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ID PMID Title PublicationDate abstract
12903526 [Effect of Tripterygium Wilfordii Hook T4 monomer on proliferation and interleukin-6 produ 2000 Apr OBJECTIVE: Tripterygium Wilfordii Hook multi-glycosides T2 has been wildly used in China in treatment of RA. T4 was abstracted from T2 and was reported much more efficient in anti-inflammatory and immune suppression than T2. This study was to investigate the effect Tripterygium Wilfordii Hook T4 monomer on proliferation and interleukin-6 production of synovial fibroblasts of patients with rheumatoid arthritis. METHODS: Synovium was obtained from patients with rheumatoid arthritis undergoing synovectomies or joint replacement. Cultures of synovial fibroblasts were established. After 3 generations, cultured synovial fibroblasts were stimulated with IL-1. Then 1.5 ng/ml, 5 ng/ml and 15 ng/ml T4 were added, and synovial fibroblasts were cultured in the presence of T4 for 48 hours. Cell proliferation was assayed using MTT method. IL-6 level of supernatant was measured by ELISA. RESULTS: Proliferation of synovial fibroblasts was inhibited by T4. The proliferation inhibition effect of T4 was dose dependent and inhibition rate was 5.18%, 10.95% and 21.37%, respectively. And T4 had no effect on IL-6 production by IL-1 stimulated synovial fibroblasts. CONCLUSIONS: T4 might control the disease activity of RA by inhibiting the proliferation of synoviocyte. And T4 might not influence the concentration of IL-6 in synovial fluid, as a central effect, since IL-6 has protective effect on articular cartilage.
10446856 Analysis of the p53 tumor suppressor gene in rheumatoid arthritis synovial fibroblasts. 1999 Aug OBJECTIVE: To determine whether mutations in the tumor suppressor gene p53 may contribute to the transformed-appearing phenotype of rheumatoid arthritis (RA) synovial fibroblasts. METHODS: We performed p53 gene mutation analysis using different molecular approaches. Synovial fibroblasts of 10 patients with RA were cultured and RNA and DNA were harvested after 3-5 passages in cell culture. Sequence analysis of all exons of the p53 gene was performed using 3 different techniques: 1) single-strand conformational polymorphism, 2) nonisotopic RNase cleavage assay, and 3) base excision sequence scanning T-scan, followed by sequence analysis of specific gene segments. RESULTS: Although p53 antigen could be detected by immunocytochemistry in numerous cultured fibroblasts, gel electrophoresis analysis of products obtained using all 3 methods and subsequent sequence analysis showed no specific mutation pattern in the genome of the synovial fibroblasts from patients in Germany, including the known "hot spots" within the p53 genome. However, p53 mutations were identified in different clones of 3 additional RA synovial fibroblast populations from the United States. Sequence analysis of the p53 promoter did not reveal mutational base changes. CONCLUSION: The findings of the study support the hypothesis that the majority of the mutations of the p53 gene observed in RA synovium are not derived from the genome of RA synovial fibroblasts, and that the variability of the mutation pattern reflects, in part, the heterogeneity of the disease.
9281390 Analysis of the molecular basis of synovial rheumatoid factors in rheumatoid arthritis. 1997 Sep The objective of this study was to better understand the molecular basis of IgM rheumatoid factor in rheumatoid arthritis (RA). We recently generated 10 different monoclonal IgM RF (mRF) molecules isolated from the synovium of a single patient with RA. The heavy (H) and light chain (L) variable region (V) genes of these 10 mRFs were cloned and sequenced. Six mRFs used kappa light chains and 4 mRFs used lambda light chains. Of particular interest, 8 of 10 heavy chains used the JH4 joining region gene, and all five VH4 heavy chains used the DK4 diversity region gene with the JH4. Four of the VH4 clones used the same germline gene, likely representing a novel but closely related germline gene to VH4.18, and may be clonally related because of the extensive homology in their heavy chain sequence. Two VH4 clones shared the same light chain gene, VkappaIIIb kv325 (99% homology) and the same JK4 joining region gene, while three VH4 clones used two different light chain genes, an uncommon Vkappa4 and a Vlambda4 gene, respectively. In this RA patient, there was recurrent utilization of VH4-DK4-21/10-JH4 genes and a recurring association with gene elements Vkappa3 and Vlambda4. Recurring usage of Vkappa3 (kv325) and Vlambda4 (lv418) gene elements may result from a light chain editing process whereby immature autoreactive B cells encountering self-antigen attempt, and often succeed, in altering their specificities through secondary Ig light chain gene rearrangement. Moreover, the oligoclonality of these RFs suggest clonal relatedness secondary to an antigen-driven response.
