tbuckley/cabot-search huggingface dataset:
Abstract 9976: Human Atrial Fibrillation Initiates by Formation of a Dominant Spiral Wave at the Site Where Triggers Cause Dynamic Conduction Slowing
Authors: Amir Schricker, Gautam Lalani, David E Krummen, Sanjiv M Narayan
Journal: Circulation (2012)

Introduction Triggers may initiate human atrial fibrillation (AF), but by unclear mechanisms. We hypothesized that triggers would dynamically slow atrial conduction velocity, to enable the formation of a single localized spiral wave or repetitive focal beat that may drive the atria into AF. Methods We studied 13 patients at clinically-indicated AF ablation (5 persistent, age 63±11 years, LA size 43±6mm) in whom we placed 64-pole basket catheters (Boston Scientific, Natick, MA) in both atria. AF was initiated by accelerating pacing initially from 120 beats/min to AF onset. We constructed isochronal maps of both atria for beats leading to and including the first cycles of AF. We computed conduction time to each bi-atrial electrode at each rate, thus defining rate-dependence (restitution) of conduction throughout the atria. Results AF initiated in the left atrium in 13/13 patients. Notably, atrial conduction slowed dynamically with rate at the site of AF onset in 8 patients, either gradually (Figure A) or abruptly. In all patients, spatial mapping showed that triggers initiated AF at a site of dynamic conduction slowing (76%±60%) by the formation of a single spiral wave (n=7; figure B) or repetitive focal beat (n=1). Notably, these regions were not the slowest to activate at baseline. Figure A shows dynamic conduction velocity slowing only at faster rates (Fig A, steep curve) at a site in the septal posterior LA, which enabled block (Figure B, site marked *) and formation of a spiral wave (Fig B, curved arrow) that initiates AF. Conclusions Triggers initiate human AF by causing dynamic conduction slowing, enabling the formation of a single reentrant spiral wave (or repetitive focal beat) that drives the atria into AF. Of note, these sites did not exhibit conduction slowing at baseline, showing the central dynamic role of the trigger in AF initiation. Future studies should modulate conduction slowing from a trigger to prevent AF initiation.
Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation
Authors: Megan R. Schwarzman, Janet M. Ackerman, Shanaz H. Dairkee, Suzanne E. Fenton, Dale Johnson, Kathleen M. Navarro, Gwendolyn Osborne, Ruthann A. Rudel, Gina M. Solomon, Lauren Zeise, Sarah Janssen
Journal: Environmental Health Perspectives (2015)

BackgroundCurrent approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk.MethodsBased on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC.ResultsThe HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist.ConclusionsThis approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor β activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.CitationSchwarzman MR, Ackerman JM, Dairkee SH, Fenton SE, Johnson D, Navarro KM, Osborne G, Rudel RA, Solomon GM, Zeise L, Janssen S. 2015. Screening for chemical contributions to breast cancer risk: a case study for chemical safety evaluation. Environ Health Perspect 123:1255–1264; http://dx.doi.org/10.1289/ehp.1408337
Abstract 168: Prevention of Endothelial Cell Dysfunction and Apoptosis Through the Induction of Heme Oxygenase-1 Normalizes Blood Pressure in Diabetic Spontaneously Hypertensive Rats
Authors: Shinji Omura, Adam L Kruger, Marco Di Pascoli, David Sacerdoti, Luigi F Rodella, Sergio Rosini, Eri Terada, Nader G Abraham
Journal: Circulation (2006)

