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ID PMID Title PublicationDate abstract
1734906 Regulation of B cell function by lobenzarit, a novel disease-modifying antirheumatic drug. 1992 Feb OBJECTIVE: Lobenzarit (disodium 4-chloro-2,2'-iminodibenzoate [CCA]) is a novel disease-modifying drug for the treatment of rheumatoid arthritis (RA). Although its clinical efficacy has been demonstrated, its mechanism of action remains unclear. We therefore examined the effects of CCA on in vitro IgM and IgM rheumatoid factor (IgM-RF) production by human B cells. METHODS: IgM and IgM-RF production was induced from highly purified B cells from 8 healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus factors generated from mitogen-activated T cells (TCF) or with immobilized anti-CD3-activated CD4+ T cells. RESULTS: CCA suppressed the production of IgM-RF as well as IgM at concentrations of 25-50 micrograms/ml (therapeutic serum concentrations of the drug), although the IgM-RF production induced by SAC plus TCF was suppressed at lower concentrations of CCA (1-3 micrograms/ml). Whereas CCA suppressed interleukin-2 (IL-2) production by anti-CD3-activated CD4+ T cells, its suppressive effects on B cells were not overcome by addition of IL-2 or TCF. CCA did not inhibit the initial stages of B cell activation in either culture system, but rather, suppressed the maturation of previously activated B cells. Cell cycle analysis by acridine orange staining indicated that CCA-mediated inhibition of B cell responsiveness induced by anti-CD3-activated CD4+ T cells was the result of a block at the G1-S interphase. CONCLUSION: These results indicate that CCA suppresses the production of IgM and IgM-RF by directly inhibiting activated B cells. Thus, one of the actions of CCA in RA may be the suppression of the function of activated B cells.
8457226 Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuc 1993 Apr OBJECTIVE: To examine whether T cell reactivity toward heat-shock proteins (HSP) contributes to cartilage destruction in rheumatoid arthritis (RA). METHODS: An in vitro system was used, in which human cartilage explants were cocultured with hsp60-activated synovial fluid mononuclear cells (SFMC) from patients with RA, and proteoglycan (PG) synthesis was measured. RESULTS: The hsp60-activated SFMC suppressed cartilage PG synthesis. This effect was dependent on the production of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). CONCLUSION: Mycobacterial 60-kd heat-shock protein can activate rheumatoid SFMC to suppress human cartilage PG synthesis. This suppression is mediated by IL-1 and TNF alpha.
7517975 Expression of functional B7 and CTLA4 on rheumatoid synovial T cells. 1994 Aug 1 To assess the role of B7, CTLA4, and CD28 in the pathogenesis of chronic synovitis we analyzed the expression and function of these cell surface molecules in patients with rheumatoid arthritis, osteoarthritis, and psoriatic arthritis, and in normal controls. Immunoperoxidase staining of rheumatoid synovial membranes showed reactivity of 30% of T cells with anti-B7 mAb, in contrast to osteoarthritic and normal synovial membranes, in which no such staining was seen. In addition, rheumatoid synovial fluid T cells were positive by flow cytometric analysis for B7 (mean 20%, range 0 to 96%), as measured by staining with anti-B7 mAb or the CTLA4 Ig fusion protein, whereas no B7 expression was detected on peripheral blood T cells (mean 1%). To analyze the functional importance of B7 expressed on synovial fluid T cells, we used these cells as stimulator cells in primary allogeneic MLC. Purified synovial fluid T cells were far stronger stimulator cells compared with paired peripheral blood T cells and resulted in a fivefold greater increase in allogeneic T cell proliferation. Furthermore, the proliferation induced by purified synovial T cells was markedly inhibited by addition of the CTLA4 Ig fusion protein (77%). Moreover, anti-B7 mAb (37%), anti-CTLA4 mAb (33%), and Fab fragments of anti-CD28 mAb (52%) partially inhibited the primary MLC. The expression of functional B7, together with the increased expression of MHC class II molecules, indicates that synovial T cells may serve as functional APCs and may be capable of autocrine stimulation via the CD28 activation pathway.
