tbuckley/cabot-search huggingface dataset:
FRI0440 Trends in rheumatoid arthritis related resource utilization in british columbia, canada: A population based cohort study
Authors: N. Bansback, E. Fu, H. Sun, D. Guh, A. Anis, D. Lacaille
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> RA related health resource use and direct costs may be influenced by prevalence, disease management, and available medications, and understanding trends is crucial for policy makers. Previous costing studies in RA have been limited by unrepresentative RA populations, small numbers, lack of costing data and relatively short follow-up. <h3>Objectives</h3> To determine the trend in components of resource utilization in a large, representative, RA cohort based on administrative health data. <h3>Methods</h3> RA patients were identified for each fiscal year from 1996/97 to 2004/05 if they had at least two rheumatologist visits with an RA diagnosis, one in the study year and another in a span from the previous to the following year, using administrative health data from British Columbia. The costs of drugs, physician visits and hospitalizations were calculated from administrative data records using standard procedures and inflated to 2005 Canadian dollars. <h3>Results</h3> The number of patients identified increased steadily from 6,525 in 1996/97 to 10,068 in 2004/05. A total of 22,756 individuals with RA provided 71,200 person-years of follow-up. While annual total costs for this RA cohort increased from $13.5M in 1996 to $33.0M in 2004/05, the annual cost per person year increased from $2,077 to $3,289 (Figure 1). The proportion of costs attributable to hospitalizations markedly decreased (from 59.4% to 21.1% of the total per person annual cost), while since 2001 the proportion of costs attributable to medications has increased, predominantly through biologics which have grown from 17.4% to 48.4% of the total costs. <h3>Conclusions</h3> The type of resources consuming health care dollars has changed dramatically. We are currently in the process of extending this analysis to 2010 data. As decisions are made on future management and policy strategies, understanding causal relationships between components, for example whether increased biologic use has led to reduced hospitalisations will be crucial and is the subject of future research. <h3>Disclosure of Interest</h3> None Declared
Cholinergic Contraction Is Altered in nNOS Knockouts
Authors: MASAHIRO KAKUYAMA, AMRITA AHLUWALIA, JOSE RODRIGO, PATRICK VALLANCE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Endogenous nitric oxide (NO) is a bronchodilator but its physiologic role in small airways is not clear. In this study, we investigated the role of endogenous NO in the regulation of bronchiolar tone in the small airways of wild type and NO synthase (NOS) isoform (eNOS and nNOS)-knockout mice. Pretreatment with the cyclooxygenase inhibitor indomethacin significantly enhanced electrical field stimulation (EFS)-induced contraction in the airways from all types of mice by approximately 60 to 170% (n = 8 in each case), whereas pretreatment with the NOS inhibitor, N G-nitro-l-arginine methyl ester (l-NAME) did not (n = 8). Combined pretreatment with l-NAME and indomethacin enhanced airway contraction of wild-type and eNOS-knockout mice to a significantly greater extent (i.e., by 140 to 290%) than did indomethacin alone (n = 8 for each). This potentiation by l-NAME was not seen in nNOS knockout mice (n = 8). Neither indomethacin nor l-NAME alone affected carbachol (CCh) potency or maximal efficacy in the airways of wild-type mice, whereas the combined pretreatment slightly enhanced the maximal response without altering the potency of CCh (n = 6). Our results show that both NO and prostaglandins modulate neuronal contraction of murine small airways. NO is produced by nNOS, which may be located in nerves, and its overall effects are tonically inhibited by cyclooxygenase products. Kakuyama M, Ahluwalia A, Rodrigo J, Vallance P. Cholinergic contraction is altered in nNOS knockouts: cooperative modulation of neural bronchoconstriction by nNOS and COX.
142O Single-agent capecitabin maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of mCRC
Authors: R. Xu, Y. Li, H. Luo, W. Wang, Z. Wang, X. Yuan, D. Ma, F.H. Wang, D. Zhang, D.R. Lin, J. Jia, X.H. Hu, J.W. Peng, Y.C. Lin
Journal: Annals of Oncology (2015)
OP0200 Thromboembolism in Rheumatology: Investigation of the Risks of Deep Vein Thrombosis and Pulmonary Embolism in Inflammatory Arthritis, Connective Tissue Diseases, Vasculitis and Myositis:
Authors: J.J. Lee, J.E. Pope
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> We performed a meta-analysis investigating the risk of developing deep vein thrombosis (DVT) and/or pulmonary embolisms (PE) in patients with inflammatory arthritis, vasculitis, and connective tissue diseases (CTD) [SLE, Sjogren9s syndrome, inflammatory myositis and systemic sclerosis]. <h3>Objectives</h3> The objectives were to determine the rate and relative increase in venous thromboembolic events in various inflammatory rheumatologic conditions compared to age and sex matched controls. <h3>Methods</h3> PubMed, Embase, Cochrane Databases, and Medline were searched to identify full text English publications in adults related to rheumatologic inflammatory diseases and VTE. Data regarding rates of DVTs and PEs were extracted. Using random effects models, pooled estimates for VTE in individual and pooled diseases compared with age, sex and co-morbidity matched populations where possible. Studies were excluded if VTEs were in the setting of pregnancy, post-operative outcomes or antiphospholipid antibody syndrome solely but entire SLE cohorts were included. <h3>Results</h3> Most of the 3,929 studies were excluded due to lack of rate or incidence of VTE. Twenty studies remained for analysis. Eight studies of RA identified 5,273,942 patients and 891,530,181 controls with a cumulative incidence of 2% (95% CI:2–3%) and OR 2.23 (95% CI:2.02–2.47) compared to age, sex, and comorbidity matched population. Six studies included 36,582 SLE patients with a cumulative incidence of 9% (95% CI:6–11%). Three Sjogren9s syndrome studies with 16,180 subjects demonstrated a VTE cumulative incidence of 3% (95% CI:2–3%). Four studies of inflammatory myositis (N=8,245) yielded a VTE cumulative incidence of 4% (95% CI:2-6%). There were more VTE in SSc (3 studies), ANCA vasculitis (3), PAN (2) and AS (2). Table shows characteristics of some studies included with descriptive statistics on rates of VTEs. <h3>Conclusions</h3> Overall, these inflammatory rheumatologic diseases studied were associated with high rates of VTEs, but not all diseases were represented <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2537
Assessment of Transient Left Ventricular Dilatation on Rest and Exercise on Tc-99m Tetrofosmin Myocardial SPECT
Authors: Noriyuki Kinoshita, Hiroki Sugihara, Yoshihiko Adachi, Tomoki Nakamura, Akihiro Azuma, Yoshio Kohno, Masao Nakagawa
Journal: Clinical Nuclear Medicine (2002)

