tbuckley/cabot-search huggingface dataset:
Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure.
Authors: R DMagorien, C VLeier, A JKolibash, T JBarbush, D VUnverferth
Journal: Circulation (1984)

Rest and exercise systemic hemodynamic parameters, coronary blood flow, and myocardial energetics were assessed before and 15 min after the sublingual administration of 20 mg of nifedipine in 10 patients with idiopathic congestive cardiomyopathy. When compared with control, nifedipine increased rest and exercise cardiac index by 37% and 28%, respectively (p less than .001). Peripheral vasodilation was demonstrated with a drop in systemic arterial pressure, exercise pulmonary capillary wedge pressure, and systemic vascular resistance (p less than .05). The calcium-channel blocker did not alter myocardial oxygen consumption; however, coronary blood flow increased by 32% at rest (p less than .01) while coronary vascular resistance diminished both at rest and after exercise compared with control (p less than .05). Nifedipine elicited a decrease in the rest and exercise aortocoronary sinus oxygen difference while the coronary sinus oxygen saturation increased (p less than .01). In this group of patients with i...
Volume-pressure analysis of reflex changes in forearm venous function. A method by mental arithmetic stress and radionuclide plethysmography.
Authors: V JRobinson, D EManyari, J VTyberg, G HFick, E RSmith
Journal: Circulation (1989)

Mental arithmetic stress is known to cause forearm arterial dilation, but the venous responses, including possible changes in the volume-pressure relation, have not been defined. Hence, 10 apparently normal subjects, eight men and two women, mean age 46 +/- 9 years, were studied before and during mental arithmetic stress. Changes in forearm venous volume were estimated with 99mTc blood pool scintigraphy. Group variability of this measurement technique was 1.8 +/- 2.3%. A brachial blood pressure cuff was used to obtain venous occluding pressures of 0, 10, 20, and 30 mm Hg. Mental arithmetic stress increased group systolic and diastolic blood pressure from 126 +/- 12 to 152 +/- 20 mm Hg and from 83 +/- 8 to 93 +/- 15 mm Hg, respectively (p less than 0.001). Heart rate increased from a mean of 75 +/- 15 to 85 +/- 17 beats/min (p less than 0.01). There was no evidence of interaction between or nonlinearity of the volume-pressure plots. Linear regression then yielded the equations V = 99.8 + 0.96P before and V...
Regulation of myosin heavy chain genes in the heart.
Authors: EMorkin
Journal: Circulation (1993)

Advances in our knowledge of the regulation of cardiac myosin isoforms made possible by molecular cloning of the alpha- and beta-MHCs genes are reviewed. Expression of these genes in heart does not seem to require MyoD or related proteins of the skeletal muscle myogenic program. Cardiac MHC genes are under the control of T3, which stimulates transcription of the alpha-MHC gene and inhibits beta-MHC mRNA production both in vivo and in cultured heart cells. The responsiveness of the genes to T3 varies in different mammals, however. The genes are most responsive in rat and rabbit, intermediate in sensitivity in calf and subhuman primate (baboon), and very resistant in the dog. The human alpha-MHC gene is T3-inducible in ventricle, but the degree of response has not been quantified. Introduction of chimeric plasmids containing 5' flanking sequences of cardiac MHC genes fused to the CAT gene into cultured heart cells and transgenic animals has permitted identification of regulatory elements. Although the genes...
Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients.
Authors: H RMiddlekauff, W GStevenson, L WStevenson
Journal: Circulation (1991)

