tbuckley/cabot-search huggingface dataset:
P253 Association of Defective Monocyte-Derived Macrophage Phagocytosis with Clinical Phenotypes in Stable COPD
Authors: R Singh, KK Chana, LL Wright, DS Garcha, BS Kowlessar, ARC Patel, AJ Mackay, PS Fenwick, GC Donaldson, PJ Barnes, JA Wedzicha, LE Donnelly
Journal: Thorax (2012)

<h3>Introduction</h3> Macrophages play an important role in clearing inhaled particles and bacteria from the lung, thus maintaining its sterility. Defective phagocytosis of bacteria has been demonstrated in both alveolar and monocyte-derived macrophages (MDMs) from COPD patients and may play a role in the aetiology of the frequent exacerbator phenotype. We hypothesised that defective phagocytosis may also be associated with lower airway bacterial colonisation (LABC) and other clinical parameters in stable COPD. <h3>Methods</h3> Whole blood and sputa were collected from stable patients in the London COPD cohort. Stable COPD was defined as no symptom-defined exacerbations recorded on prospectively completed diary cards in the preceding four weeks and subsequent two weeks. Monocytes were isolated from the whole blood and cultured with GM-CSF (2 ng/ml) for 12 days to generate MDMs. MDM phagocytosis of fluorescently-labelled polystyrene beads, <i>Haemophilus influenzae</i> (HI) and <i>Streptococcus</i><i>pneumoniae</i> (SP) was measured by fluorimetry. LABC was defined as detection of HI, SP or <i>Moraxella catarrhalis</i> (MC) in sputum using quantitative PCR. <h3>Results</h3> MDMs were cultured from 26 COPD patients. 54% were male, mean age 70.0 years (SD 8.3), FEV1 predicted 55.3% (20.3), 46% were current smokers, median daily inhaled corticosteroid (ICS) dose was 1000 (640–2000) mcg (beclomethasone equivalent dose) and median exacerbation frequency per year was 1.8 (1.0–2.9) based on diary card events. Phagocytosis of HI was significantly less with increasing exacerbation frequency (p=0.002, r=–0.58, Figure 1), although no significant associations were demonstrated between exacerbation frequency and phagocytosis of inert beads or SP (p=0.27 and p=0.22 respectively). 13 patients (50%) with LABC did not demonstrate any significant difference in phagocytosis of either beads (p=0.29), HI (p=0.66) or SP (p=0.88) compared with non-colonised patients. There was no significant association between phagocytosis of beads, HI or SP with age, FEV<sub>1</sub>%predicted, smoking pack year history, ICS dose or BMI (all p&gt;0.05). <h3>Conclusion</h3> In stable COPD patients, decreasing phagocytosis of HI was associated with increasing exacerbation frequency. Phagocytosis was not related to LABC suggesting that macrophage activity alone may not determine bacteria colonisation. Further work is needed to elucidate the mechanisms of reduced phagocytosis in COPD and its relationship to exacerbation frequency.
PMO-006 Out of hours gastrointestinal bleed service in the UK: inter-hospital transfer of patients for endoscopy is safe
Authors: B N Shokouhi, M Khan, S Greenfield
Journal: Gut (2012)

<h3>Introduction</h3> Acute Upper Gastrointestinal Bleeding (AUGIB) results in 25 000 in-patient admissions annually in the UK (1). Patients admitted at weekends with AUGIB have significantly increased mortality (2). Current guidelines advise availability of out-of-hours (OOH) endoscopy (3). We present data from our service in the UK involving inter-hospital transfer of patients. <h3>Methods</h3> We pooled resources of two neighbouring general hospitals, just North of London: Emergency endoscopy is performed at start of the list followed by elective endoscopy in the endoscopy unit on Saturday and Sunday morning. From Friday evening until Sunday morning, patients admitted to Queen Elizabeth II (QEII) Hospital are medically stabilised and transferred to Lister Hospital by ambulance (13 miles apart, fast freeway). <h3>Results</h3> A total of 240 endoscopies were performed OOH from December 2007 to March 2011. Of these, 54 patients were transferred: nine had emergency endoscopy at QEII as they were medically unstable; eight of the patients transferred required therapeutic intervention for active bleeding. The mean pre-endoscopy Rockall score of those transferred was 2.5 (range 0–6). We examined the medical records of 51 (of 54) of the patients transferred. There were three deaths within 30 days of endoscopy, but these were not associated with the transfer process. A total of 19 (37%) of patients had reduced hospitalisation after having their endoscopy at the weekend, as opposed to waiting for endoscopy on Monday. <h3>Conclusion</h3> The introduction of the OOH endoscopy service has had multiple benefits. Patients consistently receive timely emergency endoscopy. Patients may be discharged earlier once they have had the endoscopy. There is significantly reduced disruption to emergency operating theatres. Participation of endoscopy nurses ensures a better and safer experience for the patients, and better endoscopy decontamination. Routine elective weekend endoscopy has reduced waiting lists and generated revenue for the hospitals, justifying the cost of setting up the service. We suggest that our model is safe and it is feasible for other small units wishing to set up their own OOH endoscopy service to adopt. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Palmer KR.</b> Haematemesis and melaena. <i>Postgrad Med J</i> 2003;<b>31</b>:19–24. 2. <b>Shaheen AA</b>, <i>et al.</i> Weekend versus weekday admission and mortality from gastrointestinal hemorrhage caused by peptic ulcer disease. <i>Clin Gastroenterol Hepatol</i> 2009;<b>7</b>:303–10. 3. <b>British Society of Gastroenterology Endoscopy Committee</b>. Non-variceal upper gastrointestinal haemorrhage: guidelines. <i>Gut</i> 2002;<b>51</b>(Suppl IV):iv1e6.
