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ID PMID Title PublicationDate abstract
18320137 The evaluation of latent tuberculosis in rheumatologic diseases for anti-TNF therapy: expe 2008 Sep It is recommended to evaluate the presence of latent tuberculosis infection (LTBI) before initiating antitumor necrosis factor alpha (anti-TNF) therapy for rheumatologic diseases. We aimed to present the follow-up results of 192 patients with rheumatologic diseases before anti-TNF therapy for LTBI. We enrolled 192 patients who were given anti-TNF therapy for their rheumatologic diseases between April 2005 and January 2008. The demographic characteristics of the patients were recorded. Chest X-ray was obtained and tuberculin skin test (TST) was performed in all patients before anti-TNF therapy. LTBI was assessed by detailed history of close contact with infectious cases within the last year, abnormal chest radiography, and positive TST (> or =5 mm) before initiating anti-TNF therapy. Patients with anti-TNF therapy were followed with 2-month intervals for active tuberculosis by pulmonary and extrapulmonary symptoms, physical examination, and chest X-ray. Of 192 patients, 104 (54.2%) patients were women, age (mean +/- SD) 43.1 +/- 12.7 years and 88 (45.8%) patients were men, age (mean +/- SD) 39.3 +/- 11.2 years. Ninety-one (47.4%) of them had rheumatoid arthritis (RA); 92 (47.9%) had ankylosing spondylitis (AS), and nine (4.7%) had psoriatic arthritis. Isoniazid treatment was started in 129 (67.2%) patients in whom LTBI was detected. No significant difference was observed for TST positivity (TST > or = 5 mm) between the patients with RA and AS (p = 0.101). Similarly, no significant difference was also observed for TST positivity between the patients who received immunosuppressive therapy and those who did not (p = 0.154). Only three (1.6%) patients developed active tuberculosis at the study period. We suggested that in despite of the presence of rheumatologic disease and/or immunosuppressive therapy, TST is an acceptable and available diagnostic test for detecting LTBI before anti-TNF therapy.
17225928 Safety of etanercept therapy in rheumatoid patients undergoing surgery: preliminary report 2007 Sep This is a preliminary report on a case-series of rheumatoid patients that underwent various kinds of elective surgery but did not withdraw etanercept therapy in spite of physician advise. Elective surgery consisted of right knee surgical prosthesis, bilateral cataract, bilateral hallux valgus, right hip prosthesis, bladder stone by cystoscopy and left inguinal hernia. All the patients had a regular healing rate. During follow-up (6-12 months) no one of these patients were suffering from infective complications after surgery. According to same recent literature results, our data suggest that it is the time to value rheumatoid patient preferences through a correct information about cost-benefit of this treatment to establish together with patients if etanercept therapy has to be discontinued before and after elective surgery. Finally, we think that adverse drug reaction surveillance has to be boosted, and editors of leading scientific journal should publish more papers on case-series about drug safety and tolerability in particular conditions.
17932565 Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the inte 2007 Nov Fibrin deposition within joints is a prominent feature of arthritis, but the precise contribution of fibrin(ogen) to inflammatory events that cause debilitating joint damage remains unknown. To determine the importance of fibrin(ogen) in arthritis, gene-targeted mice either deficient in fibrinogen (Fib-) or expressing mutant forms of fibrinogen, lacking the leukocyte receptor integrin alphaMbeta2 binding motif (Fibgamma390-396A) or the alphaIIbbeta3 platelet integrin-binding motif (FibgammaDelta5), were challenged with collagen-induced arthritis (CIA). Fib- mice exhibited fewer affected joints and reduced disease severity relative to controls. Similarly, diminished arthritis was observed in Fibgamma390-396A mice, which retain full clotting function. In contrast, arthritis in FibgammaDelta5 mice was indistinguishable from that of controls. Fibrin(ogen) was not essential for leukocyte trafficking to joints, but appeared to be involved in leukocyte activation events. Fib- and Fibgamma390-396A mice with CIA displayed reduced local expression of TNF-alpha, IL-1beta, and IL-6, which suggests that alphaMbeta2-mediated leukocyte engagement of fibrin is mechanistically upstream of the production of proinflammatory mediators. Supporting this hypothesis, arthritic disease driven by exuberant TNF-alpha expression was not impeded by fibrinogen deficiency. Thus, fibrin(ogen) is an important, but context-dependent, determinant of arthritis, and one mechanism linking fibrin(ogen) to joint disease is coupled to alphaMbeta2-mediated inflammatory processes.
