tbuckley/cabot-search huggingface dataset:
Abstract 3500: Rescue and Worsening of Electrocardiographic Abnormalities in Two Experimental Transgenic Murine Models of Congenital Heart Block
Authors: Eddy Karnabi, Yongxia Qu, Mohamed Boutjdir
Journal: Circulation (2008)

Congenital Heart Block (CHB) is a passively acquired autoimmune disease associated with the transfer of maternal autoantibodies anti-SSA/Ro -SSB/La through the placenta causing AV block and sinus bradycardia. We previously established a murine model for CHB in which pups born to wild type (WT) mothers immunized with Ro and/or La recombinant proteins developed conduction abnormalities similar to those seen in the clinical settings and inhibited L-type Ca channels (LTCC) responsible for electrogenesis at the AV and SA node. Here, we hypothesized that overexpression of cardiac LTCC should prevent or reduce the electrocardiographic abnormalities seen in the pups, whereas LTCC knockout should exhibit severe conduction abnormalities and increased mortality. Transgenic (TG) mice overexpressing LTCC and LTCC knockouts were immunized with Ro and La antigens. Following the immunization and boosters, a high antibody titer was demonstrated both in mothers and pups. ECG parameters were measured from pups born to immunized and to WT mothers. Ca channel overexpressing pups had significantly lesser sinus bradycardia and AV block compared to their non-TG (NTG) litter mates and WT pups. Sinus bradycardia was seen in 10% (n= 90) of TG pups v.s. 19.7% in WT (n=76, p&lt;0.05) vs. 22% NTG littermates (n=109, p&lt;0.05) and AV block in 8.8% of TG (n=90) v.s. 25% in WT (n= 76, p&lt;0.05) v.s. 27.5% in NTG (n=109, p&lt;0.05). On the other hand, Ca channel knockout pups had a significantly higher sinus bradycardia and a higher percentage of AV bock; 100% in knockout pups (n=16, p&lt;0.05), 42.3% in heterozygotes (n=52, p&lt;0.05), and 18.2% in NTG (n=33, p&lt;0.05). No electrocardiographic abnormalities were observed in control WT pups (nonimmunized). Cardiac specific overexpression of LTCC significantly rescues the incidence of AV block and sinus bradycardia in pups exposed to circulating maternal anti-Ro/La autoantibodies. Whereas exposure of LTCC knockout pups to anti-Ro/La autoantibodies significantly worsened the conduction abnormalities. This finding support the hypothesis that maternal antibodies’ inhibition of LTCC contributes to the development of CHB. Altogether the results are relevant for future novel therapies for CHB.
A Phase 2 Study of ABT-199 (GDC-0199) in Patients with Acute Myelogenous Leukemia (AML)
Authors: Marina Konopleva, Daniel A. Pollyea, Jalaja Potluri, Brenda J. Chyla, Todd Busman, Evelyn McKeegan, Ahmed Salem, Ming Zhu, Justin L. Ricker, William Blum, Courtney D. DiNardo, Martin Dunbar, Rachel Kirby, Nancy Falotico, Joel D. Leverson, Rod A. Humerickhouse, Mack Mabry, Richard M. Stone, Hagop M. Kantarjian, Anthony G. Letai
Journal: Blood (2014)
13-cis-Retinoic Acid Plus Interferon- 2a in Locally Advanced Squamous Cell Carcinoma of the Cervix
Authors: S. M. Lippman, J. J. Kavanagh, M. Paredes-Espinoza, F. Delgadillo-Madrueno, P. Paredes-Casillas, W. K. Hong, G. Massimini, E. E. Holdener, I. H. Krakoff
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article 13- cis -Retinoic Acid Plus Interferon-α2a in Locally Advanced Squamous Cell Carcinoma of the Cervix Get access Scott M. Lippman, Scott M. Lippman Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston Correspondence to : Scott M. Lippman, M.D., Department of Medical Oncology, Box 80, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar John J. Kavanagh, John J. Kavanagh Departments of Medical Oncology and Gynecology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Mario Paredes-Espinoza, Mario Paredes-Espinoza Department of Medicine, Hospital Civil de GuadalajaraGuadalajara, Mexico Search for other works by this author on: Oxford Academic PubMed Google Scholar Fernando Delgadillo-Madrueño, Fernando Delgadillo-Madrueño Department of Medicine, Hospital Civil de GuadalajaraGuadalajara, Mexico Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia Paredes-Casillas, Patricia Paredes-Casillas Department of Medicine, Hospital Civil de GuadalajaraGuadalajara, Mexico Search for other works by this author on: Oxford Academic PubMed Google Scholar Waun Ki Hong, Waun Ki Hong Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Giorgio Massimini, Giorgio Massimini F. Hoffmann-La-Roche, Basel, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Eduardo E. Holdener, Eduardo E. Holdener F. Hoffmann-La-Roche, Basel, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Irwin H. Krakoff Irwin H. Krakoff Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 6, 17 March 1993, Pages 499–500, https://doi.org/10.1093/jnci/85.6.499 Published: 17 March 1993 Article history Received: 17 December 1992 Accepted: 21 December 1992 Published: 17 March 1993
Abstract 1572: Single Histidine Button in Cardiac Troponin I Sustains Heart Performance in Response to Severe Hypercapnic Respiratory Acidosis In Vivo
Authors: Nathan J Palpant, Louis G D’Alecy, Joseph M Metzger
Journal: Circulation (2008)

