tbuckley/cabot-search huggingface dataset:
Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia.
Authors: G APantely, S AMalone, W SRhen, C GAnselone, AArai, JBristow, J DBristow
Journal: Circulation Research (1990)

The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 a...
De subitaneis mortibus. XXVI. Fatal electrical instabiltiy of the heart associated with benign congenital polycystic tumor of the atrioventricular node.
Authors: T NJames, IGalakhov
Journal: Circulation (1977)

Benign congenital polycystic tumors of the atrioventricular (A-V) node are an unusual but not very rare cause of heart block. Two such cases are presented and discussed in conjunction with the reported experience of other. The tumor is always within and only very near the A-V node, seldom involves more than the proximal end of the His bundle, and has not been reported to occur in the sinus node. Although sudden death has been reported in conjunction with these tumors, a surprising number of other patients have lived to old age and died of causes unrelated to the A-V nodal tumor. As a corollary it is important to consider a diagnosis of A-V nodal tumor in any patient of any age who presents with otherwise unexplained heart block or syncope. From accumulated experience it appears that such patients do not tolerate electronic pacing safely and some possible explanations for this are discussed. Escape rhythm in all reported cases has been characterized by QRS complexes which are narrow and a ventricular rate ...
Functional characterization of CD4+ T cell receptors crossreactive for SARS-CoV-2 and endemic coronaviruses
Authors: Arbor G. Dykema, Boyang Zhang, Bezawit A. Woldemeskel, Caroline C. Garliss, Laurene S. Cheung, Dilshad Choudhury, Jiajia Zhang, Luis Aparicio, Sadhana Bom, Rufiaat Rashid, Justina X. Caushi, Emily Han-Chung Hsiue, Katherine Cascino, Elizabeth A. Thompson, Abena K. Kwaa, Dipika Singh, Sampriti Thapa, Alvaro A. Ordonez, Andrew Pekosz, Franco R. D’Alessio, Jonathan D. Powell, Srinivasan Yegnasubramanian, Shibin Zhou, Drew M. Pardoll, Hongkai Ji, Andrea L. Cox, Joel N. Blankson, Kellie N. Smith
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. Recent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due to crossrecognition by T cells specific for common cold coronaviruses (CCCs). True T cell crossreactivity, defined as the recognition by a single TCR of more than one distinct peptide-MHC ligand, has never been shown in the context of SARS-CoV-2.
143P Physician perceptions of barriers to epidermal growth factor receptor mutation (EGFRm) testing in advanced (stage IIIb/IIIc/IV) non-small cell lung cancer (NSCLC)
Authors: J. Subramanian, Y-L. Choi, T-Y. Chou, J. Gregg, R. Hui, N. Leighl, A. Marchetti, N. Navani, T. Bailey, M. Silvey, R. Makin, D.A. Kahangire, M. Chau, A. Taylor, F. Griesinger
Journal: Journal of Thoracic Oncology (2021)
Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study.
Authors: HTsuji, F JVenditti, E SManders, J CEvans, M GLarson, C LFeldman, DLevy
Journal: Circulation (1994)

BACKGROUNDThe prognostic implications of alterations in heart rate variability have not been studied in a large community-based population.METHODS AND RESULTSThe first 2 hours of ambulatory ECG recordings obtained on original subjects of the Framingham Heart Study attending the 18th biennial examination were reprocessed to assess heart rate variability. Subjects with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1 hour of recording time, processed time < 50% of recorded time, and those taking antiarrhythmic medications were excluded. The associations between heart rate variability measures and all-cause mortality during 4 years of follow-up were assessed. There were 736 eligible subjects with a mean age (+/- SD) of 72 +/- 6 years. The following five frequency domain measures and three time domain measures were obtained: very-low-frequency power (0.01 to 0.04 Hz), low-frequency power (0.04 to 0.15 Hz), high-frequency power (0.15 to 0.40 Hz), total power (0.01 to 0.40 Hz),...
Intracellular sodium and the positive inotropic effect of veratridine and cardiac glycoside in sheep Purkinje fibers.
Authors: D MBrill, J AWasserstrom
Journal: Circulation Research (1986)

