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ID PMID Title PublicationDate abstract
18476430 [Clinical observation of Shuxuetong Injection in treating patients with active rheumatoid 2008 Mar OBJECTIVE: To observe the efficacy and adverse reaction of Shuxuetong Injection (SXTI, the extracted liquor from Pheretima and Hirudo) in treating patients with active rheumatoid arthritis (RA). METHODS: Ninety-seven patients with active RA assigned in the SXTI group were treated with high or low dose SXTI (6 mL/d or 8 mL/d) combined with conventional therapy and the 30 in the control group treated with conventional therapy alone. Thompson index, Ritchie index, time of morning stiffness (TMS), erythrocyte sedimentation rate (ESR) and plasma fibrinogen (Fib) in patients were determined before treatment (T0), by the end of the 1st (T1), second (T2) and 4th (T3) week of treatment, respectively, as well as the SXTI associated adverse reaction monitored. RESULTS: Marked improvement of all indexes, including Thompson index, Ritche index, TMS, ESR and Fib, was shown in the SXTI groups at T1 (P < 0.01), but in the control group, it only appeared at T3 (P < 0.01). Compared with the control group, TMS, ESR and Fib at T1, Thompson index and Ritche index at T2 in the SXTI groups were significantly improved (P < 0.01), especially significant in the high dose group (P < 0.01). However, hands edema appeared in 2 patients, foot edema in 1 and fullness sensation of head in 1 in the high dose SXTI group. The dose was forced to redue to 6 mL/d, and then all the symptoms were improved. CONCLUSION: SXTI shows good efficacy with less adverse reaction in treating patients with active RA, and better efficacy was obtained at the dose of 8 mL/d.
17216583 The functional haplotype of peptidylarginine deiminase IV (S55G, A82V and A112G) associate 2007 Mar Peptidylarginine deiminase IV (PADI4) posttranslationally converts peptidylarginine to citrulline. It plays an essential role in immune cell differentiation and apoptosis. A haplotype of single-nucleotide polymorphisms (SNPs) in PADI4 is functionally relevant as a rheumatoid arthritis (RA) gene. It could increase enzyme activity leading to raised levels of citrullinated protein and stimulating autoantibody. Previously, our study showed that inducible PADI4 causes haematopoietic cell death. Herein, we further investigate whether RA risk PADI4 haplotype (SNP PADI4; S55G, A82V and A112G) and the increase of its enzymatic activity induce apoptosis. In the tetracycline (Tet)-On Jurkat T cells, ionomycin (Ion) only treatment didn't induce apoptosis however it promoted inducible PADI4-decreased cell viability and -enhanced apoptosis. Through in vitro and in vivo PADI enzyme activity assay, we demonstrated that PADI4 enzyme activity of SNP PADI4 was higher than RA non-risk PADI4 haplotype (WT PADI4). The effect of SNP PADI4-induced apoptosis was superior to WT PADI4. In addition, both Ion and SNP PADI4 synergistically provoked apoptosis were compared with both Ion and WT PADI4. Concurrently, in the conditionally inducible SNP PADI4 cells of Ion treatment-induced apoptosis, not only the expression of Bcl-xL was down-regulated and Bax up-regulated, but also cytochrome c was released from mitochondria to cytoplasm in significant amounts. Western blotting data showed the increase in apoptosomal caspase activation during programmed cell death in the inducible SNP PADI4 cells subsequent to Ion treatment. These data demonstrated that both SNP PADI4 increasing their enzyme activity could enhance apoptosis through the mitochondrial pathway and further provide a conceivable explanation in the pathogenesis of RA following the upregulation of PADI4 activity in its SNPs.
