tbuckley/cabot-search huggingface dataset:
Comparison of enzymatic and anatomic estimates of myocardial infarct size in man.
Authors: D BHackel, K AReimer, R EIdeker, E MMikat, T DHartwell, C BParker, E BBraunwald, MBuja, H KGold, A SJaffe
Journal: Circulation (1984)

Enzymatic estimates of myocardial infarct size based on plasma levels of MB creatine kinase (MB-CK) were compared with anatomic infarct size in 49 human hearts obtained at autopsy. The patients studied had been enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study program within 18 hr of the onset of acute infarction and were treated at one of five participating hospitals. Infarct size was estimated from serial measurements of plasma MB-CK made at the core laboratory for CK analysis. Hearts obtained at autopsy were studied independently by the core pathology laboratory without knowledge of the MB-CK levels or clinical results. Data from the two laboratories were compared at the data coordinating center. Of 49 hearts, 12 were excluded either because anatomic infarct size could not be established or because the infarct occurring at the time of enrollment in the MILIS study could not be distinguished with certainty from other infarcts. Of the remaining 37 hearts, peak MB-CK le...
Abstract 14740: Sympathetic Down-regulation With Zamicastat Reduces Arrhythmogenicity in Isolated Hearts From Rats With Pulmonary Hypertension
Authors: Nuno Pires, Bruno Igreja, Luis Magalhaes, Maria-Joao Bonifacio, eric chevalier, Patricio Soares-da-Silva
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is a disease often causing right ventricular failure and death. During disease progression, structural and electrical remodeling of the right ventricle creates proarrhythmic substrates and triggers for arrhythmias. Studies of PAH patients show a hyperstimulation of the sympathetic nervous system (SNS) indicating that PAH may be mediated by SNS hyperactivation. Zamicastat (ZAM) is a reversible dopamine β-hydroxylase inhibitor that modulates SNS by reducing the biosynthesis of norepinephrine in peripheral sympathetic nerves. ZAM improves survival in the monocrotaline (MCT) rat model of PAH. Hypothesis: To evaluate the effect of ZAM on electrophysiological parameters in isolated hearts from MCT-treated rats. Methods: Male Wistar Han rats were randomized in 3 groups, Sham (n=6), MCT (n=15) and MCT+ZAM (n=17). On day zero, MCT and MCT+ZAM groups received MCT (60 mg/kg, SC) and Sham group received saline. Starting on day 12, MCT+ZAM rats were daily administered ZAM (30 mg/kg, PO) while all other animals were given vehicle. On day 28, hearts were excised and mounted on a Langendorff system. A bipolar circuit of two electrodes was placed on the epicardium for ECG recording. Provoked arrhythmias were induced with a burst pacing protocol (50Hz, 1 second) and the recovery time was measured as the time needed to reach 3 consecutive stable R-R intervals. Results: MCT increased the proportion of hearts exhibiting bundle branch blocks, 3 rd degree atrioventricular (AV) blocks, atrial fibrillation (AF), ventricular fibrillation (VF) and premature ventricular contractions (PVCs) when compared to Sham group. ZAM treatment suppressed 3 rd degree AV blocks, AF and VF. In addition, PVCs were less frequent in hearts from MCT+ZAM animals as compared to MCT group. Isolated hearts naturally entered a pause following overpacing-induced VF. MCT hearts showed a non-significant 1.7-fold increase in recovery time compared to Sham group. Hearts from MCT+ZAM animals had a significant ≈50% reduction in post-fibrillation pause. Conclusions: These data suggest that treatment with Zamicastat yields a lower proarrhythmic cardiac tissue decreasing the incidence of cardiac arrhythmias.
Potassium Channel Modulators.
Authors: S. A REES
Journal: Cardiovascular Research (1993)

Potassium Channel Modulators. Get access SIAN A REES SIAN A REES London, UK Edited by A H Weston and T C Hamilton. (Pp 513; £79.50.) Oxford: Blackwell Scientific Publications, 1992. ISBN 0-632-03044-5. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 10, October 1993, Page 1887, https://doi.org/10.1093/cvr/27.10.1887 Published: 01 October 1993
Chronic localized hypotension and resetting of carotid sinus baroreceptors. Electrophysiological and histological studies in the dog.
Authors: F OIgler, J HDonegan, K CHoo, M EKorns, J PKampine
Journal: Circulation Research (1981)