BACKGROUNDAtrial fibrillation is common in advanced heart failure, but its prognostic significance is controversial.METHODS AND RESULTSWe evaluated the relation of atrial rhythm to overall survival and sudden death in 390 consecutive advanced heart failure patients. Etiology of heart failure was coronary artery disease in 177 patients (45%) and nonischemic cardiomyopathy or valvular heart disease in 213 patients (55%). Mean left ventricular ejection fraction was 0.19 +/- 0.07. Seventy-five patients (19%) had paroxysmal (26 patients) or chronic (49 patients) atrial fibrillation. Compared with patients with sinus rhythm, patients with atrial fibrillation did not differ in etiology of heart failure, mean pulmonary capillary wedge pressure on therapy, or embolic events but were more likely to be receiving warfarin and antiarrhythmic drugs and had a slightly higher left ventricular ejection fraction. After a mean follow-up of 236 +/- 303 days, 98 patients died: 56 (57%) died suddenly, and 36 (37%) died of prog...
Research related to medical treatment of cardiovascular disease.
Authors: R SRoss
Journal: Circulation (1979)

Medical treatment of heart disease has improved significantly in the past 30 years. The spectacular change in the natural history of rheumatic heart disease is apparent from a 1948 article that reported that 42% of children with rheumatic heart disease died of rheumatic infection or bacterial endocarditis. Antibiotics and cardiac surgery have improved the outcome from rheumatic heart disease. Cardiopulmonary resuscitation has had a major impact on the treatment of myocardial infarction and on the management of sudden death. The fundamental principle underlying the discovery of cardiopulmonary resuscitation is reviewed, and recent developments emphasizing the importance of intrathoracic pressure in the hemodynamics of cardiopulmonary resuscitation are highlighted. The important new drugs of the last 30 years include the oral diuretics, the antihypertensives and the antiarrhythmic agents. The development of the beta-blocking agents is cited as an example of the translation of basic physiological research to...
Role of angiotensin II in the altered renal function of congestive heart failure.
Authors: IIchikawa, J MPfeffer, M APfeffer, T HHostetter, B MBrenner
Journal: Circulation Research (1984)

Glomerular and tubule functions were assessed by micropuncture in rats with extensive myocardial infarction produced by ligation of the left coronary artery 4 weeks prior to study. When compared to sham-operated control rats, rats with myocardial infarction involving 40 +/- 4% of the left ventricular circumference had lower mean arterial pressure (96 +/- 5 vs. 122 +/- 4 mm Hg, P less than 0.005), and higher left ventricular end-diastolic pressure (24 +/- 3 vs. 5 +/- 0 mm Hg, P less than 0.001). Renal cortical microcirculatory dynamics of rats with myocardial infarction were characterized by reduced glomerular plasma flow rate (75 +/- 8 vs. 165 +/- 17 nl/min, P less than 0.005), but a proportionately lesser decline in single nephron glomerular filtration rate (28.0 +/- 2.8 vs. 41.7 +/- 3.1 nl/min, P less than 0.025), accounting for the observed rise in single nephron filtration fraction (0.38 +/- 0.02 vs. 0.25 +/- 0.02, P less than 0.005). These renal hemodynamic alterations in myocardial-infarcted rats we...
Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts
Authors: Qian Zhang, Larry D. Mesner, Gina M. Calabrese, Naomi Dirckx, Zhu Li, Angela Verardo, Qian Yang, Robert J. Tower, Marie-Claude Faugere, Charles R. Farber, Thomas L. Clemens
Journal: Journal of Clinical Investigation (2021)

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.
The incidence and clinical implications of coronary artery spasm.
Authors: R AChahine, A ERaizner, TIshimori, R JLuchi, H DMcIntosh
Journal: Circulation (1975)

The total incidence of coronary artery spasm during coronary angiography has been reported to be between 0.26% and 0.93%. The rarity of this phenomenon has been invoked to minimize its clinical significance. Review of a one-year experience in our catheterization laboratory showed that coronary spasm occurred in eight of 274 coronary angiograms (2.93%). In three instances, spasm could not be ascribed to catheter tip irrigation, and was considered to be spontaneous. Since multiple factors during coronary arteriography might inhibit the occurrence of coronary spasm, it is believed that the incidence of spontaneous spasm may be higher than can be documented during angiography. Coronary spasm may have important clinical significance in various chest pain syndromes and greater methodical attention should be directed toward this phenomenon.
Abstract 16957: Ascending Thoracic Aortic Aneurysm Wall Stresses Evolve in Parallel With Diameter Growth
Authors: Arushi Gulati, Zhongjie Wang, Yue XUAN, JOSEPH LEACH, Michael D Hope, David Saloner, Julius Guccione, Liang Ge, Elaine E Tseng
Journal: Circulation (2020)

