tbuckley/cabot-search huggingface dataset:
Collagen-stimulated human platelet aggregation is mediated by endogenous calcium-activated neutral protease.
Authors: TToyo-oka, W SShin, YOkai, YDan, MMorita, MIizuka, TSugimoto
Journal: Circulation Research (1989)

To clarify the physiological role of calcium-activated neutral protease (CANP) in human platelets, we loaded the platelets with a Ca2+ -sensitive fluorescent dye, fura-2, and measured the degree of aggregation, cytosolic calcium ion concentration [( Ca2+]i), and proteolysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). At physiological concentration of Ca2+ (1 mM) in the incubation medium, [Ca2+]i was below 0.5 microM and platelet aggregation was not shown. Ionomycin (0.15 microM) or collagen (50 micrograms/ml), but not ADP (10 microM), sharply enhanced the [Ca2+]i to near 1 microM and caused the aggregation. A calcium entry blocker, verapamil, completely abolished both the [Ca2+]i rise and the aggregation. NCO-700, a membrane permeable inhibitor against cysteine proteases (including CANP), dose-dependently blocked the aggregation but did not change the [Ca2+]i transient. SDS-PAGE revealed that filamin, talin, and 70 kDa protein were specifically degraded when platelets were agg...
Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials
Authors: Zi-Xian Wang, Hao-Xiang Wu, Li Xie, Wu-Hao Lin, Fei Liang, Jin Li, Zhi-Min Yang, Rui-Hua Xu
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Progression-free survival (PFS) exhibits suboptimal performance as the surrogate endpoint for overall survival (OS) in trials studying immune checkpoint inhibitors (ICIs). Here we propose a novel surrogate endpoint, modified PFS (mPFS), which omits the events of disease progression (but not deaths) within 3 months after randomization. Methods PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized trials studying ICIs in advanced solid tumors with available PFS and OS data up to May 2020. Individual patient-level data (IPD) for PFS and OS were reconstructed for eligible trials. A simulation-based algorithm was used to match the reconstructed, disconnected PFS and OS IPD, and 1000 independent simulated datasets of matched PFS-OS IPD were generated for each trial. mPFS durations and statuses were then measured for each of the matched PFS-OS IPD. Trial-level correlation between Cox HRs for PFS or mPFS and HRs for OS was assessed using Pearson correlation coefficient (r p ) weighted by trial size; patient-level correlation between PFS or mPFS and OS was assessed using Spearman’s rank correlation coefficient (r s ). Findings were further validated using the original IPD from two randomized ICI trials. Results Fifty-seven ICI trials totaling 29,429 participants were included. PFS HR showed moderate correlation with OS HR (r p =0.60), and PFS was moderately correlated with OS at the patient level (median r s =0.66; range, 0.65–0.68 among the 1000 simulations). In contrast, mPFS HR achieved stronger correlation with OS HR (median r p =0.81; range, 0.77–0.84), and mPFS was more strongly correlated with OS at the patient level (median r s =0.79; range, 0.78–0.80). The superiority of mPFS over PFS remained consistent in subgroup analyses by cancer type, therapeutic regimen, and treatment setting. In both trials with the original IPD where experimental treatment significantly improved OS, mPFS successfully captured such clinical benefits whereas PFS did not. Conclusions mPFS outperformed PFS as the surrogate endpoint for OS in ICI trials. mPFS is worthy of further investigation as a secondary endpoint in future ICI trials.
Determinants of left ventricular hypertrophy and oxygen supply in chronic aortic valve disease.
Authors: R STrenouth, N CPhelps, W ANeill
Journal: Circulation (1976)

