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ID PMID Title PublicationDate abstract
17038478 Interleukin-7 induced immunopathology in arthritis. 2006 Nov Interleukin (IL)-7 is a potent immunoregulatory cytokine that is detected in joints of patients with rheumatoid and juvenile idiopathic arthritis and which correlates with parameters of disease. Several synovial cell types that play an important role in inflammation and immunopathology, such as macrophages, dendritic cells, and fibroblasts, produce IL-7. IL-7 induces cytokines produced by arthritogenic T cells (for example, interferon gamma (IFNgamma), IL-17), T cell differentiating factors (for example, IL-12), chemokines capable of attracting inflammatory cells (for example, macrophage induced gene (MIG), macrophage inflammatory protein (MIP)-1alpha) as well as molecules involved in cell adhesion, migration, and costimulation (for example, lymphocyte function associated antigen (LFA)-1, CD40, CD80). In addition, IL-7 can induce bone loss by stimulating osteoclastogenesis that is dependent on receptor activator of nuclear factor kappaB ligand (RANKL). IL-7 induces tumour necrosis factor alpha (TNFalpha) secretion by T cells and by monocytes after T cell dependent monocyte/macrophage activation. Importantly, induction of both IL-7 and IL-7 induced effects seems to be able to operate independent of TNFalpha. Together this suggests that IL-7 is an important cytokine in several rheumatic conditions, capable of inducing inflammation and immunopathology. Thus it may be an important target for immunotherapy.
17219147 High-resolution MRI of the wrist and finger joints in patients with rheumatoid arthritis: 2007 Aug The goal of this study was to compare magnetic resonance (MR) image quality at different field strengths for evaluating lesions in wrist and finger joints of patients with rheumatoid arthritis (RA) in order to determine whether the higher field strength provides diagnostic gain. The hand mainly affected in 17 RA patients was examined at 1.5 Tesla (T) and 3.0 T with comparable MR imaging (MRI) protocols. MR images were reviewed twice by two experienced radiologists using the Rheumatoid Arthritis MRI Scoring System (RAMRIS) of the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) group. Image quality was rated on a five-point scale using Friedmann's test and Kendall's W-test for statistical analysis. Image comparison revealed better image quality at higher field strength. Image quality of T1-weighted images was rated 14-22% better at 3.0 T compared with 1.5 T by both readers. Moreover, the rating for the T2-weighted-images acquired at 3.0 T was one point better in the five-point scale used. Inter-reader correlation for image quality, bone erosions/defects, edema and synovitis ranged between 0.6 and 0.9 at 3.0 T and between 0.6 and 0.8 at 1.5 T. Intra-reader correlation for these parameters was high at 0.8-1.0. MRI image quality of RA hands is superior at 3.0 T, while an acceptable image quality is achieved at 1.5 T, which improves the evaluation of extent of bone edema, synovitis and identification of small bone erosions.
17353582 Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic sympto 2007 Feb OBJECTIVES: a) To evaluate the effect of Neptune Krill Oil (NKO) on C-reactive protein (CRP) on patients with chronic inflammation and b) to evaluate the effectiveness of NKO on arthritic symptoms. METHODS: Randomized, double blind, placebo controlled study. Ninety patients were recruited with confirmed diagnosis of cardiovascular disease and/or rheumatoid arthritis and/or osteoarthritis and with increased levels of CRP (>1.0 mg/dl) upon three consecutive weekly blood analysis. Group A received NKO (300 mg daily) and Group B received a placebo. CRP and Western Ontario and McMaster Universities (WOMAC) osteoarthritis score were measured at baseline and days 7, 14 and 30. RESULTS: After 7 days of treatment NKO reduced CRP by 19.3% compared to an increase by 15.7% observed in the placebo group (p = 0.049). After 14 and 30 days of treatment NKO further decreased CRP by 29.7% and 30.9% respectively (p < 0.001). The CRP levels of the placebo group increased to 32.1% after 14 days and then decreased to 25.1% at day 30. The between group difference was statistically significant; p = 0.004 at day 14 and p = 0.008 at day 30. NKO showed a significant reduction in all three WOMAC scores. After 7 days of treatment, NKO reduced pain scores by 28.9% (p = 0.050), reduced stiffness by 20.3% (p = 0.001) and reduced functional impairment by 22.8% (p = 0.008). CONCLUSION: The results of the present study clearly indicate that NKO at a daily dose of 300 mg significantly inhibits inflammation and reduces arthritic symptoms within a short treatment period of 7 and 14 days.
