tbuckley/cabot-search huggingface dataset:
Abstract 16602: Pulmonary Vascular Response to Metaboreflex Stimulation During Submaximal Exercise in Heart Failure
Authors: Erik H VanIterson, Eric M Snyder, Bruce D Johnson, Thomas P Olson
Journal: Circulation (2014)

Introduction: Neural feedback from skeletal muscle during exercise contributes to changes in pulmonary pressures in healthy individuals. Heart failure patients (HF) often develop pulmonary hypertension; however, the relationship between muscle afferent feedback and the pulmonary vasculature in HF remains unclear. Hypothesis: We examined the influence of metaboreceptor stimulation on pulmonary vascular capacitance using a validated non-invasive gas exchange equivalent (GX CAP ) in HF. Methods: Eleven HF patients (age 51±5 yrs; EF, 32±3%; NYHA class, 1.6±0.2) and 11 controls (CTL; age 43±3 yrs) completed 3 cycling session (4-min at 60% of peak oxygen consumption, VO 2 ). Session one: baseline control trial. Sessions 2 and 3: bilateral upper-thigh tourniquets inflated suprasystolic for 2 min at end-exercise (regional circulatory occlusion, RCO) with or without addition of inspired CO 2 to maintain end-exercise end-tidal CO 2 (P ET CO 2 ) (RCO+CO 2 ) (randomized). Rest, exercise, and recovery heart rate (HR), P ET CO 2 , and VO 2 were measured. O 2 pulse (VO 2 /HR) and GX CAP (O 2 pulseхP ET CO 2 ) were calculated. Results: During all conditions at end-exercise, HF demonstrated significantly lower GX CAP compared to CTL (p&lt;0.01). Percent change in GX CAP from end-exercise to 2 min post-exercise was attenuated in HF compared to CTL (41±5% vs 64±1%, respectively, p&lt;0.01) during the baseline trial. During RCO, HF had a 55±6% reduction in GX CAP from end-exercise compared to 77±2% in CTL (p&lt;0.01). During RCO+CO 2 , HF had a 49±4% reduction in GX CAP from end-exercise compared to 69±2% in CTL (p&lt;0.01). GX CAP was similar between sessions within HF. The CTL group demonstrated an attenuated return of GX CAP during RCO compared to both baseline and RCO+CO 2 (p&lt;0.01) with no difference between baseline and RCO+CO 2 . Conclusion: These data suggest the exercise mediated rise and post-exercise recovery of pulmonary vascular capacitance are attenuated in HF during constant-load submaximal exercise compared to CTL. Additionally, our data confirm previous reports that locomotor muscle afferent feedback influences pulmonary vascular capacitance in CTL; however, this model of locomotor muscle metaboreflex stimulation appears to a differential response in HF compared to CTL.
Respiratory physiotherapy for patients with LRTI: The patients' perspective
Authors: Ana Oliveira, Cátia Pinho, Alda Marques
Journal: European Respiratory Journal (2014)

Lower respiratory tract infections (LRTI) are a major cause of health and economic burden worldwide. Respiratory physiotherapy (RP) has shown to improve lung function and functional recovery on these patients; however, their perspectives about the outcomes achieved in RP interventions have never been explored. This study assessed the perspectives of patients with LRTI about their participation in a RP intervention.  27 patients with LRTI (58.6±17.2yrs; 10 male) were recruited from the emergency department of a hospital and enrolled in a 3 week RP intervention. RP included breathing retraining, airway clearance techniques, aerobic training and education about LRTI. After the intervention, semi-structured interviews were conducted and audio recorded. Interviews were analysed (thematic analysis) by 2 independent judges.  All participants reported that the intervention had high impact in their respiratory condition and symptoms, specifically by improving their perceived breathlessness (n=9), fatigue (n=4), sputum expectoration (n=4) and wheezing (n=2). Patients also reported to have acquired self-management skills to prevent and control future LRTI, such as risk behaviour modification (i.e., smoking; sedentary lifestyles; polluted environments and nutrition; n=10), breathing and airway clearance techniques to control respiratory symptoms (n=12).  RP improves patients9 symptoms and well-being during LRTI, but also seems to enhance their skills in the management of future infections. Thus, PR interventions may be a key component to enhance patients9 treatment, prevent recurrent LRTI and ultimately reduce healthcare costs. Further research is needed to explore the long-term impact of RP in patients with LRTI.
Recurrent Swellings of the Parotid Gland, Sialectasis and Mikulicz's Syndrome
Authors: John Maynard
Journal: Journal of the Royal Society of Medicine (1979)

