Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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15201935 | [Biological modulation of IL-1 activity: role and development of its natural inhibitor IL- | 2004 Jan | IL-1 and TNF-alpha are potent inducers of matrix metalloproteinases (MMP), eicosanoids, nitric oxide oxydase (iNOS), receptor activator of NF-kB ligand (RANKL), products involved in the destruction of the extracellular matrix, the cartilage and in bone resorption. IL-1, particularly important at the local level, is more potent than TNF-alpha in stimulating MMP and specifically in impeding cartilage repair. However, IL-1 and TNF-alpha strongly synergize in multiple biological functions. Blockade of IL-1 by IL-1 receptor antagonist (IL-1Ra, sIL-1RII) in combination with the soluble IL-1 accessory protein (IL-1R AcP) result in a long-term beneficial effect in chronic inflammatory diseases. The association with anti-TNF-alpha therapy may also represent a logical approach, considering the number of patients that do not respond to either compound alone. | |
15041166 | HLA-DRB1 alleles encoding the "shared epitope" are associated with susceptibility to devel | 2004 Mar | The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+ ) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences in proportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRB1 allele encoding the SE was significantly increased in RA cases as compared to controls (p(c) = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE+ cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF. | |
12440497 | Long-term clinical results and radiographic changes in the nonresurfaced patella after tot | 2002 Oct | We evaluated total knee arthroplasty without patellar resurfacing retrospectively in 50 patients (78 knees; 4 men (7 knees) and 46 women (71 knees) having a mean age of 63 (34-78) years and mean weight of 52 (32-72) kg). The preoperative diagnosis was osteoarthrosis in 26 patients (43 knees) and rheumatoid arthritis in 24 (35 knees). The mean follow-up was 12 (9-14) years. Only 3 patients (4 knees) had patellar pain and they all showed patellar subluxation. The latter was found in 13 other knees, all pain-free. We detected no differences between the knees with osteoarthrosis and rheumatoid arthritis concerning the incidence of patellar pain and patellar subluxation. No patient needed revision surgery for patellar problems. We question the need to resurface the patella routinely in total knee arthroplasty if it is congruous and well-aligned. | |
15084912 | Collagen-induced arthritis mediated by HLA-DR1 (*0101) and HLA-DR4 (*0401). | 2004 Apr | Although associations between the expression of particular HLA genes and susceptibility to specific autoimmune diseases has been known for some time, the role HLA molecules play in the autoimmune response is unclear. Through the establishment of chimeric HLA-DR/I-E transgenes, the authors examined the function of the rheumatoid arthritis (RA) susceptibility alleles HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) in presenting antigenic peptides derived from the model antigen, type II collagen (CII), and in mediating an autoimmune response. As a transgene, these chimeric DR molecules confer susceptibility to an autoimmune arthritis induced by immunization with human CII. Both the DR1 and DR4-restricted T cell responses to CII are focused on an immunodominant determinant CII(263-270). Peptide binding studies revealed that the majority of the CII-peptide binding affinity for DR1 and DR4 is controlled by the Phe at 263 and, unexpectedly, the adjacent Lys. Only these 2 CII amino acids were found to provide binding anchors. Amino acid substitutions at the remaining positions had either no effect or significantly increased the affinity of the hCII peptide. These data indicate that DR1 and DR4 bind this CII peptide in a nearly identical manner and that the primary structure of CII may dictate a different binding motif for DR1 and DR4 than has been described for other peptides. In all, these studies demonstrate that DR1 and DR4 are capable of binding peptides derived from human type II collagen (hCII) and support the hypothesis that autoimmune responses to hCII play a role in the pathogenesis of RA. | |
15642148 | Mast cells in inflammatory arthritis. | 2005 | Mast cells are present in limited numbers in normal human synovium, but in rheumatoid arthritis and other inflammatory joint diseases this population can expand to constitute 5% or more of all synovial cells. Recent investigations in a murine model have demonstrated that mast cells can have a critical role in the generation of inflammation within the joint. This finding highlights the results of more than 20 years of research indicating that mast cells are frequent participants in non-allergic immune responses as well as in allergy. Equipped with a diversity of surface receptors and effector capabilities, mast cells are sentinels of the immune system, detecting and delivering a first response to invading bacteria and other insults. Accumulating within inflamed tissues, mast cells produce cytokines and other mediators that may contribute vitally to ongoing inflammation. Here we review some of the non-allergic functions of mast cells and focus on the potential role of these cells in murine and human inflammatory arthritis. | |
