tbuckley/cabot-search huggingface dataset:
Risk of stricture after endoscopic submucosal dissection for large rectal neoplasms
Authors: Yoshiko Ohara, Takashi Toyonaga, Shinwa Tanaka, Tsukasa Ishida, Namiko Hoshi, Tetsuya Yoshizaki, Fumiaki Kawara, Ka Lui, Kanokkan Tepmalai, Alisara Damrongmanee, Mitsuru Nagata, Yoshinori Morita, Eiji Umegaki, Takeshi Azuma
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Improvements in the endoscopic submucosal dissection (ESD) technique have made circumferential ESD in the rectum possible. However, little is known about the clinical course after extensive ESD in the rectum. The aim of this study was to determine the stricture risk in the rectum after total or subtotal circumferential ESD. <b>Patients and methods:</b> A total of 69 patients with 69 rectal tumors that required ≥ 75 % circumferential resection were identified at Kobe University Hospital and an affiliated hospital between April 2005 and May 2014. Among the patients, 61 were available for evaluation of stricture development, either by follow-up colonoscopy or by surgical specimens. The rate and possible risk factors of post-ESD strictures were investigated. <b>Results:</b> Post-ESD rectal strictures developed in 12 patients (19.7 %). Patients who underwent total circumferential ESD developed a stricture (5/7, 71.4 %) more frequently than those with subtotal (≥ 90 %) ESD (7/16, 43.8 %). Patients undergoing an ESD procedure that involved < 90 % of the circumference did not develop strictures. The strictures were membranous or < 10 mm long in all cases. Of the patients with stricture, 11 received endoscopic balloon dilation and one received bougie with short-caliber-tip transparent hood; all strictures improved following dilation therapy. Statistical analysis revealed that ≥ 90 % circumferential resection was an independent risk factor for stricture, whereas morphology and size were not. <b>Conclusions:</b> Patients who underwent total or subtotal circumferential ESD of a rectal tumor had a high risk of stricture formation. Dilation helped to alleviate the stenosis. Study registered at University Hospital Medical Information Network (UMIN 000016559).
Managing drug misuse in general practice
Authors: E. Keenan, J. Barry, E. van Teijlingen, M. Ryan, C. Matheson, C. Bond
Journal: BMJ (1999)

Improving access to medical care General practice cooperatives are coping wellEditor-Cooperatives present patients with the easiest access to a doctor of any part of the NHS.We have led the way in modernising out of hours primary care, and we have been arguing for, and in many areas creating, a "whole systems approach" to access.It was therefore galling to read that "patients may have bypassed general practices and cooperatives as phone lines became overwhelmed; and accident and emergency staff often had no other options but to admit." 1 These unfounded assertions are damaging.The evidence set out in the report Winter Pressures on Primary Care by the Health Economics Consortium, which was commissioned by the Department of Health, showed that primary care, and cooperatives in particular, coped admirably.It is just as likely that patients would have phoned their cooperatives when faced with long delays in accident and emergency departments.Indeed, I triaged several calls made from Maidstone accident and emergency department last Boxing Day.About 1-2% of the population contacted primary care out of hours services between 24 December 1998 and 2 January 1999.It wasn't primary care that collapsed under the strain, but a secondary service that is always working almost flat out and therefore has no spare capacity.This is because we spend less on health as a percentage of gross national product than almost any other westernised nation.
Abstract 17445: NF2 Regulates Mst1 Activation and Ischemia Reperfusion Injury
Authors: Dominic Del Re, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation (2011)