Treatment of hepatic abscess by EUS-guided fine needle aspiration and lavage: case report
Authors: Shi Wei, Tang Yu, Qiangyuan De, Li Yu, Binsun Xiao, Wang Qiong, Zhao Cong
Journal: Endoscopy (2011)

A 37-year-old woman presented with persistent right upper abdominal pain radiating to back, nausea, vomiting, chill and fever (39°C) of 7 days' duration. Other symptoms included anorexia, fatigue and mild weight loss. Physical examination revealed mid and right upper abdominal tenderness, rebound pain without muscle defense or any mass palpated, and percussion pain over hepatic region. Laboratory tests included the following: white blood cell count, 15.58×109/L (normal: 4.0-10.0×109/L); neutrocyte percentage, 77.5% (normal: 50%-70%); AFP, 1.54ng/ml (<20ng/ml). Biochemical tests of liver function were within normal ranges. Transabdominal B ultrasound indicated a 5.7×4.0-cm hypoechoic mass in hepatic caudate lobe while CT demonstrated a 5.0×5.5-cm, oval, low density mass with somewhat densified boarder in the hepatic caudate lobe. Enhanced scanning during arterial and portal stage exhibited circumferetial enhancement of the boarder of the low density lesion with surrounding edema. Thus hepatic abscess was considered. EUS image showed in caudate lobe of liver a 4.6×3.5cm hypoechoic mass with distinct 0.5cm even-thickness cyst wall and cyst cavity filled with evenly densified spots. The mass isn't adherent to gastric wall and was diagnosed as caudate lobe hepatic abscess. 1.0g of Prepenemtm (Imipenem and Cilastatin; Choogwae Pharma Corporation) had been intravenously administrated three times a day 1 week before aspiration and lavage.
A8.17 The Role of CXCR2 Signalling in Articular Cartilage Homeostasis
Authors: J Sherwood, J Bertrand, G Nalesso, P Achan, C Pitzalis, T Pap, F Dell’Accio
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> The production of ELR+ CXC chemokines is widely studied in arthritis and is thought to contribute to the inflammatory phenomena that lead to cartilage breakdown. Healthy articular chondrocytes however, also express their own chemokine receptors and ligands, however their function in these cells is puzzling because chondrocytes are encased in a dense extracellular matrix and are not known to migrate in vivo. This study aims to identify the function of this signalling mechanism in articular cartilage. <h3>Materials and Methods</h3> Adult human articular chondrocytes were expanded in monolayer culture under standard conditions. CXCR1 and CXCR2 expression was confirmed using semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Chemokine receptors and ligands were detected in human articular cartilage from healthy and osteoarthritis patients and in mouse articular cartilage using immunohistochemistry. CXCR1/2 signalling was blocked at specific receptor level in human chondrocytes using validated blocking antibodies and siRNA. Chondrocyte phenotypic gene expression was assessed using real time RT-PCR. The content of highly sulphated proteoglycans in chondrocyte micromasses was analysed using Alcian blue staining, guanidine HCl extraction and spectrophotometric quantification. Surgical destabilisation of the medial meniscus (DMM) was used to induce instability into the left knees of 8 week old CXCR2<sup>-/-</sup> mice and wild type BALB/C controls (N = 10 per group). Right knees were sham operated as control. 8 weeks following surgery, mice were culled, knee joints were paraffin embedded and sectioned. Representative sections were stained using Safranin orange and osteoarthritis severity was assessed by Chambers scoring. <h3>Results</h3> ELR+ CXC chemokines and their receptors, CXCR1 and CXCR2 were expressed in normal human articular cartilage. CXCR1 and CXCR2 were expressed in articular cartilage from osteoarthritis patients, however their ligands, CXCL8 and CXCL6, were lost from the territorial matrix of chondrocytes. Blockade of CXCR1/2 signalling at receptor level in chondrocytes resulted in a significantly reduced extracellular matrix sulphated glycosaminoglycan content of micromass cultured chondrocytes and a significantly reduced expression of the chondrocyte differentiation markers COL2A1, Aggrecan and SOX9. CXCR2 and CXCL5 were expressed in unchallenged wild type mouse articular cartilage. CXCR2<sup>-/-</sup> mice subjected to the DMM model and analysed 8 weeks following surgery developed a significantly more severe osteoarthritis phenotype than wild type controls. <h3>Conclusions</h3> Our findings indicate that CXCR1/2 signalling is required for the maintenance of phenotypic stability of articular chondrocytes. We show that mouse CXCR2 signalling is required for articular cartilage homeostasis and is chondroprotective during conditions of challenge in vivo.
