Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3259737 | HLA-DP in rheumatoid arthritis. | 1988 Feb | Frequencies of HLA-DR, Dw and DPw specificities were compared between rheumatoid arthritis (RA) patients, Felty's syndrome (FS) patients and normal controls. It was confirmed that the frequency of DR4 was increased in RA patients (54% (n = 111) vs 23% (n = 272), relative risk (RR) = 3.98, P less than 0.001). Cellular typing showed a highly significant increase in HLA-Dw14 in the entire RA population (17% (n = 32) vs 2% (n = 242), RR = 11.90, P less than 0.001), and a tendency towards an increase of HLA-Dw14 in DR4+ RA patients compared to DR4+ controls (28% (n = 32) vs 11% (n = 47), RR = 3.29, P less than 0.05). Regarding DPw specificities, the only significance was for a negative association with DPw3 (13% vs 22% (n = 254), RR = 0.51, P less than 0.05), with an additional tendential decrease of DPw1 (11% vs 19%, RR = 0.53, not significant (NS]. The decrease of DPw3 was more marked in DR4- RA patients (RR = 0.33, P less than 0.05) than in DR4+ RA patients (RR = 0.69, NS). In FS patients, 96% of whom were DR4+, decreased DPw1 was very marked, whereas the frequency of DPw3 was unaltered compared to DR4+ normals. These alterations in frequencies were not caused by linkage disequilibria between HLA-DR and -DP alleles. Thus, taken together, these data suggest that, in the presence of the major DR4-associated "susceptibility" gene(s) for RA, DPw1 may have "protective" effects, whereas in the absence of DR4, the presence of DPw3 has significant "protective" activity. | |
| 1903212 | Elastolytic activity of human monocytes from synovial fluid and blood of patients with art | 1991 | Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (MøE) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood MøE was lower in OA than in IH, both measured as basal MøE activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF MøE was higher than MøE in blood (p less than 0.01). This increase in SF MøE could be mimicked in vitro by prestimulation of blood Mø with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF MøE, IL-6 and sIL-2R in patients with IH, points to a stimulation of Mø and lymphocytes in the joint. | |
| 2048859 | Evaluation of Social Security disability in claimants with rheumatic disease. | 1991 Jul 1 | We compared the Social Security Administration's (SSA) judgment of disability with uninvolved rheumatologists' evaluations of ability to work. With the cooperation of the SSA, 52 new disability claimants who alleged rheumatoid arthritis, osteoarthritis, or systemic lupus erythematosus were identified at the beginning of their claim. At the same time that their claim was being formally reviewed, they had a standardized examination by an independent rheumatologist who was not involved with their care, and they had a standardized test of observed performance. Rheumatologists' judgments of ability to work were compared with the SSA judgments. Rheumatologist and SSA judgments were in agreement for 35 of the 52 claimants (67%). All 11 claimants who met or equaled the SSA medical evaluation criteria were judged work-disabled by the rheumatologist. Of 27 judged able to work by the SSA, the rheumatologist judged 11 to be unable. Agreement between the SSA judgment of residual functional capacity and observed performance was no more than would be expected by chance. Most SSA judgments agree with a clinician's evaluation but a standardized physical evaluation by a rheumatologist and performance-based tests appear to add important information. | |
| 2626677 | Long term study of ketoprofen SR in elderly patients. | 1989 | Elderly patients are often chronically treated with different drugs. As rheumatic conditions are very common in this population, NSAIDs are widely used on a chronic basis. To determine the safety profile of ketoprofen, an international prospective study was set up to monitor the effects of the drug over a 12-month period. Four hundred and sixty five patients were enrolled mostly for osteoarthritis (86%) and rheumatoid arthritis (14%) and received a 200 mg SR tablet o.d. Sex ratio (women/men) was 3/1 and mean age was 70.8 +/- 5.8 years (range: 62-95). The pain as evaluated by the VAS decreased from 50 +/- 2.8 mm at baseline to 20 +/- 1.7 mm at the end of the study. 33.3% of patients complained of side-effects mostly related to GI tract (18%), CNS (4%) and skin (2%). After 12 months of treatment, the maintenance rate was 71.6%. No relationship was evidenced between side-effect incidence and age or cumulative dose, even for severe GI side-effects. 13.3% patients withdrew from the study for side-effects, nearly always related to GI tract (11.2%), 60% of which occurred during the first month. Skin side-effects were always benign. In conclusion, ketoprofen, a short half-life NSAID, administered on a long-term basis in elderly patients has a favorable safety profile and displays no increase in toxicity with age. | |
