tbuckley/cabot-search huggingface dataset:
Effects of III-IV linker mutations on human heart Na+ channel inactivation gating.
Authors: H AHartmann, A ATiedeman, S FChen, A MBrown, G EKirsch
Journal: Circulation Research (1994)

Na+ channel inactivation, a critical determinant of refractoriness, differs in cardiomyocytes and neurons. In rat brain type IIa (rB2a) Na+ channels, a critical residue in the cytoplasmic linker between domains III and IV regulates fast inactivation such that a Phe-->Gln substitution (F1489Q) inhibits inactivation by at least 85%. Since this residue is conserved in voltage-gated Na+ channels, we tested whether F1485Q, the analogous mutation in human heart (hH1a) Na+ channels, has a similar functional effect. We found that fast inactivation in wild-type (WT) channels expressed in Xenopus oocytes was complete within 15 milliseconds at a test potential of 0 mV, and its time course was biexponential with time constants of 0.4 and 2 milliseconds. But in contrast to rB2a, the FQ mutation inhibited inactivation by < 50% and increased mean single-channel open time by only twofold. Residual fast inactivation was monoexponential, with a time constant similar to that of the slower phase of normal inactivation (2 mil...
Studies of the absorption and removal of propranolol in hypertensive patients during therapy.
Authors: C AChidsey, PMorselli, GBianchetti, AMorganti, GLeonetti, AZanchetti
Journal: Circulation (1975)

The variability of plasma propranolol concentrations has been determined in a large group of patients being treated with the drug. Although the average patient achieved a therapeutic plasma level with 160 mg/day, there was marked interpatient variation. This was found to be primarily the result of differences in effective absorption of the drug, which averaged 46% of the oral dose but ranged from 20 to 80%. Propranolol disappeared from plasma with a half-life of 4.7 hours and its removal appeared to follow dose independent kinetics with no evidence of saturation of hepatic metabolism. The derived pharmacokinetic values of volume of distribution and clearance rate have been used to provide guidelines for initiating propranolol therapy intravenously, and the schedule of 8 mg as a loading dose and 0.02 mg/min as a sustaining dose has been suggested.
Prediction of long-term clinical outcome with final translesional pressure gradient during coronary angioplasty.
Authors: J MHodgson, SReinert, A SMost, D OWilliams
Journal: Circulation (1986)

The final translesional pressure gradient measured during coronary angioplasty correlates with immediate angiographic and clinical results. Whether the pressure gradient is of value in predicting late clinical outcome has not been determined. We therefore obtained complete follow-up information on 159 patients with single-vessel disease who underwent successful coronary angioplasty. Mean follow-up time was 15 +/- 10 months. The occurrence of repeat angioplasty, coronary bypass surgery, recurrent anginal chest pain, or a positive postangioplasty stress test were considered clinical events indicative of late failure. Of the variables age, gender, initial and final translesional pressure gradient, extent of initial and final arterial narrowing, site of dilatation, type of balloon catheter used, number of inflations, and maximal inflation pressure, only the final translesional pressure gradient was predictive of late failure when analyzed by multivariate techniques. Thus, the final translesional pressure grad...
Physical training increases ventricular fibrillation thresholds of isolated rat hearts during normoxia, hypoxia and regional ischemia.
Authors: T DNoakes, LHigginson, L HOpie
Journal: Circulation (1983)

The effect of exercise training on cardiovascular mortality is controversial. The purpose of this study was to determine the effect of a period of treadmill training on the ventricular fibrillation threshold of the isolated rat heart. Trained hearts had higher threshold values during standard, control perfusion conditions, and when exposed to hypoxia, hypoxia plus isoproterenol infusion, or when subjected to coronary artery ligation. Myocardial metabolic studies failed to define the mechanism for the effect of running training. However, in coronary ligated hearts, the content of the arrhythmogenic substance 3',5' cyclic adenosine monophosphate (cyclic AMP) was reduced in the ischemic zone of hearts from trained rats. Cyclic AMP levels were also lower in trained hearts during control perfusions. We conclude that running training increases the resistance of the heart to ventricular fibrillation by mechanisms that are largely unknown, although they may involve cyclic AMP.
Energy levels at systole vs. diastole in normal hamster hearts vs. myopathic hamster hearts.
Authors: RSievers, W WParmley, TJames, JWikman-Coffelt
Journal: Circulation Research (1983)