Recurrent parotitis has been a confused subject for many years.In 1892, Mikulicz described a case of lacrimal gland, submandibular gland and parotid gland swelling in a 42-year-old Prussian farmer.Biopsy of the parotid showed a 'uniformly arranged tissue consisting of small round cells'.In 1925 Gougerot (a French dermatologist) described patients with progressive atrophy of the salivary glands, lacrimal, nasal, laryngeal and vulval glands.In 1933, Sjogren described similar cases and was particularly interested in keratoconjunctivitis sicca.In 1953 Morgan & Castleman for the first time linked Mikulicz's syndrome and Sjogren's disease as probably the same disease process.Godwin (1952) described 10 cases with benign lymphoepithelial lesions which were histologically identical with the findings in Sjogren's and Mikulicz's disease.This collection of diseases has now been recognized to have an autoimmune basis.Antibiotics to salivary-duct epithelium have been demonstrated and serum protein studies have shown characteristic abnormalities associated with autoimmune disease.Amidst this collection of diseases there appears to be a group of patients with recurrent swelling of the parotid glands, who have no associated keratoconjunctivitis sicca or associated arthritis and no abnormality of their serum protein suggestive of an autoimmune process.Although this group is recognized it has been thought by some authors to represent an incomplete form of Sjogren's disease (Shearn 1971).Nearly 300 of such patients have been collected, treated and followed up over the last fifteen years.The initial investigation started in 1963 (Maynard 1965) and consisted of a study of the natural history, an investigation of the aetiology and an attempt to find an alternative to parotidectomy as treatment for patients with severe symptoms.
Abstract 2381: Heritability of Platelet Aspirin Responsiveness
Authors: Nauder Faraday, Lisa R Yanek, Rasika Mathias, J. E Herrera-Galeano, Taryn F Moy, Paul F Bray, Lewis C Becker, Diane M Becker
Journal: Circulation (2006)

Background: Variability in platelet responsiveness to the inhibitory effect of aspirin (ASA) is associated with differences in cardiovascular outcome among individuals at increased risk. Genetic va...
The Search for a Safe and Effective Anticoagulation Regimen in Pregnant Women With Mechanical Prosthetic Heart Valves⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Uri Elkayam, Sorel Goland
Journal: Journal of the American College of Cardiology (2012)
Abstract 5568: CYP17A1 and abiraterone: Implications for breast cancer endocrine therapy
Authors: Cameron P. Capper, Michael D. Johnson, José M. Larios, James M. Rae
Journal: Cancer Research (2014)

Abstract The cytochrome P450 17A1 (CYP17A1) inhibitor abiraterone, which blocks synthesis of all steroid hormones including androgens and estrogens, is an effective treatment for castrate resistant prostate cancer. Its utility for treating hormone receptor-positive breast cancer has yet to be established. In prostate cancer, the anti-proliferative effects of abiraterone are mediated by inhibiting CYP17A1 activity resulting in a significant reduction in circulating concentrations of the sex steroids dehydroepiandrosterone (DHEA), androstenedione, testosterone, and dihydrotestosterone (DHT). Recently, it has been proposed that the reduction in aromatizable androgens by abiraterone may make this drug useful for the management of hormone-dependent breast cancer. However, data from our lab suggests that abiraterone has estrogenic properties and can induce proliferation in breast cancer cells expressing the estrogen receptor (ER). Crystal violet assays were used to assess abiraterone-induced proliferation in the ER-positive, estrogen-dependent breast cancer cell lines MCF-7 and T47D. We show that abiraterone induced a dose dependent increase in cell proliferation with an IC50 of 3.7 μM and maximal stimulation (200%) observed at 8μM, compared to vehicle treated cells. Abiraterone also induced the expression of the ER response gene, GREB1. Abiraterone-induced proliferation and gene expression was blocked by increasing doses of the selective estrogen receptor down-regulator (SERD) fulvestrant. Abiraterone induced the dose-dependent expression of luciferase in MCF-7 cells transfected with an estrogen responsive luciferase reporter construct. In conclusion, our data suggest that abiraterone can induce ER-positive breast cancer cell proliferation in vitro by acting as a weak ER agonist. Further studies are underway to determine whether estrogenic effects of abiraterone are also observed using in vivo models of ER response. If abiraterone exhibits estrogenic effects in vivo then these data would suggest that abiraterone should be combined with an ER antagonist if used for the clinical management of women with ER+ tumors. Citation Format: Cameron P. Capper, Michael D. Johnson, José M. Larios, James M. Rae. CYP17A1 and abiraterone: Implications for breast cancer endocrine therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2014-5568
Selection to medical school in Great Britain
Authors: C M. Steel, D. Jackson, D. W Sinclair, S. R Magee, D A Levison, D Parratt, J M Bland, S. M Gore, C. McManus
Journal: BMJ (1999)

