tbuckley/cabot-search huggingface dataset:
Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis.
Authors: F ANicolini, PLee, GRios, KKottke-Marchant, E JTopol
Journal: Circulation (1994)

BACKGROUNDWe evaluated the effects of a novel platelet fibrinogen receptor antagonist, Integrelin, and a direct thrombin inhibitor, recombinant hirudin, given together with recombinant tissue plasminogen activator (rTPA) in a canine experimental model of intracoronary thrombosis. We tested the hypothesis that combination of both agents at low doses would have an additive antithrombotic effect, resulting in a significant improvement in the efficacy of rTPA.METHODS AND RESULTSThirty-two dogs with an electrically induced coronary thrombus were treated with rTPA (1 mg/kg over 20 minutes) together with one of the following adjunctive treatments in a random fashion. Eight dogs received saline for 90 minutes; Integrelin (5 micrograms.kg-1.min-1 for 90 minutes) was given to 8 dogs; 8 dogs received recombinant hirudin (20 micrograms.kg-1.min-1 for 90 minutes); and 8 dogs were treated with a low-dose combination of Integrelin (2.5 micrograms.kg-1.min-1) plus recombinant hirudin (10 micrograms.kg-1.min-1) for 90 min...
"Fade" of hyperpolarizing responses to vagal stimulation at the sinoatrial and atrioventricular nodes of the rabbit heart.
Authors: J JSalata, JJalife
Journal: Circulation Research (1985)

Previous studies have suggested that maintained vagal stimulation or acetylcholine infusion results in a fade of responses in the sinoatrial node but not in the atrioventricular node, implying different muscarinic receptor subtypes in the two regions. We investigated this hypothesis in 23 isolated rabbit atrial preparations made quiescent by continuous superfusion with verapamil (1 microgram/ml). Transmembrane potentials were recorded simultaneously from cells in the sinoatrial pacemaker region and from the N region of the atrioventricular node. Postganglionic vagal stimulation was achieved by the application of trains of pulses (50-150 microseconds; 10-20 V; 200 Hz). Simultaneous application of long-lasting (1-10 sec) vagal trains produced hyperpolarizations which were nearly identical for both nodal regions. Maximal hyperpolarizations (approximately or equal to 24 mV for sinoatrial node; 26 mV for atrioventricular node) were reached about 500 msec after initiation of the vagal train. Thereafter, hyper...
A Simulation Analysis to Evaluate the Effect of Prospective Biomarker Testing on Progression-Free Survival (PFS) in DLBCL
Authors: Edith Szafer-Glusman, Juan Liu, Franklin V. Peale, Thalia A. Farazi, Jill Ray, Carsten Horn, Mikkel Z. Oestergaard, Martin Kornacker, Laurie H. Sehn, Günter Fingerle-Rowson, Jeffrey M. Venstrom, Michelle Byrtek, Elizabeth Punnoose
Journal: Blood (2017)
Effects of volume loading during experimental acute pulmonary embolism.
Authors: IBelenkie, RDani, E RSmith, J VTyberg
Journal: Circulation (1989)

Volume loading is used to treat hemodynamically compromised patients with acute pulmonary embolism despite data to suggest that volume loading after embolism might cause a leftward shift of the ventricular septum with a subsequent decrease in left ventricular (LV) end-diastolic volume and stroke work. We studied 10 closed-chest, anesthetized, and ventilated dogs to assess the effects of volume loading after pulmonary embolism caused by autologous clot. LV, right ventricular, and right atrial pressures as well as LV anteroposterior, septum-to-right ventricular, and septum-to-LV free wall diameters (sonomicrometry) were measured. Pericardial pressure was measured with flat, liquid-containing balloons. The effects of volume loading were assessed before embolism, after one episode of embolization, and after repeated embolizations. The LV area index (as a reflection of LV volume) increased during volume loading before embolism (2,870 +/- 430 to 3,080 +/- 520 mm2; p less than 0.05), did not change significantly...
Sick sinus syndrome after surgery for congenital heart disease.
Authors: R DGreenwood, ARosenthal, L JSloss, MLaCorte, A SNadas
Journal: Circulation (1975)

