tbuckley/cabot-search huggingface dataset:
Thyroxine-induced left ventricular hypertrophy in the rat. Anatomical and physiological evidence for angiogenesis.
Authors: W MChilian, R DWangler, K GPeters, R JTomanek, M LMarcus
Journal: Circulation Research (1985)

We examined anatomical and physiological responses of the left coronary vascular system to thyroxine-induced myocardial hypertrophy. Wistar-Kyoto rats (1 and 5 months old) were administered thyroxine (0.25 mg/kg per day) or the saline vehicle (sham-treated controls) for 2 months. At the ages of 3 and 7 months, each group of animals was used for one of three experimental protocols: determination of numerical capillary density in perfusion-fixed hearts, measurement of coronary reactive hyperemic responses following a 20-second coronary occlusion (peak-to-resting blood flow velocity) as an index of coronary reserve, and assessment of myocardial perfusion under resting conditions and during maximum coronary dilation (dipyridamole infusion) for the calculation of minimum coronary resistance per unit weight of the left ventricle or minimum coronary resistance of the total left ventricle. In both groups of thyroxine-treated animals, the left ventricular weight-to-body weight ratio increased by 35-40%. Capillary ...
Procainamide and retrograde atrioventricular nodal conduction in man.
Authors: MShenasa, C JGilbert, D HSchmidt, MAkhtar
Journal: Circulation (1982)

Recent studies that show a depressant effect of procainamide (PA) on retrograde conduction in patients with atrioventricular (AV) nodal reentrant tachycardia (RT) have suggested possible incorporation of AV nodal bypass tracts. Electrophysiologic effects of i.v. PA, 10 mg/kg, on retrograde AV nodal conduction were examined in 13 patients without RT, demonstrable AV nodal refractory period curves, or accessory pathways. Ventriculoatrial (VA) conduction was recorded before and after PA using intracardiac electrograms, incremental ventricular pacing and extrastimulation. With incremental pacing during the control, VA block occurred at a mean cycle length (CL) of 364.6 +/- 87.9 msec. After PA, VA conduction was abolished in five of 13 patients due to onset of retrograde block in the AV node; in seven of 13, VA block occurred at a longer paced CL after PA (344.2 +/- 51.2 msec vs 477.1 +/- 93.2 msec). In one patient, PA did not affect VA conduction. PA invariably produced prolongation in the VA interval at comp...
Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers. Relationship to potassium and cycle length.
Authors: D MRoden, B FHoffman
Journal: Circulation Research (1985)

Marked QT prolongation with induction of polymorphous ventricular tachycardia (Torsades de Pointes) is a well-described phenomenon during quinidine therapy, frequently occurring at low plasma quinidine concentrations, low serum potassium, and slow heart rates. We have therefore assessed the dose-electrophysiological effects of quinidine as a function of extracellular potassium and cycle length in canine Purkinje fibers, using standard microelectrode techniques. Quinidine (1 microM) prolonged action potential at 90% repolarization, while leaving phase zero upstroke slope (Vmax) unchanged at a cycle length 300-8000 msec; at 10 microM, Vmax depression became evident. Increases in the action potential at 90% repolarization were most marked at long cycle lengths and low extracellular potassium (in contrast to Vmax depression) and were partially reversed by tetrodotoxin (1 microM). The relationship between log of cycle length and action potential at 90% repolarization was linear (for cycle length 300-8000 mse...
Gene therapy for ALS: A review
Authors: Defne A. Amado, Beverly L. Davidson
Journal: Molecular Therapy (2021)

