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ID PMID Title PublicationDate abstract
10852270 Cellular immune response to Klebsiella pneumoniae antigens in patients with HLA-B27+ ankyl 2000 Jun OBJECTIVE: To study the reactivity of peripheral blood mononuclear cells (PBMC) of patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and healthy controls to Klebsiella pneumoniae antigens and to the GroEL-like proteins from K. pneumoniae (HSP60Kp) and Mycobacterium leprae recombinant heat shock protein 65 (rHSP65Ml). METHODS: PBMC of 13 patients with AS and 9 with RA and 10 controls were stimulated in vitro by heat shock induced K. pneumoniae antigens in a cell blot assay, by insolubilized HSP60Kp, by cytosolic proteins (CP) from K. pneumoniae cultivated at 37 degrees C or 45 degrees C, by soluble HSP60Kp, or by rHSP65Ml. RESULTS: In the cell blot assay 7/13 AS and 3/9 RA patients responded to fraction 4, which contains mainly HSP60Kp, and no controls responded (AS vs. controls: p = 0.007). The response to the insolubilized HSP60Kp was positive in 6/13 AS patients but negative in RA patients and controls (p = 0.004). The response to CP45 degrees C was positive in 7/13 AS, in 2/9 RA, and no controls (AS vs controls: p<0.015). Response to the soluble HSP60Kp was found in 7/13 AS and 5/9 RA patients, but no controls (AS vs. controls: p = 0.0075). Response to rHSP65Ml was positive in 3/13 AS, 7/9 RA patients, and 1/10 controls (AS vs RA: p = 0.027; RA vs. controls: p = 0.005; AS vs. controls: nonsignificant). CONCLUSION: In PBMC of the majority of patients with AS and in some with RA, but not in healthy controls, there are cells that proliferate in the presence of HSP60 of K. pneumoniae.
11357167 The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoi 2001 Apr BACKGROUND: Interleukin (IL)-1 has been associated with joint inflammation and damage in rheumatoid arthritis (RA). Endogenous IL-1 receptor antagonist (IL-1Ra) may inhibit IL-1-mediated effects by binding to the IL-1 receptors. OBJECTIVES: These studies were conducted to determine the efficacy and safety of human recombinant IL-1 receptor antagonist (IL-1ra) in blunting the effects of IL-1 in patients with RA. METHODS: Three randomized clinical trials have been completed. First, in a 24-week, double-blind, placebo-controlled study of 472 patients with severe RA, patients were randomly placed into 4 groups: placebo or IL-1ra at 30, 75, or 150 mg/d. In a second study, 309 patients from the placebo-controlled trial enrolled in a 24-week extension study. Patients who had been receiving placebo were randomized into 1 of the 3 treatment groups. Those receiving treatment continued to receive their previous dosages. Finally, in a second double-blind, placebo-controlled study, 419 patients with RA receiving methotrexate at 12.5 to 25 mg/wk for at least 6 months were randomly placed into 1 of 6 groups: placebo or IL-1ra at 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg/d. RESULTS: In the first study, the primary therapeutic endpoint-an American College of Rheumatology 20% response (ACR20)-was reached by 27% of the placebo group, compared with 43% of the IL-1ra 150-mg/d group. Individual clinical responses, as well as the arrest of joint damage, were also superior in treated patients. In the second trial, 52% of the randomized patients achieved an ACR20. This was maximal (71%) in those receiving the highest treatment dosage. Of patients continuing with the same dosage, 49% maintained an ACR20 at 48 weeks. Radiologic evaluation showed that the reduced rate of cartilage degradation observed in treated patients during the first 24 weeks was maintained, and the rate of joint erosion was slowed even more significantly in the second phase of the study. In the third study, significantly more patients receiving IL-1ra at 1.0 (46%, P =.001) or 2.0 (38%, P =.007) mg/kg/d achieved an ACR20 at week 12 than those receiving placebo (19%). Similar responses were noted at week 24. IL-1ra was generally well tolerated, with injection site reaction the most frequent adverse event. No serious adverse events attributable to IL-1ra treatment were observed. CONCLUSIONS: These studies suggest an important role for IL-1ra as a novel therapeutic agent in the treatment of RA.
10544658 [Molecular mimicry of bacteria as a factor in bacterial pathogenicity]. 1999 Structural and functional homology between bacterial proteins and host antigens, called molecular mimicry, is considered as significant pathogenic factor involved in several autoimmune diseases. The most important examples of this phenomenon reviewed in this work, involve rheumatic fever, Graves' disease, ankylosing spondylitis, Reiter's syndrome and rheumatic arthritis caused by infections with Streptococcus, Yersinia, Klebsiella, Escherichia coli, respectively.