Introduction: Guidelines for ascending thoracic aortic aneurysm (ATAA) repair use ATAA diameter, with repair recommended at ≥5.5cm, but ATAA biomechanics may better predict acute type A dissection (ATAD) risk. However, little is known regarding changes in wall stresses among clinically followed patients with &lt;5.5cm ATAA over time. This information is important for patient risk stratification. Hypothesis: We hypothesized that peak ATAA wall stresses would change over time in a patient-specific fashion alongside diameter. Methods: 31 nonsurgical ATAA patients (&lt;5.5cm and growth &lt;0.5cm/year) with computed tomography angiography (CTA) scans taken 3 to 5 years apart were identified. Images were used to construct patient specific three-dimensional ATAA models. Peak diastolic circumferential stresses were determined along the ascending aorta (AA), sinotubular junction (STJ), and aortic sinuses using finite element analysis. Diameters at both time points were measured from CTA scans by a single radiologist blinded to stress results. Stress and diameter distributions were compared using paired t-tests. Results: In the overall population, ATAA diameter increased over time (4.39±0.4 cm vs. 4.43±0.4 cm, p=0.02), while diastolic circumferential stresses along the aorta did not significantly change. However, we found two distinct patient groups: one where wall stresses increased and one where stresses decreased over time. Separate analysis of these groups showed significant changes in circumferential stress in all three aortic regions (488 ± 120 vs. 340 ± 63 kPa for the sinuses, 472 ± 127 vs 345 ± 76 kPa for the STJ and 337 ± 54 vs 277 ± 28 kPa for AA, p&lt;0.001), and significant increase in diameter in the group with increasing stresses (p=0.02). Conclusions: In this nonsurgical group, there is no statically significant change of peak ATAA wall stresses at diastole over 3-5 years. The patients with increased stress were found to be associated with increases in diameter during the corresponding time period. More patient specific data is required to investigate the interaction between wall biomechanics and aortic remodeling. Our results lay the foundation for developing patient-specific ATAD risk predictors for ATAD using patient-specific wall stress changes.
Abstract 2638: The Factor VII Activating Protease (FSAP) Polymorphism (G534E) Is Associated With An Increased Risk For Stroke And Mortality
Authors: Douwe Pons, Sandip M Kanse, Stella Trompet, J. Wouter Jukema
Journal: Circulation (2008)

FSAP is a plasma serine-protease that is localized within atherosclerotic lesions. The FSAP-Marburg I polymorphism (G534E) has been shown to be associated with late complications of carotid stenosi...
The incidental malignant melanoma.
Authors: B E Monk, M I Clement, A C Pembroke, A du Vivier
Journal: BMJ (1983)

