Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8346977 | Self report functional disability scores and the use of devices: two distinct aspects of p | 1993 Jul | OBJECTIVES: Self report scores of physical disability and the use of devices or assistance in performing activities are sometimes integrated in one index of physical function, although they are aimed at measuring different dimensions of physical disability. The properties of both parameters were evaluated in two groups of patients with rheumatoid arthritis (RA). METHODS: A group of patients with RA of recent onset was compared with a group with established disease on four parameters of disability: use of devices, use of personal assistance, and scores on a validated Dutch version of the Health Assessment Questionnaire Disability Index, with and without integrating the use of devices or assistance. Correlation coefficients among disability parameters were calculated. In multiple regression analysis the influence of disease duration on the disability parameters was determined after disease activity, psychological wellbeing, and demographical characteristics had been controlled. RESULTS: Functional disability scores were mainly related to inflammatory activity and psychological wellbeing, whereas the uses of devices had a strong relation with disease duration, independent of current disease activity. Integrating these parameters of disability yielded a parameter that was still mainly associated with disease activity. CONCLUSION: Self report scores of functional disability and the use of devices represent distinct dimensions of physical function in RA. Integrating both parameters into one measure of physical disability does not provide an index adequately reflecting both dimensions. The use of both parameters to measure outcome in long term clinical studies is recommended. | |
| 8712873 | Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis. | 1996 Feb | OBJECTIVE: To investigate the influence of breast feeding, use of the oral contraceptive pill (OCP), and parity on rheumatoid arthritis (RA). METHODS: One hundred and seventy six women with RA were compared with 145 control subjects; all had at least one child. RA patients were classified as having severe (n = 82) or mild disease (n = 89) according to clinical joint evaluation, radiological score, biological inflammation, and the presence of HLA-DR1 or -DR4 alleles. RESULTS: The mean age of RA patients was 58 years, and the mean age at the time of diagnosis of RA was 46 years. The mean time between onset of RA and the first birth was 23.6 (SD 3.8) years. The OCP user rates were 33% in the RA group and 47.6% in the control group (p < 0.02). OCP use was related to the mother's year of birth. The relative risk for developing RA was 0.598 (95% confidence interval (CI) 0.33 to 1.1) in women who had used OCP for more than five years compared with those who had never used OCPs. In contrast, the age at which the first pregnancy occurred, the number of children breast fed, and the duration of breast feeding were comparable in RA patients and healthy subjects. Among the RA patients, parity, duration of breast feeding, and the number of breast fed children were significantly increased in those with severe disease. Having more than three children increased the risk of developing severe disease 4.8-fold when adjusted for age and OCP use. Forty six percent of women with severe RA had a history of breast feeding duration greater than six months before disease onset, compared with 26% of patients with mild disease (p < 0.008). Having more than three breast fed children increased the risk of poor disease prognosis 3.7-fold. In contrast, OCP use had a protective role in the course of RA (44% of RA patients with mild disease were OCP users, compared with 21.7% of those with severe RA; p < 0.001). Among those using OCP for more than five years, the relative risk of developing severe disease was 0.1 (95% CI 0.01 to 0.6), after adjustment for age, parity, and breast feeding. CONCLUSION: Our results suggest that parity, and to a lesser extent breast feeding, before RA onset worsened RA prognosis, whereas OCP use had a protective role. Prolactin and oestrogen may have a role in these effects. | |
