tbuckley/cabot-search huggingface dataset:
Inhibition of smooth muscle cell proliferation by an antisense oligodeoxynucleotide targeting the messenger RNA encoding proliferating cell nuclear antigen.
Authors: ESpeir, S EEpstein
Journal: Circulation (1992)

BACKGROUNDThe process by which normally quiescent vascular smooth muscle cells (SMCs) change into proliferating cells, which express and respond to multiple growth factors, plays a major role in restenosis after coronary angioplasty. We are attempting to inhibit SMC proliferation by interventions that inhibit specific factors involved in signal transduction pathways leading to cell division. To date, all studies taking this approach have attempted to block the effects of mitogens acting on the cell surface. In contrast, we have focused on a strategy that bypasses cell surface-mediated events by directly inhibiting the expression of proliferating cell nuclear antigen (PCNA), an intranuclear protein that functions in a final common pathway shared by diverse mitogen-induced signals. In the present investigation, we determined whether antisense oligodeoxynucleotides (ODNs) complementary to the messenger RNA of PCNA will inhibit PCNA expression and thereby reduce SMC proliferation.METHODS AND RESULTSWhen antis...
Correlation of pharmacological 99mTc-sestamibi myocardial perfusion imaging with poststenotic coronary flow reserve in patients with angiographically intermediate coronary artery stenoses.
Authors: D DMiller, T JDonohue, L TYounis, R GBach, F VAguirre, M DWittry, H MGoodgold, B RChaitman, M JKern
Journal: Circulation (1994)

BACKGROUNDThe physiological assessment of angiographically intermediate-severity stenoses remains problematic. Functional measurements of poststenotic intracoronary Doppler coronary flow reserve can be performed in humans but have not been correlated with hyperemic myocardial perfusion imaging or angiographic data in this patient population.METHODS AND RESULTSThirty-three patients undergoing diagnostic quantitative coronary angiography (QCA) for assessment of intermediate-severity coronary artery disease (mean QCA percent diameter stenosis, 56 +/- 14%) were studied. Proximal and distal poststenotic Doppler coronary flow velocities were measured (left anterior descending coronary artery, 16; right coronary artery, 10; left circumflex artery, 7 patients) before and during peak maximal hyperemia with intracoronary adenosine (8 to 12 micrograms). Intravenous pharmacological stress (adenosine, 20 patients; dipyridamole, 13 patients) 99mTc-sestamibi tomographic perfusion imaging was performed within 1 week of c...
Pressure-diameter relations during early diastole in dogs. Incompatibility with the concept of passive left ventricular filling.
Authors: H NSabbah, P DStein
Journal: Circulation Research (1981)

We studied left ventricular (LV) pressure-diameter relations in 13 open-chest mongrel dogs to explore whether ventricular filling is passive, active, or a combination of both. Left ventricular internal diameter along the minor axis and thickness of the LV free wall were measured with ultrasonic dimension gauges. Pressures in the LV, left atrium (LA), and aorta were measured with catheter-tip micromanometers. Pressure in the LV during the rapid filling phase of diastole decreased from 13 +/- 1 mm Hg to 3 +/- 0.4 mm Hg (mean +/- SE). During this period, LV internal diameter increased from 32.6 +/- 1.5 to 36.7 +/- 1.5 mm, and this represented 49% of the total change of LV diameter that occurred during diastole. The pressure-diameter relation that we observed during the rapid phase of filling suggests that active enlargement rather than passive distension of the left ventricle occurred. Reduction of pressure within the left ventricle during rapid filling, while the ventricular diameter increased, appears to b...
Nonfasting Plasma Total Homocysteine Level and Mortality
Authors: Mark D. Eisner
Journal: Annals of Internal Medicine (2000)

