tbuckley/cabot-search huggingface dataset:
Duchenne muscular dystrophy
Authors: Hannah Fox, Luke Millington, Indu Mahabeer, Henriette van Ruiten
Journal: BMJ (2020)

### What you need to know Duchenne muscular dystrophy (DMD) is a progressive and disabling neuromuscular condition that is often diagnosed late.1 In the UK the mean age of diagnosis has remained fairly static over the past 30 years, currently around 4.3 years of age.2 On average it takes 1.6 years from first parental concern to diagnosis of DMD,2 by which time muscle function has already declined (box 1, case study). Delayed diagnosis of DMD can be devastating for patients and their families. Outcomes for people with DMD can be improved with optimum care at the earliest opportunity, and patients are now living into their fourth decades.34 Early diagnosis also enables parents to make informed decisions about family planning and can provide access to innovative treatments and clinical trials. International guidelines for diagnosis and management of DMD have been established by the DMD Care Considerations Working Group.567 Box 1 ### Case study of a delayed diagnosis Patient A presented with speech delay at age 2 and poor fine and gross motor skills at 2.5 years. He had been referred to several different teams for these symptoms, including physiotherapy for his poor motor skills and behavioural psychology. He initially walked at … RETURN TO TEXT
Amelioration of the effects of ischemic cardiac arrest by the intracoronary administration of cardioplegic solutions.
Authors: G JTodd, G FTyers
Journal: Circulation (1975)

Interruption of coronary flow during cardiac surgical procedures provides a bloodless flaccid heart and allows precise and rapid correction of complex cardiac defects. However, myocardial damage occurs in direct proportion to the duration of the ischemia. As the induction of cardioplegia simulataneous with the initiation of cardiac ischemia helps to preserve cardiac energy reserves and thus myocardial integrity, the identification of a consistently reliable cardioplegic technique is desirable. Isolated perfused working rat hearts were made ischemic for one hour by aortic cross-clamping and were compared with hearts rendered cardioplegic at the onset of ischemia by the intracoronary administration of 5 ml of a hypothermic solution: 1) Krebs-Henseleit buffer, 2) Ringer's lactate, 3) tetrodotoxin, 4) potassium chloride, or 5) potassium citrate. Cardiac output, heart rate, aortic pressure and coronary flow were determined pre and post-ischemia. When compared to time-matched controls and hearts arrested with p...
Response of the left ventricle in coronary artery disease to postextrasystolic potentiation.
Authors: R IHamby, AAintablian, GWisoff, M LHartstein
Journal: Circulation (1975)

Left ventricular volumes and contractile patterns were evaluated during the first sinus beat after a compensatory pause resulting from ventricular arrhythmia and were compared to the second sinus beat (control beat) in order to evaluate the effect of postextrasystolic potentiation. Twelve patients had no evidence of heart disease (group I). Fifty patients had coronary artery disease and included 14 patients (group IIa) with no prior myocardial infarction and a normal left ventricular contractile pattern and 19 pateints (group IIb) with an abnormal contractile pattern. Seventeen pateints (group IIc) had a documented transmural myocardial infarction as well as an abnormal left ventricular contractile pattern. In all patients the first postextrasystolic sinus beat, when compared to the second sinus beat, demonstrated increases in stroke volume and ejection fraction and decrease in end-systolic volume. There were no qualitative changes in the contractile pattern in the immediate postextrasystolic beat in the ...
Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism
Authors: Emily R. Watts, Andrew J.M. Howden, Tyler Morrison, Pranvera Sadiku, Jens Hukelmann, Alex von Kriegsheim, Bart Ghesquiere, Fiona Murphy, Ananda S. Mirchandani, Duncan C. Humphries, Robert Grecian, Eilise M. Ryan, Patricia Coelho, Gio Rodriguez Blanco, Tracie M. Plant, Rebecca S. Dickinson, Andy Finch, Wesley Vermaelen, Doreen A. Cantrell, Moira K. Whyte, Sarah R. Walmsley
Journal: Journal of Clinical Investigation (2021)

