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Permanent Rheumatology Job in Northeast Georgia Georgia with Enterprise Medical Services
Well established multi-specialty group 40 minutes NE of Atlanta, GA in need of 3rd 100% Rheumatologist due to patient demand. Call 1:3 with very dynamic and female Rheumatologist in group. Financial
Permanent Rheumatology Job in Academics, $50,000 Signing Bonus, No State Income Tax, Top-Ranked Golf Course, #3362 Texas with Timeline Recruiting
Your chance to make a real difference! Take a new look at Rheumatology. Enjoy all the security and benefits of a faculty appointment with one of the most esteemed universities in the Southwestalong
Permanent Rheumatology Job in Denver Colorado with Horton Smith Associates
POSITION Our client seeks a BE/BC Rheumatologist to serve a fast growing medical community in the south Denver suburbs . There is a huge unmet demand for this service, since there is currently

Arthritis Research & Therapy - Latest articles

What do biomarkers tell us about the pathogenesis of ankylosing spondylitis?
Walter P Maksymowych Wed, 07 Jan 2009 00:00:00 -0000
Biomarkers may provide information that promotes understanding of prognosis, disease activity, and pathogenesis in ankylosing spondylitis. Biomarkers reflecting disease activity (metalloproteinase-3) and inflammatory lesions on magnetic resonance imaging (MRI) predict new bone formation and are ameliorated by anti-tumor necrosis factor (TNF) therapy yet this treatment may not prevent new bone formation. Moreover, elevated levels of biomarkers reflecting tissue repair (bone-specific alkaline phosphatase) post-treatment together with MRI indicates such treatment may even promote repair through new bone formation. TNF regulation of Dickkopf-1 may constitute a molecular brake that controls osteoblastogenesis through wingless and bone morphogenetic proteins in an established inflammatory lesion in AS.
MRI bone oedema scores are higher in the arthritis mutilans form of psoriatic arthritis and correlate with high radiographic scores for joint damage
Yu M Tan, Mikkel Ostergaard, Anthony Doyle, Nicola Dalbeth, Maria Lobo, Quentin Reeves, Elizabeth Robinson, William J Taylor, Peter B Jones, Karen Pui, Jamie Lee and Fiona M McQueen Tue, 06 Jan 2009 00:00:00 -0000
IntroductionThe aim of this study was to investigate the magnetic resonance imaging (MRI) features of bone disease in the arthritis mutilans (AM) form of psoriatic arthritis (PsA) Methods: 28 patients with erosive psoriatic arthritis were enrolled (median disease duration 14 years). Using x-rays (hands and feet), 11 patients were classified as arthritis mutilans and 17 as non-arthritis mutilans by 2 observers. Magnetic resonance imaging scans (1.5T) of the dominant hand (wrist and fingers scanned separately) were obtained using standard contrast-enhanced T1 weighted and fat saturated T2 weighted sequences. Scans were scored separately by 2 readers for bone erosion, oedema and proliferation using a psoriatic arthritis magnetic resonance imaging scoring system. X-rays were scored for erosions and joint space narrowing. Results: 1013 bones were scored on MRI by both readers. Reliability for scoring erosions and bone oedema was high: intraclass correlation coefficients = 0.80 and 0.77 respectively, but only fair for bone proliferation (intraclass correlation coefficient = 0.42). MRI erosion scores were higher in arthritis mutilans patients (53.0 vs 15.0, p = 0.004) as were bone oedema and proliferation scores (14.7 vs 10.0, p = 0.056 and 3.6 vs 0.7, p = 0.003 respectively). MRI bone oedema scores correlated with MRI erosion scores and X-ray erosion and joint space narrowing scores (r= 0.65, p=0.0002 for all) but not DAS28CRP or pain scores. Conclusions: In this psoriatic arthritis patient group, MRI bone oedema, erosion and proliferation were all more severe in the arthritis mutilans-form. Bone oedema scores did not correlate with disease activity measures but were closely associated with X-ray joint damage scores. These results suggest that MRI bone oedema may be a pre-erosive feature and that bone damage may not be coupled with joint inflammation in psoriatic arthritis.
Interactions among type I and II interferon, tumor necrosis factor, and beta-estradiol in the regulation of immune response-related gene expressions in systemic lupus erythematosus
Hooi-Ming Lee, Toru Mima, Hidehiko Sugino, Chieko Aoki, Yasuo Adachi, Naoko Yoshio-Hoshino, Kenichi Matsubara and Norihiro Nishimoto Sat, 03 Jan 2009 00:00:00 -0000
IntroductionSystemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by various clinical manifestations. Several cytokines interact and play pathological roles in SLE, although the etiopathology is still obscure. Here, we investigated the network of immune response-related molecules expressed in the peripheral blood of SLE patients and the effects of cytokine interactions on the regulation of these molecules. Methods: Gene expression profiles of the peripheral blood from SLE patients and healthy women were analyzed using DNA microarray. Differentially expressed genes categorized into "Immune Response" were selected and analyzed using bioinformatics tools. Since interactions among tumor necrosis factor (TNF), interferon (IFN)-gamma, beta-estradiol (E2), and IFN-alpha may regulate the expression of interferon-inducible (IFI) genes, stimulating and co-stimulating experiments were carried out on peripheral blood mononuclear cells (PBMCs) followed by analysis using quantitative reverse transcription-polymerase chain reaction. Results: Thirty-eight down and sixty-eight up-regulated genes were identified in the functional category "Immune Response". Overexpressed IFI genes were confirmed in SLE patient peripheral bloods. Using network-based analysis on these genes, several networks including cytokines, such as TNF and IFN-gamma, and E2 were constructed. TNF-regulated genes were dominant in these networks, but in vitro TNF stimulation on PBMCs showed no differences in the above gene expressions between SLE and healthy individuals. Co-stimulating with IFN-alpha and one of TNF, IFN-gamma, or E2 revealed that TNF has repressive while IFN-gamma essentially has synergistic effects on IFI gene expressions in vitro. E2 showed variable effects on IFI gene expressions among three individuals. Conclusions: TNF may repress the abnormal regulation by IFN-alpha in SLE while IFN-gamma may have synergistic effect. Interactions between IFN-alpha and one of TNF, IFN-gamma, or E2 appear to be involved in the pathogenesis of SLE.
Monocytes are essential for inhibition of synovial T cell glucocorticoid mediated apoptosis in rheumatoid arthritis
Dimitrios Makrygiannakis, Shankar Revu, Petra Neregard, Erik af Klint, Omri Snir, Cecilia Grundtman and Anca Irinel Catrina Fri, 19 Dec 2008 00:00:00 -0000
IntroductionRheumatoid arthritis (RA) is characterized by synovial inflammation with local accumulation of mononuclear cells such as macrophages and lymphocytes. We previously demonstrated that intraarticular glucocorticoids decrease the synovial tissue (ST) T cell population, and therefore aimed to investigate if this is mediated through modulation of apoptosis. Methods: Apoptosis and cell phenotype were evaluated by immunohistochemistry and dual immunofluorescence in synovial biopsy sections from 12 RA patients before and after a mean of 11 days of an intraarticular triamcinolone knee injection. In vitro, RA synovial fluid (SF) derived T cells were evaluated for Annexin V expression by multi-color flow cytometry after 24 hours exposure to dexamethasone, methylprednisolone or triamcinolone. We also tested induction of apoptosis by dexamethasone on psoriatic arthritis SF derived T cells using the same method. Results: Intraarticular glucocorticoids reduced ST T cells but not macrophage number. ST apoptosis levels were unchanged following treatment, virtually absent from lymphoid aggregates and minimal in CD3+ cells both before and after treatment. RA SF T cells were resistant to glucocorticoid-induced apoptosis when cultured in the presence of monocytes, but rendered sensitive to all three tested compounds upon SF isolation. Furthermore, transwell coculture of monocytes and T cells demonstrated that soluble factor(s) and not cellular contact are essential for T cell resistance to glucocorticoid-mediated apoptosis. This feature is RA specific as far as dexamethasone-induced apoptosis in non-isolated SF T cells obtained from psoriatic arthritis patients. Conclusions: We demonstrate that monocytes rescue synovial T cells from glucocorticoid-induced apoptosis, a feature that is specific for RA. To overcome this we propose the use of monocyte-targeted therapies rather than T cell apoptosis inducing therapies.
Increased expression of lipocalin-type prostaglandin D2 synthase in osteoarthritic cartilage
Nadia Zayed, Xinfang Li, Nadir Chabane, Mohamed Benderdour, Johanne Martel-Pelletier, Jean-Pierre Pelletier, Nicolas Duval and Hassan Fahmi Thu, 18 Dec 2008 00:00:00 -0000
No abstract available
Interferon-induced versus chemokine transcripts as lupus biomarkers
Mary K Crow and Kyriakos A Kirou Thu, 18 Dec 2008 00:00:00 -0000
Compelling support for a central role for interferon-alpha in lupus pathogenesis has led to new focus on the role of innate immune system activation in the generation of pathogenic mediators. These insights have been extended in translational studies of patients with well characterized disease activity and clinical manifestations in order to identify informative molecular biomarkers. Chemokines are among the interferon-inducible genes, and new data support an association between expression of chemokines and both lupus disease activity and organ damage. Longitudinal studies that relate molecular biomarkers to disease activity will be needed to validate these promising data and establish a sensitive measure of change for interventional studies and patient care.

