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ID PMID Title PublicationDate abstract
23006144 Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: di 2012 Sep 24 INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis. The effects of alefacept treatment on IL-20 expression in the synovium of patients with psoriasis and PsA are currently unknown. METHODS: Eleven patients with active PsA and chronic plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an open-label study. Skin biopsies were taken before and after 1 and 6 weeks, whereas synovial biopsies were obtained before and 4 and 12 weeks after treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n = 10) were used as disease controls. Immunohistochemical analysis was performed to detect IL-20 expression, and stained synovial tissue sections were evaluated with digital image analysis. Double staining was performed with IL-20 and CD68 (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression in skin sections (n = 6) was analyzed semiquantitatively. RESULTS: IL-20 was abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA patients decreased significantly (P = 0.04) 6 weeks after treatment and correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20 expression in PsA synovium was not affected by alefacept. CONCLUSIONS: Conceivably, the relatively limited effectiveness of alefacept in PsA patients (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in part by persistent FLS-derived IL-20 expression.
21265798 Glycoconjugate markers of joint diseases. 2011 Jan A number of different types of glycoconjugate are found associated with joint tissue and fluids, comprising glycoproteins, glycolipids and glycosaminoglycans. Oligosaccharide chains of glycoconjugates are degraded by exoglycosidases, and the dominant exoglycosidase found in human blood, synovial fluid, the synovial membrane and chondrocytes of articular cartilage is HEX (N-acetyl-β-hexosaminidase). HEX is localized mostly intracellularly in synovial cells. Serum activity of HEX may be used to monitor the course and efficiency of treatment of Lyme arthritis, and activity of HEX, above 10 μkat/kg of protein in the synovial fluid, suggests rheumatoid disease. There is a shortage of HEX inhibitors able to penetrate synoviocytes, so the development of drugs which inhibit synthesis and/or the activity of HEX will be a promising field for future investigations.
22208140 Periodontal infections: a risk factor for various systemic diseases. 2011 Jul A healthy periodontium is vital for the general well-being of an individual. However, periodontal diseases are common and periodontal infections are increasingly associated with systemic diseases. We aimed to critically evaluate the literature on the association between periodontal infections and systemic diseases. We searched the PubMed database over a 20-year period for literature on periodontal diseases and their links to various systemic diseases, and examined the strength of association between periodontal disease and each systemic disease, the dose-response relationship, and the biological plausibility. We found that individuals with periodontal disease may be at higher risk for adverse medical outcomes including cardiovascular diseases, respiratory infections, adverse pregnancy outcomes, rheumatoid arthritis and diabetes mellitus. Many cohort, in vitro and animal studies suggest that systemic inflammation due to pathogens associated with periodontal disease may play a role in the initiation and progression of some systemic diseases. Periodontal infections should therefore be considered as a risk factor for various systemic diseases.
22308023 Therapeutic effects of systemic administration of chaperone αB-crystallin associated with 2012 Mar 23 The therapeutic benefit of the small heat shock protein αB-crystallin (HspB5) in animal models of multiple sclerosis and ischemia is proposed to arise from its increased capacity to bind proinflammatory proteins at the elevated temperatures within inflammatory foci. By mass spectral analysis, a common set of ∼70 ligands was precipitated by HspB5 from plasma from patients with multiple sclerosis, rheumatoid arthritis, and amyloidosis and mice with experimental allergic encephalomyelitis. These proteins were distinguished from other precipitated molecules because they were enriched in the precipitate as compared with their plasma concentrations, and they exhibited temperature-dependent binding. More than half of these ligands were acute phase proteins or members of the complement or coagulation cascades. Consistent with this proposal, plasma levels of HspB5 were increased in patients with multiple sclerosis as compared with normal individuals. The combination of the thermal sensitivity of the HspB5 combined with the high local concentration of these ligands at the site of inflammation is proposed to explain the paradox of how a protein believed to exhibit nonspecific binding can bind with some relative apparent selectivity to proinflammatory proteins and thereby modulate inflammation.
