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ID PMID Title PublicationDate abstract
11123079 Use of biologics in the treatment of childhood rheumatic diseases. 2000 Aug Over the last two decades, progression in the knowledge of molecular biologic techniques has led to a better understanding of immunopathogenesis and identification of several cytokines, which propagate chronic arthritis in both adult and pediatric patients. A number of biologic agents have been developed in targeting different immune markers or mediators with the hope that they may help in controlling the inflammation in the group of patients who are resistant to disease-modifying antirheumatic drugs (DMARDs) and may alter the natural history of the diseases. Tumor necrosis factor (TNF)-alpha is the first to be targeted and its antagonists have been approved. Other biologic agents targeting different markers/mediators have followed and have been tested in clinical trials especially in adult rheumatoid arthritis (RA). Experiences in pediatric use are limited and agents proved to be effective in adult RA are not always transferred the same efficacy in different subtypes of juvenile idiopathic arthritis (JIA). It is reasonable to see the efficacy, and more importantly the safety profiles of each agent before the decision is made to use them in children. This article reviews the published and anecdotal reports of biologic agents that have been used in children with JIA and also focuses on the potential use of other biologic agents in JIA that have been used in trials to combat adult RA.
11233881 [Microbiological and immunological monitoring in polyarticular rheumatoid arthritis after 2001 Feb 9 HISTORY AND ADMISSION FINDINGS: A 51-year-old man with polyarticular rheumatoid arthritis since the age of 10 years, which had required three total joint replacements, presented in a generally good condition for replacement of the left elbow joint, which was swollen and had reduced movement. TREATMENT AND COURSE: The postoperative condition was without complication until the 7th day when arthritic signs set in, interpreted as part of the underlying disease, and cortisone was administered. After microbiological tests had been done and the patient's general state had deteriorated, antibiotic treatment with flucloxacillin and gentamycin as well as local irrigation and suction-drainage of all involved joints was started. Granulocyte and monocyte functions were analysed. Staphylococcal isolates from the patient induced reduced "respiratory burst" activity of the neutrophil granulocytes, apparently the cause of the septic dissemination. He was discharged on the 32. postoperative day, to be followed-up as an out-patient. CONCLUSION: Both adequate antibiotic administration and, especially, thorough local reduction of pathogens are needed for efficacious treatment. Rapid restoration of granulocyte function and of the "immunocompetence" of monocytes within normal limits are part of the reason for a good therapeutic response. This indicates the need for up-to-date preoperative immunological diagnosis in patients with suppressed immunity to assess the risk of infection and thus plan elective intervention.
11247331 Changes in systemic levels of insulin-like growth factors and their binding proteins in pa 2001 Jan OBJECTIVE: To determine whether circulating levels of insulin-like growth factors and their binding proteins are altered in patients with adult onset rheumatoid arthritis. METHODS: Plasma-levels of insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding-protein 2 (IGFBP-2), and IGFBP-3 were measured by radioimmunoassay in 53 patients with clinically active rheumatoid arthritis (RA) and in 51 control subjects. RESULTS: In RA patients plasma levels of IGF-II were lower (601 +/- 34 vs. 731 +/- 32 micrograms/L (mean +/- SEM); p = 0.005; Mann-Whitney rank sum test) than in age- and sex-matched controls (n = 30 per group). In contrast, plasma levels of IGFBP-2 (412 +/- 40 vs. 254 +/- 20 micrograms/L; p = 0.003) and IGFBP-3 were elevated in RA patients (3.34 +/- 0.19 vs. 2.87 +/- 0.21 mg/L; p = 0.019) as compared with the matched controls. The molar ratio of IGF-I to IGFBP-3 was significantly reduced in subjects with RA (0.18 +/- 0.01 vs. 0.24 +/- 0.02; p = 0.008). Furthermore, in RA patients plasma levels of IGFBP-2 were positively (r = 0.45), and levels of IGF-2 negatively (r = -0.45) correlated with circulating levels of C-reactive protein (p < 0.01 in both cases; Spearman rank correlation). CONCLUSION: Increased levels of IGFBPs in RA may result in the reduced availability of free IGFs that can bind to IGF receptors. The observed changes in the IGF system may thus participate in the catabolic processes in rheumatoid arthritis.
