tbuckley/cabot-search huggingface dataset:
P261 Tiotropium Safety And Performance In Respimat(R) (tiospir ): Safety And Efficacy In Patients Naive To Treatment With Anticholinergics
Authors: R. Wise, P. Calverley, R. Dahl, D. Dusser, N. Metzdorf, A. Mueller, A. Fowler, A. Anzueto
Journal: Thorax (2014)

<h3>Introduction</h3> The TIOSPIR™ trial showed similar safety and exacerbation efficacy profiles for tiotropium Respimat<sup>®</sup> and HandiHaler<sup>®</sup> in patients with chronic obstructive pulmonary disease (COPD). We present here the results for patients who were naïve to anticholinergic treatment at baseline. <h3>Methods</h3> TIOSPIR™ (n = 17,135), a 2–3 year, randomised, double-blind, parallel-group, event-driven trial, compared safety and efficacy of once-daily tiotropium Respimat<sup>®</sup> 5 and 2.5 µg with HandiHaler<sup>®</sup> 18 µg in patients with COPD. Primary endpoints were time to death (noninferiority of Respimat<sup>®</sup> 5 or 2.5 μg versus HandiHaler<sup>®</sup>) and time to first COPD exacerbation (superiority of Respimat<sup>®</sup> 5 μg versus HandiHaler<sup>®</sup>). Safety, including cardiovascular safety, was assessed. <h3>Results</h3> Overall, 6966 patients from TIOSPIR™, naïve to anticholinergic treatment at baseline, were randomised and treated (n = 2345, n = 2312 and n = 2309 for tiotropium Respimat<sup>®</sup> 2.5 and 5 µg and HandiHaler<sup>®</sup> 18 µg). There was similar risk of death (vital status follow up) (measured as time to death) for the Respimat<sup>®</sup> groups versus HandiHaler<sup>®</sup> (Respimat<sup>®</sup> 5 µg: hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.75–1.17; Respimat<sup>®</sup> 2.5 µg: HR, 1.05; 95% CI, 0.84–1.30) with similar results for the on-treatment sensitivity analysis (Respimat<sup>®</sup> 5 µg: HR, 0.91; 95% CI, 0.71–1.17; Respimat<sup>®</sup> 2.5 µg: HR, 1.11; 95% CI, 0.87–1.40). Risk of exacerbation was also similar for the Respimat<sup>®</sup> groups versus HandiHaler<sup>®</sup> (measured as time to first exacerbation) (Respimat<sup>®</sup> 5 µg: HR, 0.99; 95% CI, 0.90–1.08; Respimat<sup>®</sup> 2.5 µg: HR, 1.04; 95% CI, 0.95–1.14). Risk of major adverse cardiovascular event (MACE) or fatal MACE were similar for the Respimat<sup>®</sup> groups versus HandiHaler<sup>®</sup> (MACE: Respimat<sup>®</sup> 5 µg: HR, 1.20; 95% CI, 0.88–1.63; Respimat<sup>®</sup> 2.5 µg: HR, 1.11; 95% CI, 0.81–1.51; fatal MACE: Respimat<sup>®</sup> 5 µg: HR, 1.14; 95% CI, 0.75–1.71, Respimat<sup>®</sup> 2.5 µg: HR, 1.12; 95% CI, 0.75–1.69). <h3>Conclusions</h3> Analogous to the global analysis, patients naïve to anticholinergic treatment and treated with tiotropium Respimat<sup>®</sup> 2.5 or 5 µg or HandiHaler<sup>®</sup> in the TIOSPIR™ trial exhibited similar safety and exacerbation efficacy profiles.
GALLIDM-67 UPTAKE AS A MARKER OF RATES OF TUMOR GROWTH
Authors: Brian C. Lentle, Gerhard Theyer, Nellie Auersperg, Donald Lyster, David Chaplin, Ann Worth, Jean LeRiche
Journal: Clinical Nuclear Medicine (1988)