| 8130290 | Promoting self-care in clients with arthritis. | 1993 Sep | Preliminary work regarding the development and pilot study of an individualized instructional program for rheumatoid arthritis clients is presented. The effect of the individualized instructional program was tested with 31 outpatients. Using analysis of covariance, the experimental group subjects scored significantly higher on the knowledge post-test when compared to scores of control group subjects (P = 0.0045). Analysis of variance for repeated measures revealed no significant difference in performance of tasks for the control group and experimental group (P = 0.08). In a follow-up study, the effect of the self-instructional program, practice time, and contracting were explored for their effect on adherence to self-care activities. Experimental groups (n = 42) scored significantly better than the control group (n = 11) on the knowledge post-test (P < 0.01), performance of joint protection practices (P = 0.01), range of motion exercises (P = 0.01), and adherence to joint protection practices at home (P < 0.01). Groups did not differ on adherence to range of motion exercises at home (P = 0.83). | |
| 8324953 | T cell vaccination in humans: the experience in rheumatoid arthritis. | 1993 Mar | To determine the effects of T cell vaccination (TCV) in patients with rheumatoid arthritis (RA), thirteen RA patients were inoculated with attenuated synovial T lymphocytes which contain the putatively pathogenic cells. The procedure was technically feasible and free from toxicity. Variable clinical and immunological responses were found. However, in one patient with recent onset disease and treated with a defined T cell clone, a temporary beneficial response coincided with depressed mitogen reactivity and a decrease of rheumatoid factors. This study may serve as a lead for future research on TCV in humans. | |
| 1416553 | The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. | 1992 Nov 15 | OBJECTIVE: To explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis. DESIGN: Case series of patients with seropositive rheumatoid arthritis. SETTING: The outpatient clinic of the Division of Rheumatology, Mayo Clinic. PATIENTS: One hundred and two patients with seropositive, erosive rheumatoid arthritis and a minimum disease duration of 3 years. MEASUREMENTS: Patients were genotyped for both HLA-DRB1 alleles and were categorized according to the expression of one or two disease-linked HLA-DRB1 alleles. Identification of HLA-DRB1 alleles was done by the polymerase chain reaction and subsequent oligonucleotide hybridization. Homozygosity for allelic variants was confirmed by sequence analysis. Immunogenetically defined patient subgroups were retrospectively evaluated for joint destruction and patterns of disease manifestation, including rheumatoid organ disease. RESULTS: Of 102 patients, 98 (96%) expressed the disease-linked sequence polymorphism. Forty-seven patients (46%) carried a double dose of the relevant sequence stretch: Twenty-eight patients expressed HLA-DRB1*04 variants on both alleles, and 19 combined an HLA-DRB*04 variant with HLA-DRB1*0101 or DRB1*1402. Nodular disease was present in 100% of patients typed as HLA-DRB1*04/04 and in 59% of patients typed as HLA-DRB1*04 and who had inherited only a single dose of the disease-linked sequence polymorphism (P < 0.0001). Major organ systems were involved in 61% and 11% of these two patient groups, respectively (P < 0.0001); and joint surgery was required in 61% and 25% (P < 0.002), respectively. Patients typed as HLA-DR*04/01 had intermediate clinical courses. CONCLUSION: Genotyping patients with rheumatoid arthritis for both HLA-DRB1 alleles identifies clinical subsets with distinct profiles of disease manifestations. | |
| 7801053 | Learned helplessness and its correlation to impairment, pain, anxiety and depression in rh | 1994 | A Swedish version of the self-report instrument Arthritis Helplessness Index (AHI) is presented. Validity and reliability of the translation has been analyzed. 100 consecutive patients with rheumatoid arthritis (RA) were studied, 78 of which completed 2 self-administered questionnaires with AHI, impairment, pain, anxiety and depression. Furthermore 20 of the patients were interviewed with regard to AHI. Forty-two other patients with RA were analyzed for correlation between AHI and biochemical activity and Signals of Functional Impairment (SOFI). We conclude that the Swedish version of AHI has satisfactory validity and reliability. It correlates with age, physical impairment, pain, anxiety and depression but not with sex or disease activity. Five of the original 15 items could for various reasons be omitted, leaving a 10 statement instrument. AHI is promising as a variable in future outcome studies of RA. | |
