tbuckley/cabot-search huggingface dataset:
Is CRP-guided antibiotic treatment a safe way to reduce antibiotic use in severe hospitalised patients with exacerbations of COPD?
Authors: Henk-Jan Prins, Tjip S. van der Werf, Wim G. Boersma
Journal: European Respiratory Journal (2019)

We thank M. Miravitlles and colleagues for their interest in our work [1]. They express concern about our failure rate: 24% at 10 days, and 45% at day 30; they feel that 31% of patients of the C-reactive protein (CRP) group and 46% of patients of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy group treated with antibiotics for acute COPD exacerbation is low in this high-risk population of hospitalised patients. Although treatment failure is high in our study, it reflects the severity of our population. Indeed, the proportion of patients on antimicrobials is lower than the outpatient study population in a recently published trial from the UK [2]; however, our COPD population is more severe and consists of hospitalised patients. Their concern is safety: have we caused harm in our patients by withholding antimicrobial treatment? First, in our study population, there was no significant difference in failure rates at days 10 and 30 between the CRP and GOLD group, which strongly argues against their point that antimicrobial treatment might have prevented harmful events (table 1). Neither failure during admission, nor relapse was significantly different between both study arms. Indeed, relapses among patients with acute exacerbation of COPD admitted to hospital are common [3], especially among individuals with a low forced expiratory volume in 1 s, but antimicrobial treatment may not necessarily prevent this, in particular among those that had low inflammatory markers. Slow recovery and early relapse have also been associated with increased inflammation, e.g. reflected by persistently increased CRP, and in patients characterised by chronic bronchitis [4], but whether these individuals might benefit from antimicrobial treatment if their CRP is below a given threshold has not been addressed in clinical studies [5]. An earlier study suggested that patients with CRP >50 mg·L−1 benefit more from antibiotic treatment compared to patients with CRP below this threshold [6]. Second, they argue that perhaps the active study arm treated with co-amoxiclav as the primary antimicrobial agent might have been inadequate. Although antimicrobial susceptibility data have not been listed in our paper, Pseudomonas spp. or other high-risk pathogens were covered if retrieved from sputum, and patients known to have colonisation with high-risk pathogens were provided with tailored antimicrobial regimens. CRP-guided antibiotic treatment reduces antibiotic prescription in acute exacerbation without change in treatment failure <http://bit.ly/33IweWG>
Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis
Authors: Josiah E. Hardesty, Banrida Wahlang, Russell A. Prough, Kim Z. Head, Daniel Wilkey, Michael Merchant, Hongxue Shi, Jian Jin, Matthew C. Cave
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Polychlorinated biphenyls (PCBs) are signaling disrupting chemicals that exacerbate nonalcoholic steatohepatitis (NASH) in mice.They are epidermal growth factor receptor (EGFR) inhibitors that enhance hepatic inflammation and fibrosis in mice.OBJECTIVES: This study tested the hypothesis that epidermal growth factor (EGF) administration can attenuate PCB-related NASH by increasing hepatic EGFR signaling in a mouse model.METHODS: C57BL/6 male mice were fed a 42% milk fat diet and exposed to Aroclor 1260 (20 mg=kg) or vehicle for 12 wk.EGF (0:2 lg=g) or vehicle were administered daily for 10 d starting at study week 10.Liver and metabolic phenotyping were performed.The EGF dose was selected based on results of an acute dose-finding study (30 min treatment of EGF at 0.2, 0.02, 0:002 lg=g of via intraperitoneal injection).Hepatic phosphoproteomic analysis was performed using liver tissue from this acute study to understand EGFR's role in liver physiology.RESULTS: Markers of EGFR signaling were higher in EGF-treated mice.EGF + PCB-exposed mice had lower hepatic free fatty acids, inflammation, and fibrosis relative to PCB-only exposed mice.EGF-treated mice had higher plasma lipids, with no improvement in hepatic steatosis, and an association with higher LXR target gene expression and de novo lipogenesis.EGF-treated mice showed more severe hyperglycemia associated with lower adiponectin levels and insulin sensitivity.EGF-treated mice had higher hepatic HNF4a, NRF2, and AhR target gene expression but lower constitutive androstane receptor and farnesoid X receptor target gene expression.The hepatic EGF-sensitive phosphoproteome demonstrated a role for EGFR signaling in liver homeostasis.DISCUSSION: These results validated EGFR inhibition as a causal mode of action for PCB-related hepatic inflammation and fibrosis in a mouse model of NASH.However, observed adverse effects may limit the clinical translation of EGF therapy.More data are required to better understand EGFR's underinvestigated roles in liver and environmental health.
The interaction of verapamil and norverapamil with beta-adrenergic receptors.
Authors: R DFeldman, G DPark, C YLai
Journal: Circulation (1985)

