tbuckley/cabot-search huggingface dataset:
Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST).
Authors: J LAnderson, E VPlatia, AHallstrom, R WHenthorn, T ABuckingham, M DCarlson, P ECarson
Journal: Circulation (1994)

BACKGROUNDThe Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular ectopy with antiarrhythmic drugs after a myocardial infarction reduces the incidence of sudden arrhythmic death. Patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The encainide and flecainide arms of the study were discontinued in 1989 (CAST-I) and the moricizine arm in 1991 (CAST-II) because of excess mortality. To explore the mechanisms of these adverse outcomes, we examined the interaction of baseline characteristics with the hazard of therapy with encainide, flecainide, or moricizine compared with their respective placebos.METHODS AND RESULTSCAST-I comprised 755 patients assigned to flecainide or encainide and 743 patients assigned to placebo, whereas in CAST-II, 502 patients received moricizine and 491 patients received placebo. Clinical and laboratory baseline vari...
Renal intracortical blood flow distribution, function, and sodium excretion in unanesthetized dogs following vena caval ligation.
Authors: R AGutman, R LMcRae
Journal: Circulation Research (1975)

We studied the renal function and the intrarenal blood flow of nine dogs whose thoracic inferior vena cava had been previously ligated (caval dogs) and nine other dogs. Following preparative surgery which included placement of a left atrial catheter, a femoral artery catheter, and bilateral ureteral catheters, the caval dogs gained an average of 2.1 kg of fluid weight, whereas the normal dogs gained no weight. Although neither the caval dogs' blood pressure (114 plus or minus 7 vs 120 plus or minus 4 mm Hg) nor their inulin clearance (0.64 plus or minus 0.06 vs. 0.79 plus or minus 0.06 ml/min g-1 kidney weight) was significantly reduced, their estimated renal blood flow (Cpah/[1-hematocrit]) was considerably lower (2.30 plus or minus 0.24 vs. 3.25 plus or minus 0.15 ml/min g-1). During the clearance study, the caval dogs' excretion of sodium (79 plus or minus 18 vs. 158 plus or minus 17 muEq/min) and their fractional clearance of sodium (2.0 plus or minus 0.4 vs. 3.4 plus or minus 0.5%) were reduced. Stud...
Comment on the Relationship Between Common Variant Schizophrenia Liability and Number of Offspring in the UK Biobank
Authors: Rebecca B. Lawn, Hannah M. Sallis, Amy E. Taylor, Robyn E. Wootton, George Davey Smith, Neil M. Davies, Gibran Hemani, Abigail Fraser, Ian S. Penton-Voak, Marcus R. Munafò
Journal: American Journal of Psychiatry (2019)
Radionuclide angiographic evaluation of right and left ventricular function during exercise after repair of transposition of the great arteries. Comparison with normal subjects and patients with congenitally corrected transposition.
Authors: M DParrish, T PGraham, H WBender, J PJones, JPatton, C LPartain
Journal: Circulation (1983)

We assessed the incidence, clinical significance and etiology of ventricular dysfunction after intraatrial repair of d-transposition of the great arteries in 11 patients, mean age 9 +/- 3 years, who had had Mustard operations. We compared the results to 15 patients who were considered to have normal ventricular function, two patients who had Rastelli operations and five patients with congenitally corrected transposition. Gated equilibrium radionuclide angiography with supine exercise stress testing was used to assess these children. We found no significant difference between our patient groups in exercise capacity, heart rate, or blood pressure response to exercise. However, we found a high incidence of right ventricular dysfunction in the patient groups, manifested by an abnormal right ventricular ejection fraction response to dysfunction in the patient groups, manifested by an abnormal right ventricular ejection fraction response to exercise in six of 11 patients with a Mustard repair, both patients wit...
Electrophysiological findings and long-term follow-up of patients with the permanent form of junctional reciprocating tachycardia treated by catheter ablation.
Authors: W WChien, T JCohen, M ALee, M DLesh, J CGriffin, N BSchiller, M MScheinman
Journal: Circulation (1992)

