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ID PMID Title PublicationDate abstract
16014684 Women with early rheumatoid arthritis are referred later than men. 2005 Aug OBJECTIVE: To evaluate lag times between disease onset and rheumatological encounter in patients with early rheumatoid arthritis (RA). METHODS: All referred patients with early RA over a 1 year period were prospectively registered. The lag time between disease onset and the first encounter with a physician was recorded as the "patient's delay". The time between this encounter and the referral to our department was recorded as the "physician's delay". The lag time between referral and rheumatological encounter was recorded as the "hospital's delay". RESULTS: The median total lag time between onset of RA and rheumatological encounter was 16 weeks, with no difference between men and women. Women were referred significantly later than men ("physician's delay" median 10 weeks v 3 weeks). The "patient's delay" and the "hospital's delay" were a median of 4 weeks each. CONCLUSION: Women with early RA were referred later than men and the total lag time between disease onset and rheumatological encounter was quite long for both sexes.
16248289 Social, health, and age differences associated with depressive disorders in women with rhe 2005 Depression in women with rheumatoid arthritis (RA) may be related to social role experiences, physical health, and age. The purpose of this study was to examine the social and health factors contributing to depression in two age groups of women with RA. One-hundred and thirty-eight midlife and late-life women with a diagnosis of RA participated in this cross sectional survey study. Multiple regression analysis indicated that social role balance, functional status, number of co-existing health problems, and age were significant predictors of depression in midlife and late-life women with RA. Role balance was the strongest factor contributing to a woman's depression score. Compared to midlife women, late-life women reported significantly higher role balance and lower depression scores, despite poorer functional status and more concomitant health problems.
16395748 A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined w 2006 Jan OBJECTIVE: A placebo controlled, double-blind trial (DBT) was conducted for Japanese patients with active rheumatoid arthritis (RA) despite treatment with low dose methotrexate (MTX) to evaluate the efficacy and safety of infliximab. Extended treatment with infliximab was conducted in an open-label trial (OLT). METHODS: In the DBT, 147 patients were randomly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0, 2 and 6, combined with MTX. In the OLT, 129 patients from the DBT received 3 mg/kg infliximab every 8 weeks. RESULTS: The mean dose of MTX was 7.2 +/- 2.0 mg/week. Significantly more patients receiving 3 mg/kg (61.2%) and 10 mg/kg (52.9%)infliximab achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria at Week 14, compared to placebo (23.4%) (p < 0.001). There was no significant difference in incidence of adverse events among the treatment groups. In patients receiving infliximab in the DBT, 11.6% of patients with serum infliximab just before the OLT developed antibodies to infliximab (ATI) in the OLT, whereas 62.2% of patients without serum infliximab did. In patients receiving placebo in the DBT, 43.9% developed ATI. CONCLUSION: The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study. The data from the DBT and OLT also supported the importance of an induction treatment of infliximab, followed by a maintenance treatment without a long interval, giving stable serum concentrations in order to prevent formation of ATI.
16248381 Detection of alveolar epithelial injury by Tc-99m DTPA radioaerosol inhalation lung scan i 2005 Sep Rheumatoid arthritis (RA) is a systemic autoimmune disorder primarily involving the joints. Lung alterations in RA may be primary or secondary to pharmacological treatments and may involve the alveoli, interstitium, airways and/or pleura. Technetium-99m diethylenetriaminepentaacetic acid (Tc-99m DTPA) aerosol inhalation scintigraphy is a sensitive and noninvasive test commonly employed to assess pulmonary epithelial membrane permeability. The purpose of the this study was a) to investigate the changes of pulmonary alveolar epithelial permeability in patients with RA, b) to determine the relationship between the clearance rate of Tc-99m DTPA and pulmonary function test (PFT) results, and c) to determine the relationship between the clearance rete of Tc-99m DTPA and clinical parameters of disease. Twenty-five patients with RA but without lung alterations were included in the study. The patients were 22 females, and 3 males; mean age 53.6 +/- 8.7 years. Technetium-99m DTPA aerosol inhalation scintigraphy was performed on the study and healthy control groups. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. There were no significant differences in the mean T1/2 or mean PI values between the RA patients and control subjects. No correlation was found between the mean T1/2 values of Tc-99m DTPA clearance and activity of RA, clinical values, or the spirometric measurements except FEV1/FVC and functional status in RA patients (p = 0.02, p = 0.01, respectively). However, a weak correlation was found between duration of disease and T1/2 values of Tc-99m DTPA clearance (p = 0.006). PI values tended to correlate with FEF25-75, although, this was not statistically significant (p = 0.057). This study shows that no changes occur in alveolar-capillary permeability in RA patients without lung alterations.
