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ID PMID Title PublicationDate abstract
23135691 Rituximab in critically ill patients. 2013 Feb Rituximab is a monoclonal chimeric antibody used in the treatment of CD20-positive B-cell malignancies and rheumatoid arthritis. However, it is used in several other off-label indications including acute graft-versus-host disease. We sought to critically examine the role of rituximab in the treatment of acute graft versus host disease (aGVHD) in critically ill patients and the potential associations with infectious complications in transplant recipients.
23118591 Involvement of caspase-3 in stilbene derivatives induced apoptosis of human neutrophils in 2012 Jun Chronic inflammatory diseases, e.g. rheumatoid arthritis or cystic fibrosis, are characterised by neutrophil infiltration in inflamed tissues. Dysregulated neutrophil death may contribute to the pathogenesis of diseases where neutrophils play a role. Stilbene derivatives are reported to activate apoptosis in different cell lines. Neutrophils from healthy volunteers were incubated in vitro with resveratrol, pterostilbene, pinosylvin or piceatannol (1-100 µmol/l), and cytotoxicity and apoptosis were measured by luminometry and flow cytometry, respectively. Enhancement and/or inhibition of human recombinant caspase-3 enzyme activity were measured by luminometry. None of the stilbene derivatives tested increased ATP liberation from human neutrophils, thus showing no direct cytotoxicity effect. Resveratrol and piceatannol (100 µmol/l) treated neutrophils had a higher rate of apoptosis compared to non-treated cells. Pterostilbene and pinosylvin (1 µmol/l), yet not resveratrol or piceatannol, increased the activity of caspase-3. However in the concentration of 100 µmol/l, all stilbene derivatives tested inhibited caspase-3 activity. Their effects on human neutrophil apoptosis differed according to the structure of the molecule. Additional studies are required to get insight into the mechanisms involved in the effects of the substances tested on neutrophil viability.
23056959 The swindon foot and ankle questionnaire: is a picture worth a thousand words? 2012 Objectives. Despite increased awareness of the high prevalence and significance of foot and ankle problems in rheumatoid arthritis (RA), feet remain neglected. Reasons may include the perception that feet are difficult to assess, they are not included in the DAS28, and lack of freely available foot screening tools specific for RA. Methods. The Swindon Foot and Ankle Questionnaire (SFAQ) is a simply worded 10-point foot and ankle screening questionnaire with diagrams of feet and ankles for use in general rheumatology outpatients. All RA patients on our electronic database were invited to complete the questionnaire and attend clinic for assessment. Patients assessed clinically were scored out of 10 using the parameters from the questionnaire. The SFAQ was compared to the Manchester Foot Pain and Disability Index (MFPDI), DAS28, HAQ, HAD, and OSRA scores. Results. 597 questionnaires were sent, 301 (50%) returned, and 137 seen in clinic. There was good correlation between the postal SFAQ score, clinic score (r = 0.63), and the MFPDI (r = 0.65). Neither of the foot scores correlated with other RA disease outcome measures. 75% patients completed the picture. 73% corresponded to clinical findings. 45% of patients required an intervention following clinical review and trended towards higher scores. Conclusions. The SFAQ was quick to complete and correlated with the MFPDI. Lack of association with standard RA outcome measures suggests that relying on these scores alone may miss foot pathology. The diagrams were a useful complement. This simple screening tool could aid identification of RA foot and ankle problems.
23012798 [Activation of osteoclasts by RAAS and strategy of target therapy on bone metabolic diseas 2012 Sep Angiotensin II is a potent stimulator of vascular smooth mustle cells that increases blood pressure, and angiotensin type 1 receptors have been identified on osteoblasts; thus, the renin-angiotensin system has been suggested to be involved in bone metabolism. The authors reported that angiotensin II significantly increased TRAP-positive multinuclear osteoclasts with the up-regulation of RANKL expression through extracellular kinase of osteoblast. These effects were abolished with co-treatment of angiotensin converting enzyme (ACE) inhibitors or angiotensin type 1 receptor blockers (ARB). Recently, RANK-RANKL-OPG system is proved to be involved in vascular calcification and RAAS also might be involved in the development of the disease. Thus, target therapy for RAAS might bring additional beneficial effects on bone metabolic diseases such as osteoporosis, rheumatoid arthritis and vascular calcification other than blood pressure lowering effect.
