tbuckley/cabot-search huggingface dataset:
Abstract 3398: Comparison of Once Versus Twice a Day Valsartan Dosing in Heart Failure -Results of the DESTINY Trial
Authors: Inder S Anand, Anita Deswal, Dean J Kereiakes, Alan Steljes, Dion H Zappe, William L Daley
Journal: Circulation (2007)

Background. Valsartan causes a sustained 24-hour reduction in blood pressure (BP) in hypertensive patients, when given once a day (q.d.). Because many CHF patients have low baseline BP and concomitant chronic kidney disease, valsartan was prescribed twice a day (b.i.d.) in Val-HeFT (Valsartan in Heart Failure Trial) to avoid any possible adverse effects like symptomatic hypotension and worsening renal dysfunction with the q.d. dosing. Methods and Results. DESTINY-HF ( D iovan E valuation of S afety T w I ce vs o N ce dail Y study in H eart F ailure) was a 10-week double blind randomized trial designed to test the safety of q.d. (n=55) vs b.i.d. (n=60) dosing of valsartan in patients with NYHA class II–III heart failure receiving diuretics (87%), ACE-I (98%), beta-blockers (92%), aldosterone antagonists (25%) and digoxin (32%) over a 12-week period. Valsartan was started in the dose of 40 mg b.i.d. vs 80 mg q.d. and titrated to a maximum of 320 mg per day by doubling the dose every 2 weeks. Clinical and biochemical measurements were made at 2, 4, 6, and 10 weeks. The baseline characteristics of the two groups were similar. The average dose of valsartan at the end of study was 245 mg vs 256 mg in the bid vs qd dose groups (p=NS). The % of patients who tolerated the up-titration regimen at week 2, 4 and 6 and at the end of study were not significantly different between the dose groups (b.i.d. vs q.d., 75 vs 75, 74 vs 85, 77 vs 78, and 67 vs 68; p=NS). There was no difference in the reduction of systolic or diastolic BP, or in the incidence of hypotension, renal impairment, orthostatic dizziness or syncope between the groups at any time point. Changes in serum K + , creatinine, cystatin-C, and estimated GFR were also not different between the groups at any time point. Brain natriuretic peptide decreased, and by the same amount in both groups at all time points. Conclusions. These data demonstrate that the use of valsartan in q.d. dosing has the same safety profile as b.i.d. dosing in patients with moderate to severe heart failure.
Abstract 2972: Functional Characterization of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Shugo Tohyama, Mitsushige Murata, Fumiyuki Hattori, Tomofumi Tanaka, Hao Chen, Hiromi Yamashita, Yusuke Sato, Toru Egashira, Tomohisa Seki, Hisayuki Hashimoto, Yohei Ohno, Yuichi Tamura, Shinsuke Yuasa, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2009)

[Background] Although many genetic cardiac disorders have been identified, their underlying genetic mechanisms are largely unknown. In this regard, human induced pluripotent stem (iPS) cells may pr...
New Anti-BSE Rules Imposed
Authors: Tracy Hampton
Journal: JAMA (2004)

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
Abstract P195: Hypertension is Associated With an Abnormal Pressor Response to Voluntary Apnea
Authors: Noah Jouett, Ryan Mason, Dorene Niv, Donald E Watenpaugh, Michael L Smith
Journal: Circulation (2015)

Background: Cardiovascular diseases are commonly associated with elevated sympathetic nerve activity (SNA). Previously, we have shown that the blood pressure response to a voluntary apnea is closely correlated with the SNA response in patients with sleep disordered breathing (SDB) and thus may serve as an index of SNA responsiveness. In the current study, we hypothesized that the pressor response to apnea is 1) reduced with effective treatment of SDB in SDB patients, and 2) that it is exaggerated in hypertensive patients (HTN) when compared to healthy control subjects. Methods: 22 OSA patients (14 treated and 8 untreated), 19 treated hypertensive patients and 23 healthy normotensive control subjects were recruited from the UNTHSC Primary Care Center and Sleep Consultants of Texas. Subjects completed a medical history questionnaire and Epworth Sleepiness survey. Blood pressure was measured by standard auscultatory assessment in the seated position. Baseline blood pressure was obtained in triplicate during quiet rest. Then after practicing a voluntary breath hold, subjects repeated three voluntary 20-second breath holds each beginning at end-expiration. Comparisons were made 1) between treated and untreated SDB patients, and 2) between HTN patients and healthy control subjects using a Student t test. Results: Importantly, as in prior studies the pressor response to apnea was not different from zero in the healthy control subjects (-1.0 ± 4.2 mmHg, p&gt;0.05). In the SDB patients, the pressor response was significantly greater than zero in both treated (11.4 ± 3.9 mm Hg) and untreated (24.5 ± 9.8 mm Hg) SDB patients (p&lt;0.001), and was significantly reduced in the treated SDB patients (p&lt;0.001). In addition, the pressor response was significantly greater in the HTN patients (10.5 ± 5.3 mmHg, p&lt;0.001) compared to the healthy control subjects. Conclusions: These data support our hypotheses that the pressor response to voluntary apnea is exaggerated in both untreated SDB and treated HTN patients and that effective treatment of SDB reduces this response, but does not normalize the response. These data suggest that the pressor response to apnea may be a simple physiologic index of exaggerated sympathetic responsiveness.
Pharmaceutical Industry Funding for Residencies Sparks Controversy
Authors: Bridget M Kuehn
Journal: JAMA (2005)

