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ID PMID Title PublicationDate abstract
12605321 Anti-TNF-alpha-induced systemic lupus syndrome. 2003 Feb Anti-TNF-alpha therapies are promising new strategies in the treatment of rheumatoid arthritis (RA). Despite good clinical efficacy and tolerance, the possible occurrence of drug-induced autoimmune disorders remains a matter of concern. Induction of antinuclear (ANA) and anti-DNA antibodies is observed in some patients treated with TNF-alpha inhibitors (anti- TNF-alpha antibodies) or soluble TNF-alpha receptor. Of concern is the possibility of induction of true lupus erythematosus by TNF blockers. Few cases without major organ involvement were reported to be associated with infliximab treatment that resolved after anti-TNF discontinuation. Only four cases have been described with the use of etanercept. We report a new case of infliximab-induced lupus syndrome and two new cases of etanercept-induced lupus syndrome in three patients with RA, all of whom had previous isolated positive ANA.
15571208 Two inhibitors of DNA-synthesis lead to inhibition of cytokine production via a different 2004 Oct Methotrexate (MTX) and mycophenolic acid (MPA) are used in the clinic for their immunosuppressive properties. MTX is widely used for the treatment of rheumatoid arthritis (RA). MPA is used to prevent graft rejection and is now experimentally used in systemic lupus erythematosis and RA. It is known that both drugs interfere with DNA synthesis. However, the precise mechanism of action is still debated. We have analysed the effect of the drugs on cytokine production in whole blood during short cultures. The production of T-cell cytokines was inhibited by both drugs. MTX inhibits cytokine production because MTX induces apoptosis in activated T-cells. MPA inhibits cytokine production by preventing T-cells to progress to the S-phase of the cell cycle. Cytokine production by monocytes was slightly decreased by the drugs. The reason for this inhibition is not clear. These results indicate that T-cells are the main target cells of the immunosuppressive drugs MPA and MTX.
11879550 Expression of interleukin-18 receptor in fibroblast-like synoviocytes. 2002 An excess of the proinflammatory substance IL-18 is present in joints of patients with rheumatoid arthritis (RA), and expression of IL-18 receptor (IL-18R) regulates IL-18 bioactivity in various cell types. We examined the expression of IL-18R alpha-chain and beta-chain and the biologic effects of IL-18 in fibroblast-like synoviocytes (FLS) after long-term culture. The presence of both IL-18R chains was a prerequisite for IL-18 signal transduction in FLS. However, all FLS cultures studied were either resistant or barely responsive to IL-18 stimulation as regards cell proliferation, expression of adhesion molecules ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and the release of interstitial collagenase and stromelysin, IL-6 and IL-8, prostaglandin E2, or nitric oxide. We conclude that the presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA.
12626797 Lower level of synovial fluid interferon-gamma in HLA-B27-positive than in HLA-B27-negativ 2003 Mar OBJECTIVES: To compare the synovial fluid (SF) concentrations of various cytokines in rheumatoid arthritis (RA) and in reactive arthritis, and to look for a correlation between cytokine levels and the presence of HLA-B27 antigen in reactive arthritis patients. METHODS: Concentrations of interleukin (IL) 10, IL-12, IL-18, interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) were determined by commercially available enzyme-linked immunosorbent assays (ELISA) in the SF from 48 patients with reactive arthritis, 33 with RA and 13 with osteoarthritis (non-inflammatory controls). RESULTS: The SF concentrations of IL-10 were significantly lower in patients with reactive arthritis (median 2.3 pg/ml) than in RA patients (median 14.6 pg/ml). The SF levels of IFN-gamma were not significantly different but the ratios of IFN-gamma to IL-10 were significantly higher in patients with reactive arthritis (median 9.2) than in RA patients (median 0.83). When the subset of patients with Chlamydia trachomatis reactive arthritis was considered, the SF concentration of IFN-gamma was significantly lower in HLA-B27-positive (median 2.9 pg/ml) than in HLA-B27-negative patients (median 42.4 pg/ml). After 2 yr of follow-up, two HLA-B27-positive patients, who had low SF levels of IFN-gamma, had a chronic course of arthritis, whereas after 1 yr all HLA-B27-negative patients had complete resolution of arthritis. CONCLUSIONS: The lower IFN-gamma concentrations in HLA-B27-positive patients with C. trachomatis reactive arthritis could be related to the tendency of these patients to have more severe or chronic arthritis.
