tbuckley/cabot-search huggingface dataset:
Alterations in carotid sinus reflex control of arterial hemodynamics associated with experimental hyperlipemia in the racing greyhound.
Authors: R HCox, R JBagshaw, D KDetweiler
Journal: Circulation Research (1980)

We administered a high cholesterol diet to racing greyhounds and studied its effects on the characteristics of carotid sinus reflex control of arterial pressure-flow relations. Dogs were anesthetized with halothane, and pressure and flow were simultaneously measured in the ascending aorta and the celiac, mesenteric, renal, and iliac arteries. The carotid sinuses were isolated bilaterally and perfused with a physiological salt solution under controlled conditions. The variation of regional pressure-flow relations and regional vascular resistance was assessed as a function of mean carotid sinus pressure (MCSP) with the vagi bilaterally sectioned to eliminate aortic arch afferents. Some differences were found in set point (i.e., MCSP = mean arterial pressure) values of hemodynamic variables; cardiac output and renal and iliac flows were significantly lower. Control and set point values of mean arterial pressure were not significantly different between the two groups. The variation of every hemodynamic variab...
Rat cardiac muscle single cell automaticity responses to alpha- and beta-adrenergic agonists and antagonists.
Authors: KHermsmeyer, RMason, S HGriffen, PBecker
Journal: Circulation Research (1982)

Isolated cardiac muscle cells from neonatal rat ventricular myocardium have both alpha- and beta-adrenergic, positive chronotropic responses, with sensitivity to applied adrenergic agents more than 100 times greater than the intact neonatal heart. These highly sensitive isolated single cells and small groups of cells also reveal partial agonist activity of the alpha-adrenergic antagonist, phentolamine, and the beta-adrenergic antagonist, propranolol. The most likely explanation for the high sensitivity is the lack of a desensitization process that could involve both a desensitization substance and changes in receptors. These experiments suggest that all adrenergic antagonists could possibly show partial agonist activity.
Pulmonary vasodilatory action of endogenous atrial natriuretic factor in rats with hypoxic pulmonary hypertension. Effects of monoclonal atrial natriuretic factor antibody.
Authors: BRaffestin, MLevame, SEddahibi, IViossat, PBraquet, P EChabrier, MCantin, SAdnot
Journal: Circulation Research (1992)

We administered ascitic fluid containing atrial natriuretic factor (ANF) monoclonal antibody to rats after 3 weeks of exposure to hypoxia while the rats were still hypoxic. In additional chronically hypoxic rats, we infused synthetic rat ANF. In conscious chronically instrumented rats, after a bolus dose of 5 micrograms i.v. ANF, pulmonary arterial pressure fell significantly from 26.5 +/- 2 to 21 +/- 2 mm Hg (p less than 0.01), reaching its nadir at 5 minutes without change of systemic arterial pressure, cardiac output, or heart rate. Pulmonary arterial pressure increased gradually from 26 +/- 4 to 34 +/- 4 mm Hg within 30 minutes (p less than 0.05) after acute administration of ANF monoclonal antibody and decreased transiently to return to baseline within 15 minutes after infusion of control ascitic fluid containing monoclonal antibody against an apolipoprotein. Cardiac output and heart rate remained unchanged after both ANF monoclonal antibody and control ascitic fluid. In normoxic rats, acute administ...
Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle.
Authors: C JCohen, H AFozzard, S SSheu
Journal: Circulation Research (1982)

Changes in stimulation rate alter the electrical and mechanical characteristics of myocardial cells. We have investigated the possibility that intracellular sodium activity (aiNa) changes with stimulation and correlates with changes in contraction strength. Two kinds of liquid membrane Na+-selective microelectrodes were used to measure aiNa in guinea pig and sheep ventricular muscle and in sheep Purkinje strands. Stimulation produced a rate- and time-dependent elevation of aiNa. Small increases in aiNa were seen at stimulation rates as slow as 0.2 Hz, and faster rates of stimulation elevated aiNa by over 30%. The changes seen in Purkinje strands and ventricular muscle were similar. Following a period of stimulation, aiNa and Vm returned to their pre-stimulus levels with the same time courses. This is consistent with the suggestion that the post-stimulation hyperpolarization is the result of an increased rate of electrogenic Na+ extrusion. The effects of stimulation on aiNa and tension were compared with t...
TCTAP A-022 The Impact of Side Branch Dilatation for the Treatment of Bifurcations: An In Vitro Study
Authors: Jaryl Ng, Valeria Paradies, Shengjie Lu, Georgios Vlachojannis, Hwa Liang Leo, Philip Wong, Nicolas Foin, Hui Ying Ang
Journal: Journal of the American College of Cardiology (2021)
Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers.
Authors: J LFleg, GGerstenblith, A BZonderman, L CBecker, M LWeisfeldt, P TCosta, E GLakatta
Journal: Circulation (1990)

