Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7818569 | Validity and reliability of the twenty-eight-joint count for the assessment of rheumatoid | 1995 Jan | OBJECTIVE: To investigate the validity of the 28-joint count for assessment of joint involvement in patients with rheumatoid arthritis (RA). METHODS: Joint involvement as determined by the 28- and the 66/68-joint count was compared using data from 735 prospectively studied RA patients. RESULTS: The joints included in the 28-joint count were more commonly involved than other joints, and findings from the 28-joint count correlated highly with those from the 66/68-joint count in all analyses. CONCLUSION: The 28-joint count is a reliable and valid measure for joint assessment. It is easier to perform than the 66/68-joint count, and it addresses the joints that are critically involved. | |
| 8111299 | [The immunopharmacodynamics of mival]. | 1993 Nov | The authors studied in vitro the immunopharmacodynamics of the new silantrane mival. It was shown that mival possessed mitogenic effects on mononuclear cell proliferation in donors and patients with rheumatoid arthritis. The drug stimulated mononuclear cell proliferation, by acting selectively on T lymphocytes, enhancing T-cell growth lymphokine production, T-suppressor cell activity, and inhibiting prostaglandin E2 production. | |
| 7983637 | Seronegative and weakly seropositive rheumatoid arthritis differ from clearly seropositive | 1994 Aug | OBJECTIVE: To study the role of HLA class II genes in conferring susceptibility to seronegative vs seropositive rheumatoid arthritis (RA). METHODS: The distribution of DRB1 and DPB1 alleles in 33 seronegative, 20 weakly seropositive, 79 distinctly seropositive patients with RA, and in 181 healthy controls was determined by genomic typing: IgM rheumatoid factor (RF) seronegativity was ascertained in Waalers' latex, and ELISA tests. RESULTS: DRB1*0101/2 (encoding variants of DR1) was associated with weakly seropositive RA (and possibly seronegative RA) but not the clearly seropositive disease. In contrast DRB1*0401 and DRB1*0408 (encoding the Dw4 and Dw14.2 variants of DR4, respectively) were associated with clearly seropositive RA but were not increased among patients having weakly seropositive or seronegative RA. DRB1*0404 (encoding the Dw14.1 variant of DR4) was increased to some extent in all examined RA subsets. The distribution of DPB1 alleles in the patients was as in the controls. CONCLUSION: Seronegative and weakly seropositive RA differ from clearly seropositive RA in HLA class II associations. | |
| 8853170 | Circulating intercellular adhesion molecule 1 in rheumatoid arthritis--relationship to sys | 1996 Jul | Intercellular adhesion molecule-1 (ICAM-1) is a membrane bound molecule that plays an important role in the pathogenic inflammatory responses observed in vasculitis. The aim of this study was to determine whether levels of soluble ICAM-1 sICAM-1) shedding into the circulation reflect the vascular injury found in nailfold capillaroscopy as well as systemic vasculitis in RA patients. We determined serum levels of sICAM-1 and soluble interleukin-2 receptor (sIL-2R) by an enzyme-linked immunosorbent assay in 79 RA patients. Serum levels of sICAM-1 were significantly increased in RA patients compared to 30 healthy controls. RA patients with clinical signs of systemic vasculitis showed significantly higher levels of sICAM-1 than those without vascular involvement. Although no significant correlation between sICAM-1 levels and the capillaroscopy findings were found, 75% of the patients with severe vascular changes in capillaroscopy exceeded normal sICAM-1 cut off value. Serum sICAM-1 concentrations correlated significantly with the erythrocyte sedimentation rate and serum sIL-2R, but not with the duration of RA, radiological stages, Ritchie index, age or type of treatment. These findings suggest that increased levels of sICAM-1 in serum of RA patients reflect systemic vascular involvement rather than a local vascular injury. | |
| 8023585 | [Therapy with oral type II collagen as a new possibility of selective immunosuppression in | 1994 Mar | Suppressor T cells in the mucosa of the gut are activated by absorbed antigen in order to avoid a systemic immune response to this antigen. This long known phenomenon of oral tolerance is now used in the treatment of rheumatoid arthritis with oral collagen type II which is the most important protein of cartilage. Although the role of collagen II in initiating and maintaining the immune response in the joint is not clear, these suppressor CD8+T cells can be stimulated in a trigger-specific and effector-nonspecific way by contact with collagen II in the joint. It is assumed that a local immunosuppression then takes place through the secretion of inhibitory cytokines, mainly TGF beta. Clinical studies in the treatment of rheumatoid arthritis are presently being conducted in Boston and Berlin. | |
