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Permanent Rheumatology Job in Muskogee, OK Oklahoma with Enterprise Medical Services
Multi-specialty group in Muskogee, Oklahoma looking to add a BC/BE Rheumatologist-Job #16518 due to growth and retirement. This clinic offers the highest quality medical care to the citizens of their
Permanent Rheumatology Job in Northern California with Carson Kolb Healthcare Group
Northern California Instant Referral Base One hour to the Bay Area 100% Rheumatology Opportunity No Primary Care required Instant Referral Base - GIs, IMs and Surgeons in your group Stability of a
Permanent Rheumatology Job in 45 minutes from Raleigh North Carolina with Enterprise Medical Services
Seeking BC/BE Rheumatologist to join one other in practice. There will be no medical call. Every other month call for Rheumatology. Competitive 1st year income guarantee. Production base from two

Annals of the Rheumatic Diseases current issue

[Editorials] Standardisation in clinical laboratory medicine: an ethical reflection
Bossuyt, X., Louche, C., Wiik, A. Fri, 11 Jul 2008 00:00:00 -0000

[Hypothesis] A biography of the chondrocyte
Simkin, P A Fri, 11 Jul 2008 00:00:00 -0000
Significant gaps persist in our understanding of chondrocyte biology. We do not know when, how, or even whether these cells are replenished throughout the normal, human life span. We are taught that as much as 90% of the cartilage is "metabolically inert" interterritorial matrix, but we do not know how this substance is regularly replaced (as it is known to be) by the distant chondrocytes, We recognise that the "tidemark" is the most conspicuous histological feature within cartilage, but we do not understand why that layer stains with haematoxylin or what that may imply for the biology of the tissue. These, and other issues may be clarified if the lifetime of each chondrocyte begins as a mesenchymal stem cell at the articular margin, plays out over years on an arcing trajectory along collagenous guidelines, and ends as an extracellular deposit of intracellular remains at the interface between uncalcified and calcified cartilage. This hypothesis is presented here, and some of its potential implications are considered.
[Extended reports] Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus
Nikpour, M, Dempsey, A A, Urowitz, M B, Gladman, D D, Barnes, D A Fri, 11 Jul 2008 00:00:00 -0000
Objective: To determine whether peripheral blood gene expression of patients with systemic lupus erythaematosus (SLE) correlates with disease activity measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). Methods: RNA was isolated from peripheral blood of 269 patients with SLE and profiled on a custom microarray. Hierarchical clustering and a heat map were used to categorise samples into major clusters based on gene expression pattern. Correlates, including demographic and disease-related characteristics such as SLEDAI-2K score, of the major sample clusters were compared using multivariate regression models. Results: A set of 31 interferon (IFN)-regulated genes were seen to be driving the separations of samples into two clusters, one characterised by a relatively high IFN-regulated gene signature (n = 150) and the other by a relatively low IFN-regulated gene signature (n = 119). Disease activity measured using the SLEDAI-2K was significantly correlated with the high IFN gene signature. In multivariate regression analysis the immunological component of the SLEDAI-2K was a significant correlate of the high IFN gene signature as was presence of antibodies to U1RNP. There were no discernable correlates of the 156 non-IFN regulated genes profiled on the custom array. Conclusion: Peripheral blood gene expression profiling (GEP) in SLE allows patients to be categorised into two groups based on a high or low IFN gene signature. Disease activity measured using the SLEDAI-2K is correlated with the high IFN gene signature, indicating that GEP may be a useful biomarker of disease activity in SLE.
[Extended reports] CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
Mamtani, M, Rovin, B, Brey, R, Camargo, J F, Kulkarni, H, Herrera, M, Correa, P, Holliday, S, Anaya, J-M, Ahuja, S K Fri, 11 Jul 2008 00:00:00 -0000
Objectives: There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1-gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE. Methods: We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5. Results: Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual’s CCL3L1–CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential recruitment of leukocytes in subjects with lupus nephritis. The CCR5 HHE/HHG*2 genotype was associated with the maximal risk of developing SLE. Conclusion: CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1–CCR5 axis in the pathogenesis of SLE.
[Extended reports] Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial
Genant, H K, Peterfy, C G, Westhovens, R, Becker, J-C, Aranda, R, Vratsanos, G, Teng, J, Kremer, J M Fri, 11 Jul 2008 00:00:00 -0000
Objective: Assess the effect of abatacept on progression of structural damage over 2 years in patients with rheumatoid arthritis who had an inadequate response to methotrexate. Methods: 539 patients entered an open-label extension of the AIM (Abatacept in Inadequate responders to Methotrexate) trial and received abatacept. Radiographic assessment of the hands and feet was performed at baseline, year 1 and year 2. At year 2, each patient’s radiographs were scored for progression blinded to sequence and treatment allocation. Results: In patients treated with abatacept for 2 years, greater reduction in progression of structural damage was observed in year 2 than in year 1. The mean change in total Genant-modified Sharp scores was reduced from 1.07 units in year 1 to 0.46 units in year 2. Similar reductions were observed in erosion and joint space narrowing scores. Following 2 years of treatment with abatacept, 50% of patients had no progression of structural damage as defined by a change in the total score of <=0 compared with baseline. 56% of patients treated with abatacept had no progression during the first year compared with 45% of patients treated with placebo. In their second year of treatment with abatacept, more patients had no progression than in the first year (66% vs 56%). Conclusions: Abatacept has a sustained effect that inhibits progression of structural damage. Furthermore, the mean change in radiographic progression in patients treated with abatacept for 2 years was significantly lower in year 2 versus year 1, suggesting that abatacept may have an increasing disease-modifying effect on structural damage over time.
[Extended reports] Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study
Bruyn, G A W, Tate, G, Caeiro, F, Maldonado-Cocco, J, Westhovens, R, Tannenbaum, H, Bell, M, Forre, O, Bjorneboe, O, Tak, P P, Abeywickrama, K H, Bernhardt, P, van Riel, P L C, for the RADD study group Fri, 11 Jul 2008 00:00:00 -0000
Objectives: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. Methods: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. Results: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient’s assessment of pain, and patient’s and physician’s global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. Conclusions: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.

