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ID PMID Title PublicationDate abstract
11075396 [Value of anti-TNF-alpha molecules in inflammatory and infectious diseases]. 2000 Oct INTRODUCTION: The pathophysiological interest of tumor necrosis factor-alpha (TNF-alpha) has been recently reported in inflammatory and infectious diseases. Thus, TNF-alpha blockade has become a new field of therapeutical research. CURRENT KNOWLEDGE AND KEY POINTS: Several biological agents specifically directed against TNF-alpha are available: anti-TNF-alpha monoclonal antibodies on the one hand--either mainly murine sequence (cA2), partially humanized (CDP 571) or fully human (D2E7)--and TNF-alpha soluble receptors on the other hand (lenercept or etanercept). The first clinical studies reveal interesting results. In rheumatoid arthritis (cA2, etanercept), these molecules may be used either alone or in synergistic combination with methotrexate. They produce a significant response compared to placebo or methotrexate alone, without loss of efficacy in medium-term treatment. In Crohn's disease (cA2 CDP571), they reduce significantly the activity of the disease, compared to placebo, and cA2 makes it possible to accelerate closure of the fistulas. The studies of severe sepsis did not reveal a significant efficacy, however, and only one study has been published on malignant disease, with a possible interesting effect. Even if these medications are usually well tolerated, the frequency of infections is slightly increased. The development of anti-DNA antibodies has also been reported, but drug-induced lupus is highly unusual. FUTURE PROSPECTS AND PROJECTS: Further studies will define the place of anti-TNF-alpha biological agents among the other available treatments of rheumatoid arthritis and Crohn's disease. Because of their high cost, these drugs will probably be limited to patients with active inflammatory disease despite more conventional treatments.
9894908 Peripheral blood monocytes of rheumatoid arthritis patients do not express elevated TNF al 1998 Dec 1 We have compared three monocyte isolation procedures for their suitability in the analysis of cytokine mRNA expression in circulating monocytes. Monocytes were isolated from peripheral blood (1) using antiCD14 coated magnetic beads, (2) by Ficoll centrifugation, or (3) by Ficoll centrifugation followed by plastic adherence. The effect of the isolation procedure on the cytokine mRNA expression levels of the isolated monocytes was evaluated by RT-PCR. Results show that the expression of cytokine mRNAs determined in monocytes isolated using antiCD14 coated magnetized beads reflects best the cytokine mRNA levels in circulating monocytes. We subsequently applied this method to the analysis of cytokine mRNA expression levels in rheumatoid arthritis and control monocytes, which revealed that RA and control monocytes isolated by antiCD14 beads produce similar, very low TNF alpha, IL-1beta, and IL-8 mRNA levels.
9474020 Increased concentrations of serum pentosidine in rheumatoid arthritis. 1998 Feb Advanced glycosylation end products (AGEs) are thought to play an important role in the development of diabetic complications. Oxidative reactions are essential for the formation of some AGEs, termed glycoxidation products. Increased concentrations of pentosidine, one of such products, are found in tissue and serum in diabetes mellitus and in end-stage renal disease, suggesting that hyperglycemia and impaired renal function are important factors in AGE accumulation. We hypothesized that increased concentrations of pentosidine would also be found in pathological conditions associated with increased oxidative stress. We measured pentosidine in sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus, and diabetes. Increased serum pentosidine was found in RA (108.4 +/- 146.5 nmol/L, P < 0.002) and in diabetes (69.6 +/- 42.4 nmol/L, P < 0.001) as compared with healthy subjects (48.3 +/- 12.0 nmol/L). These results prove that AGEs may accumulate in the absence of hyperglycemia or impaired kidney function.
