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

ID PMID Title PublicationDate abstract
23897045 Osteoclast formation and differentiation: an overview. 2012 Nov 8 Osteoclasts are multinucleated cells of hematopoietic origin which are unique in their ability to resorb bone. Osteoclasts are generated from myeloid progenitors through a progression that involves the fusion of mononuclear precursor cells. The identification of RANK-RANKL signaling as the main signal regulating osteoclast differentiation was a major breakthrough in the bone biology field. In addition remarkable discoveries have been made to broaden the knowledge of the molecular mechanisms of osteoclast formation and differentiation. Despite the vital requirement of osteoclasts in bone modeling and remodeling, bone-related conditions like osteoporosis, Paget's disease and rheumatoid arthritis where accelerated bone resorption takes place pose a major socioeconomic burden to the society. Hence, a better understanding of the pathways leading to osteoclast differentiation is vital in successfully managing such diseases. This is an attempt to give a birds-eye-view of the players in osteoclast formation and differentiation in a brief and concise manner.
22120060 Menopause in patients with autoimmune diseases. 2012 May Menopause represents a time of significant clinical and hormonal change. Given the incompletely understood interrelationship between gonadal hormones and the immune system, it is possible that menopause may affect, or be affected by, the presence of autoimmune disease. Menopause has significant effects on a number of organ systems including the cardiovascular, skeletal, central nervous and genitourinary systems. Premature ovarian failure is related to autoimmune factors in a proportion of cases, but is not generally associated with systemic autoimmune disorders unless secondary to treatment with alkylating agents such as cyclophosphamide. Gonadal hormones have been suggested to relate to both onset and activity in certain autoimmune diseases. For patients with systemic lupus erythematosus, disease activity is lower, and damage accrual higher, in the postmenopausal years, but the mechanisms responsible may relate to age, duration of disease, menopause changes, long-term effects of therapy, or some combination of these factors. Early menopause is a risk factor for rheumatoid arthritis, and post-menopausal status in RA is associated with greater damage and disability. Systemic sclerosis and giant cell arteritis may also be adversely affected by onset of menopause. Importantly, autoimmune disease and menopause may have an additive effect on risk for common comorbidities such as cardiovascular disease and osteoporosis.
22086322 [Celiac disease and intestinal obstruction by T cell lymphoma]. 2011 Jul A male patient, 55 years old, born in Ayacucho, with Spanish ancestors, was hospitalized through emergency referring abdominal pain, and 10 kilograms weight loss. Six months before he was diagnosed as having irritable bowel syndrome. His previous diseases were rheumatoid arthritis and intolerance to lactose. Laboratory results were: Hb 12 gr./dL, white cells 5200 per mm3, albumin 2.7 gr./dL, erythrocyte sedimentation rate 32 mm/hr., and tumor markers were negative. Radiographic study of the small bowel showed barium fragmentation, and a focal dilation in distal jejunum. Chest X-ray and CT scan of thorax, abdomen and pelvis were normal. Colonoscopy was normal for colonic mucosa, but in ileum it showed an irregular mucosa, little nodules and fewer folds than usual. Biopsy from ileum demonstrated unspecific inflammation. Upper endoscopy showed gastritis, a duodenum scar ulcer and an irregular mosaic pattern pink and white. Duodenum biopsy demonstrated short villi, chronic inflammation and an increase in the number of intraepithelial lymphocytes, all these was consistent with celiac disease Marsh 3. Antibodies anti-endomisium and anti-transglutaminase were positive. After some days he developed signs of bowel obstruction and was operated.