Protection of vasculature endothelial cells (EC) by induction of heme oxygenase (HO) may account for its previously noted anti-hypertensive effects. HO degrades heme, a pro-oxidant, into bilirubin, an anti-oxidant, and CO an anti-apoptotic vasodilator. We explored the anti-hypertensive mechanism of HO in diabetic spontaneously hypertensive rats (SHR). We hypothesized that HO prevents hypertension, worsened by diabetes, through reduction of oxidative stress and inhibition of EC apoptosis which increases vascular contraction to phenylephrine. SHR and WKY (control) rats were treated with streptozotocin (STZ) to induce diabetes and SnCl2 to upregulate HO-1. SHR blood pressures were significantly elevated compared to WKY (P<0.05) and worsened by diabetes (P<0.05) while treatment with SnCl2 attenuated this increase (P<0.01). SnCl2 increased HO-1 protein and HO activity leading to decreased levels of COX-2 and 3-NT, markers of oxidative stress by 65% and 49% respectively. The reduction in oxidative stress resulted in increased expression of the anti-apoptotic proteins Akt and Bcl-2. The restoration of these anti-apoptotic proteins contributed to reduced circulating endothelial cells (CEC) in the peripheral blood (cells/mL), a maker of endothelial dysfunction (30 ± 5 in SHR vs. 7 ± 2 in WKY, P<0.005). Diabetic SHR demonstrated a greater increase in CEC (47 ± 5) compared with non-diabetic; Treatment with SnCl2 significantly reduced CEC in diabetic (17 ± 6, P<0.005 vs. untreated) and non-diabetic (7 ± 3, P<0.005 vs. untreated) SHR. Diabetes significantly increased contractility but this increase was attenuated by induction of HO activity. HO induction in diabetic rats restored non-diabetic levels of contractility in WKY and partially (71%) reduced contraction in SHR. These results suggest that pharmacological induction of HO-1 in diabetic hypertensive rats reduces oxidative stress, allows EC to maintain an anti-apoptotic environment through increased anti-apoptotic protein expression and restores endothelial responses to prevent hypertension.
Improved outcome in adult B-cell acute lymphoblastic leukemia
Authors: D Hoelzer, WD Ludwig, E Thiel, W Gassmann, H Loffler, C Fonatsch, H Rieder, G Heil, B Heinze, R Arnold, D Hossfeld, T Buchner, P Koch, M Freund, W Hiddemann, G Maschmeyer, A Heyll, C Aul, T Faak, R Kuse, TH Ittel, M Gramatzki, H Diedrich, K Kolbe, K Uberla
Journal: Blood (1996)
Statins reduce the incidence of lung cancer: A study of half a million U.S. veterans
Authors: V. Khurana, R. Kochhar, H. R. Bejjanki, G. Caldito, C. Fort
Journal: Journal of Clinical Oncology (2005)

1006 Background: Statins (HMG CoA reductase inhibitors) are commonly used cholesterol-lowering agents that are noted to suppress tumor growth in several animal models, however clinical data for a chemoprotective role of statins in lung cancer is lacking. We investigated the effect of statins on the development of lung cancer in the US veteran population. Methods: The VISN 16 database, which contains clinical and demographic information about all veterans (>1.4 million patients) cared for in the South Central VA Health Care Network, was queried from Oct 1998 to June 2004. Retrospective case control design was used. Patients were included in the statin users group if they were using statins prior to the diagnosis of lung cancer but the dose, duration and type of statin used was not factored into the analysis. Statistical analysis was performed using SAS software version 9.0 (Chicago, IL). Multiple logistic regression analysis was used with calculation of odds ratios and 95% confidence intervals. The data was adjusted for age, gender, smoking and alcohol use. Results: A total of 484,226 patients were studied. The mean age was 61.2 (SD+/−15.1) years and 91.7% were men, 164,645 (34%) were using statins. Lung cancer (ICD code of 162) was seen in 7280 (1.5%); 1994 (1.2%) statin users and 5286 (1.7%) statin non-users. Statin users were less likely to develop lung cancer (Odds ratio 0.52: 95% CI 0.49–0.55). The data was controlled for age (OR 1.038, 95% CI for OR 1.036–1.039, p=<0.0001), gender (OR 0.42, 95% CI for OR 0.36–0.49, p=<0.0001), smoking (OR 1.80, 95% CI for OR 1.66–1.95, p=<0.0001), and alcohol use (OR 1.13, 95% CI for OR 1.08–1.19, p=<0.001). All these were highly significant covariates. Conclusions: Statins are associated with a 48% risk reduction of lung cancer after controlling for age, gender, smoking and alcohol use. An internal consistency of the database is reflected by an increased risk associated with documented risk factors. Our data should be evaluated with caution, given the limitations of the population, the database and the fact that this is a case control study. Some factors known to increase the risk of lung cancer like asbestos exposure were not incorporated into the study. No significant financial relationships to disclose.
Abstract 12650: Unexpected Response to Atrial Fibrillation Reduction in Patients With Cardiac Resynchronization Therapy
Authors: Hamid Assadi, Hossein Shenasa, Shahriar Heidary, Mohammad Shenasa
Journal: Circulation (2014)