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardi...
The role of vascular capacitance in the coronary arteries.
Authors: JLee, D EChambers, SAkizuki, J MDowney
Journal: Circulation Research (1984)

When the left coronary artery was perfused with nonpulsatile pressure, the onset of diastole was accompanied by a capacitance overshoot in flow with an exponential decay back to a steady state. Time constant for that decay ranged from 55 msec when tone was present to 105 msec with maximal dilation. Since the transient resulted from a fall in tissue pressure, this represents an estimation of intramural arterial capacitance only. Transients in perfusion pressure, which would also affect epicardial arteries, yielded similar time constants. We concluded that most of the coronary capacitance resides in the small intramural vessels. Analysis of transients yielded a value for capacitance of between 0.01 and 0.05 ml/mm Hg per 100 g. We then used the data from the transients to construct coronary pressure flow curves which were free of any back flow from capacitance. When coronary tone was present, the curves indicated that flow ceased at 30 mm Hg. With maximal dilation, flow ceased at only 18 mm Hg. Long diastole...
Ibrutinib Inhibits VLA-4–Dependent Adhesion in CLL—Reply
Authors: Sarah E.M. Herman, Adrian Wiestner
Journal: Clinical Cancer Research (2016)

We thank Zucchetto and colleagues for their valuable comments on our article (1). They make two points: first, in their hands, in contrast to our report, inhibition of integrin β-1 (CD29) and integrin α-4 (CD49d) was equally effective in reducing chronic lymphocytic leukemia (CLL) cell adhesion. Repeating our original assay (Fig. 5B) with three anti-CD29 antibodies (clones: 4B7R, P5D2, and P4G11; R&D Systems), we found that our experiments may have underestimated the effect of CD29 blockade on cell adhesion, confirming the findings by Zucchetto and colleagues. However, for each of the clones, there was considerable interpatient and interclonal variability in the effect size.Second, Zucchetto and colleagues note that ibrutinib in vitro reduced but did not abolish adhesion. The results of in vitro assays presented in our Supplementary Fig. S2A and S2B are in agreement with this conclusion (1). In contrast, in vivo, ibrutinib abrogated the ability of CLL cells to adhere to fibronectin as measured in ex vivo assays with cells obtained from patients on day 28 of ibrutinib treatment (Fig. 2A and B; ref. 1). This appears to be the result of cumulative drug exposure, given that adhesion of cells collected on day 2, after just one dose of ibrutinib, was only partially inhibited (1). Thus, treatment with ibrutinib in vivo has a much stronger inhibitory effect on cell adhesion then captured by experiments (both ours and Zucchetto and colleagues') that drug cells in vitro.We used samples from patients treated with single-agent ibrutinib to investigate the basis for our previous observation that upon starting ibrutinib treatment, most patients develop a transient rise in absolute lymphocyte count that is due to the release of cells from the lymph node (2). VLA-4–dependent adhesion is regulated by chemokines and B-cell receptor (BCR) signaling, referred to as “inside-out signaling,” affecting both conformation (PKC/DAG dependent) and substrate affinity (IP3/Ca+ dependent) of the integrin (3). BCR signaling and chemokine binding occur primarily in the microenvironment of the secondary lymphoid tissues. In vivo, ibrutinib potently inhibits BCR and chemokine signaling (4, 5). We posit that sustained in vivo inhibition of inside-out signaling leads to more profound changes in VLA-4 function than short-term drugging of cells in vitro, resulting in a more profound reduction in integrin-mediated adhesion. Future experiments could address this hypothesis and we thank Zucchetto and colleagues for suggesting a tool that could be used to evaluate changes in VLA-4 confirmation and affinity.See the original Letter to the Editor, p. 3410A. Wiestner reports receiving a commercial research grant from Acerta Pharmaceuticals and Pharmacyclics. No potential conflicts of interest were disclosed by the other author.This research was supported by the Intramural Research Program of the National, Heart, Lung, and Blood Institute. A. Wiestner received research funding from Pharmacylics.
Chemoprevention of Prostate Cancer
Authors: Goutham Vemana, Robert J. Hamilton, Gerald L. Andriole, Stephen J. Freedland
Journal: Annual Review of Medicine (2013)

Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence.
Importance of intraluminal pressure on hemodynamics and vasoconstriction responses of stenotic arteries.
Authors: MGhods, RMangal, A SIskandrian, W PSantamore
Journal: Circulation (1992)

