tbuckley/cabot-search huggingface dataset:
Calcium depletion in rabbit myocardium. Ultrastructure of the sarcolemma and correlation with the calcium paradox.
Authors: J SFrank, T LRich, SBeydler, MKreman
Journal: Circulation Research (1982)

The ultrastructure of the Ca-depleted myocardial sarcolemma (via Ca-free and Ca-free plus EGTA perfusion at 28 degree C and 37 degree C) was studied in the vascularly perfused interventricular septum of the rabbit. Thin-section and freeze-fracture electron microscopy was used. Two major structural defects in the sarcolemma were found. (1) Ninety percent of the Ca-depleted cells have between 30 and 40% of their glycocalyx separated from the bilayer. With tannic acid staining, the separation is seen to occur between the external lamina and the surface coat. (2) Freeze-fracture data showed an apparent decrease in intramembrane particles on the P face of unidirectionally shadowed replicas. Quantitation of rotary-shadowed replicas showed no decrease in density of intramembrane particles. It was concluded from this that there was no loss of intramembrane particles, but rather a reorientation in the plane of the bilayer after Ca depletion. Both glycocalyx and bilayer changes were present after perfusion of the h...
Phase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide
Authors: Johann S. de Bono, Mark T. Fleming, Judy S. Wang, Richard Cathomas, Manuel Selvi Miralles, John Bothos, Mary Jane Hinrichs, Qu Zhang, Peng He, Marna Williams, Anton I. Rosenbaum, Meina Liang, Kapil Vashisht, Song Cho, Pablo Martinez, Daniel P. Petrylak
Journal: Clinical Cancer Research (2021)

Abstract Purpose: MEDI3726 is an antibody–drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This phase I study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy. Patients and Methods: MEDI3726 was administered at 0.015–0.3 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary objective was to assess safety, dose-limiting toxicities (DLT), and MTD/maximum administered dose (MAD). Secondary objectives included assessment of antitumor activity, pharmacokinetics, and immunogenicity. The main efficacy endpoint was composite response, defined as confirmed response by RECIST v1.1, and/or PSA decrease of ≥50% after ≥12 weeks, and/or decrease from ≥5 to &amp;lt;5 circulating tumor cells/7.5 mL blood. Results: Between February 1, 2017 and November 13, 2019, 33 patients received MEDI3726. By the data cutoff (January 17, 2020), treatment-related adverse events (TRAE) occurred in 30 patients (90.9%), primarily skin toxicities and effusions. Grade 3/4 TRAEs occurred in 15 patients (45.5%). Eleven patients (33.3%) discontinued because of TRAEs. There were no treatment-related deaths. One patient receiving 0.3 mg/kg had a DLT of grade 3 thrombocytopenia. The MTD was not identified; the MAD was 0.3 mg/kg. The composite response rate was 4/33 (12.1%). MEDI3726 had nonlinear pharmacokinetics with a short half-life (0.3–1.8 days). The prevalence of antidrug antibodies was 3/32 (9.4%), and the incidence was 13/32 (40.6%). Conclusions: Following dose escalation, no MTD was identified. Clinical responses occurred at higher doses, but were not durable as patients had to discontinue treatment due to TRAEs.
Hypertension following arterial baroreceptor denervation in the unanesthetized dog.
Authors: C SIto, A MScher
Journal: Circulation Research (1981)

