Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 3763222 | [Surgical therapy of chronic polyarthritis of the hand]. | 1986 Aug | Surgical therapy and the common surgical procedures for the rheumatoid hand are presented: synovectomy, boutonnière deformity, swan-neck deformity, arthroplasty, and surgical therapy of the rheumatoid thumb. The indications, early and late results, and the prophylactic value of synovectomy are discussed and compared with synoviorthesis (intra-articular injection of radioisotopic beta-emitters) in early stages of synovitis. In general, radioisotope synovectomy has reduced the need for early operative synovectomy. If synoviorthesis has no significant effect or if biomechanical factors are predominant in the affected joint (tenosynovitis, massive distension of the capsule and extensor mechanism or large masses of fibrin), then operative synovectomy is indicated. Multicenter studies have confirmed that pain can be relieved and joint swelling reduced by synovectomy for over 10 years after the operation. However, no significant preventive or retarding effects could be proven with regard to the progression of deformity or further radiologic changes. The risks in tenosynovectomy are minimal and the prognosis for improved function and prevention of ruptures is excellent. Restorative procedures on tendons are discussed in conjunction with restoration of joint function. Pathogenetic mechanisms of boutonnière and swan-neck deformities and their therapeutical consequences (soft tissue procedures and arthroplasty of the respective joints) are discussed. Because of the unpredictability of joint resection arthroplasty, many attempts have been made to develop joint prostheses. Surgical experience with cemented components, constrained hinges and prostheses with a fixed axis has been disappointing and forbids their routine clinical use. The most widely used device is the silastic spacer developed by Swanson, a silicone rubber implant acting as flexible hinge to maintain the joint relationship and improve resection arthroplasty. Several authors have obtained good long-term results using the Swanson silastic prosthesis for MP and interphalangeal arthroplasty. However, the silastic spacer still leaves room for improvement, which is particularly evident in patients with constitutional or drug-induced (steroid hormones) ligamentous laxity where bone resorption can be seen due to the piston effect and abrasion of the silicone as well as to sinking and often breakage of the prosthesis. Attempts to prevent this effect are reported. To obtain good functional results with MP arthroplasty, adequate function of the interphalangeal joints and thumb is essential.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 3050083 | Phospholipase A2 activity associated with synovial fluid cells. | 1988 | High activity of phospholipase A2 (PLA2) has been detected in synovial fluids (SF) in inflammatory arthritides. Since the source(s) of SF PLA2 has not been identified, we tested PLA2 content in SF cells obtained from 11 SF. Cell sonicates were prepared at 5 X 10(6) cells/ml. In the supernatants of the sonicated SF cells (n = 11), PLA2 activity ranged from 38-755 U/ml, mean 368 +/- 243 (SD) U/ml, compared to 5-64 U/ml, mean 31 +/- 15 (SD) U/ml in sonicates of normal peripheral blood PMN (n = 5) (p less than 0.0001). Spontaneous release of PLA2 from unstimulated SF cells ranged from 26-365 U/ml, mean 131 +/- 144 (SD) U/ml (n = 5), whereas spontaneous release from peripheral blood PMN was negligible. Neither 10(-8) M FMLP nor 5 X 10(-6) M dexamethasone altered extracellular PLA2 release. To assess whether PLA2 adsorbs passively to cell membranes through hydrophobic interaction, normal peripheral PMN were incubated in crude SF (n = 7) with PLA2 ranging from 4,000-24,300 U/ml, or with purified human SF PLA2 or Naja naja PLA2. We found that soluble PLA2 adsorbed to PMN membranes in a concentration dependent fashion. PLA2 activity in sonicates of PMN incubated in crude SF ranged from 185-358 U/ml compared to controls of 21-64 U/ml. Sonicates of PMN incubated with purified human SF PLA2 (5,000-30,000 U/ml) showed progressive concentration dependent increase in PLA2 from 7 +/- 4 to 212 +/- 11 (SD) U/ml (p less than 0.001). PMN incubated with Naja naja PLA2 also showed marked increase in the content of PLA2.