To determine the effect of calcium-channel blockers on beta-adrenergic receptors, we studied the interactions of verapamil, diltiazem, and nifedipine with both human lymphocyte beta 2-adrenergic receptors and rat myocardial beta 1-adrenergic receptors by means of radioligand binding assays. We also determined the functional consequences of these interactions by measuring adenylate cyclase activity. Radioligand binding studies in vitro demonstrated a Ki of verapamil for the lymphocyte beta 2-receptor of 32 +/- 4 microM. Diltiazem and nifedipine were much less potent. In studies of adenylate cyclase activity, verapamil was shown to act as a competitive beta-receptor antagonist. Also, norverapamil, the active metabolite of verapamil, had the highest affinity for the beta-receptor of any of the calcium-channel blockers studied (Ki = 4.2 +/- 0.8 microM). After 1 week of verapamil administration in six normal subjects, isoproterenol-stimulated adenylate cyclase activity in lymphocytes was increased from 60 +/- ...
Spontaneous course of ST-segment elevation in acute anterior myocardial infarction.
Authors: REssen, WMerx, SEffert
Journal: Circulation (1979)

The spontaneous course of ST-segment elevation (sigmaST) in 24 patients with acute anterior myocardial infarction (AMI) was studied by precordial ST-segment mapping, which was recorded at 2-hour intervals during the first 48 hours after admission. Change of sigmaST between two registrations was expressed as mV/hr, and was compared with clinical and hemodynamic parameters, course of MB-CK curve, calculated infarct mass and arrhythmias. After an initial rapid increase, there was a decrease of sigmaST, which reaches a plateau-like curve approximately 12 hours after the onset of chest pain. A second new increase of sigmaST exceeding a value of 0.6 mV/hr correlates well with extension of necrosis, verified by re-elevation of MB-CK. During the first 2 days, extension of necrosis could be detected in 50% of our patients. As new ischemic episodes and extension of necrosis in AMI occur frequently and are promptly indicated by an increase of sigmaST, the physician should, while monitoring therapeutic interventions,...
De Subitaneis mortibus. XVI. Intractable tachycardia in infancy.
Authors: CBrechenmacher, PCoumel, T NJames
Journal: Circulation (1976)

Intractable tachycardia in a boy proved fatal at the age of one year. A cousin still living has the same problem. Special electrocardiographic studies in the boy demonstrated a consistent abnormality which included complete atrioventricular dissociation with a normal atrial rate but a ventricular rate usually about 240 beats/minute; a His bundle comples preceded each QRS and all QRS complexes were narrow and uniform in configuration without a delta wave. At postmortem examination there were changes due to congestive failure and the heart was enlarged but otherwise normal except for the His bundle. In its midportion the His bundle was split into several thin and irregular longitudinally oriented strands, within which there were many areas of focal degeneration. There was no myocarditis and no focal degeneration elsewhere in the heart. Although the etiology of this process is uncertain, some possibilities are discussed.
The relationship of pulmonary valve motion to the motion of surrounding cardiac structures: a two-dimensional and dual M-mode echocardiographic study.
Authors: S EGreen, R LPopp
Journal: Circulation (1981)

To assess the relationship of late diastolic pulmonary valve motion to motion of adjacent cardiac structures, we performed two-dimensional and dual M-mode echocardiography on 15 pulmonary normotensive (group A) and nine pulmonary hypertensive subjects (group B). Simultaneous pulmonary valve and posterior aortic wall a-waves were less prominent in group B than in group A (p less than 0.001), and their amplitudes were linearly related within each group (r = 0.83). Analysis of two-dimensional studies confirmed a relationship between pulmonary valve and posterior aortic wall late diastolic motion. No subject had independent presystolic motion of the pulmonary valve within the pulmonary artery. Subjects with shallow a-waves had impaired left atrial emptying compared with those with normal a-wave amplitudes (p less than 0.01). We conclude that the pulmonary valve a-wave does not represent independent valvular displacement, but rather, reflects motion of the entire cardiac base. Variations in a-wave morphology m...
Regression of coronary aneurysms in patients with Kawasaki syndrome.
Authors: MTakahashi, WMason, A BLewis
Journal: Circulation (1987)