Ventricular mass and O2 supply of the myocardium were evaluated in patients with left ventricular hypertrophy due to stenosis or insufficiency of the aortic valve and in control patients without cardiac disease. Calculation of left ventricular mass from the angiogram was verified by autopsy data in seven patients. Total mass, O2 consumption, and coronary blood flow, each was related quantitatively to left ventricular total load (force) in all patients. Left ventricular equatorial tension, however, was greater in proportion to mass in aortic stenosis than in aortic insufficiency patients. This discrepancy could be explained by the more eccentric shape of the left ventricle in aortic stenosis. Oxygen consumption and coronary blood flow per gram of myocardium were normal at rest in patients with hypertrophy. Tachycardia induced by atrial pacing provoked myocardial lactate production in half of the patients with aortic stenosis but in none of the patients with aortic insufficiency. Surgical mortality was rela...
Assessment of Patient-Preferred Language to Achieve Goal-Aligned Deprescribing in Older Adults
Authors: Ariel R. Green, Hélène Aschmann, Cynthia M. Boyd, Nancy Schoenborn
Journal: JAMA Network Open (2021)

<h3>Importance</h3> How clinicians communicate about deprescribing, the structured process of reducing or stopping unnecessary, potentially harmful, or goal-discordant medicines, may be associated with the extent to which older adults are willing to do it. <h3>Objective</h3> To examine older adults' preferences regarding different rationales a clinician may use to explain why a patient should stop an unnecessary or potentially harmful medication. <h3>Design, Setting, and Participants</h3> This cross-sectional survey study was conducted from March 25 to April 19, 2020, among a nationally representative, probability-based online survey panel (KnowledgePanel). KnowledgePanel members aged 65 years and older were recruited by random digit dialing and address-based sampling. Data were analyzed from May 4 to July 8, 2020. <h3>Exposures</h3> The survey presented 2 vignettes involving hypothetical older adults. One described a statin being used for primary prevention by a person with functional impairment and polypharmacy. The second described a sedative-hypnotic, such as zolpidem, being used for insomnia by a person with good functional status. <h3>Main Outcomes and Measures</h3> After each vignette, participants expressed preferences using a best-worst scaling method for 7 different phrases a clinician may use to explain why they should reduce or stop the medication. Conditional logistic regression was used to quantify respondents' relative preferences. <h3>Results</h3> A total of 1193 KnowledgePanel members were invited, and 835 respondents (70.0%) completed the survey. The mean (SD) age was 73 (6) years, 414 (49.6%) were women, and 671 (80.4%) self-identified as White individuals. A total of 496 respondents (59.8%) had ever used a statin, and 124 respondents (14.9%) had ever used a sedative-hypnotic. For both medications, the most preferred phrase to explain deprescribing focused on the risk of side effects. For statins, this phrase was 5.8-fold (95% CI, 5.3-6.3) more preferred than the least preferred option, which focused on the effort (treatment burden) involved in taking the medicine. For sedative-hypnotics, the phrase about side effects was 8.6-fold (95% CI, 7.9-9.5) more preferred over the least preferred option, "This medicine is unlikely to help you function better." <h3>Conclusions and Relevance</h3> These findings suggest that among older adults, the most preferred rationale for deprescribing both preventive and symptom-relief medicines focused on the risk of side effects. These results could be used to inform clinical practice and improve effective communications around deprescribing in older adults.
4P Prevalence of MET exon 14-mutations or MET amplification in non-small cell lung cancer in Swiss patients
Authors: S. Savic Prince, M. Bihl, S. Eppenberger-Castori, M.S. Matter, N. Zellweger, S.I. Rothschild, L. Bubendorf
Journal: Journal of Thoracic Oncology (2021)
Detection of coronary artery stenosis in children with Kawasaki disease. Usefulness of pharmacologic stress 201Tl myocardial tomography.
Authors: CKondo, MHiroe, TNakanishi, ATakao
Journal: Circulation (1989)

This study determined the feasibility and accuracy of quantitative 201Tl myocardial single-photon emission computed tomography (SPECT) after dipyridamole infusion to detect coronary obstructive lesions in children with Kawasaki disease. 201Tl distribution after dipyridamole infusion was measured in 23 normal children, and with these normal values, quantitative analysis of SPECT was performed in 49 patients. Thirty-four patients had coronary stenosis 90% or greater on angiograms. Side effects resulting from systemic vasodilation were observed in about 70%. Angina pectoris and ischemic ST changes were observed only in patients with coronary stenosis. These symptoms disappeared after aminophylline infusion. Results of visual and quantitative analysis of SPECT were compared. SPECT data were shown on two-dimensional polar maps, and the extent and severity scores were calculated. The sensitivity of SPECT for detection of overall coronary stenosis was 91% (visual analysis) and 88% (quantitative analysis). The sp...
Long-Lasting Lumen Apposing Metal Stents In The Management Of Biliary Disorders In Excluded Jejunal Limb: Long Term Results And Adverse Events
Authors: A Spota, F Cereatti, S Derhy, G Donatelli
Journal: Endoscopy (2021)

