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ID PMID Title PublicationDate abstract
16945141 Fine mapping of genes within the IDDM8 region in rheumatoid arthritis. 2006 The IDDM8 region on chromosome 6q27, first identified as a susceptibility locus for type 1 diabetes, has previously been linked and associated with rheumatoid arthritis (RA). The region contains a number of potential candidate genes, including programmed cell death 2 (PDCD2), the proteosome subunit beta type 1 (PSMB1), delta-like ligand 1 (DLL-1) and TATA box-binding protein (TBP) amongst others. The aim of this study was to fine map the IDDM8 region on chromosome 6q27, focusing on the genes in the region, to identify polymorphisms that may contribute to susceptibility to RA and potentially to other autoimmune diseases. Validated single nucleotide polymorphisms (SNPs; n = 65) were selected from public databases from the 330 kb region of IDDM8. These were genotyped using Sequenom MassArray genotyping technology in two datasets; the test dataset comprised 180 RA cases and 180 controls. We tested 50 SNPs for association with RA and any significant associations were genotyped in a second dataset of 174 RA cases and 192 controls, and the datasets were combined before analysis. Association analysis was performed by chi-square test implemented in Stata software and linkage disequilibrium and haplotype analysis was performed using Helix tree version 4.1. There was initial weak evidence of association, with RA, of a number of SNPs around the loc154449 putative gene and within the KIAA1838 gene; however, these associations were not significant in the combined dataset. Our study has failed to detect evidence of association with any of the known genes mapping to the IDDM8 locus with RA.
17133581 The -169C/T polymorphism in FCRL3 is not associated with susceptibility to rheumatoid arth 2006 Dec OBJECTIVE: In Japanese individuals, the -169C/T single-nucleotide polymorphism (SNP) in FCRL3 has been reported to be associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroid diseases. The objective of this study was to test the association of this SNP with RA and SLE, in a case-control study of Korean individuals. METHODS: The -169C/T SNP in FCRL3 was genotyped in 1,060 patients with RA, 457 patients with SLE, and 697 unaffected control subjects, using the MassARRAY SNP genotyping system. Associations were tested by multivariate logistic regression, with adjustments for age and sex. RESULTS: No association was detected between the -169C/T SNP and RA (odds ratio [OR] 1.11, 95% confidence interval [95% CI] 0.83-1.48, P = 0.50) or SLE (OR 1.00, 95% CI 0.73-1.37, P = 0.99). This SNP was not associated with rheumatoid factor status, shared epitope status, radiographic severity in patients with RA, or disease manifestations in patients with SLE. CONCLUSION: The association of the -169C/T SNP in FCRL3 with RA and SLE that was observed in Japanese patients was not replicated in a Korean population.
16357750 Biologic therapies in clinical development for the treatment of rheumatoid arthritis. 2005 Jun The therapeutic objective in patients with rheumatoid arthritis (RA) is reduction of disease activity with an ultimate goal of disease remission. Limitations of currently available disease-modifying antirheumatic drugs and biologic therapies suggest that there remains an unmet need for agents that advance these goals in a greater proportion of patients. Progress in our understanding of the regulatory molecules and pathways that mediate the immune and inflammatory responses necessary for the initiation and perpetuation of RA has led to the identification of new targets for therapy. It is expected that the therapeutic modulation of these targets, which include proinflammatory cytokines, T and B cells, adhesion molecules, chemokines, and intra- and extracellular signaling pathways, can provide new treatment strategies in patients with RA and other autoimmune disorders. Toward this end, a series of novel agents with diverse mechanisms of action are in development. Although many of these agents are still beyond the clinical horizon, several of them have shown promise in recent trials. This article reviews a few of the many treatment strategies currently being evaluated, which are hoped to lead to greater benefits and better disease management in the clinical setting.