| 8329287 | Variability in the stereoselective disposition of ibuprofen in patients with rheumatoid ar | 1993 Jun | 1. Patients suffering from rheumatoid arthritis received oral doses of 600 mg racemic ibuprofen (n = 25; RAC) or 400 mg (S)-ibuprofen (n = 25; S-IBU) in a double-blind, randomized parallel-group study. 2. The pharmacokinetic parameters of (S)-ibuprofen were not statistically different between treatments (P > 0.05). Comparing (S)- and (R)-ibuprofen within the group receiving the racemate significantly higher Cmax (20.3 +/- 5.3 vs 17.7 +/- 4.4 micrograms ml-1; P < 0.02; 95% confidence interval for differences (CI): 0.5-4.6), AUC (86.2 +/- 23.5 vs 67.6 +/- 26.6 micrograms ml-1 h; P < 0.001; CI: 9.5-27.6), mean residence time (4.5 +/- 1.1 vs 4.1 +/- 1.2 h; P < 0.01; CI: 0.1-0.6) and renal clearance (0.8 +/- 0.6 vs 0.0 +/- 0.0 ml min-1; P < 0.001; CI: 0.5-1.0) values were observed for the (S)-enantiomer. 3. No difference was found (P > 0.05) between treatments in the percentage of the dose recovered in the urine as (R)- or (S)-ibuprofen plus metabolites (S-IBU: 80.2 +/- 8.47 vs RAC: 74.1 +/- 14.0%). 4. Interindividual variation in the pharmacokinetics of (S)-ibuprofen following administration of the racemate was similar to that following the administration of the single isomer suggesting that chiral inversion is not a major factor contributing to variability in the disposition of this drug. | |
| 8826997 | Assessing the relative sensitivity to change of rheumatoid arthritis activity measures: is | 1996 Oct | Observational studies and meta-analyses of controlled clinical trials have been used to identify which measures of rheumatoid arthritis activity are most sensitive to change. These analyses often pool studies of different drugs, although it is not known if arthritis activity measures are differentially responsive to different drugs. In meta-analyses, estimates of the relative sensitivity to change of different measures may also be confounded by differences in drug efficacy, if studies of different drugs contribute different measures to the meta-analysis. To determine if the type of treatment acts as an important effect modifier or confounder in studies of the relative sensitivity to change of arthritis activity measures, we computed effect sizes for four measures (weighted tender joint count, grip strength, duration of morning stiffness, and erythrocyte sedimentation rate) used in each of 16 trials of five different disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, cyclosporin A, intramuscular gold, and D-penicillamine) in rheumatoid arthritis. In a complete factorial analysis of variance, effect sizes differed significantly among drugs (p = 0.0006), but differed only marginally among measures (p = 0.08). No interaction was detectable between drugs and measures. These results suggested that effect modification by drugs was not present, but that pooled estimates of the sensitivity to change of different measures may be confounded in meta-analyses, if trials of more efficacious drugs contribute different measures than trials of less efficacious drugs. In a similar analysis of 26 trials of nine nonsteroidal anti-inflammatory drugs, we found significant differences in effect sizes among measures (p < 0.0001), but no differences among drugs (p = 0.96), and no interaction between drugs and measures. This study suggests that pooled analyses of the relative sensitivity to change of arthritis activity measures based on trials of different disease-modifying drugs may be confounded by drug effects, but confounding by drug effects is unlikely if these meta-analyses are based on trials of different nonsteroidal anti-inflammatory drugs. Although the power of these analyses to detect small interaction effects was limited, effect modification by drugs was not observed, indicating that the measures we examined were not strongly differentially responsive to different drugs. | |
| 8574616 | Autoimmunity. Insights provided by the SCID mouse model. | 1995 Jul | CB17 SCID mice have severe combined immunodeficiency as a result of a mutation on chromosome 16 responsible for deficient activity of an enzyme involved in DNA repair. Because VDJ rearrangement does not occur, the humoral and cellular immune systems fail to mature. SCID mice do not reject human cells. They have been used to study the development of human tumors, human hematopoiesis and humoral responses in antibody-dependent organ-specific autoimmune diseases and in systemic lupus erythematosus. Studies involving grafting of synovial membrane under the renal capsule or in the subcutaneous tissue of SCID mice have provided information on the cells involved in the pathogenesis of rheumatoid arthritis. SCID mice have also been used to study adhesion molecules that play a role in the recruitment of lymphocytes in rheumatoid synovial tissue. The SCID mouse model provides new means of investigating immunologic treatments for rheumatoid arthritis. | |
