Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2093440 | D-penicillamine. | 1990 Dec | D-Pen represents an effective treatment for a proportion of patients with RA and PSS. Its status in the treatment of juvenile RA is uncertain. The best results will be obtained by a skillful, careful physician maintaining careful surveillance for toxicity. Neither the mode of action nor the mechanisms of toxicity are well understood in RA. Consequently, safer and more effective analogues of D-pen have not been produced. | |
| 3272816 | HLA, C4, Bf, Gm and autoantibodies in rheumatoid arthritis. | 1988 | Sera from 48 subjects with rheumatoid arthritis (RA), more than 80% of which were seropositive, were examined for the presence of antibodies to intact nuclei (ANA) by immunofluorescence, extractable nuclear antigens (ENA), double-stranded DNA by immunoassay and immunoglobulins, i.e. rheumatoid factors (RF) by haemagglutination. The genetic markers of HLA, the fourth complement component (C4) and properdin factor (Bf), which are all coded for within the major histocompatibility complex and Gm immunoglobulin allotypic markers were all analysed in relation to various parameters of these autoantibodies. The only significant association to emerge was between low ENA antibody affinities and the Bf Fs phenotype (p less than 0.02). Although weak associations between individual autoantibody parameters and the other immunogenetic markers were detected, there were no significant HLA, C4 or Gm association with either ANA subsets or RF, a finding which agrees with, and also extends previous HLA studies of predominantly seropositive RA cohorts. | |
| 3318427 | Evaluation of nabumetone in the treatment of active adult rheumatoid arthritis. | 1987 Oct 30 | The safety and efficacy of nabumetone and placebo were compared in a three-week, multicenter, double-blind, randomized, parallel evaluation involving patients with class II or III definite or classical rheumatoid arthritis. No patient received concomitant treatment with other nonsteroidal anti-inflammatory agents; however, disease-modifying agents (gold, steroids) were permitted. Of the 139 patients who entered the double-blind phase of the study, all were evaluable for safety, and 113 were evaluable for efficacy. Sixty-one patients received 1,000 mg of nabumetone per day at bedtime, and 50 were given placebo tablets; patients in both groups were permitted up to 3,250 mg of acetaminophen per day as needed for pain. After three weeks, nabumetone-treated patients exhibited a greater degree of improvement from baseline than did the placebo-treated patients, and the degree of improvement was statistically significant for four of seven variables. | |
| 1749946 | Therapy for rheumatoid arthritis: combinations of disease-modifying drugs and new paradigm | 1991 Oct | The last 10 years have witnessed a change in the way rheumatologists view rheumatoid arthritis (RA). It is no longer considered a slowly progressive disease limited to the joints, but rather an aggressive systemic disease that results in clinically significant morbidity early in its course and can contribute to excess mortality. Heightened awareness of the health impact of RA has spurred a search for effective therapy to be applied early in the course of disease for patients with moderate to severe RA. Combinations of disease-modifying antirheumatic drugs (DMARD) have become an increasingly popular alternative to sequential monotherapy. In this report, we review published series of patients with RA who have been treated with combinations of DMARDs, sometimes including chemotherapeutic agents, with some critical comment. Published paradigms of treatment are also reviewed and a new strategy is presented. The "step-down bridge" strategy allows early treatment with at least four DMARDs, but may place some patients with mild disease at an inappropriately high risk of adverse effects. The "sawtooth" strategy gives little guidance as to which DMARD(s) should be chosen for initial treatment. We describe a "graduated-step" strategy that provides numerical grading to match disease severity and disease activity with appropriate initial therapy and that facilitates therapeutic decisions throughout the course of treatment. | |