| 2694791 | [Cardiac manifestations of connective tissue diseases]. | 1989 Mar | We have studied the cardiac manifestations of connective tissue diseases. In 213 files of patients with connective tissue disease of the Department of Medicina I, Hospital Santa Maria, during 21 years. Cardiac manifestations were observed in 63 (90%) SLE. Pericarditis was the most frequent manifestation and occurred in 33 patients (43%). The cardiac manifestations were observed in 40 (41%) RA. Pericarditis appeared in 11 patients, valvulopathy in 12 patients and coronaropathy in 11 patients. In 10 of PD diagnosed patients, ECG abnormalities were the only findings. Arrhythmias, conduction disturbances, cardiac failure and coronaropathy were the cardiac manifestations of PSS in 11 patients. Polyarteritis Nodosa patients had myocardial ischemia and another had a malignant hypertension diagnosis. We found pericardial effusion in one patient and angina in another one with MCTD diagnosis. We did'nt find any cardiac manifestation in AS. Cardiac manifestations are frequent in connective tissue diseases. The ECG, ECO and pathology show abnormal findings. Although there is not clinical cardiological expression of the disease we suggest the use of ECG. ECO Holter electrocardiography and isotopic myocardial perfusion scan technics in the clinical evaluation of such patients. | |
| 3491701 | Defective production of leucocytic endogenous mediator (interleukin 1) by peripheral blood | 1986 Jul | Leucocytic endogenous mediator is one of the activities ascribed to the cytokine or family of cytokines known as interleukin 1. In this study we have examined the ability of circulating blood leucocytes from patients with rheumatic diseases to produce this mediator in vitro. Leucocytic endogenous mediator production was found to be significantly decreased below normal values (mean 107 units, s.e.m. +/- 25) in systemic sclerosis (-6 units +/- 18), systemic lupus erythematosus (-25 units +/- 13), rheumatoid arthritis (-3 units +/- 13) and mixed connective tissue disease (-4 units +/- 40). A control group of ill patients with cancer produced 57 units +/- 8. | |
| 1929719 | [Acute rheumatoid aortic insufficiency treated by valve replacement. Apropos of a case]. | 1991 Jul | Rheumatoid valvular heart disease and aortic valve replacement for a rheumatoid lesion have been previously reported in the literature. The authors report the first case of emergency surgery for acute aortic regurgitation due to necrosis and rupture of a rheumatoid granuloma: the anatomopathological lesions observed were patholognomic. | |
| 3279962 | Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. | 1988 Feb | Twenty-six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue to receive the drug in a long-term prospective study. At 36 months, 16 patients remained in the study. Over this period of time, significant improvement was noted in the number of painful and swollen joints, physician and patient global assessments, erythrocyte sedimentation rate, and prednisone dose. Adverse reactions occurred in 16 patients (62%), including nausea, alopecia, headache, stomatitis, herpes zoster, and diarrhea. Mild leukopenia (3 patients), thrombocytopenia (3 patients), and elevated transaminase levels (8 patients) resolved with temporary drug discontinuation. No patient withdrew due to drug toxicity. Liver biopsy specimens in 17 patients after 24 months of treatment showed no evidence of fibrosis or cirrhosis. A significant increase in the percentage of T3 and T4 blood cells and increases in lymphocyte proliferation to concanavalin A and purified protein derivative of tuberculin were found after 2 years of therapy. Our findings indicate that methotrexate has remained effective over 36 months of therapy, with acceptable toxicity levels and no evidence of systemic immunosuppression. | |