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2443146 | Plasma from rheumatoid arthritis patients does not contain abnormally high levels of alpha | 1987 Aug | We measured the levels of alpha 2-macroglobulin (alpha 2M)-proteinase complexes in the plasma of 18 patients with classic rheumatoid arthritis, 11 age-matched patients with noninflammatory back pain and osteoarthritis, and 8 healthy volunteers. In contrast with previous reports, we found no evidence of alpha 2 M-proteinase complexes in the plasma samples from individuals in any of the groups. In our assays, all activity that might have been the result of the presence of such complexes in the plasma samples proved instead to be an artifact attributable to contamination of the anti-alpha 2M antibody immobilized on the AffiGel solid phase with a trypsin-like proteinase. When the contaminating activity was eliminated by pretreatment of the antibody with 1 mM diisopropyl fluorophosphate, no degradation of substrate was detected with any of the plasma samples. However, the ability of the solid-phase assay to detect and quantitate alpha 2M-proteinase complexes when they are present was confirmed in control experiments with plasma samples to which performed alpha 2M-trypsin complexes had been added, or in which alpha 2M-kallikrein complexes had been generated by activation of Hageman factor (coagulation factor XII). We therefore conclude that neither normal plasma nor that from rheumatoid arthritis patients contains measurable amounts of alpha 2M-proteinase complexes. | |
| 2437932 | Identification of class II HLA alloantibodies in placenta-eluted gamma globulins used for | 1987 Apr | Placenta-eluted gamma globulins (PEGG) have been recently and successfully used in the treatment of patients with rheumatoid arthritis. PEGG, eluted at acid pH from large pools of human placentas, contained 99% IgG material. Sephacryl S300 gel filtration revealed a main fraction (76%) of native IgG accompanied by 10% aggregates and 14% digested fragments (as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoelectrophoresis with specific antisera). Previous in vitro data had suggested that alloantibodies to class II HLA antigens were present in this preparation. This study confirms that PEGG and F(ab')2 fragments were able to inhibit stimulating cells in mixed lymphocyte reactions. Additional findings showed that: IgG from PEGG were cytotoxic for the non-T cell population; IgG or F(ab')2 from PEGG bound only to class II HLA-bearing cells; F(ab')2 from PEGG were able to block the complement-mediated cytotoxicity of anti-HLA-DR and anti-DQw1 alloantibodies. These data confirm the presence of class II HLA alloantibodies in PEGG. These antibodies may account for the clinical improvement reported in patients with rheumatoid arthritis. Our findings are similar to recent data showing that the injection of anti-Ia antibodies in experimental animal models decreases the autoimmune process. | |
| 3037685 | Suppression of superoxide generation by normal polymorphonuclear leukocytes preincubated i | 1987 | Polymorphonuclear leukocytes (PMN) isolated from patients with Felty's syndrome (FS) generate fewer superoxide anions (O-2) upon stimulation with fmet-leu-phe than PMN from normal controls or patients with rheumatoid arthritis (RA). In this study, plasma samples were obtained from 12 patients with RA and 12 patients with FS. Incubation of normal PMN in plasma from Felty patients resulted in a significant reduction in both the rate and total quantity of O-2 generation when activated with fmet-leu-phe. This was not observed with plasma from RA patients. The capacity of a plasma sample to suppress O-2 generation correlated with plasma IgG-PMN-binding activity (IgG-PBA) and, to a lesser extent, with the content of circulating immune complexes (CIC). These data suggest that IgG-PBA and possibly CIC have a pathogenetic role in both qualitative and quantitative defects in PMN in Felty patients. | |
| 2827590 | Comparison of the immune response to Epstein-Barr virus and cytomegalovirus in sera and sy | 1987 Nov | The immune response against two herpesviruses has been determined in sera and matched synovial fluids of patients with rheumatoid arthritis (RA) and compared with that of a healthy control population. The increased level of antibody to Epstein-Barr virus (EBV) induced antigens in patients with RA resembles the antibody pattern observed against cytomegalovirus (CMV) induced antigens, which suggests the presence of a pathological condition in patients with RA that can reactivate latent viral infections. The antibody response against EBV and CMV observed in synovial fluids excludes the local production of specific antibodies against EBV and CMV antigens. | |