22018177 History of the development of corticosteroid therapy. 2011 Sep The first clinical evidence that an extract of animal adrenocortical tissue could counteract human adrenal failure was demonstrated in 1930. As chemical analyses of cortical extracts proceeded, mainly in the laboratories of Kendall at the Mayo Clinic and Reichstein in Zurich, it became evident that there is not one cortical hormone, but that all are steroids. By 1940 it was understood that there are two categories: those that cause sodium and fluid retention and those that counteract shock and inflammation. Structurally the presence or lack of oxygenation at C11 on the steroid skeleton was critical. In 1948 the first patient with rheumatoid arthritis was treated with cortisone and soon thereafter other rheumatologic patients received cortisone or, to stimulate native cortisone production, ACTH. Oral and intra-articular administration of cortisone and hydrocortisone began in 1950-51. Several lines of research to produce cortisone semi-synthetically showed some success by 1952. Between 1954 and 1958 six synthetic steroids were introduced for systemic anti-imflammatory therapy. By 1960 all of the toxic effects of chronic corticosteroid administration had been described, as well as protocols to withdraw such drugs while minimising symptoms of cortical insufficiency. To enable use of lower corticosteroid dosages, companion use of non-steroidal anti-inflammatory drugs began in the late 1950s, with phenylbutazone the first. In the 1970s the introduction of methotrexate and other anti-metabolites further circumscribed the dosages and indications for corticosteroids in the rheumatic diseases.
22060220 United States medical eligibility criteria for contraceptive use 2010: a review of changes 2011 Nov In the late 1990s, the World Health Organization (WHO) created the Medical Eligibility Criteria for Contraceptive Use (MEC), which provide evidence-based recommendations for safe and effective contraception in women with medical problems. The WHO MEC incorporate the best available evidence, are periodically updated, and are designed to be modified for specific populations. The US Centers for Disease Control and Prevention published US MEC in 2010. Changes to WHO guidelines for use in the US population include the following areas: breastfeeding, intrauterine device use, valvular heart disease, ovarian cancer, uterine fibroids, and venous thromboembolism. Medical conditions not covered by WHO recommendations but added to the US MEC include contraceptive guidance for women with inflammatory bowel disease, history of bariatric surgery, rheumatoid arthritis, endometrial hyperplasia, history of peripartum cardiomyopathy, and history of solid organ transplant. This article reviews the changes and additions to WHO MEC found in the US MEC.
22036829 Rituximab - shadow, illusion or light? 2012 Jun Rituximab (Rituxan, Mabthera) is a monoclonal therapeutic anti-CD20 antibody approved for use in lymphoma and rheumatoid arthritis but not for use in systemic lupus erythematosus (SLE). Nonetheless, over the past decade many reports based on case series and observational studies have suggested benefits in selected groups of SLE patients with this monoclonal. It is also clear that off-label use of rituximab in SLE is not uncommon in many countries in the world. However, two randomized controlled clinical trials of rituximab failed to demonstrate a benefit for this agent, raising important questions on how to assess the potential role of rituximab in SLE. In this article I will review the available data and provide some comments that may be of use for the practicing clinician.
21969926 A case of adalimumab-induced pneumonitis in a 45-year-old man with Crohn's disease. 2011 Sep Adalimumab is a human monoclonal antibody against tumour necrosis factor-alpha that has been associated with acute lung toxicity, mainly in patients with rheumatoid arthritis. Descriptions of similar patterns of lung injury in patients treated with adalimumab for inflammatory bowel disease are emerging in the literature. A case involving a 45-year-old man with Crohn's disease who developed a nonbronchiolitis inflammatory nodular pattern of lung injury after starting adalimumab is reported.
32938022 On-line liquid chromatography neutral loss-triggered electron transfer dissociationmass sp 2011 Feb 1 Citrullination is a post-translational modification of proteins which deiminates arginine, increasing the mass by 0.98 Da. Protein citrullination is a known biomarker for multiple sclerosis and a potential biomarker for rheumatoid arthritis. Collision-induced dissociation (CID) tandem mass spectrometry of citrullinated peptides produces a dominant neutral loss of isocyanic acid (HNCO, -43 Da) from the deiminated arginine amino acid side-chain. Here we show that the loss of isocyanic acid in CID can be used as a trigger for targeted analysis by supplemental activation electron transfer dissociation (saETD). Unlike CID, post-translational modifications (PTMs) are retained on peptide backbone fragments produced by saETD, improving the confidence in assignment of both peptide sequence and PTM site. The method is demonstrated for four synthetic peptides spiked into complex trypsin-digested saliva samples and a commercial six protein tryptic mixture. In contrast to CID alone, the neutral-loss triggered ETD approach results in high confidence identification of three of the four peptides, including an unexpected disulfide-bound dimer, and zero false positives.