17251823 Tarsoconjunctival pedicle flap for the management of a severe scleral melt. 2007 Feb PURPOSE: To describe the use of a tarsoconjunctival pedicle flap for the repair of a large scleral melt in a patient with rheumatoid arthritis. METHODS: Case report and literature review. RESULTS: A 36-year-old woman with a history of rheumatoid arthritis presented to the Rocky Mountain Lions Eye Institute with a large scleral melt in the right eye. Ophthalmic examination revealed a visual acuity of 20/400 and a superior scleral melt measuring 15 x 30 mm. After instituting systemic immunosuppression, a tarsoconjunctival pedicle was used to provide tectonic support to the globe. At her 3-month postoperative visit, her vision improved to 20/30, and the scleral melt was completely epithelialized. CONCLUSIONS: A tarsoconjunctival pedicle flap provides an excellent alternative to help restore scleral integrity in patients with severe autoimmune necrotizing scleritis.
16738904 Interleukin-6 levels in synovial fluids of patients with rheumatoid arthritis correlated w 2006 Oct To compare the histological appearance of synovial membrane and interleukin (IL)-6 levels in synovial fluids of patients with rheumatoid arthritis (RA). Synovial tissue and synovial fluids were obtained from 51 knee joints with RA undergoing synovectomy or joint replacements. A histological inflammation score was determined based on the hyperplasia of the synovial lining and infiltration of inflammatory cells. The concentrations of IL-6 in synovial fluids were measured by ELISA. The association between IL-6 levels and histological findings was evaluated. We found a positive correlation between the infiltration of inflammation cells in synovial tissues and the concentration of IL-6 in synovial fluids. The IL-6 level in synovial fluid partially reflects histological synovial inflammation.
18388527 Malignancy and biologic therapy in rheumatoid arthritis. 2008 May PURPOSE OF REVIEW: Owing to the complex functions of the inflammatory response systems--potentially or clearly of importance in human carcinogenesis--that biological therapies interfere with uncertainty regarding their safety profile for malignancy is more or less expected. This uncertainty has been further sparked by the apparent discordance between trial data and observational studies of anti-TNF agents, and the methodological challenges inherent in addressing the safety profile of new drugs for delayed and multifactorial events like cancer. RECENT FINDINGS: This review provides a summary of the pattern of cancer seen in patients with rheumatoid arthritis not treated with biologics, and the currently published data on cancer risk following treatment with biologics in patients with rheumatoid arthritis, primarily anti-TNF therapy. SUMMARY: Published data currently do not exclude clinically important increased risks, nor do they refute beneficial effects. As per definition, much of the currently available safety data from trials or clinical practice do not capture the impact of either any effect that biological therapy might have on early events in carcinogenesis, or of sustained exposure to biologics. Beyond the risk of de-novo cancer development, several other clinically important aspects of cancer safety remain to be addressed, including issues of prognosis, progression, and relapse.
18083042 Characterization of synovial cell clones isolated from rheumatoid arthritis patients: poss 2008 Jan To elucidate the role of the synovium in bone destruction by osteoclasts in rheumatoid arthritis (RA), primary synovial cells isolated from RA patients were cultured and characterized. The cultured primary cells did not produce RANKL (TRANCE/ODF/OPGL/TNFSF11/CD254), an inducer of osteoclast differentiation, but constitutively produced its inhibitor, osteoprotegerin (OPG). Addition of TNF-alpha to the primary cultures of synovial cells reduced the cell viability and strongly suppressed OPG production. We then established nine synovial cell clones, including SYM-1, responsible for OPG production from primary synovial cell cultures. TNF-alpha induced apoptosis of SYM-1 cells within 24h and decreased OPG levels, while infliximab, a chimerical form of the anti-TNF-alpha antibody drug, suppressed the apoptosis and restored OPG levels. These results suggest the existence of fibroblastic cells producing OPG in the synovium, while TNF-alpha suppresses OPG production by inducing apoptosis in those cells. Further, infliximab is considered to inhibit bone destruction through restoration of OPG levels in RA.
