tbuckley/cabot-search huggingface dataset:
Altered spectrum of nitroglycerin action in long-term treatment: nitroglycerin-specific venous tolerance with maintenance of arterial vasodepressor potency.
Authors: D JStewart, DElsner, OSommer, JHoltz, EBassenge
Journal: Circulation (1986)

The study of venodilator tolerance to nitroglycerin has been complicated by reflex compensation and by problems in analyzing venous tone in the presence of multiple determinants of venous pressure. We assessed venous tone as total effective vascular compliance (TEVC) under autonomic blockade in six dogs, in the nontolerant state, and during a 5 day infusion of nitroglycerin (1.5 micrograms/kg/min). Under long-term treatment, baseline TEVC was unaffected and the nitroglycerin dose-response relationship for TEVC was shifted to greater than 10-fold higher doses, whereas baseline mean arterial pressure (MAP) was lowered by 17 +/- 3 mm Hg without any shift in nitroglycerin responsiveness. This lowering of MAP was observed only after autonomic blockade. In six additional dogs instrumented with aortic flow probes, nitroglycerin (1.5 micrograms/kg/min) induced a 15 +/- 1% decline in peripheral vascular resistance (PVR) under autonomic blockade, but with reflexes intact these dogs showed no change in PVR and a 21 ...
Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study.
Authors: SKansal, DRoitman, L TSheffield
Journal: Circulation (1979)

Septal and left ventricular posterior wall (LVPW) thicknesses and their ratios were studied at the left ventricular outflow tract and left ventricular cavity in 66 patients with echocardiographically diagnosed left ventricular concentric hypertrophy, 20 with idiopathic hypertrophic subaortic stenosis (IHSS), and 34 normal subjects. Concentric hypertrophy was due to hypertension in 41 subjects and to valvular disease in 15 subjects. Septal thickness in normal subjects was related to body surface area (p less than 0.02). In 12% of normal subjects, 39% of patients with concentric hypertrophy and 95% with IHSS, the septal/LVPW ratio was greater than or equal to 1.3. Thirty-two percent of patients with hypertension, 78% with aortic stenosis, and 60% with aortic insufficiency had septal/LVPW ratios greater than or equal to 1.3 at left ventricular midcavity level. In conclusion, a septal/LVPW thickness ratio of greater than or equal to 1.3 is common in patients with concentric left ventricular hypertrophy and ma...
Microbial Nourishment for Undernutrition
Authors: Wendy S. Garrett
Journal: New England Journal of Medicine (2021)

Hippocrates wrote “let food be thy medicine.” Although access to nourishing food seems to be an obvious solution to the global health crisis of childhood undernutrition, the solution is not simple from a social or metabolic perspective, or even from the perspective of a microbiologist. To effectively address childhood undernutrition, clinicians need to be mindful that both our human and microbial selves need specific nourishment to restore and maintain healthy development and growth. The laboratory of Dr. Jeffrey Gordon has provided fundamental insight into what constitutes healthy microbiota in children from across the world1,2 and has shown that in moderate . . .
Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial
Authors: Angelo L. Gaffo, David A. Calhoun, Elizabeth J. Rahn, Suzanne Oparil, Peng Li, Tanja Dudenbostel, Daniel I. Feig, David T. Redden, Paul Muntner, Phillip J. Foster, Stephanie R. Biggers‐Clark, Amy Mudano, Sebastian E. Sattui, Michael B. Saddekni, S. Louis Bridges, Kenneth G. Saag
Journal: Arthritis & Rheumatology (2021)

To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect.We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed.Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events.Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.
Precordial ST-segment mapping. 2. Effects of oxygen inhalation on ischemic injury in patients with acute myocardial infarction.
Authors: J EMadias, N EMadias, W BHood
Journal: Circulation (1976)

