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

ID PMID Title PublicationDate abstract
7746929 [Arthrodesis of the first metatarsophalangeal joint]. 1994 INTRODUCTION: The goal of this study was to evaluate the place of arthrodesis of the first metatarso-phalangeal joint in surgery of the fore foot. MATERIAL AND METHOD: The authors studied 225 arthrodesis of the first metatarso-phalangeal joint. 195 had a follow up of from two to fifteen years. The indications were: hallux valgus 52.5 per cent, hallux rigidus 20 p. 100, rheumatoid arthritis 12.5 per cent. The procedure used a stable axial fixation with an antero-posterior screw. The preparation of the joint surfaces allowed equalization of the length of the first two toes. RESULTS: The study found a patient subjective satisfaction rate of 89.6 per cent. There was no pain for 90 per cent of them. Activities returned to normal 80 per cent of patients. There was radiographic evidence of lack of fusion in 25 cases (13 per cent). Only two cases were painful and justified a revision. In 15 per cent of the cases slight pain at the inter phalangeal joint was noted due to excessive joint function. DISCUSSION: The best results were obtained with a dorsal flexion angle between twenty and thirty degrees. Restricted dorsal flexion concerning ankle or inter phalangeal joint is a contra-indication of the procedure. Stable fixation is essential but weight bearing on the fore-foot is not allowed for six weeks. CONCLUSION: Arthrodesis of the first metatarso-phalangeal joint restores painless satisfying function and normal use of shoes.
1463770 Identification of two novel amyloid A protein subsets coexisting in an individual patient 1992 Dec 10 Amyloid A protein (AA), the major fibril protein in AA-amyloidosis, is an N-terminal cleavage product of the precursor protein, serum amyloid A (SAA). Using mass spectrometry and amino-acid sequencing, we identified and characterized two novel AA protein subsets co-deposited as amyloid fibrils in an patient having AA-amyloidosis associated with rheumatoid arthritis. One of the AA proteins corresponded to positions 2-76 (or 75) of SAA2 alpha and the other corresponded to positions 2-76 (or 75) of known SAA1 subsets, except for position 52 or 57, where SAA1 alpha has valine and alanine and SAA1 beta has alanine and valine in position 52 and 57, respectively, whereas the AA protein had alanine at the both positions. Our findings (1), demonstrate that not only one but two SAA subsets could be deposited together as an AA-amyloid in a single individual and (2), support the existence of a novel SAA1 allotype, i.e., SAA152,57Ala.
7636219 Autoimmunity induction by human T cell leukemia virus type 1 in transgenic mice that devel 1995 Aug 1 We recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T cell leukemia virus type 1 genome. In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated. Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular immune response to IIC as well as that to heat shock proteins were activated. Moreover, these mice became immunologically responsive to exogenously administered IIC and developed arthritis, in contrast to their nontransgenic littermates, which showed little response to IIC. Taken together, the results suggest that human T cell leukemia virus type 1 can cause immune system hyperreactivity and induce autoimmunity. The possibility that elevated cytokine and/or MHC gene expression are involved in the development of autoimmunity and arthropathy are discussed.
8571251 [The clinical instrumental characteristics of the locomotor involvement in patients who ha 1995 Locomotor system has been studied in 24 patients with a history of Lyme's disease. All of them had arthralgia, 11 had relapsing arthritis, chronic arthritis occurred in 6 examinees. Arthritis presented as recurrent asymmetric mono-oligoarthritis affecting primarily joints of the lower limbs. Periarticular disorders were detected in 12 patients. Serologically, 18 of 24 patients had elevated titers of antibodies to Borrelia burgdorferi in indirect immunofluorescence test. Scintigraphy revealed polyarticular lesions in many cases, ultrasound investigation of the joints confirmed inflammatory nature of the pathological changes. It is inferred that combined methods of examination in diagnosis of Lyme's arthritis (titers to antibodies to Borrelia burgdorferi, ultrasound investigations, scintigraphy of the joints) provide most complete information.