Neurofibromin 2 (NF2)/merlin is a tumor suppressor that can regulate activation of the hippo pathway in Drosophila and the mammalian liver, thereby inhibiting cell growth and promoting apoptosis. We have shown previously that the mammalian homologue of hippo, Mst1, has a similar function in the heart. Therefore, we sought to determine whether NF2 can mediate activation of Mst1 in the heart and modulate cardiac ischemia/reperfusion (I/R) injury. Both NF2 and Mst1 are activated by oxidative stress in isolated cardiomyocytes in vitro and in the heart following I/R. Increased expression of NF2 in cardiomyocytes increased Mst1 phosphorylation (2.9±0.2-fold vs LacZ, p&lt;0.05) and elicited apoptosis (4.8±1.7-fold vs LacZ, p&lt;0.05) that was prevented by co-expression of kinase inactive Mst1 (61±12% decrease vs. NF2, p&lt;0.05). To examine the importance of endogenous NF2 in I/R injury, we employed two different genetic models - systemic heterozygous nf2 deletion ( nf2 +/- ) and cardiomyocyte-specific disruption using nf2 floxed mice crossed with αMHC-Cre transgenic mice ( nf2 +/flox Cre). We performed global I/R (30/60min) injury on isolated perfused hearts using the Langendorff method. Functional parameters and infarct size were determined following the reperfusion phase. While nf2 +/- hearts showed no difference in function and infarct size (45±5% vs 48±7%, NS) compared to WT, nf2 +/flox Cre hearts had significantly smaller infarcts (22±5% vs 53±8%, p&lt;0.05) and improved function versus nf2 +/flox controls. nf2 +/- hearts also failed to protect against I/R injury in vivo as Infarct/AAR (34±3% vs 32±2%, NS) and myocyte apoptosis (1.5±0.2% vs 1.7±0.3%, NS) were unchanged despite significant attenuation of Mst1 activation in ventricular homogenates (71±8% reduced vs WT, p&lt;0.05). Preliminary experiments to determine the effect of cardiomyocyte nf2 deletion show a trend toward protection (Infarct/AAR, 23±6% vs 33±6%, n=4) in nf2 +/flox Cre versus nf2 +/flox control mice. Based on these data we conclude that nf2 disruption in cardiomyocytes is protective against I/R injury through inhibition of Mst1 activity. However, NF2 signaling in residential non-myocytes appears beneficial for the heart and obscures the detrimental function of NF2 in cardiomyocytes during I/R.
Use of long-acting, vs short-acting, opioids for chronic pain was linked to unintentional overdose
Authors: Anne Holbrook
Journal: Annals of Internal Medicine (2015)

Source Citation Miller M, Barber CW, Leatherman S, et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern Med. 2015;175:608-15. 25686208
Abstract 3641: Hemoglobin is a Predictor of All-Cause Mortality and Cardiovascular Mortality in Patients Undergoing Exercise Treadmill Testing
Authors: Michael J Lipinski, Frederick E Dewey, George W Vetrovec, Victor F Froelicher
Journal: Circulation (2006)

Background: While hemoglobin is a known predictor of cardiovascular (CV) death following acute myocardial infarction, little is known about the role of hemoglobin level in predicting all-cause and ...
Abstract 15901: Adverse Post-Ischemic Cardiac Remodeling in Chronic Hindlimb Ischemia: Proteomic Identification of a Novel Molecular Mechanism
Authors: Gabriele G Schiattarella, Cinzia Perrino, Anna Franzone, Giuseppe Gargiulo, Gianluigi Pironti, Alessandro Cannavo, Anna Sannino, Federica Serino, Fabio Magliulo, Federica Ilardi, Andrea Scaloni, Nicola Zambrano, Giovanni Esposito
Journal: Circulation (2011)

Peripheral arterial disease is an important manifestation of atherosclerosis, commonly complicated by myocardial infarction or stroke. In this study we investigated whether chronic hindlimb ischemi...
Abstract 17031: Epigenetic Modifications at VEGFR1 Locus in Response to Angiogenic Signal
Authors: Debasree Dutta, Soumen Paul
Journal: Circulation (2011)

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR1/VEGFR2) are primary regulators of angiogenesis. Among them, VEGFR1 has a dual role of either stimulating or suppressing angiogene...
Abstract 2928: Sudden Arrhythmic Death Syndrome-Diagnostic Yield Of Combined Clinical &amp; Genetic Screening In A British Specialist Clinic
Authors: Pier D Lambiase, Juan C Kaski, Eileen Firman, Perry M Elliott, Akbar K Ahmed, Anthony W Chow, Mary Sheppard, Martin D Lowe, Michael Christiansen, William J McKenna
Journal: Circulation (2007)