Intracellular acidosis is a profound negative regulator of myocardial performance. The purpose of this study was to determine whether titrating myofilament calcium sensitivity could protect the whole animal physiological response to acidosis in vivo. We hypothesized that single histidine substituted cardiac troponin I (A164H) transgenic (Tg) mice would confer cardio-protection during a severe respiratory acidosis challenge in vivo . Severe hypercapnic acidosis was induced in mice by ventilation with 40% CO 2 . Echocardiographic analysis showed that systolic function and ventricular geometry were maintained in Tg mice. By contrast, nontransgenic (Ntg) littermates experienced marked deterioration in systolic performance and significant LV dilation during this same challenge (ejection fraction during hypercapnia: [Ntg, n =5] 23.6 ± 4.9 vs. [Tg, n=7] 67.8 ± 4.5% P &lt; 0.05; volume at systole during hypercapnia: [Ntg, n = 5] 40.6 ± 5.1 vs. [Tg, n = 7] 14.4 ± 3.4 mm 3 P &lt; 0.05). Using radio-telemetry to monitor blood pressure in freely moving animals, Tg mice maintained significantly higher peripheral arterial blood pressures compared to Ntg mice during a long term acidosis challenge (change in mean arterial pressure: [Ntg, n = 4] −81.5 ± 18.4 vs. [Tg, n = 7] −37.7 ± 6.3 mmHg P &lt; 0.05). For detailed hemodymanic assessment, pressure-conductance analysis was performed. To specifically isolate cardiac performance, animals were treated with a beta blocker, esmolol, during a 40% CO 2 challenge. Survival and load independent measures of contractility were significantly greater in Tg vs. Ntg mice (preload recruitable stroke work: [Ntg, n = 6] 78.6 ± 9.5 vs. [Tg, n = 7] 147.2 ± 9.6 P &lt; 0.05). Furthermore, hemodynamic analysis during beta blockade and hypercapnia showed that Ntg mice underwent marked cardiac decompensation and death within five minutes of acidosis compared to Tg mice that maintained contractility and survived the challenge (survival curve [Ntg, n = 6; Tg n = 7], P &lt; 0.0002). This study shows that, independent of any beta adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains contractile function and improves survival during severe hypercapnic acidosis in vivo . This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota &amp; Wisconsin).
Chronic exposure to higher BP in young adults is associated with cardiac dysfunction in middle age
Authors: S. Mayor
Journal: BMJ (2015)

Young adults with blood pressure at the higher end of the normal range that continues into middle age have a raised risk of left ventricular dysfunction, says a 25 year follow-up study published in the Journal of the American College of Cardiology , which suggests recommending lifestyle changes in younger people to reduce elevated blood pressure.

