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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16622722 Pneumocystis jiroveci pneumonia associated with low-dose methotrexate treatment for rheuma 2006 Low-dose methotrexate (MTX) therapy is widely used for rheumatoid arthritis (RA) because of its favorable efficacy and toxicity profile. Although Pneumocystis jiroveci pneumonia (PCP) is most often seen in severely immunosuppressed patients, PCP complicating low-dose MTX therapy for RA has been reported to sometimes occur. We herein report two cases of patients who developed PCP during treatment with low-dose MTX, and discuss the importance of prophylaxis for this opportunistic infection.
18415966 Generic quality-of-life assessment in rheumatoid arthritis. 2008 Apr BACKGROUND: Generic health status measures are commonly used in the evaluation of rheumatoid arthritis (RA) patients. The reliability, validity, and sensitivity of the instruments in the assessment of quality of life (QOL) in RA, and how they correlate to other clinical measurements, have longbeen questioned. OBJECTIVE: Analyze the performance of a commonly used generic health status measure, the Medical Outcomes Study 36-Item Short Form (SF-36), against the Outcome Measures in Rheumatology(OMERACT) criteria. METHODS: Data were analyzed from 7 double-blind, randomized controlled trials that examined the effectiveness of 1 or more interventions in RA. The primary outcome measures evaluated were the Mental and Physical Component Scores of the SF-36. Comparators were 1 or more of the following: the Health Assessment Questionnaire scores, tender joint count (TJC), the Disease Activity Score, and the American College of Rheumatology Responder Index (ACR20,ACR50, ACR70). The ability to detect a treatment effect in the study outcomes was evaluated using 3 measures: treatment difference,standardized response mean, and relative efficiency in relation to the TJC. RESULTS: As a generic QOL measure, the SF-36 is better suited to capture the holistic health of the patient, as reflected in the World Health Organization definition of health as being not only the avoidance of disease but the physical,emotional, and social well-being of the patient. Furthermore, use of the SF-36 permits comparisons of physical and mental aspects of QOL in the RA patient population, as well as comparisons of QOL parameters between patients with RA, other patient groups, and the general population. CONCLUSION: The SF-36 deserves serious consideration for inclusion in the core set of outcomes in RA trials.
17527089 Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial gia 2007 Jun We recently demonstrated that CSF1, the ligand of the tyrosine kinase receptor, CSF1R, can be translocated in pigmented villonodular synovitis (PVNS) and tenosynovial giant cell tumor (TGCT). In this study, we evaluated the staining characteristics of PVNS/TGCT and reactive synovitides for CSF1 and CSF1R by in situ hybridization and immunohistochemistry on tissue microarrays and correlated these findings with the recently described translocation. We collected specimens of TGCT/PVNS from 60 patients and of rheumatoid arthritis and other reactive synovitides from 74 patients. We identify 2 groups of PVNS and TGCT cases by the presence of CSF1 translocation and CSF1 expression. The first group (35 of 57 cases; 61%) had both the CSF1 translocation and high expression of CSF1 RNA, confirming our previous findings. Interestingly, a second group (22 of 57 cases; 39%) was identified that showed high expression of CSF1 RNA or CSF1 protein but did not have the translocation. The rheumatoid arthritis and reactive synovitis specimens showed localization of CSF1 RNA and protein to the synovial lining cells, implying a possible role for CSF1 in the pathogenesis of these lesions. As the CSF1 translocation is postulated to play an important role in the biology of PVNS/TGCT, the consistent presence of CSF1 expression in translocation-negative cases implies that other mechanisms can lead to CSF1 up-regulation. The consistent presence of CSF1 overexpression in all cases of PVNS/TGCT and reactive synovitides suggests both an important role for CSF1 in the spectrum of synovial pathologies and the possibility of targeting the CSF1/CSF1R interaction therapeutically.
16538391 Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis. 2007 Jan Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.
17946419 Semi-automated analysis of coronary flow Doppler images: validation with manual tracings. 2006 Coronary flow velocity reserve (CFVR) is conventionally obtained by manual tracings of Doppler profiles, as ratio of stress vs baseline diastolic peak velocity. When <1.9, this parameter evidences reduced coronary flow and possible microcirculatory disease. Our goals were: 1) to develop a novel technique for semi-automated detection of Doppler flow velocity profile, allowing the automated computation of CFVR and other parameters; 2) to validate this technique in comparison with conventional measurements obtained by manual tracing; 3) to test for differences between normal (N) subjects and patients with rheumatoid arthritis (RA). Linear correlation and Bland-Altman analyses showed that the proposed method was highly accurate and repeatable compared to the manual measurements. Comparison between N and RA groups evidenced significant differences in some of the automated parameters.