16518573 Local cell proliferation in rheumatoid synovial tissue: analysis by cyclin expression. 2006 Nov The immunohistochemical staining of cyclins was done to evaluate the proliferating cells in synovial tissue of rheumatoid arthritis (RA). Synovial specimens obtained from 18 patients with RA, 12 with osteoarthritis (OA), and 8 with traumatic arthritis (TA) were used for immunostaining of cyclins A and B1 and proliferating cell nuclear antigen (PCNA). The positive cells in lining layer (synoviocytes) and sublining layer (lymphoid and nonlymphoid cells) were counted. Moreover, the relationship between the frequency of their positive cells and clinical data of RA patients was analyzed statistically. In general, cyclin-A-, cyclin-B1-, and PCNA-positive cells in RA were more frequently observed as compared with those in OA and TA. Significant differences were found between RA and OA or TA in cyclin-A-, cyclin-B1-, and PCNA-positive sublining lymphoid cells, between RA and OA or TA in cyclin-B1- and PCNA-positive sublining nonlymphoid cells, and between RA and OA in cyclin-B1-positive synoviocytes. The ratio of cyclin-A- or cyclin-B1-positive cells per PCNA-positive cells was significantly higher in sublining lymphoid cells in RA than TA and in sublining lymphoid and nonlymphoid cells of RA than OA or TA. Moreover, a better relationship was observed between the frequency of cyclin-A-positive synoviocytes and age and between cyclin-A-positive sublining nonlymphoid cells and duration of the disease in RA patients. Our data demonstrated clearly that synoviocytes, as well as sublining lymphoid and nonlymphoid cells, could divide in situ, and more frequent cell division and a higher ratio of cyclin-A- or cyclin-B1-positive/PCNA-positive sublining cells could occur in RA than OA and TA.
17075400 Hearing loss in rheumatoid arthritis. 2006 Nov OBJECTIVE: The objective of this study was to evaluate whether patients with rheumatoid arthritis (RA) are more likely to have subclinical hearing loss compared with persons without RA. METHODS: This is a case-control cross-sectional study of 29 patients with RA with disease duration greater than 5 years. Five males and five females were recruited into each decade category (age 40-49, 50-59, and 60-69). These cases were matched in a 1:1 ratio by sex and age to 30 control subjects. A comprehensive set of audiometric and disease severity assessments were performed. RESULTS: Seventeen (59%) of 29 patients with RA had abnormal hearing for at least one frequency (four in one ear, 13 in two ears) by audiometry as did 14 (47%) of 30 control subjects (five in one ear, nine in two ears). The percentage of patients with hearing loss (% RA vs. % control subjects) was: 45% versus 40% sensorineural, 10% versus 7% conductive, and 3% versus 0% mixed hearing loss. In RA versus control subjects, acoustic reflex threshold was abnormal in 17% versus 7%; speech reception threshold was abnormal in 10% versus 3%. Tympanometry and otoacoustic emission findings were similar in both groups. Word recognition did not differ between patients with RA and control subjects. In patients with RA/control subjects, hearing handicap, dizziness, and health assessment questionnaires were abnormal in 28%/7%, 14%/3%, and 72%/7%, respectively. CONCLUSION: There was no difference found in objective audiometric measurements in patients with RA compared with non-RA control subjects. Subjectively patients with RA were more likely to perceive themselves as having hearing disturbances, which may be related to overall disease related functional impairment.
16808310 [Influence of recombinant human erythropoietin (rHuEPO) on plasma levels of selected hormo 2005 Aug During recent years, it was shown, that treatment with recombinant human erythropoietin (rHuEPO) stimulates erythropoiesis in patients both with renal and nonrenal anaemia. Additionally in patients with chronic renal failure treated with rHuEPO a significant, however only transient, influence on function of endocrine glands was also found. The present study aimed to asses for the first time the influence of rHuEPO on function of endocrine organs in anaemic patients with rheumatoid arthritis and normal renal function. Twenty two woman with rheumatoid arthritis and concomitant anaemia (Ht < or = 30%) were enrolled into the study. In 13 of them rHuEPO was used during 4 months (5000 IU 2 times per week s.c.). The rest 9 woman with similar degree of anaemia did not receive rHuEPO therapy. In woman of both groups intensive clinical and biochemical monitoring during 4 months period was performed. Blood samples were withdrawn before and after 4 months of rHuEPO therapy or clinical observation only. In these blood samples plasma concentrations of somatotropin (HGH), insulin (IRI), aldosterone (ALD), atrial natriuretic peptide (ANP), 25-hydroxycholecalciferol (25OHD3), intact parathyroid hormone (iPTH) and plasma renin activity (PRA) were estimated. After 4 months of rHuEPO therapy significant increase of plasma IRI, ANP concentrations and significant decrease of PRA and plasma ALD, HGH concentrations were found. Therapy with rHuEPO does not influence significantly plasma iPTH and 25OHD3 concentration. During 4 months of clinical observation in patients not treated with rHuEPO, plasma concentrations of HGH, IRI, ALD, ANP, 25OHD3, iPTH and plasma renin activity (PRA) did not change significantly. Results obtained in this study suggest, that rHuEPO therapy does influence the function of endocrine organs also in patients with rheumatoid arthritis with normal renal function.
