tbuckley/cabot-search huggingface dataset:
Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study.
Authors: D NSharpe, JMurphy, RCoxon, S FHannan
Journal: Circulation (1984)

A number of studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure treated with angiotensin converting-enzyme inhibitors. The long-term efficacy of the oral long-acting converting-enzyme inhibitor enalapril remains to be established in controlled studies. We evaluated this drug in 36 patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy. After baseline assessment of symptoms, exercise capacity, and results of echocardiographic examination and right heart catheterization, patients were randomly assigned to treatment with 5 mg enalapril twice daily (n = 18) or placebo (n = 18) in a double-blind fashion. The two groups had similar clinical, echocardiographic, and hemodynamic characteristics before treatment. After 3 months of treatment, the enalapril group showed a significant improvement as judged by subjective patient impression, functional class, and exercise dura...
Tubeimoside-1 induces TFEB-dependent lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting mTOR
Authors: Xiaojia Liu, Mingxiao Yin, Jingwen Dong, Genxiang Mao, Wenjian Min, Zean Kuang, Peng Yang, Lu Liu, Na Zhang, Hongbin Deng
Journal: Acta Pharmaceutica Sinica B (2021)

Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) cascade is an effective therapeutic target for immune checkpoint blockade (ICB) therapy. Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity. Using flow cytometry-based assay, we identify tubeimoside-1 (TBM-1) as a promising antitumor immune modulator that negatively regulates PD-L1 level. TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1. Furthermore, TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma (LLC) and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell immunity. Mechanistically, TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent, autophagy-independent pathway. TBM-1 selectively binds to the mammalian target of rapamycin (mTOR) kinase and suppresses the activation of mTORC1, leading to the nuclear translocation of TFEB and lysosome biogenesis. Moreover, the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells. Our findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.
Optimal diagnosis in acute myocardial infarction. A cost-effectiveness study.
Authors: PGrande, CChristiansen, APedersen, M SChristensen
Journal: Circulation (1980)

The predictive value of a diagnostic test estimates the likelihood for presence or absence of disease in a patient with a positive or negative test result (PVpos or PVneg). We evaluated the predictive values of serum activities of the heart-specific creatine kinase isoenzyme MB (CK-MB), aspartate aminotransferase, lactate dehydrogenase, CK, and ECG in 401 consecutively admitted patients suspected of acute myocardial infarction (AMI). The study showed that CK-MB (PVpos = 0.98, PVneg = 1.00) was better than the other enzymes (single as well as serial) and ECG, evaluated both separately and in combinations. In all cases of AMI CK-MB was positive within 17 hours from admission. Replacement of the standard enzymes with CK-MB provides a faster and safer diagnosis of AMI and reduces hospitalization time considerably for patients without AMI.
Prediction of parasitological cure in children infected with Trypanosoma cruzi using a novel multiplex serological approach: an observational, retrospective cohort study
Authors: Laura Jurado Medina, Emeric Chassaing, Griselda Ballering, Nicolas Gonzalez, Lola Marqué, Peter Liehl, Hans Pottel, Jasper de Boer, Eric Chatelain, Maan Zrein, Jaime Altcheh
Journal: The Lancet Infectious Diseases (2021)
Development of the ductus arteriosus in right ventricular outflow tract obstruction.
Authors: M ASantos, J NMoll, CDrumond, W BAraujo, NRomao, N BReis
Journal: Circulation (1980)

We studied the morphology of the ductus arteriosus in 14 infants, ages 2--90 days. Eight (group 1) had pulmonary atresia (structural and functional) with an intact interventricular septum; six (group 2) had pulmonary atresia with a ventricular septal defect. The inferior angle of the ductus arteriosus at the aortic junction was measured in each patient. In group 1, this angle was obtuse in all but one patient. In group 2, the angle was acute in all. Further study of intracardiac anatomy suggested that in group 1, the obtuse inferior angle of the ductus arteriosus was the result of a late and progressive obstructive phenomenon that allowed normal right-to-left flow through the ductus arteriosus during much of fetal life. In group 2, the direction of ductus arteriosus flow (normally from the pulmonary trunk to the aorta) was reversed, and flowed from the aorta to the pulmonary trunk. This reversal of flow was probably of early onset in the fetus, the aorta receiving the total combined ventricular output, an...
Lower-Extremity Amputation Trends Among People With Diabetes in a Large Urban Environment
Authors: Kiran K. Chatha, Brad Walsh, Javier La Fontaine, Michael E. Bowen, Luigi Meneghini
Journal: Diabetes Care (2020)

Nontraumatic lower-extremity amputations (NLEAs) are a disabling and costly complication of uncontrolled diabetes (1). Factors influencing NLEAs include glycemic control, vascular disease, foot ulcer, and diabetes prevention practices (2,3). Texas has high rates of underinsured individuals, high prevalence of diabetes, a growing Hispanic population, and high rates of NLEAs (4). We examine trends of lower-extremity amputation rates among adults with diabetes in Dallas County between 2015 and 2019.