Coronary aneurysms were demonstrated echocardiographically in 34 of 186 patients who presented with Kawasaki syndrome between 1979 and 1983. The aneurysms were confirmed by selective coronary angiography in 27 patients and by postmortem examination in one. The 27 surviving patients with proven aneurysms were followed for 2 to 40 months (mean 15), during which they received low dose (5 to 10 mg/kg) aspirin daily. Progressive improvement and resolution of aneurysms were observed by serial echocardiography in 18 patients and confirmed by angiography in 14. Coronary aneurysms persisted, however, in nine other patients for 14 to 40 months (mean 25.7). The incidence of aneurysm resolution was higher in children less than 1 year of age at the onset of the illness than in patients older than 1 year (100% vs 50%; p less than .001). Aneurysms were more likely to resolve in girls than in boys (100% vs 42%; p less than .001). Fusiform aneurysms tended to resolve more frequently than saccular lesions (80% vs 18%; p le...
Treatment of restenosis of coarctation by percutaneous transluminal angioplasty.
Authors: J SKan, R IWhite, S EMitchell, E JFarmlett, J SDonahoo, T JGardner
Journal: Circulation (1983)

Percutaneous transluminal angioplasty (PTA) was used successfully to treat coarctation restenosis in seven patients. The patients were 10 months to 17 years old at the time of the angioplasty, and the initial coarctation repair had been performed 10 months to 16 1/2 years previously. PTA reduced the systolic pressure gradient across the coarctation from a mean of 58 mm Hg before the procedure to a mean of 13 mm Hg immediately after PTA. Follow-up has been from 1 to 14 months and indicates that the decrease in the systolic pressure gradient is persistent.
Hormonal responses to cardiac tamponade: inhibition of release of atrial natriuretic factor despite elevation of atrial pressures.
Authors: G BMancini, M JMcGillem, E RBates, A BWeder, S FDeBoe, R JGrekin
Journal: Circulation (1987)

Atrial distension, rather than change in intra-atrial pressure, has been suggested as a principal mediator of release of atrial natriuretic factor (ANF). During cardiac tamponade, atrial pressures rise whereas transmural pressures and atrial stretch may not be affected. The roles of atrial pressure and atrial distension were investigated in six open-chest dogs subjected to cardiac tamponade and rapid volume expansion as disparate means of affecting intra-atrial pressures and atrial stretch. Hemodynamic measurements, immunoreactive ANF (ir-ANF), plasma renin activity, antidiuretic hormone, epinephrine, and norepinephrine were monitored before, during, and after three interventions: (1) tamponade, (2) rapid volume loading followed by tamponade, and (3) volume loading during tamponade. Volume expansion increased right atrial pressure and caused a significant rise in ir-ANF. Elevations of right atrial pressure caused by tamponade were comparable to those induced by volume infusion, but an increase in ir-ANF w...
Dysphagia as Inaugural Presentation of Lymphoma: a Diagnosis Hard to Swallow
Authors: M Bento-Miranda, M João, E Gravito-Soares, M Gravito-Soares, P Souto, P Figueiredo
Journal: Endoscopy (2021)

Results An 18-year-old woman, with no relevant medical history, presented at the Emergency Department for progressive dysphagia, initially for solids and later for liquids, associated with weight loss of 10 kg within 9 months. She had a mild increase in C-reactive protein (3.18 mg/dL; N <0.5). A stenosis of the middle third of the esophagus was identified in esophagogastroduodenoscopy, patent only to the ultra-thin endoscope with normal mucosa, suggesting extrinsic compression. Biopsies of the stenosis showed nonspecific infiltration of the mucosa by normal B lymphocytes. Cervicothoracic CT scan revealed thickening of the upper half of the esophagus, densification of the mediastinal fat and lung parenchyma, and peri-tracheal and hilar adenopathies. The 18-FDG-PET-scan revealed hypermetabolic uptake of the esophagus, supra-diaphragmatic lymph nodes, pleuropulmonary tissue, muscle and bone marrow, suggestive of high-grade malignancy. Days later, the patient developed right cervicobraquial paraesthesia in relation to a growing cervical mass causing spinal compression from C5 to D1 vertebrae. A guided-ultrasound biopsy followed by a first surgical biopsy of this mass were also inconclusive, so we performed a second surgical macrobiopsy, which finally allowed the definitive diagnosis of an unclassifiable non-Hodgkin B-cell lymphoma, after an extensive workup excluding infectious, autoimmune, immunodeficiency or other malignancy causes. The patient started chemotherapy regimen with R-CHOP followed by R-EPOCH, with symptomatic remission and complete response on 1-month 18-FDG-PET-scan after completion of therapeutic protocol.
PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH.
Authors: R CKukreja, H AKontos, M LHess, E FEllis
Journal: Circulation Research (1986)