9926946 The natural history of tibial radiolucent lines in a proximally cemented stemmed total kne 1999 Jan A total of 207 tibial components in total knee arthroplasty (TKA) have been reviewed at a maximum of 10 years after replacement. Twelve knees developed aseptic femoral loosening and were reviewed separately from the remaining 195. All tibial components were fixed with cement confined to the proximal surface of the implant combined with an uncemented stem. In the 195 TKAs with well-fixed femoral components and (presumably) low wear, 15% of tibiae developed early-onset, nonprogressive partial radiolucent lines (RLLs), typically in relation to preoperative sclerosis. Tibial component vertical migration was measured in 36 components: no migration was detected over the course of 5 years whether or not an RLL was present. There was no case of tibial osteolysis, no tibial component was revised for aseptic loosening, and no implant was radiologically loose. In 12 knees, the femoral component loosened with subsidence exposing peripheral bone that caused severe HDP wear. Tibial RLLs were present in 9, and osteolysis was present in 11 (although the tibial component was actually loose in only 1). This material has been used to study 1) the natural history of RLLs in cemented TKA and 2) the outcome of using cement confined to the proximal part of the tibial interface. We conclude that in low-wear prostheses RLLs are due to a failure to inject cement into sclerotic bone. Such lines are nonprogressive and do not affect fixation. In the presence of severe wear, however, they may provide a portal for the entry of debris into the interface causing progression of the RLL and lysis. Proximal cement plus an uncemented stem furnishes adequate tibial fixation, provided that the HDP wear rate is low.
11518655 Histologic study of effects of radiation synovectomy with Rhenium-188 microsphere. 2001 Aug Rhenium-188 microsphere is a relatively new radiation synovectomy agent developed for the treatment of rheumatoid arthritis. It has been shown that the levels of unwanted extra-articular radiation are negligible with this agent. A histologic study was conducted to assess the effect of radiation synovectomy on synovium and articular cartilage after intra-articular injection of various doses of Re-188 microspheres into the knee joints of rabbits. Intra-articular injection of Re-188 microspheres into rabbit knee joints resulted in mild reactive inflammation and thrombotic occlusion of vessels which subsided rapidly. Sclerosis of subsynovium could be seen 12 weeks after injection. No evidence of damage to articular cartilage was noted. There was no significant difference in the articular pattern after injection of 0.3 or 0.6 mCi Re-188 microspheres. This study suggests that a treatment dose of Re-188 microspheres causes transient inflammation of synovium without any detectable damage to the articular cartilage of knee joint.
9059139 Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive reactive arthritis. 1997 Jan OBJECTIVE: To study HLA class II association in reactive arthritis. METHODS: 63 patients with reactive arthritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined by standard microcytotoxity test or by PCR. HLA-B27 subtyping was made by sequencing. RESULTS: 46 (73%) of 63 patients with reactive arthritis were HLA-B27 positive and 24 (38%) were HLA-DRB1*04 positive. When haplotypes were inferred according to the known associations between DRB1 and DQB1 alleles, the frequency of DRB1*04-DQB1*0301 haplotype was found to be 13% (12/92) in HLA-B27 positive reactive arthritis patients, in contrast to 0% in HLA-B27 negative reactive arthritis (P = 0.04) and 1% in random controls (P = 0.0009). However, this combination was also found in 5% of 84 HLA-B27 positive control haplotypes, showing a linkage disequilibrium between B27 and this particular class II haplotype. HLA-DRB1*0408 subtype was found in 8/24 (33%) of the HLA-DRB1*04 alleles in patients with reactive arthritis, accounting for most DQB1*0301 haplotypes, but only in 5/55 (9%) of the DRB1*04 alleles in random controls (P = 0.017). All reactive arthritis patients with this subtype were positive for HLA-B27. DRB1*04-DQB1*0302 haplotype was increased in patients with rheumatoid arthritis (28/92, 30%) compared with reactive arthritis (12/126, 10%) or with the controls (12/100, 12%; P = 0.003). HLA-B*2705 was by far the dominant B27 subtype both in reactive arthritis patients with the particular DRB1*0408-DQB1*0301 haplotype and in controls. It was found in 11 out of 12 DR analysed patients, as well as in 10 out of 11 randomly selected B27 positive controls. CONCLUSIONS: Although no single class II allele was found to be increased among patients with reactive arthritis, HLA-B27, DRB1*0408, and DQB1*0301 might exert a haplotypic effect in the pathogenesis of reactive arthritis, or they may be markers of a subset of B27 haplotypes conferring susceptibility.
