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

ID PMID Title PublicationDate abstract
2675492 [Initial clinical experiences in the treatment of chronic polyarthritis with a new monokin 1989 May Cytokines such as Interleukin-1 (IL-1) are important modulators of the cell-mediated immune response and play a paramount role in inflammatory autoimmune disease. We report on preliminary clinical experiences with a new, tricyclic substance [( 10-Methoxy-4H-benzo[4,5]cyclo-hepta-[1,2-b]thiophene-4- ylidene]acetic acid, MW 284), which inhibits the release of interleukin-1 alpha and -beta from cultured murine macrophages or human mononuclear cells. The study included 12 patients (rheumatoid arthritis, n = 9; hemochromatotic arthropathy, n = 1; psoriatic arthropathy, n = 1; seronegative spondylarthropathy, n = 1). Eight patients were treated for a total of 8 weeks, receiving a median dose of 800 mg/d of the substance. Due to significant clinical benefits, two patients continued for a total of six months. Administration of the drug was discontinued in two patients because of severe urticaria and lack of compliance, respectively. Four out of 10 patients showed clinical improvement according to Ritchie-Index, pain score, ESR and CRP. Side effects were diffuse gastrointestinal symptoms (4/12), temporary impairment of liver function (4/12) and allergic skin reactions (3/12).
1980315 Challenging the pyramid. A new look at terapeutic approaches for rheumatoid arthritis. Pat 1990 Nov The goals of therapy for rheumatoid arthritis (RA) address alleviation of pain; prevention of joint destruction, deformity, and disability; and maintenance of life style. Disease modifying antirheumatic drugs (DMARD) are among the most important agents to accomplish these goals, but guidelines for their introduction into management have not been clearly established. In 1986 a survey regarding DMARD usage was conducted among 1057 specialists in arthritis. The key criteria used in patient selection were progressive pattern of disease, persistent synovitis, and the degree of swollen joints. Eighty-four percent of respondents waited 3 to 6 months from the time of initial diagnosis of RA before starting DMARD. Parenteral gold was then the most preferred DMARD.
1796618 [Determination of lymphocyte subpopulations and their activation status in patients with r 1991 Dec In patients with systemic rheumatoid arthritis (RA) and extraarticular manifestation treated with plasma exchange or prednisolute-pulse-therapy, respectively, and followed by an additional immunosuppression by cyclophosphamide we have assessed the lymphocyte subpopulations of the peripheral blood and the cells expressing activating markers by means of monoclonal antibodies using fluorescence microscopy or fluorescence flow cytometry. Before therapy the patients showed a very different level of lymphocyte subpopulations tested. During treatment in both groups of patients there was not any uniform tendency in CD3, CD4 and CD8 positive cells. The percentage of activated lymphocytes was initially elevated and we found significant reduction, mainly in the 4th week after starting of therapy. Following in the most cases the level recovered to the state before therapy. For the single patients an individual pattern of reaction was evident in relation to the initial position before treatment.
1810225 Binding of C-reactive protein (CRP) by human peripheral blood lymphocytes in vivo. 1991 Antigenicity of C-reactive protein (CRP) on the surface of human lymphocytes was investigated by use of indirect immunofluorescence technique with anti-CRP antibodies. CRP on the lymphocyte surface (sd-CRP) belongs to two different categories: i) CRP produced by lymphocytes and inserted into cell membrane (s-CRP), ii) CRP produced primarily by the liver and bound by the lymphocytes (sb-CRP) in calcium-dependent manner. In human peripheral blood of healthy donors approximately 2.5% of lymphocytes expressed membrane CRP (s-CRP) and 1.5% of lymphocytes bound CRP in calcium-dependent manner (sb-CRP). Percentage of s-CRP lymphocytes increased in patients with rheumatoid arthritis, while population of sb-CRP lymphocytes did not change significantly, except cases where serum CRP concentration reached more than 50 micrograms/ml. Thus, it can be concluded that CRP is bound to the distinct population of lymphocytes, bearing specific membrane receptors.