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
Role of hyperglycemia-induced thioredoxin-interacting protein (TXNIP) in metastatic breast cancer
Authors: Francesco Turturro, Ellen Friday, Gang Ye, Martin Watts, Tomas Welbourne
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

429 

Epidemiologic studies have addressed the risk of breast cancer and abnormalities of the glucose metabolism. In vertebrates, it becomes difficult to discriminate glucose effects on gene transcription from those related to either insulin or glucagon. We analyzed the gene expression in response to glucose from 5 mM (normoglycemia) to 20 mM (hyperglycemia/diabetes) by microarray analysis (Affimetrix) in breast cancer derived cell line MDA-MD-231. We identified 8 patterns (groups) of gene expression related to glucose concentration with ≥ 1.5 fold change compared to controls. Particularly, we identified the thioredoxin interacting protein (TXNIP) gene in group 1 (514 genes), hence this gene has been recently shown to contain carbohydrate responsive elements (ChoREs), and the RNA level of which increased as gene product particularly sensitive to the variation of the level of glucose in culture media. Furthermore, based on the recent acquisition that TXNIP acts as a modulator of the redox system through binding of thioredoxin (TRX), we also assessed the status of TRX RNA expression by semi-quantitative PCR analysis in MDA-MD-231 cells. Whereas the levels of TXNIP RNA steadily increased with the concentration of glucose (0.21±0.03/5mM ratio/βactin vs 0.95±0.1/20mM, P=0.03), TRX RNA remained unchanged (1.7±0.001/5mM vs 1.9±0.12/20mM) after 24h of incubation at the given concentration of glucose. Subsequently, we further validated our initial data on TXNIP RNA expression either in non-tumorigenic mammary epithelial cells (MCF10A) or in tumorigenic MCF-7 and T47D cells by semi-quantitative PCR analysis after 24 h in tissue culture at various concentrations of glucose. The glucose-mediated TXNIP gene expression response was present in all the cell lines tested, though, the order of magnitude of the TXNIP gene response in MDA-MD-231 cells was on average 4-fold higher compared to the rest of the cells (other cell lines /1.23±0.26 vs MDA-MD-231/4.63±1.21 fold increase 5 vs 20 mM standardized to βactin). A recent study has shown that the TXNIP expression measured by immunohistochemistry in cells from colon/gastric primary tumor tissues is reduced compared to adjacent normal tissue from the primary sites of the tumors. Although these studies favor the hypothesis that the level of TXNIP decreases with the malignant transformation of the cell phenotype, our data show that the magnitude of the glucose-induced TXNIP gene regulation rather than the TXNIP level or the mechanism of glucose-response regulating its level seems to be associated with the highly metastatic phenotype in MDA-MD-231 cells. This finding was unexpected since malignant cells highly depend upon glycolysis and hyperglycemia-induced TXNIP may have an unfavorable function, the relevance of which will be investigated.
The impact of aerobic exercise on lung inflammation and remodeling in experimental emphysema
Authors: Isabela Guimarães, Gisele Padilha, Miquéias Lopes-Pacheco, Patricia Marques, Mariana Antunes, Nazareth Rocha, Edson Assis, Hugo Faria-Neto, Raquel Magalhaes, Debora Xisto, Patricia Rocco
Journal: European Respiratory Journal (2011)

