism. In addition, sleep disruptions, which are common among people with RA, ...

382

Novel multiplex technology for diagnostic characterization of rheumatoid arthritis  

PubMed Central

Introduction The aim of this study was to develop a clinical-grade, automated, multiplex system for the differential diagnosis and molecular stratification of rheumatoid arthritis (RA). Methods We profiled autoantibodies, cytokines, and bone-turnover products in sera from 120 patients with a diagnosis of RA of < 6 months' duration, as well as in sera from 27 patients with ankylosing spondylitis, 28 patients with psoriatic arthritis, and 25 healthy individuals. We used a commercial bead assay to measure cytokine levels and developed an array assay based on novel multiplex technology (Immunological Multi-Parameter Chip Technology) to evaluate autoantibody reactivities and bone-turnover markers. Data were analyzed by Significance Analysis of Microarrays and hierarchical clustering software. Results We developed a highly reproducible, automated, multiplex biomarker assay that can reliably distinguish between RA patients and healthy individuals or patients with other inflammatory arthritides. Identification of distinct biomarker signatures enabled molecular stratification of early-stage RA into clinically relevant subtypes. In this initial study, multiplex measurement of a subset of the differentiating biomarkers provided high sensitivity and specificity in the diagnostic discrimination of RA: Use of 3 biomarkers yielded a sensitivity of 84.2% and a specificity of 93.8%, and use of 4 biomarkers a sensitivity of 59.2% and a specificity of 96.3%. Conclusions The multiplex biomarker assay described herein has the potential to diagnose RA with greater sensitivity and specificity than do current clinical tests. Its ability to stratify RA patients in an automated and reproducible manner paves the way for the development of assays that can guide RA therapy.

2011-01-01

383

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

SciTech Connect

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

Wood, W.W. [Los Alamos National Lab., NM (United States). Theoretical Div.

1995-09-01

384

Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritis  

PubMed Central

Introduction Smoking increases the risk of developing rheumatoid arthritis (RA) and affects the severity of established RA. Smoking can impact on Th17 lymphocyte differentiation and function through activation of the aryl hydrocarbon receptor (AHR), a process with implications for the pathogenic mechanisms in RA that involve the cytokine, interleukin (IL)-17A. The objective of this study was to establish any effect of smoking on the inflammatory tissue lesions of rheumatoid arthritis via the AHR and IL-17A. Methods Twenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established. Expression of AHR, CYP1A1, AHRR, IL6, IL17A, IL17F, IL22, IL23, IL23R, IFNG, TBX21, IDO1 and FOXP3 genes were assessed in tissues and cultured cells using real-time PCR. Two-colour immunofluorescence was used to co-localise AHR and CYP1A1 protein in synovial tissues. The response of monocytes and monocyte-derived dendritic cells (mo-DCs) to the AHR agonist, benzo(a)pyrene (BaP) was compared in vitro. Results AHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia. Expression was not influenced by smoking in either tissue. Evidence of AHR activation, indicated by CYP1A1 and AHRR gene expression, was found only in synovia from patients who smoked. However, IL17A gene expression was lower in synovia from smokers. TBX21 and FOXP3 expression was not affected by smoking. Within the synovial tissues of smokers the principal cell type with evidence of AHR activation was a subset of synovial DCs. This observation was consistent with the sensitivity of human mo-DCs to BaP stimulation demonstrated in vitro. Exposure to BaP affected mo-DC function as demonstrated by decreased IL6 expression induced by PolyI:C, without affecting indoleamine 2,3 dioxygenase (IDO)1 expression. Conclusion Our findings show that one effect of smoking on inflamed rheumatoid synovial tissue involves activation of the AHR pathway. A subset of synovial DCs is important in the response to cigarette smoke. The potential for smoking to affect DC behaviour in joint tissues has relevance to both early and late phases of RA pathogenesis and warrants further investigation.

2012-01-01

385

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

PubMed Central

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

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

1993-01-01

386

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

Microsoft Academic Search

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

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

2004-01-01

387

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

National Technical Information Service (NTIS)

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 anal...

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

1995-01-01

388

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

PubMed Central

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 population. Citation: Irwin MR; Olmstead R; Carrillo C; Sadeghi N; FitzGerald JD; Ranganath VK; Nicassio PM. Sleep loss exacerbates fatigue, depression, and pain in rheumatoid arthritis. SLEEP 2012;35(4):537-543.

