tbuckley/cabot-search huggingface dataset:
Accidental Hypothermia in the Elderly
Authors: F. M. Taylor
Journal: BMJ (1964)

BRIC JOS 1463 weight rapidly, which, curiously enough, has provoked some nurses and doctors to argue that this might in some way be detrimental, but the evident success of the method usually overcomes the objections.Certainly if one told a farmer that his young livestock were growing and gaining weight too fast he would laugh in one's face !But then, Sir, he has the advantage of having his feet placed firmly on the good earth.-Iam, etc., Stock, Essex.IAN G. WICKES.SIR,-I was astonished to see no reference at all to the development of the teeth in Dr. D. MacCarthy's article (21 November, p. 1309).Surely one of the main advantages of breast-feeding is that the teeth in later life will be harder and more durable than they would be with artificial feeding.Recently I went to see a girl who happened to be out.The mother said she had an appointment with her dentist; she complained that she was always there, whereas her two sons never needed any dental treatment.I said that was an easy one: the girl had been artificially fed and the boys had been breastfed.This proved to be the case.It would be interesting to have a dental surgeon's opinion.-Iam, etc.,
Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function.
Authors: P MRidker, C LGaboury, P RConlin, E WSeely, G HWilliams, D EVaughan
Journal: Circulation (1993)

BACKGROUNDRecent clinical trial data indicate that the use of angiotensin converting enzyme (ACE) inhibitors among patients with left ventricular dysfunction results in reduced rates of coronary thrombosis, a provocative finding that suggests a potential interaction between the renin-angiotensin system and fibrinolytic function.METHODS AND RESULTSIn four normotensive subjects and six hypertensive patients, we investigated whether infusion of angiotensin II (Ang II) affected circulating levels of plasminogen activator inhibitor-1 (PAI-1), the most important physiological inhibitor of tissue-type plasminogen activator (t-PA). Overall, mean levels of PAI-1 antigen increased significantly from 20.1 ng/mL before Ang II infusion to 36.0 ng/mL at the end of Ang II infusion (p = 0.008), whereas no change in PAI-1 was observed for control subjects infused with 5% dextrose (p = 0.46). Among the normotensive subjects for whom graded doses of Ang II were infused at 0, 1, 3, and 10 ng.kg-1.min-1, mean PAI-1 levels inc...
The relationship of various measures of end-systole to left ventricular maximum time-varying elastance in man.
Authors: M RStarling, R AWalsh, L JDell'Italia, G BMancini, J CLasher, J LLancaster
Journal: Circulation (1987)

This investigation was designed to calculate left ventricular maximum time-varying elastance (Emax), to define the relationship between Emax and pressure-volume (P-V) relations at other, more easily defined measured of end-systole, and to determine whether these measures of left ventricular contractile function can be normalized in man. Accordingly, we studied 10 subjects with simultaneous high-fidelity micromanometer left ventricular and ascending aortic pressure recordings and biplane contrast cineangiograms at control conditions and during infusion of methoxamine and nitroprusside. Emax was defined as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. Left ventricular end-systole was also defined for each loading condition as: the time of the maximum P-V ratio (maxPV), minimum ventricular volume (minPV), (-)dP/dtmin [(-)dP/dtPV], and zero systolic flow approximated by the central aortic dicrotic notch (AodiPV). The m...
Mechanisms for vagal modulation of ventricular repolarization and of coronary occlusion-induced lethal arrhythmias in cats.
Authors: LRosenshtraukh, PDanilo, E PAnyukhovsky, S FSteinberg, VRybin, KBrittain-Valenti, VMolina-Viamonte, M RRosen
Journal: Circulation Research (1994)

Our goal was to better understand the mechanisms underlying muscarinic receptor actions on the ventricle in vivo. Therefore, we studied the effects of vagal stimulation on ventricular repolarization and of vagal tone on lethal arrhythmias induced by 30 minutes of left anterior descending coronary artery ligation in anesthetized cats. Experimental groups included normal control cats subjected only to coronary ligation and cats pretreated with atropine, pertussis toxin (PTX), or propranolol. All cats received bilateral cervical vagal stimulation (Vstim) at 1, 3, and 5 Hz for 1 minute at 10-minute intervals. Before coronary ligation, Vstim slowed sinus rate, prolonged the PR interval, and lowered blood pressure. Most important from the point of view of electrophysiological function was a vagally induced acceleration of ventricular repolarization in paced and unpaced hearts, which could be explained by the effects of acetylcholine (ie, shortening the subepicardial muscle action potentials). The effect on repo...
Effects of dietary supplementation with cod-liver oil on endothelium-dependent responses in porcine coronary arteries.
Authors: HShimokawa, J YLam, J HChesebro, E JBowie, P MVanhoutte
Journal: Circulation (1987)