| 8723576 | Epoetin alfa for autologous blood donation in patients with rheumatoid arthritis and conco | 1996 Apr | In patients scheduled for major orthopedic surgery, the presence of anemia can preclude the donation of sufficient autologous blood (AB) to meet transfusion requirements. Although a number of studies have investigated the use of epoetin alfa (in conjunction with parenteral iron supplementation) to facilitate AB donation and reduce exposure to allogeneic blood in this patient population, the optimum treatment regimen and route of administration has yet to be defined. In rheumatoid arthritis (RA) patients with a low predonation hematocrit (Hct; < or = 39%), intravenous (i.v.) treatment with epoetin alfa 300 IU/kg twice weekly for 3 weeks was the optimum dosage for facilitation of AB donation and minimization of the decrease in Hct prior to elective orthopedic surgery. However, the subcutaneous (s.c.) route of epoetin alfa administration may allow lower dosages of epoetin alfa to be used. Indeed, epoetin alfa 100 IU/kg s.c. twice weekly for 3 weeks (in conjunction with a single i.v. bolus of 200 IU/ kg at the first s.c. dose) was as effective as 300 IU/kg i.v. administered according to the same schedule. The number of AB units collected, total red blood cell (RBC) volume donated, and peak proportion of reticulocytes were similar regardless of the route of administration. Both treatment groups were associated with a significant reduction in allogeneic blood exposure compared with historical controls. Findings consistent to all of these studies were that epoetin alfa was well tolerated, and that i.v. iron supplementation was necessary to maximize its beneficial effects. | |
| 7960505 | Elastase- and plasmin-mediated fibrinolysis in rheumatoid arthritis. | 1994 | Selected coagulation and fibrinolytic factors were evaluated in plasma and synovial fluid (SF) of 10 rheumatoid arthritis (RA) patients. Increased levels of fibrinogen were observed in plasma (p < 0.01), but only a trace amount of structurally intact fibrinogen was detected in the SF of RA patients, while immunostaining showed deposits of insoluble fibrin in their synovial membranes. Reduced levels of protein C, antithrombin III and coagulation factors II, V, VII, VIII, IX, XII and XIII (p < 0.01), and high levels of thrombin-antithrombin III (TAT) complexes (p < 0.01), were found in SF as compared to their corresponding plasma levels. The increased levels of fibrinogen, TAT complexes, B beta 15-42 peptide and plasminogen activator inhibitor-1 (PAI-1) in plasma (p < 0.01) are consistent with an enhanced fibrin turnover and endothelial perturbation due to a systemic inflammatory state. Plasminogen and alpha 2-plasmin inhibitor activity in SF were significantly reduced as compared to the plasma levels (p < 0.01), whereas an increase in PAI-1 activity was found in SF as compared to plasma (p < 0.01). The detection of D-dimer and B beta 15-42 peptide (p < 0.01) in SF suggests an involvement of plasmin in the degradation of fibrin generated in synovial tissue. The high levels of elastase-alpha 1-proteinase inhibitor complexes and of thrombin-increasable fibrinopeptide A, as well as the pattern of fibrinogen degradation as identified in SF by double-dimension immunoelectrophoresis, suggest that elastase released from exudated granulocytes may play an important role in fibrino(geno)lysis and tissue damage in RA joints. | |
| 7921750 | Prediction of severe rheumatoid arthritis using Epstein-Barr virus. | 1994 Oct | One of the immunological abnormalities in patients with RA is increased synthesis of immunoglobulins (Ig) in cultures of Epstein-Barr virus (EBV-) stimulated lymphocytes. We set out to investigate whether this feature, seen early in the disease, associated with later severe RA. We studied prospectively 45 patients with recent onset RA and, 41 healthy individuals. From 0-6 months after admission, blood lymphocytes were cultured in the presence of EBV for 4 weeks and Ig in the supernatants were assayed. To assess the severity of disease, clinical, laboratory and radiological evaluations were performed every 6 months for 2 yr. The association of increased Ig production with the severity of RA was then analysed. During the follow-up period, 30 of the