tbuckley/cabot-search huggingface dataset:
De subitaneis mortibus. XXVII. Histological abnormalities in the sinus node, atrioventricular node and His bundle associated with coarctation of the aorta.
Authors: T NJames, D AJackson
Journal: Circulation (1977)

A twenty-year-old carpenter died suddenly and unexpectedly nine years after surgical treatment of coarctation of the aorta. Both before and after surgery he had paroxysmal atrial fibrillation, T wave inversions in the ECG and persisting cardiac hypertrophy. At postmortem examination there was focal fibromuscular dysplasia narrowing the sinus node artery, but other small coronary arteries were normal and there was no focal fibrosis of the ventricular myocardium. Within the sinus node there were several small glomera surrounding branches of the sinus node artery. Pericardial fibrosis was present over much of the heart, including margins of the sinus node. The central fibrous body was thickened, particularly on the left, and the His bundle was smaller than normal in cross section. The His bundle appeared displaced toward the right. The artioventricular (A-V) node was split into an upper and lower half tenuously connected through the central fibrous body which divided it. In its lower half the A-V node was di...
Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium.
Authors: J LVanoverschelde, WWijns, CDepré, BEssamri, G RHeyndrickx, MBorgers, ABol, J AMelin
Journal: Circulation (1993)

BACKGROUNDEven in the absence of a previous myocardial infarction, patients with coronary artery disease often present with chronic regional wall motion abnormalities that are reversible spontaneously or after coronary revascularization. In these patients, regional dysfunction has been proposed to result either from prolonged postischemic dysfunction (myocardial stunning) or from adaptation to chronic hypoperfusion (myocardial hibernation). This study examines which of these two mechanisms is responsible for the chronic regional dysfunction often detected in patients with angina and noninfarcted collateral-dependent myocardium.METHODS AND RESULTSTwenty-six anginal patients (19 men; mean age, 60 +/- 9 years old) with chronic occlusion of a major coronary artery but without previous infarction were studied. Positron emission tomography was performed to measure absolute regional myocardial blood flow with 13N-ammonia at rest (n = 26) and after intravenous dipyridamole (n = 11). The kinetics of 18F-deoxyg...
Changes in ischemic blood flow distribution and dynamic severity of a coronary stenosis induced by beta blockade in the canine heart.
Authors: J DBuck, H FHardman, D CWarltier, G JGross
Journal: Circulation (1981)

The effects of equipotent beta 1-receptor-blocking doses of propranolol, metoprolol and sotalol on distal coronary pressure, stenosis resistance and regional myocardial blood flow (endo/epi) were studied in anesthetized dogs with a severe noncircumferential stenosis of the left circumflex coronary artery. No significant differences between the three beta blockers were observed for overall hemodynamics and regional myocardial blood flow. After drug treatment, subendocardial blood flow (0.47 +/- 0.05 to 0.78 +/- 0.05 ml/min/g) and endo/epi (0.67 +/-0.04 to 1.18 +/- 0.04) increased significantly (p less than 0.05) in the ischemic region. These changes were associated with a marked increase in distal coronary perfusion pressure and a decrease in heart rate. Resistance across the stenosis decreased significantly (p less than 0.05) after beta-receptor blockade (3.2 +/- 0.3 to 1.4 +/- 0.2 units). Atrial pacing to control heart rate only partially attenuated these changes. These results suggest that a favorable r...
Utrophin localization in normal and dystrophin-deficient heart.
Authors: FPons, ARobert, EFabbrizio, GHugon, J CCalifano, J AFehrentz, JMartinez, DMornet
Journal: Circulation (1994)

BACKGROUNDThe localization of dystrophin at the sarcolemma of cardiac skeletal fibers and cardiac Purkinje fibers has been described. Dystrophin deficiency produces clinical manifestations of disease in skeletal muscles and hearts of patients with Duchenne and Becker muscular dystrophy. Utrophin (or dystrophin-related protein), a dystrophin homologous protein, was found to be expressed in fetal muscles and reexpressed in dystrophin-deficient skeletal muscle fibers. We therefore examined utrophin expression in normal and in dystrophin-deficient hearts.METHODS AND RESULTSThe expression and subcellular distribution of utrophin was examined in cardiac muscle by immunoblot and immunofluorescence analysis in normal bovine heart compared with dystrophin. Utrophin expression was also examined in normal and dystrophin-deficient hearts of MDX mice. Three monoclonal antibodies reacting with dystrophin and utrophin solely or reacting with both proteins along with two polyclonal antibodies reacting with either utrophi...
Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes.
Authors: JBelik, A JHalayko, KRao, N LStephens
Journal: Circulation Research (1993)