22900713 Interleukin-18 in pulmonary inflammatory diseases. 2012 Oct The proinflammatory cytokine interleukin (IL)-18 was originally discovered as an interferon-γ-inducing factor in 1995. IL-18 is known to play an important role in Th1/Tc1 polarization and promoting the production of Th2 cytokines (e.g., IL-4, IL-5, IL-9, and IL-13) by T cells, NK cells, basophils, and mast cells. IL-18 can act as a cofactor for Th2 cell development and IgE production, and also plays an important role in the differentiation of Th17 cells. IL-18 is a key player in the pathogenesis of inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, adult-onset Still's disease, Sjögren's syndrome, and inflammatory bowel diseases. Furthermore, many lines of evidence suggest that IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases, including bronchial asthma and chronic obstructive pulmonary disease. Here, we review the pathological roles of IL-18 in pulmonary inflammatory diseases.
22711395 Spectrum of paranasal sinus mycoses in coastal India. 2012 Jun Fungal infections of the nose and paranasal sinuses are uncommon, and the disease they cause can be identified from their histopathologic appearance. The aim of this study was to assess the incidence of fungal infection and histopathologic changes in specimens sent for evaluation of chronic sinusitis and correlate with culture findings wherever possible. The records of 200 consecutive cases coded as paranasal sinuses over a period of 3 years were retrieved from the Department of Pathology, Kasturba Medical College, Mangalore, India. Twenty nine out of a total of 200 specimens (14.5%) were positive for fungal elements on histopathologic examination. The most common etiologic agents in our study were Aspergillus spp (37.9%); only 1 culture (3.4%) was positive for a Candida species. Eight of 29 patients with fungal sinusitis (27.6%) had diabetes, and 1 patient was being treated for rheumatoid arthritis. Eight of the 29 patients had allergic fungal sinusitis, 8 had chronic granulomatous sinusitis, and 1 had acute fulminant invasive sinusitis. Fungi have been increasingly recognized as an important pathogen in chronic sinusitis. It is imperative for patient management not only that paranasal sinus mycoses be diagnosed but also that the specific histologic category be identified.
22399412 Neurologic manifestations of systemic immunopathological diseases. 2012 Jun Systemic immunopathological diseases with prominent neurological features include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's Syndrome (SS), and the systemic vasculitides. These systemic conditions can affect the nervous system in diverse ways. In many cases, the neurological disease heralds the onset of the systemic condition. Recognizing the pattern of neurological and systemic features of these conditions is critical in order to uncover the systemic condition in a timely manner. Although treatment of these conditions is usually directed at the underlying systemic disease, discovery of certain types of neurological involvement such as rapidly progressive mononeuritis multiplex may often necessitate more robust immunosuppressive therapy. The larger treatment trials addressing optimal therapy in these conditions are coordinated by rheumatologists and rarely address the neurological complications in isolation. As such, the evidence supporting neurology-specific therapy regimens is generally an extrapolation of findings that apply to the systemic condition as a whole and cannot be considered as Class I. Less severe neurological manifestations are often treated with glucocorticoids and immunosuppressive treatments such as azathioprine as a steroid-sparing strategy. More severe neurological involvement requires early and aggressive therapy with powerful immunosuppressive agents, often in combination with glucocorticoids and plasma exchange. Cyclophosphamide is the most established immunosuppressive therapy in this context but is limited by its toxicity. Rituximab is emerging as a highly promising alternative although its high cost is a major limitation.