Resetting of carotid sinus (CS) baroreceptors to chronically elevated systemic pressure in hypertension has been demonstrated. The effects of chronic system hypotension on CS baroreceptor afferents has not been elucidated, however. The purpose of the present study was to determine the electrophysiological and histological characteristics of CS baroreceptors exposed to chronic hypotension. Chronic unilateral hypotension was produced by anastomosis of the common carotid artery to the external jugular vein. CS nerve activity and histology of the normotensive sinus (mean CS pressure +/- SD = 96 +/- 10.9 torr) were compared to those of the hypotensive sinus (mean CF pressure 50 +/- 14.2 torr) 44-49 days after anastomosis in nine mongrel dogs. An isolated CS pouch preparation was used to produce standard pressure changes. Threshold pressure for hypotensive sinuses (15.5 +/- 5.19 torr) was significantly less (P less than 0.05) than for normotensive sinuses (40.6 +/- 9.73 torr). Saturation pressure was also signi...
Drug resistance in malaria.
Authors: W Peters
Journal: BMJ (1966)

Mumps of the HeartDeath from congestive cardiac failure eight months after probable mumps is sufficiently rare to attract attention.Nevertheless, a report by W. C. Roberts and S. M. Fox' leaves no doubt about the correctness of the diagnosis, while necropsy showed hypertrophy of the heart and the histological changes of diffuse interstitial myocardial fibrosis.
The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model
Authors: Alessandro Matte, Enrica Federti, Charles Kung, Penelope A. Kosinski, Rohini Narayanaswamy, Roberta Russo, Giorgia Federico, Francesca Carlomagno, Maria Andrea Desbats, Leonardo Salviati, Christophe Leboeuf, Maria Teresa Valenti, Francesco Turrini, Anne Janin, Shaoxia Yu, Elisabetta Beneduce, Sebastien Ronseaux, Iana Iatcenko, Lenny Dang, Tomas Ganz, Chun-Ling Jung, Achille Iolascon, Carlo Brugnara, Lucia De Franceschi
Journal: Journal of Clinical Investigation (2021)

Anemia in β-thalassemia is related to ineffective erythropoiesis and reduced red cell survival. Excess free heme and accumulation of unpaired α-globin chains impose substantial oxidative stress on β-thalassemic erythroblasts and erythrocytes, impacting cell metabolism. We hypothesized that increased pyruvate kinase activity induced by mitapivat (AG-348) in the Hbbth3/+ mouse model for β-thalassemia would reduce chronic hemolysis and ineffective erythropoiesis through stimulation of red cell glycolytic metabolism. Oral mitapivat administration ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice. Increased ATP, reduced reactive oxygen species production, and reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance suggested enhanced metabolism following mitapivat administration in β-thalassemia. The amelioration of responsiveness to erythropoietin resulted in reduced soluble erythroferrone, increased liver Hamp expression, and diminished liver iron overload. Mitapivat reduced duodenal Dmt1 expression potentially by activating the pyruvate kinase M2-HIF2α axis, representing a mechanism additional to Hamp in controlling iron absorption and preventing β-thalassemia–related liver iron overload. In ex vivo studies on erythroid precursors from patients with β-thalassemia, mitapivat enhanced erythropoiesis, promoted erythroid maturation, and decreased apoptosis. Overall, pyruvate kinase activation as a treatment modality for β-thalassemia in preclinical model systems had multiple beneficial effects in the erythropoietic compartment and beyond, providing a strong scientific basis for further clinical trials.
Induction of iatrogenic electrocardiographic patterns during electrophysiologic studies.
Authors: MAkhtar, A NDanato, C JGilbert-Leeds, W PBatsford, C PReddy, J AGomes, A HCalon, M SDhatt
Journal: Circulation (1977)

Indwelling cardiac catheters by producing local mechanical stimulation or trauma can induce electrocardiographic (ECG) patterns which simulate known electrophysiologic phenomena. Catheter-induced ECG patterns were analyzed in 447 consecutive patients undergoing electrophysiologic studies. Iatrogenic nature of these patterns was suggested by 1) absence prior to placement of catheter; 2) sudden appearance with catheter placement and disappearance with catheter repositioning; 3) reoccurrence with remanipulation of catheters; and 4) simulation (in some cases) by programmed electrical stimulation from the catheter. Common catheter-induced patterns were 1) right bundle branch block (RBBB) lasting less than 24 hours occurred in 19 patients; 2) transient third degree atrioventricular block in His-Purkinje system developed in 3/13 patients with pre-existing left BBB; 3) catheter-induced ventricular pre-excitation which simulated ECG patterns of type B Wolff-Parkinson-White syndrome; 4) fortuitous synchronization o...
Impact of Severe Fibrosis in the Outcome Of Endoscopic Submucosal Dissection: A Comparative Study in a European Center
Authors: C Félix, C O’neill, R Mendo, P Barreiro, C Chagas
Journal: Endoscopy (2021)