11407693 T cell signaling abnormalities in systemic lupus erythematosus are associated with increas 2001 Jun OBJECTIVE: T cells from patients with systemic lupus erythematosus (SLE) display antigen receptor-mediated signaling aberrations associated with defective T cell receptor (TCR) zeta chain protein and messenger RNA (mRNA) expression. This study was undertaken to explore the possibility that coding-region mutations/polymorphisms of the TCR zeta chain could account for its decreased expression and altered signaling in SLE T cells. METHODS: TCR zeta chain mRNA from 48 SLE patients, 18 disease controls, and 21 healthy volunteers was reverse transcribed, amplified by polymerase chain reaction, and cloned, and complementary DNA (cDNA) was sequenced. DNA sequences from multiple clones were analyzed for silent single-nucleotide polymorphisms, mutations, and splice variations, to promote the identification of heterozygosity. RESULTS: DNA sequence analysis revealed several widely distributed missense mutations and silent polymorphisms in the coding region of the TCR zeta chain, which were more frequent in SLE patients than in patients with other rheumatic diseases or healthy controls (P < 0.0001). Several of the missense mutations were located in the 3 immunoreceptor tyrosine activation motifs or the GTP binding domain, and this could lead to functional alterations in the TCR zeta chain. A splice variant of the TCR zeta chain with a codon CAG (glutamine) insertion between exons IV and V was found in half of the SLE and control samples. Two larger spliced isoforms of the TCR zeta chain, with an insertion of 145 bases and 93 bases between exons I and II, were found only in SLE T cells. We also identified various alternatively spliced forms of the TCR zeta chain resulting from the deletion of individual exons II, VI, or VII, or a combined deletion of exons V and VI; VI and VII; II, III, and IV; or V, VI, and VII in SLE T cells. The frequency of the deletion splice variants was significantly higher in SLE than in control samples (P = 0.004). These variations were observed in cDNA and may not reflect the status of the genomic DNA. CONCLUSION: These findings demonstrate that heterogeneous mutations/polymorphisms and alternative splicing of TCR zeta chain cDNA are more frequent in SLE T cells than in T cells from non-SLE subjects and may underlie the molecular basis of known T cell signaling abnormalities in this disease.
11261813 Expression of tyrosine kinase receptors Tie-1 and Tie-2 in giant cell tumor of the tendon 2001 We have recently demonstrated that Tie-1 and Tie-2 are expressed in synovial cells from rheumatoid arthritis (RA). To elucidate the possible involvement of Tie receptors in synovial proliferation, we analyzed their expression by immunostaining in five cases of giant cell tumor of tendon sheath (GCTTS), which represents a proliferating lesion of synovial cells. Strong immunoreactivity for both Tie-1 and Tie-2, regardless of the individual patient's profile, was observed in all cases of GCTTS. Six sets of double immunohistochemical stainings for Tie-1/Tie-2 and fibronectin, CD68, or CD34 were carried out to determine the phenotype of Tie-1 and Tie-2-positive tumor components. In these studies, both Tie-1 and Tie-2 immunoreactivity were widely observed in the fibronectin-positive fibroblastic and the CD68-positive histiocytic mononuclear cells, as well as in the osteoclast-like giant cells. In tumor vasculature, Tie receptors were expressed in the CD34-positive endothelial cells possessing proliferating cell nuclear antigen (PCNA) immunoreactivity. We also evaluated the correlation of Tie-1/Tie-2 expression and proliferating cells in GCTTS by using double staining of Tie-1/Tie-2 together with PCNA. Overexpression of PCNA immunoreactivity was frequently found in Tie receptors-positive cells with no obvious differences in the expression pattern of Tie-1 and Tie-2. These findings suggest the possible involvement of Tie receptors in the pathogenesis of GCTTS other than solely via their involvement in angiogenesis and subsequent vascularization. It was demonstrated that Tie-2 immunoreactivity was restricted to the fibroblastic, but not histiocytic, phenotype in RA synovium, suggesting different regulatory control of Tie-2 expression in GCTTS and RA synovium. Overexpression of Tie receptors in GCTTS may imply a biological role for these receptors in synovial proliferation.
