tbuckley/cabot-search huggingface dataset:
Imaging of vascular injury with 99mTc-labeled monoclonal antiplatelet antibody S12. Preliminary experience in human percutaneous transluminal angioplasty.
Authors: D DMiller, F JRivera, O JGarcia, J CPalmaz, H JBerger, H FWeisman
Journal: Circulation (1992)

BACKGROUNDTo evaluate the in vivo safety, biodistribution, and diagnostic accuracy of a monoclonal Fab' antibody (S12) that is specific for the platelet membrane glycoprotein (GMP-140) expressed during platelet activation at vascular injury sites, 11 peripheral percutaneous transluminal angioplasty (PTA) patients (age, 61 +/- 8 years) with severe vascular disease had serial 99mTcS12 radionuclide imaging at 5 and 90 minutes, 4-6 hours, and 20-24 hours after a total of 23 angiographically successful PTA procedures. No acute allergic reactions or hematologic toxicity occurred.METHODS AND RESULTSThe average PTA percent angiographic diameter stenosis (DS) at all 23 sites decreased from 85 +/- 12% to 12 +/- 11%, with a mean before-to-after-PTA change of 73 +/- 14% (p less than 0.01). The mean radionuclide image-derived ratio of 99mTc S12 activity in PTA versus contralateral non-PTA arterial segments for all angioplasty sites was 1.6 +/- 0.5. Vascular 99mTc S12 antibody activity was qualitatively evident in the ...
Synthetic Lethality in Cancer Therapeutics: The Next Generation
Authors: Jeremy Setton, Michael Zinda, Nadeem Riaz, Daniel Durocher, Michal Zimmermann, Maria Koehler, Jorge S. Reis-Filho, Simon N. Powell
Journal: Cancer Discovery (2021)

Abstract Synthetic lethality (SL) provides a conceptual framework for tackling targets that are not classically “druggable,” including loss-of-function mutations in tumor suppressor genes required for carcinogenesis. Recent technological advances have led to an inflection point in our understanding of genetic interaction networks and ability to identify a wide array of novel SL drug targets. Here, we review concepts and lessons emerging from first-generation trials aimed at testing SL drugs, discuss how the nature of the targeted lesion can influence therapeutic outcomes, and highlight the need to develop clinical biomarkers distinct from those based on the paradigms developed to target activated oncogenes. Significance: SL offers an approach for the targeting of loss of function of tumor suppressor and DNA repair genes, as well as of amplification and/or overexpression of genes that cannot be targeted directly. A next generation of tumor-specific alterations targetable through SL has emerged from high-throughput CRISPR technology, heralding not only new opportunities for drug development, but also important challenges in the development of optimal predictive biomarkers.
Flow-dependent coronary artery dilatation in humans.
Authors: HDrexler, A MZeiher, HWollschläger, TMeinertz, HJust, TBonzel
Journal: Circulation (1989)

To determine the role of endothelium-mediated flow-dependent coronary dilatation in humans, we studied the coronary dilatation exerted by maximal pharmacologic increase of coronary flow in 14 patients with normal coronary arteries. Biplane views of the circumflex (Cx) and left anterior descending (LAD) coronary arteries were obtained before and 80 seconds after inducing a maximal increase in flow selectively in the Cx by injecting 7 mg papaverine through a 2F infusion catheter in the midportion of the Cx (n = 10). The diameter of the proximal Cx segment (exposed to increased flow but not to papaverine directly) increased with papaverine by 11.1 +/- 4% (range, 5.2-16.4%, p less than 0.001 vs. control), whereas the LAD diameter did not change. LAD and Cx diameters increased by 18.3% and 21.2% after nitroglycerin given into the left main artery, which showed the preserved capability of the LAD to dilate. In four patients with normal coronary arteries and six patients with coronary artery disease (CAD, non-fl...
Characterization of <i>Ntrk</i> fusions and Therapeutic Response to Ntrk Inhibition in Hematologic Malignancies
Authors: Justin Taylor, Christina Marcelus, Dean Pavlick, Ryma Benayed, Akihide Yoshimi, Emiliano Cocco, Benjamin H Durham, Jaclyn F Hechtman, Young Rock Chung, Kerry Mullaney, Justin M Watts, Eli L Diamond, Lee A Albacker, Tariq I Mughal, Kevin Ebata, Brian B. Tuch, Nora Ku, Maurizio Scaltriti, Maria E. Arcila, Siraj M Ali, David M. Hyman, Omar Abdel-Wahab, Jae H. Park
Journal: Blood (2017)
Echocardiography of the tricuspid valve in congenital left ventricular-riht atrial communication.
Authors: N CNanda, RGramiak, J AManning
Journal: Circulation (1975)