Using data from the Dallas-Fort Worth Hospital Council Educational and Research Foundation (DFWHC) and the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System (BRFSS), we calculated age-adjusted rates for major, minor, and overall NLEAs between 1 October 2015 and 30 September 2019. We followed the methodology used by Geiss et al. (3) and calculated age-adjusted NLEA rates per 1,000 adults with diabetes, using four adult age categories, with denominator data (numbers of adults with diabetes) estimated using BRFSS Dallas County diabetes prevalence data. Because of the transition of the ICD-9 to ICD-10 coding system on 1 October 2015, the 2015 quarter 4 data were annualized to account for quarters 1–3 that were coded using the prior ICD-9 system and therefore not used. The 2019 data were annualized to …
Regulation of blood-brain barrier endothelial cells by nitric oxide.
Authors: DJanigro, G AWest, T SNguyen, H RWinn
Journal: Circulation Research (1994)

Nitric oxide (NO) synthesized by vascular endothelial cells is a potent vasodilator substance. The actions of NO extend well beyond its vasodilatory properties, and increasingly, NO has been recognized as an important signal for intercellular and intracellular communication. Recently, NO has been implicated in the regulation of vascular and blood-brain barrier permeability. NO has also been shown to modulate ion channels in excitable cells, thus affecting neuronal firing. We report the results of patch-clamp experiments that show a modulatory action of NO as well as cGMP and cAMP on a hyperpolarization-activated current (Iha) carried by both Na+ and K+ ions in blood-brain barrier endothelial cells. Iha was recorded in cells dialyzed with 0.2 mmol/L GTP-gamma-S to inhibit a large inwardly rectifying potassium current. This ionic current and its modulation by NO may play a role in the regulation of the transport of ions, nutrients, and other molecules to the brain and serve as an integral part of the blood-...
103P First-line avelumab in combination with cetuximab and chemotherapy in patients with advanced squamous non-small cell lung cancer (NSCLC)
Authors: Z.G. Andric, G. Gálffy, M. Cobo Dols, B. Szima, G. Stojanovic, M.D. Petrovic, E. Felip Font, D. Vicente Baz, S. Ponce Aix, O. Juan-Vidal, S. Tehenes, Z. Szalai, G. Losonczy, A. Calles Blanco, R. Bernabe, K. Duecker, D. Zhou, A. Schroeder, G. Guezel, F. Ciardiello
Journal: Journal of Thoracic Oncology (2021)
Metabolic oxidation of pyruvate and lactate during early myocardial reperfusion.
Authors: BRenstrom, S HNellis, A JLiedtke
Journal: Circulation Research (1990)

We have previously described the rates of oxidation for long-chain fatty acids and glucose in stunned myocardium during early reflow after moderately severe regional ischemia. The purpose of these studies was to characterize the rates of pyruvate and lactate oxidation during comparable periods of reflow. In the main protocol, pyruvate oxidation was defined at two conditions of coronary flow and at two levels of fatty acids in the coronary perfusate. Twenty animals were prepared using the extracorporeally perfused, working swine heart model. In five control (group 1) hearts, flow in the left anterior descending coronary artery was maintained at aerobic levels during a 115-minute perfusion trial. In 15 hearts (groups 2 and 3), flow was held at aerobic levels for 30 minutes, reduced acutely by 60% for 45 minutes, and restored again to aerobic levels for the final 40-minute reflow. In the five control hearts and in 10 of the reperfused hearts (group 2), 20% Intralipid (KabiVitrum, Alameda, California) with he...
Effect of exercise conditioning on the intrinsic contractile state of cat myocardium.
Authors: J FWilliams, R DPotter
Journal: Circulation Research (1976)

Fourteen adult cats were exercised on a motor-driven treadmill 5 days each week for 6 weeks to determine the effect of exercise conditioning on the intrinsic contractile state of the myocardium. The exercise program was sufficient to produce a cardiovascular training effect manifested by slower exercising heart rates and resting heart rates after atropine by the end of the 6th week. The mechanical function of the isolated right ventricular papillary muscle from exercised cats was compared with that of 17 sedentary adult cats. There were no significant differences between exercised and control cats in in heart weight-body weight ratios, resting and active lenght - tension relations, maximal rate of isometric force development at the peak of the length-tension curve (Lmax), time to peak force at Lmax, maximal force development with paired stimulation and norepinephrine, or force-velocity relations. These results indicate that the intrinsic state of feline myocardium is unaffected by exercise conditioning.
Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster.
Authors: J MCapasso, E HSonnenblick, PAnversa
Journal: Circulation Research (1990)