| 1717225 | Etodolac. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases and | 1991 Aug | Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) effective in the treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, and in the alleviation of postoperative pain. Etodolac also provides relief of other types of pain, including that arising from gouty conditions and traumatic injury. In all indications, etodolac appears to be at least as effective as other NSAIDs. The incidence of clinical adverse effects other than abdominal pain and dyspepsia is similar to that observed with placebo, and etodolac has been associated with a low rate of gastrointestinal ulceration and other serious events. Data from preliminary animal studies have suggested that etodolac may provide more selective inhibition of prostaglandin synthesis at sites of inflammation than some other currently available NSAIDs. Thus, available evidence indicates that etodolac, with its low incidence of gastrointestinal events, is an effective and well tolerated alternative to other NSAIDs in the treatment of arthritic diseases and pain of various aetiologies and should be considered a first-line therapy. | |
| 2885986 | [Sulfasalazine (Azulfidine RA) versus aurothioglucose in therapy of chronic polyarthritis- | 1987 Mar | In a current German multicenter comparative study a minimum of 2 X 58 patients with active rheumatoid arthritis (RA) will be treated 36 weeks with sulfasalazine or aurothioglucose. The total time of observation will be 2 years. Up to September 1986 191 patients were recruited in the study, 81 patients divided into two treatment groups were treated for 36 weeks. A preliminary evaluation shows a significant reduction of the parameters of disease activity in both groups. In the sulfasalazine group favourable changes occur earlier than in the gold group. In comparison with gold sulfasalazine shows up to advantage concerning benefit/risk-ratio measured by the rate of side effects causing cessation of therapy and the rate of positive therapeutic response. On the basis of the preliminary data a comparison of grade and duration of ameliorations and of long-term tolerance of the two treatment regimens is not possible. | |
| 2964098 | Analysis of the antigen specific helper T cell function and HLA-DR of Israeli patients wit | 1987 Nov | Forty-three patients with rheumatoid arthritis (RA) were studied for their ability to respond to the synthetic polypeptide antigen (T, G)-A-L as measured by the production of a T cell helper factor by their antigen activated T cells. Sixteen patients (37%) responded to (T, G)-A-L by the production of an antigen specific helper T cell factor, a percentage not significantly different from healthy donors. The production of antigen specific T cell helper factors was affected, although not significantly, by immune modulating drugs and by the presence of rheumatoid factor in sera of patients. The high incidence of HLA-DR 4 reported for RA patients was not observed in this group of RA patients. | |
| 2202458 | Double blind placebo controlled trial of pulse treatment with methylprednisolone combined | 1990 Aug 4 | OBJECTIVE: To assess whether monthly treatment with intravenous methylprednisolone enhances or accelerates the effect of disease modifying drugs in patients with rheumatoid arthritis. DESIGN: A 12 month double blind, placebo controlled, multicentre trial in which patients with active rheumatoid arthritis were randomly allocated to receive pulses of either methylprednisolone or saline every four weeks for six months. At the start of the pulse treatment all patients were started on penicillamine or azathioprine. SETTING: Four rheumatology departments in Denmark. PATIENTS: 97 Patients (71 women, 26 men) aged 23-84 (mean 60) who had active rheumatoid arthritis of at least four weeks' duration despite treatment with non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Monthly clinical recording of morning stiffness, number of tender and swollen joints, blinded observers' evaluation of therapeutic effect, and patients' self assessed condition. Concomitant laboratory measurements of erythrocyte sedimentation rate and concentrations of C reactive protein and haemoglobin. Radiography to determine the number of erosions at the start of treatment and after 12 months. RESULTS: 57 Patients completed the trial, taking the same disease modifying drug throughout. Evaluation four weeks after each pulse treatment and at 12 month follow up showed no significant differences between the methylprednisolone and placebo groups in any of the clinical or laboratory variables. Radiography showed the same degree of progression of erosions in both groups. Evaluation of the total data on 97 patients and on the 57 who completed the trial showed the same lack of significance between the treatment groups. CONCLUSIONS: Intravenous pulse treatment with steroids can be recommended only for rapid temporary relief of flares of disease in patients with rheumatoid arthritis. The response is short lived. Repeated pulses of methylprednisolone at four week intervals do not improve the results of treatment with drugs that induce remission such as penicillamine and azathioprine. | |