20358579 MicroRNAs and their role in gynecological tumors. 2011 Nov There have been only few events in the history of molecular biology that could be compared to the discovery of microRNAs and their role in cell physiology and pathology. MicroRNAs are small, single-stranded, noncoding RNAs composed of 19-25 nucleotides (∼22 nt), which have been proven to regulate gene expression at the posttranscriptional level. The regulatory function of microRNAs was demonstrated in normal and diseased conditions. In particular, it has been linked to cell cycle regulation, cell proliferation and differentiation, inflammatory response, and apoptosis. Altered expression profiles of microRNA have been observed in many pathologies, including diabetes, rheumatoid arthritis, and several cancers. To date, more than 700 human microRNAs have been identified and in silico-based analyses estimate at least 500 more to be identified. The purpose of this review is to present the current perspective on microRNAs structure and biogenesis as well as their contribution to the etiopathogenesis of gynecological tumors. We discuss results of the recent publications that indicate possibilities of microRNAs use as novel markers for tumors screening, early diagnosis, and treatment monitoring. The possible utilization of microRNAs as prognostic factors and specific therapy targets is also reviewed.
19622600 The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part I. 2011 CD4(+) effector cells, based on cytokine production, nuclear receptors and signaling pathways, have been categorized into four subsets. T-helper-1 cells produce IFN-γ, TNF-β, lymphotoxin and IL-10; T-helper-2 cells produce IL-4, IL-5, IL-10, IL-13, IL-21 and IL-31; T-helper-3, or regulatory T-cells, produce IL-10, TGF-β and IL-35; and the recently discovered T-helper-17 cell produces IL-17, IL-17A, IL-17F, IL-21, IL-26 and CCL20. By producing IL-17 and other signaling molecules, Th17 contributes to the pathogenesis of multiple autoimmune diseases including allergic inflammation, rheumatoid arthritis, autoimmune gastritis, inflammatory bowel disease, psoriasis and multiple sclerosis. In this article, we review the differential regulation of inflammation in different tissues with a major emphasis on enhancement of neuroinflammation by local production of IL-17 in the brain. By understanding the role of pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting Th17 and associated cytokine activities and signaling pathways to repair the intestinal and blood-brain barriers for their patients with autoimmunities, in particular, those with neuroinflammation and neurodegeneration.
23853619 Non-contraceptive benefits of oral hormonal contraceptives. 2013 Winter It is becoming evident that oral hormonal contraceptives-besides being well established contraceptives-seem to become important medications for many functional or organic disturbances. So far, clinical effectiveness has been shown for treatment as well as prevention of menstrual bleeding disorders and menstrual-related pain symptoms. Also this is true for premenstrual syndrome (PMS) and premenstrual disphoric disorder (PMDD). Particular oral contraceptives (OCs) containing anti-androgenic progestogens were shown to be effective medications for treatment of androgenisation symptoms (seborrhea, acne, hirsutism, alopecia). Through perfect suppression of the hypothalamic-pituitary-ovarian axis OCs have proven to be effective in elimination of persistent follicular cysts. Endometriosis/adenomyosis related pain symptoms are well handled similar to other drugs like Gonadotropine Releasing Hormone agonists but are less expensive, with less side effects, and possibility to be used for longer periods of time. This is also true for myoma. Pelvic inflammatory disease, rheumatoid arthritis, menstrual migraine, and onset of multiple sclerosis are prevented or delayed. Bone density is preserved and asthma symptoms improved. Endometrial hyperplasia and benign breast disease can be controlled. There is definitely a significant impact on risk reduction regarding endometrial, ovarian, and colon cancers. In conclusion, it needs to be recognized that oral combined hormonal contraceptives (estrogen/ progestogen combination) are - besides being reliable forms of contraception - are cost-effective medications for many medical disorders in women. Therefore, these contraceptives drugs are important for female and global health and should be used in clinical practice.
