tbuckley/cabot-search huggingface dataset:
Comparison of measures of left ventricular contractile performance derived from pressure-volume loops in conscious dogs.
Authors: W CLittle, C PCheng, MMumma, YIgarashi, JVinten-Johansen, W EJohnston
Journal: Circulation (1989)

Three measures of left ventricular (LV) performance derived from pressure (P)-volume (V) loops have been proposed: the end-systolic P-V (PES-VES) relation, the stroke work-end-diastolic V (SW-VED) relation, and maximum dP/dt-VED (dP/dtmax-VED) relation. We evaluated the variability of repeated determinations, and inotropic and load sensitivity of these relations in conscious dogs. LVV was determined from three orthogonal LV diameters measured by sonomicrometry. Three to six sets of variably loaded P-V loops were generated by transient caval occlusions before and again after increasing inotropic state by infusing dobutamine (6 +/- 1 microgram/kg/min, mean +/- SD) and after increasing PES by 49 +/- 17 mm Hg with phenylephrine following autonomic blockade. The slope (MSW) of the SW-VED relation was the least variable at constant inotropic state (coefficient of variation, 4 +/- 3%) compared with the slope (EES) of the PES-VES relation (8 +/- 3%) or the slope (dE/dtmax) of the dP/dtmax-VED relation (11 +/- 6%,...
Do Oral Contraceptives Prevent Rheumatoid Arthritis?
Authors: J. M. W. Hazes
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Del Junco et al<sup>1</sup>state that the use of oral contraceptives has no protective effect against the development of rheumatoid arthritis. Their conclusion is based on the calculation of the relative risk for developing definite or classic rheumatoid arthritis for ever users (1.1) and current users (1.3) relative to never users. With the age at diagnosis as the cutoff point, the use of oral contraceptives in the total control group proved to be roughly comparable with the expected prevalence of current use in the general population: 11.3% and 13.7%, respectively. It is conceivable that a protective effect of oral contraception, if any, will be more pronounced in the subgroup of definite and classic rheumatoid arthritis patients. The percentage of current users in the matched controls of this subgroup was only 9%, which is considerably lower than the expected prevalence in the general population (13.7% ). Estimation of
Studies on the nature of a prostaglandin receptor in canine and rabbit vascular smooth muscle.
Authors: SGreenberg, P JKadowitz, J PLong, W RWilson
Journal: Circulation Research (1976)

The contractile response of rabbit renal arteries and canine tibial arteries to prostaglandins A2, B2, F2alpha, E1, E2, D2, and B1 was associated with a reduction in total sulfhydryl group content of smooth muscle. The total sulfhydryl content of rabbit renal and canine tibial arteries and was not affected by norepinephrine or potassium chloride. Reduction of disulfide groups with dithiothreitol (DTT) selectively inhibited contractile responses to angiotensin and prostaglandins; 5,5'-Dithiobisnitrobenzoic acid (DTNB), a sulfhydryl group-oxidizing agent, reversed the inhibitory effect of DTT on the contractile responses to prostaglandins. Alkylation of free sulfhydryl groups with ethacrynic acid did not affect the contractile response of isolated canine tibial or rabbit renal arteries to any agonist studied. Ethacrynic acid added to muscle strips exposed to DTT resulted in alkylation of sulfhydryl groups produced by reduction of disulfide bonds and irreversibly prevented DTNB-induced reversal of DTT inhibi...
De subitaneis mortibus. XIX. On the cause of sudden death in pheochromocytoma, with special reference to the pulmonary arteries, the cardiac conduction system, and the aggregation of platelets.
Authors: T NJames
Journal: Circulation (1976)

Pheochromocytoma may cause sudden and unexpected death. In this study of three fatal cases of pheochromocytoma the small pulmonary arteries were narrowed by a variety of chronic and acute processes which included medial hypertrophy and fibrosis, endothelial proliferation and fibrosis, and endothelial cellular edema; within the sinus node, atrioventricular (A-V) node and His bundle of all three cases there was focal degeneration and fibrosis similar to that also observed throughout the ventricular myocardium; and in addition to the focal narrowing of many small coronary arteries produced by medial hypertrophy, intimal fibrosis, and fibromuscular dysplasia, there were also focal aggregations of platelets clogging the lumen and occasionally mixed with a varying amount of fibrin. In patients known to have pheochromocytoma it may be necessary to direct new attention to the possibility of abnormal pulmonary vascular resistance, instability of normal cardiac rhythm, and perhaps difficulty in restoring it when di...
Regional contractility. Selective depression of ischemic myocardium by verapamil.
Authors: H JSmith, R AGoldstein, J MGriffith, K MKent, S EEpstein
Journal: Circulation (1976)

