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

ID PMID Title PublicationDate abstract
8546719 The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis synovium. 1996 Jan OBJECTIVE: To investigate the expressions of co-stimulatory molecules CD86 (B7-2, B70) and CD28 by cells obtained from the synovial tissues (ST) and synovial fluids (SF) of patients with rheumatoid arthritis (RA). METHODS: Monoclonal antibodies (MAb) against CD86 and CD28 were used for immunochemical study of synovia from 18 RA patients, 4 osteoarthritis (OA) patients, and 4 normal subjects. These MAb were also used for flow cytometry of isolated ST cells from 8 RA and 5 OA patients and of SF mononuclear cells from 5 RA and 5 OA patients. RESULTS: Immunohistochemical examination revealed that CD86+ cells occurred in 11 of the 18 RA synovia, but in none of the 4 OA or 4 normal synovia. Most of the positive cells had macrophage-like morphology, and surrounded lymphoid aggregates. Most cells within lymphoid aggregates were stained positively for CD28. Flow cytometry showed that CD86+ cells comprised 2.9-33.4% (average 14.3%) of the total ST cells and 2.1-14.9% (average 6.1%) of the total SF mononuclear cells from RA patients. Approximately 40% of the CD86+ cells expressed CD14. A majority (mean 72%, range 57-89%) of the T cells in ST and SF expressed CD28. RA synovia expressed more CD86 molecules than did OA synovia (mean frequency of positive cells 14.3% versus 2.8%; mean fluorescence intensity 104.6 versus 40.9).
8156285 Bioavailability of hydroxychloroquine tablets in patients with rheumatoid arthritis. 1994 Mar Nine patients with RA received two doses of 155 mg racemic hydroxychloroquine each, as a tablet and by i.v. infusion, in a randomized cross-over design study. Blood concentrations over the first 32 h following each dose were determined. Bioavailability was estimated using a sequential exponential least squares deconvolution method. The mean fraction absorbed from the tablet was 0.79 (range 0.39 to 1.27). The mean absorption lag-time was 1.3 h (range 0.5 to 3.7 h) and the mean time for 50% absorption was 4.3 h (range 1.9 to 10.3 h). Mean rate and extent of hydroxychloroquine absorption were not significantly different from that previously reported for healthy volunteers, although the interindividual variability in absorption parameters was greater in the patient group. Variability in the extent of absorption would lead to differences in steady-state hydroxychloroquine concentrations between patients, potentially contributing to the variability in response observed in clinical practice.
8465132 [If I had chronic polyarthritis--current ideas on basic therapy]. 1993 Mar 23 Rheumatoid arthritis (RA) is a chronic inflammatory disorder of largely unknown etiology and complex multifactorial pathogenesis. To date, the medical management has been less than optimal and has consisted primarily of drugs that modulate the acute inflammatory process. Over the years a treatment program referred to as the classical therapeutic pyramid has evolved. A new concept and a controversial one in therapy of RA is that already at the time of definitive diagnosis, a more concerted effort towards vigorous treatment using second-line drugs such as methotrexate, should be made. It is very likely that over the next 5 years interventions such as monoclonal antibodies directed against predetermined T-cell subpopulations and anti-cytokines such as TNF-alpha binding proteins will evolve as new concepts in therapy of RA.
8210923 The safety profile of sustained-release etodolac. 1993 The safety profile of a new sustained-release (SR) form of etodolac was evaluated in 539 young and elderly patients with osteoarthritis or rheumatoid arthritis. Four long-term, open-label studies were conducted in nine different countries totaling 3,827 patient-months' exposure to etodolac SR. Patients were treated with either 400 mg or 600 mg etodolac SR once a day for up to 52 weeks. Withdrawals due to adverse reactions were low, occurring in only 5% (26/539) of all patients. The most common drug-related study events were GI-related, occurring in < 8% of patients. Elderly persons (> or = 65 years of age) were not at greater risk for adverse reactions or drug-related study events than were younger patients. Serious GI-related study events were rare (0.2%). The low level of serious GI effects was consistent with a separate study measuring gastrointestinal (GI) blood loss. Etodolac SR produced significantly less GI blood loss than naproxen in normal subjects. Because of its favorable safety profile, etodolac SR can serve as an alternative to conventional etodolac, providing the convenience of once-daily administration.
