Browse

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

ID PMID Title PublicationDate abstract
9335364 Mechanical stability of the cementless acetabular component with three spikes. 1997 Oct We studied the stability of our cementless acetabular component (socket) with 3 spikes in 65 joints of 65 patients who were followed for over 5 years. In 1 case, there was osteolysis around the femoral component (stem) but not around the socket. The movement of the socket and the radiolucent line was observed in 11 cases of osteoarthritis with acetabular hypoplasia (a mean of 43 degrees of the sharp angle) and 3 cases with rapidly destructive coxarthrosis. We could obtain favorable stability in 50 patients, including 38 with osteoarthritis (a mean of 41 degrees of the sharp angle), 8 with aseptic necrosis, 2 with rapidly destructive coxarthrosis, and 2 with rheumatoid arthritis. Our socket is very effective in preventing osteolysis and is expected to provide more stable mechanical stability by arranging an insertion angle (35 degrees of the optimal open angle and 10 degrees of the anteversion angle) and a full bone graft in osteoarthritic patients.
9409646 Autonomic nervous dysfunction in systemic lupus erythematosus (SLE) and rheumatoid arthrit 1997 Dec Autonomic nervous dysfunction has been previously reported in SLE, RA and systemic sclerosis, but the pathogenesis of such a complication is poorly understood. In the present study, four standard cardiovascular autonomic function tests were performed in 34 female patients with connective tissue diseases and in 25 healthy control subjects, and results expressed as cardiovascular (CV) test scores. Moreover, in each subject the presence of circulating complement-fixing autoantibodies directed against sympathetic and parasympathetic nervous structures, represented by superior cervical ganglia and vagus nerve, respectively, was simultaneously assessed by an indirect immunofluorescent complement-fixation technique, using rabbit tissue as substrate. None of the patients reported autonomic symptoms. However, an abnormal CV test score (> or = 5) was detected in 15% of the patients and in none of the healthy control subjects, approaching statistical significance (P = 0.07). No correlation was found between CV test results and disease duration, type of therapy or presence of conventional autoantibodies. One or two autoantibodies to autonomic nervous structures were detected in six patients (18%) and not in the control subjects (P < 0.05). Values of deep breathing test were significantly lower in autoantibody-positive patients compared with those amongst the control subjects (P < 0.05), and an abnormal CV test score was significantly associated with the presence of autoantibodies to autonomic nervous structures (P < 0.05). In conclusion, we confirm that autonomic nervous function can be impaired in patients with connective tissue diseases, and suggest that autoantibodies directed against autonomic nervous system structures may play a role in the pathogenesis of the autonomic dysfunction.
11069062 Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis. 2000 Oct OX40 ligand (OX40L) and OX40 (CD134) are a pair of cell surface molecules belonging to the TNF/TNF receptor family. Interaction of OX40L with its receptor OX40 is thought to be important in T cell activation through T cell/antigen-presenting cell interaction. However, involvement of these molecules in the pathogenesis of rheumatoid arthritis (RA) remains unclear. To explore the contribution of OX40/OX40L interaction to the pathogenesis of RA in vivo, we evaluated the effect of a neutralizing anti-OX40L monoclonal antibody (mAb) on the development of collagen-induced arthritis (CIA) in DBA/1 mice as an animal model for RA. Administration of anti-OX40L mAb into type II collagen (CII) -immunized DBA/1 mice dramatically ameliorated the disease severity. In vivo treatment with anti-OX40L mAb did not inhibit the expansion of CII-reactive T cells, but suppressed IFN-gamma and anti-CII IgG2a production. Therefore, OX40/OX40L interaction appears to play a critical role in the development of CIA by enhancing Th1-type autoimmune response. In addition, T lymphocytes in synovial fluid and synovial tissue from RA patients expressed OX40, while OX40L was expressed on sublining cells in synovial tissue. These results indicate that OX40/OX40L interaction may play a critical role in the development of RA.