15259529 | Omega-3 fatty acids. | 2004 Jul 1 | Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Fatty fish, such as salmon and tuna, and fish oil are rich sources of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Flaxseed, canola oil, and walnuts also are good dietary sources of omega-3 fatty acids. In addition to being antiarrhythmic, the omega-3 fatty acids are antithrombotic and anti-inflammatory. In contrast, omega-6 fatty acids, which are present in most seeds, vegetable oils, and meat, are prothrombotic and proinflammatory. Omega-3 fatty acids also are used to treat hyperlipidemia, hypertension, and rheumatoid arthritis. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g per day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardioprotection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2 to 4 g per day) and to reduce morning stiffness and the number of tender joints in patients with rheumatoid arthritis (at least 3 g per day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids. | |
12102474 | Clarithromycin in rheumatoid arthritis patients not responsive to disease-modifying antirh | 2002 May | OBJECTIVE: In 1996 we found by serendipity that 2 patients with rheumatoid arthritis (RA) who were taking clarithromycin (CM) to eradicate Helicobacter pylori experienced a regression of their RA symptoms. Following this observation, we tested the hypothesis that this reduction in symptoms could have been caused by CM administration. METHODS: We performed a 6-month, open, uncontrolled pilot study on 18 patients (14 females and 4 males, mean age 62 yrs.) with RA who had previously received DMARDs (mean 2.6) and discontinued the treatment at least one month earlier because lack of efficacy or severe side effects. Patients were treated with CM at the dose of 500 mg twice per day for the first 10 days, followed by a daily maintenance dose of 250 mg twice per day. RESULTS: 4/18 patients did not complete the treatment, 2/18 were not responsive to the treatment and 2/18 discontinued the treatment. Following ACR criteria the improvement was: 10 patients ACR 20; 6 patients ACR 50; and 2 patients ACR 70. The remaining 4 patients did not reach ACR 20 since either the number of tender or swollen joints was not to the level required. Reductions in PGE2 and soluble phospholipase A2 plasma levels were closely related to CM plasma levels. CONCLUSIONS: Ourfindings suggest that CM treatment can be beneficial in those patients who are not responsive to or cannot tolerate DMARDs. No definitive conclusions can be drawn based on the present study, due to the small sample size involved. | |
14737874 | Pharmacologic interventions in the treatment of temporomandibular disorders, atypical faci | 2003 Fall | AIMS: To carry out a systematic review of the literature in order to assess the pain-relieving effect and safety of pharmacologic interventions in the treatment of chronic temporomandibular disorders (TMD), including rheumatoid arthritis (RA), as well as atypical facial pain (AFP), and burning mouth syndrome (BMS). METHODS: Study selection was based on randomized clinical trials (RCTs). Inclusion criteria included studies on adult patients (> or = 18 years) with TMD, RA of the temporomandibular joint (TMJ), AFP, or BMS and a pain duration of > 3 months. Data sources included Medline, Cochrane Library, Embase, and Psych Litt. RESULTS: Eleven studies with a total of 368 patients met the inclusion criteria. Four trials were on TMD patients, 2 on AFP, 1 on BMS, 1 on RA of the TMJ, and 3 on mixed groups of patients with TMD and AFP. Of the latter, amitriptyline was effective in 1 study and benzodiazepine in 2 studies; the effect in 1 of the benzodiazepine studies was improved when ibuprofen was also given. One study showed that intra-articular injection with glucocorticoid relieved the pain of RA of the TMJ. In 1 study, a combination of paracetamol, codeine, and doxylamine was effective in reducing TMD pain. No effective pharmacologic treatment was found for BMS. Only minor adverse effects were reported in the studies. CONCLUSION: The common use of analgesics in TMD, AFP, and BMS is not supported by scientific evidence. More large RCTs are needed to determine which pharmacologic interventions are effective in TMD, AFP, and BMS. | |
