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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
20585478 Folgoration as an Example of Pathergy in a Patient Affected by Pyoderma Gangrenosum and Ta 2009 Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. Clinical manifestations of PG are characterized by destructive, necrotizing, and noninfective ulceration of the skin. 20-30% of cases are initiated and aggravated by minor trauma or surgery, a phenomenon named pathergy. PG is related to several autoimmune diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, and monoclonal gammopathy. The association with Takayasu's arteritis (TA), a chronic inflammatory and stenotic disease of large and medium-sized arteries, is instead less common. We report a case of PG associated with TA that was induced by an accident with folgoration of the skin; in this case the folgoration can be considered as an exemple of Pathergy, that is, a characteristic feature of PG.
19714334 Coexisting relapsing polychondritis and sarcoidosis: an unusual association. 2010 Sep Relapsing polychondritis is an episodic and progressive systemic inflammatory disease characterized by auricular chondritis, polyarthritis, nasal and respiratory tract chondritis. About 30% of the patients have additional autoimmune and or hematological diseases, most frequently systemic vasculitis, rheumatoid arthritis, myelodysplastic syndromes or systemic lupus erythematosus. So far, only one case of coexisting relapsing polychondritis and sarcoidosis in a patient with AIDS has been reported. We describe here a case of sarcoidosis and relapsing polychondritis in an immunocompetent patient. Physicians should be aware of this possible association.
19703952 Case presentation: xenograft resistance to protease degradation in a vasculitic ulcer. 2009 Sep Vasculitic ulcers are related to numerous underlying etiologies including autoimmune disease, rheumatoid arthritis and other inflammatory conditions.The resulting ulcerations are associated with high levels of pain, inflammation and tissue necrosis. Current therapies, including surgical intervention, are limited by the underlying inflammatory process and complications secondary to the wound etiology. conservative care has been relatively unsuccessful in promoting wound closure.This case presentations reviews the successful results of using a xenograft in the treatment of an inflammatory ulcer associated with cryoglobulinemia and vasculitis. Product integrity was maintained postoperatively, compared to an allograft, thereby allowing the wound treatment site to progress to closure.The type of cross linkage of acellular grafts may have a direct effect on product stability and treatment outcomes.
19456279 Selective MMP-12 inhibitors: WO-2008057254. 2009 Jul Amino-substituted xanthene, thioxanthene and carbazole sulfonamido-carboxylic acid of carboxamido carboxylic acid derivatives, their use to treat metalloprotease mediated conditions, and especially to inhibit MMP-12, and to treat osteoarthritis, rheumatoid arthritis, atherosclerosis, heart failure, fibrosis, pulmonary emphysema, tumour growth, asthma and chronic obstructive pulmonary disorder (COPD). Compounds of this category are suggested to be particularly useful in the treatment of COPD.
19358082 [Asynchronous lumbar synovial cysts after surgical resection: a case report]. 2009 Mar Lumbar synovial cysts represent a rare condition, they are believed to arise from defects of the joint capsule due to degeneration, trauma, rheumatoid arthritis or spondylosis. The symptom spectrum ranges from neural claudication to neurological deficits. We report the case of a contralateral asynchronous facet joint cyst after surgical resection and review the literature.
20422637 Adjusting for nonignorable missingness when estimating generalized additive models. 2010 Apr Generalized additive models (GAMs) have been widely used for flexible modeling of various types of outcomes. When the outcome in a GAM is subject to missing, practical analyses often assume that missingness is missing at random (MAR). This assumption can be of suspicion when the missingness is not by design. Evaluating the potential effects of alternative nonignorable missing data mechanism on the MAR inference from a GAM can be important but often challenging due to the complicatedness of alternative nonignorable models. We apply the index approach to local sensitivity (Troxel, Ma, and Heitjan (2004). Statistica Sinica 14, 1221-1237) to evaluate the potential changes of the GAM estimates in the neighborhood of the MAR model. The approach avoids fitting any complicated nonignorable GAM. Only MAR estimates are required to calculate the resulting sensitivity index and adjust the GAM estimates to account for nonignorable missingness. Thus the proposed approach is considerably simpler to conduct, as compared with the alternative methods. The simulation study shows that the index provides valid assessment of the local sensitivity of the GAM estimates to nonignorable missingness. We then illustrate the method using a rheumatoid arthritis clinical trial data set.
