tbuckley/cabot-search huggingface dataset:
Update on survival from the original phase II trial of bevacizumab and irinotecan in recurrent malignant gliomas
Authors: S. A. Wagner, A. Desjardins, D. A. Reardon, J. Marcello, J. E. Herndon, J. A. Quinn, J. N. Rich, S. Sathornsumetee, H. S. Friedman, J. J. Vredenburgh
Journal: Journal of Clinical Oncology (2008)

2021 Background: Recurrent grade III-IV malignant gliomas have a dismal prognosis and effective salvage therapies are limited. Methods: From 4/05–2/06, a phase II trial was conducted at Duke University using bevacizumab and irinotecan in patients with recurrent malignant gliomas. 2 cohorts were enrolled that included 33 grade III and 35 grade IV patients. The first cohort received bevacizumab at 10mg/kg plus irinotecan (dose based on patient's anticonvulsant) every two weeks. The second cohort received bevacizumab at 15mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Results: Overall response rates for both grade III and IV were 59% (grade III 61%, grade IV 57%). 6 month PFS and OS for grade III were 59% and 79% and for grade IV 43% and 74% respectively. In 12/07, we evaluated all patients enrolled in the trial to determine the 2 yr OS. From the 2 cohorts, 22% (15/68) of the patients are still alive (11 grade III, 4 grade IV). For the grade IV patients, the 2yr OS is 15%. All four of the grade IV patients completed 9 cycles of therapy. Two (2/4) progressed (8mo and 17mo) and both reinitiated bevacizumab and irinotecan with radiographic response. The other two have been progression free since the end of treatment (11mo and 18mo). Surprisingly, both of these patients had only partial resections at the time of diagnosis. For the grade III patients, the 2 yr OS is 33%. All but one patient has progressed; ranging from 1 to 14 months. 4 patients are currently on bevacizumab-based therapy. 1 on carboplatin, 2 on etoposide and 1 on bevacizumab alone for radiation necrosis. The remaining patients are on metronomic temozolomide (2), etoposide (1), and a phase I clinical trial (2). 2 patients are currently being followed off therapy. The one patient who did not progress only received a partial cycle on study and had to discontinue secondary to TTP and has been off treatment for the last 21 months. Conclusions: The combination of bevacizumab and irinotecan provides a clinically meaningful treatment option for patients with recurrent malignant gliomas. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech
Abstract 8787: Comparative Study of Angiotensin Receptor Blocker with or Without PPAR-γ Properties on Endothelial Function and Aortic Stiffness in Hypertensive Patients with Chronic Kidney Disease and the Metabolic Syndrome
Authors: Hideki Watanabe, Kunio Nakagawa, Masaaki Kakihana
Journal: Circulation (2011)

Background: Chronic kidney disease (CKD) and the metabolic syndrome(MetS) are recognized as risk factors for cardiovascular disease. Recently it has been reported that telmisartan and irbesartan, angiotensin receptor blockers (ARB), has an action of PPAR - γ agonist. We compared the effects on endothelial function and aortic stiffness in hypertensive patients with CKD and MetS between angiotensin receptor blockers with PPAR-γ properties (telmisartan and irbesartan) and without PPAR-γ properties (losartan and valsartan). Methods: Ninety six untreated hypertensive patients with CKD (stage 3) and the metabolic syndrome were randomized to receive telmisartan (Telmisartan group, n=26, 20-40 mg/day), irbesartan (Irbesartan group, n=23 100-200 mg/day), losartan (Losartan group, n=22, 50-100 mg/day) or valsartan (Valsartan group, n=25, 80-160 mg/day). Flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of brachial artery were measured by using ultrasound system. Pulse wave velocity (PWV) was measured by using oscilometric technique (form PWV/ABI ® , Colin Co, Japan). We also assessed insulin resistance by HOMA-IR. Measurements were performed at baseline, and then at 6 and 12 months after the treatments. Results: At baseline, there were no differences in FMD, PWV, and HOMA-IR between the four groups. After 12 months, there was no difference in blood pressure between four groups. FMD were significantly increased, and PWV was significantly decreased in four groups as compared with the baseline. However, these improvements were much better in the telmisartan group and the irbesartan group as compared with the losartan group and the valsartan group, and HOMA-IR was improved only in the telmisartan group and the irbesartan group. Conclusion: Telmisartan and irbesartan with PPAR-γ properties improve not only insulin resistance, but also endothelial function and aortic stiffness in hypertensive patients with CKD and MetS.
How To Do It: Make an application for flexible (part time) training
Authors: J. Morrell, A. Roberts
Journal: BMJ (1995)