The course and prognosis of 16 infants and children with sick sinus syndrome associated with cardiac surgery is reviewed. The dysrhythmia was observed most ofter after extensive atrial reconstructive surgery in patients with transposition of the great arteries and with atrial septal defect. In 12 (75%) of the patients, sick sinus syndrome was detected in the immediate postoperative period. Tachyarrhythmias and bradyarrhythmias were presnet in 12 and isolated bradyarrhythmias in four. Temporary pacing was used in two and permanent pacing was required in five. Death in two non-paced patients was attributable to arrhythmias. Postmortem examination in one patient revealed a suture in the sinoatrial node. Careful attention to the anatomy of the sinoatrial node, its artery and the internodal tracts during surgery may prevent the development of sick sinus syndrome. In patients with dysrhythmia, a careful search should be undertaken to document the abnormal rhythm with the use of Holter monitoring. The insertion ...
Up-front carfilzomib, lenalidomide, and dexamethasone with transplant for patients with multiple myeloma: the IFM KRd final results
Authors: Murielle Roussel, Valerie Lauwers-Cances, Soraya Wuilleme, Karim Belhadj, Salomon Manier, Laurent Garderet, Martine Escoffre-Barbe, Clara Mariette, Lotfi Benboubker, Denis Caillot, Cécile Sonntag, Cyrille Touzeau, Jehan Dupuis, Philippe Moreau, Xavier Leleu, Thierry Facon, Benjamin Hébraud, Jill Corre, Michel Attal
Journal: Blood (2021)
Mechanism of abnormal septal motion in patients with right ventricular volume overload: a cross-sectional echocardiographic study.
Authors: A EWeyman, SWann, HFeigenbaum, J CDillon
Journal: Circulation (1976)

To evaluate the mechanism of paradoxical septal motion in patients with right ventricular volume overload (RVVO), short axis cross-sectional, echocardiographic studies of the left ventricle (LV) and interventricular septum (IVS) were performed in 19 patients with paradoxical septal motion due to RVVO and in 20 normal subjects. Short axis study in normal subjects revealed the left ventricle to be a relatively circular structure during both diastole and systole. In patients with RVVO a change in LC diastolic shape was observed. This change in shape varied from a slight flattening of the LV and IVS during diastole to total reversal of the normal direction of septal curvature such that the IVS became concave toward the RV and convex toward the LV. During systole the LV and IVS returned to their normal relatively circular configuration. This change in LV shape from diastole to systole resulted in net motion of the IVS toward the right ventricle (paradoxically). This study therefore suggests that paradoxical se...
Morphological effects of coronary balloon angioplasty in vivo assessed by intravascular ultrasound imaging.
Authors: JHonye, D JMahon, AJain, C JWhite, S RRamee, J BWallis, Aal-Zarka, J MTobis
Journal: Circulation (1992)

BACKGROUNDHistological examination of the effects of balloon angioplasty have been described from in vitro experiments and a limited number of pathologic specimens. Intravascular ultrasound imaging permits real time cross-sectional observation of the effect of balloon dilation on the atherosclerotic plaque in vivo.METHODS AND RESULTSThe morphological effects of coronary angioplasty were visualized at 66 lesions in 47 patients immediately after balloon dilatation with an intravascular ultrasound imaging catheter. Cross-sectional images were obtained at 30 frames per second as the catheter passed along the length of the artery. Quantitative and qualitative assessments of the dilated atherosclerotic plaque were made from the angiograms and the ultrasound images. Six morphological patterns after angioplasty were appreciated by ultrasound imaging. Type A consists of a linear, partial tear of the plaque from the lumen toward the media (seven lesions); Type B is defined by a split in the plaque that extends to t...
Adenosine alters glucose use during ischemia and reperfusion in isolated rat hearts.
Authors: B AFinegan, G DLopaschuk, C SCoulson, A SClanachan
Journal: Circulation (1993)