The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical...
Non Variceal Upper Gastrointestinal Bleeding During Covid 19 Outbreak. Incidence And Clinical Characteristics
Authors: B Garcia-Sague, E Brunet, L LLovet, P Garcia-Iglesias, E Frisancho, L Melcarne, E Martinez- Bauer
Journal: Endoscopy (2021)

Aims During the COVID 19 pandemic, healthcare was predominantly for the treatment of COVID patients. This raised concerns about the impact on health care for unrelated illnesses.The aims of this study was to determine if COVID19 has produced changes in the incidence and clinical characteristics of non-variceal upper gastrointestinal bleeding (NVUGB) compared to a period of time prior to the pandemic.
The effect of vasoactive agents on the left ventricular end-systolic pressure-volume relation in closed-chest dogs.
Authors: G LFreeman, W CLittle, R AO'Rourke
Journal: Circulation (1986)

The left ventricular end-systolic pressure-volume relation has received intense interest as a relatively load-insensitive measure of cardiac performance. In clinical studies, pharmacologic manipulation of blood pressure has been used to determine this relation. Since previous studies have shown that acute changes in the resistance and impedance of the arterial circulation influence the left ventricular end-systolic pressure-volume relation, the use of vasoactive drugs in its determination may affect the results achieved. This study was undertaken to determine whether clinically used vasoactive drugs influence the left ventricular end-systolic pressure-volume relation. Sixteen dogs were previously instrumented with micromanometer pressure transducers and three sets of piezoelectric crystals to permit determination of left ventricular pressure and volume. The dogs were studied after autonomic blockade and sedation. End-systolic pressure-volume relations were generated by caval occlusion at control levels of...
Improving compliance with therapeutic regimens in hypertensive patients in a community health center.
Authors: JTakala, NNiemelä, JRosti, KSievers
Journal: Circulation (1979)

A 1-year, randomized study was conducted to test the possibility of improving compliance with therapeutic regimens in hypertensives by means of certain simple arrangements. Patients were given written treatment instructions concerning hypertension, a personal blood-pressure follow-up card, and, for those who failed to attend their blood-pressure check-up, an invitation for a new check-up. Using matched pairs, 202 Finnish hypertensives were randomly allocated either to an ordinary or a reorganized treatment group. By means of the latter system, patient compliance could be significantly (p less than 0.01) improved: Only 4% of the patients in this group dropped out of treatment, compared with 19% in the ordinary treatment group. By the end of the year, blood pressure had been lowered by at least 10% in 95% of the patients in the reorganized group and in 78% of those in the ordinary group (p less than 0.01). This was achieved in approximately 60% of cases using chlorthalidone alone.
Ca2+ and segment length dependence of isometric force kinetics in intact ferret cardiac muscle.
Authors: W OHancock, D AMartyn, L LHuntsman
Journal: Circulation Research (1993)

The influence of Ca2+ and sarcomere length on myocardial crossbridge kinetics was studied in ferret papillary muscle by measuring the rate of force redevelopment following a rapid length step that dropped the force to zero. Tetanic stimulation with 5 mumol/L ryanodine was used to obtain a steady-state contraction, and segment length was measured and controlled using a sense-coil technique that measures changes in the cross-sectional area of the central region of the muscle. The rate constant for the recovery of force (ktr) following a rapid length release was obtained by fitting the data with a single exponential function. Contrary to results from skinned skeletal fibers in which ktr increases almost 10-fold from low to maximal activation levels, ktr was found not to increase at higher activation levels in this study. Similarly, although force increased with segment length under all conditions, ktr never increased with length. Data presented here are consistent with a model of myocardial Ca2+ activation i...
Beneficial effect of SPM-5185, a cysteine-containing nitric oxide donor, in rat carotid artery intimal injury.
Authors: J PGuo, K AMilhoan, R STuan, A MLefer
Journal: Circulation Research (1994)

We studied the effects of an organic nitric oxide (NO) donor SPM-5185 in a rat carotid artery intimal injury model. Seven days after injury, the two end segments of the injured carotid arteries were studied for endothelial release of NO, and the middle segments were used for histological measurement of the intimal-to-medial (I/M) ratio and scanning electron microscopy of the luminal surface. The NO donor SPM-5185 or its non-NO-donating control compound SPM-5267 were infused intravenously at 30 micrograms/d. Full vasorelaxant responses of rat carotid arterial rings were obtained with the endothelium-dependent vasodilators acetylcholine (ACh), A23187, and the endothelium-independent vasodilator acidified NaNO2 in sham-operated control rings. Impaired relaxation occurred with 10 mumol/L ACh and 1 mumol/L A23187 in injured rings but not in rings infused with SPM-5185 for 7 days. Relaxation to 100 mumol/L acidified NaNO2 was not significantly different among any of the groups, indicating a normal vascular smoo...
The effects of premature stimulation of the His bundle on epicardial activation and body surface late potentials in dogs susceptible to sustained ventricular tachyarrhythmias.
Authors: J FSpear, D ARichards, G JBlake, M BSimson, E NMoore
Journal: Circulation (1985)