| 7528077 | [Palindromic rheumatism disclosing Whipple's disease. Study of 2 personal cases]. | 1994 Jan | Two patients with palindromic rheumatism were diagnosed with Whipple's disease 5 years after onset of the joint symptoms. Twenty-one previously published cases of Whipple's disease with palindromic rheumatism as the first manifestation were identified. Statistically significant differences were found between palindromic rheumatism in patients with and without Whipple's disease. Patients with Whipple's disease were more likely to be male and to exhibit fever and elevated erythrocyte sedimentation rates during joint symptom flares, whereas they were less likely to have involvement of the metacarpophalangeal and proximal interphalangeal joints. None of the patients with Whipple's disease had either skin manifestations of palindromic rheumatism (nodules or paraarthritis) or positive tests for rheumatoid factor. Patients with palindromic rheumatism exhibiting these features should have an intestinal biopsy to look for Whipple's disease. | |
| 7945483 | Stress fractures of the distal fibula presenting as monarticular flares in patients with r | 1994 Oct | Monarticular flares occurring in patients with rheumatoid arthritis (RA) usually signify either a worsening of the underlying condition or a superimposed septic process. This report describes 2 patients with RA who had stress fractures of the fibular head, masquerading as monarticular flares of ankle arthritis. | |
| 1506748 | [Immunohistochemical localization of interleukin-1 and lipopolysaccharide (LPS) of experim | 1992 May | Sprague Dawley (SD) rats were immunized by subcutaneous injections with heat-killed E. coli 0:14 and lipopolysaccharide (LPS) extracted from E. coli for 15, 29 and 39 weeks which induced arthritis in the ankle. Localization of interleukin-1 (IL-1) and LPS in the ankle joints were investigated immunohistochemically. Serum IgM rheumatoid factor-like substance (RFLS) and anti-LPS IgM were detected by enzyme-linked immunosorbent assay (ELISA). Rats immunized with LPS for 39 weeks developed synovial lining cell hyperplasia in 25 of 40 ankles and lymphoid cell infiltration in 25 and pannus formation in 23, the rates of which were significantly higher than those of control and rats immunized with LPS for 15 and 29 weeks. The induction rate of arthritis in rats immunized with LPS was the same as that in rats immunized with E. coli. LPS and IL-1 were located in synovial cells and pannus in arthritic joints. Changes of RFLS level in rats immunized with LPS were elevated more gradually than those in rats immunized with E. coli. These findings suggest that LPS could stimulate IL-1 and RFLS production and may induce arthritis in rats resembling rheumatoid arthritis. | |
| 8957107 | Immunoregulatory circuits and potential treatment of connective tissue diseases. | 1996 Dec | Connective tissue diseases are generated by different immunoregulatory alterations. Their better knowledge may lead to new treatment modalities. In systemic lupus erythematosus (SLE), increased IL-10 production by non-T cells might exert an inhibitory effect on Thl CD4+ T cells which would explain the decreased T cell functions observed in these patients. In rheumatoid arthritis (RA) patients, there may be a balance within the synovium, where the local production of IFN-gamma may limit the anti-inflammatory properties of IL- 10, thus leading to chronic damage. This article shows that rational approaches to therapy need to be individualized. In SLE, the potential therapeutic use of monoclonal antibodies to IL-10 seems to be gathering strength, whereas in RA exactly the opposite is contemplated: IL-10 is tried for its potential therapeutic use. | |