BACKGROUNDAdenosine possesses marked cardioprotective properties, but the mechanisms for this beneficial effect are unclear. The objective of this study was to determine the effect of adenosine given before ischemia or at reperfusion on mechanical function, glucose oxidation, glycolysis, and metabolite levels in isolated, paced (280 beats per minute) working rat hearts.METHODS AND RESULTSHearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microU.mL-1 insulin at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Adenosine (100 microM) pretreatment or adenosine (100 microM) at reperfusion markedly increased the recovery of mechanical function (from 44% to 81% and 96%, respectively) after 60 minutes of low-flow ischemia (coronary flow, 0.5 mL.min-1). Glucose oxidation (mumol.min-1 x g dry wt-1) was inhibited during ischemia (from 0.44 +/- 0.04 to 0.12 +/- 0.01), and this was not altered by adenosine (100 microM). During reperfusion, glucose oxida...
Mitochondrial NADP+ is essential for proline biosynthesis during cell growth
Authors: Diem H. Tran, Rushendhiran Kesavan, Halie Rion, Mona Hoseini Soflaee, Ashley Solmonson, Divya Bezwada, Hieu S. Vu, Feng Cai, John A. Phillips, Ralph J. DeBerardinis, Gerta Hoxhaj
Journal: Nature Metabolism (2021)

Nicotinamide adenine dinucleotide phosphate (NADP+) is vital to produce NADPH, a principal supplier of reducing power for biosynthesis of macromolecules and protection against oxidative stress. NADPH exists in separate pools, in both the cytosol and mitochondria; however, the cellular functions of mitochondrial NADPH are incompletely described. Here, we find that decreasing mitochondrial NADP(H) levels through depletion of NAD kinase 2 (NADK2), an enzyme responsible for production of mitochondrial NADP+, renders cells uniquely proline auxotrophic. Cells with NADK2 deletion fail to synthesize proline, due to mitochondrial NADPH deficiency. We uncover the requirement of mitochondrial NADPH and NADK2 activity for the generation of the pyrroline-5-carboxylate metabolite intermediate as the bottleneck step in the proline biosynthesis pathway. Notably, after NADK2 deletion, proline is required to support nucleotide and protein synthesis, making proline essential for the growth and proliferation of NADK2-deficient cells. Thus, we highlight proline auxotrophy in mammalian cells and discover that mitochondrial NADPH is essential to enable proline biosynthesis. NADPH exists in separate cellular pools within the cytosol and mitochondria. Tran et al. find that mitochondrial NADPH is essential to enable proline biosynthesis during cell growth.
Effects of nifedipine on myocardial perfusion and ischemic injury in dogs.
Authors: P DHenry, RShuchleib, L JBorda, RRoberts, J RWilliamson, B ESobel
Journal: Circulation Research (1978)

To determine whether nifedipine, a calcium antagonist, protects ischemic myocardium, conscious dogs were subjected to coronary occlusion and given nifedipine by intravenous infusion beginning 30 minutes after the onset of ischemia and lasting for 24 hours while systemic arterial pressure, left atrial pressure, and cardiac output were monitored. Local myocardial perfusion at selected intervals after coronary occlusion was assessed with radioactive microspheres injected into the left atrium. In regions of myocardium exhibiting moderately depressed flow 29 minutes after occlusion in control dogs (n = 8), flow was significantly greater 3 and 23.5 hours later, reflecting increases in collateral perfusion. Corresponding zones of myocardium in treated dogs (n = 9) exhibited significantly greater increases in flow at each interval after occlusion (P less than 0.05). Furthermore, myocardial creatine kinase depletion (which correlated well with morphometric estimates of necrosis) in myocardium matched for ischemia ...
Neurohormonal inhibition and hemodynamic unloading during prolonged inhibition of ANF degradation in patients with severe chronic heart failure.
Authors: TMünzel, SKurz, JHoltz, RBusse, HSteinhauer, HJust, HDrexler
Journal: Circulation (1992)

