tbuckley/cabot-search huggingface dataset:
Studies on magnesium's mechanism of action in digitalis-induced arrhythmias.
Authors: M JSpecter, ESchweizer, R HGoldman
Journal: Circulation (1975)

The mechanism by which magnesium affects digitalis-induced arrhythmias was studied in dogs with and without beta-receptor blockade. Digoxin was infused at a rate of 2.5mug/kg/min until ventricular tachycardia developed, then half the animals were given MgSO4, the other half saline. In animals given MgSO4, sinus rhythm was immediately re-established; in animals given saline, ventricular tachycardia persisted. In animals with beta-receptor blockade, MgSO4 was as effective in abolishing ventricular tachycardia as in those without beta-receptor blockade. We found no evidence that magnesium re-activated digoxin-inhibited (Na+, K+)-ATPase, altered myocardial or microsomal digoxin binding, or acted via the autonomic nervous system. Magnesium's direct effect on calcium and potassium fluxes across the myocardial cell membrane may be the mechanism of its antiarrhythmic action in digitalis-toxic arrhythmias.
Plasma and lipoprotein cholesterol and triglyceride concentrations in the Pima Indians: distributions differing from those of Caucasians.
Authors: B VHoward, M PDavis, D JPettitt, W CKnowler, P HBennett
Journal: Circulation (1983)

Plasma and lipoprotein cholesterol and triglyceride concentrations were measured in Pima Indians, a genetically homogeneous population with a high prevalence of obesity and diabetes and a low frequency of coronary heart disease. The data for nondiabetic Pima Indians were compared with those of U.S. Caucasians measured during the Lipid Research Clinics Prevalence Study. Plasma total and low-density lipoprotein (LDL) cholesterol levels in Pima men older than 30 years of age and in women over 25 were lower than those of U.S. Caucasians, and in men the total and LDL cholesterol levels did not increase with age. In Pima male subjects of all ages high-density lipoprotein (HDL) cholesterol levels were lower than that in Caucasian male subjects, and in Pima female subjects HDL cholesterol levels averaged 11 mg/dl lower than those in female Caucasian subjects. On the other hand, plasma triglyceride levels in Pima male subjects up to 35 years of age and in female subjects up to 55 years old were higher than those o...
Comment on Johnson et al. Cost-effectiveness Analysis of Routine Screening Using Massively Parallel Sequencing for Maturity-Onset Diabetes of the Young in a Pediatric Diabetes Cohort: Reduced Health System Costs and Improved Patient Quality of Life. Diabetes Care 2019;42:69–76
Authors: Jane Frances Grace Lustre Estrella, David Simmons
Journal: Diabetes Care (2019)

We welcome the report by Johnson et al. (1) demonstrating cost-effectiveness of routine targeted massively parallel sequencing for known genes associated with monogenic diabetes in a pediatric cohort in Western Australia. This is an important approach that we hope can be implemented in other parts of Australia and beyond. Most of the benefit in this cohort was through the transition of therapy from insulin to sulfonylureas in patients with known variants of genes associated with sulfonylurea responsiveness such as HNF4A- diabetes.

However, not all patients with HNF4A- diabetes can be successfully transitioned to sulfonylureas from insulin (estimated at 80% for the Markov modeling [1]). We now report a case …
Pathological features of coronary arteries in children with Kawasaki disease in which coronary arterial aneurysm was absent at autopsy. Quantitative analysis.
Authors: TFujiwara, HFujiwara, HNakano
Journal: Circulation (1988)

Coronary arteries in six children who had Kawasaki disease but lacked coronary arterial aneurysms were examined. Four children died of myocarditis at the acute stage, and two children died of bacterial sepsis or as a result of an occurrence during cineangiography at the healed stage. Twenty-one children without Kawasaki disease were examined as controls. The six children with Kawasaki disease had no thrombi, recanalization, or stenosis greater than 50% in the major coronary arteries. Three patients had dilatation of the major coronary arteries at the acute stage. Two of the three patients died during the acute stage, and autopsy showed slight dilatation of coronary arteries and abnormal intimal thickening due to panvasculitis. In the third child, who died at the healed stage, dilatation of the coronary arteries detected by two-dimensional echocardiography at the acute stage had disappeared at the healed stage. No dilatation of the major coronary arteries was seen at autopsy. However, abnormal fibrous inti...
Transcatheter ablation of ectopic atrial tachycardia in young patients using radiofrequency current.
Authors: E PWalsh, J PSaul, J EHulse, L ARhodes, A JHordof, J EMayer, J ELock
Journal: Circulation (1992)