11716380 Metal-backed and all-polyethylene tibial components in total knee replacement. 2001 Nov One hundred seventy-five patients with 243 consecutive primary Press Fit Condylar cruciate-substituting total knee replacements were evaluated at a mean of 5.5 years. One hundred thirteen knees had modular metal-backed tibial components and 130 had all-polyethylene tibial components. The mean knee score and functional score for the patients with unrevised components was not significantly different. The incidence of osteolysis and synovitis was higher in patients in the modular metal-backed tibia group (5%; five patients, six knees). No patients in the all-polyethylene tibia group had osteolysis or synovitis. Five revision operations were necessary: four for osteolytic defects and one for synovitis, all in patients in the modular metal-backed tibia group. All of the retrieved polyethylene inserts had evident backside wear. The best case rate of survival of the all-polyethylene tibial components was 96%+/-0.8% at 7 years and for the modular metal-backed components it was 75%+/-10% at 7 years. Metal backing and modularity were added to the Press Fit Condylar total knee replacement design to improve fixation durability. However, the superiority of the modular metal-backed implants remains in question.
11120852 Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the d 2000 Dec 15 Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) produce IL-6 and IL-8, which contribute to inflammation and joint damage. The promoters of both cytokines possess binding sites for NF-kappaB, C/EBPbeta, and c-Jun, but the contribution of each to the regulation of IL-6 and IL-8 in RA FLS is unknown. We employed adenoviral-mediated gene delivery of a nondegradable IkappaBalpha, or dominant-negative versions of C/EBPbeta or c-Jun, to determine the contribution of each transcription factor to IL-6 and IL-8 expression. Inhibition of NF-kappaB activation significantly reduced the spontaneous and IL-1beta-induced secretion of IL-6 and IL-8 by RA FLS and the IL-1ss-induced production of IL-6 and IL-8 by human dermal fibroblasts. Inhibition of C/EBPbeta modestly reduced constitutive and IL-1beta-induced IL-6 by RA FLS, but not by human dermal fibroblasts, and had no effect on IL-8. Inhibition of c-Jun/AP-1 had no effect on the production of either IL-6 or IL-8. Employing gel shift assays, NF-kappaB, C/EBPbeta, and c-Jun were constitutively activated in RA FLS, but only NF-kappaB and c-Jun activity increased after IL-1beta. The reduction of cytokines by IkappaBalpha was mediated through inhibition of NF-kappaB activation, which resulted in decreased IL-6 and IL-8 mRNA. NF-kappaB was essential for IL-6 expression, because fibroblasts in which both NF-kappaB p50/p65 genes were deleted failed to express IL-6 in response to IL-1. These findings document the importance of NF-kappaB for the regulation of the constitutive and IL-1beta-stimulated expression of IL-6 and IL-8 by RA FLS and support the role of inhibition of NF-kappaB as a therapeutic goal in RA.
11286540 Chemokines have diverse abilities to form solid phase gradients. 2001 Apr Chemokines play critical roles in leukocyte recruitment into sites of inflammation such as rheumatoid arthritis (RA). While chemokines immobilized on endothelium (solid-phase), but not soluble chemokines, direct rolling leukocytes to firmly adhere to endothelium, soluble and solid-phase chemokine gradients may play important roles in leukocyte extravasation into the tissue. In this study, we have sought to determine (1) if chemokines can be immobilized on structures in the extravascular space, (2) the mechanisms by which chemokines may be immobilized, and (3) if different chemokines have similar potentials to form solid-phase gradients. While secreted alkaline phosphatase (SEAP)-tagged chemokines SLC (CCL21), TARC (CCL17), and RANTES (CCL5) bound to mast cells and the extracellular matrix (ECM) in RA synovium under physiologic salt conditions, MCP1 (CCL2), MIP1 alpha (CCL3), MIP1 beta (CCL4), and fractalkine (FKN, CX3CL1) fusion proteins did not detectably bind. Chemokine binding to ECM and mast cells in situ and to immobilized heparin was inhibited by high salt and glycosaminoglycans (GAGs) heparin, heparan sulfate, chondroitin sulfate, and dermatan sulfate, but not by dextran or hyaluronan, indicating that the chemokines bind to highly sulfated GAGs. Chemokine binding to synovial structures correlated strongly with avidity of chemokine binding to heparin (SLC > TARC > RANTES > MIP1 beta > MCP1 > MIP1 alpha > FKN). A RANTES mutant with decreased avidity for heparin was not able to bind to ECM or mast cells. Thus, these data indicate that chemokines can bind to ECM and mast cell granule constituents in situ via interactions with GAGs. Further, only a subset of chemokines were able to bind efficiently to structures in the extravascular space, indicating that chemokines may form different types of gradients based on their GAG binding ability and that chemotactic gradients in tissues may be quite complex.
