tbuckley/cabot-search huggingface dataset:
Age-related changes in beta-adrenergic neuroeffector systems in the human heart.
Authors: MWhite, RRoden, WMinobe, M FKhan, PLarrabee, MWollmering, J DPort, FAnderson, DCampbell, A MFeldman
Journal: Circulation (1994)

BACKGROUNDAging decreases cardiac beta-adrenergic responsiveness in model systems and in humans in vivo. The purpose of this study was to comprehensively evaluate the age-related changes in the beta-receptor-G protein-adenylyl cyclase complex in nonfailing human hearts.METHODS AND RESULTSTwenty-six nonfailing explanted human hearts aged 1 to 71 years were obtained from organ donors and subjected to pharmacological investigation of beta-adrenergic neuroeffector systems. When the population was subdivided into the 13 youngest and 13 oldest subjects, total beta-receptor density assessed by maximum [125I]ICYP binding (beta max) was reduced in older hearts by 37% in left ventricles and 31% in right ventricles (both P < .05), and the downregulation was confined to the beta 1 subtype (r = .78 left ventricle beta 1 density versus donor age). Older donor hearts exhibited a 3- to 4-fold rightward shift of ICYP-isoproterenol (ISO) competition curves and demonstrated 43% fewer receptors in a high-affinity agonist bin...
Time to scrap creatinine clearance?
Authors: D Lui, P J Ell
Journal: BMJ (1986)

new glomerular filtration rate may be calculated using the direct linear relation between glomerular filtration rate and the reciprocal of the plasma creatinine.This approach would prevent errors arising from the interpretation of the plasma creatinine value alone by the application of an inappropriate reference range but allows changes in renal function to be noticed promptly so that treatment may be started.Recent developments in enzymatic methods for measuring plasma creatinine concentrations are claimed to offer improved reproducibility, par- ticularly for values within the present reference range (coefficient of variation 3-3% at 67 pmol/l (0-76 mg/100 ml)3), and reduced non-specific interference from ketone bodies, antibiotics, etc.Although these methods are not yet widely used in the near future they may, in conjunction with more complete reference data, enable plasma creatnine values to be interpreted more reliably, particularly those within the present normal range.Until then a balanced approach to assessing renal function using plasma creatinine concentrations, supplemented with clearance measure- ments when indicated, would be appropriate.
Local changes in myosin types in diseased human atrial myocardium: a quantitative immunofluorescence study.
Authors: PBouvagnet, JLéger, C ADechesne, GDureau, MAnoal, J JLéger
Journal: Circulation (1985)

Two monoclonal antibody groups were prepared from adult human atrial and ventricular myosin heavy chains. Using these two groups, we were able to identify two myosin variants in human atria and to classify human atrial fibers into alpha-, mixed, or beta-fibers according to the reactivity of the two monoclonal antibody groups to alpha- and beta-myosin heavy chains of normal young and hypothyroid rat ventricles, respectively. The alpha-fiber percentage of the left atria in two normal human hearts was 15% higher than in the right atria. The auricles contained two to three times more alpha-fibers than beta-fibers, whereas the proportion was reversed in the crista terminalis. The mean fiber diameter of the alpha- and beta-fibers was 13.6 +/- 3 micron. A complete alpha- to beta-fiber transition was observed in all atrial regions of two hearts with severe ventricular myocardial infarction; a moderate alpha- to beta-fiber transition was observed only in the left atria of two hearts with primary congestive cardiom...
We've only just begun
Authors: William G. Lycan
Journal: Behavioral and Brain Sciences (1995)

Abstract Block contends that the concept of consciousness is a mongrel concept and that researchers go astray by conflating different notions of “consciousness.” This is certainly true. In fact, it is truer than Block acknowledges, because his own notion of P-consciousness runs together two, or arguably three, quite different and separable features of a sensory state.
Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise.
Authors: PThéroux, MBaird, MJuneau, WWarnica, PKlinke, WKostuk, PPflugfelder, ELavallée, CChin, EDempsey
Journal: Circulation (1991)