original 45 patients developed erosive disease. At onset, these 30 patients did not differ from the 15 with non-erosive disease when assessed by several parameters reflecting rheumatoid activity. However, EBV-induced production of Ig was significantly higher in the erosive compared with the non-erosive group of patients (P < 0.001). Using Ig synthesis, it was possible to identify a subgroup of 9-14 patients, depending on the isotype studied, who would later develop severe erosive disease (PVpos = 90-100%). These results show that high EBV-induced production of Ig early in RA associates with later severe disease, particularly with joint erosions. This feature identifies, with over 90% likelihood, the third of patients who will later develop most severe disease. | |
| 1465171 | [An outbreak of mostly extrapulmonary tuberculosis in a family practice]. | 1992 Dec 12 | An outbreak of mainly extrapulmonary tuberculosis (TB) in a group of about 550 patients with rheumatoid arthritis (RA) is described. These patients had been attending the practice of a former general practitioner who treated cases of rheumatoid arthritis with phenylbutazone and steroids. The number of diagnosed TB cases was 55. Six cases had a contagious lung localisation. The possible sources of the outbreak were analysed. Both a visit on a same day as a sputum positive patient (chi 2-trend: 20.4; p < 0.001) and the administration of steroids (odds ratio (OR): 36.2; 95% confidence interval (CI): 8.8-313) were independent risk factors. There also appeared to be a relationship between TB and RA (OR: 4.4; 95%-BI: 2.2-9.1). Exogenous re(infection) and endogenous reactivation are possible causes of this outbreak. | |
| 8493580 | [Clinical study of rheumatoid interstitial lung disease evaluated by high resolution CT]. | 1993 Feb | High resolution computed tomographic (HRCT) scans were obtained in 215 patients with rheumatoid arthritis to assess pulmonary fibrosis (PF). We classified the HRCT appearances as five-point scale (0-4) based on the degrees of PF. The results were as follows: 1. We found 117 cases (54.4%) of PF on HRCT. 2. Patients with PF (grade 1-4) showed significantly increased leucocyte cell counts and significantly worsened pulmonary function test than patients without PF (grade 0). 3. Patients with advanced articular involvement had significantly higher prevalence of PF than others without them. 4. Patients who were previously or currently receiving gold sodium thiomalate (GST) injection or administration of methotrexate had higher prevalence of PF than others. However, patients who were receiving long term GST therapy (1 year long or sigma 1000 mg) had slightly lower prevalence of PF than others. This finding suggests that dose-dependent lung injury is not related to GST therapy. 5. Patients with advanced PF (grade 3, 4) had high prevalence of male sex, smoker, extraarticular manifestation. | |
| 7697146 | Surgical correction of rheumatoid forefoot deformities. | 1995 Jan | Surgical correction of severe rheumatoid forefoot deformities with resection arthroplasties of the lesser metatarsal phalangeal joints and arthrodesis of the first metatarsal phalangeal joint resulted in a significant long-term improvement with respect to shoe wear, pain, and the ability to stand and walk in 95% of the patients. Ninety percent had a good or excellent functional result. There was minimal recurrence of deformity. Modifications of the procedure with maintenance of the proximal phalangeal bases and K-wire fixation of the metatarsal phalangeal arthroplasty and interphalangeal joints resulted in an improved cosmetic result and simplified postoperative management with an equal functional result and no increase in recurrence of deformity or complications. | |
| 8039286 | HLA-DPB1 alleles in patients with rheumatoid arthritis. | 1994 Mar | The distribution of HLA-DPB1 alleles was studied in 94 adult Caucasian RA patients (65 = seropositive, 29 = seronegative) and 40 normal controls. The DPB1 alleles were defined by oligonucleotide typing of polymerase chain (PCR)-amplified genomic DNA. The prevalence of the DPB1*0402 allele was higher in seropositive RA patients and DPB1*0201 was higher in seronegative RA patients. These differences were not significant, however. It is likely that DPB1 alleles do not play an important role in susceptibility to RA. | |