| 3545222 | Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovi | 1987 Jan | Pathologic changes in the basement membrane (BM) of postcapillary venules (PCV) and capillaries in rheumatoid arthritis (RA) synovium were studied by immunoelectron microscopy, using a monoclonal antibody against human type IV collagen, C(IV)22, and by electron microscopic morphometric analysis. The sublining region of RA synovium was classified into lymphocyte-rich areas, transitional areas, and interstitial areas, according to their pattern of cellular infiltration. In lymphocyte-rich areas, the BM of the PCV and capillaries were minimally thickened; disruption of the lamina densa was seldom seen. Transitional areas, which contained macrophages, lymphocytes, and plasma cells, had numerous PCV and capillaries. The BM was markedly thickened and partially multilamellated, and there were many disruptions in the lamina densa. The BM contained degenerated endothelial cells and cell debris. On immunostaining of this BM with monoclonal antibody C(IV)22, type IV collagen stained heavily, mainly in the disrupted lamina densa; this indicates that the thickening was, at least in part, the result of an increase in BM collagen. In uninfiltrated interstitial areas, BM were moderately thickened and multilamellated, and showed few disruptions of the lamina densa; there were similar increases in type IV collagen, but cell debris was seldom observed. Measurement of the BM width, the ratio of BM width to vessel diameter, and the fraction of vascular cross-sectional area occupied by BM demonstrated that the thickness of the BM of both PCV and capillaries was greatest in transitional areas and was smallest in lymphocyte-rich areas (P less than 0.01). Since macrophages and macrophage-derived factors have been found to promote synthesis of BM collagen type IV, and since transitional and interstitial areas are rich in macrophages and histiocytes, respectively, it is suggested that these mononuclear cells and the factors secreted by them play a significant role in the thickening of the BM of PCV and capillaries in RA synovitis. | |
| 2877850 | Pharmacological and biochemical actions of sulphasalazine. | 1986 | This review considers recent pharmacological and biochemical studies of sulphasalazine and its colonic metabolites, 5-aminosalicylic acid and sulphapyridine, in relation to the use of the parent drug for the treatment of ulcerative colitis and, more recently, rheumatoid arthritis. Several factors make it difficult to analyse the mode of action of sulphasalazine, such as the aetiology and variable course of the conditions it is used to treat, lack of suitable animal models, and the question of which moiety of the drug is active. An important feature of the pharmacokinetics of the drug after oral administration is the significance of the azo cleavage of sulphasalazine due to bacterial action. The effects of sulphasalazine on the metabolism of arachidonic acid to prostaglandins and leukotrienes have been widely studied because of the evidence that these substances are formed in increased amounts in inflammatory bowel diseases. The effects are complex, but it appears that sulphasalazine and 5-aminosalicylic acid are weak and very weak inhibitors, respectively, of both cyclo-oxygenase- and lipoxygenase-dependent pathways. The overall pharmacological profile may favour a more marked inhibition of the lipoxygenase pathway because of the additional ability of 5-aminosalicylic acid to enhance prostanoid production and of sulphasalazine to inhibit prostaglandin inactivation. Drugs with selective lipoxygenase inhibitory actions in the colon should thus be sought so as not to compromise the prostaglandin pathway. Other properties of sulphasalazine, including its immunosuppressive, antifolate, lymphocyte inhibitory and leucocyte modulatory actions, are also discussed in the context of the therapeutic uses of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3553067 | Total condylar knee prosthesis with posterior stability. A mid-term follow-up of 74 cases | 1986 Sep | The midterm results of 74 posterior stability total condylar prostheses were studied (average follow-up 3 1/2 years). The average age of the patients was 65 years with a predilection for females (73%). The most frequent diagnosis was osteoarthritis (70%) followed by rheumatoid arthritis (28%): in 20% of the cases previous operations had been performed. Most of the patients had severe deformity which was not susceptible to other surgical treatment. The most frequent deformity was varus (average 13 degrees), followed by valgus (average 25 degrees), and flexion contracture (average 37 degrees). Bone defect in the tibia requiring surgical treatment were present in 18% of the cases. The most frequent general complication was pulmonary embolism (5%), which was never fatal; minor complications related to wound healing were observed in 17.5% of the cases. The results, evaluated with a numerical recording form devised by the Hospital for Special Surgery (New York) were: excellent 72%, good 21%, fair 4%, poor 3%. Of the 4 fair results, one had lateral laxity following lysis for valgus knee, one had loosening of the tibial component, and one had painful patellar clicks. Painless, small patellar clicks were observed in 4 other patients. The two poor results were due to low-grade infection and detachment of both components. Seventy per cent of the knees had normal or almost normal function with maximum flexion averaging 100 degrees. In 78% of the cases a study of the cement-bone interface revealed either no radiotranslucent line or present in only one area of the tibia. Radiotranslucent lines around the femoral or patellar component was rare and of no clinical significance. | |
