Browse

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

ID PMID Title PublicationDate abstract
8025803 [3 nonidiopathic forms of bronchiolitis obliterans organizing pneumonia]. 1994 May Bronchiolitis obliterans organizing pneumonia is the most serious disease of the bronchioli. An idiopathic form of the disease important for differential diagnosis in incipient forms of pulmonary fibrosis has been reported in the literature, along with other forms associated to drug use, infections, and collagen and localized diseases. We describe 3 patients with bronchiolitis obliterans organizing pneumonia, one associated with rheumatoid arthritis and consumption of gold salts, one with HIV infection and one localized form associated with pulmonary hydatidosis.
8643873 [Vaccination against influenza in patients with rheumatoid arthritis: clinical and antibod 1996 Apr The question whether influenza vaccine could lead to a clinical flare in patients with rheumatoid arthritis (RA), and whether it could induce an effectively protective antibody response to the infection is still much debated. Based on these data, we have performed an open study in 40 patients with RA. Patients were divided into two groups according to their disease activity (those with RA in remission and those with active RA, respectively), and their clinical and serum antibody response was assessed following the vaccine administration in the 1991-92 winter seasons. A group of age and sex matched, healthy controls were also vaccinated. Our results suggest that immunization against influenza does not modify the clinical picture of RA, even though some differences between the two groups mentioned above were noticed. In addition, side-effects or adverse reactions occurred with similar frequency in patients with RA and in the controls; as to the antibody response in patients with RA, in the majority of cases the immune response proved adequate to provide significant protection from the infection.
7933578 [Cytokines and vasculitis]. 1994 Aug Humoral and cellular immune mechanisms are thought to be involved in various forms of vasculitis and glomerulonephritis. Recent clinical and experimental results point to a role of cytokines in ANCA-positive vasculitides. In patients with malignant rheumatoid arthritis (MRA) which is characteristically induced by vasculitis in extra-articular lesions, serum soluble IL-2 receptor level was significantly higher than in rheumatoid arthritis patients without vasculitis. In Wegener's granulomatosis, TNF-alpha, IL-1 beta and IL-2 receptor positive infiltrating cells were observed in the kidneys of these patients, and in these patients, plasma levels of TNF-alpha and soluble IL-2 receptor were markedly increased. These results suggest that in ANCA-positive vasculitis TNF-alpha and IL-1 beta are produced in situ by activated infiltrating mononuclear cells and resident renal cells. In patients with giant cell arteritis and Kawasaki disease, increased levels of leukaemic inhibitory factor (LIF) and TNF-alpha were observed, respectively. These inflammatory cytokines increased in the vascular tissues and circulation may be a result of increased production by infiltrated cells or vascular cells such as endothelial cells or may be a result of endothelial cell lysis.
1282007 The intrinsic migratory capacity of memory T cells contributes to their accumulation in rh 1992 Dec OBJECTIVE: Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites. METHODS: The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed. RESULTS: Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29bright, CD11abright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA-DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2-3-fold increase in migratory capacity over normal and RA PBTL: CONCLUSION: These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin-. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.
8358909 Extensile triradiate approach for complex acetabular reconstruction in total hip arthropla 1993 Sep The triradiate approach as described by Mears has been used for open reduction of complex dual-column acetabular fractures. Mears extended the anterior limb of this incision to the symphysis pubis by the ilioinguinal approach. From a consecutive series of 43 total hip revisions, this approach was used successfully in seven cases in which extensile exposure was necessary to revise complicated acetabular reconstructions for arthroplasty. The approach was used also to perform complex acetabular reconstruction after en bloc tumor resection. Three patients had severe intrapelvic component protrusio and anterior column deficiency where close proximity of the prosthesis and femoral neurovascular bundle were detected before surgery. Massive allograft and pelvic reconstructions were used to span large anterior column defects and to stabilize pelvic dehiscence. Complications included one hip dislocation and one posterior flap tip necrosis. Follow-up ranged from six to 34 months. No graft failure has been noted.
