tbuckley/cabot-search huggingface dataset:
Endogenous adenosine blunts beta-adrenoceptor-mediated inotropic response in hypoperfused canine myocardium.
Authors: HSato, MHori, MKitakaze, STakashima, MInoue, AKitabatake, TKamada
Journal: Circulation (1992)

BACKGROUNDAdenosine attenuates beta-adrenoceptor-mediated inotropic responses through GTP-binding protein in vitro. The goal of the present study was to test the hypothesis that endogenous adenosine released from the ischemic myocardium blunts the inotropic response to beta-adrenergic stimulation.METHODS AND RESULTSIn 45 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. Coronary perfusion pressure was reduced so that coronary blood flow was decreased to 60% of the basal level by partial occlusion of the bypass tube, and the reduced coronary perfusion pressure was kept constant thereafter. Inotropic responses to isoproterenol were assessed by fractional shortening of the myocardium in the perfused area. After the onset of hypoperfusion, lactate extraction ratio (18.8 +/- 1.2%) and fractional shortening (20.7 +/- 1.1%) were significantly decreased to -8.4 +/- 8.0% and 5.9 +/- 1.5%, respectively, and coronary arteriovenou...
Hormone receptors of the baboon cardiovascular system. Biochemical characterization of myocardial cytoplasmic androgen receptors.
Authors: A LLin, H CMcGill, S AShain
Journal: Circulation Research (1981)

Using the synthetic androgen R1881 (17 beta-hydroxy-17alpha-methyl-estra-4, 9, 11-trien-3-one) as probe, we identified cytoplasmic androgen receptors in baboon myocardium. The relative binding affinity of selected steroids for the androgen receptor was R1881, 100%; 5alpha-dihydrotestosterone, 32.6%; testosterone, 29.6%, progesterone, 7.2%; R5020, 1.0%; and estradiol-17beta, 5.8%. The androgen receptor migrated on low ionic strength linear sucrose density gradients as a macromolecule with a sedimentation coefficient of 8.5S. Saturation analysis performed at 2 degrees C (available sites) showed that the androgen receptor content of baboon myocardial cytoplasmic extracts was 5.9 +/- 1.4 fmol/mg protein and that the dissociation constant for R1881 was 1.16 +/- 0.30 nM. These cytoplasmic androgen receptors are indicated to be physiologically functional by previous autoradiographic studies (McGill et al., 1980; McGill and Sheridan, 1981) that showed localization of radioisotope in nuclei of myocardial fibers fo...
Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits.
Authors: HKumagai, HSuzuki, MIchikawa, YMatsumura, MJimbo, MRyuzaki, TSaruta
Journal: Circulation Research (1993)

This study was designed to elucidate how central and peripheral arginine vasopressin (AVP) interacts with the sympathetic nervous system and the renin-angiotensin system to maintain blood pressure in two-kidney, one-clip hypertensive rabbits. We recorded renal sympathetic nerve activity (RSNA) in the conscious state as an index of sympathetic nervous system function. The changes in mean arterial pressure, heart rate, and RSNA were recorded continuously for 60 minutes after intravenous administrations of captopril (2.5 mg/kg) and nicardipine (3.2 micrograms.kg-1.min-1) in eight identical rabbits. Despite equivalent reductions in mean arterial pressure (10 +/- 1 mm Hg), the increase in RSNA was significantly larger with captopril than that with nicardipine, and the plasma concentration of AVP was elevated (from 100% to 255 +/- 24%) with captopril. Mean arterial pressure was reduced, and RSNA was increased by intravenous infusion of AVP antagonist d(CH2)5Tyr(Me)AVP (n = 8), whereas vertebral artery infusion ...
Disruption of microtubules as an early sign of irreversible ischemic injury. Immunohistochemical study of in situ canine hearts.
Authors: KIwai, MHori, AKitabatake, HKurihara, KUchida, MInoue, TKamada
Journal: Circulation Research (1990)