19066178 FOXP3 expression in blood, synovial fluid and synovial tissue during inflammatory arthriti 2009 Dec OBJECTIVE: To analyse the distribution of FOXP3+CD25+CD4+ regulatory T cells (Treg) in peripheral blood, synovial fluid and tissue of patients with rheumatic disease during relapse and after local treatment. METHODS: FOXP3 expression was assessed by flow cytometry, immunohistochemistry, immunofluorescence and real-time polymerase chain reaction (RT-PCR). The functional suppressive capacity of Treg was analysed after co-culture with effector CD4+CD25- T cells through assessment of proliferation and cytokine secretion. RESULTS: It was shown that FOXP3 protein and mRNA expression in synovial fluid T cells was not confined solely to CD25(bright) T cells as seen in blood, but included CD25(intermediate) and even CD25(neg) T cells. Indeed, synovial fluid CD25(high) T cells showed similar suppressive capacity as CD25(bright) T cells, indicating the presence of functional Treg in T cells with lower intensity of CD25. In synovial tissue, FOXP3+ cells were present in low numbers within T-cell infiltrates and decreased further after intra-articular glucocorticosteroid administration, in parallel with the general reduction in inflammation. CONCLUSIONS: Identification of synovial fluid FOXP3+ Treg with varying intensities of CD25 opens up possibilities for thorough characterisation of this important T-cell subset in the inflammatory compartment. However, only scarce synovial membrane expression of FOXP3 was found even in the absence of overt inflammation, suggesting that the synovial membrane is a site that would benefit therapeutically from Treg expansion.
17075483 [Ileal and right colonic strictures due to prolonged non steroidal anti-inflammatory drug 2006 Oct Ileal and right colonic strictures due to long term NSAID intake are well known but rare. We report the case of a patient with rheumatoid arthritis presenting with one ileal, as well as a right and transverse colonic stricture. The latter two were treated by dilatation under colonoscopy, but due to an associated recurrence, and the necessity of treating the ileal stricture which was inaccessible, a transverse ileocolonic shunt was proposed under local anesthesia. Ileal and colonic strictures due to long term NSAID intake should first be treated, if possible, by discontinuing the drug, then by pneumatic dilatations and finally, if necessary, by surgery usually resection. The advantage of a gastrointestinal shunt is that it can be performed under local anesthesia in patients who are often in poor condition.
17317320 Analyses of immunosenescent markers in patients with autoimmune disease. 2007 May The objective of this study was to evaluate the degree of immunosenescence in patients with autoimmune disease. T cell receptor excision circles (TREC) and the percentage of CD4+CD28null T cells were studied as markers of immunosenescence in 175 patients with chronic autoimmune arthritis, other connective tissue autoimmune diseases, multiple sclerosis and 60 healthy controls. In both the rheumatoid arthritis (RA) and multiple sclerosis patient group, TREC numbers were age-inappropriately declined which points to an accelerated thymic output. Furthermore, enhanced percentages of CD4+CD28null T cells could be detected in a significant proportion of patients included in this study. These immunosenescent phenomena seemed to be present already early in the disease process. High percentages of CD4+CD28null T cells were associated with the presence of RA linked HLA DR4 alleles and with plasma reactivity to cytomegalovirus. Further analysis of CD4+CD28null T cells provided indications for a restricted T cell receptor (TCR) BV gene expression and cytoplasmic stores of various cytotoxic molecules. This study indicates that the immune system of patients with autoimmune diseases shows signs of an accelerated aging. Both genetic factors, such as HLA DR4, and environmental factors, like CMV infection, might speed up this immunosenescence and contribute in this way to disease pathogenesis.