BACKGROUNDThe permanent form of junctional reciprocating tachycardia (PJRT) commonly presents as recurrent drug-refractory, narrow-complex tachycardia. We studied the efficacy and safety of catheter ablation in treating these patients.METHODS AND RESULTSSix patients with the diagnosis of PJRT were treated at our institution with direct-current catheter ablation. The study cohort comprised three men and three women with a mean age of 33.8 +/- 4.5 years. The mean time from onset of symptoms to ablation was 129 +/- 44.7 months. All failed multiple drug therapy (mean number of drugs failed was 5.3 +/- 0.5). The left ventricular ejection fractions were calculated by echocardiography and were greater than 60% in all except two patients, whose ejection fractions were 25% and 32%. Symptom duration was significantly longer in those with depressed ejection fraction compared with normal patients (258 versus 64.5 months, p less than 0.01). Electrophysiological findings revealed evidence of an atrioventricular recipro...
Increased thromboxane biosynthesis in type IIa hypercholesterolemia.
Authors: GDavì, MAverna, ICatalano, CBarbagallo, AGanci, ANotarbartolo, GCiabattoni, CPatrono
Journal: Circulation (1992)

BACKGROUNDIncreased platelet thromboxane (TX)A2 production has been described in type IIa hypercholesterolemia. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo, we studied the urinary excretion of its major enzymatic metabolites in 46 patients with type IIa hypercholesterolemia and 20 age-matched controls.METHODS AND RESULTSUrinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. The excretion rate of 11-dehydro-TXB2 was significantly (p less than 0.001) higher in patients (68.7 +/- 35.1 ng/hr, mean +/- SD) than in controls (22.4 +/- 9.4 ng/hr), with metabolite excretion greater than 2 SD of the normal mean in 74% of the patients. Urinary 11-dehydro-TXB2 was significantly (p less than 0.01) correlated with the threshold aggregating concentration of collagen (r = -0.641) and arachidonate (r = -0.734) and with agonist-induced platelet TXB2 production in vitro (r = 0.647 and 0.748, respectively). Moreove...
Increased Volume and Distinct Pattern of Silent Cerebral Infarcts in Healthy, Young Adults with Sickle Cell Trait
Authors: Andria L Ford, Melanie E Fields, Kristin P Guilliams, Dustin K Ragan, Chen Yasheng, Georges Guillaume, Joshua S Shimony, Katie D Vo, Morey Blinder, Allison King, Monica L Hulbert, Robert C McKinstry, Hongyu An
Journal: Blood (2017)
Identifying Novel Drug Targets by iDTPnd: A Case Study of Kinase Inhibitors
Authors: Hammad Naveed, Corinna Reglin, Thomas Schubert, Xin Gao, Stefan T. Arold, Michael L. Maitland
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Current FDA-approved kinase inhibitors cause diverse adverse effects, some of which are due to the mechanism-independent effects of these drugs. Identifying these mechanism-independent interactions could improve drug safety and support drug repurposing. Here, we develop iDTPnd (integrated Drug Target Predictor with negative dataset), a computational approach for large-scale discovery of novel targets for known drugs. For a given drug, we construct a positive structural signature as well as a negative structural signature that captures the weakly conserved structural features of drug-binding sites. To facilitate assessment of unintended targets, iDTPnd also provides a docking-based interaction score and its statistical significance. We confirm the interactions of sorafenib, imatinib, dasatinib, sunitinib, and pazopanib with their known targets at a sensitivity of 52% and a specificity of 55%. We also validate 10 predicted novel targets by using in vitro experiments. Our results suggest that proteins other than kinases, such as nuclear receptors, cytochrome P450, and MHC class I molecules, can also be physiologically relevant targets of kinase inhibitors. Our method is general and broadly applicable for the identification of protein–small molecule interactions, when sufficient drug–target 3D data are available. The code for constructing the structural signatures is available at https://sfb.kaust.edu.sa/Documents/iDTP.zip.
Neutrophil to T-Lymphocyte Ratio (NLR) and Neutrophil to Monocyte Ratio (NMR) Are Promising Biomarkers in Chronic Lymphocytic Leukemia Prognostic Assessment
Authors: Annalisa Chiarenza, Francesco Di Raimondo, Nunziatina Laura Parrinello, Anna Triolo, Giuseppina Rizzo, Angelo Curto Pelle, Cinzia Maugeri, Anastasia Laura Caruso, Giovanna Motta, Amalia Figuera, Alessandra Romano, Valerio Leotta, Mary Ann Di Giorgio, Cesarina Giallongo, Daniele Tibullo
Journal: Blood (2017)
Innervation of the human cardiac conduction system. A quantitative immunohistochemical and histochemical study.
Authors: S JCrick, JWharton, M NSheppard, DRoyston, M HYacoub, R HAnderson, J MPolak
Journal: Circulation (1994)

