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ID PMID Title PublicationDate abstract
19634006 Content comparison of worker productivity questionnaires in arthritis and musculoskeletal 2009 Dec BACKGROUND: Worker productivity outcome is essential in examining the rehabilitation of workers with arthritis and other musculoskeletal conditions. There is great variation in the contents of worker productivity questionnaires. The International Classification of Functioning Disability and Health (ICF) offers the possibility to serve as a reference to describe and compare the contents of these questionnaires. METHODS: A literature review identified published self-report worker productivity questionnaires. All meaningful concepts were identified and linked to the corresponding ICF category according to established rules. RESULTS: Eighteen questionnaires were identified which contained a total of 519 meaningful concepts and which were linked to 64 unique 2nd level ICF categories. All questionnaires addressed Activities and Participation, thirteen (72%) addressed Body Functions, seven (39%) addressed Environmental Factors, seven (39%) addressed Personal Factors and only one questionnaire (6%) for Body Structures component. Overall, Work Role Functioning (WRF) questionnaire addressed the most number of different categories while Quantity and Quality method contained only one ICF category. The Rheumatoid Arthritis-Work Instability Scale had the highest number of categories for Body Functions, the Work Activity Limitations Scale and WRF had the most number of categories for Activities and Participation. The Health and Labour Questionnaire had the highest number of categories referring to unpaid work participation. The Health and Work Questionnaire was the only that included contextualization of both Environmental and Personal Factors. CONCLUSION: Self-report worker productivity questionnaires differed largely in their contents. This content analysis study could guide us in selecting an appropriate questionnaire for a specific study question.
19252817 Systemic effects of intra-articular corticosteroids. 2009 Jul The objective of this study was to review all the published articles in the English literature about the systemic effects of intra-articular corticosteroid injection (IACI) in humans. Reports were searched through Pubmed using the terms intraarticular or intra-articular and steroids, corticosteroids, or glucocorticosteroids up and including the year 2007. Reports were also located through references of articles. Only objective findings outside the injected joint were included. The overwhelming majority of the studies was done at the knee joint and in rheumatoid arthritis/juvenile idiopathic arthritis patients. Many of the studies were done on the hypothalamic-pituitary-adrenal axis. Serum cortisol decreased within hours with a nadir after usually 24-48 h following the IACI. Recovery to baseline takes 1-4 weeks and sometimes longer depending on the type and dose of IACI and on the number of injected joints. Serum cortisol levels were blunted following adrenocorticotropic hormone stimulation in a small proportion of patients following methylprednisolone acetate injection and more common following other preparations. IACI resulted in a transient increase in blood glucose levels over few days in controlled diabetic patients with knee osteoarthritis. Peak levels are around 300 mg%. IACIs are associated with reduction in inflammatory markers like C-reactive protein and erythrocyte sedimentation rate that start few days following the IACI and could last for months. The effect on inflammatory cytokines is immediate with significant decrease within hours. IACI may induce remission also in patients with oligo-/polyarthritis and/or in patients with extra-articular manifestations. Other metabolic, hematologic, vascular, allergic, visual, psychologic, and other effects were also reported.