10668525 Leflunomide versus methotrexate: a comparison of the European and American experience. 1999 This paper compares and contrasts the results of two major Phase III clinical trials that compared the efficacy and safety of leflunomide, a new disease-modifying antirheumatic drug (DMARD), and methotrexate. In both the American trial (US301) and the multinational trial (MN302), patients with active rheumatoid arthritis (RA) were given either leflunomide (20 mg/day after a loading dose of 100 mg/day for 3 days) or methotrexate (7.5-15 mg/week) for 52 weeks. US301 was also placebo-controlled. Folate supplementation was mandatory in US301 but was given to < 10% of the patients in MN302. In US301, American College of Rheumatology (ACR) 20% response rates and improvement in tender and swollen joints were significantly better than placebo in both treatment groups, but were not significantly different from each other. Both treatments significantly retarded radiographically assessed progression of RA compared to placebo, but the degree of retardation was significantly greater with leflunomide. In MN302, the ACR response rate and improvement in tender and swollen joints with leflunomide were similar to those seen in US301. The ACR response rate and improvements in all efficacy variables with methotrexate were significantly greater than with leflunomide, however. Radiographically assessed disease progression was not statistically different with the two treatments. Use of methotrexate without folate in MN302 was associated with a higher incidence of clinically significant elevations of liver enzyme levels. These results indicate that both leflunomide and methotrexate are effective DMARDs. The symptomatic relief provided by both drugs is similar when they are given with folate supplementation.
11263767 Influence of shared epitope-negative HLA-DRB1 alleles on genetic susceptibility to rheumat 2001 Mar OBJECTIVE: Most patients with rheumatoid arthritis (RA) express the shared epitope (SE). It is not known whether SE-negative HLA-DRB1 alleles influence the development of RA. This study examined the influence of SE-negative HLA-DR alleles (DRB1*X) on the development of RA in 3 different French populations. METHODS: HLA-DRB1 alleles were defined by polymerase chain reaction with sequence-specific oligonucleotide hybridization or sequence-specific primers. SE-negative alleles were classified according to the electric charge of their P4 pocket. HLA-DRB1 alleles *0103, *0402, *07, *08, *11 (except *1107), *12, and *13 have a neutral or negative P4 charge and are called DRB1*XP4n. HLA-DRB1*03, *0403, *0406, *0407, *0901, *1107, *14, *15, and *16 have a positive P4 charge and are called DRB1*XP4p. RESULTS: Among the SE-negative subjects, DRB1 genotypes with 1 or 2 DRB1*XP4n alleles were significantly overrepresented in the control subjects compared with the RA patients, whereas DRB1*XP4p/XP4p genotypes were equally represented in the patients and controls. In single-dose SE-positive subjects, SE/XP4n genotypes were equally represented in the patients and controls. However, SE/XP4p genotypes were significantly overrepresented in the RA patients. CONCLUSION: The DRB1*X allele polymorphism influences susceptibility to RA. Alleles that have a neutral or negative electric charge in their P4 pocket (DRB1*XP4n), such as DRB1*0103, *0402, *07, *08, *11 (except *1107), *12, and *13, protect against RA. Alleles that have a positive electric charge in their P4 pocket (DRB1*XP4p), such as DRB1*03, *0403, *0406, *0407, *0901, *1107, *14, *15, and *16, have no influence on the predisposition to RA.