1444625 Relative contribution of contact and complement activation to inflammatory reactions in ar 1992 Oct Although both the complement and contact system are thought to contribute to the inflammatory reaction in arthritic joints, only activation of complement has so far been well established, whereas contact activation and its contribution to arthritis has not been systematically explored. Complement and contact activation were assessed in 71 patients with inflammatory arthropathies and 11 with osteoarthritis using sensitive assays for C3a, and C1-inhibitor (C1INH)-kallikrein and C1INH-factor XIIa complexes respectively. Increased plasma concentrations of kallikrein-and factor XIIa-C1INH complexes were found in two and seven of the 71 patients with inflammatory arthropathies, respectively, and in none of the patients with osteoarthritis. Increased synovial fluid concentrations of kallikrein and factor XIIa complexes occurred in 13 and 15 patients with inflammatory joint diseases respectively, and in two patients with osteoarthritis. Contact system parameters did not correlate with clinical symptoms, local activity, or neutrophil activation. In contrast, synovial fluid concentrations of C3a and C1INH-C1 complexes were increased in all patients and in 20 patients with inflammatory arthropathies respectively, and were higher in patients with a higher local activity score. Synovial fluid C3a correlated with parameters of neutrophil activation such as lactoferrin. Increased plasma concentrations of C3a and C1INH-C1 complexes occurred in 13 and 11 patients with inflammatory joint diseases, and in one and two patients with osteoarthritis respectively. Plasma concentrations of C3a correlated with the number of painful joints. Thus contact activation occurs only sporadically in patients with arthritis and contributes little if anything to the local inflammatory reaction and neutrophil activation. These latter events are significantly related to the extent of complement activation.
8187445 Prospidine versus methotrexate pulse in highly active rheumatoid arthritis: a controlled 6 1994 Mar Twenty-seven patients with highly active, refractory rheumatoid arthritis (RA) were treated with the new anti-rheumatic drug prospidine, in view of selecting the optimum pulse regimen and comparing its short-term use with methotrexate (MTX). Prospidine was administered intravenously 500 mg every 3-5 days in the hospital and then monthly. Fifteen patients received MTX (30 mg/week intravenously in hospital and then monthly. Fifteen patients received MTX (30 mg/week intravenously in hospital and then orally 7.5-15 mg/week). The randomisation code was 2:1. We assessed 7 clinical and 4 lab data. The clinical improvement was noticed statistically after 2-4 weeks in 85% prospidine-patients and sustained up to 6 months in 73% (cp. 40% and 57% by the MTX). Only in the prospidine patients were a significant reduction of the mean daily prednisolone dose and the levels of rheumatoid factor and immune complexes observed. Prospidine and MTX had a similar incidence of side effects (39% and 43%), but all drop-outs in prospidine pulse were due to lack of response (26%) and to initial intolerance (4%). Drop-outs in MTX pulse were connected both with drug toxicity (14%) and with lack of response (7%). Alternate prospidine pulse, as highly anti-inflammatory, rapidly acting and well-tolerated regimen, may be used in treating severe forms of RA.
8055207 Fatal cholestatic hepatitis caused by D-penicillamine. 1994 Aug A 37-yr-old woman with RF-positive RA developed cholestatic hepatitis after 10 days of D-penicillamine therapy. This was discontinued immediately. The cholestasis persisted for the remaining 14 months of her life. Severe hypercholesterolemia developed with xanthelasmata and eventually pancytopenia, which was caused by a massive infiltration of the bone marrow by lipid-containing foam cells. The patient died of sepsis. Review of the literature shows intrahepatic cholestasis to be a rare and idiosyncratic complication of D-penicillamine therapy. To our knowledge, ours is the first documented case of persistent cholestatic icterus.
