tbuckley/cabot-search huggingface dataset:
PTH-060 Acute Upper Gastrointestinal Bleeding to be Endoscoped within 24 Hours of Admission - Are we Meeting BSG and Nice Guidelines? The Experience of a District General Hospital
Authors: J Barbour, S Smith, K St-Louis
Journal: Gut (2013)

<h3>Introduction</h3> BSG and NICE guidelines recommend that all patients with a suspected GI bleed have an endoscopy within 24 hours of admission. The Queen Elizabeth Hospital (QEH), Gateshead (a District General Hospital serving a population of approximately 200,000) provides an urgent out of hours GI bleed service. Additionally there is an 8.30am slot in endoscopy from Monday to Friday allocated to patients who have symptoms of an upper GI bleed. We audited our compliance to the 24 hour guideline. <h3>Methods</h3> The electronic reporting system ‘Endosoft’ was searched using the terms: <i>Upper GI bleed; Malaena; or Haematemesis</i>, for all referrals for gastroscopy between January 1st 2011 and December 31st 2011. The date, time of endoscopy, findings and interventions were noted. Time of admission, theatre use and In-patient and 4 week mortality were also noted. <h3>Results</h3> 162 patients were admitted with acute GI bleeding over the 12 month period. Overall 126 (78%) were endoscoped within 24 hours. 35 of the 36 patients endoscoped in theatre had their procedure within 24 hours of admission. 16 (44%) of the 36 patients outside the 24 hour window were admitted on a Friday evening or Saturday. Of the 36 patients that suffered a delay to endoscopy: 5 had oesophageal varices; 1 a gastric varix; 6 peptic ulcer disease (4 high risk stigmata and 2 low risk); 2 Mallory Weiss tear, and 22 were normal. Of the 36 patients who went straight to theatre, 34 (94%) had an endoscopic cause for bleeding identified. 20 (56%) had variceal bleeds, 12 had peptic ulcer disease (10 high risk stigmata and 2 low risk). Overall in-patient mortality of those found to have an upper GI cause for bleeding was 16% (15 of 91) and 4 week mortality was 18% (17 of 91). Five (29%) of those that died were cirrhotic patients and 8 (47%) had peptic ulcer disease with high risk stigmata. 3 of the 17 deaths occurred in the patients who were delayed prior to endoscopy, one of whom came in at a time when there was no allocated 8.30am slot the following morning. All 3 of the mortalities who waited over 24 hours for their procedure had endoscopic intervention. There was however no significant difference (chi-square test) between mortality of the delayed patients and those scoped within 24hrs (8% compared to 11%). <h3>Conclusion</h3> During 2011 the QEH appropriately identified sick patients suitable for the out of hours GI bleed service, with 94% of theatre cases requiring endoscopic intervention. The NICE and BSG guidelines of endoscoping patients referred for a GI bleed within 24 hours of admission was met in 78% of cases. Allocated 8.30am endoscopy slots on Saturday and Sunday would improve these figures, but it is currently unclear if this would affect the patient outcome. <h3>Disclosure of Interest</h3> None Declared.
Marathon without a colon: salt and water balance in endurance running ileostomates.
Authors: P. Isaacs
Journal: British Journal of Sports Medicine (1984)

Five trained ileostomates completed a marathon in a cool environment without ill effect. During the race, the ileostomy losses of sodium (1.0-2.7 mmol.h-1) and of water (9.2-19 ml.h-1) were small, but urinary excretion of sodium was very low (0.2-0.75 mmol.h-1) despite drinking a combination of water and glucose-electrolyte solution. The concentration of potassium in the ileostomy discharge tended to increase, also suggesting a sodium retaining state. Healthy ileostomates after suitable training are successful marathon runners, but the prevalence of mild salt depletion in ileostomates generally suggests that it may be advisable for them to take only glucose-electrolyte solutions when competing at any ambient temperature or when preparing for a marathon which is to take place in a warm environment.
Cardiovascular Management in Pregnancy
Authors: M. Elizabeth Brickner
Journal: Circulation (2014)