11508581 Influence of longterm therapy with methotrexate and low dose corticosteroids on type 1 and 2001 Aug OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease with predominance of type I cytokine [interleukin 2 (IL-2), interferon-gamma (IFN-gamma)] production. In this prospective study, we evaluated the influence of longterm therapy with methotrexate (MTX) in combination with low dose corticosteroids on the type 1/type 2 cytokine balance in RA. METHODS: Peripheral blood mononuclear cells were isolated from 10 controls and 20 patients with RA before therapy and after 12 mo of therapy with MTX in combination with low dose corticosteroids. Using flow cytometry, the intracellular production of IL-2, IFN-gamma, and IL-4 was measured in CD4+ and CD8+ T lymphocytes. RESULTS: Compared with healthy controls, patients with RA before therapy showed an increased percentage of IL-2 positive CD4+ and CD8+ T cells (p = 0.002, p = 0.01, respectively). An increased percentage of IFN-gamma positive CD8+ T cells was found (p = 0.0006) compared with the control group. After 12 months of therapy, a significantly decreased percentage of IL-2 positive CD4+ T cells and IFN-gamma positive CD4+ and CD8+ T lymphocytes was observed (p = 0.0003, p = 0.0007, p = 0.001). The percentage of IL-4/IFN-gamma positive CD4+ and CD8+ T cells was significantly higher after 12 months of therapy (p = 0.01, p = 0.02). There was a positive correlation between the percentage of IFN-gamma positive CD4+ T cells and disease activity variables (Ritchie Index and number of swollen joints) in RA patients before therapy (r = 0.6, p = 0.04 and r = 0.4, p = 0.05). CONCLUSION: Longterm therapy with MTX in combination with low dose corticosteroids for RA influenced the predominance of type 1 cytokines toward normalization of the cytokine balance in both CD4+ and CD8+ T lymphocytes.
9002047 Qualitative and quantitative analysis of HLA-DRB gene expression. 1997 Jan Determination of the molecular mechanisms influencing HLA-DRB gene expression would allow better understanding of the regulation of the immune response in normal as well as in pathological conditions. We started an extensive sequencing analysis of the proximal promoter regions of the DRB genes and observed a nucleotide polymorphism involving the classical regulatory regions of the DRB promoters. These nucleotide substitutions were observed to induce variations of the promoter activities as assessed by chloramphenicol acetyl transferase assays and the quantification of DRB transcripts. Similar analysis performed in patients with rheumatoid arthritis strongly suggests dysregulation of HLA-DRB gene expression.
11145022 Combination benefit of treatment with the cytokine inhibitors interleukin-1 receptor antag 2000 Dec OBJECTIVE: To determine the potential for additive or synergistic effects of combination therapy with the recombinant anticytokine agents interleukin-1 receptor antagonist (IL-1Ra) and PEGylated soluble tumor necrosis factor receptor type I (PEG sTNFRI) in established type H collagen-induced arthritis (CIA) and developing adjuvant-induced arthritis (AIA) in rats. METHODS: Rats with established CIA or developing AIA were treated with various doses of IL-1Ra in a slow-release hyaluronic acid vehicle or with PEG sTNFRI, either alone or in combination with the IL-1Ra. The effects of treatment were monitored by sequential caliper measurements of the ankle joints or hind paw volumes, final paw weights, and histologic evaluation with particular emphasis on bone and cartilage lesions. RESULTS: Combination therapy with IL-1Ra and PEG sTNFRI in rats with CIA resulted in an additive effect on clinical and histologic parameters when moderately to highly efficacious doses of each protein were administered. Greater-than-additive effects were seen when an inactive dose of IL-1Ra was given in combination with moderately to minimally active doses of PEG sTNFRI. Plasma levels associated with the latter effect (for both proteins) were similar to those seen in rheumatoid arthritis (RA) patients in clinical trials with these agents. Combination therapy in the AIA model generally resulted in additive effects, but some parameters showed a greater-than-additive benefit. CONCLUSION: The results provide preclinical support for the hypothesis that IL-1Ra administered in combination with PEG sTNFRI might provide substantially more clinical benefit to RA patients than either agent alone at blood levels that are currently achievable in patients.