10759781 Humoral autoreactivity directed against surfactant protein-A (SP-A) in rheumatoid arthriti 2000 Apr SP-A is found principally in the lung, and has been associated with lamellar bodies also found in the synovial joint. Both SP-A and C1q contain collagen-like regions, and SP-A and C1q have some structural similarities, both having a globular head region and a collagen-like tail. Here we are able to show that (i) autoreactivity to SP-A, as expressed by IgG and IgM autoantibodies, is present in synovial fluid (SF) isolated from patients with rheumatoid arthritis (RA); (ii) in absorption experiments only a limited degree of cross-reactivity between autoantibodies reactive with C1q and SP-A is observed; (iii) there is no cross-reactivity between autoantibodies reactive with type II collagen (CII) and those reactive with SP-A or C1q; (iv) autoantibodies react with polymeric (dimers and larger) SP-A, but not with monomeric SP-A subunits, indicating that a degree of quaternary structure is required for antibody binding. Unlike CII, which not accessible in the normal joint, both SP-A and C1q are available within the SF in patients with RA and may therefore provide antigens driving an autoimmune response directed against collagen-like structures.
9180317 The Norway elbow replacement. Design, technique and results after nine years. 1997 May The Norway elbow prosthesis is a non-constrained cemented total replacement. It depends on intact collateral ligaments for stability, and allows a full range of movement. The system includes several sizes of components, all freely interchangeable, and semi-constraint can be provided by a locking ring if damaged collateral ligaments make dislocation possible. The prosthesis has been used in more than 350 elbows in Norway and the detailed results for 118 elbows studied prospectively since 1987 are reported. It is inserted through a posterolateral triceps-splitting incision with minimal muscle disruption and bone resection, preserving the collateral ligaments. The results as regards pain relief and range of movement were comparable with those of other elbow prostheses, but there were fewer serious complications. At a mean follow-up of 4.3 years, the failure rate was 3.4%.
10091464 Bronchoalveolar lavage (BAL) in newly diagnosed patients with collagen vascular diseases. 1998 Oct Collagen vascular diseases (CVD) are commonly associated with interstitial lung diseases. Bronchoalveolar lavage (BAL) fluid analysis has important diagnostic value when considered in conjunction with other information. The present study was undertaken in newly diagnosed patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) at presentation to characterise BAL cellular constituents and elucidate the cellular picture in patients with and without pulmonary symptoms and in those with and without radiological (high resolution computed tomography) features of interstitial lung disease. All the patients were non-smokers and had not received any form of treatment for their diseases. The means of percentages of lymphocytes, neutrophils, and macrophages were 23.3%, 6.2%, 70.5% respectively. There was a significant BAL lymphocyte predominance in patients with pulmonary symptoms, and a lymphocyte and neutrophil predominance in those having radiological evidence of interstitial lung disease.
10863179 [Chronic lymphocytic leukemia revealed by atypic pemphigus]. 2000 May BACKGROUND: Bullous diseases are occasionally reported during chronic lymphocytic leukemia. We report the case of a woman in which a bullous disease of difficult nosologic classification has revealed chronic lymphocytic leukemia. CASE REPORT: A 57-year-old woman, well-known for a rheumatoid arthritis, developed a bullous eruption. It was associated with voluminous lymphadenopathies, and laboratory investigations revealed a chronic lymphocytic leukemia. Clinicopathological aspect and immunofluorescence studies argued for a paraneoplastic pemphigus but immunoblot showed only antibodies against desmoglein 1. DISCUSSION: Paraneoplastic pemphigus is an autoimmune bullous disease defined by the criteria of Anhalt, including autoantibodies mostly directed against cytoplasmic proteins of the plakin family. Our case is unusual for the absence of these antibodies and for the presence of antibodies directed against a cell surface target, desmoglein 1. Such a case confirms the overlapping auto-immune responses in pemphigus.
