tbuckley/cabot-search huggingface dataset:
In at-risk patients without CVD, polypill plus aspirin reduced a composite of major CV events at 4.6 y
Authors: Michael Tanner
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubApril 2021In at-risk patients without CVD, polypill plus aspirin reduced a composite of major CV events at 4.6 yMichael Tanner, MDMichael Tanner, MDNYU Grossman School of Medicine, New York, New York, USA (M.T.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202104200-041 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationYusuf S, Joseph P, Dans A, et al. Polypill with or without aspirin in persons without cardiovascular disease. N Engl J Med. 2021;384:216-28. https://pubmed.ncbi.nlm.nih.gov/33186492Clinical Impact RatingsGIM/FP/GP: Cardiology: Nephrology: References1 Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326:1419. [PMID: 12829553] Google Scholar2 Roshandel G, Khoshnia M, Poustchi H, et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular disease (PolyIran): a pragmatic, cluster-randomised trial. Lancet. 2019;394:672-83. [PMID: 31448738] Google Scholar Author, Article, and Disclosure InformationAffiliations: NYU Grossman School of Medicine, New York, New York, USA (M.T.)Disclosures: The commentator has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7315.This article was published at Annals.org on 6 April 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics April 2021Volume 174, Issue 4Page: JC41KeywordsAspirinCardiovascular diseasesDrugsHeartHeart failureMyocardial infarctionPharmacogenomicsRevascularizationStatinsStroke ePublished: 6 April 2021 Issue Published: April 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Percutaneous polymeric stents in porcine coronary arteries. Initial experience with polyethylene terephthalate stents.
Authors: J GMurphy, R SSchwartz, W DEdwards, A RCamrud, R EVlietstra, D RHolmes
Journal: Circulation (1992)

BACKGROUNDTo test the feasibility of percutaneous deployment of intracoronary polymeric stents, a prototype polyethylene terephthalate (PET) stent and a catheter-based delivery system were developed.METHODS AND RESULTSPolymeric stents were deployed in the coronary arteries of 11 Yucatan swine: six stents were placed in the left anterior descending coronary artery, four stents were placed in the circumflex artery, and one stent was placed in the right coronary artery. Stent deployment was achieved by withdrawal of an outer delivery sheath, thus allowing the PET stent to self-expand to a preformed configuration. Two animals died during surgery, one during stent placement and the other several hours after implantation due to intracoronary thrombus formation. Two animals were electively sacrificed within 24 hours of stent implant to examine the adequacy of stent deployment within the coronary vessel. The remaining seven animals survived until the termination of the study 4-6 weeks later. Light microscopic exa...
Occurrence of oxidative stress during reperfusion of the human heart.
Authors: RFerrari, OAlfieri, SCurello, CCeconi, ACargnoni, PMarzollo, APardini, ECaradonna, OVisioli
Journal: Circulation (1990)

We have investigated the relation between occurrence of myocardial oxidative stress and functional recovery during postischemic reperfusion in 20 selected patients subjected to aortocoronary bypass grafting. Patients were selected for having normal percent ejection fraction and left ventricular end-diastolic pressure before the operation. Occurrence of oxidative stress was assessed by measuring the formation and release of oxidized glutathione (GSSG) in the coronary sinus immediately before aortic cross-clamp, 1, 5, 10, and 20 minutes after removal of aortic cross-clamp, and 10 and 20 minutes after the end of cardiopulmonary bypass. Reduced glutathione (GSH), lactate, and creatine phosphokinase release were also monitored with the same timing. Standard hemodynamic measurements were recorded by means of a triple-lumen thermodilution pulmonary artery catheter before sternotomy, 15 minutes after the end of cardiopulmonary bypass, and during the 24 hours after termination of cardiopulmonary bypass. Reperfusio...
Monohydroxyeicosatetraenoic acids (5-HETE and 15-HETE) induce pulmonary vasoconstriction and edema.
Authors: K EBurhop, W MSelig, A BMalik
Journal: Circulation Research (1988)

