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ID PMID Title PublicationDate abstract
11527077 Suppression of collagen-induced arthritis in rats by continuous administration of dae-bang 2001 Although dae-bang-poong-tang (an herbal formula of 15 herbs)-treated rats exhibited a mild inflammation, the significant histological changes including a marked infiltration of inflammatory cells in the synovium and damaged articular cartilages were not observed. The staining abilities of the cartilage such as periodic acid Schiff s reaction in the interterritorial matrix of hyaline cartilage, alcian blue and aldehyde fuchsin staining in the capsule of chondrocytes and in the interterritorial matrix of articular cartilage and Con A, sWGA and BSL-1 affinities of chondrocytes tended to decrease in the rats with collagen-induced arthritis compared with normal rats. Decreased stainabilities and affinities were almost recovered in the dae-bang-poong-tang-treated rats. In the collagen-induced rats, iNOS expression in the synovial lining cells and subsynovial tissue were significantly increased and numerous strong immunoreactive cells were demonstrated in the subsynovial tissue. Somewhat decreased immunoreaction of iNOS was shown in the synovial lining cells and subsynovial tissue of dae-bang-poong-tang-treated rats. It was concluded that dae-bang-poong-tang showed a notable protection against histological changes and histochemical staining, and it acted as an inhibitor of iNOS expression. Dae-bang-poong-tang may be used as a complementary therapeutic agent to alleviate the rheumatoid arthritis.
11324787 Up-regulation of CD44 in rheumatoid chondrocytes. 2001 The adhesion molecule CD44 is thought to play an important role in the inflammatory process. To identify the expression of CD44 in articular chondrocytes in rheumatoid arthritis (RA), monoclonal anti-CD44 antibodies were immunohistochemically used to react with articular cartilage specimens of 15 patients with RA, 9 with osteoarthritis (OA), and 6 with femoral neck fracture (FF). The proportion of CD44-positive chondrocytes in RA was 93 +/- 2% (N=16), which was significantly higher than that in OA (59 +/- 7%, N=9, p<0.001) and FF (46 +/- 5%, N=6, p<0.001). Among CD44 isoforms examined, the hemopoietic form was dominant in chondrocytes in RA. Therefore, up-regulation of CD44 on chondrocytes may play a significant role in cartilage degeneration in RA.
10672800 Comparative results of resection of the distal ulna in rheumatoid arthritis and post-traum 1999 Dec The purpose of this study was to determine whether the results of resection of the distal ulna differed depending upon the underlying aetiology of the condition. Patients with rheumatoid arthritis were compared with patients with post-traumatic wrist complaints. Fifty resections in 40 patients (eight male, 32 female) were assessed with respect to pain, range of motion, and grip strength. Of the 23 rheumatoid wrists, 86% were pain-free following surgery; however, only 36% of the patients in the trauma group reported pain relief postoperatively. Pain relief in post-traumatic patients was more predictable when distal radioulnar joint arthrosis was identified as the sole cause of wrist pain.
10844354 [Comparative study of fixation mode in total knee arthroplasty with preservation of the po 2000 May PURPOSE OF THE STUDY: We performed a prospective randomized study to compare two fixation modes, with and without cement, for total knee arthroplasty. MATERIAL AND METHODS: The study series was composed of 96 cemented or noncemented total knee arthroplasties performed between May 1993 and October 1995. The only difference was the diamond interface used for cemented prostheses and the mesh interface used for uncemented prostheses. The operator was unaware of the type of fixation until the bone slices had been obtained. We assessed outcome in 73 cases with a mean follow-up of 27 months. The two populations were comparable for preoperative clinical status, bone tophicity and surgical procedure. RESULTS: The mean duration of the operation was sgnificantly longer (> 10 min) for the cemented protheses. The complication rates were comparable but we did have two mobilizations of the tibial implant in the noncemented group. The total scores (127 +/- 29 in the cemented group versus 135 +/- 20 in the uncemented group) were significantly different. There were however more cases with degradation of the controlateral knee in the cemented group although the difference was not significant. When these cases were excluded from the analysis, the total scores for two groups were similar (143 and 140 respectively). Radiographic outcome was quite different with mobilization of the tibial implant in 2 cases and the rate of lucent borders was significantly higher in the noncemented group. DISCUSSION AND CONCLUSION: While the clinical outcome was comparable, the quality of the fixation was significantly better with cemented arthroplasty, which remains the gold standard.