Lentle, Brian C.; Theyer, Gerhard; Auersperg, Nellie; Lyster, Donald; Chaplin, David; Worth, Ann; LeRiche, Jean Author Information
RT-18 * TARGETING MPS1 ENHANCES RADIOSENSITIZATION OF HUMAN GLIOBLASTOMA BY MODULATING DNA REPAIR PROTEINS
Authors: U. Maachani, T. Scott, R. Hanson, S. Zhao, O. Celiku, U. Shankavaram, N. Caplen, K. Camphausen, A. Tandle
Journal: Neuro-Oncology (2014)

During the cell cycle, genomic stability requires accurate chromosome segregation. Errors in this process can cause aneuploidy, leading to tumorigenesis. To ensure faithful chromosome segregation, cells use the spindle assembly checkpoint (SAC) mechanism. However, in aneuploid cancer cells components of the SAC machinery are frequently altered. Thus, targeting the components of SAC machinery required for the growth of aneuploid cells may thus offer a cancer cell specific therapeutic approach. Monopolar spindle 1 (MPS1) is an essential SAC kinase involved in determining spindle integrity. MPS1 is overexpressed in a wide range of tumors and is required for tumor cell proliferation; there is thus increased interest in targeting MPS1 for cancer treatment. In this study, we have analyzed the mechanistic basis of the effects of inhibiting MPS1 in glioblastoma multiforme (GBM). We show that the inhibition of MPS1 in conjunction with radiation reduces GBM cell growth, and clonogenic survival and that this is associated with mitotic cell arrest and induction of mitotic catastrophe. MNS-P715 not alone, but along with fractionated doses of radiation significantly enhanced the tumor growth delay. Using gene expression profiling of GBM cells in which MPS1 was silenced we identified altered expression of genes associated with DNA damage, DNA repair, and DNA replication, including PRKDC, the DNA-dependent protein kinase (DNAPK). Inhibition of MPS1 blocked two important DNA repair pathways, non-homologous end joining and homologous recombination. To our knowledge, this is the first report demonstrating a role for MPS1 in DNA repair. Data mining of publically available databases showed the clinical relevance of MPS1 as an important cancer target in GBM. We conclude that inhibiting MPS1 kinase in combination with DNA damage, including irradiation, could represent a promising new approach to cancer therapy.
Abstract 5108: A combined processing and assessment workflow for SNV and indel calling on exome sequencing of tumor samples
Authors: Swee Seong Wong, John N. Calley, Jian Wang, Jason C. Ting, Isabella H. Wulur, Shuyu Dan Li, Yong Gang Yue, Thomas D. Barber, Amit Aggarwal, Gregory P. Donoho
Journal: Cancer Research (2012)

Abstract A workflow for exome sequencing is established using multiple callers for SNV and indel. A spectrum of measures is looked at to understand the diversity and characteristics of the samples. Two common workflows for variant calling are used, namely GATK unified genotyper and Samtools mpileup. Illumina paired end 90 base reads are mapped to the human genome using BWA. Variants called by GATK and Samtools are compared and merged to give a unified set of calling in VCF format. This approach gives additional confidence in calls supported by both callers as there are technical differences in the two workflows. dbSNP rate and TI/TV ratio are used to assess the general quality (sensitivity and specificity) of the calls. It is observed that tumor samples with very low and high TI/TV novel ratio are largely lung and melanoma samples respectively. They are likely to be UV and smoking induced DNA mutation. This affects the overall TI/TV ratio. A handful of samples also exhibit high variant count that is uniquely found (private) in the sample alone. This correlates with lower than expected dbSNP rate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5108. doi:1538-7445.AM2012-5108
Unilateral Vesicoureteral Reflux Detected by Diuretic Renography Without Voiding
Authors: SHINSAKU TSUCHIMOCHI, MASAYUKI NAKAJO, HIROAKI TANABE, MEGUMI JINGUJI, YOSHIAKI NAKABEPPU, ATSUSHI TANI
Journal: Clinical Nuclear Medicine (2003)