20506263 Therapeutic control of B cell activation via recruitment of Fcgamma receptor IIb (CD32B) i 2010 Jul OBJECTIVE: To exploit the physiologic Fcgamma receptor IIb (CD32B) inhibitory coupling mechanism to control B cell activation by constructing a novel bispecific diabody scaffold, termed a dual-affinity retargeting (DART) molecule, for therapeutic applications. METHODS: DART molecules were constructed by pairing an Fv region from a monoclonal antibody (mAb) directed against CD32B with an Fv region from a mAb directed against CD79B, the beta-chain of the invariant signal-transducing dimer of the B cell receptor complex. DART molecules were characterized physicochemically and for their ability to simultaneously bind the target receptors in vitro and in intact cells. The ability of the DART molecules to negatively control B cell activation was determined by calcium mobilization, by tyrosine phosphorylation of signaling molecules, and by proliferation and Ig secretion assays. A DART molecule specific for the mouse ortholog of CD32B and CD79B was also constructed and tested for its ability to inhibit B cell proliferation in vitro and to control disease severity in a collagen-induced arthritis (CIA) model. RESULTS: DART molecules were able to specifically bind and coligate their target molecules on the surface of B cells and demonstrated a preferential simultaneous binding to both receptors on the same cell. DART molecules triggered the CD32B-mediated inhibitory signaling pathway in activated B cells, which translated into inhibition of B cell proliferation and Ig secretion. A DART molecule directed against the mouse orthologs was effective in inhibiting the development of CIA in DBA/1 mice. CONCLUSION: This innovative bispecific antibody scaffold that simultaneously engages activating and inhibitory receptors enables novel therapeutic approaches for the treatment of rheumatoid arthritis and potentially other autoimmune and inflammatory diseases in humans.
19219532 Sjögren's syndrome: an old tale with a new twist. 2009 Jan Sjögren's syndrome (SjS) is chronic autoimmune disease manifested by the loss of saliva and/or tear secretion by salivary and/or lacrimal glands, respectively. The pathogenesis of the disease remains elusive, perhaps due to the multiple triggers of the disease. However, substantial advances have been made in attempting to resolve the complexity of SjS using both animal models and human subjects. The primary objectives of this review are to provide a better understanding of the disease processes with major emphasis on the use of mouse models, how genetic predisposition plays a role in the natural history of the disease, as well as a presentation of new findings pertaining to the role of T(H)1, T(H)2, and T(H)17 cells in the pathogenesis of SjS.
20702682 Factors associated with increased pain communication by older adults. 2011 Mar The purpose of this secondary analysis study was to identify factors associated with increased pain communication by older adults. Data were obtained from 312 older adults with osteoarthritis pain. Content analysis was conducted using criteria from the American Pain Society's "Guidelines for the Management of Pain in Osteoarthritis, Rheumatoid Arthritis, and Juvenile Chronic Arthritis" to identify important pain management information described by the older adults in response to general questions about their pain. Gender was the only factor associated with increased pain communication from the predictor variables of age, education, gender, ethnicity, race, marital status, pain intensity, functional pain interference, treatment from a practitioner for arthritis and for pain, and pain relief. The lack of association between pain communication and factors such as pain intensity suggests that practitioners should routinely elicit specific pain information from older adults who have a history of chronic painful conditions such as osteoarthritis.
19327174 Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1beta-stimula 2009 INTRODUCTION: The objective of this study was to determine the anti-inflammatory, nociceptive, and antiarthritic effects of piperine, the active phenolic component in black pepper extract. METHODS: The in vitro anti-inflammatory activity of piperine was tested on interleukin 1beta (IL1beta)-stimulated fibroblast-like synoviocytes derived form patients with rheumatoid arthritis. The levels of IL6, matrix metalloproteinase (MMPs), cyclo-oxygenase 2 (COX-2), and prostaglandin E2 (PGE2) were investigated by ELISA and RT-PCR analysis. The analgesic and antiarthritic activities of piperine were investigated on rat models of carrageenan-induced acute paw pain and arthritis. The former were evaluated with a paw pressure test, and the latter by measuring the squeaking score, paw volume, and weight distribution ratio. Piperine was administrated orally to rats at 20 and 100 mg/kg/day for 8 days. RESULTS: Piperine inhibited the expression of IL6 and MMP13 and reduced the production of PGE2 in a dose dependant manner at concentrations of 10 to 100 microg/ml. In particular, the production of PGE2 was significantly inhibited even at 10 microg/ml of piperine. Piperine inhibited the migration of activator protein 1 (AP-1), but not nuclear factor (NF)kappaB, into the nucleus in IL1beta-treated synoviocytes. In rats, piperine significantly reduced nociceptive and arthritic symptoms at days 8 and 4, respectively. Histological staining showed that piperine significantly reduced the inflammatory area in the ankle joints. CONCLUSIONS: These results suggest that piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model. Thus, piperine should be further studied with regard to use either as a pharmaceutical or as a dietary supplement for the treatment of arthritis.
