tbuckley/cabot-search huggingface dataset:
POST KALA-AZAR DERMAL LEISHMANIASIS
Authors: D. D. Munro, Anthony Vivier, W. H. Jopling
Journal: British Journal of Dermatology (1972)

Journal Article POST KALA‐AZAR DERMAL LEISHMANIASIS Get access D. D. MUNRO, D. D. MUNRO Department of Dermatology, St Bartholomew's Hospital, London, E.C.I Search for other works by this author on: Oxford Academic Google Scholar ANTHONY du VIVIER, ANTHONY du VIVIER Department of Dermatology, St Bartholomew's Hospital, London, E.C.I Search for other works by this author on: Oxford Academic Google Scholar W. H. JOPLING W. H. JOPLING Department of Dermatology, St Bartholomew's Hospital, London, E.C.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 87, Issue 4, 1 October 1972, Pages 374–378, https://doi.org/10.1111/j.1365-2133.1972.tb07425.x Published: 01 October 1972 Article history Accepted: 25 April 1972 Published: 01 October 1972
The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs.
Authors: K AReimer, J ELowe, M MRasmussen, R BJennings
Journal: Circulation (1977)

Irreversible ischemic myocardial cell injury developes in an increasing number of cells as the duration of coronary occlusion is prolonged. The present study quantitates myocardial necrosis produced by 40 minutes, 3 hours, or 6 hours of temporary circumflex coronary occlusion (CO) followed by 2 to 4 days of reperfusion, or by 24 or 96 hours of permanent circumflex ligation in pentobarbital anesthetized open chest dogs. After 40 minutes of ischemia, myocyte necrosis was subendocardial but with increasing duration of coronary occlusion, irreversible injury progressed as a wavefront toward the subepicardium. Transmural necrosis was 38 +/- 4% after 40 min, 57 +/- 7% after 3 hours, 71 +/- 7% after 6 hours and 85 +/- 2% after 24 hours of ischemic injury. These results document the presence of a subepicardial zone of ischemic but viable myocardium which is available for pharmacologic or surgical salvage for at least three and perhaps six hours following circumflex occlusion in the dog.
Alterations in ventricular mass and performance induced by exercise training in man evaluated by echocardiography.
Authors: A NDeMaria, ANeumann, GLee, WFowler, D TMason
Journal: Circulation (1978)

Few data are available regarding the effects of exercise training upon cardiac structure and performance in man. We evaluated the echograms of 24 normals before (PRE) and after (POST) 11 weeks of endurance exercise training. Conditioning consisted of a walk-jog-run protocol at 70% maximal heart rate for one hour four days per week. Training reduced heart rate and increased maximal duration and estimated oxygen consumption of treadmill exercise. Compared to PRE, the echogram in the POST training period revealed an increased left ventricular (LV) end-diastolic dimension (EdD), a decreased end-systolic dimension (EsD) and thus an increased stroke volume (EdD3-EsD3) and shortening fraction (EdD-EsD)/EdD). Cardiac output (CO) and peripheral vascular resistance (BP/CO X 80) were identical PRE and POST conditioning. Importantly, an increase in mean fiber shortening velocity was observed POST training as were increases in LV wall thickness, ECG voltage of S in V1 + R in V5, and LV mass. Thus endurance training wa...
Amiodarone: biochemical evidence for binding to a receptor for class I drugs associated with the rat cardiac sodium channel.
Authors: R SSheldon, R JHill, N JCannon, H JDuff
Journal: Circulation Research (1989)

Amiodarone has multiple pharmacological effects in heart. Electrophysiological data suggest that among its other effects, amiodarone is a sodium channel blocker. Using a radioligand assay, we determined whether amiodarone interacted with a previously described receptor for type I agents associated with the cardiac sodium channel. The radioligand was [3H]batrachotoxinin A 20 alpha-benzoate ([ 3H]BTXB), a toxin that binds to the activated state of the sodium channel. We have previously shown that class I antiarrhythmic drugs inhibit [3H]BTXB binding. The purpose of this study was to assess whether amiodarone and other class III agents interact with this receptor. Amiodarone inhibited [3H]BTXB binding in a dose-dependent fashion, with an estimated IC50 value of 3.6 microM. This IC50 value is similar to reported clinically effective serum concentrations of amiodarone. In contrast to amiodarone, the IC50 values for other class III drugs (bretylium, sotalol, bethanidine, N-acetylprocainamide) were much higher t...
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.
Authors: J THii, D GWyse, A MGillis, H JDuff, M ASolylo, L BMitchell
Journal: Circulation (1992)

