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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
8882131 Antibody deficiency associated with gold treatment: natural history and management in 22 p 1996 Sep OBJECTIVE: To perform a clinical and immunological study of patients with rheumatoid arthritis who develop subnormal serum immunoglobulins on gold treatment; to clarify the nature of the defect in antibody production and determine the natural history of this adverse reaction; to use this information to suggest guidelines for the detection, investigation, and management of this complication. METHODS: 22 patients who developed subnormal levels of one or more immunoglobulin isotypes while receiving gold treatment were recruited over a 10 year period from the practice of a single rheumatologist. Antibody production was assessed by measurement of total immunoglobulins and of specific antibody production against polysaccharide and protein antigens, with test immunisation if necessary. RESULTS: Two broad patterns of antibody deficiency were identified: (1) (n = 11) mild, affecting only one immunoglobulin isotype and with normal specific antibody production. These patients were in general able to continue gold without further deterioration in antibody production. (2) (n = 11) severe, affecting two or three immunoglobulin isotypes, with defective specific antibody production. Six patients developed significant infections and were treated with immunoglobulin. Gold was discontinued in all. Normal antibody production recovered in nine patients, and in all but one followed for more than one year. No relation was seen between duration/dose of gold and antibody deficiency. CONCLUSIONS: Gold-induced antibody deficiency may be more common than usually recognised. A spectrum of deficiency exists, with some patients developing infective complications. Antibody production should be monitored in patients on gold treatment.
8406626 Synovial mononuclear phagocytes in rheumatoid arthritis and osteoarthritis: quantitative a 1993 Jul Macrophages are normal constituents of synovial tissue, and in inflammatory synovitis the number of synovial macrophages increases. Synovial macrophages and their secretory products are important in initiating, propagating, and maintaining the synovial inflammation in rheumatoid arthritis (RA). The purpose of this study was to determine the absolute numbers of macrophages in synovia resected from patients with RA and osteoarthritis (OA) and to determine their abilities to produce and/or functionally express tumor necrosis factor (TNF), interleukin-1 (IL-1), and tissue factor (thromboplastin). Results demonstrate that synovial tissue from RA patients (as compared to that from OA patients) weighed more, contained more cells, more macrophages, and more multinucleated giant cells (macrophage polykaryons). Also, isolated cells from both OA and RA patients had tissue factor activity and could produce TNF and IL-1 with in vitro culture, but these parameters were not different in cells from OA and RA patients. RA patients receiving glucocorticoid treatment for their arthritis had fewer total synovial cells than did patients not on glucocorticoids, but treatment with nonsteroidal anti-inflammatory agents did not alter cell numbers. Patient treatment with glucocorticoids or non-steroidal anti-inflammatory drugs did not influence the ability of their isolated cells to produce TNF or IL-1.
8356413 Rifamycin SV versus triamcinolone in local treatment of rheumatoid synovitis. 1993 This study was aimed to evaluate the usefulness of rifamycin SV as an agent for local treatment of rheumatoid synovitis. Rifamycin SV was compared with triamcinolone acetonide in a randomized controlled trial on 87 patients with rheumatoid arthritis and with persistent knee synovitis. The treatment with rifamycin consisted of several weekly intra-articular injections, whereas triamcinolone was given as a single intra-articular injection. At the end of the therapy, 27 (61.4%) of the 44 rifamycin patients and 39 (91%) of the 43 steroid patients responded well to the treatment, and this difference was significant (p < 0.01). Rifamycin SV was responsible for unpleasant local side effects in all cases. In both groups, after 1 year of follow-up the synovitis had relapsed in about 42% of cases. We conclude that rifamycin SV is less useful than triamcinolone acetonide in the local treatment of rheumatoid synovitis.