17143973 Risk factors associated with incident clinical vertebral and nonvertebral fractures in Jap 2007 Feb OBJECTIVE: To evaluate the association between potential risk factors and incident clinical fractures in Japanese patients with rheumatoid arthritis (RA). METHODS: A total of 1733 female patients with RA over age 50 years were enrolled in a prospective observational cohort study. Participants were followed for 54 months from October 2000 to March 2005, and classified into 4 groups according to incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture); and those with any new nonvertebral fracture. Cox proportional hazard models were used to analyze independent contributions of various risk factors to fracture incidence. RESULTS: During the followup period, 33, 34, and 98 patients developed a vertebral, a main nonvertebral, and any nonvertebral fracture, respectively. The Japanese Health Assessment Questionnaire (J-HAQ) score was associated with relative risks (RR) of 2.42 (95% confidence interval 1.42-4.14), 1.76 (95% CI 1.07-2.89), and 1.73 (95% CI 1.29-2.32) for vertebral, main nonvertebral, and all nonvertebral fractures. The risks of vertebral and any nonvertebral fractures were increased for age over 70 years compared with age in the 50s (RR 3.25, 95% CI 1.19-8.86; and RR 2.22, 95% CI 1.20-4.10, respectively). Clinical variables and medications were associated with a new fracture. CONCLUSION: HAQ, age, history of any prior fracture, and orthopedic surgery for RA appear to be associated with fractures in Japanese women with RA.
16192290 Prospective 7 year follow up imaging study comparing radiography, ultrasonography, and mag 2006 May OBJECTIVE: To perform a prospective long term follow up study comparing conventional radiography (CR), ultrasonography (US), and magnetic resonance imaging (MRI) in the detection of bone erosions and synovitis in rheumatoid arthritis (RA) finger joints. METHODS: The metacarpophalangeal and proximal interphalangeal joints II-V (128 joints) of the clinically dominant hand of 16 patients with RA were included. Follow up joint by joint comparisons for erosions and synovitis were made. RESULTS: At baseline, CR detected erosions in 5/128 (4%) of all joints, US in 12/128 (9%), and MRI in 34/128 (27%). Seven years later, an increase of joints with erosions was found with CR (26%), US (49%) (p<0.001 each), and MRI (32%, NS). In contrast, joint swelling and tenderness assessed by clinical examination were decreased at follow up (p = 0.2, p<0.001). A significant reduction in synovitis with US and MRI (p<0.001 each) was seen. In CR, 12 patients did not have any erosions at baseline, while in 10/12 patients erosions were detected in 25/96 (26%) joints after 7 years. US initially detected erosions in 9 joints, of which two of these joints with erosions were seen by CR at follow up. MRI initially found 34 erosions, of which 14 (41%) were then detected by CR. CONCLUSION: After 7 years, an increase of bone erosions was detected by all imaging modalities. In contrast, clinical improvement and regression of synovitis were seen only with US and MRI. More than one third of erosions previously detected by MRI were seen by CR 7 years later.
18198642 [Comparative study on characteristics of Chinese and Western medicine for treatment of rhe 2007 Dec OBJECTIVE: To analyse the cartilage erosion related blood biochemical and immune factors in rheumatoid arthritis (RA) and to explore the special influences of Chinese medicine (CM) and Western medicine (WM) on these factors. METHODS: Three hundred and ninety-seven patients, with confirmed diagnosis of active RA, were randomly assigned to the WM group (194 patients) and the CM group (203 patients). The WM applied covered non-steroid anti-inflammatory agents and slow acting medicine; and the CM given included basic remedy and syndrome differentiating medication. Related blood biochemical and immunological indexes were determined before and after treatment to screen out the cartilage erosion related factors and to compare the influence of CM and WM on them. RESULTS: Patients' peripheral red blood cell (RBC) and platelet (PLT) count were changed closely along with their degree of cartilage erosion. RBC count increased in the CM group and PLT count lowered in the WM group after treatment, all showed statistical significance; comparison of the two indexes between the two groups showed that statistical difference presented in RBC but not in PLT count. CONCLUSION: Both WM and CM can ameliorate the cartilage erosive factor in RA, but they are acting in different ways.
