tbuckley/cabot-search huggingface dataset:
Abstract 4215: Defining the Best Approach for Stenosis Quantification by Dual-Source CT - A Comparative Study Involving Intravascular Ultrasound and Invasive Coronary Angiography
Authors: Hiram G Bezerra, Ricardo Loureiro, Ammar Sarwar, Jose Rocha, T Pflederer, M Marwan, Milena Petranovic, Christopher O Raffel, Udo Hoffmann, Iris A McNulty, Thomas Brady, I K Jang, Stephan Achenbach, Ricardo C Cury
Journal: Circulation (2008)

Background: Dual-source computed tomography (DSCT) permits reliable noninvasive detection of coronary stenosis based on qualitative visual assessment. The purpose of this study was to determine the...
Abstract 13916: A Novel Biomarker of Oxidative Stress is Predictive of Incident Death and Myocardial Infarction in Patients with Coronary Artery Disease
Authors: Riyaz S Patel, Nima Ghasemzadeh, Danny J Eapen, Salman Sher, Shawn Arshad, Emir Veledar, Habib Samady, A. Maziar Zafari, Laurence Sperling, Viola Vaccarino, Dean P Jones, Arshed A Quyyumi
Journal: Circulation (2014)

Introduction: Oxidative stress (OS) is implicated in cellular damage and atherosclerosis, yet clinical experience of free radical scavengers has been uniformly disappointing, promoting the concept that clinically important OS may be mediated by alternative non-free radical processes. Hypothesis: We hypothesized that novel aminothiol markers of non-free radical mediated OS would predict incident adverse outcomes in patients at high risk for CAD Methods: 1411 consecutive patients undergoing coronary angiography (mean age 63 years, male 66%), were recruited from the Emory Cardiovascular Biobank study. Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were measured by high performance liquid chromatography at baseline and patients followed prospectively for a primary composite endpoint of death or non-fatal MI. Results: During a mean follow up of 3.9± 2.2 years, 19% died or suffered a non-fatal MI. The adjusted hazard ratios for all cause death/MI based on high vs low cut-points for the oxidized disulphide cystine was 1.65 (95% CI, 1.27-2.15); for reduced glutathione was 0.69 (0.52-0.92), and for the ratio of cystine/glutathione was 1.79 (1.39-2.30). Compared to a model containing clinical risk factors and CRP, addition of the cystine/glutathione ratio improved the C-Statistic (p=0.03) and also correctly reclassified 17% of events and 23% of non-events. When combined with high/low CRP into a 3 level multi-marker score, those with 2 high markers had an annualized event rate of 12.8% compared to 4.5% and 1.4% for those with 1 raised marker or none, respectively. Similar associations were found for all-cause and cardiovascular death endpoints and also in stratified analysis for those with and without significant CAD. Conclusions: A high extracellular oxidant burden and reduced intracellular antioxidant capacity quantified by the plasma aminothiols, cystine, glutathione and their respective ratio, is associated with adverse events in patients with CAD, a finding that is independent of and additive to any inflammatory burden. Further studies are needed to validate these findings, which support an alternative model of oxidative stress independent of free radical biology.
Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator
Authors: Joo In Jung, Ashleigh R. Price, Thomas B. Ladd, Yong Ran, Hyo-Jin Park, Carolina Ceballos-Diaz, Lisa A. Smithson, Günther Hochhaus, Yufei Tang, Rajender Akula, Saritha Ba, Edward H. Koo, Gideon Shapiro, Kevin M. Felsenstein, Todd E. Golde
Journal: Molecular Neurodegeneration (2015)