1375491 [The Sauvé-Kapandji operation. Analysis and results of 69 cases]. 1992 The authors present the results of 69 cases operated between 1983 and 1989. The indications were dominated by two aetiologies: degenerative lesions of the inferior radio-ulnar joint in rheumatoid arthritis: 58% of cases, and traumatic sequelae, predominantly secondary to fractures of the distal radius: 34% of cases. The authors stress the effects of distant lesions: skeletal lesions of the two bones of the forearm or the superior radio-ulnar joint. A third group of rarer indications consisted of painful dislocations of the inferior radio-ulnar joint in Madelung's disease (indication only applied to adults). There were two types of complications: complications due to excessively long or intra-articular screws, which were treated by removal of the screws and, more severe, ossifications of the zone of diaphyseal resection (5 cases) which interfered with the functional result in terms of mobility. Three cases required extensive diaphyseal resection. The results are analysed for each aetiological group in terms of pain, mobility prehensile strength after more than one year of follow-up. Good results were obtained in 80% of cases of post-traumatic lesions (16 cases). The insufficient results were related to associated lesions of the elbow or the 2 bones of the forearm. A good result was obtained in 3 out of 4 cases of Madelung's disease and one case, operated elsewhere and revised by pseudoarthrodesis, obtained a moderate result. Lastly, in rheumatoid arthritis, the results in terms of pain, mobility and prehensile strength were good, apart from 2 failures due to progression of rheumatoid disease (cases unsuitable for this treatment). Radiographic analysis according to Youm and Mac Murtry's criteria showed minimal regression in the carpoulnar translation index (pre-op: 0.28; post-op: 0.22). Overall, the Sauvé-Kapandji operation provided good quality clinical results when the indications and technique were rigorously applied.
7927126 [Biventricular inflow tract compression by chronic organized hemopericardium in Caplan syn 1994 Jun We report the case of a 59-year old patient with the rare combination of silicosis and rheumatoid arthritis, which is called Caplan's syndrome. The patient presented with right heart failure caused by a pericardial tumor compressing the right and the left ventricle. By means of several imaging techniques it was possible to elucidate the topographic relations of the tumor. Definite signs of malignant growth were not found. Despite his elevated perioperative risk we decided to operate on the patient. During the operation macroscopic and histologic evidence revealed that the tumor was not a neoplastic process but consisted of an organized hemopericardium. This demonstrates that pericarditis in rheumatoid arthritis can be hemorrhagic and can mimick a malignant pericardial tumor. The decision to operate was first supported by the findings of the applied imaging techniques, the normal endomyocardial biopsy, and the clinical course and were later confirmed in situ.
8996467 Methotrexate update. 1996 Methotrexate (MTX) has become one of the most widely prescribed second-line agents world-wide for rheumatoid arthritis (RA). Studies have established efficacy in populations which have failed other second-line agents. Although MTX must be considered as a potential hepatotoxin, studies have shown that liver histologic changes can be predicted by monitoring of serum albumin and AST at four to eight week intervals. MTX pulmonary toxicity appears to be more common than liver disease. It most often presents with a subacute course with dry cough and dyspnea with or without fever. Clinicians must be aware of this presentation and withhold the drug when these symptoms appear. MTX may also cause mild renal impairment when used with NSAIDs. This effect has been observed with higher mean weekly doses in the 15 to 20 mg range, but not with a starting dose of 7.5 mg. Although MTX may exhibit a variety of effects in in vitro systems its mechanism of action in patients with RA has not yet been determined.
8810674 Handicap in inflammatory arthritis. 1996 Sep Two instruments measuring handicap were evaluated and compared with clinical, laboratory and disability measures. Participants were 133 patients attending a rheumatology follow-up clinic in a district general hospital, of whom 102 were followed up after 3 months. Measurements included acute-phase response, early morning stiffness, pain, wellbeing, joint involvement (impairments), the Stanford Health Assessment Questionnaire (disability), the Disease Repercussion Profile and the London Handicap Scale (handicap). A substantial burden of disability and handicap was recorded. There were moderate correlations between impairments (0.4 < rho < 0.6), and moderate to strong correlations between disability and handicap measures (0.4 < rho < 0.8). Correlations between impairment and disability/handicap were weak (rho < 0.4). Mean changes in all variables over 3 months were small, and none was statistically significant. A comprehensive description of the impact of disease and treatment requires measurements to be made of impairments, disabilities and handicaps. The use of clinical and laboratory variables alone may be misleading.