17285224 Low serum level of COMP, a cartilage turnover marker, predicts rapid and high ACR70 respon 2007 Aug The aim of this study was to evaluate serum biomarkers, used in clinical routine, to predict the American College of Rheumatology (ACR) response to long-term anti-TNF alpha treatment (adalimumab). Sera from 29 consecutive rheumatoid arthritis patients were analysed for anti-cyclic citrullinated peptide (anti-CCP), cartilage oligomeric matrix protein (COMP) and IgM and IgA RFs (class-specific rheumatoid factors) at the start of treatment with adalimumab and after 3, 6 and 12 months. The response to the therapy was evaluated by ACR 20, 50, 70 and by DAS 28 scores. The mean serum COMP level of the population did not change after treatment. However, patients with low serum COMP levels (<10 U/l) at baseline showed a significant (p<0.02) higher ACR70 response (>50%) within 3 months, and also at 6 months, than patients with higher COMP values (ACR70<20%). This was also reflected by significantly higher decrease in DAS score at 3 (p<0.02) and 6 months (p<0.01) treatments. The IgM RF titre decreased significantly (p=0.02) after the therapy, but the percentage of serum positivity for anti-CCP and IgA/IgM RF did not change. No significant correlation was shown between serum COMP levels and C-reactive protein/erythrocyte sedimentation rate during the follow-up. Neither were any correlations shown between ACR/DAS 28 scores and anti-CCP, Ig M/IgA RFs. Our data indicate that low (<10 U/l) serum COMP before starting anti-TNF alpha treatment predicts a rapid (within 3 months) and high ACR70 response compared to RA patients with higher COMP values. This might reflect different mechanisms in the cartilage process in the RA disease at that time of treatment with different therapeutic sensitivity to anti-TNF alpha treatment.
18759290 Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RN 2008 Sep OBJECTIVE: Genetic variation in the gene for interleukin-6 (IL-6) contributes to the pathogenesis of inflammatory arthritis, but the role, if any, of epigenetic variability has not been reported. The aims of this study were to compare the DNA methylation status of the IL6 promoter in rheumatoid arthritis (RA) patients and control subjects and to study the effects on gene expression. METHODS: Genomic DNA was isolated from peripheral blood mononuclear cells (PBMCs) obtained from RA patients and healthy controls. Macrophages from healthy controls were isolated and stimulated with lipopolysaccharide (LPS). Methylation status was determined using bisulfite genomic sequencing and IL6 messenger RNA (mRNA) levels by quantitative polymerase chain reaction. Gel shift assays were performed with methylated or unmethylated probes and HeLa cell nuclear extract. RESULTS: The proximal CpG motifs (-666 to +27) were predominantly unmethylated and the upstream motifs (-1099 to -1001) were highly methylated in PBMCs from patients and controls. Methylation of individual CpG motifs was similar, except at -1099C, which was less methylated in the patients than in the controls (58% versus 98%; P = 1 x 10(-6)). To test whether this observation might relate to gene regulation, LPS-stimulated macrophages were grouped according to their IL6 mRNA stimulation index (SI). The level of methylation at -1099C was significantly lower in the group with high (SI >75) compared with the group with low (SI <10) induced mRNA levels (71% versus 93%; P = 0.007). Gel shift assays revealed decreased protein binding to the -1099C unmethylated probe. CONCLUSION: These data suggest that methylation of a single CpG in the IL6 promoter region may affect IL6 gene regulation and may play a role in the pathogenesis of RA.
16617917 Anesthetic implications for patients receiving exogenous corticosteroids. 2006 Apr Opposing views exist about perioperative replacement of corticosteroids and appropriate replacement dosages. Anesthesia providers must be aware of the need for corticosteroid replacement not only in patients who have primary adrenal insufficiency but also in patients who have adrenal insufficiency resulting from long-term corticosteroid therapy. Without adequate knowledge, the anesthesia provider may fail to prepare the patient to withstand the stress of surgery and may open the way for life-threatening hemodynamic abnormalities that accompany inadequate amounts of corticosteroids. The purpose of this article is to review the literature explaining the rationale and the proper perioperative dosing with corticosteroids for patients with long-standing asthma, rheumatoid arthritis, or Crohn disease. The review of literature reflects articles on endogenous hormones, exogenous hormones, diseases that require long-term corticosteroid therapy, the hypothalamus-pituitary-adrenal axis, and corticosteroid replacement therapy.