Letters2 May 2000Nonfasting Plasma Total Homocysteine Level and MortalityMark D. Eisner, MDMark D. Eisner, MDUniversity of California, San Francisco; San Francisco, CA 94135 (Eisner)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-9-200005020-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In an important epidemiologic study, Kark and colleagues (1) reported the association between elevated plasma homocysteine level and a greater risk for all-cause mortality. Using Cox proportional-hazards regression, the authors examined the relation between quintile of homocysteine level and survival. To test for exposure-response trend, the log-transformed homocysteine level was examined as a continuous predictor variable. Unfortunately, this trend analysis is misleading. By treating homocysteine level as a continuous variable, the authors implicitly tested the hypothesis that higher homocysteine levels (after logarithmic transformation) are linearly related to a greater risk for all-cause mortality. Further compounding the problem, ...References1. Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, et al . Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999;131:321-30. LinkGoogle Scholar2. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295-300. CrossrefMedlineGoogle Scholar3. Greenland S. Dose-response and trend analysis in epidemiology: alternatives to categorical analysis. Epidemiology. 1995;6:356-65. CrossrefMedlineGoogle Scholar4. Witte JS, Greenland S. A nested approach to evaluating dose-response and trends. Ann Epidemiol. 1997;7:188-93. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of California, San Francisco; San Francisco, CA 94135 (Eisner) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNonfasting Plasma Total Homocysteine Level and Mortality in Middle-Aged and Elderly Men and Women in Jerusalem Jeremy D. Kark , Jacob Selhub , Bella Adler , Jaime Gofin , Joseph H. Abramson , Gideon Friedman , and Irwin H. Rosenberg Nonfasting Plasma Total Homocysteine Level and Mortality Jeremy D. Kark , Joseph H. Abramson , and Irwin H. Rosenberg Metrics 2 May 2000Volume 132, Issue 9Page: 759-760KeywordsBlood plasmaEpidemiologyMortalityPrevention, policy, and public healthRisk management Issue Published: 2 May 2000 CopyrightCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Increased glomerular capillary pressure alters glomerular cytokine expression.
Authors: S JShankland, HLy, KThai, J WScholey
Journal: Circulation Research (1994)

Increased glomerular capillary hydrostatic pressure (PGC) is an important hemodynamic determinant of glomerular injury, but the molecular events responsible for this association are poorly understood. PGC is normal in spontaneously hypertensive rats (SHR), but uninephrectomy leads to an increase in PGC and accelerated glomerulosclerosis. Since recent studies have implicated transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived growth factor sought to determine if uninephrectomy increased mRNA levels for TGF-beta 1 and PDGF in glomeruli of SHR. Since treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril lowers PGC and prevents glomerulosclerosis in uninephrectomized SHR, we also sought to determine if ACE inhibitor lowered mRNA levels for TGF-beta 1 and PDGF in the glomeruli of uninephrectomized SHR. PGC increased from 53 +/- 1 to 64 +/- 1 mm Hg 1 week after uninephrectomy in SHR (P < .05). The increase in PGC was associated with a sixfold rise in mRNA levels for TGF-beta...
Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics.
Authors: D SCelermajer, SCullen, J EDeanfield
Journal: Circulation (1993)

BACKGROUNDEndothelial injury may be an important event in the pathophysiology of pulmonary hypertension. We therefore investigated whether endothelial dysfunction occurs early in children with congenital heart defects who are at risk of developing pulmonary vascular disease.METHODS AND RESULTSIn 25 children aged 3-16 years, we studied the response of the pulmonary circulation to graded infusions of acetylcholine (an endothelium-dependent vasodilator) and nitroprusside (a dilator not dependent on endothelial function). Diameter of a bronchopulmonary segment artery and pulmonary blood flow velocity were measured using quantitative angiography and intra-arterial Doppler catheters in 10 children aged 4-16 years with normal pulmonary hemodynamics (controls), seven children aged 3-12 years with left-to-right shunt lesions resulting in increased pulmonary flow, and eight children aged 3-14 years with established pulmonary vascular disease. In the controls, there was a dose-dependent increase in flow velocity in ...
Early differentiation of infarcted and noninfarcted reperfused myocardium in dogs by quantitative analysis of regional myocardial echo amplitudes.
Authors: R VHaendchen, KOng, M CFishbein, WZwehl, SMeerbaum, ECorday
Journal: Circulation Research (1985)