17976235 Rheumatoid arthritis patients' experiences of wearing therapeutic footwear - a qualitative 2007 Nov 1 BACKGROUND: Specialist 'therapeutic' footwear is recommended for patients with diseases such as rheumatoid arthritis (RA) as a beneficial intervention for reducing foot pain, improving foot health, and increasing general mobility. However, many patients choose not to wear this footwear. Recommendations from previous studies have been implemented but have had little impact in improving this situation. The aim of this study was to explore RA patients' experiences of this footwear to ascertain the factors which influence their choice to wear it or not. METHOD: Ten females and three males with RA and experience of wearing specialist footwear were recruited from four National Health Service orthotic services. Semi-structured interviews were carried out in the participants own homes. A hermeneutic phenomenological analysis of the transcripts was carried out to identify themes. RESULTS: The analysis revealed two main themes from both the female and male groups. These were the participants' feelings about their footwear and their experiences of the practitioner/s involved in providing the footwear. In addition, further themes were revealed from the female participants. These were feelings about their feet, behaviour associated with the footwear, and their feelings about what would have improved their experience. CONCLUSION: Unlike any other intervention specialist therapeutic footwear replaces something that is normally worn and is part of an individual's body image. It has much more of a negative impact on the female patients' emotions and activities than previously acknowledged and this influences their behaviour with it. The patients' consultations with the referring and dispensing practitioners are pivotal moments within the patient/practitioner relationship that have the potential to influence whether patients choose to wear the footwear or not.
18984413 Relationship of Sjögren's syndrome to other connective tissue and autoimmune disorders. 2008 Nov Sjögren's syndrome is a systemic autoimmune disease that frequently presents concomitantly with other systemic connective tissue or organ-specific autoimmune diseases. This association is well described for systemic lupus erythematosus and rheumatoid arthritis. The presence of Sjögren's syndrome influences the expression of the other autoimmune disease to some degree, for instance by increasing fatigue and lymphoma risk. The etiopathogenic mechanism for the simultaneous or sequential development of multiple autoimmune diseases in one individual is not well understood. Common genetic backgrounds and additional immunogenetic, environmental, or hormonal factors may be responsible for the formation of subsets of autoimmune disease clustering. While the most currently accepted classification criteria (American European Consensus Criteria) designate these cases as secondary Sjögrens syndrome, the terms overlapping or associated Sjögren's syndrome are frequently used in the literature to describe these cases.
17242913 [Peripheral nerve entrapment syndrome of the upper extremities in cases of inflammatory, r 2007 Feb Entrapment neuropathy of the upper extremities could be detected by electroneurophysiological investigations in one third of our patients with rheumatoid arthritis. These neuropathies are often overlooked and therefore not treated appropriately. The functional impairment of arms and hands should not be neglected. In this report, we summarize the symptoms, the diagnostic tools and the surgical treatment of entrapment neuropathies according to their topography. Typical cases are presented.
18666027 Cachexia in rheumatoid arthritis is associated with inflammatory activity, physical disabi 2008 Sep OBJECTIVES: To examine the impact of inflammation, insulin-like growth factor (IGF-1) and its regulating binding protein (IGFBP-1) on lean body mass (LBM) in patients with rheumatoid arthritis (RA). METHODS: In 60 inpatients (50 women), inflammatory activity was measured by Disease Activity Score 28 (DAS28), C-reactive protein (CRP), and interleukin (IL)-6, and physical disability by the Health Assessment Questionnaire (HAQ). LBM was assessed by dual-energy X-ray absorptiometry (DXA) and fat free mass index (FFMI; kg/m(2)) and fat mass index (FMI; kg/m(2)) were calculated. RESULTS: Median age was 65 years and disease duration 13 years. Fifty per cent of the patients had FFMI below the 10th percentile of a reference population and 45% had FMI above the 90th percentile, corresponding to the condition known as rheumatoid cachexia (loss of muscle mass in the presence of stable or increased FM). DAS28, CRP, and IL-6 correlated negatively with LBM (p = 0.001, 0.001, and 0.018, respectively), as did HAQ (p = 0.001). Mean (confidence interval) IGF-1 was in the normal range, at 130 (116-143) microg/L. IGFBP-1 levels were elevated in patients (median 58 microg/L in women and 59 microg/L in men) compared with a normal population (33 microg/L in women and 24 microg/L in men). The ratio IGF-1/IGFBP-1, which reflects bioavailable IGF-1, was low (2.0 microg/L) and was positively correlated with LBM (p = 0.015). In multiple regression analysis, 42% of the LBM variance was explained by IGF-1/IGFBP-1, HAQ score, and DAS28. CONCLUSION: A large proportion of RA inpatients, mainly women, had rheumatoid cachexia. The muscle wasting was explained by inflammatory activity and physical disability as well as low bioavailable IGF-1.