Ductal carcinoma in situ of the breast Has author carried out an audit?Editor-We were interested in Silverstein's review on ductal carcinoma in situ. 1 He states that he performs mammography every 6 months on the ipsilateral breast and every year on the contralateral breast.Has he been able to audit the usefulness of this practice-namely, how many times has the mammogram predated the development of clinical recurrence?
The increase in allergy and extended challenges
Authors: A. Linneberg
Journal: Allergy (2011)

The prevalence of allergic diseases shows a well-documented increase in developed countries over several decades. Currently, 20-25% of European adults are affected. Westernisation, urbanisation, and affluence contribute to allergy development, so allergy is expected to increase in developing countries in the future. Identifying primary causes, developing new therapies, and increasing treatment access may interrupt the allergic epidemic.
Abstract 1516: Does A Normal Coronary Angiography Really Mean A Good Prognosis In Patients With Acute Coronary Syndromes?
Authors: Dariusz Dudek, Rafal Depukat, Bernadeta Chyrchel, Zbigniew Siudak, Artur Dziewierz, Lukasz Rzeszutko, Jacek Legutko, Jacek S Dubiel
Journal: Circulation (2007)

Introduction: Coronary angiography remains gold standard for diagnosis of coronary artery disease (CAD) and acute coronary syndrome (ACS). Among patients (pts) referred to cath-lab with diagnosis of ACS exists a subgrup presenting symptoms of myocardial ischaemia and no criticial coronary lesions in angiography. The long-term outcome is not well established and managing treatment for such patients is still challenging. Aim: Evaluation of clinical outcome and received pharmacotherapy in pts with ACS and no significant coronary lesions. Methods: We collected data of consecutive pts admitted to cath-lab between July 2004 and June 2006 with diagnosis of ACS and coronary angiography considered as normal or near-normal (lesions under 50% of stenosis assessed visually). We analyzed demographic data, angiographic, electrocardiographic and laboratory tests results. During long-term follow-up received treatment, major adverse cardiac events were assessed. Results: One hundred eight pts (56 females; mean age 58.5 +/−13.5 years) admitted to cath-lab with diagnosis of acute myocardial infarction (38%) or unstable angina (62%) had normal or near normal coronary angiography. Mean LVEF was 52.6 +/− 12.9%, prevalence of CAD risk factors was: hypertension 72.2%, hypercholesterolemia 51.8%, diabetes mellitus 13.0%. The treatment administered during the hospitalization and follow-up is shown in table . During the mean follow-up of 16.5 months (range 6–30 months) all-cause mortality rate was 9.3%, cardiovascular mortality rate was 7.4%, repeat hospitalization for cardiovascular reasons 20.4%. Conclusions: Long-term outcome of patients with ACS and nonobstructive coronary angiography is not as benign as it is commonly thought. These patients have high rate of major adverse cardiac events and rehospitalization for cardiovascular reasons. They also are not receiving therapy directed at aggressive antiatherosclerotic therapy with statins, ACE-I and b-blockers. Treatment administered during the hospitalization, at discharge and during the follow-up
Abstract 323: Dronedarone Impairs Cardiac Mitochondrial Oxidative Phosphorylation in Dose-Dependent Manner
Authors: Larisa Emelyanova, Sirisha Gudlawar, Farhan Rizvi, Ekhson Holmuhamedov, Monika Thakur, Mahek Mirza, Arshad Jahangir
Journal: Circulation Research (2014)