The population of adults with CHD continues to expand,and thus the number of women with CHD who contemplate pregnancy or become pregnant is also growing. Mothers with low-risk defects can be managed by general cardiologist,whereas those with more complex defects should be managed by or with the assistance of ACHD cardiologists. It is important to acknowledge that all patients with CHD may have unique anatomy or physiology, despite their classification as having a simple, moderate, or complex defect. As such, clinicians evaluating these patients should have adequate knowledge and expertise when assessing patient's risk for pregnancy,when performing imaging or hemodynamic studies, and when managing these patients during pregnancy. The American Board of Medical Specialties has recently recognized ACHD as a subspecialty of cardiovascular disease to treat the specialized needs of these patients in adulthood. ACHD experts can provide expertise in the management of specific defects or lesions, imaging techniques, prepregnancy risk assessment,and can manage these patients or comanage them with other medical providers during their pregnancy. Because many of these ACHD patients are lost to follow-up in adulthood, pregnancy represents a time when these patients seek medical care(and for some, represents a time of vulnerability and increased risk). This represents an opportunity to establish or reestablish care with ACHD specialists and to reestablish continuing long-term care for their CHD. Pregnancy also provides an opportunity to create partnerships between primary care physicians,adult cardiologists, and ACHD specialists to provide optimal care for these women throughout their lives.
Different respiratory phenotypes are associated with isocyanate exposure in spray painters
Authors: A. Pronk, L. Preller, G. Doekes, I. M. Wouters, J. Rooijackers, J-W. Lammers, D. Heederik
Journal: European Respiratory Journal (2009)

Associations have been observed between exposure to isocyanates, consisting mainly of oligomers, and respiratory symptoms and isocyanate specific sensitisation in spray painters. The aim of the present study was to assess associations between isocyanate exposure and more objective respiratory effect measures such as bronchial hyperresponsiveness (BHR), baseline spirometry and exhaled nitric oxide (eNO) in a subset of spray painters. Methacholine challenge and eNO measurements were performed in 229 workers. Questionnaires and blood samples were obtained. Specific immunoglobulin (Ig)E and IgG to hexamethylene di-isocyanate were assessed in serum using various assays. Personal exposure was estimated by combining personal task-based inhalatory exposure measurements and time-activity information. Workers with higher isocyanate exposure were more often hyperresponsive (prevalence ratio comparing the 75th versus 25th percentile of exposure 1.8). In addition, significant exposure-related decreased forced expiratory volume in one second (FEV 1 ), FEV 1 /forced vital capacity ratio and flow–volume parameters independent of BHR were found. BHR was more prevalent among sensitised workers. This was statistically significant for only IgG-ImmunoCAP (Phadia, Uppsala, Sweden) positive workers. eNO was not associated with exposure although slightly elevated eNO levels in specific IgG positive subjects were found. The current study provides evidence that exposure to isocyanate oligomers is related to asthma with bronchial hyperresponsiveness as a hallmark, but also shows independent chronic obstructive respiratory effects resulting from isocyanate exposure.
Estimation and Uncertainty Analysis of Impacts of Future Heat Waves on Mortality in the Eastern United States
Authors: Jianyong Wu, Ying Zhou, Yang Gao, Joshua S. Fu, Brent A. Johnson, Cheng Huang, Young-Min Kim, Yang Liu
Journal: Environmental Health Perspectives (2013)

Climate change is anticipated to influence heat-related mortality in the future. However, estimates of excess mortality attributable to future heat waves are subject to large uncertainties and have not been projected under the latest greenhouse gas emission scenarios.We estimated future heat wave mortality in the eastern United States (approximately 1,700 counties) under two Representative Concentration Pathways (RCPs) and investigated sources of uncertainty.Using dynamically downscaled hourly temperature projections for 2057-2059, we projected heat wave days that were defined using four heat wave metrics and estimated the excess mortality attributable to them. We apportioned the sources of uncertainty in excess mortality estimates using a variance-decomposition method.Estimates suggest that excess mortality attributable to heat waves in the eastern United States would result in 200-7,807 deaths/year (mean 2,379 deaths/year) in 2057-2059. Average excess mortality projections under RCP4.5 and RCP8.5 scenarios were 1,403 and 3,556 deaths/year, respectively. Excess mortality would be relatively high in the southern states and eastern coastal areas (excluding Maine). The major sources of uncertainty were the relative risk estimates for mortality on heat wave versus non-heat wave days, the RCP scenarios, and the heat wave definitions.Mortality risks from future heat waves may be an order of magnitude higher than the mortality risks reported in 2002-2004, with thousands of heat wave-related deaths per year in the study area projected under the RCP8.5 scenario. Substantial spatial variability in county-level heat mortality estimates suggests that effective mitigation and adaptation measures should be developed based on spatially resolved data.
Perception of pain after resistance exercise.
Authors: K F Koltyn, R W Arbogast
Journal: British Journal of Sports Medicine (1998)