11136881 Toxicity of anti-rheumatic drugs in a randomized clinical trial of early rheumatoid arthri 2000 Dec OBJECTIVE: To evaluate the toxicity of slow-acting anti-rheumatic drugs (SAARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) in early rheumatoid arthritis. METHODS: Patients were randomized to receive a SAARD-hydroxychloroquine (HCQ; n=120), i.m. gold (n=114) or methotrexate (MTX; n=118)-or a NSAID only (n=67). Patients in the three SAARD groups were allowed to take NSAIDs. Follow-up included 545 patient-years (p-yr). Adverse effects were attributed to specific medications using the Naranjo scoring method. RESULTS: Fifty-five per cent of the patients suffered from adverse effect(s). Adverse effects were most common during i.m. gold therapy (87 per 100 p-yr), which led to permanent discontinuation of this treatment in 31 cases. The incidences of adverse effects that were probably attributable to NSAIDs in patients treated simultaneously with a SAARD were similar for the three SAARD groups. The mean period until the first adverse effect was longer in the MTX group (39 weeks) than in the HCQ group (27 weeks). Baseline clinical and sociodemographic parameters were not predictive of the occurrence of adverse effects. CONCLUSION: No adverse effect could be classified as definitely related to either SAARDs or NSAIDs by the Naranjo scoring method. The incidence of possible adverse effects of NSAIDs and SAARDs was 72 per 100 p-yr, and adverse effects led to permanent discontinuation of the therapy in 56 cases (13%) (31 patients receiving i.m. gold, 12 receiving MTX, 10 receiving HCQ and three receiving NSAID only).
9691097 Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritis promo 1998 Aug 1 Thymic nurse cells are known to interact with T cells and play a role in their functional maturation. However, the role of nurse cells in B cell maturation and differentiation is less well established, especially at extralymphoid sites. To address this issue, nurse-like cell clones from bone marrow and synovial tissue of patients with RA (RA-NLC) were established and characterized. RA-NLC constitutively expressed CD29, CD49c, CD54 (ICAM-1), CD106 (VCAM-1), CD157 (BST-1), and class I MHC molecules, and secreted IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Bone marrow-derived and synovial RA-NLC differed in that the former secreted IL-7 and expressed a greater density of CD157 constitutively and after stimulation with IFNgamma, whereas the latter secreted G-CSF and more IL-6. Stimulation of both bone marrow and synovial RA-NLC induced expression of CD40 and class II MHC, but not CD154 (CD40L) or CD35. RA-NLC rescued peripheral B cells from spontaneous apoptosis and promoted survival of B cells for > 4 wk. B cell survival was blocked by antibodies to CD106 or CD157. RA-NLC also increased Ig production from B cells. After long-term culture (4-6 wk) with RA-NLC, but not alone or with fibroblasts, outgrowth of B cells was observed. All B cell lines derived from these cultures had been transformed by EBV, although the RA-NLC themselves were not infected with EBV. Precursor frequency analysis indicated that approximately 1 in 12,500 peripheral B cells could give rise to these EBV-transformed B cell lines upon coculture with RA-NLC. These results indicate that RA-NLC from bone marrow and synovium have the capacity to rescue B cells from spontaneous apoptosis, facilitate Ig production, and promote the outgrowth of EBV-transformed B lymphoblastoid cells. These findings suggest that RA-NLC may play a role in the local and systemic hyperreactivity of B cells characteristic of rheumatoid arthritis.