Amyotrophic lateral sclerosis (ALS) has historically posed unique challenges for gene-therapy-based approaches, due to a paucity of therapeutic targets as well as the difficulty of accessing both the brain and spinal cord. Recent advances in our understanding of disease mechanism and ALS genetics, however, have combined with tremendous strides in CNS targeting, gene delivery, and gene editing and knockdown techniques to open new horizons of therapeutic possibility. Gene therapy clinical trials are currently underway for ALS patients with SOD1 mutations, C9orf72 hexanucleotide repeat expansions, ATXN2 trinucleotide expansions, and FUS mutations, as well as sporadic disease without known genetic cause. In this review, we provide an in-depth exploration of the state of ALS-directed gene therapy, including antisense oligonucleotides, RNA interference, CRISPR, adeno-associated virus (AAV)-mediated trophic support, and antibody-based methods. We discuss how each of these approaches has been implemented across known genetic causes as well as sporadic ALS, reviewing preclinical studies as well as completed and ongoing human clinical trials. We highlight the transformative potential of these evolving technologies as the gene therapy field advances toward a true disease-modifying treatment for this devastating illness. Amyotrophic lateral sclerosis (ALS) has historically posed unique challenges for gene-therapy-based approaches, due to a paucity of therapeutic targets as well as the difficulty of accessing both the brain and spinal cord. Recent advances in our understanding of disease mechanism and ALS genetics, however, have combined with tremendous strides in CNS targeting, gene delivery, and gene editing and knockdown techniques to open new horizons of therapeutic possibility. Gene therapy clinical trials are currently underway for ALS patients with SOD1 mutations, C9orf72 hexanucleotide repeat expansions, ATXN2 trinucleotide expansions, and FUS mutations, as well as sporadic disease without known genetic cause. In this review, we provide an in-depth exploration of the state of ALS-directed gene therapy, including antisense oligonucleotides, RNA interference, CRISPR, adeno-associated virus (AAV)-mediated trophic support, and antibody-based methods. We discuss how each of these approaches has been implemented across known genetic causes as well as sporadic ALS, reviewing preclinical studies as well as completed and ongoing human clinical trials. We highlight the transformative potential of these evolving technologies as the gene therapy field advances toward a true disease-modifying treatment for this devastating illness.
Estimation of myocardial involvement in patients with acute myocardial infarction by two-dimensional echocardiography.
Authors: J VNixon, K ANarahara, T CSmitherman
Journal: Circulation (1980)

To determine whether real-time two-dimensional echocardiography (2-D echo) can estimate the extent of myocardial involvement in patients with acute myocardial infarction (MI), regional wall motion on serial short-axis 2-D echo recordings was analyzed and the summed scores were compared with estimates of infarct involvement by thallium-201 reperfusion (Tl) and technetium-99m stannous pyrophosphate (99mTc-PYP) scintigraphy. Thirty-two consecutive male patients admitted with their first MI were studied; 10 patients had anterior, 16 had inferior and six had subendocardial MIs. Two patients were technically unsuitable for 2-D echo studies. Twenty patients had Tl scintigrams and 29 had 99MTc-PYP scintigrams. Summed 2-D echo scores correlated closely with estimates of infarct involvement by Tl (r = 0.87) and with estimates of infarct size by 99mTc-PYP (r = 0.74). The location of MI by 2-D echo agreed with the electrocardiographic location in 26 of 29 patients; discrepancies occurred in one inferior and two suben...
Exaggerated vascular response due to endothelial dysfunction and role of the renin-angiotensin system at early stage of renal hypertension in rats.
Authors: JHoshino, TSakamaki, TNakamura, MKobayashi, MKato, HSakamoto, TKurashina, AYagi, KSato, ZOno
Journal: Circulation Research (1994)

We investigated whether endothelial dysfunction might contribute to the exaggerated vasoconstriction that was induced by the administration of norepinephrine at the early stage of one-kidney, one-clip renal hypertension (1K1C) in rats. We also studied the role of the renin-angiotension system in this phenomenon. Male Wistar rats were killed 48 hours after the induction of renal artery stenosis or sham operation, and ring preparations of the thoracic aorta were obtained. The isometric contraction and relaxation of aortic strips produced by norepinephrine and acetylcholine, respectively, were recorded with a force-displacement transducer. The aorta of 1K1C rats showed a significantly (P < .05) exaggerated contractile response to norepinephrine as compared with that of control rats. Rubbing the endothelium and treatment with methylene blue or NG-monomethyl L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in 1K1C rats; therefore, the responses o...
Antiarrhythmic drug effect mimicked by spontaneous variability of ventricular ectopy.
Authors: R AWinkle
Journal: Circulation (1978)

Twenty patients with frequent ventricular ectopic beats had a 5 1/2 hour ECG rhythm strip recorded. Individual patients showed a marked spontaneous variability from one half-hour to the next in the total number of ectopic beats (-99% to +1100%) and the occurrence of pairs or salvos. Although no patient received antiarrhythmic drugs, some patients showed a spontaneous change in arrhythmia which mimicked either  suppression or drug-induced worsening of arrhythmias. If an antiarrhythmic  had been given to these patients after the first half-hour, 65% would have been termed drug responders, using the criteria of 50% reduction in ectopic beats and elimination of pairs or salvos during any half-hour period in the subsequent three hours. Spontaneous variability in ventricular ectopic beats causes serious problems when using ECG monitoring to evaluate antiarrhythmic  response in individual patients. The arrhythmias averaged for the entire group remained stable during the recording period. Evaluating...
The association between citrus consumption and melanoma risk in the UK Biobank*
Authors: A.R. Marley, M. Li, V.L. Champion, Y. Song, J. Han, X. Li
Journal: British Journal of Dermatology (2021)

