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Site: MedicineNet Arthritis General

Muscle Cramps
Title: Muscle Cramps
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 3/18/2010

Brief Meditation Training Brings Pain Relief
Title: Brief Meditation Training Brings Pain Relief
Category: Health News
Created: 3/17/2010 4:45:00 PM
Last Editorial Review: 3/18/2010

Menopause
Title: Menopause
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 3/17/2010

High-Impact Sports Might Not Harm Knee Replacements
Title: High-Impact Sports Might Not Harm Knee Replacements
Category: Health News
Created: 3/12/2010 10:10:00 AM
Last Editorial Review: 3/15/2010

Health Tip: IBD May Contribute to Other Health Problems
Title: Health Tip: IBD May Contribute to Other Health Problems
Category: Health News
Created: 3/11/2010 10:10:00 AM
Last Editorial Review: 3/12/2010

New Knee May Improve Balance
Title: New Knee May Improve Balance
Category: Health News
Created: 3/11/2010 10:10:00 AM
Last Editorial Review: 3/12/2010

Long-Term Use of Osteoporosis Drugs Linked to Fractures
Title: Long-Term Use of Osteoporosis Drugs Linked to Fractures
Category: Health News
Created: 3/11/2010 2:10:00 PM
Last Editorial Review: 3/12/2010

Jump in Kids' Sports Injuries Due to Overuse
Title: Jump in Kids' Sports Injuries Due to Overuse
Category: Health News
Created: 3/10/2010 10:10:00 AM
Last Editorial Review: 3/11/2010

Youth Baseball Injuries Becoming More Common
Title: Youth Baseball Injuries Becoming More Common
Category: Health News
Created: 3/10/2010 10:10:00 AM
Last Editorial Review: 3/11/2010

High Natural Estrogen Might Raise Women's Stroke Risk
Title: High Natural Estrogen Might Raise Women's Stroke Risk
Category: Health News
Created: 3/10/2010 12:10:00 PM
Last Editorial Review: 3/11/2010

Deep Vein Thrombosis (DVT)
Title: Deep Vein Thrombosis (DVT)
Category: Diseases and Conditions
Created: 2/15/2000 10:55:00 PM
Last Editorial Review: 3/10/2010

Psychotherapy Can Help People With Lupus Cope
Title: Psychotherapy Can Help People With Lupus Cope
Category: Health News
Created: 3/9/2010 6:10:00 PM
Last Editorial Review: 3/10/2010

Site: Arthritis Research & Therapy - Latest Articles

B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B cell maturation antigen-immunoglobulin
IntroductionB-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor (TNF) family that regulate B cell maturation, survival, and function. They are overexpressed in a variety of autoimmune diseases and reportedly exist in vivo not only as homotrimers, but also as BLyS/APRIL heterotrimers. Methods: A proprietary N-terminal trimerization domain was used to produce recombinant BLyS/APRIL heterotrimers. Heterotrimer biologic activity was compared with that of BLyS and APRIL in a 4-hour signaling assay using transmembrane activator and CAML interactor (TACI)-transfected Jurkat cells and in a 4-day primary human B cell proliferation assay. A bead-based immunoassay was developed to quantify native heterotrimers in human sera from healthy donors (n = 89) and patients with systemic lupus erythematosus (SLE; n = 89) or rheumatoid arthritis (RA; n = 30). Heterotrimer levels were compared with BLyS and APRIL homotrimer levels in a subset of these samples. Results: The recombinant heterotrimers mostly consisted of 1 BLyS and 2 APRIL molecules. Heterotrimer signaling did not show any significant difference compared with APRIL in the TACI Jurkat assay. Heterotrimers were less potent inducers of B cell proliferation than homotrimeric BLyS or APRIL (EC50, nM: BLyS 0.02, APRIL 0.17, heterotrimers 4.06). The soluble receptor fusion proteins atacicept and B cell maturation antigen (BCMA)-immunoglobulin (Ig) neutralized the activity of BLyS, APRIL, and heterotrimers in both cellular assays, whereas B cell activating factor of the TNF family receptor (BAFF-R)-Ig only neutralized the activity of BLyS. In human sera, significantly more patients with SLE had detectable BLyS (67% versus 18%; P < 0.0001), APRIL (38% versus 3%; P < 0.0002), and heterotrimer (27% versus 8%; P = 0.0013) levels compared with healthy donors. Significantly more patients with RA had detectable APRIL, but not BLyS or heterotrimer, levels compared with healthy donors (83% versus 3%; P < 0.0001). Heterotrimer levels weakly correlated with BLyS, but not APRIL, levels. Conclusions: Recombinant BLyS/APRIL heterotrimers have biologic activity and are inhibited by atacicept and BCMA-Ig, but not BAFF-R-Ig. A novel immunoassay demonstrated that native BLyS/APRIL heterotrimers, as well as BLyS and APRIL homotrimers, are elevated in patients with autoimmune diseases.

