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ID PMID Title PublicationDate abstract
22261016 Phosphospecific flow cytometry for pharmacodynamic drug monitoring: analysis of the JAK-ST 2012 Sep 8 Cytokines of the IL-2 receptor family act via activation of the JAK-STAT (janus tyrosine kinase-signal transducer and activator of transcription) signaling pathway. These cytokines are pivotal for the development and function of lymphocyte subsets involved in the immune response after organ transplantation including T, B and natural killer cells. The new small drug molecule and JAK1/3 inhibitor, tofacitinib, is currently being tested in phase II and III clinical trials for rheumatoid arthritis, psoriasis and in organ transplantation. This agent specifically targets the JAK-STAT signaling pathway. Here we discuss phosphospecific flow cytometry as a novel tool to monitor the JAK-STAT signaling pathway in kidney transplant patients and speculate that through the use of this pharmacodynamic tool the efficacy of immunosuppressive drugs can be assessed enabling optimization of the immunosuppressive therapy for individual transplant patients.
22255758 Recognition-based segmentation and registration method for image guided shoulder surgery. 2011 For any image guided surgery, independently of the technique which is used (navigation, templates, robotics), it is necessary to get a 3D bone surface model from CT or MR images. Such model is used for planning, registration and visualization. We report that graphical representation of patient bony structure and the surgical tools, interconnectively with the tracking device and patient-to-image registration are crucial components in such a system. For Total Shoulder Arthroplasty (TSA), there are many challenges, The most of cases that we are working with are pathological cases such as rheumatoid arthritis, osteoarthritis disease. The CT images of these cases often show a fusion area between the glenoid cavity and the humeral head. They also show severe deformations of the humeral head surface that result in a loss of contours. This fusion area and image quality problems are also amplified by well-known CT-scan artifacts like beam-hardening or partial volume effects. The state of the art shows that several segmentation techniques, applied to CT-Scans of the shoulder, have already been disclosed. Unfortunately, their performances, when used on pathological data, are quite poor [1, 2]. The aim of this paper is to present a new image guided surgery system based on CT scan of the patient and using bony structure recognition, morphological analysis for the operated region and robust image-to-patient registration.
22236892 Thoracic manifestations of collagen vascular diseases. 2012 Jan Collagen vascular diseases are a diverse group of immunologically mediated systemic disorders that often lead to thoracic changes. The collagen vascular diseases that most commonly involve the lung are rheumatoid arthritis, progressive systemic sclerosis, systemic lupus erythematosus, polymyositis and dermatomyositis, mixed connective tissue disease, and Sjögren syndrome. Interstitial lung disease and pulmonary arterial hypertension are the main causes of mortality and morbidity among patients with collagen vascular diseases. Given the broad spectrum of possible thoracic manifestations and the varying frequency with which different interstitial lung diseases occur, the interpretation of thoracic images obtained in patients with collagen vascular diseases can be challenging. The task may be more difficult in the presence of treatment-related complications such as drug toxicity and infections, which are common in this group of patients. Although chest radiography is most often used for screening and monitoring of thoracic alterations, high-resolution computed tomography can provide additional information about lung involvement in collagen vascular diseases and may be especially helpful for differentiating specific disease patterns in the lung. General knowledge about the manifestations of thoracic involvement in collagen vascular diseases allows radiologists to provide better guidance for treatment and follow-up of these patients.
22178433 Effects of yoga interventions on pain and pain-associated disability: a meta-analysis. 2012 Jan We searched databases for controlled clinical studies, and performed a meta-analysis on the effectiveness of yoga interventions on pain and associated disability. Five randomized studies reported single-blinding and had a higher methodological quality; 7 studies were randomized but not blinded and had moderate quality; and 4 nonrandomized studies had low quality. In 6 studies, yoga was used to treat patients with back pain; in 2 studies to treat rheumatoid arthritis; in 2 studies to treat patients with headache/migraine; and 6 studies enrolled individuals for other indications. All studies reported positive effects in favor of the yoga interventions. With respect to pain, a random effect meta-analysis estimated the overall treatment effect at SMD = -.74 (CI: -.97; -.52, P < .0001), and an overall treatment effect at SMD = -.79 (CI: -1.02; -.56, P < .0001) for pain-related disability. Despite some limitations, there is evidence that yoga may be useful for several pain-associated disorders. Moreover, there are hints that even short-term interventions might be effective. Nevertheless, large-scale further studies have to identify which patients may benefit from the respective interventions. PERSPECTIVE: This meta-analysis suggests that yoga is a useful supplementary approach with moderate effect sizes on pain and associated disability.