16226649 Site-specific intraoperative efficacy of arthroscopic knee joint synovectomy in rheumatoid 2005 Oct PURPOSE: To assess the intraoperative reduction of inflammatory infiltrates achieved by arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) with special regard to the removal site, using preoperative and postoperative synovial tissue (ST) samples. TYPE OF STUDY: A histologic and immunohistochemical study. METHODS: Eleven patients with treatment-refractory RA knee synovitis underwent arthroscopic synovectomy. In each patient, ST specimens were obtained immediately before and after synovectomy from 9 defined sites covering the whole joint. The samples were graded using an acute synovitis score (ASS; presence of polymorphonuclear neutrophilic leukocytes [PMN] and fibrin) and a chronic synovitis score (CSS; e.g., lining cell hyperplasia, presence of diffuse and lymphoid aggregates). Immunohistologic analyses were performed using 7 monoclonal antibodies directed against PMN, macrophages, and T-cell subsets (total of 1,584 preparations). Knee function was assessed after an average follow-up of 28 months by Lysholm score (modified by Klein and Jensen), Insall functional and knee scores, and Lequesne score. RESULTS: Arthroscopic synovectomy led to an overall significant (P between .005 and .05) reduction of the acute inflammatory infiltrates (ASS) by 82.1%, but to a significant reduction of chronic inflammatory infiltrates (CSS) by only 62.5%. Accordingly, the density of PMN was reduced by 81.8%, whereas that of macrophages and different T-cell subsets was only decreased by < or = 61.6%. With respect to the anatomic regions, a significantly (P < or = .05) less marked reduction of inflammatory infiltrates was observed in the upper lateral and central recess, at the medial and lateral capsule, as well as at the femoral insertion of the anterior cruciate ligament. All knee joint scores showed a significant (P < or = .01) improvement over preoperative values at follow-up. CONCLUSIONS: Arthroscopic synovectomy effectively reduces acute and chronic inflammatory infiltrates in patients with RA who have refractory synovitis of the knee joint (immediately after synovectomy) and improves knee function (28-month follow-up). However, the reduction of inflammatory infiltrates appears to depend on the anatomic region of the joint. LEVEL OF EVIDENCE: Level III.
16052586 RANK and RANKL expression as markers of dendritic cell-T cell interactions in paired sampl 2005 Aug OBJECTIVE: The RANK/RANKL pathway is critical in bone destruction in conditions such as rheumatoid arthritis (RA). Since RANK/RANKL-deficient mice show major lymph node (LN) abnormalities, undertook this study to investigate the expression of RANK/RANKL in paired samples of synovium and LNs from RA patients. METHODS: Using immunohistochemistry, RANK/RANKL expression by dendritic cell (DC) and T cell subsets was studied in this unique set of samples and in RA synoviocytes stimulated with interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and IL-17. RESULTS: In RA synovium, RANKL+ cells were detected in the lining layer and the lymphocytic infiltrates, whereas RANK expression was restricted to the perivascular infiltrates. In LNs, RANK+ and RANKL+ cells were diffusely expressed in the T cell zone and in germinal centers. Double staining of paired RA synovium and LN sections showed that some immature CD1a+ DCs expressed RANK and RANKL, while some mature DC-LAMP+ DCs expressed only RANK. Some CD3+, CD4+, interferon-gamma+, and IL-17+ cells expressed RANKL, while none expressed RANK. Treatment of synoviocytes with TNFalpha or IL-1beta in combination with IL-17 was particularly potent at inducing RANKL expression. CONCLUSION: This study shows the involvement of RANK/RANKL in DC-T cell interactions during an inflammatory process. RANK expression appears to be limited to the sites of immune reaction, both in the synovium and in LNs. Therapeutic control of these targets may have both positive and negative consequences for the immune system.
