Naorp :: Medicine :: Medical Specialties :: Rheumatology (3)

Permanent Rheumatology Jobs

Rheumatology jobs
Mon, 06 Feb 2012 22:52:05 -0500
All Rheumatology jobs for Mon Feb 6 2012
Rheumatology jobs in "Rheumatology - North Carolina (90 minutes to Winston-Salem, 2 hours to Charlotte and Asheville)" - NC
Thu, 02 Feb 2012 13:27:44 -0500
090526-697 Rheumatology - North Carolina (90 minutes to Winston-Salem, 2 hours to Charlotte and Asheville) NC Seeking BC/BE rheumatologist for multi-specialty group The practice currently has two
Rheumatology jobs in "Western Arizona's Colorado River resort - 2 hours to Phoenix, 1 hour to Bullhead City" - AZ
Thu, 02 Feb 2012 13:27:44 -0500
Lake Havasu City, "America's Home for the London Bridge", A Mecca of outdoor recreation, ideal climate, captivating scenery, beautiful yet rugged mountains, tranquil desert plus the

Arthritis Research & Therapy - Latest Articles

Low copy number of the FCGR3B gene and rheumatoid arthritis: a case control study and meta-analysis
Scott GrafSue LesterHans NossentCatherine HillSusanna ProudmanAnita LeeMaureen Rischmueller Tue, 07 Feb 2012 00:00:00 -0000
IntroductionLow copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease. This receptor for IgG is present almost exclusively on neutrophils and plays a role in their interaction with immune complexes. At present the relationship between FCGR3B and rheumatoid arthritis (RA) is unclear. The aim of this study was to investigate whether low CN of the FCGR3B gene is associated with susceptibility to RA.MethodFCGR3B CN was determined using a custom Taqman(R) copy number assay (Applied Biosystems, Hs04211858) in 197 RA patients, recruited from a tertiary setting, and 162 population matched controls. Odds ratios for low CN (2), both relative to the normal diploid two CN, were estimated by logistic regression. Results: A significant association between RA and low FCGR3B CN was observed, with frequencies of 13.7% in RA patients compared to 6.2% in controls (OR 2.5 95%CI 1.2-5.4 p=0.017). No association was observed between low CN and the presence of rheumatoid factor (RF), anti-CCP antibodies or radiographic erosions in RA patients. A meta-analysis, including six previous studies, confirmed an association between RA and low FCGR3B CN (OR 1.47, 95% CI 1.13, 1.92, p = 0.004) Conclusions: This study confirms that low CN of the FCGR3B gene is associated with susceptibility to RA. The association may be stronger in patients recruited from a tertiary setting, which may relate to disease severity and/or complications. The mechanism of susceptibility remains unclear and further study is required.
Pre-disease pregnancy complications and systemic sclerosis: pathogenic or pre-clinical?
Eliza Chakravarty Mon, 06 Feb 2012 00:00:00 -0000
The fetal microchimerism theory of the pathogenesis of systemic sclerosis (SSc) has compelling biologic support including the female predominance of the disease, mean age of onset after the childbearing years, similarities between diffuse cutaneous SSc and graft-versus-host-disease, as well as the detection of microchimeric cells in peripheral blood and skin of SSc patients. This issue of Arthritis Research and Therapy presents findings of a positive association between pregnancy complications and future diagnosis of SSc in parous women. However, before interpreting results of this epidemiologic study as support of fetal microchimerism, other theories of the observed associations must be considered.
Takayasu's arteritis is associated with HLA-B*52, but not with B*51, in Turkey
Ziver SahinMuge BicakcigilKenan AksuSevil KamaliServet AkarFatos OnenOmer KaradagZeynep OzbalkanAskin AtesHuseyin OzerVuslat YilmazEmire SeyahiMehmet OzturkAyse CefleVeli CobankaraAhmet OnatErcan TuncNursen DuzgunSibel AydinNeslihan YilmazIzzet FreskoYasar KaraaslanSedat KirazNurullah AkkocMurat InancGokhan KeserFatma UyarHaner DireskeneliGuher Direskeneli Mon, 06 Feb 2012 00:00:00 -0000
IntroductionHLA-B*51 and B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (B*51 with Behcet's disease and B*52 with Takayasu's arteritis-TAK) with major clinical and immunological differences. This study aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and B*52 as susceptibility and severity factors. Methods: TAK patients (n=330) followed by 15 centers were included in the study. The mean age of the patients was 37.8 years and 86% were women. DNA samples from the patients and healthy controls (n=210) (HC) were isolated and the presence of HLA-B*51 or B*52 was screened by using polymerase chain reaction (PCR) with sequence specific primers (SSP). Results: B*52 has shown a significant association with TAK (20.9% vs. HC= 6.7%, P=0.000, OR: 3.7, CI: 2.02 to 6.77). The distribution of B*51 did not differ between TAK and HC (22.7% vs. 24.8%, OR: 0.9, CI: 0.60 to 1.34). The presence of B*52 decreased in late-onset (>40 years) patients (12.0%, P=0.024, OR: 0.43, CI: 0.20 to 0.91). Patients with angiographic Type I disease with limited aortic involvement had also a lower presence of B*52 compared to all other subtypes (13.1% vs. 26%, P= 0.005, OR: 0.43, CI: 0.23 to 0.78). Conclusions: In this study, the previously reported association of TAK with B*52 in other populations was confirmed in patients from Turkey. The functional relevance of B*52 in TAK pathogenesis has to be further explored.