BACKGROUNDSilent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear.METHODS AND RESULTSSixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minut...
160P Non-interventional cohort study on patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping in the US
Authors: A. Ryder, D. Oksen, A. Vlahiotis, E. Boutmy, L.A. Dietz, C. Stroh, A. Johne, M. Walker
Journal: Journal of Thoracic Oncology (2021)
Calcium-dependent enhancement of myocardial diastolic tone and energy utilization dissociates systolic work and oxygen consumption during low sodium perfusion.
Authors: D GRenlund, E GLakatta, E DMellits, GGerstenblith
Journal: Circulation Research (1985)

The relationships and correlations among functional, metabolic, and ionic consequences of low sodium perfusion were studied in isovolumic, retrograde-aortic perfused working rat hearts by 31P nuclear magnetic resonance, oxygen consumption, and atomic absorption spectrometry. Reduction of perfusate sodium from 144 to 74, 51, 39, and 25 mM in four separate groups of hearts via lithium substitution for 15 minutes decreased cell sodium to mean values of 62, 51, 43, and 36 mumol/g dry weight, respectively (P less than 0.001 vs. control of 107). There was a transient rise and then a fall in developed pressure and a decline in phosphocreatine and adenosine triphosphate, all of which were graded and correlated with perfusate sodium (P less than 0.01 for all parameters vs. perfusate sodium). This was accompanied by a 2- to 7-fold elevation of diastolic pressure while oxygen consumption remained near control levels. All parameters except adenosine triphosphate returned toward baseline values when normal perfusate s...
Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery.
Authors: YMiyoshi, YNakaya, TWakatsuki, SNakaya, KFujino, KSaito, IInoue
Journal: Circulation Research (1992)

ATP-sensitive K+ channels with a conductance of 30 pS in smooth muscle cells of porcine coronary artery were found to be highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2+ (greater than 10(-4) M). In the inside-out configuration, these channels were activated by extracellular Ca2+ and blocked by cytosolic ATP and glibenclamide. Endothelin applied to the pipette specifically blocked these channels in a concentration-dependent manner in the cell-attached configuration (half-maximal inhibition, 1.3 x 10(-9) M). A K+ channel opener, nicorandil, activated these channels even in the presence of 10(-8) M endothelin. In the whole-cell current-clamp method, the cell membrane was depolarized by endothelin and then repolarized by nicorandil. The membrane depolarization is closely related to contraction of smooth muscle cells. These results suggest that the ATP-sensitive K+ channels are important in controlling the vascular tone of the corona...
Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work.
Authors: D DGlower, J ASpratt, N DSnow, J SKabas, J WDavis, C OOlsen, G STyson, D CSabiston, J SRankin
Journal: Circulation (1985)