23155441 Cancer risk of anti-TNF-α at recommended doses in adult rheumatoid arthritis: a meta-anal 2012 BACKGROUND: The risk of malignancies on TNF-α antagonists is controversial. The aim of this survey was to assess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, including the five marketed drugs (infliximab, etanercept, adalimumab, golimumab and certolizumab) used in line with the New Drug Application. Furthermore, the relative interest of modified intention to treat or per protocol analyses to assess such sparse events remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Data sources were MEDLINE, CENTRAL, ISI Web of Science, ACR and EULAR meeting abstracts, scientific evaluation of the drugs leading to their marketing approval, and clinicaltrials.gov, until 31 December 2012.We selected double-blind randomized controlled trials in adult rheumatoid arthritis patients, including at least one treatment arm in line with New Drug Application. We performed random effect meta-analysis, with modified intention to treat and per protocol analyses. Thirty-three trials were included. There was no excess risk of malignancies on anti-TNF-α administered in line with New Drug Application in the per protocol model (OR, 0.93 95%CI[0.59-1.44]), as well as in the modified intention to treat model (OR, 1.27 95%CI[0.82-1.98]). There was a non-significant tendency for an excess non-melanoma skin cancer risk in both models (respectively, 1.37 [0.71-2.66] and 1.90 [0.98-3.67]). With fixed effect Peto model restricting to trials during at least 52 weeks, the overall cancer risk was respectively 1.60 [0.97-2.64] and 1.22 [0.72-2.08]. Whatever the model, modified intention to treat analysis led to higher estimations than per protocol analysis. The later may underestimate the treatment effect when assessing very sparse events and when many patients dropped out in placebo arms. In metaregression, there was no differential risk among the five drugs. CONCLUSIONS/SIGNIFICANCE: This study did not find any evidence for an excess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, but an excess cancer risk after several years of exposure cannot be ruled out. Both modified intention to treat and per protocol analyses should be presented in such safety analyses.
22275239 Hierarchical Bayesian formulations for selecting variables in regression models. 2012 May 20 The objective of finding a parsimonious representation of the observed data by a statistical model that is also capable of accurate prediction is commonplace in all domains of statistical applications. The parsimony of the solutions obtained by variable selection is usually counterbalanced by a limited prediction capacity. On the other hand, methodologies that assure high prediction accuracy usually lead to models that are neither simple nor easily interpretable. Regularization methodologies have proven to be useful in addressing both prediction and variable selection problems. The Bayesian approach to regularization constitutes a particularly attractive alternative as it is suitable for high-dimensional modeling, offers valid standard errors, and enables simultaneous estimation of regression coefficients and complexity parameters via computationally efficient MCMC techniques. Bayesian regularization falls within the versatile framework of Bayesian hierarchical models, which encompasses a variety of other approaches suited for variable selection such as spike and slab models and the MC(3) approach. In this article, we review these Bayesian developments and evaluate their variable selection performance in a simulation study for the classical small p large n setting. The majority of the existing Bayesian methodology for variable selection deals only with classical linear regression. Here, we present two applications in the contexts of binary and survival regression, where the Bayesian approach was applied to select markers prognostically relevant for the development of rheumatoid arthritis and for overall survival in acute myeloid leukemia patients.
21763053 [Cardiovascular disorders and rheumatic disease]. 2011 Sep Cardiovascular disease is a common and under-recognized problem in patients with systemic rheumatic conditions. Patients may present with disease associated heart involvement at the time of diagnosis or later in the course of the illness. The manifestations vary by disease, and all structures in the heart can be affected and may result in significant morbidity and mortality. Manifestations of cardiac disease in these patients range from subclinical to severe and may require aggressive immunosuppressive therapy. Early recognition is important for prompt institution of appropriate therapy. Treatment of disease associated cardiac involvement is based on severity of disease with more severe manifestations often requiring a combination of corticosteroid and cytotoxic agent. Premature atherosclerosis has been increasingly recognized in patients with systemic lupus erythematosus and rheumatoid arthritis and may result in premature coronary death when compared to the general population. Aggressive control of systemic inflammation in these diseases may result in a reduction in the risk of ischemic heart disease. Although aggressive treatment of the primary rheumatic disease has been associated with an improvement in mortality rates, specific guidelines for prevention of ischemic heart disease in this group of patients have not been formulated and recommendations at this time include aggressive control and monitoring of traditional risk factors.