22248048 Large molecular size EDTA-resistant complexes containing S100A12, ERAC, in serum during in 2012 Apr The pro-inflammatory, leukocyte-derived S100A12 protein occurs as calcium-dependent oligomers in serum, while EDTA plasma from the majority of healthy individuals contains only monomers. Addition of 5 mM EDTA to serum leads to a rapid dissociation of the oligomers in most samples. However, using gel permeation chromatography, we have found that sera from some patients and seemingly healthy individuals contain molecular complexes in the 400-1000 kDa range reacting with anti-S100A12 even in the presence of EDTA; for these we introduce the name ERAC (EDTA Resistant S100A12 Complexes). Based upon monoclonal antibodies and the lateral flow principle, we have developed a quantitative rapid ERAC test giving results within 10 minutes. The highest prevalence of ERAC positivity was found in sera from patients with concomitant rheumatoid arthritis and coronary heart disease. The structure of ERAC is not yet known. Further studies are needed to analyse the mechanism behind the appearance of ERAC and the possible association with inflammatory-related diseases.
22132847 Primary orbital extraskeletal osteosarcoma. 2011 Dec The authors describe a case of orbital extraskeletal osteosarcoma. A 78-year-old man with a history of rheumatoid arthritis on long-term corticosteroids had a left medial canthal basal cell carcinoma excision followed by adjuvant radiotherapy. Twelve months later, he re-presented with a large rapidly-growing calcified mass involving his left medial canthus and orbit. An incisional biopsy demonstrated an infiltrate of atypical cells exhibiting mitotic activity with a rosette arrangement around partially calcified necrotic tissue. The patient underwent orbital exenteration and a partial maxillectomy. Histopathology demonstrated an extraskeletal osteosarcoma. It is extremely rare for this tumor to occur in the orbit. Immunosuppression and adjuvant radiotherapy were possible predisposing factors in the development of this tumor. Extraskeletal osteosarcoma (ESOS) is a malignant tumour that produces osteoid. It develops in soft tissue without continuity to bone or periosteum. It is rare and comprises fewer than 5% of all osteosarcomas. Extraskeletal osteosarcoma primarily affects patients above 50 years of age and has a poor prognosis. In this report, we describe the clinical, radiologic, and pathologic records of a rare case of primary ESOS of the orbit.
22002688 Multiple stress fractures of the lower extremity in healthy young men. 2012 Jun Stress fractures result from abnormal stresses imposed on normal bones by the continued and repeated actions of muscles or from normal stresses imposed on abnormal bones. The risk factors that can cause such stress fractures include excessive use, such as, in soldiers or athletes, nutritional deficiencies, and endocrine disorders. In addition, disease may arise from long-standing rheumatoid arthritis, osteoporosis, corticosteroid therapy, joint stiffness or contracture, or the correction of angular deformity. In these cases, stress fractures may occur in one area or multiple areas. However, no case of multiple stress fractures in a young man who was not a professional athlete and who had no stress fracture risk factor, such as, an endocrine disease, has been previously reported.
21953620 Detection of a minor amorphous phase in crystalline etoricoxib by dynamic mechanical analy 2012 Feb Detection and quantification of the amorphous phase of etoricoxib bulk drug substances, a selective cycloogenase-2 inhibitor used for the treatment of osteoarthritis, rheumatoid arthritis, and dental pain, was carried out using modulated differential scanning calorimetry (MDSC), dynamic mechanical analysis (DMA), and Raman spectroscopy. Detection of amorphous content in pharmaceutical powders by DMA is a special application of dynamic mechanical spectroscopy. DMA was found to be a sensitive technique, able to detect the presence of an amorphous phase in a crystalline phase at concentrations as low as 0.5%. The limit of detection (LOD) determined for DMA was 2.5%. In comparison, Raman spectroscopy and MDSC had LOD values of 2% and 5% amorphous, respectively.
21952480 Basic science for the clinician 53: mast cells. 2011 Oct Mast cells stand at the interface between the innate immune system and the acquired (adaptive) immune response, serving as sentinels detecting invaders and directing a concerted and coordinated response. Mast cells reside immediately under body surfaces and within lymph nodes, near blood vessels and nerves, perfectly situated to for early detection and defense. They secrete a wide array of prostanoids, cytokines, chemokines, and other proteins mediators and modifiers of a variety of immune and inflammatory functions and bear surface markers suggesting broad functions, including as antigen-presenting cells. Although usually not given their due in medical school lectures, there is great likelihood that mast cells will be implicated in the pathogenesis of rheumatoid arthritis, scleroderma, multiple sclerosis, and perhaps cancer. Thus, better insights into mast cell functions and mast cell-derived effector molecules should command our attention as we move forward in better understanding disease immunopathogenesis and directed intelligent therapeutics development.