19155489 B7RP-1 blockade ameliorates autoimmunity through regulation of follicular helper T cells. 2009 Feb 1 Autoimmune diseases are marked by the presence of class-switched, high-affinity autoantibodies with pathogenic potential. Costimulation plays an important role in the activation of T cells and the development of T cell-dependent B cell responses. ICOS plays an indispensable role in the development of follicular helper T cells (T(FH) cells), which provide cognate help to germinal center (GC) B cells. We show that the levels of T(FH) cells and GC B cells in two different models of autoimmunity, the New Zealand Black/New Zealand White (NZB/NZW) F(1) mouse model of systemic lupus erythematosus and the collagen-induced arthritis model of rheumatoid arthritis, are dependent on the maintenance of the ICOS/B7RP-1 pathway. Treatment with an anti-B7RP-1 Ab ameliorates disease manifestations and leads to a decrease in T(FH) cells and GC B cells as well as an overall decrease in the frequency of ICOS(+) T cells. Coculture experiments of Ag-primed B cells with CXCR5(+) or CXCR5(-) T cells show that blocking B7RP-1 does not directly impact the production of IgG by B cells. These findings further support the role of ICOS in autoimmunity and suggest that the expansion of the T(FH) cell pool is an important mechanism by which ICOS regulates Ab production.
20554144 US-guided interventional joint procedures in patients with rheumatic diseases--when and ho 2011 Sep OBJECTIVE: To describe the main indications and the technical steps to perform ultrasound guided procedures in patients with rheumatic diseases. To access procedures accuracy, safety and effectiveness. MATERIALS AND METHODS: 27 patients with pain related to articular complications of rheumatic diseases and according to previous radiographic or US exam were submitted to several US-guided procedures. 42% of patients (n=11) had rheumatoid arthritis, 11% (n=3) spondyloarthropathies, 18% (n=5) psoriatic arthritis, 15% (n=4) undifferentiated arthritis, 3% (n=1) Sjögren syndrome and 11% (n=3) had gout. Described procedures are synovial biopsies, intra-articular injections of corticosteroids, radiation synovectomy and synovial cysts drainage procedures. When a therapeutical procedure was made, patients were evaluated by 2 rheumatologists. Corticosteroids used were Prednisolone and Triamcinolone. Yttrium-90 was used for synovectomy. RESULTS: In all cases success was achieved with correct needle placement inside the joint. After injection/aspiration symptoms successfully solved with all patients improving their health status. No complications were recorded during follow-up period. CONCLUSIONS: US-guidance is very reliable to afford a safety procedure always checking the injection, biopsy or aspiration. Guided-biopsy has high success rates obtaining several samples. Thus is also possible to use more powerful/long acting therapeutic drugs aggressive to extra-articular structures avoiding complications.
27713312 Suppression of Autoimmune Arthritis by Small Molecule Inhibitors of the JAK/STAT Pathway. 2010 May 12 A skewed ratio of pro-inflammatory to anti-inflammatory cytokines, elevated growth factor synthesis and T- and B-lymphocyte activation are 3 hallmarks of rheumatoid arthritis (RA) pathology. Interleukin-6 (IL-6), IL-7, IL-17, IL-12/IL-23 and growth factors, granulocyte macrophage-colony stimulating factor, IL-3, and erythropoietin activate the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway. Evidence showed that STAT protein phosphorylation (p-STAT) by activated JAKs is permissive for p-STAT to act as transcription factors by binding to STAT-responsive gene promoter sequences. This event is critical for perpetuating RA, in part, by up-regulating pro-inflammatory cytokine gene transcription. Activation of JAK/STAT by cytokines and growth factors can induce 'cross-talk' with other signaling pathways by which Stress-Activated Protein/Mitogen-Activated Protein Kinase (SAP/MAPK) and Phosphatidylinositide-3-Kinase (PI3K)-mediated signaling are also activated. JAK-specific small molecule inhibitors (SMIs) were developed to test whether JAK/STAT pathway blockade would regulate autoimmune-mediated inflammation. JAK-specific SMI blockade inhibited p-STAT induced by pro-inflammatory cytokines in vitro. Systemically administered JAK-specific SMI blockade also ameliorated biomarkers of inflammation in well-validated arthritis animal models. A few JAK-specific SMIs have made their way into RA clinical trials. In fact, the JAK3-specific SMI, CP-690,500 is the first JAK/STAT SMI to be assessed for clinical efficacy in a Phase III RA trial.
