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ID PMID Title PublicationDate abstract
10063319 A case of pancytopenia secondary to low-dose pulse methotrexate therapy in a patient with 1999 Jan Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved. In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy.
9456010 Depressed fibromyalgia patients are equipped with an emphatic competence dependent self-es 1997 Nov Employing a recently developed questionnaire we studied the self-esteem structure of 61 female fibromyalgia (FM) patients by comparing them with i) 40 healthy psychology students and ii) 37 patients suffering from rheumatoid arthritis. Depressed FM patients (n=36) had a high need to gain self-esteem through competence and others' approval combined with a low basic sense of self-esteem. In this regard they differed significantly from the healthy controls who had a more equal amount of the two types of self-esteem. These patients had also a more demanding and "hard-driving" self-esteem structure than either control group and exhibited a lower self-assertiveness and less emotional candour than the healthy controls. The non-depressed FM patients did not display this self-esteem pattern. In conclusion, FM patients are probably not a homogeneous group. Furthermore, we suggest that an emphatic competence-dependent self-esteem is one vulnerability factor which, in proper genetic and environmental conditions, increases susceptibility to fibromyalgia and depression.
9194211 Elevated levels of insulin-like growth factor (IGF) binding protein-3 in rheumatoid arthri 1997 The objective of this study was to quantify insulin-like growth factor (IGF) binding proteins (IGFBPs) in the synovial fluid (SF) and plasma of patients with rheumatic diseases and to study the role of these proteins in the regulation of cartilage proteoglycan (PG) synthesis. Immunological determination of IGFBP-2, IGFBP-3, IGF-I, IGF-II, interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) was undertaken in the SF and plasma of 115 patients with rheumatoid arthritis (RA; n = 53), osteoarthritis (OA; n = 44) and other rheumatic disorders. We also determined the effects of SF on bovine cartilage PG synthesis in culture. IGFBP-2 and IGFBP-3 were elevated in the plasma (by 38% and 28%, respectively) and SF (by 56% and 59%, respectively) of patients with RA compared to age- and sex-matched OA controls (determined by RIA and confirmed by Western ligand blot). IGF-I and IGF-II did not differ significantly between the two groups. OA SF, and, to a lesser extent, RA SF stimulated cartilage PG synthesis in culture, and more than 60% of this activity was neutralised by a specific monoclonal anti-IGF-I antibody. Human IGFBP-3 dose-dependently inhibited the stimulation of cartilage PG synthesis effected by SF or human IGF-I. In RA patients, the SF concentration of IGFBP-3 was positively correlated with SF levels of IL-1 beta and TNF alpha, with the serum levels of C-reactive protein and with the erythrocyte sedimentation rate. We concluded that IGF-I is, under the conditions studied, the most important anabolic factor in human SF with respect to articular cartilage PG synthesis. The bioactivity of IGF-I in joints is modulated by IGFBP-3, which is elevated in RA SF compared to OA SF. Elevated IGFBP-3 in RA SF may reduce the availability of IGF-I to articular chondrocytes, thus interfering with cartilage PG synthesis in RA.
11296947 Serum levels of interleukin 6 and stress related substances indicate mental stress conditi 2001 Mar OBJECTIVE: To evaluate the influence of mental stress on the neuroendocrine-immune system in patients with rheumatoid arthritis (RA). METHODS: Twenty-two patients with RA and 8 patients with osteoarthritis (OA) who underwent total knee or hip arthroplasties under general anesthesia were enrolled in the study. The blood levels of interleukin 6 (IL-6) and other substances related to stress were measured just before administering anesthesia on the day of the operation when the patients lay on the operating table and roughly 30 min later when the patients were under general anesthesia without mental stress. These values were compared with those at the same time on the day before the operation, which were considered the control levels. RESULTS: In patients with RA, the levels of IL-6, cortisol, and epinephrine in the peripheral blood were significantly increased under mental stress, before anesthesia (p < 0.01). However, under general anesthesia, the IL-6, cortisol, and epinephrine were significantly decreased, compared with the levels before anesthesia (p < 0.01). Such changes were not apparent in patients with OA. The levels of other substances in the peripheral blood known to be related to stress, such as corticotropin-releasing factor, dopamine, and norepinephrine, showed no changes in patients with RA or OA. CONCLUSION: In patients with RA, excessive mental stress should be eliminated to modify the interaction between the stress-immune system and stress-endocrine system as a method to better control disease activity.