16199168 Mapping of a novel susceptibility gene for rheumatoid arthritis in the telomeric MHC regio 2005 Oct 21 Rheumatoid arthritis (RA) is a complex heterogeneous disease with an estimated genetic contribution to of 30-50%. Approximately one third arises from the major histocompatibility complex (MHC) at 6p21.3. The contribution of specific DRB1 alleles encoding the shared epitope has been well described, however, several recent studies have suggested that additional telomeric genetic influences may exist. This region is difficult to study as a result of the presence of strong linkage disequilibrium (LD) within the MHC and high gene density particularly in the central class III region. In this article we review the current data supporting the existence of a non-DRB1 susceptibility gene for rheumatoid arthritis, in particular within the class III region.
17079158 Increased adiponectin is negatively linked to the local inflammatory process in patients w 2006 Sep Adiponectin has been shown to exert insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties in metabolic diseases. It has been suggested that adiponectin may play a role in rheumatoid arthritis (RA). To assess adiponectin in serum and synovial fluid from patients with RA and osteoarthritis (OA), and in serum from healthy controls. Adiponectin and CRP levels were analyzed by ELISA. The clinical activity of RA patients was assessed according to the 28 joint count Disease Activity Score. Synovial fluid adiponectin was significantly higher in RA than in OA patients (p<0.001). Adiponectin was negatively associated with the leukocyte count in RA synovial fluid (r=-0.45, p<0.05). Serum adiponectin was higher in RA compared to healthy controls (p<0.02), however comparable to OA patients. Serum adiponectin was higher than in synovial fluid in both diseases (p<0.001). In general, women had higher adiponectin levels than men. Adiponectin was not related to age, disease duration, body mass index, or disease activity of RA patients. Adiponectin is decreased in synovial fluid compared to serum indicating that peripheral fat stores are major producers of adiponectin into the blood stream. However, increased synovial fluid adiponectin in RA patients may counterpart the local inflammatory process.
16139566 MHC II molecules in inflammatory diseases: interplay of qualities and quantities. 2005 Nov It is generally accepted that MHC II molecules confer susceptibility to inflammatory diseases because of the different abilities they possess for binding and presenting peptides to T cells. A new study suggests that the level of MHC II gene expression is also a risk factor for such diseases. It shows that a polymorphism in the promoter of the MHC II transactivator (MHC2TA) gene (which encodes CIITA), leads to reduced MHC2TA expression, and hence reduced production of MHC II molecules. This predisposes to rheumatoid arthritis, multiple sclerosis and myocardial infarction.
15915221 Sequences in drug discovery. 2005 Apr Sequences in Drug Discovery is a new series of distinct brief reports on breaking topics in the field of drug R&D. This month's Sequences in Drug Discovery contains the following reports: Spotlight on West Nile virus vaccines. p38alpha MAPK--a dynamic target in rheumatoid arthritis. The need for new contraceptives: targeting PDE3. Vasopeptidase inhibition with a triple mode of action. Current advances in the development of 5-HT(6) receptor antagonists.