This study tests the hypothesis that ischemic but viable reperfused myocardium can be differentiated from infarcted reperfused myocardium by regional analysis of myocardial echo amplitudes. In eight closed-chest, anesthetized dogs, the left anterior descending coronary artery was occluded for 3 hours, followed by 1 hour of reperfusion, and sacrifice. Infarct size was measured by the triphenyl tetrazolium chloride technique in a 1-cm-thick mid-left ventricular transverse slice, and matched with a corresponding end-diastolic two-dimensional echo short-axis cross-section. Outlining of epi- and endocardial surfaces, along with construction of a mid-myocardial outline, allowed measurements of regional myocardial echo intensities and grey-level histograms in subendo- and subepicardial regions. In 36 eventually infarcted subendocardial segments (greater than 20% wall necrosis), average pixel intensity (arbitrary units) was 73.7 +/- 33.1 (SD) in control, 75.8 +/- 33.0 at 3 hours of occlusion, and 107.8 +/- 40.9 a...
Morning increase in platelet aggregability. Association with assumption of the upright posture.
Authors: D ABrezinski, G HTofler, J EMuller, SPohjola-Sintonen, S NWillich, A ISchafer, C ACzeisler, G HWilliams
Journal: Circulation (1988)

The frequencies of onset of myocardial infarction and sudden cardiac death are increased between 6 AM and 12 noon. Platelet aggregability, which may play a role in the cause of these disorders, has been observed to increase after the normal morning activities of awakening, arising, and ambulating. To determine which morning activity or activities are responsible for this aggregability increase, we measured platelet aggregation in 16 normal subjects on a control day of delayed arising (i.e., subjects remained supine until 12:30 PM) and on a day in which normal morning activities were divided into three isolated components of awakening (8 AM), assumption of upright posture (9:30 AM), and ambulating (11 AM). Blood samples to assess platelet aggregability were drawn at 8 AM before activity and 90 minutes after the initiation of each activity (i.e., at 9:30 AM, 11 AM, and 12:30 PM). For the group, in vitro platelet responsiveness to adenosine diphosphate and epinephrine increased only after assumption of the u...
Immediate effect of expiratory loading on left ventricular stroke volume.
Authors: T KNatarajan, R AWise, MKaram, SPermutt, H NWagner
Journal: Circulation (1987)

While the steady-state effects of positive pleural pressure on the circulation have been extensively studied, less is known about the immediate effects of positive intrathoracic pressure on cardiac dynamics. Therefore, we performed electrocardiographically gated radionuclide ventriculography with a respiratory gating technique in nine healthy subjects during quiet breathing and during expiration against a 24 cm H2O expiratory threshold load. During expiration, respiratory loading caused an increase in stroke counts by 29.4% (p less than .001) due to an increase in end-diastolic counts of 26.1% (p less than .001). End-systolic counts also rose 18.8% (p less than .05). The ejection fraction did not change significantly. These findings indicate that the increase in left ventricular stroke volume that occurs during the first 1 or 2 beats of a loaded expiration is due to an increase in left ventricular filling and not to augmentation of left ventricular ejection. This immediate increase in pulmonary venous ret...
QT intervals at heart rates from 50 to 120 beats per minute during 24-hour electrocardiographic recordings in 100 healthy men. Effects of atenolol.
Authors: MViitasalo, JKarjalainen
Journal: Circulation (1992)

BACKGROUNDConflicting reports about changes in QT intervals suggest that QT values should be compared at similar heart rates.METHODS AND RESULTSRelations between QT and RR intervals were determined after measurement of QT values by Holter recording at heart rates of 50, 60, 70, 80, 90, 100, 110, and 120 beats per minute in 100 healthy young men. Fifteen men underwent a second recording during acute treatment with the beta-blocking agent atenolol. At heart rates between 80 and 120 beats per minute, the QT interval was significantly longer (from 9 to 16 msec), and at a heart rate of 50 beats per minute significantly shorter (26 msec), than values calculated from Bazett's formula. Sleep prolonged QT values by 18 msec at a heart rate of 60 beats per minute and by 21 msec at a heart rate of 50 beats per minute compared with the waking state. Atenolol lengthened QT intervals significantly (by 11-14 msec) at heart rates between 90 and 110 beats per minute and shortened them (by 12 msec) at a heart rate of 60 bea...
TCTAP A-040 Common Femoral Artery Anatomy and Relations to Bony Landmarks: A Computed Tomography Angiogram Among Egyptian Population
Authors: Mahmoud Khalil, Ahmed Shahin, Mohamed Abouelasaad, Ahmed El Shall, Mohamed Senara, Ahmed M. Elsharkawy, Ahmed Mashaly, Alaa Mohamed Reda, Amr Elsheikh, Osama Shoeib
Journal: Journal of the American College of Cardiology (2021)
The dependence of electrophysiological derangements on accumulation of endogenous long-chain acyl carnitine in hypoxic neonatal rat myocytes.
Authors: M TKnabb, J ESaffitz, P BCorr, B ESobel
Journal: Circulation Research (1986)