16881110 Hypothalamic-pituitary-adrenal hormonal responses to exercise stress test in patients with 2006 Aug OBJECTIVE: There is controversy about hormonal dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis that is supposed to contribute to the development or persistence of rheumatoid arthritis (RA). We investigated whether there is an altered and blunted response of the HPA axis when stimulated by exercise stress in patients with RA. METHODS: Twenty women with RA and 15 matched healthy controls were included in the study. All subjects took an ergospirometric exercise test on the treadmill to determine anaerobic threshold (AT). On another day, blood was collected for basal plasma levels of growth hormone (GH), insulin-like growth factor-I, cortisol, and adrenocorticotrophic hormone (ACTH); and subjects exercised on treadmill at an intensity above their AT. Blood was collected again to measure hormone levels just after the exercise stopped and 60 minutes later. RESULTS: Two subjects left the study, so 19 patients and 14 controls were evaluated. Peak oxygen consumption (VO(2)), VO(2) at AT, exercise test duration, and basal hormone levels were similar in groups. In both groups, GH slightly increased just after the exercise (0 min), and decreased at 60 min compared to baseline, but the change was not different between groups. Cortisol levels decreased significantly at 0 and 60 min in both groups, ACTH levels did not change in time, and there was no difference between groups. CONCLUSION: There was no perturbation in HPA axis stimulated by exercise stress test in patients with RA and all the variables measured were similar to those of the control group.
17222722 Improved wrist pannus volume measurement from contrast-enhanced MRI in rheumatoid arthriti 2007 Jan BACKGROUND: Contrast-enhanced MRI is of value in assessing rheumatoid pannus in the hand, but the images are not always easy to quantitate. OBJECTIVE: To develop and evaluate an improved measurement of volume of enhancing pannus (VEP) in the hand in human rheumatoid arthritis (RA). METHODS: MR images of the hand and wrist were obtained for 14 patients with RA at 0, 1 and 13 weeks. Volume of enhancing pannus was measured on images created by subtracting precontrast T1-weighted images from contrast-enhanced T1-weighted images using a shuffle transformation technique. Maximum intensity projection (MIP) and 3D volume rendering of the images were used as a guide to identify the pannus and any contrast-enhanced veins. RESULT: Visualisation of pannus was much improved following the shuffle transform. Between 0 weeks and 1 week, the mean value of the within-subject coefficient of variation (CoV) was 0.13 and the estimated total CoV was 0.15. There was no evidence of significant increased variability within the 13-week interval for the complete sample of patients. CONCLUSION: Volume of enhancing pannus can be measured reproducibly in the rheumatoid hand using 3D contrast-enhanced MRI and shuffle transform.
17580545 [NSAID prescription in patients with rheumatoid arthritis and cardiovascular disease]. 2006 Nonsteroidal anti-inflammatory drugs are the first choice in the tretment of rheumatic diseases. Nonsteroidal-antiinflammatory drugs show high efficacy, but they could be responsible for gastrointestinal and cardiovascular adverse events. When the gastrointestinal risk is generally accepted, cardiovascular risk is still without consensus. Did the discussion about potential cardiovascular risk with nonsteroidal anti-inflammatory drugs influenced their prescription in real life? Data on 201 patients with rheumatoid arthritis show that the prescription of nonselective, nonsteroidal anti-inflammatory drugs remain unchanged. More than two third of the patients use nonsteroidal anti-inflammatory drugs despite they have established cardiovascular disease.