7880185 The total costs of drug therapy for rheumatoid arthritis. A model based on costs of drug, 1995 Mar OBJECTIVE: We created a model to estimate the total medication costs of treating patients with rheumatoid arthritis with 6 second-line agents for the first 6 months of treatment. METHODS: Drug costs were obtained from a survey of pharmacies; monitoring costs were calculated from utilization information obtained in a survey of rheumatologists; toxicity costs were obtained using decision trees to represent the evaluation and treatment of potential toxicities. Monitoring and toxicity costs were estimated using costs from the Boston University Medical Center or, for hospitalizations, using appropriate diagnosis-related group categories. The sum of the 3 components determined the total medication costs. RESULTS: The least expensive medication was penicillamine, at $10.62/week, and the most expensive was injectable gold, at $30.89/week. In terms of monitoring costs, methotrexate had the highest costs associated with necessary laboratory tests and office visits. Hydroxychloroquine had the lowest monitoring costs for office visits, and oral gold had the lowest for laboratory costs. Hematologic toxicities were the largest component of toxicity costs for all 6 medications, and renal toxicities were costly for patients taking oral gold, penicillamine, and injectable gold. Total medication costs revealed oral gold as the least expensive medication and injectable gold as the most expensive. The combination of monitoring and toxicity costs accounted for more than 60% of the total costs for all medications except injectable gold. In all cases, the cost of treating toxicities was the smallest of the 3 components. CONCLUSION: When calculating the costs of drug therapy, it is important to consider not only the price of the drug, but also the costs of monitoring and treating the toxicities that might occur. Failure to do so will result in underestimating the true costs of treatment with these medications.
10136848 Importance of sensitivity to change as a criterion for selecting health status measures. 1992 Jun OBJECTIVE: To assess the sensitivity to change over time of four health status instruments in relation to patients with rheumatoid arthritis. DESIGN: Observational three month study of four self assessed instruments (arthritis impact measurement scales (AIMS), health assessment questionnaire (HAQ), Nottingham health profile (NHP), functional limitations profile (FLP)). SETTING: One rheumatology unit. PATIENTS: 101 patients with definite or classic rheumatoid arthritis. MAIN MEASURES: Change scores for dimensions of instruments, as determined by effect size (mean change in score/baseline standard deviation of variable) and conventional rheumatological measures, at baseline and after three months. RESULTS: Change scores for comparable dimensions (mobility, activities of daily living, household, pain, mood or emotion, and social scales) of the instruments were compared among 30 patients who considered their health status to have improved over three months. For all dimensions of health status the magnitude of change varied considerably according to the instrument. Maximum range in effect size was for social scales (AIMS 0.06, NHP 0.24, FLP 0.60). No single instrument seemed consistently to show the most change over all dimensions. CONCLUSION: Selection of health status instruments for audit or evaluation may have a considerable impact on the pattern of results obtained, and the "responsiveness" of such scales should be as carefully examined as their reliability and acceptability when selecting outcome measures.
1325138 beta-Adrenergic receptor density and function of peripheral blood mononuclear cells are in 1992 Jun An increased density of beta-adrenergic receptors was demonstrated on peripheral blood mononuclear cells (PBMCs) from patients with progressive or relapsing-remitting multiple sclerosis (MS). The same observation was made in patients with chronic active rheumatoid arthritis, but not in those with myasthenia gravis. The affinity of the receptors was within the normal range in all tested groups of patients and there was a positive correlation between density and function as determined by intracellular cyclic AMP production after stimulation with isoproterenol. A putative link between inflammatory process and the functional upregulation of beta-adrenergic receptors on PBMCs was tested by in vitro studies with the soluble mediators interleukin-1 and hydrocortisone. A functional upregulation of beta-adrenergic receptors was observed when PBMCs from normal control subjects were cultured in the presence of either mediator, whereas the already upregulated receptor density on PBMCs from patients with MS remained unchanged. Whether this represents a recovery mechanism to inflammation in MS or a blunting of homeostatic immunoregulatory mechanisms requires further investigation.