In myocardial perfusion imaging, multiple-vessel involvement of coronary artery disease (CAD) sometimes makes diagnosis difficult. Transient left ventricular (LV) dilatation on Tl-201 myocardial SPECT is a useful finding that enables the clinician to identify patients with multiple-vessel disease. The aim of this study was to confirm the utility of measuring transient LV dilatation for the detection of multiple-vessel CAD in exercise Tc-99m tetrofosmin myocardial SPECT. The participants were 55 CAD patients and 20 controls who underwent Tc-99m tetrofosmin myocardial SPECT exercise and resting imaging. During exercise, 370 MBq (10 mCi) Tc-99m tetrofosmin was injected. Exercise images were obtained 30 minutes after injection. At 210 minutes after injection, 740 MBq (20 mCi) Tc-99m tetrofosmin was administered intravenously. The rest SPECT images were acquired 30 minutes later. Thirty-six radii at every 10 degrees were generated from the center of short-axis images. An area surrounded by 36 maximal points of the myocardial Tc-99m tetrofosmin counts on each radius was calculated for exercise and rest images. The area surrounded by the 36 maximal points in the same slice of the exercise and rest images was assigned the variables A (Ex) and A(R), respectively. The transient dilatation index (TDI) of the left ventricle was calculated using the formula mean A (Ex)/A(R) in the apical, middle, and basal myocardial short-axis images. In the controls, the TDI was 0.970 ± 0.021. In patients with CAD, the TDIs of one-vessel disease, two-vessel disease, and three-vessel disease were 1.034 ± 0.032, 1.093 ± 0.046, and 1.131 ± 0.076, respectively. The TDIs were significantly greater in patients who had more occluded coronary arteries (P < 0.01). If the mean + 2SD of the TDI (1.012) in controls were assumed to be the normal upper limit, the sensitivity, specificity, and accuracy of this method in detecting two-vessel or three-vessel disease would be 91.4%, 76.9%, and 84%, respectively. The TDI is a useful index for evaluating subendocardial ischemia noninvasively and detecting multiple-vessel disease clinically.
The Safety of Transdermal Nicotine as an Aid to Smoking Cessation in Patients with Cardiac Disease
Authors: Anne M. Joseph, Suzanne M. Norman, Linda H. Ferry, Allan V. Prochazka, Eric C. Westman, Bonnie G. Steele, Scott E. Sherman, Minot Cleveland, David O. Antonuccio, Neil Hartman, Paul G. McGovern
Journal: New England Journal of Medicine (1996)