22034790 Proximal tibial stress fracture associated with mild osteoarthritis of the knee: case repo 2011 Mar Stress fractures are considered as multifactorial overuse injuries occurring in 0.3%-0.8% of patients suffering from rheumatic diseases, with rheumatoid arthritis being the most common underlying condition. Stress fractures can be classified according to the condition of the bone affected as: 1) fatigue stress fractures occurring when normal bone is exposed to repeated abnormal stresses; and 2) insufficiency stress fractures that occur when normal stress is applied to bone weakened by an underlying condition. Stress fractures are rarely associated with severe forms of knee osteoarthritis, accompanied with malalignment and obesity. We present a patient with a proximal tibial stress fracture associated with mild knee osteoarthritis without associated malalignment or obesity. Stress fracture should be considered when a patient with osteoarthritis presents with sudden deterioration, severe localized tenderness to palpation and localized swelling or periosteal thickening at the pain site and elevated local temperature. The diagnosis of stress fractures in patients with rheumatic diseases may often be delayed because plain film radiographs may not reveal a stress fracture soon after the symptom onset; moreover, evidence of a fracture may never appear on plain radiographs. Triple phase nuclear bone scans and magnetic resonance imaging are more sensitive in the early clinical course than plain films for initial diagnosis.
28839619 Premedications for infliximab infusions do not impact the risk of acute adverse drug react 2011 Oct OBJECTIVE: The purpose of this study was to identify the association of premedication with the adverse drug reaction (ADR) rate in infliximab infusions. DESIGN: A retrospective chart review of 684 patients who received 4077 infusions in a network of community clinics over 16.5 months. Data collected included age, weight, sex, diagnosis, dose, premedications and ADR information, which was coded for time of onset, severity and outcome. SETTING: Community infusion clinics located in Ontario, Canada. PATIENTS: Patients aged 12-91 years who receive regular infliximab infusions to treat their autoimmune condition, mainly either Crohn's disease or rheumatoid arthritis. MAIN OUTCOME MEASURES: The number of infusions to the occurrence of an acute ADR by presence of premedication. RESULTS: ADRs are not significantly different (χ(2)(1, n=644, p=0.651)=0.204) between those who always received premedications and those who never did. When controlling for age, sex, weight and diagnosis, patients receiving premedications were just as likely to experience an ADR as patients who never received any (OR 1.1, 95% CI 0.7 to 1.9, p=0.5). When assessing the number of infusions to the occurrence of an ADR using the Kaplan-Meier method, no significant difference was found between the two groups. CONCLUSIONS: The use of premedications is not associated with a decreased risk of ADR in patients receiving infliximab. This held true for patients who had never had an ADR prior to receiving premedications and while controlling for age, sex, weight and diagnosis.
21852390 Denosumab for bone diseases: translating bone biology into targeted therapy. 2011 Dec Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.
21787412 Vaughan-Jackson-like syndrome as an unusual presentation of Kienböck's disease: a case re 2011 Jul 25 INTRODUCTION: Kienböck's disease is a condition of osteonecrosis of the lunate bone in the hand, and most patients present with a painful and sometimes swollen wrist with a limited range of motion in the affected wrist. Vaughan-Jackson syndrome is characterized by the disruption of the digital extensor tendons, beginning on the ulnar side with the extensor digiti minimi and extensor digitorum communis tendon of the small finger. It is most commonly associated with rheumatoid arthritis. We describe a case of a patient with an unusual presentation of Kienböck's disease with symptoms similar to those of Vaughan-Jackson syndrome. CASE PRESENTATION: A 40-year-old man of Indian ethnic origin with no known history of trauma presented to our clinic with a ten-day history of an inability to extend his right little and ring fingers with associated pain in his right wrist. He was being treated with long-term steroids but had no other significant medical history. His examination revealed an inability to extend the metacarpal and phalangeal joints of the right ring and little fingers with localized tenderness over the lunate bone. Spontaneous disruption of the extensor tendons was diagnosed clinically and, after radiological investigation, was confirmed to be secondary to dorsal extrusion of the fragmented lunate bone. The patient underwent surgical repair of the tendons and had a full recovery afterward. CONCLUSION: Kienböck's disease, though rare, is an important cause of spontaneous extensor tendon rupture. The original description of Vaughan-Jackson syndrome was of rupture of the extensor tendons of the little and ring fingers caused by attrition at an arthritic inferior radioulnar joint. We describe a case of a patient with Kienböck's disease that first appeared to be a Vaughan-Jackson-like syndrome.