The effects of verapamil (0.02-0.2 mg/kg) on contractility in normal and partially ischemic myocardium were compared with the changes following propranolol (0.01-1.0 mg/kg). Regional contractile function was studied in open-chest dogs with ultrasonic crystals and ischemia was controlled by graded occlusion of a carotid-to-coronary artery shunt. Reduction in shunt perfusion pressure (40-55 mm Hg) resulted in hypokinesia. Verapamil depressed contractility in ischemic myocardium in 5/5 dogs, but did not alter the maximum velocity of shortening (max V) or end-diastolic segment length in normal myocardium. Propranolol in doses sufficient to depress ischemic myocardium also depressed contractile function in normal myocardium. In two dogs without coronary occlusion, verapamil (up to 1.0 mg/kg) increased end-diastolic segment length but did not reduce max V. We conclude that verapamil selectively depresses ischemic myocardium, a finding that may have clinical implication since ischemic injury can be decreased by ...
Detection and characterization of acute myocardial infarction in man with use of gated magnetic resonance.
Authors: M TMcNamara, C BHiggins, NSchechtmann, EBotvinick, M JLipton, KChatterjee, E GAmparo
Journal: Circulation (1985)

To evaluate the capability of magnetic resonance imaging (MRI) in the detection and characterization of alterations in signal intensity and T2 relaxation time in acutely infarcted relative to normal myocardium 16 adult patients and normal volunteers were studied by electrocardiographically gated proton MRI. The seven volunteers were entirely asymptomatic and had no history of cardiovascular abnormality. The nine patients had each suffered an acute myocardial infarction within 5 to 12 days before the MRI studies. The diagnosis in each patient was confirmed by electrocardiographic (ECG) criteria and elevated levels of fractionated creatine kinase (CK) isoenzymes. Electrocardiographically gated MRI was performed with a superconducting system operating at 0.35 tesla. MRI demonstrated infarcted myocardium as a region of high signal intensity relative to that of adjacent normal myocardium; regions of high intensity corresponded anatomically to the site of infarction as defined by the ECG changes. The mean perce...
Aging of Preleukemic Thymocytes Drives CpG Island Hypermethylation in T-Cell Acute Lymphoblastic Leukemia
Authors: Juliette Roels, Morgan Thénoz, Bronisława Szarzyńska, Mattias Landfors, Stien De Coninck, Lisa Demoen, Lien Provez, Anna Kuchmiy, Steven Strubbe, Lindy Reunes, Tim Pieters, Filip Matthijssens, Wouter Van Loocke, Tim Lammens, Barbara De Moerloose, Marc R. Mansour, Utpal Dave, Steven Goossens, David J. Curtis, Tom Taghon, Małgorzata Dawidowska, Sofie Degerman, Pieter Van Vlierberghe
Journal: Blood (2020)
TCTAP A-015 Impact of Urgent and Elective Percutaneous Coronary Intervention on Outcome of Left Main Coronary Artery Bifurcational Stenosis
Authors: Batmyagmar Khuyag, Bum-Erdene Batbayar, Oyunkhand Buyankhishig, Surenjav Chimed, Lkhagvasuren Zundui
Journal: Journal of the American College of Cardiology (2021)
Efficacy and Safety of Very Low-Volume Bowel Preparation With 1L Plenvu Comparison With 2L Peg-Asc: Multicenter, Randomized, Endoscopist-Blinded Study
Authors: SN Hong, Lee CK, J PIm, Choi CH, Byeon JS, Cho YS, Jung SA, Kim TI, Jeen YT
Journal: Endoscopy (2021)

Aims Polyethyleneglycol (PEG)-based bowel preparation is effective and safe but required high volume intake, which reduces adherence and tolerability. Although 2L PEG-Asc enables small volume preparation, lower-volume bowel preparation is beneficial for patients.
Cardiac manifestations of the mucopolysaccharidoses.
Authors: R MSchieken, R EKerber, V VIonasescu, HZellweger
Journal: Circulation (1975)