10648019 Levels of serum and synovial fluid pyridinium crosslinks in patients with rheumatoid arthr 2000 Jan OBJECTIVE: To elucidate the major source of pyridinium crosslinks in rheumatoid arthritis (RA). METHODS: Serum samples were collected from 75 patients with RA and 41 healthy controls, and synovial fluid (SF) samples were collected from 20 patients with RA and 13 with osteoarthritis (OA). Paired samples of serum and SF were collected at the same time from 26 patients with RA. Levels of pyridinium crosslinks were determined by a recently developed high sensitivity assay method using high pressure liquid chromatography. RESULTS: The levels of serum pyridinoline (PYD) and serum deoxypyridinoline (DPD) were significantly higher in patients with RA than in healthy controls, and significantly correlated with laboratory variables indicating disease activity and severity. The levels of SF DPD, but not SF PYD, were significantly higher in patients with RA than in patients with OA. The levels of SF PYD and SF DPD both showed a significantly positive correlation with those of either SF interleukin 1beta or SF interleukin 6 in patients with RA. Finally, the levels of PYD, but not DPD, were higher in SF than in serum in all paired RA samples collected at the same time, with significant correlation between the members of each pair. CONCLUSION: These observations suggest than an increase of PYD in RA serum may originate mostly from affected joints and that an increase of DPD in RA serum may be influenced more by systemic bone resorption.
11669154 Delayed referral of female patients with rheumatoid arthritis. 2001 Oct OBJECTIVE: To analyze whether sex differences in referral exist in patients with rheumatoid arthritis (RA). METHODS: At the Department of Rheumatology of the Leiden University Medical Center, a special early arthritis clinic (EAC) was established. General practitioners (GPs) were encouraged to refer patients with joint complaints to the EAC. Subsequently, the diagnosis RA was made by a rheumatologist. RESULTS: In this report, 142 women and 82 men were included. The delays in patient's first encounter with a GP for both sexes were comparable. However, a significant difference in the GP's delay in referring female patients with RA to the EAC in comparison with male patients was observed (median of 93 days vs 58 days; p = 0.008). CONCLUSION: This report determined GP referral delay of female patients to a rheumatologist. GPs should be made aware that early detection and early referral of patients with RA are crucial for early treatment.
9264173 Schizophrenia, rheumatoid arthritis and natural resistance genes. 1997 Jun 20 The strong negative correlation between schizophrenia and rheumatoid arthritis might provide clues as to the aetiology of these two diseases. An immunological explanation has been sought in the HLA sector of the major histocompatibility complex, which has been shown to have a role in the development of rheumatoid arthritis. The search for an association between schizophrenia and HLA haplotypes, however, has yielded only controversial results. Nevertheless, an autoimmune aetiology is still suspected. The recent demonstration of geographical co-occurrence of high rates of schizophrenia and flavivirus infection suggests, for the first time, that a natural resistance gene (NRG) might be involved in the aetiology of schizophrenia. Such a NRG is carried by the C3H/RV mouse, providing protection against lethal infection by flavivirus, but not by the histocompatible C3H/He mouse. Furthermore, the C3H/He mouse has proved to be a good model for the development of Lyme arthritis, resulting from infection by Borrelia burgdorferi. It is suggested that there is a possibility that the C3H/RV mouse, which is known to be resistant to both flavivirus and rickettsia, may also be resistant to borrelia, since the Ixodid tick vector of flavivirus is the vector for all three of these organisms. If so, then the C3H/RV mouse would resist infection by borrelia, and could not develop Lyme arthritis. It is hypothesised, therefore, that despite the histocompatibility of these two strains, while the C3H/He mouse is vulnerable to Lyme arthritis, the C3H/RV mouse may be resistant. As a consequence, NRGs may play a part in triggering autoimmune disease, with HLA antigens responsible for its further development. This would indicate that the negative association of schizophrenia and rheumatoid arthritis could result from resistance or vulnerability to certain infections.