20886247 Impact of tight control strategy on rheumatoid arthritis in Sarawak. 2011 May The aim of our study is to describe the impact of tight control strategy on the care of RA patients in Sarawak General Hospital. We performed a prospective study of all patients with a diagnosis of RA who received treatment at the Rheumatology Clinic in Sarawak General Hospital over a 1-year period. Systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS 28-ESR <2.6) were carried out in the clinic over the 1-year period. Disease activity and treatment regimes of all 142 patients were collected for at baseline and 1 year later for statistical analysis. Our patients have a significantly lower DAS 28 with a mean of 2.99 ± 0.95 compared with baseline of 4.31 ± 1.34 (p < 0.000). More patients were in remission 1 year later compared to baseline (36.6% vs 11.3%). Tight control strategy has a positive impact on the care of RA patients in our centre. By optimising the care of RA through tight control strategy, RA can be better controlled in our centre.
21807788 Overview of the patient perspective at OMERACT 10--conceptualizing methods for developing 2011 Aug This overview draws out the main conclusions from the 4 workshops focused on incorporating the patient perspective into outcome assessment at the 10th Outcome Measures in Rheumatology (OMERACT 10) conference. They raised methodological issues about the choice of outcome domains to include in clinical trials, the development or choice of instruments to measure these domains, and the way these instruments might capture the impact of a disease and its treatment. The need to develop a more rigorous conceptual model of quantifying the way conditions affect health, and the need to ensure patients are directly involved in the decisions about domains and instruments, emerged clearly. The OMERACT participants voted to develop guidelines for domain and instrument selection, and conceptual and experimental work will be brought forward to revise and upgrade the OMERACT Filter.
21893583 Long-term safety, efficacy and inhibition of radiographic progression with abatacept treat 2011 Oct OBJECTIVE: To evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX). METHODS: Patients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥ 1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE. RESULTS: 433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score). CONCLUSION: In MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.
21453534 Agreement between aggregate and individual-level measures of income and education: a compa 2011 Mar 31 BACKGROUND: The association between lower socioeconomic status and poorer health outcomes has been observed using both individual-level and aggregate-level measures of income and education. While both are predictive of health outcomes, previous research indicates poor agreement between individual-level and aggregate-level measures. The purpose of this study was to determine the level of agreement between aggregate-level and individual-level measures of income and education among three distinct patient groups, specifically asthma, diabetes, and rheumatoid patients. METHODS: Individual-level measures of annual household income and education were derived from three separate surveys conducted among patients with asthma (n = 359), diabetes (n = 281) and rheumatoid arthritis (n = 275). Aggregate-level measures of income and education were derived from the 2001 Canadian census, including both census tract-and dissemination area-level measures. Cross-tabulations of individual-level income by aggregate-level income were used to determine the percentage of income classifications in agreement. The kappa statistic (simple and weighted), Spearman's rank correlations, and intra-class correlation coefficient (ICC) were also calculated. Individual-level and aggregate-level education was compared using Chi-Square tests within patient groups. Point biserial correlation coefficients between individual-level and aggregate-level education were computed. RESULTS: Individual-level income was poorly correlated with aggregate-level measures, which provided the worst estimations of income among patients in the lowest income category at the individual-level. Both aggregate-level measures were best at approximating individual-level income in patients with diabetes, in whom aggregate-level estimates were only significantly different from individual-level measures for patients in the lowest income category. Among asthma patients, the proportion of patients classified by aggregate-level measures as having a university degree was significantly lower than that classified by individual-level measures. Among diabetes and rheumatoid arthritis patients, differences between aggregate and individual-level measures of education were not significant. CONCLUSIONS: Agreement between individual-level and aggregate-level measures of socioeconomic status may depend on the patient group as well as patient income. Research is needed to characterize differences between patient groups and help guide the choice of measures of socioeconomic status.