8935050 The clinical diagnosis of temporomandibular disorders in the orthodontic patient. 1995 Dec Because many of the diseases and disorders that affect the temporomandibular joint (TMJ) and associated masticatory muscles occur in the age group of patients generally seen by the orthodontist, their recognition is of great importance in planning and performing orthodontic therapy. This article discusses the diagnosis and clinical significance of the various conditions that may be encountered.
8216404 In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and b 1993 Oct OBJECTIVE: To determine the major source of eicosanoid release in arthritic joint tissues and to examine the modulation of this release by indomethacin and diclofenac. METHODS: Release of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, leukotriene B4 (LTB4), and LTC4 was measured in supernatants of synovial tissue, cartilage, and bone incubates from patients with osteoarthritis, active rheumatoid arthritis (RA), inactive RA, and pseudogout. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids. RESULTS: Addition of the divalent cation ionophore A23187 resulted in significant release of all eicosanoids measured from synovial tissue, but not from cartilage, cortical bone, or cancellous bone. PG release was significantly inhibited by the addition of indomethacin or diclofenac at either 10(-5) moles/liter or 10(-7) moles/liter. The amount of LTC4 released from cartilage and bone was only slightly above the detection limit of the RIA, whereas large amounts were released from synovial tissue. Neither indomethacin nor diclofenac had an effect on LTC4 release. LTC4 release from synovial tissue of patients with inactive RA was significantly decreased in comparison with the levels from synovial tissue of patients with the other joint diseases. There was no significant difference in PG release among patients in the various disease groups. CONCLUSION: Synovial tissue appears to be the major source of eicosanoids in synovial fluid. Indomethacin and diclofenac inhibit the release of PG, but not LT, from various joint tissues.
8630114 Epstein-Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis. 1996 Apr OBJECTIVE: A causative role for Epstein-Barr virus (EBV) in the development of lymphoma in patients with rheumatoid arthritis (RA) has been proposed. We investigated the molecular features of EBV-positive diffuse large cell lymphomas in 2 patients with RA. METHODS: Southern blot analysis for immunoglobulin gene rearrangements, terminal repeat analysis for clonality of the EBV genome, and double-labeling of the lymphoma cells by in situ hybridization and immunoperoxidase staining were performed. RESULTS: In both cases, double-labeling studies localized the EBV genome to the malignant B cells. Both neoplasms contained clonal immunoglobulin gene rearrangements and clonal EBV genomes. CONCLUSION: Our data indicate that EBV infection was an early step in the development of these neoplasms. The findings further extend knowledge on the similarity of this subset of lymphomas to posttransplantation lymphomas and emphasize the role of immunosuppression in their genesis.
8081333 The Herbert cannulated bone screw in rearfoot arthrodesis. 1994 May Herbert 4.5- and 6.5-mm. cannulated bone screws were used to fixate nine talocalcaneal and six talonavicular arthrodeses in 12 patients in 2 years. All arthrodesis sites were clinically and radiographically fused within 8 to 12 weeks of operation. The authors describe proper use of the Herbert cannulated bone screw and discuss its advantages and limitations, compared with those of the traditional lag screw in rearfoot arthrodesis.
8981899 Primary cementless hip arthroplasty with a titanium plasma sprayed prosthesis. 1996 Dec One hundred two patients underwent 105 primary uncemented total hip arthroplasties and were reviewed at a minimum of 5 years after operation (mean, 6.1 years). The components were titanium alloy with a titanium plasma spray coating. The acetabular revision rate was 11.4%. Acetabular cavitary lytic lesions were identified in 25.5% at 5 years. All acetabular revisions were performed for a combination of wear and osteolysis. One femoral revision was performed to facilitate an acetabular revision, but the femoral revision rate for aseptic loosening was 0%. In addition, no femoral components had subsided or were thought to be loose radiographically. Thigh pain was present in 4% at 5 years. Despite the 25.5% incidence of acetabular osteolysis, distal femoral lysis was not seen and only 5% showed focal osteolysis in the trochanteric region proximal to the circumferential porous coating of the femoral component. Component design features were thought to be critical to the excellent performance of the femoral component and to the poor performance of the acetabular component.