10068071 Ultrasound of the plantar aponeurosis (fascia). 1999 Jan OBJECTIVE: To assess the plantar aponeurosis origin (plantar fascia) using high-resolution ultrasound. DESIGN: The sonographic appearance of the plantar fascia in asymptomatic volunteers was compared with the appearance in: (1) clinical idiopathic plantar fasciitis, (2) inflammatory arthropathy without clinically active plantar fasciitis and (3) Achilles tendon or ankle ligament injury. Patients. There were 48 asymptomatic volunteers (96 heels), 190 patients with idiopathic plantar fasciitis (297 heels), 35 with rheumatoid factor negative spondyloarthropathy (70 heels), 17 with rheumatoid arthritis (34 heels), 62 with clinical Achilles tendinitis (93 heels) and 17 with instability secondary to previous ankle ligament injury (17 heels). RESULTS: Compared with the asymptomatic volunteers, the symptomatic plantar aponeurosis demonstrated significant thickening in patients with clinically unilateral (P<0.001) and bilateral (P<0.001) idiopathic plantar fasciitis as well as in patients with spondyloarthropathy (P<0.001). However, the plantar aponeurosis on the asymptomatic side in patients with unilateral idiopathic plantar fasciitis (P<0.2), rheumatoid arthritis (P<0.2) and ankle injury (P<0.1) demonstrated no significant thickening. In patients with idiopathic plantar fasciitis, abnormal plantar aponeurosis echogenicity was seen in 78% and subcalcaneal bone spurs in 24%. Peritendinous edema was present in 5% of all symptomatic heels, subcalcaneal bone erosion in 4% and intratendinous calcification in 3% of heels. Retrocalcaneal bursitis was present in 7% of patients with idiopathic plantar fasciitis, 40% with spondyloarthropathy and 19% with rheumatoid arthritis. CONCLUSION: Ultrasound allows confirmation of the clinical diagnosis in plantar fasciitis and may provide information as to its etiology.
10181565 Keeping patients with arthritis out of the hospital. 1998 Jun The use of nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis and rheumatoid arthritis is frequently associated with gastrointestinal complications, particularly gastric bleeding. The author outlines a strategy for avoiding these complications, thereby decreasing the risk for hospitalization and/or death.
9487253 Comparative immunolocalization studies of collagenase 1 and collagenase 3 production in th 1998 Jan The degradation of fibrillar type II collagen is a major feature of cartilage destruction in rheumatoid arthritis (RA). Since collagenase 3 is produced by chondrocytes and preferentially degrades type II cartilage collagen, it seemed likely that this enzyme would have a prominent role in the destruction of rheumatoid joints. Using immunolocalization techniques, we have examined and compared the production and distributions of collagenase 1 and collagenase 3 in cells and tissues derived from rheumatoid knee arthroplasties. Primary cultures of chondrocytes stimulated with interleukin-1 beta showed that most of the cells produced collagenase 1, whereas only a minority (approximately 5-10%) produced collagenase 3; a few chondrocytes demonstrated the co-ordinate production of both enzymes. Primary cultures of rheumatoid synoviocytes produced collagenase 1, but not collagenase 3. Both enzymes were demonstrated in the rheumatoid lesion. Collagenase 1 was more commonly observed in both synovium and cartilage (22 of the 28 specimens), was especially prominent at cartilage erosion sites, and most of the positive specimens demonstrated extracellular enzyme. By contrast, collagenase 3 was observed less frequently (7/28 specimens) and was produced by relatively few chondrocytes and synovial cells, this usually being much less than that observed for chondrocytes of osteoarthritic cartilage. These observations suggest different regulatory mechanisms for the production of collagenases 1 and 3 in the rheumatoid lesion, and demonstrate that the distribution and production of collagenase 1 are far more prevalent than those for collagenase 3.
9645358 Expression of matrix metalloproteinases by human plasma cells and B lymphocytes. 1998 Jun Matrix metalloproteinases (MMP) are proteolytic enzymes that play a key role in tissue remodelling during physiological and pathological processes, by initiating the degradation of extracellular matrix. MMP overexpression can lead to tissue destruction which is characteristic of chronic inflammatory diseases such as rheumatoid arthritis and scleritis. Plasma cells are often abundant at such sites of chronic inflammation. In the present study we investigated whether plasma cells could contribute to matrix degradation by their expression of MMP In situ hybridization and immunohistochemical analyses on diseased synovial and scleral tissue demonstrated the expression of stromelysin-1 (MMP-3) and gelatinase B (MMP-9), but little or no tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) mRNA, by IgG-positive plasma cells. Northern blot analysis of RNA extracted from a human plasma cell line (ARH-77), Epstein-Barr virus-transformed B cells, and purified peripheral blood B cells, demonstrated expression of stromelysin mRNA. TIMP-1 mRNA was only detected by the more sensitive reverse transcription PCR method in these cell types. Plasma cells and B lymphocytes cultured in the presence of monensin demonstrated cytoplasmic gelatinase B. Gelatin and casein zymography on conditioned media (CM) derived from cytokine treated plasma cells revealed the induction of secreted gelatinase and stromelysin activity. Western blotting confirmed the presence of stromelysin-1 and TIMP-1 proteins in plasma cell CM. These data suggest that plasma cells are not only capable of modulating an inflammatory response by antibody and cytokine production, but also by their ability to produce MMP. Secretion of MMP from focal aggregates of plasma cells may play a critical role in tissue destructive diseases such as rheumatoid synovitis and scleritis.