Anticentromere antibody positive Sjogren's Syndrome: a retrospective descriptive analysis
IntroductionA subgroup of patients with primary Sjogren's syndrome (SS) and positive anticentromere antibodies (ACA) were recognized as having features intermediate between SS and systemic sclerosis (SSc). Our goal was to describe this group clinically and serologically and define its tendency to evolve to full blown SSc. Methods: Among 535 patients with primary SS we identified 20 ACA positive (ACA+/SS). We compared them to 61 randomly selected ACA negative SS patients (ACA-/SS), 31 ACA positive SSc patients with sicca manifestations [SSc/(+) sicca] and 20 ACA positive SSc patients without sicca manifestations [SSc/(-) sicca]. Results: Prevalence of ACA amongst SS patients was 3.7%. Cases and controls did not differ in sex ratio and age at disease onset. ACA+/SS patients had a lower prevalence of dry eyes, hypergammaglobulinaemia, anti-Ro and anti-La antibodies and a higher prevalence of Raynaud's phenomenon and dysphagia compared to ACA-/SS patients. They also had lower prevalence of telangiectasias, puffy fingers, sclerodactyly, Raynaud's phenomenon digital ulcers and gastroesophageal reflux in comparison to both of the SSc subgroups and a lower prevalence of dyspnoea and lung fibrosis compared to the SSc/(+) sicca subgroup. Two patients originally having ACA+/SS evolved to full blown SSc. Four deaths occurred, all among SSc patients. Kaplan Meier analysis showed a significant difference between cases and controls in time from disease onset to development of gastroesophageal reflux, telangiectasias, digital ulcers, arthritis, puffy fingers, xerostomia, hypergammaglobulinaemia and dysphagia. Conclusions: ACA+/SS has a clinical phenotype intermediate between ACA-/SS and SSc and shows little tendency to evolve to SSc.

Limited educational attainment and radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis using data from the Johnston County (North Carolina) Osteoarthritis Project
IntroductionApplying a cross-sectional analysis to a sample of 2627 African American and Caucasian adults aged [greater than or equal to]45 years from the Johnston County Osteoarthritis Project, we studied the association between educational attainment and prevalence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis. Methods: Age- and race-adjusted associations between education and osteoarthritis outcomes were assessed by gender-stratified logistic regression models, with additional models adjusting for body mass index, knee injury, smoking, alcohol use, and occupational factors. Results: In an analysis of all participants, low educational attainment (<12 years) was associated with higher prevalence of 4 knee osteoarthritis outcomes (unilateral and bilateral radiographic and symptomatic osteoarthritis). Women with low educational attainment had 50% higher odds of having radiographic knee osteoarthritis and 65% higher odds of symptomatic knee osteoarthritis compared with those with higher educational attainment ([greater than or equal to]12 years), using fully adjusted models. In the subset of postmenopausal women, these associations tended to be weaker but little affected by adjustment for hormone replacement therapy. Men with low educational attainment had 85% higher odds of having symptomatic knee osteoarthritis using fully adjusted models, but the association with radiographic knee osteoarthritis was explained by age. Conclusions: After adjustment for known risk factors, educational attainment, as an indicator of socioeconomic status, is associated with symptomatic knee osteoarthritis in both men and women and with radiographic knee osteoarthritis in women.

Slit3 inhibits Robo3-induced invasion of synovial fibroblasts in rheumatoid arthritis
IntroductionThe repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. However, until today no data are available on whether these repellent factors are involved in the regulation of synovial fibroblast (SF) activity in rheumatoid arthritis (RA). Methods: mRNA expression in primary synovial fibroblasts was quantified by quantitative reverse transcription PCR and protein expression was measured by fluoresence activated cell sorting (FACS) analysis. Different functional assays were performed with rheumatoid arthritis synovial fibroblasts (RASF): proliferation, migration and a novel in-vitro cartilage destruction assay. Results: First, we found increased expression of Robo3 expression in RASF compared to normal SF. Interestingly, analysis of data from a recently published genome-wide association study suggests a contribution of ROBO3 gene polymorphisms to susceptibility of RA. Functional assays performed with RASF revealed induction of migration and cartilage destruction by Robo3 and increased matrix metalloproteinase (MMP)1 and MMP3 expression. Treatment of RASF in early passages with Slit3 led to inhibition of migration whereas RASF in later passages, having reduced Robo3 expression in cell culture, were not inhibited by Slit3 treatment. Here, reduction of Robo3 expression from passage 3 to 10 might reflect an important step in losing repulsive activity of Slit3. Conclusions: Taken together, our data showed that deregulation of the Robo3 receptor in synovial fibroblasts in RA correlates with aggressiveness of the fibroblasts. Slit3 reduces the migratory activity of synovial cells from patients with RA, potentially by repulsion of the cells in analogy to the neuronal system. Further studies will be necessary to prove Slit activity in vivo.

Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints
IntroductionInflammatory joint destruction in rheumatoid arthritis (RA) may be triggered by autoantibodies, the production of which is supported by autoreactive T cells. Studies on RA and animal models of the disease suggest that T cells recruited in the joints can locally initiate or propagate arthritis. Herein, we investigated the role of joint-homing versus lymphoid organ-homing T cells in the development of proteoglycan-induced arthritis (PGIA), an autoimmune model of RA. Methods: To identify T cells migrating to the joints before and during development of autoimmune arthritis, we transferred fluorescence-labeled T cells, along with antigen-presenting cells, from BALB/c mice with PGIA to naive syngeneic severe combined immunodeficient (SCID) mice. We then monitored the recruitment of donor T cells in the ankle joints and joint-draining lymph nodes of the recipients using in vivo two-photon microscopy and ex vivo detection methods. To limit T-cell access to the joints, we selectively depleted T cells in the blood circulation by treatment with FTY720, an inhibitor of lymphocyte egress from lymphoid organs. Reduction of T cell presence in both lymphoid organs and blood was achieved by injection of donor cells from which T cells were removed prior to transfer. T and B cells were quantitated by flow cytometry, and antigen (PG)-specific responses were assessed by cell proliferation and serum antibody assays. Results: Despite development of adoptively transferred arthritis in the recipient SCID mice, we found very few donor T cells in their joints after cell transfer. Treatment of recipient mice with FTY720 left the T-cell pool in the lymphoid organs intact, but reduced T cells in both peripheral blood and joints. However, FTY720 treatment failed to inhibit PGIA development. In contrast, arthritis was not seen in recipient mice after transfer of T cell-depleted cells from arthritic donors, and serum autoantibodies to PG were not detected in this group of mice. Conclusions: Our results suggest that antigen-specific T cells, which home to lymphoid organs and provide help to B cells for systemic autoantibody production, play a greater role in the development and progression of autoimmune arthritis than the small population of T cells that migrate to the joints.

Vasculogenesis in rheumatoid arthritis
Decreased number and impaired functions of endothelial progenitor cells (EPCs) leading to impaired vasculogenesis have been associated with rheumatoid arthritis (RA). Defective vasculogenesis has also been implicated in premature atherosclerosis in RA. Recently, early outgrowth, monocytic and late outgrowth, hemangioblastic EPC subsets have been characterized. Hemangioblastic EPCs may exert increased numbers in active RA and may play a role in vascular repair underlying RA.

Effectiveness of adalimumab in treating patients with ankylosing spondylitis associated with enthesitis and peripheral arthritis
IntroductionTo investigate the effectiveness of adalimumab in enthesitis and peripheral arthritis in patients with ankylosing spondylitis (AS). Methods: Adults with active AS (Bath ankylosing spondylitis disease activity index [BASDAI] [greater than or equal to]4) received adalimumab 40 mg every other week with standard antirheumatic therapies in a 12-week, open-label study. Effectiveness in enthesitis was assessed using the Maastricht ankylosing spondylitis enthesitis score (MASES, 0-13) and by examining the plantar fascia in patients with enthesitis ([greater than or equal to]1 inflamed enthesis) at baseline; effectiveness in peripheral arthritis was evaluated using tender and swollen joint counts (TJC, 0-46; SJC, 0-44) in patients with peripheral arthritis ([greater than or equal to]1 swollen joint) at baseline. Overall effectiveness measures included assessment of spondyloArthritis international society 20% response (ASAS20). Results: Of 1,250 patients enrolled, 686 had enthesitis and 281 had peripheral arthritis. In 667 patients with MASES [greater than or equal to]1 at baseline, the median MASES was reduced from 5 at baseline to 1 at week 12. At week 12, inflammation of the plantar fascia ceased in 122 of 173 patients with inflammation at baseline. The median TJC in 281 patients with SJC [greater than or equal to]1 at baseline was reduced from 5 at baseline to 1 at week 12; the median SJC improved from 2 to 0. ASAS20 responses were achieved by 70.5% of 457 patients with no enthesitis and no arthritis; 71.0% of 512 patients with only enthesitis, 68.0% of 107 patients with only arthritis; and 66.7% of 174 patients with both. Conclusions: Treatment with adalimumab improved enthesitis and peripheral arthritis in patients with active AS.Trial registration: ClinicalTrials.gov NCT00478660.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study
IntroductionWork disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. Methods: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K U.S dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA, and clinical status of patients who continued working or had stopped working in high-GDP vs. low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. Results: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one-third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had began during the 2000s, the probability of continuing to work was 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working vs. stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. Conclusions: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

DNA microarray analysis of rheumatoid arthritis (RA) susceptibility genes identified by genome-wide association studies (GWAS)
No description available

Gait changes precede overt arthritis and strongly correlate with symptoms and histopathological events in pristane-induced arthritis.
IntroductionPristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed. Methods: Arthritis was induced in DA.rats by injection of 150 micro-l 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods. Results: Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred prior to disease onset. A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis. Conclusions: Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction in patients suffering from inflammatory arthritis.