10531072 Expression of laminins and their integrin receptors in different conditions of synovial me 1999 Nov OBJECTIVE: To demonstrate the expression of laminins (Lns) and their integrin (Int) receptors in different synovial samples and synovial membrane-like interface tissues from well fixed and aseptically loosened total hip replacement (THR), and the potential role of Ln-Int interaction in the production of collagenases and cytokines. METHODS: Immunohistochemical staining was done to detect the distribution of EHS Ln, Ln alpha2, alpha3, alpha5, beta1, beta2 chains and Int alpha1, alpha2, alpha3, alpha6, beta1, beta4 subunits in different samples. Double immunofluorescence labelling was used to find colocalisation of Int alpha6 subunit and collagenase-1/collagenase-3/TNFalpha/IL6. RESULTS: General Ln immunoreactivity was detected in all specimens. Ln alpha5, beta1 and beta2, but not alpha2 and alpha3 chains were seen in the synovial lining and the basement membrane of blood vessels with the intensity/extent of labelling in the following rank order: rheumatoid arthritis (RA) loosened prostheses, osteoarthritis, well fixed prostheses, traumatic knees. Among Int subunits, staining for beta1 was usually the strongest, followed by staining for Int alpha6, alpha1, alpha3, and alpha2 subunits, with the same rank order for overall expression of Lns. Int beta4 subunit was not detectable in most of the specimens. Double labelling focused on Int alpha6 subunit disclosed its frequent colocalisation with collagenases 1 and 3 and with tumour necrosis factor alpha and interleukin 6 in synovial lining. CONCLUSION: Synovial lining contains Ln-10, Ln-11, and Int alpha6beta1 and alpha1beta1 receptors. In aseptic loosening of THR, interface tissue has a similar Ln subtype and Int receptor composition as RA synovium, which confirms its "lining-like" phenotype. Synovial lining does not contain Ln-5 (alpha3beta3gamma2) or Int alpha6beta4, which are components of epithelial hemidesmosomes. The expression of Lns and their Int receptors is upregulated in inflammation. The close spatial relation between Ln and its Int receptors in synovial lining cells containing proteinases and cytokines suggests a potential role in joint destruction and prosthetic loosening.
10922071 T cell homeostasis in patients with rheumatoid arthritis. 2000 Aug 1 The immune system is equipped with an extremely large spectrum of structurally diverse receptors to recognize all potential antigens. This fundamental principle of receptor diversity is no longer upheld in patients with rheumatoid arthritis (RA), who have a marked contraction of the T cell receptor repertoire. In this study, the ability of RA patients to produce T cells and to maintain T cell homeostasis was examined. CD4 T cells containing T cell receptor rearrangement excision circles (TREC) were substantially reduced in RA patients; TREC levels in young adult patients matched those of controls 20 years older. Increased self-replication of T cells in RA was indicated by age-inappropriate erosion of telomeres in circulating T cells with almost complete attrition of telomeric reserves in patients 20-30 yr of age. The degree of telomere loss was not related to disease duration or the use of disease-modifying medication and was most pronounced in CD4(+)CD45RO(null) (naive) T cells. The loss of TREC-positive T cells could be a consequence of a primary defect in peripheral T cell homeostasis. Alternatively, RA patients may have impaired thymic function with the increased turnover of peripheral T cells being a secondary compensatory event.
9833247 IgM anti-dsDNA antibodies in systemic lupus erythematosus: negative association with nephr 1998 Antibodies against dsDNA of the IgM class were measured in sera of 352 patients with systemic lupus erythematosus, 81 blood donors and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgM anti-dsDNA antibodies were found in 52.3% of the sera from patients with systemic lupus erythematosus, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 37 laboratory parameters was calculated. There was a highly significant negative correlation between IgM anti-dsDNA antibodies and nephritis as well as all the laboratory parameters indicating renal disease (elevated serum creatinine concentration, proteinuria, erythrocyte casts in the urine). IgM anti-dsDNA antibodies indicate protection of lupus patients against the development of lupus nephritis. Further experiments will show whether application of IgM anti-dsDNA antibodies is effective in treating lupus nephritis.