8923361 Sulfasalazine has a better efficacy/toxicity profile than auranofin--evidence from a 5 yea 1996 Nov OBJECTIVE: To compare results of medium to longterm sulfasalazine and auranofin treatment in active rheumatoid arthritis (RA). METHODS: 200 patients with active RA were enrolled in a prospective, randomized trial comparing sulfasalazine (target dosage, 40 mg/kg/day) with auranofin (6-9 mg/day). Patients were assessed annually for 5 years, using clinical and laboratory measures of disease activity. Risk of discontinuing treatment was compared using life table analysis. RESULTS: 31% of patients continued sulfasalazine for at least 5 years, compared to only 15% continuing auranofin (p < 0.05). Patients previously given intramuscular (i.m.) gold did particularly badly during auranofin treatment (only 1/26 continued therapy for 5 years), but after excluding all patients previously treated with i.m. gold from both groups more patients continued sulfasalazine for > 5 years (p < 0.05). Patients continuing therapy at 5 years had significantly milder disease at enrollment than those who did not. The patients continuing auranofin treatment at 5 years were no better than at the outset of the trial, and may represent a subgroup of patients with a good prognosis. Patients continuing sulfasalazine, however, showed sustained response over the 5 year period. CONCLUSION: Sulfasalazine therapy was more likely to be continued for 5 years, suggesting better tolerability and/or efficacy than auranofin, and produced evidence of continuing benefit. Patients previously withdrawn from i.m. gold therapy because of inefficacy or minor toxicity should not be given auranofin therapy.
7715074 [Initiation of hematopoietic recovery by recombinant human granulocyte-macrophage colony-s 1995 Jan A 65-year-old female with severe aplastic anemia induced by gold salt, whose hematopoietic recovery was initiated by rhGM-CSF therapy, was reported. The patient has been given a total of 500 mg of gold-sodium thiomalate for treatment of her rheumatoid arthritis. Two months after the final administration of it, she was admitted to our hospital with complaints of palpitation and shortness of breath. The hemogulobin was 5.9 g/dl, the platelet count was 0.5 x 10(4)/microliter, and the leukocyte count was 800/microliters with 19% neutrophils. Her bone marrow showed aplasia, and both of Ham and sugar-water tests were positive. Three times of bolus-methylprednisolone treatment, with or without methenolone acetate, resulted in no definite improvement of peripheral pancytopenia and marrow aplasia. Subsequent subcutaneous rhGM-CSF, 300 micrograms daily for 28 days with oral prednisolone 5 mg and methenolone acetate 40 mg daily, initiated hematopoietic recovery of all three cell lineages in both peripheral blood and bone marrow. The same doses of prednisolone and methenolone acetate were continued after rhGM-CSF administration, and three months later peripheral cytopenia and positive Ham and sugar-water tests disappeared completely.
8371231 Effect of exercise on the bone mineral density and bone remodelling indices in women with 1993 Jul Two premenopausal women with rheumatoid arthritis of 16 years' duration were enrolled in a one year conditioning exercise program consisting of walking and low impact aerobics. The effect of exercise on the markers of bone formation (serum bone specific alkaline phosphatase and osteocalcin), bone resorption (urinary calcium/creatine and serum tartrate resistant acid phosphatase), and vertebral bone mineral density as determined by dual photon absorptiometry are discussed.
8265233 A 43-year-old woman with right hip pain. 1993 Aug Although tuberculous arthritis is currently uncommon in the United States, the hip joint is a common location. Tuberculous arthritis usually presents as a mild, slowly progressing process. It often involves a single joint. Radiological findings include osteopenia of the involved joint, soft tissue swelling, bone destruction without evidence of bone formation, and sequestrum formation. Several conditions should be considered in the differential diagnosis. The detailed roentgenographic appearances and many of the differential diagnoses are included in this paper. Final diagnosis is made by positive culture results or finding the bacillus histologically.