7912633 Methotrexate and sulphasalazine as combination therapy in rheumatoid arthritis. 1994 Jul Sulphasalazine (SASP) and methotrexate (MTX) are well-established treatments for RA but the use of these drugs in combination has been avoided as both have antifolate activity. In this paper we report our experience with 32 patients treated with the combination MTX/SASP and compare the toxicity and tolerability of the combination with 63 patients treated with MTX alone. The median duration of exposure to the combination was 23 months. Nineteen patients have continued this regime for over 18 months. Five patients on MTX/SASP combination discontinued MTX, in four cases due to toxicity and in one because MTX/SASP was ineffective. In 17 patients on MTX alone, the drug was withdrawn permanently. In seven cases the cause was toxicity including two patients with severe reactions. In patients known to tolerate SASP alone, the combination of MTX/SASP is also well tolerated. In our experience of 48 patient-years of such combination therapy, there is no increase in toxicity compared to therapy with MTX alone in RA.
8856609 Inflammatory polyarthritis in the community is not a benign disease: predicting functional 1996 Aug OBJECTIVE: To predict which patients with early inflammatory polyarthritis presenting to primary care will be functionally disabled one year after presentation, in order to inform treatment and referral decisions. METHODS: The study population consisted of 381 patients notified to the Norfolk Arthritis Register, a primary care based inception cohort of patients with inflammatory polyarthritis. Patients were regarded as functionally disabled if they had a Health Assessment Questionnaire (HAQ) score of one or more. Clinical, laboratory, and demographic variables easily measured at baseline were analyzed for their ability to predict future disability. Recursive partitioning was used to create a simple decision tree to predict those patients who would be disabled at one year. A logistic regression model was generated on a sample of 277 patients and tested on an independent sample of 104 patients. This was compared with other models, one of which consisted of the 1987 ARA criteria. RESULTS: 112 (29%) patients had a HAQ score of at least 1 at one year. The strongest predictors of future disability were a high baseline HAQ, large joint involvement, female sex, and longer disease duration. The decision tree predicted disability accurately in 67% of patients. CONCLUSION: It is possible to predict functional outcome at one year among patients with early inflammatory polyarthritis presenting to primary care using simple clinical variables measured at baseline. Satisfying the 1987 ARA criteria could not be used to predict future disability.
1386142 Purification and characterization of RHP (factor H) and study of its interactions with the 1992 Jul RHP has been purified from the plasma of both normal individuals and patients with rheumatoid arthritis (RA). RHP from both these sources was shown to be identical with Factor H by reaction with antisera and N-terminal amino acid sequence analysis. Factor H, from both normal and RA sera, inhibited the solubilization of immune precipitates but did not affect prevention of immune precipitation. Factor H was shown to inhibit the haemolytic activity of fluid-phase C1, but unlike C1-inhibitor, it had little effect on C1 bound to EA (EAC1). Factor H was shown to complex with intact C1, to isolated C1q and to the C1r:C1s tetramer. However, binding of factor H to C1 did not dissociate the C1 macromolecule. A C1-Factor H complex was detected in the serum and plasma from normal individuals and patients with systemic lupus erythematosus and RA. Serum levels of this complex were reduced, by EDTA-treatment of serum and by activation of complement by the classical pathway.
7913504 Sulfasalazine induced lupus in rheumatoid arthritis. 1994 Apr We describe 2 cases of a lupus syndrome induced by sulfasalazine in rheumatoid arthritis. All symptoms resolved and antihistone antibodies disappeared when sulfasalazine was discontinued. In one patient, perinuclear antineutrophil cytoplasmic antibodies with specificity for myeloperoxidase were found critically increased just before the occurrence of vasculitis.