Aims Although effective and safe, endoscopic submucosal dissection (ESD) of lesions with severe fibrosis has been associated with worse outcomes, such as lower curative resection rate and higher incidence of complications. These observations result mainly from oriental studies, and its true impact in ESD performed in the west is still unknown. This study aims to investigate the relation between severe submucosal fibrosis and rectal ESD outcomes in a European center.
Colon Polyps Endoscopic Detection Versus Microscopic Confirmation
Authors: B Ud-din, I Wazir, R Krishnamoorthy
Journal: Endoscopy (2021)

Aims Colon polyps mucosal protrusions occurring in the colon lumen most commonly sporadic or as part of other syndromes. Bowel polyps are very common, affecting around 1 in 4 people aged 50 or over. Serrated polyps have been recognized in the last decade as important premalignant lesions accounting for between 15 % and 30 % of colorectal cancers.
Addition Of Neutralizer To Duodenoscope Samples Increases Yield Of Cultures Acquired After High Level Disinfection
Authors: J Kwakman, M Bruno, M Vos
Journal: Endoscopy (2021)

Aims A reliable culturing method is necessary to properly monitor contamination of duodenoscopes. The CDC advises addition of neutralizers to culture samples to neutralize remaining detergents or disinfectants. However, evidence that this method promotes appropriate outcomes of culturing and circumvents false negative results is not available. This study compares the yield of cultures with and without addition of a neutralizer.
Intravenous Nesiritide, a Natriuretic Peptide, in the Treatment of Decompensated Congestive Heart Failure
Journal: New England Journal of Medicine (2000)

Background Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. We investigated the clinical use of nesiritide in such patients. Methods Patients hospitalized because of symptomatic congestive heart failure were enrolled in either an efficacy trial or a comparative trial. In the efficacy trial, which required the placement of a Swan–Ganz catheter, 127 patients with a pulmonary-capillary wedge pressure of 18 mm Hg or higher and a cardiac index of 2.7 liters per minute per square meter of body-surface area or less were randomly assigned to double-blind treatment with placebo or nesiritide (infused at a rate of 0.015 or 0.030 µg per kilogram of body weight per minute) for six hours. In the comparative trial, which did not require hemodynamic monitoring, 305 patients were randomly assigned to openlabel therapy with standard agents or nesiritide for up to seven days. Results In the efficacy trial, at six hours, nesiritide infusion at rates of 0.015 and 0.030 µg per kilogram per minute decreased pulmonary-capillary wedge pressure by 6.0 and 9.6 mm Hg, respectively (as compared with an increase of 2.0 mm Hg with placebo, P<0.001), resulted in improvements in global clinical status in 60 percent and 67 percent of the patients (as compared with 14 percent of those receiving placebo, P<0.001), reduced dyspnea in 57 percent and 53 percent of the patients (as compared with 12 percent of those receiving placebo, P<0.001), and reduced fatigue in 32 percent and 38 percent of the patients (as compared with 5 percent of those receiving placebo, P<0.001). In the comparative trial, the improvements in global clinical status, dyspnea, and fatigue were sustained with nesiritide therapy for up to seven days and were similar to those observed with standard intravenous therapy for heart failure. The most common side effect was dose-related hypotension, which was usually asymptomatic. Conclusions In patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Intravenous nesiritide is useful for the short-term treatment of decompensated congestive heart failure. (N Engl J Med 2000;343:246-53.)
Intra-aortic balloon pumping in infants and children.
Authors: L GVeasy, R CBlalock, J LOrth, M MBoucek
Journal: Circulation (1983)