Background: Cardiac resynchronization therapy (CRT) is known to improve left ventricular (LV) systolic function and symptoms of systolic heart failure. The effect of CRT on atrial fibrillation (AF) burden is less clarified. Methods: 18 patients mean age of 77 ± 11 (72% male) underwent CRT implantations. There were no changes to concomitant anti-arrhythmic medication and permanent AF patients were excluded. Echocardiograms were obtained six month before and after device implantation. LV ejection fraction (LVEF), LV end diastolic dimension (LVEDd), left atrial (LA) dimension, and magnitude of mitral regurgitation (MR) were measured by echocardiogram before and after CRT. The burden of AF was evaluated by 24-hour Holter monitoring before and by device arrhythmic log after implantation. There were no concomitant medication changes. The results were later divided into presence (Group I) and absence (Group II) of paroxysmal or persistent AF. No patient was in permanent AF at the time of CRT implantation. Results: LVEF improved after CRT in both groups. Patients with AF showed the most beneficial effects of LVEF with average improvement of 41% (P-value=0.004) in comparison to 13% improvement in patients without AF (P-value=0.044). The LVEDd was improved by 11.9% in patients with AF (P-value=0.01) while it was improved by only 5.6% in patients without AF (P-value=0.08). LA Dimension was decreased by 4.4% in patients with AF (P-value=0.038). MR was reduced on average from moderate to mild for both groups. The number of AF episodes and duration of the AF were also decreased in all of our AF patients. The pre and post effect of CRT in patients with and without AF is shown in the table below: Conclusions: The AF burden in patients who received CRT was significantly reduced. There were excellent correlations between improvement of LVEF, LVEDd, LA dimension, and AF burden. This may be due to LV and LA remodeling. Further studies need to elaborate the mechanisms of this finding.
Extensile exposure
Authors: Craig Gerrand
Journal: BMJ (2007)

There is evidence from in vitro systems that the extent of neuronal loss in acute central nervous system ischaemia can be reduced by manoeuvres which restrict availability of glucose to the ischaemic area. Experiments were designed to test whether hypoglycaemia induced with insulin is associated with improved behavioural outcome in a recovery model of stroke. Rats learned a maze task as a test of working memory, believed to be subserved by the hippocampus, and then had a period of cerebral ischaemia, followed by reperfusion. After an interval of 14 days they were tested on the same maze, where lesioned animals had very significant (p less than 0.0001) impairment of working memory, whereas lesioned and treated (2.0 u/kg-1 insulin, minimum single plasma glucose value: 3.1 mmol/l-1) animals were indistinguishable from control animals. It is concluded that a striking degree of protection can be obtained with levels of mild hypoglycaemia which may be acceptable and practicable for use in humans.
Transduction of Primitive Human Marrow and Cord Blood-Derived Hematopoietic Progenitor Cells With Adeno-Associated Virus Vectors
Authors: Saswati Chatterjee, Wei Li, Christie Ann Wong, Grace Fisher-Adams, Di Lu, Mausumee Guha, James A. Macer, Stephen J. Forman, K.K. Wong
Journal: Blood (1999)
A Text-Book of the Surgical Dyspepsias.
Authors: A.J. Walton
Journal: JAMA (1924)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Endoscopy as Related to Diseases of the Bronchus, Esophagus, Stomach, and Peritoneal Cavity
Authors: Edward Benson Benedict
Journal: JAMA (1952)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Reconstructing Illness: Studies in Pathography
Authors: Anne Hunsaker Hawkins
Journal: JAMA (1993)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pathophysiology of LV Remodeling in Survivors of STEMI
Authors: David Carrick, Caroline Haig, Sam Rauhalammi, Nadeem Ahmed, Ify Mordi, Margaret McEntegart, Mark C. Petrie, Hany Eteiba, Mitchell Lindsay, Stuart Watkins, Stuart Hood, Andrew Davie, Ahmed Mahrous, Naveed Sattar, Paul Welsh, Niko Tzemos, Aleksandra Radjenovic, Ian Ford, Keith G. Oldroyd, Colin Berry
Journal: JACC. Cardiovascular imaging (2015)

The aim of this study was to investigate the clinical significance of native T1 values in remote myocardium in survivors of acute ST-segment elevation myocardial infarction (STEMI).The pathophysiology and prognostic significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) reveals myocardial function and pathology. Native T1 (relaxation time in ms) is a fundamental magnetic resonance tissue property determined by water content and cellularity.A total of 300 STEMI patients (mean age 59 years; 74% male) gave informed consent. A total of 288 STEMI patients had evaluable native T1 CMR, and 267 patients (91%) had follow-up CMR at 6 months. Health outcome information was obtained for all of the participants (median follow-up 845 days). Infarct size was 18 ± 13% of left ventricular (LV) mass. Two days post-STEMI, native T1 was lower in remote myocardium than in the infarct zone (961 ± 25 ms vs. 1,097 ± 52 ms; p < 0.01). In multivariable regression, incomplete ST-segment resolution was associated with myocardial remote zone native T1 (regression coefficient 9.42; 95% confidence interval [CI]: 2.37 to 16.47; p = 0.009), as were the log of the admission C-reactive protein concentration (3.01; 95% CI: 0.016 to 5.85; p = 0.038) and the peak monocyte count (10.20; 95% CI: 0.74 to 19.67; p = 0.035). Remote T1 at baseline was associated with log N-terminal pro-B-type natriuretic peptide at 6 months (0.01; 95% CI: 0.00 to 0.02; p = 0.002; n = 151) and the change in LV end-diastolic volume from baseline to 6 months (0.13; 95% CI: 0.01 to 0.24; p = 0.035). Remote zone native T1 was independently associated with post-discharge major adverse cardiac events (n = 20 events; hazard ratio: 1.016; 95% CI: 1.000 to 1.032; p = 0.048) and all-cause death or heart failure hospitalization (n = 30 events during admission and post-discharge; hazard ratio: 1.014; 95% CI: 1.000 to 1.028; p = 0.049).Reperfusion injury and inflammation early post-MI was associated with remote zone T1, which in turn was independently associated with LV remodeling and adverse cardiac events post-STEMI. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850).
Abstract 15821: ArcLight: a Genetically Encoded Fluorescent Voltage Indicator Faithfully Reports Transmembrane Potentials in Embryonic Stem Cell-Derived Cardiomyocytes
Authors: Jordan S Leyton-Mange, Robert W Mills, Vincenzo S Macri, Patrick T Ellinor, David J Milan
Journal: Circulation (2013)

