tbuckley/cabot-search huggingface dataset:
Platelet survival time in patients with hypoxemia and pulmonary hypertension.
Authors: PSteele, J HEllis, H SWeily, EGenton
Journal: Circulation (1977)

Platelet survival time (autologous labeling with 51chromium) was measured in 63 patients in order to evaluate the role of platelets in the thromboembolic complications of patients with hypoxemia and pulmonary hypertension. Thirty-eight of these patients had chronic obstructive airways disease; 13, primary pulmonary hypertension; seven, recurrent pulmonary embolism; four, the Eisenmenger syndrome; and one, multiple pulmonary arteriovenous fistula. Forty-three patients were hypeakly associated with arterial oxygen tension ( r = 0.50), but not with the arterial carbon dioxide tension or the level of pulmonary artery pressure. Sulfinpyrazone lengthened platelet survival in 12 of 24 (50%) treated patients but this drug did not alter either arterial oxygen tension arterial carbon dioxide tension, or pulmonary artery pressure. Our results suggest that hypoxemia is associated with shortened platelet survival time and that platelets may, therefore, be involved in the thromboembolic complications that develop in pa...
S-Gene Target Failure as a Marker of Variant B.1.1.7 Among SARS-CoV-2 Isolates in the Greater Toronto Area, December 2020 to March 2021
Authors: Kevin A. Brown, Jonathan Gubbay, Jessica Hopkins, Samir Patel, Sarah A. Buchan, Nick Daneman, Lee William Goneau
Journal: JAMA (2021)

Baha Abdalhamid, MD, PhD; Peter C. Iwen, PhD; Michael R. Wiley, PhD; Catherine B. Pratt, MS; Steven H. Hinrichs, MD
Exercise capacity for survivors of cardiac transplantation or sustained medical therapy for stable heart failure.
Authors: L WStevenson, KSietsema, J HTillisch, VLem, JWalden, J AKobashigawa, JMoriguchi
Journal: Circulation (1990)

Cardiac transplantation is predicted to improve survival for patients with severe symptoms of heart failure and ejection fraction of 20% or less, but the exercise capacity after cardiac transplantation is less than normal. Patients responding to vasodilators and diuretics have progressive improvement in exercise capacity despite low ejection fraction. We hypothesized that among patients currently considered appropriate for transplantation who could nonetheless subsequently be stabilized on medical therapy tailored to hemodynamic goals, survivors after 6 months of sustained medical therapy would demonstrate exercise capacity comparable to that of survivors of transplantation. Of 146 patients referred, 118 (81%) were discharged on tailored therapy without transplantation, and 88 (60%) were stable for at least 1 month. Stability after discharge was more likely in patients with lower right atrial pressures and better renal function on therapy. Of the 88 stable patients, 45 patients were listed for transplant,...
Comparative hemodynamic effects of chewable isosorbide dinitrate and nitroglycerin in patients with congestive heart failure.
Authors: EMikulic, J AFranciosa, J NCohn
Journal: Circulation (1975)