Aims The endoscopic ultrasound (EUS)-guided positioning of lumen apposing metal stents (LAMS) allows the creation of endoscopic anastomosis of the digestive tract (EDA) to have access to the surgically excluded biliary tract in patients with biliary disorders and previous foregut surgeries.
Calcium current in single cells isolated from normal and hypertrophied rat heart. Effects of beta-adrenergic stimulation.
Authors: FScamps, EMayoux, DCharlemagne, GVassort
Journal: Circulation Research (1990)

The L-type calcium current was investigated in normal and hypertrophied rat ventricular myocytes as a possible cause of the action potential lengthening that has been reported during hypertrophy. Regulation of the calcium current (ICa) by a beta-adrenergic agonist (isoproterenol) was also analyzed since beta-agonist-induced positive inotropy is less marked in hypertrophied heart. Left ventricular hypertrophy was induced by stenosis of the abdominal aorta. For recording ICa, the whole-cell patch-clamp technique was used. Potassium currents were suppressed by replacing K+ ions with Cs+ ions in both the extracellular and intracellular media, and sodium current was blocked by 50 microM tetrodotoxin. The Ca2+ current was larger in hypertrophied cells (2.2 +/- 0.6 nA [n= 31]) than in normal cells (1.2 +/- 0.5 nA [n = 33]). However, if one relates ICa amplitude to the cell membrane area, as estimated by membrane capacitance measurement, no significant difference was observed in current density (8.5 +/- 2.5 pA/pF...
Prevalence of cardiovascular risk factors in rural and urban Costa Rica.
Authors: HCampos, LMata, XSiles, MVives, J MOrdovas, E JSchaefer
Journal: Circulation (1992)

BACKGROUNDCoronary artery disease (CAD) is becoming more prevalent in developing countries, particularly in the urban areas, in contrast to the CAD mortality trends observed in some industrialized nations.METHODS AND RESULTSWe determined the prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, obesity, total cholesterol greater than or equal to 240 mg/dl and greater than or equal to 200 less than or equal to 239 mg/dl, low density lipoprotein (LDL) cholesterol greater than or equal to 160 mg/dl and greater than 130 less than or equal to 159 mg/dl, and high density lipoprotein (HDL) cholesterol less than 35 mg/dl) in 222 men and 243 women from rural and urban areas of Puriscal, Costa Rica, using the American Cholesterol Education Program guidelines. Urban Puriscal men had a significantly (p less than 0.05) higher prevalence of borderline high-risk total cholesterol (26% versus 14%), borderline high-risk LDL cholesterol (21% versus 11%), smoking (32% versus 13%), and higher prevalence...
QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest.
Authors: AAlgra, J GTijssen, J RRoelandt, JPool, JLubsen
Journal: Circulation (1991)

BACKGROUNDQTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance.METHODS AND RESULTSIn the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compare...
Validation of continuous-wave Doppler echocardiographic measurements of mitral and tricuspid prosthetic valve gradients: a simultaneous Doppler-catheter study.
Authors: G TWilkins, L DGillam, G LKritzer, R ALevine, I FPalacios, A EWeyman
Journal: Circulation (1986)

