tbuckley/cabot-search huggingface dataset:
Diagnosis and treatment of cardiac amyloidosis. A position statement of the European Society of Cardiology <scp>W</scp>orking <scp>G</scp>roup on <scp>M</scp>yocardial and <scp>P</scp>ericardial <scp>D</scp>iseases
Authors: Pablo Garcia‐Pavia, Claudio Rapezzi, Yehuda Adler, Michael Arad, Cristina Basso, Antonio Brucato, Ivana Burazor, Alida L.P. Caforio, Thibaud Damy, Urs Eriksson, Marianna Fontana, Julian D. Gillmore, Esther Gonzalez‐Lopez, Martha Grogan, Stephane Heymans, Massimo Imazio, Ingrid Kindermann, Arnt V. Kristen, Mathew S. Maurer, Giampaolo Merlini, Antonis Pantazis, Sabine Pankuweit, Angelos G. Rigopoulos, Ales Linhart
Journal: European Journal of Heart Failure (2021)
The relationship between ventricular ectopic beat frequency and heart rate.
Authors: R AWinkle
Journal: Circulation (1982)

We examined the relationship between the frequency of premature ventricle complexes (PVCs) and underlying heart rate in 24 patients with frequent PVCs using 24-hour ambulatory ECG recordings. Plots of PVC frequency vs heart rate were made at 1-beat/min intervals for all heart rates that were recorded for at least 5 minutes of the 24 hours. Heart rates during 24 hours ranged from 56 +/- 10.0 to 102.2 +/- 15.4 beats/min. Twenty-three of the 24 patients had a distinct relationship between PVC frequency and heart rate. Patterns included an approximate log-linear increase in PVCs at higher heart rates in 12 patients, a log-linear decrease (overdrive suppression) in one patient, flat curves in three patients, and a complex relationship (e.g., more PVCs at low rates and suppression at high rates) in seven patients. Patterns were reproducible in 21 of the 24 patients on repeat ambulatory ECG monitorings done 1 day to 2 months later. We conclude that most patients with frequent PVCs have a characteristic relations...
Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis.
Authors: PGolino, J HAshton, JMcNatt, PGlas-Greenwalt, S KYao, R AO'Brien, L MBuja, J TWillerson
Journal: Circulation (1989)

Dynamic changes of the thrombus after its formation due to platelet activation may affect the speed of thrombolysis. In the present study, we wanted to evaluate the role played by thromboxane A2 (TXA2) and serotonin (5HT) in mediating platelet activation during lysis of intracoronary thrombi with human recombinant tissue-type plasminogen activator (t-PA). Coronary thrombi were induced in 26 anesthetized, open-chest dogs by inserting a copper coil into the left anterior descending coronary artery (LAD). LAD blood flow was monitored throughout the experiment by means of a Doppler flow probe placed proximally to the coil. Presence of the thrombus was documented for 30 minutes. The dogs were then assigned to one of four groups as follows: group 1 dogs (n = 8), serving as controls, received a bolus of heparin (200 units/kg) and a bolus of t-PA (80 micrograms/kg) followed by a continuous infusion (8 micrograms/kg/min) for up to 90 minutes or until reperfusion was achieved; group 2 dogs (n = 10) received, immedi...
Sustained ventricular tachycardia in recent canine myocardial infarction.
Authors: HGaran, J TFallon, J NRuskin
Journal: Circulation (1980)

To study recurrent ventricular tachycardia in the late phase or myocardial infarction (MI), transmural anteroapical infarcts were created by ligation of the left anterior descending (LAD) coronary artery in 25 dogs. Twenty dogs survived LAD ligation and underwent an open-chest electrophysiologic study an average of 20 days after MI. Programmed electrical stimulation was carried out using the extrastimulus technique and short bursts of rapid ventricular pacing via bipolar electrodes positioned at multiple left ventricular endocardial sites. Sixteen dogs had electrically induced ventricular tachycardia, and in 11, sustained ventricular tachycardia was reproducibly initiated and terminated by programmed ventricular stimulation. Short bursts of rapid left ventricular pacing from areas in periinfarct zone was the most effective technique for initiating ventricular tachycardia. The electrophysiologic phenomena in this model of sustained ventricular tachycardia in 3-week-old MI included electrically induced chan...
Integrated ATAC-Seq and Chemosensitivity Profiling Identifies Rational Drug Combinations in Ibrutinib-Treated CLL Patients
Authors: Gregory Ian Vladimer, Christian Schmidl, Andre Renderio, Susanne Schnabl, Tea Pemovska, Berend Snijder, Thomas Krausgruber, Nikolaus Krall, Mohammad Araghi, Rainer Hubmann, Anna Ringler, Dita Demirtas, Oscar Lopez de la Fuente, Martin Hilgrath, Cathrin Skrabs, Edit Anna Porpaczy, Michaela Gruber, Gregor Hoermann, Stefan Kubicek, Philipp Bernhard Staber, Medhat M. Shehata, Giulio Superti-Furga, Christoph Bock, Ulrich Jaeger
Journal: Blood (2017)
Contribution of systemic venous hypertension to the development of pulmonary edema in dogs.
Authors: W CMiller, W WSimi, D LRice
Journal: Circulation Research (1978)