BACKGROUNDEctopic atrial tachycardia (EAT) is a reversible cause of cardiomyopathy but may be quite difficult to control with conventional therapy. Transcatheter ablation with radiofrequency current was tested as an alternative to medical or surgical treatment of this condition.METHODS AND RESULTSTwelve young patients (aged 10 months to 19 years) with drug-resistant EAT were treated with direct transcatheter ablation of the ectopic focus using radiofrequency (RF) energy. All had depressed left ventricular contractility by echocardiographic criteria, involving shortening fractions of 10-26% (median, 20%; normal, 28-35%). The EAT was mapped to the left atrium in seven cases and to the right atrium in five. Local atrial activation at the ectopic site preceded the onset of the surface P wave by 20-60 msec (median, 42 msec). Tachycardia terminated 0.5-13.0 seconds (median, 2.0 seconds) into a successful RF application. The ablation effectively eliminated EAT in 11 of 12 patients (92%), all of whom were dischar...
Correction: Dual Inhibition of Canonical and Noncanonical NF-κB Pathways Demonstrates Significant Antitumor Activities in Multiple Myeloma
Authors: Claire Fabre, Naoya Mimura, Kathryn Bobb, Sun-Young Kong, Güllü Gorgun, Diana Cirstea, Yiguo Hu, Jiro Minami, Hiroto Ohguchi, Jie Zhang, Jeffrey Meshulam, Ruben D. Carrasco, Yu-Tzu Tai, Paul G. Richardson, Teru Hideshima, Kenneth C. Anderson
Journal: Clinical Cancer Research (2019)

In the original version of this article (1), Fig. 4E was missing splice lines at p50 and p52, between TNFα and PBS-1086, and consequently the Nucleolin panel did not line up with the other two blots. These errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret these errors.
Prodrugs and prodrug-activated systems in gene therapy
Authors: Semira Sheikh, Daniel Ernst, Armand Keating
Journal: Molecular Therapy (2021)

The inclusion of genes that control cell fate (so-called suicide, or kill-switch, genes) into gene therapy vectors is based on a compelling rationale for the safe and selective elimination of aberrant transfected cells. Prodrug-activated systems were developed in the 1980s and 1990s and rely on the enzymatic conversion of non-active prodrugs to active metabolites that lead to cell death. Although considerable effort and ingenuity has gone into vector design for gene therapy, less attention has been directed at the efficacy or associated adverse effects of the prodrug systems employed. In this review, we discuss prodrug systems employed in clinical trials and consider their role in the field of gene therapy. We highlight potential drawbacks associated with the use of specific prodrugs, such as systemic toxicity of the activated compound, the paucity of data on biodistribution of prodrugs, bystander effects, and destruction of genetically modified cells, and how these can inform future advances in cell therapies. The inclusion of genes that control cell fate (so-called suicide, or kill-switch, genes) into gene therapy vectors is based on a compelling rationale for the safe and selective elimination of aberrant transfected cells. Prodrug-activated systems were developed in the 1980s and 1990s and rely on the enzymatic conversion of non-active prodrugs to active metabolites that lead to cell death. Although considerable effort and ingenuity has gone into vector design for gene therapy, less attention has been directed at the efficacy or associated adverse effects of the prodrug systems employed. In this review, we discuss prodrug systems employed in clinical trials and consider their role in the field of gene therapy. We highlight potential drawbacks associated with the use of specific prodrugs, such as systemic toxicity of the activated compound, the paucity of data on biodistribution of prodrugs, bystander effects, and destruction of genetically modified cells, and how these can inform future advances in cell therapies.
Inhibition of adrenergic vasoconstriction by endothelial cell shear stress.
Authors: BTesfamariam, R ACohen
Journal: Circulation Research (1988)

Isolated perfused rabbit carotid arteries were used to determine the effects of endothelial cell shear stress on the response to adrenergic nerve stimulation. Arterial segments with and without endothelium were cannulated and perfused with physiological salt solution. Adrenergic nerves were activated by transmural electrical field stimulation. Neurogenic vasoconstriction was significantly greater in segments without endothelium when compared with that of segments with endothelium. In segments with endothelium only, vasoconstriction was depressed when shear stress was increased by increasing the viscosity of the perfusate with dextran. Perfusion with methylene blue (2 X 10(-6) M), a guanylate cyclase inhibitor, increased vasoconstriction in segments with endothelium only. In the presence of methylene blue, vasoconstriction was no longer different between segments with and without endothelium, and perfusion with dextran had no effect. In a perfusion-cascade system, perfusion with dextran of donor segments w...
Evolution of Barrett’s Assessment in a Tertiary Referral Center Over Time
Authors: J Rasool, F Janjua, O Aoko, B Christopher, D Cheriyan, S Patchett
Journal: Endoscopy (2021)