The Frank-Starling relationship generally has been examined with filling pressure as the index of preload, resulting in a curvilinear function that plateaus at higher filling pressures. To investigate this relationship further in the intact heart, 32 dogs were chronically instrumented with left ventricular and pleural micromanometers and with regional (10 dogs) or global (22 dogs) ultrasonic dimension transducers. Seven days after implantation, left ventricular pressure and regional or global dimensions were recorded in the conscious state. After autonomic blockade, preload was varied by vena caval occlusion. Myocardial function was assessed by calculating regional or global stroke work, and preload was measured as end-diastolic segment length or chamber volume. The relationship between stroke work and either end-diastolic segment length or chamber volume (termed the preload recruitable stroke work relationship) was highly linear in every study (mean r = .97) and could be quantified by a slope (MW) and x-...
Clinical Trials of Systemic Chemotherapy for Resectable Pancreatic Cancer
Authors: Michail N. Mavros, Dimitrios Moris, Paul J. Karanicolas, Matthew H. G. Katz, Eileen M. O’Reilly, Timothy M. Pawlik
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Adjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC) based on level 1 evidence, but some studies suggest that a neoadjuvant approach (which is standard for borderline resectable PDAC) may be preferable for upfront resectable PDAC. An in-depth review was conducted of all randomized clinical trials that investigated neoadjuvant and adjuvant treatment of patients with resectable or resected PDAC, focusing on trial design, characteristics of enrolled population, and long-term outcomes. <h3>Observations</h3> The existing resectable PDAC trials have good internal validity but variable applicability because of their restrictive eligibility criteria. In these trials, overall survival is the criterion standard end point, but disease-free survival is more feasible, proximate, and specific to the assigned intervention (at the cost of subjective outcome assessment) and thus an acceptable end point in certain contexts. The prolonged survival in the PRODIGE 24 trial highlights both the success of mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) and the importance of patient selection. Neoadjuvant and perioperative trials have shown promising preliminary results; however, the number of patients who are not subsequently eligible for surgery reflects the limitations of this approach. Head-to-head comparisons of neoadjuvant and adjuvant treatments are limited to date in Western countries. Precision oncology with genomic and somatic testing for actionable mutations has promising preliminary results and may refine the management of PDAC, although the implications for early-stage disease and neoadjuvant therapy are unknown. <h3>Conclusions and Relevance</h3> This review found that adjuvant chemotherapy with mFOLFIRINOX is currently the standard of care in fit patients with resected PDAC; however, the role of neoadjuvant treatment is expanding. Precision oncology may help individualize the treatment regimen and sequence and improve outcomes. Enrollment of patients with resectable PDAC in clinical trials is strongly encouraged.
The opposing effects of chronic angiotensin-converting enzyme blockade by captopril on the responses to exogenous angiotensin II and vasopressin vs. norepinephrine in rats.
Authors: FSpertini, H RBrunner, BWaeber, HGavras
Journal: Circulation Research (1981)

To study the influence of acute and chronic angiotensin-converting enzyme blockade on the pressor response to exogenous angiotensin II, vasopressin and norepinephrine, we gave normal female Wistar rats 100 mg of captopril or 1 ml of 5% glucose twice daily by gavage for 2 weeks. On the 15th day, rats were anesthetized with pentobarbital, and dose-response curves to angiotensin II, lysine-vasopressin, and norepinephrine were obtained before and after intraperitoneal injection of 100 mg/kg of captopril or 1 ml of 5% glucose. Acute as well as chronic converting enzyme blockade enhanced the pressor response to exogenous angiotensin II. Similarly, sensitivity to exogenous vasopressin was increased by both acute and chronic converting enzyme inhibition. In contrast, chronic converting enzyme blockade significantly blunted the response to exogenous norepinephrine, whereas acute blockade tended to accentuate its pressor effect. These results suggest that chronic angiotensin-converting enzyme blockade may partly in...
Reflex alpha-adrenergic coronary vasoconstriction during hindlimb static exercise in dogs.
Authors: RAung-Din, J HMitchell, J CLonghurst
Journal: Circulation Research (1981)

We studied 18 alpha-chloralose-anesthetized dogs to determine if alpha-adrenergic coronary vasoconstriction occurs with hindlimb static exercise. Exercise was elicited by spinal cord ventral nerve root stimulation. Regional coronary blood flow was determined by the radioactive microsphere method. Animals were studied under four experimental conditions: control rest and static exercise, rest and static exercise after beta-adrenergic blockade with propranolol (2 mg/kg), rest and exercise after alpha-adrenergic blockade with phentolamine (.35 mg/kg), and rest and exercise after combined alpha- and beta-adrenergic blockade. Myocardial oxygen consumption during exercise was determined during control and during alpha-adrenergic blockade conditions. Control hindlimb static exercise resulted in significant increases in systolic (10.6%) and diastolic (12.5%) arterial pressures, heart rate (12.2%), and double product (24.6%). Associated with the increased demand for oxygen, myocardial oxygen consumption increased (...
Paget's disease of bone.
Authors: D J Hosking
Journal: BMJ (1981)