19911311 Prolactin and autoimmunity. 2011 Feb The relationship between prolactin and the immune system has been demonstrated in the last two decades, opening new windows in the field of the immunoendocrinology. Prolactin has an important role in the innate and adaptive immune response. Increased prolactin levels have been described in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, and systemic sclerosis among others. Hyperprolactinemia is associated with active disease and organ involvement in systemic lupus erythematosus. Therefore, prolactin is an integral member of the immunoneuroendocrinology network and seems to have a role in pathogenesis of autoimmune diseases. Few controlled studies of dopamine agonist treatment in humans with autoimmune disease have been conducted only in systemic lupus erythematosus patients, which support the potential efficacy of such agents even during pregnancy and postpartum. Further studies are necessary to elucidate the mechanisms by which prolactin affects autoimmune disease activity, increase the inflammatory mechanism, and determine the role of anti-prolactinemic drugs to regulate the immune/inflammatory process.
23200063 Does the gut microbiota trigger Hashimoto's thyroiditis? 2012 Nov Hashimoto's thyroiditis is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as the trigger of the disease. A growing body of evidence suggests involvement of viral infection in the development of Hashimoto's thyroiditis. However, not only pathogenic microorganisms but also non-pathogenic commensal microorganisms induce proinflammatory or regulatory immune responses within the host. In accordance, series of studies indicate a critical role of intestinal commensal microbiota in the development of autoimmune diseases including inflammatory bowel diseases, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. In contrast, the role of the gut and indigenous microorganisms in Hashimoto's thyroiditis has received little attention. Whereas activation of innate pattern recognition receptors such as Toll-like receptors and disturbed intestinal epithelial barrier may contribute to thyroiditis development, only a few studies have addressed a link between the gut and Hashimoto's thyroiditis and provided just indirect and weak evidence for such a link. Despite this unsatisfactory situation, we here focus on the possible interaction between the gut and thyroid autoimmunity. Further studies are clearly needed to test the hypothesis that the gut commensal microflora represents an important environmental factor triggering Hashimoto's thyroiditis.
23028410 Signal transduction pathways in chronic inflammatory autoimmune disease: small GTPases. 2012 Ras superfamily small GTPases represent a wide and diverse class of intracellular signaling proteins that are highly conserved during evolution. These enzymes serve as key checkpoints in coupling antigen receptor, growth factor, cytokine and chemokine stimulation to cellular responses. Once activated, via their ability to regulate multiple downstream signaling pathways, small GTPases amplify and diversify signaling cascades which regulate cellular proliferation, survival, cytokine expression, trafficking and retention. Small GTPases, particularly members of the Ras, Rap, and Rho family, critically coordinate the function and interplay of immune and stromal cells during inflammatory respones, and increasing evidence indicates that alterations in small GTPase signaling contribute to the pathological behavior of these cell populations in human chronic inflammatory diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Here, we review how Ras, Rap, and Rho family GTPases contribute to the biology of cell populations relevant to human chronic inflammatory disease, highlight recent advances in understanding how alterations in these pathways contribute to pathology in RA and SLE, and discuss new therapeutic strategies that may allow specific targeting of small GTPases in the clinic.
22778467 Spontaneous haemorrhagic perforation of gallbladder in acute cholecystitis as a complicati 2012 Jul 9 An older lady presented 1 week after being discharged from hospital with acute cholecystitis. She suffered a sudden onset lower abdominal pain and was in hypovolaemic shock upon arrival. It was noted that she had been on antiplatelet therapy after suffering a recent myocardial infarction, an immunosuppressor and steroids for rheumatoid arthritis. Her admission bloods revealed a platelet count of 83 with normal clotting factors. After resuscitation, a CT scan confirmed fluid in the abdomen possibly arising from the right subhepatic space. During laparotomy, bleeding was noted from a perforated and ischaemic-looking gallbladder, with an intact cystic artery and duct and no biliary calculi evident. The gallbladder was removed and the patient was transferred to intensive therapy unit. She recovered well within the subsequent 8 days and was discharged. Her histology described 'haemorrhage within the gallbladder wall along with oedema, fibrosis and patchy inflammation and no signs of malignancy or gangrene'.