Vasodilators are known to be effective in improving the hemodynamics of congestive heart failure by increasing cardiac output and reducing left ventricular filling pressure (LVFP). Long acting agents are needed to augment the practicality and availability of chronic vasodilator therapy. In the present study the vascular effects of chewable isosorbide dinitrate (CHIS), sublingual nitroglycerin (NTG) and placebo (P) were compared in eight patients with high LVFP due to heart failure. Patients with LVFP (pulmonary wedge pressure) over 14 mm Hg were given CHIS, 10 mg, NTG, 0.6 mg, and P, two chewable tablets, in random fashion. Heart rate (HR), blood pressure (BP) and LVFP were monitored for three hours after each drug. HR was not significantly affected by any drug, although it rose slightly after NTG and fell after CHIS. Significant reduction of BP occurred only after NTG, with peak effect at five minutes, but lasting only 15 minutes. NTG reduced LVFP 5.1 mm Hg (19.5%, P, less than 0.05), at peak effect, but...
Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trial
Authors: Veerle Stouten, René Westhovens, Sofia Pazmino, Diederik De Cock, Kristien Van der Elst, Johan Joly, Delphine Bertrand, Patrick Verschueren
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To compare outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years. Methods Patients with RA completing the 2-year CareRA randomised controlled trial were eligible for the 3-year observational CareRA-plus study. 5-year outcomes after randomisation to initial methotrexate (MTX) monotherapy with glucocorticoid bridging (COBRA-Slim) were compared with MTX step-up without glucocorticoids or conventional synthetic disease-modifying antirheumatic drug (DMARD) combinations with glucocorticoid bridging, per prognostic patient group. Disease activity (Disease Activity Score based on 28 joints calculated with C reactive protein (DAS28-CRP)) and functionality (Health Assessment Questionnaire (HAQ)) were compared between treatment arms using longitudinal models; safety and drug use were detailed. Results Of 322 eligible patients, 252 (78%) entered CareRA-plus, of which 203 (81%) completed the study. Treatments for high-risk patients resulted in comparable DAS28-CRP (p=0.539) and HAQ scores over 5 years (p=0.374). Low-risk patients starting COBRA-Slim had lower DAS28-CRP (p&lt;0.001) and HAQ scores (p=0.041) than those starting only on MTX. At study completion, 114/203 (56%) patients never had their original DMARD therapy intensified, with comparable rates between all treatments. Safety was comparable between treatments in high-risk patients. In low-risk patients, there were 18 adverse events in 10 COBRA-Slim and 36 in 17 patients treated with initial MTX monotherapy (p=0.048). Over 5 years, 22% of patients initiated biologics, 25% took glucocorticoids for &gt;3 months and 17% for &gt;6 months outside the bridging period. Conclusions All intensive treatments with glucocorticoids bridging demonstrated excellent 5 year outcomes. Initiating COBRA-Slim was comparably effective as more complex treatments for high-risk patients with early RA and more effective than initial MTX monotherapy for low-risk patients with limited need for biologics and chronic glucocorticoid use.
Targeted replacement of full-length CFTR in human airway stem cells by CRISPR-Cas9 for pan-mutation correction in the endogenous locus
Authors: Sriram Vaidyanathan, Ron Baik, Lu Chen, Dawn T. Bravo, Carlos J. Suarez, Shayda M. Abazari, Ameen A. Salahudeen, Amanda M. Dudek, Christopher A. Teran, Timothy H. Davis, Ciaran M. Lee, Gang Bao, Scott H. Randell, Steven E. Artandi, Jeffrey J. Wine, Calvin J. Kuo, Tushar J. Desai, Jayakar V. Nayak, Zachary M. Sellers, Matthew H. Porteus
Journal: Molecular Therapy (2021)

Cystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the CF transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction of the most common pathogenic mutation, there are many other pathogenic mutations throughout the CF gene. An autologous airway stem cell therapy in which the CFTR cDNA is precisely inserted into the CFTR locus may enable the development of a durable cure for almost all CF patients, irrespective of the causal mutation. Here, we use CRISPR-Cas9 and two adeno-associated viruses (AAVs) carrying the two halves of the CFTR cDNA to sequentially insert the full CFTR cDNA along with a truncated CD19 (tCD19) enrichment tag in upper airway basal stem cells (UABCs) and human bronchial epithelial cells (HBECs). The modified cells were enriched to obtain 60%–80% tCD19+ UABCs and HBECs from 11 different CF donors with a variety of mutations. Differentiated epithelial monolayers cultured at air-liquid interface showed restored CFTR function that was >70% of the CFTR function in non-CF controls. Thus, our study enables the development of a therapy for almost all CF patients, including patients who cannot be treated using recently approved modulator therapies. Cystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the CF transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction of the most common pathogenic mutation, there are many other pathogenic mutations throughout the CF gene. An autologous airway stem cell therapy in which the CFTR cDNA is precisely inserted into the CFTR locus may enable the development of a durable cure for almost all CF patients, irrespective of the causal mutation. Here, we use CRISPR-Cas9 and two adeno-associated viruses (AAVs) carrying the two halves of the CFTR cDNA to sequentially insert the full CFTR cDNA along with a truncated CD19 (tCD19) enrichment tag in upper airway basal stem cells (UABCs) and human bronchial epithelial cells (HBECs). The modified cells were enriched to obtain 60%–80% tCD19+ UABCs and HBECs from 11 different CF donors with a variety of mutations. Differentiated epithelial monolayers cultured at air-liquid interface showed restored CFTR function that was >70% of the CFTR function in non-CF controls. Thus, our study enables the development of a therapy for almost all CF patients, including patients who cannot be treated using recently approved modulator therapies.
Response to Comment on Nunley et al. Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes. Diabetes Care 2015;38:1768–1776
Authors: Karen A. Nunley, Christopher M. Ryan, Judith A. Saxton, Tina Costacou, Trevor J. Orchard, Caterina Rosano
Journal: Diabetes Care (2016)