17540510 Disease-specific expression patterns of proteases in synovial tissues. 2007 To assess whether protease expression patterns can be discriminated according to matrix degradation mechanisms in aseptic prosthesis loosening (APL), rheumatoid arthritis (RA), and osteoarthritis (OA), we immunohistochemically examined the expressions of matrix metalloproteinase-1 and cathepsins B, D, and L in periprosthetic synovial-like interface tissues from 32 patients with failed prosthetic hips, from 29 RA-patients with hip synovial membranes, and from 35 patients with primary OA. Numerical values, calculated for the positivity of each protease, were used to rank the staining patterns, and a multivariate analysis was carried out to examine the discriminant probabilities. As a result of stepwise linear discriminant analyses, the three groups were successfully discriminated with probabilities of 100%, 62.1%, and 77.1%, respectively. Cathepsin L was significantly related to the discrimination of APL from RA and primary OA. Disease-specific protease activation pathways might exist, and cathepsin L can be a key enzyme for APL pathogenesis. LEVEL OF EVIDENCE: Prognostic study, level III (retrospective study).
25160719 Daily diaries reveal influence of pessimism and anxiety on pain prediction patterns. 2008 The match/mismatch model of pain prediction was tested with a group of rheumatoid arthritis patients (N = 227) in a natural setting. Daily diary measures of pain prediction and pain experience were obtained over 30 days. Results revealed a greater number of underpredictors (N = 147) than over predictors (N = 58) in our sample, with a minority (N = 22) overpredicting and underpredicting with equal frequency. Further, people modified their predictions to a greater degree after an over prediction than they did after an under prediction. As expected, anxious participants were less accurate and more prone to over predicting their pain than their less anxious counterparts. In contrast, participants who reported low levels of daily pessimism were more likely than their more pessimistic counterparts to under predict their pain. The findings suggest that people continued to under predict their pain despite repeated disconfirmations and that low levels of pessimism may have accounted for this pattern.
17262825 Expression of large tenascin-C splice variants in synovial fluid of patients with rheumato 2007 May Tenascin-C (TN-C) is a hexameric glycoprotein component of extracellular matrix, and alternative RNA splicing creates two major TN-C size variants (the small and large variants). The large TN-C variants play key roles in many pathologic conditions in adults, including tumorigenesis, regeneration, and inflammation. This cross-sectional study compared levels of large TN-C variants in synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Synovial fluid samples were obtained from knees of 26 patients with advanced RA and 79 with advanced OA. Expression of TN-C splice variants was examined using Western blotting. The levels of large TN-C variants in synovial fluid were determined by an enzyme-linked immunosorbent assay. Synovium were analyzed for TN-C by immunohistochemistry. Immunoblotting showed the presence of large TN-C variants in synovial fluid from patients with RA and OA. However, levels of large TN-C variants were fourfold higher in RA samples compared with OA samples (p < 0.01). Synovial fluid levels of TN-C in RA did not correlate with C-reactive protein levels. Immunohistochemistry of the synovium showed stronger reactivity in RA samples than in OA samples. These results indicate that local synthesis of TN-C is increased during rheumatic disease.