| 2458191 | Clinical biochemical measurements in rheumatology. | 1988 Apr | Despite 50 years of intensive research in the field of RFs, autoimmunity and chronic inflammation, some of the serological tests used for measuring autoantibodies remain an anachronism. Clinical chemistry has the potential technology to provide the rheumatologist with automated quantitative antibody/antigen measurements. It can also widen the range of tests available for disease monitoring, which would be helpful in the management of the chronic rheumatic diseases. Traditional laboratory tests must be superseded by new developments, derived from fundamental research, if we are to improve the diagnosis and management of the rheumatic diseases. | |
| 3320428 | Malignant lymphomas in patients with autoimmune diseases: a report of 6 cases and a review | 1987 Aug | Six patients with malignant lymphomas in autoimmune diseases are described. Four patients who had Sjögren's syndrome (SS) alone or with progressive systemic sclerosis (PSS) or rheumatoid arthritis (RA) developed non-Hodgkin's lymphomas of the B cell type. One patient who had systemic lupus erythematosus (SLE) developed a B cell lymphoma. Another patient with chronic thyroiditis (ChTD) and idiopathic thrombocytopenic purpura (ITP) had a T cell (OKT3/T4) lymphoma. In 5 patients, the autoimmune diseases (2SS, SS/PSS, SS/RA and SLE) preceded B cell lymphomas by one to 11 years. In the patient with ChTD/ITP, ChTD and a malignant lymphoma were found simultaneously. A review of Japanese reports on lymphoproliferative disorders associated with these autoimmune diseases is given. This report offers the suggestion that disorders in the immunoregulatory system caused by autoimmune diseases may predispose lymphoproliferative disorders. | |
| 1981136 | [Sulfasalazine in rheumatology]. | 1990 Jul | Sulphasalazine (SLZ) has proved to be a drug effective in inducing clinical improvement or remission in chronic inflammatory rheumatic diseases (other than inflammatory bowel diseases) such as rheumatoid arthritis (RA) and some seronegative spondyloarthropathies, in a fashion similar to that of long-acting, second-line drugs in RA. Several clinical studies agree upon the efficacy of the compound employed at a dose of 2-3 g/day and upon the incidence of side effects, which appear to be equivalent to or lower than those related to traditional disease-modifying drugs employed in RA. The following points should be clarified and developed with regard to the use of SLZ in chronic rheumatic diseases: main mechanism(s) of action, improvement of therapeutic strategy (i.e.: combined treatments, maintenance therapy), prevention and control of main side effects, and its preferential use or limits in the management of a larger number of inflammatory rheumatic diseases. | |
| 3827960 | Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. | 1987 Feb | Immunization with chondroitinase ABC-digested fetal human cartilage proteoglycan and Freund's complete adjuvant induced polyarthritis and ankylosing spondylitis in female BALB/c mice. The initial external symptoms of the joint inflammation were swelling and redness. This was associated with edema of the synovium and periarticular tissues and gross proliferation of cells, which reached a peak during weeks 7-9 of the experiment. Mononuclear cell infiltration, with perivascular concentration and occlusion of small vessels, was common. Synovitis increased in severity, villous pannus developed, and erosions of bone, articular cartilage, and occasionally, growth plate were observed. The lumbar spine and the proximal intervertebral discs of the tail also exhibited inflammatory and degenerative changes. As the arthritis progressed, sometimes with acute inflammatory exacerbations, more joints became involved and, by the sixteenth to the twentieth weeks of the experiment, a progressive polyarthritis, with gross joint deformities and restricted function, developed in the majority of the limb joints. Clinical and morphologic features of the disease correlated well with radiologic analysis and with an increased deposition of 99mTc-methylene diphosphonate (determined by radionuclide imaging). The development of this arthritis was accompanied by the expression of cell-mediated and humoral immunity to the immunizing antigen. However, this immunity was also observed, although it was generally less well developed, in mice that received the intact or digested proteoglycan without adjuvant. These mice did not usually develop arthritis. Control mice that received only adjuvant did not develop arthritis. | |