To determine whether accumulation of long-chain acyl carnitine contributes to electrophysiological abnormalities induced by hypoxia, we characterized effects of normoxic and hypoxic perfusion on the subcellular distribution of endogenous long-chain acyl carnitine and transmembrane potentials of cultured rat neonatal myocytes. Hypoxia increased long-chain acyl carnitine more than 5-fold. Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (10 microM), a carnitine acyltransferase inhibitor, precluded accumulation of long-chain acyl carnitine induced by hypoxia. Tissue was processed for electron microscopy by a procedure specifically developed for selective extraction of endogenous short-chain and free carnitine but retention of endogenous long-chain acyl carnitine. In normoxic-perfused cells, long-chain acyl carnitine was concentrated in mitochondria and cytoplasmic membranous components. Only small amounts were present in sarcolemma. Hypoxia increased mitochondrial long-chain acyl carnitine by 10-fo...
Precordial ST-segment depression during acute inferior myocardial infarction: clinical, scintigraphic and angiographic correlations.
Authors: R SGibson, R SCrampton, D DWatson, G JTaylor, B ACarabello, N DHolt, G ABeller
Journal: Circulation (1982)

The cause and associated pathophysiology of precordial ST-segment depression (ST decreases) during acute inferior myocardial infarction (IMI) are controversial. To investigate this problem, electrocardiographic findings in 48 consecutive patients with acute IMI were prospectively compared with results of coronary angiography, submaximal exercise thallium-201 (201TI) scintigraphy and multigated blood pool imaging, all obtained 2 weeks after IMI, and with clinical follow-up at 3 months. Patients were classified according to the admission ECG obtained 3.3 +/- 3.1 hours after the onset of chest pain. Twenty-one patients (group A) had no or less than 1.0 mm ST decreases, and 27 (group B) had greater than or equal to 1.0 mm ST decreases in two or more precordial (V1-6) leads. Patients in group B had more prolonged chest pain after admission to the coronary care unit than those in group A (2.8 +/- 3.0 vs 1.2 +/- 1.1 hours, p less than 0.03), greater summed ST-segment elevation in leads II, III, aVF (6.7 +/- 4.7 ...
Assessment of myocardial ischemia with proton magnetic resonance: effects of a three hour coronary occlusion with and without reperfusion.
Authors: D LJohnston, T JBrady, A VRatner, B RRosen, J BNewell, G MPohost, R DOkada
Journal: Circulation (1985)

Proton (hydrogen-1) magnetic resonance imaging techniques have potential for the detection and characterization of changes associated with myocardial ischemia. Since image contrast is dependent on T1 and T2 relaxation times, we examined these parameters in a canine preparation of occlusion of the left anterior descending coronary artery. Of 16 dogs studied, seven underwent 3 hr of coronary artery occlusion and nine underwent 3 hr of occlusion followed by 1 hr of reperfusion. After the dogs were killed, the hearts of four from each group were imaged in a small bore, 1.4 tesla magnet. From all hearts myocardial segments were obtained from the normal zone and the central ischemic zone (CZ). These segments were divided into epicardial and endocardial sections and studied in a spectrometer (20 MHz). After 3 hr of occlusion, CZ endocardial T1 and T2 increased significantly (p less than .01 and p less than .05, respectively). Changes in CZ epicardial relaxation times were not as marked. Although T1 and T2 tended...
Effect of L-arginine on coronary endothelial function in cardiac transplant recipients. Relation to vessel wall morphology.
Authors: HDrexler, T AFischell, F JPinto, AChenzbraun, JBotas, J PCooke, E LAlderman
Journal: Circulation (1994)

BACKGROUNDCoronary endothelial vasodilator dysfunction is a common finding in cardiac transplant recipients and may represent an early marker for the development of intimal thickening and graft atherosclerosis. The present study tested the hypothesis that endothelial dysfunction precedes intimal thickening and that administration of L-arginine, the precursor of endothelium-derived relaxing factor, improves endothelial vasodilator function of coronary conduit and resistance vessels if given at an early stage of graft atherosclerosis.METHODS AND RESULTSAcetylcholine (10(-6), 10(-5), 10(-4) mol/L) was infused into the left anterior descending or circumflex artery and repeated after intravenous infusion of L-arginine (10 mg.kg-1.min-1 over 20 minutes) in 18 cardiac transplant recipients. Epicardial responses were evaluated by quantitative angiography, and the microcirculation was studied by determination of coronary blood flow with a Doppler flow velocity wire. Intimal thickening was assessed by intravascular...
Albumin in Advanced Liver Diseases: The Good and Bad of a Drug!
Authors: Rakesh Kumar Jagdish, Jaswinder Singh Maras, Shiv Kumar Sarin
Journal: Hepatology (2021)