8474075 Performance of scored palpation, a point count, and dolorimetry in assessing unsuspected n 1993 Feb Nonarticular tenderness was measured in 152 patients, 51 with rheumatoid arthritis, 50 with psoriatic arthritis, and 51 with human immunodeficiency virus infection. Three methods for assessing tenderness were used: a 14-site point count, scored tenderness at 10 sites (6 fibrositic and 4 control), and dolorimetry at the same 10 sites. The data from the 3 separate measures were converted into a common scale of standard deviation units for further analysis. There were strong correlations among the 3 measures. In particular, the scored tenderness at just 6 fibrositic sites provided as much information about the presence and severity of widespread tenderness as the other 2, more complex measures. At the interface between nontender and tender, the 2 methods based on palpation were significantly more sensitive to differences among individuals, than was dolorimetry. However, the palpation scales used did not evaluate different degrees of nontenderness. In 102 of the 152 subjects, there were 842 sites scored zero by palpation, and which showed widely different thresholds of tenderness by dolorimetry, significantly associated with diagnosis and sex. For screening and epidemiological purposes, scored tenderness at a limited number of accessible sites may be adequate and feasible, using the 18 point count of the new standard criteria as a gold standard for confirmation. For the assessment of generally acting factors affecting tenderness, dolorimetry is currently superior.
7897260 T cell receptor analysis in rheumatoid arthritis: what have we learnt? 1994 Many clues point to a role for T lymphocytes in the pathogenesis of rheumatoid arthritis (RA), although the importance of these cells and their position within the rheumatoid pathogenic scheme remain unknown. Encouraged by data from animal models of T-lymphocyte-mediated autoimmunity, a major focus of research into the role of T lymphocytes in RA has been the usage of T cell receptor V genes in rheumatoid synovitis. Despite many methodologic problems, involving choice of patients and controls, choice of specimens, and technical factors, several conclusions can be drawn from the published research. In particular, synovial T lymphocyte populations, as a whole, frequently show biased V gene usage and restricted clonality within those T lymphocyte subsets that utilize over-represented V gene families. Continued research into these synovial T lymphocyte subsets should provide important insights into the pathogenesis of RA, particularly if solutions to the identified methodologic problems are implemented.
7535355 Lack of evidence for human T cell lymphotrophic virus type I or II infection in patients w 1994 Dec OBJECTIVE: Human retroviruses including human immunodeficiency virus (HIV) and human T cell lymphotrophic virus Types I and II (HTLV-I/II) have been associated with forms of connective tissue autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We looked for evidence of HTLV-I/II infection in a large population of SLE, RA, and control patients. METHODS: One hundred fifteen patients with connective tissue autoimmune disease and other rheumatological disorders were screened for antibodies to HTLV-I/II by Western immunoblots (WIB). Due to the transforming characteristic of these retroviruses, the patients' peripheral blood mononuclear cells (PBMNC) were cultured in attempts to establish continuous cell lines. Furthermore, PBMNC culture supernatants were analyzed for reverse transcriptase activity and/or HTLV-I/II gag antigen production. The presence of HTLV-I/II proviral sequences in short term culture and fresh PBMNC was determined by Southern blot analysis and polymerase chain reaction (PCR), respectively. respectively. RESULTS: All 115 patients were HTLV-I/II and HIV seronegative. Seventy-four attempts to establish PBMNC cell lines from 65 patients were unsuccessful with a mean culture survival time of 3.6 (+/- 1.4) months. Reverse transcriptase activity and HTLV-I/II gag antigen production were not detected in 51 and 16 culture supernatants tested, respectively. Cells from 11 patients tested by Southern blot analysis and from 57 patients tested by PCR were negative for HTLV-I/II related sequences. CONCLUSION: Our results failed to establish an association between human retroviruses (HTLV-I/II and HIV) and SLE, RA, or other rheumatological disorders. However, these results do not rule out other exogenous or endogenous retroviruses that may play a role in the initiation and/or promotion of these diseases.