11466334 CD44 is the physiological trigger of Fas up-regulation on rheumatoid synovial cells. 2001 Aug 1 CD44 is a ubiquitous molecule known as a hyaluronan receptor. However, the relevance of CD44 to inflammatory processes, for example, rheumatoid synovitis, remains unclear. In this study, we propose a novel function for CD44 using synovial cells from rheumatoid arthritis (RA) patients and demonstrated that CD44 cross-linking augmented Fas expression and subsequent Fas-mediated apoptosis of the cells: 1) cross-linking of CD44 on RA synovial cells markedly augmented Fas expression and its mRNA transcription; 2) engagement of CD44 up-regulated Fas on the cells within 3 h, much more than IL-1beta and TNF-alpha did; 3) the Fas-mediated early apoptotic change of the cells was amplified by CD44 cross-linking; and 4) hyaluronan, especially when fragmented, also augmented Fas-mediated early apoptosis of the cells. Based on these findings, we postulate a new concept: that interaction of CD44 on RA synovial cells with hyaluronan fragments present in the surrounding extracellular matrix augments Fas expression as well as Fas-mediated apoptosis of synovial cells. This may lead to spontaneous growth arrest through Fas-Fas ligand pathway observed in synovial cells of RA synovitis in vivo.
11520249 New therapeutic approaches to the management of rheumatoid arthritis. 2001 Rheumatoid arthritis (RA) is a common disease that affects up to 1% of the population, and causes significant morbidity and early mortality. The aetiology of RA is unknown; however, in the last 10 to 15 years significant advances in molecular technology have provided a greater understanding of the pathogenesis of the disease. This has led to the development of new approaches to the treatment of RA. The disease modifying antirheumatic oral agent leflunomide inhibits the proliferation of activated T cells that are important in the inflammation and degradation of synovial tissues. The 2 biological agents approved for the treatment of RA, infliximab and etanercept, are inhibitors of the pro-inflammatory cytokine, tumour necrosis factor-alpha (TNFalpha). Infliximab is a chimeric human/mouse monoclonal antibody which is administered by intravenous infusion and binds with high affinity to TNFalpha, thereby neutralising its effects. Etanercept is a recombinant, soluble TNF receptor molecule which is administered subcutaneously and binds to TNFalpha in the serum rendering it biologically inactive. The protein A immunoadsorption column is a medical device that in conjunction with plasmapheresis can be used in patients with refractory RA. These agents have provided new and effective therapies for the treatment of patients with RA.
10686511 Characterization of tissue outgrowth developed in vitro in patients with rheumatoid arthri 2000 Jan BACKGROUND: The aim of this study was to analyze cellular and cytokine interactions governing the development of synovial tissue outgrowth in patients with rheumatoid arthritis (RA). METHODS: A single-cell suspension of dissociated synovial tissues of RA patients was cultured for a long period to develop tissue outgrowth. The resulting tissue outgrowth was characterized by immunohistochemical staining and ELISA. RESULTS: The tissue outgrowth developed in vitro included various cell types, such as macrophage-like synovial cells, fibroblast-like synovial cells and lymphocytes. Even after prolonged cultivation, synovial cells devoid of infiltrating T lymphocytes did not form tissue outgrowth. The outgrowth contained CD3+ cells, LeuM3 (CD14)+ cells and HLA-DR+ cells. The T cells expressed lymphocyte function-associated antigen (LFA)-1 and CD2, and the synovial cells expressed intracellular adhesion molecule (ICAM)-1 and LFA-3, suggesting possible interactions via LFA-1/ICAM-1 and CD2/LFA-3. Production of T-cell derived IFN-gamma and IL-17 and synovial-cell-derived fibroblast growth factor (FGF)-1 and IL-15 was confirmed in the tissue outgrowth as well as in RA synovial tissue. These cell types stimulate each other by secreting cytokines, leading to the secretion of proinflammatory cytokines and matrix metalloproteinase (MMP)-1 by the tissue outgrowth and proliferation of both lymphocytes and synovial cells. CONCLUSION: This study emphasizes the importance of cellular interactions between T cells and synovial cells, via adhesion molecules and the secretion of cytokines with stimulatory activity towards other cell types, for the hyperactivity of RA synovial cells.