10599371 Mucocutaneous side effects and continuation of aurotherapy in patients with rheumatoid art 1999 AIM: To examine the possibility of the continuation of therapy after achieving clinical improvement in patients with mucocutaneous side-effects of parenteral gold compound therapy (Tauredon, "Byk Gulden", Germany). METHODS AND RESULTS: 40 patients with active seropositive rheumatoid arthritis (average age 42.8 years, average duration of disease 2.8 years) received Tauredon in a dosage of 50 mg/week intramuscularly. 19 patients (47.5%) developed mucocutaneous side effects. Four of them were excluded from the study because of severe skin reactions. In 15 patients with mild or moderate side-effects (local skin rash and stomatitis) aurotherapy was continued after the resolution of adverse reactions. Four out of the 15 patients were withdrawn from the study after restarting the lower dose treatment due to recurrence of dermatitis. 11 out of 19 patients finished 1 year of study with low dose Tauredon. Clinical remission occurred in 4 patients (36.4%) while improvement was registered in 6 patients (54.5%). In one patient (9.1%) no clinical effect was observed. None of these 11 demonstrated any Tauredon toxicity. CONCLUSION: The development of mucocutaneous side-effects should not be considered as an absolute contraindication for the continuation of gold compound therapy. A low dose regimen may allow maintenance of therapeutic effect and improve tolerance in this group of patients. Gold salts, such as disodium aurothiomalate (ATMO have been used in the treatment of rheumatoid arthritis (RA) for over 70 years. They suppress inflammation and retard radiological progression of joint damage [1], but their use is limited by a high incidence of toxic side-effects in about 30% of patients. The commonest side-effect of chrysotherapy is skin toxicity, accounting for up to 60% of all adverse reactions [2]. Rash is most frequent in the first year of therapy, but can occur at any time. Stomatitis occurs in 1-12% of patients and may occur concomitantly with skin rash. The causes of skin rash and stomatitis are still unknown. When mucocutaneous reactions develop, the drug should be withheld until the condition resolves [3]. Approximately 2-3% of patients have to stop treatment because of severe skin rash and mouth ulcers [4]. However we, together with other authors [5, 6, 7, 8, 9] consider that mild to moderate mucocutaneous reactions are not an absolute contraindication for the continuation of gold therapy. The aim of our study is to examine the possibility for the continuation of therapy after achieving clinical improvement in patients with skin rash and stomatitis as a result of treatment with ATM (Tauredon, "Byk Gulden", Germany).
11673647 The thixotropic effect of the synovial fluid in squeeze-film lubrication of the human hip 2001 The thixotropic (shear-thinning) effect of the synovial fluid in squeeze-film lubrication of the human hip joint is evaluated, taking into account filtration of the squeezed synovial film by biphasic articular cartilage. A porous, homogeneous, elastic cartilage matrix filled with the interstitial ideal fluid, with the intact superficial zone (of lower permeability and stiffness in compression) already disrupted or worn away, models an early stage of arthritis. Due to a high viscosity of the normal synovial fluid at very low shear rates, the squeezed synovial film at a fixed time after the application of a steady load is found to be much thicker in a small central part of the lubricated contact area. In the remaining part, the film is thin as it corresponds to the Newtonian fluid with the same high-shear-rate viscosity. Filtration is lower for the normal cartilage with the intact superficial zone due to its lower permeability and compression stiffness. But even in the fictitious case of zero filtration, calculations show that the effect of thixotropy on the increase of the minimum synovial film thickness would manifest itself as late as after several tens of seconds since the physiologic load application. At that time, this thickness would be as low as about 0.3 microm. It follows that thixotropy of the normal synovial fluid (and so much more of the inflammatory fluid) is irrelevant in squeeze-film lubrication of both the normal and arthritic human hip joints.