Part time training posts are advertised in the BMJ each year in August or September in an advertisement placed by the Department of Health. Although the advertisement is placed by the department and manpower approvals are allocated centrally, each region runs its own scheme, and the first person to approach is the regional postgraduate dean (most regions have an assistant dean responsible for flexible training). If an application is successful then part time trainees are interviewed by the same appointments committee as full time applicants and they are judged by the same criteria. Manpower approval is granted to applicants who reach the same standard as full time applicants, but there may be a waiting list if there are more suitable applicants than training places available. The next stage is to gain educational approval from the relevant higher training committee for the proposed training programme, followed by funding from the region.
Renal Functions of Enuretic and Nonenuretic Children: Hypernatriuria and Kaliuresis as Causes of Nocturnal Enuresis
Authors: Nureddin Vurgun, Bilali H. Gümüş, Aydin Ece, Zeki Ari, Serdar Tarhan, Mustafa Yeter
Journal: European Urology (1997)
Abstract 026: Adherence to Weight Loss Treatment Across Three Self-Monitoring Approaches and the Association with Weight Change
Authors: Lora E Burke, Mindi A Styn, Molly B Conroy, Le Ye, Karen Glanz, Mary Ann Sevick, Linda J Ewing, Susan M Sereika
Journal: Circulation (2012)

Background: Adherence to the multiple components of a weight loss intervention is critical for successful short- and long-term outcomes. The purpose of this analysis was to determine if there was a difference in adherence to the five components of a standard behavioral weight loss intervention across three methods of self-monitoring diet and exercise in the 24-month SMART trial. Methods: In the SMART trial, 210 adults were randomized with equal allocation to one of three self-monitoring methods: 1) paper diary, 2) personal digital assistant (PDA) and 3) PDA + daily tailored feedback message (PDA+FB). The five treatment components included: attending group sessions; meeting the daily energy and fat goals and the weekly exercise goal; and self-monitoring eating and exercise behaviors. The cognitive-behavioral intervention was delivered in 39 group sessions over 18 months plus a maintenance session in the 21 st month. Attendance was measured objectively, whereas adherence to the other four components was based on self-report. Generalized mixed modeling was used to examine adherence over time and among the three groups as well as the association of adherence with weight loss. Results: The sample was predominantly female (84.8%), White (78.6%) and well educated (Mean±SD: 15.7±3.0 years). Mean BMI was 34.01±4.48 kg/m 2 . Initially, adherence was 100% for attendance, nearly 100% for self-monitoring, 60-80% for exercise, and less than 60% for the dietary goals. On average, participants in the PDA+FB and the PDA groups were more adherent to the treatment protocol than participants in the paper diary group for attendance (p&lt;.05), self-monitoring (p&lt;.05), energy goals (p&lt;.05), fat goals (p=.07), and exercise goals (p&lt;.05). Over time, there was a non-linear decline in adherence to all five components in all three groups. We also found a significant group by time interaction for adherence to each of the five components and a significant association between adherence to each component and weight change (ps&lt;.0001). Conclusion: Compared to the paper diary group, adherence was usually higher in the groups using a PDA to self-monitor. Better weight loss was associated with better adherence to the five treatment components. These results suggest that using an electronic diary such as the PDA improves treatment adherence. The increasing availability of additional mobile devices for self-monitoring lifestyle and receiving real time feedback offers potential opportunity to build on these findings and possibly improve adherence and weight loss outcomes.
Abstract 4695: PISA and Vena Contracta have Significant Inter-Observer Variability in the Assessment of Mitral Regurgitation, A Multicenter International Echocardiographic Study
Authors: Simon Biner, Asim Rafique, Farhad Rafii, Christopher Chien, Omid Noorani, Kirsten Tolstrup, Robert Siegel
Journal: Circulation (2008)
Abstract 16860: Warfarin Dosing in Patients with the CYP2C9*5 Variant
Authors: Kathryn Lindley, Nita Limdi, Larisa H Cavallari, Minoli Perera, Petra Lenzini, Julie Johnson, Alan Wu, Paul Ridker, Shitalben Patel, Cristi King, Shimoli Shah, Charles Eby, T Mark Beasley, Brian F Gage
Journal: Circulation (2010)