18505431 The nexus between atopic disease and autoimmunity: a review of the epidemiological and mec 2008 Jul There has been considerable interest in defining the relationship between the expression of allergic and autoimmune diseases in populations of patients. Are patients with autoimmune disease 'protected' from developing allergic (immunoglobulin E-mediated) diseases? Does the establishment of an atopic phenotype reduce the risk of the subsequent development of autoimmune diseases? Although there are clinical studies addressing this question, methodological problems, particularly in identification of atopic subjects, limits their usefulness. Moreover, an immune-based explanation of the observed epidemiological findings has relied on a paradigm that is currently undergoing increased scrutiny and modification to include newly defined effector cell subsets and the interaction between genetic and environmental factors, such as early endotoxin or mycobacterial exposure. To address this question, we reviewed a series of clinical reports that addressed coincidence or co-prevalence of atopy with four autoimmune diseases: psoriasis, rheumatoid arthritis, multiple sclerosis and type I diabetes mellitus. We present a model whereby active T helper type 1 (Th1) inflammation may suppress the development of atopy, and atopy may suppress the severity but not necessarily the onset of autoimmunity, and then discuss our model in the context of mechanisms of adaptive immunity with particular reference to the Th1/Th2 paradigms. Because the ultimate goal is to ameliorate or cure these diseases, our discussion may help to predict or interpret unexpected consequences of novel therapeutic agents used to target autoimmune or atopic diseases.
16802344 Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fib 2006 Jul OBJECTIVE: Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow-derived fibroblasts in terms of their ability to support survival of T cells and neutrophils. METHODS: Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured. RESULTS: Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon-beta. However, synovial and bone marrow fibroblasts shared an enhanced site-specific ability to maintain CD4 T cell survival in the absence of proliferation, an effect that was independent of fibroblast activation or proliferation but required direct T cell-fibroblast cell contact. In contrast, fibroblast-mediated neutrophil survival was less efficient, being independent of the site of origin of the fibroblast but dependent on prior fibroblast activation, and mediated solely by soluble factors, principally granulocyte-macrophage colony-stimulating factor. CONCLUSION: These results suggest an important functional role for fibroblasts in the differential accumulation of leukocyte subsets in a variety of tissue microenvironments. The findings also provide a potential explanation for site-specific differences in the pattern of T cell and neutrophil accumulation observed in chronic inflammatory diseases.
17255133 Clinical characteristics of Japanese patients with anti-OJ (anti-isoleucyl-tRNA synthetase 2007 May OBJECTIVES: The clinical and laboratory characteristics of seven patients with anti-aminoacyl-tRNA synthetase (ARS) autoantibodies, specifically anti-OJ (anti-isoleucyl-tRNA synthetase), were examined and compared with previously published findings. METHODS: Serum samples from 1135 Japanese patients with various autoimmune diseases and 48 normal individuals were screened for anti-OJ antibodies using RNA and protein immunoprecipitation assays. The patients whose sera contained anti-OJ antibodies were assessed regarding clinical symptoms, clinical course, laboratory findings, chest radiography and chest computed tomography. RESULTS: Sera from seven patients were found to contain anti-OJ antibodies. These autoantibodies were associated with interstitial lung disease (ILD) and myositis. The diagnoses of the seven patients were idiopathic interstitial pneumonias (IIPs) in three, polymyositis (PM) in three and PM-rheumatoid arthritis (RA) overlap in the remaining one. All patients had ILD, but muscle weakness and polyarthritis were seen only in four. Raynaud's phenomenon and sclerodactyly were absent in all patients. CONCLUSIONS: These results indicate that the presence of anti-OJ autoantibodies may distinguish a subtype of anti-ARS syndrome that is more closely associated with ILD than myositis or Raynaud's phenomenon.