7980850 Lack of relationship between the Epstein-Barr virus and the antiperinuclear factor/'perinu 1994 Aug Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-positive and 50 APF-negative sera from RA patients were examined for the presence of antibodies to six different EBV antigens. APF was tested in the serum of 40 patients with acute infectious mononucleosis (IM), 48 PNA-expressing donors and 29 non-PNA-expressing donors. The EBV genome was sought in the saliva and buccal cells of both types of donors. The targeted granules of cells from a PNA-expressing donor were studied by electron-microscopy. The prevalence of anti-EBV antibodies was similar in RA patients with and without APF, whereas the APF-positive sera was elevated in acute IM. The titres of anti-EBV antibodies did not correlate to the expression of PNA in the buccal cells of the donors. There was no relationship between this expression and the presence of the EBV genome in the material obtained from 'positive' donors, relative to 'negative' donors. No virus-like particles could be detected inside the granules by electron microscopy. These results indicate that there are no direct relationships between EBV and the APF/PNA system, although APF was present in a number of patients with IM.
8371203 Renal effects of low dose methotrexate in rheumatoid arthritis. 1993 Jul OBJECTIVE: Methotrexate (MTX) treatment at high doses may cause renal failure. The effects of treatment with low MTX doses on kidney function are, however, unknown. The objective of our study was to investigate the effect of low MTX doses on kidney function. METHODS: The glomerular filtration rate was measured as the plasma clearance of 51Cr-EDTA and the clearance of 99mTc-dimercaptoacetyl-triglycine (correction of triglycerine) (99mTc-MAG3), a new renal tubular function agent, was used to measure tubular effects of MTX. RESULTS: Significant decrease of both 51Cr-EDTA clearance from 92 +/- 7 to 83 +/- 5 ml/min x 1.73 m2 (mean +/- SEM) and of the 99mTc-MAG3 clearance from 360 +/- 18 to 309 +/- 15 ml/min x 1.73 m2 (p < 0.05) was observed. CONCLUSION: Our results indicate that low dose MTX treatment (15 mg weekly) may significantly impair kidney function which has to be considered particularly in situations with combined treatment with other potentially nephrotoxic substances.
8583053 Bioabsorbable rods and pins for fixation of metacarpophalangeal arthrodesis of the thumb. 1995 Nov We report results on the use of bioabsorbable pins and intramedullary rods made of high-molecular-weight polylactic acid in both experimental and clinical conditions. In the experimental study, bioabsorbable rods were implanted in rabbit femora. Histologic assessment on nondecalcified bone showed that resorption of the material began at 4 months after implantation and gradually fragmented over a period of 3 years. In 12 patients 13 metacarpophalangeal joints of the thumb were arthrodesed by using one bioabsorbable intramedullary rod with one or two oblique pins. All joints fused within 6 to 8 weeks. During that period there was no sign of inflammation, and there were no nonunions. Postoperative magnetic resonance imaging assessment was done in all rabbits and eight patients. This modality is a useful tool in postoperative evaluation of the position and shape of the rod but is not sufficiently sensitive to assess the presence of local inflammation and the rate of resorption of the rods.
8746610 Effects of the neuropeptide, substance P, on lymphocyte proliferation in rheumatoid arthri 1995 Nov There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10(-10) M to 10(-6) M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.
1335282 Accumulation of multiple T cell clonotypes in the synovial lesions of patients with rheuma 1992 Nov T cell activation in the characteristic synovial lesions of rheumatoid arthritis may play a major role in the pathogenesis of this autoimmune disease. Analysis of T cell clonal diversity in these sites remains equivocal. Using the PCR and subsequent single-strand conformation polymorphism analysis it is possible to assess the degree of junctional diversity in the TCR with minimal selection bias. Concentrating on the beta-chain of the TCR, a paucity of clonotypic T cell expansion is demonstrated in the peripheral blood of healthy individuals. After polyclonal stimulation in vitro (with concanavalin A or phytohemagglutinin) this pattern does not change. In contrast, some T cell clonotypes appear following in vitro stimulation with purified protein derivative. Analysis of the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis indicated many dominant T cell clonotypes. These data argue for a clonally diverse T cell response in the affected tissues of rheumatoid arthritic subjects.