Two patients, ages 14 and 18, with congenital left ventricular-right atrial communication through a defect in the tricuspid valve were studied by echocardiography. Proof was obtained by angiocardiography and surgery in one and ultrasonic contrast injection and angiocardiography in the other. Both presented clinically as uncomplicated ventricular septal defects. Echocardiography consistently demonstrated a high frequency, low amplitude flutter of the tricuspid valve in systole and none in diastole. Following surgical correction of the defect in one patient, there was complete disappearance of the systolic flutter. Systolic flutter has not been observed with tricuspid incompetence nor with other forms of ventricular septal defects. Fistulous communication from the aorta to the right atrium just above the tricuspid valve did not demonstrate systolic flutter in one patient studies. Tricuspid valve systolic flutter appears to be caused by the passage of the left ventricular jet blood into the right atrium thro...
Preload-induced curvilinearity of left ventricular end-systolic pressure-volume relations. Effects on derived indexes in closed-chest dogs.
Authors: J BSu, BCrozatier
Journal: Circulation (1989)

End-systolic pressure-volume relations (ESPVRs) were analyzed in 10 closed-chest autonomically blocked dogs before and after volume loading that restored end-diastolic volume to its value measured in the control conscious state. Dogs had been previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals for measurements of major, anteroposterior, and septum-free wall diameters. Left ventricular volume was calculated with an ellipsoidal model in the left ventricular cavity. ESPVRs obtained during caval occlusion after volume loading were curvilinear as shown by the division of the relation into two parts. The initial part of the relation had a significantly smaller ESPVR slope (Ees, 12.0 +/- 1.8 mm Hg/ml) and ESPVR volume-axis intercept (Vd, - 3.5 +/- 0.8 ml) than the final part of the relation (19.5 +/- 3.1 mm Hg/ml and 0.0 +/- 0.6 ml, respectively, p less than 0.01). The end-diastolic volume-peak dP/dt relation showed a similar curvilinearity when end-diastolic volumes w...
Abnormalities of right ventricular function following Mustard's operation for transposition of the great arteries.
Authors: T PGraham, G FAtwood, R JBoucek, R CBoerth, H WBender
Journal: Circulation (1975)

Postoperative data were obtained at cardiac catheterization in twelve patients studied 6-29 months following Mustard's operation for transposition of the great arteries (TGA) to assess the incidence and severity of abnormalities of right ventricular (RV) function. Age at operation was 5-13 months in seven patients (infant group) and 19-25 months in the remaining five patients. RV end-diastolic volume (EDV) decreased in all patients following surgery and averaged 123% of normal in the postoperative group (NS). RV ejection fraction (EF) was depressed postoperatively averaging 0.45 (69% of normal (P less than 0.001) as was RV systolic output (78% of normal, P less than 0.01). LVEDV averaged 65% of normal (P less than 0.001), LVEF 0.67 (103% of normal, NS), and LV systolic output 67% of normal (P less than 0.001) following operation. Left atrial (systemic venous) volume was decreased in all postoperative patients averaging only 39% of normal (P less than 0.001). A high incidence (greater than 50%) of partial ...
A randomized, double-blind, placebo-controlled phase 1 trial of inhaled and intranasal niclosamide: A broad spectrum antiviral candidate for treatment of COVID-19
Authors: Vibeke Backer, Ulf Sjöbring, Jesper Sonne, Anne Weiss, Morten Hostrup, Helle Krogh Johansen, Victoria Becker, David P. Sonne, Torben Balchen, Mads Jellingsø, Morten Otto Alexander Sommer
Journal: The Lancet Regional Health - Europe (2021)
Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death.
Authors: AAlgra, J GTijssen, J RRoelandt, JPool, JLubsen
Journal: Circulation (1993)

BACKGROUNDLow heart rate variability has been implicated as a risk factor for sudden death. However, no large epidemiological studies using sudden death as an outcome event have been reported.METHODS AND RESULTSA total of 6,693 consecutive patients who underwent 24-hour ambulatory ECG were followed up for 2 years; of these, 245 patients died suddenly. Clinical data at the time of 24-hour ambulatory ECG were collected for all patients who died suddenly and for a random sample of 268 patients from the study cohort. In all patients in sinus rhythm with or without occasional supraventricular arrhythmias at the 24-hour ECG (193 patients who died suddenly and 230 patients from the sample), heart rate variability parameters were derived. Patients with low short-term RR interval variability (mean during 24 hours of per-minute standard deviations [SD] of RR intervals   or ...
Effect of pulse separation between two sequential biphasic shocks given over different lead configurations on ventricular defibrillation efficacy.
Authors: E EJohnson, C AAlferness, P DWolf, W MSmith, R EIdeker
Journal: Circulation (1992)