We would like to thank van Broekhoven and Nefs (1) for their thoughtful comment that depression may explain the high rate of cognitive impairment (28%) we reported among adults with type 1 diabetes (T1D) (2). As our objective was to investigate the biological correlates of cognitive impairment in this patient population, the original article did not address depression. We do, of course, agree that this is an important topic, with studies showing lingering deleterious effects of depression on cognition even after depressive symptoms subside (3). Even so, our knowledge regarding depressive symptoms in adults with childhood-onset T1D remains limited. We therefore appreciate this opportunity …
The recent advances in scaffolds for integrated periodontal regeneration
Authors: Hyun Nyun Woo, Young Joon Cho, Solaiman Tarafder, Chang H. Lee
Journal: Bioactive Materials (2021)

The periodontium is an integrated, functional unit of multiple tissues surrounding and supporting the tooth, including but not limited to cementum (CM), periodontal ligament (PDL) and alveolar bone (AB). Periodontal tissues can be destructed by chronic periodontal disease, which can lead to tooth loss. In support of the treatment for periodontally diseased tooth, various biomaterials have been applied starting as a contact inhibition membrane in the guided tissue regeneration (GTR) that is the current gold standard in dental clinic. Recently, various biomaterials have been prepared in a form of tissue engineering scaffold to facilitate the regeneration of damaged periodontal tissues. From a physical substrate to support healing of a single type of periodontal tissue to multi-phase/bioactive scaffold system to guide an integrated regeneration of periodontium, technologies for scaffold fabrication have emerged in last years. This review covers the recent advancements in development of scaffolds designed for periodontal tissue regeneration and their efficacy tested in vitro and in vivo. Pros and Cons of different biomaterials and design parameters implemented for periodontal tissue regeneration are also discussed, including future perspectives.
CD148 Deficiency in Fibroblasts Promotes the Development of Pulmonary Fibrosis
Authors: Konstantin Tsoyi, Xiaoliang Liang, Giulia De Rossi, Stefan W. Ryter, Kevin Xiong, Sarah G. Chu, Xiaoli Liu, Bonna Ith, Lindsay J. Celada, Freddy Romero, Matthew J. Robertson, Anthony J. Esposito, Sergio Poli, Souheil El-Chemaly, Mark A. Perrella, YuanYuan Shi, James Whiteford, Ivan O. Rosas
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: CD148/PTRJ (receptor-like protein tyrosine phosphatase η) exerts antifibrotic effects in experimental pulmonary fibrosis via interactions with its ligand syndecan-2; however, the role of CD148 in human pulmonary fibrosis remains incompletely characterized.Objectives: We investigated the role of CD148 in the profibrotic phenotype of fibroblasts in idiopathic pulmonary fibrosis (IPF).Methods: Conditional CD148 fibroblast-specific knockout mice were generated and exposed to bleomycin and then assessed for pulmonary fibrosis. Lung fibroblasts (mouse lung and human IPF lung), and precision-cut lung slices from human patients with IPF were isolated and subjected to experimental treatments. A CD148-activating 18-aa mimetic peptide (SDC2-pep) derived from syndecan-2 was evaluated for its therapeutic potential.Measurements and Main Results: CD148 expression was downregulated in IPF lungs and fibroblasts. In human IPF lung fibroblasts, silencing of CD148 increased extracellular matrix production and resistance to apoptosis, whereas overexpression of CD148 reversed the profibrotic phenotype. CD148 fibroblast-specific knockout mice displayed increased pulmonary fibrosis after bleomycin challenge compared with control mice. CD148-deficient fibroblasts exhibited hyperactivated PI3K/Akt/mTOR signaling, reduced autophagy, and increased p62 accumulation, which induced NF-κB activation and profibrotic gene expression. SDC2-pep reduced pulmonary fibrosis in vivo and inhibited IPF-derived fibroblast activation. In precision-cut lung slices from patients with IPF and control patients, SDC2-pep attenuated profibrotic gene expression in IPF and normal lungs stimulated with profibrotic stimuli.Conclusions: Lung fibroblast CD148 activation reduces p62 accumulation, which exerts antifibrotic effects by inhibiting NF-κB–mediated profibrotic gene expression. Targeting the CD148 phosphatase with activating ligands such as SDC2-pep may represent a potential therapeutic strategy in IPF.
Ending the Sale of Cigarettes at US Pharmacies—Reply
Authors: Troyen A. Brennan, Steven Schroeder
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Disparate electrophysiological alterations accompanying dysrhythmia due to coronary occlusion and reperfusion in the cat.
Authors: P APenkoske, B ESobel, P BCorr
Journal: Circulation (1978)