12404032 [Analgesic dose range finding of lornoxicam compared to diclofenac. Crossover double blind 2002 Jul OBJECTIVE: To evaluate the therapeutic action and safety of lornoxicam, a new non steroidal anti-inflammatory drug, in 2 oral daily dose regimens of 8 and 16 mg in comparison with oral diclofenac 150 mg/day in patients with rheumatoid arthritis. METHODS: Double blind double-dummy cross-over, controlled trial. The two treatments were given for ten-day periods, separated by a three-day wash-out interval. Patients of both sexes with classical or definite rheumatoid arthritis according to the A.R.A. criteria were enrolled in the study. RESULTS: Fourteen patients (12F, 2M) were admitted, mean age 61.6 years +/- 6.7 (+/-SD), duration of illness 12.7 years +/- 11.9. Lornoxicam 8 and 16 mg/day showed a good therapeutic activity, comparable with diclofenac 150 mg/day. Two patients complained adverse events with diclofenac. CONCLUSIONS: Lornoxicam 16 mg/day was associated with a more sharp action and a better tolerability than diclofenac in rheumatoid arthritis. The twice a day dosage of lornoxicam revealed to be appropriate.
15763928 Differential stimulation of three forms of hyaluronan synthase by TGF-beta, IL-1beta, and 2004 This study compares the regulation of three isoforms of hyaluronan synthase (HAS1, HAS2, and HAS3) transcripts and hyaluronan (HA) production by cytokines in human synovial fibroblastic cells derived from tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Levels of HAS mRNA of the cells with or without stimulation were detected using a real-time fluorescence polymerase chain reaction detection system. Concentrations of HA in the culture supernatants of the cells were measured by a sandwich binding protein assay. Molecular weight of HA was evaluated by agarose gel electrophoresis. The relative proportions of the expression pattern of HAS isoforms was similar between RA and OA tissue-derived cells. HAS1 mRNA was upregulated by transforming growth factor-beta and HAS3 mRNA was upregulated by interleukin-1beta and somewhat by tumor necrosis factor-alpha in the RA cells. HAS2 remained unchanged. Differences in the expression pattern of HAS1, HAS2, and HAS3 mRNA by cytokines suggest that these three isoforms are independently and differentially regulated, and each isoform of HAS may have a different role in arthritic joint disease.
15238147 Neutrophil CD177 (NB1 gp, HNA-2a) expression is increased in severe bacterial infections a 2004 Jul The NB1 glycoprotein (CD177, HNA-2a antigen) is exclusively expressed on human neutrophils. As the clinical significance of CD177 expression is unknown, we investigated its expression in healthy individuals before and after stimulation with granulocyte colony-stimulating factor (G-CSF), in patients with rheumatoid arthritis, viral hepatitis, severe bacterial infections and polycythaemia vera. Expression was quantitatively determined by flow cytometry and by real time polymerase chain reaction. Only G-CSF-stimulated individuals and patients with severe bacterial infections and polycythaemia showed a significantly (P < 0.001) increased CD177 expression compared with healthy individuals, indicating that neutrophil CD177 expression can increase significantly in certain clinical conditions.
12918864 The carpometacarpal joint of the thumb: stability, deformity, and therapeutic intervention 2003 Jul The carpometacarpal (CMC) of the thumb is a saddle joint that permits a wide range of motion and is largely responsible for the characteristic dexterity of human prehension. This joint, located at the very base of the thumb, is subject to large physical stresses throughout life. Osteoarthritis (posttraumatic or idiopathic), rheumatoid arthritis, and postmenopausal laxity of the capsular ligaments can predispose structural instability and impairment of this important joint. The instability is characterized by varying and often progressive dislocation of the joint surfaces, resulting in a displaced axis of rotation and abnormal actions of thumb muscles. The main consequence of the instability is most often pain and weakness, most notably during pinch and grasping actions. This paper is conceptually divided into 2 sections. The first section describes the anatomic structures that maintain stability in the normal CMC joint of the thumb and how disease or trauma can cause instability and ultimate deformity. The second section describes both nonsurgical and surgical interventions that are most often used to treat an unstable CMC joint. This paper is intended primarily as an overview for the physical therapist who does not specialize in the treatment of the hand, although desires basic information on this important topic.
15046432 The fate of augments to treat type-2 bone defects in revision knee arthroplasty. 2004 Mar We report the five- to-ten year results of Anderson Orthopaedic Research Institute type-2 bone defects treated with modular metal augments in revision knee surgery. A total of 102 revision knee arthroplasties in patients with type-2 defects treated with augments and stems were prospectively studied. Seven patients (seven knees) had incomplete follow-up and 15 patients (16 knees) died with the arthroplasty in situ. The mean follow-up of the 79 remaining knees was 7 +/- 2 years (5 to 11). The presence of non-progressive radiolucent lines around the augment in 14% of knees was not associated with poorer knee scores, the range of movement, survival of the component or the type of insert which was used (p > 0.05). The survival of the components was 92 +/- 0.03% at 11 years (95% CI, 10.3 to 11.2). We recommend the use of modular augmentation devices to treat type-2 defects in revision knee surgery.