AB0823-HPR Developing nurse autonomy in a rheumatology nurse led clinic
Authors: N. Harrington, G. Byrne, H. Reynolds, M. McGovern, C. Silke, B. Whelan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In routine rheumatology clinics, return visits can account for 75% of a rheumatologists case load reducing the time available for new patients or patients who require urgent care (1) In a systematic review of the literature rheumatology nurse led clinics proved to be an invaluable addition to the effective running of rheumatology clinics (2). <h3>Objectives</h3> 1)To Identify the feasibility of an independent nurse led rheumatology clinic, and 2) Assess nurse autonomy and barriers to same in the clinic setting. <h3>Methods</h3> Over a 4 week period in October 2011, return patients with inflammatory arthritis on DMARD’s were allocated to the clinical nurse specialist (CNS) led clinic. Following the clinics patient review data was analysed to establish the number of patients that were managed autonomously by the CNSs and the barriers identified to same. <h3>Results</h3> From a total of 118 patients, 22 patient’s (19%) were managed autonomously by the CNSs, 43 patients (37%) were managed by CNSs with medical sign off for renewal of prescriptions, x-ray and dexa scan requests, or referral to Occupational Therapy and Physiotherapy. Fifty three patient’s (45%) required medical consultation for intra-articular joint injections, medication review or general medical queries. <h3>Conclusions</h3> There is the potential to expand the nurses scope of practice in the rheumatology clinic to include medication prescribing, x-ray, occupational therapy and physioth erapy prescribing along with the administration of intra-articular joint injections where appropriate. This could greatly alleviate the time pressures on rheumatologists in the clinic. A review of present local and national policies in consultation with local stakeholders is recommended <h3>References</h3> Kirwan JR, Snow SM, et al (1991)Which patients see a rheumatologist? British Journal Rheumatology. 30 pp 285-287. Van Eijk-Hustings, Y et al (2012)Eular recommendations for the role of the nurse in the management of chronic inflammatory arthritis. Ann Rheum Disease; 71pp 13-19 <h3>Disclosure of Interest</h3> None Declared
AB0323 Vitamin D receptor gene polymorphisms in rheumatoid arthritis
Authors: C.C. Bacanlı, N.S. Çeşmeli, N. Ç. Ekinci, O. Yeğin, T. Tuncer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The etiology of rheumatoid arthritis (R.A.), an autoimmune, polygenic, inflammatory disease, has not yet been clarified despite the intense research<sup>1</sup>. In addition to its more commonly known metabolic effects such as those associated with calcium homeostasis, vitamin D has, in general, suppressive effects on the immune system, especially on T helper cell function. T cells are critical in the development of autoimmune reactions and autoimmune diseases. Low vitamin D levels have been associated with the risk of development of R.A., an autoimmune disease<sup>2</sup>. Vitamin D functions are mainly accomplished through vitamin D receptor (VDR). Several VDR gene polymorphisms have been described, and they may affect the function of vitamin D<sup>3</sup>. <h3>Objectives</h3> The aim of this study is to detect whether the frequence of 4 VDR gene polymorphisms (ApaI, BsmI, FokI ve TaqI) differ in R.A. patients with respect to healthy controls. Whether these polymorphisms cause a difference in several clinical activation parameters (ESR, CRP, RF, DAS28 and Sharp score) of the patients was also determined. <h3>Methods</h3> Study groups consisted of a R.A. group of 100 patients and 100 healthy controls. ApaI, BsmI, FokI and TaqI gene polymorphisms were studied by using polymerase chain reaction. <h3>Results</h3> Statistically significant difference was only detected in only one of the 4 VDR gene polymorphisms, the BsmI gene, in the study. BB genotype of BsmI gene was more common in the R.A. group with respect to controls (p&lt;0.05, odds ratio: 3.6, confidence interval: 1,4-9,7, chi2:1,03). There was no significant difference in the other 3 VDR genes. Within the clinical features studied, only CRP showed statistically significant difference in patients with any VDR gene polymorphism. High CRP was determined to be significantly more common in the R.A. patients with TaqI polymorphism with respect to the other patients (p=0.025). <h3>Conclusions</h3> In this study, no significant correlation was found between VDR gene polymorphisms and RA activity. Statistically significant difference was only detected in only one of the 4 VDR gene polymorphisms, the BsmI gene. BB genotype of BsmI gene was more common in the R.A. group. BsmI polymorphism may be a preventing feature of R.A development. <h3>References</h3> Seldin MF, Amos CI, Ward R, Gregersen PK. The genetics revolution and the assault on rheumatoid arthritis. Arthritis Rheum. Jun 1999;42(6):1071-1079. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood). Dec 2004;229(11):1136-1142. Guo SW, Magnuson VL, Schiller JJ, Wang X, Wu Y, Ghosh S. Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE review of genetic association studies. Am J Epidemiol. Oct 15 2006;164(8):711-724. <h3>Disclosure of Interest</h3> None Declared