15297281 Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha. 2005 Mar BACKGROUND: Research on autoantibody formation in patients treated with TNF alpha inhibitors has produced contradictory results. OBJECTIVE: To study the prevalence of autoantibodies in patients with rheumatoid arthritis treated with the TNF alpha inhibitor infliximab. METHODS: 53 patients (48 female, 11 male) treated with infliximab for rheumatoid arthritis were followed for autoantibody production before treatment and after 14, 30, and 54 weeks. Six patients treated with etanercept were studied for comparison. The analyses included antibodies against nuclear antigens (ANA), extractable nuclear antigens, double stranded (ds)DNA (by ELISA, IIF on Crithidia luciliae for IgM and IgG, and Farr assay), nucleosomes, cardiolipin, smooth muscle, mitochondria, proteinase 3, and myeloperoxidase antigens. RESULTS: The number of patients treated with infliximab who developed antibodies against dsDNA of both IgG and IgM class (tested by IIF) increased significantly. The prevalence of patients positive for IgG class increased to 66% at 30 weeks and 45% at 54 weeks, and of IgM class to 85% and 70%, respectively. The titre and number of patients expressing antibodies against nucleosomes and ANA also increased significantly. The number of rheumatoid factor or anticardiolipin positive patients was stable and there was no increase in antibodies against the other antigens. A lupus-like syndrome was seen in one patient. No patient treated with etanercept developed any of these autoantibodies. CONCLUSIONS: Patients treated with infliximab may develop anti-dsDNA antibodies of both IgM and IgG class, anti-nucleosome antibodies, and ANA, with a gradual increase until 30 weeks.
16271291 Genome-wide single nucleotide polymorphism analyses of rheumatoid arthritis. 2005 Because of the limitations of candidate gene studies and linkage analyses for common diseases, genome-wide association studies are now recognized as a powerful approach to mapping responsible genes with modest effects on various diseases. We performed whole genome case-control linkage disequilibrium (LD) mapping for rheumatoid arthritis (RA)-associated genes in Japanese subjects using single nucleotide polymorphisms (SNPs) mainly discovered in gene-containing regions. We identified RA-associated polymorphisms in two genes/loci, PADI4 and SLC22A4/A5 cluster. PADI4 catalyzes the conversion of arginine residues to citrulline in proteins. Recent reports on the high specificity of autoantibodies against citrullinated proteins to RA and the results of our study suggest that citrullination by PADI4 is a fundamental phenomenon of RA. On the other hand, the functions of SLC22A4/A5 have not been studied in detail, but SLC22A4/A5 have been reported to have multiple polymorphisms associated with several autoimmune diseases. Thus, large-scale LD mapping appears to be effective for identifying RA-associated polymorphisms.
16490750 RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion 2006 Sep OBJECTIVES: Receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) have been demonstrated to be critical regulators of osteoclast generation and activity. In addition, RANKL has been implicated as an important mediator of bone erosion in rheumatoid arthritis (RA). However, the expression of RANKL and OPG at sites of pannus invasion into bone has not been examined. The present study was undertaken to further elucidate the contribution of this cytokine system to osteoclastogenesis and subsequent bone erosion in RA by examining the pattern of protein expression for RANKL, OPG and the receptor activator of NF-kappaB (RANK) in RA at sites of articular bone erosion. METHODS: Tissues from 20 surgical procedures from 17 patients with RA were collected as discarded materials. Six samples contained only synovium or tenosynovium remote from bone, four samples contained pannus-bone interface with adjacent synovium and 10 samples contained both synovium remote from bone and pannus-bone interface with adjacent synovium. Immunohistochemistry was used to characterize the cellular pattern of RANKL, RANK and OPG protein expression immediately adjacent to and remote from sites of bone erosion. RESULTS: Cellular expression of RANKL protein was relatively restricted in the bone microenvironment; staining was focal and confined largely to sites of osteoclast-mediated erosion at the pannus-bone interface and at sites of subchondral bone erosion. RANK-expressing osteoclast precursor cells were also present in these sites. OPG protein expression was observed in numerous cells in synovium remote from bone but was more limited at sites of bone erosion, especially in regions associated with RANKL expression. CONCLUSIONS: The pattern of RANKL and OPG expression and the presence of RANK-expressing osteoclast precursor cells at sites of bone erosion in RA contributes to the generation of a local microenvironment that favours osteoclast differentiation and activity. These data provide further evidence implicating RANKL in the pathogenesis of arthritis-induced joint destruction.