16877603 The management of failed ankle replacement. 2006 Aug Advances in the design of the components for total ankle replacement have led to a resurgence of interest in this procedure. Between January 1999 and December 2004, 16 patients with a failed total ankle replacement were referred to our unit. In the presence of infection, a two-stage salvage procedure was planned. The first involved the removal of the components and the insertion of a cement spacer. Definitive treatment options included hindfoot fusion with a circular frame or amputation. When there was no infection, a one-stage salvage procedure was planned. Options included hindfoot fusion with an intramedullary nail or revision total ankle replacement. When there was suspicion of infection, a percutaneous biopsy was performed. The patients were followed up for a minimum of 12 months. Of the 16 patients, 14 had aseptic loosening, five of whom underwent a revision total ankle replacement and nine a hindfoot fusion. Of the two with infection, one underwent fusion and the other a below-knee amputation. There were no cases of wound breakdown, nonunion or malunion. Management of the failed total ankle replacement should be performed by experienced surgeons and ideally in units where multidisciplinary support is available. Currently, a hindfoot fusion appears to be preferable to a revision total ankle replacement.
16868648 Comparison of taurine chloramine and taurine bromamine effects on rheumatoid arthritis syn 2007 Fibroblast-like synoviocytes (FLS) participate in rheumatoid arthritis (RA) chronic synovitis by producing pro-inflammatory cytokines (IL-6, IL-8), growth factors (VEGF) and other inflammatory mediators (PGE2, NO). We have previously reported that Tau-Cl, generated by neutrophils, inhibits in vitro some of these pathogenic RA FLS functions. Taurine bromamine (Tau-Br) originates from eosinophils and neutrophils, and its immunoregulatory activities are poorly known. Therefore, we investigated the effects of Tau-Br on RA FLS functions and compared it to Tau-Cl anti-inflammatory action. When applied at noncytotoxic concentrations: (i) Tau-Br inhibited IL-6 and PGE2 production with potency similar to Tau-Cl (IC50 approximately 250 microM), (ii) Tau-Br failed to affect VEGF and IL-8 synthesis, while Tau-Cl exerted inhibitory effect (IC50 approximately 400 microM), (iii) none of these compounds affected NO generation and iNOS expression. Thus, Tau-Cl is more effective than Tau-Br in normalization of pro-inflammatory RA FLS functions.
17009229 Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthriti 2006 Oct OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) have an increased risk of fracture, and to estimate their long-term absolute fracture risk. METHODS: We studied patients with RA ages >or=40 years in the British General Practice Research Database, each matched by age, sex, calendar time, and practice to 3 control patients. Incident fractures, as recorded in the computerized medical records, were ascertained over a median followup of 7.6 years. The fracture rate in RA patients compared with controls was adjusted for smoking, body mass index (BMI), and several clinical risk factors, and Cox proportional hazards models were used to calculate the relative risk (RR) of fracture in RA. A risk score was then developed to provide an estimate of the 5- and 10-year fracture risk among RA patients. RESULTS: There were 30,262 patients with RA, of whom 2,460 experienced a fracture during followup. Compared with controls, patients with RA had an increased risk of fracture, which was most marked at the hip (RR 2.0, 95% confidence interval [95% CI] 1.8-2.3) and spine (RR 2.4, 95% CI 2.0-2.8). Indicators of a substantially elevated risk of fracture (at the hip) included >10 years' duration of RA (RR 3.4, 95% CI 3.0-3.9), low BMI (RR 3.9, 95% CI 3.1-4.9), and use of oral glucocorticoids (RR 3.4, 95% CI 3.0-4.0). Modeling of the long-term risk profiles revealed that, for example, in a woman age 65 years with longstanding RA whose risk factors also included low BMI, a history of fracture, and frequent use of oral glucocorticoids, the 5-year risk of hip fracture was 5.7% (95% CI 5.3-6.1%). CONCLUSION: Patients with RA are at increased risk of osteoporotic fractures. This increased risk is attributable to a combination of disease activity and use of oral glucocorticoids.