11555410 Significantly depressed percentage of CD27+ (memory) B cells among peripheral blood B cell 2001 Oct CD27 has been found to be expressed on somatically mutated B cells and is thus a positive marker for memory B cells in peripheral blood (PB). Since abnormal immunogloblin (Ig) production is characteristic of the autoimmune diseases primary Sjögren's syndrome (pSS) and rheumatoid arthritis (RA), we have analyzed in detail the CD27 expression on PB B cell from these patient groups. Staining of PB B cells with monoclonal antibodies (MoAb) specific for CD19 and CD27 revealed a significantly depressed percentage of CD27+ PB B cells in patients with pSS (14.8 +/- 1.6%) compared to both healthy donors (31.3 +/- 4.7%, P = 0.005) and patients with RA (40.8 +/- 4.1%, P = 0.0001). In addition, the percentages of both the IgD+CD27+ and the IgD-CD27+ B-cell subpopulations were significantly lower in pSS patients compared to RA patients and healthy donors. However, the relative proportion of IgD- and IgD+ cells among the CD27+B cells were almost the same for the three groups. Our data suggest a disturbance in the differentiation of peripheral B cells and possibly a bias towards plasma cell differentiation, resulting in a depressed percentage of CD27+ memory PB B cells in pSS. These results are potentially of pathological significance and of diagnostic value.
11591802 T cell activation in rheumatoid synovium is B cell dependent. 2001 Oct 15 Rheumatoid arthritis results from a T cell-driven inflammation in the synovial membrane that is frequently associated with the formation of tertiary lymphoid structures. The significance of this extranodal lymphoid neogenesis is unknown. Microdissection was used to isolate CD4 T cells residing in synovial tissue T cell/B cell follicles. CD4 T cells with identical TCR sequences were represented in independent, nonadjacent follicles, suggesting recognition of the same Ag in different germinal centers. When adoptively transferred into rheumatoid arthritis synovium-SCID mouse chimeras, these CD4 T cell clones enhanced the production of IFN-gamma, IL-1beta, and TNF-alpha. In vivo activity of adoptively transferred CD4 T cells required matching of HLA-DRB1 alleles and also the presence of T cell/B cell follicles. HLA-DRB1-matched synovial tissues that were infiltrated by T cells, macrophages, and dendritic cells, but that lacked B cells, did not support the activation of adoptively transferred CD4 T cell clones, raising the possibility that B cells provided a critical function in T cell activation or harbored the relevant Ag. Dependence of T cell activation on B cells was confirmed in B cell depletion studies. Treatment of chimeric mice with anti-CD20 mAb inhibited the production of IFN-gamma and IL-1beta, indicating that APCs other than B cells could not substitute in maintaining T cell activation. The central role of B cells in synovial inflammation identifies them as excellent targets for immunosuppressive therapy.
11093690 Progressive appearance of overlap syndrome together with autoantibodies in a patient with 2000 Nov We describe an extraordinary patient with overlap syndrome (systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis) having positive autoantibodies against Sm, double stranded DNA, DNA topoisomerase I, and centromere, together with rheumatoid factor. The patient had multiple organ involvement resulting from thrombotic microangiopathy that mimicked so-called normotensive scleroderma renal crisis, and died mainly of massive pulmonary hemorrhage caused by thrombotic thrombocytopenic purpura. The clinical presentations of the case support the concept of strong associations between disease-specific autoantibodies and clinical features.
