Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1439482 | Phenotypic analysis of functionally associated molecules on peripheral blood and synovial | 1992 | Surface expression of 16 different membrane molecules was analyzed in peripheral blood and synovial fluid monocytes from patients with rheumatoid arthritis and reactive arthritis compared to controls. The most significant findings were modulated expression of function-associated FcRI, CR1, CR3, MHC class II and activation-associated CD31, M5, and M6 molecules in arthritis patients compared to controls. Of these molecules, only upregulated expression of MHC class II has previously been reported in synovial fluid monocytes of patients with rheumatoid arthritis. | |
| 1472122 | Auranofin-induced vasomotor reaction. | 1992 Dec | Vasomotor reactions after administration of gold sodium thiomalate (GST) are well recognized, but such reactions have not been reported to occur in association with oral gold treatment. We describe a woman with rheumatoid arthritis who experienced typical nitritoid reactions after treatment with GST, and later, with auranofin. | |
| 1502858 | [Plasma GM-CSF concentrations in rheumatoid arthritis, systemic lupus erythematosus and sp | 1992 May | Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent hematopoietic growth factor, which is mainly produced by T-cells and stromal cells. Beside the stimulating effects on mature granulocytes, it induces the expression of HLA class II-antigen on synovial tissue-cells in patients with rheumatoid arthritis. The concentrations of GM-CSF in the plasma of 87 patients with rheumatoid arthritis, 48 patients with spondyloarthropathy, 17 patients with systemic lupus erythematosus (SLE), and 43 healthy control persons were investigated. We used an immunoradiometric assay (IR-MA) with a detection limit of 30 pg/ml to measure the GM-CSF concentrations in plasma. The GM-CSF levels of 29 patients with severe rheumatoid arthritis (366 +/- 61 pg/ml, p less than 0.05), 58 patients with moderate rheumatoid arthritis (376 +/- 44 pg/ml, p less than 0.0001), and of 17 patients with SLE (256 +/- 41 pg/ml, p less than 0.05) were elevated compared to the control group (174 +/- 18 pg/ml). No significant differences in the mean GM-CSF plasma levels between the patients with spondyloarthropathy (190 +/- 32 pg/ml) and the control group were found. GM-CSF concentrations as high as 1300 pg/ml were detected in the synovial fluids of patients with rheumatoid arthritis. GM-CSF concentrations in the plasma of patients with severe rheumatoid arthritis were correlated with the plasma concentrations of the soluble interleukin-2-receptor (sCD25) (R = +0.53). | |
| 8721274 | Total and free methotrexate pharmacokinetics in rheumatoid arthritis patients. | 1996 Apr | The pharmacokinetics of total and free methotrexate (MTX) were investigated in 50 patients with rheumatoid arthritis. Each patient received 10 mg MTX intramuscularly. The free and total plasma concentrations of MTX were measured over a 36-h period after drug administration by using the Abbott TDx fluorescence polarization immunoassay. Plasma concentrations of MTX were described by a biexponential function. The mean terminal elimination half-lives of total and free MTX were 9.4 and 8.4 h, respectively, and the corresponding mean residence times, 8.5 and 9.2 h. No difference in these parameters was found by comparing total and free MTX. Total plasma clearance of the free fraction averaged 215 ml/min. The statistical comparison of the variations with time of the ratio of free to total MTX during the 36 h after the dose showed that the free fraction was significantly increased for 8 h after drug administration (p < 0.001). To describe these variations, the changes of the free MTX concentrations (unbound) were related to the changes of the total MTX concentrations by using the Hill equation. Mean plasma protein binding ranged from 20 to 57% for these patients. | |
| 7788170 | Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid ar | 1995 May | The pharmacokinetic profile of total and free methotrexate (MTX) and the effect of piroxicam on MTX pharmacokinetics was studied in 20 rheumatoid arthritis patients receiving a stable dosage of MTX (10 mg/week). Plasma protein binding ranged from 25 to 55%. To describe the variations with time of the unbound fractions a mathematical characterization relationship between the total and free MTX was used. Total and free MTX were correlated with the sigmoid maximum effect model. The slope factor (gamma) was proportional to the number of binding sites. The free fraction for a given patient can be evaluated from this relationship. Total clearance of MTX was not statistically different with piroxicam (8.0 l/h for total MTX, 13.7 l/h for free MTX) vs without piroxicam. Likewise, there were no significant difference in tmax, area under the plasma concentration vs time curve, distribution and elimination half-lives, mean resonance time, and volumes of distribution. Although the highest observed total MTX concentration was significantly lower with piroxicam, there were no significant pharmacokinetic interactions between low-dose MTX and piroxicam. | |