11817612 Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the I 2002 Jan OBJECTIVE: To evaluate whether coffee, tea, and caffeine consumption are risk factors for rheumatoid arthritis (RA) onset among older women. METHODS: These factors were evaluated in a prospective cohort study that was initiated in 1986 and that included 31,336 women ages 55-69 years without a history of RA. Risk factor data were self-reported using a mailed questionnaire. Through 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (95% CI) were used as the measures of association and were adjusted for age, alcohol use, smoking history, age at menopause, marital status, and the use of hormone replacement therapy. RESULTS: Compared with those reporting no use, subjects drinking > or =4 cups/day of decaffeinated coffee were at increased risk of RA (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA. Multivariable adjustment for a number of potential confounders did not alter these results. The associations of RA onset with the highest categories of decaffeinated coffee consumption (RR 3.10, 95% CI 1.75-5.48) and tea consumption (RR 0.24, 95% CI 0.06-0.98) were stronger in women with seropositive disease compared with those with seronegative disease (RR 1.54, 95% CI 0.62-3.84 and RR 0.93, 95% CI 0.27-3.20, respectively). CONCLUSION: Decaffeinated coffee intake is independently and positively associated with RA onset, while tea consumption shows an inverse association with disease onset. Further investigations of decaffeinated coffee and tea intake as arthritis risk factors are needed to verify these findings and explore their biologic basis.
15144128 CD69 expression on neutrophils from patients with rheumatoid arthritis. 2004 May OBJECTIVE: Since the early activation antigen CD69 has been implicated in the pathogenesis of some inflammatory diseases, we evaluated the expression of the molecule on peripheral blood (PB) and synovial fluid (SF) neutrophils obtained from RA patients and its possible correlation with PB and SF cytokine concentration. METHODS: CD69 membrane expression (and CD11b as control marker) was assessed by indirect immunofluorescence and flow cytometry analysis on purified PB and SF neutrophils. Cytokine levels (GM-CSF, IFN-gamma, TNF-alpha) in plasma and SF supernatants were measured by ELISA. RESULTS: CD69 was absent on control neutrophils, while it was expressed on PB neutrophils from RA patients although no detectable GM-CSF, IFN-gamma or TNF-alpha was observed in their plasma. CD69 expression was still more evident on SF neutrophils from RA patients; 59% had detectable levels of INF-gamma in their SF while GM-CSF and TNF-alpha were detectable in SF from 95% and 33% of RA patients, respectively. However, no correlation was observed between cytokine concentrations and CD69 expression on SF neutrophils. SF but not PB neutrophils from RA patients expressed increased amounts of CD11b when compared to control PB neutrophils without any correlation with CD69 membrane expression. CONCLUSION: The activation antigen CD69 is significantly expressed on PB and SF neutrophils from RA patients. However, the mechanism(s) of induction and its possible role in the pathogenesis of RA remain to be defined.
12928808 [Suspected cases of severe side effects after infliximab (Remicade) in Germany]. 2003 Aug 15 BACKGROUND: Remicade is a chimeric, human-murine, monoclonal antibody. Remicade was approved in the EU in August 1999 for the treatment of active refractory Crohn's disease, and for treating fistulas in subjects with refractory Crohn's disease, and in December 2000 for preventing disease progression in subjects with methotrexate-resistant rheumatoid arthritis. In May 2003, infliximab was approved in the EU for the treatment of ankylosing spondylitis in patients with severe symptoms and elevated serologic parameters of inflammation, who have been refractory to standard treatment. RESULTS: On the basis of the so-called spontaneous capture, the Paul Ehrlich Institute was notified of 44 adverse drug reactions leading to the death of the patient after the application of infliximab in Germany. 18 of these patients had rheumatoid arthritis, eight Crohn's disease, 13 graft-versus-host disease, and five other diseases. 24 of those patients had sepsis or serious infections. According to the manufacturer, 20,000 patients have been treated in Germany with infliximab. DISCUSSION AND CONCLUSION: We discuss, in this article, the question of causal relation with the medication and make recommendations for the safe use of infliximab.
