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ID PMID Title PublicationDate abstract
12355125 Forearm bone mineral density in patients with rheumatoid arthritis. 2002 The aims of the present study were to determine whether patients with rheumatoid arthritis (RA) show significantly lower forearm bone mineral density (BMD) than sex- and age-matched healthy controls, and to identify significant factors that are associated with their BMD loss. One hundred eighty-four patients with RA and 185 sex- and age-matched healthy controls were enrolled in the study: 71 men 37-68 years of age (RA, 31; controls, 40), 129 premenopausal women 30-48 years of age (RA, 67; controls, 62), and 169 postmenopausal women 48-69 years of age (RA, 86; controls, 83). The correlation of forearm BMD, measured by dual energy X-ray absorptiometry with anatomic grade in the wrist, functional class, duration of disease, steroid use, modified health assessment questionnaire (HAQ) score for the upper and lower extremities, levels of serum C-reactive protein and rheumatoid factor, erythrocyte sedimentation rate, and years since menopause (YSM) were examined by multiple regression analysis. In men with RA, no clinical factors were significantly correlated with forearm BMD, and the BMD did not differ significantly from that in controls (0.329 +/- 0.060 [mean +/- SD] vs. 0.351 +/- 0.069 g/cm(2)). In premenopausal women with RA, the HAQ score for the upper extremities was positively correlated with forearm BMD ( P < 0.05), but the BMD did not differ significantly from that in controls (0.298 +/- 0.085 vs. 0.324 +/- 0.088 g/cm(2)); in postmenopausal women with RA, YSM and anatomic grade in the wrist were negatively correlated with forearm BMD ( P < 0.01 and P < 0.05), and the BMD was significantly lower than in controls (0.192 +/- 0.063 vs. 0.223 +/- 0.076 g/cm(2), P < 0.01). These findings suggest that forearm BMD loss in patients with RA may be accelerated in women after menopause, and that YSM and disuse of the wrist may be significant determinants of their forearm BMD loss.
12197898 In vivo activated T cells in rheumatoid synovitis. Analysis of Th1- and Th2-type cytokine 2002 Sep T-cell cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). Their detection in the joint, however, is impaired by the complex network present in the synovium. Although many synovial T cells show signs of previous activation, only a few express interleukin (IL)-2 receptor, marker of recent activation. The aim of this study was to analyse the cytokine production by in vivo activated (IL-2R +) T cells from RA at different stages of the disease. For this purpose, T cells were isolated from peripheral blood and synovial fluid of four patients with active RA, two at the onset of the disease, one in the early phase during treatment, one in long-lasting chronic phase. One patient was studied at the onset of the disease and 52 months later. Cells were initially expanded with a low dose of IL-2, cloned and analysed for cytokine production. The results showed a strong predominance of T helper (Th) 1 clones in the blood and a slight prevalence of Th0 clones in the joint of all the four patients. Interferon-gamma and IL-2 production was higher in the long-lasting RA, whereas IL-4 synthesis was prevalent in early RA. Enrichment in IL-10-producing clones was present only in the joint of the untreated patients. The longitudinal study confirmed the differences in cytokine production between early and late phases of disease. These data confirm that RA is mainly a Th1-driven condition. However, in vivo activated synovial T cells produce also Th2-type anti-inflammatory cytokines, such as IL-4 and IL-10. The synthesis of both cytokines is a feature of the very early phase of RA, although the selective recruitment of IL-10-producing T cells is quickly lost.
12611472 Environmental risk factors for rheumatoid arthritis. 2002 Oct In this review we examine the association between rheumatoid arthritis (RA) and exposure to silica and other environmental toxicants. We performed a series of meta-analyses of peer-reviewed studies, using 10 studies for silica, and 5 studies for other exposures published between 1986 and 2001. Before the meta-analyses, all studies were reviewed and evaluated for heterogeneity and publication bias. We detected a significant heterogeneity among studies on silica and calculated a combined estimator of relative risk (RR), using the random effect model. Most studies reported consistent elevation in the risk of RA with exposure to silica. The combined RR for silica exposure was 3.43 195% confidence interval (95% CI) 2.25-5.22] for all studies, and 4.45 (95% CI 2.24-8.86) for male cohorts. The combined RR for male farmers was 1.40 [95% CI 1.18-1.66] and was 1.29 [95% CI 0.84-1.97] for pesticide exposure. The combined RR for hair dressers was 1.52 [95% CI 1.04-2.20]. The findings of this study suggest a significant elevation in the risk of RA from exposure to silica. Further studies assessing the dose-response effect would greatly aid in determining whether the observed association is causal.