22640807 Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic 2012 Jul Th17 cells that secrete the cytokines IL-17A and IL-17F and express lineage-specific transcription factor RORC (RORγt in mice) represent a distinct lineage of CD4(+) T cells. Transforming growth factor-β and inflammatory cytokines, such as IL-6, IL-21, IL-1β, and IL-23, play central roles in the generation of Th17 cells. Th17 cells are critical for the clearance of extracellular pathogens, including Candida and Klebsiella. However, under certain conditions, these cells and their effector molecules, such as IL-17, IL-21, IL-22, GM-CSF, and CCL20, are associated with the pathogenesis of several autoimmune and inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, inflammatory bowel disease, and allergy and asthma. This review discusses these disease states and the various therapeutic strategies under investigation to target Th17 cells, which include blocking the differentiation and amplification of Th17 cells, inhibiting or neutralizing the cytokines of Th17 cells, and suppressing the transcription factors specific for Th17 cells.
22490998 Risk factors in lateral epicondylitis (tennis elbow): a case-control study. 2013 Feb Lateral epicondylitis is a common condition, but relatively little is known about its aetiology and associated risk factors. We have undertaken a large case-control study using The Health Improvement Network database to assess and quantify the relative contributions of some constitutional and environmental risk factors for lateral epicondylitis in the community. Our dataset included 4998 patients with lateral epicondylitis who were individually matched with a single control by age, sex, and general practice. The median age at diagnosis was 49 (interquartile range 42-56) years . Multivariate analysis showed that the risk factors associated with lateral epicondylitis were rotator cuff pathology (OR 4.95), De Quervain's disease (OR 2.48), carpal tunnel syndrome (OR 1.50), oral corticosteroid therapy (OR 1.68), and previous smoking history (OR 1.20). Diabetes mellitus, current smoking, trigger finger, rheumatoid arthritis, alcohol intake, and obesity were not found to be associated with lateral epicondylitis.
22460124 Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond. 2012 Mar 30 The direct or indirect targeting of antibody Fc receptors (FcRs) presents unique opportunities and interesting challenges for the treatment of inflammatory diseases, cancer and infection. Biological responses induced via the Fc portions of antibodies are powerful, complex and unusual, and comprise both activating and inhibitory effects. These properties can be exploited in the engineering of therapeutic monoclonal antibodies to improve their activity in vivo. FcRs have also emerged as key participants in the pathogenesis of several important autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Therapeutic approaches based on antagonizing FcR function with small molecules or biological drugs such as monoclonal antibodies and recombinant soluble FcR ectodomains have gained momentum. This Review addresses various strategies to manipulate FcR function to overcome immune complex-mediated inflammatory diseases, and considers approaches to improve antibody-based anticancer therapies.
22293759 Fracture healing under healthy and inflammatory conditions. 2012 Jan 31 Optimal fracture treatment requires knowledge of the complex physiological process of bone healing. The course of bone healing is mainly influenced by fracture fixation stability (biomechanics) and the blood supply to the healing site (revascularization after trauma). The repair process proceeds via a characteristic sequence of events, described as the inflammatory, repair and remodeling phases. An inflammatory reaction involving immune cells and molecular factors is activated immediately in response to tissue damage and is thought to initiate the repair cascade. Immune cells also have a major role in the repair phase, exhibiting important crosstalk with bone cells. After bony bridging of the fragments, a slow remodeling process eventually leads to the reconstitution of the original bone structure. Systemic inflammation, as observed in patients with rheumatoid arthritis, diabetes mellitus, multiple trauma or sepsis, can increase fracture healing time and the rate of complications, including non-unions. In addition, evidence suggests that insufficient biomechanical conditions within the fracture zone can influence early local inflammation and impair bone healing. In this Review, we discuss the main factors that influence fracture healing, with particular emphasis on the role of inflammation.