BACKGROUNDCardiac conduction is influenced by peptidergic mechanisms as well as classic neurotransmitters. The distribution of peptide-containing nerves has not been well defined.METHODS AND RESULTSImmunofluorescence and histochemical techniques were used to visualize the innervation of the human conduction system and to distinguish nerve subpopulations according to their peptide and enzyme content. Nerve fibers and fascicles displaying immunoreactivity for protein gene product 9.5 (PGP 9.5) were more numerous in the sinus and atrioventricular nodes than in the penetrating bundle, bundle branches, and adjacent myocardium. The relative density of innervation was greater in the central region of the sinus node than in the peripheral regions. Nerve densities were also higher in the transitional region of the atrioventricular node compared with its compact region. Acetylcholinesterase (AChE)-positive nerves were the main subtype identified in the sinus and atrioventricular nodes, representing half to two thir...
スタニオカルシン1は心筋細胞においてサイトゾルCa 2+ 過負荷および細胞超拘縮を抑制する
Authors: Koizumi Keiichi, Hoshiai Minako, Ishida Hideyuki, Ohyama Kenji, Sugiyama Hisashi, Naito Atsushi, Toda Takako, Nakazawa Hiroe, Nakazawa Shinpei
Journal: Circulation (2007)
Rapid Spread of SARS-CoV-2 in a State Prison After Introduction by Newly Transferred Incarcerated Persons — Wisconsin, August 14–October 22, 2020
Authors: Rebecca B. Hershow, Hannah E. Segaloff, Abigail C. Shockey, Kelsey R. Florek, Sabrina K. Murphy, Weston DuBose, Tammy L. Schaeffer, Jo Anna Powell, MPH, Krystal Gayle, Lauren Lambert, Amee Schwitters, Kristie E.N. Clarke, Ryan Westergaard
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

SARS-CoV-2, the virus that causes COVID-19, can spread rapidly in prisons and can be introduced by staff members and newly transferred incarcerated persons (1,2).On September 28, 2020, the Wisconsin Department of Health Services (DHS) contacted CDC to report a COVID-19 outbreak in a state prison (prison A).During October 6-20, a CDC team investigated the outbreak, which began with 12 cases detected from specimens collected during August 17-24 from incarcerated persons housed within the same unit, 10 of whom were transferred together on August 13 and under quarantine following prison intake procedures (intake quarantine).Potentially exposed persons within the unit began a 14-day group quarantine on August 25.However, quarantine was not restarted after quarantined persons were potentially exposed to incarcerated persons with COVID-19 who were moved to the unit.During the subsequent 8 weeks (August 14-October 22), 869 (79.4%) of 1,095 incarcerated persons and 69 (22.6%) of 305 staff members at prison A received positive test results for SARS-CoV-2.Whole genome sequencing (WGS) of specimens from 172 cases among incarcerated persons showed that all clustered in the same lineage; this finding, along with others, demonstrated that facility spread originated with the transferred cohort.To effectively implement a cohorted quarantine, which is a harm reduction strategy for correctional settings with limited space, CDC's interim guidance recommendation is to serial test cohorts, restarting the 14-day quarantine period when a new case is identified (3).Implementing more effective intake quarantine procedures and available mitigation measures, including vaccination, among incarcerated persons is important to controlling transmission in prisons.Understanding and addressing the challenges faced by correctional facilities to implement medical isolation and quarantine can help reduce and prevent outbreaks.
Fibrin is a determinant of neutrophil sequestration in the lung.
Authors: J ACooper, S KLo, A BMalik
Journal: Circulation Research (1988)

We investigated the role of fibrin in the sequestration of neutrophils in lungs challenged with microembolism. Lungs of chronically prepared awake sheep were imaged after infusion of 111In-neutrophils and 131I-fibrinogen. Thrombin (80 units/kg) was administered to induce fibrin sequestration in the lung. One group received tranexamic acid (4 mg/kg i.v.) to inhibit fibrinolysis, and the control group received a saline infusion. Thrombin infusion increased both 131I-fibrinogen and 111In-neutrophils in the lung, but the increases were greater and more prolonged in the fibrinolysis-inhibited group. We examined the adherence of isolated neutrophils to fibrin matrix to investigate how neutrophil-fibrin interactions could mediate neutrophil sequestration. Unstimulated neutrophils showed a 37.5 +/- 3.1% adherence to fibrin in contrast to a 3.9 +/- 0.4% neutrophil adherence to endothelium and a 6.5 +/- 0.5% adherence to agarose. Neutrophil adherence to fibrin increased to 81.7 +/- 6.2% with activation by phorbol m...
Influence of ribose, adenosine, and "AICAR" on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog.
Authors: MMauser, H MHoffmeister, CNienaber, WSchaper
Journal: Circulation Research (1985)