15370719 Correlation between soluble intercellular adhesion molecule 1 level and extracellular supe 2004 OBJECTIVE: We investigated serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and the activity of extracellular superoxide dismutase (EC-SOD) in rheumatoid arthritis (RA). We also considered whether there was a correlation between sICAM-1 and EC-SOD and disease activity. METHODS: Levels of sICAM-1 were measured in serum from 42 patients with active RA and 30 control subjects by enzyme-linked immunosorbent assay (ELISA). EC-SOD activity was determined in sera isolated from patients with active RA and from controls. RESULTS: The serum levels of sICAM-1 were significantly higher in patients with RA than in control subjects (p<0.001). In contrast, the activity of EC-SOD was significantly lower in RA patients than in healthy controls (p<0.001). A significant negative correlation was found between the levels of sICAM-1 and EC-SOD activity (r=-0.39, p<0.01). There was a statistically positive correlation between sICAM-1 levels with Ritchie articular index (RAI) score and C-reactive protein (CRP) (r=0.32, p<0.05; r=0.44, p<0.01, respectively). CONCLUSIONS: These results show that the increased levels of sICAM-1 present in active RA patients might be due to the decreased activity of EC-SOD, and increased levels of sICAM-1 may also reflect disease status or activity.
15270253 Clinical study of qingluo tongbi granules in treating 63 patients with rheumatoid arthriti 2004 Jun The study is to observe the therapeutic effects of qingluo tongbi granules (QTG) in patients with rheumatoid arthritis (RA) and the changes of immune indexes. In this series there are 63 patients with RA of the type of yin-deficiency and heat in collaterals treated with QTG as the treated group and 55 patients of the same type treated with Tripterygium glycosides as the control group. As a result, in the treated group, the curative rate is 9.52% and markedly effective rate 38.10%, with a total effective rate of 90.48%, while the corresponding rates in the control group are 0, 20.00% and 83.64%, respectively. The curative effect in the treated group is better than that in the control group (P<0.05). Besides, no obvious adverse reactions are found in the treated group. Therefore it is concluded that as a new medicinal preparation QTG is safe and effective in the treatment of RA.
12915159 Pharmacological treatment of established rheumatoid arthritis. 2003 Oct Rheumatoid arthritis (RA) is a chronic, inflammatory condition of unknown aetiology that affects about 1% of the general population. Although the optimal care of RA patients requires various modalities, pharmacotherapy remains the cornerstone of treatment for established RA. The current therapeutic model encourages a step-up approach that safely incorporates several currently available classes of agents: non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors, glucocorticoids, disease-modifying anti-rheumatic drugs, and biological agents (tumour necrosis factor-alpha inhibitors and interleukin-1 receptor antagonist). Non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors and glucocorticoids, which offer a quick onset of symptom relief, are used mainly as adjunctive therapies. Disease-modifying anti-rheumatic drugs and biologicals have been successful in altering disease outcome and slowing radiographic progression. The indications, efficacy and safety of these agents in clinical trials and practice are reviewed in this chapter.
15020327 Joint erosion in rheumatoid arthritis: interactions between tumour necrosis factor alpha, 2004 Apr BACKGROUND: Osteoclasts, specialised bone resorbing cells regulated by RANKL and M-CSF, are implicated in rheumatoid joint erosion. Lymphocyte-monocyte interactions activate bone resorption, this being attributed to tumour necrosis factor alpha (TNFalpha) and interleukin 1 beta (IL1beta) enhanced osteoblast expression of RANKL. In animal studies, TNF potently increases osteoclast formation in the presence of RANKL. RANKL-independent osteoclastogenesis also occurs, though IL1 is required for resorptive function in most studies. These inflammatory cytokines have a pivotal role in rheumatoid arthritis, OBJECTIVE: To study the interactions of TNFalpha and IL1beta with RANKL, particularly the time course of the interactions and the role of lymphocytes. METHOD: Cultures of lymphocytes and monocytes (osteoclast precursors) or of purified CD14(+) cells alone (osteoclast precursors) were exposed to various combinations of TNFalpha, RANKL, and IL1beta or the inhibitors osteoprotegerin, IL1 receptor antagonist, or neutralising antibodies to RANKL or to IL1. Osteoclastogenesis and resorptive activity were assessed on microscopy of dentine slices. RESULTS: TNFalpha potently increased osteoclast proliferation/differentiation in the presence of RANKL. This effect was greatest when RANKL was present before but not after exposure of osteoclast precursor cells to TNFalpha. The resorptive activity of osteoclasts generated by TNFalpha in the absence of RANKL was critically dependent upon IL1, which was expressed by lymphocyte-monocyte interaction. CONCLUSION: TNFalpha potently enhances RANKL mediated osteoclast activity. Interactions between TNFalpha and IL1 also result in osteoclastic activity independently of RANKL. These findings will inform therapeutic approaches to the prevention of joint erosion in rheumatoid arthritis.