Systemic venous hypertension (SVH) is a frequent finding in pulmonary edema. To study the possible contributory or even causal role of SVH in pulmonary edema, a dog model was developed in which balloon catheters were placed in the left and right atria. Inflation of the left atrial balloon produced a tendency to pulmonary edema by causing pulmonary venous hypertension (PVH) (pulmonary artery wedge pressure of 20 mmHg). Inflation of the right atrial balloon produced SVH (central venous pressure of 15 mm Hg). After 2 hours, dogs with SVH with or without PVH demonstrated a greater amount of lung fluid accumulation (P less than 0.01) compared to controls or PVH alone. There was no significant difference in lung water in SVH dogs with or without PVH. Pulmonary blood flow was not significantly different between the experimental groups, each of which was less than control. Impairment of pulmonary lymphatic flow is one possible mechanism producing the worsening edema; however, bronchial venous hypertension or neur...
Early changes in extracellular potassium in ischemic rabbit myocardium. The role of extracellular carbon dioxide accumulation and diffusion.
Authors: W ECascio, G XYan, A GKléber
Journal: Circulation Research (1992)

The role of local accumulation and diffusion of CO2 to modify cellular loss and extracellular accumulation of K+ during the initial, reversible phase of myocardial ischemia was investigated in isolated, cylindrical papillary muscles of the rabbit. The muscles were blood-perfused through their vascular tree and placed in a (permanently flowing) humidified gas mixture with predetermined partial pressures of N2, O2, and CO2. Ischemia was produced by total arrest of perfusion and O2 withdrawal from the gas mixture. With surface PCO2 kept constant during ischemia, [K+]o varied markedly with muscle geometry. After 10 minutes of ischemia, K+ accumulation was approximately 2.5 mM in muscles with a radius of 0.35 mm and approximately 14 mM in muscles with a radius of 0.9 mm, indicating that a large fraction of K+ accumulation was dependent on diffusion of a volatile metabolite. Computer simulation of CO2 accumulation and diffusion within a tissue cylinder suggested a close phenomenological relation between PCO2 an...
Regnase-1 is essential for B cell homeostasis to prevent immunopathology
Authors: Numana Bhat, Richard Virgen-Slane, Parham Ramezani-Rad, Charlotte R. Leung, Cindi Chen, Daniel Balsells, Ashima Shukla, Elaine Kao, John R. Apgar, Mingui Fu, Carl F. Ware, Robert C. Rickert
Journal: The Journal of Experimental Medicine (2021)

Regnase-1 is an emerging regulator of immune responses with essential roles in the posttranscriptional control of immune cell activation. Regnase-1 is expressed in B cells; however, its B cell–specific functions remain unknown. Here, we demonstrate that Regnase-1 prevents severe autoimmune pathology and show its essential role in maintaining B cell homeostasis. Using Cre driver mice for ablation of Regnase-1 at various stages of B cell development, we demonstrate that loss of Regnase-1 leads to aberrant B cell activation and differentiation, resulting in systemic autoimmunity and early morbidity. The basis of these findings was informed by gene expression data revealing a regulatory role for Regnase-1 in the suppression of a transcriptional program that promotes B cell activation, survival, and differentiation. Overall, our study shows that Regnase-1 exerts critical control of B cell activation, which is required for prevention of immunopathology.
Ryanodine and caffeine prevent ventricular arrhythmias during acute myocardial ischemia and reperfusion in rat heart.
Authors: F TThandroyen, JMcCarthy, K PBurton, L HOpie
Journal: Circulation Research (1988)