7794040 Novel 68 kDa autoantigen detected by rheumatoid arthritis specific antibodies. 1995 May OBJECTIVE: To improve the understanding of the pathogenesis of rheumatoid arthritis (RA) by identifying novel, disease specific autoantibodies. METHODS: Total protein preparations from synovial membranes were separated electrophoretically and immunoblotted. Sera from RA patients were screened for predominant immunoreactions by blotting. A 68 kDa antigen target of the most predominant reaction was detected and further characterised. RESULTS: The dominant immunoreaction in most of the RA sera tested was with a 68 kDa antigen. The antigen is probably ubiquitously expressed. It has an isoelectric point of 5.1, is O-glycosylated, and is located in the endoplasmic reticulum, the cytoplasm, or both. Antibodies to the 68 kDa autoantigen were present in 64% of 167 RA patients tested, and could also be detected in seronegative RA patients, but were present in only 1% of 98 patients with other rheumatic diseases. They could not be detected in 55 healthy controls. CONCLUSIONS: Because of its high sensitivity (64%) and specificity (99%), the anti-68 kDa autoantibody not only provides another valuable parameter for diagnosis, but also represents an antibody that may be involved in the pathological mechanisms leading to RA. This hypothesis can be tested by investigating if 68 kDa specific T cells are present in RA patients.
8469925 Partial biochemical characterization and purification of IgG2b inducing factor as a new cy 1993 Apr Rheumatoid arthritis synovial fluid (RA-SF) contains a novel biological activity, which selectively induces IgG2b antibody production in lipopolysaccharide (LPS)-activated mouse spleen cells in vitro and in vivo. Our previous studies have shown that this activity is not functionally identical to other well-known cytokines and interleukins. In this study we demonstrate the partial purification and biochemical characterization of the IgG2b inducing activity in RA-SF. Biochemical characterization revealed that the IgG2b inducing activity in RA-SF has the following properties: it is a protein, sensitive to pH > 11 and < 4, which is precipitated by 50% of saturated ammonium sulphate and has a molecular weight of 50-70 kDa; it binds to Cibacron-blue and heparin and its activity is not mediated by immunoglobulins or immune complexes, which are present in RA-SF. Biochemical characteristics of the IgG2b inducing activity also differ from other cytokines and interleukins. The term IgG2b inducing factor is proposed for this novel activity.
1629823 High dose intravenous methotrexate for refractory rheumatoid arthritis. 1992 Feb Eight patients with active rheumatoid arthritis were given high dose intravenous methotrexate (MTX) (500 mg/m2) followed by oral leucovorin every 2 weeks for up to 6 months. All patients enrolled had previously failed conventional MTX therapy. Five patients completed 6 months of therapy. Three withdrew early, one due to inefficacy, one due to gastrointestinal intolerance and one due to sciatica requiring hospital admission. Fifty percent or greater improvements were seen in 5 of 8 clinical variables in those patients who completed 6 months of therapy. Six of 8 improvements achieved statistical significance at 24 weeks. Upon discontinuing therapy, patients flared within 8 to 12 weeks. Those who were maintained by low dose MTX after the high dose protocol were able to sustain their improvement throughout the subsequent 6 months of followup.
8137567 Morphological and functional renal effects of long-term low-dose cyclosporin A treatment i 1994 Jan To explore the possible nephrotoxic effects of low-dose cyclosporin A (CyA) treatment, we analyzed the data from 10 patients, aged 35-66 years (mean 51.8 years), who had a clinical diagnosis of rheumatoid arthritis and no known kidney disease. The study protocol included consecutive kidney biopsies and a pretreatment biopsy in all cases. A second biopsy was taken after 5-20 months (mean 17.8 months) of treatment and, in seven patients, a third biopsy was performed after 30-46 months (mean 38.6 months). Evaluation of the kidney biopsies included a semiquantitative estimation of different histological parameters as well as assessment of a chronicity index (CI). Transmission electronmicroscopic examination was performed on all biopsies. There was a significant reduction of glomerular function at the time of both the second (n = 10; p < 0.01) and third (n = 7; p < 0.05) biopsies. Five patients showed an increase in CI on the second biopsy and five on the third biopsy in comparison to pretreatment values. Only one patient showed a progressive increase in CI on three consecutive biopsies. The mean CI increased on both the second (n = 10) and third (n = 7) biopsies compared with baseline, but there was no increase on the third biopsy from the second. The morphological findings were, as a rule, slight or moderate, and focal interstitial fibrosis, tubular atrophy and arteriolar hyalinosis were the most consistent findings. Although even low-dose CyA treatment may be nephrotoxic and may induce morphological alterations in the kidney, such changes do not occur in all patients and may not necessarily be progressive.(ABSTRACT TRUNCATED AT 250 WORDS)
8078923 Divergent T-cell cytokine patterns in inflammatory arthritis. 1994 Aug 30 A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune disease. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon gamma expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic disease by means of inhibitory cytokines.