10895380 RANTES gene polymorphism in polymyalgia rheumatica, giant cell arteritis and rheumatoid ar 2000 May OBJECTIVE: To investigate whether a biallelic polymorphism (A or G) occurring within the promoter region of the RANTES gene (position-403) is associated with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and rheumatoid arthritis (RA). METHODS: A PCR-RFLP method was used to genotype cases and controls for this polymorphism. 3 groups of patients were examined; these comprised GCA patients who did not exhibit features of PMR (n = 30), PMR patients who did not exhibit features of GCA (n = 53) and RA patients (n = 99). All patients and controls (n = 65) originated from the area surrounding Lugo, Galicia, NW Spain. RESULTS: A significant increase in the frequency of allele A was found in PMR patients compared with normal controls. A marginal increase of this allele frequency was observed in RA but not in GCA patients. CONCLUSION: This is the first report of an association of a RANTES gene polymorphisms with PMR and RA. Our data suggest a possible role for of RANTES in the development of both PMR and RA.
10615997 Identification of multiple loci linked to inflammation and autoantibody production by a ge 1999 Dec OBJECTIVE: Proteoglycan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA), both in terms of its pathology and its genetics. PGIA can only be induced in susceptible murine strains and their F2 progeny. As with RA, the genetics are complex, containing both major histocompatibility complex (MHC)-related and non-MHC-related components. Our goal was to identify the underlying non-MHC-related loci that confer PGIA susceptibility. METHODS: We used 106 polymorphic markers to perform simple sequence-length polymorphism analysis on F2 hybrids of susceptible (BALB/c) and nonsusceptible (DBA/2) strains of mice. Because both strains of mice share the H2d haplotype, this cross permits identification and analysis of non-MHC-related genes. RESULTS: We identified a total of 12 separate quantitative trait loci (QTL) associated with PGIA, which we have named Pgia1 through Pgia12. QTLs associated with the inflammatory symptoms of PGIA were linked to chromosomes 7, 9, 15 (2 separate loci), 16, and 19. QTLs associated with autoantibody production were identified on chromosomes 1, 2, 7, 8, 10, 11, 16, and 18. QTLs on chromosomes 7 and 16 showed linkage to both inflammation and autoantibody production, suggesting a shared regulatory component in arthritis induction. The first inflammation QTL on chromosome 15 and the autoantibody QTL on chromosome 7 originate from the DBA/2 background, which indicates that as in RA, susceptibility genes can originate from heterogeneous backgrounds. CONCLUSION: These data demonstrate the complexity of PGIA, where QTLs may be involved in multiple traits or even originate from a genetic background previously determined to be resistant.
10817565 Differential regulation of Fas-mediated apoptosis of rheumatoid synoviocytes by tumor necr 2000 May OBJECTIVE: Fas-mediated apoptosis is associated with the pathophysiology of rheumatoid arthritis (RA). However, the molecular mechanisms of this process remain to be elucidated in rheumatoid synovium. We investigated the behavior of intracellular signaling molecules that regulate Fas-mediated apoptosis in RA synoviocytes. METHODS: Anti-Fas monoclonal antibody (mAb) was added to RA synoviocytes after treatment with tumor necrosis factor alpha (TNFalpha) or basic fibroblast growth factor (bFGF) for 5 days. The cytotoxic activity was measured using a lactate dehydrogenase-release assay. The expression of apoptosis-related molecules in RA synoviocytes was examined by immunoblot analysis. The enzymatic activities of caspases 3 and 8 under Fas ligation were examined. Transfer of the FADD (Fas-associated death domain) protein and the FLIP(L) (long form of the FLICE [FADD-like interleukin-1beta-converting enzyme]-inhibitory protein) gene into RA synoviocytes was performed using adenoviral vectors. RESULTS: Following a 5-day treatment with TNFalpha or bFGF, Fas ligation with its agonistic mAb induced apoptosis of almost all TNFalpha-treated RA synoviocytes but only showed a weak apoptotic activity in bFGF-treated synoviocytes. Although there was no correlation between the induction of Fas-mediated apoptosis and the expression of apoptosis-related molecules among these cells, a high enzymatic activity of caspases 3 and 8 was observed only in the TNFalpha-treated RA synoviocytes after Fas ligation. The bFGF-treated RA synoviocytes were relatively resistant to apoptosis induced by FADD gene transfection, as compared with the TNFalpha-treated synoviocytes. In addition, the expression of FLIP(L), an inhibitory molecule of Fas-mediated apoptosis, was reduced in TNFalpha-treated RA synoviocytes, and the expression of FLIP43 was augmented in bFGF-treated RA synoviocytes. Moreover, Fas-mediated apoptosis in TNFalpha-treated RA synoviocytes was partially inhibited by FLIP(L) gene transfection. CONCLUSION: Our results suggest that Fas-mediated apoptosis of RA synoviocytes is differentially regulated by TNFalpha and bFGF. In addition, the regulatory mechanisms of apoptosis involve the formation of the death-inducing signaling complex, especially at the level of caspase 8 activation, and this process may be partly associated with FLIP expression.