5-, 15-, and 12-HETE (monohydroxyeicosatetraenoic acids) are products of the lipoxygenation of arachidonic acid. We investigated their role as possible mediators of pulmonary vasoactivity and pulmonary edema. Pulmonary artery pressure (Ppa), capillary pressure (Pcap), the change in lung wet weight (delta wt) from baseline, and capillary filtration coefficient (Kf) (as a measure of vascular permeability) were determined following an intravenous injection of each mono-HETE in lungs perfused at constant flow with either a phosphate-buffered Ringer's-albumin solution (PBR) or diluted blood. Injection of 2 micrograms of each compound into the pulmonary artery of lungs perfused with either PBR or diluted blood did not produce any effect. However, in PBR-perfused lungs, 4 micrograms 15-HETE induced increases in Ppa, Pcap, and lung wet weight (p less than 0.05), which were greater than the increases observed after 4 micrograms 5-HETE. Kf increased following both 5- and 15-HETE. The pulmonary vasoconstrictor and e...
Swelling-induced chloride-sensitive current in canine atrial cells revealed by whole-cell patch-clamp method.
Authors: SSorota
Journal: Circulation Research (1992)

An isoproterenol-induced chloride current has been detected in ventricular myocytes from guinea pig and rabbit but has not been found in canine ventricular cells. This investigation was undertaken to determine whether canine atrial cells possessed such a current. Steady-state currents were examined with potassium currents blocked by cesium. In whole-cell patch-clamp experiments, an isoproterenol-induced chloride current could not be detected shortly after patch rupture. However, whole-cell current in the absence of isoproterenol increased over time after patch rupture. The spontaneously activating steady-state current was outwardly rectifying with a reversal potential of approximately -25 mV. The current that developed over time was sensitive to variation in extracellular chloride concentration and was partially blocked by anthracene-9-carboxylic acid. Isoproterenol could enhance the amplitude of this current once it developed. Although isosmotic pipette filling and extracellular solutions were used, cell...
Direct measurement of changes in intracellular calcium transients during hypoxia, ischemia, and reperfusion of the intact mammalian heart.
Authors: YKihara, WGrossman, J PMorgan
Journal: Circulation Research (1989)

In studies of ischemia and reperfusion, a major experimental problem has been the inability to measure intracellular ionized calcium ([Ca2+]i) in the intact heart. We have developed a new approach in which the bioluminescent calcium indicator aequorin is used to measure [Ca2+]i in the isolated, coronary-perfused ferret heart. Aequorin is loaded into subepicardial myocytes of the left ventricle, and the signals are recorded simultaneously along with isovolumic left ventricular (LV) pressure at a constant pacing rate. This system shows 1) no attenuation or change of time course of LV pressure development or coronary perfusion pressure after aequorin loading; 2) consistent responses to physiological interventions and drugs; 3) individual aequorin and pressure signals that do not require signal averaging for analysis; and 4) [Ca2+]i levels comparable with those reported in tissue or isolated myocyte cell preparations. During 5 minutes of hypoxia, diastolic [Ca2+]i and LV diastolic pressure increased while the...
Imaging of thrombi with tissue-type plasminogen activator rendered enzymatically inactive and conjugated to a residualizing label.
Authors: J MOrd, JHasapes, ADaugherty, S RThorpe, S RBergmann, B ESobel
Journal: Circulation (1992)

BACKGROUNDContemporary cardiovascular practice relies increasingly on thrombolysis as a therapeutic modality. Its optimal use requires prompt, noninvasive delineation of thrombotic occlusion in arterial beds and rapid detection of reocclusion after initially successful thrombolysis.METHODS AND RESULTSWe have been developing an approach to noninvasively image thrombi in which plasminogen-activating properties of tissue-type plasminogen activator (t-PA) are attenuated by treatment with D-Phe-L-Pro-L-Arg-chloromethyl ketone (PPACK) and have shown that the inactive t-PA avidly and promptly binds to clots in vitro. In the present study, we conjugated this material to a residualizing label, radioiodinated dilactitol tyramine (*I-DLT), and characterized the potential use of the inactivated, conjugated t-PA as a radiopharmaceutical for imaging thrombi in vivo. The approach developed requires not only avid binding of the tracer to thrombi but also rapid clearance from plasma and a lack of prompt release of radiola...
Effect of angiotensin II and enalapril on transfer of low-density lipoprotein into aortic intima in rabbits.
Authors: L BNielsen, SStender, KKjeldsen, B GNordestgaard
Journal: Circulation Research (1994)