9667613 A fistful of T cells. 1998 Jun Evidence incriminating T cells in rheumatoid arthritis (RA) is strong but circumstantial--like a smoking gun at the scene of a crime. To investigate this, T lymphocytes were studied in health and disease. The effect of mutations in the groove of HLA-A2 on peptide presentation to T cells was studied to investigate normal T cell function. This allowed a detailed description of the interactions between individual MHC residues and antigens. Subsequently, T cells in the autoimmune disease, multiple sclerosis, were studied, to investigate the mechanisms for breakdown in peripheral tolerance. T-cell clones that recognized both autoantigens and viral proteins were isolated, suggesting that infection may trigger disease. Autoantigens would need to be defined to use this strategy in RA. T-cell responses to type II collagen, a candidate auto-antigen, were therefore studied in RA and an epitope successfully defined. The search for microbial 'mimics' triggering RA, and novel forms of immunotherapy are now possible--with potential rehabilitation of T cells.
11327406 Alarming wear of the first-generation polyethylene liner of the cementless porous-coated B 2001 Feb Wear of the socket liner and resulting osteolysis are the major causes of failure in cementless hip arthroplasties. We report alarming wear of the first-generation polyethylene liner of the cementless porous-coated Biomet Universal cup. Radiographs of 107 primary hip arthroplasties were analyzed retrospectively. The mean follow-up time was 74 (47-91) months. The linear wear of the polyethylene liners was assessed using a modification of the Livermore method. The median linear wear was 1.0 (0-6.2) and the median linear wear rate was 0.17 mm/year. There was a statistically significant difference between the 28 mm and 32 mm femoral head groups both in the volumetric wear and in the volumetric wear rate. The median linear wear was 0.28 mm/year and 0.14 mm/year for the 32 mm and 28 mm heads, respectively. So far, 14 revisions have been performed or have been scheduled because of excessive wear of the polyethylene liner. In regression analysis, the factors related to the wear rate were the 32 mm size of the femoral head and screw fixation of acetabular shell. We found that the cases with calcar rounding were associated with significantly greater wear. Possible reasons for increased wear of the Hexloc liner may be the cylindrical design, thin polyethylene, and poor quality of the polyethylene. Regular clinical and radiographic follow-ups are recommended especially for hips with 32 mm femoral heads or with screw fixation. If progressive wear of the liner is observed, revision must be considered.
10535607 Long-term follow-up of the changes in circulating cytokines, soluble cytokine receptors, a 1999 Sep To investigate the mechanism of the long-lasting efficacy of chimeric monoclonal anti-TNFalpha antibody (cA2) therapy for rheumatoid arthritis (RA), eight patients with refractory RA were treated with a single infusion of cA2 and the changes in circulating cytokines (IL-1, IL-6, TNFalpha, and IL-10), soluble cytokine receptors (TNF-RI, RII, and sIL-6R) and peripheral white blood cell (WBC) subset counts were followed up long-term (12 weeks) after cA2 therapy in them. Significant clinical responses (>20% improvement according to Paulus' criteria) were observed just after cA2 infusion and lasted more than 4 weeks in all patients, as reported elsewhere. Moreover, five of the eight patients showed prolonged clinical responses (>12 weeks). The elevated serum IL-6 and sTNF-RI (or RII) levels before treatment rapidly decreased after treatment. The serum IL-10 levels also significantly elevated before treatment. The elevations of serum IL-10 levels were augmented after treatment and stayed higher than the baseline in four patients with prolonged clinical responses. No significant TNFalpha, IL-1alpha and -beta, or sIL-6R were detected in the sera of the patients before treatment and during the whole study period. On the other hand, peripheral lymphocytes as well as total WBC and neutrophils increased for 4 weeks after treatment. However, thereafter, only the lymphocyte count decreased gradually and stayed below the baseline long-term (12 weeks). FACS analysis revealed the predominance of T lymphocytes in the decrease in lymphocyte counts. These results suggest that the augmentation of IL-10 production and the decrease in T cells might partly contribute to the long-lasting efficacy of cA2 treatment in RA.
10627719 Total elbow replacement in the treatment of rheumatoid disease. 1999 Sep Improvements in total elbow arthroplasty during the last 20 years have resulted in clinical outcomes which now are comparable with the results of hip arthroplasty. The main types of prostheses used are unlinked prostheses or semiconstrained hinged prostheses. The unlinked prostheses require the preservation of bone stock and the ability to reconstruct the collateral ligaments to achieve stability. Semiconstrained, hinged prostheses have inherent stability but humeral loosening was initially a problem. Stress transfer through the humeral stem can be reduced by using a prostheses with anterior flanges (Coonrad-Morrey or GSB3). Survivorship analyses beyond 10 years now are becoming available for these prostheses. There has been no universal agreement as to which outcome measure should be used for total elbow replacements. Future developments will include an evolution of principles as understanding of elbow biomechanics progresses. Operative technique is likely to be modified by the development of alignment aids and jigs.