| 1747134 | Rheumatoid arthritis in women. Incidence rates in group health cooperative, Seattle, Washi | 1991 Dec | As part of a prospective case-control study of newly diagnosed rheumatoid arthritis (RA) in women, we identified all cases of probable, definite, or classic RA diagnosed in 1987-1989 in 18-64-year-old women who were members of a health maintenance organization based in the Seattle, Washington area. Using both the 1958 and the 1987 American Rheumatism Association criteria for the diagnosis of RA and enrollment data from the health maintenance organization, we calculated the incidence by age and diagnostic class. Rates of RA incidence in women increased steadily with age. The incidence of probable, definite, or classic RA ranged from 13.1 per 100,000 person-years at risk for 18-29-year-old women to 82.1 per 100,000 person-years for 60-64-year-old women. The overall incidence rate, age-adjusted to the 1980 US female population, was 27.9/100,000 person-years. The overall incidence rate for definite/classic RA, age-adjusted to the 1980 US female population, was 23.9 per 100,000 person-years. When compared with adjusted rates of incidence of definite RA in Rochester, Minnesota, in 1950-1974, the incidence rates we found were 44.7% lower. Methodologic differences, changes in diagnostic criteria, and a declining incidence of RA among women over time may all be partial explanations for these results. The possible effects of reproductive factors, including oral contraceptives use, are discussed. | |
| 3180564 | Should the patella be resurfaced in total knee arthroplasty? Efficacy of patellar resurfac | 1988 Nov | To assess the long-term efficacy of patellar resurfacing, 100 knees were evaluated in 84 patients. The operations were performed between 1978 and 1982. The follow-up period ranged from 60 to 103 months. The diagnosis was degenerative joint disease (DJD) in 83%, rheumatoid arthritis in 12%, and miscellaneous in 5% of the knees. The implant (47 knees) and nonimplant (53 knees) groups were comparable with respect to age, body size, and length of follow-up period. The analysis revealed equivocal results. Considering all diagnostic categories combined, rest pain was marginally better in the resurfaced group (p = 0.04), but this difference resulted from an unequal distribution of subjects between mild and zero pain categories. Pain with walking, maximum walking distance, ability to climb stairs and rise from a chair, active arc of motion, extensor lag, and quadriceps strength were similar in the two groups. When the DJD group was considered separately, no significant difference emerged. There was little evidence to support a recommendation for routine patellar resurfacing in total knee arthroplasty. | |
| 1777011 | Genetic control of inflammatory arthritis and glomerulonephritis in congenic lpr mice and | 1991 Aug | MRL-lpr/lpr mice spontaneously develop a complex immunological disease characterized by glomerulonephritis, inflammatory erosive arthritis and the production of rheumatoid factors (RF) and anti-DNA antibodies. We have previously reported that, of congenic lpr strains, only MRL-lpr/lpr mice develop synovial pathology suggesting that both the lpr gene and another gene(s) in the MRL background are necessary for the development of arthritis. To define further the genetics of arthritis and its relationship to glomerulonephritis and autoantibody production, we studied disease expression in MRL-lpr/lpr and C57BL/6-lpr/lpr mice and their offspring (BM-lpr/lpr and MB-lpr/lpr). At 6 months of age these mice were killed and bled, and their kidneys and knee joints were removed for pathological studies. Fourteen of 28 MB-lpr/lpr mice displayed synovial hypertrophy, while eight of 28 had significant synovial inflammation. BM-lpr/lpr mice showed similar changes: nine of 22 and eight of 22 exhibited synovial hypertrophy and inflammation respectively. Joints from MRL-lpr/lpr mice revealed 13 of 17 with synovial hypertrophy and 12 of 17 with inflammation, while none of 14 B6-lpr/lpr mice had synovial changes. Renal pathology was minimal in the F1 mice with only mild hypercellularity in seven