Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
8448642 Renal morphology after cyclosporin A therapy in rheumatoid arthritis patients. Internation 1993 Mar Because cyclosporin A (CyA) has the potential of causing structural damage to renal tissue, kidney biopsies from 41 patients with RA treated with CyA at a maximum dose of 4.6 +/- 1.2mg/kg/day (mean +/- SD) for 16 +/- 7 months, were compared to kidney biopsies from 11 RA patients not treated with CyA and 41 sex- and age-matched control subjects without RA (kidney donors). Four patients in the CyA group but none in the control groups had morphological features of CyA nephropathy, defined as at least moderate focal interstitial fibrosis with tubular atrophy, arteriolar alterations or both. The dose of CyA and the initial serum creatinine level, but not treatment duration, were higher in patients with CyA nephropathy than in those without it. None of the 24 patients whose CyA dose did not exceed 5 mg/kg/day and whose serum creatinine did not rise by 50% or more above his or her pre-CyA level developed CyA nephropathy. These results indicate that the therapeutic conditions which have been shown to minimize the risk of CyA nephropathy in other autoimmune diseases can also prevent its occurrence in RA, and that CyA nephropathy can be avoided when the following rules are observed: the initial dose should be 2 or 3 mg/kg/day; the maximum dosage should not exceed 5 mg/kg/day; serum creatinine should be monitored regularly for as long as CyA is administered, and the dose should be decreased each time creatinine rises by more than 30% above the pre-CyA level.
8639180 Prevention and reversal of cartilage degradation in rheumatoid arthritis by interleukin-10 1996 May OBJECTIVE: Inflammation-induced articular cartilage degradation is a major problem in rheumatoid arthritis (RA). Type 1 T cell activity (characterized by interferon-gamma/interleukin-2 [IL-2] production), and consequently, the production of the proinflammatory cytokines IL-1 and tumor necrosis factor alpha (TNF alpha), have been reported to play a major role in cartilage damage. IL-10 and IL-4, both produced by type 2 T cells, are cytokines with the capacity to down-regulate proinflammatory responses. The present study was undertaken to investigate the way in which these cytokines affect activated mononuclear cells (MNC) of RA patients in relation to human articular cartilage degradation in vitro. METHODS: MNC from synovial fluid and peripheral blood of RA patients were stimulated with bacterial antigen and treated with IL-10 and/or IL-4. Bacterial antigen is known to activate type 1 T cells and to induce proinflammatory IL-1/TNF alpha-dependent cartilage damage. Cytokine production and effects of conditioned media, as well as effects of IL-10 and IL-4 on proteoglycan (PG) turnover (as a measure for cartilage damage), were determined. RESULTS: IL-10 and IL-4 inhibited proinflammatory cytokine production of stimulated RA MNC and completely reversed inhibition of cartilage PG synthesis induced by these stimulated RA MNC. IL-10 was more potent than IL-4 in this respect, and the combination of IL-10 and IL-4 had an additive effect. In addition, IL-10 directly stimulated cartilage PG synthesis. CONCLUSION: IL-10 reverses the cartilage degradation induced by antigen-stimulated MNC, and IL-4 has an additive effect on this process. Furthermore, IL-10 has a direct stimulatory effect on PG synthesis, and IL-4, as a growth factor for type 2 T cells, can reduce the ratio of type 1 to type 2 T cell activity. These results provide evidence in favor of the use of a combination of the two cytokines in the treatment of RA.
8862737 Plasma selenium levels in rheumatoid arthritis. 1996 Summer The plasma selenium (Se) levels were determined in patients with rheumatoid arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found to be significantly lower than those in 60 normal, healthy controls (p < 0.001). Similar significant differences were determined in sex-matched comparisons between patients and controls (p < 0.001) but there was no significant difference in plasma Se levels in sex-matched comparisons in both groups (p > 0.05). Our results suggest that Se is an important factor in RA.
8228049 Revision total wrist arthroplasty. 1993 Sep Biaxial design total wrist arthroplasty was used to salvage 13 failed total wrist arthroplasties of various designs. After a follow-up period of 31 months, two wrists had undergone further prosthetic revision for loosening and one wrist was arthrodesed. In the remaining 10 wrists, 8 had no pain, 1 had mild pain, and 1 had moderate pain. Eight patients reported feeling much better, one reported feeling better, and one reported no change. Postoperative range of motion averaged 36 degrees of extension, 19 degrees of flexion, 6 degrees of radial deviation, and 15 degrees of ulnar deviation. X-ray films at follow-up evaluation showed that two revision arthroplasties still in place were loose. The majority of patients had a satisfactory clinical result after revision total wrist arthroplasty with a biaxial design. Loosening of the revision is a significant problem.
