tbuckley/cabot-search huggingface dataset:
Cardiac microcirculatory effects of beta-adrenergic blockade during sympathetic stimulation.
Authors: D FCousineau, C AGoresky, C PRose, A JSchwab
Journal: Circulation Research (1991)

The effects of beta-adrenergic blockade on cardiac transcapillary exchange were examined at rest and during sympathetic stimulation. Multiple indicator dilution experiments were carried out in closed-chest anesthetized dogs at rest and during carotid occlusion, either under basal conditions or after beta-adrenergic blockade with alprenolol. beta-Adrenergic blockade at rest had no effect on coronary flow or transcapillary exchange in comparison with the control situation, but it abolished the increase in coronary flow and in the permeability/surface area product for labeled sucrose produced by carotid occlusion. High coronary resistance values in beta-blocked animals with carotid occlusion were associated with a high degree of heterogeneity in capillary transit times, but the overall relation between coronary flow and the capillary permeability/surface area product was unchanged. The findings indicate that beta-blockade increases coronary resistance during sympathetic stimulation and, simultaneously, decre...
Parkinson disease among patients treated for benign prostatic hyperplasia with α1 adrenergic receptor antagonists
Authors: Rahul Sasane, Amy Bartels, Michelle Field, Maria I. Sierra, Sridhar Duvvuri, David L. Gray, Sokhom S. Pin, John J. Renger, David J. Stone
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDRecently the α1 adrenergic receptor antagonist terazosin was shown to activate PGK1, a possible target for the mitochondrial deficits in Parkinson disease related to its function as the initial enzyme in ATP synthesis during glycolysis. An epidemiological study of terazosin users showed a lower incidence of Parkinson disease when compared with users of tamsulosin, an α1 adrenergic receptor antagonist of a different class that does not activate PGK1. However, prior research on tamsulosin has suggested that it may in fact potentiate neurodegeneration, raising the question of whether it is an appropriate control group.METHODSTo address this question, we undertook an epidemiological study on Parkinson disease occurrence rate in 113,450 individuals from the United States with 5 or more years of follow-up. Patients were classified as tamsulosin users (n = 45,380), terazosin/alfuzosin/doxazosin users (n = 22,690), or controls matched for age, sex, and Charlson comorbidity index score (n = 45,380).RESULTSIncidence of Parkinson disease in tamsulosin users was 1.53%, which was significantly higher than that in both terazosin/alfuzosin/doxazosin users (1.10%, P < 0.0001) and matched controls (1.01%, P < 0.0001). Terazosin/alfuzosin/doxazosin users did not differ in Parkinson disease risk from matched controls (P = 0.29).CONCLUSIONThese results suggest that zosins may not confer a protective effect against Parkinson disease, but rather that tamsulosin may in some way potentiate Parkinson disease progression.FUNDINGThis work was supported by Cerevel Therapeutics.
Mechanical alternans during acidosis in ferret heart muscle.
Authors: C HOrchard, EMcCall, M SKirby, M RBoyett
Journal: Circulation Research (1991)

Acidosis leads to mechanical alternans (i.e., alternation of large and small contractions) in ferret papillary muscles. This alternation in the size of the contraction is paralleled by alternation in the size of the intracellular Ca2+ transient (monitored using the photoprotein aequorin). In isolated myocytes, the large contraction is accompanied by a prolonged action potential. Mechanical alternans also can be induced by acidosis in isolated myocytes during a train of voltage-clamp pulses. Thus, it appears unlikely that the mechanical alternans is secondary to changes in action potential duration; it is more likely that the observed changes in action potential duration are secondary to changes in the size of the Ca2+ transient. The observation that a Ca2(+)-activated inward current also shows alternation during mechanical alternans provides a possible mechanism for the link between Ca2+ and action potential duration. The alternation in the size of the Ca2+ transient may be secondary to the slowed mechani...
Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction.
Authors: H CStrauss, J TBigger, A LSaroff, E GGiardina
Journal: Circulation (1976)