The electrophysiologic changes associated with dysrhythmias induced by coronary occlusion and by subsequent reperfusion were characterized with six complimentary approaches in chloralose-anesthetized cats (n = 57) with proximal occlusion of the left anterior descending (LAD) coronary artery. Occlusion led to reproducible ventricular dysrhythmia which abated in 35 minutes. The electrophysiologic effects of reperfusion initiated at this time could be studied. Simultaneous bipolar electrograms (epi-, myo- and endocardial) from ischemic and normal zones were analyzed by computer. Before the onset of the dysrhythmia induced by occlusion, conduction was markedly slowed, with dV/dt decreasing to 34% +/- 6% of control and conduction time (endo- to epicardial activation) prolonged to 328 +/- 77% of control. However, these values returned toward normal with reperfusion, even though it also consistently induced dysrhythmia. The idioventricular escape rate (determined by intense vagal stimulation) was 62 +/- 6 beats/...
Role of veins and cerebral venous pressure in disruption of the blood-brain barrier.
Authors: W GMayhan, D DHeistad
Journal: Circulation Research (1986)

The goal of this study was to determine whether increases in cerebral venous pressure contribute to, and may account for, disruption of the blood-brain barrier during acute hypertension and hyperosmolar stimuli. We studied the relation between pial venous pressure and disruption of the blood-brain barrier during acute arterial hypertension, superior venae cavae occlusion, and superfusion with hyperosmolar arabinose. Sprague-Dawley rats were studied using intravital fluorescent microscopy and fluorescein-labelled dextran (mol. wt. = 70,000). Disruption of the blood-brain barrier was characterized by the appearance of microvascular leaky sites and quantitated by the clearance of fluorescein dextran. We measured pressure (servo null) in pial arterioles and venules 40-60 micron in diameter. Acute hypertension, occlusion of the superior venae cavae, and hyperosmolar arabinose produced leaky sites primarily in venules. Acute hypertension increased arteriolar pressure and also venular pressure, from 7 +/- 1 (mea...
Polyp Excision Rates Post-Covid-19: Personal Protective Equipment Does Not Impair Performance
Authors: T Matthews, N Breslin, D McNamara, A O’Connor, O Sarah, B Ryan
Journal: Endoscopy (2021)

Aims The UK JAG on GI Endoscopy's minimum standard for polyp detection rates (PDR) in colonoscopy is 15 %. The COVID-19 pandemic precipitated the use of restrictive personal protective equipment (PPE) which might reduce dexterity and decrease PDRs. We audited our polyp excision rates both prior to and post the COVID-19 pandemic in order to assess whether restrictive PPE led to a diminution therein.
Submucosal Tunneling Diverticular Septotomy (Stesd) by Diverticular Peroral Endoscopic Myotomy (D-Poem) for Treatment of Diverticula of the Middle and Lower Esophagus
Authors: S Nagl, SK Goelder, A Ebigbo, H Messmann
Journal: Endoscopy (2021)

Aims Esophageal diverticula are rare conditions, causing symptoms such as dysphagia and regurgitation. Large symptomatic diverticula are mostly managed by surgical myotomy and fundoplication. However, surgery can be challenging due to its extensive invasiveness. Minimal invasive endoscopic approaches such as diverticular peroral endoscopic myotomy (D-POEM) may be a less-invasive, transoral treatment option. We prospectively analysed the technical and clinical success after D-POEM.
Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation.
Authors: G CCheng, H MLoree, R DKamm, M CFishbein, R TLee
Journal: Circulation (1993)