This study investigates the possible role of oscillatory release of calcium from sarcoplasmic reticulum in the genesis of ventricular arrhythmias during acute myocardial ischemia and reperfusion in isolated rat hearts. We used ryanodine and caffeine, which are known to modulate the oscillatory release of calcium from sarcoplasmic reticulum. During 30 minutes of left main coronary artery ligation, all 13 control hearts developed ventricular premature beats (number of beats, 225 +/- 51) and ventricular tachycardia (duration, 123 +/- 21 seconds); five hearts developed ventricular fibrillation. In a separate series of experiments, reperfusion after 15 minutes of coronary artery ligation caused ventricular fibrillation to occur within 15 seconds in all 12 hearts. Ryanodine (10(-9) to 10(-7) M) abolished ventricular arrhythmias during coronary artery ligation and prevented reperfusion ventricular fibrillation. Ryanodine (10(-9), 10(-8), and 10(-7) M) caused 15%, 23%, and 74% decreases in the maximal rate of ris...
Characterization of the cardiomyopathy in infants of diabetic mothers.
Authors: H PGutgesell, M ESpeer, H SRosenberg
Journal: Circulation (1980)

A transient form of hypertrophic cardiomyopathy has been previously described in infants of diabetic mothers (IDMs). The purpose of this study was to determine the incidence, natural history and pathologic features of this cardiomyopathy in symptomatic and asymptomatic IDMs. We studied 47 IDMs for evidence of cardiomyopathy. Among 24 symptomatic IDMs, five had marked septal hypertrophy with echocardiographic features suggesting left ventricular outflow obstruction and five had hypertrophy of the right ventricular free wall. With the exception of mild septal hypertrophy, these abnormalities resolved during the first 6 months of life, and echocardiograms in the first-degree family members were normal. Of 23 asymptomatic IDMs, three had septal hypertrophy and two had right ventricular free wall hypertrophy; none of the asymptomatic IDMs had evidence of outflow obstruction. One symptomatic IDM died, and autopsy revealed a hypertrophic septum that distorted both ventricular cavities. Microscopic examination re...
A Correction to the Research Article Titled: “Mucosal Imprinting of Vaccine-Induced CD8 <sup>+</sup> T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors” by F. Sandoval, M. Terme, M. Nizard, C. Badoual, M.-F. Bureau, L. Freyburger, O. Clement, E. Marcheteau, A. Gey, G. Fraisse, C. Bouguin, N. Merillon, E. Dransart, T. Tran, F. Quintin-Colonna, G. Autret, M. Thiebaud, M. Suleman, S. Riffault, T.-C. Wu, O. Launay, C. Danel, J. Taieb, J. Richardson, L. Zitvogel, W. H. Fridman, L. Johannes, …
Journal: Science Translational Medicine (2013)
The pumping ability of the left heart and the effect of coronary occlusion.
Authors: GElzinga, NWesterhof
Journal: Circulation Research (1976)

In an isolated preparation of cat heart we studied the pumping capacity of the left heart while left atrial filling pressure was kept constant. We used the source impedance concept to quantify the pumping capacity. In this source impedance concept the relation between left ventricular output and left ventricular pressure is given by the formula (see article) where Zs = source impedance, Plv = left ventricular pressure, Iao = flow in the ascending aorta, and omega = 2pif, f being frequency.. The pressure obtained at zero flow is called the hydromotive pressure (HMP). Only the mean values of pressure and flow were studied. We studied the behavior of 10 hearts in three different experimental situations and in the following sequence: (1) control conditions, (2) after ligating a part of the left coronary arterial system, and (3) after restoring left ventricular output to control level by raising left atrial filling pressure. It was found that source resistance was not significantly different in the three situa...
Re: Randomized Double-Blind Factorial Trial of Three Treatments to Reduce the Prevalence of Precancerous Gastric Lesions
Authors: Robertino Mera, Elizabeth T. H. Fontham, Luis E. Bravo, Juan C. Bravo, M. Blanca Piazuelo, M. Constanza Camargo, Pelayo Correa
Journal: JNCI Journal of the National Cancer Institute (2006)
Murine model of accelerated transplant arteriosclerosis.
Authors: CShi, M ERussell, CBianchi, J BNewell, EHaber
Journal: Circulation Research (1994)

To define the role of specific gene deletions and mutations in the development of transplant arteriosclerosis, we generated an accelerated model of the disease in mice. Carotid arteries were transplanted between B.10A(2R) (H-2h2) donor mice and C57BL/6J (H-2b) recipients and compared with arteries isografted between H-2b mice. Immunosuppressive drugs were not used. Within 7 days, the allografted carotid artery formed a neointima composed of mononuclear leukocytes (CD45+) that were predominantly monocytes or macrophages (ie, CD11b+ cells with single-lobed nuclei). CD4+ and CD8+ cells were present as well. By 30 days, the neointima became exuberant, and mononuclear leukocytes were largely replaced by smooth muscle cells. Cells staining for proliferating-cell nuclear antigen were abundantly present in the intima at both early and late time points, indicating the proliferation of mononuclear leukocytes and smooth muscle cells. The area of the intima increased from day 7 to day 30 (P < .0005), as did the numbe...
Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero
Authors: Johannes Mofors, Håkan Eliasson, Aurelie Ambrosi, Stina Salomonsson, Amanda Skog, Michael Fored, Anders Ekbom, Gunnar Bergman, Sven-Erik Sonesson, Marie Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2019)