| 2572572 | [Unusual cutaneous angiofibromatosis following gold therapy of primary chronic polyarthrit | 1989 Sep | An unusual case of late cutaneous intolerance reaction following gold therapy for rheumatoid arthritis is reported. In keloidlike angiofibromatoid lesions that were spread over the upper part of the trunk and the arms, perivascular macrophages carrying gold deposits inside lysosomes were detected with two recently introduced methods--energy-dispersive X-ray microanalysis (EDX) and electron spectroscopic imaging (ESI)--for definitive ultrastructural localization. | |
| 2678821 | [Detection of endotoxin in synovial tissue of patients with inflammatory-rheumatic disease | 1989 Jul | The etiology of inflammatory rheumatic diseases is unknown. The hypothesis, that bacteriae may play a part in the induction of a rheumatic synovialitis is further substantiated by the detection of Endotoxin (Lipid A) in the synovial membranes of five of eleven patients with early synovitis (disease duration shorter than 6 months) by using anti Lipid A monoclonal antibodies. Endotoxin (Lipid A) is a component of gram-negative bacteriae and Chlamydiae. It is a potent immunogen, and could be the link between infection of the gut or the urogenital system and the rheumatic synovialitis. | |
| 2175685 | Longitudinal analysis of antibodies to histones, Sm-D peptides and ubiquitin in the serum | 1990 Sep | A longitudinal analysis of 12 lupus patients has been undertaken to assess their autoantibody reactivity by ELISA with histones, Sm-D peptides, ubiquitin and DNA. As controls patients with rheumatoid arthritis and tuberculosis were studied. Whereas the control groups showed little evidence of autoantibody reactivity 25% or more of the lupus patients had raised levels of autoantibodies against eight of the nine antigens tested. Of particular note was the fact that approximately 70% of the blood tested possessed antibodies reacting with Sm-D peptide 1-20. In contrast only one patient had anti-Sm antibodies by counter immunoelectrophoresis. In general the levels of antibodies to core histones reflected disease activity unlike the levels of anti-H1 antibodies. High levels of antibodies to ubiquitin often seemed to correlate inversely with active lupus and DNA antibody levels. | |
| 3484727 | C1 activation, with C1q in excess of functional C1 in synovial fluid from patients with rh | 1986 | Free Clq, in functionally active form was present in increased amounts in the synovial fluid of patients with rheumatoid arthritis. The presence of free Clq was associated with low concentrations of hemolytic C1, low C4 and raised amounts of C3dg/d fragments in the synovial fluid. The findings suggested intra-articular C1 activation with dissociation of C1 into free C1q and complexes containing C1r, C1s, and C1 inactivator. However, the immunochemical properties of synovial fluid C1r-C1s-C1 inactivator complexes appeared to differ from those of the complexes formed in serum, which hampered quantification with the assay used. Control patients with osteoarthritis or spondylarthritic syndromes did not show evidence of intra-articular complement activation, even though 1 patient with Reiter's disease had unexplained low concentrations of synovial fluid C4 and C3. The concentrations of circulating complement components were largely normal in the patients. Slightly increased concentrations of free C1q and C1r-C1s-C1 inactivator complexes in serum and C3dg/d fragments in EDTA plasma were observed, particularly in the patients with rheumatoid arthritis. | |
| 2783895 | Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases | 1989 Mar | Lymphocytes upon activation release a soluble form of interleukin 2 receptor (IL-2R). Systemic autoimmune disorders are characterized by immune system disregulation associated with cellular activation; therefore we sought to determine the levels of soluble IL-2R molecules in the serum of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjogren's syndrome (1 degree SS). Utilizing an enzyme immunoassay method we found increased serum levels of soluble IL-2R in 65.4% (34/52) of RA, in 34.9% (15/43) of SLE, and in 25.0% (13/52) of 1 degree SS patients, compared to 4.2% (1/24) of healthy individuals. High serum levels of soluble IL-2R correlated with several indices of disease activity in RA and SLE patients, as well as with disease progression to extraglandular involvement and to pseudolymphoma or lymphoma in patients with 1 degree SS. By gel filtration analysis, the soluble IL-2R circulating in the serum of a RA patient corresponded to a high molecular weight molecule (greater than 90 kDa) compared to the 65-kDa soluble IL-2R molecule released by phytohemagglutinin-stimulated normal peripheral lymphocytes. | |