Annals of the Rheumatic Diseases current issue

[Editorials] Just released from the ASAS factory! First steps towards a disease activity score for ankylosing spondylitis
Boers, M. Tue, 16 Dec 2008 00:00:00 -0000

[Reviews] Aspiration of normal or asymptomatic pathological joints for diagnosis and research: indications, technique and success rate
Pascual, E, Doherty, M Tue, 16 Dec 2008 00:00:00 -0000
Although joint aspiration is a basic clinical skill, aspiration of normal joints, or asymptomatic clinically quiescent joints, is only rarely undertaken. There are two main indications for this procedure. Firstly, for definitive diagnosis of crystal-associated arthritis (gout and pseudogout) during the intercritical period and for subsequent monitoring of treatment success of gout; and secondly, to obtain normal synovial fluid for biomarker research. The justification for these indications, the success rate and the technical aspects related to this procedure are presented in this article.
[Recommendation] EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT
Zhang, W, Doherty, M, Leeb, B F, Alekseeva, L, Arden, N K, Bijlsma, J W, Dincer, F, Dziedzic, K, Hauselmann, H J, Kaklamanis, P, Kloppenburg, M, Lohmander, L S, Maheu, E, Martin-Mola, E, Pavelka, K, Punzi, L, Reiter, S, Smolen, J, Verbruggen, G, Watt, I, Zimmermann-Gorska, I Tue, 16 Dec 2008 00:00:00 -0000
Objectives: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. Results: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. Conclusion: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
[Clinical and epidemiological research] Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis
Lukas, C, Landewe, R, Sieper, J, Dougados, M, Davis, J, Braun, J, van der Linden, S, van der Heijde, D, for the Assessment of SpondyloArthritis international Society Tue, 16 Dec 2008 00:00:00 -0000
Objectives: To develop a new index for disease activity in ankylosing spondylitis (ASDAS) that is truthful, discriminative and feasible, and includes domains/items that are considered relevant by patients and doctors. Methods: Eleven candidate variables covering six domains of disease activity, selected by ASAS experts in a Delphi exercise, were tested in a three-step approach, similar to the methodology used for the disease activity score in rheumatoid arthritis. Data on 708 patients included in ISSAS (International Study on Starting tumour necrosis factor blocking agents in Ankylosing Spondylitis) were used. Cross validation was carried out in the OASIS cohort (Outcome in Ankylosing Spondylitis International Study). Results: Principal component analysis disclosed three factors with eigenvalues >0.75: patient assessments, peripheral joint assessments and acute phase reactants. Discriminant function analysis resulted in a correct classification in ~72% of the cases (prior probability ~50%). Regression analysis resulted in an index with five variables (total back pain, patient global assessment, duration of morning stiffness, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)). Three additional candidate indices were designed using similar methodology while omitting either ESR or CRP or patient global assessment. All four scores correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; r = 0.67–0.80), patient (0.58–0.75) and physician’s global assessment (0.41–0.48) of disease activity. All four candidate ASDAS indices performed better than BASDAI or single-item variables in discriminating between high and low disease activity state, according to doctors as well as patients in the OASIS cohort. Conclusion: The first steps in the development of a new assessment tool of disease activity in AS derived four candidate indices with good face and construct validity, and high discriminant capacity.
[Clinical and epidemiological research] Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials
Salliot, C, Dougados, M, Gossec, L Tue, 16 Dec 2008 00:00:00 -0000