To evaluate the smooth muscle mechanical and biochemical changes associated with persistent pulmonary hypertension syndrome of the newborn, we studied 31 fetal sheep in which the ductus arteriosus was ligated at 125 days of gestation. Sixty-one noninstrumented and six sham-operated fetuses served as controls. All animals were delivered by cesarean section at 137-140 days of gestation, and the experimental group had the ductus arteriosus ligated for 12 +/- 3 days. The ligated group demonstrated a higher mean (+/- SEM) pulmonary artery pressure (72.3 +/- 3.8 versus 54.1 +/- 2 mm Hg, p < 0.01) and right ventricular mean free wall weight (12.5 +/- 0.7 versus 6.8 +/- 0.3 g, p < 0.01) as compared with the sham-operated group. Significant changes in the pulmonary vascular smooth muscle of the ligated group were observed. The myosin content of vessels from the second through fifth generation demonstrated a significant increase in actin and myosin content (p < 0.01), but given their disproportional changes, the no...
Complications Of Endoscopic Ultrasound of the Upper GI Tract
Authors: I Budimir, T Pavić, N Baršić, M Živković, V Ratkajec, A Ratković, M Nikolić
Journal: Endoscopy (2021)

Aims The aim of this retrospective trial is to show complications of endoscopic ultrasound (EUS) of the upper GI tract. The data of complications of EUS in Southeastern Europe do not exist.
Effect of thyroid hormone on the expression of mRNA encoding sarcoplasmic reticulum proteins.
Authors: MArai, KOtsu, D HMacLennan, N RAlpert, MPeriasamy
Journal: Circulation Research (1991)

The purpose of this study was to determine the expression of genes encoding various sarcoplasmic reticulum components that are functionally coupled with calcium release, uptake, and storage function during cardiac hypertrophy induced by thyroid hormone. Hyperthyroidism was induced in two groups of rabbits by the injection of 200 micrograms/kg L-thyroxine (T4) daily for 4 days (T4-4-day group) and 8 days (T4-8-day group). Hypothyroidism was induced in another group of rabbits by adding 0.8 mg/ml propylthiouracil to the drinking water for 4 weeks. The relative expression level of mRNA encoding different sarcoplasmic reticulum proteins was determined by RNA slot blot and Northern blot analysis. In hyperthyroid hearts, the steady-state level of cardiac ryanodine receptor mRNA and sarcoplasmic reticulum cardiac/slow-twitch Ca(2+)-ATPase mRNA were both increased to 147% (T4-4-day group) and 186% (T4-8-day group) of control, respectively, but decreased to 71% and 75%, respectively, in hypothyroid ventricles. The...
Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathetic neural recordings.
Authors: D WFerguson, W JBerg, J SSanders, P JRoach, J SKempf, M GKienzle
Journal: Circulation (1989)

Digitalis glycosides exert both excitatory and inhibitory autonomic actions in animals and produce vasoconstriction in normal humans but produce vasodilation in heart failure patients. To determine whether or not these contrasting vascular responses are due to differing autonomic actions of the drug, we compared the responses to intravenous administration of Cedilanid-D (0.02 mg/kg) in eight normal subjects (mean age, 23 +/- 1 years) and eight patients with moderate-to-severe heart failure (mean age, 52 +/- 5 years, NYHA Class III-IV). Hemodynamics and efferent sympathetic nerve activity to muscle (MSNA) were measured during 5-minute periods before (control) and 20 minutes after drug administration. In the heart failure patients, Cedilanid-D significantly increased systolic and pulse pressures, whereas mean arterial pressure was unchanged. There was a decrease in right atrial pressure and a tendency for a decrease in pulmonary artery diastolic pressure with a slowing of heart rate. Cardiac index increased...
Scintigraphic assessment of regional cardiac adrenergic innervation.
Authors: M WDae, J WO'Connell, E HBotvinick, TAhearn, EYee, J PHuberty, HMori, M CChin, R SHattner, J MHerre
Journal: Circulation (1989)