17182267 Long-term results of infliximab therapy in rheumatoid arthritis: experience acquired by th 2007 Jan OBJECTIVE: Infliximab is effective in patients with rheumatoid arthritis (RA). Add-on infliximab therapy in patients on methotrexate results in a rapid gain in effectiveness, which lasts at least 1 year. The objective of this study was to evaluate the effectiveness and continuation rate of infliximab in patients with RA after the first year of treatment. METHODS: The first 50 patients with RA who were given infliximab in the North-Pas-de-Calais region of France were included in a multicenter open-label study. The patients had severe RA or failed to respond to conventional medications. Infliximab was given in a dosage of 3 mg/kg every 8 weeks in combination with methotrexate. Effectiveness was evaluated using the DAS28-3 score and EULAR response criteria. The dates and reasons of infliximab discontinuations were recorded. RESULTS: The 2-year infliximab continuation rate was 70%. Serious adverse events requiring infliximab discontinuation occurred in 7 patients. Mean DAS28-3 scores in the 35 patients who took infliximab for at least 2 years were 6.42 at baseline, 4.33 after 30 weeks, 4.31 after 54 weeks, and 3.86 after 102 weeks. According to EULAR criteria after 102 weeks, there were 12 good responders, 18 moderate responders, and 5 nonresponders. CONCLUSION: Experience acquired in the North-Pas-de-Calais district of France suggests that infliximab is continued for more than 2 years in more than two-thirds of patients and remains effective over this period.
16125192 Efficient promotion of collagen antibody induced arthritis (CAIA) using four monoclonal an 2005 Sep An antibody response to defined epitopes located on the triple helical portion of type II collagen (CII) is associated with the development of collagen-induced arthritis (CIA) and rheumatoid arthritis (RA). Monoclonal antibodies to epitopes associated with arthritis, but not antibodies specific for epitopes not associated with arthritis, induce arthritis in mice, the so-called collagen antibody induced arthritis (CAIA) model. We have selected monoclonal IgG antibodies specific for four well-defined major epitopes on triple helical CII, the C1, J1, D3 and U1 epitopes. These antibodies bind the epitopes specifically as determined using recombinant or synthetic triple helical epitopes. They are encoded from somatically mutated V genes. They all bind cartilage in vivo in normal mice. All of the antibodies induce mild arthritis after injection intravenously and if injected as a cocktail they induce severe clinical arthritis. Intravenous injection of a total of 4 mg antibodies (0.5 mg antibodies per clone) induced arthritis in several different mouse strains without any secondary immune stimulus and intraperitoneal injection of LPS 7 days later dramatically raised the severity. Thus, this method is recommended as a new protocol for the induction of CAIA.
16447221 Activation of p38 MAPK is a key step in tumor necrosis factor-mediated inflammatory bone d 2006 Feb OBJECTIVE: To investigate whether activation of p38 MAPK is a crucial signaling factor in inflammatory bone destruction mediated by tumor necrosis factor (TNF). Mice overexpressing TNF were treated with 2 different inhibitors of p38 MAPK, and the effect of this treatment on joint inflammation and structural damage was assessed. METHODS: Human TNF-transgenic mice received systemic treatment with 2 different p38 MAPK inhibitors (RO4399247 and AVE8677). Treatment was started at the time of symptom onset and lasted for 6 weeks. Mice were assessed for clinical signs of arthritis, bone erosion, and cartilage damage. In addition, the effect of these inhibitors on osteoclast generation in vitro and in vivo was assessed. RESULTS: Both p38 MAPK inhibitors significantly reduced clinical signs of TNF-mediated arthritis. This was attributable to reducing synovial inflammation by 50% without affecting the cellular composition of the infiltrate. Synovial expression of interleukin-1 and RANKL was reduced upon p38 MAPK blockade, and activation of the molecular target MAPK-activated protein kinase 2 (MAPKAP-2) was also inhibited. Proteoglycan loss of articular cartilage was reduced by 50%, although p38 MAPK inhibition did not change matrix molecule synthesis by cultivated chondrocytes. Importantly, bone loss was almost completely prevented by p38 MAPK inhibition. The numbers of synovial osteoclasts and precursors were dramatically reduced, and both p38 MAPK inhibitors also inhibited in vitro osteoclastogenesis at micromolar concentrations and blocked activation of MAPKAP-2 as well as differentiation markers in cultured osteoclast precursors. CONCLUSION: These results suggest the major importance of p38 MAPK for TNF-mediated inflammatory bone destruction in arthritis and suggest that inhibition of p38 MAPK might be an important tool for reducing structural damage in rheumatoid arthritis.