10433432 Hand surgery and quality of life. 1999 Jun The outcome in patients having surgery to the hand was assessed subjectively using a questionnaire that covered activities of daily living (ADL), hand pain and psychological well-being. The questionnaires were completed on average 6.9 months preoperatively and 20.6 months postoperatively by 15 patients with osteoarthritis undergoing trapeziectomy and 25 patients with rheumatoid arthritis undergoing Swanson arthroplasties of the metacarpophalangeal joints. Surgery resulted in significant improvements in reported ADL and hand pain, in both groups. Improvement in perception of hand function and health was only seen in the osteoarthritic group. There was no improvement in arthritis activity, mood or quality of life in either group. These results confirm that surgery for arthritis of the hand relieves pain and improves ADL. However, it has a greater effect in patients with localized osteoarthritis than in those with rheumatoid arthritis.
11324791 Were the patterns of treatment for rheumatoid arthritis during 1977-1992 consistent with m 2001 OBJECTIVE: Quality assessment of the long-term treatment of patients with rheumatoid arthritis (RA). METHODS: Treatment patterns in a cohort of 70 local and 77 distant RA patients during 1977-1992 were reviewed retrospectively and compared to modern clinical guidelines. RESULTS: In 1977 disease-modifying anti-rheumatic drugs (DMARDs) were given to 62% of the new, hospitalised patients, systemic corticosteroids to 7%, and corticosteroid joint injections to 24%. Patients with short disease duration and/or serious disease were selected for DMARD-treatment. Rheumasurgery was performed on 21%. During follow-up of local patients 54% were recorded with DMARDs for a mean duration of 29 months; approximately 1/5 of the follow-up period. Methotrexate was used infrequently. Local and systemic corticosteroids were recorded in approximately 20%. Rheumasurgery, predominantly non-prosthetic, was performed on 27%. CONCLUSIONS: Patients with early and serious disease were selected for DMARD-therapy, but the treatment duration was too short for modern requirements. Pharmaceutical and surgical treatment patterns were otherwise mainly consistent with present guidelines.
9566352 Purification of filaggrin from human epidermis and measurement of antifilaggrin autoantibo 1998 Apr BACKGROUND: The so-called antikeratin antibody (AKA) and the antiperinuclear factor (APF) that recognize proteins related to human epidermal filaggrin belong to the most specific serological markers of rheumatoid arthritis (RA). However, assays for the detection of AKA and APF are currently based on immunofluorescence, a method that is subject to arbitrary interpretation and inadequate standardization of the substrates. METHODS: Proteins extracted from human epidermis were separated by reversed-phase high-performance liquid chromatography (HPLC). Filaggrin-containing fractions, identified in immunoblotting by monoclonal antifilaggrin antibodies, were then subjected to gel filtration HPLC and, finally, to a second reversed-phase HPLC step. Tryptic digestion, amino acid sequencing and mass spectrometry were used to confirm the identity of the purified protein. Filaggrin was used as antigen in enzyme-linked immunosorbent assay (ELISA) to measure IgG class antifilaggrin antibodies. RESULTS: The filaggrin preparation obtained gave a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, binding monoclonal antifilaggrin antibody in immunoblotting. Amino acid sequences of all 10 tryptic peptides analyzed were shown to originate from human filaggrin. Antifilaggrin antibody levels exceeded the 99th percentile level of 100 middle-aged blood donors in 26/55 (47%) RA sera. At a similar cutoff level 28/55 (51%) of the RA sera were positive in the AKA test. Of the 26 antifilaggrin-positive sera, 21 were also AKA-positive. CONCLUSION: Human filaggrin can be purified by standard biochemical techniques, despite the heterogeneity of the protein, and used in ELISA for testing autoantibodies to filaggrin. The sensitivity of the assay equals that of the AKA test.