BACKGROUNDTwo sequential biphasic shocks delivered over separate lead configurations markedly improve defibrillation efficacy compared with a single shock alone. We investigated the effect of varying the intershock interval between sequential biphasic shocks on defibrillation.METHODS AND RESULTSDefibrillation thresholds (DFTs) were obtained in six dogs for shock separations ranging from 0.2 to 125 msec. The first shock was given from a catheter electrode in the right ventricular apex to a patch on the left lateral thorax; the second was from a small patch on the left ventricular apex to a catheter electrode in the right ventricular outflow tract. When the interval between shocks was less than or equal to 10 msec or greater than or equal to 75 and less than or equal to 125 msec, the mean DFTs were less than that previously found for the first shock by itself (4.2 versus 7.4 J, p = 0.002). At a separation of 50 msec, however, there was a marked rise in the DFT to 27 J. The mean DFT for the second shock at a...
Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy
Authors: Pataje G Prasanna, Deborah E Citrin, Jeffrey Hildesheim, Mansoor M Ahmed, Sundar Venkatachalam, Gabriela Riscuta, Dan Xi, Guangrong Zheng, Jan van Deursen, Jorg Goronzy, Stephen J Kron, Mitchell S Anscher, Norman E Sharpless, Judith Campisi, Stephen L Brown, Laura J Niedernhofer, Ana O’Loghlen, Alexandros G Georgakilas, Francois Paris, David Gius, David A Gewirtz, Clemens A Schmitt, Mohamed E Abazeed, James L Kirkland, Ann Richmond, Paul B Romesser, Scott W Lowe, Jesus Gil, Marc S Mendonca, Sandeep Burma, Daohong Zhou, C Norman Coleman
Journal: JNCI Journal of the National Cancer Institute (2021)

Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction of tumor cell senescence is also one of the underlying mechanisms by which cancer therapies exert antitumor activity. However, an increasing body of evidence from preclinical studies demonstrates that radiation and chemotherapy cause accumulation of senescent cells (SnCs) both in tumor and normal tissue. SnCs in tumors can, paradoxically, promote tumor relapse, metastasis, and resistance to therapy, in part, through expression of the senescence-associated secretory phenotype. In addition, SnCs in normal tissue can contribute to certain radiation- and chemotherapy-induced side effects. Because of its multiple roles, cellular senescence could serve as an important target in the fight against cancer. This commentary provides a summary of the discussion at the National Cancer Institute Workshop on Radiation, Senescence, and Cancer (August 10-11, 2020, National Cancer Institute, Bethesda, MD) regarding the current status of senescence research, heterogeneity of therapy-induced senescence, current status of senotherapeutics and molecular biomarkers, a concept of "one-two punch" cancer therapy (consisting of therapeutics to induce tumor cell senescence followed by selective clearance of SnCs), and its integration with personalized adaptive tumor therapy. It also identifies key knowledge gaps and outlines future directions in this emerging field to improve treatment outcomes for cancer patients.
Learning is shaped by abrupt changes in neural engagement
Authors: Jay A. Hennig, Emily R. Oby, Matthew D. Golub, Lindsay A. Bahureksa, Patrick T. Sadtler, Kristin M. Quick, Stephen I. Ryu, Elizabeth C. Tyler-Kabara, Aaron P. Batista, Steven M. Chase, Byron M. Yu
Journal: Nature Neuroscience (2021)
The effects of a cardioselective (metoprolol) and a nonselective (propranolol) beta-adrenergic blocker on the response to dynamic exercise in normal men.
Authors: JSklar, G DJohnston, POverlie, J GGerber, H LBrammell, JGal, A SNies
Journal: Circulation (1982)

We compared the effects of a cardioselective beta-adrenergic blocking drug, metoprolol, with a nonselective beta-adrenergic blocker, propranolol, on the response of 10 normal men to dynamic treadmill exercise. The volunteers underwent a standard graded exercise test to exhaustion while receiving placebo; propranolol, 40 mg every 6 hours; propranolol, 80 mg every 6 hours; metoprolol, 50 mg every 6 hours; or metoprolol, 100 mg every 6 hours. The drugs were given in a double-blind fashion for 48 hours before exercise. Five days were allowed between successive drug administrations and the order of drug administration was randomized. Heart rate, arterial pressure, oxygen consumption, minute ventilation and CO2 production were monitored. Plasma drug concentrations were measured at the time of exercise. Judged by plasma levels, propranolol was about three times more potent than metoprolol in attenuating heart rate. Both drugs produced a wide variation in plasma levels after a given oral dose, and both drugs atte...
Suppression of eicosanoid biosynthesis during coronary angioplasty by fish oil and aspirin.
Authors: G ABraden, H RKnapp, G AFitzGerald
Journal: Circulation (1991)