Melanoma incidence has been dramatically increasing worldwide. Psoralen, a known photocarcinogen, is naturally abundant in citrus products, leading to the hypothesis that high citrus consumption may increase melanoma risk.To investigate the association between total citrus consumption and melanoma risk, and the association between individual citrus products and melanoma risk, and to test for interactions between total citrus intake and established melanoma risk factors.Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between citrus consumption and melanoma risk among 1592 cases and 197 372 controls from the UK Biobank cohort. Citrus consumption data were collected via five rounds of 24-h recall questionnaires. International Classification of Diseases codes were used to determine melanoma outcome.After adjusting for potential confounders, participants in the highest category of total citrus intake (> 2 servings per day) had a significantly increased risk of melanoma (OR 1·63, 95% CI 1·24-2·12) relative to those with no consumption. For individual citrus products, participants with the most orange and orange juice consumption (> 1 serving per day) had a significantly increased melanoma risk relative to those with no consumption (OR 1·79, 95% CI 1·07-2·78 and OR 1·54, 95% CI 1·10-2·10, respectively). Fair- or very fair-skinned participants with high citrus consumption had an even greater melanoma risk (OR 1·75, 95% CI 1·31-2·29).High citrus consumption was associated with an increased risk of melanoma in a large, prospective, population-based cohort. Further validation of these findings could lead to improved melanoma prevention strategies.
The amino acid composition of actin and myosin and Ca2+-activated myosin adenosine triphosphatase in chronic canine congestive heart failure.
Authors: R RRaszkowski, J DWelty, M BPeterson
Journal: Circulation Research (1977)

The Ca2+-activated myosin ATPase and the amino acid compositions of actin and myosin were determined for preparations from chronically failing dog hearts. Hypertrophy and congestive heart failure were produced by combined tricuspid valve insufficiency and pulmonary artery stenosis. Control, shamoperated, and noncardiac circulatory failure (inferior vena cava constriction) dogs also were studied. All hearts were divided into right ventricle, septum and left ventricle and each sample was individually analyzed. Calcium-activated ATPase decreased in the failing hearts and showed a distinct gradient of depression from right to left ventricles. There were no changes in ATPase activity among the other groups. The amino acid composition of actin was the same regardless of origin. The amino acid composition of myosin was unaltered except that cystine/2 residues were markedly decreased in failing heart myosin. The same gradient of depression was present as was found for Ca2+-activated myosin ATPase. This study sugg...
In vivo thrombin inhibition enhances and sustains arterial recanalization with recombinant tissue-type plasminogen activator.
Authors: I KJang, H KGold, R CLeinbach, J TFallon, DCollen
Journal: Circulation Research (1990)

The effects of heparin and the synthetic competitive thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (Argatroban) on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) was studied in groups of six or seven rabbits with arterial thrombosis. The model consisted of a whole-blood clot produced in a 1-cm isolated femoral arterial segment with superimposed endothelial damage and distal high-grade stenosis. rt-PA was injected as an intravenous bolus of 0.45 mg/kg body wt at 15-minute intervals until recanalization, or up to a maximum of four boluses. In seven rabbits given an intravenous injection of 17 mg/kg aspirin, rt-PA induced transient reflow in only one animal. In seven rabbits that received intravenous heparin (200 units/kg over 60 minutes), rt-PA administration produced reflow in five animals, which was persistent in two rabbits. Combined administration of aspirin and heparin in seven rab...
Proposals for US National Health Insurance
Authors: V. Velanovich
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Aspirin and Cancer Risk
Authors: Luigi Zorcolo, Mario Scartozzi, Angelo Restivo
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Effects of adrenergic amines on electrophysiological properties and automaticity of neonatal and adult canine Purkinje fibers: evidence for alpha- and beta-adrenergic actions.
Authors: M RRosen, A JHordof, J PIlvento, PDanilo
Journal: Circulation Research (1977)