Twenty patients of mean age 66.2 years, with suspected sinus node dysfunction, underwent extensive electrophysiologic study. Sinus bradycardia (18), sinus pauses (3), and  block (1) were identified in their ECGs prior to study. Also 11 patients had some abnormality of atrioventricular nodal and/or intraventricular conduction prior to study. At the  of electrophysiological study, 10/20 patients (50%) had a mean cycle length exceeding 1000 msec, and mean P-V interval exceeded 210 msec in 7/20 (35%). The estimated sinoatrial conduction time exceeded 215 msec in 6/16 (38%) patients. The maximum first escape cycle following pacing at six different rates exceeded a value equal 1.3 X the mean value of the control cycle length + 101 msec (slope of regression line + Y intercept + 1 SD) in 13/9 (68%) patients. Nineteen patients received 1 mg atropine intravenously and mean cycle length decreased by 19%, from 891 +/- 175.8 msec to 718 +/- 182.9 msec. Graded infusion of isoproterenol was employed in 1...
Altered left ventricular remodeling with beta-adrenergic blockade and exercise after coronary reperfusion in rats.
Authors: B HOh, SOno, EGilpin, JRoss
Journal: Circulation (1993)

BACKGROUNDbeta-Adrenergic blockade is known to improve the survival of patients after acute myocardial infarction and to reduce myocardial infarct size in experimental coronary occlusion. However, the effects of beta-blockade on global and regional left ventricular (LV) remodeling have not been characterized after coronary occlusion with reperfusion. In rats subjected to coronary occlusion and reperfusion, we have demonstrated beneficial effects of reperfusion in sedentary rats with a hypertrophic response to exercise in the surviving outer wall of the infarcted zone, and in this study we investigated whether such remodeling is modified by beta-blockade in both sedentary and exercised rats.METHODS AND RESULTSFemale Sprague-Dawley rats were randomized into groups at 5 days after 45 minutes of left coronary artery occlusion followed by reperfusion to produce nontransmural infarction. Animals completing the experiment included a propranolol-treated sedentary group (750 mg/l drinking water) (n = 20) and a pro...
Novel Technology To Improve Safety Of ESD In Western Setting
Authors: E Hossain, M Abdelrahim, P Bhandari
Journal: Endoscopy (2021)

Intra-procedural and delayed bleed have been significant risk factors in ESD leading to increased complications thereby steepening the learning curve especially in Western settings. In this video we demonstrate the Olympus EVIS X1 endoscopy system with its novel Red Dichromatic Imaging (RDI) which enhances the visibility of deep blood vessels and bleeding sources.The video clearly demonstrates both the above advantages of RDI. We also demonstrate the use of dual knife with its tip withdrawn and using spray/swift coagulation can result in effective haemostasis thereby minimising instrument exchange and reducing the risk of losing visibility of the bleeding point.
Chinese herb microneedle patch for wound healing
Authors: Junjie Chi, Lingyu Sun, Lijun Cai, Lu Fan, Changmin Shao, Luoran Shang, Yuanjin Zhao
Journal: Bioactive Materials (2021)

Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement. Attempts in this area tend to develop new forms to make their applications more convenient and wider. Here, we propose a novel Chinese herb microneedle (CHMN) patch by integrating the herbal extracts, Premna microphylla and Centella asiatica, with microstructure of microneedle for wound healing. Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold. Because the leaves of the Premna microphylla are rich in pectin and various amino acids, the CHMN could be imparted with medicinal efficacy of heat clearing, detoxicating, detumescence and hemostatic. Besides, with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica, the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant, anti-inflammatory and anti-bacterial activity. Taking advantages of these pure herbal compositions, we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria, inhibiting inflammatory, collagen deposition, angiogenesis and tissue reconstruction during the wound closure. These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.
Abstract 921: Novel clinical targets revealed by kinome reprogramming in mutant <i>ESR1</i> metastatic breast cancer
Authors: Derek Dustin, Guowei Gu, Doug Chan, Amanda Beyer, David Edwards, Arnoldo Corona-Rodriguez, Matthew Ellis, Suzanne Fuqua
Journal: Cancer Research (2019)