Amyloid-β (Aβ) 42 has been implicated as the initiating molecule in the pathogenesis of Alzheimer’s disease (AD); thus, therapeutic strategies that target Aβ42 are of great interest. γ-Secretase modulators (GSMs) are small molecules that selectively decrease Aβ42. We have previously reported that many acidic steroids are GSMs with potencies ranging in the low to mid micromolar concentration with 5β-cholanic acid being the most potent steroid identified GSM with half maximal effective concentration (EC50) of 5.7 μM. We find that the endogenous cholesterol metabolite, 3β-hydroxy-5-cholestenoic acid (CA), is a steroid GSM with enhanced potency (EC50 of 250 nM) relative to 5β-cholanic acid. CA i) is found in human plasma at ~100-300 nM concentrations ii) has the typical acidic GSM signature of decreasing Aβ42 and increasing Aβ38 levels iii) is active in in vitro γ-secretase assay iv) is made in the brain. To test if CA acts as an endogenous GSM, we used Cyp27a1 knockout (Cyp27a1−/−) and Cyp7b1 knockout (Cyp7b1−/−) mice to investigate if manipulation of cholesterol metabolism pathways relevant to CA formation would affect brain Aβ42 levels. Our data show that Cyp27a1−/− had increased brain Aβ42, whereas Cyp7b1−/− mice had decreased brain Aβ42 levels; however, peripheral dosing of up to 100 mg/kg CA did not affect brain Aβ levels. Structure-activity relationship (SAR) studies with multiple known and novel CA analogs studies failed to reveal CA analogs with increased potency. These data suggest that CA may act as an endogenous GSM within the brain. Although it is conceptually attractive to try and increase the levels of CA in the brain for prevention of AD, our data suggest that this will not be easily accomplished.
Evaluation Of Allogeneic Hematopoietic Cell Transplantation (HCT) Outcomes Of One Hundred Thirty-Two Patients With Myelodysplastic Syndrome (MDS) Or Chronic Myelomonocytic Leukemia (CMML) Up To Age Seventy-Five and The Effect Of Pre-Transplant 5-Azacitidine
Authors: Teresa Field, Janelle Perkins, Marcie Tomblyn, Ryan Hillgruber, Taiga Nishihori, Asmita Mishra, Joseph Pidala, Ernesto Ayala, Frederick L Locke, Melissa Alsina, Brian C. Betts, Eric Padron, Hugo F Fernandez, Jeffrey E Lancet, Alan List, Rami S Komrokji, Mohamed A. Kharfan-Dabaja, Claudio Anasetti
Journal: Blood (2013)
Conjunction of follicular, papillary and medullary thyroid carcinomas in a young woman
Authors: M E Sayegh, N R Griffin
Journal: Journal of the Royal Society of Medicine (1999)

subcutaneous tissues by dissection along structures passing into the periphery including the great vessels and psoas muscles4. When there is no evident peritoneal gas, abdominal symptoms and signs tend to be absent and generalized peritonitis seldom develops although in this patient the colon was defunctioned. Plain X-rays are useful in diagnosis (contrast studies cannot be relied upon2), and for distinguishing intraperitoneal from extraperitoneal perforations. In cases such as this conservative treatment has been widely advocated, sometimes including intravenous fluids and antibiotics. Deterioration with such treatment is an indication for urgent laparotomy5. REFERENCES
Truncus arteriosus type IV.
Authors: G Thiene, C Frescura, V Gallucci
Journal: Circulation (1978)

strated in only four of 10 patients with SAM and no evidence of ASH.There is a need for further studies to delineate both normal and abnormal responses to inhalation of amyl nitrite in both male and female subjects.Further studies are also needed to determine if the data of Mintz et al. can be confirmed.Until that time, the significance of true SAM in the absence of ASH continues to be un- known.
Doctors in rich world claim patient care is declining
Authors: David Spurgeon
Journal: BMJ (2001)

Doctors in five wealthy western countries who took part in a survey thought that the quality of patient care was declining despite an increase in spending on health. The survey covered Australia, Canada, New Zealand, the United Kingdom, and the United States.

“The findings of this five-country survey are stark,” said a report in Health Affairs (2001; 20:233-43). “Despite increased national spending on health care in each of the five countries and substantial improvements in medical technology, practising physicians believe that the quality of care provided to their patients is deteriorating.