8554698 Detection of T cell receptors in early rheumatoid arthritis synovial tissue. 1995 Synovial tissue is rarely available from patients with early synovitis, with the exception of synovial biopsies. However, T cell populations early in the development of synovitis may be enriched in antigen-specific cells and critical to disease pathogenesis. To investigate the T cell repertoire in early synovitis, we utilized a PCR protocol for detection of T cell receptor (TCR) transcripts present in small amounts of synovial tissue. To expand the substrate for PCR, preamplification of cDNA was performed with a 3' constant region primer plus either a mixture of variable region primers or random hexanucleotides. Utilizing this method improved the sensitivity of detection. This technique is applied here to the analysis of TCR transcripts in synovial biopsies from individuals with early rheumatoid arthritis (RA) and non-RA synovitis. TCR alpha-chain transcripts were detectable in 5/5 RA and 4/4 non-RA specimens evaluated, with beta-chain transcripts detected in 4/5 early RA and 4/4 non-RA specimens evaluated. Confirmation of transcripts by sequencing of cloned PCR products verified the specificity of amplification. The most frequently expressed TCR V region families in early RA synovitis were V alpha 11, V alpha 14, V alpha 28, V beta 7, V beta 9 and V beta 17. Several of these V regions have previously been implicated in studies of chronic RA synovitis. J alpha and J beta region usage was similar to that seen in chronic RA, and conserved N region motifs were apparent. We conclude that it is possible to detect TCR transcripts in small synovial biopsies from individuals with early arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
1629819 Clinical liver disease in patients with rheumatoid arthritis taking methotrexate. 1992 Feb Between 1981 and 1989, 3 of 134 patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) developed clinically significant hepatic dysfunction and showed histologic evidence of severe liver disease (fibrosis and cirrhosis). Factors identified in these patients that may have been linked to liver toxicity included diabetes, congestive heart failure and Felty's syndrome. In the patient group that received a post-MTX liver biopsy, pulmonary fibrosis and obesity were significantly associated with hepatic fibrosis/cirrhosis. Severe liver disease may occur in patients with RA treated with low dose MTX (less than 3%). Early liver biopsy is recommended in selected cases.
7547091 The effects of age and gender on the pharmacokinetics of tenidap sodium in patients with r 1995 1. This open-label study was conducted to evaluate the effects of age and gender on the pharmacokinetics of tenidap sodium in patients with either rheumatoid arthritis (RA) or osteoarthritis (OA). 2. A total of 145 male and female patients, 80 with RA (aged 22-91 years) and 65 with OA (aged 45-83 years) each received a single dose of 120 mg tenidap sodium. Pharmacokinetic parameters were estimated from individual tenidap plasma concentration-time curves determined up to 120 h post-dose. Tenidap plasma protein binding was determined in the youngest and oldest age groups for both RA and OA patients. 3. In RA patients, age and gender did not significantly affect the disposition of tenidap or the percentage of unbound tenidap in plasma. Only for tmax were statistically significant effects in the analysis of covariance observed and these were attributed to very high tmax values in two female patients. Likewise, in patients with OA, age and gender did not significantly affect the pharmacokinetics of tenidap, although patients with larger body weights had lower Cmax values. 4. Pharmacokinetic parameters were not significantly different between RA and OA patients, except for t1/2, where two outlier RA patients had low values that caused the mean value to be significantly lower in RA (24 h) than in OA (26 h) patients. Pharmacokinetic parameters for pooled values from RA and OA patients were as follows: t1/2 = 25 h, AUC = 538.4 micrograms ml-1 h, Cmax = 21.9 micrograms ml-1, tmax = 3.2 h.(ABSTRACT TRUNCATED AT 250 WORDS)
1405091 [A case of bucillamine-induced pneumonitis]. 1992 Apr A 65-year-old woman with rheumatoid arthritis was treated with gold (gold sodium thiomalate), bucillamine, and other drugs. Gold was discontinued because of rash. Consequently she presented with high fever and alopecia, and was admitted with dyspnea. Chest X-ray showed diffuse bilateral reticulolinear infiltrates. The percentage of lymphocytes was increased and OKT4/8 ratio was decreased to 0.22 in bronchoalveolar lavage fluid (BALF). In lung tissue specimens obtained by TBLB, alveolitis with Masson's bodies was seen on light microscopy, and electron micrography showed interstitial edema with desquamated macrophages in the alveolar space and lipid-laden pericytes, secondary to extensive destruction of the alveolar-capillary barrier. After discontinuation of drugs, her symptoms and infiltrates on the chest X-ray resolved. Furthermore, the results of drug lymphocyte stimulation test (DLST) were positive for both drugs. We diagnosed this case as bucillamine-induced pneumonitis, since the symptoms developed after the administration of bucillamine; however, an interaction between bucillamine and gold may have contributed to the occurrence.