BACKGROUNDThe purpose of this study was to investigate the therapeutic potential of prolonged inhibition of atrial natriuretic factor (ANF) degradation in patients with severe chronic heart failure.METHODS AND RESULTSThe effects of repeated doses of the endopeptidase inhibitor candoxatrilat (150 mg i.v.) were examined over a 24-hour period in patients with severe chronic heart failure (New York Heart Association class III-IV). Plasma alpha-hANF(99-126) was elevated at baseline (235 +/- 59 pg/ml), increased 2.5-fold at 2 hours after the first dose, and remained significantly elevated throughout the 24-hour protocol. In contrast, pro-hANF(31-67) decreased from 3,151 +/- 616 to 2,072 +/- 362 pg/ml (p less than 0.05). Cardiac index (CI) increased only transiently after the first dose of candoxatrilat (CI, 2.11 +/- 0.2 to 2.67 +/- 0.28 l/min/m2, p less than 0.05). Sodium excretion increased sixfold (p less than 0.05) 2 hours after the first dose of candoxatrilat and remained significantly elevated throughout t...
Abstract 13590: β-adrenergic Signaling Promotes Survival and Proliferation of Mouse Cardiac Progenitor Cells Prior to Lineage Commitment
Authors: Mohsin Khan, Sadia Mohsin, Daniele Avitabile, Jonathan Nguyen, Natalie Gude, Mark A Sussman
Journal: Circulation (2012)

Rationale: Short term β-adrenergic stimulation promotes contractility in response to stress, but is ultimately detrimental in the failing heart due to accrual of cardiomyocyte death. Endogenous myo...
EUS-Guided Biliary Drainage With Electrocautery-Enhanced Lumen-Apposing Metal Stent Placement Should Replace Ptbd After ERCP Failure In Patients With Distal Tumoral Biliary Obstruction: Retrospective Study
Authors: C Ginestet, S Geyl, R Legros, V Hummel, F Sanglier, A Rouchaud, H Lepetit, M Dahan, P Carrier, V Loustaud-Ratti, D Sautereau, J Albouys, J Jacques
Journal: Endoscopy (2021)

Aims In the context of malignant distal biliary obstruction, ERCP is the reference technique for bile duct drainage. In case of failure, the alternative techniques are percutaneous transhepatic biliary drainage and more recently endoscopic ultrasound-guided biliary drainage. A new type of stent called the electrocautery-enhanced lumen-apposing metal stent has been developed to enable the performance of biliodigestive anastomosis under EUS-guidance in a single step, without prior bile duct puncture or the need for a guidewire. The aim of our study was to compare the real-life efficacies of PTBD and EUS-BD with the EC-LAMS for cases of ERCP failure in patients with malignant biliary obstruction.
18F-FDG and 68Ga-FAPI PET/CT in the Evaluation of Ground-Glass Opacity Nodule
Authors: Haojun Chen, Yizhen Pang, Tinghua Meng, Xiuyi Yu, Long Sun
Journal: Clinical Nuclear Medicine (2021)

Abstract A 50-year-old woman with a newly detected pulmonary ground-glass opacity (GGO) nodule underwent PET/CT to determine the likelihood of malignancy. This patient was enrolled in the prospective study (NCT04588064) to determine the effectiveness of 18 F-FDG and 68 Ga-FAPI PET/CT for characterization of the GGO nodule. On PET/CT images, minimal 18 F-FDG uptake but intense 68 Ga-FAPI uptake was observed in this GGO nodule. This patient subsequently underwent video-assisted thoracoscopic surgery, and postoperative pathological examination confirmed the diagnosis of invasive adenocarcinoma. This case presented an example where 68 Ga-FAPI PET/CT showed higher tracer uptake than 18 F-FDG in the malignant GGO nodule.
Health-Related Quality of Life With Trastuzumab Monotherapy Versus Trastuzumab Plus Standard Chemotherapy as Adjuvant Therapy in Older Patients With HER2-Positive Breast Cancer
Authors: Naruto Taira, Masataka Sawaki, Yukari Uemura, Tsuyoshi Saito, Shinichi Baba, Kokoro Kobayashi, Hiroaki Kawashima, Michiko Tsuneizumi, Noriko Sagawa, Hiroko Bando, Masato Takahashi, Miki Yamaguchi, Tsutomu Takashima, Takahiro Nakayama, Masahiro Kashiwaba, Toshiro Mizuno, Yutaka Yamamoto, Hiroji Iwata, Yasuo Ohashi, Hirofumi Mukai, Takuya Kawahara
Journal: Journal of Clinical Oncology (2021)

