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ID PMID Title PublicationDate abstract
11094435 Citrullination: a small change for a protein with great consequences for rheumatoid arthri 2000 A new autoantibody activity, which is almost 100% specific for rheumatoid arthritis (RA), has been found. The essential part of the B-cell epitope is a modified form of arginine (ie citrulline). The conversion of protein-contained arginine to citrulline is an enzymatic process that is carried out by peptidylarginine deiminase (PAD), an enzyme that appears to be hormonally controlled. Because of its remarkable specificity, citrullination and related processes might open new possibilities for studying the aetiology of RA.
9456013 Subcutaneous T-cell lymphoma in a patient with rheumatoid arthritis not treated with cytot 1997 Nov This case report describes an 81-year-old patient with prolonged rheumatoid arthritis (RA), which was complicated by the occurrence of a subcutaneous T-cell lymphoma. During the course of his illness the patient had not been treated with disease-modifying agents (i.e. cytotoxic agents), but only symptomatically with anti-inflammatory drugs. This finding demonstrates a previously undescribed association between RA and a rare from of subcutaneous T-cell lymphoma, which may add more information to the controversial issue of emergence of malignancy in RA.
9034983 A hidden immunoglobulin G2 in patients with rheumatoid arthritis detected by nuclear magne 1997 Feb OBJECTIVE: The ratios of immunoglobulin (Ig) G1 and IgG2 in patients with rheumatoid arthritis (RA) were examined by nuclear magnetic resonance (NMR) and the results were compared to data obtained by ELISA. METHODS: The IgG of 11 patients with RA were prepared with a DE-52 column and the specific signals for IgG1 and IgG2 were measured by NMR. The ratios of IgG1 and IgG2 were determined by the intensity of this signal. The samples were also measured by ELISA. RESULTS: The ratios of IgG2 in patients with RA measured by NMR were increased significantly compared to controls. However, there were no significant differences in the data determined by ELISA. Thus, a discrepancy exists in the analysis of IgG2 ratios between NMR and ELISA methods. CONCLUSION: There was a discrepancy in the IgG2 ratios of patients with RA between NMR and ELISA methods, and we attribute this to a conformational difference in IgG2 in patients with RA.
10835684 Therapeutic activity of agonistic monoclonal antibodies against CD40 in a chronic autoimmu 2000 Jun The use of agonistic monoclonal antibody against CD40 has emerged as one the most effective ways to boost immune responses against infectious agents or to fight cancer. Here, we report that the same monoclonal antibodies against CD40 (FGK45 and 3/23) previously used to elicit protective immune responses treated the autoimmune inflammatory process of chronic collagen-induced arthritis in DBA/1-TCR-beta transgenic mice, as well as collagen-induced arthritis in DBA/1 mice, both animal models of rheumatoid arthritis. This study indicates that agonistic monoclonal antibody against CD40 can potentially be used to treat chronic autoimmune inflammatory processes.
11128668 A comparison of agreement and sensitivity to change between AIMS2 and a short form of AIMS 2000 Dec OBJECTIVE: To examine the agreement between and compare the sensitivity to change of the Arthritis Impact Measurement Scale (AIMS2) and AIMS2 Short Form (AIMS2-SF) in a large sample of rheumatoid arthritis (RA) patients examined within the framework of a longitudinal observational study. METHODS: Data were collected from patients in a community based RA register by a postal survey in April 1994 (1,030 respondents) and again in 1996 (1,153 respondents), comprising AIMS2, Modified Health Assessment Questionnaire (MHAQ), Medical Outcome Survey SF-36, and other commonly used health status measures. The degree of agreement was examined by plotting differences between AIMS2 and AIMS2-SF against the mean of the 2 scores for the 5 main components. The upper and lower limits of agreement (mean diff. +/- 1.96 SD) were calculated and plotted. The intraclass correlation coefficients were computed by repeated measurement ANOVA. Validity was assessed on the basis of external indicators of health status, and responsiveness on the basis of standardized response means. RESULTS: The AIMS2 and AIMS2-SF showed substantial to near-perfect agreement. Best agreement was seen for the physical and affect components. Better agreement for the symptom component was obtained when replacing item 42 with item 38. Internal consistency was high in all components. The 2 forms correlated similarly with scores from other instruments within the same domains, showing similar construct validity. There was no difference in responsiveness between the 2 forms when using changes in patient assessed global disease activity as external indicator of change in health status, and responsiveness for the physical and symptom dimension was similar to other instruments (SF-36, MHAQ). CONCLUSION: The AIMS2-SF is amenable for use in large surveys with a modification of one item in the symptom scale.