To study the effect of dietary supplementation with fish oil on endothelium-dependent responses, Yorkshire pigs were maintained on a normal diet or on a low (0.6 ml/kg/day) or a high (1.0 ml/kg/day) dose of cod-liver oil for 4 weeks. Endothelium-dependent responses were examined in vitro in rings of proximal left anterior descending coronary arteries taken from control and treated animals studied in parallel. Endothelium-dependent relaxations in response to bradykinin, serotonin, adenosine diphosphate, and thrombin were facilitated in arteries from treated but not in those from control animals, whereas the relaxations in response to A23187 were unaltered. The facilitated relaxations were not altered by indomethacin but significantly inhibited by methylene blue. Aggregating platelets from control and treated pigs induced comparable, facilitated endothelium-dependent relaxations in rings taken from treated pigs. The platelet-induced contractions were significantly reduced in rings with endothelium taken fro...
Pulmonary leukostasis and its relationship to pulmonary dysfunction in sheep and rabbits.
Authors: S WFountain, B AMartin, C EMusclow, J DCooper
Journal: Circulation Research (1980)

Pulmonary leukostasis, as a result of complement activation, has been invoked as a cause of pulmonary dysfunction. To investigate this phenomenon, we studied the pulmonary response to infusion of autologous complement-activated plasma in sheep and rabbits. Complement activation was produced by plasma incubation with zymosan. Leukopenia, with selective loss of polymorphonuclear leukocytes into the lungs, occurred in all animals immediately after the onset of plasma infusion. Complement-activated plasma infusion in sheep produced a significant fall in the arterial PO2 and a marked rise in pulmonary vascular resistance, whereas no such effects were observed in rabbits. Pretreatment of the sheep with sulfinpyrazone eliminated the pulmonary response to complement-activated plasma without altering the leukopenic response. Pulmonary histology in rabbits and sheep confirmed the presence of intracapillary leukostasis after the plasma infusions, whether or not sulfinpyrazone had been administered previously. The pu...
Significance of chronic bifascicular block without apparent organic heart disease.
Authors: R CDhingra, CWyndham, RBauernfeind, PDenes, DWu, SSwiryn, K MRosen
Journal: Circulation (1979)

Eighty-six of 452 patients (19%) with chronic bifascicular block were found to have no clinically apparent associated organic heart disease (OHD) and were defined as having primary conduction disease (PCD). Comparison of patients with PCD and OHD revealed a significantly lower incidence of the following clinical variables in the PCD patients (p less than 0.001): exertional angina, dyspnea, congestive heart failure, cardiomegaly, functional class I (all by study design), left bundle branch block and premature ventricular contractions. Both mean AH and HV intervals were significantly shorter in patients with PCD (p less than 0.01). The incidence of HV prolongation was 21% in PCD and 41% in OHD patients (p less than 0.001). All patients were prospectively followed for 21-2998 days with a mean +/- SEM of 1209 +/- 66 days for PCD and 1172 +/- 36 days for OHD. Atrioventricular (AV) block developed in three patients from the PCD group and 26 from the OHD group (NS), with spontaneous block occurring in one (1%) P...
Abstract 304: Selective Targeting of a Novel Epsin-VEGFR2 Interaction Promotes VEGF-mediated Angiogenesis
Authors: Hong Chen
Journal: Circulation Research (2016)