More than half of the doctors in …
Rescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for ST-Segment Myocardial Infarction
Authors: Harindra C. Wijeysundera, Ram Vijayaraghavan, Brahmajee K. Nallamothu, JoAnne M. Foody, Harlan M. Krumholz, Christopher O. Phillips, Amir Kashani, John J. You, Jack V. Tu, Dennis T. Ko
Journal: Journal of the American College of Cardiology (2007)
Abstract 5372: In Vivo Myocardial Distribution of Adult Stem Cells Immediately Following Intracoronary Delivery in a Swine Model of Myocardial Infarction
Authors: Hung Ly, Kozo Hoshino, Irina Pomerantseva, Yoshiaki Kawase, Ryuichi Yoneyama, Yoshiaki Takewa, Carrie Vooght, John V Frangioni, Roger J Hajjar
Journal: Circulation (2008)

Background: Cardiac cell-based therapy (CCT) has emerged as a promising therapeutic strategy. There are few data comparing the fate of different stem cell (SC) populations delivered by the intracoronary injection (ICI). Aim: Document the in vivo myocardial distribution of SC delivered by ICI following recent myocardial infarction. Methods: In a myocardial infarction swine model, near-infrared (NIR) fluorescence was used to provide high sensitivity in vivo tracking of SC in the immediate phase (&lt; 60 minutes) after ICI of 2x107 cells. After labeling with the NIR fluorophore, IR-786, the NIR signal intensities and myocardial distribution patterns of mesenchymal (MSC), bone marrow-(BMMNC) and peripheral blood-mononuclear (PBMNC) cells were compared using an open-chested fluorescence imaging system. Results: The SC populations of interest were successfully loaded with IR-786. While all SC populations readily distributed along the vascular territory of the infarct-related artery immediately after injection, there was a mean SI intensity drop of 29.8% and 14.1% for PBMNC and BMNC (p&lt;0.05), respectively, which correlated with poor cell retention. No significant SI change was found in MSC-injected swine, which was associated with less cell loss after delivery. There was also evidence of MSC-related vessel plugging in some swine (Figure ). Conclusion: Our in vivo findings suggest that immediately after injection (during the first 60min ICI), there is already evidence of poor SC retention and distribution vary depending on cell population, potentially impacting clinical efficacy and safety of CCT.
Abstract P365: Use of AHA Ideal Cardiovascular Health vs. the Framingham Risk Score to Measure the Effect of a 24-month Lifestyle Intervention in Overweight and Obese Women
Authors: Bethany Barone Gibbs, John M Jakicic
Journal: Circulation (2013)

Introduction:  The AHA definition of Ideal Cardiovascular Health (AHA) consists of 7 components (nonsmoker, BMI  2 , cholesterol    Methods:  Females (n=146, age 38 ± 5 years, BMI 33 ± 4 kg/m 2 ) were randomized to a group-based lifestyle intervention, where all subjects were given an initial dietary prescription between 1200-1500 kcal/day and 1 of 4 exercise prescriptions based on intensity and duration. The study tracked progress through group meetings and calls over 24 months. Number of AHA components and the FRS were calculated at baseline and 24 months in the combined study population (no group differences were observed). Further analyses identified which components contributed to changes in each score.   Results:  At 24 months, participants had maintained a 5% weight loss and there were no differences across groups. Changes in AHA score and FRS were correlated (r=-0.58, p   Conclusions:  AHA score improved while FRS did not change in overweight and obese women participating in a lifestyle intervention, demonstrating the sensitivity of the AHA score for tracking positive health changes during an intervention in pursuit of primordial cardiovascular disease prevention.
Abstract 639: Site specific conjugation of ARX-788, an antibody drug conjugate (ADC) targeting HER2, generates a potent and stable targeted therapeutic for multiple cancers
Authors: Robin C. Humphreys, Jessica Kirtely, Amha Hewit, Sandra Biroc, Nick Knudsen, Lillian Skidmore, Alan Wahl
Journal: Cancer Research (2015)