11103558 [Need for and availability of services by nursing insurance for patients with rheumatoid a 2000 Oct Although rheumatoid arthritis is amongst those functional disabling diseases requiring massive help and care, there is as yet no study on how RA patients master their everyday lives, nor are there reports on how many of those patients are in need of and/or do in fact receive benefits from the German Nursing Care Insurance. METHODS: In a representative sample of considerably disabled RA patients (functional capacity < 67%) in rheumatological care it was investigated how many patients received nursing care insurance benefits and how many more would have been entitled to receive them. Standardized interviews exploring functional capacity, amount of help and care needed and help-seeking behaviour were conducted to determine which patient-related and resource-related characteristics were associated with unmet need regarding the patients entitlement to benefits of nursing care insurance. Using the relation between justified need for nursing care insurance benefits and the functional status score, a coefficient was computed by logistic regression to project the expected proportion of RA patients entitled to care insurance benefits. RESULTS: A projected 5.4% of all RA patients needed benefits from the nursing care insurance, but only 63% of those did in fact receive benefits. It was found that unmet need was almost exclusively due to the fact that patients actually eligible for insurance benefits did not apply for it, whereas unjustified rejection of applications by insurance experts made up for only a marginal proportion. CONCLUSION: Applying for nursing care insurance benefits is still not a matter of course. It must be considered that about one third of all obviously care-dependent RA patients either claim care insurance benefits too late or never do. To avoid unmet need, experts should encourage particularly those patients who are unaware of their right to ask for help.
9389324 The HLA-DQ7 and -DQ8 associations in DR4-positive rheumatoid arthritis patients. A combine 1997 Nov Several different lines of evidence have demonstrated that inherited susceptibility to rheumatoid arthritis (RA) is associated with the DRB1 genes encoding the HLA-DR4 and HLA-DR1 molecules. A contrasting hypothesis has recently been proposed, suggesting that, in general, the DRB1 locus is associated with protection to RA and that the RA-associated DRB1 alleles are not responsible for the primary disease association but merely permissive for the susceptibility conferred by the HLA-DQ alleles with which they are in linkage disequilibrium. We have performed a critical review of the literature on the HLA association in RA with special emphasis on studies in which both an HLA-DR and -DQ association has been investigated. Our analyses provide strong evidence against the hypothesis that HLA-DQ molecules play a major role in the general susceptibility to RA. Thus, the strongest association in rheumatoid arthritis is with DRB1 genes rather than DQB1 genes.
11196696 IL-6 promoter polymorphisms in rheumatoid arthritis. 2000 Jun We investigated the possible association between the IL-6 promoter polymorphisms, at positions -622 and -174, and susceptiblity to, and/or outcome of, rheumatoid arthritis (RA). A total of 163 patients with RA and 157 healthy controls were genotyped for IL-6 using a PCR-RFLP method. The -622 and -174 alleles were in complete linkage disequilibrium. No difference was observed in the distribution of IL-6 promoter genotype or allele frequencies between RA patients and controls. However, a significant difference in the mean age at disease onset between IL-6 genotypes was observed. The present data appear to rule out an important role of IL-6 promoter polymorphisms in the susceptibility to RA. However, IL-6 genotypes may contribute to the pathogenesis of the disease by influencing the age at disease onset.