Purified PGH synthase when acting on arachidonic acid in the presence of reduced nicotinamide-adenine dinucleotide or reduced nicotinamide-adenine dinucleotide 3'-phosphate generated superoxide in burst-like fashion. In eight experiments using different batches of enzyme, the mean +/- SE rate of superoxide generation from 100 U of enzyme measured as the superoxide dismutase-inhibitable reduction of cytochrome c was 5.06 +/- 0.19 nmol/min in the first minute and 0.35 +/- 0.03 nmol/min subsequently. Optimum rates of superoxide were seen at concentrations of reduced nicotinamide-adenine dinucleotide in excess of 80 microM and reduced nicotinamide-adenine dinucleotide 3'-phosphate in excess of 100 microM. Using prostaglandin G2 or linoleic acid as substrate rather than arachidonate also resulted in superoxide generation. When prostaglandin H2 was used as substrate, no superoxide was generated. The rate of superoxide generation was markedly inhibited by cyclooxygenase inhibitors. Superoxide generation was also...
Author Correction: Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons
Authors: Hope Kronman, Angélica Torres-Berrío, Simone Sidoli, Orna Issler, Arthur Godino, Aarthi Ramakrishnan, Philipp Mews, Casey K. Lardner, Eric M. Parise, Deena M. Walker, Yentl Y. van der Zee, Caleb J. Browne, Brittany F. Boyce, Rachael Neve, Benjamin A. Garcia, Li Shen, Catherine J. Peña, Eric J. Nestler
Journal: Nature Neuroscience (2021)
Abstract 2626: Intramyocardial High-Energy Phosphate Depletion during Ventricular Fibrillation Correlates with Electrocardiographic Change
Authors: David D Salcido, James J Menegazzi, Eric S Logue, Brian P Suffoletto, Lawrence D Sherman
Journal: Circulation (2007)

Background: Ventricular fibrillation (VF) is highly energy-wasteful, producing no perfusion. High-energy phosphates (HEPs) deplete rapidly during VF, adding to metabolic/ischemic stress and adversely affecting VF. We have shown that the scaling exponent (ScE) of the VF waveform predicts rescue shock outcome and can be used to guide decision-making during CPR. Hypotheses: We hypothesized that intramyocardial HEPs would rapidly diminish during untreated VF, and that this decrease would correlate with changes in the ScE. Methods: We anesthetized and instrumented 18 domestic swine (26.6 ± 1.9 kgs). We systematically assigned them (6 per group) to 5, 10, or 15 minutes of untreated VF, which was induced with a transthoracic shock. At the predetermined timepoint open-chest biopsies were taken from the left ventricle. Biopsied tissue samples were immediately flash frozen in a slurry of dry ice and isopentane (-90 o C), and HEPs were extracted with 1% trichloroacetic acid. Levels of ATP and ADP were measured luminometrically with an ADP/ATP ratio kit. ATP and ADP levels were assayed in duplicate, and the average recorded (reported in nmol/mg myocardial tissue). Fifteen seconds of ECG signal was digitally recorded (for ScE analysis) immediately prior to biopsy. ScE values were paired with ATP and ADP for calculation of linear regression. HEPs vs. time were compared with ANOVA. Results: Mean ATP/ADP were 1.20/0.21 at 5 min, 0.94/0.12 at 10 min, and 0.45/0.11 at 15 min. ATP correlated with ScE (r=.63, p=0.009) but ADP did not (r=.35, p=0.17). Both ATP (p=0.004) and ADP (p=0.024) differed over time. Conclusions: HEPs rapidly diminish during untreated VF. ATP depletion correlates with ScE change.
Heart rate adjustment of ST segment depression for improved detection of coronary artery disease.
Authors: PKligfield, OAmeisen, P MOkin
Journal: Circulation (1989)