BACKGROUNDPatients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times.METHODS AND RESULTSThirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable ...
Calcium-dependent mechanical oscillations occur spontaneously in unstimulated mammalian cardiac tissues.
Authors: A AKort, E GLakatta
Journal: Circulation Research (1984)

In quiescent rat ventricular myocardium, bathed in solution of 2 mM Ca++ or less, it has been previously demonstrated that spontaneous microscopic oscillatory cell motion is present and interacts with an incident laser beam to produce scattered light intensity fluctuations which can be monitored to quantify the underlying motion. The present study shows that scattered light intensity fluctuations are not present under any conditions in frog atrial or ventricular preparations, but do occur in each type of mammalian cardiac tissue studied in the unstimulated state. The magnitude of scattered light intensity fluctuations in mammalian tissues varies with species and cellular Ca++ loading. In some tissues, e.g., rabbit or ferret ventricle, either an increase in the Ca++ concentration in the perfusate [( Ca++]e), reduction of perfusate Na+ concentration [( Na+]e), or addition of cardiac glycosides was required to elicit scattered light intensity fluctuations; in other tissues, however, e.g., the canine Purkinje...
The selective inhibition of serotonin-induced contractions of rabbit cerebral vascular smooth muscle by calcium-antagonistic dihydropyridines. An investigation of the mechanism of action of nimodipine.
Authors: RTowart
Journal: Circulation Research (1981)

I studied the role of calcium in the activation of isolated rings of saphenous and basilar arteries of the rabbit by comparing the effect of calcium withdrawal with the effect of the calcium antagonist nimodipine [isopropyl(2-methoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate]. Serotonin-induced contractions of both vessels were inhibited quickly by incubation in calcium-free solution, showing the contractions of both vessels to be dependent on extracellular calcium. Potassium-induced contractions of both vessels were inhibited markedly by nimodipine (basilar: ID50 = 1.7 X 10(-10) mol/liter; saphenous: ID50 = 2.6 X 10(-10) mol/liter), showing depolarization-induced calcium influx (probably through potential sensitive  PSCs) to be sensitive to nimodipine. In the basilar artery the sustained, tonic phase of serotonin-induced contractions (probably through receptor operated channels, ROCs) was potently inhibited (ID50 = 7.3 X 10(-10) mol/liter) by nimodipine. Howe...
Effects of oxidant stress on endothelium-derived relaxing factor-induced and nitrovasodilator-induced cGMP accumulation in vascular cells in culture.
Authors: NMarczin, U SRyan, J DCatravas
Journal: Circulation Research (1992)

The effects of hydrogen peroxide (H2O2) on the action of basally produced endothelium-derived relaxing factor (EDRF) were investigated by measuring cGMP accumulation in single and cocultures of calf pulmonary artery endothelial cells (CPAEs) and rabbit pulmonary artery smooth muscle cells (RPASMs) as a model for determining the contribution of EDRF dysfunction to altered vascular tone and reactivity frequently associated with oxidant-induced vascular injury. Higher cGMP levels in long-term cocultures (20.4 +/- 1.8 pmol/mg protein/15 min) than in single-cell cultures (CPAE, 9.6 +/- 0.9 pmol/mg protein/15 min; RPASM, 3.7 +/- 0.2 pmol/mg protein/15 min), and CPAE-induced increases (fivefold) in intracellular RPASM cGMP content in short-term cocultures suggest basal release of EDRF. Basal generation and release of an L-arginine-derived endothelial labile factor accounted for the increases in cGMP, since the response was completely blocked by pretreatment of CPAEs with NG-monomethyl L-arginine. Pretreatment of...
Pulmonary venous responses to thromboxane A2 analogue and atrial natriuretic peptide in lambs.
Authors: J URaj, JAnderson
Journal: Circulation Research (1990)