To assess the mechanism behind a possible atherosclerosis-promoting effect of angiotensin II, the influence of angiotensin II, noradrenaline, and enalapril on transfer of low-density lipoprotein (LDL) into the arterial wall was investigated in conscious rabbits. Intravascular infusion of angiotensin II (1.4 micrograms/kg per minute) initially increased the mean blood pressure from 70 to 80 mm Hg to 125 to 150 mm Hg; this effect was transient, and the blood pressure returned to baseline values within 2 hours, despite continuous infusion of angiotensin II. The normalized influx of LDL into the aortic intima, determined after in vivo exposure to 125I-LDL for 1 hour, was 88 +/- 17 (n = 6), 12 +/- 12 (n = 5), and 28 +/- 6 (n = 5) nL/cm2 per hour (mean +/- SEM) during angiotensin II infusion at high blood pressure, during angiotensin II infusion after the blood pressure had been normalized, and during continuous saline infusions, respectively (P < .05 for high blood pressure versus low blood pressure and saline...
N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.
Authors: JStamler, M EMendelsohn, PAmarante, DSmick, NAndon, P FDavies, J PCooke, JLoscalzo
Journal: Circulation Research (1989)

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-deriv...
Transient outward current prominent in canine ventricular epicardium but not endocardium.
Authors: S HLitovsky, CAntzelevitch
Journal: Circulation Research (1988)

Previous studies have denied the presence of a transient outward current (Ito) in ventricular myocardium of dog, sheep, and calf. Using conventional microelectrode techniques, we provide evidence for a significant contribution of Ito to epicardial, but not endocardial, activity of canine ventricular myocardium. The epicardial action potential when compared with that of endocardium shows a smaller phase 0 amplitude, a much more prominent phase 1, and a phase 2 amplitude that is greater than that of phase 0. Epicardial action potentials, unlike those of endocardium, display a  and  morphology that becomes progressively more accentuated at slower stimulation rates. Using the restitution of phase 1 amplitude as a marker for the process responsible for the spike and dome phenomenon, we were able to delineate two exponential components: 1) a slow component that recovers with a time constant of 350-570 msec and 2) a fast component with a time constant of 41-85 msec. The slow component was largely abol...
Adjuvant Nivolumab in Esophageal Cancer — A New Standard of Care
Authors: David H. Ilson
Journal: New England Journal of Medicine (2021)

Esophageal cancer is a leading cause of cancer-related illness and death throughout the world. Because there is no effective screening or early detection, most patients present with locally advanced or overt metastatic disease. Esophageal squamous-cell carcinoma is the most common histologic type worldwide in high-incidence areas such as East Asia, and adenocarcinoma is the dominant histologic type in the West. A review of surgical outcomes in nearly 84,000 patients with esophageal squamous-cell cancer in 1980 indicated the daunting challenge of treating esophageal cancer.1 Surgical exploration was performed in 58% of the patients, 39% underwent resection (30% died during or soon . . .
Rapid detection of cell death in a bioluminescent human breast cancer cell line subjected to hyperthermia.
Authors: Renshu Zhang, Liang Shang, Yanfei Zhou, Paul Wang, Rajagopalan Sridhar
Journal: Cancer Research (2007)