12938511 Effect of Sinomenine on IL-8, IL-6, IL-2 produced by peripheral blood mononuclear cells. 1999 The effect of Sinomenine on IL-8, IL-6, IL-2 and mIL-2R produced by peripheral blood mononuclear cells was investigated by using cell culture, radioimmunoassay and flow cytometry. It was showed that production of IL-8 and mIL-2R was inhibited, but the levels of IL-6 were enhanced by Sinomenine. Our results also demonstrated that Sinomenine did not have any effect on the production of IL-2. The study demonstrated that Sinomenine was able to regulate the production of cytokines. This may be one of the mechanisms by which Sinomenine works on rheumatoid arthritis.
11752504 The prevalence of Mycoplasma fermentans in patients with inflammatory arthritides. 2001 Dec OBJECTIVES: To search for evidence that Mycoplasma fermentans is involved in the pathogenesis of some forms of human arthritis by testing for the presence of mycoplasmal DNA in joint material. METHODS: M. fermentans DNA was detected by the identification of a 104-base pair amplification product of the polymerase chain reaction (PCR). RESULTS: M. fermentans DNA was detected in synovial fluid samples from six (17%) of 35 patients with rheumatoid arthritis (RA) and 18 (21%) of 85 patients with seronegative arthritis. These detection rates were significantly greater than in samples from patients with osteoarthritis or crystal synovitis, none of 26 of these being positive. CONCLUSIONS: M. fermentans could be involved in the pathogenesis of some forms of inflammatory arthritis and this possibility is worthy of further study.
9214433 Use of T cell receptor/HLA-DRB1*04 molecular modeling to predict site-specific interaction 1997 Jul OBJECTIVE: To use molecular modeling tools to analyze the potential structural basis for the genetic association of rheumatoid arthritis (RA) with the major histocompatibility complex (MHC) "shared epitope," a set of conserved amino acid residues in the third hypervariable region of the DRbeta chain. METHODS: Homology model building techniques were used to construct molecular models of the arthritis-associated DRB1*0404 molecule and a T cell receptor (TCR) from T cell clone EM025, which is specific for DR4 molecules containing the shared epitope sequence. Interactive graphics techniques were used to orient the TCR on the DR molecule, guided by surface complementarity analysis. RESULTS: The predicted TCR-MHC-peptide complex involved multiple interactions and specificity for the shared epitope. TCR residues CDR1beta D30, CDR2beta N51, and CDR3beta Q97 were positioned to potentially participate in hydrogen bond interactions with the shared epitope DRbeta residues Q70 and R71. CONCLUSION: These results suggest a structural mechanism in which specific TCR recognition and possibly Vbeta selection are directly influenced by the disease-associated MHC polymorphisms.
11488086 [Anti-TNF alpha in rheumatoid arthritis]. 2001 Jun Thanks to the better understanding of the physiopathological mechanisms in action in rheumatoid arthritis (RA), new therapeutic weapons have appeared, which have dramatically modified our approach of the disease. These so-called "biological" therapies antagonize the action of the cytokine at the top of the cascade which maintains the synovial inflammation, and leads to the joint destruction, i.e. the Tissue Necrosis Factor alpha (TNF alpha). Several controlled clinical studies have clearly demonstrated their short and middle term efficacy and safety profile, and they will soon become at the Belgian clinicians disposal. They have a rapid and dramatic effect on the signs and symptoms of RA and they slow down the radiologic progression. Some questions remain unresolved concerning their place in the general therapeutic strategy against RA, due to the uncertainties of their use in the long run, and to their cost.
10384153 Altered memory T cell differentiation in patients with early rheumatoid arthritis. 1999 Jul 1 The chronic immune response in rheumatoid arthritis (RA) might be driven by activated Th1 cells without sufficient Th2 cell differentiation to down-modulate inflammation. To test whether disordered memory T cell differentiation contributes to the typical Th1-dominated chronic inflammation in RA we investigated differentiation of resting CD4+ memory T cells in patients with early (6 wk to 12 mo) untreated RA and in age- and sex-matched healthy controls in vitro. No difference in cytokine secretion profiles of freshly isolated memory T cells was detected between patients and controls. A cell culture system was then employed that permitted the differentiation of Th effectors from resting memory T cells by short term priming. Marked differences were found in response to priming. Th2 cells could be induced in all healthy controls by priming with anti-CD28 in the absence of TCR ligation. By contrast, priming under those conditions resulted in Th2 differentiation in only 9 of 24 RA patients. Exogenous IL-4 could overcome the apparent Th2 differentiation defect in seven patients but was without effect in the remaining eight patients. In all patients a marked decrease in IL-2-producing cells and a significant increase in well-differentiated Th1 cells that produced IFN-gamma but not IL-2 were evident after priming with anti-CD3 and anti-CD28. The data suggest that CD4+ memory T cells from patients with early untreated RA manifest an intrinsic abnormality in their ability to differentiate into specific cytokine-producing effector cells that might contribute to the characteristic Th1-dominated chronic (auto)immune inflammation in RA.