19609086 Enhanced expressions of mRNA for neuropeptide Y and interleukin 1 beta in hypothalamic arc 2009 OBJECTIVE: Food intake is activated by hypothalamic orexigenic neuropeptide Y (NPY), which is mainly under the dual control of leptin and ghrelin. Rat adjuvant arthritis (AA), similarly as human rheumatoid arthritis, is associated with cachexia caused by yet unknown mechanisms. The aim of our study was to evaluate NPY expression in hypothalamic arcuate nuclei (nARC) under the conditions of AA-induced changes in leptin, ghrelin and adiponectin. Since IL-1beta is involved in the central induction of anorexia, we studied its expression in the nARC as well. METHODS: AA was induced to Lewis rats using complete Freund's adjuvant. On days 12, 15 and 18 after complete Freund's adjuvant injection, the levels of leptin, adiponectin, ghrelin and IL-1beta were determined by RIA or ELISA. The mRNA expressions for NPY, leptin receptor (OB-R), ghrelin receptor (Ghsr) and IL-1beta were determined by TaqMan RT-PCR from isolated nARC. RESULTS: In AA rats, decreased appetite, body mass and epididymal fat stores positively correlated with reduced circulating and epididymal fat leptin and adiponectin. Ghrelin plasma levels were increased. In nARC, mRNA for OB-R, Ghsr and NPY were overexpressed in AA rats. AA rats showed overexpression of mRNA for IL-1beta in nARC while circulating, and spleen IL-1beta was unaltered. CONCLUSION: During AA, overexpression of orexigenic NPY mRNA in nARC along with enhanced plasma ghrelin and lowered leptin levels occur. Decreased food intake indicates a predominant effect of the anorexigenic pathway. Activated expression of IL-1beta in nARC suggests its role in keeping AA-induced anorexia in progress. The reduction in adiponectin may also contribute to AA-induced anorexia.
18408253 Non-steroidal anti-inflammatory drug use does not appear to be associated with increased c 2009 Mar OBJECTIVES: There is controversy about the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular disease (CVD) mortality. The aim of this study was to explore associations between NSAID use and mortality in patients with inflammatory polyarthritis (IP). SUBJECTS AND METHODS: A total of 923 patients with new onset (IP), recruited to the UK Norfolk Arthritis Register (NOAR) between 1990-1994, were followed up to the end of 2004. Current medication was recorded annually for the first 6 years and then every 2-3 years. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured. Logistic regression was used to calculate all cause and CVD mortality odds ratios (OR) for NSAID use at baseline and during follow-up, adjusting for gender and time-varying covariates: RF, CRP, joint counts, smoking, steroid use, DMARD use and other medication use. RESULTS: By 2004 there were 203 deaths, 85 due to CVD. At baseline, NSAIDs were used by 66% of patients. In final multivariate models, baseline NSAID use was inversely associated with all cause mortality (adjusted OR 0.62, 95% CI 0.45 to 0.84) and CVD mortality (adjusted OR 0.54, 95% CI 0.34 to 0.86). Interval NSAID use had weaker mortality associations: all cause mortality (adjusted OR 0.72, 95% CI 0.52 to 1.00), CVD mortality (adjusted hazard ratio (HR) 0.66, 95% CI 0.40 to 1.08). CONCLUSION: No excess CVD or all cause mortality was observed in NSAID users in this cohort of patients with IP. This is at variance with the literature relating to NSAID use in the general population. It is unclear whether this represents unmeasured confounders influencing a doctor's decision to avoid NSAIDs in the treatment of IP.