16613273 [Clinical observation on liang's anti-rheumatism and rheumatoid granule in rheumatoid arth 2006 Mar OBJECTIVE: To evaluate the therapeutic effect of Liang's anti-rheumatism and rheumatoid granule (LARG) in treating patients with rheumatoid arthritis (RA) at the active stage. METHODS: Fifty patients were administered orally with LARG in the treated group, 30 patients were treated with Wangbi granule in the control group. Symptoms, physical signs and relevant laboratory indexes in the 2 groups were observed and compared before treatment and after being treated for 2 months. RESULTS: The total effective rate and curative-markedly effective rate in the treated groups were superior to those in the control group (P <0.01). The improvement in aspects of integral scoring of symptom and physical signs, including arthragia, tumefaction, dysfunction indexes, morning stiffness and 15m walking time, and laboratory indexes, including blood sedimentation rate, rheumatoid factor, C creative protein, immunoglobin, as well as hemorheology relevant indexes in the treated group after treatment were significantly different to those before treatment and those in the control group (P <0.05 or P <0.01). CONCLUSION: LARG has obvious therapeutic effect on RA at the active stage.
16026086 [Autoantibodies]. 2005 Jun The autoantibody test gives significant information for diagnosis of autoimmune diseases. Since the finding of the LE-cell in 1948, dozens of autoantibodies have been found. Anti nuclear antibody (ANA) is the essential test for the screening of autoantibodies. Indirect immunofluorescence (IIF) is the conventional method for the detection of ANA. IIF can detect a wide spectrum of ANA and gives abundant information obtained from a staining pattern. However under the recent circumstances of using advanced fluorescent microscopes and reagents we often have difficulty interpreting positive results seen in normal individuals and in detailed staining patterns. ELISA (enzyme-linked immunosorbent assay), detecting disease specific autoantibodies alone, is one solution. Some antibodies such as anti-DNA or anti-ENA (extractable nuclear antigen) have a strong relation to specific diseases. These autoantibodies have been detected by IIF, RIA (radioimmunoassay) or DID (double immune diffusion). With the progress of molecular biology many autoantigens have been characterized. Now ELISA is a typical way to detect autoantibodies because purified or recombinant antigens are easily available. Though RF (rheumatoid factor) is the historical autoantibody detected in RA patients, the specificity to RA is low. The new anti-CCP is promising from its high specificity and sensitivity. Now we can choose various kind of autoantibody tests, not only conventional ones but also newly developed ones. For diagnosis and treatment of autoimmune diseases, understanding of both clinical significance and methodology is important.
15743473 Inhibition of antithrombin by hyaluronic acid may be involved in the pathogenesis of rheum 2005 Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis, proinflammatory processes, and proliferation of fibroblast-like cells. Abnormalities in these processes are primary features of rheumatoid arthritis (RA) in synovial tissues. Tissue destruction in joints causes the accumulation of large quantities of free hyaluronic acid (HA) in RA synovial fluid. The present study was conducted to investigate the effects of HA and several other glycosaminoglycans on antithrombin, a plasma inhibitor of thrombin. Various glycosaminoglycans, including HA, chondroitin sulfate, keratan sulfate, heparin, and heparan, were incubated with human antithrombin III in vitro. The residual activity of antithrombin was determined using a thrombin-specific chromogenic assay. HA concentrations ranging from 250 to 1000 mug/ml significantly blocked the ability of antithrombin to inhibit thrombin in the presence of Ca2+ or Fe3+, and chondroitin A, B and C also reduced this ability under the same conditions but to a lesser extent. Our study suggests that the high concentration of free HA in RA synovium may block antithrombin locally, thereby deregulating thrombin activity to drive the pathogenic process of RA under physiological conditions. The study also helps to explain why RA occurs and develops in joint tissue, because the inflamed RA synovium is uniquely rich in free HA along with extracellular matrix degeneration. Our findings are consistent with those of others regarding increased coagulation activity in RA synovium.