| 2273518 | Safety issues related to DMARD therapy. | 1990 Nov | The old pyramidal approach to treatment of rheumatoid arthritis depended most fundamentally upon the beliefs that the most effective agents were also the most toxic, that toxic-therapeutic ratios of different drug categories were about the same, and that one should first use the least effective and least toxic drugs. Recent data, however, demonstrate the often severe toxicity of the nonsteroidal antiinflammatory drugs and the surprisingly good safety record of certain disease modifying antirheumatic drugs. New analyses tend, in general, to support less aggressive monitoring strategies. Some of the fundamental assumptions of the old pyramidal strategy are shown to have been inaccurate. | |
| 2384101 | Dysprosium (165Dy) hydroxide macroaggregates for radiation synovectomy--animal studies. | 1990 | This paper reports the development of a new chemical formulation, Dy-HMA, to utilise the advantages of dysprosium 165 in radiation synovectomy of certain forms of arthritis. Dy-HMA is a sterile suspension of dysprosium hydroxide macroaggregates (approximately 6 mg Dy/ml) in saline with the majority of particles in the 3-5 microns range. The absence of ferric hydroxide and a higher concentration of dysprosium in the formulation offer advantages over dysprosium ferric hydroxide macroaggregates, Dy-165-FHMA. Biodistribution studies in rats and rabbits with Dy-HMA show less leakage than with Dy-FHMA and considerably less leakage than with yttrium silicate colloid. Rabbits treated with intra-articular injections of Dy-HMA equivalent to 10-30 times the typical clinical dose showed no signs of any toxic effects. | |
| 2198976 | Immunohistological reassessment of accessory cell populations in normal and diseased human | 1990 Aug | Accessory cell populations in normal and diseased synovial tissue have been reanalyzed following the development of the monoclonal antibody, EBM11, directed against the CD68 epitope which is expressed by macrophages in all locations so far examined. Previous studies used as a macrophage marker the monoclonal antibody RFD7 which binds only a proportion of (mature) macrophages. Using double indirect immunofluorescence, normal and rheumatoid synovial samples were examined for the presence of cells which bind the putative dendritic cell marker, RFD1, in conjunction with either RFD7 or EBM11. RFD1 positive cells were found in five of 40 normal synovia. Of these cells, 30-35% were negative for RFD7 or EBM11 and, when closely apposed to T-lymphocytes, showed a typical interdigitating morphology. In contrast, all of ten rheumatoid synovia contained RFD1 positive cells; the extent of double labelling with macrophage markers varied with the position of the cells in the tissue. As expected, EBM11 stained a larger number of cells with macrophage morphology than RFD7. The combination of RFD1 and EBM11 appears to be a useful method for identifying interdigitating dendritic cells in connective tissue, these cells being characterized by positive RFD1 and negative EBM11 binding. On this criterion, interdigitating dendritic cells were plentiful in rheumatoid synovium and present, albeit infrequently, in normal synovium. | |
| 1855703 | The Keller resection arthroplasty: a 13-year experience. | 1991 Feb | The clinical results following Keller resection arthroplasty were reviewed in 54 feet with a 2- to 10-year follow-up. Patients were evaluated by radiographs, physical examination, and questionnaire. The primary indication for surgery was painful hallux valgus with associated degenerative changes of the first metatarsophalangeal joint. Additionally, rheumatoid arthritis was the underlying diagnosis in four feet. Seventy-five percent of all patients had complete relief of their symptoms. There was significant (P less than .01) improvement in both the metatarsophalangeal and intermetatarsal angles, but a decreased range of motion in the first metatarsophalangeal joint, with a complete lack of plantarflexion in 67%. Application of the Bonney and MacNab2 grading system yielded a 72% rate of good and excellent results. The subjective patient satisfaction rate was 87.5%. Patient satisfaction was most strongly associated with the use of a K-wire for postoperative fixation (P = .03), and a limited resection of the proximal phalanx (P = .03). We conclude that the Keller resection arthroplasty is a reasonable alternative for the treatment of hallux valgus in the presence of degenerative changes in the first metatarsophalangeal joint. | |