Introduction: The narrow therapeutic range of warfarin can lead to bleeding complications from trial-and-error dosing. Pharmacogenetic dosing can improve accuracy and safety of warfarin therapy in Caucasians, but is less accurate in populations of African ancestry. The cytochrome P450 2C9*5 (CYP2C9*5) SNP affects warfarin metabolism and is common in African Americans. In-vitro studies suggest CYP2C9 *5 is associated with reduced clearance of warfarin, but current dosing algorithms do not account for this variant. Quantifying the association between this SNP and warfarin requirements may improve dose prediction, especially in African Americans. Hypothesis: The CYP2C9*5 SNP is associated with lower warfarin dose requirements. Methods: This was a multi-centered, cross-sectional analysis of patients taking warfarin for a variety of indications. To improve statistical power, the cross-section analysis was enriched with patients known to have the CYP2C9*5 SNP. The main outcome measure was the magnitude of reduc...
EU examines accuracy of tests for genetically modified foods
Authors: Doug Payne
Journal: BMJ (2000)

The European Union has moved a step closer to being able to show when genetically modified material has been added to what people eat. It has just completed an international validation programme, the first of its kind for processed food, aimed at harmonising testing standards for genetically modified organisms across Europe.

Coordinated by the European Union's Joint Research Centre, the validation testing involved …
Biodegradable Polymer Versus Permanent Polymer Drug-Eluting Stents and Everolimus- Versus Sirolimus-Eluting Stents in Patients With Coronary Artery Disease
Authors: Robert A. Byrne, Adnan Kastrati, Steffen Massberg, Anna Wieczorek, Karl-Ludwig Laugwitz, Martin Hadamitzky, Stefanie Schulz, Jürgen Pache, Massimiliano Fusaro, Jörg Hausleiter, Albert Schömig, Julinda Mehilli
Journal: Journal of the American College of Cardiology (2011)
Effects of regional ischemia on metabolism of glucose and fatty acids. Relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with effects of anoxia.
Authors: Opie Lh
Journal: Circulation Research (1976)

The rate of coronary flow reaching the oxygen-linited heart appears to be crucial in determining the myocardial tissue metabolic response. The tissue metabolic response to anoxia, well studied in hearts perfused with anoxic media, differs in many important ways from the response to ischemia. In regional ischemia (developing infarction) there is still a residual oxygen uptake which is reduced approximately to the same extent as the delivery of O2; there is also decreased delivery of substrates and decreased removal of CO2, H+, and lactate, with increased concentrations of these metabolites. Contents of hexose monophosphates rise rather than fall in anoxia. Measurements of glycolytic intermediates show an initial burst of accelerated glycolytic flux lasting less than 1 minute after coronary artery ligation; thereafter rates of flux decrease to control values or even less at 120 minutes. Relative inhibition of phosphofructokinase (PFK) activity may be explained by a slow rate of fall of ATP and a developing intracellular acidosis. In this model, glucose accounts for a greater part of the residual oxidative metabolism than does free fatty acid (FFA).
Abstract 3822: Different microRNA In Mouse Heart, Cardiac Stem Cells And Cardiac Stem Cells With GATA4, Indicate Different Sets Of microRNA Involved In Stem Cell Differentiation By Gene Repression
Authors: Edilamar M de Oliveira, Yao Liang Tang, Keping Qian, leping Shen, Luvena Ong, M.Ian Phillips
Journal: Circulation (2008)