7677442 Detection of cytokine producing cells in the synovial membrane from patients with rheumato 1995 Aug OBJECTIVES: To develop and evaluate a new immunohistochemical method to study the localisation and phenotype of individual cytokine producing cells in synovial biopsy specimens in rheumatoid arthritis. METHODS: Cryopreserved sections of synovial tissue from nine patients with rheumatoid arthritis were incubated with carefully selected cytokine specific antibodies detecting 19 different cytokines, after fixation of the specimens with paraformaldehyde and using saponin to permeabilise the cell membranes. RESULTS: The immunohistochemical method yielded reproducible and distinct staining patterns, in which the cytokines accumulated mainly in the Golgi apparatus of producer cells, indicating that the method preferentially detected local synthesis rather than cytokine uptake. The cytokine production patterns varied considerably between biopsy specimens from different patients. CONCLUSION: The present modified immunohistochemical method may provide a simple and rapid way to determine the local production of a wide array of cytokines in the synovium. The data obtained with this method also indicated that more T cell derived cytokines than previously recognised were present in active synovitis, as located and sampled by arthroscopy.
8764557 Expression of the activation antigen CD27 in rheumatoid arthritis. 1996 Aug Differentiation of CD4+ T-cells is reflected by the change from the CD45RA+CD27+ phenotype via CD45RO+CD27+ to the CD45RO+CD27- phenotype. To provide insight into the migration and activation of T-cells at the site of inflammation in rheumatoid arthritis (RA), CD27 expression by T-cells in peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST) as well as the levels of the soluble form of CD27 (sCD27) in plasma and SF were studied in patients with RA. Since CD4+CD27+ T-cells are involved in providing helper activity for B-cells, we also investigated the levels of rheumatoid factors in serum and SF in relation to CD27 expression. The mean level of sCD27, which is produced by CD27+ cells, and the mean percentage of CD27 T-cells within the CD4+CD45RA- subset were higher in SF than in PB. SF sCD27 levels were higher in the patients with RA than in the patients with osteoarthritis, who served as controls. In ST infiltration by CD4+CD45RO+CD27+ T-cells, could be demonstrated in the rheumatoid perivascular lymphocytic aggregates with a relative increase in the percentage of CD27- T-cells in the diffuse lymphocytic infiltrate. The sCD27 levels and the percentages of CD4+CD27+ cells in SF correlated positively with the levels of rheumatoid factors in serum and SF. The findings presented in this study suggest a continuous influx of preactivated CD4+CD45RO+CD27+ cells from the PB into the rheumatoid ST and further activation and differentiation to CD4+CD45RO+CD27- cells in situ, followed by migration to the SF. These activated T-cells are likely to play a role in synovial inflammation.
7674250 Methotrexate related B lymphoproliferative disease in a patient with rheumatoid arthritis. 1995 Jun A 57-year-old woman receiving low dose methotrexate (MTX) for rheumatoid arthritis (RA) developed a B lymphoproliferative disease (LPD) that was initially considered as large cell non-Hodgkin's lymphoma of B cell phenotype. Epstein-Barr virus (EBV) cytotoxic latent membrane protein-1 (LMP-1) expression was found in some large cells. The lymphoproliferative disease reversed with MTX discontinuation and without chemotherapy. These EBV-associated LPD in patients with RA receiving MTX or other immunosuppressive agents seem to be similar to those triggered by EBV in transplant patients receiving cyclosporine A. MTX withdrawal and short followup should be considered before chemotherapy since spontaneous regression is possible.
8835244 Rheumatoid synovial cell proliferation, transformation and fibronectin secretion in cultur 1995 Nov OBJECTIVE: There is some experimental evidence that patients with rheumatoid arthritis (RA) have a defect in the control of cellular proliferation. To examine this further, synovial cells from patients with RA and osteoarthritis controls (OA) were studied for phenotypic characteristics of transformation and proliferation. METHODS: Synovial cells grown in vitro were studied to determine the extent of proliferation, anchorage-independent growth, growth under reduced serum conditions, fibronectin secretion, and the presence of cell proliferation antigens. RESULTS: RA synovial cell proliferation was less than that recorded for normal skin fibroblasts and was not increased compared to OA synovial cells. Studies of growth in soft agarose showed no colony formation by RA or OA synovial cells after 28 days, indicating that anchorage-independent growth does not occur. At low serum concentrations RA and OA synovial cells showed similar growth. Fibronectin was constant for each cell line studied, irrespective of the cell number or diagnosis. RA cells did not show an increased rate of fibronectin secretion. RA cells did not show an increased expression of proliferating cell antigens. CONCLUSION: These studies do not support the concept that defective proliferation of synovial cells is a major factor in the pathogenesis of RA.
8268833 The therapeutic action of cyclosporin A (Sandimmun): its application in rheumatoid arthrit 1993 Apr The main properties, mechanism of action, mode of administration, side effects and therapeutic indications of Cyclosporin A are reviewed, with special emphasis on its applications in rheumatoid arthritis (RA). The drug administration in small doses, only in patients with severe RA, refractory to the usual antirheumatic therapy, was effective in a significant proportion of cases.