An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis
David McErlainVeronica UliciMark DarlingJoe GatiVasek PitelkaFrank BeierDavid Holdsworth Fri, 03 Feb 2012 00:00:00 -0000
IntroductionSubchondral bone cysts (SBC) have been identified in patients with knee Osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA. Methods: Eight rodents underwent anterior cruciate ligament transection and partial medial meniscectomy (ACLX) of the right knee. In vivo 9.4 T MRI and micro-computed tomography (micro-CT) scans were performed consecutively prior to ACLX and 4, 8, and 12 weeks post-ACLX. Resultant images were co-registered using anatomical landmarks, which allowed for precise tracking of SBC size and composition throughout the study. The diameter of the SBC was measured, and the volumetric bone mineral density (vBMD) was calculated within the bone adjacent to SBC. At 12 weeks, the ACLX and contralateral knees were processed for histological analysis, immuno-histochemistry, and OARSI pathological scoring. Results: At 4 weeks post-ACLX, 75 % of the rodent knees had at least 1 cyst that formed in the medial tibial plateau; by 12 weeks all ACLX knees contained SBC. Imaging data revealed the SBC originate in the presence of a subchondral bone plate breach, with evolving composition over time. The diameter of the SBC increased significantly over time (p = 0.0033) and the vBMD significantly decreased at 8 weeks post-ACLX (p = 0.033). Histological analysis demonstrated positive staining for bone resorption and formation surrounding the SBC, which were consistently located beneath the joint surface with the greatest cartilage damage. Trabecular bone adjacent the SBC lacked viable osteocytes and - combined with bone marrow changes - indicated osteonecrosis. Conclusions: This study provides insight into the mechanisms leading to SBC formation in knee OA. The expansion of these lesions is due to stress-induced bone resorption from the incurred mechanical instability. Therefore we suggest these lesions can be more accurately described as a form of OA-induced osteonecrosis, rather than 'subchondral cysts'.
Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies
Chih Long LiuStephanie TangsombatvisitJacob RosenbergGil MandelbaumEmily GillespieOr GozaniAsh AlizadehPaul Utz Thu, 02 Feb 2012 00:00:00 -0000
IntroductionAutoreactivity to histones is a pervasive feature of several human autoimmune disorders including systemic lupus erythematosus (SLE). Specific post-translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones. Methods: We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen. Results: We confirmed specificity toward acetyl-modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the IgG and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE. Conclusions: Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified.
Therapy of lupus nephritis: lessons learned from clinical research and daily care to patients
Frédéric Houssiau Tue, 31 Jan 2012 00:00:00 -0000
Despite numerous randomized clinical trials over the last three decades for identifying the optimal treatment option for lupus nephritis, renal involvement still significantly impacts the survival and quality of life of patients with lupus and the search for the ideal immunosuppressive regimen is far from complete. The purpose of this review is to summarize the major recent achievements in the field. More specifically, the following topics will be discussed: intravenous cyclophosphamide versus mycophenolate mofetil (MMF) for induction; azathioprine versus MMF for maintenance; targeted therapies. The review will address clues for optimal global care, such as the need for complete initial evaluation, the importance of patient education, the unmasking of non-compliance to therapy, the reason for an early treatment switch in non-responding patients, the need for prolonged immunosuppression, optimal renal protection, and prevention of cardiovascular disease and other comorbidities.