Transdermal nicotine therapy is widely used to aid smoking cessation, but there is uncertainty about its safety in patients with cardiac disease.
"A PRACTICAL TROCAR AND CANNULA FOR REMOVING ASCITIC FLUID"
Authors: J. Harris Pierpont
Journal: JAMA (1922)

To the Editor:  —I have just read with interest the article contributed by Dr. William W. Duke (The Journal, July 8, p. 134) in which he describes and illustrates an improved trocar and cannula. He concludes his article by saying, The advantages of this cannula would appear to offset its only disadvantage, slightly increased cost. This quotation impels me to write of an improvement I had made in a cannula about fifteen years ago, and following somewhat the lines of Dr. Duke's instrument, but which can be had at practically no added cost to the instrument in common use.  Two oval openings near the end of the cannula were made corresponding to the size of the inlet, and perfectly smooth, so that they could not interfere with the entrance of the trocar into the cavity to be drained. To avoid weakening the lumen of the cannula, these openings were not
PMO-090 Galectin-3 induces secretion of cytokines from vascular endothelium that enhance cancer cell-endothelium adhesion: a novel mechanism for galectin-3-mediated metastasis promotion
Authors: C Chen, Q Zhao, J M Rhodes, L G Yu
Journal: Gut (2012)

<h3>Introduction</h3> Galectin-3 is a galactoside-binding protein whose concentration is increased up to 31-fold in the bloodstream of patients with cancer including colorectal cancer. We have recently shown that circulating galectin-3 promotes metastasis. This effect of galectin-3 is partly due to its interaction with the transmembrane mucin protein MUC1 expressed by the tumour cells, leading to clustering of MUC1 and exposure of adhesion molecules that increases cancer cell heterotypic adhesion to vascular endothelium and cancer cell homotypic aggregation to form micro-tumour emboli. We also showed that circulating galectin-3 has another, as yet unidentified, MUC1-independent action that contributes to its promotion of metastasis. <h3>Methods</h3> Cytokine release was assessed using a protein array that includes the 36 commonest human cytokines. Galectin-3–induced adhesion of MUC1-negative human colon cancer HCT116 and melanoma ACA19- cells to microvascular lung endothelial cells (HMVECs) were assessed. <h3>Results</h3> The presence of galectin-3 at concentrations seen in sera of cancer patients increased the secretion of IL-6, sICAM-1, G-CSF and GM-CSF from cultured HMVECs in a galectin-3 dose- and time-dependent manner. A 117.67±13.25% (p&lt;0.01), 37.84±11.89% (p&lt;0.05), 100.33±14.55% (p&lt;0.01) and 31.47±11.36% (p&lt;0.05) increased secretion of IL-6, sICAM-1, G-CSF and GM-CSF from HMVECs to the culture medium were seen with 1 μg/ml galectin-3 after 24 hr. The culture supernatant from galectin-3-treated HMVECs increased adhesion of HCT116 (74.01±14.33%, p&lt;0.05) and ACA19- (43±6.67%, p&lt;0.05) cells to fresh HMVECs monolayers when compared to the supernatant from non-galectin-3 treated HMVECs. This effect was largely inhibited by the presence of a combination of neutralising antibodies against IL-6, ICAM-1, G-CSF and GM-CSF or the presence of galectin-3 inhibitor lactose. Treatment of HMVECs with galectin-3 increased the expressions of HMVEC cell surface adhesion molecules integrinα<sub>v</sub>β<sub>1,</sub> E-selectin and ICAM-1 which was largely prevented by the presence of the four neutralising anti-cytokine antibodies in combination. Serum galectin-3 concentrations were seen to be correlated (p=0.045) with serum G-CSF (but not that of the other three cytokines) in colon cancer patients (n=50). <h3>Conclusion</h3> Galectin-3, at concentrations found in the bloodstream of cancer patients, induces secretion of cytokines from the vascular endothelium that enhances cancer cell- endothelial adhesion as a result of up-regulation of the endothelial cell surface adhesion molecules. As cancer cell adhesion to blood vascular endothelium is an important step in metastasis, the secretion of those cytokines likely makes important contribution to galectin-3-mediated metastasis promotion. <h3>Competing interests</h3> None declared.
Correction: Routine Pediatric Enterovirus 71 Vaccination in China: a Cost-Effectiveness Analysis
Authors: Joseph T. Wu, Mark Jit, Yaming Zheng, Kathy Leung, Weijia Xing, Juan Yang, Qiaohong Liao, Benjamin J. Cowling, Bingyi Yang, Eric H. Y. Lau, Saki Takahashi, Jeremy J. Farrar, Bryan T. Grenfell, Gabriel M. Leung, Hongjie Yu
Journal: PLoS Medicine (2016)