We report findings on quality of life (QoL) in the RESPECT trial, which compared adjuvant trastuzumab monotherapy with trastuzumab plus chemotherapy in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC).Patients age 70-80 years with human epidermal growth factor receptor 2-positive surgically treated breast cancer were randomly assigned to receive trastuzumab (T) or trastuzumab plus chemotherapy (T + C). QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Philadelphia Geriatric Center Morale Scale, Hospital Anxiety and Depression Scale, Patient Neurotoxicity Questionnaire, and Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline and after 2, 12, and 36 months. Comparisons were based on individual changes from baseline and were performed by Fisher's test or mixed-model repeated-measures.Among 275 patients in the parent study, 231 (84%) (average age: 74 years) were included in the analysis. At 2, 12, and 36 months, 198, 177, and 178 patients completed surveys, and the mean FACT-G scores at each survey point were 78.9, 80.4, 82.7, and 79.1 in group T and 79.5, 74.5, 78.4, and 78.5 in group T + C. Compared with group T + C, the proportion of patients showing QoL deterioration (≥ 5 points decrease from baseline in FACT-G) was significantly lower at 2 months (31% v 48%; P = .016) and 12 months (19% v 38%; P = .009). In group T, the Hospital Anxiety and Depression Scale score (P = .003) and the proportion of severe sensory peripheral neuropathy (P = .001) were significantly lower at 2 months, and Philadelphia Geriatric Center Morale Scale and Tokyo Metropolitan Institute of Gerontology Index of Competence scores were significantly higher (P = .024, .042) at 12 months. At 36 months, there were no significant differences in any QoL items.Detrimental effects of adjuvant chemotherapy on global QoL, morale, and activity capacity lasted for at least 12 months but were not observed at 36 months.
Ischemic preconditioning preserves creatine phosphate and intracellular pH.
Authors: MKida, HFujiwara, MIshida, CKawai, MOhura, IMiura, YYabuuchi
Journal: Circulation (1991)

BACKGROUNDIschemic preconditioning slows ATP depletion and ultrastructural damage during the final episode of ischemia. To define the influence of creatine phosphate (CP) and intracellular pH (pHi) on this effect, CP and pHi were serially measured in porcine hearts without collateral circulation by using 31P-NMR spectroscopy and ultrastructural examination.METHODS AND RESULTSFarm pigs weighing 12-15 kg were anesthetized with Fluothane. The control group underwent a single occlusion (20 minutes or 60 minutes); the preconditioned group underwent four episodes of 5-minute occlusion and 5-minute reperfusion followed by a sustained occlusion (20 minutes or 60 minutes). After ischemic preconditioning, CP increased to 115 +/- 11% (p less than 0.05) of preischemic value and ATP decreased to 84 +/- 8% (p less than 0.05) of preischemic value, but pHi returned to preischemic value. At 5 and 10 minutes of sustained ischemia, CP was significantly preserved in the preconditioned group (control group, 19 +/- 3% versus p...
Author Correction: Skill levels and gains in university STEM education in China, India, Russia and the United States
Authors: Prashant Loyalka, Ou Lydia Liu, Guirong Li, Elena Kardanova, Igor Chirikov, Shangfeng Hu, Ningning Yu, Liping Ma, Fei Guo, Tara Beteille, Namrata Tognatta, Lin Gu, Guangming Ling, Denis Federiakin, Huan Wang, Saurabh Khanna, Ashutosh Bhuradia, Zhaolei Shi, Yanyan Li
Journal: Nature Human Behaviour (2021)
Propagating depolarization in anisotropic human and canine cardiac muscle: apparent directional differences in membrane capacitance. A simplified model for selective directional effects of modifying the sodium conductance on Vmax, tau foot, and the propagation safety factor.
Authors: M SSpach, P CDolber, J FHeidlage, J MKootsey, E AJohnson
Journal: Circulation Research (1987)