9058644 In situ expression of protooncogenes and Fas/Fas ligand in rheumatoid arthritis synovium. 1997 Mar OBJECTIVE: To examine the relationship among the expression of protooncogenes such as c-fos and c-myc, Fas antigen, Fas ligand, and apoptosis in the synovial tissue of patients with rheumatoid arthritis (RA). METHODS: The expression of c-fos, c-myc, Fas antigen, and Fas ligand was examined in synovial tissues of 6 patients with RA and 4 with osteoarthritis (OA) using in situ reverse transcriptase (RT) assay and immunohistochemical staining. Apoptosis was detected by TUNEL method in situ. RESULTS: Expression of protooncogenes, c-fos, and c-myc was detected in all samples from patients with RA, but in only a few cells of OA synovium. 30 to 90% of cells in RA synovium positive for these protooncogenes also coexpressed Fas antigen. Fas positive cells in RA synovium underwent apoptosis to a significant degree. Fas ligand mRNA was detected only in mononuclear cells in RA synovium. CONCLUSION: The expression of protooncogenes is closely related to Fas mediated apoptosis in RA synoviocytes.
11171698 Measurement of cytokine and adhesion molecule expression in synovial tissue by digital ima 2001 Mar OBJECTIVE: Digital image analysis (DIA) offers the opportunity to quantify the stained area and staining intensity when synovial tissue (ST) is investigated by immunohistochemical analysis. This study aimed at determining the sensitivity of DIA compared with semiquantitative analysis (SQA). METHODS: Paired ST samples were obtained from the knee joint of 10 patients with rheumatoid arthritis (RA) with active disease and after follow up when complete clinical remission was achieved. ST samples of 10 subjects with non-inflammatory knee pain served as controls. Immunohistochemistry with antibodies against interleukin 1beta (IL1beta) and vascular cell adhesion molecule 1 (VCAM-1) was applied using two staining protocols with 3-amino-9-ethylcarbazole (AEC) or p-diethylaminobenzaldehyde (DAB) as dye. All sections were analysed semiquantitatively (0-4) and DIA of up to a maximum of 60 high power fields (HPF). The average integrated optical density was calculated as the product of the stained area (corrected for total tissue area) and the optical density. RESULTS: Both SQA and DIA enabled the assessment of differences in IL1beta and VCAM-1 expression between ST from active RA, RA in remission, and controls. SQA and DIA showed excellent correlations (IL1beta rs=0.867; p<0.0001: VCAM-1 rs=0.828; p<0.0001). A limited analysis of one region with six HPF still allowed adequate discrimination compared with an extended analysis of three regions with a total of 60 HPF. In general, the red dye (AEC) resulted in better discrimination than the brown (DAB) staining. CONCLUSION: DIA offers a reliable, reproducible, and sensitive analysis of ST sections stained for cytokines and adhesion molecules.
11505512 [Dynamics of interleukin (IL)-18 in serum, synovial fluid and synovial membrane in the pat 2001 Jun OBJECTIVES: IL-18 is a novel cytokine that plays an important role in the Th1 response. The aim of this study is to investigate the dynamics of IL-18 in serum, synovial fluid and synovial membrane in the patients with rheumatoid arthritis. MATERIALS AND METHODS: The serum, synovial fluid and synovial membrane were obtained from RA patients at operation. The levels of IL-18 in the serum and synovial fluid were measured by ELISA. We then examined the expression of IL-18 in synovial tissues using anti-human IL-18 monoclonal antibody in immunohistochemical study. RESULTS: The levels of IL-18 in serum and synovial fluid in RA patients were 193.7 +/- 109.7 pg/ml and 258.8 +/- 238.0 pg/ml, respectively. Compared with OA patients and normal volunteers, the level of IL-18 in RA patients was higher in both serum and synovial fluid. (P < 0.05) In synovial membrane, the cells positive for anti IL-18 antibody were confirmed not only in RA (n = 26) but also in OA (n = 7) patients. The positive cells were the synovial lining cells, macrophages, fibroblasts and endothelial cells. However, a large number of positive cells were demonstrated in synovial tissues in RA compared with OA patients.