| 1748495 | Misoprostol in the treatment of NSAID-induced gastroduodenal lesions. | 1991 Oct | The cytoprotective effect of misoprostol co-administered with non-steroidal anti-inflammatory drugs (NSAIDs) was assessed in a double blind, placebo controlled study. Thirty-seven patients with rheumatoid arthritis receiving NSAIDs, having upper gastrointestinal symptoms and endoscopically confirmed gastric and/or duodenal lesions, were randomised to receive either misoprostol 200 micrograms or placebo tablets twice daily for 4 weeks. Of 31 evaluable cases, 13 of 16 (81%) patients receiving misoprostol showed endoscopic improvement as compared to 10 of 15 (67%) receiving placebo (P:NS). A significant decrease in mean (+/- SEM) mucosal lesion score was observed with misoprostol (from 3.38 +/- 0.32 to 1.32 +/- 0.44; P less than 0.001) but no change was seen with placebo (from 2.80 +/- 0.42 to 1.60 +/- 0.53; P:NS). Symptomatic relief was similar in both groups, being 44% and 40% respectively. Two patients complained of diarrhea in each group and one developed menorrhagia with misoprostol. It is concluded that though misoprostol decreased the number of NSAID-induced mucosal lesions, it was unable to relieve gastrointestinal symptoms. | |
| 2250958 | [Statistical results of 700 electrophysiologic tests (ERG) in patients without ophthalmolo | 1990 May | 737 adapto-electroretinograms are registered on patients treated by chloroquine for a rheumatoid arthritis (RA) or for a lupus. Their ophthalmological examinations are completely normal. In term of the cumulative doses, the statistical results of the electrological characteristics of the different waves of the ERG issued from white, red and blue stimulations show: a great stability of the latencies of the "a" and "b" waves; a gradual decrease of the "b" wave amplitudes for the RA; a gradual increase of the "b" wave amplitudes till a level dose reached between 800 and 900 g and then a decrease of the "b" wave amplitudes, for the lupus. We discuss the electrophysiological criterions for a beginning intoxication. As a standard, for the R.A., it seems that a certain amount of "b" wave amplitude decrease could be admitted but the "a" and "b" wave latencies must be very constant. For the lupus, the hyper normality or at least stability of the "b" wave amplitude can be admitted till a dose around 800 g, associated to a good stability of the "a" and "b" wave latencies. Beyond these statistically established limits a beginning intoxication should be suspected. | |
| 3120307 | Distribution of immunoglobulin classes in plasma cells in various kinds of synovitis. | 1987 | Sixty-five cases of synovitis corresponding to eight groups (seropositive and seronegative rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, post-traumatic arthritis, osteoarthritis, osteonecrosis and unclassified synovitis) were investigated in specimens stored as paraffin blocks. Immunoglobulin class content (heavy chains: G, A, M and their associated light chains: K, L) of the plasma cells was determined by the immunoperoxidase method. Plasma cells were observed in all cases in both RA groups but not in all cases of the other groups. All three classes of immunoglobulins were observed. The proportion of IgM cells was numerically larger in seropositive rheumatoid arthritis than in seronegative RA. However, due to the great case-to-case dispersion and small group size, this difference was not significant. A routine investigation of intracellular immunoglobulins cannot, therefore--at least with present knowledge--contribute to the diagnosis or prognosis of a given case of synovitis. | |
| 2053087 | [Chronotherapy of tenoxicam]. | 1991 Mar | A study was carried out in order to investigate the chronotherapy (dosing time dependency) of an NSAID, the tenoxicam administered in ankylosing spondylitis, rheumatoid arthritis and osteoarthritis of the hip. These variations in efficacy exist as much for pain as for stiffness and maximum efficacy is obtained with administration at 8 am or 12 pm. Since the tolerance was good, we recommend midday as an optimal once-a-day dosing time. |