tbuckley/cabot-search huggingface dataset:
Training and Competency Evaluation for Interpretation of 12-Lead Electrocardiograms: Recommendations from the American College of Physicians*
Authors: Stephen M. Salerno, Patrick C. Alguire, Herbert S. Waxman
Journal: Annals of Internal Medicine (2003)

This paper is part 1 of a 2-part series on interpretation of 12-lead resting electrocardiograms (ECGs). Part 1 is a position paper that presents recommendations for initial competency, competency assessment, and maintenance of competency on ECG interpretation, as well as recommendations for the role of computer-assisted ECG interpretation. Part 2 is a systematic review of detailed supporting evidence for the recommendations. Despite several earlier consensus-based recommendations on ECG interpretation, substantive evidence on the training needed to obtain and maintain ECG interpretation skills is not available. Some studies show that noncardiologist physicians have more ECG interpretation errors than do cardiologists, but the rate of adverse patient outcomes from ECG interpretation errors is low. Computers may decrease the time needed to interpret ECGs and can reduce ECG interpretation errors. However, they have shown less accuracy than physician interpreters and must be relied on only as an adjunct interpretation tool for a trained provider. Interpretation of ECGs varies greatly, even among expert electrocardiographers. Noncardiologists seem to be more influenced by patient history in interpreting ECGs than are cardiologists. Cardiologists also perform better than other specialists on standardized ECG examinations when minimal patient history is provided. Pending more definitive research, residency training in internal medicine with Advanced Cardiac Life Support instruction should continue to be sufficient for bedside interpretation of resting 12-lead ECGs in routine and emergency situations. Additional experience or training in ECG interpretation when the patient's clinical condition is unknown may be useful but requires further study. *This guideline was developed for and approved by the American College of Physicians Education Committee on 17 June 2002. Members of the Committee were Barbara L. Schuster, MD (Chair); Allan H. Goroll, MD (Vice Chair); Kevin B. Weiss, MD, MPH; R. Hal Baker, MD; Richard J. Simons, MD; Patricia Hale, MD, PhD; Barbara M. Alving, MD; Jeffrey Glassroth, MD; Scott Litin, MD; Isabel V. Hoverman, MD; Kelly O'Brien-Falls, MD; Lawrence G. Smith, MD; and Francine C. Wiest, MD. The guideline was endorsed by the Board of Regents on 14 July 2002. Deceased.
Comment on: Stefanovski et al. Estimating Hepatic Glucokinase Activity Using a Simple Model of Lactate Kinetics. Diabetes Care 2012;35:1015–1020
Authors: Loranne Agius
Journal: Diabetes Care (2012)

Current understanding of the role of hepatic glucokinase activity in hepatic glucose disposal has emerged largely from studies on hepatocytes and animal models. The lack of availability of simple noninvasive methods for determining hepatic glucokinase flux in vivo has been a major hurdle for studying glucokinase in man. Thus the recent report of a noninvasive method for determining glucokinase flux from lactate kinetics after intravenous glucose loading is an exciting new development (1). In hepatocyte models, glucokinase activity is a major determinant of both glycogen synthesis and glycolysis (2,3). Glucokinase is regulated acutely by adaptive interaction with a glucokinase regulatory protein (GCKR), which sequesters glucokinase in the nucleus …
Loss of <i>SOD3</i> (EcSOD) Expression Promotes an Aggressive Phenotype in Human Pancreatic Ductal Adenocarcinoma
Authors: Brianne R. O'Leary, Melissa A. Fath, Andrew M. Bellizzi, Jennifer E. Hrabe, Anna M. Button, Bryan G. Allen, Adam J. Case, Sean Altekruse, Brett A. Wagner, Garry R. Buettner, Charles F. Lynch, Brenda Y. Hernandez, Wendy Cozen, Robert A. Beardsley, Jeffery Keene, Michael D. Henry, Frederick E. Domann, Douglas R. Spitz, James J. Mezhir
Journal: Clinical Cancer Research (2015)

Pancreatic ductal adenocarcinoma (PDA) cells are known to produce excessive amounts of reactive oxygen species (ROS), particularly superoxide, which may contribute to the aggressive and refractory nature of this disease. Extracellular superoxide dismutase (EcSOD) is an antioxidant enzyme that catalyzes the dismutation of superoxide in the extracellular environment. This study tests the hypothesis that EcSOD modulates PDA growth and invasion by modifying the redox balance in PDA.
Traumatic rupture of a retro-oesophageal aortic arch with congenital vascular ring.
Authors: P de Mozzi, U Bortolotti, D Casarotto, D Betti, A Fracasso, V Gallucci
Journal: Thorax (1979)