OBJECTIVES: The main objective was to assess the influence of resistance exercise on pain threshold and pain ratings. Secondary objectives included measuring state anxiety, body awareness, systolic blood pressure, diastolic blood pressure, and heart rate responses. METHODS: Pressure (3 kg force) was applied to the middle digit of the left hand for two minutes using a Forgione-Barber pain stimulator before and after (five minute and 15 minutes) resistance exercise and quiet rest. Resistance exercise consisted of 45 minutes of lifting three sets of 10 repetitions at 75% of an individual's one repetition maximum. Quiet rest consisted of sitting quietly in a room free from distractions. RESULTS: Data were analysed by repeated measures analysis of variance for multifactor experiments. Pain threshold was significantly higher (p&lt;0.05) and pain ratings were significantly lower (p&lt;0.05) five minutes after resistance exercise. Changes in pain perception were accompanied by changes in heart rate, systolic blood pressure, and body awareness after exercise. CONCLUSION: A single bout of resistance exercise is capable of modifying the sensation of experimentally induced pain.
Thinking developmentally about counterfactual possibilities
Authors: Kevin J. Riggs, Sarah R. Beck
Journal: Behavioral and Brain Sciences (2007)

Abstract Byrne implies that working memory development underpins children's ability to represent counterfactuals as possibilities at 3 to 4 years of age. Recent findings suggest that (1) developments in the ability to consider alternatives to reality in children of this age are underpinned by improvements in inhibitory control, not working memory, and (2) children do not develop an understanding of counterfactuals as possibilities until mid-childhood.
Analysis of Spontaneous Tumor-Specific CD4 T-cell Immunity in Lung Cancer Using Promiscuous HLA-DR Telomerase-Derived Epitopes: Potential Synergistic Effect with Chemotherapy Response
Authors: Yann Godet, Elizabeth Fabre, Magalie Dosset, Michele Lamuraglia, Emeline Levionnois, Patrice Ravel, Nadine Benhamouda, Aurélie Cazes, Françoise Le Pimpec-Barthes, Beatrice Gaugler, Pierre Langlade-Demoyen, Xavier Pivot, Philippe Saas, Bernard Maillère, Eric Tartour, Christophe Borg, Olivier Adotévi
Journal: Clinical Cancer Research (2012)

To investigate the presence and impact of spontaneous telomerase-specific CD4 T-cell responses in cancer patients.A multistep approach was used to design novel pan-HLA-DR-restricted peptides from telomerase. T-cell clones isolated from cancer patients were used to characterize the polarization of telomerase-specific CD4 response. The presence of spontaneous CD4 T-cell response against telomerase was monitored in 84 metastatic non-small cell lung cancer (NSCLC) patients before first-line chemotherapy (CT) using IFN-γ ELISPOT assay. Then we analyzed the impact of the pretherapeutic telomerase-specific CD4 T immunity on clinical outcome in patients according to their respective response to CT.We described four novel telomerase-derived CD4 epitopes referred as universal cancer peptides (UCP) that effectively bind to most commonly found human MHC class II alleles. UCP-specific CD4 T-cell repertoire is present in human and UCP-specific CD4 T-cell clones generated from cancer patients exhibited high avidity and are Th1 polarized. Significant frequency (38%) of naturally occurring UCP-specific T-cell responses were detected before CT in advanced NSCLC but not in healthy volunteers. This response was shown to significantly increase overall survival (OS) of patients responding to CT (Median OS: 53 vs. 40 weeks, P = 0.034).These results show for the first time a potential synergistic effect of telomerase-specific CD4 T-cell response with CT response in NSCLC and underline the potential role of tumor-specific CD4 T-cell response on the efficiency of conventional anticancer therapy.
Distribution and Prevalence of Hyperpolarization-Activated Cation Channel (HCN) mRNA Expression in Cardiac Tissues
Authors: Wenmei Shi, Randy Wymore, Hangang Yu, Jiying Wu, Rigel T. Wymore, Zongming Pan, Richard B. Robinson, Jane E. Dixon, David McKinnon, Ira S. Cohen
Journal: Circulation Research (1999)