Arthritis Care & Research

A randomized, double-blind, multicenter, controlled clinical trial of chicken type II collagen in patients with rheumatoid arthritis
Ling-Ling Zhang, Wei Wei, Feng Xiao, Jian-Hua Xu, Chun-De Bao, Li-Qing Ni, Xing-Fu Li Tue, 24 Jun 2008 08:47:00 -0000
To assess the efficacy and safety of chicken type II collagen (CCII) in rheumatoid arthritis (RA) compared with methotrexate (MTX).We conducted a prospective, 24-week, followup, multicenter, double-blind, controlled study of CCII (0.1 mg/day) versus MTX (10 mg/week) in patients with active RA. Clinical assessments were performed at screening and at 12, 18, and 24 weeks of treatment.A total of 236 RA patients were included; 211 patients (89.4%) completed the 24-week followup. In both groups there was a decrease in pain, morning stiffness, tender joint count, swollen joint count, Health Assessment Questionnaire score, and investigator and patient assessment of function; all differences were statistically significant. In the MTX group, erythrocyte sedimentation rate and C-reactive protein level decreased. Rheumatoid factor did not change in either group. At 24 weeks, 68.57% of patients in the CCII group and 83.02% in the MTX group met the American College of Rheumatology 20% improvement criteria (ACR20), and 40.95% and 57.54%, respectively, met the ACR50 criteria. The ACR20 and ACR50 response rates in the CCII group were lower than those in the MTX group, and this difference was statistically significant (P < 0.05). Gastrointestinal symptoms were common in both groups. There were fewer and milder side effects in the CCII group than the MTX group. The difference in incidence of adverse events between the 2 groups was statistically significant (P < 0.05).CCII is effective in the treatment of RA. CCII is well tolerated, and the incidence of adverse events of CCII is lower than that of MTX.
Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis in response to disease-modifying antirheumatic drug treatment and correlation with radiologic outcome
David Haynes, Tania Crotti, Helen Weedon, John Slavotinek, Virginia Au, Mark Coleman, Peter J. Roberts-Thomson, Michael Ahern, Malcolm D. Smith Tue, 24 Jun 2008 08:47:00 -0000
To demonstrate the effect of treatment with disease-modifying agents on the expression of osteoprotegerin (OPG) and RANKL in the synovial tissue from rheumatoid arthritis (RA) patients and to correlate these changes with radiologic damage measured on sequential radiographs of the hands and feet.Synovial biopsy specimens were obtained at arthroscopy from 25 patients with active RA (16 of whom had a disease duration 20% after disease-modifying antirheumatic drug (DMARD) treatment. Successful DMARD treatment resulted in an increase in OPG expression and a decrease in RANKL expression at the synovial tissue level, which correlated with a reduction in erosion scores measured on annual radiographs of the hands and feet.Successful treatment-induced modulation of OPG and RANKL expression at the synovial tissue level, resulting in a reduction in the RANKL:OPG ratio, is likely to have a significant impact on osteoclast formation and joint damage in patients with active RA.
Rheumatoid arthritis patients' perceptions of mutuality in conversations with spouses/partners and their links with psychological and physical health
Shelley Kasle, Mari S. Wilhelm, Alex J. Zautra Tue, 24 Jun 2008 08:47:00 -0000
Mutuality, measured as subjects' perceptions of responsiveness in conversations with their spouse/partners, is linked with women's psychological health. Our objectives were to examine physical and psychological health outcomes of married/partnered patients with rheumatoid arthritis (RA) in relation to their perceptions of their own responsiveness (self-mutuality), their partner's responsiveness (partner-mutuality), and combined responsiveness (overall mutuality), and to examine potential sex differences in the links between mutuality and depressive symptoms.Symptoms of depression and anxiety, physical disability, and arthritis impact reported by RA patients were examined in correlation matrices with their perceptions of overall mutuality, partner-mutuality, and self-mutuality in conversations with spouses/partners in the whole sample (n = 148) and separately for men (n = 34) and women (n = 114). Sex moderation of the links between mutuality and depression was tested in hierarchical regressions.In the whole sample and among women, all mutuality measures had significant inverse correlations with all health outcomes. In men, physical disability was unrelated to mutuality measures, but otherwise correlations approximated those in the whole sample and for women. Sex (being female) interacted with self-mutuality, but not overall or partner-mutuality, in predicting fewer depressive symptoms.RA patients' perceptions of mutuality in conversations with spouses/partners predicted better health across a spectrum of outcomes. Overall mutuality and partner-mutuality predicted fewer depressive symptoms for both men and women, but self-mutuality appeared more important for women than for men. The clinical relevance of findings and their implications for behavioral interventions with RA patients are discussed.

Arthritis & Rheumatism

In this Issue
Tue, 24 Jun 2008 08:56:00 -0000
No abstract.
Is CCR2 the right chemokine receptor to target in rheumatoid arthritis?
Amanda E. I. Proudfoot Tue, 24 Jun 2008 08:56:00 -0000
No abstract.
Glomerular targets of nephritogenic autoantibodies in systemic lupus erythematosus
Casandra C. van Bavel, Kristin A. Fenton, Ole P. Rekvig, Johan van der Vlag, Jo H. Berden Tue, 24 Jun 2008 08:56:00 -0000
No abstract.

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