1412164 Depression of tissue-type plasminogen activator and enhancement of urokinase-type plasmino 1992 Aug 3 Inflammatory processes are accompanied by extravascular deposition and breakdown of fibrin. We measured fibrinolytic parameters in synovial fluid (SF) and in plasma of 36 patients with rheumatoid arthritis (RA). As a control, SF of 13 patients with blunt knee trauma, and plasma of 17 healthy volunteers were studied. In RA patients, extravascular t-PA mediated plasminogen activation was depressed: mean SF tissue-type plasminogen activator (t-PA:Ag) concentration (2.1 +/- 1.6 ng/ml) was four-fold lower, and plasminogen activator inhibitor (PAI) activity (284 +/- 212%) four-fold higher than the plasma values of the same patients or of healthy donors. In contrast, u-PA related plasminogen activation was strongly enhanced: urokinase-type plasminogen activator (u-PA) antigen (23.1 +/- 12.4 ng/ml) was more than four-fold higher, single-chain u-PA (scu-PA) (5.3 +/- 1.9 ng/ml) three-fold higher than in plasma of the same patients or of healthy donors, and active two-chain u-PA (tcu-PA) was detected in 14 of the 36 SF samples of RA patients. All of these changes in extravascular fibrinolytic parameters correspond with those induced by inflammatory mediators in cell cultures. In joint effusions of patients with a blunt knee trauma, the effects were intermediate: u-PA related parameters showed moderate changes in the same direction as in arthritis; t-PA antigen was also decreased. The only exception was that PAI was not increased. We conclude that the findings in traumatic effusions reflect transient effects as a reaction to trauma. In joint inflammation, the depressed t-PA mediated plasminogen activation, although more than compensated by the enhanced u-PA mediated plasminogen activation, results in protraction of fibrin removal. Besides, the enhanced u-PA activation might lead to proteolytic damage of the cartilage.
1613715 Fever, hepatitis and acute interstitial nephritis in a patient with rheumatoid arthritis. 1992 May We describe a patient with rheumatoid arthritis (RA) who developed hypersensitivity after 3 weeks of therapy with azathioprine with fever, jaundice and renal insufficiency. A percutaneous liver biopsy was compatible with hypersensitivity hepatitis. During azathioprine rechallenge, the symptoms recurred within a few days, consistent with the diagnosis of an acute hypersensitivity reaction. This report is the first to describe the association of an azathioprine induced hypersensitivity simultaneously involving the liver and the kidneys, in the same patient with RA, with resurgence after rechallenge.
7697212 Comparative studies of collagenase and stromelysin-1 expression by rheumatoid synoviocytes 1995 Matrix metalloproteinases such as collagenase and stromelysin are recognised as important cartilage-degrading enzymes in the pathophysiology of rheumatoid arthritis. Synovial fibroblasts and macrophages are the major cellular components of rheumatoid synovium, but the regulation and relative expression of collagenase and stromelysin by these two cell types remains uncertain. Using in vitro cultures of adherent rheumatoid synovial cells we have examined the coordinate or separate expression of collagenase and stromelysin-1 by dual immunolocalisation and Western blotting techniques. Synovial fibroblasts, when activated by macrophage-derived products in primary culture or by interleukin-1/phorbol myristate acetate in subcultures, released significant quantities of collagenase and stromelysin in their inactive, precursor forms. The ratio of released procollagenase: prostromelysin varied between different synovial cell preparations. Dual immunolocalisation studies demonstrated both coordinate and separate expression of the two enzymes by single cells. Approximately 80% of the activated fibroblasts, especially those with stellate morphology, showed co-expression of both enzymes. By contrast synovial macrophages had a modest or negligible capacity to elaborate either enzyme under the same in vitro conditions. In many fibroblastic cells both collagenase and stromelysin were co-localised to the perinuclear Golgi region and the same cytoplasmic compartments. Vesicular structures appear to provide intracellular transport for both enzymes to sites of secretion. Both enzymes showed preferential pericellular binding to a collagenous substratum rather than any association with the plasma membrane/cell surface.