The value of the general medical examination in the early recognition of asymptomatic disease is now universally appreciated.'Yet in such schemes of examination the skin, the largest organ of the body and the one most readily accessible to direct inspection, is almost invariably neglected.'In the past year we have seen five patients in the skin department at this hospital in whom superficial malignant melanoma was diagnosed inci- dentally to the patient's presenting complaint.A further such patient was seen by the ear, nose, and throat department.We consider that a thorough examination of the skin is an essential part of the general medical examination and that it will lead to more cases of this potentially lethal tumour being recognised early and treated effectively. Case reportsCase 1-A 48 year old woman was referred with a fungal infection of the foot and a secondary toxic erythema of the trunk and limbs.On general examination she was found to have a deeply pigmented lesion 0-5 cm in diameter on her back which she said had been there all her life.Histological examination of the excised lesion con- firmed the clinical diagnosis of superficial malignant melanoma.Case 2-A 26 year old woman presented with a histiocytoma on the right thigh.On examination she was found also to have a deeply pigmented lesion on the back of the left calf, of which she was un- aware.The lesion was excised and the clinical diagnosis of superficial malignant melanoma was confirmed histologically.
Analysis of flow characteristics in poststenotic regions of the human coronary artery during bypass graft surgery.
Authors: FKajiya, KTsujioka, YOgasawara, YWada, SMatsuoka, SKanazawa, OHiramatsu, STadaoka, MGoto, TFujiwara
Journal: Circulation (1987)

Poststenotic blood flow velocities were evaluated in nine patients with 75% to 99% stenosis of the left anterior descending coronary artery (LAD) during coronary artery bypass graft surgery. We used the 20 MHz 80-channel pulsed Doppler velocimeter developed in our laboratory. An operator placed a specially designed probe on the native LAD with his fingers. Before induction of extracorporeal circulation, LAD blood velocities were measured at several locations distal to the stenosis. The poststenotic flow velocities were rich in systolic flow component with reduced diastolic component. The velocity configuration in the poststenotic portions was characterized by the presence of reverse flow velocities and/or irregularity of the velocity pattern near the vessel wall, indicating the existence of flow separation and recirculation in the regions. The broadening of the velocity spectrum observed at central axial regions suggested the occurrence of flow disturbances. After grafting, the velocity waveform in the LA...
Estimated Projection of US Cancer Incidence and Death to 2040
Authors: Lola Rahib, Mackenzie R. Wehner, Lynn M. Matrisian, Kevin T. Nead
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Coping with the current and future burden of cancer requires an in-depth understanding of trends in cancer incidences and deaths. Estimated projections of cancer incidences and deaths will be important to guide future research funding allocations, health care planning, and health policy efforts. <h3>Objective</h3> To estimate cancer incidences and deaths in the United States to the year 2040. <h3>Design and Setting</h3> This cross-sectional study's estimated projection analysis used population growth projections and current population-based cancer incidence and death rates to calculate the changes in incidences and deaths to the year 2040. Cancer-specific incidences and deaths in the US were estimated for the most common cancer types. Demographic cancer-specific delay-adjusted incidence rates from the Surveillance, Epidemiology, and End Results Program were combined with US Census Bureau population growth projections (2016) and average annual percentage changes in incidence and death rates. Statistical analyses were performed from July 2020 to February 2021. <h3>Main Outcomes and Measures</h3> Total cancer incidences and deaths to the year 2040. <h3>Results</h3> This study estimated that the most common cancers in 2040 will be breast (364 000 cases) with melanoma (219 000 cases) becoming the second most common cancer; lung, third (208 000 cases); colorectal remaining fourth (147 000 cases); and prostate cancer dropping to the fourteenth most common cancer (66 000 cases). Lung cancer (63 000 deaths) was estimated to continue as the leading cause of cancer-related death in 2040, with pancreatic cancer (46 000 deaths) and liver and intrahepatic bile duct cancer (41 000 deaths) surpassing colorectal cancer (34 000 deaths) to become the second and third most common causes of cancer-related death, respectively. Breast cancer (30 000 deaths) was estimated to decrease to the fifth most common cause of cancer death. <h3>Conclusions and Relevance</h3> These findings suggest that there will be marked changes in the landscape of cancer incidence and deaths by 2040.
A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation.
Authors: C HLuo, YRudy
Journal: Circulation Research (1994)