20049797 In vivo visualization of macrophage infiltration and activity in inflammation using magnet 2009 May Because macrophages play a key role on host defense, visualization of the migration of these cells is of high relevance for both diagnostic purposes and the evaluation of therapeutic interventions. The present article addresses the use of iron oxide and gadolinium-based particles for the noninvasive in vivo detection of macrophage infiltration into inflamed areas by magnetic resonance imaging (MRI). A general introduction on the functions and general characteristics of macrophages is followed by a discussion of some of the agents and acquisition schemes currently used to track the cells in vivo. Attention is then devoted to preclinical and clinical applications in the following disease areas: atherosclerosis and myocardial infarction, stroke, multiple sclerosis, rheumatoid arthritis, and kidney transplantation.
20025593 Metabolic changes in autoimmune diseases. 2009 Dec Metabolomics is a recently emerging member of the "omics" technologies. It aims at detecting and quantifying all detectable small molecules, the so-called metabolites, present in a biological sample. Because of the lower number of metabolites compared with the number of genes and proteins identified in genomics and proteomics approaches, data of metabolic studies are less complex and may therefore be more informative. Metabolomics may thus significantly contribute to our understanding of disease mechanisms. Autoimmune diseases are of growing clinical relevance, and due to the chronic nature of these diseases successful treatment is often challenging. In the past years, a variety of studies have been published about the metabolome of autoimmune diseases such as Crohn's disease and rheumatoid arthritis. However, our understanding of the role of different metabolites in the pathogenesis of autoimmune diseases is still far from being complete.
19772838 A new mechanism of blood vessel growth - hope for new treatment strategies. 2009 Jun Growth of new blood vessels (angiogenesis) is essential for embryo development as well as for wound healing and progression of a number of diseases such as cancer, inflammatory conditions, eye diseases, psoriasis, and rheumatoid arthritis in the adult. Current paradigms explain blood vessel growth entirely by sprouting angiogenesis or by vessel splitting through so called intussusceptive angiogenesis. However, these mechanisms are mainly derived from experiments on the developing embryo while less is known about angiogenesis in the adult during, e.g., wound healing, tumor growth, and inflammation. Recently we showed that blood vessel growth in the adult can be induced and directed by mechanical forces that naturally develop during healing or remodeling of tissues. In contrast to sprouting and intussusception, the new biomechanical hypothesis assumes that functional blood vessels are passively translocated which, if found generic, may drastically change the approach for developing anti- and pro-angiogenic therapies in the treatment of a variety of diseases.
19585133 [Myalgia in polymyalgia rheumatica, temporal arteritis and other vasculitides]. 2009 Aug Myalgias most commonly occur in polymyalgia rheumatica (PMR). About 45% of patients with giant cell arteritis present with symptoms of PMR. Other vasculitides may also lead to arthralgia and myalgia. While shoulder and pelvic pain is characteristic for PMR pain often also occurs in the back of the neck and in the region of the thoracic spine. In addition, patients often present with malaise, morning stiffness and weight loss. CRP and ESR are elevated. Ultrasound and MRI delineate minor synovitis, tenosynovitis and bursitis in the shoulder. Hip joint synovitis and trochanteric bursitis are also commonly seen. PMR should be distinguished from rheumatoid arthritis. The initial treatment comprises a prednisolone dose of 15-25 mg/day, followed by a weekly decrease of 1-2.5 mg. Once 10 mg/day has been reached the dose should be reduced more slowly.
20832177 Therapeutic potential of interleukin-6 antagonism in bipolar disorder. 2011 Jan Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder. Its underlying neurobiology remains largely unclear. A significant body of evidence indicates that inflammatory activation expressed by increased cytokines is relevant in its pathophysiology. IL-6 is one of the most important cytokines involved in the pathogenesis of immune and inflammatory disorders. Several studies recently showed increased levels of IL-6 in manic and depressive episodes and also during euthymia in subjects with BD. Tocilizumab is an IL-6 receptor antagonist being marketed for the treatment of rheumatoid arthritis and Castleman's disease. In this article we discuss the possibility that tocilizumab may have a therapeutic role in treatment of BD through its anti-inflammatory action.
19962631 Clues on the MDHAQ to identify patients with fibromyalgia and similar chronic pain conditi 2009 Nov Patients with fibromyalgia and chronic pain conditions report high levels of pain and fatigue, and multiple symptoms. These phenomena may be recorded quantitatively on a self-report multidimensional health assessment questionnaire (MDHAQ). These responses are likely to differ in people with fibromyalgia or chronic pain conditions compared with people with an inflammatory rheumatic disease, such as rheumatoid arthritis. Data from the MDHAQ provide clues to the presence of fibromyalgia/chronic pain conditions, including patients with inflammatory diseases who also have concomitant fibromyalgia/chronic pain conditions.