Introduction: A major recent advance in disease modeling has been the demonstration that induced pluripotent stem cell (hiPSC) technology can faithfully recapitulate cardiac arrhythmia syndromes. D...
PF-114, a Novel Selective Pan BCR/ABL Inhibitor Targets The T315I and Suppress Models Of Advanced Ph+ ALL
Authors: Afsar Mian, Anahita Rafiei, Anna Metodieva, Isabella Haberbosch, Alexey Zeifman, Ilya Titov, Victor Stroylov, Oleg Stroganov, Fedor Novikov, Oliver G. Ottmann, Ghermes Chilov, Martin Ruthardt
Journal: Blood (2013)
Ursodeoxycholic Acid in Patients With Chronic Heart Failure
Authors: Stephan von Haehling, Joerg C. Schefold, Ewa A. Jankowska, Jochen Springer, Ali Vazir, Paul R. Kalra, Anja Sandek, Günter Fauler, Tatjana Stojakovic, Michael Trauner, Piotr Ponikowski, Hans-Dieter Volk, Wolfram Doehner, Andrew J.S. Coats, Philip A. Poole-Wilson, Stefan D. Anker
Journal: Journal of the American College of Cardiology (2012)
JAKARTA: A phase III, multicenter, randomized, double-blind, placebo-controlled, three-arm study of SAR302503 in patients with intermediate-2 or high-risk primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF with splenomegaly.
Authors: Animesh Dev Pardanani, Jorge E. Cortes, Francisco Cervantes, Claire N Harrison, Francesco Passamonti, Claudia Lebedinsky, Frank Neumann, Pamela Cohen, Ayalew Tefferi
Journal: Journal of Clinical Oncology (2012)

TPS6639 Background: SAR302503 is an orally administered selective JAK-2 inhibitor being evaluated for the treatment of MF. In a phase 1 study, SAR302503 reduced spleen size and disease-related symptoms and provided clinical benefit, including a reduction in the JAK2V617F allele burden, with an acceptable safety profile in patients with primary MF, post-PV MF, or post-ET MF (J Clin Oncol 2011;29:789). An ongoing open-label extension of this trial confirmed the durability of those results and found that doses between 400–500 mg/day of SAR302503 represented the optimal balance between safety and efficacy (Pardanani, ASH 2011;Abs 3838). These results led us to initiate a Phase 3 trial in December 2011 to evaluate SAR302503 at doses of 400 mg/day and 500 mg/day, compared with placebo, for the treatment of patients with MF (NCT01437787; EFC12153). Methods: Eligibility criteria include age of at least 18 years, platelets &gt;50,000/µl, ECOG PS 0–2, and a diagnosis of high- or intermediate-risk 2 primary MF, post-PV MF, or post-ET MF according to IPSS criteria (Blood 2009;113:2895). Patients are being randomized (1:1:1) to receive 400 mg or 500 mg of SAR302503 or placebo orally once a day for at least 6 consecutive 28-day cycles. Assigned treatment will continue as long as patients are deriving benefit or until progression or unacceptable toxicity. Cross-over is allowed after 6 cycles or in case of progression before completion of 6 cycles according to predefined criteria. The primary endpoint is spleen response (≥35% reduction in spleen volume by MRI/CT at the end of cycle 6). Key secondary objectives are symptom response rate and durability of spleen response. Additional secondary endpoints include assessment of allele burden and bone marrow fibrosis reduction. It is planned to randomize 75 patients per treatment group at approximately 130 sites worldwide.