3698359 Smoking and peptic ulcer in rheumatoid arthritis. 1986 Jan The prevalence of chronic peptic ulcer among 152 out-patients with rheumatoid arthritis attending a district general hospital was found to be 16.4% (25 patients), as against 6.6% (10 patients) among an equal number of matched control out-patients with other diagnoses. There was no evidence that any form of anti-inflammatory treatment increased ulcer risk, but smoking was significantly associated with a higher prevalence of ulcer. This relationship was shown to be quantitative and to depend upon an increased frequency of duodenal ulcer in women who smoked. It is possible that greater numbers would have shown the effect of smoking to apply to both sexes, and that for all patients with rheumatoid arthritis abstention from smoking could diminish the high risk of peptic ulceration associated with this disease.
3707626 A multicenter study of annual health service utilization and costs in rheumatoid arthritis 1986 Apr The economic impact of chronic illness has important implications for medical practice and health policy. To determine the yearly costs of illness for those who have rheumatoid arthritis, a detailed, self-administered questionnaire was developed. The questionnaire was completed by 940 patients. Direct costs (recorded as charges) include the average annual expenditures by all patients and third party payers for: hospital care ($913), physician costs ($206), other health professional visits ($71), medications ($436), laboratory tests ($217), radiographs ($116), assistive devices ($24), and nontraditional therapies ($22). The total annual medical costs per patient were $2,533. In a multivariate analysis that controlled for age, sex, education, and disease duration, the outpatient costs, inpatient costs, and total costs were all positively related to the Health Assessment Questionnaire Disability Index (P f less than 0.01) and global health (P f less than 0.01), but were not associated with self-reported pain.
2052906 Sympathetic innervation of normal and rheumatoid synovial tissue. 1991 Fresh synovial tissue was taken from two normal subjects and five patients with rheumatoid arthritis, and treated so that catecholaminergic sympathetic nerve fibres could be seen. A fluorescent network of varicose fibres was visible in normal as well as in rheumatoid synovial tissue. In the rheumatoid inflammatory tissue an increased number of fluorescent sympathetic nerve fibres could be seen in close proximity to blood vessels, even in the smallest synovial plica, indicating that the proliferation of inflammatory vessels is accompanied by simultaneous sympathetic nerve proliferation. A nervous component might thus contribute to the inflammatory process in human rheumatoid arthritis.
2672343 Corticosteroids in rheumatoid arthritis. 1989 Aug This report has presented evidence to support a disease-modifying role for corticosteroids in rheumatoid arthritis. It would appear that the efficacy of these agents in retarding the destructive course of rheumatoid disease has been substantially underestimated. Consideration for more liberal use of corticosteroids in the management of rheumatoid arthritis is warranted. Further study on new approaches to corticosteroid delivery is proposed.
2324139 Total condylar knee replacement in patients who have rheumatoid arthritis. A ten-year foll 1990 Apr Eighty knee replacements with a total condylar prosthesis in patients who had rheumatoid arthritis were followed for ten years. At ten years, nineteen knees needed revision and sixty-one prostheses were still functioning. The major reasons for revision were loosening of the tibial component or late bacteremic seeding from another site. Radiolucency at the bone-cement interface adjacent to the tibial component was statistically related to malposition of the tibial component. According to the system of The Hospital for Special Surgery, the mean scores were 64 points preoperatively and 85 points postoperatively. Synovitis recurred in only 3 per cent of the knees. When revision, pain, or radiographic evidence of loosening were considered an indication of failure, the ten-year cumulative survival was 75 per cent.