1455046 Immunoglobulin V genes in rheumatoid arthritis. 1992 Nov Recent studies have revealed that a broad spectrum of Ig V genes (VH, V kappa, V lambda) contribute to the rheumatoid factor (RF) and non-RF produced by B cells in patients with rheumatoid arthritis (RA). This result contrasts with the restricted V gene use of paraprotein IgM RF. Certain VH and VL genes, however, appear more often in RA than expected from random expression, including some of the paraprotein-associated V genes. Many V genes expressed in RA are the same as those found in the fetal/CD5+ repertoire, suggesting an important role for CD5+ B cells in RA. Somatic mutations suggest that the B-cell response in RA is at least in part antigen-driven, although many Ig in RA have little or no mutation. Improved detection of V-gene polymorphisms now enable study of Ig V gene RFLP in RA.
9026492 [Status of the endoprosthesis in rheumatic metacarpophalangeal joints. Long-term results o 1996 Sep Advanced rheumatoid destruction of the metacarpophalangeal joints frequently requires implant arthroplasty. Among many different types of implants, the Swanson-Silastic-spacer is widely used. The long-term results of 102 arthroplasties of the metacarpophalangeal joint were assessed in 28 rheumatoid patients (34 hands) 10.1 years postoperatively on the average. Marked relief of pain was found in all patients. 75% of the patients reported functional improvement of the hand. Active range of motion decreased from 42 degrees preoperatively to 36 degrees postoperatively on the average. Ulnar drift was corrected from an average of 34 degrees preoperatively to 12 degrees postoperatively. The average extension deficit had improved from 33 degrees at surgery to 11 degrees at the time of follow-up. Grip strength remained unchanged. The radiographical findings showed surrounding osteolysis in 89.4% of the implants and 27.5% broken spacers. In comparison to other types of finger implants, Silastic-spacers showed similarly limited all over results, however, there seem to be less problems in salvage procedures.
7681283 Detection of increased levels of circulating intercellular adhesion molecule 1 in some pat 1993 Apr OBJECTIVE: To compare the levels of circulating intercellular adhesion molecule 1 (cICAM-1) and vascular cell adhesion molecule 1 (cVCAM-1) in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Levels of cICAM-1 and cVCAM-1 were measured in both plasma and synovial fluid using monoclonal antibody sandwich enzyme-linked immunoassays. RESULTS: Levels of both cICAM-1 and cVCAM-1 were significantly increased (P < 0.001) in RA patients compared with normal controls. In contrast, only cVCAM-1, and not cICAM-1, was increased in patients with SLE. Levels of cICAM-1 and cVCAM-1 were significantly elevated in synovial fluid compared with plasma in paired samples from patients with RA. There was no correlation between levels of cICAM-1 and levels of cVCAM-1, in either plasma or synovial fluid. Whereas levels of cVCAM-1 correlated significantly with the erythrocyte sedimentation rate (ESR) and C-reactive protein level in RA patients and with the ESR in SLE patients, no significant correlations were found between cICAM-1 and either of these indices of disease activity. CONCLUSION: These observations indicate that levels of cICAM-1 and cVCAM-1 reflect separate pathophysiologic processes. Both may be useful markers for the diagnosis and management of patients with rheumatic diseases.
7622193 Interferon-gamma but not granulocyte/macrophage colony-stimulating factor augments proteog 1995 Feb Immunization of BALB/c mice with human cartilage proteoglycan (aggrecan) produces a progressive polyarthritis, similar in many aspects to human rheumatoid arthritis, and autoreactive T cells are necessary for initiation of the disease. To study the immunopathological mechanisms operating in the synovium of arthritic mice, we isolated a proteoglycan (PG)-specific arthritogenic T-cell hybridoma, 5/4E8, and examined the presentation of PG to this T-cell hybridoma by mouse synovial cells and chondrocytes. Both cell types expressed very low levels of major histocompatibility complex (MHC) class II following isolation and culture and were unable to present PG to the hybridoma. However, following stimulation with interferon-gamma (IFN-gamma), both synovial cells and chondrocytes showed a marked increase in MHC class II expression and consequently were able to present PG very effectively. The PG-specific responses of the hybridoma were abrogated by an anti-Ia monoclonal antibody. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the most abundant cytokines in the rheumatoid synovium, had no effect on the antigen-presenting capacity of synovial cells and chondrocytes, either on its own or together with IFN gamma.