Traumatic rupture of the aorta at the level of the arch is an exceptionally rare lesion (Charles et al, 1977).To our knowledge no report of a traumatic rupture of a retro-oesophageal aortic arch, in a patient with a congenital vascular ring, has been published. Case reportA 21-year-old man suffered a closed chest injury on 6 August 1977 in a motor accident.On ad- mission to the intensive care unit of an out-of- town hospital the patient showed some clinical signs of shock: his blood pressure was 85/65 mmHg and the pulse rate 112 and regular.He was on August 20,
Toll-like receptor 9–induced type I IFN protects mice from experimental colitis
Authors: Kyoko Katakura, Jongdae Lee, Daniel Rachmilewitz, Gloria Li, Lars Eckmann, Eyal Raz
Journal: Journal of Clinical Investigation (2005)

Experimental colitis is mediated by inflammatory or dysregulated immune responses to microbial factors of the gastrointestinal tract. In this study we observed that administration of Toll-like receptor 9 (TLR9) agonists suppressed the severity of experimental colitis in RAG1–/– but not in SCID mice. This differential responsiveness between phenotypically similar but genetically distinct animals was related to a partial blockade in TLR9 signaling and defective production of type I IFN (i.e., IFN-α/β) in SCID mice upon TLR9 stimulation. The addition of neutralization antibodies against type I IFN abolished the antiinflammatory effects induced by TLR9 agonists, whereas the administration of recombinant IFN-β mimicked the antiinflammatory effects induced by TLR9 agonists in this model. Furthermore, mice deficient in the IFN-α/β receptor exhibited more severe colitis than wild-type mice did upon induction of experimental colitis. These results indicate that TLR9-triggered type I IFN has antiinflammatory functions in colitis. They also underscore the important protective role of type I IFN in intestinal homeostasis and suggest that strategies to modulate innate immunity may be of therapeutic value for the treatment of intestinal inflammatory conditions.
The Development and Validation of a Neuropathy- and Foot Ulcer-Specific Quality of Life Instrument
Authors: Loretta Vileikyte, Mark Peyrot, Christine Bundy, Richard R. Rubin, Howard Leventhal, Pablo Mora, Jonathan E. Shaw, Paul Baker, Andrew J.M. Boulton
Journal: Diabetes Care (2003)

OBJECTIVE—The purpose of this study was to develop a questionnaire that measures patients’ perceptions of the impact of diabetic peripheral neuropathy and foot ulcers on their quality of life and to assess the psychometric properties of this instrument in a sample of patients with varying severity and symptomatology of diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS—The neuropathy- and foot ulcer-specific quality of life instrument (NeuroQoL), generated from interviews with patients with (n = 47) and without (n = 15) diabetic peripheral neuropathy, was administered to 418 consecutive patients with diabetic peripheral neuropathy (35% with foot ulcer history) attending either U.K. (n = 290) or U.S. (n = 128) diabetes centers. Psychometric tests of NeuroQoL included factor analyses and internal consistency of scales; a series of multivariate analyses were performed to establish its criterion, construct, and incremental validity. Results were compared with those obtained using the Short Form (SF)-12 measure of health-related functioning. RESULTS—Factor analyses of NeuroQoL revealed three physical symptom measures and two psychosocial functioning measures with good reliability (α = 0.86–0.95). NeuroQoL was more strongly associated with measures of neuropathic severity than SF-12, more fully mediated the relationship of diabetic peripheral neuropathy with overall quality of life, and significantly increased explained variance in overall quality of life over SF-12. CONCLUSIONS—NeuroQoL reliably captures the key dimensions of the patients’ experience of diabetic peripheral neuropathy and is a valid tool for studying the impact of neuropathy and foot ulceration on quality of life.
Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis
Authors: A. Kroesbergen, Q. Jöbsis, E.H.d Bel, W.C.j Hop, J.C. de Jongste
Journal: European Respiratory Journal (1999)