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

2012-01-01

389

Radiographic Severity of Rheumatoid Arthritis in African-Americans: Results from the CLEAR Registry  

PubMed Central

Objective To describe radiographic changes in African-Americans with rheumatoid arthritis (RA) from the CLEAR (Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis) Registry, a multicenter observational study. Methods Self-declared African-American patients, were enrolled in CLEAR I, a longitudinal cohort of early RA (disease duration <2 years) from 2000 to 2005; or in CLEAR II, a cross-sectional cohort (any disease duration), from 2006 to the present. Demographic and clinical data were obtained, and sets of hand/wrist and foot radiographs were scored using the modified Sharp/van der Heijde scoring system. Results A total of 357 and 418 patients, respectively, have been enrolled into CLEAR I and CLEAR II. We report here an interim analysis of radiographic severity in these patients. For the CLEAR I cohort, 294 patients had a mean radiographic score of 2.89 at the baseline visit; 32.0% showed either erosions (25.9%) or joint space narrowing (JSN) (19.4%). At the 36-month visit the mean score was 5.65; 44.2% had erosions, 41.5% JSN and 55.4% had either. Among those patients without radiographic damage at baseline, 18.9% had progressed at the 36-month visit, compared to 57.1% of those with baseline damage (p<0.0001). For the CLEAR II cohort, 167 patients with RA of any duration, 65.3% exhibited joint erosions, 65.3% JSN and 74.8% exhibited either. The mean radiographic score was 33.42. Conclusion This is the largest radiographic study of African American RA patients. Damage occurs early in the disease and is associated with radiographic progression at 3 years of disease duration. The CLEAR Registry will provide a valuable resource for future analyses of genetic, clinical, and environmental factors associated with radiographic severity of RA in African-Americans.

Bridges, S. Louis; Causey, Zenoria L.; Burgos, Paula I.; Huynh, B. Quynh N.; Hughes, Laura B.; Danila, Maria I.; van Everdingen, Amalia; Ledbetter, Stephanie; Conn, Doyt L.; Tamhane, Ashutosh; Westfall, Andrew O.; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard; Moreland, Larry W.; Alarcon, Graciela S.; van der Heijde, Desiree M.

2010-01-01

390

Prevalence of hepatitis B infection in rheumatoid arthritis patients.  

PubMed

Rheumatoid arthritis is a progressive and destructive inflammatory disease of the joints. They had increased mortality depend to use of immunosuppressive drugs. Hepatitis B virus infection is also a health problem in the world. Iran is moderate prevalence endemic area for Hepatitis B virus and it is come too reduced recently by children vaccination. Aim of this study is determined prevalence and screening of Hepatitis B virus infection in rheumatoid arthritis patients. This study is a descriptive cross-sectional which all patients with rheumatic arthritis recruited to study in Tehran in 2012. Then HbsAg and HbcAb assayed for each subjects. In 268 rheumatoid arthritis patients which (82.2%) were female and the average age is 46 +/- 14 years old. HbsAg and HbcAb were positive in 4 (1.49%) and 9 (3.35%), respectively. Only between duration of rheumatoid arthritis and HbcAb had significant association (p < 0.014). The present study highlights Rheumatoid arthritis patients treated with immunosuppressive drugs are at increased risk to reactivation of hepatitis B virus, so screening for Hepatitis B virus infection should be performed prior to immunosuppressive therapy. PMID:24506005

Alishiri, Gholam Hossein; Ghorbani, Gholam Ali; Ahmad, Salimzadeh

2013-08-01

391

In vitro synthesis of immunoglobulin by rheumatoid synovial membrane  

PubMed Central

A technique for the in vitro culture of rheumatoid synovial tissue with 14C-amino acids and isolation and quantitation of the newly synthesized immunoglobulins has been developed. This technique has been used to compare immunoglobulin synthesis of 12 rheumatoid synovia with that of synovia from nonarthritic patients and with that of normal human lymph nodes and spleen. In addition, the spleen of a patient with Felty's syndrome has also been examined. Immunoglobulin synthesis in rheumatoid synovia has been shown to be quantitatively and qualitatively similar to that of normal human spleen and lymph nodes although somewhat less active than the Felty's syndrome spleen examined. 79% of the immunoglobulin produced in rheumatoid synovia was of the IgG type, whereas IgM comprised 10% and IgA, 11% of the total. Less than 10% of the IgM synthesized was found to be rheumatoid factor. A fraction containing approximately 90% of its radioactivity in the form of IgG has been obtained for further studies.

Smiley, J. Donald; Sachs, Charlotte; Ziff, Morris

1968-01-01

392

Rheumatoid arthritis and bronchiectasis. A retrospective study of fourteen cases.  

