tbuckley/cabot-search huggingface dataset:
Kinetics of restitution of left ventricular relaxation.
Authors: S DPrabhu, G LFreeman
Journal: Circulation Research (1992)

Although the kinetics of cardiac systolic force restitution have been well described, the restitution kinetics of left ventricular relaxation have not been examined. To define relaxation restitution behavior, we studied seven dogs chronically instrumented with left ventricular high-fidelity micromanometers and piezoelectric dimension crystals. After a priming period at a basic cycle length of 375 msec, test extrastimuli were introduced after a range of extrasystolic intervals (ESIs). Relaxation behavior of control and extrasystolic beats was characterized by the time constant of isovolumic relaxation, tau. Relaxation restitution can be described by two concatenated monoexponential curves, an early phase described by a rapid time constant and a late phase described by a slower time constant (TC1, 36.21 +/- 7.90 msec; TC2, 75.94 +/- 10.65 msec; p less than 0.05). The first phase of relaxation restitution parallels systolic force restitution over the same range and displays faster recovery (TCs, 58.93 +/- 10...
Simulation-Based Estimation of SARS-CoV-2 Infections Associated With School Closures and Community-Based Nonpharmaceutical Interventions in Ontario, Canada
Authors: David Naimark, Sharmistha Mishra, Kali Barrett, Yasin A. Khan, Stephen Mac, Raphael Ximenes, Beate Sander
Journal: JAMA Network Open (2021)

Resurgent COVID-19 cases have resulted in the reinstitution of nonpharmaceutical interventions, including school closures, which can have adverse effects on families. Understanding the associations of school closures with the number of incident and cumulative COVID-19 cases is critical for decision-making.To estimate the association of schools being open or closed with the number of COVID-19 cases compared with community-based nonpharmaceutical interventions.This decision analytical modelling study developed an agent-based transmission model using a synthetic population of 1 000 000 individuals based on the characteristics of the population of Ontario, Canada. Members of the synthetic population were clustered into households, neighborhoods, or rural districts, cities or rural regions, day care facilities, classrooms (ie, primary, elementary, or high school), colleges or universities, and workplaces. Data were analyzed between May 5, 2020, and October 20, 2020.School reopening on September 15, 2020, vs schools remaining closed under different scenarios for nonpharmaceutical interventions.Incident and cumulative COVID-19 cases between September 1, 2020, and October 31, 2020.Among 1 000 000 simulated individuals, the percentage of infections among students and teachers acquired within schools was less than 5% across modeled scenarios. Incident COVID-19 case numbers on October 31, 2020, were 4414 (95% credible interval [CrI], 3491-5382) cases in the scenario with schools remaining closed and 4740 (95% CrI, 3863-5691) cases in the scenario for schools reopening, with no other community-based nonpharmaceutical intervention. In scenarios with community-based nonpharmaceutical interventions implemented, the incident case numbers on October 31 were 714 (95% CrI, 568-908) cases for schools remaining closed and 780 (95% CrI, 580-993) cases for schools reopening. When scenarios applied the case numbers observed in early October in Ontario, the cumulative case numbers were 777 (95% CrI, 621-993) cases for schools remaining closed and 803 (95% CrI, 617-990) cases for schools reopening. In scenarios with implementation of community-based interventions vs no community-based interventions, there was a mean difference of 39 355 cumulative COVID-19 cases by October 31, 2020, while keeping schools closed vs reopening them yielded a mean difference of 2040 cases.This decision analytical modeling study of a synthetic population of individuals in Ontario, Canada, found that most COVID-19 cases in schools were due to acquisition in the community rather than transmission within schools and that the changes in COVID-19 case numbers associated with school reopenings were relatively small compared with the changes associated with community-based nonpharmaceutical interventions.
Biden outlines plans to reduce US gun violence
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

“Gun violence in this country is an epidemic, and it’s an international embarrassment,” President Joe Biden said at a White House meeting on 8 April at which he described how he plans to tackle the problem. Reducing gun violence is not a partisan matter, he said, but one that most people and most gun owners support.1