20981317 Suppression of ongoing experimental arthritis by a chinese herbal formula (huo-luo-xiao-li 2011 Rheumatoid arthritis (RA) is one of the major autoimmune diseases of global prevalence. The use of the anti-inflammatory drugs for the treatment of RA is associated with severe adverse reactions and toxicity. This limitation has necessitated the search for novel therapeutic products. We report here a traditional Chinese medicine-based herbal formula, Huo luo xiao ling dan (HLXL), which has potent antiarthritic activity as validated in the rat adjuvant-induced arthritis (AA) model. HLXL (2.3 g/Kg) was fed to Lewis (RT.1(1)) rats daily by gavage beginning at the onset of arthritis and then continued through the observation period. HLXL inhibited the severity of ongoing AA. This suppression of arthritis was associated with significant alterations in the T cell proliferative and cytokine responses as well as the antibody response against the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65). There was a reduction in the level of the proinflammatory cytokines IL-17 and IL-1β but enhancement of the anti-inflammatory cytokine IL-10 level. In addition, there was inhibition of both the anti-Bhsp65 antibody response and the serum level of nitric oxide. Thus, HLXL is a promising CAM modality for further testing in RA patients.
20826754 Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte membrane 2010 Oct 1 CD18 integrins are adhesion molecules expressed on the cell surface of leukocytes and play a central role in the molecular mechanisms supporting leukocyte migration to zones of inflammation. Recently, it was discovered that CD11a/CD18 is shed from the leukocyte surface in models of inflammation. In this study, we show that shedding of human CD11/CD18 complexes is a part of synovial inflammation in rheumatoid arthritis and spondyloarthritis but not in osteoarthritis. In vivo and in vitro data suggest that the shedding is driven by TNF-α, which links the process to central events in the inflammatory response. The shed complexes contain multiple heterodimers of CD11/CD18, are variable in size, and differ according to the type of synovial inflammation. Furthermore, the differential structures determine the avidity of binding of the complexes to the ICAM-1. With the estimated concentrations of CD11/CD18 in plasma and synovial fluid a significant coverage of binding sites in ICAM-1 for CD18 integrins is expected. Based on cell adhesion experiments in vitro, we hypothesize that the large soluble complexes of CD11/CD18 act in vivo to buffer leukocyte adhesion by competing with the membrane-bound receptors for ICAM-1 binding sites. As reported here for synovial inflammation changes in the concentration or structure of these complexes should be considered as likely contributors to disease activity.
21056727 Macrophage proinflammatory activation and deactivation: a question of balance. 2010 Macrophages play key roles in inflammation. During the onset of the inflammatory process, these phagocytic cells become activated and have destructive effects. Macrophage activation, which involves the induction of more than 400 genes, results in an increased capacity to eliminate bacteria and to regulate many other cells through the release of cytokines and chemokines. However, excessive activation has damaging effects, such as septic shock, which can lead to multiple organ dysfunction syndrome and death. In other situations, persistence of proinflammatory activity results in the development of chronic inflammation, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. To prevent undesirable effects, several mechanisms have evolved to control the excess of activation, thereby leading to macrophage deactivation and the resolution of inflammation. In this review, we discuss several mechanisms that mediate macrophage deactivation.
20857810 [Arthroscopy of the elbow]. 2010 Jul Elbow arthroscopy has become an indispensable method of surgical care of injuries and their consequences and damages that affect the elbow. The advantages of elbow arthroscopy in comparison to classical open surgery are multiple. Primarily, arthroscopy allows an excellent view of intra-articular structures and thus a detailed overview of the entire joint which enables us to perform complete surgery without opening the joint. Furthermore, morbidity is significantly smaller, rehabilitation is faster, and return to daily activities is also faster. Basic requirements for successful application of elbow arthroscopy are careful planning of the procedure, very good knowledge of regional anatomy of the elbow, strictly following the rules of performing the procedure, good technique and an experienced surgeon. Pathologies that can currently be addressed arthroscopically include osteochondritis dissecans of elbow, lateral epicondylitis, synovial plica syndrome, elbow osteoarthritis, elbow contracture, as well as the diseases where the synovectomy is needed, such as rheumatoid arthritis, pigmented villonodular synovitis, synovial chondromatosis and hemophiliac synovitis.