21787222 The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. 2011 Oct Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by a defect in immune tolerance and exacerbated by both the innate and adaptive arms of the immune response. SLE-associated immune hyperactivity can be detected systemically as elevations in levels of cytokines along with their upregulated receptors expressed by hematopoietic cells. Importantly, increased levels of cytokines and their receptors can be observed in target organs, and it is clear that they have important roles in disease pathogenesis. Recent therapeutic strategies have focused on proximal cytokines, such as interferon-α, interleukin (IL)-1, IL-6, and tumor necrosis factor as a result of the efficacious use of biologic agents for intervention in rheumatoid arthritis and other autoimmune diseases. Despite the recent advances in understanding the cytokine networks involved in autoimmune diseases and more specifically in SLE, the diagnosis and prognosis of lupus remain a challenge. Lupus is heterogeneous and unpredictable; moreover, the frequency and severity of flares can be difficult to determine and treat. A better understanding of the regulation of expression of key cytokines and their receptors can likely provide important clues to the pathogenic mechanisms underlying specific forms of SLE, and pave the way toward more effective therapeutics.
21783193 Emerging role of high density lipoproteins as a player in the immune system. 2012 Jan High density lipoproteins (HDL) possess a number of physiological activities. The most studied and, perhaps, better understood is the ability of HDL to promote excess cholesterol efflux from peripheral tissues and transport to the liver for excretion, a mechanism believed to confer protection against atherosclerotic cardiovascular disease. The ability of HDL to modulate cholesterol bioavailability in the lipid rafts, membrane microdomains enriched in glycosphingolipids and cholesterol, is evolutionary conserved and affects the properties of cells involved in the innate and adaptive immune response, tuning inflammatory response and antigen presentation functions in macrophages as well as B and T cell activation. Also sphingosine-1 phosphate (S1P), a major active sphingolipid carried by HDL, is of relevance in the pathogenesis of several immuno-inflammatory disorders through the modulation of macrophage and lymphocyte functions. Furthermore, HDL influence the humoral innate immunity by modulating the activation of the complement system and the expression of pentraxin 3 (PTX3). Finally, in humans, HDL levels and functions are altered in several immune-mediated disorders, such as rheumatoid arthritis, systemic lupus eritematosus, Crohn's disease and multiple sclerosis as well as during inflammatory responses. Altogether these observations suggest that the effects of HDL in immunity could be related, to either the ability of HDL to modulate cholesterol content in immune cell lipid rafts and to their role as reservoir for several biologically active substances that may impact the immune system.
25083207 Immunogenicity and other problems associated with the use of biopharmaceuticals. 2011 Jun Biopharmaceuticals are used widely for the treatment of cancer, chronic viral hepatitis, inflammatory, and autoimmune diseases. Biopharmaceuticals such as interferons are well tolerated for the most part with the most common adverse events observed being 'flu-like' symptoms that resolve rapidly after initial treatment. Prolonged treatment is associated, however, with more serious adverse events including leucopenia, thrombocytopenia, and neuropsychiatric effects, which may necessitate dose reduction or even cessation of treatment in some patients. Recombinant growth factors, such as erythropoietin (EPO), granulocyte colony-stimulating factor, or granulocyte macrophage colony-stimulating factor, are for the most part well tolerated, although severe complications have been reported in patients with cancer or chronic kidney disease treated with EPO. Similarly, treatment of patients with cancer with high doses of interleukin-2 is associated with significant toxicity. Treatment of chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and Crohn's disease, with antitumor necrosis factor-alpha monoclonal antibodies is associated with an increased risk of granulomatous infections and, in particular, tuberculosis. The monoclonal antibody, natalizumab, that targets alpha4 integrins is effective in the treatment of multiple sclerosis but is associated with the activation of JC virus and development of progressive multifocal leukoencephalopathy. Repeated administration of recombinant proteins can cause a break in immune tolerance in some patients resulting in the production of a polyclonal antibody response that can adversely affect pharmacokinetics and clinical response. In addition, neutralizing antibodies that cross react with nonredundant essential proteins such as EPO can cause severe autoimmune reactions.
21533026 Shared molecular and functional frameworks among five complex human disorders: a comparati 2011 Apr 21 BACKGROUND: Genome-wide association studies (gwas) are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and functional framework hosting the susceptibility genes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the relationships among five neurodegenerative and/or autoimmune complex human diseases (Parkinson's disease--Park, Alzheimer's disease--Alz, multiple sclerosis--MS, rheumatoid arthritis--RA and Type 1 diabetes--T1D) by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks. In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently. Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and, surprisingly, in Alzheimer's disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz. CONCLUSIONS/SIGNIFICANCE: The systems biology approach highlighted several known pathogenic processes, indicating that changes in these functions might be driven or sustained by the framework linked to genetic susceptibility. Moreover, the comparative analyses among the five genetic interactomes revealed unexpected genetic relationships, which await further biological validation. Overall, this study outlines the potential of systems biology to uncover links between genetics and pathogenesis of complex human disorders.