Aims Barrett’s oesophagus is associated with 24 fold increase in risk of Oesophageal cancer. Seattle biopsy protocol is gold standard in Barrett’s surveillance. Adherence to Seattle protocol increases dysplasia detection rate (DDR). In addition, the inclusion of chromoendoscopy with Narrow band imaging (NBI) and Acetic Acid spray (AA) is also associated with improved dysplasia detection rate. Our aim was to review how our assessment of Barrett’s oesophagus with regards to the use of chromoendoscopy, adherence to Seattle Protocol and documentation of Prague classification has evolved over time at our institute and if dysplasia detection rate improved concomitantly.
The usefulness of x-ray computed tomography for the diagnosis of myocardial infarction.
Authors: YMasuda, HYoshida, NMorooka, SWatanabe, YInagaki
Journal: Circulation (1984)

Conventional and enhanced computed tomographic (CT) examinations were performed in 103 patients with myocardial infarction for evaluation of the diagnostic usefulness of CT. After intravenous bolus injection of contrast material, an initial filling defect and late enhancement of the infarcted myocardium appeared on the cardiac CT images. These two findings were direct evidence of myocardial infarction; the former was found mostly in the patient with recent myocardial infarctions, and the latter was recognized both in those with recent and those with remote infarctions. Wall thinning at the site of infarction was found by enhanced CT mostly in patients with anteroseptal or extensive anterior infarctions, and was rarely found in patients with inferoposterior infarctions. Left ventricular aneurysms and ventricular thrombi were found by enhanced CT in 39 and 23 of the 103 subjects, respectively, and the sensitivity of CT in detecting intracardiac thrombi was higher than that of two-dimensional echocardiogra...
Pericardial effusion in the course of myocardial infarction: incidence, natural history, and clinical relevance.
Authors: EGalve, HGarcia-Del-Castillo, AEvangelista, JBatlle, GPermanyer-Miralda, JSoler-Soler
Journal: Circulation (1986)

Incidence and significance of pericardial effusion in patients with acute myocardial infarction (AMI) have not been established. To evaluate these issues, we studied prospectively 138 consecutive patients with AMI. An echocardiogram was obtained in each 1, 3, and 10 days and 3 and 6 months after admission. Fifty four patients with unstable angina and 57 without heart disease were studied as controls. Echocardiographic diagnostic criteria of pericardial effusion were established from 33 additional patients undergoing surgery. Pericardial effusion was found in 28% of patients with AMI. Twenty-five percent of patients with AMI had pericardial effusion on the third day, vs 8% of patients with unstable angina (p less than .02) and 5% of patients without heart disease (p less than .01). At 1, 3, and 10 days and 3 and 6 months prevalence of pericardial effusion was 17%, 25%, 21%, 11%, and 8%, respectively. There was no case of tamponade. Pericardial effusion was more common in anterior AMI (p less than .02) and ...
EUS-Guided Gastroenterostomy As Treatment Of Benign Gastric Outlet Obstruction
Authors: L Sánchez-Delgado, FJ García-Alonso, C Chavarría, R Sánchez-Ocana, C Maroto-Martín, E Fuentes-Valenzuela, R Nájera-Muñoz, C de la Serna-Higuera, M Pérez-Miranda
Journal: Endoscopy (2021)

Aims The role of endoscopic ultrasound-guided gastroenterostomy (EUS-GE) in benign gastric outlet obstruction (GOO) remains unclear. We aimed at evaluating the clinical efficacy and safety of EUS-GE in benign GOO.
Vasectomy and increased risk of prostate cancer
Authors: D. W. Cramer
Journal: JAMA (1993)