Objective Congenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings. Methods Data from patients with CHB (n= 119) and their siblings (n= 128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n= 1,190) and their siblings (n= 1,071), were retrieved from the Swedish National Patient Register. Analyses were performed by Cox proportional hazard modelling. Results Individuals with CHB had a significantly increased risk of cardiovascular comorbidity, with cardiomyopathy and/or heart failure observed in 20 (16.8%) patients versus 3 (0.3%) controls, yielding a HR of 70.0 (95% CI 20.8 to 235.4), and with a HR for cerebral infarction of 39.9 (95% CI 4.5 to 357.3). Patients with CHB also had a higher risk of infections. Pacemaker treatment was associated with a decreased risk of cerebral infarction but increased risks of cardiomyopathy/heart failure and infection. The risk of systemic connective tissue disorder was also increased in patients with CHB (HR 11.8, 95% CI 4.0 to 11.8), and both patients with CHB and their siblings had an increased risk to develop any of 15 common autoimmune conditions (HR 5.7, 95% CI 2.83 to 11.69 and 3.6, 95% CI 1.7 to 8.0, respectively). Conclusions The data indicate an increased risk of several cardiovascular, infectious and autoimmune diseases in patients with CHB, with the latter risk shared by their siblings.
Cryosurgical ablation of the A-V node-His bundle: a new method for producing A-V block.
Authors: LHarrison, J JGallagher, JKasell, R HAnderson, EMikat, D BHackel, A GWallace
Journal: Circulation (1977)

A cryosurgical instrument was used to ablate atrioventricular conduction. The procedure was carried out in 20 dogs and subsequently in three patients with drug resistant, life-threatening supraventricular tachycardias. In patients, the cryosurgical unit lowered the temperature of the His bundle area to 0 degrees C, effecting complete but reversible heart block. Rewarming resulted in resumption of normal atrioventricular conduction. The His bundle region then was cooled to -60 degrees C; complete heart block was produced with two or more 90-120 second freezes. Postoperative evaluations revealed persistent atrioventricular conduction block. The lesion showed no tendency to rupture, form aneurysm, or interfere with valvular function. In the clinical cases, postoperative studies demonstrated a stable pacemaker arising proximal to the branching portion of the His bundle. A potential application of the cryosurgical technique might be ablation of sites of dysrhythmia (i.e., ectopic foci, re-entry circuits, acces...
Thromboxane mediates diapedesis after ischemia by activation of neutrophil adhesion receptors interacting with basally expressed intercellular adhesion molecule-1.
Authors: GGoldman, RWelbourn, J MKlausner, C RValeri, DShepro, H BHechtman
Journal: Circulation Research (1991)

Ischemic injury is characterized by neutrophil (PMN)--endothelial cell adhesion and diapedesis associated with thromboxane (TX) generation. Neutrophil-endothelial cell interaction is regulated in part by the leukocyte adhesion receptor CD 18 glycoprotein complex and the endothelial intercellular adhesion molecule-1 (ICAM-1). This study tests the role of TX in ischemia-induced diapedesis and evaluates whether the diapedesis is regulated by neutrophil or endothelial adhesion receptors. Plasma derived from rabbit hind limbs made ischemic for 3 hours (n = 6) and reperfused for 10 minutes had increased levels of TXB2 3,450 pg/ml, which was higher than sham rabbit (n = 6) values of 653 pg/ml (p less than 0.05). When introduced into abraded skin chambers placed on the dorsum of other normal rabbits (n = 6), this ischemic plasma induced 1,000 pg/ml of new TX synthesis and diapedesis of 1,235 PMN/mm3. The total TX concentration and PMN accumulations in blister fluid were correlated (r = 0.88, p less than 0.05). In...
The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris.
Authors: F LGobel, L ANorstrom, R RNelson, C RJorgensen, YWang
Journal: Circulation (1978)