1439627 Efficacy of Arthrotec in the treatment of rheumatoid arthritis. 1992 In a double-blind study, 346 patients with active rheumatoid arthritis were randomly assigned to receive Arthrotec, a combination of 50 mg of diclofenac and 200 *g of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 12 weeks. At weeks 4, 8, and 12 of treatment, no clinically significant differences between the two treatment groups were noted on measures of joint tenderness, pain, and swelling or on physicians' and patients' assessments of disease severity.
7757107 Disease distribution of beta 2-glycoprotein I-dependent anticardiolipin antibodies in rheu 1995 Feb We investigated the clinical significance of IgG beta 2-glycoprotein I (GPI)-dependent anticardiolipin antibodies (aCL) in rheumatic diseases. Three hundred and seventeen patients were entered. They consisted of 133 patients with SLE, 60 with RA, 45 with SSc, 37 with PM, 23 with overlap syndrome (overlap), and 19 with unclassified connective tissue disease (UCTD). IgG beta 2-GPI-dependent aCL were examined by ELISA. While IgG beta 2-GPI-dependent aCL were detected in 13% of patients with SLE, these aCL were positive in two patients with SSc, two with overlap and 14 with UCTD. A significant association between IgG beta 2-GPI-dependent aCL and thrombosis was found. Clinical manifestations were studied in 32 patients with secondary APS based on SLE and 14 with primary APS (PAPS). Incidence of malar rash, arthritis, renal disorder, leucopenia, immunological disorders and hypocomplementemia were significantly less frequent in patients with PAPS. IgG beta 2-GPI-dependent aCL were detected in all patients with PAPS and in 34% of secondary APS. This difference was significant. These data suggest that IgG beta 2-dependent aCL are useful for identifying a subset in patients with APS.
8523339 The second course of gold. 1995 Sep OBJECTIVE: To determine the outcomes in patients who receive more than one course of intramuscular gold therapy. METHODS: Gold clinic records of all patients who had received more than one course of gold at the Arthritis Centre, Vancouver, British Columbia were reviewed to extract clinical and laboratory data. RESULTS: Between 1949 and 1992, 1148 patients received injectable gold in the gold clinic of the Arthritis Centre, Vancouver, British Columbia. Forty-two patients received 2 courses and 3 patients 3 courses of gold separated by intervals of greater than 8 months. Twenty-one patients were markedly improved when the first course of gold was discontinued. Twenty of these 21 patients experienced a similar marked improvement from a 2nd course of gold. Three patients who received 3 courses had marked improvement with each course. Only 1 patient who experienced marked improvement with the first course of gold failed to respond to a 2nd course. CONCLUSION: In contrast to the published literature, our experience suggests that the response to the 2nd course of gold is similar to the response to the first in most patients with arthritis.
8560056 [Patient with tricuspid atresia undergoing orthopedic surgery: anesthetic considerations]. 1995 Oct We describe a 52-year-old patient with rheumatoid arthritis, interventricular communication and pulmonary stenosis. After an accidental fall she was scheduled for total hip replacement. The main objective of anesthetic management was to preserve pulmonary blood circulation at arterial pressures that would assure adequate tissue perfusion. Other objectives were to maintain hydration to prevent decreases in hematocrit levels, avoid systemic embolization and allow for antibiotic prophylaxis.
7612222 Immunology of reactive arthritides. 1995 Reactive arthritis (ReA) and Lyme arthritis together comprise a pair of chronic inflammatory diseases of the joints. Although differing in detail, these relatively rare diseases are related in their immunopathology to the much commoner rheumatoid arthritis (RA), for which they serve as both model and control. The trigger for rheumatoid arthritis is unknown, but for these rarer diseases triggering occurs by certain well-defined bacterial infections. Arthritis is an uncommon outcome of these infections, for reasons unknown, and the development of chronic, as distinct from brief, arthritis is even rarer; again, the reasons are unknown. Not only does knowing the trigger greatly assist us in understanding these diseases, so also does knowing the contrasting pattern of Th1 versus Th2 cytokines observed in RA and ReA. ReA and Lyme arthritis are here considered in the wider setting of infections where chronic morbidity arises first from hypersensitivity, and perhaps finally from autoimmunity, such as occurs in some of the major tropical diseases. The immunology of ReA and Lyme disease is surveyed in detail, concentrating on T cells and including an update on the Lyme vaccine(s). Additional sections deal with the enigma of HLA B27, with epidemiological findings relevant to the chronicity of ReA and to the need for enlarged prospective studies of ReA in the setting of a developing country.