To  Editor.  —Concern about recent studies linking vasectomy and prostate cancer has been tempered by  absence of any clear biologic rationale for  association. In dismissing as unlikely  role for hormonal mechanisms, Giovannucci et al 1 have overlooked evidence that may be linked to prostate cancer by disrupting gametogenesis and increasing gonadotropins. This mechanism is similar to that proposed for ovarian cancer, 2 which may share other epidemiologic features with prostate cancer. Experimental studies show that ligation of  vas causes Sertoli cell damage and Leydig cell hypertrophy. Seventy years ago, Steinach 3 recognized this effect in men and proposed vasoligation to rejuvenate aging men after observing that it produced a cycle of growth... of  male generative gland by causing the expansion of  interstitial tissue at  expense of  generative tissue. Sertoli cell damage may decrease inhibins with  consequent increase in follicle-stimulating hormone.
Ventricular reentry around a fixed barrier. Resetting with advancement in an in vitro model.
Authors: R CBernstein, L HFrame
Journal: Circulation (1990)

We studied an in vitro model of reentrant tachycardia in a ring of ventricular endocardial tissue surrounding the canine mitral and aortic valves to understand how the response of a reentrant tachycardia to premature impulses can provide insight into the underlying tachycardia mechanism, circuit characteristics, and nature of the central barrier. Reproducible regular reentrant tachycardias (cycle length range, 177-450 msec) were induced with programmed stimulation in 19 intact preparations studied at 34-38 degrees C. Tachycardias were sustained and stable until terminated by programmed stimulation in 95% of preparations. Reentry was reliably reinitiated during experiments lasting 2-15 hours. Data supporting reentry as the mechanism of these tachycardias included sequential activation around the ring that spanned the cycle length of the tachycardia, unidirectional block during initiation of the reentrant rhythm, and termination of the tachycardia after interruption of the circuit. Tachycardias in 13 prepar...
Morphometric evidence for non-pressure-related arterial wall thickening in hypertension.
Authors: J LLiu, S PBishop, H WOverbeck
Journal: Circulation Research (1988)

To investigate the relation of pressure and vascular wall thickening in hypertension, we coarcted the abdominal aorta upstream to the renal arteries in 14 rats. Sham-coarcted (n = 16) and two-kidney, one-clip (Goldblatt) hypertensive rats (n = 13) served as controls. Tail, femoral, and carotid arterial pressures rose (p less than 0.01) in the two-kidney, one-clip hypertensives; only carotid pressure rose (p less than 0.01) in the coarcted rats, tail and femoral pressures remaining normal (p greater than 0.25). Thus, the hindquarters of the coarcted rats remained normotensive. Four to six weeks after surgery we perfusion-fixed vascular tissues of the hindquarters, including kidneys, with formalin at in vivo levels of pressure. Glycol methacrylate-embedded tissues were sectioned at 1 micron thickness and vessels quantitatively evaluated. The outer medial and lumen perimeters of abdominal aorta, femoral artery, and renal arterioles were measured; from these measurements, vessel outer and lumen diameters, med...
Culture of renal arteriolar smooth muscle cells. Mitogenic responses to angiotensin II.
Authors: R KDubey, ARoy, H WOverbeck
Journal: Circulation Research (1992)

We cultured smooth muscle cells from rat renal preglomerular arterioles by injecting a suspension of iron oxide into the left ventricle, separating the arterioles magnetically, and growing cells from explants. In passaged cultures we ascertained vascular smooth muscle purity of > 98% by morphology; contraction to norepinephrine and angiotensin; positive immunofluorescence staining through the sixth passage with monoclonal antibodies to smooth muscle-specific alpha- and gamma-isoactins, myosin, and desmin; and the absence of von Willebrand factor. Angiotensin II (10(-12)-10(-5) M) induced dose-dependent DNA synthesis and proliferation of subcultured (three times) arteriolar smooth muscle cells from a growth-arrested state (p < 0.01). Angiotensin II (10(-5) M) also induced the cells to express c-fos mRNA. We find no previous report of culture of smooth muscle cells from renal preglomerular arterioles. Our findings also provide evidence that angiotensin II is mitogenic to arteriolar muscle cells and thus may...
Postpolypectomy Syndrome - an Underrated Complication After Endoscopic Polypectomy? Which Risk Factors Lead to a Postpolypectomy Syndrome?
Authors: E Leventi, A Genthner, F Straulino, S Kangalli, I Reiffenstein, N Tscherwinski, A Eickhoff
Journal: Endoscopy (2021)

Aims The postpolypectomy syndrome is a serious complication after endoscopic polypectomy. We want to analyze the prevalence of a postpolypectomy syndrome and the risk factors associated with the development of postpolypectomy syndromes.
Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats.
Authors: J RTeerlink, J MPfeffer, M APfeffer
Journal: Circulation Research (1994)