9737778 Genetic linkage of progressive pseudorheumatoid dysplasia to a 3-cM interval of chromosome 1998 Jul Progressive pseudorheumatoid dysplasia (PPD), MIM 208230, is an autosomal-recessive disorder, clinically characterized by spondyloepiphyseal dysplasia and progressive arthropathy. Linkage analysis of three families of different geographic and ethnic origin, including 11 affected individuals, showed strong evidence for localization of a gene for progressive pseudorheumatoid dysplasia to chromosome 6q with a maximum two-point lod score for D6S1647 of 8.34 at theta=0. Analysis of regions of homozygosity placed the gene in a 3-cM interval between D6S 1594 and D6S432. No significant shared haplotype was found for markers of the linked interval in the three families analyzed. Five genes encoding collagen and one encoding a specific procollagen-processing enzyme that map near this interval represent good candidates for the PPD gene.
9783767 Microscopic measurement of cellular infiltration in the rheumatoid arthritis synovial memb 1998 Sep Microscopic measurement of inflammation in synovial tissue may be important in studies of clinical status, prognosis and response to treatment. The aim of this study was to compare quantitative microscopic analysis of inflammation with a semiquantitative grading system in rheumatoid arthritis (RA) synovial membrane. Knee synovial membrane samples from 16 patients with RA, including paired samples taken before and after treatment in nine patients, were immunostained with anti-CD68 and anti-CD3 monoclonal antibodies using standard techniques. The intensity of macrophage and T-lymphocyte infiltration was measured both by quantitative and semiquantitative techniques, and the results were compared. In a cross-sectional comparison, both methods correlated significantly for lining layer macrophage infiltration, as well as sublining layer macrophage and T-cell infiltration. However, in some patients demonstrating a clinical response to treatment, semiquantitative analysis lacked sensitivity to biologically relevant changes in mononuclear cell infiltration. These observations have important implications for future studies of therapeutic modalities.
9300721 Defective TCR-mediated signaling in synovial T cells in rheumatoid arthritis. 1997 Sep 15 In rheumatoid arthritis (RA), the functional status of T cells is incompletely understood. Synovial T cells display phenotypic evidence of former activation, but there is poor production of T cell-derived cytokines in the synovium. In addition, synovial T cell proliferation upon mitogenic and antigenic stimulation was decreased compared with that in peripheral blood T cells. Moreover, previous reports revealed that early Ca2+ rises induced by TCR/CD3 stimulation were decreased in RA T cells compared with those in healthy controls. To investigate the molecular mechanisms of RA synovial T cell hyporesponsiveness, we analyzed the TCR/CD3-mediated protein tyrosine phosphorylation in RA peripheral blood and synovial fluid (SF) T cells. SF T cells exhibited a decreased overall tyrosine phosphorylation pattern upon stimulation. Most notably, the induction of phosphorylation of p38 was virtually absent. Moreover, we found that tyrosine phosphorylation of the TCR zeta-chain, one of the most proximal events in TCR signaling, is clearly diminished in RA SF T cells. The decrease in tyrosine phosphorylation was accompanied by a decrease in detectable levels of zeta-protein within synovial T cells. These results suggest that a defective TCR signaling underlies the hyporesponsiveness of synovial T cells in RA.