9795437 [Bicondylar knee replacement--an intermediate term evaluation of the Genesis prosthesis]. 1998 Jul 65 knee arthroplasties in 60 patients (5 x both sided, 49 x female, 11 x male) with a Genesis Total Knee System (54 x cemented, 6 x cementless, 4 x tibial cemented/femoral cementless, 1 x tibial cementless/femoral cemented) were evaluated according to the Knee Society Score and the HSS Score with a medium follow up of 4 years und 5 months (3 years and 4 months to 5 years and 11 months). In 48 patients the diagnosis was gonarthrosis, in 17 patients it was rheumatoid arthritis. The medium postoperative Knee Score was 80.9 points, the Function Score was 73.7 points. The HSS Score obtained 80.9 points. 87.7% of the patients were excellent or good. The Genesis Total Knee arthroplasty has proved to be reliable for osteoarthritis and rheumatoid arthritis in medium term.
11107061 Molecular mechanism of monocyte predominant infiltration in chronic inflammation: mediatio 2000 Nov A novel monocyte chemotactic factor, a cross-linked homodimer of S19 ribosomal protein (RP S19) was initially isolated from a rheumatoid arthritis synovial lesion. The RP S19 dimer causes the monocyte specific chemotaxis in vitro and the monocyte predominant infiltration in vivo, via its agonistic and antagonistic effects on the C5a receptors of monocytes and polymorphonuclear leukocytes, respectively. The agonistic effect is attributed to the similarity of regional structures between RP S19 and C5a, the complement C5-derived leukocyte chemotactic factor, although overall homology of the amino acid sequence between these molecules is only 4%. The antagonistic effect depends upon the C-terminal portion of RP S19. The RP S19 dimer is produced and released by apoptotic cells, and this dimer recruits monocytes from the circulation to the apoptotic lesion. The infiltrated monocytes/macrophages engulf the apoptotic cells, translocate to regional lymph nodes via lymphatics and present the antigenic information of the apoptotic cells to the T cell repertoire. In this manner, the apoptotic cell clearance system connects to the acquired immune system. The innate and acquired immune mechanisms, mediated by the RP S19 dimer, participate in the pathology of inveterate chronic inflammation such as rheumatoid arthritis.
9355010 Stiffness of trabecular bone of the tibial plateau in patients with rheumatoid arthritis o 1997 Oct Stiffness of subchondral proximal tibial trabecular bone is a factor in the stability of prostheses implanted into that bone. The stiffness of trabecular bone in osteoarthritis (OA) has been documented. Trabecular bone in rheumatoid arthritis (RA) is osteopenic in numerous sites and morphologically abnormal in the proximal tibia. Reliable data on proximal tibial bone in RA are lacking, although 1 study failed to identify abnormalities. The purposes of this study were (1) to document the stiffness of the proximal tibial cancellous bone in patients with RA, (2) to determine the effect of angular deformity on bone stiffness in rheumatoid patients, and (3) to compare RA stiffness values with those in published reports for OA. Fifteen tibial plateau were obtained from patients with RA during surgery. Each plateau was horizontally seated in a mold and covered with cement. The plateau was divided into 6 regions, which were used to facilitate comparison between specimens and the existing literature. Indentation tests were conducted with a 4-mm-diameter cylindrical indentor controlled by an MTS machine. The indentor descended at a rate of 2 mm/min to a maximum depth of 1.0 mm; load and displacement data were digitally recorded. Stiffness was calculated from the slope of the linear region of the curve using best-fit linear regression. Where varus deformity was present, stiffness in the medial plateau was higher overall than for the other compartment; whereas in the case of valgus deformity, stiffness of the lateral side was significantly higher (P < .05 for each observation). In comparison to older normal specimens, both the medial compartment of the varus RA specimens (P < .01) and the posterolateral compartment of the valgus RA specimens (P < .01) had significantly lower stiffness. Comparison with OA specimens showed that in varus RA, the posteromedial region had significantly lower stiffness than in varus OA at the same site (P < .01). In valgus RA, the lateral region had significantly lower stiffness than in valgus OA at the same site (P < .01). The mean stiffness ratio of the valgus RA was significantly (P < .01) altered from normal, and for the varus RA, it was significantly (P < .01) different from normal posteriorly. The stiffness ratios for the varus RA were significantly (P < .01) different from those for varus OA; there was no difference between valgus RA and valgus OA. It is concluded that RA affected bone has significantly lower stiffness than normal and osteoarthritic bone. The loaded plateau is stiffer than the unloaded plateau in angular deformity, but is still less stiff than normal bone and osteoarthritic plateaus with corresponding deformities.