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues.
Enhanced sensitivity to hypoxia-induced diastolic dysfunction in pressure-overload left ventricular hypertrophy in the rat: role of high-energy phosphate depletion.
Authors: L FWexler, B HLorell, SMomomura, E OWeinberg, J SIngwall, C SApstein
Journal: Circulation Research (1988)

Isolated buffer-perfused rat hearts with pressure-overload hypertrophy develop a greater decrease in left ventricular (LV) diastolic distensibility and a greater impairment in extent of LV relaxation in response to hypoxia than do normal hearts. Using 31P-NMR spectroscopy, we tested the hypothesis that the enhanced susceptibility of hypertrophied hearts to develop hypoxia-induced diastolic dysfunction is due to an accelerated rate of ATP and/or creatine phosphate depletion. Twelve minutes of hypoxia were imposed on isolated isovolumic (balloon-in-left-ventricle) buffer-perfused hearts from 14 rats with pressure-overload hypertrophy (LVH; LV/body wt ratio = 3.43 +/- 17) secondary to hypertension induced by uninephrectomy plus deoxycorticosterone and salt treatment and from 17 age-matched controls (LV/body wt ratio = 2.22 +/- 0.12, p less than 0.001). Coronary artery flow per gram left ventricle was matched in the LVH and control groups during baseline oxygenated conditions and held constant thereafter. Bal...
Defibrillation efficacy. Comparison of defibrillation threshold versus dose-response curve determination.
Authors: D LJones, W DIrish, G JKlein
Journal: Circulation Research (1991)

When an automatic defibrillator is implanted, it is essential to determine the efficacy of the defibrillating system accurately, while balancing the need to keep the number of fibrillation episodes to a minimum. Two methods have evolved to assess  efficacy: 1) the defibrillation  which requires few ventricular fibrillation episodes, and 2) the   which requires many ventricular fibrillation episodes and relates percent success to energy. The purpose of this study was to compare these two methods directly. Twenty open-chest anesthetized pigs had triplicate  threshold determinations. To produce a dose-response curve, six shocks then were delivered at 0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 times the mean  threshold, in a balanced randomized order, during separate episodes of ventricular fibrillation. The data were fitted by logistic regression, conversions of the logistic regression, and a saturable exponential and nonsaturable growth expo...
Chronic Administration of Anticholinergics in Rats Induces a Shift from Muscarinic to Purinergic Transmission in the Bladder Wall
Authors: Pieter Uvin, Mathieu Boudes, Aurélie Menigoz, Jan Franken, Sílvia Pinto, Thomas Gevaert, Ruth Verplaetse, Jan Tytgat, Rudi Vennekens, Thomas Voets, Dirk De Ridder
Journal: European Urology (2013)
Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart.
Authors: PButtrick, AMalhotra, SFactor, DGreenen, LLeinwand, JScheuer
Journal: Circulation Research (1991)

The mechanisms by which the aged heart adapts to a superimposed pressure load such as hypertension have not been described. We therefore investigated biochemical and molecular genetic adaptations in the 24-month-old rat heart subjected to renovascular hypertension. Compared with 4-month-old rats, aging was associated with a 68% increase in left ventricular mass without any change in heart weight-to-body weight ratio, a 33% reduction in calcium-activated myosin ATPase activity, and a shift from a V1 to a V3 predominant myosin heavy chain (MHC) isoform distribution. A 46% reduction in alpha-MHC mRNA and a reciprocal increase in beta-MHC mRNA was seen. When hypertension was superimposed, there was a further 75% increase in ventricular mass, a 63% increase in heart weight-to-body weight ratio, and a 19% reduction in myosin ATPase. Myosin isozyme distribution was further shifted to V3, and the ratio of alpha-MHC to beta-MHC mRNA was reduced. In addition, with hypertension a significant (greater than 50%) reduc...
Efflux of metabolized and nonmetabolized fatty acid from canine myocardium. Implications for quantifying myocardial metabolism tomographically.
Authors: K AFox, D RAbendschein, H DAmbos, B ESobel, S RBergmann
Journal: Circulation Research (1985)