Studies were conducted on unanesthetized dogs (1) in the control state, (2) after carotid sinus denervation plus section of the cervical aortic nerves (SCAD), and (3) after carotid sinus denervation plus section of intrathoracic vegal branches which innervate arterial and cardiopulmonary baroreceptors, the heart, lungs, and other structures (STD). Mean values and standard deviations of blood pressure and heart rate were measured during many 75-minute recording sessions. The control mean arterial pressure was 94.8 +/- 8.9 mm Hg. The mean pressure after SCAD was 105.5 +/- 9.5 mm Hg, 10.0 mm Hg higher (P less than 0.05) than in the control state, whereas after STD, the mean pressure was 119.5 +/- 16.8 mm Hg, 25.3 mm Hg higher (P less than 0.001) than in the control state. The standard deviation of pressure was increased (P less than 0.01) by either denervation procedure. The mean pressure after STD was higher than after SCAD (P less than 0.05). Ten of 12 animals with SCAD showed residual baroreceptor reflexe...
Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer—The Penelope-B Trial
Authors: Sibylle Loibl, Frederik Marmé, Miguel Martin, Michael Untch, Hervé Bonnefoi, Sung-Bae Kim, Harry Bear, Nicole McCarthy, Mireia Melé Olivé, Karen Gelmon, José García-Sáenz, Catherine M. Kelly, Toralf Reimer, Masakazu Toi, Hope S. Rugo, Carsten Denkert, Michael Gnant, Andreas Makris, Maria Koehler, Cynthia Huang-Bartelett, Maria Jose Lechuga Frean, Marco Colleoni, Gustavo Werutsky, Sabine Seiler, Nicole Burchardi, Valentina Nekljudova, Gunter von Minckwitz
Journal: Journal of Clinical Oncology (2021)

About one third of patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metastatic setting. PENELOPE-B (NCT01864746) is a double-blind, placebo-controlled, phase III study in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer without a pathological complete response after taxane-containing NACT and at high risk of relapse (clinical pathological staging-estrogen receptor grading score ≥ 3 or 2 and ypN+). Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib 125 mg once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). Primary end point is invasive disease-free survival (iDFS). Final analysis was planned after 290 iDFS events with a two-sided efficacy boundary P < .0463 because of two interim analyses. One thousand two hundred fifty patients were randomly assigned. The median age was 49.0 years (range, 19-79), and the majority were ypN+ with Ki-67 ≤ 15%; 59.4% of patients had a clinical pathological staging-estrogen receptor grading score ≥ 3. 50.1% received aromatase inhibitor, and 33% of premenopausal women received a luteinizing hormone releasing hormone analog in addition to either tamoxifen or an aromatase inhibitor. After a median follow-up of 42.8 months (92% complete), 308 events were confirmed. Palbociclib did not improve iDFS versus placebo added to ET-stratified hazard ratio, 0.93 (95% repeated CI, 0.74 to 1.17) and two-sided weighted log-rank test (Cui, Hung, and Wang) P = .525. There was no difference among the subgroups. Most common related serious adverse events were infections and vascular disorders in 113 (9.1%) patients with no difference between the treatment arms. Eight fatal serious adverse events (two palbociclib and six placebo) were reported. Palbociclib for 1 year in addition to ET did not improve iDFS in women with residual invasive disease after NACT.
Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris.
Authors: TAoyama, YYui, HMorishita, CKawai
Journal: Circulation (1990)

To investigate the prostaglandin I2 (PGI2) half-life regulated by high density lipoprotein (HDL) in patients with coronary artery disease (CAD), we determined the stability of PGI2 and serum apolipoprotein A-I (Apo A-I) and apolipoprotein A-II (Apo A-II) levels in four age-matched groups of patients: controls (n = 17), angina pectoris (n = 18), unstable angina pectoris (n = 17), myocardial infarction (n = 19) (acute phase, 3.6 +/- 1.7 hours from onset; subacute phase, 75 +/- 15 hours from onset in the same patients). Serum PGI2 half-life and total serum Apo A-I levels were lower in the CAD group than in the control group. PGI2 was least stable in patients with unstable angina and the acute phase of myocardial infarction. In these patients, the molar ratio of Apo A-I to Apo A-II and HDL-associated Apo A-I levels were decreased, and free Apo A-I levels were increased. After in vitro incubation of HDL with increasing amounts of Apo A-II, Apo A-I in HDL was displaced by Apo A-II, with the parallel decrease in...
Technical Variant of EUS-Guided Recanalization For Complete Esophageal Stenosis: Balloon-target Assisted Rendezvous Approach
Authors: J Velaszquez-Rodriguez, S Maisterra, JB Gornals
Journal: Endoscopy (2021)