| 2273459 | Effect of aspirin and sulindac on methotrexate clearance. | 1990 Sep | The pharmacokinetics of low dose methotrexate (MTX) were evaluated in 12 rheumatoid arthritis patients in the presence and absence of steady-state levels of salicylic acid (ASA) and sulindac (SU). Using a Latin square design, patients were given MTX plus ASA (mean 3.4 g/day), MTX plus SU (mean 400 mg/day), or MTX alone. On a background of at least one year of regular MTX therapy, patients received 10 mg/m2 MTX iv (mean 17.8 mg) given after at least 2 weeks of treatment with each of the above regimens. Plasma concentrations of MTX and 7-hydroxymethotrexate (7-OH-MTX) were measured using HPLC. No differences in MTX clearance (Cl) were found comparing MTX alone, MTX + ASA, and MTX + SU. However, if one particular subject that had a very low clearance when receiving MTX alone was excluded, there was a statistically significant decrease in MTX clearance when either ASA or SUL were present. It is also noteworthy that ASA significantly increased the exposure of the subject to 7-OH-MTX and, to a lesser extent, so did sulindac. Since 7-OH-MTX has been shown to be an active metabolite when given for cytotoxic effects at higher doses and because it has been show to be nephrotoxic at doses a thousand-fold greater than used in rheumatoid arthritis, nonsteroidal anti-inflammatory drugs should be used cautiously with MTX until further large scale safety studies are conducted. The data indicate that if a clinically significant interaction were to occur, ASA is more likely than SU to interact with MTX. | |
| 2016610 | Radial head replacement in capitellocondylar total elbow arthroplasty. 2- to 6-year follow | 1991 Mar | We reviewed six capitellocondylar metal-to-plastic total elbow replacement prostheses with radial head components, implanted in patients with rheumatoid arthritis. At an average of 4.7 +/- 1.5 years, relief of pain, improvement of function, and a functional range of motion were preserved. Five of the six elbows (83%) were clinically rated good or excellent. Radiolucent lines were seen at the bone-cement interface in 50% of the humeral component stems and in all ulnar component boats within 2 years after surgery; none had progressed at subsequent examination. Most were less than or equal to 1 mm wide, and none were associated with clinical deterioration. Only one of the humeral components was radiographically loose. No radiolucent lines were seen along the stems of the ulnar or radial components. There were no postoperative dislocations when the radial component was used, presumably because the prosthetic radial head provided increased constraint. None of these elbows have required revision. Radial head replacement in capitellocondylar arthroplasty had been discontinued because radiolucent lines were observed at early review. However, the absence of clinical failure, dislocation, or progression of radiolucency at long-term follow-up examination favor radial head replacement in primary unconstrained total elbow arthroplasty. | |
| 3262732 | How useful are combinations of blood tests in "rheumatic panels" in diagnosis of rheumatic | 1988 Sep | Laboratory tests are sometimes combined into "panels," presumably to facilitate a swift and accurate diagnosis. "Rheumatic panels" were available from 16 of 17 members of the American Clinical Laboratory Association. Panels included an average of five tests (range three to 11). Panel prices ranged from $25 to $189. The three tests most common in the available panels were those for rheumatoid factor, antinuclear antibody, and uric acid level. A panel combining these three tests would have a positive predictive value of only 34.6% in identifying rheumatoid arthritis, systemic lupus erythematosus, or gout in a population with joint pain, in which the combined prevalence of these diseases is estimated to be 10%. Therefore, 65.4% of persons with a "positive" test would not have one of these three rheumatic diseases. Lack of independence between diseases and second tests (for example, positive antinuclear antibodies in rheumatoid arthritis) increases misclassification errors. A careful history and physical examination along with serial ordering of a few selected tests appear optimal to establish a clinical diagnosis of a rheumatic disease. | |
| 3372556 | Loosening of the porous coating in total knee replacement. | 1988 May | We reviewed 40 cementless Porous Coated Anatomic knee replacements in 34 consecutive patients. The average follow-up was 12.9 months (range 6 to 36 months). At review, loose beads were identified in 23 knees, in 11 on the femoral side and in 16 on the tibial side (in five knees on both sides). One loose bead was adjacent to the patella. In four knees there were intra-articular beads. Radiolucent lines at the interface between bone and prosthesis were seen in 19 knees, in six on the femoral side and in 16 on the tibial side (in three knees on both sides). In relation to the tibial component loose beads were associated with a radiolucent line in all except one case. Progressive loosening with an increasing number of loose beads was seen in three knees. At this early stage of follow-up there was no correlation between the clinical results and the presence of loose beads. |