18718986 Inhibition of radiographic progression with combination etanercept and methotrexate in pat 2009 Jul OBJECTIVE: To determine the effect of changing from etanercept or methotrexate monotherapy to etanercept plus methotrexate combination therapy on radiographic progression in rheumatoid arthritis (RA) patients. METHODS: Patients enrolled in this 1-year open-label study previously completed a 3-year blinded study in which they received methotrexate or etanercept monotherapy or the combination of both. All patients received the combination of etanercept 25 mg subcutaneously twice weekly plus oral methotrexate up to 20 mg/week. The primary radiographic endpoint was a change in modified total Sharp score (TSS), as assessed by blinded readers. RESULTS: At baseline, patients previously receiving methotrexate monotherapy (etanercept-added, n = 52) or etanercept monotherapy (methotrexate-added, n = 68) had moderate disease activity levels (mean disease activity score (DAS) of 2.6 and 2.5, respectively), whereas patients previously receiving combination therapy (n = 90) had a low disease activity level (mean DAS of 2.0). The addition of etanercept to methotrexate monotherapy resulted in a significant reduction in radiographic progression (p<0.05). Mean TSS changes in the previous year versus the current year were +1.79 versus +0.25 for the etanercept-added group (p<0.05); +0.51 versus -0.18 for the methotrexate-added group (NS) and +0.42 versus +0.24 for the combination group (NS). CONCLUSION: In these RA patients with on average moderate disease activity despite previous methotrexate monotherapy, combination treatment with etanercept and methotrexate inhibited radiographic progression and improved radiographic outcomes. These data, in conjunction with the previously published clinical data, support the use of combination therapy in RA patients with moderate disease activity.
18419803 Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanaly 2008 Apr 17 BACKGROUND: To analyse available evidence on the efficacy and safety of anti-TNFalpha drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA). METHODS: We searched systematically for randomised controlled clinical trials on treatment of RA with anti-TNFalpha drugs, followed by a systematic review with metaanalysis. Trials were searched from MEDLINE, EMBASE and Cochrane Library databases. The American College of Rheumatology (ACR) efficacy response criteria were used. Safety parameters provided by the trials were also assessed. Positive and undesired effects were estimated using combined relative risks (RR), number needed to treat (NNT) and number needed to harm (NNH). Heterogeneity was evaluated by Cochrane's Q and I2 statistics. RESULTS: Thirteen trials (7087 patients) met the inclusion criteria. The combined RR to achieve a therapeutic response to treatment with recommended doses of any anti-TNFalpha drug was 1.81 (95% CI 1.43-2.29) with a NNT of 5 (5-6) for ACR20. NNT for ACR50 [5 (5-6)] and ACR70 [7 (7-9)] were similar. Overall therapeutic effects were also similar regardless of the specific anti-TNFalpha drug used and when higher than recommended doses were administered. However, lower than recommended doses elicited low ACR70 responses (NNT 15). Comparison of anti-TNFalpha drugs plus methotrexate (MTX) with MTX alone in patients with insufficient prior responses to MTX showed NNT values of 3 for ACR20, 4 for ACR50 and 8 for ACR70. Comparison of anti-TNFalpha drugs with placebo showed a similar pattern. Comparisons of anti-TNFalpha drugs plus MTX with MTX alone in patients with no previous resistance to MTX showed somewhat lower effects. Etanercept and adalimumab administered as monotherapy showed effects similar to those of MTX. Side effects were more common among patients receiving anti-TNFalpha drugs than controls (overall combined NNH 27). Patients receiving infliximab were more likely to drop out because of side effects (NNH 24) and to suffer severe side effects (NNH 31), infections (NNH 10) and infusion reactions (NNH 9). Patients receiving adalimumab were also more likely to drop out because of side effects (NNH 47) and to suffer injection site reactions (NNH 22). Patients receiving etanercept were less likely to drop out because of side effects (NNH for control versus etanercept 26) but more likely to experience injection site reactions (NNH 5). CONCLUSION: Anti-TNFalpha drugs are effective in RA patients, with apparently similar results irrespective of the drug administered. Doses other than those recommended are also beneficial. The main factor influencing therapeutic efficacy is the prior response to DMARD treatment. The effect of treatment with etanercept or adalimumab does not differ from that obtained with MTX. The published safety profile for etanercept is superior but the fact that no patients are treated with higher than recommended doses requires explanation.