The cardiovascular manifestations of the mucopolysaccharidoses (MPS) have not been well characterized. We studied nine children with various forms of MPS, using noninvasive cardiac diagnostic techniques. The echocardiograms of two brothers with Type I H/S MPS showed slow mitral valve early diastolic closure velocities (MVEDC) (18, 29 mm/sec) consistent with mitral stenosis. Each had a soft opening snap, low frequency presystolic murmurs and X-ray evidence of calcific mitral stenosis. Three patients with Type II A MPS had echocardiographic evidence of impaired left ventricular function, suggesting the presence of myocardial damage. One of these had an abnormal electrocardiogram; non had murmurs. No cardiac abnormalities were discovered in two patients with Type III A and IV MPS. One patient with Type VI A MPS had presystolic, holostolic and early diastolic murmurs. A soft opening snap was recorded. The echocardiogram showed a slow MVEDC (18 mm/sec) and a slightly enlarged left atrial dimension (2.2 cm/m2)....
Phorbol ester increases the dihydropyridine-sensitive calcium conductance in a vascular smooth muscle cell line.
Authors: R DFish, GSperti, W SColucci, D EClapham
Journal: Circulation Research (1988)

In vascular smooth muscle, phorbol esters cause a slowly developing contraction and an associated transmembrane calcium flux, both of which are inhibited by dihydropyridine calcium channel antagonists. In the A7r5 cultured vascular cell line, we used the whole-cell voltage-clamp technique to identify voltage-dependent calcium conductances and investigate the effect of phorbol esters on that conductance having characteristic dihydropyridine sensitivity (slowly inactivating, high-threshold, L-type). With barium as the charge carrier, large-amplitude (100-800 pA) inward currents of two types were characterized by their kinetics and voltage dependence. With holding potential--80 mV, a rapidly inactivating, low-threshold current (T-type) was activated by depolarizations above-40 mV and was maximal at -10 mV. With holding potential -30 mV, this component was inactivated, and a second slowly inactivating, high-threshold current was activated above -10 mV and was maximal at +10 to +20 mV. These currents are s...
OCT Angiography Artifacts in Glaucoma
Authors: Alireza Kamalipour, Sasan Moghimi, Huiyuan Hou, Rafaella C. Penteado, Won Hyuk Oh, James A. Proudfoot, Nevin El-Nimri, Eren Ekici, Jasmin Rezapour, Linda M. Zangwill, Christopher Bowd, Robert N. Weinreb
Journal: Ophthalmology (2021)
Beta-adrenergic receptor stimulation increases unloaded shortening velocity of skinned single ventricular myocytes from rats.
Authors: K TStrang, N KSweitzer, M LGreaser, R LMoss
Journal: Circulation Research (1994)

In vitro biochemical experiments have suggested that stimulation of beta-adrenergic receptor may increase the rate of crossbridge cycling in mammalian myocardium, but recent attempts to demonstrate a mechanical correlate have yielded conflicting results. To investigate this issue, we measured the effect of isoproterenol (ISO) and cAMP-dependent protein kinase (PKA) on unloaded shortening velocity (Vo). Vo is thought to be determined by the rate-limiting step of the crossbridge cycle, ie, the rate of crossbridge detachment from actin, and is therefore an index of the cycling rate. Single rat ventricular myocytes were enzymatically isolated, incubated in Ringer's solution without (control) or with 0.1 mumol/L ISO, and then rapidly skinned. Some control cells were subsequently treated with 3 micrograms/mL PKA for 40 minutes. Vo was then measured during maximal activation (pCa 4.5) in control, ISO-treated, and PKA-treated cells using the slack-test method. To test the efficacy of the agonist treatments, Ca2+ ...
Does Conservative Management In Upper Gi Bleeding During Covid-19 Lead On To Adverse Outcomes?
Authors: A Ghodeif, A Al-Rifaie, A Gawn, Y Yeo, M Thoufeeq
Journal: Endoscopy (2021)