Background: Tumour necrosis factor blockers in rheumatoid arthritis are known to increase the risk of serious infections defined as life-threatening, requiring hospitalisation or intravenous antibiotics. Recently, new biological agents have become available. Their safety is an important issue. Purpose: To assess if biological agents, ie rituximab, abatacept and anakinra increase the risk of serious infections in patients with rheumatoid arthritis in published randomised controlled trials. Data source: A systematic review of the literature using PUBMED, EMBASE, Cochrane library and abstracts databases (American College of Rheumatology and European League Against Rheumatism annual meetings) was performed up to October 2007. This search was completed with data from the Food and Drug Administration, the European Agency for the Evaluation of Medicinal Products and manufacturers. Data extraction: Three fixed-effect meta-analyses were performed to compare serious infection rates between each biological agent and placebo. Pooled odds ratios (ORs) were calculated, using the Mantel–Haenszel method with a continuity correction. Data synthesis: Twelve randomised controlled trials with data concerning serious infections were analysed (three for rituximab, five for abatacept and four for anakinra). They included 745 patients, 1960 patients, 2062 patients and 2112 patients treated by rituximab, abatacept, anakinra and placebo respectively. The overall pooled ORs did not reveal a statistically significant increased risk of serious infection for abatacept and rituximab; this risk was increased for high doses of anakinra (>=100 mg daily) versus low dose and placebo (ORs = 9.63 (95% CI, 1.31 to 70.91) and 3.40 (95% CI, 1.11 to 10.46) respectively). Conclusions: These meta-analyses did not reveal a significant increase in the risk of serious infections during rituximab or abatacept treatments in patients with rheumatoid arthritis; however, high doses of anakinra may increase this risk, especially when patients have comorbidity factors. Large studies must be performed to confirm this safety profile in daily practice.
[Clinical and epidemiological research] The effectiveness of leflunomide as a co-therapy of tumour necrosis factor inhibitors in rheumatoid arthritis: a population-based study
Finckh, A, Dehler, S, Gabay, C, on behalf of the SCQM doctors Tue, 16 Dec 2008 00:00:00 -0000
Background: Randomised trials have demonstrated that the efficacy of anti-tumour necrosis factor (TNF) agents is significantly increased by concomitant methotrexate (MTX) in rheumatoid arthritis (RA). In clinical routine, anti-TNF agents are commonly prescribed with other disease-modifying antirheumatic drugs (DMARDs) than MTX, however their effectiveness in combination with anti-TNF agents is not well established. Objective: To compare the effectiveness of leflunomide (LEF) and other conventional DMARDs with MTX as co-therapy to anti-TNF agents in RA. Methods: All patients on anti-TNF agents and conventional DMARDs within the Swiss Clinical Quality Management (SCQM)-RA database were included (n = 1218) and categorised according to the type of co-therapy into anti-TNF+MTX (n = 842), anti-TNF+LEF (n = 260) and anti-TNF+other DMARDs (n = 116). Drug discontinuation rates and incidence of toxic side effects were analysed using Cox proportional hazard models. Progression of radiographic damage, the evolution of functional disability and the improvement of RA disease activity were analysed using longitudinal regression models, adjusting for potential confounders. Results: The overall discontinuation rates of anti-TNF and conventional DMARD combination therapies were relatively high with a median survival of only 16 months (interquartile range (IQR): 10–37), but they did not differ between the three regimens (p = 0.69). The progression of radiographic damage (p = 0.77), functional disability (p = 0.09) and RA disease activity (p = 0.33) were also similar between the different regimen. In addition, no significant difference in the frequency of adverse events emerged. Conclusion: Overall these results suggest that LEF and potentially other conventional DMARDs offer an effective and safe alternative to MTX as co-therapy in combination with anti-TNF agents.