28509217 Scleroderma renal crisis in a newly diagnosed mixed connective tissue disease resulting in 2013 May Mixed connective tissue disease (MCTD) is a rheumatic disease with a combination of multiple connective tissue disorders, which includes dermatomyositis or polymyositis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. It affects various organs of the body, which includes the lungs, heart, kidneys, joints, muscles and the haematological system. Here, we report a case of MCTD consisting of scleroderma, Sjögren's syndrome and polymyositis complicated by scleroderma renal crisis (SRC) but with negative anti-nuclear antibody (ANA), anti-Scl 70 and anti-centromere antibodies. The patient was started on captopril for the treatment of SRC but developed chronic kidney disease despite adequate blood pressure control with angiotensin-converting enzyme inhibitor (ACEi).
23366388 Volumetric ultrasound and computer-assisted analysis at the point-of-care: a musculoskelet 2012 In this paper we motivate the hypothesis that the use of volumetric ultrasound imaging and automated image analysis tools would improve clinical workflows as well as outcomes at the point-of-care. To make our case, this paper presents results from a rheumatoid arthritis (RA) study where several image analysis techniques have been applied to volumetric ultrasound, highlighting anatomy of interest to better understand disease progression. Pathologies related to RA in joints, manifest themselves commonly as changes in the bone (e.g. erosions) and the region enclosed by the joint-capsule (e.g. synovitis). Automated tools for detecting and segmenting such structures would help significantly towards objective and quantitative assessment of RA in joints. Extracted bone coupled with a simple anatomical model of the joint provides a coarse localization of the joint-capsule region. A probabilistic speckle model is then used to iteratively refine the capsule segmentation. We illustrate the performance of proposed algorithms through quantitative comparisons with expert annotations as well as qualitative results on over 30 scans obtained from 11 subjects.
23185646 Giant cell tumor of the tendon sheath: experience with 65 cases. 2012 OBJECTIVE: No consensus exists on the etiology, prognostic factors, or recurrence rate of giant cell tumors of the tendon sheath. This article presents a series of 65 cases supplemented by a literature review that examines the epidemiology, presentation, gross and microscopic characteristics, and recurrence rate of giant cell tumor of the tendon sheath. METHODS: The authors completed a retrospective review of one surgeon's practice from 1976 to 2001, evaluating 65 cases of giant cell tumor of the tendon sheath. The authors conducted a literature search and compared the case series with historical data. RESULTS: The tumor most commonly presented as a firm, nontender mass in the dominant hand. Our cases showed a slight female predominance of 54%, compared with the literature average of 64%. A pseudocapsule was present in 51% of cases. Overall recurrence rate was 10%. No association was noted between recurrence and pseudocapsule presence, rheumatoid arthritis, or osteoarthritis. Satellite lesions at the first excision were noted in 80% of recurrent cases; however, satellite lesions were not a risk factor for recurrence per se. CONCLUSIONS: Our study shows similar findings to the literature, with the notable addition of satellite lesions in recurrent tumors. Marginal excision is the treatment of choice, but may be complicated when the tumor is attached to vital structures. Therefore, an appropriate balance between resection of tumor and maintenance of function must be achieved due to the possibility of recurrence.
23020579 TRPA1: A gatekeeper for inflammation. 2013 Tissue damage evokes an inflammatory response that promotes the removal of harmful stimuli, tissue repair, and protective behaviors to prevent further damage and encourage healing. However, inflammation may outlive its usefulness and become chronic. Chronic inflammation can lead to a host of diseases, including asthma, itch, rheumatoid arthritis, and colitis. Primary afferent sensory neurons that innervate target organs release inflammatory neuropeptides in the local area of tissue damage to promote vascular leakage, the recruitment of immune cells, and hypersensitivity to mechanical and thermal stimuli. TRPA1 channels are required for neuronal excitation, the release of inflammatory neuropeptides, and subsequent pain hypersensitivity. TRPA1 is also activated by the release of inflammatory agents from nonneuronal cells in the area of tissue injury or disease. This dual function of TRPA1 as a detector and instigator of inflammatory agents makes TRPA1 a gatekeeper of chronic inflammatory disorders of the skin, airways, and gastrointestinal tract.