Structural disruption of the cytoskeleton may be involved in irreversible ischemic injury. In the present study, ischemic changes in microtubules during various periods of myocardial ischemia were studied with an immunohistochemical technique in open-chest dogs. In intact myocardium, microtubules were stained as a filamentous network throughout cytoplasm and a circular network around the nucleus, which disappeared with colchicine treatment. In brief ischemia of less than 15 minutes, microtubule patterns were unaltered. After 20 minutes, however, characteristic microtubule stains were partly lost in patchy lesions. As an increase in ischemic period, lesions of loss of microtubule stains were increased in number and size. After 120 minutes of reperfusion following 60 minutes of ischemia, the lesions with intact actin filaments but with disrupted microtubules were replaced by the severely injured cells in which the regular myofibrillar registrations were distinctly disrupted. After 24 hours of reperfusion fo...
Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1
Authors: Sander F. Garrelfs, Yaacov Frishberg, Sally A. Hulton, Michael J. Koren, William D. O’Riordan, Pierre Cochat, Georges Deschênes, Hadas Shasha-Lavsky, Jeffrey M. Saland, William G. van’t Hoff, Daniel G. Fuster, Daniella Magen, Shabbir H. Moochhala, Gesa Schalk, Eva Simkova, Jaap W. Groothoff, David J. Sas, Kristin A. Meliambro, Jiandong Lu, Marianne T. Sweetser, Pushkal P. Garg, Akshay K. Vaishnaw, John M. Gansner, Tracy L. McGregor, John C. Lieske
Journal: New England Journal of Medicine (2021)

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase.
Prenatal diagnosis and postnatal management of critical aortic stenosis.
Authors: J CHuhta, R JCarpenter, K JMoise, R LDeter, D AOtt, D GMcNamara
Journal: Circulation (1987)

Fetal echocardiography has yet to have an impact on the treatment of congenital heart disease. Critical aortic valve stenosis was diagnosed by echocardiography before birth in a 35 week gestation fetus. The risks to the fetus and mother associated with prolonged rupture of membranes prompted their transport to a hospital with cardiac surgical and high-risk perinatal facilities. Prenatal and postnatal echocardiographic findings agreed regarding the diagnostic criteria for critical aortic stenosis and primary forms of cardiomyopathy were excluded. Results of fetal Doppler examination were consistent with valvular aortic stenosis and excluded mitral regurgitation. Determination of the left ventricular size excluded ventricular hypoplasia. The infant was delivered by cesarean section and underwent successful emergency aortic valvotomy at 12 h of age. Fetal echocardiography, in combination with a multidisciplinary postnatal approach, can be used in the successful treatment of a severe form of congenital heart ...
Microvascular spasm in the cardiomyopathic Syrian hamster: a preventable cause of focal myocardial necrosis.
Authors: S MFactor, TMinase, SCho, RDominitz, E HSonnenblick
Journal: Circulation (1982)

The cardiomyopathic Syrian hamster develops focal myocardial necrosis beginning at 1 month of age, which leads to eventual ventricular failure within 1 year. The pathogenesis of this myocytolytic necrosis is unknown. Based on the nature of the cell necrosis, cytochemical evidence of vascular alterations, and the sensitivity of the hamsters to catecholamines and other vasoactive substances, we believe that the cardiomyopathy may be mediated by abnormalities of the microcirculation. Nonetheless, until the present study, no significant changes have been observed in these vessels. To elucidate the pathogenesis of this disease, we perfused living cardiomyopathic hamsters with silicone rubber solutions, which revealed numerous areas of microvascular constriction, diffuse vessel narrowing and luminal irregularity. Fixed structural lesions in these vessels could not be demonstrated. Pretreatment of young hamsters with verapamil during the period when they normally develop myocardial necrosis prevented myocytolyti...
Clinical judgment and statistics. Lessons from a simulated randomized trial in coronary artery disease.
Authors: K LLee, J FMcNeer, C FStarmer, P JHarris, R ARosati
Journal: Circulation (1980)

A simulated randomized clinical trial in coronary artery disease was conducted to illustrate the need for clinical judgment and modern statistical methods in assessing therapeutic claims in studies of complex diseases. Clinicians should be aware of problems that occur when a patient sample is subdivided and treatment effects are assessed within multiple prognostic categories. In this example, 1073 consecutive, medically treated coronary artery disease patients from the Duke University data bank were randomized into two groups. The groups were reasonably comparable and, as expected, there was no overall difference in survival. In a subgroup of 397 patients characterized by three-vessel disease and an abnormal left ventricular contraction, however, survival of group 1 patients was significantly different from that of group 2 patients. Multivariable adjustment procedures revealed that the difference resulted from the combined effect of small imbalances in the distribution of several prognostic factors. Anoth...
Research on neck dissection for oral squamous-cell carcinoma: a bibliometric analysis
Authors: Zhou Jiang, Chenzhou Wu, Shoushan Hu, Nailin Liao, Yingzhao Huang, Haoran Ding, Ruohan Li, Yi Li
Journal: International Journal of Oral Science (2021)