16633928 A case of idiopathic portal hypertension associated with rheumatoid arthritis. 2006 A 53-year-old woman who had been diagnosed with rheumatoid arthritis was found to have thrombocytopenia, splenomegaly, and gastric varices. She was diagnosed as having idiopathic portal hypertension on the basis of liver biopsy and angiography. Treatment with prednisolone was not sufficiently effective for thrombocytopenia. After transabdominal devascularization with splenectomy, thrombocytopenia subsided and gastric varices disappeared. In this case, the autoimmune mechanism as well as hypersplenism was suspected of being involved in the mechanism of thrombocytopenia.
17255310 Osteoclasts: what do they do and how do they do it? 2007 Feb As Americans live longer, degenerative skeletal diseases, such as osteoporosis, become increasingly prevalent. Regardless of cause, osteoporosis reflects a relative enhancement of osteoclast activity. Thus, this unique bone resorptive cell is a prominent therapeutic target. A number of key observations provide insights into the mechanisms by which precursors commit to the osteoclast phenotype and how the mature cell degrades bone. The osteoclast is a member of the monocyte/macrophage family that differentiates under the aegis of two critical cytokines, namely RANK ligand and M-CSF. Tumor necrosis factor (TNF)-alpha also promotes osteoclastogenesis, particularly in states of inflammatory osteolysis such as that attending rheumatoid arthritis. Once differentiated, the osteoclast forms an intimate relationship with the bone surface via the alphavbeta3 integrin, which transmits matrix-derived, cytoskeleton-organizing, signals. These integrin-transmitted signals include activation of the associated proteins, c-src, syk, Vav3, and Rho GTPases. The organized cytoskeleton generates an isolated microenvironment between the cell's plasma membrane and the bone surface in which matrix mineral is mobilized by the acidic milieu and organic matrix is degraded by the lysosomal protease, cathepsin K. This review focuses on these and other molecules that mediate osteoclast differentiation or function and thus serve as candidate anti-osteoporosis therapeutic targets.
17521246 Arthritis burden and impact are greater among U.S. women than men: intervention opportunit 2007 May OBJECTIVES: To summarize arthritis burden and impact among women compared with men, using updated surveillance and impact measures; to describe public health approaches to arthritis; and to review effective, evidence-based arthritis self-management interventions. RESULTS: Arthritis continues to burden the U.S. population as the leading cause of physical disability and affects women disproportionately: women with arthritis report greater prevalence of activity and work limitations, psychological distress, and severe joint pain than their male counterparts. Three main public health interventions can reduce arthritis impact: self-management education, physical activity, and weight management. Self-management education programs are proven to reduce pain and depression, delay disability, improve self-efficacy, physical function, and quality of life, and reduce healthcare costs. Appropriate physical activity decreases pain, improves function, and delays disability. The American College of Rheumatology recommends maintaining a healthy weight to benefit patients with hip or knee osteoarthritis. Women appear more receptive to certain information delivery methods (i.e., physician counseling) than men, suggesting gender-specific targeting of interventions may be of use. CONCLUSIONS: Effective interventions remain underused. The Centers for Disease Control and Prevention Arthritis Program and its partners, including state arthritis programs, continue their efforts to build the arthritis public health science base, monitor burden and impact, evaluate and disseminate evidence-based interventions, and work to decrease and delay disability, and increase quality of life among those with arthritis. As new approaches are developed, women and other disproportionately impacted groups merit particular consideration in tailoring and delivering programs to reduce arthritis burden.