To assess the feasibility of noninvasively imaging the regional distribution of myocardial sympathetic innervation, we evaluated the distribution of sympathetic nerve endings, using 123I metaiodobenzylguanidine (MIBG), and compared this with the distribution of myocardial perfusion, using 201Tl. Twenty dogs were studied: 11 after regional denervation, and nine as controls. Regional denervation was done by left stellate ganglion removal, right stellate ganglion removal, and application of phenol to the epicardial surface. Computer-processed functional maps displayed the relative distribution of MIBG and thallium in multiple projections in vivo and excised heart slices in all animals. In six animals, dual isotope emission computed tomograms were acquired in vivo. Tissue samples taken from innervated and denervated regions of the MIBG images were analyzed for norepinephrine content to validate image findings. Normal controls showed homogeneous and parallel distributions of MIBG and thallium in the major left...
Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS–MAPK Reactivation
Authors: Noritaka Tanaka, Jessica J. Lin, Chendi Li, Meagan B. Ryan, Junbing Zhang, Lesli A. Kiedrowski, Alexa G. Michel, Mohammed U. Syed, Katerina A. Fella, Mustafa Sakhi, Islam Baiev, Dejan Juric, Justin F. Gainor, Samuel J. Klempner, Jochen K. Lennerz, Giulia Siravegna, Liron Bar-Peled, Aaron N. Hata, Rebecca S. Heist, Ryan B. Corcoran
Journal: Cancer Discovery (2021)

Abstract Mutant-selective KRASG12C inhibitors, such as MRTX849 (adagrasib) and AMG 510 (sotorasib), have demonstrated efficacy in KRASG12C-mutant cancers, including non–small cell lung cancer (NSCLC). However, mechanisms underlying clinical acquired resistance to KRASG12C inhibitors remain undetermined. To begin to define the mechanistic spectrum of acquired resistance, we describe a patient with KRASG12C NSCLC who developed polyclonal acquired resistance to MRTX849 with the emergence of 10 heterogeneous resistance alterations in serial cell-free DNA spanning four genes (KRAS, NRAS, BRAF, MAP2K1), all of which converge to reactivate RAS–MAPK signaling. Notably, a novel KRASY96D mutation affecting the switch-II pocket, to which MRTX849 and other inactive-state inhibitors bind, was identified that interferes with key protein–drug interactions and confers resistance to these inhibitors in engineered and patient-derived KRASG12C cancer models. Interestingly, a novel, functionally distinct tricomplex KRASG12C active-state inhibitor RM-018 retained the ability to bind and inhibit KRASG12C/Y96D and could overcome resistance. Significance: In one of the first reports of clinical acquired resistance to KRASG12C inhibitors, our data suggest polyclonal RAS–MAPK reactivation as a central resistance mechanism. We also identify a novel KRAS switch-II pocket mutation that impairs binding and drives resistance to inactive-state inhibitors but is surmountable by a functionally distinct KRASG12C inhibitor. See related commentary by Pinnelli and Trusolino, p. 1874. This article is highlighted in the In This Issue feature, p. 1861
Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas
Authors: Gregory K. Friedman, James M. Johnston, Asim K. Bag, Joshua D. Bernstock, Rong Li, Inmaculada Aban, Kara Kachurak, Li Nan, Kyung-Don Kang, Stacie Totsch, Charles Schlappi, Allison M. Martin, Devang Pastakia, Rene McNall-Knapp, Sameer Farouk Sait, Yasmin Khakoo, Matthias A. Karajannis, Karina Woodling, Joshua D. Palmer, Diana S. Osorio, Jeffrey Leonard, Mohamed S. Abdelbaki, Avi Madan-Swain, T. Prescott Atkinson, Richard J. Whitley, John B. Fiveash, James M. Markert, G. Yancey Gillespie
Journal: New England Journal of Medicine (2021)

Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue.
Metformin pretreatment rescues olfactory memory associated with subependymal zone neurogenesis in a juvenile model of cranial irradiation
Authors: Daniel Derkach, Tarlan Kehtari, Matthew Renaud, Mohsen Heidari, Nishanth Lakshman, Cindi M. Morshead
Journal: Cell Reports Medicine (2021)

Cranial irradiation (IR) is an effective adjuvant therapy in the treatment of childhood brain tumors but results in long-lasting cognitive deficits associated with impaired neurogenesis, as evidenced in rodent models. Metformin has been shown to expand the endogenous neural stem cell (NSC) pool and promote neurogenesis under physiological conditions and in response to neonatal brain injury, suggesting a potential role in neurorepair. Here, we assess whether metformin pretreatment, a clinically feasible treatment for children receiving cranial IR, promotes neurorepair in a mouse cranial IR model. Using immunofluorescence and the in vitro neurosphere assay, we show that NSCs are depleted by cranial IR but spontaneously recover, although deficits to proliferative neuroblasts persist. Metformin pretreatment enhances the recovery of neurogenesis, attenuates the microglial response, and promotes recovery of long-term olfactory memory. These findings indicate that metformin is a promising candidate for further preclinical and clinical investigations of neurorepair in childhood brain injuries.
Mechanism of decreased left ventricular stroke volume during inspiration in man.
Authors: MKaram, R AWise, T KNatarajan, SPermutt, H NWagner
Journal: Circulation (1984)