16079172 Patient reported outcomes in a trial of combination therapy with etanercept and methotrexa 2006 Mar OBJECTIVE: To compare patient reported measures of function, health related quality of life (QoL), and satisfaction with medication among patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), etanercept, or both for up to 1 year. METHODS: In a 52 week, double blind, clinical trial, patients with active RA were randomised to receive etanercept 25 mg twice weekly, methotrexate up to 20 mg weekly, or combination therapy. The Health Assessment Questionnaire (HAQ) disability index, EuroQoL health status visual analogue scale (EQ-5D VAS), patient global assessment, and patient general health VAS were administered at baseline and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52. Satisfaction with the medication was compared at 52 weeks. RESULTS: Of 682 enrolled patients, 522 completed 52 weeks of treatment. Mean improvement from baseline in HAQ score was 0.65, 0.70, and 1.0 for MTX, etanercept, and the combination, respectively. The mean percentage and absolute improvement in the HAQ was significantly higher (p<0.01) for combination therapy than for either of the monotherapies. Combination therapy produced significantly more rapid achievement of HAQ < or =0.5 sustained for 6 months than either of the monotherapies (p<0.01). Compared with patients receiving monotherapy, those receiving combination therapy achieved a significantly better (p<0.05) health state as measured by the EQ-5D VAS (mean (SD) 63.7 (3.2), 66.8 (3.2), 72.7 (3.1) for MTX, etanercept, and the combination, respectively). Results were similar for other assessments (p<0.01). Patients in combination and etanercept groups were significantly more likely (p<0.0001, p = 0.0009, respectively) to report satisfaction with the medication. CONCLUSIONS: Combination therapy with etanercept and methotrexate improved function, QoL, and satisfaction with the medication significantly more than monotherapy.
18501677 Role of GADD45 beta in the regulation of synovial fluid T cell apoptosis in rheumatoid art 2008 Aug Rheumatoid arthritis (RA) is characterized by persistent Th1 cell infiltration and production of inflammatory cytokines in the location of joint lesion. It is known that infiltrated Th1 cells in the synovial fluid (SF) of RA patients are resistant to apoptosis. Here we demonstrate that Th1 cells accumulated in patient SF expressed a high level of GADD45 beta (Growth Arrest and DNA Damage-inducible 45 beta) which further inhibited Th1 cell apoptosis. Interestingly, in vitro culture of T cells with SF from RA patients increased GADD45 beta expression in Th1 cells and inhibited their apoptosis. Silencing of GADD45 beta by RNAi abolished the anti-apoptotic effect of RA SF, which was accompanied by down-regulation of Bcl-2 and up-regulation of Bax. Further analysis showed that TNF-alpha and IL-12 in RA SF could stimulate GADD45 beta expression in Th1 cells and inhibit their apoptosis. Taken together, our results suggest a novel mechanism by which specific cytokines in the RA SF elevate GADD45 beta expression in local Th1 cells and subsequently leading to the enhanced T cell survival.
17869312 Implication of cytosolic phospholipase A2 (cPLA2) in the regulation of human synoviocyte N 2007 Sep 8 NADPH oxidase Nox2 is involved in the production of superoxide by rheumatoid synovial cells, constitutively and after pro-inflammatory cytokine treatment. The aims of the study were to evaluate the capacity of these cells to produce the superoxide anion in response to arachidonic acid (AA), and to study the involvement of cytosolic phospholipase A(2) (cPLA(2)) in the cytokine regulation of Nox2. Superoxide production was quantified in synovial cells obtained from six patients with rheumatoid arthritis (RA) and six with osteoarthritis (OA), stimulated with (i) AA, and (ii) PLA(2) inhibitors prior to IL-1beta or TNF-alpha treatment. Total cellular AA concentrations and PLA(2) activity were measured; effects of cytokines and NADPH oxidase inhibitors on the AA-activatable proton channel opening were also studied. Our results demonstrated that AA enhanced superoxide production in RA and OA cells; this production was significantly inhibited by iodonium diphenyl and apocynin. cPLA(2) inhibitors inhibited both IL-1beta and TNF-alpha-induced superoxide production in RA and OA cells. Basal PLA(2) activity was significantly more important in RA cells than in OA cells; PLA(2) activity was increased in IL-1beta and TNF-alpha pre-treated RA cells, and cPLA(2) inhibitors inhibited this activity. Opening of the AA-activatable proton channel was amplified when RA cells were pre-treated with both IL-1beta and TNF-alpha, and iodonium diphenyl and apocynin inhibited these cytokine effects. We concluded that AA is an important cofactor for synovial NADPH oxidase activity. Despite their direct effects on p47-phox phosphorylation, cytokines can also regulate the Nox2 activity though the AA-activatable associated H(+) channel.