10813276 A histochemical study of the rheumatoid synovium: focus on nitric oxide, nerve growth fact 2000 May OBJECTIVE: The synovium of patients with rheumatoid arthritis (RA) is characterized by massive cell proliferation, neoangiogenesis, and apoptosis. The nature of potential repressors/inducers of these phenomena is still largely unknown. We investigate if nitric oxide (NO) and nerve growth factor (NGF) can be considered potential mediators in these phenomena in RA. METHODS: Synovium of 15 patients with RA in active phase and synovium of 14 patients without synovial inflammation were processed for histochemical (NADPH-diaphorase) and immunohistochemical visualization of different isoforms for the NO synthesis enzyme NO synthase (NOS) and for NGF high affinity receptor trkA. RESULTS: Inducible NOS (iNOS) immunoreactivity and NADPH-diaphorase positivity were found in synoviocytes, fibroblast-like synoviocytes, fibroblasts, and inflammatory cells in the rheumatoid synovium. In the same areas and in the same cell types, although not in the same cells, we also found positivity for the NGF high affinity receptor trkA. CONCLUSION: We suggest that all elements involved in the transduction pathway that is activated by NGF and that proceeds through NO and tumor suppressor p53 are present in the synovium during RA, controlling cell cycle arrest, cell differentiation, and apoptosis.
11694922 Arthroscopic excision of the radial head: Clinical outcome in 12 patients with post-trauma 2001 Nov PURPOSE: We performed arthroscopic radial head excision in a series of patients with either post-traumatic arthritis after a radial head fracture or rheumatoid arthritis of the elbow as an expanded indication for elbow arthroscopy. The purpose of the study was to critically examine the results of arthroscopic chondroplasty of the radial head to determine the safety and effectiveness of the procedure. TYPE OF STUDY: Outcome study and retrospective analysis. METHODS: From 1990 to 1997, arthroscopic radial head resection was performed in 12 patients with either post-traumatic arthritis (n = 10, Mason type II or III) or with rheumatoid arthritis (n = 2). Functional outcome and radiographs were analyzed after a mean follow-up period of 39 months (range, 12 to 97 months). Elbow arthroscopy was performed using a standardized technique. The anterior three quarters of the radial head and 2 to 3 mm of the radial neck were resected with the abrader in the anterolateral portal and the arthroscope in the proximal medial portal. For resection of the posterior portion of the radial head, the abrader may be transferred to the mediolateral portal. This permits resection of the remnants of the radial head posteriorly and also at the proximal radioulnar joint. RESULTS: Preoperatively, patients lacked 23 degrees (range, 5 degrees to 40 degrees ) of extension of the elbow on average. Mean flexion was 111 degrees (range, 60 degrees to 145 degrees ). Patients had unrestricted pronation (limitation of 5 degrees in 2 patients). Two patients had a lack of supination of 15 degrees and 30 degrees. Mean follow up was 39 months (range, 12 to 97 months). Postoperatively, patients lacked 9 degrees (range, 0 degrees to 20 degrees ) of extension of the elbow on average. Mean flexion was 136 degrees (range, 90 degrees to 150 degrees ). No patient had subjective or objective evidence of instability of the elbow. All patients except one reported significant improvement in pain relief and complete relief of mechanical symptoms. CONCLUSIONS: This technically demanding surgical procedure should be reserved for situations of persistent, restricted range of motion and chronic pain. Arthroscopic radial head resection combined with arthroscopic synovectomy relieves elbow stiffness. The surgeon is able to deal with the intrinsic joint pathology, as well as with accompanying symptoms such as synovitis, capsular contracture, or loose bodies.