Precordial ST-segment mapping was serially applied in the Coronary Care Unit for the study of the effect of oxygen inhalation on the ischemic injury in 17 patients with acute anterior transmural myocardial infarction. A 49-lead ECG system was used. The sum of all ST elevations (sigmaST) recorded was taken as an index of magnitude of ischemic injury and the number of recording sites showing ST elevation (NST) was taken as an index of extent of ischemic damage. Stability of the precordial maps was observed over a period of one hour while the patients were on ambient air. Oxygen inhalation for a mean of 66 min resutled in a fourfold increase of PaO2 and a mean of 16% reduction of both sigmaST and NST. When the patients were returned to ambient air breathing, a mean of 13% increase of sigmaST and 19% of NST from the levels recorded during oxygen inhalation were observed. Levels of sigmaST and NST on ambient air following discontinuation of oxygen inhalation were not significantly different from the correspond...
Role of basic fibroblast growth factor in vascular lesion formation.
Authors: VLindner, D ALappi, ABaird, R AMajack, M AReidy
Journal: Circulation Research (1991)

In the present study we investigated whether basic fibroblast growth factor (bFGF) plays a role in the proliferative response of smooth muscle cells (SMCs) to denuding injury. Rat carotid smooth muscle was found to express the mRNA for bFGF, and bFGF protein was found to be present in rat aorta by immunoblot analysis. Systemically administered bFGF was a potent mitogen for vascular SMCs in arteries denuded with a balloon catheter, increasing replication from 11.5% in controls to 54.8%. Denudation with a device (filament loop), which causes only minimal damage to medial SMCs, showed a similar increase in replication (1.3% versus 43.3%) after bFGF infusion. In unmanipulated vessels, however, SMCs were unresponsive to infused bFGF. Infusion of a mitotoxin (bFGF conjugated to saporin) caused a greater than 50% decrease in the number of viable SMCs in the arterial wall after balloon injury. Prolonged administration of bFGF (12 micrograms/day for 2 weeks) after balloon injury caused an approximately twofold i...
Adrenergic responsiveness after abrupt propranolol withdrawal in normal subjects and in patients with angina pectoris.
Authors: JLindenfeld, M HCrawford, R AO'Rourke, S PLevine, M MMontiel, L DHorwitz
Journal: Circulation (1980)

Adrenergic responsiveness after abrupt propranolol withdrawas during exogenous and esdogenous catecholamine stimulation was assessed in 10 normal subjects and 10 patients with angina pectoris. Propranolol, 160 mg/day, was administered for 2 weeks and then stopped. During an epinephrine infusion, period (p < 0.005). There were no differences from control 96 hours after the drug had been stopped in both groups or at 144 hours in the angina patients who were studied for a longer time. At 48 hours of heart rate and the pressure-rate product were significantly less than control level in the angina patient, but not in the normal subjects. Similar results were observed during exercise in both groups. The epinephrine-induced increase in free fatty acids was blocked by propranolol (p < 0.005), was still attenuated at 48 hours of withdrawals (p < 0.05), but returned to control levels thereafter in both groups. Resting serum triiodothyromine levels decreased with propranolol ( < 0.005) and remaind low throughout the...
总编导读
Authors: 杨秉辉
Journal: BMJ (2010)

导读是指导阅读的意思.其实,看医学杂志,医生们都会的,本也无需别人指导,所以也有许多医学杂志并无导读之设.我想就像旅游,游山玩水人人都会的,但如有位导游提示一下呢,那会省些时间,也容易看出点门道来.所以各位如果时间充裕,我建议您从头到尾通读一遍,开卷有益必有收获.如果您太忙,或是已经通读,那么,我告诉您,下列各篇您是必定应该看的,或者是应该仔细看看的.
Predicting Clearance of ‘Difficult’ Biliary Stones in the Cholangioscopy ERA
Authors: H Martin, S Patel, P Virdee, T El Menabawey, C Parisinos, S Phillpotts, M Chapman, G Webster
Journal: Endoscopy (2021)