Arthritis Care & Research

Patient-reported outcomes for arthritis: Time to focus on personal life impact measures?
Tessa Sanderson, John Kirwan Tue, 30 Dec 2008 07:17:00 -0000
No abstract.
Patient-reported outcomes in a randomized trial comparing four different treatment strategies in recent-onset rheumatoid arthritis
S. M. van der Kooij, J. K. de Vries-Bouwstra, Y. P. M. Goekoop-Ruiterman, J. A. P. M. Ewals, K. H. Han, J. M. W. Hazes, P. J. S. M. Kerstens, A. J. Peeters, D. van Zeben, F. C. Breedveld, T. W. J. Huizinga, B. A. C. Dijkmans, C. F. Allaart Tue, 30 Dec 2008 07:17:00 -0000
To investigate the effectiveness of 4 different treatment strategies for recent-onset rheumatoid arthritis (RA) on 2-year patient-reported outcomes, including functioning and quality of life.A total of 508 patients with recent-onset RA were randomly assigned to 1) sequential monotherapy, 2) step-up combination therapy, both starting with methotrexate, 3) initial combination therapy, including a tapered high-dose prednisone, or 4) initial combination therapy with methotrexate and infliximab. Treatment was adjusted every 3 months if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis Patient Preference Disability Questionnaire, the Short Form 36 (SF-36), and scores for pain, global health, and disease activity measured on a 100-mm visual analog scale (VAS) were compared between groups at baseline and every 3 months thereafter for 2 years.After 2 years, all patient-reported outcomes had improved significantly from baseline, irrespective of the treatment strategy. SF-36 subscale scores approached population norms for 3 physical components, and achieved population norms (P > 0.05) for bodily pain and 4 mental components. Improvement in functioning, VAS scores, and physical items of the SF-36 occurred significantly earlier in patients treated with initial combination therapies (all comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus groups 3 and 4).All 4 DAS-driven treatment strategies resulted in substantial improvements in functional ability, quality of life, and self-assessed VAS scores after 2 years. Initial combination therapy led to significantly faster improvement in all patient-reported measures.
Differences in long-term disease activity and treatment of adult patients with childhood- and adult-onset systemic lupus erythematosus
Aimee O. Hersh, Emily von Scheven, Jinoos Yazdany, Pantelis Panopalis, Laura Trupin, Laura Julian, Patricia Katz, Lindsey A. Criswell, Edward Yelin Tue, 30 Dec 2008 07:17:00 -0000
To compare differences in long-term outcome between adults with childhood-onset (age at diagnosis <18 years) systemic lupus erythematosus (SLE) and with adult-onset SLE.Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 885 adult subjects with SLE (90 childhood-onset [cSLE], 795 adult-onset [aSLE]). Baseline and 1-year followup data were obtained via structured 1-hour telephone interviews conducted between 2002 and 2006. Using self-report data, differences in organ involvement and disease morbidity, current disease status and activity, past and current medication use, and number of physician visits were compared, based on age at diagnosis of SLE.Average disease duration for the cSLE and aSLE subgroups was 16.5 and 13.4 years, respectively, and mean age at followup was 30.5 and 49.9 years, respectively. When compared with aSLE subjects, cSLE subjects had a higher frequency of SLE-related renal disease, whereas aSLE subjects were more likely to report a history of pulmonary disease. Rates of clotting disorders, seizures, and myocardial infarction were similar between the 2 groups. At followup, cSLE subjects had lower overall disease activity, but were more likely to be taking steroids and other immunosuppressive therapies. The total number of yearly physician visits was similar between the 2 groups, although cSLE subjects had a higher number of nephrology visits.This study demonstrates important differences in the outcomes of patients with cSLE and aSLE, and provides important prognostic information about long-term SLE disease activity and treatment.

Arthritis & Rheumatism

In this issue
Tue, 30 Dec 2008 07:15:00 -0000
No abstract.
The future of folic acid antagonist therapy in rheumatoid arthritis
Christoph Fiehn Tue, 30 Dec 2008 07:15:00 -0000
No abstract.
Naturally acquired microchimerism: For better or for worse
J. Lee Nelson Tue, 30 Dec 2008 07:15:00 -0000
No abstract.

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