of 21 MB-lpr/lpr and five of 22 BM-lpr/lpr mice. All MRL-lpr/lpr mice, in contrast, had marked glomerular changes with 12 of 17 exhibiting glomerular crescents. Only one F1 mouse had both arthritis and renal abnormalities. IgM RF levels were elevated in all four experimental groups, but did not correlate with the presence or severity of arthritis. IgG RF levels were elevated in the MB-lpr/lpr and MRL-lpr/lpr mice, but did not correlate with the degree of arthritis. These results indicate that renal disease and arthritis develop independently in lpr mice, possibly on a genetic basis, and that the presence and titer of autoantibodies do not correlate with tissue injury. | |
| 3321208 | Cellular immunity in the joints of patients with rheumatoid arthritis and other forms of c | 1987 Aug | Rheumatoid arthritis (RA), although a systemic illness, is primarily a synovial disease. Morphologic and functional studies of immune cells within the synovium strongly suggest that disordered cellular immunity is key to the pathogenesis of RA. This article describes in detail the various cells found within the rheumatoid joint and compares them with those found in nonrheumatoid synovitis and in normal peripheral blood. | |
| 2825876 | Long-term experience with total joint prosthetic replacement for the arthritic great toe. | 1987 Fall | A report on the use of 130 double-stemmed flexible hinge silicone elastomer implants as total joint replacements for the metatarsophalangeal (MTP) joint of the great toe in 98 patients since 1971. Of the total number of patients involved, 11 were men and 87 were women; the average age per joint was 57 years. The report is based on a minimum follow-up of 12 months, an average follow-up of 9.4 years, and a maximum follow-up of 16 years. Seven patients (10 joints) were lost to follow-up. In the 57 patients with osteoarthritis, 81 joints were replaced; in the 30 patients with rheumatoid arthritis, 37 joints were replaced. Five patients were revised from a failed excisional hemiarthroplasty, and four patients (with five joints involved) were revised from a failed silicone implant hemiarthroplasty. Two patients had a surgically arthrodesed MTP joint taken down and revised to a total joint arthroplasty. The results were graded excellent, good, fair, or poor based on relief of pain and cosmesis. The overall results were good. On the basis of these findings, the author concludes that there is a place for total joint prosthetic replacement with this device in the surgical reconstruction of the painful, destroyed MTP joint of the great toe. | |
| 2585399 | Lack of association of HLA-DR4 with interleukin 1 beta secretion from peripheral blood mon | 1989 Aug | The possible association between HLA-DR4 and interleukin 1 beta (IL-1 beta) secretion from peripheral blood monocytes was analyzed using 34 female patients, with definite rheumatoid arthritis (RA). RA monocytes in serum-free medium or medium supplemented with 10% fetal calf serum secreted IL-1 spontaneously. The level of secretion was enhanced by stimulation with pyrogen-free type II collagen as determined by comparison with 30 healthy individuals matched for age and sex. No association between HLA-DR4 and spontaneous or stimulated IL-1 release from RA monocytes was observed. | |
| 2877172 | Identification of HLA-Dw14 genes in DR4+ rheumatoid arthritis. | 1986 Nov 1 | Genes of the major histocompatibility complex, HLA, are associated with susceptibility to rheumatoid arthritis (RA), but the aetiology of this chronic inflammatory disease is not known. Synthetic oligonucleotide DNA probes were constructed to distinguish between two closely related but distinct alleles encoding the HLA-DR4 specificity in patients with RA. With these allele-specific oligonucleotide probes an uncommon DR4 genetic variant, Dw14, was identified in 6 of 7 RA patients homozygous for HLA-DR4. This allele may play an important part in susceptibility to RA. | |
