tbuckley/cabot-search huggingface dataset:
Electrophysiologic mechanisms underlying arrhythmias due to reperfusion of ischemic myocardium.
Authors: S MPogwizd, P BCorr
Journal: Circulation (1987)

The mechanisms responsible for malignant ventricular arrhythmias associated with reperfusion of ischemic myocardium were delineated with a computerized, three-dimensional mapping system, with simultaneous eight-level transmural recordings from 232 bipolar sites. In six chloralose-anesthetized cats, regional ischemia was induced for 10 min by occlusion of the left anterior descending coronary artery, followed by reperfusion. At 10 min after ischemia, just before reperfusion, total ventricular activation time during sinus rhythm was significantly delayed (63 +/- 8 vs 25 +/- 2 msec before ischemia, p less than .001). Ventricular tachycardia (VT) occurred within 15 sec after reperfusion and in three animals culminated in ventricular fibrillation. In 75% of cases of nonsustained VT, initiation occurred in the subendocardium, at the border of the reperfused zone via a mechanism not involving reentry, as determined by the fact that continuous activation was not apparent and the time from the end of the sinus bea...
Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications.
Authors: J TWillerson, PGolino, JEidt, W BCampbell, L MBuja
Journal: Circulation (1989)

We have speculated previously that the abrupt conversion from chronic stable to unstable angina and the continuum to acute myocardial infarction may result from myocardial ischemia caused by progressive platelet aggregation and dynamic vasoconstriction themselves caused by local increases in thromboxane and serotonin at sites of coronary artery stenosis and endothelial injury. Platelet aggregation and dynamic coronary artery vasoconstriction probably result from the local accumulation of thromboxane and serotonin and also relative decreases in the local concentrations of endothelially derived vasodilators and inhibitors of platelet aggregation, such as endothelium-derived relaxing factor (EDRF) and prostacyclin. With severe reductions in coronary blood flow caused by these mechanisms, platelet aggregates may increase, and an occlusive thrombus composed of platelets and white and red blood cells in a fibrin mesh may develop. When coronary arteries are occluded or narrowed for a sufficient period of time by...
Doppler hemodynamic profiles of 82 clinically and echocardiographically normal tricuspid valve prostheses.
Authors: H MConnolly, F AMiller, C LTaylor, J MNaessens, J BSeward, A JTajik
Journal: Circulation (1993)

BACKGROUNDNormal Doppler hemodynamics for tricuspid prostheses have not been well characterized in a large group of patients. Therefore, we analyzed comprehensive Doppler echocardiographic examinations of 82 patients with tricuspid prostheses that were normal by clinical and two-dimensional echocardiographic examinations to establish the normal hemodynamics of various types and sizes of tricuspid prostheses.METHODS AND RESULTSThe earliest complete postoperative echocardiographic study from each patient was chosen for analysis. Doppler examinations were analyzed on an off-line station from tapes or Doppler strip charts. Early velocity, atrial velocity, end-diastolic velocity, pressure half-time, and mean gradient were obtained by digitizing tricuspid velocity curves. The incidence of physiological tricuspid prosthetic regurgitation was noted. Ten Doppler cycles were measured for each patient, and maximal, minimal, and average measurements were recorded. The mean values +/- SD of early velocity, atrial ve...
A Crater in the Stomach?
Authors: M Gonzalez Haba Ruiz, A Teijo Quintans, O Alonso Casado, M Garcia Casas, JL Calleja Panero
Journal: Endoscopy (2021)

A 60 years old patient underwent upper endoscopy for dyspepsia, in which a large depression was seen in the distal body, lined with normal appearing mucosa.
Rhemitt Score: Predicting the Risk of Rebleeding for Patients with Mid-Gastrointestinal Bleeding Submitted to Small Bowel Capsule Endoscopy: A Prospective Validation
Authors: R de Sousa Magalhães, B Sousa-Pinto, T Cúrdia Gonçalves, P Boal Carvalho, B Rosa, MJ Moreira, J Cotter
Journal: Endoscopy (2021)