BACKGROUNDPercutaneous transluminal coronary angioplasty (PTCA) is an acute, localized stimulus to platelet and vascular function. Periprocedural cardiovascular complications are reduced by moderate-dose aspirin (ASA), presumably due to inhibition of thromboxane (TX) A2.METHODS AND RESULTSExcretion of TXA2 and prostacyclin (PGI2) metabolites in urine increased during PTCA. Pretreatment for 3 days with either moderate- (325 mg/day) or low-dose (80 mg/day) ASA inhibited the increase in both eicosanoids. Pretreatment for 3 weeks with fish oil (10 g/day) only partially suppressed TXA2. Formation of trienoic eicosanoids and accumulation of omega-3 fatty acids in platelet membranes confirmed fish oil ingestion. Although basal PGI2 was not inhibited, the PTCA-related increment was suppressed.CONCLUSIONSPTCA results in an acute, transient alteration of eicosanoid biosynthesis consistent with accelerated platelet-vascular interactions. Pretreatment for 3 days with moderate or low doses of ASA suppresses TXA to a s...
MVP Combined with FC As Lymphocyte-Depleting Chemotherapy before CAR-T Treatment Can Reduce the Incidence of Severe Cytokine Release Syndrome for Relapsed/Refractory ALL Patients with High Tumour Burden
Authors: XiaoWen Tang, Zheng Li, Ting Xu, Haiping Dai, Jia Yin, Xiaopeng Tian, Shengli Xue, Yang Xu, Xiaming Zhu, Liqing Kang, Yujie Xia, Lei Yu, Depei Wu
Journal: Blood (2017)
Comparative study on the proarrhythmic effects of some antiarrhythmic agents.
Authors: SDhein, AMüller, RGerwin, WKlaus
Journal: Circulation (1993)

BACKGROUNDA main side effect of antiarrhythmic drug therapy is the tendency of these drugs to promote arrhythmia within the therapeutic concentration range, i.e., the proarrhythmic activity of these drugs. However, a model for in vitro assessment, quantification, and comparison of proarrhythmic drug activities was still lacking, and only sparse data were available.METHODS AND RESULTSTo analyze the arrhythmogenic risk of common antiarrhythmic drugs in a quantitative and comparative manner, isolated perfused rabbit hearts were treated with increasing concentrations of antiarrhythmic drugs corresponding to low, medium, and high therapeutic concentrations. For analysis of the epicardial activation process, an epicardial mapping (256 unipolar leads) was performed. For each electrode, the activation time was determined. From these data, the origins of epicardial activation (breakthrough points [BTP]) were determined. At each electrode, an activation vector (VEC) was calculated giving direction and velocity of...
Cardiovascular responses during static exercise. Studies in patients with complete heart block and dual chamber pacemakers.
Authors: TAlexander, D BFriedman, B DLevine, J APawelczyk, J HMitchell
Journal: Circulation (1994)

BACKGROUNDDuring static exercise in normal subjects, the mean arterial pressure increases as a result of an increase in heart rate and thereby cardiac output with no significant change in stroke volume or systemic vascular resistance. We hypothesized that if one component of the blood pressure response to static exercise, ie, heart rate, were fixed, plasticity of the neural control mechanisms during exercise would allow for preservation of the blood pressure response by alternative mechanisms.METHODS AND RESULTSThirteen patients 20 to 68 years old with structurally normal hearts, complete heart block, and dual chamber pacemakers performed static exercise during three conditions: (1) normal dual chamber sensing and pacing mode, (2) heart rate fixed at the resting value obtained in the DDD mode of 78 +/- 4 beats per minute, and (3) heart rate fixed at the peak value obtained during exercise in the DDD mode of 94 +/- 4 beats per minute. Heart rate, blood pressure, and cardiac output were measured and stroke ...
Fetal Cardiac Imaging for Congenital Heart Disease—Is Cardiac Magnetic Resonance Imaging the Future?
Authors: Bhawna Arya
Journal: JAMA Network Open (2021)

Daniel Ryd, MD; Katrin Fricke, MD; Misha Bhat, MD; Håkan Arheden, MD, PhD; Petru Liuba, MD, PhD; Erik Hedström, MD, PhD
Effect of coronary stenosis on myocardial blood flow during exercise in the chronically pressure-overloaded hypertrophied left ventricle.
Authors: R JBache, LWright, D DLaxson, X ZDai
Journal: Circulation (1990)