| 7638818 | Sleep apnoea syndrome secondary to rheumatoid arthritis. | 1995 Jun | A patient who developed severe sleepiness and sleep apnoea in association with adult acquired retrognathia and subluxation of the cervical spine at the level of C3-C4, both resulting from rheumatoid arthritis, is described. The possible causative factors of the association between sleep apnoea and rheumatoid arthritis include reduction of the size of the upper airway by temporomandibular joint destruction, brainstem compression due to rheumatoid arthritis affecting the cervical spine, sleep fragmentation, and drug effects. | |
| 1642032 | [Results of resection of the head of the ulna]. | 1992 May | A follow up of 57 wrists with resection of caput ulnae shows different value to different groups of patients. The painful arthrosis of distal radioulnar joint gives indication in posttraumatic cases. Release of pain and improvement of range of motion will be achieved; loss of strength is the most impairing problem for younger patients. 13 patients out of 21 with posttraumatic deformities were satisfied with the post-operative outcome; 13 patients showed significant loss of strength, too. In case of rheumatoid arthritis with caput-ulnae-syndrome the resection is without alternative, needs to be combined with the arthrodesis of radiolunar-joint, if necessary. 20 of 34 rheumatics were satisfied with the outcome after resection of caput ulnae; in 6 cases an ulnar drift was evident, which implied simultaneous or later partial arthrodesis of the wrist. For all patients release of pain decided on their satisfaction with surgery. | |
| 8608678 | Prevalence of metacarpal osteopenia in young rheumatoid arthritis patients. | 1995 Nov | The aim of this study was to assess the prevalence of and diagnostic role of metacarpal osteopenia in rheumatoid arthritis (RA) and to evaluate its detectability using receiver operating characteristic (ROC) analysis. Metacarpal bone mineral density was measured in 98 patients with classical RA using a computer-assisted measure of 6 metacarpal diameters (radiogrammetry) in patients aged less than 50 years. Sensitivity and specificity of the technique in discriminating the RA patients from 85 normal controls and osteopenic RA subjects from their normopenic counterparts, was determined by standard statistical techniques. Clinical, laboratory and radiological variables were compared in their ability to explain the variance of metacarpal bone density. The prevalence of metacarpal osteopenia in RA was 55%. Prolonged disease and reduced function significantly differentiated osteopenic from non-osteopenic RA patients. Discriminant analysis of RA and control groups showed that measurement of 6 metacarpals was more accurate than the 2nd metacarpal measurement alone in predicting the RA patients. The sum of 6 metacarpal combined cortical width (CCW) had a sensitivity of 61% and specificity of 68% in discriminating the RA patients from the controls. Receiver operating characteristics curves showed, not surprisingly, that objective measurement of bone diameters was superior to clinical or laboratory measures of disease activity in correctly classifying a randomly chosen RA patient as osteopenic or not. Metacarpal osteopenia is common in RA and it may be a useful measure of the disease in young patients. | |
| 7895399 | Phospholipase A2 activity in peripheral blood cells of rheumatoid arthritis patients treat | 1994 Nov | OBJECTIVE: To measure the activity of phospholipase A2 (PLA2) in peripheral blood mononuclear cells (PBMC), polymorphonuclear leukocytes (PMN) and platelets in patients with rheumatoid arthritis (RA) before and during treatment with methotrexate (MTX). METHODS: Nine patients with RA treated with MTX were studied for six months. PBMC, PMN, and platelets were isolated at baseline and at monthly intervals thereafter. PLA2 activity was measured in lysates of the various cell fractions by the hydrolysis of radiolabeled lysocholine from phosphatidylcholine, L-Dipalmitoyl using thin layer chromatography. Data were calculated as pmol of 14C choline released per hour per milligram of cellular protein. RESULTS: At baseline, compared to normal controls, PLA2 activity was significantly increased in platelets (p = 0.02) but not in PBMC (p = 0.32) nor in PMN (p = 0.23). Seven of the nine patients responded clinically to treatment with MTX. In these 7 patients over the six-month treatment course, there was a significant decrease in PLA2 activity in the platelets which correlated with improvement in disease activity (R = 0.82, p = 0.03). PLA2 activity also decreased in PBMC and PMN, but the correlation with disease improvement was not statistically significant (R = 0.71, p = 0.07 for PBMC; and R = 0.43, p = 0.33 for PMN). CONCLUSION: PLA2 activity in platelets but not in PBMC or PMN is significantly increased in patients with RA compared to normal controls. Although PLA2 activity decreased in all the cells during treatment with MTX, only PLA2 activity in platelets correlated significantly with improvement in disease activity. | |
| 8924339 | [New metacarpal osteotomy: metacarpal cervicocapital shortening osteotomy of the rheumatoi | 1996 | Volar dislocation of the four long fingers is a common situation in rheumatoid hands. Surgical reduction is rather difficult because of soft tissue retraction, especially interosseous muscles, and requires large releases. The authors propose the use of Weil's osteotomy, initially described in foot surgery. This is an oblique cervico-capital osteotomy which shortens the metacarpal bone, fixed by two screws. This makes soft tissue release less extensive and facilitates relocation of the extensor tendon. Two cases are reported. | |
| 7671613 | Destructive corneal and scleral disease associated with rheumatoid arthritis. Medical and | 1995 Jul | The onset of necrotizing scleritis (NS) and peripheral ulcerative keratitis (PUK) in the clinical course of rheumatoid arthritis (RA) may reflect the presence of systemic, potentially lethal vasculitis. In an effort to better characterize this subset of patients with severe RA-associated corneal and/or scleral inflammation and to analyze the efficacy of therapy, we reviewed our experience in the medical and surgical management of 16 tertiary referral cases (25 eyes) unresponsive to aggressive conventional therapy with topical and systemic steroids as well as with systemic nonsteroidal drugs. Cytotoxic immunosuppressive therapy was instituted in all patients with NS and/or PUK. Cyclophosphamide and methotrexate were the most successful agents used. Cytotoxic immunosuppressive drugs in conjunction with early aggressive surgical treatment halted the relentlessly progressive inflammation and preserved the integrity of the globe in 92% of eyes. Visual acuity could be stabilized or improved in 83% of patients with NS and in 68% of patients with PUK. | |
| 8052930 | [Two cases of rheumatoid arthritis presenting autoimmune hepatic diseases]. | 1994 Jun | We report on two cases of rheumatoid arthritis (RA) presenting autoimmune hepatic diseases. The first patient, who had been diagnosed as RA at the age of 63, was hospitalized in order to undergo surgery for total left knee replacement at the age of 69. She acquired acute serum hepatitis as a result of blood transfusion she received during the operation. Five years later, she visited our clinic suffering from polyarthritis. She was found to have hyper-alkaline phosphatase (ALP) and hyper rGTP, but no AMA. The second patient, a 60-year-old female whose onset of RA was at the age of 45, complained of general fatigue, and was admitted to the hospital because of persistent liver dysfunction. When corticosteroid was administered to these patients, ALP and rGTP levels in the first case, and AST and ALT levels in the second case were reduced to values in the normal range. ANA in the first case continued to register negative, but ANA in the second case became positive after the patient developed acute hepatitis. Both patients were found to have anti-p25 triplet liver/kidney microsome antibody. We discuss the clinical significance of this antibody. | |
| 8448632 | Monotherapy in rheumatoid arthritis. | 1993 Mar | In the past few years there has been considerable debate regarding the optimal therapy for patients with RA. The arguments have been phrased in a variety of ways and frequently involve the concept of therapy with multiple drugs. The underlying assumption is that current therapy is inadequate and that the whole therapeutic approach to RA needs rethinking. The evidence on which these assumptions are made is reviewed here. Additionally, this paper argues for a more discriminating approach using prognostic indicators to identify the minority of patients with persistent unresponsive disease (and poor outcome) for whom more aggressive therapy should be reserved. | |