The following studies were carried out to examine energy metabolites and cardiac performance of the failing heart (hereditary cardiomyopathy) of the Syrian hamster (strain UM-X7.1) perfused either by normal or stress conditions, and to determine whether cyclical changes in energy-related metabolites occurred in the glucose-perfused hearts of both normal and heart failure animals. Hamster hearts from 250-day-old animals with moderate heart failure were removed and perfused either as nonworking hearts (Langendorff method, an afterload pressure of 90 mm Hg and 2.5 mM calcium in the perfusate) or as working hearts with stress conditions [an afterload of 110 mm Hg, high calcium concentrations in the perfusate (3.5 mM), and 10(-8) M isoproterenol]. Mechanical parameters (developed pressure and max dP/dt) and measurements of oxygen consumption indicated that both contractility and oxygen consumption had fallen 50% in myopathic hearts, compared with those of normal hamsters perfused with either of the two conditi...
Effects of nitroprusside and dopamine on pulmonary arterial vasculature in children after cardiac surgery.
Authors: L WStephenson, L HEdmunds, RRaphaely, D FMorrison, W SHoffman, L JRubis
Journal: Circulation (1979)

The hemodynamic effects of nitroprusside and dopamine were studied in 28 children early after intracardiac repair. Children were placed in six groups, five according to their anatomic lesion and one made up of those who had postoperative pulmonary artery hypertension, to evaluate the possible differences in response of the pulmonary arterial vasculature to the drugs. Seven children had repair of an atrial septal defect; six, repair of tetralogy of Fallot; four, repair of ventricular septal defect; five, surgery for pulmonary stenosis; one, closure of a left ventricular to right atrial tunnel; and five, postoperative pulmonary artery hypertension. Dopamine was infused at 8 microgram/kg/min, and nitroprusside at 3 microgram/kg/min. With dopamine, the heart rate increased an average of 10% and the cardiac index 11%; both increases were statistically significant. Changes in systemic and pulmonary vascular resistance, however, were not. With nitroprusside, the heart rate increased an average of 9% and the card...
Blood platelet count and function are related to total and cardiovascular death in apparently healthy men.
Authors: EThaulow, JErikssen, LSandvik, HStormorken, P FCohn
Journal: Circulation (1991)

BACKGROUNDExperimental animal and clinical studies indicate that blood platelets have an important role in atherosclerosis and formation of thrombi. Prospective studies presenting evidence of an association between blood platelet count and cardiovascular mortality have not been performed.METHODS AND RESULTSFrom 1973 to 1975, blood platelets were counted, and their responsiveness to aggregating agents was studied in healthy middle-aged men. The aim was to assess the possible association between these variables and coronary heart disease. At 13.5 years of follow up, a significantly higher coronary heart disease mortality was observed among the 25% of subjects with the highest platelet counts. Platelet aggregation performed in a random subsample (150 of the 487 men), moreover, revealed that the 50% with the most rapid aggregation response after ADP stimulation had significantly increased coronary heart disease mortality compared with the others. These associations could not be explained by differences in age...
Time to Smoke First Morning Cigarette and Lung Cancer in a Case–Control Study
Authors: Fangyi Gu, Sholom Wacholder, Stephanie Kovalchik, Orestis A. Panagiotou, Carolyn Reyes-Guzman, Neal D. Freedman, Sara De Matteis, Dario Consonni, Pier Alberto Bertazzi, Andrew W. Bergen, Maria Teresa Landi, Neil E. Caporaso
Journal: JNCI Journal of the National Cancer Institute (2014)

Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive detection in lung cancer screening. We evaluated whether time to first cigarette after waking (TTFC), a single-item measure of nicotine dependency, could improve stratification of lung cancer risk beyond standard smoking metrics (intensity, duration, and pack-years). In 3249 ever-smokers (n = 1812 case subjects; n = 1437 control subjects) from a population-based case–control study in Italy, we examined the association between TTFC and lung cancer using logistic regression and estimated lung cancer incidence by levels of TTFC, and intensity, duration, and pack-years using absolute risk regression. Significance tests were two-sided. Compared with smokers with TTFC greater than 60 minutes, the lung cancer odds ratios for TTFC of 31 to 60 minutes, 6 to 30 minutes, and 5 or fewer minutes (by increasing dependency) were 2.57 (95% confidence interval [CI] = 2.03 to 3.26), 2.27 (95% CI = 1.79 to 2.88), and 3.50 (95% CI = 2.64 to 4.64), respectively (Ptrend < .0001). The average lung cancer incidence rates for smokers of 1 to 10, 11 to 20, 21 to 30 and more than 30 cigarettes per day were consistently higher among smokers with TTFC of 60 or fewer minutes vs more than 60 minutes (64.1 vs 11.7; 125.6 vs 28.6; 130.1 vs 40.7; and 260.8 vs 108.9 per 100000 person-years, respectively). The slopes of increase in lung cancer rates with smoking duration and pack-years were statistically significantly greater among smokers with higher dependency (Pinteraction < .001). Lung cancer risk increases with shorter TTFC; this simple nicotine dependency measure increases lung cancer risk stratification beyond standard smoking measures. Assessing TTFC may improve lung cancer risk prediction and could be useful in lung cancer screening and smoking cessation programs.
Characterization of Invasive Superficial Colonic Cancer Using High Resolution Endoscopy with Virtual Chromoendoscopy (BLI) with Or Without Magnification Before Endoscopic Resection
Authors: G Lherault, R Hallit, M Barret, E Abouali, A Belle, B Goullet, R Coriat, A Rouquette, B Terris, S Chaussade
Journal: Endoscopy (2021)

Aims Polyps characterization during colonoscopy has been developed with the use of high definition and electronic chromo-endoscopy. Detecting the presence of cancer before endoscopic resection is capital, in order to choose the most suitable management.This detection is difficult, with variable performances between western and japanese endoscopists(10 % of concordance vs 60 %). Not much studies have been done in Europe so far on this topic.The aims of this study were to determine the incidence of cancer according to the endoscopic description of the lesions, and to define which endoscopic classification is mostly associated with a neoplastic risk.
Long-Term Incidence of Advanced Colorectal Neoplasia in Patients With Serrated Polyposis Syndrome
Authors: D Rodríguez-Alcalde, G Castillo-López, J López-Vicente, L Hernández, M Lumbreras-Cabrera, D Moreno-Sánchez
Journal: Endoscopy (2021)

Aims Serrated polyposis syndrome (SPS) implies an increased risk of colorectal cancer (CRC), so intensive endoscopic surveillance has been recommended. Although a low incidence of CRC has been described under follow-up, few studies have evaluated long-term risk of developing advanced colorectal neoplasia in these patients.
Effects of milrinone on coronary hemodynamics and myocardial energetics in patients with congestive heart failure.
Authors: E SMonrad, D SBaim, H SSmith, ALanoue, EBrauwald, WGrossman
Journal: Circulation (1985)