19149089 [The role of anti-cyclic citrullinated peptide (anti-CCP) antibodies in serologic diagnosi 2008 Oct Anti-cyclic citrullinated peptide (anti-CCP) antibodies are used as highly specific and sensitive markers in the diagnosis of rheumatoid arthritis (RA), in recent years. The aim of this prospective and cross-sectional study was to measure the levels of anti-CCP and rheumatoid factor (RF) in patients with RA and osteoarthritis, and healthy volunteers to evaluate the specificity and possible diagnostic value of anti-CCP and RF, as well as their correlations with parameters of disease activity. Thirty-four patients with RA (mean age: 53.8 +/- 8.6; 29 female), 32 patients with osteoarthritis (mean age: 53.1 +/- 8.1; 26 female) and 32 healthy controls (mean age: 49.6 +/- 6.7; 24 female) were evaluated between July 2004-July 2005. RA diagnosis was done on the basis of criteria recommended by American College of Rheumatology (ACR). Clinical parameters, including disease activity score (DAS28) and health assessment questionnaire (HAQ) indices for physical capacity were detected for RA patients. As a result, 25 (73.5%) of the patients with RA were found positive for anti-CCP (mean value: 74.6 +/- 64.9 RU/ml), while 24 (70.6%) were positive for RF (mean value: 62.6 +/- 84.8 IU/ml). Serum levels of anti-CCP and RF showed statistically significant increase in patients with RA in comparison with osteoarthritis patients (all were negative for anti-CCP; 6.2% were positive for RF) and healthy controls (all were negative for anti-CCP anf RF) (p < 0.001). Twenty-two of the RA patients (64.7%) yielded positive results for both anti-CCP and RF, while seven (20.6%) were negative for both of the parameters. The sensitivity and specificity of anti-CCP reactivity for RA patients diagnosed based on ACR criteria were detected as 73.5% and 100%, respectively; the corresponding results for RF were 70.6% sensitivity and 96.8% specificity. The mean DAS28 and HAQ scores of RA patients with anti-CCP and RF were higher than the patients without anti-CCP and RF, however these differences were not statistically significant (p > 0.05). Furthermore, a correlation between serum anti-CCP levels and HAQ score was determined, while there was no correlation between DAS28 and anti-CCP levels. In conclusion, antibodies against CCP were thought to be more specific than RF for RA, and the determination of anti-CCP in addition to RF could be helpful in serological diagnosis and monitorization of patients with RA.
16278286 Genome scan meta-analysis of rheumatoid arthritis. 2006 Feb OBJECTIVE: Genome scans for rheumatoid arthritis (RA) have yielded inconsistent results. The absence of replication of linkage might be due to lack of power of individual studies. We performed a genome scan meta-analysis of published data to increase statistical power and to assess evidence for linkage of RA across genome scan studies. METHODS: Four RA whole-genome scans containing 767 families with 964 sibling pairs were included for the genome scan meta-analysis (GSMA). The GSMA method was applied to pool the results obtained from four genome scans. For each study, 120 genomic bins of approximately 30 centimorgans were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted and summed across all studies. The summed rank for each bin was assessed empirically for significance using permutation methods. RESULTS: A total of nine bins lay above the 95% confidence level (P=0.05) and four bins were above the 99% confidence level (P=0.01) in the RA GSMA, suggesting that these bins contain RA-linked loci: bins 6.2, 6.4, 8.1, 18.3, 12.3, 12.2, 1.5, 6.3 and 16.2. The strongest evidence for linkage occurred on chromosome 6p22.3-6p21.1 (bin 6.2), containing the HLA region (P(sumrnk)=0.0000008). CONCLUSION: This RA GSMA confirmed the evidence for HLA loci as the greatest susceptibility factor to RA and showed evidence for linkage at non-HLA loci, such as chromosomes 1p, 6, 8p, 12, 16 and 18q, across studies. These data may provide a basis to carry out targeted linkage and candidate gene studies, particularly in the regions.
17154104 [Rheumatoid arthritis and osteoporosis: trends in their treatments]. 2006 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damages, which consist of joint destruction and systemic osteoporosis. During the pathological process, pro-inflammatory cytokines such as TNF-alpha are largely produced from inflamed synovium and cause activation of osteoclasts deviated from bone remodeling cycle, resulting in joint destruction. On the other side, systemic osteoporosis, mainly caused by glucocorticoid (GC) is often complicated in RA, in which GC decreases number of osteoblasts, reduces synthesis of bone matrix proteins from them and enhances bone resorption, resulting in impairment of bone remodeling. Thus, joint destruction and systemic osteoporosis are brought about by different mechanisms. However, recent treatment strategies have improved managements of RA-related joint destruction as well as GC-induced osteoporosis. Treatments using biologics including infliximab and etanercept, effective for treating RA disease activity, also reduce joint destruction. Also, bisphosphonate is well known to be effective for not only treatment but also prevention of GC-induced osteoporosis. Thus, it is a clinical trend that physicians treat joint destruction as an inflammatory disease and osteoporosis as a metabolic disease.