Human serum albumin is the most abundant plasma protein, and it regulates diverse body functions. In patients with advanced and decompensated cirrhosis, serum albumin levels are low because of a reduction in the hepatocyte mass due to disease per se and multiple therapeutic interventions. Because of their oncotic and nononcotic properties, administration of human albumin solutions (HAS) have been found to be beneficial in patients undergoing large‐volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis. Albumin also improves the functionality of the immune cells and mitigates the severity and risk of infections in advanced cirrhosis. Its long‐term administration can modify the course of decompensated cirrhosis patients by reducing the onset of new complications, improving the quality of life, and probably providing survival benefits. There is, however, a need to rationalize the dose, duration, and frequency of albumin therapy in different liver diseases and stages of cirrhosis. In patients with acute‐on‐chronic liver failure, potentially toxic oxidized isoforms of albumin increase substantially, especially human nonmercaptalbumin and 2, and nitrosoalbumin. The role of administration of HAS in such patients is unclear. Determining whether removal of the pathological and dysfunctional albumin forms in these patients by “albumin dialysis” is helpful, requires additional studies. Use of albumin is not without adverse events. These mainly include allergic and transfusion reactions, volume overload, antibody formation and coagulation derangements. Considering their cost, limited availability, need for a health care setting for their administration, and potential adverse effects, judicious use of HAS in liver diseases is advocated. There is a need for new albumin molecules and economic alternatives in hepatologic practice.
Concordance of End-of-Life Care With End-of-Life Wishes in an Integrated Health Care System
Authors: David P. Glass, Susan E. Wang, Paul M. Minardi, Michael H. Kanter
Journal: JAMA Network Open (2021)

<h3>Importance</h3> There is widespread consensus on the challenges to meeting the end-of-life wishes of decedents in the US. However, there is broad but not always recognized success in meeting wishes among decedents 65 years and older. <h3>Objective</h3> To assess how well end-of-life wishes of decedents 65 years and older are met in the last year of life. <h3>Design, Setting, and Participants</h3> This quality improvement study involved 3 planned samples of family members or informants identified as the primary contact in the medical record of Kaiser Permanente Southern California decedents. The first sample was 715 decedents, 65 years or older, who died between April 1 and May 31, 2017. The second was a high-cost sample of 332 decedents, 65 years or older, who died between June 1, 2016, and May 31, 2017, and whose costs in the last year of life were in the top 10% of the costs of all decedents. The third was a lower-cost sample with 655 decedents whose costs were not in the top 10%. The survey was fielded between December 19, 2017, and February 8, 2018. <h3>Main Outcomes and Measures</h3> Meeting end-of-life wishes, discussions with next of kin and physicians, types of discordant care, and perceptions of amount of care received. <h3>Results</h3> Surveys were completed by 715 of the 2281 next of kin in the all-decedent sample (mean [SD] decedent age, 80.9 [8.9] years; 361 [50.5%] male) for a 31% response rate; in 332 of the 1339 next of kin in the high-cost sample (mean [SD] decedent age, 75.5 [7.1] years; 194 [48.4%] male) for a 25% response rate; and in 659 of 2058 in the lower-cost sample (mean [SD] decedent age, 81.6 [8.8] years) for a 32% response rate. Respondents noted that high percentages of decedents received treatment that was concordant with their desires: 601 (88.9%) had their wishes met, 39 (5.9%) received a treatment they did not want, and 554 (84.1%) filled out an advance directive. A total of 509 respondents (82.5%) believed the amount of care was the right amount. Those with the highest costs had their wishes met at lower rates than those with lower costs (250 [80.1%] vs 553 [89.6%]). <h3>Conclusions and Relevance</h3> In this Kaiser Permanente Southern California cohort, a large proportion of decedents 65 years and older had end-of-life discussions and documentation, had their wishes met, and received the amount of care they thought appropriate.