17186742 [Research and prospect on reducing the toxicity and enhancing the efficacy of Tipterygium 2006 Nov Researches in recent close to dozen years concerning Tripterygium wilfordii (TW) toxicity-reducing and efficacy-enhancing by combined use of Chinese medicine in treating intractable diseases such as rheumatoid arthritis, nephropathy, psoriasis etc. were summarized in this paper. Furthermore, the therapeutic mechanisms and adverse reaction of TW were elaborated and how to arrange properly the TCM hebal drugs used in combination was analyzed.
16781404 Early failure of modern metal-on-metal total hip arthroplasty using a Wagner standard cup. 2006 Jun In 54 patients (1 man and 53 women), 55 hips underwent primary metal-on-metal total hip arthroplasty (Metasul) with a Wagner standard cup (44-48 mm in outer diameter) and were followed for a minimum of 3 years. All patients received the same type of cementless femoral component (Natural Hip Stem) and femoral head (28 mm in diameter). Twelve (21.8%) of the 55 Wagner standard cups showed aseptic loosening over a mean period of 31 months postoperatively, and there were no bone anchors on the outer surface of the 9 retrieved cups. From our experience, the small Wagner standard cup does not achieve sufficient osteointegration and we do not recommend use of this cup, especially for dysplastic hips.
16720636 The -308 tumour necrosis factor-alpha gene polymorphism predicts therapeutic response to T 2007 Jan OBJECTIVE: To examine whether the G-to-A polymorphism at position -308 in the promoter of the tumour necrosis factor-alpha (TNFalpha) gene influences the therapeutic response to TNFalpha-blockers in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: A total of 54 patients with RA, 10 with PsA and 22 with AS were genotyped by polymerase chain reaction for the -308 TNFalpha promoter polymorphism. They were treated with infliximab (n = 63), adalimumab (n = 10) or etanercept (n = 13). Clinical response was assessed after 24 weeks by the Disease Activity Score in 28 joints (DAS28) for RA and PsA, and the Bath Ankylosing Spondylitis Activity Index (BASDAI) for AS patients. RESULTS: All patients with the A/A genotype (n = 3, all RA) and two patients with the A/G genotype (AS) failed to respond to anti-TNF treatment. Irrespective of the underlying disease, moderate response (n = 44) was predominantly associated with the A/G genotype (A/G 18/22, G/G 4/22), whereas good response (n = 59) was exclusively seen in patients with the G/G genotype. The average improvement in the DAS28 score was 0.83 in the A/A, 1.50 in the A/G and 2.64 in the G/G group of RA and PsA patients (P < 0.0001). The BASDAI score in AS improved on average by 1.21 in the A/G and by 3.30 in the G/G group (P < 0.005). CONCLUSIONS: The data suggest that humans with a TNFalpha -308 G/G genotype are better responders to anti-TNFalpha treatment than those with A/A or A/G genotypes independent of the treated rheumatic disease (RA, PsA or AS).
18203327 Easy and accurate diagnosis of rheumatoid arthritis using anti-cyclic citrullinated peptid 2008 Mar OBJECTIVE: To determine an easy-to-use diagnostic criterion for early rheumatoid arthritis (RA) that may be useful for general physicians, using anti-cyclic citrullinated peptide (CCP) antibody. METHODS: We prospectively studied 435 patients who first visited the hospital with arthritic symptoms within 24 months, including 264 visitors within 6 months. The diagnosis was made on their first visit by examination and laboratory tests including anti-CCP antibodies, rheumatoid factor (RF) and C-reactive protein (CRP), and radiograph. RESULTS: The diagnostic specificity and positive predictive value (PPV) of anti-CCP2 assay were 94.9% and 87.8%, respectively, and those of anti-CCP2 plus RF were 96.9% and 90.9% for the patients who first visited having morning stiffness, arthralgia, and/or joint swelling within 3 months from onset (n = 165). For the patients who first visited later, but within 24 months from onset (n = 260), the diagnostic specificity and PPV were extremely high, 98.7% and 95.5%, when anti-CCP2 assay was coevaluated with RF, CRP, and more than 3 swollen joints. Respective combinations of anti-CCP2 assay plus either 2 of 3 measures were also highly specific. CONCLUSION: A diagnostic criterion including anti-CCP2 assay in combination with RF, CRP, and/or swollen joints is less sensitive but highly specific, and accurately predicts future development of RA among those with arthritic symptoms who first consulted doctors within 2 years after onset. It should be highly useful for the general physician without special techniques or devices.