22045978 The influence of stress on the development and severity of immune-mediated diseases. 2011 Nov Evidence that psychological stress can increase inflammation and worsen the course of immune-mediated inflammatory disease (IMID) is steadily accumulating. The majority of data supporting this hypothesis come from studies in patients with inflammatory bowel disease (IBD). While there is no evidence to suggest that stress is a primary cause of IBD, many, although not all, studies have found that patients with IBD experience increased stress and stressful life events before disease exacerbations. Further, the disease itself can cause psychological stress, creating a vicious cycle. In addition to reviewing the epidemiological evidence supporting a stress-IMID relationship, this article also briefly discusses how stress-related changes in neural, endocrine, and immune functioning may contribute to the pathogenesis of immune diseases, IBD in particular. The effects of different pharmacological and nonpharmacological interventions, including stress management and behavioral therapy, on stress, mood, quality of life (QOL), and activity of the underlying IMID are also summarized.
21833686 Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventio 2011 Nov Tocilizumab, a monoclonal antibody targeting the IL-6 receptor, has recently been added to the therapeutic armamentarium against rheumatoid arthritis (RA). Despite its overall safety, concerns have been raised regarding diverticular perforation in patients receiving the drug. The aim of our research was to document the incidence of diverticular disease in RA patients treated in the pre-disease-modifying anti-rheumatic drug (DMARD) era, following treatment with conventional DMARDs, and subsequent to tocilizumab therapy. We performed a systematic literature review in MEDLINE, EMBASE, Conference Proceedings Citation Index-Science, Cochrane Central Register of Controlled Trials and Current Controlled Trials up to Nov. 2010. The publication titles and abstracts were independently assessed by two reviewers for relevance and quality, and the review was conducted following guidelines from the Centre for Reviews and Dissemination. In the pre-DMARD period of RA management, where patients were largely treated with NSAIDs and corticosteroids, gastrointestinal (GI) complications were a substantial cause of mortality with diverticulitis and colonic ulcers accounting for almost a third of GI-related deaths. In contrast, our search did not reveal any evidence of diverticular perforation in patients treated with conventional DMARDs. Eighteen cases of lower GI perforation (16 of whom had diverticulitis) have been documented in recent conference proceedings following tocilizumab treatment in clinical trials, with a lower GI perforation rate of 1.9 per 1,000 patient years (PY). This lies between the reported rate of GI perforations for corticosteroids and anti-TNF-α agents in the United Health Care database, with rates of 3.9 per 1,000 PY (95% CI 3.1-4.8) and 1.3 per 1,000 PY (95% CI 0.8-1.9), respectively. The majority of these patients were concurrently prescribed NSAIDs and/or long-term corticosteroids. Traditional DMARD therapy for RA appears not only to have modified the risk of lower GI perforation but prevented it. The risk of diverticular perforation may be slightly higher in patients treated with tocilizumab compared with conventional DMARDs or anti-TNF agents, but lower than that for corticosteroids. The mechanism of action of IL-6 antagonism in the pathophysiology of diverticular perforation has yet to be elucidated.
21558139 Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosu 2011 May Systemic lupus erythematosus (SLE) is characterized by abnormalities in the function of T and B lymphocytes and in the signaling pathways induced through their receptors. Cbl-b is an intracellular adaptor protein that plays a key role in the negative regulation of lymphocyte activity. We explored the expression and function of Cbl-b in T lymphocytes from SLE patients. In addition, the possible association of SLE and a single nucleotide polymorphism (SNP) of the Cblb gene was determined. We studied 150 SLE patients, 163 healthy individuals, and 14 patients with rheumatoid arthritis (RA). The expression of Cbl-b was analyzed in the peripheral blood mononuclear cells, and the negative regulatory function of Cbl-b was assessed by analyzing actin polymerization and the phosphorylation of JNK and c-Jun induced through CD3. Furthermore, the 2126(A/G) SNP of the Cblb gene was detected by real-time polymerase chain reaction. We found a significant small reduction in the expression of Cbl-b as well as increased levels of activation of c-Jun and actin polymerization in T lymphocytes from patients with SLE compared with healthy controls or RA patients. In addition, a significant association between the 2126(A/G) SNP and SLE was detected. Our data suggest that Cbl-b may contribute to the deregulated activation of T lymphocytes observed in SLE.