10089029 Clonal expansion of gammadelta-T lymphocytes in an HTLV-I carrier, associated with chronic 1999 Feb We report on an HTLV-I carrier showing clonal proliferation of gammadelta-T lymphocytes associated with chronic neutropenia and rheumatoid arthritis (RA). A 75-year-old Japanese woman had a 20-year history of RA and was found to have neutropenia and lymphocytosis by routine examinations. Her white cell count was 5,800/microl with 89% lymphocytes. The proliferating gammadelta-lymphocytes did not show the typical morphology of large granular lymphocytes (LGL) and were positive for CD3, TCRdelta1, and HLA-DR but negative for CD4, CD8, and deltaTCS1. Clonally rearranged TCRgamma-chain (Jgamma) and TCRbeta-chain (Cbeta1) genes were detected by Southern blot analysis. Clonality of these proliferating gammadelta-T cells was confirmed by CDR3 size analysis for the TCRdelta-chain. Anti-HTLV-I antibody was positive and the pX region of HTLV-I proviral DNA was detected by PCR analysis, but clonal integration of HTLV-I proviral DNA was not detected by Southern blotting analysis. The patient's clinical course has been stable, except for infrequent infectious episodes. The association of HTLV-I/II infection with T-LGL leukemia has been reported by several groups, although most cases exhibit TCRalphabeta+ type T cells. Analysis of the junctional sequence of TCR on T-LGL leukemia cells may clarify the role of HTLV-I/II infection in clonal T-cell proliferation.
11927997 Hy-Flex II total knee system and range of motion. 2002 Apr We developed the Hy-Flex II total knee and ligament balancing system (Hy-Flex II total knee) which provides (1) a flexion angle of at least 120 degrees or more, (2) a range of motion (ROM) comparable to or greater than that before surgery, and (3) occasional full flexion. The system design has several features: small posterior femoral condyle radius, a 4 degrees posterior tilting of the tibial joint surface, and equal tension of the bilateral soft tissues obtained by using a ligament tensor. From September 1997 to June 1999, Hy-Flex II total knee arthroplasty was carried out on 114 joints of 84 patients with rheumatoid arthritis. One year after surgery, the average flexion in our series was 122.1 degrees +/-15.0 degrees. The number of knees operated on which had a flexion angle of 120 degrees or greater was 82 (71.9%) 1 year after surgery among the total of 114 knees. In total, 94 (82.5%) joints obtained the same level or better than the preoperative flexion; 26 (22.8%) attained full flexion 4 weeks after the operation and 15 (13.1%), 1 year after the operation. These results suggest that this system will be able to achieve our aims in almost all rheumatoid knees.
9117183 Why intramuscular methotrexate may be more efficacious than oral dosing in patients with r 1997 Jan In order to compare the relative bioavailability of orally administered methotrexate (MTX) with i.m. administration in patients with rheumatoid arthritis, we compared the pharmacokinetics of MTX at both the usual starting dose of 7.5 mg and at higher established maintenance dosages in 21 patients. Pharmacokinetic measures were repeated approximately 6 and 18 months after baseline while patients consumed their usual maintenance doses of MTX (17.0 +/- 3.8 mg). The relative bioavailability of the usual maintenance dose of MTX was reduced by 13.5% compared with the initial dose of 7.5 mg (P = 0.026). Area under the serum concentration vs time curve (AUC) was significantly reduced with oral vs i.m. administration at usual maintenance doses (decrease of 0.729 mumol.h/l by oral administration, P = 0.027), but not at a 7.5 mg dose of MTX. Clinicians using MTX should not assume constant and complete bioavailability across the dose range used to treat patients with rheumatoid arthritis. Our observations explain the reported clinical success of switching from an oral to a parenteral route of administration in patients receiving maintenance doses of MTX.