TSUCHIMOCHI, SHINSAKU M.D., PH.D.; NAKAJO, MASAYUKI M.D., PH.D.; TANABE, HIROAKI M.D.; JINGUJI, MEGUMI M.D.; NAKABEPPU, YOSHIAKI M.D., PH.D.; TANI, ATSUSHI M.D., PH.D. Author Information
S53 Neural Respiratory Drive And Symptoms Limiting Exercise Capacity In Chronic Obstructive Pulmonary Disease
Authors: C. Jolley, Y. Luo, J. Steier, K. Sylvester, W. Man, G. Rafferty, M. Polkey, J. Moxham
Journal: Thorax (2014)

<h3>Introduction</h3> Exercise capacity in chronic obstructive pulmonary disease (COPD) is limited both by abnormal pulmonary mechanics, reported as breathlessness, and by leg muscle fatigue. To improve functional capacity it is important to understand the primary physiological constraint. Neural respiratory drive (NRD), measured using the diaphragm electromyogram expressed as a proportion of maximum (EMG<sub>di</sub>%max), quantifies the load on the respiratory muscles imposed by abnormal pulmonary mechanics, and relates closely to breathlessness. We hypothesised that end-exercise EMG<sub>di</sub>%max would be higher in patients stopping because of breathlessness than in those stopping because of leg fatigue. <h3>Methods</h3> EMG<sub>di</sub>, ventilation (V<sub>E</sub>), oxygen consumption (VO<sub>2</sub>) and ventilatory reserve (V<sub>E</sub>/MVV%) were measured in 23 COPD patients (median (IQR) FEV<sub>1</sub> 39 (30.0 to 56.8)%predicted) during exhaustive cycle ergometry. Differences in physiological variables between groups of patients stopping because of breathlessness, leg fatigue or both were examined using 1-way ANOVA. <h3>Results</h3> EMG<sub>di</sub>%max was higher in patients stopping because of breathlessness (n = 12, EMG<sub>di</sub>%max 75.7 (69.5 to 77.1)%) than in those stopping because of leg fatigue (n = 8, EMG<sub>di</sub>%max 44.1 (39.4 to 63.3)%, p &lt; 0.05). There were no significant differences in end-exercise V<sub>E</sub> or VO<sub>2</sub>. V<sub>E</sub>/MVV% tended to higher levels in the breathless group. <h3>Discussion</h3> These results suggest that patients limited by breathlessness due to ventilatory constraints can be identified as those reaching near-maximal levels of NRD during exercise. Measurement of EMG<sub>di</sub>%max during exercise could prove useful in identifying patients whose functional performance would be best optimised by improving pulmonary mechanics rather than interventions to train peripheral muscle groups.
INHIBITION OF APOPTOSIS SIGNAL-REGULATING KINASE 1 (ASK1) REDUCES MYOCARDIAL ISCHEMIA-REPERFUSION INJURY IN THE MOUSE
Authors: Stefano Toldo, David Breckenridge, Eleonora Mezzaroma, Benjamin Van Tassell, Harsha R. Kannan, John Shryock, Norbert F. Voelkel, Antonio Abbate
Journal: Journal of the American College of Cardiology (2012)
Hemophilia in the First Year of Life
Authors: Robert L. Baehner, Herbert S. Strauss
Journal: New England Journal of Medicine (1966)