11589252 Rofecoxib: clinical pharmacology and clinical experience. 2001 Sep BACKGROUND: Rofecoxib is a member of a subgroup of nonsteroidal anti-inflammatory drugs (NSAIDs) known as cyclooxygenase-2 (COX-2)-selective inhibitors. It has been studied in adult and elderly patients in a number of painful conditions (primary dysmenorrhea, acute pain after dental and orthopedic surgery, osteoarthritis [OA], and rheumatoid arthritis). OBJECTIVE: This review discusses the clinical pharmacology of and clinical experience with rofecoxib, and the role of COX-2-selective inhibitors in clinical practice. METHODS: Pertinent studies were identified through searches of MEDLINE and EMBASE, as well as the Web sites and proceedings of relevant scientific meetings. RESULTS: Although the published literature is limited, the data indicate that rofecoxib is an effective analgesic agent for the painful conditions in which it has been studied. As a COX-2-selective inhibitor, rofecoxib offers safety advantages over traditional NSAIDs. In clinical trials, gastrointestinal (GI) toxicity, including mucosal damage, perforation, ulcers, and bleeding, occurred significantly less often in healthy volunteers and patients treated with rofecoxib than in those who received NSAIDs such as ibuprofen, naproxen, or diclofenac (all comparisons, P < 0.001). In terms of renal toxicity, rofecoxib does not appear to offer a safety advantage over traditional NSAIDs. Rofecoxib has not been shown to affect platelets (bleeding time and platelet aggregation), unlike traditional NSAIDs. CONCLUSIONS: Rofecoxib is an appropriate choice for patients who do not obtain adequate analgesia with acetaminophen and those who have not obtained adequate analgesia from, cannot tolerate, or are at risk for GI toxicity with traditional NSAIDs. Patients who require chronic analgesic medication (ie, those with OA), including those who take other medications daily for comorbid conditions, may also benefit from the once-daily dosing regimen of rofecoxib.
10637275 Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interle 2000 Jan 17 Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation, host defense, and the neuro-immuno-endocrine network. IL-1 receptor antagonist (ra) is an endogenous inhibitor of IL-1 and is supposed to regulate IL-1 activity. However, its pathophysiological roles in a body remain largely unknown. To elucidate the roles of IL-1ra, IL-1ra-deficient mice were produced by gene targeting, and pathology was analyzed on different genetic backgrounds. We found that all of the mice on a BALB/cA background, but not those on a C57BL/6J background, spontaneously developed chronic inflammatory polyarthropathy. Histopathology showed marked synovial and periarticular inflammation, with articular erosion caused by invasion of granulation tissues closely resembling that of rheumatoid arthritis in humans. Moreover, elevated levels of antibodies against immunoglobulins, type II collagen, and double-stranded DNA were detected in these mice, suggesting development of autoimmunity. Proinflammatory cytokines such as IL-1beta, IL-6, and tumor necrosis factor alpha were overexpressed in the joints, indicating regulatory roles of IL-1ra in the cytokine network. We thus show that IL-1ra gene deficiency causes autoimmunity and joint-specific inflammation and suggest that IL-1ra is important in maintaining homeostasis of the immune system. Possible involvement of IL-1ra gene deficiency in RA will be discussed.
11249645 Technology evaluation: MFG-IRAP, University of Pittsburgh. 2000 Apr The University of Pittsburgh is developing MFG-IRAP, a retroviral vector carrying the human interleukin-1 receptor antagonist protein (IRAP) cDNA for potential treatment of arthritis. MFG-IRAP gene therapy was effective in local gene delivery to synovial lining of joints and systemically to hematopoietic stem cells, in preclinical studies. Intra-articular expression of IRAP, although transient (4 to 6 weeks), was efficacious in several animal models of arthritis. On the other hand, systemic transgene expression was prolonged (15 months), but was relatively less efficacious. Clinical data on the safety of MFG-IRAP therapy per se are limited, however, recombinant IRAP studies in humans have not resulted in any serious adverse effects. Phase II studies, including a trial in arthritis patients should provide the much anticipated MFG-IRAP efficacy data.