3947026 A case of rheumatoid hyperviscosity syndrome with characterization of the serum immune com 1986 Jan The clinical and immunologic data in a case of rheumatoid arthritis complicated by serum hyperviscosity are reported. The elevation in the serum viscosity was accompanied by the presence of intermediate immune complexes which were partially purified from the patient's serum by gel filtration chromatography. These complexes had a molecular weight of approximately 510,000 daltons and contained polyclonal IgG and IgA immunoglobulins. The hyperviscosity syndrome in this patient was likely due to the presence of intermediate complexes and unrelated to the rheumatoid factor activity which was found predominantly within the IgM fraction of the serum. This case demonstrates that the hyperviscosity syndrome may, in rare cases, develop as a complication of rheumatoid arthritis. It is important to consider this possibility before the clinical symptoms of increased serum viscosity become manifest.
2773570 [Mycoplasma arthritis in man and mechanisms of its pathogenesis]. 1989 Possible etiologic contribution of mycoplasma to human rheumatoid arthritis (RA) is supported by their recovery from synovial fluid of RA patients, as well as Mycoplasma antigens and antibodies detection in the bloodstream. The detectability of free antigens of M. arthritidis (Ma) and M. fermentans (Mf) in the sera of patients was 22.4%, and that of antibodies against those, 52.7%. Considerable difference between the detectability of Mycoplasma antigens and antibodies can be attributed to the fact that the bulk of the antigens form part of immune complexes and cannot be detected by serologic tests. Mitogenic effect of arthritogenic Mycoplasma and their ability to produce a cytotoxic effect on various cells, including lymphocytes, appears to be a mechanism of immune process developing in association with human RA. A study of immunobiological properties of individual Ma and Mf cell components has shown that a protein factor translocated into the culture medium is responsible for mitogenic action. Ma cytotoxicity in respect of target cells is related to its cytoplasmatic membrane. Mf produces a factor, acting directly on rat lymphocytes; its synthesis is apparently taking place on the cell membrane.
2379344 Adjuvant arthritis in the rat during pregnancy. 1990 May Pregnancy is known to have a beneficial effect on some forms of peripheral arthritis in man. We have examined the effect of pregnancy on the development and severity of adjuvant arthritis in the rat. Pregnancy does modify the development of adjuvant arthritis, but once the arthropathy is established, the changes seen with pregnancy are not the same as with rheumatoid arthritis.
2014717 Bone grafting for acetabular protrusion in hip arthroplasty. 27 cases of rheumatoid arthri 1991 Apr An acetabular bone graft with spongious bone chips was performed in 27 primary total hip arthroplasties in 23 patients with rheumatic disease. There were no major complications. After 5 (2-8) years, the grafts were well incorporated; after 1 year, remodeling had produced a normal cancellous bone structure. Clinical assessment showed overall good results.
3236298 Antidepressant analgesia in rheumatoid arthritis. 1988 Nov Forty-seven patients with definite rheumatoid arthritis (RA) were treated in a 32 week, double blind, crossover trial of amitriptyline, desipramine, trazodone, and placebo. All drug regimens produced significant changes on pain measures relative to baseline, but only amitriptyline exceeded placebo. Amitriptyline was associated with a significant reduction in the number of painful/tender joints. Our study supports the efficacy of a moderate dose of amitriptyline as an adjunct drug for the treatment of pain in both depressed and nondepressed patients with RA.
2897743 The restoration of proliferation and differentiation of peripheral blood mononuclear non-a 1988 The ability of enzyme-dissociated synovial adherent cells (SAC) obtained from patients with active rheumatoid arthritis to restore the proliferation and differention of peripheral blood mononuclear non-adherent cells (NAC) into immunoglobulin-secreting cells (ISC) was investigated. Autologous combinations of cells were used in this study to eliminate allogeneic reactions. Peripheral blood NAC, prepared by glass adherence and leucine methylester treatment to remove monocytes, almost completely lost their capacity to proliferate and differentiate into ISC in response to pokeweed mitogen. The response of NAC was restored by adding 12.5% of 'fresh SAC', which was obtained by glass-adherence after an overnight culture of non-rosette forming, enzyme-dissociated rheumatoid synovial cells. Although the response was also restorable by adding more than 25% fresh SAC, this was less satisfactory than adding 12.5% SAC. 'Old SAC', obtained by glass-adherence after 7 days culture of enzyme-dissociated synovial cells, did not restore the response of NAC. Immunohistochemical studies showed that 55% of fresh SAC and 3% of old SAC expressed HLA-DR antigens. When 100 units/ml of interferon gamma was present, 25% of old SAC remained HLA-DR-positive and some of these cells retained a dendritic morphology after 7 days culture. The results indicate that rheumatoid synovia contain macrophage-like cells that can effectively support the ultimate differentiation of lymphocytes to ISC.