This study investigated the impact of aerobic exercise on lung inflammation and remodeling in experimental emphysema. 32 BALB/c mice were assigned into 2 groups. In control (C) animals, saline was intratracheally ( it ) injected, whereas emphysema mice received porcine pancreatic elastase (ELA, 0.1 UI, it ). Saline and ELA were it injected once a wk during 4 wks. After the last wk, C and emphysema groups were further randomized into subgroups: sedentary and exercise. Exercise mice ran on a motorized treadmill, at moderate intensity (8-12 m.min-1), 5% grade, 30 min/day, 3 times a wk for 4 wks. 24-h after the last session, lung mechanics and morphometry, as well as cytokines and total cell count in bronchoalveolar lavage fluid (BALF) and blood were measured. Echocardiographic analysis was done before and after emphysema induction and at the end of the experiment. The sedentary emphysema group presented, compared to C: 1) reduced lung static elastance; 2) increased lung hyperinflation and elastic fiber content; 3) augmented levels of KC [murine interleukin (IL)-8 homolog], tumor necrosis factor-α, interferon-γ, and IL-10; and 4) pulmonary arterial hypertension, evidenced by increased pulmonary flow acceleration. Aerobic exercise: 1) improved lung mechanics, 2) reduced lung hyperinflation, and the number of cells and levels of these cytokines in BALF and blood, 3) diminished elastic fiber content, and 4) restored pulmonary flow acceleration to C values. In conclusion, in the present elastase-induced emphysema model, 4 weeks of aerobic exercise modulated the inflammatory process and acted on lung remodeling, improving pulmonary function.

Supported by: INCT-INOFAR, FAPERJ, PRONEX, CNPq
Myopia
Authors: M. Barnes
Journal: BMJ (2002)

Editor—In his article on myopia Fredrick said that most research into myopia has been limited by its retrospective nature and lack of control group and follow up.1-1 We conducted a prospective, controlled, three year follow up study of myopia and showed direct evidence of myopic shift in students reading and doing intensive near work compared with children who were not attending school, schoolchildren who did not read much, and skilled manual labourers.1-2

Fredrick mentioned three possible causes for the development of myopia: retinal blur, accommodation, and familial factors. A fourth possibility exists: convergence. Convergence, rather than accommodation, could be an important factor in myopic progression.1-3–1-5

In their three year follow up study Parssinen et al showed that neither the use of bifocals nor avoiding the use of myopic spectacles in reading slowed down myopic progression.1-3 Parssinen and Lyyra found more myopic progression in subjects needing less accommodation than in those needing more.1-4 They concluded that if accommodation played a significant part in myopic progression, reading with undercorrected glasses or without glasses would probably halt the process through a feedback mechanism. In our study we observed a significant axial length elongation during near fixation both with and without cycloplegia (with and without accommodation).1-5

These results do not support the hypothesis of accommodation as a significant cause of myopia. Rather, axial elongation during near focusing suggests that convergence may be one factor inducing myopia. Parssinen et al and Parssinen and Lyyra thought that constant saccadic eye movements during reading could cause repeated pressure and stretch pulses on the eye.

I think therefore that axial elongation, which is a main cause of myopic progression, seems to result from the effect of accommodative convergence rather than accommodation itself. Much use of convergence may be one of the contributing factors in adult onset and adult progression of myopia.
Mortality and Ratio of Blood Products Used in Patients With Severe Trauma
Authors: Hunter B. Moore, Ernest E. Moore, Eduardo Gonzalez
Journal: JAMA (2015)

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
Abstract 17029: Selective Inhibition of Late Sodium Current Suppresses Arrhythmogenic Markers in Models of Long QT Syndrome
Authors: Donglin Guo, Gongxin Liu, Sridharan Rajamani, Luiz Belardinelli
Journal: Circulation (2014)