12691174 | Gene polymorphisms, inflammatory diseases and cancer. | 2002 Nov | Genes whose products play a critical role in regulation of the immune response include the human leucocyte antigen (HLA) and cytokine families of genes. The HLA genes are the most polymorphic found in the human genome, and the bulk of this polymorphism results in functional differences in expressed HLA molecules, resulting in inter-individual differences in presentation of peptide antigens to T-cells. In addition, a considerable number of cytokine-associated gene polymorphisms have been identified, the bulk of which occur in the upstream promoter sequences of these genes, which in many cases results in differential in vitro expression of the respective pro- or anti-inflammatory gene product. Particular HLA polymorphisms result in well-defined associations with a large number of immunologically-mediated diseases, including some diseases with known dietary risk factors. For example, individuals of HLA-DQA1*0501, DQB1*0201 genotype have a greater than 200-fold increased risk of developing intolerance to dietary wheat gluten (coeliac disease), and additional HLA-related factors may influence the development of malignant lymphoma within pre-existing coeliac disease. Similarly, HLA-DRB1 alleles sharing a common sequence motif constitute the primary known genetic risk factor for rheumatoid arthritis. The influence of polymorphisms associated with differential cytokine expression on disease susceptibility is currently of much interest. Most attention has been focused on associations with susceptibility to benign immunologically-mediated diseases, including a number of gut diseases. However, recent work from our laboratory indicates that cytokine polymorphisms may influence susceptibility to and prognosis in a number of different cancers, including malignant melanoma skin cancer and solid tumours which may be influenced by diet, such as prostate cancer (collaboration with the CRC/BPG UK Familial Prostate Cancer study). In addition, preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy human subjects may be genotype dependent. | |
12379517 | Atopic disorders in ankylosing spondylitis and rheumatoid arthritis. | 2002 Nov | BACKGROUND: The prevalence of atopic disorders in ankylosing spondylitis (AS) is unknown. AS and rheumatoid arthritis (RA) exhibit divergent T helper (Th) cell cytokine patterns. OBJECTIVE: To test the hypothesis that Th2 polarised atopic disorders may be decreased in Th1 polarised RA but increased in AS, which is characterised by an impaired Th1 cytokine pattern, by assessing the prevalence of atopic disorders in AS and RA. METHODS: 2008 subjects (380 patients with AS, 728 patients with RA, 900 controls) from Berlin, Germany, were considered in this cross sectional study. A questionnaire incorporating questions from the European Community Respiratory Health Service (ECRHS) and the International Study of Asthma and Allergies in Childhood (ISAAC) protocol was mailed to all subjects. Disease severity was assessed by the modified Health Assessment Questionnaire (mHAQ). RESULTS: 1271 (63.3%) people responded to the questionnaire. The prevalence of any atopic disorder was 24.6% (61/248) in patients with AS, 20.7% (111/536) in controls, and 13.1% (64/487) in patients with RA (p=0.0009 for AS v RA; p=0.001 for controls v RA). Hay fever was reported by 40/248 (16.1%) patients with AS, 82/536 (15.3%) controls, and 42/487 (8.6%) patients with RA (p=0.002 for AS v RA; p=0.001 for controls v RA). Atopic dermatitis was reported by 19/248 (7.7%) patients with AS, 26/536 (4.9%) controls, and 14/487 (2.9%) patients with RA (p=0.003 for AS v RA), and asthma by 18/248 (7.3%) patients with AS, 35/536 (6.5%) controls, and 21/487 (4.3%) patients with RA. The differences were related neither to age nor to drugs. Disease severity was less in atopic patients with RA who had the atopic disorder before the onset of RA (median mHAQ 0.75) than in patients in whom RA preceded the atopic disorder (median mHAQ 1.75; p=0.027). CONCLUSIONS: Atopic disorders are decreased in RA but only slightly and non-significantly increased in AS. This may imply that atopy confers some protection from RA but only little if any susceptibility to AS. It may further indicate that the cytokine deviation towards an impaired Th1 pattern in AS is less strong than the cytokine deviation towards Th1 in RA, a finding which may affect future therapeutic approaches. | |