7783054 Soluble receptors for tumor necrosis factor and interleukin-2 in serum and synovial fluid 1995 Mar OBJECTIVE: To compare levels of soluble tumor necrosis factor receptor (TNF-R) and soluble interleukin 2 receptor (sIL-2R) in sera and synovial fluids (SF) of patients with rheumatoid arthritis (RA), reactive arthritis (ReA), and osteoarthritis (OA) in order to investigate the usefulness of soluble cytokine receptors for differentiation diagnosis and their involvement in the pathophysiology of rheumatic diseases. METHODS: Soluble TNF-R (55 kDa), sIL-2R, and TNF-alpha were measured by ELISA in sera and SF of patients with RA, ReA, and OA and correlated with serological and clinical disease activity variables. RESULTS: Serum TNF-R was significantly (p < 0.0001) elevated in RA (4.6 +/- 2.1 ng/ml, mean +/- SD) compared to ReA (2.5 +/- 0.6 ng/ml), OA (2.2 +/- 0.7 ng/ml), and healthy controls (2.0 +/- 0.4 ng/ml). In SF mean TNF-R levels were 21 +/- 9.3 ng/ml in RA, 12.5 +/- 5.1 ng/ml in ReA, and 8.7 +/- 3.7 ng/ml in OA (p < 0.0001 for RA vs ReA or OA; p < 0.02 for ReA vs OA). SF levels were significantly higher in rheumatoid factor (RF) positive than in RF negative patients with RA. In patients with RA, correlations were found between TNF-R and TNF-alpha in SF (r = 0.32, p < 0.01), and between TNF-R and early morning stiffness (r = 0.4, p < 0.003 in serum; r = 0.29, p < 0.05 in SF). However, there was no correlation with disease activity variables such as Ritchie index, erythrocyte sedimentation rate (ESR) or C-reactive protein. Serum levels of IL-2R were elevated in RA and ReA, but a significant difference was found only for RA versus OA and controls (p < 0.0005), whereas in SF significant differences existed between all 3 patient groups (RA/ReA: p < 0.004; RA/OA: p < 0.0001; ReA/OA: p < 0.0003); both in serum and SF, levels of RF positive patients with RA were higher than those of RF negative patients. In patients with RA, IL-2R correlated weakly with ESR (r = 0.24, p < 0.05), iron concentration (r = -0.35, p < 0.005), and CRP (r = 0.24, p < 0.05). CONCLUSION: In RA, in contrast to ReA and OA, TNF-R and IL-2R were not only elevated in the joint fluid but also in serum. This indicates general activation of the immune system in RA, but not in ReA and OA. Therefore the soluble receptors, especially TNF-R, might become useful diagnostic variables to distinguish RA from ReA and OA.
8976643 Thrombin receptor expression in rheumatoid and osteoarthritic synovial tissue. 1996 Nov OBJECTIVE: To investigate the possibility that synovial cells might respond to thrombin in the inflamed human joint, using immunohistochemical detection of thrombin receptors. METHODS: Frozen sections of synovial membrane from 20 patients with rheumatoid arthritis, 16 with osteoarthritis, and four normal controls were stained using a monoclonal antibody to the human thrombin receptor. Sections were also double stained for both receptors and non-specific esterase. RESULTS: Receptor positive cells were present in rheumatoid synovia, with some cells also staining positively for non-specific esterase. In contrast, both osteoarthritic and normal synovia contained very few cells expressing receptors. CONCLUSIONS: Thrombin may mediate important pathological changes during chronic inflammatory joint disease.
1455534 Angioid streaks in Uganda. 1992 Jul A study on the ophthalmoscopic appearance of angioid streaks and their suspected association with local and systemic diseases among ugandan Africans is presented. In all 40 eyes of 20 patients were studied and the results indicate an interesting association with certain diseases.