10748958 Traditional Chinese medicines as immunosuppressive agents. 2000 Jan INTRODUCTION: Traditional Chinese Medicines (TCM) have been used for centuries in China to treat various immune-mediated disorders. METHODS: This review focuses on the clinical and experimental studies that have been performed with TCM as immunosuppressive agents for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), atopic eczema and solid organ transplantation. RESULTS: The "thunder god" vine, Tripterygium wilfordii Hook F (TWHf), has been extensively used in China to treat SLE and RA. TWHf not only inhibited mitogen-stimulated lymphoproliferation, but its active derivatives have also been shown to inhibit production of proinflammatory cytokines by monocytes and lymphocytes, as well as prostaglandin E2 production via the cyclooxygenase, COX-2, pathway, a potential mechanism of action in patients with RA. Demethylzelasteral (TZ-93), a triterpenoid isolated from the root cortex of TWHf, the plant alkaloid berbamine, and the hydrophobic extract of a Chinese herbal decoction, CMX-13, were all shown to be active in prolonging allograft survival in experimental animal models of heart, skin and single lung transplants, respectively. There are few well-designed randomised placebo-controlled clinical trials demonstrating the efficacy of TCM in various diseases. Zemaphyte, a decoction of 10 herbs, has been shown to be efficacious in the treatment of atopic dermatitis in both children and adults in two randomised double-blind placebo-controlled trials. CONCLUSION: There is both laboratory and clinical evidence that the derivatives of many of these herbs may have significant beneficial immunosuppressive effects, however, concerns of toxicity must also be addressed, as exact dosing of the active derivatives is difficult to achieve with the current prescriptions of TCM.
9598883 Evaluation of a modified needle for small joint biopsies. 1998 May OBJECTIVE: To assess the value of a new short biopsy needle modified from the Parker-Pearson needle in obtaining adequate synovial tissue from small joints. METHODS: The short needle is 2.5 cm in length with a repositioned hooked biopsy notch closer to the end of the needle to allow better specimen retrieval. It can be used to obtain synovial biopsies from small joints of the hand using the usual arthrocentesis approaches. RESULTS: Ten patients underwent 12 synovial biopsies with a success rate of 92%. No complications from the procedure were observed. Samples obtained were adequate for a variety of studies including synovial histopathological evaluation, electron microscopy, and DNA extraction. CONCLUSION: The new modified short needle expands the spectrum of joints that can be biopsied for diagnostic and research purposes in an outpatient setting.
9457567 De la Caffinière thumb carpometacarpal replacements. 93 cases at 6 to 16 years follow-up. 1997 Dec The results of 93 de la Caffinière thumb joint replacements in 71 patients were reviewed between 6 and 16 years. The survival rate was 89% at 16 years. Eleven thumb joints had failed requiring revision. The commonest reason for failure was aseptic loosening of the trapezial component. The failure rate was higher in men of working age than any other group, which possibly reflects the increased demands on the prosthesis of these patients. We support the use of this implant for degenerative osteoarthritis, but caution against its use in men under 65 years.
10721101 Tryptophan catabolism in synovial fluid of various arthropathies and its relationship with 1999 Synovial fluids (SF) from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), gout, and osteoarthritis (OA) were investigated for the levels of interleukin (IL)-1 beta, IL-6 and IL-8, tryptophan (Trp) and indoleamine 2,3-dioxygenase (IDO) activity. Significant differences exist in the levels of IL-1 beta between inflammatory arthritides RA, PsA and gout and non inflammatory arthritis, such as OA. The highest concentration of IL-1 beta was found in RA, that showed high levels also of IL-6 and IL-8. In the same disease we also found the highest IDO activity and the lowest Trp concentration. In addition, IDO activity seems to be related with the decrease in Trp, as demonstrated by the inverse correlation found between these two substances in the SF of all patients.
9810076 [The hand and rheumatism]. 1997 The hand is a major site of musculoskeletal disorders. Clinical features to be studied include the patient's age and sex, pain, stiffness, range of motion of the various joints of the wrists and hands, soft tissue swelling (particularly tendons sheaths), bone excrescences, skin changes. Radiological abnormalities in the hands, if any, may confirm the clinical diagnosis. The main features of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, erosive degenerative changes, Südeck syndrome, calcium pyrophosphate dihydrate deposition disease, etc., are reviewed.
9151376 Xanthomatous infiltration of ankle tendons. 1997 Apr We present a case of type II hyperbetalipoproteinemia in a patient whose diagnosis had been previously unrecognized, and who had previously been misdiagnosed with rheumatoid arthritis and later gout. Radiographic and MR imaging features of the patient's ankles were pronounced but otherwise typical of xanthomatous infiltration. Radiologic assessment can be useful in permitting a specific diagnosis to be made in patients with periarticular and tendinous swelling.