Radionuclide ventriculography was performed in 15 healthy subjects during quiet breathing and during inspiration against a 24 cm H2O threshold load with a respiratory gating technique. Inspiratory threshold loading caused an inspiratory decrease in ejection fraction from 64% to 59% (p less than .001). Stroke counts proportional to stroke volume decreased by 9.6% (p less than .02) due to an increase in end-systolic counts of 15.9% (p less than .05). End-diastolic counts decreased in four subjects and increased in three subjects, but the mean counts did not change significantly. These findings suggest that negative pleural pressure causes an impediment to left ventricular ejection comparable to an increase in arterial pressure. Respiratory gating of radionuclide ventriculography during loaded breathing is suggested as a controlled stress on the ventricle for diagnostic purposes.
Letter by Leischik et al Regarding Article, “Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study”
Authors: Roman Leischik, Fabian Sanchis-Gomar, Alejandro Lucia
Journal: Circulation (2016)

conditions.Likewise, appropriate measures, eg, allowing sufficient recovery time between severe competitions or hard training sessions, are necessary to prevent immune deficiency with subsequent risk of cardiac complications (not triggered by the physiological-hemodynamic stress of exercise per se) and should be excluded in any cardiac resonance imaging study conducted with athletes.diSCLoSuRES
Diastolic perfusion time at ischemic threshold in patients with stress-induced ischemia.
Authors: GFerro, LSpinelli, CDuilio, MSpadafora, FGuarnaccia, MCondorelli
Journal: Circulation (1991)

BACKGROUNDTo evaluate the relevance of diastolic perfusion time on the mechanisms underlying stress-induced ischemia, 16 patients with coronary artery disease and seven patients with syndrome X underwent five randomized stress tests (upright and supine exercise with and without therapy, transesophageal atrial pacing).METHODS AND RESULTSExercise duration Time to 0.1 mV ST segment depression, heart rate, rate-pressure product, and diastolic perfusion time were evaluated for each patient during stress tests. In both groups, variability coefficients of the above-mentioned parameters were not different at rest. At ischemic threshold (0.1 mV ST segment depression) in patients with coronary artery disease, the variability coefficient of exercise duration (40.1 +/- 22.2) was significantly higher (p less than 0.0001) than those of heart rate (12.8 +/- 2.9), rate-pressure product (14.8 +/- 3.3), and diastolic perfusion time (0.39 +/- 0.1). The variability coefficient of diastolic perfusion time was also significant...
Vasodilator responses of coronary resistance arteries of exercise-trained pigs.
Authors: J MMuller, P RMyers, M HLaughlin
Journal: Circulation (1994)

BACKGROUNDThe purpose of this study was to test the hypothesis that vasodilator responses of porcine coronary resistance arteries are increased by exercise training.METHODS AND RESULTSYucatan miniature swine were randomly divided into groups of exercise-trained (ET) and sedentary (SED) control pigs. ET pigs were placed on a progressive treadmill training program lasting 16 to 20 weeks, and SED pigs remained inactive during the same time period. Coronary resistance arteries 64 to 157 microns in diameter were isolated for in vitro evaluation of relaxation responses to the endothelium-independent dilators sodium nitroprusside (1 x 10(-10) to 1 x 10(-4) mol/L) and adenosine (1 x 10(-10) to 1 x 10(-5) mol/L) and to bradykinin (1 x 10(-13) to 3 x 10(-7) mol/L), an endothelium-dependent agent. Relaxation responses to adenosine and sodium nitroprusside were not altered by exercise training. Endothelium-dependent relaxation to bradykinin was enhanced in coronary resistance arteries from ET pigs (IC50: ET, 0.07 +/-...
Endoscopic Submucosal Dissection Of Colitis-Associated Dysplasia – 8 Year Prospective Study In a Tertiary Centre
Authors: A Dhillon, A Ahmad, S Thomas-Gibson, A Wilson, N Arebi, A Hart, B Saunders, N Suzuki
Journal: Endoscopy (2021)

Aims Endoscopic submucosal dissection (ESD) is therapeutic option for colitis-associated dysplasia and offers en bloc resection, allowing precise pathological assessment. Previous studies have shown relatively high local and metachronous recurrence rates but long-term outcome data is lacking.
Cardiovascular response to static exercise during selective autonomic blockade in the conscious cat.
Authors: GDiepstra, WGonyea, J HMitchell
Journal: Circulation Research (1980)