19033084 In vivo kinematic analysis of a high-flexion, posterior-stabilized, mobile-bearing knee pr 2009 Sep The objective of this study was to evaluate the kinematics of a high-flexion, posterior-stabilized, mobile-bearing total knee arthroplasty (TKA) in weight-bearing, deep knee bending motion. Thirteen patients implanted with the Legacy Posterior Stabilized Flex (Zimmer, Warsaw, IN) mobile-bearing TKA were examined during a deep knee bending motion using fluoroscopy. Femorotibial motion was determined using a 2-dimensional to 3-dimensional registration technique, which used computer-assisted design models to reproduce the position of metallic implants from single-view fluoroscopic images. The average flexion range of motion between the metallic implants was 116 degrees . The average rotation of the femoral component was 9.3 degrees external rotation. The mean kinematic pathway was early rollback, lateral pivot with external rotation, and bicondylar rollback. We found that the kinematic pattern of the Legacy Posterior Stabilized Flex mobile-bearing TKA was different than normal knee kinematics.
18704426 A comparison study of a recombinant tumor necrosis factor receptor:Fc fusion protein (rhTN 2009 Jan The objective of this study is to evaluate the efficacy and safety of rhTNFR:Fc: a recombinant tumor necrosis factor receptor:Fc fusion protein compared with methotrexate (MTX) in patients with rheumatoid arthritis in China. We treated 238 patients with active rheumatoid arthritis with either twice weekly subcutaneous injection rhTNFR:Fc (25 mg) or weekly oral MTX (mean 15 mg per week) for 24 weeks (registration number: 2003L01264). Clinical responses were defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology (ACR-N). As compared with MTX-treated patients, more patients who received rhTNFR:Fc had ACR20 improvement in disease activity during the first 2 weeks (P < 0.05). Similarly, more patients treated with rhTNFR:Fc having ACR20, ACR50, ACR70 improvement in disease activity during 8 weeks (P < 0.05). At the end of 12-week treatment, patients received rhTNFR:Fc also had significant improvement at ACR20 (P < 0.05). Compared with oral MTX, patients received rhTNFR:Fc also had significant improvement at ACR70 at the end of 24 weeks treatment (P < 0.05). In conclusion, compared with oral MTX subcutaneous injection, rhTNFR:Fc acted more rapidly to release symptoms and signs of active RA in Chinese patients, and well tolerated in patients with rheumatoid arthritis in China.
17472989 Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citr 2007 Nov OBJECTIVES: To find out whether autoantibodies to citrullinated telopeptides of type I and II collagens and to cyclic citrullinated peptides (CCPs) predict the development of rheumatoid arthritis (RA). METHODS: A case-control study (matched for sex, age and municipality) was nested within a Finnish cohort of 19072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-7. 124 subjects developed RA by late 1989, and of these, 89 were positive for rheumatoid factor (RF). Preillness serum specimens were analysed for autoantibodies against arginine (A)- or citrulline (C)-containing synthetic telopeptides using a chemiluminescence method and for anti-CCPs Mark2 with an enzyme-linked immunosorbent assay method. RESULTS: The mean levels of autoantibodies to citrulline-containing telopeptides and the C/A ratios of type I and II collagens and to CCP were higher in subjects who later developed RF-positive RA. In the highest tertiles of C/A (I), C/A (II) ratios and anti-CCPs levels, the relative risk of RF-positive RA was significantly increased. In the multifactorial model, only anti-CCPs retained its statistical significance. However, the interaction term of C/A (II) ratio and anti-CCPs proved to be statistically significant (p = 0.02). The subjects ranked into the highest tertiles of both C/A (II) ratio and anti-CCPs had an odds ratio of 20.06 (95% confidence interval, 4.37 to 92.06) of developing RF-positive RA compared with those in the lowest tertiles of these antibodies. None of the autoantibodies predicted RF-negative RA. CONCLUSION: Autoantibodies to citrullinated telopeptides of type I and II collagen and to CCPs exert a synergistic effect on the risk of seropositive RA.