Veratridine is a sodium channel toxin that exerts a powerful positive inotropic effect and prolongs the action potential duration in the heart. To determine the basis of the inotropic action of veratridine and to examine the effects of dissimilar methods of raising intracellular sodium activity on contractility, we measured twitch tension and intracellular sodium activity using sodium-sensitive microelectrodes in stimulated sheep Purkinje fibers exposed to veratridine and in voltage-clamped fibers exposed to veratridine and cardiac glycoside. In stimulated fibers, veratridine (0.1-1 microM) produced coincident increases in intracellular sodium activity, action potential duration, and tension. In voltage-clamped fibers, veratridine (1-2 microM) and acetylstrophanthidin (0.1 microM) raised intracellular sodium activity and tension to a comparable degree. Tetrodotoxin (10 microM) abolished the mechanical, electrophysiological, and ionic changes produced by veratridine. The relationship between intracellular ...
An analysis of the cost effectiveness of the implantable defibrillator.
Authors: MKuppermann, B RLuce, BMcGovern, P JPodrid, J TBigger, J NRuskin
Journal: Circulation (1990)

The automatic implantable defibrillator has been shown to decrease the mortality of patients who have survived cardiac arrest due to ventricular tachycardia or fibrillation and are at high risk for recurrence. We performed a cost-effectiveness analysis of this seemingly expensive new technology with data obtained from the 1984 Medicare data base, the medical literature, Medicare carriers, individual pharmacies and hospitals, and expert opinion. Analyzing combinations of principal and secondary discharge diagnoses across 18 diagnosis-related groups, we estimated the cost of hospitalization for a comparison group of patients. Hospitalization costs for the defibrillator group were obtained from reported empirical data. Rehospitalization rates and other health-care use estimates were solicited from an expert panel of physicians, and mortality rates for both groups were obtained from the literature. Using a decision-analytic model, we estimated that the net cost effectiveness of the defibrillator, when used in...
Structural basis of end-stage failure in ischemic cardiomyopathy in humans.
Authors: C ABeltrami, NFinato, MRocco, G AFeruglio, CPuricelli, ECigola, FQuaini, E HSonnenblick, GOlivetti, PAnversa
Journal: Circulation (1994)

BACKGROUNDIschemic cardiomyopathy is characterized by myocyte loss, reactive cellular hypertrophy, and ventricular scarring. However, the relative contribution of these tissue and cellular processes to late failure remains to be determined.METHODS AND RESULTSTen hearts were obtained from individuals undergoing cardiac transplantation as a result of chronic coronary artery disease in its terminal stage. An identical number of control hearts were collected at autopsy from patients who died from causes other than cardiovascular disease, and morphometric methodologies were applied to the analysis of the left and right ventricular myocardium. Left ventricular hypertrophy evaluated as a change in organ weight, aggregate myocyte mass, and myocyte cell volume per nucleus showed increases of 85%, 47%, and 103%, respectively. Corresponding increases in the right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28% and 30% in the left and right ventricles, was responsible for the difference in th...
Translational activity is uncoupled from nucleic acid content in bacterial cells of the human gut microbiota
Authors: Mariia Taguer, B. Jesse Shapiro, Corinne F. Maurice
Journal: Gut Microbes (2021)

Changes in bacterial diversity in the human gut have been associated with many conditions, despite not always reflecting changes in bacterial activity. Methods linking bacterial identity to function are needed for improved understanding of how bacterial communities adapt and respond to their environment, including the gut. Here, we optimized bioorthogonal non-canonical amino acid tagging (BONCAT) for the gut microbiota and combined it with fluorescently activated cell sorting and sequencing (FACS-Seq) to identify the translationally active members of the community. We then used this novel technique to compare with other bulk community measurements of activity and viability: relative nucleic acid content and membrane damage. The translationally active bacteria represent about half of the gut microbiota, and are not distinct from the whole community. The high nucleic acid content bacteria also represent half of the gut microbiota, but are distinct from the whole community and correlate with the damaged subset. Perturbing the community with xenobiotics previously shown to alter bacterial activity but not diversity resulted in stronger changes in the distinct physiological fractions than in the whole community. BONCAT is a suitable method to probe the translationally active members of the gut microbiota, and combined with FACS-Seq, allows for their identification. The high nucleic acid content bacteria are not necessarily the protein-producing bacteria in the community; thus, further work is needed to understand the relationship between nucleic acid content and bacterial metabolism in the human gut. Considering physiologically distinct subsets of the gut microbiota may be more informative than whole-community profiling.
Changes in phosphoinositide turnover in isolated guinea pig hearts stimulated with isoproterenol.
Authors: R JSolaro, E GKranias
Journal: Circulation Research (1989)