Introduction: Dronedarone (DR), a new antiarrhythmic drug, was recently shown to worsen heart failure (HF) and mortality in patients with atrial fibrillation and left ventricular dysfunction. However, the mechanism underlying the adverse effect is not known. Since, myocardium depends on mitochondrial oxidative phosphorylation (OXPHOS), we hypothesized that DR impairs mitochondrial function, which could further compropmise energetic reserves predisposing to worsening of HF and death in patients with HF. Methods: Mitochondria isolated from rat heart (2 month old, SD) were treated with DR (1, 5, 10, 20, 50 μM), and the effect on oxygen consumption rate (OCR) in State 3 (St 3, ADP stimulated), State 4 (St 4o, oligomycin) and following FCCP addition were determined using Seahorse XF24 Analyzer in the presence of glutamate/malate (complex I substrates) and succinate/rotenone (complex II substrate). Results: DR dose dependently reduced St 3 respiration both in the presence of complex I (Fig). In the presence of glutamate/malate, DR inhibited OCR by 16%, 20%, 25%, 39% and 100% at 1, 5, 10, 20, 50 μM, respectively, when compared to untreated control. At 20 μM, DR uncoupled mitochondria and increased St 4o respiration. DR at 50 μM was toxic with complete inhibition of OCR and loss of membrane potential. Similar results were observed when succinate/rotenone were used to assess complex II activity. Conclusion: DR has dose-dependent inhibitory effect on mitochondrial respiration, inhibiting OXPHOS at low concentration (1-10 μM), uncoupling at higher (20 μM) and toxic effect at 50 μM. Impairment of mitochondrial energetics could explain DR results reported in HF patients in clinical trials.
Spirometry 360 on-line training and feedback: Spring 2011 course results and future plans
Authors: James Stout, Karen Smith, Bruce Culver, Allen Dozor
Journal: European Respiratory Journal (2011)

Although office-based spirometry is increasingly gaining acceptance in general practice, wide variations in test quality impede its use.  Spirometry 360 is a four-month interactive on-line training and feedback program currently delivered from the University of Washington to primary care practices around the U.S. It consists of: 1) Spirometry Fundamentals, a multi-media tutorial and reference tool; 2) interactive, case-based webinars led by clinical experts, and 3) an internet-based quality feedback reporting system that summarizes technique of de-identified spirograms automatically uploaded from the point of care.  We delivered the training for the second time in 2010 to 23 general practices from 4 states around the U.S. Results included a doubling of the acceptable spirograms for children younger than eight years from 40% at baseline to 80% at the end of training, and an overall increase in the acceptable spirogram rate from 49% to 71%. Among course participants, 100% reported that they would recommend the training to a colleague.  We are now delivering the course from February to June 2011 in two concurrent tracks to 70 pediatric and family practices, involving over 200 physicians and their support staffs from 35 states around the U.S.  We will present a detailed analysis of over 4,000 tests from the Spring 2011 course, with a description of the reasons for variance from the ERS/ATS 2005 Spirometry Guideline, to further understand practitioners9 needs when performing office-based spirometry. We will also report on our plans for a “Train-the-Trainer” program with a goal of establishing independent training sites for ongoing delivery of the Spirometry 360 program.
The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors
Authors: Jeffrey N. Savas, Luís F. Ribeiro, Keimpe D. Wierda, Rebecca Wright, Laura A. DeNardo-Wilke, Heather C. Rice, Ingrid Chamma, Yi-Zhi Wang, Roland Zemla, Mathieu Lavallée-Adam, Kristel M. Vennekens, Matthew L. O’Sullivan, Joseph K. Antonios, Elizabeth A. Hall, Olivier Thoumine, Alan D. Attie, John R. Yates, Anirvan Ghosh, Joris de Wit
Journal: Neuron (2015)
NHS needs plan for all acute, rehabilitative, and long stay care
Authors: P. H Millard
Journal: BMJ (2001)

EDITOR—Everyone sees the world from where he or she stands. Seeing the NHS through American eyes, Leatherman and Blackman believe that the service has fundamentally “got it right.”1 Yet, fundamentally, the NHS no longer exists, for the 1990 Community Care Act changed the legislation in 1948 that underpinned it.