21604993 Psychometric characteristics of Duruoz Hand Index in patients with traumatic hand flexor t 2011 INTRODUCTION: The aim of the study was to assess reliability, validity and responsiveness of Duruoz Hand Index (DHI), which has been developed for evaluation of activity limitation in rheumatoid arthritis in patients with traumatic hand flexor tendon injuries. MATERIAL AND METHOD: Sixty-five patients older than 16 years who underwent surgical intervention after flexor tendon injuries were enrolled. Reliability was assessed by internal consistency (with Cronbach's-α) and test-retest intraclass correlation coefficient (ICC). Construct validity was estimated correlating the scale with the DASH and VAS-hd. Also responsiveness was estimated using standardised response mean (SRM) and effect size (ES). RESULT: Mean age of the patients was 30.25 ± 11.07 years and totally 140 fingers were evaluated. Cronbach's-α and ICC values of DHI were found to be 0.87 and 0.99, respectively. In validation study, highly significant correlation was detected between DHI with DASH and VAS-hd (r = 0.86, r = 0.54, p < 0.0001, respectively). SRM values and ES values (excepting workplaces subgroup score) were higher than 0.80 for total and all subgroup scores. CONCLUSION: DHI is a reliable, valid questionnaire to assess hand-related activity limitation in patients with traumatic hand flexor tendon injuries. Also, due to its high level responsiveness DHI can be used for assessing the clinical course of the traumatic hand flexor tendon injured patient.
22730343 Serum cotinine as a biomarker of tobacco exposure and the association with treatment respo 2012 Dec OBJECTIVE: Cigarette smoking has emerged as a risk factor for the development of rheumatoid arthritis (RA). Recent studies have suggested that cigarette smoking may lead to lower treatment response rates with methotrexate (MTX) and some biologic agents in RA. Knowledge of whether tobacco exposure reduces treatment efficacy is important, since smoking could represent a modifiable factor in optimizing RA treatment. METHODS: The study participants included patients with early RA (<3 years in duration) enrolled in the Treatment of Early Aggressive Rheumatoid Arthritis study, a randomized, blinded, placebo-controlled clinical trial comparing early intensive therapy (MTX + etanercept or MTX + hydroxychloroquine + sulfasalazine triple therapy) versus initial treatment with MTX with step-up to MTX + etanercept or to triple therapy if the disease was still active at 24 weeks. Serum cotinine was measured using a commercially available enzyme-linked immunosorbent assay at baseline and at 48 weeks, with detectable concentrations at both visits serving as an indicator of smoking status. The mean Disease Activity Score in 28 joints (DAS28) was compared by smoking status, adjusting for baseline disease activity. RESULTS: Of the 412 subjects included in the analysis, 293 (71%) were categorized as nonsmokers and 119 (29%) as current smokers. There were no differences in the mean DAS28 score between 48 and 102 weeks based on smoking status for the overall group (P = 0.881) or by specific treatment assignment. CONCLUSION: Among patients enrolled in a large randomized controlled trial of early RA with poor prognostic factors, smoking status did not impact treatment responses for those receiving early combination or initial MTX with step-up therapy at 24 weeks if the disease was still active.
22736089 DNA methylome signature in rheumatoid arthritis. 2013 Jan OBJECTIVES: Epigenetics can influence disease susceptibility and severity. While DNA methylation of individual genes has been explored in autoimmunity, no unbiased systematic analyses have been reported. Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed. METHODS: Genomic DNA was isolated from six RA and five osteoarthritis (OA) FLS lines and evaluated using the Illumina HumanMethylation450 chip. Cluster analysis of data was performed and corrected using Benjamini-Hochberg adjustment for multiple comparisons. Methylation was confirmed by pyrosequencing and gene expression was determined by qPCR. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. RESULTS: RA and control FLS segregated based on DNA methylation, with 1859 differentially methylated loci. Hypomethylated loci were identified in key genes relevant to RA, such as CHI3L1, CASP1, STAT3, MAP3K5, MEFV and WISP3. Hypermethylation was also observed, including TGFBR2 and FOXO1. Hypomethylation of individual genes was associated with increased gene expression. Grouped analysis identified 207 hypermethylated or hypomethylated genes with multiple differentially methylated loci, including COL1A1, MEFV and TNF. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, transendothelial migration and extracellular matrix interactions. Confirmatory studies with OA and normal FLS also demonstrated segregation of RA from control FLS based on methylation pattern. CONCLUSIONS: Differentially methylated genes could alter FLS gene expression and contribute to the pathogenesis of RA. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate epigenetic contributions to inflammatory arthritis.