8129890 T cell receptor beta chain gene usage in rheumatoid arthritis. 1993 Feb We evaluated the T cell receptor (TCR) V beta chain family expression in the peripheral blood lymphocytes from patients with rheumatoid arthritis, psoriatic arthritis and post traumatic synovitis. We used commercially available monoclonal antibodies and flow cytometry. No significant changes were observed in the percentages of the various TCR families when patients were compared to normal control. We also evaluated TCR families in paired samples from peripheral blood and synovial fluid of 6 patients. No synovial specific changes were documented. We conclude that by means of the available monoclonal antibodies, no mono, oligo-clonal T cell expansion can be detected in rheumatoid arthritis.
8494871 HLA-DRB1 gene sequences in HLA-DR4 positive and negative patients with rheumatoid arthriti 1993 Apr The second exon of the DRB1 gene encoding for the first domain of the HLA-DR beta 1-chain was sequenced in 16 patients (10 DR4/DR1 positive, 6 DR4/DR1 negative) with seropositive rheumatoid arthritis (RA). We could confirm the strong association of susceptibility to RA with functionally equivalent conformations on otherwise distinct MHC molecules. At least one HLA-DR allele in all of the analysed DR4 or DR1 positive patients showed such an epitope with a minimal variability limited to residue 71. However, in HLA-DR4 and -DR1 negative patients such a similar epitope could not be detected.
8809443 Weight reduction in obese patients with rheumatoid arthritis, with preservation of body ce 1996 May OBJECTIVE: To reduce body weight in obese patients with rheumatoid arthritis (RA) without loss of body cell mass (BCM) and without impairment of physical performance. METHODS: Nineteen overweight RA patients were studied before, during, and after a 12-week weight reducing regime consisting of reduced dietary energy intake, supplemented with a high-protein-low-energy powder preparation, and moderate physical training. Body composition was measured by a four compartment method, which by combining determinations of total body water and total body potassium allows a distinction between the two variable components of fat free mass (FFM): BCM and extracellular water (ECW). Physical fitness was measured by a bicycle exercise test. RESULTS: Mean weight loss during the study was 4.5 kg. The patients lost 9% of their initial fat mass, 3% of initial BCM and 5% of initial ECW. Physical fitness was slightly, but significantly, improved. CONCLUSION: The regime described was successful in achieving a significant weight loss with minimal loss of BCM and maintenance of physical fitness.
1350192 Prospective trial comparing the use of sulphasalazine and auranofin as second line drugs i 1992 Apr Two hundred patients with rheumatoid arthritis were studied in a prospective open trial comparing treatment with sulphasalazine and auranofin in patients with active disease over 12 months. The two drugs improved many parameters of disease activity at 12, 24, and 48 weeks. At 12 weeks, the group treated with sulphasalazine had a lower platelet count (Mann-Whitney U test), erythrocyte sedimentation rate, and articular index, with a greater decrease in erythrocyte sedimentation rate (Students t test) and C reactive protein between 0 and 12 weeks. There were no significant differences between sulphasalazine and auranofin treatment after 24 and 48 weeks. Life table analysis showed no significant differences in the rate of side effects which caused treatment to be stopped. Sulphasalazine works more rapidly, may be a more effective disease modifying antirheumatic drug, and is as well tolerated as auranofin.
7915945 Production of interleukin-6 by monocytes isolated from rheumatoid arthritis patients recei 1994 Sep IL-6 production by peripheral blood monocytes isolated from RA patients receiving the second-line drugs auranofin (AUR), sulphasalazine (SASP) or gold sodium aurothiomalate (GST) was investigated. In patients receiving AUR a significant reduction in both basal and lipopolysaccharide (LPS) stimulated IL-6 production by isolated cells was observed. Similarly, SASP significantly reduced basal IL-6 production. In contrast, monocytes isolated from individuals receiving GST had no significant change either in basal or LPS stimulated IL-6 production. We suggest an effect by AUR and SASP either on pre-monocytic cells in the bone marrow or on monocytes in the periphery may subsequently result in a reduction in IL-6 production by these cells once they have infiltrated the RA joint. This may be one way by which these therapies contribute to the beneficial effects seen in patients receiving these treatments.