Recovery of adenosine triphosphate after myocardial ischemia is limited by the slow adenine nucleotide de novo synthesis and the availability of precursors of the nucleotide salvage pathways. We determined the adenine nucleotide de novo synthesis in the dog by infusion of [14C]glycine and the acceleration of adenine nucleotide built up by intracoronary infusion of ribose together with [14C]glycine or radiolabeled 5-amino-4-imidazolcarboxamide riboside or adenosine in the same animal model and with the same dosage of substrates (9 mmol) in postischemic and nonischemic myocardial tissue. After 45 minutes of occlusion of a side branch of the left coronary artery, the ischemic area was reperfused for 3 hours, and needle biopsies were taken for biochemical analysis. Adenine nucleotide de novo synthesis was found to be very slow (1.5 nmol/g wet weight per hour). The rate was doubled after ischemia. Adenine nucleotide synthesis was accelerated 5-fold by ribose, the basic substrate of the adenine nucleotide de no...
Relationship of blood pressure in 20-39-year-old men to subsequent blood pressure and incidence of hypertension over a 30-year observation period.
Authors: S WRabkin, F AMathewson, R BTate
Journal: Circulation (1982)

The objective of this investigation was to determine the relationship of blood pressure (BP) in young men, ages 20-39 years, to their subsequent BP from the perspective of BP tracking, position in BP distribution and later evidence of hypertensive BP values. Since 1948, the Manitoba Study group has followed 3983 men, 90% of whom were 20-39 years old at entry. BP in persons not prescribed antihypertensive medications was examined at 5-year intervals during the 30-year observation period to 1978. To adjust for age, BP was examined within 5-year age groups at entry. The correlations between entry and subsequent BP at the same length of follow-up were greater for systolic than diastolic BP and increased with older ages. The correlation decreased wtih every 5-year examination after entry for all ages. Men whose BP was below the mean at entry were less likely to have a BP greater than 1 standard deviation (SD) above the mean at any of the examinations. Men with an entry BP greater than 1 SD above the mean were ...
Pathogenesis of congestive state in chronic obstructive pulmonary disease. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery.
Authors: I SAnand, YChandrashekhar, RFerrari, RSarma, RGuleria, S KJindal, P LWahi, P APoole-Wilson, PHarris
Journal: Circulation (1992)

BACKGROUNDThe pathogenesis of salt and water accumulation in patients with chronic obstructive pulmonary disease is unclear and may differ from that in patients with congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms involved.METHODS AND RESULTSHemodynamics, water and electrolyte spaces, renal function, and plasma hormone concentrations were measured in nine patients with edema due to chronic obstructive pulmonary disease and in six patients after recovery. Mean cardiac output (3.8 +/- 0.26 l/min.m2) was normal, but right atrial (11 +/- 1 mm Hg) and mean pulmonary arterial (41 +/- 3 mm Hg) pressures were increased. Mean pulmonary arterial wedge pressure (11 +/- 1 mm Hg) was normal. Pulmonary vascular resistance (8.6 +/- 1.3 mm Hg.min.m2/l) was increased, but systemic vascular resistance (19.3 +/- 1.3 mm Hg.min.m2/l) and mean arterial pressure (83 +/- 4 mm Hg) were low. All patients were hypoxemic (PaO2, 40 +/- 2 mm Hg) and hypercapnic (PaCO2...
An angiotensin II receptor antagonist reduces myocardial damage in an animal model of myocarditis.
Authors: ATanaka, AMatsumori, WWang, SSasayama
Journal: Circulation (1994)

BACKGROUNDRecently, an angiotensin-converting enzyme inhibitor was shown to have a beneficial effect on virus-induced myocardial injury. We investigated the effect of a new angiotensin II type 1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-1H-benz imi dazole-7- carboxylate (TCV-116), in an animal model of viral myocarditis induced by encephalomyocarditis virus.METHODS AND RESULTSFour-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. TCV-116 (in 5% gum arabic) was given 1 day before (1 or 10 mg/kg) or 2 days after virus inoculation (0.3 or 3 mg/kg). Control mice received the vehicle only. All drugs were administered orally on a daily basis, and the animals were killed on day 14. When treatment was started 1 day before inoculation, the survival of mice receiving 10 mg/kg of TCV-116 improved (17 of 20 [85%] versus 14 of 22 [64%] control mice), but the difference was not significant. Heart weight (106 +/- 24 mg versu...
An Ethical Debate: The lay view
Authors: J. Neuberger
Journal: BMJ (1995)