The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both the Na(+)-Ca2+ exchanger (INaCa) and a nonspecific Ca(2+)-activated current (Ins(Ca)). The relative contributions of INaCa and of Ins(Ca) to the generation of DADs are different under different degrees of Ca2+ overload. Early afterdepolarizations (EADs) can be categorized into two types: (1) plateau EADs, resulting from a secondary activation of the L-type Ca2+ current during the plateau of an action potential, and (2) phase-3 EADs, resulting from activation of INaCa and Ins(Ca) by increased [Ca2+]i due to spontaneous Ca2+ release from the SR during the late repolarization phase. Spontaneous rhythmic activity and triggered activity are caused by spontaneous Ca2+ release from the SR under con...
Abnormal laterality and congenital cardiac anomalies. Relations of visceral and cardiac morphologies in the iv/iv mouse.
Authors: J WSeo, N ABrown, S YHo, R HAnderson
Journal: Circulation (1992)

BACKGROUNDIn the management of hearts with deranged laterality, it is essential that the left and right atrial chambers are correctly identified. There are two major approaches, which are based on venous connections or on the morphology of the atrial appendages, and there is no consensus as to which is the most useful. We used the iv/iv mouse mutant, which is known to be pertinent to this problem, to evaluate the relations of cardiac defects with atrial, venous, and other visceral morphologies.METHODS AND RESULTSThe morphology of the heart and other organs was examined in 275 iv/iv mice using criteria based on abnormal laterality in humans. The arrangement of the atrial appendages was determined by morphological examination of the junction between the appendage and the venous component of the atrium. On this basis, 45.1% of cases were shown to have usual atrial arrangement, 50.2% had mirror imagery, 1.5% had right isomerism, and 3.3% had left isomerism. Every case of atrial isomerism had a cardiac lesion;...
Phase resetting and entrainment of pacemaker activity in single sinus nodal cells.
Authors: J MAnumonwo, MDelmar, AVinet, D CMichaels, JJalife
Journal: Circulation Research (1991)

The phase-resetting and entrainment properties of single pacemaker cells were studied using computer simulations in a model of the rabbit sinus nodal cell, as well as using the whole-cell patch-clamp (current-clamp) technique in isolated rabbit sinus nodal cells. Spontaneous electrical activity in the cell model was reconstructed using Hodgkin-Huxley-type equations describing time- and voltage-dependent membrane currents. In both simulations and experiments, single subthreshold current pulses (depolarizing or hyperpolarizing) were used to scan the spontaneous cycle of the cells. Such pulses perturbed the subsequent discharge, producing temporary phasic changes in pacemaker period, and enabled the construction of phase response curves. On the basis of these results, we studied entrainment characteristics of the cells. For example, application of repetitive pulses allowed for phasic changes in the spontaneous cycle and resulted in stable 1:1 entrainment at a range of basic cycle length around the spontaneou...
Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals
Authors: Andrew Bakshi, Mabel Yan, Moeen Riaz, Galina Polekhina, Suzanne G Orchard, Jane Tiller, Rory Wolfe, Amit Joshi, Yin Cao, Aideen M McInerney-Leo, Tatiane Yanes, Monika Janda, H Peter Soyer, Anne E Cust, Matthew H Law, Peter Gibbs, Catriona McLean, Andrew T Chan, John J McNeil, Victoria J Mar, Paul Lacaze
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest. Methods We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12 712 individuals in the ASPirin in Reducing Events in the Elderly Trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed preenrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per SD) and categorical (low-risk [0%-20%], medium-risk [21%-80%], high-risk [81%-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma. Results At baseline, mean participant age was 75 years; 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20 to 1.77) and prevalent melanoma (odds ratio [OR] = 1.55 per SD, 95% CI = 1.42 to 1.69). Participants in the highest-risk PRS group had increased risk compared with the low-risk group for incident melanoma (OR = 2.51, 95% CI = 1.28 to 4.92) and prevalent melanoma (OR = 3.66, 95% CI = 2.69 to 5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma. Conclusions A genomic risk score is associated with melanoma risk in older individuals and may contribute to targeted surveillance.