16014537 Effective use of autoantibody tests in the diagnosis of systemic autoimmune disease. 2005 Jun Screening for disease-specific autoantibodies may be useful in asymptomatic ANA-positive individuals as a means of evaluating the risk of developing a systemic autoimmune disease such as systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), scleroderma (SSc), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or primary biliary cirrhosis (PBC) in the future. In patients with known or suspected systemic autoimmune disease, a panel of disease-specific markers may help to establish a diagnosis and to assess the prognosis. The great strides in autoantibody testing over the last 20 years make it feasible to use specific autoantibody markers to improve diagnostic accuracy in systemic autoimmune disease. New technology enabling screening for multiple autoantibodies may further enhance the clinical usefulness of autoantibody testing, making it possible to diagnose autoimmune disease in its earliest stages and to intervene before serious end organ damage occurs.
16920501 Dendritic cells: vehicles for tolerance induction and prevention of autoimmune diseases. 2006 Adaptive immune responses are orchestrated by specialized professional antigen-presenting cells (APCs), the dendritic cells (DCs), which play crucial roles as initiators and modulators of adaptive immune responses. A main feature of DCs is their phenotypic and functional plasticity. In the absence of any inflammation or pathogenic elements, most DCs in peripheral tissues and lymphoid organs have a resting, immature phenotype characterized by high endocytic capacity and low surface expression of MHC- and costimulatory molecules. However, upon interaction with microbial ligands, pro-inflammatory cytokines or CD40Ligand, DCs rapidly acquire an activated phenotype. These mature DCs have a very efficient T cell-priming ability as a consequence of upregulation of MHC- and costimulatory molecules on their cell surface. For this reason, DC-based vaccines have been used successfully to combat infections and malignancies. Nonetheless, evidence is accumulating that, especially immature, or semi-matured, DCs also have a potent ability to tolerize T cells or prevent undesired immune reactions. Therefore, current and prospective strategies to promote the inherent tolerogenic potential of DCs are a rational approach for the therapy of autoimmune diseases such as rheumatoid arthritis (RA). This review summarizes some aspects of the intriguing ability of DCs to steer the outcome of immunity and their potency to modulate the outcome of various pathological conditions.
16338211 The CORRONA database. 2006 Jan BACKGROUND: Large, long-term databases are needed in order to provide information on the safety and efficacy of new agents used in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). These databases can provide data which is well beyond what is available from industry-sponsored investigations. METHODS: The structure, governance, content, context and developmental plan of the CORRONA database are described. RESULTS: The CORRONA database has grown from start up in 2002 to the largest independent database in North America which collects data from both rheumatologists and patients at the time of a clinical encounter. Data are collected as often as every 3 months in RA and every 6 months in PsA. As of the time of this writing, the CORRONA database consists of approximately 9000 patients with RA and 1000 with PsA. Data can be used to elucidate toxicities found in frequencies which would be considerably less common than can be uncovered in industry-sponsored investigations. In addition, actual prescribing patterns and responses in clinical practice can be investigated and described. CONCLUSION: After 3 years of data collection, the CORRONA database is now appropriately able to make significant contributions to our understanding of the safety, efficacy of drugs, as well as demographic, and socioeconomic profiles of patients with RA and PsA. It has evolved from a nascent database to a mature one poised to make significant contributions.
17080202 Cortistatin as a potential multistep therapeutic agent for inflammatory disorders. 2006 Sep The induction of immune tolerance is critical for the prevention of autoimmunity and the maintenance of immune homeostasis. The identification of factors involved in the maintenance or restoration of such tolerance has become the focus of new therapies for inflammatory and autoimmune diseases. Cortistatin, a recently discovered cyclic neuropeptide related to somatostatin, has emerged as a potential endogenous antiinflammatory factor based on its production by, as well as its binding to, immune cells. Thus, cortistatin has been found to downregulate the inflammatory response mediated by activated macrophages. The present work reviews various recent studies involving different experimental models of sepsis, rheumatoid arthritis and inflammatory bowel disease, demonstrating that cortistatin treatment offers great benefits at both the clinical and pathological levels. These include the downregulation of both inflammatory and Th1-mediated autoimmune disease components and the emergence of regulatory T cells (Treg) that suppress autoreactive T cells, both of which contribute to the restoration of immune tolerance. While many questions need to be resolved, cortistatin appears to be an exciting and promising candidate for the treatment of several chronic inflammatory diseases and autoimmune disorders.