If elective ventilation of patients dying of rapidly progressive intracranial haemorrhage takes place, it begs several questions. The authors argue strongly that the practice is ethical. Yet that seems unlikely unless the person concerned has given express permission for this ventilation to take place and is a registered organ donor. To argue that the relatives can give consent (which legally they cannot) and see some good coming out of a tragedy is simply inadequate.

For even if the relatives believe that benefit can emerge from a tragedy and that, as a result of their consent, someone else can have a life, that does not necessarily make it ethical. It merely …
Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction.
Authors: OJin, M JSole, J WButany, W KChia, P RMcLaughlin, PLiu, C CLiew
Journal: Circulation (1990)

Recent molecular studies have suggested that viral myocarditis frequently underlies human congestive cardiomyopathy; however, only moderately sensitive and specific techniques were used. Polymerase chain reaction (PCR) gene amplification is a sensitive, specific technique ideally suited for the diagnosis of viral disease in small tissue samples where low copy numbers of the viral genome may be present. Using PCR and high stringency condition, we screened biopsies taken from 48 patients with clinically suspected myocarditis or dilated cardiomyopathy. Five patients demonstrated positive enteroviral signals by PCR; two of them had myocarditis by pathology, whereas the other three had changes consistent with cardiomyopathy. Four other patients had myocarditis diagnosed by pathology from 3 months to 1 year earlier but were now negative by both PCR and pathology. Both pathology and PCR were negative for active myocarditis in all other patients. Ventricular samples taken from left ventricular myectomy in four ad...
Intermediate-density lipoprotein and cholesterol-rich very low density lipoprotein in angiographically determined coronary artery disease.
Authors: RTatami, HMabuchi, KUeda, RUeda, THaba, TKametani, SIto, JKoizumi, MOhta, SMiyamoto, ANakayama, HKanaya, HOiwake, RTakeda
Journal: Circulation (1981)

The relationship between the concentrations of intermediate-density lipoprotein (IDL) and other lipoproteins and the extent of coronary artery disease (CAD) was studied in 182 consecutive patients evaluated by selective coronary cineangiography. On univariate analysis, the extent of CAD correlated significantly and positively with very low density lipoprotein (VLDL) cholesterol, IDL cholesterol and low-density lipoprotein (LDL) cholesterol, and negatively with high-density lipoprotein (HDL) cholesterol. Analysis of four subgroups divided by IDL cholesterol and LDL cholesterol levels indicated that moderately increased levels of IDL cholesterol were closely associated with a high frequency of CAD. Moreover, multi-variate regression analysis demonstrated that IDL cholesterol for men, LDL cholesterol for men and women and HDL cholesterol for men were significant variables of use in the final weighting procedure. IDL cholesterol was closely associated with cholesterol-rich VLDL. This study shows that IDL and ...
Left ventricular diastolic dysfunction limits use of maximum systolic elastance as an index of contractile function.
Authors: M RZile, GIzzi, W HGaasch
Journal: Circulation (1991)

We tested the hypothesis that maximum systolic elastance (Emax) fails to detect a decline in left ventricular (LV) contractile function when diastolic dysfunction is present. Canine hearts were studied in an isolated blood-perfused heart apparatus (isovolumic LV); contractile dysfunction was produced by 60 or 90 minutes of global ischemia, followed by 90 minutes of reperfusion. Nine normal hearts underwent 60 minutes of ischemia, and five underwent 90 minutes of ischemia. After the ischemia-reperfusion sequence, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 14 hearts. In the group undergoing 60 minutes of ischemia, LV diastolic pressure did not increase, whereas Emax decreased from 5.2 +/- 2.5 to 2.9 +/- 1.4 mm Hg/ml (p less than 0.05). In the group undergoing 90 minutes of ischemia, diastolic pressure increased (from 10 +/- 2 to 37 +/- 20 mm Hg, p less than 0.05), and Emax did not change significantly (from 5.1 +/- 4.3 to 4.3 +/- ...