tbuckley/cabot-search huggingface dataset:
PWE-068 Diagnostic Yield of Serious Disease and Variation in Elective Gastroscopy Rates in English General Practice: Analysis Of Administrative Data
Authors: M Shawihdi, E Thompson, N Kapoor, G Powell, M Roughton, R Sturgess, N Stern, M Pearson, K Bodger
Journal: Gut (2013)

<h3>Introduction</h3> The optimum role for gastroscopy (OGD) in managing dyspepsia and detecting oesophagogastric cancer (OG-Ca) is controversial. UK general practitioners (GPs) serve a gatekeeper role in selecting dyspeptic patients for OGD. We reported that variation in rates of OGD at the level of GP practise populations is associated with OG-Ca outcome, specifically that low rates are related to risk of poor outcome.[1] We wished to show that GP practises with low OGD rates are likely to be operating more selective referral practise with higher yield of serious pathology. <h3>Methods</h3> GP practises with ≥1 incident case of OG-Ca were selected, as described.[1.2] Using a two-year download of HES data we identified all elective OGD procedures and obtained practise data to calculate age-sex adjusted OGD rates. Practices were divided into OGD rate tertiles (Low, Medium or High). An algorithm was developed to analyse coded diagnoses for first OGDs, identifying most “serious” condition: (1) OG-Ca, (2) Major acid-peptic diseases, (3) Minor findings (e.g. gastritis), (4) Benign GI neoplasms, (5) Upper GI symptom codes, (6) Miscellaneous (all others). We compared age and proportions with serious disease (categories: 1–2) across the GP practise tertiles. <h3>Results</h3> 587,256 patients had elective OGD from 6,513 practises serving an adult population of c.39 million. Overall, yield of OG-Ca was 2.1%, major acid-peptic diseases 11.6% and the remaining 86.3% were mainly minor pathologies or symptom codes. Mean OGD rate for Low, Middle, High practises: 4.4 vs 8.1 vs 12.9 per 1,000 population. No difference in age distribution of populations across tertiles. Mean age of patients undergoing OGD was highest for low tertile practises (60.2 vs 59.5 vs 58.4 yrs; p &lt; 0.001) which had highest yield of serious disease: 16,595/108,679 (15.3%) vs 28,177/203,771 (13.9%) vs 36,026/274,806 (13.1%) (p &lt; 0.001). <h3>Conclusion</h3> Low referring practises appear to target slightly older patients and achieve higher yield of serious disease. Although higher yield may be more consistent with current guidelines, it may also indicate an increased risk of referral at a later stage in the disease process and of poorer OG-Ca outcome.[1] <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Shawihdi, M.,<i> et al. Gastroscopy rate in English general practise populations: association with outcome for oesophagogastric cancer</i>. Gut, 2012. <b>61</b>(Suppl 2):A19. Shawihdi, M., <i>et al. Emergency Hospital Admission as a Route for Oesophagogastric Cancer Diagnosis: A Marker of Poor Outcome and a Candidate Quality Indicator for Local Services</i><i>.</i> Gastroenterology, 2011. <b>140</b>( 5, Supplement 1):S207.