26000114 Pearls in autoimmunity. 2011 May This manuscript does a review of the more frequent issues published at Autoimmunity Reviews, Journal of Autoimmunity and Autoimmunity in the period of January-December 2009. The following topics were commented: (1) multiple sclerosis (MS) and its relationships with Epstein Barr infection, with vitamin D polymorphism and the new modalities of MS treatment. (2) Type 1 diabetes and genetic discovers, studies with GAD 65 and IA-2 autoantigen and the association T1D and autoimmune organ-specific diseases. (3) Autoimmune thyroid disorders and its association with susceptibility genes and polymorphisms. (4) Multiplex autoantibody profiling approaches in MS and rheumatoid arthritis. (5) Th17 cytokine in primary biliary cirrhosis, experimental autoimmune encephalomyelitis and celiac disease. (6) Vitamin D and experimental autoimmune prostatitis and pulmonary alveolar proteinosis.
21516292 Toll-like receptors in angiogenesis. 2011 Apr 19 Toll-like receptors (TLRs) are known as pattern-recognition receptors related to the Toll protein of Drosophila. After recognition of pathogen-associated molecular patterns of microbial origin, the TLRs alert the immune system, and initiate innate and adaptive immune responses. The TLR system, though, is not confined solely to the leukocyte-mediated immune defense against exogenous pathogens. Besides myeloid cells, TLR expression has been reported in multiple tissues and cell types, including epithelial and endothelial cells. Moreover, despite the microbial patterns that are commonly accepted as TLR ligands, there is increasing evidence that TLRs also recognize host-derived molecules. In this regard, recent studies point to an involvement of TLRs in various chronic inflammatory disorders and cardiovascular diseases, including atherosclerosis, rheumatoid arthritis, systemic lupus erythematosus, and even cancer. A common feature of these disorders is an enhanced so-called inflammation-induced angiogenesis. However, inflammation-induced angiogenesis is not solely a key component of pathogen defense during acute infection or chronic inflammatory disorders, but also plays a critical role in repair mechanisms, e.g., wound healing and subsequent tissue regeneration. Interestingly, the latest research could coincidentally demonstrate that TLR activation promotes angiogenesis in various inflammatory settings in response to both exogenous and endogenous ligands, although the precise mode of action of TLRs in this context still remains ambiguous. The objective of this review is to present evidence for the implication of TLRs in angiogenesis during physiological and pathophysiological processes, and the potential clinical relevance for new treatment regimes involving TLR modulation.
21447200 [Rheumatic diseases need more attention in case of the desire to have children and during 2011 Treatment of rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus and Bechterew's disease is still improving and the number of fertile patients with a wish to conceive will probably increase. New knowledge regarding the course of rheumatic diseases during pregnancy and post partum herald a change in the support of women with rheumatic diseases who desire to have children. Justified use of antirheumatic drugs before, during and after pregnancy is a key issue for a successful pregnancy. The newer agents such as tumour necrosis factor (TNF) alpha blocking agents can also be of use. Specific preconception care should be offered to women with rheumatic diseases to optimize and increase chances of a successful pregnancy.
21343403 Azathioprine-induced fever in sarcoidosis. 2011 Mar OBJECTIVE: To report a case of drug-induced fever associated with azathioprine treatment in a patient with sarcoidosis. CASE SUMMARY: A 52-year-old man with pulmonary sarcoidosis presented to the emergency department with a 1-day history of fever (temperature 39.9 °C), chills, nausea, and vomiting. One week earlier, azathioprine 50 mg/day had been started for worsening dyspnea. The patient was admitted and evaluated for acute infectious processes. All of his home medications (hydroxychloroquine, prednisone, fluticasone/salmeterol, lovastatin, pantoprazole, zolpidem, ibandronate, albuterol), except prednisone, were held. Results of chest X-ray, viral cultures, and urine and blood cultures revealed no source of infection. The patient's temperature returned to normal within 30 hours after discontinuation of azathioprine; rechallenge was not performed. DISCUSSION: Fever as an adverse drug reaction is often unrecognized, particularly in medically complex patients. Azathioprine has been reported to cause drug fever in patients with inflammatory bowel disease and in those with rheumatoid arthritis; to our knowledge, there have been no previous reports documenting azathioprine-induced fever in patients with sarcoidosis. The chronological course of febrile response and defervescence is highly suggestive of drug-induced fever. CONCLUSIONS: The rapid resolution of fever after discontinuation of azathioprine suggests that it was the likely source of fever in this patient. If azathioprine is increasingly prescribed in patients with sarcoidosis, fever as an adverse reaction may become more common.