17619821 Rheumatoid arthritis and interleukin-32. 2007 Oct The inflammatory cytokine cascade plays a pivotal role in the pathogenesis of rheumatoid arthritis. Recently, a novel human cytokine, interleukin-32, was reported to induce tumor necrosis factor (TNF)-alpha. Interleukin-32 is expressed primarily in lymphoid tissues and leukocytes, but also in stimulated epithelial cells and synovial fibroblasts. Although the interleukin-32 receptor has not been reported, interleukin-32 can induce other inflammatory cytokines such as TNF-alpha, interleukin-1beta, and interleukin-6 from monocytes/macrophages in vitro and in vivo, and it synergizes with signals from pattern-recognition receptors. Notably, in the inflamed synovial tissues from rheumatoid arthritis patients, interleukin-32 is prominently expressed and correlates with the severity of arthritis and the expression of other cytokines, including TNF-alpha and interleukin-1. In experimental mice models of arthritis, joint injection of interleukin-32 induces joint inflammation, and overexpression of interleukin-32beta in hematopoietic cells exacerbates collagen-induced arthritis. Interleukin-32 can thus be seen to play an important role in the pathogenesis of rheumatoid arthritis.
18208366 Pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT in rheumatoid arthritis and the n 2008 Feb BACKGROUND: Adult rheumatoid arthritis (RA) patients are frequently clinically depressed. Peripheral inflammation in RA may influence neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, as well as growth factor production, which can modify neural circuitry and contribute to depression. OBJECTIVE: A convergence between pro-inflammatory cytokine-induced synovial joint inflammation in RA and the effects of pro-inflammatory cytokines on the brain may occur through activation of the stress-activated/mitogen-activated protein kinases (SAPK/MAPK) and/or Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. METHODS: The PubMed and Medlines databases were critically evaluated for evidence of SAPK/MAPK and/or JAK/STAT pathway activation in RA and depression. RESULTS/CONCLUSION: Some novel anti-depression drugs that were employed in animal models of 'sickness behavior' and in human depression clinical trials suppressed clinical markers of inflammation, as well as SAPK/MAPK and/or JAK/STAT signaling in vitro. Modifying pro-inflammatory cytokine signaling pathways in the brain with antidepressants may also be useful in ameliorating peripheral inflammation in RA.
18808304 Therapeutic potential of inhaled p38 mitogen-activated protein kinase inhibitors for infla 2008 Oct BACKGROUND: Over the past two decades, p38 MAPK (mitogen-activated protein kinase) has been the subject of intense multidisciplinary research. p38 MAPK inhibitors have been shown to be efficacious in several disease models, including rheumatoid arthritis, psoriasis, Crohn's disease, and stroke. Recent studies support a role for p38 MAPK in the development, maintenance, and/or exacerbation of a number of pulmonary diseases, such as asthma, cystic fibrosis, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). OBJECTIVE: Many previous attempts to develop p38 MAPK inhibitors have failed as a result of unacceptable safety profiles. These toxicities have been varied and are believed to derive from different off-target effects. METHOD: The above concerns can be overcome by delivering the compound locally to minimize whole-body burden, resulting in low exposure to the gastrointestinal, liver, and CNS. This review discusses the role of p38 MAPK in various inflammatory diseases, followed by the toxicity concerns associated with p38 MAPK inhibition. It also highlights the possible beneficial effect of delivering drugs via the inhalation route. CONCLUSION: We present proof-of-principle confirming the therapeutic potential of inhaled p38 inhibitors for asthma and other inflammatory pulmonary diseases.
19193621 Unresolved issues in identifying and overcoming inadequate response in rheumatoid arthriti 2008 Feb Rheumatoid arthritis (RA) is a chronic, multisystem, inflammatory disorder of the joints that affects about 1% of the world population. The ultimate goals of therapy include remission of disease and prevention of joint damage. Reaching these goals has become a realistic outcome for an increasing number of patients as treatment options have expanded over the past 3 decades. In addition to older therapies, such as methotrexate (MTX), other disease modifying drugs (DMARD), and tumor necrosis factor (TNF) inhibitors, newer biologic treatments have become available. For the substantial number of patients who experience an inadequate response to standard medications, biologic response modifiers (BRM) provide an important therapeutic alternative. The availability of multiple treatment options in the absence of clear definitions or criteria for remission and inadequate response, however, makes clinical decisions about measuring outcomes, predicting response to treatment, and prescribing pharmacologic therapies challenging. In this program, distinguished rheumatologists weigh the evolving body of clinical evidence to draw sound conclusions and resolve key issues in managing inadequate response to treatment and in achieving optimal outcomes in RA.