17006703 Hypertrophic pulmonary osteoarthropathy (HPOA) (Pierre Marie-Bamberger syndrome): two case 2007 Feb We report the cases of two middle-aged male smokers who presented to the early synovitis clinic with an acute phase response, synovitis of the wrists and ankles and clubbing of the fingers, but no respiratory symptoms. Both proved to have primary lung tumours with hypertrophic pulmonary osteoarthropathy, in one case resolving promptly with treatment of the carcinoma. We review the literature, including theories on pathogenesis.
18209031 Autoantigen-specific IL-10-transduced T cells suppress chronic arthritis by promoting the 2008 Feb 1 Deficient T cell regulation can be mechanistically associated with development of chronic autoimmune diseases. Therefore, combining the regulatory properties of IL-10 and the specificity of autoreactive CD4(+) T cells through adoptive cellular gene transfer of IL-10 via autoantigen-specific CD4(+) T cells seems an attractive approach to correct such deficient T cell regulation that avoids the risks of nonspecific immunosuppressive drugs. In this study, we studied how cartilage proteoglycan-specific CD4(+) T cells transduced with an active IL-10 gene (T(IL-10)) may contribute to the amelioration of chronic and progressive proteoglycan-induced arthritis in BALB/c mice. TCR-transgenic proteoglycan-specific T(IL-10) cells ameliorated arthritis, whereas T(IL-10) cells with specificity for OVA had no effect, showing the impact of Ag-specific targeting of inflammation. Furthermore, proteoglycan-specific T(IL-10) cells suppressed autoreactive proinflammatory T and B cells, as T(IL-10) cells caused a reduced expression of IL-2, TNF-alpha, and IL-17 and a diminished proteoglycan-specific IgG2a Ab response. Moreover, proteoglycan-specific T(IL-10) cells promoted IL-10 expression in recipients but did not ameliorate arthritis in IL-10-deficient mice, indicating that T(IL-10) cells suppress inflammation by propagating the endogenous regulatory IL-10 response in treated recipients. This is the first demonstration that such targeted suppression of proinflammatory lymphocyte responses in chronic autoimmunity by IL-10-transduced T cells specific for a natural Ag can occur via the endogenous regulatory IL-10 response.
18682561 Structural basis for induced formation of the inflammatory mediator prostaglandin E2. 2008 Aug 12 Prostaglandins (PG) are bioactive lipids produced from arachidonic acid via the action of cyclooxygenases and terminal PG synthases. Microsomal prostaglandin E synthase 1 (MPGES1) constitutes an inducible glutathione-dependent integral membrane protein that catalyzes the oxidoreduction of cyclooxygenase derived PGH(2) into PGE(2). MPGES1 has been implicated in a number of human diseases or pathological conditions, such as rheumatoid arthritis, fever, and pain, and is therefore regarded as a primary target for development of novel antiinflammatory drugs. To provide a structural basis for insight in the catalytic mechanism, we determined the structure of MPGES1 in complex with glutathione by electron crystallography from 2D crystals induced in the presence of phospholipids. Together with results from site-directed mutagenesis and activity measurements, we can thereby demonstrate the role of specific amino acid residues. Glutathione is found to bind in a U-shaped conformation at the interface between subunits in the protein trimer. It is exposed to a site facing the lipid bilayer, which forms the specific environment for the oxidoreduction of PGH(2) to PGE(2) after displacement of the cytoplasmic half of the N-terminal transmembrane helix. Hence, insight into the dynamic behavior of MPGES1 and homologous membrane proteins in inflammation and detoxification is provided.