21330088 Determination of methotrexate and indomethacin in urine using SPE-LC-DAD after derivatizat 2011 May 15 A validated HPLC-DAD assay is presented for the simultaneous quantification of methotrexate and indomethacin in a drug combination which is used synergistically to intervene with tumoral or inflammatory tissue microenvironments. The analytes were isolated from urine via solid phase extraction. The method is based on derivatizing both analytes with a soluble carbodiimide coupler and 2-nitrophenylhydrazine directed to their commonly occurring carboxylate functions. The chromatographic separation was accomplished on an octylsilica column in less than 15 min using acetate buffer (pH 4; 10 mM)-methanol (60:40, v/v) as eluent at 1.5 ml/min and monitored at 400 nm. The selectivity of the method was demonstrated in a pre-dosed rheumatoid arthritis patient. Quality control samples were prepared and analyzed to reveal the validity of the method. Life samples collected from a healthy volunteer were monitored for both drugs and their urinary levels were determined.
21299962 [Deimination or citrullination, a post-translational modification with many physiological 2011 Jan Deimination or citrullination, is a post-translational modification with many facets. It is involved in several basic cellular processes, including gene regulation, embryonic development and terminal differentiation, and also in various pathophysiological mechanisms linked to severe human diseases such as multiple sclerosis and rheumatoid arthritis. Deimination, the calcium-dependent enzymatic conversion of peptidyl-arginine to peptidyl-citrulline, induces a decrease in the charge of the modified proteins with major consequences on their conformation, stability and/or interactions, and therefore on their functions. Five isotypes of peptidylarginine deiminases (1-4 and 6), exist in humans with a variable tissue expression. These highly conserved enzymes are closely regulated at transcriptional and post-transcriptional levels, probably including auto-deimination.
21184648 Micronutrients at the interface between inflammation and infection--ascorbic acid and calc 2011 Feb As explained in the first part of the article, vitamins and trace elements influence various metabolic functions that are directly related to immune function. In this context, secosteroid vitamin D has met with growing interest. The discussion has focused on whether and, if so, to what extent, vitamin D might contribute to the prevention and possibly the treatment of infections and autoimmune diseases. We know, for instance, that immune cells are capable of synthesizing calcitriol from its precursor calcidiol, whereby the former enhances the synthesis of antibacterial peptides by macrophages while simultaneously inhibiting the (auto)immune response mediated by T helper cells (Th1). Numerous observational studies support the hypothesis that a vitamin D deficit increases the risk of autoimmune diseases such as type 1 diabetes mellitus, multiple sclerosis, psoriasis and rheumatoid arthritis; however, there are few reliable interventional studies to date. In general, immune status represents a sensitive indicator of micronutrient supply. Conversely, the activity of the immune system has an effect on the status of and requirements for nutrients.
21145125 The soluble Interleukin 6 receptor: generation and role in inflammation and cancer. 2011 Jun Soluble cytokine receptors are frequently found in human serum, most of them possessing antagonistic properties. The Interleukin 6 receptor (IL-6R) is found as a transmembrane protein on hepatocytes and subsets of leukocytes, but soluble isoforms of the IL-6R (sIL-6R) are generated by alternative splicing or by limited proteolysis of the ADisintegrin And Metalloproteinases (ADAM) gene family members ADAM10 and ADAM17. Importantly, the sIL-6R in complex with its ligand Interleukin 6 (IL-6) has agonistic functions and requires cells expressing the signal transducing ß-receptor gp130 but not the membrane-bound IL-6R. We have called this process IL-6 trans-signaling. Naturally occurring isoforms of soluble gp130 (sgp130), which are generated by alternative splicing, are natural inhibitors of IL-6 trans-signaling, leaving IL-6 classic signaling via the membrane-bound IL-6R unaffected. We used recombinant sgp130Fc protein and recently generated transgenic mice expressing high levels of sgp130Fc to discriminate between classic and trans-signaling in vivo, and demonstrated that IL-6 trans-signaling is critically involved in generation and maintenance of several inflammatory and autoimmune diseases including chronic inflammatory bowel disease, rheumatoid arthritis, peritonitis and asthma, as well as inflammation-induced colon cancer.