From November 1981 to November 1982, intra-aortic balloon pumping (IABP) was used after surgery in eight patients who were from 6 weeks to 6 years old and who weighed from 4.2 to 16.2 kg. In seven patients, specially constructed intra-aortic balloons with 2.5 and 5.0 ml volumes mounted on No. 5F catheters were used. In the largest and oldest patient, a two-chamber 10 ml balloon was used. The pumping module used was the Datascope System 82. Effective diastolic augmentation of arterial pressure was accomplished in seven of the eight patients and suprasystolic diastolic augmentation was accomplished in four. The two youngest and smallest patients are the only long-term survivors. There were two short-term survivors who died 5 and 10 days after successful IABP. In only one patient was there no appreciable effect of IABP. Miniaturization of the equipment has permitted IABP to be used effectively in pediatric patients.
UDP-glucose and P2Y14 receptor amplify allergen-induced airway eosinophilia
Authors: Tadeusz P. Karcz, Gregory S. Whitehead, Keiko Nakano, Hideki Nakano, Sara A. Grimm, Jason G. Williams, Leesa J. Deterding, Kenneth A. Jacobson, Donald N. Cook
Journal: Journal of Clinical Investigation (2021)

Airway eosinophilia is a hallmark of allergic asthma and is associated with mucus production, airway hyperresponsiveness, and shortness of breath. Although glucocorticoids are widely used to treat asthma, their prolonged use is associated with several side effects. Furthermore, many individuals with eosinophilic asthma are resistant to glucocorticoid treatment, and they have an unmet need for novel therapies. Here, we show that UDP-glucose (UDP-G), a nucleotide sugar, is selectively released into the airways of allergen-sensitized mice upon their subsequent challenge with that same allergen. Mice lacking P2Y14R, the receptor for UDP-G, had decreased airway eosinophilia and airway hyperresponsiveness compared with wild-type mice in a protease-mediated model of asthma. P2Y14R was dispensable for allergic sensitization and for the production of type 2 cytokines in the lung after challenge. However, UDP-G increased chemokinesis in eosinophils and enhanced their response to the eosinophil chemoattractant, CCL24. In turn, eosinophils triggered the release of UDP-G into the airway, thereby amplifying eosinophilic recruitment. This positive feedback loop was sensitive to therapeutic intervention, as a small molecule antagonist of P2Y14R inhibited airway eosinophilia. These findings thus reveal a pathway that can be therapeutically targeted to treat asthma exacerbations and glucocorticoid-resistant forms of this disease.
Negative diastolic pressure in the intact canine right ventricle. Evidence of diastolic suction.
Authors: H NSabbah, P DStein
Journal: Circulation Research (1981)

To determine whether the canine right ventricle (RV) can develop a negative diastolic pressure indicative of suction, RV pressure was measured in 15 dogs, with catheter-tip micromanometers. Six dogs were studied only with the chest closed. In these dogs, intrapleural pressure was measured medially (near the heart) in four and laterally in two. In nine dogs, RV pressure was evaluated with the chest closed and after the chest had been opened. In all dogs, with the chest closed, minimal RV diastolic pressure during expiration was negative, -4.8 +/- 0.3 mm Hg. The lowest diastolic pressures occurred during early diastole. Intrapleural pressure during expiration was never this low. Intrapleural pressure measured medially in four dogs was positive during expiration (1.0 +/- 0.6 mm Hg). In the two dogs which it was measured in the lateral pleural space, it was somewhat negative during expiration (-2.5 and -1.3 mm Hg, respectively). After the chest had been opened (nine dogs) minimal RV pressure during early dias...
Venetoclax combinations induce high response rates in newly diagnosed acute myeloid leukemia patients ineligible for intensive chemotherapy in routine practice
Authors: Arie Apel, Yakir Moshe, Yishai Ofran, Alexander Gural, Ofir Wolach, Chezi Ganzel, Jonathan Canaani, Miri Zektser, Adrian Duek, Galia Stemer, Ilana Hellman, May Basood, Avraham Frisch, Chiya Leibovitch, Maya Koren‐Michowitz
Journal: American Journal of Hematology (2021)