Aims Mid gastrointestinal rebleeding rates are high, but difficult to predict. We created the first score to accurately predict the individual risk of small bowel rebleeding after capsule endoscopy (SBCE) – the RHEMITT score (Renal disease; Heart failure; Endoscopic findings; Major bleeding; Incomplete SBCE; Tobacco; Treatment by endoscopy), subdividing patients in 3 subgroups according to the risk of rebleeding: low risk (0-3 points); intermediate risk (4-10 points) and high risk (11-18 points).
Calcineurin inhibitors suppress acute graft-versus-host disease via NFAT-independent inhibition of T cell receptor signaling
Authors: Shizuka Otsuka, Nicolas Melis, Matthias M. Gaida, Debjani Dutta, Roberto Weigert, Jonathan D. Ashwell
Journal: Journal of Clinical Investigation (2021)

Inhibitors of calcineurin phosphatase activity (CNIs) such as cyclosporin A (CsA) are widely used to treat tissue transplant rejection and acute graft-versus-host disease (aGVHD), for which inhibition of gene expression dependent on nuclear factor of activated T cells (NFAT) is the mechanistic paradigm. We recently reported that CNIs inhibit TCR-proximal signaling by preventing calcineurin-mediated dephosphorylation of LckS59, an inhibitory modification, raising the possibility of another mechanism by which CNIs suppress immune responses. Here we used T cells from mice that express LckS59A, which cannot accept a phosphate at residue 59, to initiate aGVHD. Although CsA inhibited NFAT-dependent gene upregulation in allo-aggressive T cells expressing either LckWT or LckS59A, it was ineffective in treating disease when the T cells expressed LckS59A. Two important NFAT-independent T cell functions were found to be CsA-resistant in LckS59A T cells: upregulation of the cytolytic protein perforin in tissue-infiltrating CD8+ T cells and antigen-specific T/DC adhesion and clustering in lymph nodes. These results demonstrate that effective treatment of aGVHD by CsA requires NFAT-independent inhibition of TCR signaling. Given that NFATs are widely expressed and off-target effects are a major limitation in CNI use, it is possible that targeting TCR-associated calcineurin directly may provide effective therapies with less toxicity.
Cardiovascular and pulmonary effects of thromboxane B2 in the dog.
Authors: L SFriedman, T MFitzpatrick, M FBloom, P WRamwell, J CRose, P AKot
Journal: Circulation Research (1979)

The hemodynamic properties of thromboxane B2 (TxB2), a product of prostaglandin endoperoxide metabolism, have not been thoroughly described. TxB2 is a bronchoconstrictor, but its effects on the systemic circulation and circulating platelets are unknown. Its precursor, thromboxane A2(TxA2), is a potent vasoconstrictor as well as a platelet-aggregating agent. Using intact anesthetized dogs, we investigated the effects of TxB2 on pulmonary artery pressure (PAP), airway pressure (AP), systemic arterial pressure (SAP), and myocardial contractility (MC). Vascular responses were evaluated in relation to changes in platelet population and aggregability. Intravenous TxB2 (25 and 50 micrograms/kg) increased AP (mean 62% and 69%) and PAP (50% and 86%), respectively, whereas SAP and MC responses were inconsistent. Left ventricular injections (25 micrograms/kg) also increased AP (36%) and PAP responses were inconsistent. Left ventricular injections (25 micrograms/kg) also increased AP (36%) and PAP (36%). Intraventric...
Coronary heart disease: genetic aspects.
Authors: H NNeufeld, UGoldbourt
Journal: Circulation (1983)

Morbidity and mortality differences between populations, between ethnic groups and between individuals are not satisfactorily explained by the variation of risk factors. Differences in genetic susceptibility might be responsible for a part of the unexplained variation of coronary heart disease (CHD) rates. Genetic factors are also significant in determining the level of risk factors in individuals. Ample evidence links genetic factors to the levels of serum cholesterol, blood pressure and diabetes. Marked sex differences in CHD mortality also indicate the role of heredity in the development of the disease. The male:female ratio varies widely between different countries, as well as between different ethnic groups. These variations are difficult to explain by variation in environmental and behavioral differences between males and females alone. The degree of atherosclerosis in males and females varies, depending on the anatomic location of the atherosclerosis. Inherited disorders of metabolism and the varia...
Heterogeneous changes in epimyocardial microvascular size during graded coronary stenosis. Evidence of the microvascular site for autoregulation.
Authors: HKanatsuka, K GLamping, C LEastham, M LMarcus
Journal: Circulation Research (1990)