| 1858441 | [The course of pain with electronic diaries, real time measurements and time series analys | 1991 | Important physiological parameters such as blood pressure, ECG and others are measured today on a continuous basis or at fixed intervals and are documented together with the date and the time. Individual results and subjective data are ascertained through questioning the patient, observation or patient's self-assessment and are documented with paper and pencil, without having any certainty of the exact time of ascertainment or that such is comprehensible. Battery-operated microcomputers have been developed in the form of electronic diaries (E.D.) for patients. Upon emitting an auditory signal, the questions appear in the computer display, and the questions are then correspondingly answered by the patient. These answers are fed to the permanent data store and are transferred on-line and processed at a later time in a PC. The time and data of the entries are simultaneously registered and are included in the complete document when it is later printed out. A capacity of 64 kbytes suffices to accommodate the data collected; likewise, the battery is sufficient for constant use. The entries are made as categorical data or numerically. Free-style entries are not possible. With the aid of a specially-developed program, the courses of a chronic pain syndrome in patients with degenerative joint diseases were studied. The percentage change in the pain course, benefit risk considerations, prognoses with the aid of sequential analyses and plausibility criteria can be calculated from the data. The advantages of this new instrument are its simple handling and reliable functioning. Its disadvantage is that it lacks the possibility to allow free-style entries.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2057724 | [Cytokines, prostaglandin E2, phospholipase A and metalloproteases in synovial fluid in os | 1991 May | Concentrations of prostaglandin E2, interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha, phospholipase A2, collagenase and proteoglycanase activity were determined in synovial fluid from 26 patients with osteoarthrosis of the knee and 10 with rheumatoid arthritis. Osteoarthrosis synovial fluid was characterised by the absence of interleukin 1 beta while tumour necrosis factor alpha and interleukin 6 were present in relatively large amounts, by a very high phospholipase A2 activity contrasting with a very low concentration of prostaglandin E2, and by a collagenase/proteoglycanase activity only slightly less constant and high as in rheumatoid arthritis. In osteoarthrosis patients, the interleukin 6 concentration, but not that of tumor necrosis factor alpha, was correlated with the collagenase and proteoglycanase activity of synovial fluid. | |
| 3487321 | Alpha 1-antitrypsin phenotypes, including M subtypes, in pulmonary disease associated with | 1986 May | Alpha 1-antitrypsin is a glycoprotein that functions as the major protease inhibitor in human serum. Many genetic variants of alpha 1-antitrypsin can be detected by electrophoretic techniques. We used isoelectric focusing on ultrathin gels to determine the common M subtypes as well as other variants of alpha 1-antitrypsin in 62 white patients with rheumatoid arthritis (RA) and 51 white patients with systemic sclerosis (SSc). We found no increased prevalence of variant phenotypes in either disease group as a whole. In RA, however, the association between pulmonary interstitial fibrosis and alpha 1-antitrypsin variants was striking. Interstitial fibrosis was seen on chest roentgenogram in only 1 of 30 subjects apparently homozygous for M1 (the "wild type" or "normal" phenotype), compared with 13 of 32 patients with variant phenotypes. Seven of 15 patients with M1M2 (the most common variant phenotype) had pulmonary fibrosis. In contrast, there was no apparent association of variant phenotypes with pulmonary involvement in SSc. Our findings suggest a possible role of alpha 1-antitrypsin in the pathogenesis of interstitial fibrosis in patients with RA. The absence of such an association in SSc suggests that pulmonary involvement in these 2 rheumatic diseases may have different pathogeneses. | |
| 3490572 | In vivo activation of lymphocytes in rheumatoid arthritis. | 1986 Aug | Spontaneous in vivo proliferation of peripheral blood mononuclear cells (PBM) and T and B lymphocytes from 28 patients with rheumatoid arthritis (RA), 20 healthy individuals and 13 patients with psoriatic arthritis was evaluated. PBM, T (E+) and non-T (E-) cells from patients with active RA proliferated significantly more than the same populations from healthy individuals and patients with inactive RA. In contrast, only E+ cells from PSA patients showed a trend to increased proliferation relative to healthy individuals. AET treated sheep red blood cells (SRBC) inhibited 3HTdR incorporation of highly profilerating PBM of active RA patients. The data suggest in vivo activation of both B and T cells in patients with clinically active RA. | |