It has generally been assumed, from assessment of myocardial metabolism with [1(-11)C]palmitate and positron emission tomography, that clearance of the radiolabel from the myocardium is attributable solely to efflux of the products of oxidative metabolism. However, interpretations would differ if this assumption were unfulfilled. Furthermore, efflux of metabolized and nonmetabolized tracer has not been quantified. Accordingly, in this study, myocardium was perfused extracorporeally in 21 open-chest anesthetized dogs, and the extraction and clearance of [1(-11)C]palmitate were characterized under baseline conditions (normoxia, n = 21), and, again, with ischemia (n = 6), with hypoxia (n = 9), or under control conditions (n = 6). After intracoronary bolus injection of [1(-11)C]palmitate, myocardial time activity curves were measured with a beta-probe, and the products of oxidative metabolism (11CO2) and efflux of extracted but nonmetabolized fatty acid (back-diffusion of [1(-11)C]palmitate) were measured d...
Molecular forms of atrial natriuretic factor in normal and failing human myocardium.
Authors: R JRodeheffer, MNaruse, J BAtkinson, KNaruse, J CBurnett, W HMerrill, W HFrist, HDemura, TInagami
Journal: Circulation (1993)

BACKGROUNDAtrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart.METHODS AND RESULTSWe measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and...
Severe Atrial Functional Mitral Regurgitation
Authors: Oltion Mesi, Mohamed M. Gad, Alejandro D. Crane, Jay Ramchand, Rishi Puri, Habib Layoun, Rhonda Miyasaka, Marc A. Gillinov, Per Wierup, Brian P. Griffin, Samir R. Kapadia, Serge C. Harb
Journal: JACC. Cardiovascular imaging (2021)
Comparative mechanisms of antiarrhythmic drug action in experimental atrial fibrillation. Importance of use-dependent effects on refractoriness.
Authors: JWang, G WBourne, ZWang, CVillemaire, MTalajic, SNattel
Journal: Circulation (1993)

BACKGROUNDAntiarrhythmic drugs are considered to terminate atrial fibrillation by prolonging refractoriness, but direct experimental evaluation of this concept has been limited. The atria are activated rapidly during atrial fibrillation, and antiarrhythmic drugs are known to have important rate-dependent actions. The potential role of such properties in determining drug effects during atrial fibrillation has not been evaluated.METHODS AND RESULTSWe evaluated the effects of representative class Ia (procainamide), Ic (propafenone), and III (sotalol) antiarrhythmic drugs on sustained cholinergic atrial fibrillation and atrial electrophysiological properties in anesthetized, open-chest dogs. Loading and maintenance doses were used to produce stable plasma concentrations, and computer-based 112-electrode epicardial mapping was used to study atrial conduction and activation during atrial fibrillation. Clinically used doses of procainamide and propafenone terminated atrial fibrillation in 13 of 13 (100%) and 7 o...
Noninvasive detection and quantification of left-to-right shunts in children using oxygen-15 labeled carbon dioxide.
Authors: D MTamer, D DWatson, P JKenny, W RJanowitz, HGelband, A JGilson
Journal: Circulation (1977)

A method for the detection and quantification of left-to-right intracardiac shunts is described which utilizes a single breath inhalation of oxygen-15 labeled carbon dioxide (C15O2). The inhaled gas rapidly crosses the alveolar membrane and the oxygen-15 label is exchanged through the carbonate cycle to form oxygen-15 labeled water within the pulmonary capillary blood. Pulmonary indicator clearance curves are measured by external scintillation probes. A simplified method of shunt flow quantification was developed from indicator dilution principles and used for the analysis of the clearance curves. Inhalation studies were performed with 62 children on the day prior to cardiac catheterization. The presence or absence of left-to-right shunt was confirmed by contrast angiography in all cases. Twenty-six children were found to have no shunts by C15O2 inhalation, oximetry or angiography. Of the 36 with shunts, 34 were detected by C15O2. Two of these were designated as equivocal because they were considered to b...
Effects of ouabain and vagal stimulation on sinus nodal function in conscious dogs.
Authors: R JHariman, B FHoffman
Journal: Circulation Research (1982)