Abstract Creation of ADCs by conjugating drug linkers and toxin payloads to available native lysines or cysteines generates ADCs with highly variable drug to antibody loading and linker stability profiles. Variable drug loading, amino acid position, conjugation chemistry and linker design affect the pharmacokinetic characteristics, potency and toxicity of the ADC. We describe here the synthesis and pharmacology of an ADC comprising a site-specifically conjugated dolastatin analog to an antibody targeting the EGF family receptor, HER2. To specify the site of conjugation and drug loading, a non-natural amino acid, para acetyl phenylalanine (pAcF), was incorporated at defined sites within the antibody primary sequence. This non-natural amino acid provides a linkable platform for covalent conjugation of a diverse array of payloads through a stable oxime bond. The dolastatin analog, MMAF, was coupled via a non-cleavable linker to the HER2 antibody at two specific sites to generate the ADC; ARX-788. In vitro cytotoxicity assays of ARX-788 generated picomolar IC50's across a spectrum of HER2 + cell lines from breast, ovarian, lung and gastric cancer. Multiple in vivo murine xenograft studies demonstrated a potent increase in anti-tumor activity when compared to T-DM1. A single injection of ARX-788 in established xenograft models of HER2 positive ovarian, gastric and breast cancer cell lines (SKOV3, BT474, N-87, and HCC1954) induced rapid regression in all models. ARX-788 induced regression in a Herceptin-resistant derived breast xenograft (JIMT-1) and was significantly more effective than T-DM1 at equivalent doses. Pharmacokinetic evaluation of ARX-788 in rodent and non-human primates (NHP) revealed long term stability of 12 and 8 days respectively. Importantly, the conjugated form of ARX-788 remained intact over the course of the 3 week study in NHP. Precise payload stability and effective half-life of ARX-788 due to site-specific conjugation provides an improved therapeutic window for this HER2-targeting ADC. ARX-788 is currently completing non-human safety and PK studies in anticipation of clinical trial evaluation in 2015. Citation Format: Robin C. Humphreys, Jessica Kirtely, Amha Hewit, Sandra Biroc, Nick Knudsen, Lillian Skidmore, Alan Wahl. Site specific conjugation of ARX-788, an antibody drug conjugate (ADC) targeting HER2, generates a potent and stable targeted therapeutic for multiple cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 639. doi:10.1158/1538-7445.AM2015-639
Abstinence and fidelity are only fully effective means of prevention
Authors: A Grazioli
Journal: BMJ (1996)

EDITOR,—Alexander Dorozynski reports that the Social Commission of the French Episcopate has said, “Many competent doctors maintain that a condom of reliable quality is today the only means of prevention” against AIDS.1 At the eighth world congress of sexology, in Heidelberg, Germany, in 1987, about 800 delegates were asked …
Alexithymia: concept, measurement, and implications for treatment
Authors: Graeme J. Taylor
Journal: American Journal of Psychiatry (1984)

Alexithymia refers to a specific disturbance in psychic functioning characterized by difficulties in the capacity to verbalize affect and to elaborate fantasies. Although initially described in the context of psychosomatic illness, alexithymic characteristics may be observed in patients with a wide range of medical and psychiatric disorders. The author reviews the concept of alexithymia, including its historical background, clinical and demographic features, and possible etiology. He critically evaluates the different methods used to measure alexithymia and discusses the important implications it has for medical and psychiatric treatment.
Effect of CSM's warning about safety of third generation oral contraceptives
Authors: J. J Ferguson, M. G V Jenkins
Journal: BMJ (1996)

Since the warning of the Committee on Safety of Medicines in regard to the risk of thromboembolism associated with combined oral contraceptives the Prescription Pricing Authority has monitored the use of oral contraceptives on a monthly basis.  Use of third generation oral contraceptives containing desogestrel and gestodene fell from 55% of the total use and 70% of the total costs to 12% and 23% respectively.  Use of pills containing levonorgestrel rose from 30% to 62% of the total use and from 16% to 44% of the total costs.  Use of norgestimate which was not included in the warning increased from 7.3% of the total use to 12.3% and from 9.7% of the total costs to 23%.  The average prescription for an oral contraceptive is for 4.5 months which suggests that roughly equal numbers of prescriptions for 3 months and 6 months are supplied; after the warning the average prescription was for 3.9 months suggesting that prescribers were trying new products for a shorter period.  Prescribing now seems to be returning to its previous pattern.
Six-minute step test in healthy and sedentary individuals: Is it a safe test?
Authors: Kenia Maynard da Silva, Yves Raphael, Diego Condesso, Bianca Figueira, Adalgisa Maiworm, Mariana da Cal, Julia Parnayba, Rogério Rufino, Cláudia Costa
Journal: European Respiratory Journal (2014)