This study was performed to determine if a coronary artery stenosis would result in more-severe perfusion abnormalities in hypertrophied compared with normal canine hearts during exercise. Studies were performed in eight normal control dogs and in seven adult dogs in which a 67% increase in left ventricular mass wa produced by banding the ascending aorta at 9 weeks of age. Myocardial blood flow was measured by the microsphere method during treadmill exercise in the presence of a coronary artery stenosis that decreased distal coronary perfusion pressure to 55 or 42 mm Hg. At a coronary pressure of 55 mm Hg, mean myocardial blood flow was decreased by 23 +/- 5% in normal control dogs but was decreased by 53 +/- 10% in dogs with left ventricular hypertrophy (LVH) (p less than 0.05, comparing normal vs. LVH dogs). Similarly, at a coronary pressure of 42 mm Hg, mean blood flow was decreased by 53 +/- 6% below control in normal dogs but was decreased by 76 +/- 5% below control values in dogs with LVH (p less th...
Reversal of left ventricular dysfunction after aortic valve replacement for chronic aortic regurgitation: influence of duration of preoperative left ventricular dysfunction.
Authors: R OBonow, D RRosing, B JMaron, C LMcIntosh, MJones, S LBacharach, M VGreen, R EClark, S EEpstein
Journal: Circulation (1984)

Preoperative left ventricular systolic function is an important predictor of postoperative prognosis in patients with aortic regurgitation. Although left ventricular dysfunction is reversible after aortic valve replacement to a greater extent in patients with good preoperative exercise capacity compared with patients with impaired exercise capacity, not all patients with preserved exercise capacity demonstrate improved left ventricular function after aortic valve replacement. To determine the influence of duration of preoperative left ventricular dysfunction on postoperative reversal of left ventricular dysfunction, we studied 37 patients with aortic regurgitation who preoperatively had left ventricular dysfunction, defined as subnormal echocardiographic fractional shortening (less than 29%), and good preoperative exercise capacity, defined as completion of stage I of the NIH treadmill protocol without limiting symptoms. Eight patients were asymptomatic. In 11 patients left ventricular dysfunction was doc...
Amantadine-induced diastolic depolarization and automaticity in ventricular muscle.
Authors: J JSalata, JJalife, J LMegna, GAlperovich
Journal: Circulation Research (1982)

We studied the cardiac effects of amantadine, an antiviral and anti-Parkinson drug. Amantadine hydrochloride (100--800 microM) produced significant changes in the electrophysiological properties of isolated ventricular muscle preparations from frog, rabbit, cat, dog, and calf. At relatively low concentrations (100--300 microM), the drug increased action potential duration, decreased action potential amplitude and maximum diastolic potential, and induced phase 4 depolarization. Amantadine also caused subthreshold diastolic depolarizations, apparent upon cessation of stimulation in all preparations studied. The amplitude of the diastolic depolarizations increased as a function of time and/or concentration of drug, eventually reached threshold, and spontaneous activity ensued. In the steady state, amantadine-induced spontaneous activity was rather stable, and the rate was dependent upon the amantadine and external potassium concentrations, as well as the membrane potential. In the absence of stimulation, ama...
Effects of intracoronary infusion of arterial blood or Fluosol-DA 20% on regional myocardial metabolism and function during brief coronary artery occlusions.
Authors: HTokioka, AMiyazaki, PFung, R ERajagopalan, SKar, SMeerbaum, ECorday, J KDrury
Journal: Circulation (1987)

Effects of intracoronary infusion (50 ml/min) of arterial blood, oxygenated or unoxygenated Fluosol, or Plasmalyte A on hemodynamics, electrocardiogram, regional myocardial function, and lactate metabolism were studied in six closed-chest dogs during 2 min occlusions of the left anterior descending coronary artery followed by 10 min of reperfusion. Normal hemodynamics were maintained with infusion of arterial blood and oxygenated Fluosol, whereas unoxygenated Fluosol and Plasmalyte A resulted in hemodynamic deterioration similar to that noted with no treatment. Ischemic zone systolic fractional area change, an index of systolic function measured by two-dimensional echocardiography, remained normal during the occlusion supplemented with intracoronary arterial blood (49 +/- 7%), was moderately hypokinetic with oxygenated Fluosol (31 +/- 10%), and became severely hypokinetic with unoxygenated Fluosol (14 +/- 14%), with Plasmalyte A (2 +/- 13%), and in the absence of treatment (5 +/- 9%). Only infusion of art...