9663476 Changes in biochemical markers of joint tissue metabolism in a randomized controlled trial 1998 Jul OBJECTIVE: To determine the effects of low-dose prednisolone on joint tissue metabolism in early rheumatoid arthritis (RA). METHODS: In addition to a range of biochemical markers of cartilage, bone and synovial tissue turnover, levels of pro-matrix metalloproteinase 3 (pro-MMP-3), pro-MMP-1, and cytidine deaminase (CD) were measured in serum from 79 of 128 patients with early RA who took part in the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study. Serum concentrations of joint tissue metabolites on treatment and off treatment were compared using Student's t-test. RESULTS: Levels of the keratan sulfate epitope, 5D4, and glycosaminoglycan (GAG) were similar on and off treatment. However, the levels of synovium-derived markers, hyaluronate (HA) and N-propeptide of type III procollagen (PIIINP), were reduced by 23.9% (P < 0.01) and 25.2% (P < 0.001), respectively, during treatment with prednisolone. Serum osteocalcin (OC) was reduced by 25.8% (P < 0.001), while the levels of CD and pro-MMP-3 increased by 31.2% (P < 0.01) and 53.7% (P < 0.001) during prednisolone treatment compared with the off-treatment period. CONCLUSION: Low-dose prednisolone had no significant effect on markers of cartilage turnover (GAG, 5D4) in early RA, suggesting that early erosions do not involve cartilage surfaces. The reduction in the markers of bone turnover (OC) and synovial tissue turnover (HA and PIIINP) support the general view that prednisolone reduces synovitis and suppresses bone turnover.
10624276 Management of the patient with a total joint replacement: the primary care practitioner's 1999 Jul The primary care practitioner assumes chief responsibility for patients with arthritis. More than 40 million Americans experience some form of arthritis. Management of the patient with arthritis may include a referral to an orthopedic surgeon for surgical intervention. As estimated, up to 500,000 total joint replacement procedures are performed by orthopedic surgeons each year in the United States. Presurgical evaluation for a total joint replacement is imperative to ensure that the patient can safely undergo this surgical procedure. Postsurgical care of a patient with total joint replacement involves coordinating care with the physical therapist and orthopedic surgeon to ensure adequate follow-through with the recommended rehabilitation program, prophylactic antibiotic coverage, and observation for any complications including infection, deep-vein thrombosis, or loosening of the total-joint prosthesis.
11165717 The telomeric part of the HLA region predisposes to rheumatoid arthritis independently of 2001 Jan We have evaluated the possible contribution of genes besides DQ and DR to the association of HLA with rheumatoid arthritis (RA). To this end, we have looked at the allele distributions of six microsatellites, D6S1014, D6S2673, TNFalpha, MIB, C1-2-5, and C1-3-2 among 132 RA patients and 254 controls. We have defined 19 microsatellite clusters corresponding to previously described ancestral haplotypes. One of them was D6S1014*143-D6S273*139-TNFalpha*99-MIB*350-C1-2-5*196-C1-3-2*354, often found associated with DQB1*0201-DRB1*0301. As part of this microsatellite cluster, the allele MIB*350 was found to be a RA-predisposing factor, independent of DRB1*0301 and RA-predisposing haplotypes DQB1*03-DRB1*04 and DQB1*0501-DRB1*01. We conclude that the telomeric part of the HLA region contains a locus conferring predisposition to RA independently of HLA class II.
10879685 Proliferation of a subpopulation of human peripheral blood monocytes in the presence of co 2000 May Apart from acting on hemopoietic progenitor cells, colony stimulating factors (CSFs) have been shown to be involved in the activation, survival, proliferation and differentiation of more mature cells of the monocyte/macrophage lineage. There is evidence that a proportion of human peripheral blood monocytes can proliferate in response to CSF-1, (also known as M-CSF) and granulocyte-macrophage-CSF (GM-CSF). CSFs have been shown to be at elevated levels in the synovial fluid of RA patients and thus local proliferation of monocyte/macrophage within an inflamed lesion may contribute to the local tissue hyperplasia evident in inflammatory conditions. Flow cytometric analysis of surface antigen expression and cytokine production in response to lipopolysaccharide stimulation has been used to characterise the proliferating subpopulation of monocytes. Further characterization and subsequent isolation of this subpopulation of monocytes may provide new and important information necessary in understanding inflammatory diseases such as rheumatoid arthritis, where local proliferation at the site of inflammation may be a key factor contributing to the chronicity of the disease.