In order to evaluate hemodynamic predictors of myocardial oxygen consumption (MVO2), 27 normotensive men with angina pectoris were studied at rest and during a steady state at sympton-tolerated maximal exercise (STME). Myocardial blood flow (MBF) was measured by the nitrous oxide method using gas chromatography. MBF increased by 71% from a resting value of 57.4 +/- 10.2 to 98.3 +/- 15.6 ml/100 g LV/min (P less than 0.001) during STME while MVO2 increased by 81% from a resting value of 6.7 +/- 1.3 to 12.1 +/- 2.8 ml O2/100 g LV/min (P less than 0.001). MVO2 correlated well with heart rate (HR) (r = 0.79), with HR x blood pressure (BP) (r = 0.83), and, adding end-diastolic pressure and peak LV dp/dt as independent variables, slightly improved this correlation (r = .86). Including the ejection period (tension-time index) did not improve the correlation (r = 0.80). Thus, HR and HR x BP, both easily measured hemodynamic variables, are good predictors of MVO2 during exercise in normotensive patients with ischem...
The effect of norepinephrine on aortic 42K turnover during deoxycorticosterone acetate hypertension and antihypertensive therapy in the rat.
Authors: A WJones, P DSander, D LKampschmidt
Journal: Circulation Research (1977)

We studied the effects of norepinephrine on 42K turnover in aorta isolated from rats. The rats were given saline to drink and were made hypertensive by injections of deoxycorticosterone acetate (DOC). Other groups of rats received in addition either 6-hydroxydopamine (6-OH-DA) or a regimen of antihypertensives (Anti-Hy) consisting of reserpine, hydrochlorothiazide, and hydralazine. The weight, length, wall thickness, and circumference of the aorta also were measured. DOC hypertension was associated with increased 42K turnover (rate constant for DOC = 0.0164 +/- 0.0009 vs. 0.0090 +/- 0.0002 min-1 in controls). The responses of 42K turnover to low doses of norepinephrine (NE) were increased in DOC with an ED50 of 3.5 +/- 0.8 X 10(-9) vs. 2.7 +/- 0.5 X 10(-8) M in controls. The aortic weight, weight/length, and wall thickness were also increased. Rats treated with DOC plus 6-OH-DA had lower blood pressure and smaller changes in aortic dimensions; however 42K turnover and response to NE were similar to those ...
Barriers to new drug development in respiratory disease
Authors: Grania Brigden, Philipp du Cros, Sidney Wong
Journal: European Respiratory Journal (2015)

The recent article by Barnes et al. [1] discussing barriers to new drug development in respiratory disease is particularly pertinent to the concerning situation for new tuberculosis (TB) drugs. In Médecins Sans Frontières (MSF)'s project in Karakalpakstan, Uzbekistan, 38% of new patients present with multidrug-resistant (MDR)-TB [2]. The need for new TB drugs and regimens has never been greater, with treatment success rates of only 48% for MDR-TB patients and <20% for extensively drug-resistant (XDR)-TB [3]. Despite two new compounds, bedaquiline and delamanid, being approved for the treatment of MDR-TB [4], the pipeline for new TB drugs is inadequate. Many compounds in phase II and IIl development are repurposed antibiotics, and may have pre-existing resistance (figure 1). Innovative solutions are required for TB R&D to ensure the bold targets outlined in the WHO END TB strategy are met <http://ow.ly/TLTmQ>
Arterial and venous angiotensin II in normal subjects. Relation to plasma renin activity and plasma aldosterone concentration, and response to posture and volume changes.
Authors: W GWalker, M AMoore, J SHorvath, P KWhelton
Journal: Circulation Research (1976)

Plasma renin activity, arterial and venous angiotensin II (A II) concentrations, and plasma aldosterone concentration were measured in 16 normal subjects (mean age = 34 years) after 8 hours of recumbency, following 2 hours of ambulation, and again 30 minutes after administration of furosemide intravenously. Measurements were obtained during periods of sodium restriction and again during sodium surfeit. Both arterial and venous A II exhibited a 3-fold increase from low values of 8.8 +/- 2.5 and 8.6 +/- 2.5 pg/ml of plasma, respectively, during recumbency on high sodium intake to values of 23.9 +/- 4.1 and 26.5 +/- 6.2 pg/ml, respectively, following intravenous furosemide during sodium restriction. Corresponding values for aldosterone exhibited a 5-fold rise from 5.6 ng/100 ml to 32.0 ng/100 ml, whereas plasma renin activity (PRA) measured by an in vitro assay exhibited a 20-fold rise from 0.6 +/- 0.2 ng of angiotensin I (AI) generated per ml per hour to 13.1 ng/ml per hour. Despite the disparity in the mag...