“Every day in this country 316 people are shot,” Biden said. He recalled the killing of five people the day before in South Carolina; of 10 people in Boulder, Colorado, on 22 March; and of eight mostly Asian Americans shot at spas in Atlanta, Georgia, on 18 March. He introduced people who had lost family or friends in the Sandy Hook Elementary School shooting in Connecticut in 2012, the Marjorie Stoneman Douglas High School shooting in Florida in 2018, and the Pulse nightclub shooting in Florida in 2016. Also present was former congresswoman Gabby Giffords, who was shot in the head in …
Myocardial cell hypertrophy after myocardial infarction with reperfusion in dogs.
Authors: MKambayashi, TMiura, B HOh, KMurata, H ARockman, GParra, JRoss
Journal: Circulation (1992)

BACKGROUNDThe potential role of myocardial cell hypertrophy in the ischemic zone in the mechanism of late recovery of regional contractile function after myocardial infarction followed by reperfusion has not been examined.METHODS AND RESULTSEight chronically instrumented, conscious dogs were subjected to 90-120 minutes of circumflex coronary artery occlusion followed by reperfusion. The thickness and function of the anterior (AT) and posterior (PT) walls was measured by ultrasonic gauges at control, during occlusion, and after reperfusion. After 3 weeks, cross-sectional areas of surviving cells were determined from subepicardial (epi), midwall (mid), and subendocardial (endo) regions in six dogs and compared with those from six animals without infarction, including three sham-operated control dogs. PT systolic wall thickening showed dyskinesia during occlusion but recovered after reperfusion to 48% of control at 1 week and 67% at 3 weeks. End-diastolic thickness of the PT wall increased markedly after rep...
Cyclic elevation of intrathoracic pressure can close the mitral valve during cardiac arrest in dogs.
Authors: H RHalperin, J LWeiss, A DGuerci, NChandra, J ETsitlik, RBrower, CBeattie, EWurmb, JCadden, M LWeisfeldt
Journal: Circulation (1988)

Mitral valve closure during cardiopulmonary resuscitation may result from direct cardiac compression. An alternative hypothesis is that with a rise in intrathoracic pressure, mitral valve closure can occur but may be influenced by whether the lungs are inflated or deflated. To test this hypothesis, we placed a large-bore cannula into the thoraces of 11 dogs. Intrathoracic pressure was changed by inflating and deflating the thorax through the cannula while the airway was open, as well as by inflating and deflating the lungs with the thoracic cannula clamped. Mitral valve motion was observed with two-dimensional echocardiography from the right chest wall or esophagus in eight of the dogs. With a rise in intrathoracic pressure from thoracic inflation, all eight dogs showed closure of the mitral valve, while with thoracic deflation, all showed mitral valve opening. With lung inflation and deflation alone, however, the mitral valve remained open throughout the cycle. In seven dogs, with thoracic inflation, the...
Abstract 16427: Efficacy and Safety of Inclisiran According to Age: A Pooled Analysis of Phase III Studies (ORION 9, 10 and 11)
Authors: R Scott S Wright, Kausik K Ray, Frederick J Raal, David Kallend, Mark Jaros, Wolfgang Koenig, Lawrence A Leiter, Ulf E Landmesser, Gregory G Schwartz, Peter Wijngaard, John J Kastelein
Journal: Circulation (2020)