14991230 Calcaneus bone mineral density in Japanese women with rheumatoid arthritis. 2005 Apr OBJECTIVES: The aim of this study was to investigate the relationships among bone mineral densities (BMD) in the calcaneus and leg activity of daily living (L-ADL) in rheumatoid arthritis (RA) patients. METHODS: We measured and compared calcaneus BMD using single X-ray absorptiometry and lumbar spine and femoral neck BMD using dual X-ray absorptiometry in 158 Japanese female outpatients with RA and 358 normal controls (NC). RESULTS: Regardless of whether the women were premenopausal or postmenopausal, calcaneus and femoral neck BMDs in the RA group were significantly lower than in the NC group. Calcaneus BMD correlated with the modified health assessment questionnaire, L-ADL score, and 10-m walking time, regardless of whether the patients were premenopausal or postmenopausal (P<0.01). CONCLUSIONS: We conclude that calcaneus BMD reflects the L-ADL of RA patients very well and allows us to perform the same level of BMD evaluation as that with current BMD measurement methods.
15684036 Essential roles of Toll-like receptor-4 signaling in arthritis induced by type II collagen 2005 Mar Although bacterial LPS has been used to boost the susceptibility to antibody-induced arthritis, the mechanism of the action of LPS remains to be clarified. We investigated whether signals triggered by Toll-like receptor (TLR)-4 mediate the effects of LPS in the context of anti-type II collagen-induced arthritis. The mice defective in the Tlr-4 gene (Tlr-4(lps-d)) were markedly less susceptible than wild type to arthritis, as manifested in arthritic index, incidence and synovitis. Levels of the pro-inflammatory mediators, tumor necrosis factor-alpha and cyclooxygenase-2, in their synovial tissue were also much lower. Serum C3 deposition through the alternative pathway and de novo synthesis of C3 were lower in the Tlr-4(lps-d) mice in the post-acute phase, pointing to an influence of TLR-4 signals on the turnover rate of complement cascades. T cells from the Tlr-4(lps-d) mice failed to proliferate in response to an auto-antigen, glucose-6-phosphate isomerase (GPI), unlike those from wild-type mice, and the serum level of GPI-specific IgG antibody was significantly lower than in the wild-type mice. Interestingly, type 2 responses, such as GPI-specific IgG1 and IL-4 production, were up-regulated in the Tlr-4(lps-d) mice. Taken together, our data suggest that the TLR-4 signaling pathway plays an essential role in the initiation and progression of auto-antibody/LPS-triggered arthritis by inducing pro-inflammatory mediators, C3 deposition, auto-antigen-specific adaptive immune responses and immune deviation between type 1 and type 2 responses.
16299691 Co-existent crescentic glomerulonephritis and renal amyloidosis: a case report and literat 2005 Sep Co-existent crescentic glomerulonephritis and renal amyloidosis have only rarely been reported thus far. To our knowledge, only about eighteen convincing cases (with >50% crescents) have been described, mostly in the context of rheumatoid arthritis. In this report, we add a case from our institution and review the existing literature, including a proposed mechanism of crescent formation in this setting. Although the relationship between crescentic glomerulonephritis, renal amyloidosis, and rheumatoid arthritis needs further investigation, we suggest that one should consider the development of crescentic glomerulonephritis with amyloidosis in patients with long-standing rheumatoid arthritis and worsening renal function.
16699051 Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis. 2006 Jun BACKGROUND: Animal studies have indicated that 5-HT2A receptors could play a role in arthritic diseases. OBJECTIVE: To analyse the binding properties of 5-HT2A receptors in patients with rheumatoid arthritis. METHODS: Using a radioactive binding assay, 43 patients with rheumatoid arthritis were compared with 49 sex and age matched controls for density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin receptors. Genotyping, using polymerase chain reaction, was undertaken to exclude the possibility that differences in the genetic polymorphism T102C for the 5-HT2A receptor determine differences in receptor density. RESULTS: Mean of Bmax of 5-HT2A receptors in rheumatoid patients was significantly lower than in controls, at 45.3 v 57.4 fmol/mg protein (p = 0.004), but there was no significant difference in Kd. The T102C receptor polymorphism genotypes showed a skewed distribution between the two groups. Even when adjusted for this, there was a significant difference in Bmax between the groups. CONCLUSIONS: The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease.