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ID PMID Title PublicationDate abstract
9558851 [New methods for measuring atlanto-axial vertical subluxation in rheumatoid arthritis by M 1998 Feb We proposed two new methods of measuring atlanto-axial vertical dislocation in rheumatoid arthritis by MR imaging. One is the distance from the subdental synchondrosis of the axis to the diameter of the ring of the atlas. The other is the distance from the midpoint of the anteroposterior ends of the inferior margin of the axis to the diameter of the ring of the atlas. Values were also determined by the Ranawat method and the Redlund-Johnell method. There was good correlation between values determined by the new methods and those determined by the Ranawat method and Redlund-Johnell method.
10623431 Interleukin 6 knock-out mice are resistant to antigen-induced experimental arthritis. 1999 Dec In order to assess the potential role of IL-6 in rheumatoid arthritis (RA), we have compared IL-6 deficient (IL-6 ko) mice and their wild-type (wt) counterpart for the capacity to develop methylated bovine serum albumin (mBSA)-induced arthritis. Our data show that IL-6 ko mice are not susceptible to antigen-induced arthritis (AIA). In fact, IL-6 ko mice treated by a standard protocol of immunization with mBSA did not develop joint swelling following intra-articular mBSA injection, nor revealed the characteristic joint lesions by histological examination. Conversely, wt mice treated according to the same protocol developed arthritis about 9 days after intra-articular injection, as detected by knee joint swelling and histological confirmation. We observed that the proliferative response of splenocytes to mBSA was impaired in ko mice following arthritis induction, as compared to the strong response observed in wt mice. Furthermore, anti-mBSA IgG levels were lower in ko mice as compared to wt mice. Finally, we show that sensitivity to AIA can be reconstituted in ko mice by subcutaneous injections of recombinant human IL-6 (rhIL-6). In addition, co-administration of IL-6 with mBSA by intra-articular injection into the joint was only partially effective in conferring sensitivity to AIA, suggesting the importance of a systemic effct for IL-6, but also that an additional role for this cytokine can be envisaged in the local inflammatory reaction during establishment of AIA.
11592360 Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound thera 2001 Sep OBJECTIVE: Therapies that deplete lymphocytes often improve symptoms in patients with otherwise refractory autoimmune disease but may result in long-term lymphopenia, the consequences of which are uncertain. To assess the impact of prolonged lymphopenia on morbidity and mortality, we studied patients who had previously received lymphocytotoxic monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA). METHODS: Fifty-three patients who received the lymphocytotoxic mAb CAMPATH-1H between 1991 and 1994 in the United Kingdom were assessed for mortality and infectious and malignant morbidity, by interview and case-note review. In addition, patients were monitored via the National Health Service Central Registry, to verify notification of death. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. A retrospective, matched-cohort study of mortality was also performed with 102 control subjects selected from the European League Against Rheumatism database, which comprises patients with rheumatic disorders who have received immunosuppressive drugs. RESULTS: There was profound and persistent peripheral blood lymphopenia in the mAb-treated patients, affecting predominantly the CD4+ subset. Median CD4+, CD8+, and CD19+ peripheral blood lymphocyte counts at 73-84 months after therapy were 185 cells/microl, 95 cells/microl, and 115 cells/microl, respectively. At a median followup of 71 months (range 14-90), 13 patients had died (24.5%), compared with 18% of the matched controls, providing a mortality rate ratio of 1.45 (95% confidence interval 0.65-3.13). During 283 patient-years of followup, there were 36 infections classified as major (12.7 per 100 patient-years). The causes of death and the spectrum of infections documented were similar to those expected in a hospital-based RA cohort. Patients who received more than 1 course of therapy had more severe lymphopenia than did patients who received a single course, but this did not have an impact on mortality or morbidity. CONCLUSION: Despite the occurrence of profound and long-lasting lymphopenia following treatment with antilymphocyte mAb therapy for RA, this therapy is not associated with a large excess of mortality nor with an unusual spectrum of infections, at least during a medium-term period of followup. These data are also relevant to patients receiving lymphocytotoxic mAb therapy for other indications, and to patients receiving other lymphodepleting therapies such as autologous stem cell transplantation.
9021503 Collection of surgical specimens in total joint arthroplasty. Is routine pathology cost ef 1997 Jan A retrospective review of 715 consecutive cases of total joint arthroplasty (283 hips, 432 knees), performed for a variety of indications during 1992 and 1993, was undertaken to assess the cost effectiveness of routine pathologic examination. The charts were reviewed for preoperative, operative, and pathologic diagnosis, and any discrepancies in diagnosis were noted. Particular attention was paid to pathologic findings suggestive of neoplasia or rheumatoid arthritis that were not noted in the preoperative or operative diagnoses. Six of the 715 cases fit into this category, but all failed to have any clinical significance. No alteration in patient care resulted from routine pathologic examination. This paper questions the necessity of routinely submitting pathologic specimens in uncomplicated total hip and knee arthroplasty.
11811114 [Subreum efficacy and tolerance in patients with early rheumatic arthritis]. 2001 AIM: To evaluate effectiveness and tolerance of subreum in early rheumatoid arthritis (RA). MATERIAL AND METHODS: 44 patients with early rheumatoid arthritis. Subreum was given as a single drug and in combination with other basic drugs. Tolerance was evaluated in all the examinees, the effect--in 13 patients who finished the 6-month treatment by the articular syndrome, by ACR, DAS and HAQ criteria. RESULTS: By DAS, a good response was achieved in 2 patients (15%), a satisfactory one--in 3 (23%) patients. By ACR criteria, a 20% and 50% improvement was obtained in 3 (23%) and 4 (31%) patients. Side effects were absent in 41 (93%) patients. CONCLUSION: Subreum proved effective and well tolerable in early RA.
10386894 B lymphocyte galactosyltransferase protein levels in normal individuals and in patients wi 1998 Nov We have quantified the level of beta4-galactosyltransferase protein in human B lymphocytes using an ELISA-based assay. Between 1-10ng of beta4-galactosyltransferase was detected per mg total cellular protein, indicating that this enzyme constitutes <0.001% of B lymphocyte cellular protein. Akin to previous studies, individuals with rheumatoid arthritis exhibited reduced lymphocytic galactosyltransferase enzyme activity compared with normal controls when using ovalbumin as the acceptor substrate. The levels of enzyme protein present in B lymphocytes from patients with rheumatoid arthritis was, however, not reduced suggesting that the B lymphocyte galactosyltransferase catalytic activity may be regulated post-translationally.
11247876 Differences between female and male patients with familial rheumatoid arthritis. 2001 Apr OBJECTIVE: To determine whether there are genetic differences between female and male patients with familial rheumatoid arthritis (RA). METHODS: 45 men and 119 women from 78 families with RA who all had at least one first degree relative with RA were compared. HLA-DRB1 alleles were analysed, including DRB1*04 subtypes and associations of DRB1*04 haplotypes with DQB1*0301 or DQB1*0302 alleles, the age of the patients at disease onset, the presence of rheumatoid factor (RF), joint erosions, and rheumatoid nodules. RESULTS: HLA-DRB1*13 allele (the subtype allele of DR6, reported to be protective against the development of RA) was found in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4 allele was found slightly more often in men than women patients with familial RA (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset of RA was significantly lower in the female group (40.4 years) than in men (46.6 years, p=0.0044). CONCLUSION: The results indicate that there is stronger genetic background in familial male than female patients with RA in the genetic susceptibility defined by the studied HLA antigens. However, the earlier age of onset of the disease in female group and the increased proportion of women with RA indicate that there are additional sex related predisposing factors enhanced in familial cases.
9272292 Effect of treatment with methotrexate, hydroxychloroquine, and prednisone on lymphocyte po 1997 Jul OBJECTIVE: Polyamines are increased in activated lymphocytes, including peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA), and are important in modulating immune-mediated cellular responses. In vitro studies have suggested that methotrexate (MTX) interferes with polyamine synthesis. This study evaluated the in vivo polyamine response to MTX compared to other anti-arthritic agents, and correlated it with the clinical and immunological response. METHODS: The polyamine content of PBL was determined in 14 RA patients at initiation of treatment with MTX (n = 8), hydroxychloroquine (HCQ) (n = 3), or prednisone (n = 3), and then monthly for four months. IgM rheumatoid factor (RF) synthesis by PBL in vitro was assessed and tender joints were counted monthly. RESULTS: Polyamines (spermine and spermidine) decreased by 55% at three months in the MTX group compared to 4% and 9% in the HCQ and prednisone groups, respectively (p < 0.01). However, group differences in the clinical and immunological response were not significant. In the MTX group there was a positive correlation between polyamine levels and the joint count. Such a correlation was not observed in the other groups. CONCLUSION: These data suggest that MTX interference with the polyamine pathway is not shared by prednisone and HCQ, and is associated with its beneficial effect in RA.
9515133 [Complications and failures of total ankle prosthesis. Apropos of 21 cases]. 1997 PURPOSE OF THE STUDY: The authors relate a heterogeneous series of twenty one total ankle prosthesis performed by the same surgeon with an average follow up of 37 months. MATERIAL AND METHODS: Four types of prosthesis were implanted: 4 Ramses, 8 New Jersey, 5 Star, 4 Freeman. The etiology was seven times a rheumatoid polyarthritis, ten times post-traumatic, two idiopathic arthrosis, an hemochromatosis and a late clubfoot sequelae. RESULTS: Results were appreciated according to Bousquet's criteria: 4 excellent results, 5 good, 3 fair, 9 bad. The ankle mobility was not improved by arthroplasty. We noticed 7 loosening whose 2 septic occurring between 18 and 38 months after implantation of prosthesis. DISCUSSION: This series indicates that prosthesis should be only suggested for patients over sixty years old. No difference was found between post-traumatic and rhumatoîd. The pre-operative subtalar arthrosis promoted in significant way an unexpected failure occurrence. CONCLUSION: Indications for total ankle arthroplasty must remain selected. Arthrodesis remains in the immediate future, the best solution for young patients with post-traumatic arthrosis.
10852383 Different gene loci within the HLA-DR and TNF regions are independently associated with su 2000 Apr The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associated with rheumatoid arthritis (RA) in a population from Lugo region of northwestern Spain. RA patients (n=179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n=145) were recruited. RA susceptibility in this population was predominantly associated with DRB1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04. The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was significantly increased in seropositive patients. The rheumatoid arthritis shared epitope (SE) was associated with increased risk for seropositive and erosive disease and this appeared to operate in a dose-dependent manner. Logistic regression analyses revealed that the TNF microsatellite markers TNFc1 and b3 were associated with RA independently of DRB1*04 and the SE. Carriage of a TNF c1 allele provided an increased risk of RA in SE-negative and SE-heterozygous individuals. TNFc1 and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated with erosive disease which was independent of DRB1*04 and the SE. Further studies will be needed to establish why (TNFc1) polymorphism seemingly associated with low TNFalpha production, is a risk factor for RA.
9358076 The erythropoietic response to erythropoietin in patients with rheumatoid arthritis. 1997 Oct We studied whether orthopedic surgical patients with rheumatoid arthritis (RA) can generate an erythropoietic response to either endogenous erythropoietin or to recombinant human erythropoietin (EPO) therapy to the same extent as patients without rheumatoid arthritis (non-RA). Seventy patients (10 RA, 60 non-RA) were entered into clinical trials of aggressive autologous blood donation before elective orthopedic surgery at one institution, randomized to receive EPO (600 U/kg, iv, 6 times over 3 weeks) or placebo. RA patients given EPO had red blood cell (RBC) production that was enhanced by 624 +/- 137 ml (mean +/- SD) as compared with 271 +/- 174 ml (p = 0.02) for RA patients given placebo treatment. Preoperative RBC volume expansion in 10 RA patients was 5.9 +/- 3.7 ml/kg as compared with 7.4 +/- 3.9 ml/kg for 60 non-RA patients (p = 0.13). RA patients can benefit to the same extent as non-RA patients from aggressive blood conservation programs that incorporate erythropoietin-modulated erythropoiesis.
9480466 [The effect of low dose methotrexate on the course of rheumatoid arthritis--four years of 1997 Ninety-six patients with refractory rheumatoid arthritis were treated with methotrexate for 48 months. We analyzed the effect of low doses of methotrexate (7.5-15 mg weekly) on the activity of the disease and on the progression in damage score. Clinical improvement was observed few weeks after the study was introduced. Following 48 months observation only 32 (33%) remained in the study. Seven of them needed additionally prednisone administration. In 64 (67%) patients the drug was withdrawn: in 18 (19%) due to the side effects, in 24 (25%) due to the lack of effectiveness, in 22 (23%) due to other reasons. Methotrexate did not affect the progression of damage score in our patients. Methotrexate appeared to be usefull drug in the treatment of rheumatoid arthritis, however clinical improvement was observed only during drug administration. After discontinuous of the therapy a flare of the disease was observed.
10782811 Matrix metalloproteinase-3 serum levels are correlated with disease activity and predict c 2000 Apr OBJECTIVE: To demonstrate that serum matrix metalloproteinase-3 (MMP-3) is a variable associated with disease activity and with the response to treatment in rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured and compared to biological and clinical disease activity variables in 20 patients with active RA assessed serially during a one year prospective open label trial with methotrexate or tenidap. RESULTS: MMP-3 levels were significantly correlated with C-reactive protein (CRP) and interleukin 6 serum levels as well as with the disease activity score (DAS), not only at start in untreated patients but also during the 12 month followup period in both treated groups. Early changes (after 0.5, 1, 2, or 3 months) in MMP-3 levels were significantly associated with change in DAS observed 4 to 6 months later. CONCLUSION: In addition to CRP, a systemic marker of inflammation, serum MMP-3 may serve as a consistent synovial derived marker of RA disease activity, early changes of which predict disease outcome.
11056679 Fc gamma R expression on macrophages is related to severity and chronicity of synovial inf 2000 STATEMENT OF FINDINGS: We investigated the role of Fc gamma receptors (Fc gamma Rs) on synovial macrophages in immune-complex-mediated arthritis (ICA). ICA elicited in knee joints of C57BL/6 mice caused a short-lasting, florid inflammation and reversible loss of proteoglycans (PGs), moderate chondrocyte death, and minor erosion of the cartilage. In contrast, when ICA was induced in knee joints of Fc receptor (FcR) gamma-chain(-/-) C57BL/6 mice, which lack functional Fc gamma RI and RIII, inflammation and cartilage destruction were prevented. When ICA was elicited in DBA/1 mice, a very severe, chronic inflammation was observed, and significantly more chondrocyte death and cartilage erosion than in arthritic C57BL/6 mice. The synovial lining and peritoneal macrophages of naïve DBA/1 mice expressed a significantly higher level of Fc gamma Rs than was seen in C57BL/6 mice. Moreover, elevated and prolonged expression of IL-1 was found after stimulation of these cells with immune complexes. Zymosan or streptococcal cell walls caused comparable inflammation and only mild cartilage destruction in all strains. We conclude that Fc gamma R expression on synovial macrophages may be related to the severity of synovial inflammation and cartilage destruction during ICA.
10550221 Systemic characteristics of chronic arthritis induced by transfer of human rheumatoid syno 1999 Nov Erosive human/murine (hu/mu) SCID arthritis, caused by unilateral engrafting of human rheumatoid arthritis synovial membrane (RA-SM) in the knee joints of SCID mice, was monitored for up to 18 weeks by scintigraphic, radiological, morphological and immunohistochemical analyses.(99m)Tc-DPD scintigraphy and histology revealed secondary, oligoarticular spreading of arthritis to contralateral knees and hips, but not to forelimb joints. Also, there were no extraarticular manifestations. At 18 weeks, surviving human cells were found within the pannus, but not directly at the cartilage erosion front, where fibroblast-like cells and macrophages of murine origin predominated. The latter cells also predominated in secondarily affected joints, where no human cells were detectable. Preventive depletion of murine NK-cells by anti-asialo-GMI antibodies, to check the influence of NK cells independently of strain and MHC system, combined with application of autologous human PBMN cells, had virtually no effects on the disease process. The completeness of the SCID defect was not critical, i.e. T cells were completely absent in the organs examined, and the presence of a few B cells in the spleen did not correspond to particular disease features. The SCID defect itself had a clear impact, since, in the chronic phase, SCID.bg and RAG-2(-/-)knockout mice developed less consistent pathological/scintigraphic signs of disease than SCID mice. Thus, unilaterally-induced hu/mu SCID arthritis is an oligoarticular disorder of the hindlimbs. Murine macrophages and fibroblast-like cells appear responsible for tissue destruction in engrafted and non-engrafted arthritic joints.
9128421 [A case of malignant rheumatoid arthritis associated with myelodysplastic syndrome]. 1997 Feb The patient (57 year-old female) complained of high fever and polyarthralgia in autumn of 1994, when a diagnosis of refractory anemia, a type of myelodysplastic syndrome (MDS) was made by severe anemia (RBC: 154 x 10(4)/microliters), leucopenia (2,200/microliters) and erythroid hyperplasia, ring-nucleated myelocyte, micromegakaryocyte and less than 5% of blasts in bone marrow smear. In her further clinical course, symptoms such as episcleritis, mononeuritis multiplex, skin ulcers on bilateral lower legs and circulating disturbance on left lower leg with high titer of rheumatoid factor were appeared in six months, suggesting malignant rheumatoid arthritis (MRA). She also had rectal cancer notified by anal bleeding. In spite of the administration of large doses of glucocorticoid and disease modifying anti-rheumatic drugs, circulating disturbance on left lower leg which might be caused by vasculitis was worsened to show tissue necrosis. Finally, she died of disseminated intravascular coagulation. The association of MDS with rheumatic disorders such as rheumatoid arthritis, Behçet disease and Sjögren's syndrome is not rarely reported. However, this is the first case of MDS associated with MRA.
9675546 Suppressive effects of the new antirheumatic drug KE-298 on TNF alpha-induced production o 1998 KE-298 is a novel antirheumatic drug which suppresses various animal models of arthritis by inhibiting the production of inflammatory cytokines. In a phase II study of rheumatoid arthritis patients, ingestion of KE-298 led to significant improvements in the Lansbury index. The objective of the present study was to clarify the effects of KE-298 against synovium functions, using rheumatoid arthritis synoviocytes. We investigated the effects of KE-298 on the production of matrix metalloproteinases and tissue inhibitor-1 of metalloproteinases and bone absorptive mediators including interleukin (IL)-6 and prostaglandin (PG) E2 in tumor necrosis factor (TNF)-alpha-stimulated rheumatoid arthritis synoviocytes. Rheumatoid arthritis synoviocytes were obtained from knee joints of rheumatoid arthritis patients and type B fibroblast-like synoviocytes were stimulated with TNF-alpha, with or without KE-298. The contents of metalloproteinases and tissue inhibitor-1 of metalloproteinases and IL-6 and PGE2 in culture media were measured by enzyme-linked immunosorbent assay. KE-298 significantly suppressed TNF-alpha-induced production of promatrix metalloproteinase-1 and IL-6, in a dose-dependent manner, but not that of tissue inhibitor-1 of metalloproteinases. The potential of KE-298 to suppress the production of matrix metalloproteinase-1 and IL-6 may explain its efficacy on rheumatoid arthritis.