How to Use a Randomized Clinical Trial Addressing a Surgical Procedure
Authors: Nathan Evaniew, Alonso Carrasco-Labra, P. J. Devereaux, Kari A. O. Tikkinen, Yutong Fei, Mohit Bhandari, Gordon Guyatt
Journal: JAMA Surgery (2016)

Because surgical procedures require clinicians to develop and maintain procedural expertise and because blinding in randomized clinical trials of such therapies is often challenging, their critical appraisal raises unique issues. Risk of bias of trials of surgical procedures increases if investigators fail to rigorously conceal allocation and, where possible, to ensure blinding of those involved in the trial. Variability in surgeons' expertise can also increase bias and lead to important limitations in applicability. To address these issues, this Users' Guide to the Medical Literature reviews the use of remote randomization systems, blinding, sham-controlled trials, split-body trials, expertise-based trials, and mechanistic vs practical trials. Consideration of risk of bias and applicability issues will allow clinicians to make optimal use of trials addressing surgical procedures.
P5-05-06: Dysregulation in the Transport of Iron and Haem Is Implicated in the Aetiopathogenesis of Breast Cancer.
Authors: T Roe, F Hoar, C Tselepis
Journal: Cancer Research (2011)

Abstract Backround: Mounting evidence implicates iron in the development of a number of cancers, including breast. The responsible mechanism is poorly understood in breast cancer, although recent work has demonstrated irregular expression of various molecular iron transporters. Materials and Methods: Immunohistochemistry on archived material was used to evaluate differences in expression of iron and haem exporters, importers and storage proteins between breast cancer, DCIS and normal breast tissue. The results were corroborated by Western blotting and RT-qPCR on protein and RNA samples generated from matched normal and cancer specimens collected at mastectomy. The ability of benign and malignant breast cells in vitro to accumulate excess iron in the presence of exogenous iron/haem was evaluated with a ferrozine assay. In addition the effect of exogenous iron and haem on cell phenotype in vitro was assessed in benign and malignant cell lines. Assays utilised included viability (MTT), proliferation (BrdU), migration, anchorage-independent growth (colony formation) and invasive capacity. These assays were then repeated in the presence of iron chelators to investigate their potential utility as a therapeutic modality. Results: Statistically significant increases (p&amp;lt;0.05) were observed in expression of the iron importers DCytB, DMT1 and TfR in breast cancer relative to normal tissue. Levels of the storage protein ferritin were also significantly raised. The iron exporters ferroportin and hephaestin were significantly under-expressed in breast cancer, while hepcidin (which induces exporter degradation) was over-expressed. Levels of the haem importer HCP1 and the exporters BCRP and FLVCR were all significantly down-regulated in cancer relative to normal. Both benign and malignant breast cells were capable of importing excess iron, although only malignant cells could import excess haem. Iron induced increased viability and proliferation in benign cells but had no effect on their migratory or invasive capability, or their ability to form colonies. Haem had no effect on benign cell phenotype. Iron and haem both had significantly positive effects on all these aspects of cell phenotype when introduced to malignant breast cells in vitro. Iron chelators were capable of abrogating these positive effects. Discussion: Archived material and prospectively collected matched tissue pairs demonstrate that breast cancers exhibit altered expression of the proteins involved in transporting iron and haem through the cell. In vitro experiments reveal malignant cells to be capable of taking up both substances, which both appear to drive a more malignant phenotype. These in vitro changes can be reversed through the introduction of iron chelators, implying possible efficacy as a novel therapy in breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-05-06.