Several studies suggest that miRNA have important roles in the development of the heart and cardiac function. We hypothesized that specific miRNA are involved in the differentiation steps of cardiac stem cells to heart cells. We studied 569 unique miRNAs probes in mouse heart cells (MHtC), cardiac stem cells (CSC) and CSC with GATA4 (CSCG) . Based on Sanger miRMouse -10.1, we compared miRNAs in the following groups 1) MHtC vs. CSC, 2) CSC vs.CSCG , 3) MHtCs v CSCG. We also compared CSCs under hypoxia and normoxia. miRNAs reported in the results were confirmed by PCR As previously reported miRNA 1, 133a and 133b were highly expressed in MHt. However, we also found previously unreported, relatively high expression of miRNAs 126 –3p, 145, , 451and 499 in MHtC. MicroRNAs have not previously been reported in CSCs or CSCG. We found unique expression miRNAs 10a,10b, 31, 214 and 762 in CSCs and increased expression of miRNAs 705,709,762, and 1224 in CSCG. In MHt, miR 21 was lower compared to miR21 in CSCs . Expression of miRNA-762 was expressed significantly more in CSC-G than in CSC. Therefore, miR-762 could be the direct transcriptional target of GATA-4 in CSC and a part of the differentiation control pathway from CSC to MHtC. In addition we studied miRNA from CSCs exposed to hypoxia. Hypoxia suppressed all miRs found except miR-574 –5p, which was increased in hypoxia. The results led us to identify which genes are targeted by these miRNAs. miRNA 762 is located into the BCl-7c gene and by miRNA target predictions it was found to target activin A receptor (type IB and II-like-1) gene, bone morphogenic gene and transforming growth factor, beta receptor III (TGFβIII). Embryonic stem cells differentiate into cardiomyocytes in the presence of activin A and BMP4, therefore we suggest that the miRNA 700 family ( miR762 in particluar) in cardiac stem cells inhibits activin A and BMP4 genes, possibly through TGFβIII signaling, to maintain stem cells in the undifferentiated state. The results reveal new miRNAs in cardiac stem cells differentiation to adult heart cells and suggest their role of specific gene targeting.
Aerosolized Amphotericin B Inhalations as Prophylaxis of Invasive Aspergillus Infections During Prolonged Neutropenia: Results of a Prospective Randomized Multicenter Trial
Authors: S. Schwartz, G. Behre, V. Heinemann, H. Wandt, E. Schilling, M. Arning, A. Trittin, W.V. Kern, O. Boenisch, D. Bosse, K. Lenz, W.D. Ludwig, W. Hiddemann, W. Siegert, J. Beyer
Journal: Blood (1999)
Analysis Of EphA3 Expression In Hematologic Malignancies By Quantitative PCR
Authors: John Woronicz, Jorge E. Cortes, Jeffrey L. Jorgensen, Hagop M Kantarjian, Farhad Ravandi, Gautam Borthakur, Pramoda Challagundla, Jairo Matthews, Jennifer Ho, Jackie M. Walling, Geoffrey Yarranton, Naveen Pemmaraju
Journal: Blood (2013)
Identification Rate of Myeloma-Specific Clonotypes in Multiple Diagnostic Sample Types from Patients with Multiple Myeloma Using Next-Generation Sequencing Method
Authors: Hervé Avet-Loiseau, Jill Corre, Sabrina Maheo, Jianbiao Zheng, Malek Faham, Paul G. Richardson, Kenneth C. Anderson, Michel Attal, Nikhil Munshi
Journal: Blood (2014)
Abstract 1014: Geographical Analysis of Cardiac Interventional Services in Alabama
Authors: Barbara A Graves, Joseph Weber
Journal: Circulation (2008)

Access to Cardiac Interventional Services in Alabama: A Geographical Information System Analysis Cardiovascular disease is the leading cause of death in Alabama. The purpose of this study was to explore the geographical accessibility of persons in Alabama to cardiac interventional services (CIS) for the treatment of acute myocardial infarction (MI). A retrospective cohort and descriptive ecological study DESIGN was used. A geographical information system (GIS) was used to visually identify and empirically measure spatial relationships among the variables of myocardial infarction. The unit of analysis was by county for the 149 total counties in Alabama. The sample consisted of all deaths due to MI recorded in the state of Alabama from 1996 through 2001 as reported to the National Center for Health Statistics. County age-adjusted MI mortality rates were the outcome variable. A total of 20 hospitals with CIS were identified within Alabama. GIS analysis revealed that 58.2%, 85.9%, and 96.0% of the total Alabama population were within 30, 60, or 90 minutes travel time, respectively, of a hospital with CIS. Maps were generated to provide visualization of CIS coverage areas. One distinct area was noted at greater than 90 minutes from a hospital with CIS. This area is within the Black Belt Region and is well known for a mostly black, impoverished population who are subject to health disparities. The American College of Cardiology and the American Heart Association recommend early reperfusion treatment for patients with MI (within 2 hours). Research supports percutaneous transluminal coronary angioplasty (PTCA) as beneficial, useful, and effective in the treatment of MI. Timely transport of MI victims to a hospital with CIS within 90 minutes and a “door-to-needle” time of 30 minutes are goals that can promote prompt and effective treatment in reducing MI mortality. Use of these standards allows for a maximum travel time of 90 minutes. GIS analysis demonstrated that 96% of Alabama’s population is within 90 minutes travel time of a hospital with CIS. But for the best outcomes to occur, only 58.2% of Alabamians have access.
Abstract P121: Post-resuscitation Ionized Hypocalcemia Revisited
Authors: Ted Heyming, Scott Youngquist, John P Rosborough, James T Niemann
Journal: Circulation (2008)