17130265 Mycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheum 2006 Dec Evidence that was obtained in several experimental models and in strains of hypertensive rats indicates that infiltration of inflammatory cells and oxidative stress in the kidney play a role in the induction and maintenance of hypertension. Similar evidence is lacking in human hypertension, at least in part, because immunosuppressive treatment is unjustified in patients with hypertension. For addressing this issue, patients who were prescribed by their private physicians mycophenolate mofetil (MMF) for the treatment of psoriasis or rheumatoid arthritis and had, in addition, grade I essential hypertension and normal renal function were studied. Eight patients were studied before MMF was started, during MMF treatment, and 1 mo after MMF treatment had been discontinued. Other treatments and diet were unchanged in the three phases of the study. MMF therapy was associated with a significant reduction in systolic, diastolic, and mean BP. Urinary excretion of TNF-alpha was reduced progressively by MMF treatment and increased after MMF was discontinued. Reduction of urinary malondialdehyde, TNF-alpha, and RANTES excretion during MMF administration did not reach statistical significance but had a direct positive correlation with the BP levels. These data are consistent with the hypothesis that renal immune cell infiltration and oxidative stress play a role in human hypertension.
18987778 Total knee arthroplasty for massive joint destruction in a patient with rheumatoid arthrit 2009 We report the case of a patient requiring total knee arthroplasty (TKA) due to massive knee bone deformities caused by rheumatoid arthritis (RA) complicated with polyostotic fibrous dysplasia. Reconstruction of the knee with large osseous defect was achieved with conventional TKA by impaction bone grafting. Benign tumor-like conditions such as fibrous dysplasia may be treated with conventional TKA instead of endoprosthesis, custom-made knee prosthesis, or osteoarticular allografting.
18820621 Access to special care dentistry, part 7. Special care dentistry services: seamless care f 2008 Sep 27 Children and older people have been relatively well served by specialist dental care. Despite increasing disability amongst people in their middle years, there have been no or few dedicated dental teams with responsibility for provision of their oral care. This article explores the ethos and practicality of seamless care across the age groups and the primary/secondary care interface, with a focus on embedding oral health into general healthcare plans through the multidisciplinary team approach. The article explores four conditions--rheumatoid arthritis, Huntingdon's disease, multiple sclerosis and diabetes. It considers the features of each condition and how they can impact on both oral health and the delivery of dental services. It also considers the elements of care that contribute to a holistic and seamless approach to oral care services.
18415967 Improved health-related quality of life with effective disease-modifying antirheumatic dru 2008 Apr Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the articular synovium, resulting in bony erosions, deformity, and, ultimately, joint destruction. With associated comorbid conditions,especially cardiovascular, it can result in significant morbidity as well as early mortality. Patients with RA report impairments in health-related quality of life (HRQOL) in comparison with age- and sex-matched populations without arthritis. These decreases in HRQOL are attributed to the pain, impairment in physical function, and fatigue associated with this disease. The introduction of new disease-modifying antirheumatic drugs has revolutionized the treatment of RA, particularly the biologic agents: etanercept, infliximab,adalimumab, abatacept, and rituximab.Importantly, administration of these agents has resulted in statistically significant and clinically meaningful improvements in physical function and HRQOL. Many clinical studies confirm that with these therapies, RA patients report improvements in HRQOL, reflected by improved physical function, less fatigue, and better emotional and mental function. Maintenance of physical function is no longer the only treatment goal for RA but also to improve, restore, and preserve HRQOL. Results from pivotal clinical trials are analyzed in this article and the relevance of the data derived from the clinical studies to day-to-day clinical practice are also discussed.