8704609 [The influence of retinol, tocopherol and cimetidine on the ulcerogenic effect of Orthofen 1995 Nov The influence of retinol, alpha-tocopherol, and cimetidine on ulceration induced by ortophen, indomethacin, naproxen was studied on rats. It was shown that alfa-tocopherol, retinol, and cimetidine reduce the damaging effect of these drugs on the gastroduodenal mucosa of rats thus normalizing the phospholipid content. The influence of alpha-tocopherol and retinol on the side-effects of ortophen was studied in children with rheumatoid arthritis. Ortophen was found to cause gastroduodenal side-effects in more than 30% of patients and decrease the levels of vitamin A and E in children. The use of retinol and alpha-tocopherol in cotherapy decreases the frequency and severity of side-effects and reduces the vitamin deficiency.
8220922 Re-evaluating the need for hospitalization following synovectomy using Yttrium-90 silicate 1993 Nov In 51 patients treated with Yttrium-90 (Y-90) synovectomy for rheumatoid (inflammatory) arthritis (IA) and OA of the knee we found that decreased retained knee activity (RKA) and increased extra-articular activity in lymph nodes and liver are more likely to be found in IA than OA and following bilateral knee injections. Joint inflammation, as assessed by radionuclide blood pool scan but not by SF white cell count, correlates with decreased RKA and increased activity in lymph nodes. Intra-articular steroid had no significant effect on retention or extra-articular uptake. Strict hospital immobilization improves RKA of Y-90 in IA but not in OA. Y-90 synovectomy in OA shows good RKA and low extra-articular uptake. We recommend strict immobilization following Y-90 synovectomy, particularly in IA patients and/or those with high joint blood flow.
8607893 High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthriti 1996 Mar OBJECTIVE: To investigate T cell antigen receptor (TCR) clonotypes in rheumatoid arthritis (RA) lesions. METHODS: Reverse transcriptase-polymerase chain reaction with TCR V beta family-specific primers and subsequent single-strand conformation polymorphism (SSCP) analysis were performed. Direct nucleotide sequencing was also conducted. RESULTS: A distinct clonal expansion of T cells was observed in the synovium. Furthermore, identical bands in samples of different areas of the same lesion were obtained by SSCP analysis. Nucleotide sequencing revealed that T cell clonotypes of identical mobility on SSCP analysis had the same nucleotide sequence and thus were identical clones. In 6 RA patients, 60-100% of the expanded T cell clonotypes had identical migration patterns in 2 different samples, indicating that this percentage represents commonly existing T cell clonotypes in the affected joint. Furthermore, the J beta 2.1 gene segment was used predominantly by the TCR V beta clonotypes that commonly expanded in the different portions of the same joint. CONCLUSION: These results suggest that the immune response in RA is not random, but rather is driven by common stimuli.
1582123 The usefulness of nocturnal resting splints in the treatment of ulnar deviation of the rhe 1992 Mar Seven patients with definite RA and bilateral ulnar deviation of Fearnley grade I were included in a study of the usefulness of nocturnal resting splints. Each patient used the splint on average 17 months on one hand, randomly chosen, with the free hand as control. Joint mobility, grip strength, pain and radiographic findings were recorded at start and finish of the study. Splint treatment influenced grip strength positively, and most patients stated pain relief during the night. However, all but one patient showed progression of ulnar deviation in both hands, and there was no significant difference in progression between treated and nontreated hands. This study thus supported the use of resting splints at night for pain relief but not for prevention of ulnar deviation.
7861349 A 5-10 year follow-up of the Sheehan total knee endoprosthesis in Tayside. 1994 Oct The Sheehan total knee endoprosthesis has been widely used since 1971. It takes the form of a semi-constrained hinge with intramedullary stems cemented into the femur and tibia for fixation. In Tayside the prosthesis has been in use since 1980. The clinical impression was that the prosthesis was not performing well and formal assessment of surviving prostheses was therefore carried out using the Hospital for Special Surgery (HSS) scoring system. Thirty-seven patients were available for follow-up, 15.6% of whom had good results while 40% had poor results according to this assessment. At review, 31% of patients had undergone revision surgery or were awaiting such surgery. This compares poorly with reported results of surface joint replacements. In the light of these results the authors feel that the Sheehan knee replacement is now obsolete.