11824560 Metabolism of kalopanaxsaponin K by human intestinal bacteria and antirheumatoid arthritis 2002 Jan When kalopanaxsaponin K (KPK) from Kalopanax pictus was incubated for 24 h at 37 degrees C with human intestinal microflora, KPK was mainly metabolized to kalopanaxsaponin I (KPI) via kalopanaxsaponin H (KPH) rather than via kalopanaxsaponin J (KPJ), and then transformed to kalopanaxsaponin A (KPA) and hederagenin. Bacteroides sp., and Bifidobacterium sp. and Fusobacterium sp. transformed KPK to KPI and KPA and hederagenin via KPH or KPJ. However, Lactobacillus sp. and Streptococcus sp. transformed KPK to KPI, KPA, and hederagenin only via KPJ. The metabolite KPA of KPK showed potent antirheumatoid arthritis activity.
12296867 Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and 2002 Oct The aim of the present study was to evaluate levels of soluble CD 163 in sera and fluids from rheumatoid arthritis (RA) patients and elucidate the mechanism that regulates the shedding of CD163. Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting. To determine the effects of tissue inhibitors of metalloproteinase (TIMPs) on the shedding of CD163 from monocytes/macrophages, levels of soluble CD163 in cultures of monocytes/macrophages and the expression of CD163 on monocytes/macrophages in the presence or absence of TIMPs were examined by a sandwich enzyme immunoassay and flow cytometry, respectively. The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP. TIMP-3, but not TIMP-1 or TIMP-2, inhibited the shedding of CD163 from monocytes/macrophages. It was shown that serum levels of soluble CD163 are a sensitive and reliable marker to monitor activated macrophages in synovitis from RA patients and the results imply that the responsible proteinase for the shedding of CD163 is not a member of the matrix metalloproteinases, but is likely to be a member of ADAMs.
12860282 Endostatin action and intracellular signaling: beta-catenin as a potential target? 2003 Jun 30 Endostatin, the C-terminal part of collagen XVIII, has been shown to inhibit blood vessel formation in different pathological conditions characterized by increased angiogenesis, such as growing tumors. Subcutaneous injection of endostatin in tumor-bearing mice leads to decreased tumor growth, and even in some cases, cure of tumor disease. Endostatin has been tested in a clinical phase I study and shown not to be toxic. Whether the finding in mice that endostatin treatment does not result in development of resistance will hold true in humans is too early to tell. Endostatin binds to a specific motif in heparan sulfate, which may serve a co-receptor function. The structure of a potential primary receptor is not known. The mechanism of action of endostatin in inhibition of angiogenesis and thereby, inhibition of tumor growth, involves apoptosis of tumor cells. The most consistent effect of endostatin on endothelial cells in vitro is inhibition of endothelial cell migration, which may be due to disturbed cell-matrix interactions. An interesting candidate for transducing endostatin's effect on apoptosis and cell migration is beta-catenin, an intracellular protein which participates both in cell adhesion and in transcriptional regulation.
12637427 Mortality following primary total knee arthroplasty. 2003 Mar BACKGROUND: Total joint arthroplasty is one of the most successful orthopaedic surgical procedures. However, it carries a risk of perioperative mortality. The purpose of this study was to determine the mortality rate for patients undergoing primary total knee arthroplasty in a private-practice setting involving one surgeon in a nonteaching institution. METHODS: We analyzed 3048 consecutive primary total knee arthroplasties, performed between July 1976 and December 1996, with respect to mortality data (deaths that occurred intraoperatively, during hospitalization, and within ninety days after surgery) and comorbidities (major cardiovascular disease). RESULTS: The mortality rate was 0.46% (fourteen patients; one death per 217 procedures) within ninety days after primary total knee arthroplasty. CONCLUSIONS: Increasing patient age and the presence of associated cardiovascular comorbidities were identified as risk factors for mortality. This information, we believe, is useful to patients, their families, physicians, and health-care planners in deciding when a total knee arthroplasty is appropriate. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence.