Abstract LB-23: In vivo exposure of infant leukemia to the BH3-mimetic ABT-263 selects for a cell death-resistant phenotype
Authors: Laura M. High, Rachael A. Papa, Scott A. Armstrong, Richard B. Lock
Journal: Cancer Research (2011)

Abstract The development of acquired resistance to chemotherapy in the clinic remains a major obstacle to improve patient outcome and a better understanding of the underlying molecular events is essential to target refractory cancers, including leukemia. Infants with acute lymphoblastic leukemia involving translocations of the mixed-lineage leukemia (MLL) gene have a poorer prognosis than other age groups and this has been attributed to early relapse and resistance to traditional chemotherapies. The purpose of this study was to assess the in vivo sensitivity and mechanisms of resistance of a panel of 8 MLL xenografts established from primary biopsies in immune-deficient (NOD/SCID) mice to the BH3-mimetic and Bcl-2, Bcl-XL and Bcl-W inhibitor ABT-263. Leukaemia engraftment and progression were assessed by flow cytometric enumeration of the proportion of human CD45+ cells in the peripheral blood at weekly intervals. ABT-263 (100 mg/kg daily × 21 per oral gavage) significantly delayed the progression of 8/8 xenografts compared with vehicle-treated controls (p &amp;lt; 0.05), with progression delayed by between 2 and 27 days across the entire panel. However, quantification of Bcl-2 protein family members by immunoblot did not reveal that expression of a single member significantly correlated with in vivo ABT-263 sensitivity. Continuous ABT-263 treatment of xenografts in vivo resulted in the outgrowth of 5 independent ABT-263-resistant xenograft lines. Resistance was confirmed to be approximately 15-fold compared with passage-matched controls by in vitro cytotoxicity assay (n = 6; p &amp;lt; 0.0001). Subsequent inoculation of ABT-263-selected xenograft lines into NOD/SCID mice also confirmed their in vivo resistance compared with passage-matched controls. ABT-263-selected lines showed a 5-fold increase in cell viability compared with passage-matched control lines after 4 days of ex vivo culture (p = 0.02). Moreover, the ABT-263-selected cells were significantly resistant in vitro to 2 established drugs used in the treatment of pediatric acute lymphoblastic leukemia, dexamethasone (p = 0.001) and daunorubicin (p = 0.006). This cell death-resistant phenotype could not be attributed to altered protein expression of known ABT-263 resistance modifiers, including Bcl-2, Mcl-1 and Bim. In conclusion, this study has demonstrated that ABT-263 has significant in vivo efficacy against MLL xenografts derived from direct patient explants, but that ABT-263 resistance can readily arise in vivo leading to a cell death-resistant phenotype via a unique mechanism. (Supported in part by NCI NO1CM42216) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-23. doi:10.1158/1538-7445.AM2011-LB-23
A Comparison of Botulinum Toxin and Saline for the Treatment of Chronic Anal Fissure
Authors: Giorgio Maria, Emanuele Cassetta, Daniele Gui, Giuseppe Brisinda, Anna Rita Bentivoglio, Alberto Albanese
Journal: New England Journal of Medicine (1998)

Chronic anal fissure is a tear in the lower half of the anal canal that is maintained by contraction of the internal anal sphincter. Sphincterotomy, the most widely used treatment, is a surgical procedure that permanently weakens the internal sphincter and may lead to anal deformity and incontinence.
1120 EFFECT OF MATRIX METALLOPROTEINASE-8 DEFICIENCY ON LIVER FIBROSIS PROGRESSION AND REGRESSION
Authors: Y.O. Kim, M. Stoll, S.-Y. Weng, B. Hebich, T. Resa, R. Heck, K.-S. Park, U. Biwer, D. Schuppan
Journal: Journal of Hepatology (2013)
OP0311 Incidence of Severe Knee and Hip Osteoarthritis in Relation to the Metabolic Syndrome and its Components: A Prospective Cohort Study
Authors: S. M. Hussain, Y. Wang, F. Cicuttini, J. A. Simpson, G. Giles, S. Graves, A. Wluka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Increasing evidence suggests associations between osteoarthritis (OA) and the metabolic syndrome (MetS) and its components. <h3>Objectives</h3> The objective of this study was to examine whether components of MetS, either singly or additively, are associated with the incidence of severe knee and hip OA, and whether these associations were independent of obesity assessed by body mass index (BMI). <h3>Methods</h3> 21,837 participants who had fasting blood lipids, anthropometric and blood pressure measurements during 2003-2007 were selected from the Melbourne Collaborative Cohort Study. MetS was defined as central obesity assessed by waist circumference and any two of dyslipidaemia, hypertension or impaired fasting glycaemia (IGT). The incidence of severe OA requiring total knee and hip replacement was determined by linking the records to the Australian Orthopaedic Association National Joint Replacement Registry (AOA NJRR). <h3>Results</h3> 685 participants had knee OA and 580 had hip OA. After adjustment for age, gender, country of birth, education and BMI, central obesity (hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.20-1.91) and hypertension (1.25, 1.05-1.50) were associated with increased risk of knee OA. There was a dose-response relationship between the number of MetS components and knee OA risk, independent of BMI: one component 2.11 (1.11-4.01), two components 2.94 (1.57-5.52), three or more components 3.13 (1.66-5.91), p for trend &lt;0.001. No significant associations were observed for hip OA. <h3>Conclusions</h3> The cumulative number of MetS components and individual components of the MetS, central obesity and hypertension, are associated with increased risk of severe knee OA, independent of obesity. No association is seen for severe hip OA. The findings suggest different pathogenesis of knee and hip OA and that management of MetS may reduce the risk of knee OA. <h3>Disclosure of Interest</h3> None Declared