FÍSTULAS DE ACCESO TERAPÉUTICO (FAT) EN PATOLOGÍA BILIAR COMPLEJA CON PRÓTESIS METÁLICAS CUBIERTAS (PMC) TRANSMURALES TEMPORALES: CONCEPTO, INDICACIONES Y RESULTADOS
Authors: S Lorenzo-Pelayo, N Alcaide Suárez, C De la Serna-Higuera, L Sancho del Val, R Ruiz-Zorrilla, MT Herranz Bachiller, MP Díez Redondo, P Gil-Simón, A Caro-Patón, M Pérez-Miranda
Journal: Endoscopy (2011)

Introducción: Las PMC intraductales pueden retirarse. La USE proporciona acceso biliar transluminal (TL). La CPRE percutánea (PC) requiere apoyo quirúrgico.
AB0315 Effect of prednisone on quality of life domains in early rheumatoid arthritis - additional analyses of the camera-ii-trial -
Authors: M. Jurgens, P.M. Welsing, M.J. Geenen, M.F. Bakker, F.P. Lafeber, J.W. Bijlsma, J.W. Jacobs
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the Computer Assisted Management in Early RA trial-II (CAMERA II), addition of 10 mg prednisone (versus placebo) to an MTX-based tight control treatment strategy resulted in lower disease activity and disability, a higher proportion of patients achieving sustained remission and less joint damage.[1]However, glucocorticoids might also influence different domains of quality of life like psychological functioning. <h3>Objectives</h3> To investigate the effects of the added prednisone on different domains of quality of life over 2 years. <h3>Methods</h3> Data from the CAMERA II study was used. The questionnaire Impact of Rheumatic diseases on General Health and Lifestyle (IRGL, based on the AIMS) was used to measure quality of life (Qol) domains, including physical functioning (Mobility, Self-Care and Pain) psychological functioning (depressed mood, cheerful mood and anxiety) and social functioning (Nr. of Neighbours, Nr. of Friends, Perceived Support, Actual Support and Mutual Visit), plus 1 scale assessing the influence of the disease on daily life. Changes from baseline and either 1 or 2 years were compared between the treatment arms. Linear regression analyses were performed, correcting for demographic and prognostic variables (age, gender, baseline values), and, to study the influence of treatment independent from the effect on disease activity, for changes in disease activity. <h3>Results</h3> Changes in disease activity were clearly related to almost all domains of physical and psychological functioning and influence on daily life, showing that a lower disease activity related to an improvement in QoL. Without corrections, changes in "Self Care" over 2 years were in favour of the strategy with prednisone, butchanges in "Perceived Support" over 1 year were in favour of the strategy without prednisone. After correcting for baseline values and changes in disease activity, improvements in "Self Care" over 2 years and "Influence on Relationships" over 1 year were significantly higher in the strategy with prednisone, p=0.027 and p=0.036, respectively. <h3>Conclusions</h3> Disease activity was correlated with most domains of quality of life. Corrected for disease activity changes, prednisone exerted minor and not consistent effects on different domains of quality of life. <h3>References</h3> Bakker MF, Jacobs JWG, et al. Low-Dose Prednisone Inclusion in a Methotrexate-Based, Tight Control Strategy for Early Rheumatoid Arthritis. A Randomized Trial. Ann Intern Med 2012; 156: 329-39 <h3>Disclosure of Interest</h3> None Declared