The essential requirement for effective treatment of Paget’s disease of bone is that the characteristic abnormality of bone remodelling is predictably corrected without the occurrence of significant side effects. Although the ideal agent is not currently available, appropriate use of the calcitonins or diphosphonates goes a long way to achieving this goal. Calcitonin (50 to 100 MRC units subcutaneously daily or 3 times weekly) will generally reduce bone turnover by approximately 50% within 6 months. However, very active disease will not be controlled and bone turnover will generally increase once treatment is withdrawn. Calcitonin is without significant side effects, although some patients will develop antibody-mediated resistance to the exogenous calcitonin species. An advantage of calcitonin is that there is radiographic evidence of a return to normal bone remodelling during treatment.
Guidelines for ambulatory electrocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Ambulatory Electrocardiography).
Authors: S BKnoebel, M HCrawford, M IDunn, CFisch, J SForrester, A MHutter, H LKennedy, R LLux, L TSheffield
Journal: Circulation (1989)
Does endomyocardial biopsy aid in the diagnosis of active rheumatic carditis
Authors: JNarula, PChopra, K KTalwar, K SReddy, R SVasan, RTandon, M LBhatia, J FSouthern
Journal: Circulation (1993)

BACKGROUNDCarditis is the only component of rheumatic fever that leads to permanent disability. The diagnosis of carditis is presently made by using composite clinical criteria based on the revised Jones' criteria. Since myocardial involvement is an important component of rheumatic carditis, right ventricular endomyocardial biopsies were performed in 54 patients with clinical acute rheumatic fever and quiescent rheumatic heart disease to evaluate the role of biopsy for the diagnosis of rheumatic carditis.METHODS AND RESULTSIn 11 of the 54 patients, clinical consensus was certain about rheumatic fever and carditis based on the revised Jones' criteria (group 1). Histomorphological abnormalities in these patients were scarce. The diagnostic features of rheumatic myocarditis including Aschoff nodules or histiocytic aggregates were encountered in 3 patients (27%). Lymphocytic infiltration was sparse. A majority of patients demonstrated myocyte degeneration, interstitial degeneration, or occasional interstitial...
Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning?
Authors: HKusuoka, YKoretsune, V PChacko, M LWeisfeldt, EMarban
Journal: Circulation Research (1990)

To elucidate the mechanism of contractile dysfunction in postischemic (stunned) myocardium, time-resolved measurements of intracellular free Ca2+ concentration ([Ca2+]i) were made using gated 19F nuclear magnetic resonance in seven perfused ferret hearts loaded with the fluorinated Ca2+ indicator 5F-BAPTA. Left ventricular developed pressure decreased to 65 +/- 3% (mean +/- SEM) of control after 15 minutes of global ischemia at 37 degrees C. In stunned myocardium, diastolic [Ca2+]i (0.24 +/- 0.03 microM) was not changed from control (0.18 +/- 0.03 microM, p greater than 0.10), but peak [Ca2+]i (1.03 +/- 0.13 microM) was paradoxically higher than that in control (0.61 +/- 0.06 microM, p less than 0.02). The slope of the relation between developed pressure and Ca2+ transient amplitude in stunned myocardium was significantly lower than that in control (p less than 0.05), even after normalization by maximal Ca2(+)-activated pressure. These results indicate that contractile failure in stunned myocardium is d...
Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design
Authors: Sander A.A. Kooijmans, Olivier G. de Jong, Raymond M. Schiffelers
Journal: Advanced Drug Delivery Reviews (2021)

Extracellular vesicles (EVs) are submicron cell-secreted structures containing proteins, nucleic acids and lipids. EVs can functionally transfer these cargoes from one cell to another to modulate physiological and pathological processes. Due to their presumed biocompatibility and capacity to circumvent canonical delivery barriers encountered by synthetic drug delivery systems, EVs have attracted considerable interest as drug delivery vehicles. However, it is unclear which mechanisms and molecules orchestrate EV-mediated cargo delivery to recipient cells. Here, we review how EV properties have been exploited to improve the efficacy of small molecule drugs. Furthermore, we explore which EV surface molecules could be directly or indirectly involved in EV-mediated cargo transfer to recipient cells and discuss the cellular reporter systems with which such transfer can be studied. Finally, we elaborate on currently identified cellular processes involved in EV cargo delivery. Through these topics, we provide insights in critical effectors in the EV-cell interface which may be exploited in nature-inspired drug delivery strategies.
Potentiation of myocardial salvage by tissue type plasminogen activator in combination with a thromboxane synthetase inhibitor in ischemic cat myocardium.
Authors: A MLefer, RMentley, J ZSun
Journal: Circulation Research (1988)