5568  This study was designed to assess the feasibility of using a bioluminescence assay for rapid measurement of cell death in luciferase transfected MDA-MB-231-luc-D3-H1 human breast cancer cells subjected to 43°C hyperthermia. Colony formation assay, which takes 7 to 15 days, is the gold standard for in vitro evaluation of cell survival after exposure to radiation, hyperthermia or cancer chemotherapeutic agents. There is a need for more rapid assays which yield results that are closely related to clonogenic survival. MDA-MB-231-luc-D3H1 is a stable luciferase transfected breast cancer cell line, which lends itself to bioluminescent detection and imaging in the presence of D-luciferin. Three different assays of cell viability were used to study the response of MDA-MB 231-luc-D3H1 human breast cancer cells to 43°C hyperthermia treatment, which consisted of immersing sealed 96 well plates containing 10,000 cells per well, in a thermostatic water bath. The relative survival values determined by the three assays differed considerably. Immediate assay after 2 hours at 43°C indicated relative survival values of 30%, 68% and 2% based on clonogenicity, MTT assay and luciferin based luminometry, respectively. When the MTT assay was delayed, to allow cells to proliferate for five days post hyperthermia, the relative cell survival was 34%. The delayed MTT assay, however, covers only a narrow range of cell survival and fails to detect low levels of toxicity. After hyperthermia treatment, MDA-MB231-Luc human breast cancer cells were treated with D-luciferin (150µg/ml) for measurement of bioluminescence using a Xenogen IVIS 200 imaging system. The luminescence was related to the number of viable cells over a wide range (1000 to 500,000 cells per well). The decrease in luminescence was detectable immediately after heat treatment. This decrease was related to the duration of heating at 43°C. When compared to clonogenicity measurements, the luminometric assay overestimated the cytotoxic effect of hyperthermia. In conclusion, relative to the gold standard of clonogenic assays, MTT assay over estimates viability and covers only a narrow range of cytotoxicity, while bioluminescence underestimates viability of cells subjected to hyperthermia. Luminometric assay of response to hyperthermia is rapid in bioluminescent cells, but is not closely related to the clonogenic potential. This suggests that other ATP based assays of cell viability will also overestimate cytotoxicity when compared to clonogenicity assays. Nonetheless luminometric estimate of ATP in cells can be used for rapid screening of cytotoxic regimens. Caution has to be exercised while comparing cell viability results based on different assays.  (Supported in part by grant 2 G12 RR003048 from the RCMI Program, Division of Research Infrastructure, National Center for Research Resources, NIH and USMRMC grants DAMD17-03-1-0759, DAMD17-03-1-0123).
Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle.
Authors: M JLab, J ALee
Journal: Circulation Research (1990)

Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with the photoprotein aequorin in isolated ferret papillary muscles. Tension and length were also recorded simultaneously. Transient mechanical alternans lasting five to 20 contractions could be reliably induced in this preparation by following a 30-second rest period with stimulation at a fast rate (2-4 Hz). Production of sustained mechanical alternans, which lasted longer than 20 contractions and could persist for several hundred contractions, required additional interventions, consisting of a lower temperature (25 degrees C), a lower external calcium concentration (1 mM), and a lower pH (6.91) than control conditions (0.33-0.5 Hz, 30 degrees C, 2 mM Ca2+, pH 7.36). Transient mechanical alternans...
Myocardial dysfunction during paroxysmal supraventricular tachycardia.
Authors: M AWarnowicz, B ASantucci, H GBucheleres, PDenes
Journal: Circulation (1981)

Paroxysmal supraventricular tachycardia (PSVT) is associated with altered hemodynamics. We describe the echocardiographic features of myocardial dysfunction during a prolonged episode of PSVT in an 11-year-old male. The abnormality of the phases of cardiac activity presented as a markedly prolonged left ventricular systole (320 msec) and isovolumic relaxation phase (220 msec) and a shortened and delayed diastolic filling period (140 msec). These abnormalities reverted to normal immediately after spontaneous conversion to sinus rhythm. Propranolol, which was used to prevent PSVT in this child, may have been involved in the mechanism of the altered mechanical events.
Electrical alternans and cardiac electrical instability.
Authors: J MSmith, E AClancy, C RValeri, J NRuskin, R JCohen
Journal: Circulation (1988)

