Browse

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

ID PMID Title PublicationDate abstract
8456631 Interleukin-1 and naproxen down-regulate the expression of IL-1 receptors in cultured huma 1993 Using affinity binding of [125I]-IL-1 alpha and Scatchard analysis, we demonstrate here that exposure of cultured synovial cells (HRSC) to NPX (10(-4) M) for 96 h decreased the binding of IL-1 by 20 to 35%. This effect results from a down-regulation of the IL-1 receptors without change in the apparent binding affinity (kD: 770 pM). Pretreatment of cultures with IL-1 alpha (500 pg/ml) reduced the total binding of [125I]-IL-1 alpha on HRSC by 65%, indicating that IL-1 decreases the expression of its own receptors.
7744124 Safety profile of etodolac in the elderly population. 1994 A growing proportion of patients who require nonsteroidal anti-inflammatory drug (NSAID) therapy are elderly. Data from patients 65 years and older with osteoarthritis or rheumatoid arthritis show that etodolac is as well tolerated in elderly as in younger patients. Of 273 elderly patients treated with at least 600 mg daily, only 12% withdrew because of adverse events, a rate similar to that in the younger age-group. Notably, the incidence of etodolac-associated gastrointestinal events is no higher in elderly than in younger patients. Etodolac was no different from diclofenac and piroxicam regarding incidence and type of adverse events. In both short- and long-term studies, the 400-mg and 600-mg sustained-release etodolac formulations were well tolerated in elderly and younger patients. Thus, etodolac appears to be a first-line choice in elderly patients.
1374550 Immunohistochemical analysis of synovial membranes from inflammatory and non-inflammatory 1992 Jan Rheumatoid Arthritis (RA) synovial membranes were examined by single and dual immunohistological techniques with a number of monoclonal antibodies against lymphocyte and macrophage related antigens. CD4 positive T lymphocytes frequently expressed MHC Class II antigens and were found in sublining collections in close association with activated macrophages as well as B lymphocytes. CD8 positive T cells surrounded these collections as well as being scattered throughout the membrane and also frequently expressed MHC Class II antigens. IL2 receptor (IL2r) expression on T cells and CD5 expression on B cells were rarely seen in these synovial membranes. Similar immunohistological architecture was found in synovial membranes from patients with psoriatic arthritis (PA) and Reiter's Syndrome (RS). Normal synovium contained few T cells, with few cells expressing MHC Class II antigens. Synovium from osteoarthritis (OA) patients also demonstrated similar immunohistological changes to those found in inflammatory arthritides, suggesting that there are only quantitative rather than qualitative differences between the synovial membrane immunohistological architecture from patients with inflammatory and noninflammatory arthritides.
7979583 Measurement of hand bone mineral content by dual energy x-ray absorptiometry: development 1994 Oct OBJECTIVES--To develop a method of measuring hand bone mineral content (BMC) by dual energy x ray absorptiometry (DXA); to apply this method of measuring hand BMC to normal volunteers to ascertain causes of variability; and to measure hand BMC in patients with rheumatoid arthritis (RA) of varying duration and severity. METHODS--The x ray beam of the Hologic QDR 1000 dual energy x ray absorptiometer was hardened by introducing a perspex-aluminium plate and the analysis software altered to allow for the small tissue bulk of the hand compared with the torso. Ninety five volunteers (46 men age 24-81 and 49 women age 20-83) had scans of both hands. Eight volunteers were assessed repeatedly to establish reproducibility and effect of hand position. Fifty six patients (22 men, 34 women, age range 25-86 years) with RA of differing duration and severity, had hand BMC measurement by DXA. RESULTS--The precision of BMC measurement was 2.3% with no additional variation due to hand position. Hand dominance had no significant effect on BMC. In men, hand BMC correlated with height (r = 0.57, p < 0.0001), weight (r = 0.58, p < 0.0001), forearm span (r = 0.5, p = 0.0006) and hand volume (r = 0.66, p < 0.0001). In women hand BMC correlated with height (r = 0.66, p < 0.0001), weight (r = 0.4, p = 0.003), forearm span (r = 0.3, p = 0.03) and hand volume (r = 0.49, p = 0.0008). After correcting for all these variables, male volunteers had significantly higher hand BMC than female volunteers (p = 0.01) and patients with RA had lower hand BMC than normal volunteers (total hand BMC in male volunteers 90.9 gms, 95% CI 86.9-95, in male patients 81.7 gms, 95% CI 73.7-89.6, p < 0.004, total hand BMC in female volunteers 62.2 gms 95% CI 59.8-64.5, female patients 52.3 gms, 95% CI 48.1-56.5, p < 0.005). In patients with RA, the hand BMC showed an inverse correlation with age (r = -0.44, p = 0.01), disease duration (r = -0.62, p = 0.0003), Larsen's grades (r = -0.62, p = 0.0002) and modified Sharp's method score (r = -0.69, p < 0.0001) in female patients only. CONCLUSIONS--A new, sensitive and reproducible technique of measurement of hand bone mineral content by DXA, has been developed and this method has been applied to normal volunteers and patients with RA. Hand dominance had no significant effect on hand BMC. After correcting for physical size, men have higher hand BMC than women. Hand BMC inversely correlates in women patients with disease duration and other validated methods of assessing radiological outcome in RA. Longitudinal studies are needed to establish its role in monitoring disease progression.
1586246 Antibodies to protein P in systemic lupus erythematosus. 1992 Apr A synthetic peptide was used to develop an enzyme linked immunosorbent assay (ELISA) to detect antibodies to the ribosomal proteins P0, P1, and P2. Significantly increased levels of IgG antibodies to protein P were found in 16% (18/116) of patients with systemic lupus erythematosus but slightly increased levels were detected in 2% (2/98) of patients with rheumatoid arthritis and one normal control subject. No association was observed between the presence of IgG antibodies to protein P and either lupus psychosis or depression. Sequential studies in individual patients failed to show an association between antibody levels and the development of psychosis.
8471159 Free radicals as mediators of tissue injury and disease. 1993 A radical is any molecule that contains one or more unpaired electrons. Radicals are normally generated in many metabolic pathways. Some of these radicals can exist in a free form and subsequently interact with various tissue components resulting in dysfunction. The potential role of oxygen- or xenobiotic-derived free radicals in the pathology of several human diseases has stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. However, because free radical-mediated changes are pervasive and often poorly understood, the question of whether such species are a major cause of tissue injury and human disease remains equivocal. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents. Examples of purported free radical-mediated disorders are discussed in detail to provide insights into the controversy over whether free radicals are important mediators of tissue injury.
1432860 Negative affect and the experience of chronic pain. 1992 Dec Although it is clear from previous research that pain is associated with negative affect, the relative contribution of specific affective dimensions, e.g. depression, anxiety and anger, to the subjective experience of chronic pain is unclear. The literature is also mixed concerning the relative importance of state versus trait influences in the experience of chronic pain. The present study analyzed the ability of anxiety, anger, and depression (as measured by the State-Trait Personality Inventory, State-Trait Anger Expression Inventory, and the Beck Depression Inventory, respectively) to predict self-report of clinical pain as indicated by the McGill Pain Questionnaire (MPQ) in a sample of 60 chronic pain patients. The results of stepwise regression analyses consistently demonstrated that the state measures were more strongly related to MPQ pain ratings than trait measures. These data suggest support for the hypothesis that chronic pain adversely impacts mood rather than the opposing hypothesis that negative mood is a predisposing factor in the development of chronic pain. Furthermore, different aspects of the state emotional experience were found to be related to different components of pain report. The results of this study also suggest that attributional processes could be an important component of the relationship between negative mood and the experience of pain.