The NHS, operational research, and rehabilitation were three healthcare legacies of the second world war.2 The operational plan that underpinned …
Abstract 11338: The WISE Score: A New Index for Predicting Outcome after Cardiac Resynchronization Therapy Using Simple Clinical Data
Authors: Tetsuari Onishi, Olusegun A Oyenuga, Stephanie C Haberman, Toshinari Onishi, Evan Adelstein, Samir Saba, John Gorcsan
Journal: Circulation (2011)

Background: Response to cardiac resynchronization therapy (CRT) is variable and factors associated with response complex. The aim of this study was to test the hypothesis that a new scoring system using simple clinical, ECG, and routine echocardiographic data may predict outcome after CRT. Methods: We prospectively studied 209 consecutive CRT patients; NYHA class III/IV, QRS width ≥ 120ms, and ejection fraction ≤ 35%. Quantitative echocardiography was performed before CRT. Outcome events were pre-specified as death, transplant or left ventricular assist device. Risk factors were determined using a Cox regression model using these 4 simple clinical ECG and echo variables: disease etiology, QRS width, end-systolic dimension (indexed for body surface area) and pulsed Doppler interventricular mechanical delay (IVMD). Optimal cut-off values in continuous variables were decided by ROC curve analysis. A prognostic score was created by assigning 1 point for each: QRS Width (≤140ms), IVMD (<40 ms), Systolic dimens...
Inclusion of Physicians in Bundled Hospital Payments—Reply
Authors: Ateev Mehrotra, Peter Hussey
Journal: JAMA (2015)

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Function and developmental origin of a mesocortical inhibitory circuit
Authors: Anna Kabanova, Milan Pabst, Markus Lorkowski, Oliver Braganza, Anne Boehlen, Negar Nikbakht, Leonie Pothmann, Ankita R Vaswani, Ruth Musgrove, Donato A Di Monte, Magdalena Sauvage, Heinz Beck, Sandra Blaess
Journal: Nature Neuroscience (2015)
Abstract 3992: Modes of metastasis evolution in human and murine cancer revealed by whole exome sequencing
Authors: Scott L. Carter, Priscilla K. Brastianos, David G. McFadden, Thales Papagiannakopoulos, Amaro Taylor-Weiner, Kristian Cibulskis, Tyler Jacks, William Hahn, Gad Getz
Journal: Cancer Research (2014)

Abstract Despite that fact that 90% of cancer deaths are due to metastasis, relatively little is known about how metastases evolve from primary cancers. We subjected 101 trios consisting of primary tumor, brain metastasis, and normal reference tissue to whole exome sequencing (WES). To analyze the data, we developed novel computational tools to derive high quality allelic copy-number profiles directly from the WES data. These were used to perform an integrative analysis of somatic copy-number alterations (SCNAs) and somatic single nucleotide variants (SSNVs). This analysis allowed us to estimate the clonal architecture of the primary and metastatic samples from each patient, and to reconstruct a single phylogenetic tree relating all of the subclones detected in both samples. We determined that all of the matched metastases analyzed likely formed from a single clone. In all cases, we observed a sibling relationship between the metastasis and primary tumor samples, indicating that they share a common ancestor, but ongoing evolution in the primary tumor resulted in fully clonal mutations in the primary biopsy that were not present in the metastasis sample. An important corollary of this is that in no case was a metastasis-founding subclone detected in a primary tumor sample. Using mutational spectra associated with tobacco exposure in lung cancers, we determined that most of the evolution leading up to the brain metastasis like occurred within the lung. In contrast with these findings, analysis of related primary tumor and metastasis families in a mouse model of small cell lung cancer using identical methodology revealed evidence of more variable patterns of metastatic spread. Analysis of draining lymph nodes revealed that multiple subclones of the primary contributed to these metastases. In addition, we uncovered evidence for the sequential spread of metastases, consistent with multiregion sequencing of primary and metastatic human pancreatic cancer. The extension of this finding to a mouse cancer model suggests this may be a more frequent feature of cancer metastasis, and raises the possibility of genetically dissecting these processes in this experimental system. Citation Format: Scott L. Carter, Priscilla K. Brastianos, David G. McFadden, Thales Papagiannakopoulos, Amaro Taylor-Weiner, Kristian Cibulskis, Tyler Jacks, William Hahn, Gad Getz. Modes of metastasis evolution in human and murine cancer revealed by whole exome sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3992. doi:10.1158/1538-7445.AM2014-3992