10335740 The SF-36 Health Survey as a generic outcome measure in clinical trials of patients with o 1999 May OBJECTIVE: To evaluate the psychometric assumptions underlying the construction and scoring of SF-36 scales and summary measures among clinical trial participants with arthritis. METHODS: Cross-sectional SF-36 data from the baseline assessment of adult patients (n = 1,016) participating in four placebo-controlled clinical trials of treatment for arthritis were analyzed with blinding as to treatment. Tests of the completeness of data, scaling assumptions, internal-consistency reliability, and factor structure of SF-36 scales were performed for the combined sample. Eligible participants had at least a 6-month history of moderate to severe osteoarthritis or rheumatoid arthritis of the knee or hip. Participants meeting inclusion criteria had undergone a washout period of 3-14 days before baseline assessment to bring about a flare state in osteoarthritis or rheumatoid arthritis symptoms. Baseline sample sizes for the three osteoarthritis trials were n = 121, n = 341, and n = 187. The baseline sample size for the rheumatoid arthritis trial was n = 367. The average age of participants was 60 years, and the majority were females (72%). Measured were functional health and well-being scales and physical and mental health summary measures from the SF-36 Health Survey acute form. RESULTS: Missing responses ranged from 0.0% to 1.5% across SF-36 items, and scale scores could be computed for 96.8% to 100% of participants across trials. In all four trials, item internal consistency tests were passed (91.4%-97.1%) and item discriminant validity tests were passed (96.9%-100.0%). Across the four trials, internal-consistency reliability coefficients ranged from a low of 0.75 to a high of 0.91 for the eight scales (median = 0.84), exceeding the minimum standards for group comparisons. Ceiling effects were minimal for most scales, and floor effects were noteworthy for the role physical and role emotional scales. Physical and mental health factors identified in previous studies were replicated. CONCLUSION: The SF-36 Health Survey proved to be a psychometrically sound tool for the assessment of the health status of adult participants in clinical trials of arthritis.
11677088 Chemokines in autoimmune disease. 2001 Dec Growing evidence indicates that structural cells play a crucial role in the chronic inflammation of autoimmunity by their recruitment of chemokine-dependent cells. Members of the two functional classes of chemokines, inflammatory and homeostatic, seem to be involved in lymphocyte recruitment and survival, and in establishing ectopic lymphoid structures in the target organs of autoimmune diseases. Results from animal models suggest that chemokines are reasonable therapeutic targets in autoimmunity.
11406522 Importance of NF-kappaB in rheumatoid synovial tissues: in situ NF-kappaB expression and i 2001 Jul OBJECTIVES: To examine whether inhibition of NF-kappaB induces apoptosis of human synovial cells stimulated by tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and anti-Fas monoclonal antibody (mAb). METHODS: The expression of proliferating cell nuclear antigen (PCNA), NF-kappaB, and the presence of apoptotic synovial cells were determined in synovial tissues. Apoptosis of cultured synovial cells was induced by inhibition of NF-kappaB nuclear translocation by Z-Leu-Leu-Leu-aldehyde (LLL-CHO). The activation of caspase-3 and expression of XIAP and cIAP2 in synovial cells in LLL-CHO induced apoptosis was also examined. RESULTS: Abundant PCNA+ synovial cells were found in rheumatoid arthritis (RA) synovial tissue, though a few apoptotic synovial cells were also detected in the RA synovial tissues. Nuclear NF-kappaB was expressed in RA synovial cells. Electrophoretic mobility shift assay showed that treatment of cells with TNFalpha or IL1beta significantly stimulated nuclear NF-kappaB activity. A small number of apoptotic synovial cells expressing intracellular active caspase-3 were found after treatment of cells with LLL-CHO. Although treatment of RA synovial cells with TNFalpha or IL1beta alone did not induce apoptosis, apoptosis induced by LLL-CHO and caspase-3 activation were clearly enhanced in TNFalpha or IL1beta stimulated synovial cells compared with unstimulated synovial cells. Furthermore, induction of apoptosis of synovial cells with caspase-3 activation by anti-Fas mAb was clearly increased by LLL-CHO. The expression of cIAP2 and XIAP in synovial cells may not directly influence the sensitivity of synovial cells to apoptosis induced by LLL-CHO. CONCLUSION: The results suggest that NF-kappaB inhibition may be a potentially important therapeutic approach for RA by correcting the imbalance between apoptosis and proliferation of synovial cells in RA synovial tissue.