7779120 Autoimmune response to the spliceosome. An immunologic link between rheumatoid arthritis, 1995 Jun OBJECTIVE: To assess the significance of autoantibodies to RA33, the A2 protein of the heterogeneous nuclear ribonucleoproteins (hnRNP), and to the related hnRNP proteins A1, B1, and B2 in rheumatic diseases. METHODS: Using a partially purified preparation of hnRNP-A and hnRNP-B proteins, sera from 303 patients with various rheumatic diseases were investigated by immunoblotting. For the analysis of cross-reactivities, autoantibodies were affinity purified by blot elution. RESULTS: Anti-A2/RA33 was found in 35% of rheumatoid arthritis (RA) patients, 38% of mixed connective tissue disease (MCTD) patients, 23% of systemic lupus erythematosus (SLE) patients, and, apart from single exceptions, not in patients with other rheumatic diseases. All anti-A2/RA33-positive sera were also reactive with B1 and B2, and anti-A2/RA33 antibodies cross-reacted with both proteins. Antibodies to hnRNP-A1 were found less frequently; moreover, the majority of anti-A1-positive sera also contained anti-A2/RA33 antibodies. In anti-A1, anti-A2/RA33 double-positive sera, cross-reactivity between the 2 antibodies was generally observed. In SLE patients, the presence of anti-A2/RA33 was correlated with the presence of anti-(U1) small nuclear RNP (snRNP) and anti-Sm (P < 0.0001 and P < 0.005, respectively), but there was no evidence for cross-reactivity between antibodies to hnRNP and antibodies to snRNP antigens. CONCLUSION: Since both hnRNPs and snRNPs are essential components of the spliceosome, the data show that the immune systems of patients with RA, SLE, and MCTD react to this functional complex. However, compared with MCTD and SLE patients, RA patients have a more restricted immune response to the spliceosome: they react to hnRNP proteins, particularly to hnRNP-A2/RA33, but not to snRNPs.
8035394 A double blind study comparing the efficacy and safety of enteric coated naproxen to napro 1994 Apr OBJECTIVE: To compare efficacy and gastrointestinal (GI) tolerability of a new enteric coated formulation of naproxen (NAP-EC) with standard immediate release naproxen (NAP-STD). METHODS: One hundred seventy-nine patients with osteoarthritis (OA) and one hundred seventy-six patients with rheumatoid arthritis (RA) at high risk for developing GI side effects to nonsteroidal antiinflammatory drug (NSAID) therapy were enrolled in a double blind, parallel, multicenter study. All patients had either discontinued as NSAID during the previous one year or required cotreatment with antiulcer drugs for control of GI complaints related to NSAID use. The treatments were evenly divided in both diagnostic cohorts. RESULTS: Except for minor differences in alcohol consumption, baseline characteristics of patients in both treatment groups were statistically similar. Both naproxen formulations were highly efficacious by all variables of disease activity when changes were measured from baseline. No statistically significant between formulation difference was found in the primary efficacy variable, overall disease activity. Overall, between formulation differences in efficacy measures were few, though most favored NAP-STD. GI complaints were reduced by 15% (51% NAP-EC vs 60% NAP-STD, p = 0.077) and GI complaints thought to be drug related were reduced by 36% (16% NAP-EC vs 25% NAP-STD, p = 0.024). Withdrawals due to GI complaints were reduced by 37% in the NAP-EC group (12% NAP-EC vs 19% NAP-STD, p = 0.054), and withdrawals due to GI complaints judged to be drug related were reduced by 55% in the NAP-EC group (6% NAP-EC vs 12% NAP-STD, p = 0.025). CONCLUSION: Enteric coated naproxen is an effective treatment for OA and RA. All observed differences in GI tolerability favor NAP-EC over NAP-STD.