9299527 Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity. 1997 Sep 18 Synthetic melittin inhibited the enzymatic activity of secretory phospholipase A2 (PLA2) from various sources, including bee and snake venoms, bovine pancreas, and synovial fluid from rheumatoid arthritis patients, irrespective of substrate (e.g., [14C]-phosphatidylcholine or phosphatidylethanolamine vesicles and [3H]-oleic acid-labeled E.coli). A Lineweaver-Burk analysis showed that melittin was a noncompetitive inhibitor of bee venom PLA2, causing a change in Vmax from 200 to 50 units/min/mg of protein. The Km remained unchanged (0.75 nmole). Melittin inhibited approximately 50% of purified bee venom PLA2 activity in a 30:1 molar ratio (melittin:enzyme). Because the enzyme kinetics indicated a PLA2-melittin interaction, a melittin-sepharose affinity column was used to purify a PLA2 from human serum. Further, an enzyme-linked assay was developed to quantitate PLA2 activity in biological fluids using avidin-peroxidase and ELISA plates coated with biotinylated melittin. These observations may have potential therapeutic significance, as well as provide a convenient basis for the isolation and quantitation of PLA2.
11181651 Rheumatoid arthritis synovial T cells regulate transcription of several genes associated w 2001 Feb Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis whose pathogenesis may involve autoimmune mechanisms. Anergy is a state of T-cell nonresponsiveness characterized by downregulated IL-2 production. Paradoxically, RA T cells are hyporesponsive and proliferate poorly to antigens and mitogens, thus sharing some characteristics with anergic T cells. We analyzed the molecular basis of anergy in cloned human CD4+ T cells using differential display RT-PCR and subsequently examined the levels of differentially expressed transcripts in RA and, as control, reactive arthritis (ReA) synovium. Several transcriptional events were common to anergic T cells and RA synovium. These included downregulation of CALMODULIN:, which is critical to T-cell activation, and of cellular apoptosis susceptibility protein, which may mediate resistance to apoptosis in RA. Transcription of CALMODULIN: in RA synovium was less than 1% of that in ReA and was lower in RA synovial fluid mononuclear cells than in paired PBMCs. Following anti-TNF-alpha therapy in vivo, RA PBMC CALMODULIN: transcripts increased five- to tenfold. Pharmacological calmodulin blockade in vitro impaired antigen-specific proliferation. These data provide a link between reduced CALMODULIN: transcription and impaired T-cell responsiveness in RA. The identification of transcriptional changes common to anergic and RA synovial T cells should help interpret some of the characteristic RA cellular defects.
9022337 [Autoimmune diseases and stress proteins]. 1997 Jan The heat shock protein(hsp), one of the most conserved and ubiquitous proteins in a wide range of species from bacteria to mammals, is strongly immunogenic. High conservation and potent immunogenicity, taken along with the fact that hsp is the target molecule of some gamma/delta T cells place it at the interface between immunity and tolerance. The role of hsp on autoimmune and inflammatory disorders has been vigorously investigated. There are accumulated lines of evidence suggestive of the possible involvement of hsp in clinical disorders but they still remain circumstantial. Two questions must be addressed before the exact role of hsp in these settings is established: 1) Why a conserved protein such as hsp is so immunogenic? 2) Why a ubiquitous protein can be a target of an organ-specific autoimmunity? Our data indicated that antibodies against highly conserved hsp60 in the sera from patients with autoimmune diseases, highlighted by rheumatoid arthritis, were directed mainly against epitopes specific for bacteria such as E. coli. The role of intestinal flora on the pathogenesis of rheumatoid arthritis has long been pursued and our data might support these lines.