Introduction:  Long QT syndrome (LQTs) is characterized by reduction of net repolarizing current, increased transmural dispersion of repolarization (TDR), prolongation of QT interval and polymorphic ventricular arrhythmias ( Torsade de Pointes,  TdP ). Management of LQTs and TdP is still a challenge and an effective drug therapy has not been well established. This study tested the hypothesis that selective inhibition of late Na +  current (I NaL ) can stabilize cardiac repolarization and terminates ventricular arrhythmias. Towards this, GS-6615 (dihydrobenzoxazepinone), a potent and selective inhibitor of I NaL  that is currently in clinical development for the treatment of ventricular arrhythmias was used to determine its effect on arrhythmogenic markers in models mimicking LQT2 and 3 syndromes.   Methods:  Transmembrane action potentials (APs) were simultaneously recorded from epicardium (Epi) and endocardium (Endo) along with a transmural electrocardiogram (ECG) at different basic cycle lengths (BCL; 500, 1000 and 2000 ms) in arterially perfused rabbit left ventricular wedge preparations. E-4031 (I Kr  blocker) and  Anemonia sulcata  toxin (ATX-II, late I Na  enhancer) were used to mimic LQT2/3, respectively.   Results:  E-4031 (60 nM) and ATX-II (2 nM) caused early afterdepolarization (EADs, Fig. 1A), increased TDR (Fig 1B), prolonged QT (Fig 1C) and Tp-e intervals (Fig 1D), Tp-e/QT ratio, steeper QT-BCL and Tp-e-BCL slopes, R-on-T phenomenon (Fig. 1A) and  TdP . GS-6615 (0.1 -1 μM, n=4) in the presence of E-4031 (Fig. 1A) or ATX-II caused a concentration-dependent decrease in all the above mentioned arrhythmogenic markers. Similarly, pretreatment of wedge preparations with GS-6615 (0.3 μM, n=4), abolished the pro-arrhythmic phenotypes of E-4031 and ATX-II.   Conclusions:  Our results show that selective inhibition of late I Na  is effective in suppressing arrhythmogenic markers and ventricular arrhythmias associated with LQT2/3 syndromes.
The Functioning and Well-being of Depressed Patients
Authors: Kenneth B. Wells
Journal: JAMA (1989)

We describe the functioning and well-being of patients with depression, relative to patients with chronic medical conditions or no chronic conditions. Data are from 11 242 outpatients in three health care provision systems in three US sites. Patients with either current depressive disorder or depressive symptoms in the absence of disorder tended to have worse physical, social, and role functioning, worse perceived current health, and greater bodily pain than did patients with no chronic conditions. The poor functioning uniquely associated with depressive symptoms, with or without depressive disorder, was comparable with or worse than that uniquely associated with eight major chronic medical conditions. For example, the unique association of days in bed with depressive symptoms was significantly greater than the comparable association with hypertension, diabetes, and arthritis. Depression and chronic medical conditions had unique and additive effects on patient functioning. (<i>JAMA</i>. 1989;262:914-919)
Abstract 12246: Is Mitochondrial DNA Fragmentation a Major Contributor to Necrosis in Myocardial Infarction?
Authors: Michael V Cohen, Xi-Ming Yang, Lin Cui, Glenn L Wilson, Mikhail Alexeyev, Mark N Gillespie, James M Downey
Journal: Circulation (2014)

A fusion protein based on endonuclease III, a DNA repair enzyme with pyrimidine glycosylase/AP lyase activity, engineered to enter cells and be taken up by mitochondria (EndoIII) given to ischemic mouse hearts at reperfusion reportedly reduces infarct size (IS). We tested whether EndoIII protects ischemic myocardium by preventing mitochondrial DNA (mtDNA) fragmentation. Extracellular mtDNA can be mistaken for bacterial DNA by neighboring cells and trigger an injurious inflammatory response which in the heart could lead to spreading necrosis. In situ rat hearts were subjected to 30-min coronary occlusion/2-h reperfusion. Intravenous EndoIII just prior to reperfusion reduced IS from 43.8±1.4% of risk zone in control hearts to 24.0±1.3% with no detectable hemodynamic effect. Enzymatically inactive EndoIII offered no protection. EndoIII’s protection was comparable to that of the platelet P2Y12 antagonist cangrelor (25.0±1.8% of risk zone). Because loading with a P2Y12 receptor blocker to inhibit platelets is currently standard of care for treatment of myocardial infarction (MI), we tested whether EndoIII could further reduce IS in rats treated with a maximally protective dose of cangrelor. The combination reduced IS to 15.1±0.9%, significantly smaller than that seen with either cangrelor or EndoIII alone. Protection from cangrelor but not EndoIII was abrogated by blockade of phosphatidylinositol-3 kinase or adenosine receptors indicating differing cellular mechanisms. If released mtDNA fragments induce spreading necrosis in the reperfused tissue, then degrading extracellular mtDNA with deoxyribonuclease I (DNase I) should prevent it. Intravenous DNase I at reperfusion mimicked EndoIII’s protection supporting the hypothesis. DNase I protection was additive to that of cangrelor and it also protected Krebs-perfused hearts indicating blood cells were not involved in its protection. Combining EndoIII and DNase I provided even greater protection presumably by protecting many of the ischemic cardiomyocytes and also by preventing necrosis spreading from those cells that EndoIII could not save. Because protection from EndoIII and DNase I can add to protection from a P2Y12 blocker, it should be effective in today’s patients with acute MI.