[This corrects the article DOI: 10.1371/journal.pmed.1001975.].
Abstract 2002: Cell reprogramming by hypoxia
Authors: Varesio Luigi, Paolo Fardin, Rogier Versteeg, Fabiola Blengio, Annalisa Barla, Maria Carla Bosco
Journal: Cancer Research (2010)

Abstract Background Low oxygen tension (hypoxia) is an important determinant in tumor progression. In this study we assess the prognostic value of an in vitro derived hypoxia gene signature in neuroblastoma patients. Material and Methods l1-l2 regularization framework has been applied on gene expression profiles of 11 neuroblastoma cell lines to define the neuroblastoma hypoxia signature. We applied k-means clustering on the expression level of the signature 62 probesets to segregate 88 neuroblastoma patients and subgroups obtained by common risk factors stratification. We analyzed the classes by Kaplan-Meier curves and log-rank test for overall survival (OS) and event-free survival (EFS). Multivariate Cox analysis was performed to define the predictive power of the signature. Results The neuroblastoma hypoxia signature distinguished two groups of neuroblastoma patients classifying them as poor prognosis (21 patients), those having OS rate of 25.5% and EFS rate of 27.7%, and as good prognosis (67 patients), those having OS rate of 73.2% and EFS rate of 67.7%. The poor prognosis patients show an over-expression of the hypoxia probesets. Multivariate Cox analysis revealed that the neuroblastoma hypoxia signature is a significant independent predictor after controlling for commonly used risk factors. When applied to MYCN not amplified patients, the hypoxia signature was capable to stratify patients with OS rate of 24.2% and EFS rate of 27.3% for the patients with poor prognosis, compared with OS rate of 81.4% and EFS rate of 74.8% for the patients with good prognosis. Conclusions We demonstrate that the NB-hypo signature is a significant prognostic factor capable of stratify neuroblastoma patients. Furthermore, we obtained the proof of principle that the approach of hypoxia genes selection from in vitro controlled tumor cell lines, is a feasible method to identify specific contribution of the microenvironment to the tumors’ biology. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2002.
P01.03 * FUNCTIONAL CHARACTERISATION OF THE ISOCITRATE DEHYDROGENASE 1 (IDH 1) R132H MUTATION IN GLIOMAS
Authors: J. Biedermann, K. A. El-Ardat, M. Conde, R. Wiedemuth, M. Peitzsch, G. Eisenhofer, L. Kunz-Schughart, A. Temme, E. Schrock, B. Klink
Journal: Neuro-Oncology (2014)

INTRODUCTION: Diffuse gliomas are the most prevalent brain tumors in adults and cannot be cured. Amino-acid substitution at position 132 of cytoplasmic enzyme isocitrate dehydrogenase 1 (IDH1) are characteristic for lower grade gliomas and therefrom derived secondary glioblastomas (GBM). The most frequent mutation observed in low grade gliomas is IDH1 c.395G>A (p.R132H). The wild type IDH1 converts isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP). In contrast, IDH1 R132H produces high amounts of 2-hydroxyglutarate (2HG), which leads to a hypermethylation phenotype and is therefore considered to be an oncometabolite. Nevertheless, the accumulation of 2HG cannot explain all the observed phenomena in gliomas. We aimed to investigate other mechanisms by which IDH1 R132H mutation contributes to gliomagenesis. MATERIALS AND METHODS: We have stably transduced three cell lines (a established GBM cell line, a primary patient-derived GBM cell line, and an immortalized astrocyte cell line) with IDH1 c.395G>A cDNA using viral vectors. Transduction success was validated on DNA, RNA and protein levels using Sanger sequencing, allele-specific PCR and Western blots. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure Krebs cycle metabolite concentrations. In order to find effects independent of 2HG, we added the oncometabolite to empty vector controls. NADP+/NADPH quantification kits were used to determine the concentrations of this coenzyme. RESULTS: We confirmed the presence of IDH1 c.395G>A;p.R132H mutation in the cells transduced with the mutant variant of IDH1. There was an up to 1700-fold increase of the oncometabolite 2HG in the cells with the mutation compared to an empty vector control. The levels of glutamate significantly decreased in cells with the IDH1 mutation as well as in empty vector controls after 2HG treatment. We found a ∼50% decrease in NADPH concentration in GBM cells with the IDH1 mutation but not in astrocytes. Interestingly, there was a decrease in proliferation of GBM cells with IDH1 R132H. This effect was confirmed in 3D spheroid cell cultures. CONCLUSION: The mechanisms of how IDH1 R132H mutations contribute to gliomagenesis are still far from clear. We found that mutations in IDH1 lead to changes in Krebs cycle metabolite concentrations and energy homeostasis while decreasing proliferation in vitro. We are currently analyzing the effect of IDH1 R132H on the transcriptome level in comparison with IDH1 wt cells treated with 2HG. Based on these profiles we aim to investigate possible genetic mechanisms which are independet of the oncometabolite 2HG. These results will also be presented.
Abstract 1186: PTEN expression predicts biochemical recurrence in prostate cancer
Authors: Steven Stone, Zaina Sangale, Silvia Veneroni, Julia Reid, Maurizio Colecchia, Amy Carlson, Riccardo Valdagni, Alexander Gutin, Maria G. Daidone, Nadia Zaffaroni
Journal: Cancer Research (2010)