Aims A number of predictors of failure of biliary stone clearance at endoscopic retrograde cholangio pancreatography (ERCP) are known, including stones > 15mm, stones above strictures, Mirrizzi syndrome and intrahepatic stones(1). The introduction of single operator cholangioscopy (SOC) has improved the ability to treat difficult biliary stone disease(2). However, there have been no studies looking at predicting success or failure of biliary stone disease in the era of SOC.
Left ventricular contractility and function in Kawasaki syndrome. Effect of intravenous gamma-globulin.
Authors: J WNewburger, S PSanders, J CBurns, I AParness, A SBeiser, S DColan
Journal: Circulation (1989)

To investigate the effect of Kawasaki syndrome on myocardial function, as well as the influence of high-dose intravenous gamma-globulin therapy on resolution of functional abnormalities, we studied 98 patients with Kawasaki syndrome during five time intervals from onset of illness: 1) 10 days or less, 2) 11-31 days, 3) 1-3 months, 4) 3-12 months, and 5) 1-3 years. Normal controls included 48 children under age 8 years, without known cardiovascular disease. Using two-dimensional directed M-mode echocardiograms, we obtained chamber dimensions, fractional shortening, rate-corrected velocity of shortening (Vcfc) adjusted for end-systolic wall stress, and early diastolic function parameters that included adjusted peak rates of left ventricular dimension change, wall thinning, and their respective timing. Left ventricular systolic and diastolic dimensions were larger (both p less than 0.01) in patients than in normal subjects in period 1. Stress-adjusted Vcfc was much lower in patients in the 3 months after dis...
Differences in the electrophysiological response of canine ventricular subendocardium and subepicardium to acetylcholine and isoproterenol. A direct effect of acetylcholine in ventricular myocardium.
Authors: S HLitovsky, CAntzelevitch
Journal: Circulation Research (1990)

A prolongation of the ventricular effective refractory period in response to cholinergic agonists or vagal stimulation has been demonstrated in a number of in vivo animal models. However, exposure of isolated myocardial tissues obtained from these hearts to as much as 10(-4) M acetylcholine has been shown to produce essentially no change in action potential duration or effective refractory period. The discrepancy between the in vivo and in vitro findings generally has been explained on the basis of accentuated antagonism, whereby parasympathetic agonists exert their influence through antagonism of the effects of beta-adrenergic tone in vivo. The fact that acetylcholine exerts little if any direct effect on the electrical activity of ventricular myocardium, although well accepted, is based exclusively on studies performed using endocardial preparations. Our recent demonstration of major electrophysiological differences between canine ventricular endocardium and epicardium prompted us to examine the effects...
HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies.
Authors: J FCarlquist, R LMenlove, M BMurray, J BO'Connell, J LAnderson
Journal: Circulation (1991)

We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 hapl...
Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines.
Authors: PSimpson, AMcGrath, SSavion
Journal: Circulation Research (1982)

The role of hormones and other humoral factors in the regulation of myocardial hypertrophy has been difficult to evaluate. We asked whether myocardial cell hypertrophy could be demonstrated in cultures from the day-old rat ventricle and evaluated the effect of serum concentration and catecholamines on the growth process. Two single-cell preparations were used: serum-supplemented, bromodeoxyuridine-treated cultures and serum-free cultures with transferrin and insulin. Both preparations were characterized by myocardial cell predominance (about 75--80% of total cells) and constant cell numbers. Myocardial cell size was documented by photomicroscopy and quantified by volume (microscopic diameter of suspended cells), surface area (planimetry of attached cells), and total cell protein concentration (Lowry method and cell counts). Growth was also evaluated in pure nonmyocardial cell cultures. In cultures with 5% (vol/vol) serum, myocardial cell size increased 2- to 3-fold over 11 days in culture. Final volume, s...
Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Multivessel Angioplasty Prognosis Study Group.
Authors: S GEllis, M GVandormael, M JCowley, GDiSciascio, UDeligonul, E JTopol, T MBulle
Journal: Circulation (1990)