9460967 Cemented and non-cemented replacements of the trapeziometacarpal joint. 1998 Jan We performed 88 primary ball-and-socket arthroplasties of the trapeziometacarpal joint in 84 patients (69 women and 15 men) with a mean age of 61 years (37 to 81). Cemented de la Caffinière prostheses were implanted in 43 joints from 1988 to 1991 and 45 cementless Ledoux implants were used between 1992 and 1994. Of the 61 surviving prostheses still in situ, 51 were reviewed clinically and radiologically with a mean follow-up of 25 months for the Ledoux and 63 months for the de la Caffinière implant. The survival rate for the Ledoux prosthesis was 58.9% at 16 months and for the de la Caffinière implant 66.4% at 68 months. Loosening occurred in 15% of the Ledoux stems, in 46% of the Ledoux cups, in 24% of the de la Caffinière stems and in 28% of the de la Caffinière cups. Both prostheses behaved similarly, and it is clear that a constrained ball-and-socket prosthesis is not suitable for the trapeziometacarpal joint.
9751101 Flow cytometric single-cell analysis of cytokine production by CD4+ T cells in synovial ti 1998 Sep OBJECTIVE: To determine the cytokine profile of CD4+ T cells in the synovial tissue (ST) of rheumatoid arthritis (RA) patients at the single-cell level. METHODS: Unseparated ST cells and paired CD4+ T cells separated from the peripheral blood (PB) and ST of RA patients were stimulated for 4 hours with phorbol myristate acetate (PMA) plus calcium ionophore A23187, or for 6 hours with immobilized anti-CD3 plus anti-CD28, in the presence of brefeldin A. Cells were stained for intracellular cytokines such as interferon-gamma (IFNgamma), interleukin-2 (IL-2), IL-4, IL-10, and IL-13, in combination with cell surface markers. The percentages of cytokine-producing T cells were analyzed by flow cytometry. RESULTS: When ST cells were stimulated with PMA plus A23187 in bulk culture, IFNgamma-producing T cells were more frequently detected in the CD8+ subset, but cells producing other cytokines were found in the CD4+ subset. Purified ST CD4+ T cells, after stimulation with PMA plus A23187, were able to produce higher levels of IFNgamma but lower levels of IL-4 and IL-13, by analysis at the single-cell level, as compared with the PB CD4+, CD45RO+ T cells. The majority of IL-4- or IL-13-producing ST CD4+ cells produced IFNgamma, although PB CD4+ T cells rarely showed this cytokine pattern. IL-10-producing CD4+ T cells were more frequently found in the ST than in the PB. Of interest, most of the IL-10-producing ST CD4+ T cells were able to produce IFNgamma. IL-2-producing CD4+ T cells were similarly present in both compartments. Similar intracellular cytokine patterns were observed with anti-CD3 plus anti-CD28 stimulation, although the number of detected cells was lower. CONCLUSION: These data indicate that CD4+ T cells present within the inflamed synovium have apparently distinct cytokine profiles from those of memory CD4+ T cells in the PB, as typified by their ability to secrete both IFNgamma and IL-10.
9517782 Adjustment in patients with rheumatoid arthritis and their children. 1998 Mar OBJECTIVE: To assess everyday life stress and emotional adjustment in patients with rheumatoid arthritis (RA) and their children. METHODS: We conducted a 6 month study of 14 patients with RA with children aged 4-16 years (25 children) and 24 control families (53 children). Life event stress and functional capacity were assessed at the beginning and end of the study, and minor stressors (hassles), positive events (uplifts), and salivary cortisol were recorded weekly. Emotional adjustment was measured monthly in adults by self-report, and bimonthly in children using the Child Behavior Checklist (completed by parents). Social support and psychological coping responses were also measured. RESULTS: Patients with RA experienced fewer positive events than did controls, and they tended to have smaller support networks. Daily hassle levels correlated with severity of disability, and differences in psychological coping were also observed. Children from RA families reported nearly 50% more hassles per week than did controls, and their social networks were significantly smaller. They were rated as having greater problems of social adjustment than controls. Cortisol concentration was greater among children who experienced more life event stress over the study period, but did not differ between groups. CONCLUSION: The patients with RA in this study showed good adaptation, but experienced less pleasure in their daily lives. The children of patients with RA may have heightened vulnerability to stress related problems, with fewer social resources and difficulties in behavioral adjustment.