The concentration of nitric oxide in exhaled air, a marker of airway inflammation, depends critically on the flow of exhalation. Therefore, the aim of this study was to determine the effect of varying the flow on end-expiratory NO concentration and NO output in children with asthma or cystic fibrosis (CF) and in healthy children. Nineteen children with stable asthma, 10 with CF, and 20 healthy children exhaled from TLC while controlling expiratory flow by means of a biofeedback signal at approximately 2, 5, 10 and 20% of their vital capacity per second. NO was measured in exhaled air with a chemiluminescence analyser. Comparisons between the three groups were made by analysing the NO concentration at the endexpiratory plateau and by calculating NO output at different flows. Exhaled NO decreased with increasing flow in all children. Children with asthma had significantly higher NO concentrations than healthy children, but only at the lowest flows. Asthmatics using inhaled steroids (n=13) tended to have lower median exhaled NO than those without steroids. The slope of linearized (log-log transformed) NO/flow plots was significantly steeper in asthmatics than in healthy controls. CF patients had a significantly lower NO concentration and output over the entire flow range studied, compared to asthmatic and control subjects, with a similar NO/flow slope as control subjects. In conclusion, the nitric oxide concentration in exhaled air is highly flow-dependent, and the nitric oxide-flow relationship differs between asthmatics versus cystic fibrosis patients and control subjects. Assessment of the nitric oxide/flow relationship may help in separating asthmatics from normal children.
Cardioprotective function of cardiac macrophages
Authors: K. Fujiu, J. Wang, R. Nagai
Journal: Cardiovascular Research (2014)

The heart is composed of several cell types including cardiomyocytes, cardiac fibroblasts, endothelial, and smooth muscle cells. In addition to these major cell types, cardiac macrophages are also present in small numbers under physiological conditions. Recently, the resident macrophage is considered to have vital functions in the maintenance of tissues and homeostasis in many organs, including brain, liver, adipose tissue, lymphatic tissue, and intestinal tract. However, detailed functions of the cardiac resident macrophage are not fully understood. Although the removal of debris arising from damaged cardiomyocytes and pro-inflammatory effects after heart injuries are conventional tasks of cardiac macrophages (classically activated macrophage or M1 macrophage), novel functions like anti-inflammatory roles, adaptive response, and tissue maintenance have also been reported in recent years. Macrophages that possess these novel functions are generally so-called M2 macrophages, which are alternatively activated and show anti-inflammatory phenotype under pathological conditions. In this review, we focus on the cardioprotective function of the cardiac macrophage and discuss in light of unveiled fundamental functions of macrophages that have been also found in other organs.
Incidence of <i>EGFR</i> Exon 19 Deletions and L858R in Tumor Specimens From Men and Cigarette Smokers With Lung Adenocarcinomas
Authors: Sandra P. D'Angelo, M. Catherine Pietanza, Melissa L. Johnson, Gregory J. Riely, Vincent A. Miller, Camelia S. Sima, Maureen F. Zakowski, Valerie W. Rusch, Marc Ladanyi, Mark G. Kris
Journal: Journal of Clinical Oncology (2011)

EGFR mutations underlie the sensitivity of lung cancers to erlotinib and gefitinib and can occur in any patient with this illness. Here we examine the frequency of EGFR mutations in smokers and men.We determined the frequency of EGFR mutations and characterized their association with cigarette smoking status and male sex.We tested 2,142 lung adenocarcinoma specimens for the presence of EGFR exon 19 deletions and L858R. EGFR mutations were found in 15% of tumors from former smokers (181 of 1,218; 95% CI, 13% to 17%), 6% from current smokers (20 of 344; 95% CI, 4% to 9%), and 52% from never smokers (302 of 580; 95% CI, 48% to 56%; P < .001 for ever v never smokers). EGFR mutations in former or current smokers represented 40% of all those detected (201 of 503; 95% CI, 36% to 44%). EGFR mutations were found in 19% (157 of 827; 95% CI, 16% to 22%) of tumors from men and 26% (346 of 1,315; 95% CI, 24% to 29%) of tumors from women (P < .001). EGFR mutations in men represented 31% (157 of 503; 95% CI, 27% to 35%) of all those detected.A large number of EGFR mutations are found in adenocarcinoma tumor specimens from men and people who smoked cigarettes. If only women who were never smokers were tested, 57% of all EGFR mutations would be missed. Testing for EGFR mutations should be considered for all patients with adenocarcinoma of the lung at diagnosis, regardless of clinical characteristics. This strategy can extend the use of EGFR tyrosine kinase inhibitors to the greatest number individuals with the potential for substantial benefit.
Regulation of glycogen utilization in ischemic hearts after 24 hours of fasting
Authors: L Feng Wang
Journal: Cardiovascular Research (1999)