21468727 Increased expression of IL-1 receptors in response to IL-1β may produce more IL-6, IL-8, 2012 Jul Primary synovial cells with high passage number demonstrate increased production of proinflammatory mediators in response to inflammatory stimuli compared with cells with low passage number. This study used synovial cells to learn how different numbers of serial subculture passages affect the production of proinflammatory mediators in response to interleukin (IL)-1β. Synovial cells were serially subcultured in flasks until passage 7. During cell passage, synovial cells were treated with IL-1β for 24 h. Levels of proinflammatory mediators were analyzed by ELISA, real-time PCR, and Western blot. Synovial cells at passage 7 had elongated morphology and higher activity of β-galactosidase, a marker of senescence, than those at passage 3. Production of IL-6, IL-8, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE(2)) in response to IL-1β was significantly increased in cells at passage 7 compared with passage 3. To evaluate the mechanism of this different response, IL-1 receptor expression was studied in cells stimulated with IL-1β. Compared with cells at passage 3, cells at passage 7 had stronger expression of IL-1 receptors 1 and 2, as well as significantly increased expression of both receptors, in response to IL-1β. This finding suggests that differential production in response to inflammatory stimuli associated with cell passages should be considered when in vitro experiments are used to evaluate the production levels of proinflammatory mediators.
22986695 Multimodality imaging of intraosseous ganglia of the wrist and their differential diagnosi 2012 Dec Intraosseous ganglion (IOG) is the most frequently occurring bone lesion within the carpus and is often an incidental finding on radiographs obtained for other reasons. Two types of IOG have been described: an "idiopathic" form (or type I), the pathogenesis of which has not been completely clarified, and a "penetrating" form (or type II), caused by the intrusion of juxtacortical material (often a ganglion cyst of the dorsal soft tissue) into the cancellous bone compartment. The differential diagnosis for IOG is wide-ranging and complex, including lesions of posttraumatic (posttraumatic cystlike defects), degenerative (subchondral degenerative cysts), inflammatory [cystic rheumatoid arthritis, chronic tophaceous gout (CTG)], neoplastic (benign primary bone tumours and synovial proliferative lesions), ischaemic (Kienböck's disease or avascular osteonecrosis of the lunate) and metabolic (amyloidosis) origin. Multimodality imaging of IOGs is a useful diagnostic tool that provides complete morphological characterisation and differentiation from other intraosseous cystic abnormalities of the carpus. Thin-slice multidetector computed tomography (MDCT) can provide high-spatial-resolution images of the cortical and cancellous bone compartments, allowing detection of morphological findings helpful in characterising bone lesions, whereas magnetic resonance (MR) imaging can simultaneously visualise bone, articular surfaces, hyaline cartilage, fibrocartilage, capsules and ligaments, along with intra- and periarticular soft tissues.
22752828 Methotrexate-induced erythema multiforme: a case report and review of the literature. 2011 Sep BACKGROUND: Mucosal affectation may be a direct cytotoxic or cytostatic effect of methotrexate. OBJECTIVE: To highlight the diagnostic procedure and treatment intervention erythema multiforme complicating methotrexate-induced allergic stomatitis. CASE REPORT: The patient was a 60-year-old man suffering from stomatitis that rapidly developed into erythema multiforme. The patient had been prescribed methotrexate to treat rheumatoid arthritis. The patient presented with painful ulceration of the vermillion border of the upper and lower lips covered with necrotic tissues. We made a tentative diagnosis of methotrexate induced allergic stomatitis. On the patient's second visit to the clinic, the lesion had developed into crusted and haemorrhagic ulceration with erythematous patches on the lips. The patient was now complaining of weakness, fever and occasional seizure attack. Examination of the upper and lower extremities revealed bilateral bullous eruptions. The definitive diagnosis was that of erythema multiforme complicating methotrexate induced allergic stomatitis. withdrawal of the methotrexate yielded positive result with complete resolution of the lesions after 12 days of drug withdrawal. CONCLUSION: Early diagnosis of adverse drug reactions is essential for effective treatment, to avoid untoward systemic complications.