10341394 Changes in CD4+ T lymphocyte subsets in circulating blood and synovial fluid following fil 1999 May The purpose of this study is to determine the changes in CD4+ T lymphocyte subsets in the circulating blood and synovial fluid following filtration leukocytapheresis (LCP) therapy for patients with rheumatoid arthritis (RA). A Cellsorba column packed with polyester fibers was used for the removal of circulating leukocytes. For patients with RA, filtration LCP or sham procedures were performed 3 times with 1 week intervals between procedures. T lymphocyte surface markers in the peripheral blood and synovial fluid were measured by flow cytometry. The proportions of activated CD4+ T cells (CD4+DR+, CD4+CD25+, and CD4+CD71+) and CD4+CD29+ T cells increased significantly in the peripheral blood, but the counts of these cells were significantly reduced in the synovial fluid after 2 treatment sessions in the LCP group. No significant changes were observed in the proportion of these cells in the control group. Our findings suggest that filtration LCP may cause a redistribution of activated T cells from affected joints into the circulating blood.
9844885 [The characteristics of the clinical course and the frequency and difficulties in the diag 1998 Aug A clinical and morphological analysis was done in patients with rheumatoid arthritis (RA), that showed high incidence (61.8%) of lesions of the internals in RA. Affliction of the heart was present in 48 percent of cases, that of the lungs and pleura in 47.6 percent, renal lesions were recordable in 23 percent, serious breakdown of the liver in 16 percent, and of the alimentary canal in 22 percent of cases, with the associated visceral lesions present in a major part of the population. Considering high incidence of visceral lesions in RA and their impact on the gravity of the course of the disease and, not infrequently, on the prognosis we consider it necessary for the practitioners to bend their energies to thorough clinical examination of the RA patients when he or she first applied for medical advice. Other measures to be instituted include deliberate dynamic observation, timely prescription of adequate complex therapy and inauguration of preventive measures during the period of remission of the disease.
11111818 Immunoadsorption for the treatment of rheumatoid arthritis: final results of a randomized 2000 Oct A double-blind, randomized, placebo controlled study was conducted to determine the efficacy of a promising immunoadsorption treatment device containing staphylococcal protein A (Prosorba Immunoadsorption Column, Cypress Bioscience, Inc., San Diego, CA, U.S.A.) in patients with refractory rheumatoid arthritis (RA). Eligibility criteria required adult RA patients who had failed either methotrexate or 2 other disease modifying antirheumatic drugs (DMARD) and who had predefined active disease. All disease-modifying agents were discontinued at least 30 days prior to entry. Patients received 12 weekly procedures after being randomized to the active treatment arm or to the sham treatment arm (apheresis only). Evaluations were double-blinded and occurred at baseline and periodically for 24 weeks thereafter. Primary efficacy was assessed at 7 and 8 weeks after the completion of 12 treatments (at trial Weeks 19 and 20) using the American College of Rheumatology (ACR) definition of improvement (1,2), and results from the assessments at Weeks 19 and 20 were averaged. Ninety-nine randomized patients had a mean disease duration of 15.4 years and received an average of greater than 5 DMARD regimens prior to entry. Analysis of patients who completed all treatments and follow-up indicated that 15 of 36 (41.7%) column-treated patients responded compared to 5 of 32 (15.6%) sham-treated patients (p < or = 0.003). Intent to treat analysis of all patients who were randomized in the study indicated 15 of 52 (28.9%) column-treated patients responded compared to only 5 of 47 (10.6%) patients who received sham treatments (p = .005). Common adverse events (AEs) included joint pain, fatigue, joint swelling, and hypotension. Central line usage was clearly associated with significant AEs during this trial and is not recommended. Hemoglobin, hematocrit, and mean corpuscular volume values decreased similarly in both treatment arms, attributed to phlebotomy for laboratory and scientific studies and to small, repetitive (normal) apheresis losses. Other AEs such as nausea, rash, pruritus, flushing, and fever occurred in 1 to 6% of treatments in each arm (NS). There was no significant increase in AEs in column-treated patients compared to sham-treated patients. Protein A immunoadsorption was proven to be a new therapeutic alternative in patients with severe, refractory disease.