The purpose of this study was to determine the coronary microvascular sites of autoregulation. The epimyocardial coronary microcirculation was observed through an intravital microscope by stroboscopic epi-illumination in anesthetized open-chest dogs (n = 20). Aortic pressure and heart rate were held constant by an aortic snare and atrial pacing, respectively. Distal pressure of the left anterior descending coronary artery was controlled by a screw occluder on the proximal left anterior descending coronary artery and monitored with a 24-gauge plastic cannula inserted into the branch or distal portion of the left anterior descending coronary artery. Distal pressure of the left anterior descending coronary artery was stepwisely reduced to 59 +/- 1 mm Hg (mild stenosis, n = 20) and 38 +/- 1 mm Hg (severe stenosis, n = 16). In the left circumflex coronary artery area, myocardial blood flow measured with radioactive microspheres to subepicardium, midmyocardium, and subendocardium did not change with the mild an...
Mid-diastolic aortic valve opening in severe acute aortic regurgitation.
Authors: W FWeaver, C SWilson, TRourke, C CCaudill
Journal: Circulation (1977)

A case of severe acute aortic regurgitation is reported. Echocardiographic findings included mid-diastolic opening of the aortic valve, premature closure of the mitral valve, diastolic shuddering of the anterior mitral leaflet, probable demonstration of the flail aortic cusp in the left ventricular outflow tract, and increased left atrial and left ventricular dimensions. Correlation with hemodynamic, angiographic and surgical evidence is made.
Evidence for an increase in adrenergic nerve function in blood vessels from experimental hypertensive rabbits.
Authors: R DBevan, R EPurdy, J ABevan
Journal: Circulation Research (1975)

The possibility of changes in the adrenergic innervation of blood vessels in experimental hypertension was investigated by measuring arterial norepinephrine content, neuronal uptake of norepinephrine, and the neurogenic contractile response in rabbits made hypertensive by partial constriction of the abdominal aorta proximal to the kidneys. Two to 3 weeks after surgery, norepinephrine content was increased in the arteries above the ligature, where arterial blood pressure was increased, but not in the arteries below the ligature, where arterial blood pressure was normal, in the heart, or in the veins. Neuronal norepinephrine uptake per unit length of vessel and the neurogenic contractile response increased with the rise in arterial blood pressure. The neurogenic contractile response can be taken as an indication of an increase in transmitter release. The results taken together suggest an increase in the function and possibly the amount of the adrenergic neuroneal terminal in hypertension. Since the distribu...
Potential importance of tissue angiotensin-converting enzyme inhibition in preventing neointima formation.
Authors: HRakugi, D SWang, V JDzau, R EPratt
Journal: Circulation (1994)

BACKGROUNDAngiotensin II (Ang II) induces vascular smooth muscle cell migration and growth in vitro and induces DNA synthesis in vascular smooth muscle in vivo. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists inhibit neointimal hyperplasia in many experimental models of restenosis. However, recent clinical trials (MERCATOR and MARCATOR) reported that treatment with low (antihypertensive) doses of an ACE inhibitor (cilazapril) failed to prevent restenosis. Because ACE activity is induced in the neointima after injury, we hypothesize that the inhibition of neointimal development may be dependent on the suppression of tissue ACE activity, which in turn is dependent on the dose of the ACE inhibitor.METHODS AND RESULTSTo test this hypothesis, we treated rats with increasing doses of an ACE inhibitor, quinapril, before injury of the carotid artery. Blood pressure, serum and tissue ACE activity, and neointimal area were measured. The results demonstrated a dose-dependent in...
High resolution mapping of Koch's triangle using sixty electrodes in humans with atrioventricular junctional (AV nodal) reentrant tachycardia.
Authors: M AMcGuire, J PBourke, M CRobotin, D CJohnson, WMeldrum-Hanna, G RNunn, J BUther, D LRoss
Journal: Circulation (1993)