Introduction: The risk of major atherosclerotic CV events increases with age, as do comorbidities, polypharmacy, and greater vulnerability to adverse drug reactions/events, posing challenges in the treatment of dyslipidemia. Three Phase III placebo-controlled trials evaluated the efficacy and safety of inclisiran according to age. Objective: To assess the efficacy and safety of inclisiran in patients across age categories. Methods: Patients were categorized according to age: &lt;65 years (not old), ≥65 and &lt;75 years (old), or ≥75 years (very old). The co-primary endpoints were percentage change in LDL-C from baseline to Day 510 and time-adjusted percentage change from baseline after Day 90 up to Day 540. Efficacy and safety parameters were assessed over 18 months. Results: Of a total 3660 patients, 1737 [47.5%] were not old, 1431 [39.1%] were old, and 492 [13.4%] were very old. At baseline, the prevalence of comorbidities increased with age (not old, old, very old): stage 3 CKD (8.4%, 19.9%, 31.2%), hypertension (72.9%, 85.2%, 88.1%) and diabetes mellitus (32.2%, 40.0%, 38.0%), respectively. The placebo-corrected percentage change in LDL-C with inclisiran was similar across all ages: from baseline to Day 510 [–51.3% (not old), –49.9% (old), –51.0% (very old); P &lt;0.0001 for all] and time-adjusted from baseline to Day 90 up to Day 540 [–49.6% (not old), –51.5% (old), –50.8% (very old); P &lt;0.0001 for all]. Overall AE and SAE rates increased with age and were similar between both treatment arms in all groups, except for injection-site reactions that were higher with inclisiran vs placebo across all ages, and were more frequent in not old patients. CK levels &gt;5x ULN were more frequently elevated in the not old category (Table). Conclusion: Inclisiran lowered LDL-C similarly across all ages with an acceptable safety profile. Inclisiran added to maximally tolerated statin therapy could be a safe option for older patients with ASCVD who need more intensive lipid-lowering treatment.
Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function.
Authors: YSaito, KNakao, KNishimura, ASugawara, KOkumura, KObata, RSonoda, TBan, HYasue, HImura
Journal: Circulation (1987)

Synthetic alpha-human atrial natriuretic polypeptide was infused in patients with congestive heart failure (CHF) (New York Heart Association class III or IV) and in those without CHF. The infusion of atrial natriuretic polypeptide (ANP) at a rate of 0.1 microgram/kg/min significantly decreased pulmonary capillary wedge pressure and increased stroke volume index in all of the patients with CHF, whereas it decreased pulmonary capillary wedge pressure but caused no significant change in stroke volume index in the patients without CHF. Concomitant significant reductions in total systemic resistance were observed in both groups of patients. The ANP infusion significantly increased the urine volume, the excretion of sodium, and endogenous creatinine clearance in the patients without CHF. In the patients with CHF, it also showed a tendency to increase all these variables, but the urine volume did not correlate with the reduction in pulmonary capillary wedge pressure. The ANP infusion also decreased plasma aldost...
Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals.
Authors: D GHarrison, W MChilian, M LMarcus
Journal: Circulation Research (1986)

To determine if mature coronary collateral vascular smooth muscle contains functioning alpha-adrenergic receptors, we studied 13 dogs, 6-10 months after circumflex ameroid occlusion. Regional myocardial blood flow was measured with radioactive microspheres in a blood-perfused heart preparation at constant aortic pressure (80 mm Hg). Normal zone resistance was calculated as aortic pressure divided by normal zone flow, and transcollateral resistance was calculated as aortic pressure minus circumflex pressure distal to the ameroid constrictor divided by coronary collateral flow. Flow and resistance were measured during adenosine vasodilation before and during graded doses of a constant infusion of the alpha-adrenergic agonist methoxamine (n = 6) or the alpha 2-adrenergic agonist clonidine (n = 7). In the hearts that received methoxamine, normal zone resistance increased from a control of 0.29 +/- 0.06 to 0.39 +/- 0.06 mm Hg X min/ml per 100 g (resistance units) during infusion of 10(-5)M methoxamine (p less ...
Beat-to-beat changes in atrioventricular nodal excitability and its modulation by concealed conduction during functional 2:1 block in man.
Authors: R TSteinman, M HLehmann
Journal: Circulation (1987)

An atrial pacing model of functional 2:1 block was used in 10 patients to investigate for the first time the electrophysiologic properties of the human atrioventricular node during intermittent conduction. By varying the terminal portion of the 2:1 atrial train and using the extrastimulus technique, we characterized atrioventricular nodal (AVN) conduction and refractoriness after five different methods of AVN activation: a conducted beat (method I), a conducted beat with omission of the prior blocked beat (method II), a blocked beat (method III), a blocked beat converted to one that conducts by omission of the prior conducted beat (method IV), and finally, 1:1 conduction at twice the cycle length of the 2:1 train (control method V). Observed AVN conduction times obeyed the following relationship: method I greater than method II greater than method V, indicating a cumulative effect of concealed penetration by the blocked beats. During 2:1 block, the AVN effective refractory period (ERP) alternated with a...
Collateral circulation after renal artery occlusion in the rat.
Authors: M BSiegel, N GLevinsky
Journal: Circulation Research (1977)