| 3548154 | [Treatment with low-dose methotrexate in chronic polyarthritis. Review of the literature]. | 1986 Nov | The therapeutic effect of low-dose MTX-treatment (10-25 mg/week) in active rheumatoid arthritis can be demonstrated by an improvement in clinical and laboratory parameters of disease activity already after 4-6 weeks. The mode of action is not fully understood. Direct anti-inflammatory effects seem to be more important than the weak immunosuppressive properties. Methotrexate treatment is indicated in all very active cases of rheumatoid arthritis, which do not respond to, or do not tolerate, conventional slow-acting antirheumatic drugs. In severe, rapidly progressing diseases MTX can be given without waiting for the effect of other disease modifying drugs. MTX is administered once a week i.v., i.m. or in one oral dose before breakfast. Absorption is reduced by food. The initial weekly dose is 15-25 mg and can be reduced to a minimum of 10 mg (7.5 mg) according to the clinical effect. A combination with antimalarials or gold salts is possible. The prescription of MTX is contraindicated in cases of renal function disturbances, active liver disease, bone marrow disturbances, active infectious diseases, pregnancy and excessive alcohol consumption. The most common side-effects are nausea and vomiting, stomatitis, transient elevations of transaminases. Rare conditions are leucopenia, thrombocytopenia and lung infiltrations. The side-effects are dose-related and disappear with dose reduction. They can be avoided by administering leucovorin 12 hours after giving MTX. Before starting the treatment total blood count with differential count and platelet count, serum creatinine and liver enzymes should be done. These laboratory studies have to be repeated every week for the first month, every two weeks up to the third month and every 1-2 months thereafter. When contraindications are considered and regular controls are made methotrexate is better tolerated than other cytotoxic agents. The rate of withdrawals is lower than with gold-treatment. In low-dose MTX-treatment drug interactions do not play a major role with normal renal function. Concomitant application of nonsteroidal antirheumatic drugs can delay MTX elimination and increase toxicity. We therefore avoid giving these drugs on the day of MTX-administration as far as possible. | |
| 2673081 | Assessment of efficacy and acceptability of low dose cyclosporin in patients with rheumato | 1989 Jul | The efficacy of cyclosporin in a double blind, placebo controlled trial of four months' duration has previously been reported by us. To assess the benefit-to-risk of cyclosporin this study was followed by a one year open trial including 49 of the previous 52 patients. Cyclosporin was given at an initial dosage of 5 mg/kg/day and then modulated on the basis of efficacy and renal toxicity. During the study the drug had to be discontinued in 32 patients: because of inefficacy in 10, side effects in 11, both in nine, and in two because of unrelated events. The significant clinical improvement noted at four months persisted through one year in the 17 patients who continued to receive treatment. Nephrotoxicity of the drug (24 patients) required constant and close monitoring as well as modulation of daily drug dosage during the trial. This study indicated that cyclosporin might be valuable in the treatment of patients with advanced rheumatoid arthritis, in whom other second line agents have failed. | |
| 10105457 | Process evaluation. Assessing re-invention of community-based interventions. | 1990 Jun | Although complete program evaluation includes assessment of the program implementation process as well as examination of impact and outcome variables, such process evaluation does not always occur. During field implementation programs may be changed, or re-invented, by those adopting the innovation. A case study of the Arthritis Self-Care Project, a rural community-based intervention study, demonstrates the importance of process evaluation in determining the actual independent variable. Instances of re-invention uncovered by the Arthritis Self-Care Project are explored, and suggestions are provided for dealing with the re-invention inevitable in field research. |