As yet there is no model or simulation that accounts for the anisotropic difference in the shape of the upstroke and safety factor of propagating cardiac action potentials: fast upstrokes occur with slow transverse propagation and slow upstrokes occur with fast longitudinal propagation. The purpose of this paper is to demonstrate, however, that a simplified cable model based on directional differences in the effective membrane capacitance predicts in detail the experimentally measured directionally dependent behavior of the upstroke in response to modification of the sodium conductance. Quinidine and lidocaine produced greater relative decreases in Vmax and conduction velocity with longitudinal propagation than with transverse propagation, as predicted on the basis that the shape differences should produce an anisotropic distribution in the membrane uptake of sodium channel binding drugs. The simulation predictions of the effects of positive shifts of the take-off potential due to premature action potenti...
Implantable cardioverter-defibrillator therapy in the absence of significant symptoms. Rhythm diagnosis and management aided by stored electrogram analysis.
Authors: B GHook, D JCallans, R BKleiman, B TFlores, F EMarchlinski
Journal: Circulation (1993)

BACKGROUNDThis report describes the value of stored ventricular electrogram analysis in the diagnosis and management of patients experiencing minimal or no symptoms before implantable cardioverter-defibrillator (ICD) therapy.METHODS AND RESULTSThe study population included 48 patients who received the Cadence Tiered Therapy Defibrillator System, an investigational third-generation ICD with ventricular electrogram storage capabilities. Criteria for arrhythmia diagnosis were based on analysis of the electrogram rate, RR interval variability, and morphology. Twenty-nine of the 48 patients (60%) experienced at least one episode of antitachycardia pacing or shock (one shock or more in 25 of 29 patients) that was preceded by minimal or no symptoms during a mean follow-up of 15.1 +/- 7.8 months. There were 194 tachycardia episodes registered by the device, including 101 for which ventricular electrograms were stored and available for analysis. Of the 101 stored electrograms, 74 were classified as ventricular tac...
Exercise testing in asymptomatic or minimally symptomatic aortic regurgitation: relationship of left ventricular ejection fraction to left ventricular filling pressure during exercise.
Authors: C ABoucher, R AWilson, D JKanarek, A MHutter, R DOkada, R RLiberthson, H WStrauss, G MPohost
Journal: Circulation (1983)

Exercise radionuclide angiography is being used to evaluate left ventricular function in patients with aortic regurgitation. Ejection fraction is the most common variable analyzed. To better understand the rest and exercise ejection fraction in this setting, 20 patients with asymptomatic or minimally symptomatic severe aortic regurgitation were studied. All underwent simultaneous supine exercise radionuclide angiography and pulmonary gas exchange measurement and underwent rest and exercise measurement of pulmonary artery wedge pressure (PAWP) during cardiac catheterization. Eight patients had a peak exercise PAWP less than 15 mm Hg (group 1) and 12 had a peak exercise PAWP greater than or equal to 15 mm Hg (group 2). Group 1 patients were younger and more were in New York Heart Association class I. Group 1 patients also had a higher mean rest ejection fraction (0.64 +/- 0.08 vs 0.49 +/- 0.13, p less than 0.01, higher exercise ejection fraction (0.63 +/- 0.10 vs 0.40 +/- 0.18, p less than 0.01), lower end-...