1514984 Place of residence as a health resort for rheumatic patients. 1992 This paper deals with institutional aspects of health promotion in relation to a research programme comprising five projects currently in operation in various regions of the Federal Republic of Germany. The aim of these projects, which are supported at the federal level, is to provide locally based, interdisciplinary care for rheumatic patients throughout the course of the disease. Different organizational means are applied by the different projects to realize these goals. The project described here started in 1985 in Unna, a small town of some 60,000 inhabitants located in the Ruhr area. It involves intensive efforts in health promotion, the aim being to firmly establish self-help activities in everyday life. The following gives an overview of the project, its objective, structure and programme--especially the "cure seminars" organized on an outpatient basis--and some of the difficulties encountered with regard to practical implementation and the long-term provision of health-oriented care. The last part of the paper deals with the research component of the model.
8307234 Disorders of the temporomandibular joint. 1994 Jan Diagnostic imaging, however impressive and informative, is only one aspect of the diagnostic evaluation required to render an accurate assessment of temporomandibular disorders. A thorough patient history, detailed clinical examination, and correlation of radiographic information are essential to formulate the diagnosis, prognosis, and treatment plan.
8976646 Serum soluble interleukin-2 receptor levels in familial Mediterranean fever. 1996 Nov OBJECTIVE: To investigate serum soluble interleukin-2 receptor (sIL-2R) in familial Mediterranean fever (FMF) and assess its role in acute FMF crisis. METHODS: Serum sIL-2R concentrations were measured in patients with FMF during acute crises and during inactive periods of the disease, using an immunoenzymatic assay kit. Twenty four FMF patients during acute crisis (active FMF), 17 patients with inactive FMF, 24 healthy controls, and 20 active patients with rheumatoid arthritis (as a disease control group) were studied. RESULTS: Serum sIL-2R concentrations were increased during an acute FMF crisis compared with the values in inactive FMF patients and healthy controls (P = 0.0105 and P = 0.0012 respectively), while there was no significant difference between the mean values in active FMF and rheumatoid arthritis patients (P = 0.7325). In 14 of the FMF group whose blood samples were available in both active and inactive phases, sIL-2R concentrations were significantly higher in an acute attack than in an attack-free period (P = 0.027). CONCLUSIONS: An increase in sIL-2R may be a result of hyperreactivity of IL-2R-expressing cells during an acute inflammatory attack of FMF.
7944622 Intraindividual variability of the bioavailability of low dose methotrexate after oral adm 1994 Jul OBJECTIVES: To analyse whether the intraindividual variability of the bioavailability of oral methotrexate in rheumatoid arthritis (RA) is as high as the interindividual variability and whether the bioavailability testing can be simplified. METHODS: Fifteen mg methotrexate was given orally after an overnight fast to 10 patients with RA on two occasions, one week (n = 4) or two years (n = 6) apart, respectively. Plasma samples were taken at specific time intervals and analysed by fluorescence polarisation immunoassay. The areas under the plasma concentration versus time curves from 0 to infinity (AUC) were calculated after fitting to a two-compartment extravascular model with lag time. RESULTS: The interindividual variability of the AUCs showed a more than five fold range from 77 to 471 min x mumol/l. In contrast, the intraindividual differences of AUCs between the two visits ranged from 3 to 100 min x mumol/l, reflecting a 3-30% change in nine of 10 patients. Close correlations were found between the AUCs and the plasma concentrations with a most pronounced correlation eight hours after methotrexate intake (r = 0.975; p < 0.001). CONCLUSIONS: The high interindividual variability of the AUCs was confirmed. Conversely, only a modest intraindividual variability was disclosed. Plasma sample analysis at a single time point four to eight hours after methotrexate application could simplify estimation of the bioavailability.