Abstract Combinations of the BCL‐2 inhibitor, venetoclax, with either hypomethylating agents (HMA) or low dose cytarabine (LDAC), have shown promising results in clinical trials of AML patients unfit for intensive therapy. We report on the efficacy and safety of venetoclax combinations in AML patients treated outside of clinical trials. Complete remission (CR) + CR with incomplete count recovery (CRi) were achieved in 61% of patients, with similar CR+CRi rates in with secondary AML, and in patients who were previously treated with HMA (61% and 43%, respectively). Relapse occurred in 25% of patients, with a median event‐free survival (EFS) of 11.7 months (95% CI, 10.09–13.35) in responding patients. At a median follow up of 8.7 months, the median overall survival (OS) was 9.8 months (95% CI 6.42–13.3) in the entire cohort. In multivariate analysis adverse karyotype was the only negative predictor of CR/CRi ( p = .03), while both ECOG performance status (PS) and adverse karyotype were significantly associated with shorter OS ( p = .023 and .038, respectively). Median OS was higher in patients achieving CR/CRi and in patients proceeding to allogeneic stem cell transplantation (allo‐SCT). Treatment was well tolerated, with side effects similar to those described in the randomized clinical trials. Tumor lysis syndrome (TLS) occurred in 12% of patients. Our data support the efficacy and safety of venetoclax combinations in newly diagnosed AML patients not eligible for intensive therapy. According to our data, secondary AML patients could benefit from venetoclax combinations similarly to de‐novo AML patients, and allo‐SCT could be offered to selected patients achieving CR/CRi.
Regulation of large coronary arteries.
Authors: M AYoung, S FVatner
Journal: Circulation Research (1986)

The majority of studies on the control of coronary artery vasoactivity have examined changes in coronary blood flow and coronary vascular resistance, indices that primarily reflect regulation of small arterioles and precapillary vessels. With the emergence of coronary artery vasospasm as a significant cause of angina pectoris, myocardial infarction, and sudden death, the control of large coronary artery caliber has assumed more significance. It is clear that resistance coronary vessels and large coronary arteries differ in response to both pharmacologic and physiologic stimuli. Vasodilation of large coronary arteries may occur by direct action of agents on the arterial smooth muscle or by the indirect action of receptor occupation, changes in blood flow, or liberation of endothelial factors. These indirect factors appear to contribute also to responses to agents that constrict coronary smooth muscle directly or through the autonomic nervous system. Furthermore, the mechanisms responsible for control of la...
Left ventricular wall thickness and regional systolic function in patients with hypertrophic cardiomyopathy. A three-dimensional tagged magnetic resonance imaging study.
Authors: S JDong, J HMacGregor, A PCrawley, EMcVeigh, IBelenkie, E RSmith, J VTyberg, RBeyar
Journal: Circulation (1994)

BACKGROUNDRegional performance of the hypertrophied left ventricle (LV) in hypertrophic cardiomyopathy (HCM) is still incompletely characterized with studies variably reporting that the hypertrophied myocardium is hypokinetic, akinetic, or has normal function. Different imaging modalities (M-mode or two-dimensional echocardiography) and methods of analysis (fixed or floating frame of reference for wall motion analysis) yield different results. We assessed regional function in terms of systolic wall thickening and shortening and related these parameters to end-diastolic thickness using tagged magnetic resonance imaging and the three-dimensional volume-element approach.METHODS AND RESULTSIn 17 patients with HCM and 6 healthy volunteers, four parallel short-axis images with 12 radial tags and two mutually orthogonal long-axis images with four parallel tags were obtained at end diastole and end systole. After the LV endocardial and epicardial borders were traced, three-dimensional volume elements were constru...
Race and the Estimation of GFR: Getting it Right
Authors: Harold I. Feldman, Josephine P. Briggs
Journal: Journal of the American Society of Nephrology (2021)

By means of concurrent publication in American Journal of Kidney Diseases ( AJKD ) and Journal of the American Society of Nephrology ( JASN ), we present the interim report of a joint task force established by the National Kidney Foundation and the American Society of Nephrology to reconsider
Symptoms of anxiety and risk of coronary heart disease. The Normative Aging Study.
Authors: IKawachi, DSparrow, P SVokonas, S TWeiss
Journal: Circulation (1994)

BACKGROUNDSeveral studies have suggested an increased risk of fatal coronary heart disease (CHD) among patients with panic disorder, phobic anxiety, and other anxiety disorders. We prospectively examined this association in the Normative Aging Study.METHODS AND RESULTSAn anxiety symptoms scale was constructed out of five items from the Cornell Medical Index, which was administered to the cohort at baseline. During 32 years of follow-up, we observed 402 cases of incident coronary heart disease (137 cases of nonfatal myocardial infarction, 134 cases of angina pectoris, and 131 cases of fatal CHD: made up of 26 cases of sudden cardiac death and 105 cases of nonsudden death). A nested case-control design (involving 1869 control subjects who remained free of diagnosed CHD) was used to assess the association between anxiety and risk of CHD. Compared with men reporting no symptoms of anxiety, men reporting two or more anxiety symptoms had elevated risks of fatal CHD (age-adjusted odds ratio [OR] = 3.20, 95% conf...