Aims We aimed to assess outcomes of patients with upper gastrointestinal bleeding (UGIB) during the Covid-19 induced 1st lockdown during the pandemic in our unit who were either managed conservatively without endoscopy or with endoscopy.
Wedding of Molecular Alterations and Immune Checkpoint Blockade: Genomics as a Matchmaker
Authors: Elena Fountzilas, Razelle Kurzrock, Henry Hiep Vo, Apostolia-Maria Tsimberidou
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract The development of checkpoint blockade immunotherapy has transformed the medical oncology armamentarium. But despite its favorable impact on clinical outcomes, immunotherapy benefits only a subset of patients, and a substantial proportion of these individuals eventually manifest resistance. Serious immune-related adverse events and hyperprogression have also been reported. It is therefore essential to understand the molecular mechanisms and identify the drivers of therapeutic response and resistance. In this review, we provide an overview of the current and emerging clinically relevant genomic biomarkers implicated in checkpoint blockade outcome. US Food and Drug Administration–approved molecular biomarkers of immunotherapy response include mismatch repair deficiency and/or microsatelliteinstability and tumor mutational burden of at least 10 mutations/megabase. Investigational genomic-associated biomarkers for immunotherapy response include alterations of the following genes/associated pathways: chromatin remodeling (ARID1A, PBRM1, SMARCA4, SMARCB1, BAP1), major histocompatibility complex, specific (eg, ultraviolet, APOBEC) mutational signatures, T-cell receptor repertoire, PDL1, POLE/POLD1, and neo-antigens produced by the mutanome, those potentially associated with resistance include β2-microglobulin, EGFR, Keap1, JAK1/JAK2/interferon-gamma signaling, MDM2, PTEN, STK11, and Wnt/Beta-catenin pathway alterations. Prospective clinical trials are needed to assess the role of a composite of these biomarkers to optimize the implementation of precision immunotherapy in patient care.
Cooperative Binding of ETS2 and NFAT Links Erk1/2 and Calcineurin Signaling in the Pathogenesis of Cardiac Hypertrophy
Authors: Yuxuan Luo, Nan Jiang, Herman I. May, Xiang Luo, Anwarul Ferdous, Gabriele G. Schiattarella, Guihao Chen, Qinfeng Li, Chao Li, Beverly A. Rothermel, Dingsheng Jiang, Sergio Lavandero, Thomas G. Gillette, Joseph A. Hill
Journal: Circulation (2021)

Cardiac hypertrophy is an independent risk factor for heart failure, a leading cause of morbidity and mortality globally. The calcineurin/NFAT (nuclear factor of activated T cells) pathway and the MAPK (mitogen-activated protein kinase)/Erk (extracellular signal-regulated kinase) pathway contribute to the pathogenesis of cardiac hypertrophy as an interdependent network of signaling cascades. How these pathways interact remains unclear and few direct targets responsible for the prohypertrophic role of NFAT have been described.
A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex.
Authors: PBrugada, JBrugada, LMont, JSmeets, E WAndries
Journal: Circulation (1991)

BACKGROUNDIn the differential diagnosis of a tachycardia with a wide QRS complex (greater than or equal to 0.12 second) diagnostic mistakes are frequent. Therefore, we investigated the reasons for failure of presently available criteria, and we identified new, simpler criteria and incorporated them in a stepwise approach that provides better sensitivity and specificity for making a correct diagnosis.METHODS AND RESULTSA prospective analysis revealed that current criteria had a poor specificity for the differential diagnosis. The value of four new criteria incorporated in a stepwise approach was prospectively analyzed in a total of 554 tachycardias with a widened QRS complex (384 ventricular and 170 supraventricular). The sensitivity of the four consecutive steps was 0.987, and the specificity was 0.965.CONCLUSIONSCurrent criteria for the differential diagnosis between supraventricular tachycardia with aberrant conduction and ventricular tachycardia are frequently absent or suggest the wrong diagnosis. The...
Clinical pharmacology of propafenone.
Authors: S JConnolly, R EKates, C SLebsack, D CHarrison, R AWinkle
Journal: Circulation (1983)

We determined the efficacy, pharmacokinetics, and plasma concentration-response relationships of propafenone, a promising new antiarrhythmic drug. Thirteen patients with frequent and complex ventricular premature beats were studied after receiving four increasing doses, during drug washout and during a randomized double-blind placebo-controlled trial, to evaluate the optimal dose in each patient. A nonlinear relationship was found between propafenone dose and steady-state mean concentration with a 10-fold increase in drug concentration as dose increased threefold from 300 to 900 mg/day. There was great intersubject variability in elimination half-life (mean 6 hr, range 2.4 to 11.8), steady-state mean concentration on 900 mg/day of propafenone (mean 1008 ng/ml, range 482 to 1812), and therapeutic plasma concentration (mean 588 ng/ml, range 64 to 1044). The interaction of these three parameters in individual patients determined the duration of the antiarrhythmic action of propafenone during washout (mean ...
In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts.
Authors: RRoskoski, P GSchmid, H EMayer, F MAbboud
Journal: Circulation Research (1975)

Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After 30 days when hypertrophy and heart failure were fully established, choline acetyltransferase was quantified in vitro by a radiochemical assay. In the sham-operated group, enzyme activity expressed in terms of unit weight of cardiac tissue was greatest in the right atrium and the right ventricle and lower in th left atrium and the left ventricle (3.62 plus or minus 0.30, 2.96 plus or minus 0.52, 1.64 plus or minus 0.15, and 1.67 plus or minus 0.22 nmoles/min g-1, respectively). Enzyme activity was reduced (P less than 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 plus or minus 0.37 and 1.31 plus or minus 0.29 nmoles/min g-1, r...
Regional distribution of blood flow during arterial hypertension produced by lesions of the nucleus tractus solitarii in rats.
Authors: D WSnyder, NDoba, D JReis
Journal: Circulation Research (1978)