Fasting protects the ischemic heart from injury and infarction. Previous studies have shown that hearts from fasted animals have greater glycogen utilization and a lower cytosolic redox state (NADH/NAD+) during global ischemia. While the mechanisms of increased glycogen utilization in fasted animals have not been elucidated, animals that hibernate or are tolerant of anoxia are known to increase the tissue content of the active form of glycogen phosphorylase, phosphorylase a. Therefore, this study was designed to (a) determine whether hearts from fasted animals have increased activity of glycogen phosphorylase during ischemia and (b) define those mechanisms responsible for this increase.Hearts isolated from either fed or fasted (24 h) rats were perfused and freeze-clamped at baseline, and after 1 and 10 min of ischemia, for measurement of phosphorylase activity, phosphorylase kinase activity, and glucose-6-phosphate concentrations.Fasting increased the phosphorylase a/b ratio under both baseline and ischemic conditions. This increase was not accompanied by an increase in the activity of phosphorylase kinase, either with maximal [Ca2+] or under physiologic [Ca2+]. Glucose 6-phosphate concentrations were lower in hearts from fasted animals under baseline, but not ischemic, conditions.Fasting enhances glycogen utilization during ischemia by increasing the active form of glycogen phosphorylase. This increase is not due to a change in phosphorylation by phosphorylase kinase nor end-product inhibition by G-6P. While the precise mechanism of increased glycogen phosphorylase activity in fasted animals is not clear, one likely explanation may be the lower cytosolic redox state demonstrated in the myocardium of fasted animals.
Mild Elevation of Body Temperature Reduces Tumor Interstitial Fluid Pressure and Hypoxia and Enhances Efficacy of Radiotherapy in Murine Tumor Models
Authors: Arindam Sen, Maegan L. Capitano, Joseph A. Spernyak, John T. Schueckler, Seneca Thomas, Anurag K. Singh, Sharon S. Evans, Bonnie L. Hylander, Elizabeth A. Repasky
Journal: Cancer Research (2011)

Abstract Human and rodent solid tumors often exhibit elevated interstitial fluid pressure (IFP). This condition is recognized as a prognostic indicator for reduced responses to therapy and decreased disease-free survival rate. In the present study, we tested whether induction of a thermoregulatory-mediated increase in tissue blood flow, induced by exposure of mice to mild environmental heat stress, could influence IFP and other vascular parameters within tumors. Using several murine tumor models, we found that heating results in a sustained reduction in tumor IFP correlating with increased tumor vascular perfusion (measured by fluorescent imaging of perfused vessels, laser Doppler flowmetry, and MRI) as well as a sustained reduction in tumor hypoxia. Furthermore, when radiation therapy was administered 24 hours postheating, we observed a significant improvement in efficacy that may be a result of the sustained reduction in tumor hypoxia. These data suggest, for the first time, that environmental manipulation of normal vasomotor function is capable of achieving therapeutically beneficial changes in IFP and microvascular function in the tumor microenvironment. Cancer Res; 71(11); 3872–80. ©2011 AACR.
Ambient air pollution: a cause of COPD?
Authors: Tamara Schikowski, Inga C. Mills, H. Ross Anderson, Aaron Cohen, Anna Hansell, Francine Kauffmann, Ursula Krämer, Alessandro Marcon, Laura Perez, Jordi Sunyer, Nicole Probst-Hensch, Nino Künzli
Journal: European Respiratory Journal (2013)

The role of ambient air pollution in the development of chronic obstructive pulmonary disease (COPD) is considered to be uncertain. We review the evidence in the light of recent studies. Eight morbidity and six mortality studies were identified. These were heterogeneous in design, characterisation of exposure to air pollution and methods of outcome definition. Six morbidity studies with objectively defined COPD (forced expiratory volume in 1 s/forced vital capacity ratio) were cross-sectional analyses. One longitudinal study defined incidence of COPD as the first hospitalisation due to COPD. However, neither mortality nor hospitalisation studies can unambiguously distinguish acute from long-term effects on the development of the underlying pathophysiological changes. Most studies were based on within-community exposure contrasts, which mainly assess traffic-related air pollution. Overall, evidence of chronic effects of air pollution on the prevalence and incidence of COPD among adults was suggestive but not conclusive, despite plausible biological mechanisms and good evidence that air pollution affects lung development in childhood and triggers exacerbations in COPD patients. To fully integrate this evidence in the assessment, the life-time course of COPD should be better defined. Larger studies with longer follow-up periods, specific definitions of COPD phenotypes, and more refined and source-specific exposure assessments are needed.
The extent and nature of disability in different urticarial conditions
Authors: None POON, None SEED, None GREAVES, None KOBZA-BLACK
Journal: British Journal of Dermatology (1999)