BACKGROUNDClinical and morphological studies clearly indicate that most human coronary artery stenoses are capable of vasomotion. Variable ischemic thresholds, ischemia unrelated to work load, and variant angina further show the presence and importance of vasoconstriction in coronary artery stenosis. Despite the importance of vasoconstriction, the effect of intraluminal pressure on the hemodynamic response to vasoconstrictors has not yet been examined. Intraluminal pressure is a primary determinant of vessel size and the force opposing vasoconstriction. Accordingly, we examined the effects of intraluminal pressure on the hemodynamic response to norepinephrine (NE)-induced vasoconstriction.METHODS AND RESULTSIn canine carotid arteries perfused with physiological salt solution, pressures at the proximal and distal ends of the artery, as well as flow, were continuously recorded. We altered intraluminal pressure using three diverse interventions: changes in perfusion pressure, decreasing distal resistance, an...
MEDICAL WRITING AND MEDICAL EDUCATION
Journal: JAMA (1965)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Gap junction protein connexin40 is preferentially expressed in vascular endothelium and conductive bundles of rat myocardium and is increased under hypertensive conditions.
Authors: BBastide, LNeyses, DGanten, MPaul, KWillecke, OTraub
Journal: Circulation Research (1993)

Gap junction channels consisting of connexin protein mediate electrical coupling between cardiac cells. Expression of two connexins, connexin40 (Cx40) and connexin43 (Cx43), has been studied in ventricular myocytes from normal and hypertensive rats. Polyclonal affinity-purified rabbit antibodies to Cx43 and Cx40 have been used for immunohistochemical analysis on frozen sections from rat heart. These studies revealed coexpression of Cx43 and Cx40 in ventricular myocytes. In addition, Cx40 is preferentially expressed in three distinct regions: first, in the endothelial layer of the heart blood vessels but not in the smooth muscle layer of the arteries; second, in the ventricular conductive myocardium, particularly in the atrioventricular bundle and bundle branches, where Cx43 is not observed; and third, in the myocyte layers close to the ventricular cavities. These results suggest that Cx40 is preferentially expressed in the fast conducting areas of myocardial tissue. Expression of both Cx40 and Cx43 was al...
Circadian Effects of Drug Responses
Authors: Yaakov Nahmias, Ioannis P. Androulakis
Journal: Annual Review of Biomedical Engineering (2021)

Circadian rhythms describe physiological systems that repeat themselves with a cycle of approximately 24 h. Our understanding of the cellular and molecular origins of these oscillations has improved dramatically, allowing us to appreciate the significant role these oscillations play in maintaining physiological homeostasis. Circadian rhythms allow living organisms to predict and efficiently respond to a dynamically changing environment, set by repetitive day/night cycles. Since circadian rhythms underlie almost every aspect of human physiology, it is unsurprising that they also influence the response of a living organism to disease, stress, and therapeutics. Therefore, not only do the mechanisms that maintain health and disrupt homeostasis depend on our internal circadian clock, but also the way drugs are perceived and function depends on these physiological rhythms. We present a holistic view of the therapeutic process, discussing components such as disease state, pharmacokinetics, and pharmacodynamics, as well as adverse reactions that are critically affected by circadian rhythms. We outline challenges and opportunities in moving toward personalized medicine approaches that explore and capitalize on circadian rhythms for the benefit of the patient.
Response to “Reply to effectiveness of dutasteride in a large series of patients with FFA in real clinical practice”
Authors: Cristina Pindado-Ortega, David Saceda-Corralo, Óscar M. Moreno-Arrones, Ana R. Rodrigues-Barata, Ángela Hermosa-Gelbard, Pedro Jaén-Olasolo, Sergio Vañó-Galván
Journal: Journal of the American Academy of Dermatology (2021)
Effect of positive expiratory pressure breathing in patients with cystic fibrosis.
Authors: M S Zach, B Oberwaldner
Journal: Thorax (1992)

Body composition and exercise per- formance in patients with chronic ob- structive pulmonary disease (COPD)The original article ofDr A M W J Schols and others in the October issue of Thorax' shows that exercise performance, as indicated by the distance walked in 12 minutes, is related to the fat free mass of the patient.Fat free mass was taken to be an indicator of muscle mass, but the investigators found that arm muscle size was not well related to other measures of muscle mass.Several possible reasons for the relation- ship, two of which were related to respiratory muscle performance, were considered.There are, however, two other obvious possibilities.Firstly, muscle loss may well be from the lower limbs.If this were so, then exercise capacity could be reduced because of the smaller capacity for this type of exercise, irrespective of respiratory muscle function.Secondly, the patients who performed badly might take little regular exercise, or indeed may be limited by their symptoms in their exercise.Such patients would display lower limb muscle wasting.Consequently, performance may be related to muscle mass (particularly in the legs) by loss of activity.In the clinical evaluation of patients who are housebound with severe lung or cardiac dis- ease wasting of the quadriceps femoris and calf muscles is often a striking feature.Dr Schols and his colleagues suggest that a compromised nutritional state may con- tribute to impaired performance, and that muscle mass determines exercise performance.Unwary readers may be led to conclude that patients do badly because of malnutrition, or even that improved nutrition might be beneficial.This is not necessarily so.Correlation does not indicate cause and effect: even if there is such a relationship, which is cause and which is effect may not be self evident.
Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris.
Authors: MPine, LFavrot, SSmith, KMcDonald, C AChidsey
Journal: Circulation (1975)