Abstract Background: Approximately half of women with estrogen receptor (ER)-positive breast cancer who undergo adjuvant endocrine therapy (ET) develop disease progression and metastasis. Studies have revealed that up to 40% of metastatic patients develop tumors bearing a mutation in ESR1. ESR1 mutant (ESR1m) tumors are associated with a more aggressive metastatic disease course. Studies have shown that cancers can undergo “kinome reprogramming” in response to therapy and acquired genetic alterations within the tumor. Thus, we hypothesize that expression of ESR1 mutations induces kinome reprogramming, which presents novel potential therapeutic targets to selectively treat ESR1m metastatic breast cancer. Methods: We performed Kinobeads Precipitation (KiP) using broad specificity kinase inhibitors to capture and quantify by MS the level of active kinases in MCF-7 ESR1 wild-type and ESR1 Y537S mutant cells. We performed targeted siRNA screens and immunoblots to validate the hyperactivity of several of these kinases. Specific kinase inhibitors are being used to test their effects on proliferation and invasion in vitro, and in ex vivo organoid growth assays. Xenograft models are being used to evaluate the effects of the inhibitors on primary tumor growth and distant metastasis. Results: Hyperactivation of 169 kinases in ESR1m cells was revealed by KiP analysis. Hyperactivation of several growth factor receptors, the PI3K/Akt/mTOR pathway, and the JAK/STAT pathway was demonstrated in Y537S mutant cells. We tested specific inhibitors of these pathways, and have shown that the mutant cells have reduced proliferation when these pathways are targeted. We developed organoid growth assays using primary and metastatic tumors from MCF-7 and T47D Y537S ESR1 xenograft tumors, and the Y537S ESR1 WHIM20 PDX model, and found that ET in combination with these selected targeted kinase inhibitors decreased the growth of organoids. We are currently testing inhibitors in combination with ET in vivo, and preliminary results demonstrate a significant inhibition of distant metastatic frequency. These results suggest that selective inhibition of hyperactivated “reprogrammed” kinase pathways can restore ET sensitivity in ESR1m tumors, and may show promise for use in ER-positive metastatic breast cancer patients. Citation Format: Derek Dustin, Guowei Gu, Doug Chan, Amanda Beyer, David Edwards, Arnoldo Corona-Rodriguez, Matthew Ellis, Suzanne Fuqua. Novel clinical targets revealed by kinome reprogramming in mutant ESR1 metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 921.
6-minute walk distance as a predictor of outcome in idiopathic pulmonary fibrosis
Authors: Marco Mura
Journal: European Respiratory Journal (2014)

To the Editor: 

The interesting manuscript by du Bois et al. [1] states in the discussion section that “only two previous studies have demonstrated an independent association between 6MWD and the risk of mortality in patients with IPF”, quoting the studies of Caminati et al. [2] and of Lederer et al. [3].

It should be noted that in 2012 the European Respiratory Journal published a study demonstrating the significant and independent association between 6-min walk …
Immunologic identification of lymphocyte subsets in experimental murine myocarditis with encephalomyocarditis virus. Different kinetics of lymphocyte subsets between the heart and the peripheral blood, and significance of Thy 1.2+ (pan T) and Lyt 1+, 23+ (immature T) subsets in the development of myocarditis.
Authors: CKishimoto, KKuribayashi, KFukuma, TMasuda, NTomioka, W HAbelmann, CKawai
Journal: Circulation Research (1987)

To clarify the immune mechanism in myocarditis, immunofluorescence techniques with laser flow cytometry were used to examine serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of DBA/2 and BALB/c mice inoculated with encephalomyocarditis virus (Experiment I). B cells were identified by staining with fluorescein isothiocyanate-labelled rabbit anti-mouse immunoglobulin. T-cell subsets were identified with rat anti-Thy 1.2, and nonpolymorphic Lyt 1 and Lyt 2 monoclonal antibodies plus fluorescein isothiocyanate-labelled anti-mouse immunoglobulin. On days 7 and 14 postinfection, the percentage of Thy 1.2+ (pan T) cells in both strains had decreased in the peripheral blood; B cells showed no significant changes throughout the entire period. On the other hand, Thy 1.2+ (pan T) and Lyt 1+, 23+ (precursor and immature) T cells appeared to occupy the major portion of the myocardium on days 7 and 14 when congestive heart failure developed. To confirm this, serial immunohistologic studie...
Long-term survival with open-chest cardiac massage after ineffective closed-chest compression in a canine preparation.
Authors: K BKern, A BSanders, S FBadylak, WJanas, A BCarter, W ATacker, G AEwy
Journal: Circulation (1987)