9353151 Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell respo 1997 Oct OM-89 is a bacterial (Escherichia coli) extract used for oral administration in the treatment of RA. Given the evidence that immunity to bacterial heat shock antigens plays a critical role in the immunomodulation of arthritis and possibly inflammation in general, the purpose of the present studies was to evaluate the presence and immunogenicity of hsp in OM-89. Furthermore, we studied the effects of OM-89 in an experimental arthritis, where hsp are known to have a critical significance in disease development. In rats immunization with OM-89 was found to lead to proliferative T cell responses to hsp60 and hsp70 of both E. coli and mycobacterial origin. Conversely, immunization with hsp antigens was also found to induce T cell reactivity specific for OM-89. Based on this and the antigen specificity analysis of specific T cell lines, hsp70(DnaK) turned out to be one of the major immunogenic constituents of OM-89. Parenteral immunization with OM-89 was found to reduce resistance to adjuvant arthritis (AA), whereas oral administration was found to protect against AA. Given the arthritis-inhibitory effect of oral OM-89 in AA, it is possible that peripheral tolerance is induced at the level of regulatory T cells with specificity for hsp. This may also constitute a mode of action for OM-89 as an arthritis-suppressive oral drug.
9553358 [Antigliadin antibodies in the absence of celiac disease]. 1998 Antigliadin antibodies (AGA) mark celiac disease, but AGA are also encountered in IgA-nephritis, psoriasis, sickle-cell anemia, hepatic disorders, juvenile rheumatoid arthritis, autoimmune thyroidism and in persons who occupationally contact great amounts of wheat. AGA IgA and/or IgG were registered in 19 of 60 subjects (51 adults and 9 children) with various immunomediated diseases without symptoms of celiac disease: in 4 cases of chronic active hepatitis, in 2 of 4 cases of chronic persistent hepatitis, in 4 of 16 cases of rheumatoid arthritis, in 3 of 19 cases of IgA-deficiency, in 1 of 8 cases of SLE, in 2 cases of postvaccine reaction, in all the single cases of juvenile rheumatoid arthritis, focal scleroderma, macroglobulinemia. IgA only occurred in in 6 patients, IgG- in 6 patients, both IgA and IgG in 7 patients. The most pronounced positive reaction to AGA was recorded in 8-year-old girl with juvenile rheumatoid arthritis. The emergence of AGA in immunomediated diseases may be attributed to the response to food protein in pathological conditions and is often unrelated closely with celiac disease.
9137325 A multicase family with spondylarthropathies. 1997 Thirty six members of a family with symptoms and signs from the skin and/or the joints were examined clinically and radiologically and HLA typed. Fourteen were classified as having inflammatory joint disease, eight of them with more than one disease within the spondylarthropathy group (SpA). Four had psoriasis of the skin, two of whom had psoriatic arthritis. Ten (five males, five females) had radiological signs of sacroiliitis, eight of them fulfilled the criteria for SpA. Five (four males, one female) with sacroiliitis had radiological signs of spine involvement. One female member was classified as having rheumatoid arthritis. Seven with sacroiliitis were HLA-B27 positive, related to the same haplotype. Two with psoriasis were B27 positive and the other two had another haplotype in common. No single HLA antigen or haplotype was associated with the inflammatory joint manifestations or skin lesions. This suggests involvement of other gene loci or coincidence of multicases.
9778226 Validation of rheumatoid arthritis improvement criteria that include simplified joint coun 1998 Oct OBJECTIVE: To study the validity of response criteria for rheumatoid arthritis (RA) that included 28-joint counts instead of more comprehensive joint counts. METHODS: In a double-blind, placebo-controlled trial of 105 patients treated with methotrexate, sulfasalazine, or both, response was evaluated at week 52. Both European League Against Rheumatism and American College of Rheumatology definitions of response, with comprehensive as well as simplified joint counts, were calculated. We studied the differences between the criteria with and without simplified joint counts, the discriminating capacity between treatment groups, and the association with change in functional capacity and joint damage. RESULTS: Response criteria that included 28-joint counts classified patients' responses more conservatively. No differences between treatment groups were found with either set of response criteria. The association with change in functional capacity was significant in all cases. All response criteria were significantly associated with radiographic progression of RA. CONCLUSION: Improvement criteria that include 28-joint counts are as valid as the original improvement criteria that included more comprehensive joint counts.