IN hemophilia bleeding difficulties are infrequently encountered during the neonatal period.1 This is remarkable since the trauma even of a normal delivery can be regarded as significant, especially for a newborn infant with this disease. Circumcision is often performed during the first days of life without excessive blood loss in infants who later are found to be "bleeders." The reason for the lack of bleeding during the neonatal period is unknown. There has been contradictory evidence of whether or not transplacental passage of factor VIII (antihemophilic factor) from the mother takes place. After the newborn period major bleeding difficulties are . . .
FRI0564 Serious malformations and perinatal deaths in children of patients with rheumatic diseases observed in a national birth registry during 40 years
Authors: M. Wallenius, K. Å. Salvesen, A. K. Daltveit, J. F. Skomsvoll
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Data on congenital malformations and perinatal deaths in children of patients with inflammatory rheumatic diseases are more seldom published due to lack of large enough data sets. <h3>Objectives</h3> To study the occurrence of serious malformations and perinatal deaths in two subgroups with inflammatory rheumatic disease versus references from the general population <h3>Methods</h3> Medical data on all births in Norway since 1967 has been recorded in the Medical Birth Registry of Norway (MBRN). We used data from MBRN in the period 1967 – 2009 to assess the occurrence of serious malformations and perinatal deaths in children of patients with specified arthritis (SA) and connective tissue diseases (CTDs), respectively. The SA group constituted patients with rheumatoid arthritis, ankylosing spondylitis and juvenile idiopathic arthritis. The CTD group included patients with systemic lupus erythematosus, Sjøgren’s disease and mixed connective tissue disease. References were all other deliveries registered in MBRN during the same period where the mother was not recorded with an inflammatory rheumatic disease. The diagnoses were based on registrations in MBRN according to International Classification of Diseases (ICD)-8 (1967-1998) and ICD-10 from 1999 and onwards. Birth defects included serious (major) malformations in any organ system and were defined according to a definition by MBRN based on ICD-8 (1967-1998) and ICD-10 (1999 and onwards). All serious congenital anomalies were grouped together as one entity. Perinatal mortality included stillbirths (≥22 weeks of gestation) and early neonatal deaths (0-6 days) in live born children. Associations between the rheumatic diseases and adverse outcomes were assessed in logistic regression analyses with adjustments for maternal age at delivery and parity. <h3>Results</h3> <h3>Conclusions</h3> Serious malformations were more often observed among children of patients with SA and CTD compared with references and highest among CTD patients. Children of CTD patients had three times higher risk of perinatal death compared with references. In the SA group no higher risk of perinatal death was observed. <h3>Acknowledgements</h3> The Medical Birth Registry of Norway (data delivery) The Liaison Committee between the Central Norway Regional Health Authority and NTNU (financial support). <h3>Disclosure of Interest</h3> None Declared
ACCURACY OF ENDOSCOPIC ULTRASOUND IN PREDICTING EARLY OESOPHAGEAL NEOPLASMS
Authors: J Storm, S Sah, D McManus, M Mitchell, I Mainie
Journal: Gut (2013)

<h3>Introduction</h3> Adenocarcinoma of the oesophagus has the fastest rising prevalence of any malignancy in the Western world. The majority arise from specialized intestinal metaplasia in the oesophagus, Barrett9s oesophagus.Endoscopic ultrasound (EUS) accurately demonstrates the layers of the oesophageal wall, and is believed to be accurate for local T-staging of malignant oesophageal disease.With the introduction of conservative therapies including radiofrequency ablation, photodynamic therapy and endoscopic mucosal resection for Barrett9s oesophagus, accurate staging has become increasingly important. <h3>Aims/Background</h3> To determine whether endoscopic ultrasound is accurate for T staging of high grade dysplasia/early neoplasia compared with pathology specimens obtained using endoscopic mucosal resection or surgery <h3>Method</h3> Retrospective review of patients evaluated by EUS for assessment of early oesophageal dysplasia, between December 2008 and June 2012 in the Belfast City Hospital.: Findings are compared with subsequent surgical pathology, or endoscopy and biopsy follow up. <h3>Results</h3> This study included 38 patients(30 men) with a median age of 66. 1 patient was omitted due to an incorrect scope being used during EUS. EUS accurately predicted T status in 34 of 37 patients (92%). 2 patients thought to have submucosal carcinoma during EUS proved to have mucosal carcinoma on EMR specimens. 3 patients thought to have mucosal carcinoma during EUS were found to have submucosal carcinoma on EMR specimens. <h3>Conclusion</h3> Endoscopic ultrasound was accurate in the staging of T1 oesophageal lesions. EUS should be increasingly used in the assessment of early oesophageal neoplasms.
Abstract 3543: <i>TOP2A</i> is a therapeutic target for adrenocortical carcinoma .
Authors: Meenu Jain, Lisa Zhang, Mei He, Ya-Qin Zhang, Naris Nilubol, Min Shen, Electron Kebebew
Journal: Cancer Research (2013)