The Coronary Artery Risk Development in Young Adults (CARDIA) study followed up 2479 men and women aged 18 to 30 …
Abstract 13102: Inhibition of Hmgb1 Attenuates Smooth Muscle Cell Proliferation And Balloon Injury-Induced Neointimal Hyperplasia
Authors: Jing Chen, Jing Zhang, Changwu Xu, Jian Yang, Sisi Chen, Yunjie Wei, Hong Jiang
Journal: Circulation (2011)

BACKGROUND HMGB1, a DNA-binding protein and cytokine, is expressed by endothelial cells, vascular smooth muscle cells (VSMCs) and macrophages in atherosclerotic lesions. However, its role in vascul...
Teaching evidence based medicine
Authors: Chris Del Mar, Paul Glasziou, Dan Mayer
Journal: BMJ (2004)

Should be integrated into current clinical scenarios 

Teaching clinical epidemiology has always been challenging, seen as too mathematical and remote from normal clinical practice. Evidence based medicine (EBM) evolved to provide the skills needed to manage the potential information overload of modern medical schools, especially at McMaster, the shortest medical programme in the world. Students have to grasp two essential principles of EBM: its empirical approach to optimal clinical decisions (regardless of pathophysiology, does the bottom line of the balance sheet show gain or loss?); and its quantitative expression (how big is that gain or loss?). These require some mastery of epidemiology and statistics, both repellent to many doctors, even in teaching hospitals.1 2 Now most medical programmes in the United States attempt to teach EBM, although few succeed (the two most important barriers being inadequate access to electronic information at the point of care, and inadequate faculty training).3

What are the best ways of teaching this stuff? By breaking its elements …
Abstract 11204: Long-term Effects of Sarpogrelate, a Selective Serotonin Receptor Antagonist, in Diabetic Patients with Stable Angina and Chronic Kidney Disease
Authors: Hideki Watanabe, Kunio Nakagawa, Masaaki Kakihana
Journal: Circulation (2011)

Background: Diabetes mellitus (DM) and Chronic Kidney Disease (CKD) are known as a major risk factor for cardiovascular disease (CVD). Sarpogrelate, a selective serotonin blocker, is known to have not only the inhibitory effects of platelet aggregation and vasoconstriction, but also the improvement of albuminuria. This study was designed to investigate long-term effects of sarpogrelate in diabetic patients with stable angina and chronic kidney disease (CKD). Methods: After the standard medical therapy, seventy nine type 2 diabetic patients with stable angina and CKD (stage 3 or 4) were randomized to receive sarpogrelate (sarpogrelate group, n=42) or not to receive sarpogrelate (control group, n=37). We measured flow-mediated dilatation (FMD) of brachial artery and pulse wave velocity (PWV), and assessed exercise tolerance and renal function (estimated glomerular filtration rate, eGFR). Measurements were performed at baseline, and then at every one year after the treatments. The primary outcome was major a...
Abstract 15969: Epicardial Fat Thickness is an Overlooked Predictor of Cachexia in Heart Failure
Authors: Elif H Ozcan Cetin, Mehmet S Cetin, Ugur Canpolat, Selahattin Aydin, Yesim Akin Guray, Dursun Aras, Ahmet Temizhan, Sinan Aydogdu
Journal: Circulation (2014)

Introduction: Cachexia, as a miscellaneous phenomenon in heart failure (HF) with a prevalence of 10-15%, is associated with morbidity and mortality. Inflammation has been postulated as the hallmark factor in cachexia pathogenesis. Epicardial Fat Thickness (EFT) is the source of inflammatory mediators and has a close relationship with various cardiac diseases. Beyond other imaging modalities, echocardiography can be a simple and useful method in the evaluation of this tissue. In this study we objected to determine the relation of EFT and cardiac cachexia in heart failure MATERIALS AND METHODS: Our study consisted of totally 100 patients with heart failure with low ejection fraction (EF &lt;30%) with BMI &lt;25 kg/m2; 50 patients with cachectic HF and 50 patients with non-cachectic HF as the control group. The diagnosis of cachexia was based on the criteria as defined by Ewans WJ et al. (2008). EFT was measured with transthoracic echocardiography at systole in parasternal long axis view. RESULTS: In patients with cachectic HF (mean age 56.7±13.3, %44 male). EFT were higher than the control group (mean age 58.4±15.0, % 48 male).As a confounding factor; BMI was not different between groups (21.8±2.7 vs. 22.1±3.1, p=0.12).In correlation analysis of EFT with components of cachexia,EFT was significantly positively correlated with CRP (β=0.357 p&lt;0.001) and negatively correlated with hand grip strength (β=-0.292, p=0.003), hemoglobin (β=-0,313 p=0.002) and albumin levels (β=-0.322 p=0.001). In multivariate analysis, EFT was an independent predictor of cardiac cachexia (OR:2.213, 95% CI:1.341-3.652, P=0.002). DISCUSSION: EFT, as an indicator of cardiac inflammatory status, seems to be an important predictor of cardiac cachexia. This noninvasive, simple measurement may guide us at risk stratification of patients with heart failure.
Prospective Randomized Trial Comparing Magnetic Resonance Imaging (MRI)-guided In-bore Biopsy to MRI-ultrasound Fusion and Transrectal Ultrasound-guided Prostate Biopsy in Patients with Prior Negative Biopsies
Authors: Christian Arsov, Robert Rabenalt, Dirk Blondin, Michael Quentin, Andreas Hiester, Erhard Godehardt, Helmut E. Gabbert, Nikolaus Becker, Gerald Antoch, Peter Albers, Lars Schimmöller
Journal: European Urology (2015)
Seismic shift in policy needed to increase physical activity
Authors: M. C. Watson, J. Lloyd
Journal: BMJ (2015)