| 1327603 | Detection of the Epstein Barr viral genome by an in situ hybridization method in salivary | 1992 Jul | Sections of formalin-fixed paraffin-embedded minor labial salivary glands from 23 patients with Sjögren's syndrome associated with rheumatoid arthritis (secondary Sjögren's syndrome: sSS) and from 11 patients with keratoconjunctivitis sicca (KCS) associated with rheumatoid arthritis but without proven SS were examined by in situ hybridization using the BamH1 V (W) fragment of Epstein Barr viral (EBV) DNA. Minor labial salivary glands from 7 healthy individuals were used as the control. EBV specific DNA sequences were detected in the nuclei of epithelial cells in 16 out of 23 cases with sSS and in 3 out of 11 patients with KCS. None of the 7 salivary gland biopsies from the control group showed a positive hybridization signal. Epithelial cells containing the EBV genome were more frequently detected in areas with tissue destruction and lymphoepithelial lesions. Our results provide evidence for an increased EBV infection load in patients with sSS in comparison with control subjects and suggest that this virus may play a role in the pathogenesis of sSS. | |
| 8597339 | Some nutritional parameters in patients with rheumatoid arthritis. | 1995 | Its was our aim to appreciate the respective influence of age, sex, duration of disease, inflammatory status and treatment on protein markers in patients with rheumatoid arthritis (RA). Serum albumin (SA), thyroxin-binding prealbumin (TBPA), transferrin and retinol-binding protein (RBP) were determined in 155 RA patients. Since the cut off, levels of these proteins are highly dependent on sex and age, several groups of sex- and age-matched normal controls were evaluated. The levels of SA (p < 0.03) and RBP (p < 0.002) were reduced in the women under 45 years of age. SA and RBP reached a nadir following one year of evolution. There were inverse correlations between SA and Lee's index (p < 0.01) and TBPA and Lee's (p < 0.05) and Ritchie's index (p < 0.01). Sa correlated inversely with the inflammatory status. The complex challenge of nutritional evaluation in RA patients is thus impossible to adequately portray and results should be interpreted with caution. | |
| 8977961 | Influence of the HLA-DRB1 locus on susceptibility and severity in rheumatoid arthritis. | 1996 Nov | We examined HLA-DR genotype risk in 288 patients with rheumatoid arthritis who were carefully categorized for disease severity. Five hundred ethnically-matched bone-marrow donors were controls. A hierarchy of positive allelic associations was noted with DRB1*0401 (p < 10(-38), *0404,8 (p < 10(-43), *0405 (p < 10(-8), *10 (p < 10(-3) and *0101,2 (p < 10(-2), while DRB1*0403 was negatively associated (p = 0.02). The DRB1 genotype relative risks (and 95% CIs) for RA were: *0404,5,8/*0404,5,8 = 36.2 (15-87), *0401/*0404,5,8 = 31.3 (18-55), *401/*0401 = 18.8 (11-35), *0101,2/*0404,5,8 = 6.0 (2-14), *0101,2/*0401 = 6.4 (3-12), *0101,2/*0101,2 = 1.3 (0.3-6), *10/*0404,5,8 = 27.8 (5-148), *10/*0401 = 20.8 (5-89), *10/*0101,2 = 22.3 (5-96), *0404,5,8/DRX = 5.0 (3-8), *0401/DRX = 4.7 (3-7), *0101,2/DRX = 2.3 (1.4-4), *10/DRX = 3.4 (0.8-14). No significant correlation of DRB1 genotypes was found with severity of RA as judged by nodules or articular erosions. | |
| 7923867 | Retroviruses and autoimmune rheumatic diseases. | 1994 Oct | In autoimmune rheumatic diseases, retroviruses have been repeatedly discussed as important etiologic factors. However, despite a considerable amount of indirect evidence that retroviruses might indeed be involved in triggering or perpetuating autoimmune rheumatic diseases, clear cut direct evidence is still missing. Studies on arthropathies associated with HIV-1 or HTLV-1 infection as well as new experimental animal models like the Tax transgene mice and new data from the MLR/lpr mouse model might help to answer the questions how and by what mechanisms retroviral infection may lead to autoimmune rheumatic diseases. From data obtained in the MLR/lpr mouse it seems obvious that a potential link of retroviruses, apoptosis and autogenes to autoimmune diseases opens exciting new approaches to the study of rheumatic disease pathogenesis. | |
| 8372725 | Toxicity of antimalarial drugs in rheumatoid arthritis. | 1993 | Antimalarials have the lowest incidence of toxicity among the disease modifying antirheumatic drugs (DMARDs). Low daily dose and regular ophthalmologic examination has minimised potential retinopathy. Some toxicity may be related to the lysosomotropic action of antimalarials. DMARD toxicity may affect the variability in response to antirheumatic drugs. | |