Neck dissection for oral squamous-cell carcinoma (OSCC) is a clinically controversial issue and has therefore been the subject of abundant research. However, no one has performed a bibliometric study on this topic to date. The aim of this study was to assess the development of research on neck dissection for OSCC in terms of the historical evolution, current hotspots and future directions, particularly including research trends and frontiers from 2010 to 2019. Literature records related to research on neck dissection for OSCC were retrieved from the Web of Science Core Collection (WoSCC). CiteSpace was used as a tool to perform a bibliometric analysis of this topic. The survey included 2 096 papers. "Otorhinolaryngology" was the most popular research area. The most active institutions and countries were Memorial Sloan Kettering Cancer Center and the USA, respectively. Shah J.P. was the most cited author. Among the six identified "core journals", Head & Neck ranked first. The top three trending keywords were 'invasion', 'upper aerodigestive' and 'negative neck'. 'D'Cruz AK (2015)' was the most cited and the strongest burst reference in the last decade. The study evaluated the effect on survival of elective versus therapeutic neck dissection in patients with lateralized early-stage OSCC. The depth of invasion and the management of N0 OSCC were research frontiers in this field. The present study provides a comprehensive bibliometric analysis of research on neck dissection for OSCC, which will assist investigators in exploring potential research directions.
Self-Expandable Metal Stenting For Esophageal Fistula Closure: Increasing The Odds Of Success
Authors: R de Sousa Magalhães, T Capela, T Cúrdia Gonçalves, P Boal Carvalho, B Rosa, J Cotter
Journal: Endoscopy (2021)

Aims Esophageal self-expanding metal stent (SEMS) can be considered for treatment of anastomotic leaks and fistulas.
Relative contributions of arginine vasopressin and angiotensin II to maintenance of systemic arterial pressure in the anesthetized water-deprived rat.
Authors: C EAndrews, B MBrenner
Journal: Circulation Research (1981)

We used a structural analogue of arginine vasopressin (AVP) and investigated the role of AVP in the maintenance of mean arterial pressure (AP) in anesthetized, water-deprived rats. The administration of [1(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 4-valine-8-D-arginine] vasopressin, d(CH2)5VDAVP, completely inhibited to 30-40 mma Hg rise in AP which normally accompanied the administration of 50 mU exogenous AVP (group 1). Thus, d(CH2)5VDAVP is a specific antagonist of the vascular effects of AVP. d(CH2)5VDAVP failed to significantly alter AP in water diuretic rats (group 3) and was without effect on urine osmolality during water diuresis or antidiuresis. However, bolus injection of d(CH2)5VDAVP into water deprived rats (group 2) prompted an abrupt fall in AP from 112 +/- 4 to 94 +/- 4 mm Hg (P less than 0.001). This fall in AP was transient, with return of AP to 110 +/- 4 mm Hg within 15 minutes. Administration of saralasin, an angiotensin II antagonist, not only prevented the compensati...
Targeting RGD-binding integrins as an integrative therapy for diabetic retinopathy and neovascular age-related macular degeneration
Authors: Inge Van Hove, Tjing-Tjing Hu, Karen Beets, Tine Van Bergen, Isabelle Etienne, Alan W. Stitt, Elke Vermassen, Jean H.M. Feyen
Journal: Progress in Retinal and Eye Research (2021)

Integrins are a class of transmembrane receptors that are involved in a wide range of biological functions. Dysregulation of integrins has been implicated in many pathological processes and consequently, they are attractive therapeutic targets. In the ophthalmology arena, there is extensive evidence suggesting that integrins play an important role in diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, dry eye disease and retinal vein occlusion. For example, there is extensive evidence that arginyl-glycyl-aspartic acid (Arg-Gly-Asp; RGD)-binding integrins are involved in key disease hallmarks of DR and neovascular AMD (nvAMD), specifically inflammation, vascular leakage, angiogenesis and fibrosis. Based on such evidence, drugs that engage integrin-linked pathways have received attention for their potential to block all these vision-threatening pathways. This review focuses on the pathophysiological role that RGD-binding integrins can have in complex multifactorial retinal disorders like DR, diabetic macular edema (DME) and nvAMD, which are leading causes of blindness in developed countries. Special emphasis will be given on how RGD-binding integrins can modulate the intricate molecular pathways and regulate the underlying pathological mechanisms. For instance, the interplay between integrins and key molecular players such as growth factors, cytokines and enzymes will be summarized. In addition, recent clinical advances linked to targeting RGD-binding integrins in the context of DME and nvAMD will be discussed alongside future potential for limiting progression of these diseases.
Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale.
Authors: LGoldman, BHashimoto, E FCook, ALoscalzo
Journal: Circulation (1981)