1379132 Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived f 1992 Aug Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin VH gene repertoire of eight IgM- and 10 IgG-secreting synovial-derived hybridomas. The VH4 gene family is highly represented (38.5%) in this panel of hybridomas compared with the frequency of VH4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the VH4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of VH4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The VH gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of VH4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia.
1280884 Activation of collagen type II expression in osteoarthritic and rheumatoid cartilage. 1992 In situ hybridization and immunohistochemical techniques were applied to investigate gene expression and extracellular deposition of collagen type II in normal, osteoarthritic and rheumatoid human articular cartilage. Normal cartilage showed an essentially even extracellular distribution of type II collagen with poly- and monoclonal antibodies, while only a few cells were positive for alpha 1(II) collagen mRNA. In situ hybridization of osteoarthritic and rheumatoid cartilage, however, showed strong enhancement of type II collagen gene expression; transcripts were observed predominantly in the upper middle zone of the articular cartilage while the upper layer was mostly negative and correlated with a zone of reduced proteoglycan staining. The elevated mRNA levels frequently coincided with pericellular immunostaining for type II collagen, indicative for enhanced synthesis of the protein. In two samples, however, pericellular loss of collagen type II staining was found despite positive cytoplasmic signals with the alpha 1(II) RNA probe, suggesting enhanced collagen destruction. Control hybridization with a probe for 18S rRNA revealed very few negative cells throughout both normal and arthritic cartilage samples, ruling out major cell necrosis in the specimens investigated. Thus, our observations identify sites of activated type II collagen synthesis in osteoarthritic cartilage that were predicted by previous biochemical studies and support the notion that damaged cartilage attempts to restore matrix by enhanced synthesis of its components.
8868110 Differential expression of IL-1 and TNF receptors in inflammatory arthritis and osteoarthr 1996 Jan Pathological joint events in both inflammatory arthritis and degenerative arthritis are perpetuated by complex cytokine interactions. Two cytokines, IL-1 and TNF alpha, appear to be the major culprits in the pathogenesis of synovitis and in cartilage damage in these joint diseases. To analyze the expression of IL-1 and TNF alpha and their receptors on synovial and cartilage tissue, we performed an immunohistochemical study on knee biopsies from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA). Results identified a prevalent positivity to cytokines and their receptors of synovial cells from RA and PsA with respect to OA patients. In cartilage specimens, most RA and PsA patients showed no expression of the studied receptors, whereas the majority of OA biopsies were positive for all types of examined receptors except IL-1R2. Our study suggests that the cartilage is the main target of these cytokines in OA, while in IA IL-1 and TNF alpha exert their action in synovial tissue. In all the studied pathologies (RA, PsA, OA) the synovial tissue and the cartilage were differentially involved, indicating the importance of investigating both structures in joint disease studies.
8514483 Treatment of rheumatoid hand synovitis with a regional block technique. 1993 Apr This study reports a novel technique for treating painful rheumatoid hand synovitis using a regional block technique. Nine patients with symptomatic rheumatoid hand synovitis were treated. Assessments of symptoms, grip strength and synovial swelling were made in each hand before the injection, and at 1 and 4 weeks after the procedure. A sphygmomanometer cuff was inflated, on the side of the patients most symptomatic hand, to 220mmHg and a solution of hydrocortisone sodium succinate 50mgs and lignocaine 10mls 0.5% was injected intravenously. The cuff was deflated slowly after 20 minutes. The injected hand improved symptomatically in 7 patients at 1 week, and further improvement was reported in 6 of these 7 at 1 month. Mean grip strength increased significantly in the injected hand both at 1 week (p = 0.01) and 1 month (p = 0.018). There was no change in the other hand. This technique is safe, reduced hand pain and improved grip strength in these patients with rheumatoid hand synovitis.