Selective autonomic blockade with propranolol, atropine, and combined atropine and propranolol was used to elucidate the role of the autonomic nervous system in the cardiovascular responses that occur during voluntary static exercise in conscious cats. Seven animals were operantly conditioned to hold a bar against a fixed resistance for a constant time of 15 seconds and were then placed on an exercise regimen which consisted of small weekly increments in resistance. With a resistance of 100 g. heart rate (HR) increased by 7%. With exercise at a resistance of 200 g, HR (10%), left ventricle systolic pressure (LVSP, 16%), and LV max dp/dt (18%) increased, and significant changes in these parameters persisted throughout the remainder of the training period. beta-Adrenergic receptor blockade with propranolol abolished the increase in LV max dp/dt, whereas HR and LVSP increased. After atropine, the increase in HR was abolished at the early training stages, whereas LVSP and LV max dp/dt increased. Administratio...
A new approach for local intravascular drug delivery. Iontophoretic balloon.
Authors: AFernández-Ortiz, B JMeyer, AMailhac, EFalk, LBadimon, J TFallon, VFuster, J HChesebro, J JBadimon
Journal: Circulation (1994)

BACKGROUNDCatheter-based systems are being developed to deliver drugs directly into the vessel wall. Pressure-mediated trauma and lack of homogeneous delivery are key limitations of these approaches.METHODS AND RESULTSWe studied a new catheter-based delivery system that uses electrical current to force the drug into the vessel wall. The in vivo feasibility of this approach has been assessed by delivering 125I-hirudin into porcine carotid arteries. Vascular levels of hirudin after active iontophoresis (4 mA/cm2, 5 minutes) were 80-fold greater than those achieved by passive diffusion (without electricity). Tissue hirudin levels declined over time; by 1 hour after delivery, 80% of the drug had left the vessel wall, and by 3 hours later, the levels of hirudin within the wall were similar to those achieved by passive diffusion. Autoradiography revealed distribution of the drug throughout the entire circumference of the arterial wall within the intima, media, and adventitia. Iontophoresis-mediated vessel wall ...
Thoracic Extradural Paraganglioma Localized on 68Ga-DOTANOC PET/CT
Authors: Hemant Sachani, Madhavi Tripathi, Kumble Seetharama Madhusudan, Kapil Semalti, Shiv Shanker, Sreedharan Thankarajan ArunRaj, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2021)

Abstract We present the case of a 33-year-old woman with complaints of headache and palpitations with raised urinary catecholamines. Ultrasound of the abdomen was noncontributory, and the patient was referred for 68 Ga-DOTANOC PET/CT, which revealed tracer accumulation in the thecal sac/spinal canal at D5–D7 level, suggestive of a thoracic paraganglioma. MRI of the spine subsequently confirmed the presence of an extradural mass in the spinal canal extending from D4 to D8.
The effect of the carotid sinus baroreceptor reflex on blood flow and volume redistribution in the total systemic vascular bed of the dog.
Authors: M JBrunner, A AShoukas, C LMacAnespie
Journal: Circulation Research (1981)

To quantify the relative contribution of blood flow redistribution and active changes in vascular capacity in the regulation of cardiac output, blood flow and volumes in two parallel vascular beds were measured in response to varying carotid sinus pressures. In nine dogs, carotid sinuses were isolated and intrasinus pressure was controlled. Two external reservoirs were placed between the caval veins and the right heart to measure changes in vascular capacity in splanchnic and extrasplanchnic vascular beds. At intrasinus pressures of 50 and 200 mm Hg, we have simultaneously measured arterial resistances, compliances, changes in flows, and unstressed vascular volume, and time constants of venous drainage in the splanchnic and extrasplanchnic vascular beds. Compliances and time constants of venous drainage were found to be nearly equal in the two beds. A decrease in intrasinus pressure from 200 to 50 mm Hg resulted in a small redistribution of blood flow (about 5% of cardiac output) from the extrasplanchni...
Recommendations for standardization and specifications in automated electrocardiography: bandwidth and digital signal processing. A report for health professionals by an ad hoc writing group of the Committee on Electrocardiography and Cardiac Electrophysiology of the Council on Clinical Cardiology, American Heart Association.
Authors: J JBailey, A SBerson, AGarson, L GHoran, P WMacfarlane, D WMortara, CZywietz
Journal: Circulation (1990)