Objective : Hypocalcemia during cardiac arrest has been reported. However, hypotheses for the decrease in ionized calcium (iCa) vary and its importance unknown. The objective of this study was to assess the relationships of iCa, pH, and base excess (BE) in two porcine cardiac arrest models, and to determine the effect of exogenous calcium on postresuscitation hemodynamics. Methods : Swine were instrumented and VF was induced either electrically (EVF, n=49) or spontaneously, ischemically induced (IVF) with balloon occlusion of the LAD (n=37). Animals were resuscitated after 7 minutes of VF. BE, iCa, and pH, were determined prearrest and at 15, 30, 60 min after ROSC. Arterial lactate was also measured in 10 pigs. In three animals, 1 gm of CaCl 2 was infused over 20 min after ROSC. Results: iCa, BE, and pH declined significantly over the 60 min following ROSC, regardless of VF type (figure ). Lactate was strongly correlated with BE (r = −0.83, p&lt;0.0001). In a multivariate generalized linear mixed model, iCa was 0.007 mg/dL higher for every one unit increase in BE (95% CI 0.005– 0.008, p&lt;0.0001), while controlling for type of induced VF. CaCl 2 improved post-ROSC hemodynamics when compared to saline infusion (figure ). Conclusions : Ionized hypocalcemia occurs following ROSC. This may be due to binding by lactate as evidenced by its strong association with the decline in base excess. CaCl 2 improves post-ROSC hemodynamics suggesting that hypocalcemia may play adial dysfunction.
Training in Radial EUS: What is the Best Approach and is There a Role for the Nurse Endoscopist?
Authors: J. Meenan, S. Anderson, S. Tsang, D. Reffitt, P. Prasad, L. Doig
Journal: Endoscopy (2003)

The aim of this study was to determine the relative contribution of previous endoscopic experience, case observation, and hands-on experience to skill acquisition in radial EUS.In EUS trainees, four senior gastroenterology fellows, and a nurse endoscopist, the ability to reproduce set views from the mediastinum, stomach, and duodenum was assessed. Points were ascribed to static and dynamic stations and to the use of console controls.Trainees observed 55 - 170 cases and conducted 25 - 124 examinations. Competence was demonstrated after performing approximately 25 examinations in the mediastinum, 35 examinations in the stomach, and 78 examinations in the duodenum. The number of previous examinations conducted correlated with the ability to scan the duodenum ( P < 0.01). Observation of 100 or more further procedures early in training did not accelerate learning. The nurse endoscopist showed a comparable degree of competence in mediastinal scanning to that of the other trainees after performing a similar number of examinations.Proficiency in radial endosonography is greatly influenced by the numbers of examinations performed. Observing large numbers of cases early in training does not appear to translate into competence. A background in advanced therapeutic endoscopy is not a prerequisite for acquiring endoscopic ultrasound skills. Nurse endoscopists may be expected to train successfully in mediastinal imaging at the same pace as senior gastroenterology fellows.
Cerebral Embolism Following Transcatheter Aortic Valve Implantation
Authors: Josep Rodés-Cabau, Eric Dumont, Robert H. Boone, Eric Larose, Rodrigo Bagur, Ronen Gurvitch, Fernand Bédard, Daniel Doyle, Robert De Larochellière, Cleonie Jayasuria, Jacques Villeneuve, Alier Marrero, Mélanie Côté, Philippe Pibarot, John G. Webb
Journal: Journal of the American College of Cardiology (2010)
Is empirical imagination a constraint on adaptationist theory construction?
Authors: Thomas E. Dickins, David W. Dickins
Journal: Behavioral and Brain Sciences (2002)

Andrews et al. present a form of instrumental adaptationism that is designed to test the hypothesis that a given trait is an adaptation. This epistemological commitment aims to make clear statements about behavioural natural kinds. The instrumental logic is sound, but it is the limits of our empirical imagination that can cause problems for theory construction.
Randomized Comparison of Distal Protection Versus Conventional Treatment in Primary Percutaneous Coronary Intervention
Authors: Henning Kelbæk, Christian J. Terkelsen, Steffen Helqvist, Jens F. Lassen, Peter Clemmensen, Lene Kløvgaard, Anne Kaltoft, Thomas Engstrøm, Hans E. Bøtker, Kari Saunamäki, Lars R. Krusell, Erik Jørgensen, Hans-Henrik T. Hansen, Evald H. Christiansen, Jan Ravkilde, Lars Køber, Klaus F. Kofoed, Leif Thuesen
Journal: Journal of the American College of Cardiology (2008)