15584892 Pleural involvement in systemic disorders. 2004 Dec The collagen vascular diseases are a heterogeneous group of immunologically-mediated inflammatory disorders. Frequently, these diseases affect organ systems outside the thorax as their primary manifestation, but may involve the pleura as a single presenting feature, as part of multisystem involvement, or as an isolated manifestation of a disease that is otherwise quiescent. In this article, we review the manifestations of respiratory disease caused by rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis/dermatomyositis, mixed connective tissue disease, Sjogren's syndrome, Wegener's granulomatosis, and sarcoidosis.
12411063 The relationship between myelodysplastic syndromes and autoimmune disorders. 2002 Jun OBJECTIVE: To explore the relationship between the myelodysplastic syndromes (MDS) and autoimmune disorders (AID). METHODS: The clinical data of 117 MDS patients were reviewed. RESULTS: Nineteen (16.2%) of 117 MDS patients had AIDs. The commonest AID associated with MDS was rheumatoid arthritis (31.6%) and ulcerative colitis (26.3%). Compared with that in MDS patients without autoimmune disorders, the leukemic transformation rate was not increased in the MDS/AID but the median survival time was shorter in MDS/AID patients. CONCLUSION: MDS patients associated with autoimmune disorders may be an unfavorable factor for their prognosis.
12447632 Changes in the concentration of plasma matrix metalloproteinases (MMPs) and tissue inhibit 2002 Nov Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) have been reported to be associated with arthritis. Total joint replacement results in total resection of cartilage and synovium at the joint. We investigated longitudinal changes in plasma MMP and TIMP after total joint replacement. Eight patients with osteoarthritis (OA) and 15 patients with rheumatoid arthritis (RA) had total knee or total hip replacements. Plasma was collected from all patients before surgery and at 1 week and 6 weeks after surgery. In RA patients the plasma MMP-3 and the MMP-3/TIMP-1 ratio decreased after total joint replacement, whereas CRP and ESR did not change. Therefore, CRP and ESR reflect systemic inflammation; however, plasma MMP-3 and the MMP-3/TIMP-1 ratio may reflect inflammation and/or degeneration of the affected joint.
15301981 Patient education. 2004 Aug There are a wide range of opportunities for arthritis patient education including individual or group counselling, printed notes and the Internet. Over the past 20 years efforts have been made to evaluate patient education programmes and determine if they are effective and, more recently, whether they are cost-effective. In the short term (up to 6-12 months) structured educational programmes have been demonstrated to increase patient knowledge and improve desirable behaviours such as relaxation, exercise and compliance with medications. More controversial has been the long term outcome (>12 months) of these programmes. Some studies indicate continuing benefit, albeit at reduced levels, compared to earlier evaluation points. Other studies, including a recent Cochrane report suggest that the beneficial effects are not sustained. In conclusion, patient education programmes have a modest, but significant, benefit on patient knowledge and behaviour, at least in the short term.
15563398 Simultaneous detection of DNA synthesis, activation and cytokine secretion in collagen II 2004 T cell activation and secretion of cytokines from activated peripheral blood mononuclear cells (PBMC) in culture have traditionally been measured by 3H-thymidine incorporation for assessment of cell proliferation. However, this method has many disadvantages that limit its usage in analyzing antigen-specific T responses, because of the low specific frequencies of the cells. Collagen II (250-270) may be an important autoantigen involved in the pathology of rheumatoid arthritis (RA). To further study the specific T cells response to CII 250-270, we developed an improved method for measuring lymphocyte proliferation and activation, and intracellular cytokine production, by flow cytometry at the single cell level. BrdU, an analog of thymidine, was incorporated into cellular DNA as a marker of individual cell proliferation. The cells were fixed and permeabilized, and a monoclonal antibody against BrdU conjugated with a fluorescent dye was used to measure BrdU incorporation. A Tris staining technique for the simultaneous determination of cell surface activation markers (CD69 or CD25) and intracellular cytokine production was also used and the parameters were assessed by 3-color flow cytometry. Optimal conditions were selected to improve the sensitivity and specificity of the assays. This method allowed simultaneous detection of lymphocytic DNA synthesis, phenotype analysis and cytokine production at the single cell level, and thus it may be a useful tool for analyzing immune responses.