21582605 N-(3,4-Dimethyl-phen-yl)-4-hydr-oxy-2-methyl-2H-1,2-benzothia-zine-3-carboxamide 1,1-dioxi 2009 Mar 28 1,2-Benzothia-zines similar to the title compound, C(18)H(18)N(2)O(4)S, are well known in the literature for their biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis. The thia-zine ring adopts a distorted half-chair conformation. The enolic H atom is involved in an intra-molecular O-H⋯O hydrogen bond, forming a six-membered ring. In the crystal, mol-ecules arrange themselves into centrosymmetric dimers by means of pairs of weak inter-molecular N-H⋯O hydrogen bonds.
20402124 [Forefoot pain]. 2010 Mar 20 Forefoot chronic pain is a frequent problem in daily clinical practice. Mechanical pathology of the forefoot, usually called static metatarsalgia, represents the most frequent reason for consultation in pathology of the foot. The cause is a functionnal disorder or anatomic derangement of the forefoot architecture. Metatarsalgia can originate from a wide range of affections. Etiologies of chronic pain are described from medial to lateral with first ray pathologies (hallux valgus, hallux rigidus and sesamoid pathology) and first ray insufficiency, pathologies of the second, third and fourth ray and intermetatarsal spaces (second ray syndrome, Freiberg's disease, Morton neuroma, stress or bone insufficiency metatarsal fractures, intermetatarsal bursitis) and fifth ray pathology (lateral bursitis, quintus varus). Sometimes forefoot pain could also be caused by chronic inflammatory rheumatic diseases (rheumatoid and psoriatic arthritis) with a risk of structural metatarsophalangeal joints alteration. The pathology of the toes can, more rarely, explain a forefoot pain. So, several pathologic conditions can produce forefoot pain and the diagnostic approach must always be based on the anamnesis and clinical examination. In a second time if the cause is difficult to establish based solely on clinical findings, radiography and ultrasonography are today the most usefull auxiliary investigations.
20607500 TBK1-targeted suppression of TRIF-dependent signaling pathway of toll-like receptor 3 by a 2010 Jun Toll-like receptors (TLRs) play an important role in induction of innate immune responses. The stimulation of TLRs by microbial components triggers two branches of downstream signaling pathways: myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent signaling pathways. Auranofin, a sulfur-containing gold compound (Au[I]), has been widely used for the treatment of rheumatoid arthritis. Since dysregulation of TLRs can lead to severe systemic inflammatory and joint destructive process in rheumatoid arthritis, auranofin-mediated modulation of TLR activation may have therapeutic potential against such diseases. Previously, we demonstrated that auranofin suppressed TLR4 signaling pathway by inhibiting TLR4 dimerization induced by LPS. Here, we examined the effect of auranofin on signal transduction via the TRIF-dependent pathway induced by a TLR3 agonist. Auranofin inhibited nuclear factor-kappaB and interferon (IFN) regulatory factor 3 (IRF3) activation induced by polyinosinic-polycytidylic acid (poly[I:C]). Auranofin inhibited poly[I:C]-induced phosphorylation of IRF3 as well as IFN-inducible genes such as IFN inducible protein-10. Furthermore, auranofin inhibited TBK1 kinase activity in vitro. All the results suggest that auranofin suppress TLR signaling at multiple steps.
20185032 Reduced adult neurogenesis and altered emotional behaviors in autoimmune-prone B-cell acti 2010 Mar 15 BACKGROUND: It has been postulated that brain inflammatory processes associated with autoimmune diseases may be causative factors in emotional disorders. Accordingly, we examined emotional behaviors in autoimmune-prone cytokine B-cell-activating factor (BAFF) transgenic mice, a model of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. METHODS: Male BAFF transgenic mice were examined on a series of standard laboratory assays of emotionality. Mice were also tested for brain inflammation, stress-induced c-Fos expression, hippocampal progenitor cell proliferation, and hippocampal neurogenesis-dependent and neurogenesis-independent long-term potentiation (LTP). RESULTS: Our study revealed that older BAFF transgenic mice exhibit an anxiety-like phenotype associated with brain inflammation. Furthermore, anxious mice display an abnormal neuronal activation within the limbic system in response to mild anxiogenic stimuli. Proliferation of newly formed neurons in the subgranular zone of adult hippocampus was significantly decreased in anxious BAFF transgenic mice that also showed impaired neurogenesis-dependent and neurogenesis-independent dentate gyrus LTP. CONCLUSIONS: Our results suggest that anxiety associated with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome can be linked to brain inflammation, impaired neurogenesis, and hippocampal plasticity. BAFF transgenic mice can be used in future studies to test compounds of therapeutic value for the treatment of mood disorders associated with autoimmune diseases.