15124939 | HLA-DRB1* alleles and temporomandibular joint erosion in patients with various rheumatic d | 2004 | OBJECTIVE: To investigate the association between HLA antigens and temporomandibular joint (TMJ) erosion, salivary composition, and focal sialadenitis in patients with rheumatic diseases. METHODS: Eighty-four patients, 24 with rheumatoid arthritis (RA), 19 with mixed connective tissue disease (MCTD), 19 with ankylosing spondylitis (AS), and 22 with spondyloarthropathy (SPA) were studied. Each patient underwent clinical examination of the masticatory system, unstimulated and stimulated saliva collection, and minor salivary gland biopsy. Radiographs (OPTG) of the TMJ were obtained, and HLA allele (A, B, C and DRB1*) analysis was performed. Erosion in OPTG was scored from 0 (no erosion) to 4 (condyles totally eroded). In the analysis, scores 0-2 were grouped as normal or mild changes, and scores 3-4 as distinct erosions. One hundred healthy blood donors served as controls for HLA typing. RESULTS: Distinct erosion of the TMJ in OPTG was observed in 22 (27%) patients. It affected four (17%) of the 24 patients with RA, three (17%) of the 18 with MCTD, seven (37%) of the 19 patients with AS and eight (38%) of the 21 with SPA non-significant (NS). The mean erosion scores were 1.7 for RA, 1.3 for MCTD, 2.5 for SPA, and 1.6 for AS patients [probability (p) = 0.04]. The frequency of HLA-B27 antigen was higher in the AS and SPA patients, and that of HLA-DRB1*04 allele higher in RA patients than in control subjects. In the whole patient population, HLA-DRB1*01 allele was significantly associated with erosions 16/36 (44%) versus 6/46 (131%1) (p = 0.0014). In the SPA group, patients with HLA-DRBI*01 allele had a significantly higher occurrence of distinct erosions than patients without this allele [8/10 (80%) versus 0/11 (0%) (p = 0.0002)], whereas DRB1*06 was protective [0/8 (0%) versus 8/13 (62%) (p = 0.018)]. HLA-DRB1*04 was associated with increased salivary IgG in the RA patients. CONCLUSION: HLA antigens are significantly associated with the development of destructive lesions in the TMJ, as well as composition of saliva in patients with various rheumatic diseases. | |
12323392 | Involvement of the peripheral benzodiazepine receptor in the development of rheumatoid art | 2002 Sep 27 | In this study, the effects of different peripheral benzodiazapine receptor ligands: PK 11195 [1-(2-chloro-phenyl)-N-methyl-N-(1-methylpropyl)-1-isoquinoline carboxamide], Ro5-4864 [7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one] and the newly described SSR 180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridozine[4,5-b] indole-1-acetamide) were analysed on the progression and severity of rheumatoid arthritis in vivo in the Mrl/lpr mice model, following chronic treatment (at 3 mg/kg, i.p. for 30 days). We found that peripheral benzodiazepine receptor ligands have significant beneficial therapeutic action on the development of spontaneous rheumatoid arthritis-like signs. Concomitantly, we mapped immunoreactive peripheral benzodiazepine receptor in inflamed tissues, and we observed that in addition to the infiltrated leukocytes, peripheral benzodiazepine receptor was expressed in synovial membranes, at the cartilage pannus junction and in chondrocytes. Interestingly, we observed that peripheral benzodiazepine receptor expression in chondrocytes was reduced when Mrl/lpr mice developed the pathology and restored upon peripheral benzodiazepine receptor ligand treatment. Altogether, our data provide further evidence of a role played by peripheral benzodiazepine receptor in the regulation of inflammation processes and support new therapeutic applications for specific potent peripheral benzodiazepine receptor ligands. | |
12608045 | [Toxic lesions of the organ of vision caused by chloroquine derivatives]. | 2003 Jan | An analysis of complications resulting from a long-term administration of chloroquinine derivatives is presented in the paper. The efficacy of chloroquinine derivatives for patients with rheumatological and dermatological pathologies was demonstrated. However, the remote results showed, after the administration of the above preparations, highly serious complications in different organs and primarily in the organ of vision. As for our practice, complications of various severity degrees were found in 6 patients with rheumatoid arthritis, who received the preparations in question, such complications were classified as highly severe in 1 patient. Taking into consideration that the chloroquinine derivatives have been widely used, while many doctors are not aware of the complications caused by them. We found it advisable to compile a literature survey and to enlarge it with our own observations. Eventually, we concluded that the pathogenesis of disorders in visual functions could be explained by a toxic effect produced by the chloroquinine derivatives not only on the retina but also on the optic nerve and chiasm. Our opinion is that a thorough and differentiated approach is needed to patients with the mentioned pathologies while using the chloroquinine derivatives for treatment. | |