15140777 High production of proinflammatory and Th1 cytokines by dendritic cells from patients with 2004 Jun OBJECTIVE: To assess whether DC from RA produce altered cytokine levels and whether this is regulated by triggering of Fc gamma receptors (FcgammaR). METHODS: The production of proinflammatory (TNFalpha, IL1, IL6), Th1 (IL12, IFNgamma), and Th2 (IL10) cytokine profiles of immature DC (iDC) from patients with RA and healthy subjects upon triggering of FcgammaR dependent and independent pathways was investigated. iDC, derived from blood monocytes by standardised protocols, were stimulated with immune complexes (IC) at day 6 for 48 hours and, subsequently, for 2 days with LPS in the presence or absence of IC or IFNgamma, resulting in fully matured DC (mDC). IL1, IL6, TNFalpha, IFNgamma, IL12, and IL10 levels in supernatants were measured by ELISA and RIA. RESULTS: mDC from patients with RA showed a markedly increased production of IL1, IL6, TNFalpha, and IL10 compared with DC from healthy donors. Triggering of FcgammaR decreased the production of proinflammatory cytokines IL1, IL12, and IFNgamma by iDC and mDC in RA and controls. The production of IL6 and TNFalpha decreased in patients with RA, whereas it was increased in controls. Triggering of FcgammaR independent mechanisms using IFNgamma increased the production of proinflammatory and Th1 cytokines, which was more pronounced in RA. CONCLUSION: FcgammaR dependent pathways influence cytokine production by DC. A skewed balance towards proinflammatory and Th1 cytokines in RA can, at least partly, be restored by triggering FcgammaR on DC in RA. Insight into the mechanism which determines the FcgammaR balance might lead to new strategies to abrogate Th1 driven inflammatory processes in RA.
15046450 Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruc 2004 Mar We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs. The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector. Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation.
12904904 Intracapsular hip fractures in patients with rheumatoid arthritis. 2003 We reviewed the treatment of 43 patients with rheumatoid arthritis and femoral neck fracture. Patients' average age was 66.4 (36-80) years and average duration of RA was 20.3 (4-42) years. Thirteen patients were treated with primary total hip arthroplasty (THA), and the clinical results were comparable to patients treated conservatively or by osteosynthesis. Eighteen patients were treated with primary bipolar hip prosthesis and after an average of 6.1 (1-13) years there was no acetabular destruction. However, long-term results were inferior to patients treated with THA. Nine patients were treated with osteosynthesis, of which two later had a hip prosthesis. Three cases with impacted fractures were treated conservatively with successful union in all.
14672900 Anti-apoptogenic function of TGFbeta1 for human synovial cells: TGFbeta1 protects cultured 2004 Jan OBJECTIVE: To investigate anti-apoptogenic mechanism of transforming growth factor beta1 (TGFbeta1) towards synovial cells. METHODS: Isolated synovial cells, treated or not with TGFbeta1, were cultured in the presence or absence of anti-Fas IgM, proteasome inhibitor Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or C2-ceramide. After cultivation, apoptosis of synovial cells was examined by the presence of hypodiploid DNA(+) cells, the presence of terminal deoxy (d)-UTP nick end labelling(+) cells (TUNEL(+) cells), activation of caspases, and disruption of mitochondrial transmembrane potential (DeltaPsim). RESULTS: Activation of caspase-9 and DeltaPsim was found in anti-Fas IgM treated synovial cells. The increment of both hypodiploid DNA(+) cells and TUNEL(+) cells accompanied by the activation of caspase-8 and caspase-3 was also determined in anti-Fas IgM treated synovial cells. These hallmarks for apoptosis induced by anti-Fas IgM were significantly suppressed in TGFbeta1 treated synovial cells. LLL-CHO, etoposide, and C2-ceramide also caused DeltaPsim, the increment of both hypodiploid DNA(+) cells and TUNEL(+) cells, and the activation of both Leu-Glu-His-Asp ase (LEHDase; caspase-9 like activity) and Asp-Glu-Val-Asp ase (DEVDase; caspase-3 like activity) in synovial cells. As determined in anti-Fas IgM treatment, TGFbeta1 significantly reduced apoptotic cell death of synovial cells induced by the above chemicals. CONCLUSIONS: The protective effect of TGFbeta1 for mitochondrial homoeostasis may be important in the anti-apoptogenic function of TGFbeta1 for synovial cells.