To examine the effect of milrinone on myocardial energetics in patients with congestive heart failure, we measured systemic, pulmonary, and coronary hemodynamics in 18 patients before and after intravenous administration of milrinone (125 +/- 36 micrograms/kg). There was a 45% increase in cardiac index (2.1 +/- 0.5 to 3.0 +/- 0.6 liters/min/m2; p = .0001), a 39% fall in the pulmonary capillary wedge pressure (28 +/- 8 to 17 +/- 8 mm Hg; p = .0001), and a 42% increase in left ventricular external work (3758 +/- 1419 to 5340 +/- 1598 g-m/min; p = .0001). Both the heart rate-blood pressure product (9624 +/- 2272 to 9380 +/- 2428 mm Hg-beats/min; p = NS) and regional left ventricular myocardial oxygen consumption (7.6 +/- 2.9 to 8.1 +/- 3.1 ml O2/min; p = NS) were unchanged after milrinone, resulting in a 45% increase in calculated left ventricular external efficiency (p = .004). Although myocardial oxygen consumption did not change, regional great cardiac venous blood flow increased significantly (73 +/- 32 ...
Proteasome stress in skeletal muscle mounts a long-range protective response that delays retinal and brain aging
Authors: Mamta Rai, Zane Coleman, Michelle Curley, Anjana Nityanandam, Anna Platt, Maricela Robles-Murguia, Jianqin Jiao, David Finkelstein, Yong-Dong Wang, Beisi Xu, Yiping Fan, Fabio Demontis
Journal: Cell Metabolism (2021)
Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. A potential noninvasive marker of healing coronary endothelium.
Authors: K LGould, J PMartucci, D IGoldberg, M JHess, R PEdens, RLatifi, S JDudrick
Journal: Circulation (1994)

BACKGROUNDCholesterol lowering over 1- to 3-year trials is associated with modest regression or no progression of focal coronary artery stenoses compared with progression in controls, a decrease in cardiac events proportionately more than the modest improvement in percent stenosis, and in experimental animals improved endothelial-mediated coronary vasodilation.METHODS AND RESULTSAccordingly, we hypothesized that there would be improvement in size and severity of perfusion abnormalities by rest-dipyridamole positron emission tomography (PET) imaging in a randomized intensive cholesterol-lowering trial with each patient studied after a baseline control period, a 90-day intensive cholesterol-lowering treatment, and a final control period off cholesterol-lowering regimens. Completely automated, objective measures of size and severity of perfusion abnormalities on rest-dipyridamole PET images were made by computer algorithm in 12 patients with coronary artery disease. There were statistically significant decre...
Artificial Intelligence in the Characterization of Colorectal Polyps: A Prospective Study In a Clinical Setting Using Cadeye
Authors: C Correia, E Gravito-Soares, M Gravito-Soares, P Amaro, C Macedo, M Ferreira, M Sant’Anna, J Estorninho, M Bento Miranda, L Barreto, AM Ferreira, F Portela, R Pimentel, R Caetano Oliveira, J Madeira, M Rui Silva, MA Cipriano, P Figueiredo
Journal: Endoscopy (2021)

Aims Current guidelines recommend resection and histopathological analyses of all colorectal polyps. Real-time optical diagnosis can obviate non-neoplastic polyp resection (“diagnose-and-leave-behind”) and histopathological analyses of diminutive polyps (“predict-resect-and-discard”) reducing healthcare and cost burden. We aimed to evaluate the diagnostic accuracy of computer-aided diagnosis using CADEYE (Fujifilm, Germany) in real-time optical characterization of colorectal polyps compared to endoscopic diagnosis with histopathology as the gold-standard.
Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic
Authors: Ermias D. Belay, Joseph Abrams, Matthew E. Oster, Jennifer Giovanni, Timmy Pierce, Lu Meng, Emily Prezzato, Neha Balachandran, John J. Openshaw, Hilary E. Rosen, Moon Kim, Gillian Richardson, Julie Hand, Melissa Tobin-D’Angelo, Siri Wilson, Amanda Hartley, Cassandra Jones, Jonathan Kolsin, Hani Mohamed, Zachary Colles, Teresa Hammett, Pragna Patel, Bryan Stierman, Angela P. Campbell, Shana Godfred-Cato
Journal: JAMA Pediatrics (2021)

Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic.To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date.Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition.Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19.A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died.In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.
Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia.
Authors: R AJohns, J MLinden, M JPeach
Journal: Circulation Research (1989)