11826747 [Use of glucocorticoids in rheumatoid arthritis. Inhibition of disease progression versus 2001 Dec This is a short overview of low dose oral treatment with 5-7.5 mg prednisolone/day in RA with emphasis on radiographic progression. Short-term studies over 1-2 weeks with 7.5-15 mg prednisolone/day demonstrate advantage over placebo and--less so--over NSAID in improving RA symptoms; over 6-12 months prednisolone seems to be less superior. Older studies were unable to demonstrate an inhibition of progression seen on radiographs. In the Kirwan study, there was a significant inhibition of x-ray progression with 7.5 mg prednisolone/day versus placebo. The German low-dose prednisolone treatment (LDPT) study demonstrated a significant retardation of radiographic progression with only 5 mg prednisolone/day in addition to DMARD treatment with parenteral gold or methotrexate versus DMARD + placebo in early RA during the first year of treatment while there was no difference between both groups during the second year. These data are in favor of a "bridging" treatment with low dose prednisolone. The risks of corticosteroid treatment are discussed, including an increased mortality rate as an independent risk factor. Two randomized studies and a metaanalysis indicate the development of steroid osteoporosis in RA already with low doses. As with every treatment, benefit and risk have to be considered carefully.
11346236 A preliminary study of circadian serum cortisol concentrations in response to a 72-hour fa 2001 The aim of the study was to investigate the effects a 72-h fast upon serum total and free cortisol concentrations in RA patients not previously treated with glucocorticoids. Total serum cortisol and transcortin concentrations were measured in four RA patients with active disease at 4-h intervals during two 24-h periods (1200 h-1200 h), the first while eating a normal diet (fed state) and the second during the last 24 h of a 72-h water fast. Free cortisol concentrations were calculated from the total cortisol and transcortin values. The 3-day fast increased overall 24-h free and total cortisol concentrations by 50% and 35%, respectively. This was due largely to a marked increase in nocturnal serum cortisol concentrations during fasting, particularly at 0400 h, when mean total and free cortisol levels were increased by 170% and 260% compared to the fed state. Between 2000 and 0800 h overall total- and free cortisol concentrations were increased by 72% and 99%, respectively. These results suggest that an increase in nocturnal concentrations of cortisol occurs in response to fasting in RA patients not previously treated with glucocorticoids. These increases may mediate the beneficial clinical response previously found in studies of longer fasting periods in RA patients.
10405928 HLA-DRB1 alleles and shared amino acid sequences in disease susceptibility and severity in 1999 Jul OBJECTIVE: To examine the effects of HLA-DRB1 alleles and amino acid sequences that carry the shared epitope (SE) upon rheumatoid arthritis (RA) susceptibility and disease severity in patients from Eastern France. METHODS: HLA-DRB1 alleles were determined in 120 patients and 104 healthy controls by polymerase chain reaction/sequence specific oligonucleotide probes. Subtyping of DRB1*01 and *04 were performed using sequence specific primers. Patients were retrospectively evaluated for disease duration, age at disease onset, presence of rheumatoid factors, subcutaneous nodules, vasculitis and other extraarticular diseases, for the need for arthroplasty and immunosuppressive/immunoregulatory agents, and for radiographic damage. RESULTS: The prevalence of HLA-DRB1*04 was significantly higher in patients (46.6%) than in controls (17.3%) (Pcorr = 0.000003). HLA-DRB1*0101 and *0401 were the most prominently associated subtypes in patients with RA (33.3%, Pcorr = 0.011, and 28.3%, Pcorr = 0.00008, respectively). A significant fraction of patients (72.5%) expressed one or 2 copies of the SE (p < 0.0000001; OR 4.77, CI 2.61-8.78). The presence of double SE was associated with a higher risk of developing RA (OR 4.83, CI 1.91-12.71; p = 0.0001). No significant differences in the clinical records among patients expressing no RA linked alleles, one and 2 copies of the SE, were observed. However, analyzing the specific effect of each amino acid sequence, we observed a significant association of the QKRAA motif with vasculitis (p = 0.03) and history of joint replacement surgery (p = 0.05), suggesting a role for lysine in position 71 of the shared sequence. CONCLUSION: These findings differ from those of previous HLA-DRB1 allele studies in patients with RA from other regions of France. Thus, the heterogeneity in both the expression of DRB1 alleles and the association of these alleles with disease severity could be relevant within a country such as France.