The ultimate goal of cardiopulmonary resuscitation (CPR) is long-term, neurologically intact survival. This study examined whether open-chest cardiac massage could improve 7 day survival and neurologic function when instituted after the failure of standard closed-chest compression CPR. Twenty-nine mongrel dogs were anesthetized and then instrumented with catheters to monitor right atrial and ascending aortic pressures. Ventricular fibrillation was induced and after 3 min standard CPR was begun. Standard CPR was performed with a Thumper programmed for 2 inch chest compressions at 60/min with a 50% duty cycle. External defibrillation was attempted twice after 15 min of ventricular fibrillation. Unsuccessfully defibrillated animals were randomly assigned to either an additional 2 min of continued closed-chest compressions, or 2 min of open-chest cardiac massage. All animals underwent a period of advanced cardiac life support and were followed until they were resuscitated or died. Follow-up care, including sc...
Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation.
Authors: ARoth, EHarrison, GMitani, JCohen, S HRahimtoola, UElkayam
Journal: Circulation (1986)

We evaluated the efficacy and the safety of medium-(240 mn/day) and high-dose (360 mg/day) diltiazem alone and in combination with digoxin when used for control of heart rate in 12 patients with chronic atrial fibrillation. Medium-dose diltiazem was comparable to therapeutic dose of digoxin at rest (88 +/- 19 vs 86 +/- 12 beats/min) but superior during peak exercise (154 +/- 23 vs 170 +/- 20 beats/min; p less than .05). High-dose diltiazem resulted in better control of heart rate than digoxin both at rest (79 +/- 17 beats/min; p less than .05) and exercise (136 +/- 25 beats/min; p less than .05) but was associated with side effects in 75% of the patients. Combined therapy of digoxin and diltiazem enhanced the effect of digoxin alone and resulted in significantly better control of heart rate at rest (67 +/- beats/min with medium-dose and 65 +/- beats/min with high-dose diltiazem) and during peak exercise (132 +/- 32 and 121 +/- 24 beats/min, respectively). However, the difference in heart rate between thes...
Follow-up of patients undergoing percutaneous mitral balloon valvotomy. Analysis of factors determining restenosis.
Authors: I FPalacios, P CBlock, G TWilkins, A EWeyman
Journal: Circulation (1989)

This study reports the clinical follow-up (13 +/- 1 months) of 100 consecutive patients who underwent percutaneous mitral balloon valvotomy (PMV). Echocardiographic (n = 32) and cardiac catheterization (n = 37) data from this group are also included. Patients were divided into two groups by an echocardiographic score. PMV resulted in a good hemodynamic result (post-PMV mitral valve area, greater than or equal to 1.5 cm2) in 88% of patients with a score of 8 or less and 44% of patients with a score of more than 8. Eighty-eight percent of patients with a score of 8 or less (n = 57) were New York Heart Association (NYHA) functional Classes III and IV before PMV; at follow-up, 81% were NYHA Class I and 12% were NYHA Class II. There were no deaths; three patients underwent mitral valve replacement (MVR). Ninety-eight percent of patients with a score of more than 8 (n = 43) were NYHA Classes III and IV before PMV; at follow-up, 58% were NYHA Classes I and II. Seven patients who did not improve and were not surg...
Beta-blocker treatment of dilated cardiomyopathy. Beneficial effect of carteolol in mice.
Authors: MTominaga, AMatsumori, IOkada, TYamada, CKawai
Journal: Circulation (1991)

BACKGROUNDThe effects of carteolol, a nonselective beta-adrenergic receptor blocker with intrinsic sympathomimetic activity, were compared with those of metoprolol in a murine model of viral myocarditis and dilated cardiomyopathy caused by encephalomyocarditis virus.METHODS AND RESULTSIn the acute experiment, BALB/c and DBA/2 mice were inoculated with encephalomyocarditis virus. BALB/c mice were then given carteolol at 1 (n = 10), 10 (n = 10), 30 (n = 11), or 100 mg/kg (n = 9) daily, and DBA/2 mice were given carteolol at 1 (n = 9) or 10 mg/kg (n = 9) daily starting the day of inoculation. Controls were given distilled water (n = 23 for BALB/c mice and n = 8 for DBA/2 mice). BALB/c mice were killed on day 7, and DBA/2 mice were killed on day 14. In the subacute experiment, DBA/2 mice were inoculated with the virus and then given carteolol at 1 (n = 12) or 10 mg/kg (n = 16), or distilled water (n = 27) daily, starting on day 14. Mice were killed on day 28. Virus replication, murine survival, heart weight t...
Mortality within 24 hours of thrombolysis for myocardial infarction. The importance of early reperfusion. The GUSTO Investigators, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.
Authors: N SKleiman, H DWhite, E MOhman, A MRoss, L HWoodlief, R MCaliff, D RHolmes, EBates, MPfisterer, AVahanian
Journal: Circulation (1994)