15843582 Resistin, an adipokine with potent proinflammatory properties. 2005 May 1 The adipokine resistin is suggested to be an important link between obesity and insulin resistance. In the present study, we assessed the impact of resistin as inflammatogenic cytokine in the setting of arthritis. In vitro experiments on human PBMC were performed to assess cytokine response and transcription pathways of resistin-induced inflammation. Proinflammatory properties of resistin were evaluated in animal model by intra-articular injection of resistin followed by histological evaluation of the joint. Levels of resistin were assessed by ELISA in 74 paired blood and synovial fluid samples of patients with rheumatoid arthritis. Results were compared with the control group comprised blood samples from 34 healthy individuals and 21 synovial fluids from patients with noninflammatory joint diseases. We now show that resistin displays potent proinflammatory properties by 1) strongly up-regulating IL-6 and TNF-alpha, 2) responding to TNF-alpha challenge, 3) enhancing its own activity by a positive feedback, and finally 4) inducing arthritis when injected into healthy mouse joints. Proinflammatory properties of resistin were abrogated by NF-kappaB inhibitor indicating the importance of NF-kappaB signaling pathway for resistin-induced inflammation. Resistin is also shown to specifically accumulate in the inflamed joints of patients with rheumatoid arthritis and its levels correlate with other markers of inflammation. Our results indicate that resistin is a new and important member of the cytokine family with potent regulatory functions. Importantly, the identified properties of resistin make it a novel and interesting therapeutic target in chronic inflammatory diseases such as rheumatoid arthritis.
15750374 Ginger extract components suppress induction of chemokine expression in human synoviocytes 2005 Feb INTRODUCTION: Ginger has a long history of medicinal use, particularly as an anti-inflammatory agent for a wide variety of diseases such as arthritis. Suppression of inflammation in arthritis is attributed to suppression of proinflammatory cytokines and chemokines produced by synoviocytes, chondrocytes, and leukocytes. OBJECTIVE: This study aimed to elucidate the effect of a combination ginger extract and its individual components on chemokine expression in human synoviocytes. METHODS: Human synoviocytes were incubated with 100 microg/mL combination ginger extract (GE) of Alpinia galanga (AG) and Zingiber officinale (ZO); AG extract alone; ZO extract alone; or control media, for 1 hour at 37 degrees C, 5% CO2. Cells were next activated with 1 ng/mL of tumor necrosis factor alpha (TNF-alpha) for 1 hour to determine macrophage chemotactic factor (MCP-1) and interferon-gamma activated protein (IP-10) mRNA levels using reverse transcriptase polymerase chain reaction (RT-PCR). Secreted MCP-1 and IP-10 were quantified by enzyme-linked immunosorbent assay (ELISA) following a 24 hour incubation period. RESULTS: The GE combination was consistently more effective in decreasing chemokine mRNA and chemokine secreted protein levels than its individual components ZO or AG. In comparison, ZO was more effective than AG in suppressing chemokine expression. CONCLUSION: The present study demonstrates that GE inhibits chemokine expression, and that the combination of ZO and AG components acts synergistically. This ginger formulation may be useful for suppressing inflammation due to arthritis.
16393443 Real-world utilization of DMARDs and biologics in rheumatoid arthritis: the RADIUS (Rheuma 2006 Jan OBJECTIVE: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice. RESEARCH DESIGN AND METHODS: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5-year study. RESULTS: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy. CONCLUSIONS: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001-2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.
15966373 [Pulmonary tuberculosis with cerebellar lesion in a patient after anti-TNF-alpha (inflixim 2005 Apr We report a case of pulmonary tuberculosis in a 51-year-old Japanese woman, who received treatment with infliximab for active rheumatoid arthritis. She had cough and sputum after the second infusion of the drug, small nodular lesions of right lung field and left lower lobe on her chest CT and a small nodular lesion of right cerebellar lobe on her cranial MRI were identified. Mycobacterium tuberculosis was cultured from her sputum. Therefore, we diagnosed her illness as pulmonary tuberculosis with a cerebellar lesion. The patient was treated with anti-tuberculosis drugs and showed marked improvement in lesions of the lung and brain. We considered this case a tuberculosis reactivation after infliximab treatment because of the short interval between the administration of infliximab and the occurrence of tuberculosis, and the complication of extrapulmonary lesion that suggested brain tuberculoma.