12750940 Plasminogen activator inhibitor-1 as a link between pathological fibrinolysis and arthriti 2004 Mar Behçet's disease (BD) commonly presents with articular manifestations and thrombotic vasculopathy. Arthritis of BD characteristically demonstrates a recurrent and nondestructive course. The pathobiological basis of the thrombotic vasculopathy and protective factors against cartilage destruction in arthritis of BD have not been elucidated. Apart from being involved in fibrinolysis and thrombolysis, the plasminogen activation system can contribute to the pathogenesis of destructive joint diseases such as rheumatoid arthritis (RA). Plasminogen activator inhibitor-1 (PAI-1) is a well known fibrinolysis inhibitor. In this study, local synovial fluid and circulating plasma PAI-1 concentrations of BD were assessed in comparison to RA patients and healthy controls to investigate the nonerosive, nondestructive nature of Behçet arthritis. Twelve patients with BD (mean age 34+/-11 years, males:females 6:6), 15 with RA (mean age 36+/-8 years, males:females 3:12), and 15 healthy adults (mean age 32+/-10 years, males:females 6:9) were included in this study. Plasma PAI-1 antigen levels and PAI-1 activities were significantly greater in BD patients than in RA patients and healthy controls ( P<0.001). Synovial fluid levels of both parameters were also higher than in RA patients ( P<0.001). These results suggest that PAI-1 may promote hypofibrinolysis of Behçet's vasculopathy and also have a protective role in the arthritis of BD.
15247519 [A case of pneumocystis carinii pneumonia associated with low dose methotrexate treatment 2004 Jun A 64-year-old man was admitted to our hospital complaining of dyspnea and fever. He had been treated with low-dose methotrexate for rheumatoid arthritis. Chest radiography showed diffuse ground-glass attenuation in both lung fields, and hypoxia was detected. Pneumosystis carinii pneumonia was demonstrated on transbronchial lung biopsy, and the serum beta-D glucan level was high. We started treatment with trimethoprim-sulphamethoxazole, but respiratory failure worsened, and drug-induced pancytopenia occurred. Although trimethoprim-sulphamethoxazole was stopped, pancytopenia persisted and the patient required ventilatory support. After we changed the medication from trimethoprim-sulphamethoxazole to pentamidine, respiratory failure improved. It was thought that pneumocystis carinii pneumonia was associated with low-dose methotrexate and that trimethoprim-sulphamethoxazole interacted with methotrexate to induce severe pancytopenia.
12429533 Receptor activator NF-kappaB ligand (RANKL) expression in synovial tissue from patients wi 2002 Dec OBJECTIVES: To compare receptor activator of NF-kappaB ligand (RANKL) production in the synovial tissue from patients with active rheumatoid arthritis (RA), inactive RA, spondyloarthropathies (SpA), osteoarthritis, and from normal subjects. In addition, to establish the cell lineages expressing RANKL in these tissues. METHODS: Immunohistological analysis of frozen synovial tissue biopsy specimens was performed using a monoclonal antibody (mAb) to detect RANKL. Sections were evaluated by computer assisted image analysis and semiquantitative analysis to compare RANKL expression between groups. Dual and sequential labelling with mAb RANKL and cell lineage specific monoclonal antibodies were used to determine the types of cells expressing RANKL. RESULTS: Higher levels of RANKL were expressed in tissues from patients with active RA and SpA than in tissues from patients with inactive RA, osteoarthritis, and from normal subjects. RANKL protein was associated with CD3 antigen-positive lymphocytes and some macrophages. RANKL was predominantly associated with activated, memory T cells (CD45Ro positive cells) in patients with active RA and spondyloarthropathy (SpA). CONCLUSIONS: The highest levels of RANKL were detected in patients with RA with active synovitis and in some patients with SpA. An increase in RANKL in the inflamed joint of patients with RA, produced by infiltrating activated T cells and macrophages, is likely to be an important cause of joint erosions in RA.
15595320 Epstein-Barr virus-associated lymphoproliferative disorder in a patient with rheumatoid ar 2002 Dec Rheumatoid arthritis (RA) is an autoimmune disease associated with altered immunoregulation and resulting in a deforming polyarthritis. Methotrexate (MTX) is a commonly used second line agent for RA, and there have been several recent reports of Epstein-Barr virus (EBV)-associated polyclonal B cell lymphoproliferative disorder in MTX-treated RA patients. The patient in this report had long standing RA treated with MTX and had recently begun taking a cyclooxygenase-2 (COX-2) inhibitor. She developed a febrile illness associated with severe pancytopenia and leukocytoclastic vasculitic rash followed by diffuse adenopathy, with serologic and pathologic evidence of EBV infection. Previous studies have demonstrated the interaction of MTX and a variety of non-steroidal, anti-inflammatory drugs (NSAIDs) with various clinical manifestations including acute renal failure, pancytopenia, vomiting, diarrhea, elevated liver transaminases, jaundice, mucosal ulcerations, and pyrexia. However, we have not identified previous reports suggesting interaction between MTX and COX-2 inhibitors. We hypothesize that decreased renal elimination of MTX induced by the COX-2 inhibitor resulted in enhanced hematopoietic toxicity and immunosuppression causing the EBV-associated lymphoproliferative disease.