Background: VEGF-induced binding of VEGFR2 to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2, however the molecular determinants that govern how epsin specifically interacts with and regulates VEGFR2 were unknown. The goals for the present study were (1) to identify critical molecular determinants that drive the specificity of the epsin and VEGFR2 interaction and (2) to ascertain if such determinants were critical for physiological angiogenesis in vivo . Methods and Results: Structural modeling uncovered two novel binding surfaces within VEGFR2 that mediate specific interactions with epsin UIM. Three glutamic acid residues in epsin UIM were found to interact with residues in VEGFR2. Further, we found that the VEGF-induced VEGFR2-epsin interaction promoted c-Cbl-mediated ubiquitination of epsin, and uncovered a previously unappreciated ubiquitin-binding surface within VEGFR2. Mutational analysis revealed that the VEGFR2-epsin interaction is supported by VEGFR2 interacting specifically with the UIM and with ubiquitinated epsin. An epsin UIM peptide, but not a mutant UIM peptide, potentiated endothelial cell proliferation, migration and angiogenic properties in vitro , increased postnatal retinal angiogenesis, and enhanced VEGF-induced physiological angiogenesis and wound healing. Conclusions: Distinct residues in the epsin UIM and VEGFR2 mediate specific interactions between epsin and VEGFR2, in addition to UIM recognition of ubiquitin moieties on VEGFR2. These novel interactions are critical for pathophysiological angiogenesis, suggesting that these sites could be selectively targeted by therapeutics to modulate angiogenesis.
Patient Satisfaction of Deep Propofol Sedation Versus Moderate Midazolam and Fentanyl Sedation During Colonoscopy in Inflammatory Bowel Disease: A Randomized Controlled Trial &amp; NBSP
Authors: C Steenholdt, J Jensen, J Brynskov, Møller AM, AC Limschou, L Konge, P Vilmann
Journal: Endoscopy (2021)

Aims Colonoscopy is essential for optimal management of inflammatory bowel disease (IBD) to ensure pivotal endoscopic treatment goals, notably mucosal healing. However, colonoscopy is not favored by patients and many opt out due to unpleasantness of the procedure. We aimed to investigate if Nurse Administered Propofol Sedation (NAPS) improves patient satisfaction and attitude towards future colonoscopies.
Staged surgical management of tetralogy of Fallot in infants.
Authors: L WStephenson, SFriedman, L HEdmunds
Journal: Circulation (1978)

A cohort of 61 consecutive patients 24 months of age of younger had palliative shunts for symptoms of tetralogy of Fallot during a 12-year period. Thirty-six of these patients have been followed through definitive intracardiac repair or to death. For analysis palliative operations were separated into two six-year periods, 1965--1970. During the first period seven of 30 infants operated on died; all 31 infants operated on during the second period survived. The Waterston anastomosis was performed most frequently (67%) during the first period; the Blalock-Taussig anastomosis was performed in 68% of infants during the second period. Of 54 hospital survivors, three died before definitive intracardiac repair. Two of the three interim deaths were related to heart disease. Twenty-six of the remaining 51 patients have had definitive intracardiac repair with two deaths (8%). Twenty-four in this group had intracardiac repair since 1973 with one hospital death (4%). The cumulative mortality for the entire cohort is 2...
Enhanced alpha 1-adrenergic responsiveness in cardiomyopathic hamster cardiac myocytes. Relation to the expression of pertussis toxin-sensitive G protein and alpha 1-adrenergic receptors.
Authors: LSen, B TLiang, W SColucci, T WSmith
Journal: Circulation Research (1990)

The pathogenesis of the myopathy occurring in the heart of the cardiomyopathic strain of the Syrian hamster is not well understood but is believed to be associated with abnormal calcium handling by myopathic cells. The purpose of this study was to determine whether the cardiomyopathy occurring in strain BIO 14.6 animals is associated with an enhanced alpha 1-adrenergic receptor-mediated rise in cytosolic calcium, whether a pertussis toxin-sensitive G protein is involved in coupling the alpha 1-adrenergic receptor to changes in intracellular calcium and whether enhanced alpha 1 responsiveness is associated with an increase in the level of expression of the alpha 1-adrenergic receptor or in the pertussis toxin-sensitive G protein or proteins. To test the hypothesis that the cardiomyopathic state is associated with a greater alpha 1-receptor-mediated rise in cytosolic calcium, we studied the effect of phenylephrine (in the presence of propranolol) on time-averaged cytosolic calcium concentration ([Ca2+]i) in...
Anterior infarctional changes occurring during mid and late ventricular activation detectable by surface mapping techniques.
Authors: N CFlowers, L GHoran, J CJohnson
Journal: Circulation (1976)