We studied the effects of intravenous ouabain administration (15 micrograms/kg) and vagal stimulation on instrumented conscious dogs. In these dogs, a special electrode was implanted on the epicardial surface over the sinus node and plaque electrodes were placed on the superior vena cava and left atrial appendage. Unipolar sinus electrograms were recorded through the terminals of the sinus electrode paired with the superior vena caval electrode. An electrode also was implanted around the desheathed cervical vagosympathetic trunk, and a coiled polyethylene tube with side holes was implanted cranial to it. Ouabain administration resulted in: (1) an increase in the sinus cycle lengths and sinoatrial intervals and increase in beat-to-beat variation of the sinus cycles and sinoatrial intervals, and (2) periods of sinus pacemaker shift, sinus arrest and sinoatrial block that occurred spontaneously or after atrial overdrive stimulation delivered through the electrode on the left atrial appendage. These effects o...
Geometric remodeling is not the principal pathogenetic process in restenosis after balloon angioplasty. Evidence from correlative angiographic-histomorphometric studies of atherosclerotic arteries in rabbits.
Authors: S DGertz, L WGimple, SBanai, MRagosta, E RPowers, W CRoberts, L SPerez, I JSarembock
Journal: Circulation (1994)

BACKGROUNDRestenosis after balloon angioplasty of coronary arteries is thought to be a proliferative response of the arterial wall to injury. Recently, it has been suggested that geometric remodeling of the arterial wall, rather than intimal fibromuscular hyperplasia, may be the major pathophysiological mechanism underlying restenosis. In this study, we evaluated the relative contribution of a geometric decrease in arterial size versus neointimal growth to luminal narrowing associated with restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.METHODS AND RESULTSFocal femoral atherosclerosis was induced by endothelial desiccation injury followed by a 2% cholesterol diet. After 1 month on the high cholesterol diet, the animals were subjected to one of four strategies: (1) balloon angioplasty, (2) balloon angioplasty followed by treatment with the factor Xa inhibitor antistasin, (3) combined laser and balloon angioplasty, or (4) no angioplasty. Animals were killed 2 hours or 28 ...
Long-Term Nasogastric Feeding Tube
Authors: David Metheny
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The article on the nasogastric feeding tube is timely and valuable. My partner, Vernon Lundmark, used a similar tube... I have one suggestion. If a tube intended for nasogastric suction is rubbed with silicone fluid such as ophthalmologists use for cleaning eye glasses, the tube will not stick to a dry mucous membrane of nose or throat. It improves the comfort of the patient a great deal.
Subendocardial infarction in retrospect: pathologic, cardiographic, and ancillary features.
Authors: H DLevine
Journal: Circulation (1985)

Fifty-three patients with subendocardial infarction (SEMI) were studied at autopsy; all were elderly and the group was equally divided by sex. About half had more than one SEMI; the recurrences or extensions often involved superjacent, but not infrequently adjacent, areas. Six showed fibrinous pericarditis. This larger study showed more widespread and severe coronary narrowing than an earlier report. Six patients had thrombi in the right coronary artery. Six showed electrocardiographic evidence of concomitant anteroseptal and inferior (Roesler-Dressler) infarction, and 12 had intraventricular block generally preceding higher-grade block or arrhythmias. At some time during their terminal hospitalization, 27 patients, or half, developed distinctive protracted RS-T depression or T wave inversion. Twenty-four of the SEMIs were diagnosed on accepted criteria as transmural infarct; that diagnosis was sustained in only four. Thus neither the presence of changes in RS-T segment or T wave nor the absence of QRS ch...
The effect of vagus nerve stimulation upon vulnerability of the canine ventricle: role of sympathetic-parasympathetic interactions.
Authors: B SKolman, R LVerrier, BLown
Journal: Circulation (1975)