9446440 [Long-term experiences with elbow arthroscopy]. 1997 Sep PURPOSE: The purpose of this study was to present our long-term experience in elbow arthroscopy with special regard to diagnosis specific results. METHODS: 103 out of 121 patients after elbow arthroscopy were evaluated with a mean followed-up time of 6.2 years. The age of the patients at time of surgery ranged between 3 and 72 years. For documentation the Figgie-Score was used. The results were documented in relation to the patients pathology. RESULTS: The total score improved significantly from 49.3 to 89.3 (p < 0.05). There was no age dependency of the results, but a correlation to the preoperative duration of symptoms and the individual job situation. Between the different score parameters pain showed the highest improvement. While patients with free bodies as well as bacterial or rheumatic arthritis had a more noticeable gain, the postoperative improvement for the patients with severe degenerative arthritis was only limited. Patients with unclear preoperative problems showed no improvement at all. CONCLUSION: While patients with free joint bodies or synovitis without degenerative joint disease have a significant benefit from elbow arthroscopy, patient with severe degenerative joint disease or patients with restricted range of motion will hardly show any improvement after surgery.
10613412 Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid medi 1999 Dec OBJECTIVE: Omega-3 (omega-3) fatty acid rich-fish oil (FO) and vitamin E (vit-E) may delay the progress of certain autoimmune diseases. The present study examined the mechanism of action of omega-3 and omega-6 lipids and vit-E on the serum cytokines and lipid mediators in autoimmune-prone MRL/lpr mice (a model for rheumatoid arthritis, RA). The lpr (lymphoproliferative) gene is overexpressed in these mice causing extensive lymphoproliferation, lupus-like symptoms and accelerated aging. METHODS: Weanling female MRL/lpr and congenic control MRL/++ mice were fed 10% corn oil (CO, omega6) or FO-based semipurified diets containing two levels of vitamin E (vit-E-75, I.U. and vit-E-500 I.U./Kg diet) for four months. At the end of the experiment, serum anti-DNA antibodies, cytokines and lipid mediators levels were determined. RESULTS: The appearance of enlarged lymph nodes was delayed in the mice fed FO, and the FO-500 IU vit-E diet offered further protection against enlargement of lymph nodes. The MRL/lpr mice exhibited significantly higher levels of serum anti-dsDNA antibodies. The FO-fed mice had significantly lower serum IL-6, IL-10, IL-12, TNF-alpha, PGE2, TXB2 and LTB4 levels compared with CO-fed mice. In mice fed 500 IU vit-E diets, the serum IL-6, IL-10, IL-12 and TNF-alpha levels were significantly lower and serum IL-1beta was significantly higher compared to 75 IU-vit-E-fed mice in CO/FO or both. The levels of anti-DNA antibodies, IL-4, IL-6, TNF-alpha, IL-10 and IL-12 were higher in the sera of MRL/lpr mice. The FO diet lowered the levels of these cytokines (except IL-4) and lipid mediators. Adding 500 IU of vit-E to the FO diet further lowered the levels of IL-6, IL-10, IL-12, and TNF-alpha. CONCLUSION: It is clear from our observations that the beneficial effects of FO can be enhanced by the addition of 500 IU of vit-E in the diet. The FO diet containing 500 IU of vit-E may specifically modulate the levels of IL-6, IL-10, IL-12 and TNF-alpha and thereby may delay the onset of autoimmunity in the MRL/lpr mouse model. The observations from this study may form a basis for selective nutrition intervention based on specific fatty acids and antioxidants in delaying the progress of RA.
10928223 Prevention of bone loss with risedronate in glucocorticoid-treated rheumatoid arthritis pa 2000 The aim of the study was to assess risedronate's effect on bone mineral density in postmenopausal women with rheumatoid arthritis receiving glucocorticoids. We carried out a two center, 2 year, double-masked, placebo-controlled trial with a third year of nontreatment follow-up. We studied 120 women requiring long-term glucocorticoid therapy at > 2.5 mg/day prednisolone randomized to treatment with daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of 12 weeks). At 97 weeks, bone mineral density was maintained at the lumbar spine (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group, while significant bone loss occurred in the placebo group (-1.6%, p = 0.03; and 4.0%, p < 0.005, respectively). At the femoral neck, there was a nonsignificant bone loss in the daily 2.5 mg risedronate group (-1.0%) while in the placebo group bone mass decreased significantly (-3.6%, p < 0.001). The difference between placebo and daily 2.5 mg risedronate groups was significant at the lumbar spine (p = 0.009) and trochanter (p = 0.02) but did not reach statistical significance at the femoral neck. Although not significantly different from placebo at the lumbar spine, the overall effect of the cyclical regimen was similar to that of the daily 2.5 mg risedronate regimen. Treatment withdrawal led to bone loss in the risedronate groups that was significant at the lumbar spine. A similar number of patients experienced adverse events (including upper gastrointestinal events) across treatment groups and risedronate was generally well tolerated. Thus risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis receiving glucocorticoids while patients receiving a placebo have significant bone loss.