BACKGROUNDRecent evidence suggests that atrioventricular junctional reentrant tachycardia (AVJRT) uses a reentrant circuit that involves the atrioventricular (AV) node, the atrionodal connections, and perinodal atrial tissue. Electrogram morphology has been used to target the delivery of radiofrequency energy to the site of the slow pathway, a component of this reentrant circuit. The aim of this study was to localize precisely the sites of atrionodal connections involved in AVJRT and to examine atrial electrogram morphologies and their spatial distribution over Koch's triangle.METHODS AND RESULTSElectrical activation of Koch's triangle and the proximal coronary sinus was examined in 13 patients using a 60-point plaque electrode and computerized mapping system. Recordings were made during sinus rhythm (n = 12), left atrial pacing (n = 8), ventricular pacing (n = 12), and AVJRT (n = 12). During sinus rhythm electrical activation approached Koch's triangle and the AV node from the direction of the anterior...
Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin
Authors: Polina Kameneva, Artem V. Artemov, Maria Eleni Kastriti, Louis Faure, Thale K. Olsen, Jörg Otte, Alek Erickson, Bettina Semsch, Emma R. Andersson, Michael Ratz, Jonas Frisén, Arthur S. Tischler, Ronald R. de Krijger, Thibault Bouderlique, Natalia Akkuratova, Maria Vorontsova, Oleg Gusev, Kaj Fried, Erik Sundström, Shenglin Mei, Per Kogner, Ninib Baryawno, Peter V. Kharchenko, Igor Adameyko
Journal: Nature Genetics (2021)
Assessment of Comprehensibility of Industry Conflicts of Interest and Disclosures by Multiple Sclerosis Researchers at Medical Conferences
Authors: Sarah-Jane Martin, David P. J. Hunt
Journal: JAMA Network Open (2021)

This cross-sectional study uses length of disclosure slide display times and slide word counts to assess the comprehensibility of industry conflicts of interest (COI) disclosures by researchers presenting at the world's largest multiple sclerosis (MS) conference.
Hypoxia-inducible factor–1α–dependent induction of miR122 enhances hepatic ischemia tolerance
Authors: Cynthia Ju, Meng Wang, Eunyoung Tak, Boyun Kim, Christoph Emontzpohl, Yang Yang, Xiaoyi Yuan, Huban Kutay, Yafen Liang, David R. Hall, Wasim A. Dar, J. Steve Bynon, Peter Carmeliet, Kalpana Ghoshal, Holger K. Eltzschig
Journal: Journal of Clinical Investigation (2021)

Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor–1α (HIF1α) in the induction of miR122 and identified the oxygen-sensing prolyl hydroxylase domain 1 (PHD1) as a miR122 target. Further studies indicated that HIF1α-dependent induction of miR122 participated in a feed-forward pathway for liver protection via the enhancement of hepatic HIF responses through PHD1 repression. Moreover, pharmacologic studies utilizing nanoparticle-mediated miR122 overexpression demonstrated attenuated liver injury. Finally, proof-of-principle studies in patients undergoing orthotopic liver transplantation showed elevated miR122 levels in conjunction with the repression of PHD1 in post-ischemic liver biopsies. Taken together, the present findings provide molecular insight into the functional role of miR122 in enhancing hepatic ischemia tolerance and suggest the potential utility of pharmacologic interventions targeting miR122 to dampen hepatic injury during liver transplantation.
Outcomes of a Specialized Clinic on Rates of Investigation and Treatment of Primary Aldosteronism
Authors: Yuan-yuan Liu, James King, Gregory A. Kline, Raj S. Padwal, Janice L. Pasieka, Guanmin Chen, Benny So, Adrian Harvey, Alex Chin, Alexander A. Leung
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Primary aldosteronism (PA) is one of the most common causes of secondary hypertension but remains largely unrecognized and untreated. <h3>Objective</h3> To understand the outcomes of a specialized clinic on rates of evaluation and treatment of PA in the context of secondary factors. <h3>Design, Setting, and Participants</h3> This population-based cohort study was conducted in Alberta, Canada, using linked administrative data between April 1, 2012, and July 31, 2019, on adults identified as having hypertension. <h3>Main Outcomes and Measures</h3> We evaluated each step of the diagnostic and care pathway for PA to determine the proportion of people with hypertension who received screening, subtyping, and targeted treatment for PA. Variations in diagnosis and treatment were examined according to individual-level, clinician-level, and system-level characteristics. <h3>Results</h3> Of the 1.1 million adults with hypertension, 7941 people (0.7%) were screened for PA. Among those who were screened, 1703 (21.4%) had positive test results consistent with possible PA, and 1005 (59.0%) of these were further investigated to distinguish between unilateral and bilateral forms of PA. Only 731 individuals (42.9%) with a positive screen result received disease-targeted treatment. Geographic zones and clinician specialty were the strongest determinants of screening, subtyping, and treatment of PA, with the highest rates corresponding to the location of the provincial endocrine hypertension program. <h3>Conclusions and Relevance</h3> In this cohort, less than 1% of patients expected to have PA were ever formally diagnosed and treated. These findings suggest that a system-level approach to assist with investigation and treatment of PA may be highly effective in closing care gaps and improving clinical outcomes.
Interest of Colonoscopy in Patients With Rectorrhagia: a Single-Center Retrospective Study
Authors: R Harbi, S Mrabet, S Zaouga, I Akkari, E Ben Jazia
Journal: Endoscopy (2021)