A 64-year-old male with absolute dysphagia due to complete esophageal stenosis after oncological treatment of pharyngeal cancer.
Efficacy of Real-Time Computer-Aided Detection of Colorectal Neoplasia in a Non-Expert Setting: A Randomized Controlled Trial
Authors: A Repici, M Spadaccini, G Antonelli, R Maselli, PA Galtieri, G Pellegatta, A Capogreco, SM Milluzzo, G Lollo, EC Ferrara, A Fugazza, S Carrara, A Anderloni, A Amato, A De Gottardi, C Spada, F Radaelli, C Hassan
Journal: Endoscopy (2021)

Aims One-fourth of colorectal neoplasias are missed during screening colonoscopies; these can develop into colorectal cancer (CRC). Several deep learning based real-time computer-aided detection (CADe) systems proved their efficacy in improving the performance of expert endoscopists in neoplasia detection. We performed a multicenter, randomized trial to assess the efficacy of a CADe system in detection of colorectal neoplasias in a non-expert setting to challenge the CADe impact in a real-life scenario.
A randomized trial of intravenous and intracoronary streptokinase in patients with acute myocardial infarction.
Authors: J LAnderson, H WMarshall, J CAskins, J RLutz, S GSorensen, R LMenlove, F GYanowitz, A DHagan
Journal: Circulation (1984)

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less tha...
Myocardial free-wall rupture after acute infarction: survival aided by percutaneous intraaortic balloon counterpulsation.
Authors: CHochreiter, JGoldstein, J SBorer, TTyberg, H LGoldberg, VSubramanian, IRosenfeld
Journal: Circulation (1982)

After his first acute myocardial infarction, a 69-year-old male suffered the usually lethal complication of ventricular free-wall rupture. Early suspicion of possible rupture and immediate percutaneous insertion of an intraaortic balloon pump assist device afforded sufficient hemodynamic stability to proceed with cardiac catheterization. The diagnosis of ventricular free-wall rupture was confirmed and the extent of coronary artery disease defined. The patient underwent repair of the free-wall rupture and coronary artery bypass grafting and has returned to full activity.
Assessment of severity of coronary stenoses using a Doppler catheter. Validation of a method based on the continuity equation.
Authors: E LJohnson, P GYock, V KHargrave, J PSrebro, S MManubens, WSeitz, T APorts
Journal: Circulation (1989)

The coronary Doppler catheter has been used primarily in the measurement of coronary vasodilator reserve, most often as the ratio of peak to resting velocity in response to an intracoronary dose of papaverine. We have developed a new method based on the continuity equation using a Doppler catheter for the assessment of stenosis severity in the coronary circulation by means of quantitative velocity measurements obtained by complex spectral analysis of the Doppler signal. With this system we have been able to detect a high-velocity stenosis jet in a canine model of coronary stenosis of known cross-sectional area. Using the peak velocity obtained by complex spectral analysis, we found a strong correlation between cross-sectional areas determined by the continuity equation and known cross-sectional areas (r = 0.93, SEE = 0.23 mm2). We also found a strong correlation between the ratio of peak stenosis velocity to proximal vessel velocity and percent diameter and percent area stenosis (r = 0.91 and 0.92, respec...
Influence of cigarette smoking on human autonomic function.
Authors: O NNiedermaier, M LSmith, L ABeightol, ZZukowska-Grojec, D SGoldstein, D LEckberg
Journal: Circulation (1993)

BACKGROUNDAlthough cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control.METHODS AND RESULTSWe studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sy...
Targeting AXL kinase sensitizes leukemic stem and progenitor cells to venetoclax treatment in acute myeloid leukemia
Authors: Xiaojia Niu, Katharina Rothe, Min Chen, Sarah Grasedieck, Rick Li, Sung-Eun Nam, Xiuyan Zhang, German E. Novakovskiy, Ye-Hyeon Ahn, Irina Maksakova, Shenshen Lai, Hong Zhang, Jun Yan, Hong Liu, Yun Zhao, Depei Wu, Yubin Ge, Wyeth W. Wasserman, Arefeh Rouhi, Florian Kuchenbauer, Calvin K. Yip, Zaihui Zhang, Xiaoyan Jiang
Journal: Blood (2021)
Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis.
Authors: K PGallagher, MMatsuzaki, GOsakada, W SKemper, JRoss
Journal: Circulation Research (1983)