Reproducibility and validity are prerequisites for a useful clinical scale. We therefore prospectively tested the reproducibility and validity of the New York Heart Association criteria and the Canadian Cardiovascular Society criteria for the assessment of cardiac functional class and compared these criteria with a new Specific Activity Scale based on the metabolic costs of specific activities. The New York Heart Association estimates made by two physicians had a reproducibility of only 56%, and only 51% of the estimates agreed with treadmill exercise performance. Functional estimates based on the Canadian Cardiovascular Society criteria were significantly more reproducible (73%), but not significantly more valid. The Specific Activity Scale was as reproducible as the Canadian Cardiovascular Society criteria, and its 68% validity was significantly higher than the validities of the other systems. The easily administered Specific Activity Scale was equally reproducible and valid when used by a nonphysician....
Intracoronary alpha 2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise.
Authors: RSeitelberger, B DGuth, GHeusch, J DLee, KKatayama, JRoss
Journal: Circulation Research (1988)

Studies on the role of alpha-adrenergic constrictor tone in the coronary vascular bed during ischemia were performed in dogs running on a treadmill. The animals were instrumented with a left ventricular pressure transducer, and regional systolic wall thickening (%WTh) was assessed by sonomicrometry in the anterior and posterior walls of the left ventricle. An intracoronary catheter was implanted chronically in the circumflex coronary artery, and a hydraulic cuff was placed proximally around the artery. After beta-adrenergic blockade with propranolol (0.8 mg/kg i.v.), acute stenosis of the coronary artery was performed during running in five dogs to induce severe regional myocardial dysfunction in the posterior wall. Intracoronary infusion of the selective alpha 2-adrenergic blocking agent idazoxan (80 micrograms/kg) improved %WTh in the ischemic region from 5.1 +/- 1.6 to 10.8 +/- 2.8% (p less than 0.05), without any significant effect on the anterior wall. Blood flow to the subendocardium of the posterio...
Detection of myocardial infarct extension by CK-B radioimmunoassay.
Authors: MRothkopf, JBoerner, M JStone, T CSmitherman, L MBuja, R WParkey, J TWillerson
Journal: Circulation (1979)

Myocardial infarct extension after the acute event was defined as a second reise in the myocardial isoenzyme of serum creatine kinase (CK-B) after the initial return of CK-B to normal values. In 43 patients with acute myocardial infarcts, CK-B was measured by radioimmunoassay every 12 hours for 14 days. Nineteen patients had anterior transmural myocardial infarcts AMI, 14 had inferior transmural myocardial infarcts (IMI) and 10 had subendocardial myocardial infarcts (SEMI). Infarct extension as detectd by a second rise in serum CK-B occurred in six patients (32%) with AMI, two (14%) with IMI and two (20%) with SEMI; these differences are not statistically significant. Infarct extension for all patients combined was 23%. Four patients with AMI also had infarct extension as determined by recurrent chest pain. ECG alterations and other enzyme changes. In the other six, the infarct extension was undetected clinically. Four patients with AMI and infarct extension died within 3 weeks after hospitalization. We d...
Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs.
Authors: J DRutherford, S FVatner, EBraunwald
Journal: Circulation (1981)