Introduction: Sudden arrhythmic death syndrome (SADS) arises through disorders of ion channel function or structural heart disease. It accounts for over 400 deaths in the UK per annum. To date there has been no comprehensive analysis of the diagnostic yield and efficacy of a family screening approach in SADS index cases where the post mortem heart is structurally normal after expert pathological review. Methods: 118 SADS families where the SADS victim died between 1 and 35 years of age were evaluated in a systematic family screening programme between 2003–2006. All SADS index cases had a structurally normal heart after expert review of all available tissue. All studied relatives underwent resting, signal averaged ECG, 24h Holter, exercise ECG with V0 2 max, transthoracic echocardiography and an ajmaline challenge test after initial clinical screening. Systematic mutation analysis was performed on the known long QT (LQT)genes including SCN5A &amp; ryanodine receptor/ARVC genes when clinically suspected. Results: The most common modes of death were rest in 28%, sleep in 25% and exercise in 18%. Clinical screening identified an inherited electrical cause of SADS in 41 of the 118 families (35%)-20 Brugada, 18 LQT Syndrome, 3 Catecholiminergic Polymorphic Ventricular Tachycardia (CPVT). Structural heart disease was identified in 5 ARVC &amp; 2 DCM families. 26 ICDs have been implanted in affected family members-4 LQTS, 7 Brugada, 2 CPVT, 2 ARVC, 2 DCM and 9 on clinical grounds without a definitive diagnosis. The ECG (37%) and ajmaline challenge test (49%) had the highest diagnostic yield in families with a positive diagnosis. To date, genetic testing has increased the diagnostic yield by 5% (6/118 families-2 KCNQ1, 1 HERG, 2 SCN5A, 1 ARVC ), confirming a clinical diagnosis in 6.6%–3 KCNQ1, 3 SCN5A, 1 HERG, 1 KCNH2. Conclusions: Systematic clinical screening in relatives of SADS victims has a diagnostic yield of 35% increasing to 40% with genetic testing. Electrical causes of SADS predominate in these families. These findings demonstrate that a systematic clinical screening programme in SADS families is both achievable and effective. The full impact of gene testing (including RyR mutations) upon diagnostic yield is awaited.
Brief Communication: Direct Action of Estradiol on Rat Mammary Tumors2
Authors: Chung Lee, Ryoichi Oyasu
Journal: JNCI Journal of the National Cancer Institute (1974)

This study reports a direct action of 17-beta-estradiol on protein synthesis by 7, 12-dimethylbenz (alpha) anthracene (DMBA) induced rat mammary tumors. Sprague-Dawley female rats were given 20 mg of DMBA in sesame oil by gastric tube. Mammary tumors developed. When tumors reached 1.5 to 2 cm in diameter, animals were ovariectomized. At 4-7 days later animals were killed and tumors removed. Microscopic examination confirmed the tumors to be carcinoma of adenoid cystic variety with regressive changes. 14 tumors from 14 animals were found suitable for study. In vitro treatment with 17-beta-estradiol gave rise to a 7% increase in the rate of 3H-leucine incorporation, expressed as dpm/mg of TCA-insoluble protein. This increase was considered statistically significant (p.001). A large variation among different tumors was noted. Also results varied with differences in time after ovariectomy. Under the same incubation conditions the same percentage of increase in the rate of 3H-leucine incorporation had been observed in the study of the effect of estrogen on the uterus of ovariectomized rats. In other mammalian tissues studied those containing high levels of estrogen receptor were able to respond to direct stimulation of estrogen. It was concluded that estrogen directly stimulates protein synthesis in the mammary tumors. This supports the view that these tumors are estrogen responsive tissues.
Abstract 10273: Markedly Increased Carotid Intima-Media Thickness in the Absence of Coronary Calcium Among HIV-Infected Individuals
Authors: Priscilla Hsue, Karen Ordovas, Theodore Lee, Amanda Schnell, Jennifer E Ho, Van Selby, Jeffrey N Martin, Steven G Deeks, Peter Ganz
Journal: Circulation (2010)

Background: HIV-infected subjects have increased risk for atherosclerosis. Both carotid artery intima-media thickness (IMT) assessed by ultrasound and coronary artery calcium (CAC) detected by comp...
Abstract 5993: One-Year Clinical Outcomes of Sirolimus-Eluting vs. Paclitaxel-Eluting Stents in Unselected Patients: Results from the Multicenter EVENT Registry
Authors: Victor Novack, Donald Cutlip, Neal Kleiman, Michael Pencina, Laura Mauri, David Cohen
Journal: Circulation (2008)