BACKGROUNDAlthough rupture of an atherosclerotic plaque is considered to be the cause of most acute coronary syndromes, the mechanism of plaque rupture is controversial.METHODS AND RESULTSTo test the hypothesis that plaque rupture occurs at sites of high circumferential stress in the diseased vessel, the distribution of stress was analyzed in 24 coronary artery lesions. Histological specimens from 12 coronary artery lesions that caused lethal myocardial infarction were compared with those from 12 stable control lesions. A finite element model was used to calculate the stress distributions at a mean intraluminal pressure of 110 mm Hg. The maximum circumferential stress in plaques that ruptured was significantly higher than maximum stress in stable specimens (4,091 +/- 1,199 versus 1,444 +/- 485 mm Hg, p < 0.0001). Twelve of 12 ruptured lesions had a total of 31 regions of stress concentration of more than 2,250 mm Hg (mean, 2.6 +/- 1.4 high stress regions per lesion); only one of 12 control lesions had a s...
If rabbits can regenerate the eye's lens, will science find a way for humans to do it?
Authors: C. M. Olson
Journal: JAMA (1989)

THE ABILITY of rabbits to regenerate the lens of the eye was observed and described by French investigators in 1824. Now, Arlene Gwon, MD, Department of Ophthalmology, University of California, Irvine, and colleagues have used that model in developing techniques to induce lens regeneration. The investigators use ultrasound to break up the material within the rabbit lens capsule (phacoemulsification). The cȯntents are aspirated, and fetal cells are placed within the lens capsule. <h3>Regrowth Pattern</h3> The pattern of regrowth follows that of embryonic development. The crystallin proteins that develop are the same as in the adult lens, but in proportions similar to those found in fetal lenses, the researchers explained at the recent Research to Prevent Blindness science writers' conference in Arlington, Va. They add that this model can be used to study the influence of growth factors, either to promote or inhibit growth. Presently, 1 million Americans have cataract surgery
Ventricular loading is coupled with DNA synthesis in adult cardiac myocytes after acute and chronic myocardial infarction in rats.
Authors: J MCapasso, SBruno, WCheng, RRodgers, ZDarzynkiewicz, PAnversa
Journal: Circulation Research (1992)

To determine whether the overload associated with myocardial infarction and ventricular failure in rats is coupled with activation of DNA synthesis in the remaining left and right ventricular myocytes, flow cytometric analysis was performed on myocyte nuclei prepared from both ventricles 7 and 30 days after coronary occlusion. In addition, oral captopril was administered in separate groups of control and experimental rats to establish whether a relation existed between attenuation of ventricular loading and magnitude of DNA synthesis in myocytes. Results demonstrated that left ventricular failure and right ventricular dysfunction at 7 days after infarction were biventricularly associated with marked increases in the number of myocyte nuclei in the G2M phase of the cell cycle. In contrast, the fraction of nuclei in the G0+G1 phase decreased. In comparison with the earlier time point, the 30-day interval was characterized by a significant magnitude of cardiac hypertrophy, a moderate amelioration of ventricu...
Transcriptional regulation of left ventricular beta-adrenergic receptors during chronic hypoxia.
Authors: DBernstein, RDoshi, SHuang, EStrandness, J RJasper
Journal: Circulation Research (1992)

beta-Adrenergic receptor downregulation is the end result of cellular adaptation to prolonged agonist exposure. The factors mediating receptor downregulation include receptor phosphorylation, receptor movement from the plasma membrane to intracellular sites, and alterations in nascent receptor synthesis. We have previously demonstrated a downregulation of the left ventricular beta-receptor during chronic hypoxia in vivo. To determine the mechanism of this downregulation, we produced chronic hypoxia in seven newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 weeks. Six lambs served as normoxic controls. Sarcolemmal membrane and cytosolic fractions were prepared from left ventricular free wall samples. beta-Receptor density in each fraction was determined with the radioligand [125I]iodocyanopindolol. Steady-state levels of beta-receptor mRNA were determined by Northern blot analysis using a beta 1-adrenergic receptor cDN...