Abstract Adrenocortical carcinoma (ACC) represents one of the most resistant human cancers to systemic chemotherapy and a major clinical challenge in the field of endocrine oncology. Recent molecular characterizations of ACC suggest new opportunities for targeted therapy. The current study aimed to evaluate expression and function of TOP2A in human adrenocortical neoplasm, and anticancer activity of agents that target TOP2A. TOP2A mRNA and protein expression levels were evaluated in 112 adrenocortical tissue samples. In vitro siRNA knockdown of TOP2A in ACC cell lines (NCI-H295R and SW13) was used to determine its effect on cellular proliferation, cell cycle, anchorage-independent growth and cellular invasion. We screened 14 TOP2A inhibitors for their anticancer activity in ACC cell lines. TOP2A mRNA expression was significantly higher in ACC than in benign and normal adrenocortical tissue samples (p &amp;lt; 0.001); likewise, TOP2A protein expression was significantly higher in ACC (p &amp;lt; 0.05). Knockdown of TOP2A gene expression decreased cell proliferation, anchorage-independent growth and invasion (p &amp;lt; 0.05). Aclarubicin had the most potent antiproliferative activity out of 11 active TOP2A inhibitors, which significantly decreased proliferation and tumor spheroid size in ACC cell lines (p&amp;lt; 0.05). Our data indicate that most TOP2A inhibitors are effective compounds for ACC, with aclarubicin having the best anticancer activity. Thus, TOP2A inhibitors should be tested in future clinical trials for patients with locally advanced and metastatic ACC. Citation Format: Meenu Jain, Lisa Zhang, Mei He, Ya-Qin Zhang, Naris Nilubol, Min Shen, Electron Kebebew. TOP2A is a therapeutic target for adrenocortical carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3543. doi:10.1158/1538-7445.AM2013-3543
A Progressive Neurologic Syndrome in Children with Chronic Liver Disease
Authors: Jerry L. Rosenblum, James P. Keating, Arthur L. Prensky, James S. Nelson
Journal: New England Journal of Medicine (1981)

A progressive neurologic syndrome developed in six children with longstanding cholestatic liver disease. The neurologic abnormalities included areflexia, gait disturbance, decreased proprioceptive and vibratory sensation, and paresis of gaze. Serum vitamin E concentrations were uniformly low. Neuropathological studies carried out in two of the three fatal cases revealed degeneration of the posterior column, selective loss of large-caliber, myelinated axons in peripheral nerve, and spheroids in the gracile and cuneate nuclei. These lesions are similar to those found in animals with experimentally induced vitamin E deficiency. We therefore speculate that the neurologic syndrome in these children may be the result of chronic vitamin E malabsorption.
PWE-042 Association Between Midazolam Dose And Caecal Intubation Rate At Colonoscopy: Abstract PWE-042 Table 1
Authors: J Boyd, L Lee, S Lanzon-Miller
Journal: Gut (2014)