7542514 The antiperinuclear factor and antikeratin antibody systems. 1995 Aug Antiperinuclear factor (APF) and antikeratin antibody (AKA) have long been known to be associated with rheumatoid arthritis. Human buccal mucosa epithelial cells have hitherto been required as the substrate in the APF test, while AKAs are detected on rat esophagus sections, using an indirect immunofluorescence technique. These two autoantibodies proved to be interrelated. Cytoplasmic inclusions in buccal cells have presumptively been termed keratohyalin granules and the APF target antigen colocalizes exactly with that of antiprofilaggrin antibody within the perinuclear organelles. The latter protein has convincingly been identified as the genuine specificity of the so-called AKA.
8877916 Thrombin in the synovial fluid of patients with rheumatoid arthritis mediates proliferatio 1996 Sep OBJECTIVE: To investigate the clotting and fibrinolytic activities in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to examine the role of thrombin in synovial hyperplasia. METHODS: We measured the amounts of thrombin-antithrombin-III complex (TAT), antithrombin-III (AT-III), thrombin, plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI), and plasmin-alpha 2-antiplasmin complex (PAP) in SF of 20 patients with RA and 16 patients with osteoarthritis (OA). The proliferative response of synovial fibroblast-like cells to thrombin was measured using [3H] thymidine incorporation. Expression of platelet derived growth factors (PDGF) in conditioned medium was analyzed using a Western blot method, and expression of the mRNA of PDGF and their receptors was analyzed by reverse transcription polymerase chain reaction. RESULTS: The amounts of clotting factors (TAT, AT-III) and fibrinolytic factors (plasminogen, alpha 2-PI, and PAP) were significantly higher in the patients with RA than in patients with OA (p < 0.01). Moreover, SF thrombin concentrations of patients with RA correlated significantly with erythrocyte sedimentation rates (rs = 0.751, p < 0.01) and serum C-reactive protein concentrations (rs = 0.531, p < 0.05). Thrombin exhibits mitogenic activity toward synovial fibroblast-like cells in vitro, and this mitogenic activity is associated with an increase in the expression of mRNA of both PDGF-alpha receptor and PDGF-beta-receptor. CONCLUSION: The high levels of thrombin activity in the SF of patients with RA and strong mitogenic activity of thrombin toward the synovial fibroblast-like cells suggest that thrombin plays an important role in the pathogenesis of RA.
8724291 Antigen binding differences between secreted and cell surface expressed rheumatoid factor 1996 May OBJECTIVE: Rheumatoid factor (RF) is the predominant autoantibody in rheumatoid arthritis (RA). but its role in the pathogenesis of RA remains unclear. We hypothesized that surface RF (sRF) expressed on antigen presenting B cells (B-APC) might have different binding specificities than secreted RF. METHODS: We examined RF binding in a novel RF antigen capture enzyme linked immunoassay (ACE) that mimicked sRF binding, and compared it with a direct binding enzyme linked immunoassay (DBE) that mimicked secreted RF. RESULTS: Significant differences in binding characteristics by the same rheumatoid synovial cell (RSC) derived monoclonal RF (mRF) were observed between the ACE and the DBE. For example, several mRF that demonstrated the classical Ga binding pattern (binding to IgG1, 2, and 4) in the DBE showed considerable binding to selected IgG3 proteins in the ACE; and several mRF that bound only to rabbit IgG in DBE bound to human IgG in the ACE. CONCLUSION: These RF reactivity differences may be attributed to conformational modifications in the RF and IgG molecules that expose different epitopes or altered binding sites depending on the physical state of the antibody and/or antigen and may be important pathogenically.