Abstract —HCN cation channel mRNA expression was determined in the rabbit heart and neonatal and adult rat ventricle using RNase protection assays. In the rabbit SA node, the dominant HCN transcript is HCN4, representing &gt;81% of the total HCN message. HCN1 is also expressed, representing &gt;18% of the total HCN mRNA. Rabbit Purkinje fibers contained almost equal amounts of HCN1 and HCN4 transcripts with low levels of HCN2, whereas rabbit ventricle contained predominantly HCN2. The SA node contained 25 times the total HCN message of Purkinje fibers and 140 times the total HCN message of ventricle. No reports of hyperpolarization-activated current ( I f ) exist in rabbit Purkinje fibers, and we could not record I f in rabbit ventricular myocytes. To investigate the possible role of isoform switching in determining the voltage dependence of I f , we determined the prevalence of HCN isoforms in neonatal and adult rat ventricle. We had previously determined the threshold for activation of I f to be ≈−70 mV in neonatal rat ventricle and −113 mV in adult rat ventricle. In both neonatal and adult rat ventricle, only HCN2 and HCN4 transcripts are present. The ratio of HCN2 to HCN4 is ≈5:1 in the neonate and 13:1 in the adult. Taken together, these results suggest that different cardiac regions express different isoforms of the HCN family. The HCN1 and HCN4 isoforms are most closely associated with a depolarized threshold for I f activation, whereas the HCN2 isoform is associated with a more negative activation curve. The full text of this article is available at http://www.circresaha.org.
Pesticide Residues and Breast Cancer: The Harvest of a Silent Spring?
Authors: D. J. Hunter, K. T. Kelsey
Journal: JNCI Journal of the National Cancer Institute (1993)

During this century, age-adjusted breast cancer incidence rates have increased in the United States (7), and breast cancer incidence has also been associated with international variations in affluence (2). The search for the aspects of our 20th-century Western lifestyle that contribute to this increase in breast cancer has identified reproductive and possibly dietary variables as being partially responsible. However, it is unclear how much of the increase in breast cancer incidence these variables explain. Given this incompletely understood secular trend in breast cancer rates and a community climate of concern about the possible carcinogenic hazards of environmental pollution (especially organochlorine pesticides in the food chain), it is somewhat surprising that few investigators have examined the relationship between pesticide exposure and breast cancer. Although the one ecologic study of this relationship is consistent with the hypothesis that pesticide exposure can indeed lead to breast cancer (5), ecologic studies provide weak evidence for causal interpretation. Previous analytic studies are limited to small case-control studies that included only nine case patients (4), 20 case patients (5),
Nonmuscle and Smooth Muscle Myosin Heavy Chain Expression in Rejected Cardiac Allografts
Authors: Jun-ichi Suzuki, Mitsuaki Isobe, Masanori Aikawa, Motohiro Kawauchi, Ichiro Shiojima, Naoto Kobayashi, Akihiro Tojo, Toru Suzuki, Kenjiro Kimura, Toshio Nishikawa, Tatsuo Sakai, Morie Sekiguchi, Yoshio Yazaki, Ryozo Nagai
Journal: Circulation (1996)