We agree that there is now considerable evidence that exercise can maintain and promote health.1 However, Kamerow’s suggestions for promoting exercise seem narrow compared with the size and importance of this public health challenge.2 We need a seismic shift in public health activity and an approach that is in line with the Ottawa Charter …
Headliners: Developmental Neurotoxicity: Drug Used to Arrest Preterm Labor Sensitizes the Brain to Neurotoxicants.
Authors: Jerry Phelps
Journal: Environmental Health Perspectives (2004)

Rhodes MC, Seidler FJ, Qiao D, Tate CA, Cousins MM, Slotkin TA. 2004. Does pharmacotherapy for preterm labor sensitize the developing brain to environmental neurotoxicants? Cellular and synaptic effects of sequential exposure to terbutaline and chlorpyrifos in neonatal rats. Toxicol Appl Pharmacol 195:203–217.

A growing body of evidence suggests that exposure to environmental toxicants in utero or very early after birth can have life-long effects. This phenomenon is referred to as the fetal basis of adult disease. Hypertension, diabetes mellitus, asthma, and cardiovascular diseases are but a few of the illnesses that have been suggested as possible effects from early-life exposures. Recently, NIEHS grantee Theodore A. Slotkin of Duke University Medical Center and his colleagues investigated how separate and combined exposures to terbutaline, a drug used to arrest preterm labor, and to the organophosphate pesticide chlorpyrifos affect several indices of brain cell growth and function.

Premature labor occurs in approximately 20% of all U.S. pregnancies, with preterm delivery—a leading cause of neonatal morbidity and mortality—occurring in nearly half these cases. Drugs to arrest preterm labor, particularly terbutaline, are used in as many as 1 million pregnancies annually. Chlorpyrifos, a known developmental neurotoxicant, is used worldwide.

Rat pups were given terbutaline on days 2–5 after birth, followed by chlorpyrifos on days 11–14. Neither treatment affected the growth or viability of the young rats; however, both elicited alterations in brain cell differentiation and cholinergic innervation at day 15, persisting into adulthood at day 60. Biomarkers of brain cell number, cell size, and neuritic projections were affected by both agents alone. However, the combined exposure produced more severe effects by both additive and synergistic mechanisms.

These findings suggest that terbutaline, like chlorpyrifos, is a developmental neurotoxicant. The authors conclude that the use of terbutaline to prevent preterm labor may be creating a subpopulation that is more sensitive to the adverse neural effects of organophosphate pesticides. Further studies are needed to repeat these findings, but if the results are confirmed, use of these compounds may warrant additional scrutiny. –Jerry Phelps
Evidence based case reports
Authors: I. J Perry, D. Bates, G. Zuccala, C. Pedone, P. Carbonin, P. Glasziou
Journal: BMJ (1998)

Editor—Over the past two academic years colleagues and I have used the concept of an evidence based case report, similar to that presented by Glasziou,1 in teaching evidence based medicine in the penultimate year of our undergraduate course in epidemiology and public health.

Students are asked to submit a case report based on the management of a single patient encountered during their clinical work. They are advised to identify one key intervention in the management of the case and to summarise any evidence that supports this intervention. The submission should not exceed 1000 words, of which not more than 300 should describe the clinical details of the case. Students are advised to use no more than five references and to take care to select key papers; they must describe the Medline search strategy that they used.