8059130 [Treatment of refractory rheumatoid arthritis with cyclosporine]. 1994 Mar The efficacy of low-dose cyclosporin-A (CyA) has been clearly demonstrated for rheumatoid arthritis. However, the long-term benefit-risk ratio remains to be investigated in patients with refractory RA. Thirty one patients were included in a prospective open study (24 females, seven males, mean age = 55 years). The mean duration of RA was 11 years and refractory RA was defined by the need of corticosteroid treatment in 26 patients and the previous failure of at least five second line drugs including methotrexate in 27 patients. Initial dosage of CyA was 3 mg/kg/d and could be progressively increased up to 5 mg/kg/d. The mean duration of the study was one year (3-39 months). At 3 months, clinically relevant improvement occurred in 22 patients (71%). Seven were withdrawn due to inefficacy. The main side-effects were hypertension (22 cases) and nephrotoxicity (18 cases) requiring the withdrawal from the study, respectively in one case and in four cases. Raised serum creatinine level had required reduction of the dosage with loss of efficacy in four cases. CyA appears to be an effective therapy for severe treatment refractory RA. Despite a high incidence of side-effects, the efficacy and the monthly management of the patients lead to a good benefit/risk ratio with a percentage of continuation of treatment of 42% at one year.
8036523 Nabumetone: a clinical appraisal. 1994 Apr Nonsteroidal antiinflammatory drugs (NSAIDs) have long been used as therapy for arthritis patients. However, in some patients these drugs can cause gastrointestinal hemorrhage, perforation, or ulcer through direct topical effects, enterohepatic recirculation, and systemic effects. In an effort to address this problem, new NSAIDs have been developed. Nabumetone, which belongs to a new class of NSAID, is a nonacidic agent that has been associated with a low incidence of peptic ulcer. This article examines available clinical data on nabumetone, including studies on gastrointestinal safety and effectiveness in osteoarthritis and rheumatoid arthritis patients, and data that may provide an explanation for nabumetone's low incidence of ulceration.
7712909 [Iatrogenic osteoporsis: six case reports]. 1994 Oct Iatrogenic osteoporosis is a very common secondary osteoporosis is found in patients treated with large dosage of glucocorticosteroid of long duration. Six cases listed in this article including 2 cases of bronchial asthma, 2 cases of bronchial asthma, 2 cases of rheumatoid arthritis, 1 case of skin disease and 1 case of callagenosis (three male patients and three female patients). The age is from 27-46. The duration of treatment of primary disease with glucocorticosteroid is 1 to 3.5 years, with the average of 1.56 years. With the exception of one case treated with Dexamethasone one of 0.75g daily, the other 5 cases are treated with predinisone of 5-30mg daily. After they treated with hormone every other day and added Calcium and vitamin D and followed up 1 year, the mineral contents in the bone of all 6 patients are increased and the biochemistry indexes are improved.
7763235 The role of protein kinase in human synovial fibroblast growth. 1995 May 25 The histological features of rheumatoid arthritis (RA) consist of overgrowth of synovial cells. Several growth factors that cause synovial hyperplasia have been identified in RA synovium. The basic-fibroblast growth factor (b-FGF), representing one of these growth factors, may play an important role in the pathogenesis of RA. We examined the b-FGF-mediated intracellular signal pathway involved in synovial cell growth. b-FGF-induced synovial cell growth was inhibited by protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, but not by H7 that inhibits protein kinase C (PKC). Stimulation of synovial cells with b-FGF resulted in tyrosine phosphorylation of cellular proteins and MAP kinase activation. Our results also demonstrated that b-FGF-mediated activation of MAP kinase was inhibited by herbimycin A indicating that protein tyrosine kinase may be involved in the activation of MAP kinase in human synovial cells. However, inhibition of b-FGF-mediated MAP kinase activation by PKC downregulation did not occur.