This is a comparative body surface potential map study of 26 patients with a recent acute anterior myocardial infarction. The mean plus or minus two standard deviations (+/- 2 SD) for the voltage distribution was established at 5 msec intervals throughout the cardiac cycle in 30 normal subjects at each of 142 recording sites. Instances in which a patient's potential distribution fell outside the normal range were analyzed as to location, duration and intensity against the expected time course of ventricular activation. Only four patients had departures from the normal distribution confined to the Q time zone. Twenty patients had not only Q time zone abnormalities, but had areas of both positivity and negativity exceeding +/- 2 SD, which occurred well after 30 msec. Two patients with clearly documented diagnostic Q waves during the first few days of hospitalization had lost these findings by the date of body surface mapping. They did retain, however, departure map findings demonstrating significant abnorma...
Changes in cardiovascular and adrenal cortical responses to angiotensin III induced by sodium deprivation in the rat.
Authors: M JPeach, C ASarstedt, E DVaughan
Journal: Circulation Research (1976)

The restriction of dietary sodium intake is known to depress the cardiovascular responses to angiotensin II and increase the sensitivity of the adrenal zona glomerulosa to this steroidogenic octapeptide. In sodium-repleted animals, angiotensin III is a weak pressor substance and a potent stimulant of aldosterone biosynthesis. The effect of a low sodium diet on vascular and steroidogenic responses to angiotensin II and angiotensin III was investigated. In nephrectomized rats, angiotensin III had one-third of the pressor activity relative to angiotensin II when either normal or sodium-deprived animals were compared. When administered subcutaneously (sc) to rats, angiotensin II and III induced comparable steroidogenic responses, whereas only angiotensin II significantly elevated blood pressure. The comparison of cell suspensions from control adrenals with suspensions of adrenals from sodium-deprived animals showed that the zona glomerulosa from rats on low sodium diets had increased wet weight (20%), cell pr...
Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study
Authors: Tian X Zhao, Muhammad Aetesam-Ur-Rahman, Andrew P Sage, Saji Victor, Rincy Kurian, Sarah Fielding, Hafid Ait-Oufella, Yi-Da Chiu, Christoph J Binder, Mikel Mckie, Stephen P Hoole, Ziad Mallat
Journal: Cardiovascular Research (2021)

Abstract Aims In pre-clinical models of acute myocardial infarction (MI), mature B cells mobilize inflammatory monocytes into the heart, leading to increased infarct size and deterioration of cardiac function, whilst anti-CD20 antibody-mediated depletion of B cells limits myocardial injury and improves cardiac function. Rituximab is a monoclonal anti-CD20 antibody targeted against human B cells. However, its use in cardiovascular disease is untested and is currently contraindicated. Therefore, we assessed the safety, feasibility, and pharmacodynamic effect of rituximab given to patients with acute ST-elevation MI (STEMI). Methods and results Rituximab in patients with acute ST-elevation myocardial infarction (RITA-MI) was a prospective, open-label, dose-escalation, single-arm, phase 1/2a clinical trial, which tested rituximab administered as a single intravenous dose in patients with STEMI within 48 h of symptom onset. Four escalating doses (200, 500, 700, and 1000 mg) were used. The primary endpoint was safety, whilst secondary endpoints were changes in circulating immune cell subsets including B cells, and cardiac and inflammatory biomarkers. A total of 24 patients were dosed. Rituximab appeared well tolerated. Seven serious adverse events were reported, none of which were assessed as being related to the rituximab infusion. Rituximab caused a mean 96.3% (95% confidence interval 93.8–98.8%) depletion of circulating B cells within 30 min of starting the infusion. Maximal B-cell depletion was seen at Day 6, which was significantly lower than baseline for all doses (P &amp;lt; 0.001). B-cell repopulation at 6 months was dose-dependent, with modulation of returning B-cell subsets. Immunoglobulin (IgG, IgM, and IgA) levels were not affected during the 6 months of follow-up. Conclusions A single infusion of rituximab appears safe when given in the acute STEMI setting and substantially alters circulating B-cell subsets. We provide important new insight into the feasibility and pharmacodynamics of rituximab in acute STEMI, which will inform further clinical translation of this potential therapy. Clinical trial registration NCT03072199 at https://www.clinicaltrials.gov/
Platelet-activating factor receptor-dependent activation of the muscarinic K+ current in bullfrog atrial myocytes.
Authors: JRamos-Franco, C FLo, G EBreitwieser
Journal: Circulation Research (1993)