| 8646433 | Endogenous opioid tone in patients with rheumatoid arthritis. | 1996 May | We have previously shown that there is deficient hypothalamic-pituitary-adrenal (HPA) responsiveness in rheumatoid arthritis (RA) patients. The basis for this deficient response is not known. The purpose of the project was to investigate whether the defective HPA response in RA patients is the result of increased endogenous opioid tone secondary to chronic pain which can suppress corticotrophin-releasing hormone (CRH) production. We conducted a double-blind placebo-controlled cross-over trial to study the effect of the opiate antagonist, naloxone, on psychometric function together with plasma adrenocorticotrophic hormone (ACTH), cortisol and prolactin. Seven RA patients with active and established disease and eight healthy controls were studied. Each received either a bolus i.v. infusion of 20 mg naloxone or normal saline. After at least 72 h, they received naloxone if they had previously received normal saline or vice versa. The pain score was statistically significantly higher at baseline in the RA group compared with controls (5.7 +/- 3.25 vs 0.35 +/- 0.21, P < 0.001). No difference was found in the other psychometric assessments throughout the study. Patients receiving normal saline did not show any significant change in cortisol or ACTH. Cortisol and ACTH showed a sharp and significant rise after naloxone treatment in both RA and normal subjects (P < 0.001 and P < 0.01), but no difference was observed between the two groups. The mean prolactin level showed no significant change in both groups after any treatment. We conclude that endogenous opioid tone does not appear to be a major contributor to the HPA defect in RA. However, the number of patients studied was small and this result will require confirmation from larger trials. | |
| 8535644 | Practical clinical pharmacology and drug interactions of low-dose methotrexate therapy in | 1995 Nov | The clinical pharmacology and clinically important drug interactions of methotrexate (MTX) are reviewed. The points discussed are as follows. (a) The bioavailability of oral preparations of MTX is approximately 15-20% lower than that of intramuscular or intravenous MTX, although there is great variability in relative bioavailability. (b) Protein-binding displacements are unlikely to be of importance with this low-to-medium protein-binding drug. Because MTX is polyglutamated and remains within cells, dialysis is unlikely to be an effective mode of elimination. The principal excretory pathway of MTX is via the kidneys, although some is also excreted through the bile. These facts imply that: (i) MTX needs to be used with extreme caution, if at all, in the face of renal insufficiency; (ii) cholestyramine may be used to enhance the biliary excretion of MTX; and (iii) probenecid may be a cost-effective way to increase the efficacy of MTX. (c) Although aspirin inhibits MTX clearance more than other non-steroidal anti-inflammatory drugs (NSAIDs), clinical toxicity of aspirin is not significantly greater than that of other NSAIDs. In all cases this negative interaction is very rare (although, of course, it needs to be considered at all times). (d) It is possible that corticosteroids inhibit MTX metabolism, although this requires significant research. (e) Trimethoprim-sulphamethoxazole (TS) toxicity is well documented and may be related to synergistic anti-folate effects of MTX and TS. (f) Folic acid decreases MTX toxicity, possibly through an effect on dihydrofolate reductase. | |
| 8107348 | [A case of miliary tuberculosis after adrenocorticosteroid medication for tuberculosis of | 1994 Jan | This report is a case study of miliary tuberculosis that was induced when adrenocorticosteroid treatment for tuberculosis of the wrist was given because of a mistaken diagnosis of rheumatoid arthritis. An 85-year-old man was admitted to a hospital with a fever and chest pains. Since an examination of the chest X-ray revealed fine nodules throughout both lungs and a sputum smear tested positive for acid-fast bacilli, he was transferred to our hospital. The patient had a three-year history of pain in his left wrist joint. He had swelling on the dorsal aspect of his left wrist for 1 1/2 years, and had been diagnosed as having rheumatoid arthritis. Prednisolone had been administered in dosages of 5 mg per day for two months and 5 mg every other day for four months prior to admission. Upon admission to the hospital, an X-ray examination of the wrist revealed marked destruction of the left carpal bones. Smears of fluid aspirated from the swelling showed acid-fast bacilli, and cultures grew M. tuberculosis. He was treated with INH, RFP and SM, however, he had complications of tuberculous spondylitis and renal tuberculosis, and died nine months after admission. |