PubMed

Since 1928, 288 cases of rheumatoid arthritis and bronchiectasis have been reported in the medical literature. The interactions between these two conditions and the etiopathogenic mechanisms they involve remain unclear. During a retrospective study of 100 rheumatoid arthritis patients and 80 bronchiectasis patients, we identified 14 additional patients with both conditions. There were 10 females and four males (ratio 2.5/1). Bronchiectasis was confirmed either by computed tomography of the chest or by bronchography. The respiratory manifestations antedated the joint disease in 12 patients, by a mean interval of 28.5 years. An infectious cause was identified in six cases. Neither the age at onset nor the duration of rheumatoid arthritis were influenced by the presence of bronchiectasis. Seven patients had 15 extraarticular manifestations suggesting potentially severe joint disease. The flares of joint and respiratory symptoms were concomitant in six patients. In six patients, the respiratory manifestations worsened after onset of the joint disease. Tests for rheumatoid factors were positive in 73% of cases. Panhypogammaglobulinemia was found in one case. Ten patients underwent lung function tests, which showed evidence of nonspecific obstructive disease. Overall, our findings are consistent with previous reports in the literature. In patients with predisposing immunogenetic factors, bronchiectasis may be involved in the genesis of rheumatoid arthritis. PMID:9010967

Despaux, J; Polio, J C; Toussirot, E; Dalphin, J C; Wendling, D

1996-12-01

393

Distinctive radiological features of small hand joints in rheumatoid arthritis and seronegative spondyloarthritis demonstrated by contrast-enhanced (Gd-DTPA) magnetic resonance imaging  

Microsoft Academic Search

A series of patients with clinically early inflammatory joint disease due to rheumatoid arthritis, psoriatic arthritis and Reiter's syndrome were examined by plain film radiography and magnetic resonance imaging (MRI). The spin echo T1-weighted precontrast, T2-weighted, and, especially, T1-weighted postcontrast images demonstrated distinct differences in the distribution of inflamatory changes, both within and adjacent to involved small hand joints. Two

Vladimir Jevtic; Iain Watt; Blaz Rozman; Mojca Kos-Golja; Franci Demsar; Orest Jarh

1995-01-01

394

Comparison of the second and third generation anti-cyclic citrullinated peptide antibody assays in the diagnosis of Japanese patients with rheumatoid arthritis  

Microsoft Academic Search

The anti-cyclic citrullinated peptide (CCP) antibody has become increasingly important in the diagnosis of rheumatoid arthritis\\u000a (RA), especially for early diagnosis. The purpose of this study is to compare the diagnostic usefulness of the second and\\u000a third generation anti-CCP antibody kits among Japanese patients with RA. Anti-CCP antibody titers were measured with the second\\u000a generation (MESACUP CCP test, Medical and

Kumi ShidaraEisuke; Eisuke Inoue; Eiichi Tanaka; Daisuke Hoshi; Yohei Seto; Ayako Nakajima; Shigeki Momohara; Atsuo Taniguchi; Hisashi Yamanaka

2011-01-01

395

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

Microsoft Academic Search

Jet- and vortex-regime evolution of contrails behind cruising aircraft is investigated by focusing on the role of aircraft type. Cross-section measurements by ground-based lidar and observational analysis are combined with numerical simulations of fluid dynamics and microphysics in the wake of a two-engine aircraft. Depending on ambient humidity levels, contrail evolution behind short-\\/medium-range twin-turbofan airliners is classified into two scenarios,

Ralf Sussmann; Klaus M. Gierens

2001-01-01

396

When and where does rheumatoid arthritis begin?  

PubMed

The major strides accomplished in elucidating the pathophysiology of rheumatoid arthritis (RA) have translated into therapeutic breakthroughs in clinical practice. However, currently available treatments work only for as long as they are taken. The development of curative treatments will probably require a better understanding of the earliest phases of RA and perhaps the identification of the etiological factors, which are probably numerous. These objectives are being pursued in studies of preclinical RA. The literature review presented herein indicates that the immunological conflict probably originates outside the joints, at mucous membrane sites and, more specifically, in the upper aerodigestive tract. The preclinical phase of RA can last for many years, and some patients probably never progress to arthritis. An immunological conflict develops then spins out of control, causing increases in autoantibody titers and subsequently in levels of serum markers for inflammation, before the development of the first joint symptoms. Improved knowledge of the preclinical phase, together with information from genetic markers, will allow the identification of profiles associated with susceptibility to RA and perhaps, in the future, the development of preventive strategies. PMID:23177913

Schaeverbeke, Thierry; Truchetet, Marie-Élise; Richez, Christophe

2012-12-01

397

Rheumatoid factor, complement, and mixed cryoglobulinemia.  