The effect of vagus nerve stimulation (VNS) upon ventricular vulnerability was studied in 30 mongrel dogs subjected to varying levels of adrenergic stimulation. Vulnerability was assessed both by determining the minimum current required to produce ventricular fibrillation (VF threshold) and by plotting VF threshold throughout the vulnerable period (VF zone). Chloralose-anesthetized animals were studied by means of sequential pulses applied to the apex of the right ventricular endocardium. Testing was carried out in closed-chest dogs, in open-chest dogs with and without left stellate ganglion stimulation (LSGS), and in open- and closed-chest dogs pretreated with propranolol. In the absence of adrenergic stimulation. VNS was without significant effect on either the VF threshold or the VF zone under closed- or open-chest conditions. During LSGS, however, VNS was associated with a 93 +/- 22% (mean +/- SE) increase in VF threshold (P less than 0.01) and constriction of the VF zone. Vagus nerve stimulation comb...
Is tau a preload-independent measure of isovolumetric relaxation?
Authors: S KVarma, R MOwen, M LSmucker, M DFeldman
Journal: Circulation (1989)

Several studies have been performed in patients with a variety of myocardial diseases that have identified a prolongation of tau. However, it is not clear whether prolongation of tau represents abnormal myocardial physiology or the effect of excessive load associated with a particular disease process. Accordingly, we evaluate the effect on tau of an isolated decrease in preload induced by inferior vena cava occlusion before the appearance of reflex changes in six patients designated as normal by catheterization criteria. A computer-based digitization routine identified cardiac contractions in all patients early after inferior vena cava occlusion where left ventricular end-diastolic pressure decreased (18.3 +/- 6.3 to 9.3 +/- 5.8, p less than 0.05) while left ventricular systolic pressure (113.3 +/- 13.8 to 111.8 +/- 14.0, p = NS) and heart rate (66.0 +/- 10.0 to 65.9 +/- 10.3, p = NS) did not change. After this alteration in preload, no change in tau from baseline, as calculated by the logarithmic (TL), d...
Activation of the cardiac ATP-sensitive K+ channel by ER-001533, a newly synthesized vasorelaxant.
Authors: W KShen, R TTung, YKurachi
Journal: Circulation Research (1992)

Effects of ER-001533 (ER), a newly synthesized vasorelaxant, on the membrane currents were examined in single ventricular cells of guinea pigs. The patch-clamp technique was used in the  and  patch configurations. In the whole-cell clamp condition, ER induced a time-independent K(+)-dominant current, which was inhibited by glibenclamide (1-3 microM), suggesting that ER activated the cardiac ATP-sensitive K+ channel (KATP). To elucidate the mechanism of ER-mediated KATP channel activation, the drug was applied to the inside-out patches before and after channel run-down. Since nucleotide diphosphates could induce the channel openings after complete run-down, effects of the drug on the nucleotide diphosphate-induced channel openings were also examined. Before run-down, ER activated the KATP channel only in the presence of ATP. ER shifted the relation between [ATP]i and the channel activity to the right in a concentration-dependent fashion without a significant alteration of the slop...
Cardiovascular responses to dynamic and static effort soon after myocardial infarction. Application to occupational work assessment.
Authors: R FDeBusk, RValdez, NHouston, WHaskell
Journal: Circulation (1978)

Static and dynamic work involving the arms and the legs was performed by 40 men seven weeks after myocardial infarction. Leg ergometry produced a significantly higher peak work load, systolic blood pressure (BPs), heart rate (HR), and HR X BPs X 10(-2) product (DP) than did arm ergometry: 842 +/- 178 vs 546 +/- 135 kg-m/min, 176 +/- 24 vs 154 +/- 19 mm Hg and 256 +/- 54 vs 219 +/- 48 (SD). Peak heart rates were 145 and 142. Endpoints were primarily muscular and generalized fatigue and dyspnea. Ischemic abnormalities and ventricular ectopy were more frequent with leg ergometry. Sustained forearm lifting elicited higher HR, PBs and DP responses than sustained handgrip contraction: 95 +/- 16 vs 91 +/- 16 beats/min, 162 +/- 18 vs 152 +/- 17 mm Hg and 154 +/- 33 vs 139 +/- 33 (SD). Ischemic ST segment depression and significant ventricuar arrhythmias were infrequent with static effort. Dynamic leg testing is superior to dynamic or static arm testing in assessing the capacity of patients to perform physical wor...