7490172 Intra-articular somatostatin 14 reduces synovial thickness in rheumatoid arthritis: an ult 1995 Sixteen patients with RA (3 males, 13 females), diagnosed according to RA revised criteria, were selected and entered the study. They underwent six intra-articular injections of 750 mcg of SST14 at 15-day intervals. The thickness of the synovial membrane (SM) was measured with a 5-MHz linear sound with longitudinal and transversal scanning carried out on the upper patellar cavity. The contralateral knee was also assessed together with the injected knee in order to ascertain any systemic effect of the drug. A significant reduction of SM thickness was observed already at the first control (T3) in 14 out of 16 patients. At the 5th and 6th injections (T5 and T6) the reduction was still significant but to a lower extent. In 8 out of 16 cases a reduction of SM thickness was observed in the contralateral knee. Analysis of these data clearly shows that the intra-articular injection of SST14 is able to reduce the thickness of SM in patients with RA, and indicates that SST14 may directly reduce synovitis. This particularity has been detected in our work with a non-invasive technique such as the joint ultra-sound (US). In conclusion, our work confirms the efficacy of SST14 in the control of RA synovial hypertrophy and the reliability of US technique in the measurement of SM thickness.
1290244 [Circulating immune complexes and complement fragment iC3b in chronic polyarthritis during 1992 In the course of a double-blind randomized study lasting 1 year 19 patients suffering from ensured rheumatoid arthritis (ARA criteria) were treated with oral hydrolytic enzymes or oral gold salts. The effects of these therapies were examined in regard to changes in serum concentrations of circulating immune complexes (CIC) and the complement component iC3b. After 12 months treatment with oral enzymes we determined a therapeutically wanted significant decrease of CIC whereas CIC increased up to 6 months. The best but not significant result under therapy with oral gold salts concerning CIC was a decrease in 6 out of 9 patients after 9 months. The complement component iC3b diminished with either therapy during the first 6 months and increased afterwards. As well as the reduction of circulating immune complexes, the intensified inactivation of C3b into iC3b during the second half-year with both treatments indicates that there might be a slight improvement of the pathologically changed immunoreactions after 6 months only. Concerning the examined laboratory parameters, no significant difference was found between both therapies.
7766492 Current recommendations for surgery of the rheumatoid hand and wrist. 1995 Mar Treatment of the hand with rheumatoid arthritis has not changed significantly over the past year. Two studies indicated that methotrexate administration need not be discontinued prior to surgery. Electron microscopy has shown that rheumatoid tendons are morphologically different from normal tendons. Early synovectomy has been reintroduced as a valuable technique, and the need for a team approach in disease management has been emphasized. Several authors emphasized rigid surgical fixation to improve digital and wrist fusions. Three studies reported good long-term results from metacarpophalangeal joint arthroplasty. Derangements of the distal radioulnar joint can benefit from the Sauve-Kapandji procedure. A newer technique to stabilize the distal ulna following the Darrach procedure was introduced, also, the treatment of swan-neck and boutonniere deformities, the results of which were somewhat disappointing, was reviewed.
8456440 HLA-DR1 and rheumatoid arthritis in Israeli Jews: sequencing reveals that DRB1*0102 is the 1993 Jan Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared-epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10-91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB1*0102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB1*0101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB1*0101 or 0102 allele was associated with DQA1*0101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS)
8349984 A modified extensor carpi ulnaris tenodesis with the Darrach procedure. 1993 Jul Fourteen patients with pain and limited forearm rotation were treated with a modified Darrach procedure involving a distally based slip of the extensor carpi ulnaris tendon. Seven patients had Colles' fractures, four had rheumatoid arthritis, and three had primary osteoarthritis of the distal radioulnar joint. Patients were assigned to one of two groups: rheumatoid arthritis or Colles' fracture/osteoarthritis. The average age was 50 years. Follow-up averaged 54 months (range, 12 to 96 months). The average amount of ulnar resection was 10 mm (range, 6 to 20 mm). In the Colles' fracture/osteoarthritic group, average grip strength (a percentage of the uninvolved hand) improved from 26% preoperatively to 74% postoperatively, and in the rheumatoid arthritis group it improved from 67% to 144%. Distal ulnar instability of the dorsal side was not observed on x-ray examination. Patients were satisfied with pain relief, and all returned to their original work.
8810672 Prevalence of self-reported depression in patients with rheumatoid arthritis. 1996 Sep The prevalence of self-reported depressive symptoms was investigated in a case-control study of patients with rheumatoid arthritis (RA) attending an out-patient clinic at the Middlesex Hospital. Patients selected their own controls, matched for age and sex. Previous attempts to measure depressive symptoms in RA have suffered from measurement error due to criterion contamination, where psychological symptoms augment depressive scores. A total of 163 patients (77% of the sample) and 115 matched pairs completed the Hospital Anxiety and Depression Scale (HADS). The results indicated that RA patients are more depressed and anxious than controls. The prevalence of depression above the cut-point was 15%. This figure is comparable to other reports adjusted for criterion contamination, but is lower than that of other studies which employ 'contaminated' tools. The depression scale of the HADS appeared to be relatively free of criterion contamination. Subject to further reliability testing, the HADS may be a practical screening tool for practitioners to assess patients in need of psychological interventions.