3025298 Analysis of immune complexes in rheumatoid arthritis for Epstein-Barr virus antigens revea 1987 Jan 15 We recently defined the immunochemical characteristics of immune complexes (IC) isolated from synovial fluid (SF) of patients with rheumatoid arthritis with the use of Western blot analysis. In the present study, we probe for exogenous antigens in the IC by examining the specificity of antisera raised against the IC. Anti-IC antisera demonstrated strong reactivity against the viral capsid antigen (VCA) of Epstein Barr virus (EBV), which was not explained by preimmune reactivity, polyclonal B cell activation, or Fc-mediated binding in the immunofluorescence or ELISA systems used to measure antibody titers. However, comparable anti-VCA reactivity was detected in antisera raised against non-rheumatoid SF. This phenomenon was not due to antigen since monoclonal anti-VCA antibody probing the IC by Western blot detected only IgG, nor to idiotype/anti-idiotype interaction since normal IgG absorbed out the anti-VCA reactivity. A monoclonal anti-VCA antibody competitively inhibited the binding of anti-IgG to IgG, and Fc fragment of IgG competitively inhibited the monoclonal antibody binding to VCA. No relationship between IgG anti-VCA antibody and IgG rheumatoid factor could be demonstrated. These data demonstrate an unexpected cross-reactivity of Fc fragment of IgG and VCA of EBV through the analysis of SF IC.
2964240 Increased helper inducer and decreased suppressor inducer phenotypes in the rheumatoid joi 1988 Jan Cells isolated from the joints of patients with rheumatoid arthritis (RA) exhibit functional immune abnormalities, such as diminished suppressor activity, depressed response to mitogens, and enhanced immunoglobulin production. We sought to characterize the T lymphocyte subsets in the synovial fluid (SF) and peripheral blood (PB) of RA patients in an attempt to clarify the mechanism(s) responsible for these functional immune abnormalities. We used dual-immunofluorescence staining techniques with several combinations of monoclonal antibodies, including anti-4B4 and anti-2H4, which define, respectively, the helper inducer and suppressor inducer subsets of CD4+ (Leu-3+ and T4+) cells. Mononuclear cells from normal PB (n = 9), RA PB (n = 6), and RA SF (n = 9) were analyzed, after staining, by flow cytometry. We observed a significant increase (P less than 0.0002) in the number of cells bearing the helper inducer phenotype (CD4+, 4B4+), and a significant decrease (P less than 0.0002) in the number of cells bearing the suppressor inducer phenotype (CD4+, 2H4+), in RA SF compared with the levels in PB from RA patients or normal control subjects. We also observed that the CD8+, 2H4+ subset was significantly decreased (P less than 0.0001) in SF compared with that in PB. There was no significant difference in the lymphocyte subset levels in PB from RA patients and from normal subjects. These observations may account, in part, for the reduced suppressor activity, the poor response to mitogens, and the autologous mixed lymphocyte reaction, as well as the enhanced production of Ig and rheumatoid factor, that are observed in the rheumatoid joint.