9549373 [Drug delivery system of anti-inflammatory and anti-rheumatic drugs]. 1998 Mar Anti-rheumatic drugs such as nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease modifying anti-rheumatic drugs are valuable medications for patients with rheumatoid arthritis available for physicians now. This review provides a practical approach for increasing efficacy and minimizing adverse response of some of these drugs by the development of drug delivery system.
10947274 An investigation of the feasibility of gadolinium for neutron capture synovectomy. 2000 Jul Neutron capture synovectomy (NCS) has been proposed as a possible treatment modality for rheumatoid arthritis. Neutron capture synovectomy is a two-part modality, in which a compound containing an isotope with an appreciable thermal neutron capture cross section is injected directly into the joint, followed by irradiation with a neutron beam. Investigations to date for NCS have focused on boron neutron capture synovectomy (BNCS), which utilizes the 10B(n,alpha)7Li nuclear reaction to deliver a highly localized dose to the synovium. This paper examines the feasibility of gadolinium, specifically 157Gd, as an alternative to boron as a neutron capture agent for NCS. This alternative modality is termed Gadolinium Neutron Capture Synovectomy, or GNCS. Monte Carlo simulations have been used to compare 10B and 157Gd as isotopes for accelerator-based NCS. The neutron source used in these calculations was a moderated spectrum from the 9Be(p,n) reaction at a proton energy of 4 MeV. The therapy time to deliver the NCS therapeutic dose of 10000 RBE-cGy, is 27 times longer when 157Gd is used instead of 10B. The skin dose to the treated joint is 33 times larger when 157Gd is used instead of 10B. Furthermore, the impact of using 157Gd instead of 10B was examined in terms of shielded whole-body dose to the patient. The effective dose is 202 mSv for GNCS, compared to 7.6 mSv for BNCS. This is shown to be a result of the longer treatment times required for GNCS; the contribution of the high-energy photons emitted from neutron capture in gadolinium is minimal. Possible explanations as to the relative performance of 157Gd and 10B are discussed, including differences in the RBE and range of boron and gadolinium neutron capture reaction products, and the relative values of the 10B and 157Gd thermal neutron capture cross section as a function of neutron energy.
10416135 Early rheumatoid arthritis is associated with diminished numbers of TH1 cells in stimulate 1999 Jun Rheumatoid arthritis (RA) has been associated with an altered TH1/TH2 balance. Here we present first results with a technique to quantitate stimulated TH1 and TH2 subsets in whole blood by means of cytofluorimetric detection of intracytoplasmic TH1 and TH2 cytokines. A group of 10 patients suffering from initial stages of RA exhibited a significantly reduced percentage of TH1 cells (11.0 +/- 2.0%) in the peripheral blood as compared to 13 healthy, age matched controls (28.8 +/- 2.0%). The TH2 response, as determined by intracellular expression of IL-4, remained unchanged. The data may indicate a defect in the TH0-TH1 differentiation or/and a selective trapping of TH1 cells into the affected joints.