8727677 A trace element preparation containing zinc increases the production of interleukin-6 in h 1996 Mar The in vitro effects of a trace element preparation (béres Drops Plus, BDP) on the biosynthesis of inflammatory cytokines interleukin (IL-6, IL-1, and tumor necrosis factor-alpha (TNF-alpha) were studied in human peripheral monocytes. The production of IL-6 was studied in a glioblastoma cell line, SKMG-4, as well. The trace element preparation BDP significantly stimulated both the constitutive and the endotoxin or IL-1 induced IL-6 production in monocytes or in glial cells, respectively, but revealed no or only modest effect on IL-1 and TNF-alpha production of monocytes. Moreover, BDP was able to reduce the inhibitory effect of a synthetic corticosteroid, dexamethasone on the biosynthesis of IL-6. The positive effect of the trace element preparation on the IL-6 production of monocytes from rheumatoid arthritis (RA) patients is comparable, to that of on the monocytes from healthy individuals, and similarly to healthy individuals was negligible on the IL-1 and TNF-alpha production. The detailed analysis of the composition of the preparation suggested, that the major active component in the stimulation of IL-6 production is Zn, but for the complete effect other trace elements are also required.
7560066 Transfer of rheumatoid arthritis into severe combined immunodeficient mice. The pathogenet 1995 Oct To investigate the pathogenicity of T cells infiltrating in the rheumatoid joints, mononuclear cells (MNC), predominantly T cells, isolated from either synovial fluid or synovial tissues of the patients with RA were transferred into severe combined immunodeficient (SCID) mice by intraarticular injections. According to our observations in this experimental system, patients with RA could be classified into at least two groups. In one group of patients, the infiltrating MNC induced synovial hyperplasia in the recipient SCID mice (the positive group). Whereas, in the other group no synovial hyperplasia was observed (the negative group). The induction of synovial hyperplasia observed in the positive group was prevented by an anti-human CD3 antibody (OKT3), indicating T cell mediation. Analysis of T cell receptor (TCR) V beta usage by reverse transcriptase polymerase chain reaction in the infiltrating MNC transferred into SCID mice revealed a marked skew towards the preferential use of certain V beta genes, which was not seen in the peripheral blood MNC, in only the positive group. The patterns of TCR/V beta skew were not uniform among the patients. The analysis of the PCR-amplified genes of such skewed TCR/ V beta by single strand conformational polymorphism showed distinct bands, indicating that the T cell populations expanding in rheumatoid joints of the positive group were oligoclonal. Furthermore, the enrichment of the T cell populations expressing such skewed TCR/V beta by in vitro stimulation of peripheral blood MNC of the patients with the relevant superantigen enabled the induction of synovial hyperplasia in the SCID mice. These results suggest that the pathogenic T cells could be activated locally in rheumatoid joints by certain antigens in some, but not in all patients with RA.
7488279 CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intrav 1995 Nov OBJECTIVE: To evaluate the biologic response, tolerability, and potential clinical effect of a humanized antilymphocyte monoclonal antibody, CAMPATH-1H, in patients with rheumatoid arthritis (RA). METHODS: Forty adult patients with active, refractory RA were treated with CAMPATH-1H, given intravenously, in a multicenter, open, single-dose-escalation study. Patients were assigned to dose groups of 1, 3, 10, 30, 60, and 100 mg CAMPATH-1H. RESULTS: There was a profound, immediate, and sustained reduction of the peripheral lymphocyte count; the most susceptible were the levels of CD4+ and CD8+ cells, which remained depressed during the study period. Sixty-three percent of patients developed antibodies to CAMPATH-1H. Side effects occurred frequently throughout the first 24 hours following infusion, and included fever, headache, nausea, vomiting, and hypotension. All of the immediate drug toxicities resolved within the initial 24-hour postdosing period. One patient developed a reactivation of Mycobacterium xenopi infection 10 weeks following infusion. Sixty-five percent of patients developed a clinical response; the mean duration of response was 2 weeks. CONCLUSION: CAMPATH-1H is a lymphocyte-depleting antibody that is biologically potent even after single-dose therapy. There was no correlation between biologic effect and clinical response. Sustained lymphocyte suppression was observed. Acute infusion toxicities were observed in most patients. The role of depleting monoclonal antibodies in the treatment of RA should be reevaluated.