The case report contributes towards the students’ mark in epidemiology and public health at the end of the year. The exercise is designed to help the students relate the theory of evidence based medicine to the reality of everyday clinical practice. Marking the case reports provides good feedback on the effectiveness of our teaching in evidence based medicine. A high proportion of students display evidence of critical reading of the key references. Students tend, however, to focus on the evidence for pharmacological interventions rather than on other forms of treatment or diagnostic strategies. They are reluctant to reflect critically on the management of the case and have difficulty with formulating good questions for evidence based medicine. These observations have prompted a review of methods and content in our teaching, and we hope that the BMJ’s evidence based case reports will become a valuable teaching resource.

In this medical school, as elsewhere, we are reviewing the undergraduate curriculum. We aim to promote reflective, self critical practice combined with an understanding of the scientific method. The standard of evidence based case reports submitted by our students may emerge as a useful outcome measure for this aspect of the curriculum.
Reconstruction of the mitral anulus.
Authors: David Te, Feindel Cm
Journal: Circulation (1987)

The mitral anulus was reconstructed with autologous pericardium in nine patients. Six patients had infective endocarditis with one or more abscesses in the anulus, and three had an iatrogenically damaged anulus. In patients with disruption of the mitral anulus limited to its posterior portion, a semicircular patch of pericardium was sutured directly to the endocardium of the left ventricle. In patients with multiple defects in the anulus, circumferential reconstruction of the mitral ring with pericardium was performed. In cases in which abscesses involved the central fibrous body, pericardium was used to reconstruct both the mitral anulus and the aortic root. Eight patients survived and have remained well for a mean of 8 months. There has been no prosthetic or patch dehiscence. All patients experienced substantial functional improvement. This experience indicates that the disrupted mitral anulus can be successfully reconstructed with autologous pericardium that is sutured directly to the endocardium of the left ventricle.
Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial
Authors: Tanya Simuni, Karl Kieburtz, Barbara Tilley, Jordan J Elm, Bernard Ravina, Debra Babcock, Marina Emborg, Robert Hauser, Cornelia Kamp, John Christopher Morgan, G. Webster Ross, David K Simon, Jacci Bainbridge, Liana Baker, Ivan Bodis-Wollner, James Boyd, Franca Cambi, Julie Carter, Kelvin Chou, Nabila Dahodwala, Richard B. Dewey, Rohit Dhall, John Fang, Buff Farrow, Andrew Feigin, Sofya Glazman, John Goudreau, Pauline LeBlanc, Stephen Lee, Maureen Leehey, Mark F. Lew, Stephanie Lowenhaupt, Sheng Luo, Rajesh Pahwa, Adriana Perez, Jay Schneider, Burton Scott, Binit Shah, Kathleen M. Shannon, Saloni Sharma, Carlos Singer, Daniel Truong, Renee Wagner, Karen Williams, Anne Marie Wills, Pei Shieen Wong, Cindy Zadikoff, Richard Zweig
Journal: The Lancet Neurology (2015)
Hyperventilation and panic attacks
Authors: B Garssen, M Buikhuisen, R van Dyck
Journal: American Journal of Psychiatry (1996)

Hyperventilation has been posed as an important symptom-producing mechanism in panic attacks. Some arguments and experimental findings, such as the possibility of inducing panic symptoms by voluntary hyperventilation in panic disorder patients, seem to favor this suggestion. This study was undertaken to clarify the role of hyperventilation in panic disorder. Long-term ambulatory measurement of transcutaneous arterial CO2 pressure (PCO2) offers an opportunity to test directly the co-occurrence of panic and hyperventilation under natural conditions.Transcutaneous PCO2 was measured during three to four sessions of approximately 7 hours each in 28 panic disorder patients. Patients were instructed to expose themselves to fear-provoking situations and to press a button as soon as they experienced panic. One-half of the patients experienced one or more panic attacks during these sessions.A decrease in PCO2 was observed during only one of the 24 registered panic attacks that lasted at least 3 minutes. Even during this particular attack, the degree of hyperventilation was not impressive.These findings indicate that the hypothesis that hyperventilation is an important symptom-producing mechanism in panic may be dismissed.