The effects of aminophylline, 1 mg/kg/min infused intravenously for 10 minutes, were examined on left ventricular (LV) diameter, pressure, an indexes of myocardial contractility, as well as systemic, coronary and regional hemodynamics in conscious dogs. Aminophylline increased mean arterial pressure 12 +/- 2%, LV systolic pressure 8 +/- 1%, LV dP/dt 20 +/- 2%, velocity of myocardial fiber shortening 13 +/- 2% and heart rate 5 +/- 2%, and reduced LV end-diastolic diameter 2 +/- 0.5%. Vascular resistance rose in the systemic bed 13 +/- 5%, the coronary bed 26 +/- 3%, the mesenteric bed 26 +/- 5% and the iliac bed 36 +/- 4%, but did not rise in the renal bed. Both beta-adrenergic receptor blockade with propranolol and chronic treatment with reserpine attentuated but did not abolish the positive inotropic response induced by aminophylline. Alpha-adrenergic receptor blockade with phentolamine prevented aminophylline-induced vasoconstriction in the systemic, coronary, mesenteric and iliac beds. In contrast to t...
Improved housing versus usual practice for additional protection against clinical malaria in The Gambia (RooPfs): a household-randomised controlled trial
Authors: Margaret Pinder, John Bradley, Musa Jawara, Muna Affara, Lesong Conteh, Simon Correa, David Jeffries, Caroline Jones, Balla Kandeh, Jakob Knudsen, Yekini Olatunji, Elisa Sicuri, Umberto D'Alessandro, Steve W Lindsay
Journal: The Lancet Planetary Health (2021)

In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. We aimed to assess whether children in The Gambia received an incremental benefit from improved housing, where current best practice of insecticide-treated nets, indoor residual spraying, seasonal malaria chemoprevention in children younger than 5 years, and prompt treatment against clinical malaria was in place.
The pH of spontaneously beating cultured rat heart cells is regulated by an ATP-calmodulin-dependent Na+/H+ antiport.
Authors: P LWeissberg, P JLittle, E JCragoe, ABobik
Journal: Circulation Research (1989)

We investigated the mechanisms by which spontaneously beating cultured rat ventricular cells regulate intracellular pH (pHi). Specifically, the relative contributions of the Na+/H+ antiport, Cl-/HCO3- exchange, ATP, and calmodulin-dependent processes in regulating the pHi of cells loaded with the intracellular fluorescent pH indicator BCECF were investigated. The pHi of ventricular cells bathed in HEPES-buffered medium averaged 7.30 +/- 0.02. Subsequent exposure of the cells to CO2-HCO3- -buffered medium resulted in intracellular acidification followed by recovery to pHi levels approximately 0.1 pH units lower than in controls. Recovery was inhibited by the Na+/H+ antiport inhibitor 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The recovery from intracellular acidification, induced by a 15-mM ammonium chloride prepulse, was also dependent solely upon activation of the Na+/H+ antiport. Recovery was dependent upon extracellular sodium, was completely inhibited by EIPA, and could be modulated by changes in extrac...
The effect of changing interpulse intervals on the negative chronotropic response to repetitive bursts of vagal stimuli in the dog.
Authors: M NLevy, SWexberg, CEckel, HZieske
Journal: Circulation Research (1978)

The chronotropic responses to repetitive bursts of vagal stimulation were determined in open-chest, anesthetized dogs. Either 5 or 10 electrical pulses were included in each stimulus burst, and the interpulse interval (deltat) was varied over the range of 5 to 150 msec. As the frequency of the stimulus bursts was progressively changed, the sinoatrial (SA) nodal pacemaker cells became synchronized with the repetitive bursts of stimuli over a certain range of burst frequencies. The magnitude of this frequency range varied with deltat. For 5 and 10 pulses/burst, the values of deltat that produced the greatest magnitude of this frequency range were 30.2 and 24.3 msec, respectively. Also, over the range of values of deltat from 5 to 50 msec, the magnitude of the negative chronotropic effect of the vagal stimulus burst varied directly with deltat. It is likely that, as the interpulse interval is increased within the range of values, either more acetylcholine is released from the vagal nerve endings per pulse or...
Efferent sympathetic and vagal innervation of the canine right ventricle.
Authors: MIto, D PZipes
Journal: Circulation (1994)

BACKGROUNDThe functional pathways of efferent sympathetic and vagal innervation to the right ventricle (RV) might be important in a variety of disease states that involve the RV wall. The purpose of this study was to investigate those pathways.METHODS AND RESULTSWe determined the effects of phenol and endocardial radiofrequency ablation applied to the RV anterolateral wall and outflow tract on effective refractory period (EPR) shortening during bilateral ansae subclaviae stimulation and ERP lengthening during bilateral vagal stimulation. We found that efferent sympathetic axons to the RV are located in the superficial subepicardium and that lateral sites receive sympathetic innervation predominantly from the lateral margin of the RV near the AV groove. Medial sites close to the left anterior descending coronary artery (LAD) receive sympathetic innervation from both the right lateral atrioventricular (AV) groove and regions near the LAD. At the RV outflow tract, some sympathetic fibers are located intramur...