10332970 Predicting the short term direct medical costs incurred by patients with rheumatoid arthri 1999 May OBJECTIVE: With increasing interest in revising the mechanisms of health care funding, the ability to anticipate patients' medical expenditures as well as to identify potentially modifiable predictors would be informative for health care providers, payers, and policy makers. METHODS: Eight hundred fifty-eight patients with rheumatoid arthritis from 2 Canadian centers reported semi-annually on their health services utilization and health status for up to 12 years. Annual direct costs were calculated using 1994 Canadian prices. Regression models for the variation in total direct costs and the individual resource components (i.e., physicians, tests, medications, acute and non-acute hospital care) were estimated using previous values of age, sex, disease duration, education, methotrexate availability, employment status, global well being, pain, duration of morning stiffness, and functional disability as predictor variables. The models were developed using all available data except the last 2 observations (i.e., data collected on the last 2 self-report questionnaires) from each patient, which were reserved for model validation. The predictive abilities of the models were assessed by comparing the most recent costs with those predicted by the model using values of the predictor variables from the previous time period. Further, to assess whether the models conferred any advantage over cost estimates based only on previous costs, most recent observed costs were also compared with costs observed in the preceding time period. RESULTS: Self-reported indices of either global well being, pain, or functional disability predicted total direct costs as well as the costs of the 5 individual resource components. Being younger, female, disabled from the work force, having shorter disease duration, and receiving more formal education also predicted higher costs in at least on health resource category. However, being older predicted higher acute and non-acute care hospital costs. Regression models incorporating longitudinal data did not perform better than average costs in the preceding time period in predicting future short term costs. CONCLUSION: Global well being, pain, functional disability, and previous costs are the most important predictors of short term direct medical costs. Although we have demonstrated that regression models do not perform better than previous costs in predicting future short term costs, previous costs are a much less informative predictor than health status variables. Variables such as functional disability and pain identify potentially modifiable disease features and suggest interventions that may improve patient well being and reduce costs.
11280102 The burden of arthritis and nonsteroidal anti-inflammatory treatment. A European literatur 2001 The purpose of this literature review is to summarise data available from publications describing the burden of osteoarthritis and rheumatoid arthritis in Europe, and to highlight gaps in the literature. On the basis of extensive literature research, the epidemiology of arthritis, its treatment costs, and iatrogenic costs related to nonsteroidal anti-inflammatory drug (NSAID) treatments are described, differentiating results by country. The review shows that, as well as having a significant impact on healthcare budgets, arthritis also affects patients and caregivers. For those countries where data were available, indirect costs were found to be of comparable magnitude to direct costs. Additionally, it was found that the iatrogenic costs related to the treatment of NSAID-induced adverse events are a significant component of the total costs of arthritis. The number of publications on the burden of arthritis in Europe is rather small in comparison with what is available for the US. Comparison of national results shows wide variations between countries, which may be partly due to discrepancies in the methodology applied to estimate the burden of arthritis, the cost items included in the analysis, and the data sources used to gather cost information. Additionally, comparing the burden of arthritis by country across Europe is difficult because of the variety of ways in which results are presented, e.g. on a per-patient basis, or for the whole population. To better understand the burden of illness of arthritis in Europe, not only is more research required, but the methodology to be applied in burden-of-illness analyses must also be standardised.