1731326 Perforin and granzyme A expression identifying cytolytic lymphocytes in rheumatoid arthrit 1992 Jan 15 Lymphocytes from the synovial fluid of patients with rheumatoid arthritis were examined for the expression of granzyme A and perforin. Previous studies have demonstrated that the expression of these proteins, which are implicated as mediators of cytotoxicity, can be used to identify putative cytolytic lymphocytes in vivo. Twenty-two synovial fluid samples were analyzed by in situ hybridization and immunohistochemistry. In six patients receiving low doses of immunosuppressant, a population of granzyme A- and perforin-expressing lymphocytes could be identified. In contrast, lymphocytes from patients who were receiving high doses of immunosuppressant did not contain any granzyme A- or perforin-expressing lymphocytes. Synovial fluid lymphocytes from patients with osteoarthritis did not express either marker. The expression of these markers demonstrates the presence of potentially functional cytolytic lymphocytes, expressing proteins required to mediate killing, in the synovial fluid of patients with rheumatoid arthritis. This suggests that cytolytic lymphocytes may be involved in the pathogenesis of rheumatoid arthritis.
8062894 Peripheral blood mononuclear cells from patients with rheumatoid arthritis suppress erythr 1994 Jul Anemia is a frequent manifestation of rheumatoid arthritis, with a probably multifactorial etiology. We investigated the effect of peripheral blood mononuclear cell supernatants (PBMCS) from rheumatoid arthritis (RA) patients on hematopoietic colony formation in vitro, by using a methylcellulose assay. PBMCS from patients suppress in vitro erythroid (BFU-E), mixed-lineage (CFU-GEMM) and to a lesser degree granulocyte-macrophage (CFU-GM) progenitors. PBMCS from anemic RA patients were more suppressive for BFU-E than those from non-anemic patients. Addition of antibodies to tumor-necrosis factor alpha (TNF alpha) almost completely reversed the inhibition of BFU-E and CFU-GEMM, but had little effect on the CFU-GM colony formation. Antibodies to interferon-gamma (IFN gamma) and interleukin-1 (IL-1) were not effective. The above data suggest that PBMCS from RA patients suppress in vitro erythropoiesis via the production of TNF alpha; a pathogenetic role for TNF alpha in the anemia of RA can be implied.
1439621 The safety of Arthrotec in patients with rheumatoid arthritis or osteoarthritis: an assess 1992 Two double-blind comparative studies were conducted to determine the upper gastrointestinal safety of Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol versus 50 mg of diclofenac. In one study, rheumatoid arthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 12 weeks. Endoscopy was performed before and after treatment. At the termination of treatment, among the 290 patients with rheumatoid arthritis, gastroduodenal ulcers were found in 4% of the Arthrotec-treated patients and in 11% of the diclofenac-treated patients (P = 0.034). In the second study, osteoarthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 4 weeks. Endoscopy was performed before and after treatment. Among the 329 patients with osteoarthritis, gastroduodenal ulcers were found in none of the Arthrotec patients and in 4% of the diclofenac patients (P = 0.015).
8755766 Arteriovenous fistula as a complication of C1-2 transarticular screw fixation. Case report 1996 Aug A case is reported of a vertebral artery-to-epidural venous plexus fistula as a complication of posterior atlantoaxial facet screw fixation. The use of transarticular screws to stabilize the C1-2 joint has become an increasingly popular fixation technique, most notably for atlantoaxial instability due to trauma or rheumatoid disease. Despite the fact that this approach is technically challenging, there have been few reports of complications associated with C1-2 transarticular fixation. Although damage to the vertebral artery is a documented hazard of transarticular fixation at this level, a symptomatic arteriovenous fistula resulting from the procedure has not been described previously. The etiology, presentation, and treatment of this unusual complication are discussed.