INTRODUCTION: The data of Six-Minute Step Test (6MST) suggest that it has greater energy expenditure than the Six-Minute Walk Test (6MWT). OBJECTIVE: To compare the heart rate (HR) and oxygen saturation at the end of 1 st  and 6 st  minute of 6MST and 6MWT as well as to compare HR 6 st  minute of both tests with subjects9 submaximal HR. METHODS: Both 6MWT and 6MST were achieved in Pedro Ernesto University Hospital – State University of Rio de Janeiro/Brazil. It was randomized healthy and sedentary males and females from Rio de Janeiro city; age 20 - 80 y-o and performed chest x-Ray, EKG, respiratory function tests and fulfilled Charlson Index (CI)   1. The HR and SaO 2  were measured every minute in both tests. The submaximal HR was calculated as 85% of maximal HR. The statistical analyses: Prism Graphpath software 6. RESULTS: 253 subjects were randomized. 1 st min HR median : 6MWT was 101,9 (61-140)  vs . 107,22 (56-142) 6MST. p=  th min HR median: 6MWT was 111,47 (53-192)  vs.  124,78 (77-198) in 6MST. p=  st min SaO 2  median: 6MWT was 96,75 (74-100)  vs . 97,06 (83-100) in 6MST. p= 0,0510; 6 th min SaO2 median: 6MWT was 96,81 (78-100)  vs.  97,55 (92-100) in 6MST. p=  th min in 6MWT and 6MST. The calculated submaximal HR media: 149,91 (119,8-170) and HR median in 6 th min 6MWT was 111,47 (53-192) (p  th min 6MST was the median 124,78 (77-198) p
Abstract 11328: CHADS2 Score Predicted New-Onset Dementia in Patients With Atrial Fibrillation: A Nationwide Cohort Study
Authors: Min-Tsun Liao, Lian-Yu Lin, Chia-Ti Tsai, Jiunn-Lee Lin
Journal: Circulation (2013)

Introduction: Atrial fibrillation (AF) is associated with increased risk of dementia. CHADS2 scores were reported to be important risk factors for the development of AF. The goal of this study soug...
Brain Disease Linked With MS Drug
Authors: Rebecca Voelker
Journal: JAMA (2015)

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Abstract 12920: The Value of <sup>18</sup> FDG PET/CT in the Diagnostic Work-Up of Patients With Possible Infective Endocarditis
Authors: Fabio Chirillo, Franco Boccaletto, Paola Pantano, Alessandro De Leo, Marta Possamai, Walter O Inoiosa, Piergiorgio Scotton, Zoran Olivari
Journal: Circulation (2014)

The diagnosis of infective endocarditis (IE) is sometimes difficult when there are discrepancies between blood cultures, transesophageal echocardiography (TEE) and clinical judgment. The aim of this study was to assess the incremental diagnostic value of 18 F-FDG-PET/CT in 45 consecutive patients (73% male, mean age 61 ± 26 years) with suspected IE and inconclusive tests at admission. In 28 patients (19 with a cardiac valvular (15) or nonvalvular (4) device) with blood cultures positive for germs typically involved in IE the initial TEE was negative or inconclusive. In 10 patients presenting with fever TEE identified cardiac lesion possibly related to IE (ruptured mitral chordae, thickened valve leaflet, thickened prosthetic annulus), but blood cultures were persistently negative. Finally, 7 patients had metastatic or embolic lesions and a predisposing cardiac condition, but TEE was negative. When previous unknown lesions detected by PET/CT were confirmed by succeeding examinations, they were considered true positives. When PET/CT was negative, it was compared with the final diagnosis that was defined according to the modified Duke criteria determined during a 6-month follow-up. Thirty patients had definite IE at the end of the follow-up, 3 had possible IE, and in 12 patients the diagnosis was rejected. Twenty-seven patients (60%) exhibited abnormal FDG uptake around the cardiac valves, and 12 (27%) had extracardiac accumulation. In 5 patients the initial negative TEE became positive a mean 5 ±7 days after PET/CT had been performed The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT were as follows (95% confidence interval): 87% (68% to 95%), 67% (38% to 87%), 84% (65% to 94%), and 71% (42% to 92%), respectively. Adding abnormal FDG uptake as a new major criterion significantly increased the sensitivity of the modified Duke criteria at admission (68% [53% to 82%] vs. 96% [88% to 99%], p = 0.01). This result was due to a significant reduction (p &lt; 0.001) in the number of possible IE cases. In conclusion PET/CT increases the diagnostic accuracy for IE in the subset of patients with possible IE and may help to manage a challenging situation.