We used angiographic and microsphere methods to evaluate the anatomic and functional features of renal collateral circulation in the rat. By the microsphere method, renal parenchymal blood flow was less than 1% of control 1 hour after occlusion of the main renal artery; 2.8% of control 1-2 weeks after arterial occlusion; and 1% of control 4-9 weeks after occlusion. Radiographic observations during chronic occlusion revealed numerous collateral vessels to the kidney. These vessels readily filled with angiographic contrast medium but the intrarenal circulation did not visualize. We conclude that collateral circulation to renal parenchyma is negligible after acute or chronic occlusion of the main renal artery in the rat. The rich anatomic plexus of collateral vessels has no functional significance and is unable to preserve viability of the parenchyma.
Specific antibody to hog renal renin and its application to the direct radioimmunoassay of renin in various organs.
Authors: SHirose, R JWorkman, TInagami
Journal: Circulation Research (1979)

We produced anti-hog renin antibodies using as antigens pure hog renal renin that either had been insolubilized or conjugated to tetanus toxoid. High titer antibodies were obtained, which demonstrated different cross-reactivity with renins from other species. A direct radioimmunoassay for renin was developed using antibody, monoiodinated 125I-hog renin, and various methods for separating free and antibody-bound trace. This assay was capable of detecting 40 pg of hog renin and was applied to the determination of renin in hog blood and other organs. Based on the direct measurement of renin by this radioimmunoassay, the renin-like activity (i.e., the ability to generate angiotensin I from renin substrate preparations) of the pituitary gland was found to be due mostly to true renin, whereas the renin activity of other hog tissues, including the adrenal gland, liver, lung, spleen, and submaxillary gland, was not identified as renin and may have been due to cathepsins.
The Addition of C‐Reactive Protein and von Willebrand Factor to Model for End‐Stage Liver Disease‐Sodium Improves Prediction of Waitlist Mortality
Authors: Patrick Starlinger, Joseph C. Ahn, Aidan Mullan, Georg P. Gyoeri, David Pereyra, Roberto Alva‐Ruiz, Hubert Hackl, Thomas Reiberger, Michael Trauner, Jonas Santol, Benedikt Simbrunner, Mattias Mandorfer, Gabriela Berlakovich, Patrick S. Kamath, Julie Heimbach
Journal: Hepatology (2021)

Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of complications of portal hypertension (PH) or infections. von Willebrand factor antigen (vWF-Ag) and C-reactive protein (CRP) are simple, broadly available markers of these processes.We determined whether addition of vWF-Ag and CRP to the Model for End-Stage Liver Disease-Sodium (MELD-Na) score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in two independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD-Na, and mortality on the waiting list were recorded. Prediction of 3-month waiting list mortality was assessed by receiver operating characteristics curve (ROC-AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF-Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (n = 269) vWF-Ag and CRP both improved the predictive value of MELD-Na for 3-month waitlist mortality and showed the highest predictive value when combined (AUC: MELD-Na, 0.764; MELD-Na + CRP, 0.790; MELD-Na + vWF, 0.803; MELD-Na + CRP + vWF-Ag, 0.824). Results were confirmed in an independent validation cohort (n = 129; AUC: MELD-Na, 0.677; MELD-Na + CRP + vWF-Ag, 0.882). vWF-Ag was independently associated with PH and inflammatory biomarkers, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation.The addition of vWF-Ag and CRP-reflecting central pathophysiological mechanisms of PH, bacterial translocation, and inflammation, that are all drivers of mortality on the waiting list for LT-to the MELD-Na score improves prediction of waitlist mortality. Using the vWFAg-CRP-MELD-Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.
What Is the Optimal Model to Estimate the Benefits of Chemotherapy in Patients With Hormone Receptor–Positive, HER2-Negative, Node-Negative Breast Cancer?
Authors: Kenju Ando, Akihiko Shimomura, Kenichi Yoshimura, Yukino Kawamura, Chikako Shimizu
Journal: Journal of Clinical Oncology (2021)