We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. Control spontaneous rates for adults and neonates did not differ significantly. There was a biphasic response to all agonists such that rate decreased at low and increased at high concentrations. The decrease was greater with phenylephrine and epinephrine than with isoproterenol. The increase in rate was greater with isoproterenol and epinephrine than with phenylephrine. Propranolol shifted the dose-response curves downward and to the right for all agonists; phentolamine, shifter the curves upward and to the left. Epinephrine and isoproterenol dose-response curves for the neonates were upward and to the left of those for adults. Phenylephrine curves were identical for adults and ...
Hemodynamic-inotropic response to beta-blocker with intrinsic sympathomimetic activity in patients with congestive cardiomyopathy.
Authors: P FBinkley, R FLewe, J JLima, AAl-Awwa, D VUnverferth, C VLeier
Journal: Circulation (1986)

The rest and exercise hemodynamic-inotropic response to administration of the beta-blocker pindolol was evaluated in 10 patients with congestive cardiomyopathy to determine whether the intrinsic sympathomimetic activity (ISA) of this agent may preserve ventricular function in the setting of beta-blockade. A significant (p less than .05) rise in systemic and pulmonary vascular resistance and a decline in stroke volume and cardiac index was observed after a single 10 mg dose. The change in cardiac index was negatively correlated with free drug concentration (r = -.59, p less than .01); the change in pulmonary and systemic vascular resistance showed a positive correlation with plasma concentration (r = .67, r = .57, respectively; all p less than .05). The response to exercise reflected a predominant beta-blocking effect, with a significant decrease in peak heart rate and cardiac index and an increase in pulmonary vascular resistance. There were no significant changes in variables of right or left ventricular...
Sex differences in the determinants of left ventricular mass in childhood. The Medical College of Virginia Twin Study.
Authors: M MGoble, MMosteller, W BMoskowitz, R MSchieken
Journal: Circulation (1992)

BACKGROUNDLeft ventricular (LV) hypertrophy is a predictor of cardiovascular events in adults and has been observed in children and adolescents with hypertension. We wanted to establish the determinants of LV mass in normotensive preadolescent children. Our objectives were 1) to produce a simplified and generalizable model of the clinical variables that determine normal cardiac growth during childhood and 2) to understand better why males have an increased LV mass relative to females, even as children.METHODS AND RESULTSIn a group of 243 eleven-year-old children, we analyzed anthropometric, hemodynamic, and echocardiographic data to define which variables were predictors of echocardiographically determined LV mass. Stepwise regression was used to predict LV mass overall, by sex, and by body size (body mass index). Overall, LV mass was directly related to weight, male sex, and systolic and diastolic blood pressure and inversely related to resting heart rate and skin-fold thicknesses. Systolic blood pressur...
Academic Leadership
Authors: Shadi A. Esfahani, Rathan M. Subramaniam
Journal: Clinical Nuclear Medicine (2021)

Abstract Culture of inclusion is of utmost need in today’s practice of radiology and nuclear medicine. This article briefly describes the importance of establishing and enriching the culture of embracing different talents, perspectives, and expertise with consideration of differences in sex, ethnic, color, and socioeconomic background toward building high-performance research and clinical practice teams in academic nuclear medicine and radiology.
Termination of ventricular tachycardia by single extrastimulation during the ventricular effective refractory period.
Authors: RRuffy, K JFriday, W FSouthworth
Journal: Circulation (1983)

Termination of ventricular tachycardia by low-energy shocks delivered during the ventricular refractory period has been reported. We describe a case of reproducible termination of multiple episodes of sustained ventricular tachycardia by a low-current extrastimulus delivered during the effective refractory period of the right ventricle, from the distal bipole of a quadripolar electrode catheter.
Mechanisms of automaticity in subsidiary pacemakers from cat right atrium.
Authors: D SRubenstein, S LLipsius
Journal: Circulation Research (1989)

Intracellular recordings were made from eustachian ridge of cat right atrium to determine mechanisms responsible for subsidiary pacemaker automaticity. Pacemaker action potentials exhibited two phases of diastolic depolarization: an initial steeper slope (D1) followed by a more gradual slope (D2). Cesium (1 mM) decreased D1 (-45.6%) to a significantly greater extent than D2 (-33.6%) and increased spontaneous cycle length (SCL) (+37.7%). Tetrodotoxin (10(-6) M) had no effect on maximum rate of rise of upstroke, although it increased SLC (+23.9%). Verapamil (0.4-1.0 microM) progressively increased SCL by decreasing late diastolic slope, resulting in oscillatory potentials and eventual quiescence. Both norepinephrine (2 x 10(-9) M) and Bay K 8644 (10(-7) M) elicited a significantly greater increase in D2 than in D1, resulting in a decrease in SCL. Ryanodine (10(-6) M) caused a small but significant initial decrease (-3.7%) followed by a progressive increase in SCL (+172%). Ryanodine decreased D2 without chan...