8335947 Corticotropin-releasing hormone in synovial fluids and tissues of patients with rheumatoid 1993 Aug 1 Inflammation normally results in enhanced synthesis and secretion of hypothalamic corticotropin-releasing hormone (CRH) which, in turn, exerts antiinflammatory effects by virtue of increased adrenal glucocorticoid production. CRH and CRH binding sites are also expressed in the peripheral nervous and immune systems. Our groups have recently shown that CRH is secreted locally in acute carrageenin-induced inflammation in rats and has predominantly proinflammatory effects. We have also shown that CRH is expressed in the joints of Lewis rats with experimental arthritis. To determine if CRH is present in human inflammatory arthritis, we examined synovial fluids and tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and normal individuals. We found markedly enhanced expression of immunoreactive CRH in situ in synovium from patients, which was significantly greater in RA than in OA (p < 0.01). CRH concentrations were also significantly higher in RA (140 +/- 33 pg/ml, mean +/- SEM; n = 10) than OA (25 +/- 4 pg/ml; n = 6) synovial fluids (p < 0.005). HPLC showed immunoreactive CRH extracted from RA and OA synovial tissues and fluids coeluted with CRH 1-41. CRH mRNA was present in low levels in synovial tissue from patients with RA and, to a lesser extent, OA. In summary, immunoreactive CRH is locally secreted in the synovium of patients with RA and, at lower levels, OA. These data support the view that CRH functions as an autocrine and/or paracrine mediator of inflammation in humans.
7612151 Anti-Fc gamma receptor III autoantibody is associated with soluble receptor in rheumatoid 1995 Apr We sought to detect anti-Fc gamma receptor (Fc gamma R) autoantibodies and soluble Fc gamma R in the serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to correlate these serological abnormalities to the polymorphonuclear cell (PMN) activation state. Paired samples of blood and SF were obtained from 33 RA patients as well as blood from 25 normal adults from SF from 20 non-RA patients. Anti-Fc gamma R autoantibodies were assessed by an enzyme-linked immunosorbent assay (ELISA) using recombinant human Fc gamma R as the substrate. Soluble Fc gamma RIII was determined by an ELISA based on the combination of two monoclonal antibodies (MAb). The mean fluorescence intensity (MFI) of complement receptor 1 (CD35) and 3 (CD11b) and Fc gamma RIII (CD16) was evaluated by flow cytometry on the membrane of PMN. IgM anti-Fc gamma RIII activity was present in seven RA sera and five SF, and IgG in eight RA sera and six SF. The average concentration of soluble Fc gamma RIII was 1.80 +/- 3.50 micrograms/ml in RA patients and 0.33 +/- 0.06 micrograms/ml in normal adults (P < 0.05). This was elevated in the SF of 15 RA, while normal in that of all the non-RA patients. There was an inverse correlation between the CD16 MFI on the PMN and the serum/SF soluble Fc gamma RIII level, whereas the density of CD35 and CD11b was markedly augmented. Anti-Fc gamma RIII activity exists in RA patients, associated with soluble Fc gamma RIII. PMN activation could be due to these autoantibodies and thereby obviate the clearance of immune complexes.
1371889 [The value of biopsy of the accessory labial salivary glands for the diagnosis of amylosis 1992 Diagnosis of amyloidosis depends on the demonstration of amyloid deposits in biopsies using specific stains. Recently, in addition to classical biopsies (kidney, liver, gum, skin, rectal mucosa), labial salivary gland biopsy has been recommended as safe diagnostic method. In our recruitment, it allowed the fortuitous discovery of amyloidosis in three patients suffering from rheumatoid polyarthritis or spondylarthritis. In five other patients (2 cases of familial amyloidosis, 1 dysglobulinemia, 2 primary cardiac amyloidosis), biopsy was performed for systematic search of amyloidosis. In five of these eight cases, a sicca syndrome was associated with the salivary deposits. These deposits were stained with congo red viewed in polarized light and with T thioflavine. Besides, Wright's method allowed to know the AL or AA type of amyloidosis and thus to guide the treatment. On the whole, labial salivary gland biopsy is a highly sensitive method for diagnosis of primary and secondary amyloidosis.