Annals of the Rheumatic Diseases current issue

Canes for knee osteoarthritis: is a randomised trial necessary?
Hagen, K. B. Wed, 28 Dec 2011 19:58:21 -0800
In this issue of the Annals, Jones et al1 (pp 172) report the results of a randomised clinical trial (RCT) of canes for knee osteoarthritis. Current recommendations on the management of hip and knee osteoarthritis emphasise non-pharmacological interventions, with sticks or canes universally recommended in existing guidelines.2 According to the Osteoarthritis Research Society International (OARSI) recommendations for the management of hip and knee osteoarthritis one of 25 treatment propositions recommended is ‘Walking aids can reduce pain in patients with hip and knee OA. Patients should be given instruction in the optimal use of a cane or crutch in the contralateral hand. Frames or wheeled walkers are often preferable for those with bilateral disease.’3 In the National Institute for Health and Clinical Excellence (NICE) guideline for care and management of osteoarthritis in adults, assistive devices (such as walking sticks) are considered as...
The effect of biological agents on work participation in rheumatoid arthritis patients: a systematic review
ter Wee, M. M., Lems, W. F., Usan, H., Gulpen, A., Boonen, A. Wed, 28 Dec 2011 19:58:21 -0800
This study reviewed the effect of biological agents on participation in paid work among patients with rheumatoid arthritis (RA). A systematic literature search was performed to identify published articles reporting the effect of biological agents on employment status, sick leave and/or presenteeism. The quality of included articles was assessed according to the guidelines as proposed by the Dutch Cochrane Centre. Narrative summaries were used to present the data separately for randomised controlled trials (RCTs) as well as controlled and uncontrolled cohort studies. 19 studies (six uncontrolled cohorts, seven controlled cohorts and six RCTs) were included, in which 11 259 patients were treated with biological agents. Employment status improved in four out of 13 studies, absence from work in all 10 studies and presenteeism in seven out of nine studies that reported this outcome. For absenteeism and presenteeism the statistical significance of change or difference was not always provided and results within studies were sometimes conflicting when using different time frames or alternative outcomes. The large heterogeneity in terms of population, design, analyses and most important in outcome measures limits interpretation of the data. RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying antirheumatic drugs (DMARD), continuing the failing DMARD, the general population or the situation before the start of biological agents. The effect on employment status was more conflicting, but 50% of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status.
Impact of cane use on pain, function, general health and energy expenditure during gait in patients with knee osteoarthritis: a randomised controlled trial
Jones, A., Silva, P. G., Silva, A. C., Colucci, M., Tuffanin, A., Jardim, J. R., Natour, J. Wed, 28 Dec 2011 19:58:21 -0800
Objective To assess the impact of daily cane use during gait in relation to pain, function, general health and energy expenditure among patients with knee osteoarthritis. Method Sixty-four patients were randomly assigned to an experimental group (EG) or control group (CG). The EG used a cane every day for 2 months, whereas the CG did not use a cane in this period. The first outcome was pain and the second were function (Lequesne and WOMAC), general health (SF-36) and energy expenditure (gas analysis during the 6-minute walk test (6MWT) with and without a cane). Evaluations were performed at baseline, 30 and 60 days. Results The groups were homogeneous for all parameters at baseline. Compared with the CG, the EG significantly improved pain (ES 0.18), function - Lequesne (ES 0.13), some domains of SF-36 (role physical, ES 0.07 and bodily pain, ES 0.08) and distance on the 6MWT with the cane (ES 0.16). At the end of the 6MWT with the cane, the EG significantly improved energy expenditure (ES 0.21), carbon dioxide production (ES 0.12) and metabolic equivalents (ES 0.15) compared with the CG. Conclusion A cane can be used to diminish pain, improve function and some aspects of quality of life in patients with knee osteoarthritis. The prescription of a cane should take into account the substantial increase in energy expenditure in the first month of use, whereas energy expenditure is no longer a factor for concern by the end of the second month due to adaptation to cane use. The trial was registered in clinicaltrials.gov (NCT00698412).
Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study
Boumans, M. J. H., Houbiers, J. G. A., Verschueren, P., Ishikura, H., Westhovens, R., Brouwer, E., Rojkovich, B., Kelly, S., den Adel, M., Isaacs, J., Jacobs, H., Gomez-Reino, J., Holtkamp, G. M., Hastings, A., Gerlag, D. M., Tak, P. P. Wed, 28 Dec 2011 19:58:21 -0800
Objectives Osteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin. Methods In this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B). Results ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. Conclusions Osteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.
In early rheumatoid arthritis, patients with a good initial response to methotrexate have excellent 2-year clinical outcomes, but radiological progression is not fully prevented: data from the methotrexate responders population in the SWEFOT trial
Rezaei, H., Saevarsdottir, S., Forslind, K., Albertsson, K., Wallin, H., Bratt, J., Ernestam, S., Geborek, P., Pettersson, I. F., van Vollenhoven, R. F. Wed, 28 Dec 2011 19:58:21 -0800
Objective To investigate the 2-year clinical and radiological outcomes of patients with early rheumatoid arthritis (RA; symptom duration <1 year) who had initially responded well to methotrexate monotherapy. Methods In the SWEFOT trial, all 487 patients started methotrexate (target dose 20 mg/week). After 3–4 months, 147 had low disease activity, 28-joint based disease activity score (DAS28) ≤3.2. These patients were not randomly selected but were followed in regular care for 2 years. Clinical outcomes and radiographic progression according to the van der Heijde modified Sharp (SvdH) score were analysed. Results The majority of the 147 patients continued on methotrexate monotherapy. After 1 and 2 years, DAS28 remission was achieved in 59.6% and 71.8% and mean observed DAS28 values were 2.53 and 2.25, respectively. Despite the favourable clinical course, a proportion of the patients progressed radiographically with a mean (SD) increase in the SvdH score after 2 years of 3.90 (6.84). There was no significant difference in progression between patients in DAS28 remission versus not in remission (p=0.73). At baseline, approximately half the patients had no radiographic damage, while after 2 years the proportion was approximately 20%. Conclusion Most early RA patients who achieve low disease activity after 3–4 months of methotrexate monotherapy continue to have low disease activity during 2 years follow-up, and additional treatment is needed infrequently. Some radiological progression occurs in most patients, and may be marked or severe in some, even despite sustained DAS28 remission. Close monitoring for radiological progression is thus warranted.
The prospective association between psychological distress and disease activity in rheumatoid arthritis: a multilevel regression analysis
Overman, C. L., Bossema, E. R., van Middendorp, H., Wijngaards-de Meij, L., Verstappen, S. M., Bulder, M., Jacobs, J. W., Bijlsma, J. W., Geenen, R. Wed, 28 Dec 2011 19:58:21 -0800
Background Cross-sectional associations suggest a mutual impact of disease activity and psychological distress in rheumatoid arthritis (RA), but a prospective association has not been established. Objective To examine concurrent and prospective associations between psychological distress and disease activity. Methods Patients with RA (N=545, disease duration ≤1 year, age 18–83 years, 69% female, 64% rheumatoid factor (RF) positive) were monitored for 5 years. The Thompson joint score and erythrocyte sedimentation rate were assessed every 6 months. Depressed mood and anxiety were measured every 12 months. Multilevel regression analysis was used. RF positivity, age and female sex were included as covariates. Results Concurrent levels of psychological distress and disease activity were positively associated (p≤0.04). Prospectively, depressed mood was associated with disease activity levels 6 months later (p≤0.04). The Thompson joint score was associated with psychological distress levels 6 months later (p≤0.03) and also with an increase in depressed mood over the subsequent 6 months (p=0.02). No other significant prospective associations were found (p≥0.07). Conclusions Psychological distress and disease activity are positively associated when measured at the same time as well as when measured 6 months apart. While some support was found for the idea that a higher level of disease activity is a risk factor for an increase in psychological distress, the results do not support the notion that psychological distress is a risk factor for future exacerbation of disease activity.

Subscribe to Rheumatology RSS feed