10335741 The SF-36 Health Survey as a generic outcome measure in clinical trials of patients with o 1999 May OBJECTIVE: To evaluate the validity of SF-36 Health Survey (SF-36) scale scores and summary measure scores to describe the health burden of arthritis and to be responsive to clinical indicators of arthritis severity used in four clinical trials. METHODS: Adults participating in four double-blinded, placebo-controlled clinical trials of therapy for osteoarthritis or rheumatoid arthritis were administered the SF-36 concurrent with clinical measures of disease severity (n = 1,016). Data were collected before treatment and 2 weeks after treatment. Mean SF-36 scores for all patients with arthritis at baseline were compared to a sociodemographically equivalent national norm to test the ability of the SF-36 to describe the burden of arthritis. To test the responsiveness of SF-36 scores to clinical measures of arthritis severity, mean SF-36 scale scores were compared across patients differing in arthritis severity before treatment. Two-week mean SF-36 change scores were compared across patients who improved in arthritis severity (responders) versus patients who did not improve (nonresponders). F-statistics and relative validity coefficients were computed to determine how well each SF-36 scale and summary measure discriminated among arthritis severity levels and distinguished treatment responders from nonresponders, relative to the best scale. RESULTS: Large and statistically significant differences in mean SF-36 scale scores and summary measures were found such that trial participants scored in worse health than a sociodemographically equivalent US general population norm. In addition, the largest SF-36 scale scores were found to significantly differ across clinically defined levels of arthritis severity. Finally, it was found that the SF-36 scales that best discriminate among arthritis severity groups cross-sectionally were also best at discriminating treatment responders from nonresponders. CONCLUSION: Results of this study support the validity of the SF-36 to document the health burden of arthritis and as a measure of generic health outcome for clinical trials of alternative treatments for osteoarthritis and rheumatoid arthritis patients.
9268789 Bone-graft augmentation for acetabular deficiencies in total hip arthroplasty. Results of 1997 Aug The results of 102 consecutive primary and revision total hip arthroplasties performed with bone-grafting for acetabular bone deficiencies were reviewed at an average of 10.2 years (range, 4-18.6) after surgery. Ninety-one percent had structural bone defects and 57% had underlying developmental dysplasia of the hip. Overall acetabular revision rates for aseptic loosening were 8% at 5 years and 26% at 10 years. In addition, in the patients with developmental dysplasia who had primary hip arthroplasties, acetabular revision rates for aseptic loosening were 3 and 18% at 5 and 10 years, respectively. Ninety-six percent of all uninfected grafts incorporated. Bulk grafts fared better than particulate grafts. No difference in failure rate was noted between primary and revision hip arthroplasty, type of deficiency, or amount of graft coverage. Although early results are encouraging, acetabular failure increased significantly with longer follow-up evaluation; however, graft incorporation was successful and facilitated subsequent revision surgery.
10381035 The SHAP-HA complex in sera from patients with rheumatoid arthritis and osteoarthritis. 1999 Jun OBJECTIVE: To investigate serum derived hyaluronan (HA) associated protein-hyaluronan (SHAP-HA) complex in sera from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and determine levels of the complex in comparison with those of hyaluronan (HA), in order to assess the role of the complex as an indicator of joint inflammation. METHODS: ELISA and HA binding assays were used for quantitation of the SHAP-HA complex and HA levels in serum samples from 142 patients (114 with RA, 28 with OA) and 31 healthy controls. Clinical evaluations were also performed. RESULTS: In some RA sera, SHAP-HA complex levels were extremely high compared to control levels, but in OA sera no marked increase was observed compared to controls. This was also the case with the HA levels compared between RA and OA sera. However, in RA the levels of the SHAP-HA complex appear to be more related to clinical variables than are levels of HA, and the most significant correlations between levels of SHAP-HA complex and HA were found in the RA group. CONCLUSION: Quantitation of the SHAP-HA complex in sera may be useful as a joint marker that directly correlates to the degree of joint inflammation in RA, and offers new insight into the pathogenesis of arthritis. It may also serve as an independent criterion in the subsequent classification of RA and OA.