Abstract Prostate cancer is the most commonly diagnosed malignancy in men, but many patients have indolent disease that is unlikely to cause significant morbidity or mortality. Biomarkers that accurately predict disease severity would enable physicians to more appropriately manage patient care. Data from previous studies indicated that the molecular status of PTEN (phosphatase and tensin homolog) might be prognostic in prostate cancer patients after radical prostatectomy (RP). PTEN expression was evaluated on surgical specimens by IHC using anti-PTEN antibody 138G6 (Cell Signaling Technology) in 132 men treated with RP. Approximately half the patients also had neoadjuvant hormonal blockade therapy (BAT). PTEN IHC scores were derived from the weighted average of percent positive cells x intensity (0, 1 or 2). PTEN status (positive or negative) was determined using a predefined IHC score of ≤ 20 for negatives. Using this scoring system, 24% of the tumors were PTEN negative. Association with biochemical recurrence was evaluated using Cox PH models and likelihood ratio tests. Since we were testing a prior hypothesis about the prognostic utility of PTEN, the corresponding p-values are one-sided. In a univariate analysis on the overall series, PTEN status was associated with biochemical recurrence (p-value = 0.0046, HR = 2.3; 95% CI: 1.27, 4.33). Most of the clinical parameters typically associated with recurrence were affected by neoadjuvant therapy and rendered uninterpretable. Nevertheless, pathological tumor stage (p-value = 4.3 × 10−6, HR = 6.0; 95% CI: 2.35, 15.22) was still associated with outcome. In multivariate analyses, PTEN status was a significant predictor of outcome after adjusting for pathological stage (p-value = 0.009), neoadjuvant therapy (p-value = 0.014), or both (p-value = 0.04). These data support the hypothesis that PTEN status predicts outcome after RP, and suggest further, that PTEN may be a clinically important molecular marker for defining aggressive prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1186.
18F-FDG Uptake in Diffuse Peritoneal Lymphomatosis
Authors: Ali Fuat Yapar, Mehmet Reyhan
Journal: Clinical Nuclear Medicine (2012)

A 38-year-old man presented with declining appetite and progressive abdominal distention. Abdominal ultrasonography revealed omental and bowel wall thickening. Histopathologic examination showed a high-grade lymphoblastic Burkitt-like B-cell lymphoma. 18F fluorodeoxyglucose positron emission tomography/computed tomography images showed diffusely increased metabolic activity in the thickened omentum, intestines, mesentery, and peritoneum (omental caking). Diffuse peritoneal and omental seeding are well-known forms of dissemination of metastatic carcinoma. However, omental and peritoneal lymphomatosis are rare manifestations of high-grade lymphomas. This uncommon case demonstrates usefulness of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in omental and peritoneal involvement in lymphoma.
Transanal ileoproctostomy in a human cadaver
Authors: L Polese, E Lezoche, A Porzionato, G Lezoche, R De Caro, S Merigliano, L Norberto
Journal: Endoscopy (2012)

Objective of the study: The technical feasibility of ileorectal by-pass (ileoproctostomy), performed entirely through a transanal access, was previously evaluated and demonstrated in a porcine model. The aim of this study was to verify the technical feasibility of the same operation in a human cadaver.