10638766 Needle arthroscopy of the knee with synovial biopsy sampling: technical experience in 150 1999 Needle arthroscopy is an office-based technique allowing direct visualisation of the knee cavity and selective sampling of the synovial membrane. We performed needle arthroscopy in 150 patients with synovitis of the knee (1) to evaluate the diagnostic potential in early arthritis, (2) to perform therapeutic lavage in persistent inflammatory synovitis and (3) to assess the balance between technical feasibility, safety and patient comfort on the one hand, and the relevance of the obtained macro- and microscopic information for diagnosis and research purposes on the other. After disinfection of the leg and local anaesthesia of the skin and joint, a 1.8-2.7 mm needle arthroscope was introduced into the knee. Synovial fluid was aspirated and lavage of the joint cavity was performed to allow macroscopic evaluation of hyperaemia and hypertrophy of the synovial membrane. Biopsies were taken at inflamed sites, followed by another lavage to remove blood and debris. Needle arthroscopy of the knee is a simple and easy to perform technique made particularly attractive by the local anaesthesia and the ambulatory setting. It allows good macroscopic evaluation of synovial inflammation and selective sampling of the synovial membrane. Biopsies are suitable for RNA and DNA extraction, bacterial or lymphocyte culture, and cell isolation. Because samples were sometimes too small for representative histology, we switched from a 1.8 mm to a 2.7 mm biopsy forceps with good results. In nearly all cases the arthroscopy was well tolerated. Moreover, some patients reported relief of symptoms and even improvement of mobility after lavage of the inflamed joint. No major complications were noted. It was concluded that needle arthroscopy of the knee is a simple, safe and well-tolerated technique, with promising perspectives as a diagnostic, scientific and possibly therapeutic tool in rheumatic diseases.
10512435 Charnley low-friction arthroplasty in rheumatoid patients: a survival study up to 20 years 1999 Sep The survivorship of 1,553 consecutive Charnley low-friction arthroplasties (LFA) in 1,086 patients with rheumatoid arthritis (RA) were analyzed. There were 846 women (1,236 hips) and 240 men (317 hips), with a mean age of 53.1 years (range, 24-77 years; standard deviation, 10.7). A uniform postoperative regimen with protected weight bearing for 2 months (6 months in patients with bone grafting on the acetabular side) was used throughout the whole study. The overall survival with revision as the endpoint was 90.5% (95% confidence interval [CI], 88.7-92.2) at 10 years and 83% (95% CI, 80.3-85.7) at 15 years. The survival of the femoral component was 93.2% (95% CI, 91.8-96.7) and 89.9% (95% CI, 88.0-93.0) at 10 and 15 years, and survival of the acetabulum was 93.6% (95% CI, 92.1-95.1) and 87.1% (95% CI, 84.6-89.5) at 10 and 15 years. The indication for revision was late deep infection in 19 patients (1.2%) and in others aseptic loosening of prosthetic components. Young age, male sex, and secondary reactive amyloidosis impaired significantly the survival of LFA in the RA patients. In all, cemented LFA provided good results, and it can be justified for the treatment of hip destruction in RA.
11375417 Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced art 2001 May Dendritic cells (DCs) are specialized antigen-presenting cells that migrate from the periphery to lymphoid tissues, where they activate and regulate T cells. Genetic modification of DCs to express immunoregulatory molecules would provide a new immunotherapeutic strategy for autoimmune and other diseases. We have engineered bone marrow-derived DCs that express IL-4 and tested the ability of these cells to control murine collagen-induced arthritis (CIA), a model for rheumatoid arthritis in which Th1 cells play a critical role. IL-4-transduced DCs inhibited Th1 responses to collagen type II in vitro. A single injection of IL-4-transduced DCs reduced the incidence and severity of CIA and suppressed established Th1 responses and associated humoral responses, despite only transient persistence of injected DCs in the spleen. In contrast, control DCs and IL-4-transduced T cells or fibroblastic cells failed to alter the course of the disease. The functional effects correlated well with the differential efficiency of DC migration from various sites of injection to lymphoid organs, especially the spleen. The ability of splenic T cells to produce IL-4 in response to anti-CD3 was enhanced after the administration of IL-4-transduced DCS: These results support the feasibility of using genetically modified DCs for the treatment of autoimmune disease.
10936736 Menopause, oestrogens and arthritis. 2000 Jun 30 The menopause coincides with the appearance of many of the common arthritic conditions and with the lessening of severity of others such as SLE. The hormonal changes that occur may modulate these diseases. Thus, hormonal manipulation may have either beneficial or detrimental effects on the incidence and activity of a number of common joint diseases. We review the evidence regarding the effect of the menopause and oestrogen replacement therapy on the pathogenesis, incidence and prevalence and disease activity of osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus and carpal tunnel syndrome.