The effect of hypoxia on endothelium-dependent and endothelium-independent vasodilation was studied in phenylephrine-precontracted, isolated rings of rabbit first-branch pulmonary artery. Concentration-dependent relaxation responses to the endothelium-dependent dilators methacholine, ATP, and the calcium ionophore (A23187) as well as to the endothelium-independent dilators sodium nitroprusside and isoproterenol were obtained before, during, and after exposure to hypoxia (PO2 = 42 +/- 1 mm Hg) in the presence of indomethacin (2.8 x 10(-5) M). This moderate degree of hypoxia inhibited (p less than 0.05) endothelium-dependent but not endothelium-independent relaxation responses without producing irreversible vascular damage. In parallel experiments, cyclic GMP accumulation in pulmonary vascular rings in response to maximal doses of the above vasodilators was measured in the presence and absence of hypoxia. Cyclic GMP accumulation in response to endothelium-dependent dilators (methacholine, ATP, and A23187) w...
Cellular mechanisms of captopril-induced matrix remodeling in Syrian hamster cardiomyopathy.
Authors: GDavison, C SHall, J GMiller, MScott, S AWickline
Journal: Circulation (1994)

BACKGROUNDAlthough angiotensin-converting enzyme (ACE) inhibitors have become a mainstay of treatment for chronic congestive heart failure (CHF), it is not known whether the cardiac remodeling effects are a secondary phenomenon, resulting from ACE inhibitors' hemodynamic actions of afterload reduction, or occur through an independent mechanism.METHODS AND RESULTSWe used ultrasonic tissue characterization to define potentially salutary effects of treatment with ACE inhibitors on the material properties of the heart and its potential influence on cardiac remodeling at the cellular level. Ten 1-month-old, cardiomyopathic (CM) Syrian hamsters and 6 normal (NL) hamsters were treated with captopril (2 g/L water ad libitum), and 10 CM hamsters and 10 NL hamsters were maintained untreated for 3 months. Hearts were excised, and backscattered radiofrequency data were acquired from 1200 independent sites from each specimen with a high-resolution 50-MHz acoustic microscope for calculation of integrated backscatter (I...
Valsalva termination of ventricular tachycardia.
Authors: M BWaxman, R WWald, J PFinley, J FBonet, EDownar, A DSharma
Journal: Circulation (1980)

Nine patients with recurrent ventricular tachycardia (VT) that could be repeatedly terminated by a Valsalva maneuver are described. In two, the tachycardia would cease for only a few seconds and then resume, whereas in seven, the tachycardia could be permanently and reproducibly terminated with a Valsalva maneuver. In all patients the tachycardia ended during the strain phase of the Valsalva maneuver, when blood pressure and radiographic measurement indicated that cardiac dimensions had been reduced dramatically. The speed with which the Valsalva maneuver terminated VT incresed in direct proportion to the strain pressure. Maneuvers such as standing or nitroglycerin, which independently reduce cardiac dimensions, enhanced the potency of the Valsalva maneuvers. Pretreatment with atropine or propranolol in four patients did not alter the response of VT to the Valsalva maneuver. Thus, it appears that a strong Valsalva maneuver can terminate some forms of VT, most likely related to an abrupt reduction in cardi...
Robin Hood in SEM? What can we take from elite sport to give back to wider public health?
Authors: Jane S Thornton, Jon Patricios, Joanne Kemp, Lars Engebretsen, Jonathan Drezner
Journal: British Journal of Sports Medicine (2021)

The current pandemic has made abundantly clear that when we are forced to reduce life to the essentials, physical activity becomes more important than ever. Even before COVID-19 frustrated our daily routines, the concept of physical activity for health already had begun to enjoy a surge in popularity.

When the WHO released its 2020 Guidelines on Physical Activity and Sedentary Behaviour this past November,1 2 the message was simple—every move counts. That is, moving for even a few minutes a day is better than nothing and has proven health benefits. At the other end of the exercise spectrum, there is an increasing interest in how regular intense exercise, similar to that undertaken by elite sportspersons, may benefit health and longevity.3

Is there a role for elite sport to inform public health interventions? Influential international organizations think so, including the WHO, who renewed their partnership with a new work plan under a Memorandum of Understanding with the International Olympic Committee (IOC) last May.4 As IOC President Thomas Bach reminded us, ‘sport can save lives’ and is about more than competition.

While Bach’s words may resonate with our readership, they also challenge the established notion that sport—elite sport in particular—is somehow set …