15229947 Costs of rheumatoid arthritis in France: a multicenter study of 1109 patients managed by h 2004 Jul OBJECTIVE: The economic impact of rheumatoid arthritis (RA) is substantial, but most studies provide cost estimates specific to a US population. We performed a cost-of-illness analysis of patients with RA for French society. METHODS: A cross-sectional study among rheumatologists in 148 hospitals in France was conducted between November and December 2000. Data were collected on health resource consumption associated with RA (treatments, medical devices, physician visits, examinations, hospitalization, other health professional care) during the previous 12 months. Direct costs and social costs were evaluated for 1109 RA patients. The relation of costs to disease activity and severity was analyzed. RESULTS: The annual direct cost of RA per patient was over euro4000. The costs due to hospitalizations represented around 60% of the costs. The major reason for hospitalization was acute care for RA in a rheumatic disease ward. Patients visited a physician an average of 13 times during the 12 months, 7.7 +/- 8.6 visits to an office-based physician and 5.1 +/- 4.4 visits to a hospital-based physician. Among them, 37% of patients were receiving at least one disability pension (16.7%) or sick-leave allowance (11.9%), with an estimated cost of euro7328 per patient. The mean annual budget per patient was euro2742. Medical and social costs increased in patients with severe disease (2 times), longer disease duration since diagnosis (more than double for patients with a history longer than 10 yrs vs patients with less than 2 yrs), active disease (1.4 times), and functional status (4 times more for American College of Rheumatology class IV than for class I). CONCLUSION: Direct costs represented 59% of the total costs for patients with active RA and 57% for patients with severe RA. Social costs represented 41% of the total costs on average.
12750939 Lack of association of tumor necrosis factor alpha gene polymorphism in patients with rheu 2003 Jul The aim of this study was to investigate the association of tumor necrosis factor alpha (TNFalpha) gene promoter polymorphisms in Chinese patients with rheumatoid arthritis (RA) in central Taiwan. A total of 106 RA patients and 253 normal controls were studied. Polymerase chain reaction (PCR)-based restriction analysis was used to identify A/G polymorphism at position 308 in the promoter region of the TNFalpha, which is located at 6q21.3. For the genotype of TNFalpha-308 polymorphism, there was no statistically significant difference between RA patients and normal controls (Fisher's exact test, P=0.82). Additionally, no statistical association in the distribution of TNFalpha-308 polymorphism between rheumatoid factor (RF)-positive and -negative patients was noted. The lack of an association of TNFalpha-308 polymorphism with RA and RF in our study implies that TNFalpha-308 polymorphism cannot serve as a candidate gene marker for screening RA patients in Taiwan.
15642135 Circulating tumour necrosis factor-alpha bioactivity in rheumatoid arthritis patients trea 2005 Our objective was to clarify the heterogeneity in response to infliximab treatment in rheumatoid arthritis (RA); to this end, a bioassay was designed to explore the contribution of circulating tumour necrosis factor (TNF)-alpha bioactivity and its possible link to response. The bioassay is based on the induction of IL-6 and osteoprotegerin (OPG) production by synoviocytes in response to TNF-alpha. RA synoviocytes were cultured with TNF-alpha (5 ng/ml) and 42 RA plasma samples collected just before starting therapy. Levels of IL-6 and OPG were measured in supernatants. In 20 of the patients, plasma samples collected before and 4 hours after the first and the ninth infusions were tested in the same way. Plasma concentrations of TNF-alpha and p55 and p75 soluble receptors were measured using ELISA. TNF-alpha induced IL-6 and OPG production by synoviocytes, which was further increased with patient plasma dilutions and inhibited by infliximab. With plasma samples obtained before the first infusion, the IL-6-induced production was greater in patients with a good clinical response than in the poor responders (44.4 +/- 23.3 ng/ml versus 27.4 +/- 20.9 ng/ml; P = 0.05). This high circulating TNF-alpha bioactivity was strongly inhibited with the first infliximab infusion. The difference between IL-6 levels induced with plasma samples obtained before and 4 hours after the first infusion was greater in patients with a good clinical response (40.0 +/- 23.7 ng/ml versus 3.4 +/- 10.0 ng/ml; P = 0.001). Similar findings were obtained for OPG production (7.0 +/- 6.2 ng/ml versus 0.0 +/- 3.0 ng/ml; P < 0.05). Levels of circulating TNF-alpha bioactivity were predictive of clinical response to TNF-alpha inhibition, confirming a key role for TNF-alpha in these RA patients.
15182800 Leflunomide-induced aseptic meningitis. 2004 May Drug-induced aseptic meningitis is uncommon and occurs primarily in patients with autoimmune disease. We report the first known case of leflunomide-induced aseptic meningitis, in a patient with rheumatoid arthritis.