The therapeutic response to propranolol was evaluated in patients with documented coronary artery disease at doses varying from 40 to 320 mg/day. Therapeutic response was quantified by evaluating exercise performance on a treadmill and then related to plasma propranolol concentration. Plasma propranolol was defined in terms of beta-adrenergic blockade by comparison with dose (concentration) response curves in normal subjects. Individual therapeutic benefit occurred at doses which averaged 144 +/- 21 mg/day and at concentrations which averaged 30 +/- 7 ng/ml. There was a wide variation between both dose and concentration among the patients at maximum therapeutic response, but when the plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 to 98% of total blockade. Despite the increased exercise performance in these patients, the double product of heart rate and systolic blood pressure was always less, suggesting either an alteration of the relatio...
Role of adenosine in coronary vasodilation during exercise.
Authors: R JBache, X ZDai, J SSchwartz, D CHomans
Journal: Circulation Research (1988)

This study examined the hypothesis that increases in myocardial blood flow during exercise are mediated by adenosine-induced coronary vasodilation. Active hyperemia associated with graded treadmill exercise and coronary reactive hyperemia were examined in chronically instrumented awake dogs during control conditions, after intracoronary infusion of adenosine deaminase (5 units/kg/min for 10 minutes), and after adenosine receptor blockade with 8-phenyltheophylline. Both adenosine deaminase and 8-phenyltheophylline caused a rightward shift of the dose-response curve to intracoronary adenosine; 8-phenyltheophylline was significantly more potent than adenosine deaminase. Adenosine deaminase caused a 33 +/- 7 to 39 +/- 3% decrease in reactive hyperemia blood flow following coronary occlusions of 5-20 seconds duration, respectively, while 8-phenyltheophylline produced a 40 +/- 6 to 62 +/- 8% decrease in reactive hyperemia. Increasing myocardial oxygen consumption during treadmill exercise was associated with pr...
Selecting optimal patients with gastroparesis for G-POEM procedure
Authors: Ting Zheng, Michael Camilleri
Journal: Gut (2021)

In a very welcome article, Vosoughi and colleagues1 describe the experience from five tertiary centres (four in the USA, one in Brazil) regarding the outcomes of the gastric peroral endoscopic myotomy (G-POEM) procedure for the treatment of 80 patients with symptomatic gastroparesis refractory to standard medical therapy and confirmed by impaired gastric emptying (gastric retention >20% at 4 hours). The primary endpoint was clinical success, defined as at least one score decrease in the Gastroparesis Cardinal Symptom Index (GCSI) with ≥25% decrease in two subscales at 12 months. From this open-label, uncontrolled experience, the authors concluded that G-POEM was only modestly effective in patient with gastroparesis, with a clinical success rate of 56% at 12 months. However, serial assessment documented that the response to G-POEM was durable over the 12-month follow-up. This study also identified that baseline GCSI score >2.6 and baseline gastric retention greater than 20% at 4 hours, as well as responsiveness 1 month after the G-POEM procedure were independent predictors of clinical success 12 months after G-POEM.

The study has many strengths including the sample size of 80, of which 94% had completed 12-month follow-up, use of the validated GCSI score and subscales, and assessment of quality of life, using the 36-Item Short Form Questionnaire, at baseline and 1, 3, 6 …
Mechanism of normal splitting of the second heart sound.
Authors: E ICurtiss, R GMatthews, J AShaver
Journal: Circulation (1975)

The mode of inspiratory augmentation (1A) of the A2-P2 interval was investigated in seven normal volunteers (group 1) and six patients with pulmonary hypertension of diverse etiology (group 2) using catheter-tip micromanometers. In group 1 subjects, inspiratory widening of this interval was found to average 27.2 msec, of which 7.6 plus or minus 2.7 msec (1 sd) or 27 plus or minus 7% was due to a decrease in the Q-A2 interval. The major contribution of Q-P2 interval prolongation was divided into two components: a) Q-O was measured from the onset of the QRS to the onset of the rapid descent of the right ventricular (RV) negative dp/dt, which was felt to reflect the duration of RV electromechanical systole, b) O-P2 or Q-P2 - Q-O. Increase in the Q-O interval accounted for only 7.7 plus or minus 5.0 msec or 28 plus or minus 12% of the total IA. The major single component of IA was the increase in O-P2 which averaged 11.9 plus or minus 3.0 msec. Five of six group 2 patients demonstrated significant respiratory...