Sparano et al 1 reported the development of RSClin, a new prognostic tool to estimate the 10-year distant recurrence risk with endocrine therapy alone and the absolute benefit of chemotherapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and nodenegative breast cancer.RSClin integrates the 21-gene recurrence score (RS) assay and clinical-pathologic features using a patient-specific meta-analysis and provides more information on chemotherapy benefits than the previous tool, the RS-Pathology-Clinical tool.However, we would like to highlight several concerns that are uncertain in RSClin to improve prognostic tools.
Effect of ST segment measurement point on performance of standard and heart rate-adjusted ST segment criteria for the identification of coronary artery disease.
Authors: P MOkin, GBergman, PKligfield
Journal: Circulation (1991)

BACKGROUNDRecent reports critical of the performance of heart rate-adjusted indexes of ST depression during exercise electrocardiography have used J-point rather than ST segment measurements. However, no standard exists for the optimal time after the J-point at which to measure ST segment deviation.METHODS AND RESULTSTo assess the effect of ST segment measurement position on performance of standard exercise electrocardiographic criteria, the delta ST segment/heart rate (delta ST/HR) index, and the ST segment/heart rate (ST/HR) slope for the detection of coronary artery disease, the exercise electrocardiograms of 50 clinically normal subjects and 80 patients with known or likely coronary disease were analyzed using ST depression measured at both the J-point and at 60 msec after the J-point (J + 60). A positive exercise electrocardiogram by standard criteria, defined as 0.1 mV or more of additional horizontal or downsloping ST depression at end exercise, had a specificity of 96% when ST depression was measu...
Cardiac lysosomal derangements in mouse heart after long-term exposure to nonmetabolizable sugars.
Authors: KWildenthal, J HDees, L MBuja
Journal: Circulation Research (1977)

Hearts of late fetal mice were maintained in organ culture in the presence of 30-100 mM sucrose or mannitol. Activities of several lysosomal enzymes (cathepsin D, beta-acetylglucosaminidase, acid phosphatase) were increased by up to 30% after 18-24 hours and by up to 50% after 48-72 hours, as compared to enzyme activities in litter-matched hearts maintained in control medium or medium supplemented with equimolar urea. Simultaneously, the ratio of nonsedimentable to sedimentable enzyme activity was significantly increased, suggesting increased lysosomal fragility. Light and electron microsopic examination of the hearts revealed marked vacuolization in myocytic, interstitial, and endothelial cells. The vacuoles were limited by single membranes, often contained particulate or amorphous cellular debris resulting from autophagocytosis, and in cytochemical preparations frequently exhibited an electron-dense reaction product indicative of acid phosphatase activity. Hydrocortisone failed to prevent the marked lys...
Correlation between refractory periods and activation-recovery intervals from electrograms: effects of rate and adrenergic interventions.
Authors: C KMillar, F AKralios, R LLux
Journal: Circulation (1985)

Unipolar electrograms from ventricular epicardium in dogs were analyzed for the timing of local excitation and repolarization with computer assistance. The most rapid decrease in voltage in the QRS (dV/dt min) was used to determine local excitation time, and the maximum rate of voltage increase (dV/dt max) near the peak of the T wave was used to time local repolarization. The difference between dV/dt min and dV/dt max, the activation-recovery interval, is theoretically related to the net effect of the durations of the action potentials at that site. Paired data for refractory periods and activation-recovery intervals obtained from the same electrodes during fixed activation orders were obtained before and during repolarization changes induced by changes in cycle length, infusion of norepinephrine, and cardiac sympathetic nerve stimulation. Correlation coefficients were close to 1.00 and standard errors were 2.0 to 4.3 msec for changes at individual sites. Pooling of data from multiple sites increased stan...
Community-Acquired Pneumonia
Authors: John G. Bartlett, Linda M. Mundy
Journal: New England Journal of Medicine (1995)

Pneumonia has been recognized as a common and potentially lethal condition for nearly two centuries. Comprehensive studies of the disease in the pre-antibiotic era showed mortality rates of about 1 per 1000 per year; over 80 percent of the cases were due to Streptococcus pneumoniae, and mortality rates were generally reported at 20 to 40 percent.1,2 Community-acquired pneumonia (as distinguished from that acquired nosocomially or in a nursing home) continues to be a common and serious illness. Current estimates for the United States are 4 million cases annually, an attack rate of 12 per 1000 adults per year, about . . .