We studied the effects of a thrombolytic agent (t-PA) and a thromboxane synthetase inhibitor (CGS-13080) in a model of myocardial ischemia and reperfusion. Occlusion of the left anterior descending coronary artery for 2 hours followed by 4 hours of reperfusion in anesthetized cats results in a large washout of creatine kinase into the blood (32 +/- 7 IU/mg protein) and an area of necrotic tissue comprising 52 +/- 5% of the area at risk and 9 +/- 0.6% of the left ventricle. Intravenous administration of t-PA (500 IU/kg.min) for 30 minutes alone at reperfusion or infusion of CGS-13080 (500 micrograms/kg.hr) had no effect on washout of creatine kinase or extent of necrotic tissue development. Administration of the same doses of both t-PA and CGS-13080 together markedly attenuated creatine kinase release to 10 +/- 2 IU/mg protein (p less than 0.01) and reduced the area of necrotic tissue to 9 +/- 2% of the area at risk and only 1.3 +/- 0.3% of the left ventricle (p less than 0.001). No significant sustained e...
Relationship between plasma levels of procainamide, suppression of premature ventricular complexes and prevention of recurrent ventricular tachycardia.
Authors: R JMyerburg, K MKessler, IKiem, K CPefkaros, C AConde, DCooper, ACastellanos
Journal: Circulation (1981)

We compared the relationship between plasma levels of procainamide and suppression or prevention of various forms of ventricular arrhythmias in 18 patients, six of whom had premature ventricular complexes (PVCs) during acute myocardial infarction (AMI), six of whom had PVCs in the setting of stable chronic ischemic heart disease (CIHD), and six of whom had recurrent symptomatic ventricular tachycardia (VT) with chronic PVCs between episodes of VT. The mean plasma level of procainamide required for 85% suppression of PVCs in the AMI patients was 5.0 +/- 0.5 micrograms/ml, while that required for the CIHD patients was 9.3 +/- 0.7 micrograms/ml (p less than 0.05). The mean plasma level required for prevention of spontaneous episodes of symptomatic sustained tachycardia in the VT group was 9.1 +/- 3.4 micrograms/ml, while the mean level required for 85% suppression of PVCs in the same patients was 14.9 +/- 3.8 micrograms/ml (p less than 0.01). In the VT group, PVC frequency was decreased by a mean of only 36%...
Hemodynamic and reflex sympathetic control of transmural activation and rate of ventricular tachycardia in ischemic and hypertrophic ventricular myocardium of the dog.
Authors: J RHopson, J BMartins
Journal: Circulation (1992)

BACKGROUNDA previous study found that the electrophysiological response to ischemia is altered in hypertrophic myocardium, resulting in prolonged transmural activation time (TAT) associated with induction of sustained monomorphic ventricular tachycardia. This study investigated the role of hemodynamics in modulating TAT and the cycle length of induced ventricular tachycardia (VT) in dogs with left ventricular hypertrophy (LVH).METHODS AND RESULTSAnesthetized open-chest dogs underwent 3 hours of uninterrupted circumflex coronary occlusion. During atrial drive, TAT was recorded between endocardial and epicardial bipolar pairs on the same multipolar plunge needle placed in nonischemic and ischemic zones, documented by triphenyltetrazolium chloride staining. TAT and VT induced by up to three extrastimuli were studied during hypertension (control), during normotension produced most frequently by nitroprusside infusion (3-6 micrograms/kg/min), and during further hypertension most frequently produced by phenylep...