19122077 Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 ca 2009 Jan BACKGROUND: Clinical studies have revealed a number of important risk factors for postoperative infection following total knee arthroplasty. Because of the small numbers of cases in those studies, there is a risk of obtaining false-negative results in statistical analyses. The purpose of the present study was to determine the risk factors for infection following primary and revision knee replacement in a large register-based series. METHODS: A total of 43,149 primary and revision knee arthroplasties, registered in the Finnish Arthroplasty Register, were followed for a median of three years. The Finnish Arthroplasty Register and the Finnish Hospital Discharge Register were searched for surgical interventions that were performed for the treatment of deep postoperative infections. Cox regression analysis with any reoperation performed for the treatment of infection as the end point was performed to determine the risk factors for this adverse outcome. RESULTS: Three hundred and eighty-seven reoperations were performed because of infection. Both partial and complete revision total knee arthroplasty increased the risk of infection as compared with the risk following primary knee replacement. Male patients, patients with seropositive rheumatoid arthritis or with a previous fracture around the knee, and patients with constrained and hinged prostheses had increased rates of infection after primary arthroplasty. Wound-related complications increased the risk of deep infection. The rate of septic failure was lower after unicondylar than after total condylar primary knee arthroplasty, but the difference was not significant. The combination of parenteral antibiotic prophylaxis and prosthetic fixation with antibiotic-impregnated cement protected against septic failure, especially after revision knee arthroplasty. Following revision total knee arthroplasty, diagnosis and prosthesis type had no effect, but previous revision for the treatment of infection and wound-healing problems predisposed to repeat revision for the treatment of infection. CONCLUSIONS: There was an increased risk of deep postoperative infection in male patients and in patients with rheumatoid arthritis or a fracture around the knee as the underlying diagnosis for knee replacement. The results of the present study suggest that the infection rate is similar after partial revision and complete revision total knee arthroplasties. Combining intravenous antibiotic prophylaxis with antibiotic-impregnated cement seems advisable in revision arthroplasty.
19033291 Multinational evidence-based recommendations for the use of methotrexate in rheumatic diso 2009 Jul OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
20141563 Weak associations between human leucocyte antigen genotype and acute myocardial infarction 2010 Jul OBJECTIVES: Human leucocyte antigens (HLAs) are polymorphic molecules involved in antigen presentation. Associations between HLA type and autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis, are well established but the potential association of genetic variation affecting antigen presentation with cardiovascular disease has not been systematically investigated in large cohorts. The importance of such studies is stressed by recent experimental findings of an involvement of autoimmunity in the atherosclerotic disease process. RESULTS: An SSP-PCR method was used for HLA genotyping to determine associations of HLA-DRB1, -DQA1 and -DQB1 with cardiovascular disease in a population-based cohort of 1188 acute myocardial infarction (AMI) patients and 1191 matched healthy controls. The HLA-DRB1*0101 allele, as well as the HLA-DRB1*0101-DQA1*01-DQB1*05 haplotype, was found to be associated with increased risk for AMI (OR 1.24; 95% CI 1.00-1.54 for both). In contrast, the DRB1*07 and DQA*02 alleles (OR 0.78; 95% CI 0.65-0.95 for both), as well as the DRB1*07-DQA*02-DQB*02 haplotype, conferred protection (OR 0.79; 95% CI 0.63-0.98). An HLA risk score taking each individual's both haplotypes into account was higher amongst cases (2.43 +/- 0.92 vs. 2.29 +/- 0.95, P = 0.001). The association between HLA risk score and AMI was independent of other cardiovascular risk factors assessed. CONCLUSIONS: This study demonstrates that the associations between HLA-DRB1 and DQA1 loci and cardiovascular disease exists but that they are considerably weaker than those previously reported for other diseases with an established autoimmune aetiology such as type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.
19821804 History of incidence of autoimmune and oncological diseases in identical female twins. 2009 Dec PROBLEM: The aim of study was to investigate identical female twins born in 1977 suffered from autoimmune diseases (twin A - Sjogren's syndrome, and twin B - systemic lupus erythematosus). METHOD OF STUDY: It was refer retrospective analysis of both sisters suffered beside autoimmune alterations (Sjogren's syndrome and systemic lupus erythematosus) also from gynecological diseases (twin A - praecancerosis of cervix uteri, twin B - carcinoma vaginae). RESULTS: Relationships between disease activities and severities in the female twins were similar and the treatments were directed according to clinical symptoms and laboratory results. Dramatic change, unfortunately, occurred with twin B. The reason may be the association between SLE activity (lupus nephritis), hematological complication (leukopenia) and oncological vaginal recidivation. CONCLUSION: Association between autoimmune disease and gynecological cancer (or praecancerosis) is major risk than without immunology deviation. Twin A is periodically gynecologically observed.