10544834 Conventional monotherapy compared to a "sawtooth" treatment strategy in the radiographic p 1999 Sep OBJECTIVE: To describe the treatment with disease-modifying antirheumatic drugs (DMARDs) in two inception cohorts of rheumatoid arthritis (RA) patients and to compare their radiographic outcomes. METHODS: A recent onset RA cohort was collected in Heinola in 1973-1975, and another in Jyväskylä in 1983-1989. The cohorts were followed up prospectively and treated with available DMARDs. The radiographic outcomes of 103 and 85 seropositive cohort patients from Heinola and Jyväskylä respectively were assigned Larsen scores (0-100) for their wrist, hand and foot radiographs in years 0, 1, 3, and 8, and compared with each other. RESULTS: In this study it was seen that DMARD treatment for RA became more extensive over time. The earlier cohort patients were treated with gold sodium thiomalate, chloroquine and D-penicillamine, while 8 additional DMARDs and various DMARD combinations were used for the later cohort patients. At the 8 year visit, 23%, 33%, and 2% of the Heinola patients, and 6%, 45%, and 21% of the Jyväskylä patients respectively were being treated with chloroquine, other single DMARDs, or DMARD combinations. Destruction in the peripheral joints remained lower in the more extensively treated cohort; from 0 to 8 years the median Larsen score increased from 1 to 25.5 and from 0 to 12 (p = 0.001) for the Heinola and the Jyväskylä patients, respectively. CONCLUSION: Our result supports a role of DMARDs in preventing joint destruction in RA in the long-term.
10219258 Suppressive influences of methotrexate on the generation of CD14(+) monocyte-lineage cells 1999 Apr An adequate supply of peripheral blood monocytes, granulocytes, and platelets is necessary for an optimal inflammatory process. We have previously demonstrated that the generation of CD14(+) monocyte lineage cells from the bone marrow is accelerated in patients with rheumatoid arthritis (RA). The current studies examined the influences of methotrexate (MTX), a potent disease modifying antirheumatic drug (DMARD), on the capacity of bone marrow progenitor cells to generate CD14(+) cells in patients with RA, in order to delineate its mechanism of action. CD14(-) cells purified from bone marrow specimens of 14 patients with active RA were cultured in the presence or the absence of pharmacologically attainable concentrations of MTX (0.2 microM). After incubation for 14 days, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR. The generation of CD14(+) cells from RA bone marrow CD14(-) progenitor cells was significantly suppressed by MTX. However, the expression of HLA-DR on bone marrow-derived CD14(+) cells was not significantly influenced by MTX. There was no significant difference in the effect of MTX on the generation of CD14(+) cells between patients with prednisolone and those without prednisolone. The production of IL-12 in bone marrow cell cultures was not inhibited, but was rather enhanced, by MTX, suggesting that the suppression of the generation of CD14(+) cells might not be due to the inhibition of cytokine production. The results are consistent with the hypothesis that one of the effects of DMARDs may involve the interference with monocyte differentiation in the bone marrow. Moreover, the data suggest that the generation of CD14(+) cells and the expression of HLA-DR on such marrow-derived CD14(+) cells are regulated by different mechanisms.
9663483 Potential withdrawal of rheumatoid synovium by the induction of apoptosis using a novel in 1998 Jul OBJECTIVE: To investigate whether Fas-mediated apoptosis has potential as a new therapeutic strategy in rheumatoid arthritis (RA) by use of a novel model of RA in which human RA tissue is grafted into SCID mice. METHODS: Fresh rheumatoid synovial tissue including joint cartilage was grafted subcutaneously into the backs of SCID mice. Six weeks after engraftment, anti-Fas monoclonal antibody was injected intraperitoneally. Time-related apoptotic changes caused by anti-Fas monoclonal antibody in grafted synovium were evaluated by nick end-labeling histochemistry. RESULTS: Thirty-six hours after the injection, diffuse apoptotic changes were observed in the grafted synovia. Four weeks after the injection, rheumatoid synovial tissue diminished. CONCLUSION: This is the first report concerning the present effectiveness of anti-Fas monoclonal antibody in diminishing rheumatoid synovium in vivo, and suggests the possibility of a new strategy for treating rheumatoid arthritis by inducing Fas-mediated apoptosis.