Platelet-activating factor (PAF), a potent signaling lipid implicated as a mediator of pathological responses, has both negative chronotropic and inotropic effects on the heart, although the mechanism(s) involved is not well defined. Because activation of the muscarinic acetylcholine-activated K+ current (IK(ACh)) also produces a negative chronotropic and inotropic response in myocardium, this study examines whether PAF has effects on IK(ACh) in isolated bullfrog atrial myocytes under whole-cell voltage-clamp conditions. We find that 2 microM PAF increases the rate of GTP-gamma-S-mediated IK(ACh) activation (from 0.30 +/- 0.01 min-1 [n = 20] to 0.73 +/- 0.07 min-1 [n = 12], p < 0.005, in the absence of acetylcholine). This effect of 2 microM PAF was blocked by the PAF antagonist CV-3988 (5 microM, 0.33 +/- 0.14 min-1 [n = 12]), suggesting the presence of specific PAF receptors coupled to IK(ACh) activation. Further support for mediation by specific G protein-coupled PAF receptors derives from the inabilit...
Prediction of defibrillation success from a single defibrillation threshold measurement with sequential pulses and two current pathways in humans.
Authors: D LJones, G JKlein, G MGuiraudon, A DSharma, RYee, M JKallok
Journal: Circulation (1988)

The ultimate aim of defibrillation testing is to predict consistent defibrillation. This study tested the hypothesis that defibrillation success could be predicted from a single measurement of defibrillation threshold. We measured defibrillation threshold by using three patch electrodes and a standard protocol intraoperatively in 49 patients undergoing arrhythmia surgery. Each patient was then assigned to one of five energy subgroups (0.5, 1.0, 1.5, 2.0, or 2.5 times defibrillation threshold) for a single shock (followed by a rescue shock if necessary) for a subsequent ventricular fibrillation episode. A curve relating percent success to energy was then constructed for the group. Defibrillation threshold averaged 4.7 +/- 2.98 J for the group (mean +/- SD). There was a curvilinear relation between the energy of the defibrillation threshold ratio test shock and percent success: 33.3%, 58.3%, 81.8%, 91.7%, and 100% at mean defibrillation threshold ratios of 0.56 +/- 0.14, 1.02 +/- 0.07, 1.53 +/- 0.14, 1.88 +...
Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia.
Authors: TKuzuya, SHoshida, NYamashita, HFuji, HOe, MHori, TKamada, MTada
Journal: Circulation Research (1993)

The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4 +/- 2.0% versus 39.0 +/- 3.7%, respectively [p < 0.01]; and for the delayed occlusion, 18.8 +/- 3.4% versus 35.1 +/- 4.6%, respectively [p < 0.05]); however, when the infarction was induced 3 hours (31.2 +/- 3.7% versus 37.5 +/- 4.2%, respectively) or 12 hours (25.4 +/- 4.8% versus 35.0 +/- 5.3%, respectively) after repetitive ischemia, the...
Low Fixed Dose Hydroxyurea for the Treatment of Adults with Sickle Cell Disease in Nigeria
Authors: Titilola S. Akingbola, Bamidele Tayo, Santosh L. Saraf, Binal N. Shah, Chinedu A Ezekekwu, Omowunmi Sonubi, Lewis L. Hsu, Richard S. Cooper, Victor R. Gordeuk
Journal: Blood (2017)
Reflex chronotropic and inotropic effects of calcium channel-blocking agents in conscious dogs. Diltiazem, verapamil, and nifedipine compared.
Authors: HNakaya, ASchwartz, R WMillard
Journal: Circulation Research (1983)

In chronically instrumented, conscious dogs, rapid injection of equihypotensive doses of three calcium channel-blocking agents, verapamil (250 micrograms/kg), diltiazem (200 micrograms/kg) and nifedipine (50 micrograms/kg), produced disparate chronotropic and inotropic responses. Although they all decreased mean arterial pressure by about 10%, heart rate (93 +/- 4 beats/min) was markedly increased to 175 +/- 12 with nifedipine, to 163 +/- 15 with verapamil, and only slightly increased to 118 +/- 7 with diltiazem. Contractile responses measured before (left ventricular dP/dtmax, 2749 +/- 131 mm Hg/sec) and during left ventricular ejection (endocardial dimension dD/dtmax, 57 +/- 4 mm/sec) were increased by 24% and 14% with nifedipine, decreased by 26% and 22% with verapamil, and were unchanged with diltiazem. These chronotropic and inotropic responses to rapid intravenous administration of the three drugs were increased in a dose-dependent manner. Similar results also were observed after slow infusion of th...