Background Diagnosis of acute rejection and graft arteriosclerosis (chronic rejection) is critical to the success of cardiac transplantation, but accurate diagnosis is often difficult. We have reported that there are three types of vascular myosin heavy chain (MHC) isoforms: SM1, SM2, and SMemb. SM2 is specifically expressed in differentiated smooth muscle cells (SMCs). SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of fetal aorta. Methods and Results To evaluate the usefulness of MHC expression for diagnosis and analysis of acute and chronic rejection, heterotopic cardiac transplantation was performed in rats and monkeys. Immunohistochemistry, electron microscopy, and Northern blot assay were performed to evaluate MHC expression. SMemb was expressed in spindle-shaped cells located in acutely rejected myocardium in the rats and monkeys. These cells were also observed in areas lacking cellular infiltration. These SMemb-positive cells were activated fibroblasts or myofibroblasts. SMemb mRNA was enhanced parallel to the progression of acute rejection. In the coronary arteries of chronically rejected allografts, enhanced SMemb and reduced SM2 expression was observed in both thickened intima and media. The reduced medial SM2 expression was observed before the intimal thickening occurred. These cells were phenotypically modulated SMCs. Conclusions Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.
Chlorinated Methanes and Liver Injury: Highlights of the Past 50 Years
Authors: Gabriel L. Plaa
Journal: The Annual Review of Pharmacology and Toxicology (2000)

The chlorinated methanes, particularly carbon tetrachloride and chloroform, are classic models of liver injury and have developed into important experimental hepatoxicants over the past 50 years. Hepatocellular steatosis and necrosis are features of the acute lesion. Mitochondria and the endoplasmic reticulum as target sites are discussed. The sympathetic nervous system, hepatic hemodynamic alterations, and role of free radicals and biotransformation are considered. With carbon tetrachloride, lipid peroxidation and covalent binding to hepatic constituents have been dominant themes over the years. Potentiation of chlorinated methane-induced liver injury by alcohols, aliphatic ketones, ketogenic compounds, and the pesticide chlordecone is discussed. A search for explanations for the potentiation phenomenon has led to the discovery of the role of tissue repair in the overall outcome of liver injury. Some final thoughts about future research are also presented.
Discrete Generation of Superoxide and Hydrogen Peroxide by T Cell Receptor Stimulation
Authors: Satish Devadas, Luba Zaritskaya, Sue Goo Rhee, Larry Oberley, Mark S. Williams
Journal: The Journal of Experimental Medicine (2002)

Receptor-stimulated generation of reactive oxygen species (ROS) has been shown to regulate signal transduction, and previous studies have suggested that T cell receptor (TCR) signals may involve or be sensitive to ROS. In this study, we have shown for the first time that TCR cross-linking induced rapid (within 15 min) generation of both hydrogen peroxide and superoxide anion, as defined with oxidation-sensitive dyes, selective pharmacologic antioxidants, and overexpression of specific antioxidant enzymes. Furthermore, the data suggest the novel observation that superoxide anion and hydrogen peroxide are produced separately by distinct TCR-stimulated pathways. Unexpectedly, TCR-stimulated activation of the Fas ligand (FasL) promoter and subsequent cell death was dependent upon superoxide anion, but independent of hydrogen peroxide, while nuclear factor of activated T cells (NFAT) activation or interleukin 2 transcription was independent of all ROS. Anti-CD3 induced phosphorylation of extracellular signal-regulated kinase (ERK)1/2 required hydrogen peroxide generation but was unaffected by superoxide anion. Thus, antigen receptor signaling induces generation of discrete species of oxidants that selectively regulate two distinct redox sensitive pathways, a proapoptotic (FasL) and a proliferative pathway (ERK).
A Novel Protein Tyrosine Kinase NOK that Shares Homology with Platelet- Derived Growth Factor/Fibroblast Growth Factor Receptors Induces Tumorigenesis and Metastasis in Nude Mice
Authors: Li Liu, Xin-Zi Yu, Tie-Shi Li, Lian-Xia Song, Pei-La Chen, Ta-Lin Suo, Ying-Hua Li, Shi-Dong Wang, Yue Chen, Yong-Ming Ren, Shu-Ping Zhang, Zhi-Jie Chang, Xin-Yuan Fu
Journal: Cancer Research (2004)

Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3'-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.
Clinical trials update from the American College of Cardiology meeting: CARE‐HF and the Remission of Heart Failure, Women's Health Study, TNT, COMPASS‐HF, VERITAS, CANPAP, PEECH and PREMIER
Authors: John G.F. Cleland, Alison P. Coletta, Nick Freemantle, Periaswamy Velavan, Lwin Tin, Andrew L. Clark
Journal: European Journal of Heart Failure (2005)