14677172 | Longterm observational study of methotrexate use in a Dutch cohort of 1022 patients with r | 2003 Nov | OBJECTIVE: To study which factors are associated with longterm methotrexate (MTX) use in rheumatoid arthritis (RA). METHODS: All patients with RA who had started MTX after January 1, 1993, were selected from a regional hospital based registration system. Data on demographic and clinical features were retrieved through chart review. By means of life table analysis and Cox regression analysis, MTX survival and the relation between demographic variables, clinical features, and MTX survival were studied. RESULTS: A total of 1072 MTX treatment episodes in 1022 patients were analyzed. The cumulative MTX survival probability after 5 years was 64%, and after 9 years was 50%. Univariate analysis showed a significant relation between MTX survival probability and folic acid supplementation, attending rheumatologist, concurrent prednisolone use, concurrent sulfasalazine use, and the number of previous disease modifying drugs. In the multivariate analysis folic acid supplementation, attending rheumatologist, and concurrent prednisolone use remained significantly related to MTX survival. Age, disease duration, and creatinine clearance were not. CONCLUSION: In this retrospective study of 1022 patients with RA the cumulative MTX survival probability was 64% after 5 years and 50% after 9 years. Folic acid supplementation and to a lesser extent prednisolone were associated with a longer MTX survival. In addition, treatment strategies of individual rheumatologists influenced MTX survival. | |
15219128 | [Differential analgesic treatment in arthrosis and arthritis]. | 2004 Mar 25 | The leading symptom of arthrosis and arthritis is pain. As in the case of pharmacotherapy fortumor pain, a stepped approach is also recommended for rheumatic complaints. Mild-to-moderate pain in noninflammatory arthrosis can be ameliorated by paracetamol or low-dose ibuprofen. If inflammation is present, nonsteroidal anti-inflammatory drugs (NSAIDs) must be employed. If this treatment does not suffice to manage systemic arthritis, oral short-acting corticosteroids are applied. Intra-articular corticosteroid injections can be used to individual inflamed active joints. For chronic pain, opioids may be necessary in addition to NSAID treatment. The use of NSAIDs is limited by gastrointestinal side effects. In the case of risk patients, therefore, preventive measures must be taken, and PPI or, instead of NSAIDs, coxibs employed in addition. | |
15690700 | [Serum soluble adhesion molecules--sICAM-1, sVCAM-1, sE-selectin--in patients with systemi | 2004 Oct | Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the joints and is often associated with internal organs involvement. Cell adhesion molecules play an important role in the pathogenesis of endothelial-leukocyte interactions, angiogenesis and lymphocyte activation, leading to the progression of the disease. The objective of this study was to investigate whether the serum profile of soluble adhesion molecules is associated with clinical feature and extra-articular manifestation of RA. MATERIAL AND METHODS: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were assessed by ELISA in 29 patients with RA and 25 healthy controls. Ten out of the 29 patients had systemic lesions. RESULTS: The serum concentrations of siCAM-1, sVCAM-1, sE-selectin were significantly increased in RA patients compared with controls (p<0.001 in all cases). RA patients with extra-articular involvement showed significantly higher levels of sICAM-1 and sVCAM-1 than those without organ injury (p<0.001 and p<0.01 respectively). The serum concentrations of sICAM-1 and sVCAM-1 correlated with CRP and ESR. CONCLUSIONS: We conclude that serum levels of sICAM-1 and sVCAM-1 may be useful in the diagnosis of the systemic injury in RA patients. | |
15366323 | Monitoring methotrexate therapy in patients with rheumatoid arthritis. | 2004 Aug | OBJECTIVE: The aim of this work was to study methotrexate (MTX) kinetics and their relation to the effectiveness of the therapy in patients with rheumatoid arthritis (RA). Other aims were to analyze the influence of MTX on liver, kidney, hematopoietic function and to determine the possibility of using early drug concentrations to predict the subsequent value of the treatment. MATERIAL AND METHODS: The observations were carried out in 49 patients with RA after the first dose of MTX and after 7 months of treatment. Methotrexate concentrations in blood serum and urine were determined using fluorescence polarization immunoassay applying a TDx Abbott analyzer. RESULTS: No correlation between concentrations, pharmacokinetic parameters and the duration of the disease, its activity, clinical symptoms, observations pertaining to the disease made by physician and patients and morning stiffness of joints was seen. Of those tests for the evaluation of liver, kidney and hematopoietic function, only the mean activity of N-acetyl-beta-D-glucosaminidase (NAG) in urine was significantly elevated both before and after treatment with MTX when compared to corresponding values in the control group of healthy subjects. We have formulated equations allowing for the early recognition of patients with a risk of adverse effects due to impaired elimination of MTX from the body. CONCLUSION: Our results show that monitoring MTX therapy using concentrations in patients with RA does not significantly improve the effectiveness of the treatment, but it can play an important role in increasing the safety of this drug. | |