Changes in the fractional distribution of cardiac output (FF), organ blood flow, and regional vascular resistance were measured by the isotope dilution technique of Sapirstein using 86Rb as indicator in unanesthetized rats during acute arterial hypertension produced by bilateral lesions of the nucleus tractus solitarii (NTS). After NTS lesions, the FF was significantly reduced in skin, muscle, and colon, increased in ventricular myocardium, spleen, and adrenal glands, and was unchanged elsewhere. Because of a marked reduction in cardiac output (CO) during hypertension, the absolute organ blood flow (FF X CO) was reduced in lesioned rats to 30-40% of control in skin, muscle, and colon and between 60% and 75% of control in most of the remainder of the gastrointestinal tract and renal cortex; it was unchanged in myocardium and endocrine glands. Resistance was substantially increased (4- to 6-fold) in skin, muscle and colon but was only moderately increased (1.5- to 2.5-fold) in the remaining organs. The resu...
Isolated gonococcal pulmonary valve endocarditis: diagnosis by echocardiography.
Authors: B SDzindzio, LMeyer, ROsterholm, AHopeman, JWoltjen, A DForker
Journal: Circulation (1979)

The perplexing clinical course of a 23-year-old black male with isolated gonococcal pulmonary valvular endocarditis is presented. M-mode echocardiography provided the first clue to the presence of pulmonary valvular vegetations and the proper diagnosis. Since Neisseria gonorrhea appears to have a particular affinity for the pulmonary valve, the presence of isolated pulmonary valvular endocarditis should raise the strong possibility that Neisseria gonorrhea is the offending organism. This case report of pulmonary valvular vegetations detected by echocardiography strongly emphasizes that all four cardiac valves must be visualized in order to rule out the presence of echocardiographically detectable valvular vegetations.
Abstract 16078: Risk Classification of Familial Hypercholesterolemia Through Screening of the Electronic Health Record Within a Large Healthcare System
Authors: Samip Sheth, Jose Vargas
Journal: Circulation (2020)

Introduction: Familial hypercholesterolemia (FH) is a genetic disorder characterized by very high low-density lipoprotein cholesterol (LDL-c) levels. The heterogeneity of clinical risk within FH may lead to differential treatment, management, and outcomes. Screening the electronic health record (EHR) permits risk classification within FH at scale. We leveraged the Georgetown/MedStar Health System (MHS) EHR to perform risk classification while describing other characteristics of suspected FH patients. Methods: The Dutch Lipid Clinical Network (DLCN) remains a common scoring algorithm for FH risk classification. Applying the DLCN algorithm to the EHR of MHS enabled risk classification of approximately 1.6 million patients. The classifiers included ‘definite,’ ‘probable,’ and ‘possible’ heterozygous FH (HeFH). ‘Possible’ homozygous FH (HoFH) was determined by LDL-c &gt; 500 mg/dL. Of these suspected FH patients, current age, gender, and race as well as abnormal lipid profile data (high-density lipoprotein cholesterol (HDL-c) cholesterol &lt; 20 mg/dL, triglyceride (TG) &gt; 300 mg/dL) were descriptively described. Results: Of 1.6 million patients, the number of definite, probable, and possible HeFH patients were 83 (1:19722), 690 (1:2318), and 5945 (1:266), respectively. The number of possible HoFH patients was 8 (1:200000). The highest reported median LDL-C (IQR) for the three HeFH subpopulations was 377 (346, 430 mg/dL), 262 (251, 282 mg/dL), and 203 (mg/dL), and the majority of all subpopulations were female and non-white. Definite HeFH patients were more likely to present with very low HDL-c and approximately 1:10 suspected HeFH patients presented with very high triglycerides. Conclusion: The application of DLCN to the EHR demonstrates risk classification for FH in a large healthcare system. The implications of stratifying suspected FH patients by classifier within the EHR may optimize clinical care as well as registry management.
Correction: Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study
Authors: Uma V. Mahajan, Vijay R. Varma, Michael E. Griswold, Chad T. Blackshear, Yang An, Anup M. Oommen, Sudhir Varma, Juan C. Troncoso, Olga Pletnikova, Richard O’Brien, Timothy J. Hohman, Cristina Legido-Quigley, Madhav Thambisetty
Journal: PLoS Medicine (2020)

[This corrects the article DOI: 10.1371/journal.pmed.1003012.].