For patients with stenotic native valves, the modified Bernoulli equation (delta P = 4V2) may be applied to Doppler-measured transvalvular velocities to yield an accurate estimate of transvalvular gradients. Although it would be useful if the same approach could be used for those with stenotic prosthetic valves, no previous study has validated the Doppler technique in this setting. We therefore recorded simultaneous continuous-wave Doppler flow profiles and transvalvular manometric gradients in 12 catheterized patients in whom all atrial and ventricular pressures were directly measured (transseptal left atrial catheterization and transthoracic ventricular puncture were performed where necessary). A total of 13 prostheses were studied: 11 mitral (seven porcine, three Starr-Edwards, and one Bjork-Shiley) and two tricuspid (one porcine and one Bjork-Shiley). The Doppler-determined mean gradient was calculated as the mean of the instantaneous gradients (delta P = 4V2) at 10 msec intervals throughout diastole....
Dexamethasone selectively attenuates prostanoid-induced vasoconstrictor responses in vitro.
Authors: W CSessa, ANasjletti
Journal: Circulation Research (1990)

Glucocorticoids bind to specific vascular receptors resulting in a variety of functional consequences that may affect vascular smooth muscle behavior. We, therefore, examined in rabbits the effect of treatment with dexamethasone (2.5 mg/kg) for 6 days on vascular responses to pressor prostanoids in aortic and carotid arterial rings and in the isolated perfused kidney. Isometric tension development to prostaglandin F2 alpha and U46619, a thromboxane/prostaglandin endoperoxide mimetic, was markedly reduced in vessels from dexamethasone-treated rabbits. The inhibitory effect of dexamethasone on vascular reactivity was manifested by an increase in the concentration of agonist for threshold tension development and a reduction in the maximal response to prostaglandin F2 alpha and U46619. In contrast, reactivity to phenylephrine, potassium, histamine, or endothelin was not affected by dexamethasone treatment. In addition, pressor responses to prostaglandin F2 alpha and U46619 in Krebs'-perfused kidneys from dexa...
The inotropic effects of strophanthidin in Purkinje fibers and the sodium pump.
Authors: RBernabei, MVassalle
Journal: Circulation (1984)

The role of the inhibition of the Na pump in strophanthidin inotropy was studied in canine Purkinje fibers by correlating changes in contractile force with changes in maximum diastolic potential caused by conditions that enhance the electrogenic extrusion of Na. It was found that a brief exposure to a zero-K or to a zero-K, zero-Ca solution (but not to a zero-Ca solution) is followed by an increase in maximum diastolic potential. This hyperpolarization is reduced if NaCl is substituted by LiCl and in the presence of tetrodotoxin. In quiescent fibers exposed to tetrodotoxin, the hyperpolarization is abolished. A low concentration of strophanthidin (5 X 10(-8)M) increases contractile force but does not modify the hyperpolarization. Larger strophanthidin concentrations (5 X 10(-7)M to 10(-6)M) increase and then decrease contractile force and reduce or abolish the hyperpolarization. Metabolic inhibitors also reduce the hyperpolarization. We conclude that the positive inotropic effect of a low (therapeutic) co...
Shall The Journal be Removed to Washington?
Authors: J. N. Dixon
Journal: JAMA (1891)

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
Hospital Junior Staff
Authors: A. L. Ansdell, K. Aziz, J. Beddard, W. Caplan, J. W. Crooke, H. C. Dervish, R. C. Edibam, K. Edwardson, A. Florence, D. L. Forley, M. Y. Gindi, M. J. L. Hartley, W. Jowett, D. Keane, A. Kinnerton, P. Leighton, C. Lubkiewicz, P. McMartin, G. A. Meadows, J. M. Miller, A. R. Moossa, A. Murphy, A. Porterfield, M. Roy, E. J. Scholfield, M. Y. Shankar, A. Singh, D. Smyth, R. J. Walker, F. J. Weighill
Journal: BMJ (1966)
Transcatheter occlusion of the persistently patent ductus arteriosus. Forty-month follow-up and prevalence of residual shunting.
Authors: M CHosking, L NBenson, NMusewe, J DDyck, R MFreedom
Journal: Circulation (1991)