The purpose of the present study was to gain a better understanding of the relation between ventricular remodeling and heart failure by assessing the adaptation of the heart through time to graded myocardial injury in the presence of a patent coronary circulation. Left ventricular (LV) remodeling is a dynamic response of the heart to injury and a critical component in the development of heart failure. However, most previous studies have been in the presence of an occluded coronary vessel, which may in itself effect remodeling. Male Wistar rats received two subcutaneous injections of either 0, 85, 170, or 340 mg isoproterenol per kilogram of body weight. At 2, 6, and 16 weeks after injection, LV pressure, the pressure-volume relation, and histology were assessed. The graded myocardial necrosis produced in isoproterenol-treated rats was associated with dose-dependent increases in LV end-diastolic pressure, volume indexes, and global diastolic wall stress. In the higher dose groups, the LV continued to enlar...
Alterations in calcium antagonist receptors and sodium-calcium exchange in cardiomyopathic hamster tissues.
Authors: J AWagner, H FWeisman, A MSnowman, I JReynolds, M LWeisfeldt, S HSnyder
Journal: Circulation Research (1989)

The Syrian cardiomyopathic (CM) hamster (BIO 14.6) develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, and, eventually, cardiac dilatation and congestive heart failure. Several lines of evidence implicate cellular calcium overload as an important etiologic factor. We previously reported an increased number of receptors for calcium antagonist drugs, which block voltage-dependent calcium channels, in heart, skeletal muscle, and brain tissue of these hamsters in the early necrotic stage of the disease. To better characterize the pathophysiological significance of this abnormality we evaluated calcium antagonist receptor binding and Na+-Ca2+ exchange in CM and control hamsters at different stages of disease as documented by quantitative histopathologic assessment. In CM hamsters as young as 10 days, an age previously thought to be before the onset of disease, we identified cardiac myocyte hypertrophy, a twofold increase in calcium antagonist receptor binding in heart and bra...
Feasibility and Diagnostic Yield of Small Bowel Capsule Endoscopy in Patients with Surgically Altered Gastric Anatomy
Authors: X Dray, ME Riccioni, G Wurm Johansson, M Keuchel, G Perrod, A Martin, A Tortora, A Nemeth, P Baltes, E Pérez-Cuadrado-Robles, S Chetcuti Zammit, PS Lee, S Cadoni, I Fernández-Urien Sainz, D McNamara, R Margalit-Yehuda, H Beaumont, A Mussetto, C Spada, L Elli, M Bruno, E Rondonotti, A Robertson, P Cortegoso Valdivia, R Leenhardt, A Koulaouzidis
Journal: Endoscopy (2021)

Aims Little is known about small bowel (SB) capsule endoscopy (CE) in patients with a history of gastric surgery. This study aims to evaluate the feasibility and the diagnostic yield (DY) of orally ingested SB-CE in patients with altered gastric anatomy.
Quality Criteria In Upper Gastrointestinal Endoscopy - Can Deep Sedation Influence It?
Authors: C Correia, N Almeida, M Sant’Anna, C Macedo, C Gregório, P Figueiredo
Journal: Endoscopy (2021)

Aims In 2016, quality criteria for upper gastrointestinal endoscopy (UGE) were published by ESGE/UEG, but the problem of sedation was not addressed. However, it is known that the patient’s tolerance level is variable, assuming that some criteria may not be reached in non-sedated patients. The present research aims to determine whether the use of deep sedation influences the fulfillment of the quality criteria proposed by ESGE.
Endocardial mapping in humans in sinus rhythm with normal left ventricles: activation patterns and characteristics of electrograms.
Authors: D MCassidy, J AVassallo, F EMarchlinski, A EBuxton, W JUntereker, M EJosephson
Journal: Circulation (1984)

Endocardial catheter mapping was performed in 15 patients in sinus rhythm who had no evidence of structural heart disease and normal left ventricles. Mapping was performed with the use of 10 mm interelectrode distance from various left ventricular endocardial sites. In 10 patients a quantitative analysis of electrographic amplitude, duration, and amplitude/duration ratio was performed. The normal left ventricular bipolar electrograms had an amplitude of greater than 3 mV, a duration of less than 70 msec, and an amplitude/duration ratio of greater than 0.045. Local activation times were also assessed in the 15 patients. This analysis revealed two endocardial breakthrough sites, one on the midinferior septum and a second on the anterior wall near the insertion of the anterior papillary muscle. We therefore have defined normal quantitative characteristics of left ventricular bipolar electrograms and the normal left ventricular activation sequence in the intact normal human left ventricle.