Experiments were performed on 20 anesthetized dogs to determine the effects of premature stimulation of the His bundle on epicardial conduction and late potentials recorded on the body surface. Fifteen dogs underwent occlusion of the left anterior descending coronary for 2 hr followed by reperfusion, and five that did not undergo operation served as controls. Animals were studied 2 to 52 weeks after the induction of infarction, and four animals with infarction and four control animals exhibited no sustained arrhythmias in response to programmed ventricular extrastimulation. Five dogs with infarction and one control dog had ventricular fibrillation while the six remaining dogs had inducible sustained ventricular tachycardia. All animals with ventricular tachycardia had late potentials in the terminal portion of the signal-averaged body surface QRS complexes during sinus rhythm and QRS durations in the animals were 64 msec or greater. The voltage in the last 20 msec of the QRS complex was 13.5 microV or les...
Elevated 68Ga-FAPI Activity in the Plasmacytoma of the Ribs
Authors: Wenxin Tang, Qixin Wang, Songsong Yang, Yue Chen
Journal: Clinical Nuclear Medicine (2021)

Abstract 68 Ga-labeled quinoline-based fibroblast activation protein inhibitors ( 68 Ga-FAPIs) has been used in the evaluation of a variety of malignancies. We report the case of a patient with rib plasmacytoma, which showed elevated 68 Ga-FAPI activity. This case indicated fibroblast activation protein overexpression and some degree of fibrosis in the plasmacytoma lesion. Therefore, 68 Ga-FAPI can be a potential tracer in the evaluation of plasmacytoma.
Left ventricular geometry and function in adults with Ebstein's anomaly of the tricuspid valve.
Authors: L NBenson, J SChild, MSchwaiger, J KPerloff, H RSchelbert
Journal: Circulation (1987)

We postulated that the abnormal shape, size, and function of the right heart and adjoining ventricular septum in adults with Ebstein's anomaly of the tricuspid valve might in turn alter the shape and function of the left ventricle. Seven adult patients with uncomplicated Ebstein's anomaly were studied. Left ventricular geometry was determined by two-dimensional echocardiography. Left ventricular function was assessed by treadmill exercise and radionuclide angiography at rest and with exercise. Paradoxic ventricular septal motion was consistently present. Left ventricular eccentricity (ratio of two minor axes in the short-axis view) was uniformly abnormal, averaging 1.35 +/- 0.23 (normal = 1.02 +/- 0.05). The ratio of right to left ventricular cavity size averaged 1.70 +/- 0.44 (normal 0.65 +/- 0.30), and tricuspid valve displacement into the right ventricular cavity averaged 52% (normal 8%). Functional right atrial size averaged 27.6 +/- 5.2 cm2 (normal right atrial area = 13.1 +/- 2.2 cm2). Resting left ...
Venous smooth muscle in hypertension. Enhanced contractility of portal veins from spontaneously hypertensive rats.
Authors: SGreenberg, D FBohr
Journal: Circulation Research (1975)

In isolated bath studies smooth muscle from the rat portal vein was evaluated for its reactivity and contractility, and the whole vessel wall was evaluated for its extensibility. Smooth muscle from the spontaneously hypertensive rat (SHR) had the following characteristics when compared with that from normotensive controls: (1) Spontaneous phasic contractions were more frequent and developed more tension; (2) threshold concentrations for responses to prostaglandins A-2 and B-2 were lower, but those for responses to epinephrine, norepinephrine, KCl, BaCl-2, and SrCl-2 were similar; (3) high concentrations of calcium had a less depressant action on the responses to the prostaglandins but not on the responses to the other agonists; (4) maximal contractile tensions to all agonists were greater; and (5) passive extensibility was less. These differences, because they are in the venous system, cannot be secondary to the increase in wall stress of arterial hypertension. The decreased passive extensibility in this ...
Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data
Authors: Syed A Shah, Jennifer K Quint, Bright I Nwaru, Aziz Sheikh
Journal: Thorax (2021)

Background The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear. Methods We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016–2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting. Results From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016–2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (−0.196 episodes per person-year; p&lt;0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005–0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210–0.277 (sex), 0.159–0.367 (age), 0.068–0.590 (region). Conclusions There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.
212P_PR Language and understanding: The complexity of insight in cancer care
Authors: T. Martin, D. O'Doherty, C. Mattisa, T. Byrne, R. Keogh, C. Murphy, P. Bredin, S. Devanney, P.G. Morris, B. Hennessy, L. Grogan, O.S. Breathnach, R. O'Dwyer
Journal: Journal of Thoracic Oncology (2021)