To assess the likelihood of procedural success in patients with multivessel coronary disease undergoing percutaneous coronary angioplasty, 350 consecutive patients (1,100 stenoses) from four clinical sites were evaluated. Eighteen variables characterizing the severity and morphology of each stenosis and 18 patient-related variables were assessed at a core angiographic laboratory and at the clinical sites. Most patients had Canadian Cardiovascular Society class III or IV angina (72%) and two-vessel coronary disease (78%). Left ventricular function was generally well preserved (mean ejection fraction, 58 +/- 12%; range, 18-85%) and 1.9 +/- 1.0 stenoses per patient had attempted percutaneous coronary angioplasty. Procedural success (less than or equal to 50% final diameter stenosis in one or more stenoses and no major ischemic complications) was achieved in 290 patients (82.8%), and an additional nine patients (2.6%) had a reduction in diameter stenosis by 20% or more with a final diameter stenosis 51-60% an...
Nitric oxide accounts for dose-dependent estrogen-mediated coronary relaxation after acute estrogen withdrawal.
Authors: PCollins, JShay, CJiang, JMoss
Journal: Circulation (1994)

BACKGROUNDEstrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women, and estrogen treatment modulates endothelium-dependent vasodilation in ovariectomized, atherosclerotic monkeys. Estradiol-17 beta also induces relaxation in isolated rabbit coronary arteries as well as cerebral basilar arteries. The estrogen concentrations required to induce such relaxation are in the pharmacological range (10(-6) to 10(-5) mol/L).METHODS AND RESULTSThe present study was designed to test whether the sensitivity and specificity of the relaxing response of coronary vascular smooth muscle to exogenous estradiol-17 beta is dependent on the sex hormone status of the animal. In coronary artery rings contracted with PGF2 alpha (3 x 10(-5) mol/L), estradiol-17 beta caused significant relaxation at a physiological estrogen concentration (10(-9) mol/L), in coronary artery rings from oophorectomized, estrogen-treated and acutely estrogen-withdrawn rabbits only. Relaxation induced by estradiol-1...
Black phosphorous nanosheet: A novel immune-potentiating nanoadjuvant for near-infrared-improved immunotherapy
Authors: Wen-Hao Li, Jun-Jun Wu, Lie Wu, Bo-Dou Zhang, Hong-Guo Hu, Lang Zhao, Zhi-Bin Li, Xue-Feng Yu, Yan-Mei Li
Journal: Biomaterials (2021)
110P Real-world evaluation of pembrolizumab monotherapy for previously treated PD-L1 positive (TPS&gt;1%) advanced NSCLC in France
Authors: M. Pérol, X. Quantin, H. Lena, T. Filleron, C. Chouaid, C. Audigier Valette, C. Kaderbhai, G. Chenuc, M. Santorelli, L. Bensimon, T. Burke, G. Simon, A-L. Martin, D. Debieuvre, R. Gervais, R. Schott, M. Carton, C. Courtinard, N. Girard
Journal: Journal of Thoracic Oncology (2021)
The effects of coronary artery disease on the ventricular fibrillation threshold in man.
Authors: L NHorowitz, J FSpear, M EJosephson, J AKastor, E NMoore
Journal: Circulation (1979)

The ventricular fibrillation threshold (VFT) was measured in 28 patients at the time of cardiac surgery. The VFT was measured with a 100 Hz train of 24 rectangular pulses positioned across the ST segment and T wave. Current was applied to the epicardial surface of either ventricle with a bipolar electrode probe. In six patients, the normal right VFT was 24.3 +/- 5.2 mA, and in 10 patients the normal left VFT was 33.6 +/- mA (p less than 0.05). In 12 patients with greater than or equal to 75% obstruction of the left anterior descending coronary artery, the left VFT was 18.6 +/- 6.9 mA. This value was significantly less than the left VFT in patients without coronary artery disease (p less than 0.001). This study shows that the VFT can be measured in man and that coronary artery disease reduces this parameter.
Effects of exercise training on ventricular function in patients with recent myocardial infarction.
Authors: F RCobb, R SWilliams, PMcEwan, R HJones, R EColeman, A GWallace
Journal: Circulation (1982)