8427510 Cartilage degradation by polymorphonuclear leucocytes: in vitro assessment of the pathogen 1993 Jan Polymorphonuclear leucocytes (PMNs), which predominate in inflammatory synovial fluid, can degrade cartilage. This was measured by a novel in vitro model; PMNs were incubated for up to one hour with 2 or 3 microns sections of cartilage and the glycosaminoglycan loss determined by microdensitometry after alcian blue staining. Glycosaminoglycan loss could be as a result of damage from reactive oxygen species, proteolytic enzymes, or a combination of the two. The relative contributions of these mechanisms were evaluated using selective inhibitors. The results show that activated PMNs will degrade cartilage and that this degradation is due to proteolytic enzymes and not reactive oxygen species. There is a specificity involving elastase but not other serine proteases. It is suggested that enzyme inhibition may play a part in reducing PMN mediated cartilage damage.
1444624 Exercise induced release of von Willebrand factor: evidence for hypoxic reperfusion microv 1992 Oct Experimental evidence suggests that rheumatoid synovitis may be perpetuated by the generation of reactive oxygen species during hypoxic reperfusion injury. The latter occurs because increased intra-articular pressure during exercise exceeds synovial capillary perfusion pressure, impairing blood flow. The object of this study was to establish a marker for and the mechanism of synovial hypoxic reperfusion injury. Von Willebrand factor (vWF) is only released from endothelial cells and platelets and is an in vivo and in vitro marker of endothelial injury. In vivo exercise induced changes in plasma vWF were therefore investigated in patients with rheumatoid arthritis (RA) compared with controls and in vitro vWF release by human umbilical vein endothelial cells subjected to hypoxia reperfusion. Pre-exercise plasma vWF levels were 1001 and 817 IU/l, increasing after exercise to 1658 and 845 IU/l in patients with RA and controls respectively. Von Willebrand factor release from human umbilical vein endothelial cells followed a biphasic pattern, occurring during both hypoxia and reperfusion. Hypoxia reperfusion induced vWF release by human umbilical vein endothelial cells in vitro suggests that exercise induced vWF release in patients with RA is best explained by synovial hypoxic reperfusion injury. This study supports evidence that generation of reactive oxygen species plays a principal part in synovial hypoxic reperfusion injury and suggests vWF as a useful marker of this phenomenon.
8849354 Risk factors for septic arthritis in patients with joint disease. A prospective study. 1995 Dec OBJECTIVE: To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention. METHODS: The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-month intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis. RESULTS: There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age > or = 80 years (odds ratio [OR] = 3.5, 95% confidence interval [95% CI] 1.4-8.6), diabetes mellitus (OR = 3.3, 95% CI 1.1-10.1), rheumatoid arthritis (OR = 4.0, 95% CI 1.9-8.3), hip and/or knee prosthesis (OR = 15, 95% CI 4.1-54.3), joint surgery (OR = 5.1, 95% CI 2.2-11.9), and skin infection (OR = 27.2, 95% CI 7.6-97.1). CONCLUSION: These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection.
8153077 [Pathology of rheumatoid lung]. 1994 Feb In the framework of rheumatic illnesses, the lungs and pleura are often observed to be involved. Dependent on the basic illness in question, conditions of the bronchoalveolar system, vessels, lymphatic system, and pleura that have developed differently inter- and intra-individually can be diagnosed in topo-regionally variable forms and combinations. In the causal pathogenesis, the initial (auto-) immunological alteration of the alveolar septa plays a role. When the monocytes, macrophages, and fibroblasts are activated, as a result of a chronic inflammatory process there is increasing reparative proliferation, which finally leads to the non-specific end stage of irreversible interstitial fibrosis. The incidence and manifestation forms of lung changes show certain differences dependent on the underlying illness (e.g., rheumatoid arthritis, systemic lupus erythematosus, progressive systemic scleroderma, dermatomyositis and polymyositis, Sjögren syndrome, and mixed connective tissue disease). In addition to vasculitis and granulomatosis of the lung, therapy-induced lung changes must also be considered in the differential diagnosis since almost all basic therapeutic agents can cause this type of lung condition. Good knowledge of the parameters from the viewpoint of possible therapeutic measures is indispensable, as is close cooperation between the treating physician and the pathologist.