11195873 Osseointegrated proximal interphalangeal joint prostheses with a replaceable flexible join 2000 Dec Osseointegrated proximal interphalangeal joint prostheses with a replaceable joint spacer were used in 25 joints in 19 patients (five men and 14 women) aged 45 (16-67) years. Indications for surgery were post-traumatic arthrosis (nine joints in eight patients), primary osteoarthrosis (10 joints in eight patients), and rheumatoid arthritis (six joints in three patients). A silicone joint spacer was attached to titanium fixtures by short titanium stems that extended from the spacer and fitted into a central canal in the screws. The arthroplasty was done in one stage, which included resection of the joint followed by grafting of marrow and cancellous bone from the iliac crest into adjacent medullary cavities before insertion of the titanium fixture. Follow up at 8.5 (5-11) years showed that 47 out of 50 fixtures (94%) had successfully osseointegrated while 17 of 25 joint spacers (68%) had fractured. However, because of the design of the prostheses fractured joint spacers could easily be replaced and a new spacer could be connected to already osseointegrated screws. The joint spacer was replaced in 11 fingers once or several times. Range of movement (ROM) in the whole series (four fusions excluded) was 41 (0-85) degrees with an extension defect of 15 (0-55) degrees. In eight joints with permanently intact joint spacers the ROM was 39 (0-60) degrees with extension defects of 16 (0-40) degrees. In six joints in which the spacer was replaced once the ROM was 43 (0-85) degrees with an extension defect of 16 (0-55) degrees. Our data confirm good long-term osseointegration of titanium fixtures and that a joint spacer, if needed, can be replaced by a new spacer that can be attached to already osseointegrated screws without jeopardizing the ROM.
9203267 Negotiating spaces in home environments: older women living with arthritis. 1997 Jul Within medical geography there has been a surge of interest in applying critical concepts in social theory to empirical settings, including those for persons with disabilities. The ways through which persons with disabilities negotiate space vary widely according to material and social experiences of being disabled. For older women, chronic illness as a type of disability shapes the way in which they approach their daily lives with respect to both the physical and social aspects of their home environments. In the first half of the paper, conceptually, I take a relational view of space and argue that household, as a narrow reading of domestic space, needs to be replaced by home environment which incorporates more fully age- and ablement-sensitive readings of the spaces constitutive of domestic space. This lays the basis for a contextualized socio-spatial understanding of the ways older women with chronic illness negotiate the spaces in home environments because it accounts for the disadvantaged positionings of access to power and resources as well as the uneven distributions of income based on gender, age, and (dis)ability. It also takes into account the material and social aspects of being disabled. In the second half of the paper, I present case studies of three older women diagnosed with rheumatoid arthritis to illustrate these arguments.
9458200 The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxi 1998 Jan OBJECTIVE: To assess the efficacy of folic acid and folinic acid in reducing the mucosal and gastrointestinal (GI) side effects of low dose methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: A systematic review was carried out using the methods recommended by the Cochrane Collaboration. We used MEDLINE and performed hand searches that included bibliographic references, Current Contents, abstracts of rheumatology meetings, and 4 rheumatology journals to select double blind randomized controlled trials (RCT) in which adult patients with RA were treated with low doses of MTX (< 20 mg/week), concurrently with folic or folinic acid. The quality of the RCT was assessed. The overall treatment effect across trials (reduction in toxicity) was estimated using a fixed effects model. Disease activity was evaluated using standardized mean differences to ensure comparability across outcome measures. Sensitivity analyses were conducted evaluating different doses and the quality of the trials. Costs per month in different countries were compared. RESULTS: Of 11 trials retrieved, 7 met inclusion criteria. The total sample included 307 patients, of which 147 were treated with folate supplementation, 67 patients with folic, and 80 with folinic acid. A 79% reduction in mucosal and GI side effects was observed for folic acid [OR = 0.21 (95% CI 0.10 to 0.44)]. For folinic acid, a clinically but nonstatistically significant reduction of 42% was found [OR = 0.58 (95% CI 0.29 to 1.16)]. No major differences were observed between low and high doses of folic or folinic acid. Hematologic side effects could not be analyzed, since details by patients of each event were not provided. No consistent differences in disease activity variables were observed when comparing placebo and folic acid or folinic acid at low doses; patients receiving high dose folinic acid had increased tender and swollen joint counts. Substantial differences in costs across countries were found; folinic acid was more expensive. CONCLUSION: Our results support the protective effect of folate supplementation in reducing MTX side effects related to the oral and GI systems.
9187561 Significance of antigen-specific T cell clones in collagen diseases: analyses with a novel 1997 Apr The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.