Background: Several randomized trials have demonstrated that PCI with sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) is associated with lower rates of angiographic restenosis and target lesion revascularization (TLR). Since many of these trials have included angiographic follow-up, the generalizability of these results to routine clinical practice remains controversial. Methods and Results: We used data from the EVENT Registry a multicenter, observational study of unselected patients undergoing PCI in more than 40 US centers to compare in-hospital and 1-year clinical outcomes among patients treated with SES (n=3443) or PES (n=2592). The primary endpoint was the composite of cardiac death or MI at one year. Secondary endpoints included TLR and ARC definite or probable stent thrombosis. Logistic regression or Cox proportional hazards models were used to adjust for baseline clinical and demographic characteristics, lesion characteristics, procedural characteristics, and site characteristics (proportion SES use). Results: Baseline characteristics were generally similar between the 2 groups; however patients receiving PES were more likely to have undergone PCI in the setting of an ACS. Intervention in LAD lesions and totally occluded lesions were more common in the SES group. At 1-yr there was no difference in the composite primary end-point between the groups (SES 9.1% vs. PES 10.0%; see Table ). Incidence of death, MI and stent thrombosis did not differ between the groups. TLR rates were higher in the SES group (4.4% vs. 3.3%, p=0.048), but this difference was no longer significant after adjustment for baseline covariates including site characteristics. Conclusions: Among unselected patients undergoing non-emergent PCI, SES and PES appear to be comparable in terms of clinical outcomes at 1 year. These findings suggest that previously observed differences in TLR may be largely related to the “oculostenotic reflex”. Unadjusted and Risk-Adjusted 1-Year Clinical Outcomes
Abstract 10639: Activated Protein C Protects Against Ischemic Injury by Activating AMPK Signaling and Regulating Substrate Metabolism
Authors: Jingying Wang, Xiaoyan Yan, Qiang Fu, Mingxia Cui, Likui Yang, Alireza R Rezaie, Ji Li
Journal: Circulation (2011)

Background-  Activated Protein C (APC) is a natural anticoagulant protein, with recently discovered anti-inflammatory and anti-apoptotic effects. We recently unveiled that APC can limit cardiac ischemia/reperfusion (I/R) injury and is independent of its anticoagulant activity. Here, we elucidate the signaling pathways by which APC mediates its salutary actions.   Methods and Results-  FVB/NJ mice were subjected to 20 min ischemia  via  left coronary artery occlusion followed by 3 hr reperfusion. APC was injected  via  tail vein (0.2 μg/g) 5 min before reperfusion. Myocardial infarction (MI) was significantly reduced in the APC group (14.4 ± 2.1%  vs.  30.9 ± 2.9% saline control, n=4-5 per group,  p  vs.  saline control,  p  vs.  43±6% control,  p =NS), suggesting that AMPK mediates the APC’s cardioprotection against ischemic injury. Moreover, APC attenuated I/R-induced c-Jun N terminal protein kinase (JNK) signaling pathway, and decreased the production of pro-inflammatory cytokines, TNFα and IL-6 (all  p  vs.  I/R alone). However, the inhibition of JNK signaling by APC was abrogated in AMPKα2 KO mice, indicating that AMPK was involved in the regulation of ischemia-induced inflammation. To further address how the APC-AMPK cascade modulates inflammation and metabolism in the ischemic heart, isolated WT hearts (n=4 each group) were subjected to 20 min global ischemia followed by 30 min reperfusion with or without APC treatment in an  ex vivo  perfused system. The results demonstrated that APC increases cell surface of glucose transporter GLUT4 (2 fold  vs.  control,  p  vs.  0.38 ± 0.13 µmol/min/g,  p  vs.  0.011 ± 0.004 µmol/min/g,  p    Conclusions-  APC protects against myocardial ischemic injury by triggering AMPK signaling pathway, which modulates substrate metabolism and inflammatory response.
Abstract 8963: Role of Caveolin-Centered Adiponectin Signalsome and Neutral Ceramidase in Adiponectin's Anti-Inflammatory, Anti-Oxidative and Anti-Nitrative Signaling
Authors: Yajing Wang, Xiaoliang Wang, Wayne Bond Lau, Yuexing Yuan, Wei Yi, Yang Sun, Hui Su, Bernard Lopez, Theodore Christopher, Xin-Liang Ma
Journal: Circulation (2011)