Relationships between regional myocardial perfusion and transmural function, both during treadmill exercise and at rest, were examined in conscious dogs with varying degrees of coronary stenosis produced by a hydraulic occluder. In 13 dogs we measured myocardial blood flow with microspheres (10-12 microns in diameter) and regional systolic wall thickening (%). During exercise with coronary stenosis, myocardial blood flow was characterized by nonuniform distribution, and associated with regional dysfunction. The relationships between normalized myocardial blood flow and normalized %wall thickening during exercise with coronary stenosis were linear, with significantly different slopes (mean myocardial blood flow: y = 1.23x - 0.16, r = 0.93; subendocardial myocardial blood flow: y = 1.50x - 0.02, r = 0.86; subepicardial myocardial blood flow: y = 0.83x - 0.18, r = 0.87). To fill the gap between available subendocardial and subepicardial data during exercise with coronary stenosis and control points, however,...
Right ventricular volume characteristics before and after palliative and reparative operation in tetralogy of Fallot.
Authors: T PGraham, DCordell, G FAtwood, R JBoucek, R CBoerth, H WBender, J HNelson, W KVaughn
Journal: Circulation (1976)

Right heart volume data were obtained in 63 patients with tetralogy of Fallot. The patients were divided into three groups: 1) preoperative tetralogy (N=34); 2) post shunt procedure (N=14); 3A) post repair without outflow patch (N=10); 3B) post repair with an outflow patch (N=8). In Group 1 right ventricular end-diastolic volume (RVEDV), RV ejection fraction (EF), and RV systolic output (SO) were all mildly depressed. In post shunt patients, RVEDV was normal but RVEF remained depressed. RVEDV and RVSO increased following a shunt procedure, and these variables were larger in patients with a large versus a small shunt. In Group 3A RVEDV, RVEF, and RVSO were normal. In contrast in patients in Group 3B, RVEDV was increased averaging 177 +/- 15% of normal RVEF was depressed averaging 0.45 +/- 0.04, and RVSO was normal. RV size and pump function are abnormal in patients whose operation requires an outflow tract patch and the factors which may contribute to these abnormalities include a higher RV peak pressure, ...
Nifedipine and conventional therapy for unstable angina pectoris: a randomized, double-blind comparison.
Authors: J EMuller, Z GTuri, D LPearle, J FSchneider, D HSerfas, JMorrison, P HStone, R ERude, BRosner, B ESobel
Journal: Circulation (1984)

To characterize the potential of nifedipine in the therapy of unstable angina pectoris we implemented a blinded, randomly assigned, titrated schedule of conventional therapy (propranolol, if not contraindicated, and isosorbide dinitrate) or nifedipine for 14 days in 126 patients hospitalized in a coronary care unit for ischemic chest pain of less than 45 min duration. There were no significant differences between conventionally and nifedipine-treated patients with regard to (1) the time to relief of pain as judged by life table analysis, (2) the decrease in anginal attacks per 24 hr from day 0 to day 2 (-2.5 +/- 0.4 for conventional therapy vs; -2.8 +/- 0.3 for nifedipine), (3) the decrease in the number of nitroglycerin tablets consumed per 24 hr (-2.0 +/- 0.5 for conventional vs -2.1 +/- 0.4 for nifedipine therapy), (4) the percentage of patients requiring morphine on day 1 (13% for conventional vs 21% for nifedipine therapy), or (5) the percentage of patients who developed infarction (14% in both group...
Abstract 14235: Aortic Volume and Dimensions by Cardiovascular Magnetic Resonance Predict Incident Cardiovascular Events
Authors: Ulf Neisius, Philimon N Gona, Carol Salton, Noriko Oyama-Manabe, Michael L Chuang, Christopher J O'Donnell, Warren J Manning, Connie W Tsao
Journal: Circulation (2020)