The incorporation of 32Pi into phospholamban, troponin I, phosphatidylinositols, and inositol trisphosphates was studied in Langendorff-perfused guinea pig hearts stimulated with isoproterenol. Hearts were perfused with Krebs-Henseleit buffer containing [32P]Pk and freeze-clamped at different times during the positive inotropic response. Exposure of the hearts to 0.1 microM isoproterenol for up to 1 minute was associated with significant (up to threefold) increases in phospholamban and troponin I phosphorylation, but there was no significant increase in 32P incorporation into phospholipids. However, longer exposure (2 minutes or more) to isoproterenol was associated with increases in the degree of 32P labeling of phosphatidylinositols and phosphatidic acid. Examination of 32P labeling of inositol trisphosphates in the same hearts revealed that the radioactivity associated with these compounds decreased with time. The decreases were significant at times of exposure of 2 minutes or longer to beta-adrenergic...
Distribution of beta-adrenergic receptors in failing human myocardium. Implications for mechanisms of down-regulation.
Authors: S SMurphree, J ESaffitz
Journal: Circulation (1989)

The density of beta-adrenergic receptors is reduced in crude membranes prepared from failing human myocardium. We used quantitative autoradiography of radioligand binding sites in intact tissue slices to determine whether the total tissue content of receptors is reduced and to characterize the transmural distribution of receptors in cardiac myocytes and the coronary vasculature in hearts obtained from nine cardiac transplant patients with severe congestive failure. Binding of [125Iodo]cyanopindolol to transmural slices of human myocardium was rapid, saturable, stereoselective, and displaceable by agonists and antagonists with an appropriate rank order of potency. Binding isotherms in four normal and nine failing ventricles showed a significant reduction in the total tissue content of beta-receptors in failing myocardium (38.3 +/- 2.0 fmol/mg protein) compared with normal tissue (52.4 +/- 1.7 fmol/mg protein, p = 0.038). In the normal ventricles, the greatest receptor density was observed autoradiographica...
31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure.
Authors: SNeubauer, TKrahe, RSchindler, MHorn, HHillenbrand, CEntzeroth, HMader, E PKromer, G ARiegger, KLackner
Journal: Circulation (1992)

BACKGROUNDThe purpose of this work was to further define the value of cardiac 31P magnetic resonance (MR) spectroscopy for patients with coronary artery disease and dilated cardiomyopathy.METHODS AND RESULTSBlood-corrected and T1-corrected 31P MR spectra of anteroseptal myocardium were obtained at rest using image-selected in vivo spectroscopy localization, a selected volume of 85 +/- 12 cm3, and a field strength of 1.5 T. Nineteen volunteers had a creatine phosphate (CP)/ATP ratio of 1.95 +/- 0.45 (mean +/- SD) and a PDE/ATP ratio of 1.06 +/- 0.53; in four patients with left anterior descending coronary artery (LAD) stenosis, six patients with chronic anterior wall infarction, and four patients with chronic posterior wall infarction, CP/ATP and phosphodiester (PDE)/ATP ratios did not differ from those in volunteers. Twenty-five measurements of 19 patients with dilated cardiomyopathy yielded a CP/ATP of 1.78 +/- 0.51 and a PDE/ATP of 0.98 +/- 0.56 (p = NS versus volunteers). When these patients were group...
An update on oral drug delivery via intestinal lymphatic transport
Authors: Zichen Zhang, Yi Lu, Jianping Qi, Wei Wu
Journal: Acta Pharmaceutica Sinica B (2021)

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.
Synergy of immune checkpoint targeting and radiation when used sequentially for the treatment of melanoma brain metastases.
Authors: Christine Saraceni, Hope Kincaid, Alyson F McIntosh, Suresh Nair
Journal: Journal of Clinical Oncology (2016)

e21037 Background: Immune checkpoint targeting used sequentially with radiation (RT) in melanoma brain metastases (mets) may potentiate durable brain response. The optimal treatment sequence has not been delineated. This study reports our institutional outcomes using this combined modality approach. Methods: We retrospectively reviewed records of 30 patients with melanoma brain mets treated with immune checkpoint inhibitors (anti-CTLA-4, anti-PD1) and brain radiation (whole brain, stereotactic, or GammaKnife [GK]), concurrently ( ≤ 30 days) or non-concurrently (˃30 days). We compared overall survival (OS) and central nervous system (CNS) progression-free survival (PFS). Secondary endpoints included type of immunotherapy or RT, number of brain mets, order of therapies, and safety. Tumor responses were evaluated by immune-related response criteria. Results: Median OS in the ≤ 30 day (d) group (n = 10) was 35.71 vs. 58.00 weeks (wk) in the > 30d group (n = 20), p = 0.1209. Median CNS PFS in the ≤ 30d group was 23.29 vs. 50.71 wk in the > 30d group, p = 0.1047. Primary endpoints did not reach statistical significance, possibly due to our small sample size. A majority of patients received RT first (n = 20). In this subset, those who received immunotherapy > 30d after RT had statistically significant better OS (median OS 58.00 vs. 34.72 wk), p = 0.0493. The median CNS PFS in patients with ≤ 2 brain mets was 51.86 vs. 26.43 wk in those with > 2 brain mets (p = 0.0216). Median OS was not significantly different between groups based on the number of brain mets (58.00 vs. 37.57 wk, p = 0.1140). The majority of patients received anti-CTLA4 (76.67%) and GK (66.67%). Brain responses included partial, 42.86%; progressive, 35.71%; stable, 14.29%; and complete, 7.14%. Three patients experienced adverse events (10%). Six patients died without progression in the brain; 4 patients had CNS PFS > 1year. Conclusions: The sequential delivery of RT and immunotherapy > 30d apart may increase CNS PFS and OS in melanoma brain mets with an acceptable toxicity profile. This phenomenon may occur through RT priming the immune system. Larger prospective randomized trials are needed to test this hypothesis and further validate our findings.
Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia.
Authors: R LPage, W EWilkinson, W KClair, E AMcCarthy, E LPritchett
Journal: Circulation (1994)

BACKGROUNDParoxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are recognized clinically when patients seek treatment for symptoms due to recurrent arrhythmias; atrial fibrillation also increases the risk of stroke. The frequency with which asymptomatic arrhythmias occur in patients with these arrhythmias is unknown.METHODS AND RESULTSTwenty-two patients with paroxysmal atrial fibrillation (n = 8) or paroxysmal supraventricular tachycardia (n = 14) were studied for 29 days with two different ambulatory ECG-monitoring techniques to measure the relative frequency of asymptomatic and symptomatic arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, beta-blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events (defined as lasting at least 30 seconds) were documented using continuous ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days; symptomatic arrhythmia events were documented using transtelephonic ECG monitoring for al...
Systems analysis of adverse drug events
Authors: N. W. Dickey
Journal: JAMA (1996)

To the Editor.  —There is no question that the contributions made by Dr Bates and colleagues 1 and Dr Leape and colleagues 2 are important to our knowledge and understanding of adverse drug events. Their research could make a real difference in the health care community's ability to deliver better and safer medical care.  However, it is unfortunate that the authors needlessly chose to dramatize their work by making sweeping, scientifically invalid estimates regarding annual rates of iatrogenic injuries and deaths numbering in the millions and hundreds of thousands, respectively. It is simply not scientifically possible to estimate current national iatrogenic injury and death rates based solely on the Harvard Medical Practice Study's (MPS's) decade-old sample of patient discharge records, which included only one state (New York) during just 1 year (1984). 3   We have no desire to minimize the extent or nature of medical injuries, but we are concerned
Accurate noninvasive quantification of stenotic aortic valve area by Doppler echocardiography.
Authors: W AZoghbi, K LFarmer, J GSoto, J GNelson, M AQuinones
Journal: Circulation (1986)

Laminar flow through a conduit is equal to the mean velocity times the cross-sectional area of the orifice. Therefore, volume is equal to the time-velocity integral multiplied by the cross-sectional area. In aortic stenosis, flow in the stenotic jet is laminar and the aortic valve area should be equal to the volume of blood ejected through the valve divided by the time-velocity integral of the aortic jet velocity recorded by continuous-wave Doppler echocardiography. To test whether this concept can be used to accurately determine aortic valve area noninvasively by the Doppler method, 39 patients (age 35 to 82 years, mean 63) underwent pulsed Doppler combined with two-dimensional echocardiography for measurement of stroke volume at the aortic, pulmonic, and mitral anulus as well as continuous-wave Doppler recording of the aortic jet. Aortic valve area determined at cardiac catheterization by the Gorlin equation ranged between 0.4 and 2.07 cm2 (mean 0.89 +/- 0.45). Doppler-derived valve area, determined wit...
Calculation of left ventricular wall stress.
Authors: D MRegen
Journal: Circulation Research (1990)

Chamber-stress equations relate wall stresses to pressure and wall dimensions. Such equations play a central role in the analysis and understanding of heart-chamber function. Over the past three decades, several stress equations giving radically different results have been derived, used, and/or espoused. They can be classified into two categories, according to the definition of stress underlying the equation. The stresses in one class of equations are total forces per unit normal area, excluding ambient pressure but including pressure in the wall exerted by more external elements of the wall. The stresses in the other class of equations are fiber-pulling forces per unit normal area, that is, total forces per unit normal area excluding all pressure. The validity of stress equations can be tested at least three ways: 1) Do they predict that the pressure inside a small chamber nested in a larger chamber would be the sum of transmural pressures of the two chambers? 2) Do they satisfy the expectation from Lapl...