3714265 [Rheumatic lesions of the carpus]. 1986 Apr The wrist is frequently involved in rheumatoid arthritis. The areas where the synovial membrane is best developed are the best areas for the development of the pannus as well. Proliferation of the synovial membrane lining the joint capsules leads to loss of ligamentary support of the wrist. This is the basis for further deformation. The direction of the carpal deformation is determined by normal anatomical conditions. Destruction of the elements that are essential for the stabilization of the wrist is responsible for these deformations; these elements are described. The flexor and extensor tendons of the fingers and wrist joint are coated with synovial sheaths. These can also be infiltrated by a synovial pannus or rupture due to abrasion by osteophytes. The dislocation, elongation, or rupture of tendons also leads to deformation. In accordance with our conception of the longitudinal pillars of the carpus we classify the different possible types of rheumatic carpal deformation into three groups: deformities of the ulnar, central, and radial type. Combinations of these various types are also common in the course of the disease and lead to instability and ankylosis. Synovectomy represents the basic treatment for the rheumatic joint. It is initially performed by radiosynovectomy. If there is persistent pain and swelling, an operative synovectomy is required. The following surgical procedures are most frequently combined with synovectomy of the wrist joint: synovectomy of the extensor tendons, resection of the head of the ulna, axial realignment of the wrist joint, and reconstruction of ruptured tendons. The operative technique is described in detail. This operation is also most commonly performed in the advanced stages. This operation produces good functional results that are reliable for a prolonged period of time, so that arthrodesis or arthroplasty can be avoided. Deterioration of the radiological findings, however, is common.
1991041 Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the infla 1991 Jan 15 Proton Hahn spin-echo n.m.r. spectroscopy was employed to detect abnormal metabolites present in rheumatoid synovial fluid that are derived from the deleterious generation of reactive oxygen radical species during exercise of the inflamed rheumatoid joint. A resonance attributable to a low-molecular-mass N-acetylglucosamine-containing oligosaccharide formed by the oxygen-radical-mediated depolymerization of synovial-fluid hyaluronate was clearly demonstrable when subjects with inflammatory joint disease were exercised. Moreover, formate, which may be derived from the attack of OH.radical on synovial-fluid carbohydrates, was also readily detectable in these samples. gamma-Radiolysis of rheumatoid synovial fluid samples and aqueous solutions of hyaluronate also gave rise to the production of the low-molecular-mass hyaluronate-derived oligosaccharide species and markedly elevated concentrations of (non-protein-bound) formate in the biological fluids. As expected, corresponding spectra of gamma-irradiated blood serum samples obtained from normal volunteers did not contain the signal attributable to the low-molecular-mass oligosaccharide species, but the formate resonance (barely detectable in non-irradiated normal serum samples) became clearly visible. Additionally, a curious increase in the effective concentration of non-protein-bound low-molecular-mass metabolites such as acetate, citrate, lactate and glutamine was observed after gamma-radiolysis of all biological fluids studied. The hyaluronate-derived low-molecular-mass oligosaccharide species and formate are suggested as novel markers of reactive oxygen radical activity in the inflamed rheumatoid joint during exercise-induced hypoxic/reperfusion injury.
2805491 Total knee arthroplasty for patients younger than 55 years. 1989 Nov There are few reports in the literature that deal with the results of total knee arthroplasty in the younger patient. The present study was undertaken to evaluate the results of total knee arthroplasty in patients under the age of 55 years. Ninety-three knee arthroplasties in 62 patients were performed between 1974 and 1982. The preoperative diagnosis was rheumatoid arthritis in 76 knees and osteoarthritis in 17 knees. The total condylar knee prosthesis was used in all knees. Defects in the tibial plateau were noted in 13 knees, and supplemental support was required. Ninety knees (17 with osteoarthritis and 73 with rheumatoid arthritis) were available for follow-up study at a mean of 6.1 years. The knee rating for the entire group was 87.1. The subgroup scores for the osteoarthritis and rheumatoid arthritis groups were also 87.1. Roentgenographic evaluation revealed a lucency rate of 30%. Two implants were found to have global radiolucencies and were considered loose. Survivorship analysis resulted in a cumulative survivorship rate of 96% at ten years for the entire group. These results are comparable to the long-term results of total knee arthroplasty in the older patient and better than the results of total hip arthroplasty in the younger patient. Total knee arthroplasty in the younger patient is a reliable and durable procedure but should be used with caution despite the excellent results reported here.