Introduction Midazolam is a short acting benzodiazepine that is commonly used for sedation during colonoscopy. There is no standard dose of midazolam; however, British Society of Gastroenterology guidelines suggest a maximum of 5 mg with lower doses for elderly patients. Caecal intubation rate (CIR) is a commonly used performance indicator for colonoscopy. Data exploring the relationship between midazolam dose and CIR is limited. Methods A retrospective cohort study of all patients who had undergone a colonoscopy at Milton Keynes General hospital between January 2010 and December 2012. Patients were identified from the Endoscopy Unit database and their records were reviewed. Patient details, midazolam dose and depth of insertion were extracted into a standardised form. Caecal intubation was defined as insertion of the colonoscope to a point proximal to the ileocaecal valve so that the entire caecum could be visualised. Results 6200 patients were included for analysis. The median age was 62 years and 49.4% were male. The mean midazolam dose was 1.9 mg. 1004 patients had a low dose of midazolam (<2 mg), 4618 a standard dose (2 mg) and 578 a high dose (>2 mg). The CIR in the low dose cohort was 83.6%, in the standard dose cohort was 91.3% and in the high dose cohort was 78.7%. Procedural discomfort was significantly greater in the high dose cohort. When patients with poor bowel preparation were removed from the cohort (n = 5534), CIR was 85.2% in the low dose cohort vs. 92.1% in the standard dose cohort. Patients who received doses of midazolam <2 mg or > 2 mg had a significantly lower CIR than patients who received 2 mg, with P < 0.001 in both comparisons. View this table: Abstract PWE-042 Table 1 Conclusion In this study we demonstrate that a standard (2 mg) dose of midazolam is associated with a significantly higher caecal intubation rate than lower doses. Following stratification of patients by adequacy of bowel preparation, CIR remained lower in the low dose midazolam group. Appropriate patient selection for standard dose midazolam is important to avoid respiratory and cardiovascular compromise. Further confirmatory prospective studies are warranted. Disclosure of Interest None Declared.
Scintigraphic Evidence of Clubbing on a Bone Scan
Authors: NIR HOD, LENA PINKAS, ZAKI BEN-EZRA, TIFHA HORNE
Journal: Clinical Nuclear Medicine (2001)

HOD, NIR M.D.; PINKAS, LENA M.D.; BEN-EZRA, ZAKI B.A.; HORNE, TIFHA M.D. Author Information
Comments on "Experimental Approaches for Exposure to Sized Glass Fibers"
Authors: William E. Smith
Journal: Environmental Health Perspectives (1980)

William E. Smith (Fairleigh-Dickinson Univ., Madison, N.J. 07940): We have carried out experiments with glass fibers injected into the pleural space of hamsters. No tumors were induced by ordinary insulation-grade fibers about 5 ,gm in diameter. We have gotten tumors with fibers 1 to 1.51tm in diameter, but only when we used relatively long fibers. With these very thin fibers, we got tumors with preparations containing more than 30%o of fibers longer than 20 pm. We got no tumors with preparations in which only about 2% of fibers were longer than 10,um.
Abstract MS2-1: Trends in the Local Treatment of Breast Cancer
Authors: TM Tuttle
Journal: Cancer Research (2010)

Abstract The objective of this presentation is to evaluate recent patterns in the local treatment of breast cancer in the United States. We will concentrate on 3 specific trends: 1) mastectomy/breast-conserving surgery (BCS) rates; 2) contralateral prophylactic mastectomy (CPM) rates; and 3) use of radiation therapy (RT) after BCS. Although some single-institutional studies have reported that mastectomy rates have recently increased, a recent population-based study reported that the rates of BCS have remained stable or slightly increased over the past decade in the United States. Both single-institutional and population-based studies have reported that CPM rates have markedly increased in recent years. On the other hand, unilateral mastectomy rates have decreased. Despite the potential benefit of RT after BCS, population-based studies indicate that an increasing number of women are not receiving RT after BCS, particularly high-risk women. These trends have important potential untoward consequences, including overtreatment for some patients and undertreatment for others. Several strategies are being developed to ensure adequate local therapy for breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS2-1.