BACKGROUNDA paradoxical increased risk of death has been reported during the first 24 hours after thrombolysis for myocardial infarction. The mechanism of this phenomenon is not known, nor is its relation to the success or failure of reperfusion. The present study was a prospectively designed analysis of deaths occurring within the first 24 hours in the GUSTO trial.METHODS AND RESULTSThere were 41,021 patients enrolled in GUSTO, a randomized comparison of streptokinase with intravenous or subcutaneous heparin, accelerated tissue-type plasminogen activator (TPA), and combination of streptokinase and TPA. An angiographic mechanistic substudy examined reperfusion (using the TIMI flow grading criteria) 90 minutes after the assigned thrombolytic regimen was begun in 1567 patients. There were 1125 deaths (2.8%) within 24 hours (early deaths) and 1726 additional deaths (4.2%) after 24 hours but within 30 days (later deaths). At the time of presentation, the most potent predictors of early death were hypotens...
Relation of left ventricular hemodynamic load and contractile performance to left ventricular mass in hypertension.
Authors: AGanau, R BDevereux, T GPickering, M JRoman, P LSchnall, SSantucci, M CSpitzer, J HLaragh
Journal: Circulation (1990)

The weak relation of systolic blood pressure to left ventricular mass in hypertensive patients is often interpreted as evidence of nonhemodynamic stimuli to muscle growth. To test the hypothesis that left ventricular chamber size, reflecting hemodynamic volume load and myocardial contractility, influences the development of left ventricular hypertrophy in hypertension, we studied actual and theoretic relations of left ventricular mass to left ventricular diastolic chamber volume, pressure and volume load, and an index of contractility. Data were obtained from independently measured M-mode and two-dimensional echocardiograms in 50 normal subjects and 50 untreated patients with essential hypertension. Two indices of overall left ventricular load were assessed: total load (systolic blood pressure x left ventricular endocardial surface area) and peak meridional force (systolic blood pressure x left ventricular cross sectional area). A theoretically optimal left ventricular mass, allowing each subject to achie...
Computer Aided Diagnosis for the Characterisation of Dysplasia in Barrett’s Oesophagus with Magnification Endoscopy
Authors: M Hussein, D Lines, JGB Puyal, N Bowman, V Sehgal, D Toth, M Everson, O Ahmad, R Kader, JM Esteban, R Bisschops, M Banks, M Haefner, P Mountney, D Stoyanov, L Lovat, R Haidry
Journal: Endoscopy (2021)

Aims There have been significant advances in magnification endoscopic imaging of Barrett’s oesophagus (BE). Magnification endoscopy of mucosal and vascular patterns arising in BE can help predict non-dysplastic from dysplastic mucosa. This can inform sampling and guide endoscopic eradication therapy. We aimed to develop a computer aided detection system that can support the diagnosis of BE dysplasia on magnification endoscopy.
Two-dimensional echocardiographic identification of surgically correctable complications of acute myocardial infarction.
Authors: G SMintz, M FVictor, M NKotler, W RParry, B LSegal
Journal: Circulation (1981)

The appearance of a new, loud systolic murmur in a patient with congestive heart failure after an acute myocardial infarction suggests a surgically correctable cause of the heart failure. Using two-dimensional echocardiography, we studied 14 patients who presented in this manner. Four patients had rupture of a papillary muscle with a flail mitral valve. All four had surgery; three survived. Five patients had fibrosis of the posteromedial papillary muscle. All five had surgery; three survived. Five patients had a ventricular septal defect. Three of the five had surgery; one survived. Two-dimensional echocardiography is useful in studying patients with a new systolic murmur and congestive heart failure after acute myocardial infarction to detect surgically correctable structural defects.