Normal values for heart rate-adjusted indexes of ST segment depression during treadmill exercise electrocardiography (the ST segment/heart rate slope and the delta ST segment/heart rate index) were derived from evaluation of 150 subjects with a low likelihood of coronary artery disease, including 100 normal subjects and 50 subjects with nonanginal chest pain. Partitions chosen by the method of percentile estimation to include 95% of normal subjects remained highly specific in subjects with nonanginal pain syndromes. Sensitivities of the derived partitions for detection of myocardial ischemia were tested in an additional 150 patients with a high likelihood of coronary disease, including 100 patients with angiographically demonstrated coronary obstruction and 50 patients with stable angina. In contrast to the 68% (102 of 150 subjects) sensitivity of standard exercise electrocardiographic criteria for the detection of disease in this population, the sensitivity of an ST segment/heart rate slope partition of ...
Effect of clofibrate on intravascular coagulation in hyperlipoproteinemia.
Authors: A CCarvalho, R SLees, R AVaillancourt, R WColman
Journal: Circulation (1977)

Intravascular coagulation (IVC) was evaluated in 19 patients with type II and 11 with type IV hyperlipoproteinemia before and after clofibrate therapy by measurements of soluble fibrin complexes (SFC) in plasma; fibrinolysis was estimated by quantitation of fibrin (ogen) degradation products in serum. Untreated type II and type IV patients had increased SFC (P less than 0.01). The former also had activation of the intrinsic coagulation pathway as evidenced by decreased plasma prekallikrein (P less than 0.001), kallikrein inhibitors (P less than 0.001), and factor XII (P less than 0.02). Although clofibrate treatment of the type II patients did not change plasma lipids, it decreased intravascular coagulation, apparently via decreased factor XII activation and stimulation of fibrinolysis. In contrast, treated type IV patients had unchanged SFC and FDP levels, despite decreased plasma triglycerides (P less than 0.01). Clofibrate-induced changes in blood coagulation are independent of lipid-lowering. Clofibra...
The evolution of early fibromuscular lesions hemodynamically induced in the dog renal artery. I. Light and transmission electron microscopy.
Authors: F GBaumann, A MImparato, G EKim
Journal: Circulation Research (1976)

In view of the important roles of arterial intimal fibromuscular lesions as precursors of atherosclerotic plaque and occlusive lesions in arterial reconstructions, a model has been developed for the rapid hemodynamic induction of these lesions by anastomosis of the dog right renal artery to the inferior vena cava. Light and transmission electron microscopic observations were made on the arterial shunt after periods of rapid flow ranging form 10 minutes to 2 hours to identify initial factor(s) and evolutionary mechanisms in the etiology of the lesions. The sequence of events included aberrations in ruthenium red staining of the endothelial luminal membrane at 10 minutes, multilayered thickening of the subendothelial basement membrane (BM) at 15 minutes, and initial reorientation and migration of smooth muscle cells (SMC) into the intima along with the appearance of areas of degeneration of the internal elastic lamina (IEL) at 30 minutes. The endothelial cells were still intact in some areas overlying the S...
Estimation of infarct size by myocardial emission computed tomography with thallium-201 and its relation to creatine kinase-MB release after myocardial infarction in man.
Authors: STamaki, HNakajima, TMurakami, YYui, HKambara, KKadota, AYoshida, CKawai, NTamaki, TMukai, YIshii, KTorizuka
Journal: Circulation (1982)

We evaluated emission computed tomography (ECT) for thallium-201 (201TI) myocardial imaging in estimating infarct size (IS). In 18 patients in whom IS was estimated enzymatically at the time of the acute episode, planar 201TI perfusion scintigraphy and ECT with a rotating gamma camera were performed 4 weeks after the first myocardial infarction. From the size of 201TI perfusion defects, the infarct area in planar images and the infarct volume in reconstructed ECT images were measured by computerized planimetry. When scintigraphic IS was compared with the accumulated creatine kinase-MB isoenzyme release (CK-MBr), infarct volume determined from ECT correlated closely with CK-MBr (r = 0.89), whereas infarct area measured from planar images correlated less satisfactorily with the enzymatic IS (for an average infarct area from three views, r = 0.69; for the largest infarct area, r = 0.73). Although conventional scintigraphic evaluation is useful for detecting and localizing infarction, quantification of ischem...