PTU-121 Compliance with guidelines on viral screening and vaccination of patients with inflammatory bowel disease (IBD): Abstract PTU-121 Table 1
Authors: N Halliday, S Murray, G Parkes, V S Wong
Journal: Gut (2012)

Introduction ECCO recommends screening IBD patients for immunity to or infection with varicella zoster virus (VZV), hepatitis B (HBV) and potentially HIV, hepatitis C virus (HCV) and tuberculosis (TB) to allow monitoring or treatment if patients require immunomodulatory therapy. Patients should be offered vaccination against VZV, HBV, human papilloma virus (HPV), pneumococcus and influenza where appropriate. We audited screening practice and the reported prevalence of prior exposure and vaccination in our IBD population. Methods In 2010, IBD patients in our general gastroenterologyclinics completed a questionnaire regarding prior VZV disease, HBV infection or vaccination, influenza, pneumococcal and HPV vaccination. Results for screening tests were checked. Results Patient characteristics: 91 patients returned questionnaires. 46 were male; median age was 43 years (range 19–71). 61 had a diagnosis of ulcerative colitis, 30 of Crohn's disease. Current drug therapy included none in 13 patients, 5-aminosalicylic acid (5-ASA) drugs in 42, systemic corticosteroids in 6, purine analogues, anti-metabolites or calcineurin inhibitors in 25 and biological agents in 5. Questionnaire responses: see Abstract PTU-121 table 1. Screening: 70 patients were screened for VZV immunity and 10 had complete HBV screening (surface antibody, antigen and anti-core antibody). Levels of screening for HCV, HIV were low (18 and 3 patients respectively). TB screening was more comprehensive; 47 had chest x-rays and 2 had γ interferon release assays. Those on biological agents were more likely to have been screened for TB. Four patients reporting prior VZV disease had no evidence of immunity (out of 48 who were tested). Nine of the 15 reporting HBV vaccination were tested, 5 of whom were negative. The one patient with serology consistent with previous HBV infection had no recollection of such. Conclusion Overall compliance with ECCO guidelines was low and sporadic among our population. Other groups have reported similar low rates. Low levels of patients are taking advantage of existing immunisation programmes. Patient recall of previous vaccination may not be sufficient to imply immunity. A systematic process for assessing patients' vaccination status and active encouragement of vaccination programmes should be undertaken in the outpatient setting. View this table: Abstract PTU-121 Table 1 Questionnaire responses Competing interests None declared.
Improved Foamy Virus Vectors with Minimal Viral Sequences
Authors: Grant Trobridge, Neil Josephson, George Vassilopoulos, Jaclynn Mac, David W. Russell
Journal: Molecular Therapy (2002)

Foamy virus (FV) vectors show promise for gene therapy applications. However, existing FV vectors either retain a significant portion of the wild-type virus genome or are produced at low titers. We describe a transient cotransfection system that produces high-titer FV vectors with minimal cis-acting regions. These vector genomes have deletions in the gag, pol, env, and bel1–3 accessory genes, as well as the LTR U3 region, but retain an essential 2.5-kb cis-acting region. In addition, stop codons were introduced into the remaining gag sequences to prevent expression of viral peptides and to eliminate dominant-negative effects of a Gag-Pol fusion protein. Although these deleted foamy (ΔΦ) vectors were produced at relatively low titers with our prior packaging construct, we designed separate helper plasmids for Gag, Pol, and Env expression that allowed us to routinely produce helper-free, unconcentrated vector stocks with titers of over 105 transducing units/ml by four-plasmid transient transfection. The ΔΦ vector stocks were then concentrated by ultracentrifugation to titers over 107 transducing units/ml. A ΔΦ vector containing a 9.2-kb transgene cassette was produced at unconcentrated titers of over 105 transducing units/ml, demonstrating the utility of these deleted vectors for large therapeutic genes. Foamy virus (FV) vectors show promise for gene therapy applications. However, existing FV vectors either retain a significant portion of the wild-type virus genome or are produced at low titers. We describe a transient cotransfection system that produces high-titer FV vectors with minimal cis-acting regions. These vector genomes have deletions in the gag, pol, env, and bel1–3 accessory genes, as well as the LTR U3 region, but retain an essential 2.5-kb cis-acting region. In addition, stop codons were introduced into the remaining gag sequences to prevent expression of viral peptides and to eliminate dominant-negative effects of a Gag-Pol fusion protein. Although these deleted foamy (ΔΦ) vectors were produced at relatively low titers with our prior packaging construct, we designed separate helper plasmids for Gag, Pol, and Env expression that allowed us to routinely produce helper-free, unconcentrated vector stocks with titers of over 105 transducing units/ml by four-plasmid transient transfection. The ΔΦ vector stocks were then concentrated by ultracentrifugation to titers over 107 transducing units/ml. A ΔΦ vector containing a 9.2-kb transgene cassette was produced at unconcentrated titers of over 105 transducing units/ml, demonstrating the utility of these deleted vectors for large therapeutic genes.