We evaluated the effects of 6 months of exercise training (bicycle ergometry, walking and jogging) on exercise performance and ventricular function in patients with recent myocardial infarction. Fifteen patients were selected on the basis of myocardial infarction at least 6 weeks but not more than 6 months before the study and age younger than 65 years. The patients were evaluated by maximal treadmill exercise testing and radionuclide angiography at rest and exercise before and after training. Before exercise training, maximal treadmill exercise time ranged from 1.5 to 11 minutes, ejection fraction at rest from 18% and 67% and end-diastolic volume from 108 to 208 ml. The mean EF was 48 +/- 5% (+/- SD) at rest and did not change at maximal exercise (48.5 +/- 5%). All 11 patients who completed the exercise training program achieved a significant training effect, as defined by a reduction in heart rate at 50% maximal pretraining effort or an increase in maximal treadmill time. The mean ejection fraction and ...
Downregulation of c-myc expression by antisense oligonucleotides inhibits proliferation of human smooth muscle cells.
Authors: YShi, H GHutchinson, D JHall, AZalewski
Journal: Circulation (1993)

BACKGROUNDProliferation of smooth muscle cells (SMCs) plays an important role in vascular pathobiology, being involved in the development of coronary restenosis and atherosclerosis. The activation of nuclear proto-oncogenes appears to be a final common pathway onto which various mitogenic signals coverage. Accordingly, we attempted to determine whether the activation of the c-myc nuclear proto-oncogene is essential for human SMC proliferation and explored the possibility of inhibiting their growth using antisense oligonucleotides directed against c-myc messenger RNA (mRNA).METHODS AND RESULTSProliferation of human SMCs was associated with an increase in c-myc mRNA expression after growth stimulation. Using 15-mer phosphorothioate oligonucleotides (oligomers), we tested their growth-inhibitory effect in SMCs in vitro. Antisense oligomers directed against the translation initiation region of the human c-myc gene exhibited a significant antiproliferative effect, whereas sense and mismatched oligomers did not...
Sudden death in young athletes.
Authors: B JMaron, W CRoberts, H AMcAllister, D RRosing, S EEpstein
Journal: Circulation (1980)

The causes of sudden and unexpected death in 29 highly conditioned, competitive athletes, ages 13-30 years, are summarized. Sudden death occurred during or just after severe exertion on the athletic field in 22 of the 29 athletes. Structural cardiovascular abnormalities were identified at necropsy in 28 of the 29 athletes (97%), and in 22 (76%) were almost certainly the cause of death. The most common cause of death in this series was hypertrophic cardiomyopathy, which was present in 14 athletes. Other cardiovascular abnormalities that occurred in more than one athlete were anomalous origin of the left coronary artery from the right (anterior) sinus of Valsalva, idiopathic concentric left ventricular hypertrophy, coronary heart disease and ruptured aorta. Cardiac disease was suspected during life in only seven of the 29 patients, and in only two of the seven was the correct diagnosis made clinically. Hence, in this series of young athletes, sudden death was usually due to structural cardiovascular disease...
Will 1 April mark the beginning of the end of England's NHS? Yes
Authors: D. J. Hunter
Journal: BMJ (2013)

You do not need to be a conspiracy theorist to conclude that from 1 April the NHS in England will never be the same again. The changes ushered in by the Health and Social Care Act 2012 are different in both scope and intent from anything to which the NHS has previously been subjected. The politics of reform and the desire among many influential government figures, notably the policy minister Oliver Letwin, to dismantle the NHS, should not be underestimated.1 What other reason can there be to explain the government’s stubborn resolve to railroad its proposals through a largely supine parliament? But, as Lucy Reynolds from the London School of Hygiene and Tropical Medicine puts it, this will be a quiet rather than a big bang, and for a time few using the NHS will probably notice any difference.2 If her analysis is correct, and it is well grounded in evidence, this is all part of the plan or, to be more accurate, plot.3

Behind the NHS brand and logo a gradual and insidious hollowing out of what has up until now been a largely publicly provided service will get underway …