11399097 Nimesulide reduces interleukin-1beta-induced cyclooxygenase-2 gene expression in human syn 2001 May OBJECTIVE: To characterize the effects of nimesulide (NIM) on basal and induced cyclo-oxygenase-2 (COX-2) gene expression in human synovial fibroblasts (HSF) and to define the intracellular mechanisms that mediate the changes in COX-2 expression and synthesis in response to the drug. DESIGN: HSF were incubated with NIM and NS-398 (0, 0.03, 0.3, 3 microg/ml) in the absence or presence of the COX-2 inducers interleukin-1beta (IL-1beta) or endotoxin (LPS). Treated cells were analysed for COX-2 mRNA and protein by Northern and Western blotting analysis, respectively. Putative transcriptional, post-transcriptional, and signaling effects of NIM on basal and induced-COX-2 expression were investigated by human COX-2 promoter studies, calcium studies, reactive oxygen species (ROS) evaluations, electrophoretic mobility shift analysis (EMSA) and half-life studies of COX-2 mRNA. RESULTS: NIM inhibited IL-1beta-induced COX-2 expression and protein at sub and therapeutic concentrations (0.03-0.3 microg/ml) while the non-specific NSAID, naproxen, did not. Both drugs suppressed PGE2 release by about 95%. NIM had no effect on (1) IL-1beta-induced increases in NF-kappaB or c/EBP signaling, or (2) human COX-2 promoter activity. Stability of induced COX-2 mRNA was unaffected by NIM treatments. Pre-treatment of cells with O(2)radical scavengers (e.g. PDTC) or with Ca(++)channel blockers (e.g. verapamil) had a modest effect on IL-1beta-induced COX-2 expression. NIM blocked ionomycin+thapsigargin and H(2)O(2)-induced increases in COX-2 protein synthesis. CONCLUSION: NIM inhibits cytokine-induced COX-2 expression and protein at sub and therapeutic concentrations. At least part of this activity may be the result of NIM inhibition of calcium and/or free radical generation induced by cytokines.
9811047 The concurrence of rheumatoid arthritis and limited systemic sclerosis: clinical and serol 1998 Nov OBJECTIVE: The characteristics of 3 patients with longstanding rheumatoid arthritis (RA) and consecutive evolution of limited cutaneous systemic sclerosis (IcSSc) were evaluated and compared with those of patients with IcSSc alone (n = 20) or with RA alone (n = 120). METHODS: Clinical features of the different patient populations were compared. Serologic analyses included tests for antinuclear antibodies (ANA) and ANA subsets, in particular anticentromere antibodies (ACA) and anti-heterogeneous nuclear RNP (hnRNP)-A2/RA33 (anti-A2/RA33). RESULTS: The 3 patients with RA developed IcSSc 11, 29, or 50 years after the onset of RA. Features of IcSSc were Raynaud's phenomenon, sclerodactyly, and telangiactasias in all 3 patients, and esophageal dysmotility in 1 patient. Rheumatoid factor (RF) and anti-A2/ RA33 were each found in 2 patients, and 1 of these patients was seropositive for both RF and anti-A2/RA33. ACA titers were positive in all cases. However, similar to the development of RA prior to IcSSc, the occurrence of autoantibodies typical of RA preceded the occurrence of ACA, at least in 2 of the patients. Using affinity-purified antibodies, cross-reactivities between anti-centromere protein A (CENP-A) and anti-CENP-B antibodies with anti-A2/RA33 antigens were seen in the 2 anti-A2/RA33-positive patients. Such cross-reactivities were not found in IcSSc patients without concomitant RA. Epitope mapping revealed that both autoantibody specificities recognized the known major epitopes: anti-CENP-B reacted with the C-terminal region and anti-A2/RA33 with the second RNA binding domain in the N-terminal region of hnRNP-A2. CONCLUSION: The RA-lcSSc overlap syndrome in these 3 patients with longstanding RA was characterized by an incomplete CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) syndrome. The study demonstrated the presence of autoantibodies typical of both diseases and cross-reactivity of ACA with hnRNP-A2/RA33 in the sera of these patients.