| 7747148 | Cancer morbidity in rheumatoid arthritis patients treated with Proresid or parenteral gold | 1995 | The cancer risk was studied by comparison of 305 rheumatoid arthritis (RA) patients exposed to Proresid during a mean time of 22 months and 305 RA patients exposed to sodium aurothiomalate during a mean time of 19 months with the regional cancer register. The mean observation time was 6.9 years (2,117 person-years) for the Proresid-treated and 7.5 years (2,293 person-years) for the gold-treated patients. No increased risk of total malignancies was observed for either group. However, looking at separate tumours, an increased risk of lymphoma and leukemia was found although only significant in the gold-treated group. It was not correlated to dosage or duration of either therapy. The increased risk is consistent with earlier reports of an increased risk of hematopoietic malignancies in RA patients. Marginal over and underreporting, particularly of hematopoietic malignancies, were observed, mainly due to clinicians' failure to report and to recall false reports. | |
| 7651566 | Dialysis treatment in patients with rheumatoid arthritis. | 1995 Jul | The results of dialysis treatment in 24 rheumatoid arthritis patients, 20 chronic rheumatoid arthritis (RA) and 4 juvenile rheumatoid arthritis (JRA), were analysed. Presence of secondary amyloidosis, renal function, morbidity and survival were examined. Amyloidosis was present in 13 patients. Especially among amyloidosis patients, renal function declined rapidly in the last year before dialysis started. On average, 63 days per patient-year were spent in the hospital, 58% was dialysis-related, mainly due to vascular access problems. Hospitalization was even more widespread in amyloidosis patients (79 days, 72% dialysis-related). Median survival in RA patients with amyloidosis was 11 months; in RA patients without amyloidosis this was 29 months. Two-year survival was only 1 out of 10 for the RA amyloidosis patients; for the RA non-amyloidosis patients this was 5 out of 6 (p < 0.01). Cardiovascular causes of death were most frequent. In conclusion, high morbidity and low survival make RA patients with amyloidosis a high-risk group on renal replacement therapy. | |
| 8341862 | Reducing attrition bias with an instrumental variable in a regression model: results from | 1993 Jun 15 | This study proposes an econometric technique to reduce attrition bias in panel data. In the simplest case, one estimates two regressions. The first is a probit regression based on sociodemographic and clinical characteristics measured at baseline. The probit regression estimates the probability that subjects stay or leave over the duration of the study. We insert the predicted probabilities from the probit regression into an inverse Mills ratio (IMR) or hazard rate to form an instrumental variable. We use this instrumental variable subsequently as an additional covariate in a second regression model that attempts to explain fluctuations in the dependent variable. The second regression, which is linear, includes only subjects who remained in the study. In alternative models, instrumental variables are created using predicted values from least squares and logit regressions estimating the probability that subjects stay or leave. The use of the instrumental variables reduces the effects of attrition bias in the linear regression model. We applied the technique to a panel of patients with rheumatoid arthritis (RA) enrolled in 1981 and followed through 1990. We attempted to predict values for a measure of functional disability recorded in 1990 with use of covariates measured in 1981. The dependent variable was an index of disability in 1990 and the independent variables (covariates) included the disability index from 1981, the years of duration of RA, gender, marital status, education, and age in 1981. The correction technique suggested that ignoring attrition bias would underestimate the strength of associations between being female and the subsequent disability index, and overestimate the strength of associations between being married spouse present, age, and the initial disability index on the one hand and the subsequent disability index on the other. | |
| 1280844 | Genetic and environmental factors in the immune pathogenesis of rheumatoid arthritis. | 1992 Nov | Our experiments have led us to conclude that the rheumatoid arthritis shared epitope may act as a peptide that is important for positive and negative selection of T lymphocytes, that T lymphocytes are skewed by positive selection to recognize epitopes that are similar but not identical to self, and that peptide sequences that are similar to the RA-shared epitope are abundantly expressed by microorganisms that chronically infect most people. This combination of events could partly explain the association of the shared epitope with the severe forms of RA. The hypothesis cannot be tested directly, because we do not postulate that any unique population of autoreactive T cells is expanded in RA; however, the role of positive selection in molding the human T-cell repertoire to exogenous antigens can be tested by mapping T-cell antigenic determinants on the E. coli dnaJ protein or the gp110 protein of EBV in people with different HLA-DR types. Moreover, positive selection models imply that maternal antigens that cross the placenta can influence the T-cell repertoire. Thus, one might expect to find that the frequency of HLA-DR4 in the mothers of patients with RA who themselves lack the DR4 antigen, would be more frequent than predicted by chance alone. As the principles of positive selection are more precisely delineated in animal systems, it should become possible to ascertain more clearly how the shared epitope on HLA-DR molecules enhances the severity of autoimmune reactions; however, RA only occurs in humans; possibly because of the unique inability of human macrophages to replicate. Thus, only the direct analysis of patients can directly reveal the mechanisms of disease pathogenesis. | |
| 1387980 | [Effect of the tumor cell associated glycoconjugate (TCA) derived Kato III, human gastric | 1992 Jun | We have been developing a new treatment for patients with rheumatoid arthritis (RA) by using intradermal injection of carbohydrate molecule complex. Among them, tumor cell associated glycoconjugate (TCA), the membrane structure of Kato III is one of the effective molecules. We studied the immunomodulatory effect of TCA on the autologous mixed lymphocyte reaction (AMLR) using PWM-mitogen induced lymphoblasts as stimulator cells and peripheral blood mononuclear cells (PBMC) as responder cells. In the kinetic study of the AMLR, its maximum proliferation was observed on days five through seven and responding CD4 cells highly expressed HLA-DR antigen. Studied AMLR in 10 patients with RA, proliferative responses of AMLR in these patients were divided into two types, high and low AMLR types. In vitro examination of TCA on AMLR showed that TCA at a concentration of 250 ng/ml significantly suppressed the AMLR response (p less than 0.01, paired T-test) and this phenomenon was found more frequently in high AMLR type patients than in low AMLR type patients. The suppressive effect of TCA on AMLR had a tendency to correlate with the efficacy of TCA therapy in patients studied. These results suggest that TCA may play a role in regulating the function of autoreactive lymphocytes of patients with RA. | |
| 7667399 | Biological rhythms in the inflammatory response and in the effects of non-steroidal anti-i | 1995 May | It is well known that some signs and symptoms of rheumatoid arthritis (RA) vary within a day and between days, and the morning stiffness observed in RA patients has become one of the diagnostic criteria of the disease. Research carried out in the last 10 years confirmed these clinical observations, and circadian, circaseptan or circannual variations were detected in experimental inflammation and in patients with arthritis diseases. The human data showed also that large interindividual differences can be found in the symptoms of RA. The chronopharmacological studies carried out with the non-steroidal anti-inflammatory drugs (NSAID) revealed circadian and circannual variations in the effectiveness, toxicity and pharmacokinetics of NSAID. A review of the available data suggests that peak and trough values found in different arthritic diseases do not occur at the same hour of the day and that the side effects produced by NSAID are more important after the morning than the evening administration. This information should be used by clinicians to determine when to administer drugs to arthritic patients, to optimize the effectiveness of NSAID and/or to reduce the side effects of these drugs. These new data could also be useful to physicians who would like to individualize NSAID use in patients with different arthritic diseases. | |
| 8178070 | [The test of the synovial fluid in microcrystalline joint diseases]. | 1994 Jan 15 | The search for crystals in the synovial fluid must be carried out promptly and is very helpful in the diagnosis of microcrystalline arthropathy. If at light microscopy the fluid is negative for crystals and negative or weakly positive for alizarin red, and if the diagnosis is nevertheless suspected, analysis of the centrifuged fluid sediment facilitates the identification of crystals and increases the specificity of alizarin red (the specific stain for crystals) in the identification of apatite crystal deposits. Electronmicroscopy can the be used to confirm the presence or absence of crystals. |