17644554 Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients w 2008 Feb OBJECTIVES: A large-scale postmarketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA). METHODS: The PMS study was performed for all patients with RA who were treated with infliximab. They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospectively monitored with all adverse events noted for a period of 6 months. All case reports, which include safety-related events, were collected monthly. RESULTS: Adverse drug reactions (ADRs) were assessed for 6 months in 5000 patients who were consecutively enrolled in the PMS study. The incidence rates of total and serious ADRs were 28.0% and 6.2%, respectively. "Infections" or "respiratory disorders" were most commonly observed among serious ADRs. Bacterial pneumonia developed in 2.2%, tuberculosis in 0.3%, suspected Pneumocystis jiroveci pneumonia (PCP) in 0.4% and interstitial pneumonitis in 0.5%. Bacterial pneumonia (for which individuals of male gender, of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk) began to develop immediately after the start of treatment, while tuberculosis, PCP and interstitial pneumonitis developed about 1 month later. Serious infusion reactions were observed in 0.5% and were more likely to occur in patients who had participated in previous clinical trials of infliximab. CONCLUSION: This postmarketing surveillance study of patients treated with infliximab showed that infliximab in combination with low-dose MTX was well tolerated in Japanese patients with active RA.
17611758 The influence of postoperative coronal alignment on revision surgery in total knee arthrop 2008 Oct This study examines the association between postoperative coronal tibiofemoral alignment and revision surgery in knee arthroplasty. We retrospectively reviewed the case notes and post-operative long-leg radiographs of 197 Kinemax knee arthroplasty with mean follow-up of 9 years (SD 2.2). They were divided into three groups: neutral, valgus and varus. Revision or decision to revise was used as a hard endpoint. There was no statistical difference among the three groups (p=0.78). We conclude that aseptic failure of a total knee is multifactorial. Coronal tibio-femoral alignment may not be as important a cause of failure as has been previously thought.
17130944 [Changes in the patterns of disease after the epidemiological transition in health in Chil 2006 Jun BACKGROUND: During the twentieth century there was a change in the pattern of diseases in Europe, with an increase in the incidence of allergies and autoimmune disorders, that paralleled a decrease of infectious conditions. The Hygiene hypothesis proposes that these phenomena are causally related. AIM: To evaluate the epidemiological changes of allergic, autoimmune, and infectious diseases in Chile between 1950 and 2003. MATERIAL AND METHODS: Search for the incidence and prevalence of these diseases in the national records published by the Ministry of Health, as well as through a systematic search of national literature using PubMed and Scielo as search engines. RESULTS: The annual incidence of tuberculosis, rheumatic fever, measles, and typhoid fever has progressively diminished in Chile since 1970. Figures for the national prevalence for asthma, rheumatoid arthritis, and type I diabetes are scarce and difficult to compare, but clearly show an increasing epidemiological trend in the last 20 years. CONCLUSIONS: The national figures suggest that, although the country has only recently gone through an epidemiological transition in health problems, there are detectable changes that show the same trends described in Europe.
18952896 A functional folate receptor is induced during macrophage activation and can be used to ta 2009 Jan 8 Previous work has demonstrated that a subset of macrophages expresses a folate receptor (FR) that can mediate internalization of folate-linked molecules, including imaging and therapeutic agents. To characterize this subset, macrophages were collected from peritoneal cavities of mice injected with saline, thioglycolate, zymosan, heat-killed or live bacteria, and cell-surface markers that coexpress with FR were identified. Virtually no F4/80(+) peritoneal macrophages from saline-injected mice expressed FR, whereas numerous macrophages from mice injected with each inflammatory stimulus expressed FR. Examination of cell differentiation antigens that are up-regulated in FR(+) macrophages revealed markers characteristic of an activated state (CD80, CD86, Ly-6C/G), whereas macrophages lacking these activation markers expressed few or no FR. FR(+) macrophages also produced tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species, and production of reactive oxygen species correlated linearly with expression of FR. Synovial macrophages collected from arthritic patients were found to bind and internalize folate-linked dyes. Moreover, a folate-linked radioimaging agent was shown to image inflamed joints of rheumatoid arthritic patients. These results suggest that FR constitutes a marker for macrophage activation and that FR(+) macrophages can be targeted with folate-linked drugs without promoting drug uptake by nonactivated macrophages. This trial was registered at www.clinicaltrials.gov as #NCT00588393.