PubMed

Low serum level of complement component 4 (C4) that occurs in mixed cryoglobulinemia (MC) may be due to in vivo or ex vivo activation of complement by the classical pathway. Potential activators include monoclonal IgM rheumatoid factor (RF), IgG antibodies, and the complexing of the two in the cold, perhaps modulated by the rheology and stoichiometry of cryocomplexes in specific microcirculations. There is also the potential for activation of complement by the alternative and lectin pathways, particularly in the setting of chronic infection and immune stimulation caused by hepatitis C virus (HCV). Engagement of C1q and interaction with specific cell surface receptors serve to localize immune complexes (ICs) to the sites of pathology, notably the cutaneous and glomerular microcirculations. Defective or saturated clearance of ICs by CR1and/or Fc receptors may explain persistence in the circulation. The phlogistic potential of cryoprecipitable ICs depends upon the cleavage of complement components to generate fragments with anaphylatoxin or leukocyte mobilizing activity, and the assembly of the membrane attack complex (C5b-9) on cell surfaces. A research agenda would include further characterization of the effector arm of complement activation in MC, and elucidation of activation mechanisms due to virus and viral antigens in HCV infection. PMID:22956968

Gorevic, Peter D

2012-01-01

398

Tofacitinib Prevents Radiographic Progression in Rheumatoid Arthritis  

PubMed Central

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

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

2013-01-01

399

Clinically relevant advances in rheumatoid arthritis therapy  

PubMed Central

Owing to the success of biologics in the treatment of rheumatoid arthritis (RA), several novel drugs have been introduced in the therapeutic armamentarium, although not all of them have been approved in all countries worldwide. Among the drugs are tumour necrosis factor (TNF) inhibitors such as certolizumab pegol and golimumab (the latter of which was the first TNF blocker shown to be effective in patients who had been unsuccessfully treated with other TNF blockers and which can be applied only once a month), and the interleukin-6 receptor antagonist tocilizumab, which not only opens up a completely new field of anti-inflammatory modulation of RA pathophysiology, but also highlights the challenge of novel potential side effects. Moreover, aside from clinical studies showing efficacy in the inhibition of osteoclast activation by the anti-RANKL (receptor activator of nuclear factor-kappa B ligand) antibody denosumab, an improved form of steroid application known as slow-release ‘tempus tablet’ for treatment of RA and several developments in the small-molecule area have been addressed by clinical trials.

Neumann, Elena; Tarner, Ingo H

2009-01-01

400

Bone remodelling markers in rheumatoid arthritis.  

PubMed

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

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

2014-01-01

401

Bone Remodelling Markers in Rheumatoid Arthritis  

PubMed Central

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

Fardellone, Patrice; Sejourne, Alice; Paccou, Julien; Goeb, Vincent

2014-01-01

402

A Systems Approach to Rheumatoid Arthritis  

PubMed Central

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily attacks synovial joints. Despite the advances in diagnosis and treatment of RA, novel molecular targets are still needed to improve the accuracy of diagnosis and the therapeutic outcomes. Here, we present a systems approach that can effectively 1) identify core RA-associated genes (RAGs), 2) reconstruct RA-perturbed networks, and 3) select potential targets for diagnosis and treatments of RA. By integrating multiple gene expression datasets previously reported, we first identified 983 core RAGs that show RA dominant differential expression, compared to osteoarthritis (OA), in the multiple datasets. Using the core RAGs, we then reconstructed RA-perturbed networks that delineate key RA associated cellular processes and transcriptional regulation. The networks revealed that synovial fibroblasts play major roles in defining RA-perturbed processes, anti-TNF-? therapy restored many RA-perturbed processes, and 19 transcription factors (TFs) have major contribution to deregulation of the core RAGs in the RA-perturbed networks. Finally, we selected a list of potential molecular targets that can act as metrics or modulators of the RA-perturbed networks. Therefore, these network models identify a panel of potential targets that will serve as an important resource for the discovery of therapeutic targets and diagnostic markers, as well as providing novel insights into RA pathogenesis.

You, Sungyong; Cho, Chul-Soo; Lee, Inyoul; Hood, Leroy; Hwang, Daehee; Kim, Wan-Uk

2012-01-01

403

Rheumatoid arthritis, spondyloarthropathies, and relapsing polychondritis.  