BACKGROUNDPercutaneous closure of the persistently patent ductus arteriosus with the Rashkind prosthesis is an established effective therapeutic modality, although some patients are left with residual shunting. To evaluate this, a retrospective study of the prevalence of persistent shunting over a 40-month period in the first 190 patients was undertaken.METHODS AND RESULTSAll patients (male 45, female 145; mean age, 3.9 +/- 3.6 years; range, 5 months to 20 years) had serial clinical and color-flow echocardiographic follow-up at 6-12-month intervals (range, 6-40 months). Four patients required surgical removal of an embolized device, leaving a cohort of 186 patients in whom 196 procedures were performed, resulting in successful placement of 195 devices (43 17-mm [22%] and 152 12-mm [78%]). Complications occurred in seven of 195 procedures (3.6%). Nine of 10 attempted reocclusions (all with 12-mm devices) were successful. The prevalence of residual shunting was 38% at 1 year, 18% at 2 years, and 8% at 40 mo...
Effect of adenosine on atrioventricular conduction. II: Modulation of atrioventricular node transmission by adenosine in hypoxic isolated guinea pig hearts.
Authors: H FClemo, LBelardinelli
Journal: Circulation Research (1986)

Adenosine as well as hypoxia and ischemia are known to cause atrioventricular conduction block. To test the hypothesis that adenosine is the primary mediator of hypoxia-induced atrioventricular conduction delay in isolated perfused guinea pig hearts, we characterized a) the time courses of hypoxia-induced adenosine release and delay in atrioventricular conduction, b) the relationships between oxygen tension, adenosine concentration in the effluent, and atria-to-His-bundle interval, and c) the adenosine receptor mediating the negative dromotropic effect of hypoxia. Oxygen tension and effluent adenosine levels were linearly related with a correlation coefficient (r) of -0.85 and a slope of -6.3 +/- 0.37 pmol/min/g/torr. Likewise, oxygen tension and atria-to-His-bundle interval prolongation were linearly related with r = -0.85 and a slope of -0.180 +/- 0.013 msec/torr. The EC50 of effluent adenosine in causing atria-to-His-bundle prolongation was 0.26 +/- 0.02 microM. Adenosine deaminase, an enzyme that deam...
High-density lipoprotein subfractions in normolipidemic patients with coronary atherosclerosis.
Authors: J GBrook, MAviram, AViener, EShilansky, WMarkiewicz
Journal: Circulation (1982)

High-density lipoprotein (HDL) levels were studied in 10 male patients with severe coronary atherosclerosis and in 10 well-matched controls. All subjects were normolipidemic, and the presence of a disease or other factor influencing HDL levels were excluded. Very low density lipoprotein and low-density lipoprotein levels were similar in both groups, but HDL concentration was significantly lower in the patient group. Analysis of HDL subfractions revealed that both HDL2 and HDL3 concentrations were significantly lower in the patient group. The composition of both HDL subfractions was also altered in the patient group: an increased cholesterol-to-protein ratio was found. These data strengthen the evidence in support of an important and independent role for HDL in the pathogenesis of coronary atherosclerosis. It appears that both HDL2 and HDL3 are implicated and that both the concentration and composition of HDL are important.
Effects of thrombosis on vascular tone in rat mesenteric arteries with endothelium in vivo.
Authors: HAraki, KNishi, MJougasaki
Journal: Circulation Research (1990)

We examined the effects of thrombosis on vascular tone in vivo, using small mesenteric arteries of rats (about 300 microns i.d.) and a video recording system attached to a microscope. To induce thrombosis we damaged the vessel wall over a short segment by compression and exposed the media to the bloodstream. A thrombus mainly consisting of platelets gradually enlarged at the damaged site and caused 50-100% narrowing of the lumen. The diameter at the site downstream from the thrombus did not change as long as the blood flow was not interrupted. Instead, vasoconstrictor response to serotonin (3.0 and 30 micrograms/ml) or norepinephrine (0.1, 0.3, and 1.0 microgram/ml) given topically was significantly inhibited at the site downstream from the thrombus compared with that at the upstream site (p less than 0.01). Nonthrombotic mechanical narrowing of the vascular lumen did not affect vascular constriction by these agents. After damage to the endothelium by intra-arterial infusion of a detergent (0.3% CHAPS), t...