17068064 Consensus statement on the use of rituximab in patients with rheumatoid arthritis. 2007 Feb A large number of experts experienced in the treatment of rheumatoid arthritis were involved in formulating a consensus statement on the use of B cell-targeted treatment with rituximab in patients with rheumatoid arthritis. The statement was supported by data from randomised controlled clinical trials and the substantial literature on oncology. The statement underwent three rounds of discussions until its ultimate formulation. It should guide clinicians in the use of this newly approved biological agent in treating patients with rheumatoid arthritis.
17564785 Improved response to infliximab after leukocytapheresis in a patent with rheumatoid arthri 2007 This is the first report on effective leukocytapheresis (LCAP) in an acquired infliximab (IFM) resistant patient with rheumatoid arthritis (RA). A 44-year-old Japanese woman with RA was treated with prednisolone, cyclosporine A, and methotrexate, which failed to stabilize the disease. Infliximab was then administered and the disease activity was controlled on December 2003. However, RA became active again on June 2004 so that LCAP was administered weekly for 5 weeks. After the LCAP treatment, the ACR20% response was obtained again and IFM has regained its efficacy.
18344920 Dendritic cell subsets: their roles in rheumatoid arthritis. 2008 Jan Dendritic cells (DC) are now known to influence many different classes of lymphocytes (T, B, NK cells) and many types of T cell responses (Th1/Th2/Th17, regulatory T cells, peripheral T cell deletion). In rheumatoid arthritis (RA) DC have been described and their roles in RA pathogenesis have been implicated. This review summarizes the data obtained so far concerning the functional characterization of several DC subsets in human RA. Moreover, the effect of TNF-alpha blockade on DC phenotype and function is also discussed. As most of the studies on DC in experimental arthritis have been conducted using (immunomodulated/tolerogenic) DC as tools to ameliorate experimental arthritis, we give some examples of how these cells may induce tolerance in vivo. Although a lot of work has been performed so far, the specific and functional roles of DC subsets in human RA and in CIA remain to be established. Achieving a detailed understanding of specific DC functions in RA holds potential for modulating DC for immunotherapy by down-regulating the autoimmune response.
16247604 (18)F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resona 2006 Mar PURPOSE: The aim of this study was to assess rheumatoid arthritis (RA) synovitis with positron emission tomography (PET) and( 18)F-fluorodeoxyglucose ((18)F-FDG) in comparison with dynamic magnetic resonance imaging (MRI) and ultrasonography (US). METHODS: Sixteen knees in 16 patients with active RA were assessed with PET, MRI and US at baseline and 4 weeks after initiation of anti-TNF-alpha treatment. All studies were performed within 4 days. Visual and semi-quantitative (standardised uptake value, SUV) analyses of the synovial uptake of FDG were performed. The dynamic enhancement rate and the static enhancement were measured after i.v. gadolinium injection and the synovial thickness was measured in the medial, lateral patellar and suprapatellar recesses by US. Serum levels of C-reactive protein (CRP) and metalloproteinase-3 (MMP-3) were also measured. RESULTS: PET was positive in 69% of knees while MRI and US were positive in 69% and 75%. Positivity on one imaging technique was strongly associated with positivity on the other two. PET-positive knees exhibited significantly higher SUVs, higher MRI parameters and greater synovial thickness compared with PET-negative knees, whereas serum CRP and MMP-3 levels were not significantly different. SUVs were significantly correlated with all MRI parameters, with synovial thickness and with serum CRP and MMP-3 levels at baseline. Changes in SUVs after 4 weeks were also correlated with changes in MRI parameters and in serum CRP and MMP-3 levels, but not with changes in synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique for assessing the metabolic activity of synovitis. The PET findings are correlated with MRI and US assessments of the pannus in RA, as well as with the classical serum parameter of inflammation, CRP, and the synovium-derived parameter, serum MMP-3. Further studies are warranted to establish the place of metabolic imaging of synovitis in RA.