| 8181365 | Alveolar hemorrhage associated with antineutrophil cytoplasmic antibodies in rheumatoid ar | 1994 May | A 65-year-old woman with previously known rheumatoid arthritis and chronic renal failure of possible glomerular origin was admitted to the hospital because of hemoptysis and respiratory insufficiency. Antineutrophil cytoplasmic antibodies (ANCAs) with antimyeloperoxidase activity were detected in her serum. The lung biopsy specimen evidenced alveolar hemorrhage. Under immunosuppressive therapy with steroids and cyclophosphamide, the patient's condition improved both clinically and radiologically, and the ANCA became negative after 6 months' therapy. | |
| 1420764 | [Hepatic hemangiomas and rheumatoid arthritis in patients treated with azathioprine]. | 1992 Oct | Two clinical cases of patients with rheumatoid arthritis (RA) and poor response to conventional treatment are described. Patients received immunosuppressor treatment with azathioprine (AZA) and developed hepatic hemangiomas without detectable hepatic pathology previous to the treatment with AZA. The hepatic iatrogenesis of AZA is discussed, as well as the etiopathogenic hypothesis regarding hepatic hemangioma. | |
| 8036588 | [Free-radical oxidation in patients with rheumatoid arthritis and anemia]. | 1993 | Antioxidant system was evaluated in 70 RA patients. When the latter had anemia, their antioxidant system underwent changes involving primarily levels of SH groups, peroxide hemolysis index and SOD activity. There appeared a correlation between the shifts in the antioxidant system, anemia severity the disease activity and disturbances in iron metabolism. | |
| 1628169 | Phthalylsulphathiazole in rheumatoid arthritis. | 1992 Jul | Sixteen patients with active rheumatoid arthritis were treated with phthalylsulphathiazole (4 g/day) over a period of 24 weeks. Although there was some statistically significant improvement in plasma viscosity, IgM, pain score, morning stiffness and summated change score, this was either intermittent or not maintained. Five patients withdrew from the trial before completion, four (25%) with non-serious adverse reactions and one patient from lack of efficacy; only one patient elected to remain on the drug beyond the 24-week period. Low free and total sulphathiazole serum concentrations were found, confirming that most of the drug remained within the gut. This investigation suggests, certainly at the dose used, that phthalylsulphathiazole does not have the properties of a second-line agent. Higher doses of the drug will not be ethically feasible. | |
| 1316975 | [Current concept of the management of rheumatoid arthritis based on the pathogenesis]. | 1992 Mar | A new therapeutic concept for the management of rheumatoid arthritis (RA) is strongly required since most traditional methods have failed to introduce remission. This paper attempted to review over novel therapeutic approaches based on the advanced program especially on early stage of RA. Clinical improvement has been observed with tripple combined therapy using such as bucillamine, methotraxate, and sufphasulzopyridine. However, more basic therapeutic program would be required based on the pathogenesis of RA. Here the future development of therapeutic approach including targetting immunosuppression or gene targetting on proliferated synovium has been discussed. | |
| 8278821 | The relative toxicity of alternative therapies for rheumatoid arthritis: implications for | 1993 Oct | The traditional pyramid for the therapeutic progression in rheumatoid arthritis (RA) is based on assumptions that RA is a mild disease, that nonsteroidal antiinflammatory drugs (NSAIDs) have low toxicity, and that disease-modifying antirheumatic drugs (DMARDs) are extremely toxic. This article reviews data from ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), casting strong doubt on these assumptions. NSAIDs result in 1.3% excess gastrointestinal hospitalizations per year. Mortality rates in RA are far above those expected from age- and sex-matched populations. Individual NSAIDs show widely different overall quantitative toxicity indices, as do individual DMARDs. However, the ranges of toxicity of the two classes of drugs show nearly complete overlap. It is suggested that the new therapeutic progression in RA should emphasize initial use of DMARDs, beginning with the least toxic. | |
| 7944642 | Interleukin 1 beta, hand and foot bone mineral content and the development of joint erosio | 1994 Aug | OBJECTIVE: To assess the relationship between plasma levels of the cytokine interleukin-1 beta (IL-1 beta) and the progression of rheumatoid arthritis (RA). METHODS: Two subgroups of patients, one with persistently raised ESR (>/= 50 mm/hour, n = 16, group A) and one with persistently low ESR ( |