15506544 | Ibuprofen and Alzheimer's disease. | 2004 | There is epidemiological observation that long-term treatment of patients suffering from rheumatoid arthritis with ibuprofen results in reduced risk and delayed onset of Alzheimer's disease (AD). Chronic central nervous system inflammation in AD brain is implicated in the pathology, but how ibuprofen impacts the pathogenic AD pathways is unclear. Ibuprofen, a commonly used over-the-counter nonsteroidal anti-inflammatory drug (NSAID) that is a cyclooxygenase (COX)-1 and COX-2 inhibitor as well as a peroxisome proliferator-activated receptor (PPAR) agonist, decreases the production of nitric oxide (NO), protects neurons against glutamate toxicity and decreases the production of proinflammatory cytokines. Ibuprofen crosses the blood brain barrier and suppresses neuritic plaque pathology and inflammation in AD brain. Furthermore, ibuprofen is a potent free radical scavenger, and it could reduce lipid peroxidation and free radical generation. Because of neuroprotective activity, relative safety, and its long history of use, ibuprofen is currently being developed for clinical use in AD. Ibuprofen may be a promising new therapeutic avenue for the treatment of neurodegenerative diseases such as AD. | |
12358393 | Early patient outcomes after primary and revision total knee arthroplasty. A prospective s | 2002 Sep | There has been speculation as to how the outcome of revision total knee arthroplasty (TKA) compares with that of primary TKA. We have collected data prospectively from patients operated on by one surgeon using one prosthesis in each group. One hundred patients underwent primary TKA and 60 revision TKA. They completed SF-12 and WOMAC questionnaires before and at six and 12 months after operation. The improvements in the SF-12 physical scores and WOMAC pain, stiffness and function scores in both primary and revision TKA patients were highly statistically significant at six months. There was no statistically significant difference in the size of the improvement in the SF-12 physical and WOMAC pain, stiffness and function scores between the primary and revision patients at six months after surgery. The SF-12 mental scores of patients in both groups showed no statistically significant difference after surgery at the six- and 12-month assessments. Our findings show that primary and revision TKA lead to a comparable improvement in patient-perceived outcomes of physical variables in both generic and disease-specific health measures at follow-up at one year. | |
12242171 | Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of os | 2002 Sep 21 | OBJECTIVE: To determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and rheumatoid arthritis. DESIGN: Systematic review of randomised trials that compared at least 12 weeks' celecoxib treatment with another non-steroidal anti-inflammatory drug (NSAID) or placebo and reported efficacy, tolerability, or safety. Trials identified from manufacturer and by searching electronic databases and evaluated according to predefined inclusion and quality criteria. Data combined through meta-analysis. PARTICIPANTS: 15 187 patients with osteoarthritis or rheumatoid arthritis. EFFICACY: Western Ontario and McMaster universities osteoarthritis index; American College of Rheumatology responder index and joint scores for rheumatoid arthritis. Tolerability: withdrawal rates for adverse effects. Gastrointestinal safety: incidence of ulcers, bleeds, perforations, and obstructions. RESULTS: Nine randomised controlled trials were included. Celecoxib and NSAIDS were equally effective for all efficacy outcomes. Compared with those taking other NSAIDs, in patients taking celecoxib the rate of withdrawals due to adverse gastrointestinal events was 46% lower (95% confidence interval 29% to 58%; NNT 35 at three months), the incidence of ulcers detectable by endoscopy was 71% lower (59% to 79%; NNT 6 at three months), and the incidence of symptoms of ulcers, perforations, bleeds, and obstructions was 39% lower (4% to 61%; NNT 208 at six months). Subgroup analysis of patients taking aspirin showed that the incidence of ulcers detected by endoscopy was reduced by 51% (14% to 72%) in those given celecoxib compared with other NSAIDs. The reduction was greater (73%, 52% to 84%) in those not taking aspirin. CONCLUSION: Celecoxib is as effective as other NSAIDs for relief of symptoms of osteoarthritis and rheumatoid arthritis and has significantly improved gastrointestinal safety and tolerability. |