PubMed

The neurologic complications of rheumatic disease are highly variable and their manifestations are linked to the pathogenesis and clinical phenotype of the specific rheumatologic syndrome. In active rheumatoid arthritis (RA), the peripheral nervous system is most commonly involved and mononeuritis multiplex, nerve entrapment and vascultitic sensorimotor neuropathy are not uncommon. Central nervous system complications such as pachymeningitis and cerebral vasculitis are rare. TNF blockade therapy of RA is rarely associated with demyelinating syndromes. In the spondyloarthropathies, especially ankylosing spondylitis (AS), neurologic complications are more frequent in long-standing, advanced disease and include atlantoaxial subluxation, cauda equina syndrome, spinal stenosis, and acute vertebral fractures. Peripheral nervous system involvement in any of the spondyloarthropaties is rare. Relapsing polychondritis (RP) is characterized by recurring bouts of inflammation, destruction of cartilaginous structures, and systemic and rarely central nervous system vasculitis. Visual-oculo and auditory complications are common. Definitive treatment of the neurologic complications and prevention of subsequent ones is dependent upon effective treatment of RA, AS or RP. PMID:24365312

Ostrowski, Rochella A; Takagishi, Troy; Robinson, John

2014-01-01

404

Mesenchymal stem cells, autoimmunity and rheumatoid arthritis  

PubMed Central

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.

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

2014-01-01

405

Genetics and epigenetics of rheumatoid arthritis  

PubMed Central

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

Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

2013-01-01

406

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

PubMed

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

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

407

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)

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

Gsponer, Jörg; Haberthür, Urs; Caflisch, Amedeo

2003-04-01

408

Rheumatoid arthritis associated with myelodysplastic syndrome: a case report.  

PubMed

Myelodysplastic syndromes (MDS) are a group of refractory anemias resulting from a clonal stem cell disorder often associated with cytogenetic abnormalities. There is increasing recognition of immunological abnormalities in patients with MDS, including defective B- and T-cell function, hyper- or hypogammaglobulinemia and monoclonal gammopathy. MDS have been associated with Sjögren's syndrome, polymyalgia rheumatica, relapsing polychondritis and systemic lupus erythematosus. Although there may be various rheumatologic features, including acute arthritis in MDS, chronic inflammatory arthritis is uncommonly combined. There have been a few reports that described cases of rheumatoid arthritis (RA) concurrent with MDS, but advanced rheumatoid arthritis with typical joint deformities has rarely been reported. We report a case of rheumatoid arthritis with atlantoaxial subluxation combined with refractory anemia in a 31-year-old woman. PMID:10402176

Nam, E J; Kang, Y M; Kang, H R; Kim, J H; Rho, H J; Lee, M K; Hyun, S H; Kim, G W; Lee, J M; Kim, N S

1999-06-01

409

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)

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

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

2013-04-01

410

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

PubMed Central

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

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

2009-01-01

411

Spontaneous Bilateral Olecranon Fractures in a Rheumatoid Patient  

PubMed Central

A case is described of a patient sustaining bilateral spontaneous olecranon fractures while undergoing rehabilitation following surgery for a hip fracture. The patient's underlying rheumatoid arthritis disease process most likely caused erosions and subchondral cysts formation in the mid-trochlear notch region. This area, in turn, acts as a pivot point in elbow extension/flexion movements. During rehabilitation, the patient became dependent on her upper limbs for mobilisation. This led to significant forces being put through this already weakened region, causing spontaneous bilateral olecranon fractures. Rheumatoid patients after lower limb surgery should be careful during rehabilitation, and avoid undue strains through their upper limbs.

Kirmani, Sayyied; Draviaraj, Kingsley; Madegowda, Babu; Shahane, Shantanu

2008-01-01

412

Genetic epidemiology: Approaches to the genetic analysis of rheumatoid arthritis  

PubMed Central

The basis of susceptibility to rheumatoid arthritis (RA) is complex, comprising genetic and environmental susceptibility factors. We have reviewed the available approaches to the investigation of the genetic basis of complex diseases and how these are being applied to RA. Affected-sibling-pair methods for nonparametric linkage analysis, linkage-disequilibrium-based approaches, transmission disequilibrium testing, and disease-association studies are discussed. The pros, cons, and limitations of the approaches are considered and are illustrated by examples from the literature about rheumatoid arthritis.

John, Sally; Worthington, Jane

2001-01-01

413

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts  

SciTech Connect

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.

Kitahara, Kanako [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan); Department of Immunology, Toho University School of Medicine, Tokyo (Japan); Kusunoki, Natsuko [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan); Kakiuchi, Terutaka [Department of Immunology, Toho University School of Medicine, Tokyo (Japan); Suguro, Toru [Department of Orthopaedic Surgery, Toho University School of Medicine, Tokyo (Japan); Kawai, Shinichi [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan)], E-mail: skawai@med.toho-u.ac.jp

2009-01-09

414

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

NASA Technical Reports Server (NTRS)

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.

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

1999-01-01