1478127 [Study on anti-histone fraction antibodies in patients with rheumatic diseases]. 1992 May By using Western blot method, we studied the antihistone fraction antibodies in sera of patients with rheumatic diseases. After analysed with SDS-PAGE, the histone could be separated into H1, H3, H2B, H2A and H4 fractions. The positive rate of anti-histone fraction antibodies was highest (82.1%) in systemic lupus erythematosus (SLE) patients, especially in active stage. In 28 SLE patients, the positive rates of anti-H2B, -H1, -H3, -H2A and -H4 were 78.6%, 60.7%, 50.0%, 35.7% and 7.1% respectively. The results revealed that the determination of anti-histone fraction antibodies was beneficial to the diagnosis of SLE.
7755328 [Cover of trochanter pressure sores by V-Y musculocutaneous flap of the fascia lata]. 1994 Aug Authors report their experience with the V-Y advancement flap in the coverage of trochanteric pressure sores. Nine flaps have been performed concerning 7 patients. Trochanteric sores in paraplegia or tetraplegia may lead to suppurative arthritis of the hip, with a risk of anaerobic infection and acute septicaemia. The treatment has to be as complete as possible. The trochanteric sore is debrided, with special attention given to removing all necrotic material, the surrounding bursa, and the bony prominence of the greater trochanter. The debrided trochanteric region is then covered by a well-vascularized and thick tissue. We observed only one complication at the donor site which can be closed primarily by this technique. The V-Y advancement technique is a new, simple and safe design of tensor fasciae latae flap. The defect is covered by the thicker and the best vascularized portion of the musculo-cutaneous flap. It allows preservation of other donor sites of the gluteal region to cover other sores, which are often associated.
8215751 A reevaluation of aspirin therapy in rheumatoid arthritis. 1993 Nov 8 BACKGROUND: Aspirin therapy has been largely superseded by prescription nonsteroidal anti-inflammatory drug (NSAID) therapy in rheumatoid arthritis, in part because of premarketing studies suggesting lesser toxic effects for NSAIDs than for aspirin. This study evaluates these toxic effects in a postmarketing population of patients with rheumatoid arthritis. METHODS: We studied 1521 consecutive courses of aspirin and 4860 courses of NSAIDs in patients with rheumatoid arthritis from eight Arthritis, Rheumatism, and Aging Medical Information System Post-marketing Surveillance Centers. Toxicity index scores were generated from symptoms, laboratory abnormalities, and hospitalizations, weighted for variable severity and severity of side effect. RESULTS: The toxicity index was only 1.37 (SE = 0.10) for aspirin and 1.87 to 2.90 for selected nonsalicylate NSAIDs. These differences were consistent across centers and remained after statistical adjustment for differing patient characteristics. There was a different toxicity with different aspirin preparations, with a score for plain aspirin of 1.36 (SE = 0.23), for buffered aspirin of 1.10 (0.20), and for enteric-coated aspirin preparations of 0.92 (0.14). Most important, there were strong dose effects, with a score of 0.73 (0.09) for 651 to 2600 mg daily, 1.08 (0.17) for 2601 to 3900 mg, and 1.91 (0.38) for more than 3900 mg. The average aspirin dose taken was only 2665 mg/d, approximately eight "tablets," compared with 3600 to 4800 mg/d used in the 16 pivotal premarketing studies reviewed. Average NSAID doses were, on the other hand, lower in premarketing trials (eg, naproxen 500 mg/d vs 773 mg/d in the Arthritis, Rheumatism, and Aging Medical System clinical practices). CONCLUSIONS: Aspirin therapy, in doses commonly employed in practice, has an excellent safety profile in rheumatoid arthritis, and it is the least costly NSAID. The safety advantage is explained primarily by a dose effect and secondarily by possible differences between formulations. Newer management strategies for rheumatoid arthritis emphasize NSAID use as symptomatic therapy and use of disease-modifying anti-rheumatic drug therapy for anti-inflammatory objectives. Thus, the original recommendation for "anti-inflammatory" doses of aspirin now is less easily justified. Aspirin therapy merits reconsideration as adjunctive therapy for the management of rheumatoid arthritis.