Introduction: Pathophysiology of the aorta negatively impacts cardiovascular health. Hypothesis: Assessment of aortic anatomy facilitates population-based cardiovascular disease (CVD) risk stratification. Methods: Framingham Heart Study Offspring Cohort participants without prevalent CVD (n=1576, 64±9 years, 44% men) underwent 1.5T ECG-gated axial T2W black-blood CMR of the thoracoabdominal aorta (2002-2006). The diameters of the descending thoracic and proximal and distal abdominal aorta (infrarenal and aortic bifurcation) were measured ( Figure A ). Additionally, the maximum diameter and the total intravascular volume of the descending thoracic and abdominal aorta were calculated. Cox proportional hazards regression analyses adjusting for age, gender, systolic blood pressure, total cholesterol/HDL cholesterol ratio, diabetes mellitus, smoking, as well as treatment for hyperlipidemia, hypertension, and diabetes were undertaken to evaluate the association of aortic anatomy with incident CVD ( Figure ). Results: During follow-up (median 9.5 years, range 0 - 12.2 yrs), 163 incident CVD events occurred, of which 66 were major events (myocardial infarction, ischemic stroke, and CVD death). In multivariable-adjusted Cox regression models, each SD unit greater descending thoracic and maximum aortic diameter, as well as natural logarithmic transformed total aortic volume were associated with a &gt;20% increased risk for incident CVD (per SD Unit hazard ratio [HR]: 1.21, 95% CI: 1.03-1.42, P=0.019; HR 1.22, 95% CI: 1.04-1.43, P=0.014; HR: 1.24, 95% CI: 1.10-1.39, P&lt;0.001, respectively; Figure B ). Abdominal aortic diameters were not associated with CVD. Conclusions: In this middle-aged community-dwelling Caucasian adult cohort followed over 10 years, greater thoracoabdominal aortic dimensions and volume, predicted incident CVD. Future investigations may determine the implications of aortic size modification on CVD outcomes.
Long-term effects of ileal bypass on lipoproteins in patients with familial hypercholesterolemia.
Authors: PKoivisto, T AMiettinen
Journal: Circulation (1984)

Partial ileal bypass is effective in reducing circulating cholesterol levels. In our study the 10 year effects of the procedure on serum lipids and lipoproteins were studied in 27 patients with heterozygous familial hypercholesterolemia. The ileal bypass patients were compared with conservatively treated case controls matched for age, sex, serum cholesterol level, relative body weight, blood pressure, and smoking habits and also for the existence of diabetes and coronary heart disease. Serum triglycerides were initially slightly higher in the patients undergoing ileal bypass. During the 10 year follow-up eight surgically treated and seven control patients suffered fatal or nonfatal myocardial infarctions. Of these all but one male subject who underwent surgery had had manifest coronary heart disease at entry. Male sex, smoking, triglyceride levels, and angina were significant predictors of new coronary events. The fall in serum cholesterol in patients who underwent ileal bypass and had fatal myocardial in...
The effects of antiarrhythmic drugs, stimulation frequency, and potassium-induced resting membrane potential changes on conduction velocity and dV/dtmax in guinea pig myocardium.
Authors: J WBuchanan, TSaito, L SGettes
Journal: Circulation Research (1985)

For one-dimensional propagation, a nonlinear relationship between Vmax and  velocity is predicted by cable theory, and, under experimental conditions, Vmax and  velocity may change in opposite directions. Using standard microelectrode techniques, we have measured Vmax and  velocity in guinea pig papillary muscles exposed to tetrodotoxin and low sodium (agents expected primarily to decrease, directly, the rapid inward current), increased extracellular potassium (an agent which decreases the rapid inward current at least partially by inactivation mediated by depolarization of the resting membrane potential), and, over a wide range of stimulation frequencies, the antiarrhythmic drugs, quinidine, lidocaine, and procainamide. In all cases, except for the region of potassium-induced supernormal conduction between 5.4 and 9 mM, Vmax and  velocity varied as predicted by one-dimensional cable theory; that is, changes in Vmax were always proportional to changes in the squar...