In Vivo Indexes of Platelet and Vascular Function during Fish-Oil Administration in Patients with Atherosclerosis
Authors: Howard R. Knapp, Irene A.G. Reilly, Paola Alessandrini, Garret A. FitzGerald
Journal: New England Journal of Medicine (1986)

Populations that consume a diet rich in marine lipids may have a lower risk of atherosclerotic disease. Fish oil contains the N-3 polyunsaturated fatty acid eicosapentaenoate, and the biosynthesis of thromboxanes and prostacyclins from eicosapentaenoate (thromboxane A3 and prostaglandin I3), rather than from the usual precursor arachidonate (thromboxane A2 and prostaglandin I2), may help to reduce the risk. To examine this hypothesis, we studied the effect of eicosapentaenoate supplementation (10 g per day) for one month on the synthesis of thromboxanes and prostacyclins, as assessed by urinary metabolite excretion, in six patients with peripheral vascular disease and seven normal controls. Supplementation markedly increased the eicosapentaenoate content of phospholipids from red cells and platelets. Synthesis of the platelet agonist thromboxane A2, which was elevated in the patients at base line, declined by 58 percent during supplementation but did not reach normal values. The decline in thromboxane A2, which is synthesized from arachidonate, coincided with the formation of the inactive thromboxane A3, which is synthesized from eicosapentaenoate. A lower dose of eicosapentaenoate (1 g per day) was not sufficient to maintain the changes in thromboxane A2 synthesis. Platelet function was only moderately inhibited during eicosapentaenoate supplementation, consistent with incomplete suppression of thromboxane A2 synthesis. These studies show that a high dose of eicosapentaenoate alters the pattern of synthesis of thromboxanes and prostacyclins. However, effects comparable to those of aspirin require long-term administration in high doses. Whether other properties of fish oil might render it a more attractive antithrombotic therapy remains to be determined.
Cytopathological Findings on Vaginal Papanicolaou Smears after Hysterectomy for Benign Gynecologic Disease
Authors: Katherine F. Pearce, Hope K. Haefner, Syeda F. Sarwar, Thomas E. Nolan
Journal: New England Journal of Medicine (1996)

Periodic, routine Papanicolaou smears of cells from the vagina are commonly examined in women who have undergone a hysterectomy for benign gynecologic disease. The benefits of this method of screening are not known.We analyzed Papanicolaou smears obtained from the vaginal apex (cuff) in 6265 women at Charity Hospital in New Orleans between January 1, 1992, and December 31, 1994. Of the 10,595 vaginal smears, an estimated 9610 were obtained during follow-up examinations of 5682 women who had undergone hysterectomy for benign gynecologic disease.Among these 9610 vaginal smears, 104, from 79 women, were abnormal. The abnormal smears were categorized according to the findings, as follows: atypical squamous cells of undetermined significance, 52 (0.5 percent of all smears); low-grade squamous intraepithelial lesion, 44 (0.5 percent); high-grade squamous intraepithelial lesion, 6 (0.1 percent); and squamous-cell carcinoma, 2 (0.02 percent). In five women, biopsies revealed vaginal intraepithelial neoplasia type I or II; there were no biopsy-proved cases of vaginal cancer. The probability of an abnormal Papanicolaou smear in this group of women was 1.1 percent, and the positive predictive value of the Papanicolaou test for detecting vaginal cancer was 0 percent (95 percent confidence interval, 0 to 33 percent).The prevalence of abnormal findings on cytopathological examination of vaginal Papanicolaou smears after hysterectomy for benign gynecologic disease is extremely low.