23000633 Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases. 2013 Jun Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin's B-cell lymphoma in 1997. In the last 15years, it has emerged as a potent immunosuppressant for many immune-mediated diseases, beginning initially with rheumatoid arthritis, and now extending into several other fields, including clinical nephrology. Based on recent large clinical trials, it is FDA-approved for the treatment of ANCA-associated vasculitis and continues to be studied in off-label usage for many glomerular diseases, including membranous nephropathy, lupus nephritis, and mixed cryoglobulinemia. It has been used as a treatment in nephrotic syndrome in children and adults, including both minimal change disease and focal segmental glomerulosclerosis. Given its efficacy, tolerability and safety profile in comparison to more conventional treatment regimens, RTX is rapidly emerging as a critical treatment modality in glomerular disease.
22910888 Role of adipokines in atherosclerosis: interferences with cardiovascular complications in 2012 Patients with rheumatic diseases have an increased risk of mortality by cardiovascular events. In fact, several rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis are associated with a higher prevalence of cardiovascular diseases (CVDs). Although traditional cardiovascular risk factors have been involved in the pathogenesis of cardiovascular diseases in rheumatic patients, these alterations do not completely explain the enhanced cardiovascular risk in this population. Obesity and its pathologic alteration of fat mass and dysfunction, due to an altered pattern of secretion of proinflammatory adipokines, could be one of the links between cardiovascular and rheumatic diseases. Indeed, the incidence of CVDs is augmented in obese individuals with rheumatic disorders. Thus, in this paper we explore in detail the relationships among adipokines, rheumatic diseases, and cardiovascular complications by giving to the reader a holistic vision and several suggestions for future perspectives and potential clinical implications.
22648263 The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases. 2012 Jun This paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants "vertically" by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.
22577464 The observation of humoral responses after influenza vaccination in patients with rheumato 2012 Objective. The efficacy of influenza vaccination in patients treated with Japanese Oriental (Kampo) Medicine is unknown. The objectives of this study were to observe the efficacy of influenza vaccination in RA patients treated with Kampo. Methods. Trivalent influenza subunit vaccine was administered to 45 RA patients who had received Kampo. They were divided into 2 groups: RA patients treated without MTX ("without MTX group") and treated with MTX ("with MTX group"). Antibody titers were measured before and 4 weeks after vaccination using hemagglutination inhibition assay. Results. Geometric mean titers (GMTs) of anti-influenza antibodies significantly increased for all influenza strains. Response to the influenza vaccination in RA patients treated with Kampo was not lower than that of healthy subjects and the response in the "with MTX group" had a tendency to be higher than that in RA patients treated with MTX in the previous study. There was no significant difference in the GMT after 4 weeks between the "with MTX group" and the "without MTX group." A decreased efficacy in both seroprotection and seroconversion was not found in the "with MTX group." Conclusion. These observations may open the way for further clinical trials to establish the efficacy for the influenza vaccination in RA patients treated with Kampo.
22420757 Biologics in oral medicine: principles of use and practical considerations. 2012 Sep Oral Diseases (2012) 18, 525-536 Biologic therapies are relatively innovative treatments aimed at modulating lymphocytes or cytokines. There are currently three broad classes of biologic therapies, tumour necrosis factor-alpha inhibitors, lymphocyte modulators and interleukin inhibitors; all are increasingly used in the treatment of inflammatory immune-mediated conditions, and several have potential applications in oral medicine. Guidelines for their use in licensed indications (e.g. rheumatoid arthritis, psoriasis, inflammatory bowel disease) include recommendations and guidance for patient selection and subsequent monitoring with discussion of potential adverse effects. An understanding of these is important when managing patients receiving biologic therapy for systemic disease, and compliance is essential in any use in oral medicine. Key aspects of current guidance are presented with particular emphasis on their relevance to clinicians working within oral and maxillofacial medicine/pathology/surgery and in specialist practice.