Endothelial and vascular protective actions of adiponectin (APN) are well-recognized, but its underlying transmembrane and intracellular signaling remain largely unknown. Recently, we demonstrated that caveolin plays an essential role in the formation of a membrane-situated APN signalsome containing adiponectin receptor (AdipoR), APPL1, and adenylate cyclase (AC). However, the significance of this signalsome in APN vascular biology has not been investigated. Moreover, a very recent study suggested that AdipoR may function as a neutral ceramidase. However, the pathological importance of APN-activated ceramidase in APN’s vascular protective action remains completely unknown. Our current study investigated the relationship between caveolin-1 (Cav1) and ceramidase in APN’s anti-inflammatory, anti-oxidative, and anti-nitrative actions. Pre-treatment of HUVECs with APN (2 µg/ml) significantly increased ceramidase activity (3.7-fold, P&lt;0.01), and decreased TNFα-induced ICAM-1 expression (P&lt;0.05), iNOS/NADPH oxidase expression (P&lt;0.01), and NO/superoxide/peroxynitrite overproduction (P&lt;0.01). These indicators of APN biological function were either markedly reduced (P&lt;0.001) or completely lost in Cav1 knockdown cells. Neutral ceramidase knockdown virtually abolished the effect of APN upon TNFα-induced ICAM-1 expression, but only modestly inhibited the effect of APN upon TNFα-induced iNOS/NADPH oxidase expression or NO/superoxide/peroxynitrite overproduction. In contrast to APPL1 and AC, no Cav1/ceramidase interaction was detected during basal conditions, indicating the absence of ceramidase from the APN signalsome. However, Cav1/ceramidase complex was clearly detected when HUVECs were stimulated with APN. Finally, knockdown of AdipoR1 or both AdipoR1/R2 respectively markedly and completely abolished APN activation of ceramidase. These results demonstrate for the first time that the Cav1-centered APN signalsome plays an essential role in mediating APN’s vascular biological actions. Moreover, these results support that APN-induced Cav1-dependent recruitment of ceramidase to the APN signalsome is responsible for APN’s anti-inflammatory effects.
Targeted, Deep Sequencing of Adult AML Patients Treated on the AMLCG-2008 Trial Detects Clonal Heterogeneity in 52% of Patients at Initial Diagnosis and Reveals Patterns of Clonal Evolution
Authors: Maja Rothenberg-Thurley, Stephanie Schneider, Tobias Herold, Nikola P Konstandin, Annika Dufour, Kathrin Bräundl, Bianka Ksienzyk, Evelyn Zellmeier, Philipp A Greif, Michael Fiegl, Marion S. Subklewe, Stefan K Bohlander, Wolfgang Hiddemann, Jan Braess, Karsten Spiekermann, Klaus H. Metzeler
Journal: Blood (2014)
Abstract 3246: Skeletonization of Internal Thoracic Arteries: Is it Safe in Long-term?
Authors: Arnaud Mommerot, Raymond Cartier
Journal: Circulation (2007)

Background: Skeletonization of internal thoracic arteries (ITA) is a popular technique in OPCAB surgery to increase length of arterial conduit and feasibility of «No-touch» revascularization. Impact of skeletonized (SK) ITA on long-term survival and cardiac events is not clearly defined. Methods: We reviewed 1000 consecutive patients having undergone OPCAB surgery at the Montreal Heart Institute, between September 1996 and March 2004 that were prospectively recorded in an OPCAB database. Among them, 994 had at least one ITA bypass. Results: Skeletonized ITA was used in 558 patients (56.1%). SK patients were older (p=0.045), had significantly more risk factors [dyslipidemia (p&lt;0.001), hypertension (p&lt;0.001), obesity (p=0.002)]. Preoperative Parsonnet score was not different between SK and non-SK groups. Use of bilateral ITA (p&lt;0.001) and sequential grafting (p&lt;0.001) were more frequent in SK group (36.6% vs 25.7% and 29.9% vs 0.7%, respectively). Operative mortality was similar (SK: 1.8% vs non-SK: 1.6%; p=0.82). Sternal wound infection rate was similar, but dehiscence rate was higher in the PD group (p=0.03). Hospital (p=0.27) and ICU (p=0.09) length of stay were similar in both groups. Overall 7-year survival was 83±2% in SK group and 80±2% in non-SK group (p=0.84). Long-term freedom from major adverse cardiac events was also similar between SK and non-SK groups (83±2% and 82±2%, respectively, p=0.4). Late rate rehospitalization for heart failure or revascularization (CABG or PCI) was similar for both groups. However, 7-year freedom from myocardial infarction was significantly better for non-SK group (p=0.04). By Cox regression analysis, COPD, cardiac heart failure, peripheral vascular disease, emergency and completeness of revascularization were independent predictors of late mortality whereas diabetes, skeletonization and the number of grafts by territory of revascularization were independent predictors of late myocardial infarction. Conclusion: ITA has no influence in long-term survival or major cardiac events in an all comer OPCAB population. However, SK and diabetes were predictors of late incidence of myocardial infarction. Thus, a word of caution should be made about skeletonization of the ITA in diabetic population.