20467469 IL-17B Can Impact on Endothelial Cellular Traits Linked to Tumour Angiogenesis. 2010 IL-17B is a member of the IL-17 cytokine family which have been implicated in inflammatory response and autoimmune diseases such as rheumatoid arthritis. The founding member of this family, IL-17 (or IL-17A), has also been implicated in promoting tumour angiogenesis through the induction of other proangiogenic factors. Here we examine the potential of recombinant human IL-17B to contribute to the angiogenic process. In vitro rhIL-17B was able to inhibit HECV endothelial cell-matrix adhesion and cellular migration and also, at higher concentrations, could substantially reduce tubule formation compared to untreated HECV cells in a Matrigel tubule formation assay. This data suggests that IL-17B may act in an antiangiogenic manner.
19541524 1st Proceedings of the European American Rheumatology Association Immunotherapy in Rheumat 2009 Jul Evidence is often insufficient to answer questions in clinical practice. In an effort to fill these "gaps" between clinical investigation and daily conundrums, practicing rheumatologists use experience, logic, pathophysiology, individual patients and collegial consultation. In order to capture this science of clinical practice, a group of European and American clinicians and clinician investigators worked in investigative teams or Study Sections, each devoted to utilizing the science of clinical practice to address and critical clinical questions in Rheumatoid Arthritis, Imaging, Vasculitis and Gout that are inadequately answered by published evidence. Conclusions were summarized by a method of debate and discussion. It is anticipated that by defining uncertainty and using such an analytical and experiential method, rheumatologists can assist themselves in solving problems in their daily practice.
19491915 Systemic lupus erythematosus clinical trials-an interim analysis. 2009 Jun Since the current standards for drug approval were established nearly half a century ago, no drug has been approved for the treatment of systemic lupus erythematosus (SLE). Despite this sobering history, interest in drug development for SLE has heightened in the past few years. This enthusiasm has been fueled in large part by the success of biologic therapy for rheumatoid arthritis and other autoimmune diseases. Unfortunately, despite considerable clinical trial activity, this interest has not yet translated into the discovery of an effective treatment for SLE. This article provides an analysis of the major clinical trials in SLE, and offers an interpretation of the results that could illuminate the path forward.
19880574 Pathogenic role of anti-endothelial cell antibodies in autoimmune rheumatic diseases. 2009 Nov Anti-endothelial cells antibodies have been detected in numerous autoimmune and inflammatory diseases, including systemic lupus erythematous, rheumatoid arthritis, vasculitis and sarcoidosis. Anti-endothelial cells antibodies bind to endothelial cell antigens and induce endothelial damage. Their effects on the endothelial cell have been considered responsible, at least in part, by the vascular injury which occurs in these pathological conditions.
19280920 [Contribution of Th-1, Th-2, Th-17 or regulatory T cells to connective tissue diseases]. 2009 Mar Connective tissue diseases (or systemic autoimmune diseases), such as rheumatoid arthritis or systemic lupus erythematosus, are characterized by B cell hyperactivity and production of various autoantibodies. T cells help B cell activation in the germinal center by enhancing somatic hypermutation and generation of high affinity pathogenic autoantibodies. Previously helper T cells were divided into Th-1 and Th-2 cells. Recently, Th-17 cells and regulatory T cells have been identified as distinct T cell lineages and their roles in inflammation or immune regulation are under intensive investigation. In this review, we discuss the contribution of each T cell subset to autoantibody production and systemic autoimmune diseases.