9929929 [Will administration of omega-3 unsaturated fatty acids reduce the use of nonsteroidal ant 1998 Nov 2 BACKGROUND: An increased intake of omega-3 polyunsaturated fatty acids (PUFA) in the diet of patients with rheumatoid arthritis has a favourable effect on the course of the disease. The objective of the present work was to assess the effect of such a diet on the daily consumption of non-steroid antirheumatic drugs in children with juvenile chronic arthritis. METHODS AND RESULTS: A group of 23 children with the diagnosis of chronic juvenile arthritis was divided by the method of random numbers into two groups. The first group received in addition to ibuprofen treatment a diet with an increased content of omega-3 PUFA. The second group served as control. In the first group (13 patients, mean age 11 years) in the course of five months treatment the original ibuprofen consumption declined by 17.3% (from a mean value of 28.4 mg/kg/day to 23.4 mg/kg/day), while in the control group (10 children, mean age 9.1 years) there was a decline of 6.5% (from a mean value of 23.7 mg/kg/day to 22.7 mg/kg/day). This difference was statistically significant at the level of 0.05 (P = 0.03). CONCLUSIONS: Despite the statistically significant difference in the decline of daily consumption of the non-steroid antirheumatic drug in the investigated groups of patients and the obvious favourable effect of omega-3 PUFA the mean consumption of the drug remained in the first group after five months of treatment higher (23.4 mg/kg/day) than in the control group (22.4 mg/kg/day).
9590649 Particulate debris presenting as radiographic dense masses following total knee arthroplas 1998 Apr Two cases of failed total knee arthroplasty associated with significant titanium debris that created massive radiographic densities are reported. The similarities of the failed total knee arthroplasties are that both involve titanium femoral components with failed metal-backed patellar components. At the time of surgical intervention, patellar polyethylene dissociation from metal-backed patellar components was noted with excessive burnishing and wear of the remaining metal-backed patellar component and of the titanium femoral component. Wear of the tibial polyethylene was noted in both cases. The titanium-on-titanium wear couple produced significant debris, resulting in large mass formation about the total knee arthroplasty. Additionally, there were loculated, fluid-filled sacks of titanium debris. Histologic sections performed for both cases revealed significant deposits of titanium in combination with polyethylene. In both cases, radiographs revealed the presence of large, radiodense masses. These cases illustrate that when considering etiologies for radiodense masses about total joint arthroplasty, particulate titanium debris resulting in mass formation must be added to the differential diagnosis.
10079806 The North American experience with photopheresis. 1999 Feb Photopheresis or extracorporeal photochemotherapy (ECP) is a novel immunomodulatory therapy based upon pheresis of light-sensitive cells. Whole blood is removed from patients who have previously ingested the photosensitizing agent 8-methoxypsoralen (8-MOP) followed by leukapheresis and exposure of the 8-MOP containing white blood cells (WBCs) extracorporeally to an ultraviolet A (UVA) light source prior to their return to the patient. In 1988, the Food and Drug Administration (FDA) approved photopheresis for the treatment of cutaneous T-cell lymphoma (CTCL). Treatment of CTCL with photopheresis has been reported in over 300 patients worldwide. Photopheresis has also demonstrated encouraging results in the treatment of solid organ transplant rejection, graft versus host disease, scleroderma, and other autoimmune diseases although fewer patients have been studied. This review will focus on the North American experience with photopheresis.