Aims Lower gastrointestinal bleeding is a frequent reason for consultation in gastroenterology and emergency. The aetiologies are multiple, varying from simple internal hemorrhoids to the colorectal neoplastic process. Colonoscopy plays an essential role in the etiological diagnosis and treatment of rectal bleeding.
Acute decrease in left ventricular diastolic chamber distensibility during simulated angina in isolated hearts.
Authors: SIsoyama, C SApstein, L FWexler, W NGrice, B HLorell
Journal: Circulation Research (1987)

It is not clear what factors contribute to the prompt and reversible decrease in left ventricular diastolic chamber distensibility during angina pectoris that is induced by an increase in myocardial energy demand due to exercise or pacing tachycardia. To simulate the demand ischemia that occurs clinically during pacing-induced angina, we used isolated, blood-perfused rabbit hearts with restricted coronary flow and increased myocardial energy demand. A constant left ventricular balloon volume model was used to measure left ventricular diastolic chamber distensibility during 6 minutes of low-flow global ischemia, induced by a reduction in coronary perfusion pressure from 100 to 20 mm Hg. To investigate the influence of different levels of myocardial energy demand, the effects of two different heart rates were studied during low-flow global ischemia; pacing tachycardia (6.4 +/- 0.2 Hz, n = 7) was compared with the rabbit's baseline heart rate of 4 Hz (n = 7). Low-flow ischemia caused a marked decrease in con...
The effect of exercise training on heart rate during coitus in the post myocardial infarction patient.
Authors: R AStein
Journal: Circulation (1977)

The effect of interval exercise training on the peak coital heart rate in post myocardial infarction patients was studied. Sixteen men (ages 46-54) underwent a 16-week bicycle ergometer training program 12 to 15 weeks following their first myocardial infarction. Portable ECG tape recorders were used to record the ECG during coitus twice before and twice after the training program. The maximum minute oxygen consumption (VO2max) was measured in each subject during bicycle ergometer ECG examinations before and after the training program. A control group of six post myocardial infarction patients who were not trained was evaluated in the same manner. The exercise-trained group had an average increase in VO2max of 11.5%(2.7 to 3.0 L/min) and an average decrease in peak coital heart rate of 5.5%(127/min to 120/min). The control group demonstrated a 2% increase in VO2max and no significant change in peak coital heart rate. The increase in aerobic capacity (VO2max) and the consequent reduction in peak coital hear...
Duodenal Infusion of Feces for Recurrent <i>Clostridium difficile</i>
Authors: Jason M Hataye, Tara N Palmore, John H Powers
Journal: New England Journal of Medicine (2013)

To the Editor: Van Nood et al. (Jan. 31 issue)1 found fecal microbiota therapy to be superior to vancomycin for the treatment of recurrent Clostridium difficile infection, but the results of their study should be interpreted with caution. Small, index trials such as this one are vulnerable to exaggerated treatment effects, and subsequent trials typically show decreased effects.2 Even though the trial was randomized, the results may have been influenced by inequalities among the three treatment groups in terms of either the number of pretreatment recurrences of C. difficile infection or post-treatment exposure to an antimicrobial agent or proton-pump inhibitor (both of which are well-defined risks for recurrence).3 The cure rate in the control group treated with vancomycin was half of that reported in two randomized trials,4,5 a finding that biased the results of Van Nood et al. toward the efficacy of fecal microbiota therapy, according to the power calculation of the study. This unexpectedly low cure rate in the control group produced a P value that triggered a trial-stopping rule that led to the trial’s early termination; this in turn led to an inappropriate inflation of the efficacy of fecal microbiota therapy because of an alpha error.2 In exploratory trials of novel therapies such as this one, in which mortality was neither part of the primary outcome nor a factor in the interim analysis, the continuation of the study to its originally powered end point would have provided more rigorous and informative results.