Creatine, 2,3-Diphosphoglycerate and Anemia
Authors: A. Opalinski, E. Beutler
Journal: New England Journal of Medicine (1971)

Abstract Red-cell creatine and 2,3-diphosphoglycerate were investigated in normal persons, in patients with anemia characterized by increased age of the red-cell population (aplastic anemias), and in patients with anemias characterized by a young red-cell population (hemolytic and other bone-marrow-responsive anemias). The mean age of the red-cell population was estimated by hexokinase and glutamic oxalacetic transaminase activities. In anemias with older red-cell populations creatine levels were found to be very low, whereas the 2,3-diphosphoglycerate values were slightly increased. In anemias with a younger mean age of the red cells there was an increase in both creatine and 2,3-diphosphoglycerate. Thus, it appears that increases in creatine are chiefly related to the mean age of the red-cell population, whereas those in 2,3-diphosphoglycerate are conditioned both by the anemia and by the age of red cells.
SAT0536 Prevalence of Rheumatoid Arthritis in Serbia (The Eular Study Project)
Authors: M. I. Zlatkovic-Svenda, R. M. Stojanovic, S. Grujicic-Sipetic, F. Guillemin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Prevalence estimates for rheumatoid arthritis (RA) in Europe are very discrepant. In order to minimize sources of differences between countries, a set of RA prevalence studies was conducted in Europe using a unique methodology. <h3>Objectives</h3> To estimate the RA prevalence in Serbia, as a part of the RA prevalence study project in Europe, supported by EULAR. <h3>Methods</h3> The original telephone Questionnaire was translated into Serbian language following guidelines for crosscultural adaptation. After a successful validation (1), it was used in a detection phase on urban population from four towns: Belgrade (north) and Cacak, Uzice and Krusevac (south), randomly selected from the telephone book (every 100-th). The confirmation phase was done by rheumatologist during a second phone call, where the suspected cases were asked questions about their physician, drugs taken and the treatment institution. In case of uncertain diagnosis, complete medical investigation was done. Prevalence estimates were standardised on Serbian population for age and sex (census 2002). <h3>Results</h3> According to the study protocol, 6213 persons were contacted for detection leading to 3950 respondents (response rate 63,6%). For confirmation, 571 people were called by rheumatologist, confirming the diagnosis in 23 (4 male and 19 female), of whom 21 were previously identified as RA and 2 more at the examination. The overall standardised prevalence was 0.35% (95% CI 0.18 to 0.52), with 0.16% (95% CI 0.01 to 0.32) for men and 0.51% (95% CI 0.26 to 0.76) for women-a female to male ratio of 3.18. For the whole group, the highest age-specific rate of 1.28% was found in the 65-74 year age band. <h3>Conclusions</h3> Comparing prevalence studies using the same methodology and design, RA prevalence results from Serbia are close to France (2), but lower than those reported from Lithuania (3). <h3>References</h3> Zlatkovic-Svenda MI, Stojanovic RM, Milenkovic MP, Vlajinac HD, Le Bihan E, Guillemin F. Adaptation and validation of a telephone questionnaire – Serbian version for case detection of rheumatoid arthritis and spondyloarthropathy (multicentric Eular study). Clin Exp Rheumatol. 2007; 25 (1): 75-84 Guillemin F, Saraux A, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, Cantagrel A, Chary-Valckenaere I, Euller-Ziegler L, Flipo RM, Juvin R, Behier JM, Fautrel B, Masson C, Coste J. Prevalence of rheumatoid arthritis in France: 2001. Ann Rheum Dis. 2005 Oct; 64(10): 1427–30 Adomaviciute D, Pileckyte M, Baranauskaite A, Morvan J, Dadoniene J, Guillemin F. Prevalence survey of rheumatoid arthritis and spondyloarthropathy in Lithuania. Scand J Rheumatol. 2008 Mar-Apr;37(2):113–9 <h3>Disclosure of Interest</h3> None Declared