10225978 IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of 1999 May IL-17 is a newly discovered T cell-derived cytokine whose role in osteoclast development has not been fully elucidated. Treatment of cocultures of mouse hemopoietic cells and primary osteoblasts with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine slices. Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17-induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2). Adding IL-17 increased prostaglandin E2 (PGE2) synthesis in cocultures of bone marrow cells and osteoblasts and in single cultures of osteoblasts, but not in single cultures of bone marrow cells. In addition, IL-17 dose-dependently induced expression of osteoclast differentiation factor (ODF) mRNA in osteoblasts. ODF is a membrane-associated protein that transduces an essential signal(s) to osteoclast progenitors for differentiation into osteoclasts. Osteoclastogenesis inhibitory factor (OCIF), a decoy receptor of ODF, completely inhibited IL-17-induced osteoclast differentiation in the cocultures. Levels of IL-17 in synovial fluids were significantly higher in rheumatoid arthritis (RA) patients than osteoarthritis (OA) patients. Anti-IL-17 antibody significantly inhibited osteoclast formation induced by culture media of RA synovial tissues. These findings suggest that IL-17 first acts on osteoblasts, which stimulates both COX-2-dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL-17 is a crucial cytokine for osteoclastic bone resorption in RA patients.
10379474 Pharmacoeconomic aspects of non-steroidal anti-inflammatory drug gastropathy. 1999 Non-steroidal anti-inflammatory drugs are commonly used to reduce inflammation and pain associated with arthritis. However, non-steroidal anti-inflammatory drugs induce gastrointestinal side-effects such as dyspeptic symptoms, duodenal or gastric ulcers and, in some cases, serious complications. The aim has been to compare the benefits with the drawbacks of non-steroidal anti-inflammatory drug treatment using a hypothetical population representing patients with arthritis. A problem description was made on the basis of a literature review, and a simple and hypothetical health economic model was constructed. Including direct and indirect costs, the annual total costs in Sweden for gastrointestinal side-effects per non-steroidal anti-inflammatory drug user were estimated to be 3,420 SEK (438 US$), and the approximated costs of arthritis were 60,000 SEK (7,692 US$). The benefits of non-steroidal anti-inflammatory drug treatment were found to outweigh the drawbacks if the patient's arthritis symptoms, expressed as a difference in utility value between having and not having symptoms of arthritis, are improved by 6% or more. Costs for non-steroidal anti-inflammatory drug-induced gastrointestinal side-effects should be evaluated in relation to the benefits of non-steroidal anti-inflammatory drugs in the treatment of inflammation and pain. A simple modelling approach indicated that treatment with non-steroidal anti-inflammatory drugs may be highly cost-effective as both the clinical and economic benefits for patients responding to such treatment out-weighed possible drawbacks.
11408908 Fractured rheumatoid elbow: treatment with Souter elbow arthroplasty--a clinical and radio 2001 May We report the results in 26 patients who had 32 preoperative fractures treated with Souter elbow arthroplasty. All were rheumatoid patients with a mean disease duration of 29.7 years (range, 10 to 43). Six of the fractures were of the olecranon and 26 of the distal humerus. The time interval between fracture and arthroplasty was 9 months (mean; range, 0 to 48). Fragments were not excised, and osteosynthesis was performed. The follow-up was 2.6 years (mean; range, 0.5 to 8), when 20 of the fractures had united and 12 had not. K-wire fixation, either alone or in combination with cerclage or PDS suture, and bone grafting led to satisfactory results. Union was verified in 14 of 17 cases treated with this technique. There were no severe early complications. Six patients had late complications. In 3 cases, loosening of the humeral component was observed radiologically. One patient had a hematogenous deep infection 4 years after the operation, and 2 patients had avulsion rupture of the triceps tendon. Fracture in the badly destroyed elbow can be more reasonably treated with an arthroplasty than with an attempt of osteosynthesis before arthroplasty. If excision of the fragments is avoided, original, or near original, anatomy of the elbow joint can be better restored and acceptable outcome obtained with elbow arthroplasty.