To characterize pulmonary venous vasoactivity and the factors that modulate it, we determined venous responses to a vasoconstrictor agent, thromboxane A2 (TXA2) analogue U46619, and to a vasodilator agent, atrial natriuretic peptide (ANP), in 28 isolated blood-perfused lamb lungs under conditions of varying vascular tone and intraluminal pressures. TXA2 was given in a 5 micrograms/kg bolus followed by a steady infusion of 1 micrograms/kg/min to three groups of lungs: group 1, n = 4, with low vasomotor tone; group 2, n = 8, with moderate vasomotor tone; and group 3, n = 7, with moderate vasomotor tone and high venous intraluminal pressures. Group 3 lungs were reverse-perfused to obtain high venous pressures. ANP was given as two 10 micrograms/kg bolus injections, 5 minutes apart, to three groups of lungs: group 4, n = 4, with low vasomotor tone; group 5, n = 5, with moderate vasomotor tone; and group 6, n = 8, with high vasomotor tone. Group 6 lungs were vasoconstricted with TXA2 infusion. In all lungs, we...
The influence of left ventricular stroke volume on aortic root motion: an echocardiographic study.
Authors: R CPratt, A FParisi, J JHarrington, A ASasahara
Journal: Circulation (1976)

Aortic root motion was studied in 24 normal volunteers at rest and during the Valsalva maneuver, isometric exercise, and amyl nitrite inhalation. In addition root motion was correlated with the stroke volumes determined at cardiac catheterization in 24 patients. The root has distinct systolic movement, the amplitude and duration of which were easily measured both at rest and during the interventions. At rest,the mean (+/-1 SE) systolic amplitude of the anterior aortic wall was 11.2 +/- 0.5 mm and that of the posterior wall 9.5 +/- 0.3 mm. During the strain phase of the Valsalva maneuver anterior wall amplitude fell to 8.2 +/- 0.4 mm and the posterior wall to 7.3 +/- 0.5 mm (P less than 0.001). With release, anterior wall amplitude rebounded to 12.5 +/- 0.8 mm and the posterior wall to 10.8 +/- o.5 mm, values greater than control (P less than 0.01). With isometric exercise there was no change in amplitude compared to rest; however, amyl nitrite caused an increase in the anterior wall to 13.5 +/-0.8 mm and ...
Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.
Authors: G JHasking, M DEsler, G LJennings, DBurton, J AJohns, P IKorner
Journal: Circulation (1986)

The analysis of plasma kinetics of the sympathetic neurotransmitter norepinephrine can be used to estimate sympathetic nervous  (integrated nerve firing rate) for the body as a whole and for individual organs. In 12 patients with cardiac failure (left ventricular ejection fraction 10% to 39%), the mean arterial plasma norepinephrine concentration was 557 +/- 68 pg/ml (mean +/- SE) compared with 211 +/- 21 pg/ml in 15 subjects without heart failure (p less than .002). The difference was due to both increased release of norepinephrine to plasma (indicating increased total sympathetic activity) and reduced clearance of norepinephrine from plasma. The increase in sympathetic activity did not involve all organs equally. Cardiac (32 +/- 9 vs 5 +/- 1 ng/min; p less than .002) and renal (202 +/- 45 vs 66 +/- 9 ng/min; p = .002) norepinephrine spillover were increased by 540% and 206%, respectively, but norepinephrine spillover from the lungs was normal. Adrenomedullary activity was also increased in t...
Use of Machine Learning to Develop and Evaluate Models Using Preoperative and Intraoperative Data to Identify Risks of Postoperative Complications
Authors: Bing Xue, Dingwen Li, Chenyang Lu, Christopher R. King, Troy Wildes, Michael S. Avidan, Thomas Kannampallil, Joanna Abraham
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Postoperative complications can significantly impact perioperative care management and planning. <h3>Objectives</h3> To assess machine learning (ML) models for predicting postoperative complications using independent and combined preoperative and intraoperative data and their clinically meaningful model-agnostic interpretations. <h3>Design, Setting, and Participants</h3> This retrospective cohort study assessed 111 888 operations performed on adults at a single academic medical center from June 1, 2012, to August 31, 2016, with a mean duration of follow-up based on the length of postoperative hospital stay less than 7 days. Data analysis was performed from February 1 to September 31, 2020. <h3>Main Outcomes and Measures</h3> Outcomes included 5 postoperative complications: acute kidney injury (AKI), delirium, deep vein thrombosis (DVT), pulmonary embolism (PE), and pneumonia. Patient and clinical characteristics available preoperatively, intraoperatively, and a combination of both were used as inputs for 5 candidate ML models: logistic regression, support vector machine, random forest, gradient boosting tree (GBT), and deep neural network (DNN). Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using Shapley Additive Explanations by transforming model features into clinical variables and representing them as patient-specific visualizations. <h3>Results</h3> A total of 111 888 patients (mean [SD] age, 54.4 [16.8] years; 56 915 [50.9%] female; 82 533 [73.8%] White) were included in this study. The best-performing model for each complication combined the preoperative and intraoperative data with the following AUROCs: pneumonia (GBT), 0.905 (95% CI, 0.903-0.907); AKI (GBT), 0.848 (95% CI, 0.846-0.851); DVT (GBT), 0.881 (95% CI, 0.878-0.884); PE (DNN), 0.831 (95% CI, 0.824-0.839); and delirium (GBT), 0.762 (95% CI, 0.759-0.765). Performance of models that used only preoperative data or only intraoperative data was marginally lower than that of models that used combined data. When adding variables with missing data as input, AUROCs increased from 0.588 to 0.905 for pneumonia, 0.579 to 0.848 for AKI, 0.574 to 0.881 for DVT, 0.5 to 0.831 for PE, and 0.6 to 0.762 for delirium. The Shapley Additive Explanations analysis generated model-agnostic interpretation that illustrated significant clinical contributors associated with risks of postoperative complications. <h3>Conclusions and Relevance</h3> The ML models for predicting postoperative complications with model-agnostic interpretation offer opportunities for integrating risk predictions for clinical decision support. Such real-time clinical decision support can mitigate patient risks and help in anticipatory management for perioperative contingency planning.
The effect of propranolol on canine myocardial CPK distribution space and rate of disappearance.
Authors: J ACairns, G AKlassen
Journal: Circulation (1977)