Chronic forms of urticaria are common, often adversely impacting on quality of life. No formal studies have assessed the extent and nature of disability in different types of urticaria. The Dermatology Life Quality Index (DLQI) is a simple and validated 10-item questionnaire designed to measure and compare disability in different skin conditions. In this study, we aimed to assess the disability in different urticarial groups using the DLQI, allowing comparison with previously published DLQI scores in common skin diseases. The DLQI was administered to 170 consecutive patients attending a specialist urticaria clinic over a 4-month period. Consistent with previous studies using the DLQI, mean scores were not influenced by gender or age. Patients with chronic idiopathic urticaria without a concurrent physical urticaria (n = 47) suffered moderate quality of life impairment (mean +/- SD DLQI 25 +/- 24%). In comparison, patients with chronic idiopathic urticaria with concurrent delayed pressure urticaria (DPU) (n = 26) suffered significantly higher quality of life impairment (mean +/- SD DLQI 43 +/- 23%, 95% confidence interval for difference 7-29%). Disability in this group was greatest in the dimensions of work/study, symptoms/feelings and leisure. Subjects with another form of physical urticaria, cholinergic urticaria, also endured high levels of disability (n = 9, mean +/- SD DLQI 50 +/- 34%). From our urticaria study group, we have shown that subjects with DPU and cholinergic urticaria endure the most quality of life impairment. The mean DLQI scores demonstrated in these groups are comparable with those previously seen in severe atopic dermatitis out-patients (60%) and higher than those seen in out-patients with psoriasis (29.7%), acne (24.3%) and vitiligo (16.1%).
Pseudoprogression and Immune-Related Response in Solid Tumors
Authors: Victoria L. Chiou, Mauricio Burotto
Journal: Journal of Clinical Oncology (2015)

Emerging cancer therapeutics target the immune system, stimulating host antitumor response. Tumor cells generate an immunosuppressive milieu with multiple mechanisms to evade immune destruction, including disruption of effective antigen presentation, reduction of effector T-cell function, and upregulation of pathways that promote tolerance and T-cell anergy.1 The programmed death (PD) -1/PD ligand-1 (PD-L1) pathway is a critical component of tumor-mediated immunosuppression. Antibodies to PD-1 and PD-L1 have shown potential clinical benefit in advanced solid tumors.2 The US Food and Drug Administration approved the PD-1 inhibitors pembrolizumab and nivolumab for metastatic melanoma and also recently approved nivolumab for the treatment of metastatic squamous non–small-cell lung cancer. The US Food and Drug Administration has also designated the PD-L1 inhibitor MPDL3280A as a breakthrough therapy for bladder cancer and non–small-cell lung cancer. These drugs and additional immune checkpoint inhibitors are currently under investigation in multiple clinical trials as single-agent therapy and also in combination with other agents.
Apoptotic effect of pegylated-nanoparticles of CDP bound to multitargeted sirna molecules against bmi1 and survivin conjugated with MIR-373 (termed as sevin-a) which target gastric cancer stem cells (GCSCS) overexpressing CD44 after circumvention of chemo
Authors: J. N. Giannios, S. Delis
Journal: Gut (2011)

<h3>Introduction</h3> Vinorelbine in advanced gastric Ca and other solid tumours induces potent chemoresistance caused by activation of downstream signalling pathways of antiapoptotic survivin, aurora, etc induction of endopolyploidy, and efflux proteins including MDR1/Pgp, BCRP and MRP2. <h3>Methods</h3> After vinorelbine treatment in advanced gastric Ca, we observed potent chemoresistance caused by generation of cancer stem cells which were characterised by overexpression of miR-520c, CD44, BIRC5/survivin (IAP), aurora serine/threonine kinases leading to endopolyploidy, Ras/c-Myc, Nanog, MAP4, MDR1/Pgp, BCRP/ABCG2, MRP2 (cMOAT), Hedgehog signalling pathway components including PTCH1, Gli1, Gli2 and downregulation of BRCA1, p53, PTEN and p21. The vinorelbine-induced chemoresistant (VIC) gastric cancer stem cells (GCSCs) termed as VIC-GCSCs were targeted with pegylated nanoparticles of cyclodextrin containing polycation (CDP) bound to multitargeted siRNA molecules against BMI1, and survivin conjugated with miR-373 targeting CD44. The formulation was termed as SEVIN-A. <h3>Results</h3> Post-treatment, we observed induction of D2 apoptotic stage of PCD type 1 in VIC-GCSCs leading to a bystander killing effect after downregulation of the chemoresistant antiapoptotic factors and their downstream signalling pathways, and upregulation of apoptotic tumour suppressor genes and downstream target genes. Treatment with SEVIN-A even induced apoptosis in chemoresistant endopolyploid VIC-GCSCs by downregulating Aurora-B. <h3>Conclusion</h3> Treatment with SEVIN-A eradicated vinorelbine induced chemoresistant cancer stem cells (VIC-GCSCs) of advanced gastric Ca.