We investigated the relationship between electrical alternans and cardiac electrical stability in a series of 20 dog experiments and in a pilot clinical study. Electrical alternans was detected in both the QRS complex and the ST-T wave by use of a novel multidimensional spectral technique. The magnitude of the alteration was expressed as the alternating electrocardiographic morphology index (AEMI), expressed as parts per million of waveform energy. Electrical stability in the dog preparations was assessed via the ventricular fibrillation threshold measurement, and in the clinical studies via programmed stimulation. In 10 dog experiments, systemic hypothermia resulted in a 60% decrease in ventricular fibrillation threshold (VFT) (p less than .0001) and a significant increase in both AEMI(QRS) form 3.7 +/- 3.0 to 1448 +/- 548 (p less than .0001) and AEMI(ST-T) from 43.9 +/- 18.4 to 19,178 +/- 5579 (p less than .0001). In 10 dog experiments, transient coronary artery ligation also resulted in a 60% decrease ...
A method for quantitating antifibrillatory effects of drugs after coronary reperfusion in dogs: improved outcome with bretylium.
Authors: T LWenger, SLederman, C FStarmer, TBrown, H CStrauss
Journal: Circulation (1984)

We developed a quantitative approach to assess the antifibrillatory effects of short-term interventions in a canine preparation of ventricular fibrillation caused by coronary reperfusion, and applied it to evaluate the antifibrillatory effects of bretylium tosylate. Twenty-five dogs were given 10 mg/kg infusions of bretylium over 10 min, subjected to a 20 min proximal left anterior descending coronary artery ligation followed by sudden release, and compared with 25 animals given saline placebo. Drug infusion was begun 90 min before reperfusion to avoid evaluation of outcome during the phase of drug-induced catecholamine release and to allow adequate time for bretylium uptake in the myocardium. The relationship between the likelihood of ventricular fibrillation during reperfusion and the amount of myocardium perfused by the occluded vessel (myocardium at risk) was analyzed with the logistic risk-regression model. This model was developed to control for the effects of amount of myocardium at risk on outcome...
Novel diazinone derivatives separate myofilament Ca2+ sensitization and phosphodiesterase III inhibitory effects in guinea pig myocardium.
Authors: CVentura, RMiller, H PWolf, NBeier, RJonas, MKlockow, ILues, OHano, H ASpurgeon, E GLakatta
Journal: Circulation Research (1992)

The inotropic state of the myocardium can be enhanced via an increase in cell Ca2+ loading or in myofilament responsiveness to Ca2+. Although different pharmacological agents combine these properties, no presently available drug acts predominantly as a myofilament sensitizer in situ. We have investigated the effects and the mechanism of action of novel diazinone derivatives, EMD 54622, EMD 53998, and EMD 54650 (developed by E. Merck, Darmstadt), on guinea pig myocardial preparations. Force- and ATPase-pCa relations in skinned fibers show differing potencies of these agents on myofilament sensitization: EMD 54622 greater than EMD 53998 much greater than EMD 54650. This is in contrast to their relative potencies to inhibit isolated myocardial phosphodiesterase III: EMD 54650 greater than EMD 53998 greater than EMD 54622. In isolated hearts studied at constant coronary flow, each of the three diazinone derivatives had a positive inotropic effect. In enzymatically dissociated left ventricular myocytes loaded ...
Bovine and human endothelial cell production of neutrophil chemoattractant activity in response to components of the angiotensin system.
Authors: H WFarber, D MCenter, SRounds
Journal: Circulation Research (1985)

Although there is growing evidence that angiotensin II affects macrophage-mediated inflammatory responses, it is unclear whether it can affect neutrophil-mediated inflammatory responses. Because vascular endothelial cells are capable of releasing neutrophil chemoattractant activity, we attempted to determine whether components of the angiotensin system could affect neutrophil-mediated responses indirectly by stimulating endothelial cells to release neutrophil chemoattractant substances. Cultured bovine and human endothelial cells incubated with angiotensin II released neutrophil chemoattractant activity. This activity appeared within 1 minute of exposure to angiotensin II, and was blocked by saralasin, an angiotensin II antagonist. Angiotensin I also caused release of neutrophil chemoattractant activity, but its effect required conversion to angiotensin II. Bradykinin, another substrate for angiotensin-converting enzyme, did not stimulate appearance of chemoattractant. Chemoattractant generation was not i...