Canine myocardial CPK was partially purified and injected into 11 conscious mongreal dogs. From serial serum CPK measurements in each dog, mean Kd was calculated as 0.0047 +/- 0.0009 (+/- SD) min-1. Correlation coefficients indicated that CPK disappearance rate was well described by a single exponential expression. Kd measured on consecutive days in four dogs varied minimally. CPK distribution space ranged from 74 to 134% of plasma volume. Propranolol loading with 0.3 mg/kg or 2 mg/kg, followed by hourly maintenance doses, resulted in increased Kd in eight of ten dogs, mean Kd rising from .0048 min-1 to .0059 min-1 (P less than 0.02). Propranolol appeared to increase plasma volume but had no significant effect on the relationship of CPK distribution space to plasma volume. If the serial CPK technique were used to measure infarct size, using an average Kd, propranolol might produce artifactual reduction of infarct size measuremnt by increasing Kd and possibly by increasing plasma volume. The obligation to ...
Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas
Authors: Jing Wu, Ying Yuan, Debra A. Long Priel, Danielle Fink, Cody J. Peer, Tristan M. Sissung, Yu-Ting Su, Ying Pang, Guangyang Yu, Madison K. Butler, Tito R. Mendoza, Elizabeth Vera, Salman Ahmad, Christine Bryla, Matthew Lindsley, Ewa Grajkowska, Kelly Mentges, Lisa Boris, Ramya Antony, Nancy Garren, Christine Siegel, Nicole Lollo, Christine Cordova, Orwa Aboud, Brett J. Theeler, Eric M. Burton, Marta Penas-Prado, Heather Leeper, Javier Gonzales, Terri S. Armstrong, Katherine R. Calvo, William D. Figg, Douglas B. Kuhns, John I. Gallin, Mark R. Gilbert
Journal: Clinical Cancer Research (2021)

To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma.
Changes in passive mechanical stiffness of myocardial tissue with aneurysm formation.
Authors: K BGupta, M BRatcliffe, M AFallert, L HEdmunds, D KBogen
Journal: Circulation (1994)