9653169 Human parvovirus B19 as a causative agent for rheumatoid arthritis. 1998 Jul 7 Human parvovirus B19 (B19) DNA was detected in the synovial tissues in 30 of 39 patients with rheumatoid arthritis (RA), and infrequently in those with osteoarthritis and traumatic joints. On the other hand, the expression of the B19 antigen VP-1 was specific (27/27) in RA synovium with active synovial lesions, but not in osteoarthritis and controls. The target cells of B19 were macrophages, follicular dendritic cells, T cells, and B cells, but not synovial lining cells in the synovium. B19-negative bone marrow cells, tonsil cells, and macrophage cell line U-937 cells became positive for the expression of VP-1, and more productive for interleukin 6 and tumor necrosis factor alpha when cocultured with RA synovial cells. The expression of VP-1 and the production of interleukin 6 and tumor necrosis factor alpha was significantly inhibited by the addition of neutralizing antibody for B19, suggesting that B19 detected in RA synovial cells is infective. B19 is involved in the initiation and perpetuation of RA synovitis, leading to joint lesions.
9416863 Lack of association of HLA-DRB1 genotype with radiologic progression in Japanese patients 1997 Dec OBJECTIVE: To evaluate the role of HLA-DRB1 genotypes in the development and progression of the rheumatoid arthritis (RA) disease process. METHODS: Patients with polyarthritis of < 1 year in duration were consecutively enrolled in the study. Other inclusion criteria were no diagnosis of inflammatory diseases other than RA, and no history of taking disease-modifying antirheumatic drugs or steroids. Patients were evaluated every 4 weeks, and radiographs of the hands/wrists and feet were taken at presentation and 1 year later. HLA-DRB1 genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: We enrolled 198 patients (median disease duration 5.0 months) and 150 controls. The frequency of individuals with DRB1*0405 and *0410 was significantly higher in the patients than in the controls. Homozygous states for DRB1 alleles with the RA-related shared epitope (SE) were associated with increased susceptibility for the development of polyarthritis (odds ratio 3.4, 95% confidence interval 1.5-7.7). None of the DRB1 alleles or SE genotypes correlated with the presence of bone erosion at presentation or 1 year later. CONCLUSION: DRB1 alleles with SEs were associated with the development of polyarthritis but not with early radiographic progression of the disease process.
9090764 Relations between absolute number of CD4 + CD29+ memory cells and levels of interleukin-6, 1997 Mar Synovial fluid samples from 21 rheumatoid arthritis patients were analyzed for lymphocyte subsets using flow cytometry and antibodies to the lymphocyte surface antigens CD3, CD4, CD8, CD16, CD19, CD29, and CD45RA. Synovial fluid levels of interleukin-6, rheumatoid factors and acute phase proteins were also measured. Depletion of CD45RA+ cells and predominance of CD29+ cells were found. Interleukin-6 levels were markedly elevated (1155 pg/ml; range, 24-3875 pg/ml), as were levels of IgM, IgG and IgA rheumatoid factors and of acute phase proteins. CD4 + CD29+ counts were significantly correlated with interleukin-6 levels. Interleukin-6 levels were significantly correlated with levels of all three rheumatoid factor classes but not with levels of acute phase proteins. Significant correlations were also found between CD19+ B counts and levels of all three rheumatoid factor classes. These data suggest that synovial fluid CD4 + CD29+ cells may be involved in the immune dysregulation characteristic of rheumatoid arthritis. The correlation between CD4 + CD29+ counts and interleukin-6 levels is consistent with the recent hypothesis that, together with monocytes, CD4 + CD29+ cells are an important source of the elevated levels of interleukin-6 seen in rheumatoid synovial fluid.
11360403 Development of rheumatoid arthritis in a patient with pernicious anemia: case report. 2001 Feb Very few cases of rheumatoid arthritis combined with pernicious anemia have been reported in the world literature and none in the Chinese literature. A 62-year-old female initially presented with anemia. Pernicious anemia was diagnosed by characteristic blood and bone marrow morphology. Laboratory data showed a deficiency of vitamin B12 and positive anti-gastric parietal cell antibodies. Her anemia improved after vitamin B12 therapy. Painful swelling of multiple joints developed 6 years later. The clinical presentation supported a diagnosis of rheumatoid arthritis. We report herein a rare case of rheumatoid arthritis and pernicious anemia in the same ethnic Chinese patient. We also review the literature and discuss a possible association between a non-organ-specific autoimmune disease, rheumatoid arthritis, and an organ-specific autoimmune disease, pernicious anemia.