17136010 Sleep-disordered breathing in patients with acquired retrognathia secondary to rheumatoid 2006 Dec BACKGROUND: Sleep-disordered breathing (SDB) is associated with a variety of conditions that cause upper-airway narrowing. It was hypothesized that upper-airway narrowing can occur in patients with rheumatoid arthritis (RA) when retrognathia develops secondary to temporomandibular joint (TMJ) destruction. Therefore, the aim of this study was to detect the prevalence of SDB in patients with acquired retrognathia secondary to rheumatoid arthritis and to assess the efficacy of nasal continuous positive airway pressure (nasal CPAP) therapy in patients with SDB. MATERIAL/METHODS: Employed were a questionnaire, lateral cephalometry, and overnight polysomnography in seven women and three men (mean age +/-SD: 50+/-20 years, mean body mass index: 24.2+/-5.7 kg/m(2)) with acquired retrognathia secondary to RA. RESULTS: Three patients had severe obstructive sleep apnea (OSA) with apnea+hypopnea indices (AHI) >60/hour, three had mild obstructive sleep hypopnea (AHI >10/hour), and four had AHI <10/hour. The three patients with severe OSA all had excessive daytime sleepiness and evidence of retrognathia. In these three patients the mean AHI decreased from 72/hour to 3/hour with nasal CPAP therapy. CONCLUSIONS: SDB occurs quite frequently in non-obese patients with acquired retrognathia secondary to RA. The severity of SDB is related to the degree of retrognathia and the presence of daytime sleepiness. Nasal CPAP therapy is effective and well tolerated in these patients.
17216014 [Safety of methotrexate in rheumatoid arthritis: a retrospective cohort study in clinical 2006 Oct OBJECTIVE: To evaluate the treatment duration with MTX monotherapy or in association with DMARDs or TNFalpha inhibitors and the incidence and typology of adverse events (AE) occurred in rheumatoid arthritis (RA) patients. METHODS: A retrospective large cohort study of RA outpatients, consecutively seen from January 2000 to June 2005 was performed. Study group were RA patients classified according to the 1984 ACR criteria for the classification of rheumatoid arthritis. The patients were divided in 3 groups according to the treatment regimen: MTX monotherapy, MTX in combination with DMARD or with anti TNFalpha agents. We analyzed 348 therapeutic cycles, 177 of whom using MTX monotherapy. RESULTS: The 224 RA patients accumulated 800 person-years of follow up. Follow up for each of the groups was: MTX monotherapy 479.4 person-years, MTX in combination with DMARDs 244.5, or with TNFalpha inhibitors, 75.7 person-years. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 years was 58.5 after starting MTX. The incidence of any AE was 8.87 per 100 person-years. From all, 69 (97.2%) AE were no severe. Among those, more frequently were observed at gastrointestinal tract (31%), liver (19.7%), skin (15.5%). Incidence of severe AE (lung adenocarcinoma, 1 case; pancreatitis, 1 case) was 0.25 per 100 person-years, occurring in patients taking MTX monotherapy or MTX in combination with DMARDs, respectively. CONCLUSIONS: These data confirm that methotrexate is well tolerated in clinical practice in the medium-long term. Nevertheless, the occurrence of severe AE require an accurate vigilance for methotrexate toxicity.
17981181 MR imaging of synovial disorders of the knee: an update. 2007 Nov Synovial disorders often affect the knee joint and are a common cause of morbidity. Before MR imaging, radiologists were limited in their ability to provide information about the presence or absence of synovial disease. With the advent of MR imaging, useful information can now be provided to referring clinicians, often at a time when the initiation of therapy may mitigate significantly the long-term sequelae of synovial disorders. MR imaging, owing to its superior soft-tissue contrast, is the imaging modality of choice for demonstrating and quantifying pathologic changes of the synovium. MR imaging provides invaluable information to the clinician regarding the need to either initiate or modify therapy in those patients suffering from diseases of, or affecting, the synovium.
16622902 Interstitial pneumonitis associated with infliximab therapy. 2006 Jun Interstitial pneumonitis is a well documented, rare complication of methotrexate (MTX). We describe a patient with rheumatoid arthritis (RA) taking MTX for more than 3 years who then developed severe interstitial pneumonitis after a third infliximab infusion. Other similar cases are reviewed. Infliximab may potentiate pulmonary toxicity of MTX.