BACKGROUNDMyocardium undergoes complex cellular and histochemical alterations after acute myocardial infarction. These structural changes directly affect the mechanical stiffness of infarcted and remote myocardia. Previous investigations of infarct stiffness have been limited to uniaxial testing, which does not provide a unique description of the tissue's three-dimensional material properties. This study describes the first serial measurements of biaxial mechanical properties of sheep myocardium after anteroapical infarction.METHODS AND RESULTSAnteroapical infarctions of 23.7 +/- 2.5% of the left ventricular mass were produced by coronary arterial ligation in sheep. Biaxial force-extension measurements were made on freshly excised squares (6.45 cm2) of remote, noninfarcted, and infarcted myocardia before and 4 hours, 1 week, 2 weeks, and 6 weeks after ligation. Adjacent myocardial samples were assayed for hydroxyproline content. Force-extension data and a derived constitutive equation were used to describ...
Loss‐of‐Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia
Authors: Yi Niu, Ziyou Lin, Arabella Wan, Lei Sun, Shijia Yan, Heng Liang, Siyue Zhan, Dongshi Chen, Xianzhang Bu, Peiqing Liu, Ceshi Chen, Weiling He, Xiongbin Lu, Guohui Wan
Journal: Hepatology (2021)

Background and Aims Hypoxia is a common feature of the tumor microenvironment (TME), which promotes tumor progression, metastasis, and therapeutic drug resistance through a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclinical development of this approach is lacking in the study of HCC. Approach and Results From a genome‐wide CRISPR/CRISPR‐associated 9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia. Knockdown of ALDOA in HCC cells leads to lactate depletion and consequently inhibits tumor growth. Supplementation with lactate partly rescues the inhibitory effects mediated by ALDOA knockdown. Upon hypoxia, ALDOA is induced by hypoxia‐inducible factor‐1α and fat mass and obesity–associated protein–mediated N 6 ‐methyladenosine modification through transcriptional and posttranscriptional regulation, respectively. Analysis of The Cancer Genome Atlas shows that elevated levels of ALDOA are significantly correlated with poor prognosis of patients with HCC. In a screen of Food and Drug Administration–approved drugs based on structured hierarchical virtual platforms, we identified the sulfamonomethoxine derivative compound 5 (cpd‐5) as a potential inhibitor to target ALDOA, evidenced by the antitumor activity of cpd‐5 in preclinical patient‐derived xenograft models of HCC. Conclusions Our work identifies ALDOA as an essential driver for HCC cell growth under hypoxia, and we demonstrate that inhibition of ALDOA in the hypoxic TME is a promising therapeutic strategy for treating HCC.
Interaction of fiber orientation and direction of impulse propagation with anatomic barriers in anisotropic canine myocardium.
Authors: AKadish, MShinnar, E NMoore, J HLevine, C WBalke, J FSpear
Journal: Circulation (1988)

We developed a computer model of the interaction of impulse propagation with anatomic barriers in uniformly anisotropic tissue. Its predictions were confirmed experimentally by using an in vitro cut to create a 6 X 1-mm anatomic barrier in 12 canine epicardial strips. The model predicted that long, thin barriers located parallel to the direction of impulse propagation would have little effect in delaying conduction regardless of the arrangement of cardiac fibers. In this situation, the mean experimental ratio of postcut to control conduction times across the barrier was 1.05:1.00 in 10 tissues. When impulses were proceeding perpendicular to an anatomic barrier, significant distal conduction delay was predicted and found to occur only when the conduction from pacing to recording sites was initially longitudinal to fiber orientation (mean experimental ratio, 2.34:1.00 in five tissues) but not transverse to fiber orientation (ratio, 1.08:1.00 in five tissues). We conclude that the direction of initial impuls...
Serum cholesterol and triglyceride levels in 3,446 children from a biracial community: the Bogalusa Heart Study.
Authors: R RFrerichs, S RSrinivasan, L SWebber, G RBerenson
Journal: Circulation (1976)

Serum lipid profiles of 3,446 (91% of population) children, ages 5-14 years, were determined in a biracial community (Bogalusa, Louisiana) as part of a program investigating the early natural history of atherosclerosis. Black children had significantly higher mean levels of serum cholesterol than white children (170 mg/dl vs 162 mg/dl, P less than 0.0001). On the other hand, significantly lower levels of triglycerides were found in blacks than in whites (61 mg/dl vs 73 mg/dl, P less than 0.0001). Girls had higher levels of triglycerides than boys in both races (blacks, 64 mg/dl vs 59 mg/dl, P less than 0.001; whites, 77 mg/dl vs 69 mg/dl, P less than 0.001). The racial differences in serum cholesterol and triglyceride levels were even more apparent at the 95th percentile. The serum cholesterol level remained relatively constant in all children until ages 11 and 12 years, after which a slight reduction occurred. This reduction was more pronounced in boys than in girls. In contrast, a significant increase i...