tbuckley/cabot-search huggingface dataset:
Myogenic and agonist induced responses of coronary venules after cold hyperkalaemic cardioplegia
Authors: P. F Banitt, H. B. Dai, S. Y Wang, M. Friedman, F. W Sellke
Journal: Cardiovascular Research (1995)

The aim was to examine agonist induced and myogenic venular responses after crystalloid cardioplegia in conditions simulating cardiopulmonary bypass.Hearts of pigs were arrested with cold hyperkalaemic ([K+] = 25 mM) crystalloid cardioplegic solution for 1 h under conditions of cardiopulmonary bypass. In another group, hearts were arrested and then reperfused with warm blood for 1 h while being separated from cardiopulmonary bypass. In a third group, animals were supported on cardiopulmonary bypass for 75 min without diversion of coronary blood flow. Hearts from non-instrumented animals served as controls. Coronary venules (91-197 microns in internal diameter) were studied in vitro in a pressurised no flow state using video microscopy. Agonist induced responses were assessed in vessels precontracted with the thromboxane A2 analogue U46619.Endothelium dependent relaxations to adenosine diphosphate (ADP, P = 0.11 v control), or serotonin (P = 0.67), and endothelium independent relaxations to the beta adrenergic cyclic AMP mediated agonist isoprenaline (P = 0.20), adenosine (P = 0.98), or the KATP channel opener pinacidil (P = 0.40) were not significantly altered after cold cardioplegia alone. After cardioplegia followed by 1 h of warm blood reperfusion, venular responses to ADP (P = 0.003 v control), isoprenaline (P = 0.013), adenosine (P = < 0.001), and pinacidil (P = 0.005) were reduced compared to the respective control responses, while the response to serotonin (P = 0.97) remained unchanged. Endothelium independent cyclic GMP mediated relaxation to sodium nitroprusside was similar in all groups (P > 0.90). Myogenic reactivity was assessed after incremental increases in the intraluminal pressure from 2-40 mm Hg. As intraluminal pressure was increased, the diameter of control venules increased and reached a plateau. Following cardioplegia, the pressure-diameter relationship of venules was shifted upward (P = 0.04 v control) suggesting impaired myogenic tone. After reperfusion, myogenic tone partially recovered. Extracorporeal circulation without diversion of coronary perfusion did not significantly affect venular responses.Ischaemic cardioplegia using a cold hyperkalaemic solution under conditions of cardiopulmonary bypass does not significantly alter agonist induced venular responses, whereas myogenic contraction is slightly reduced. After 1 h of reperfusion, agonist induced relaxations of coronary venules are significantly impaired, whereas myogenic contraction recovers. These findings may have implications for the control of myocardial perfusion and diastolic properties of the heart after ischaemic cardioplegia under conditions of extracorporeal circulation.
Hospital Quality for Acute Myocardial Infarction
Authors: Elizabeth H. Bradley, Jeph Herrin, Brian Elbel, Robert L. McNamara, David J. Magid, Brahmajee K. Nallamothu, Yongfei Wang, Sharon-Lise T. Normand, John A. Spertus, Harlan M. Krumholz
Journal: JAMA (2006)

ContextThe Centers for Medicare & Medicaid Services (CMS) and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) measure and report quality process measures for acute myocardial infarction (AMI), but little is known about how these measures are correlated with each other and the degree to which inferences about a hospital's outcomes can be made from its performance on publicly reported processes.ObjectiveTo determine correlations among AMI core process measures and the degree to which they explain the variation in hospital-specific, risk-standardized, 30-day mortality rates.Design, Setting, and ParticipantsWe assessed hospital performance in the CMS/JCAHO AMI core process measures using 2002-2003 data from 962 hospitals participating in the National Registry of Myocardial Infarction (NRMI) and correlated these measures with each other and with hospital-level, risk-standardized, 30-day mortality rates derived from Medicare claims data.Main Outcome MeasuresHospital performance on AMI core measures; hospital-specific, risk-standardized, 30-day mortality rates for AMI patients aged 66 years or older.ResultsWe found moderately strong correlations (correlation coefficients ≥0.40; P values <.001) for all pairwise comparisons between β-blocker use at admission and discharge, aspirin use at admission and discharge, and angiotensin-converting enzyme inhibitor use, and weaker, but statistically significant, correlations between these medication measures and smoking cessation counseling and time to reperfusion therapy measures (correlation coefficients <0.40; P values <.001). Some process measures were significantly correlated with risk-standardized, 30-day mortality rates (P values <.001) but together explained only 6.0% of hospital-level variation in risk-standardized, 30-day mortality rates for patients with AMI.ConclusionsThe publicly reported AMI process measures capture a small proportion of the variation in hospitals' risk-standardized short-term mortality rates. Multiple measures that reflect a variety of processes and also outcomes, such as risk-standardized mortality rates, are needed to more fully characterize hospital performance.
Endoscopic ultrasonography-guided biopsy for submucosal tumors: needless needling?
Authors: M. Polkowski, J. Bergman
Journal: Endoscopy (2010)

Despite their similar endoscopic appearances, submucosal tumors (SMTs) may differ substantially as to their nature and malignant potential. Overtly malignant tumors are relatively rare; potentially malignant ones are a much more common problem. The spectrum of malignancies is dominated by gastrointestinal stromal tumors (GISTs); however, other less common malignant conditions presenting as SMTs are also described, including malignant lymphoma, metastases to the wall of the gastrointestinal tract, and, surprisingly enough, primary adenocarcinoma [1]. Because endoscopic forceps biopsies usually fail to provide specimens adequate for diagnosis [2] [3] [4] [5], there is a persistent interest in endoscopic ultrasound (EUS)-guided needle biopsy, performed either with a standard aspiration needle (fine-needle aspiration, FNA) or a special cutting device (trucut biopsy, TCB). Recently, several publications on this topic have appeared [5] [6] [7] [8] [9] [10], and this issue of Endoscopy contains two more. Philipper et al. present EUS-FNA results obtained in a group of 47 patients, 12 with esophageal, 32 with gastric, and 3 with duodenal SMTs [11], and Fernández-Esparrach et al. report on a study conducted in 40 patients with gastric hypoechoic tumors 2 cm or more in size [12]. Both studies stand out because of their prospective design; an additional advantage of the latter study is that it was the first to directly compare the diagnostic yield of EUS-FNA and EUS-TCB in the setting of SMTs.
The 1995 update of recommendations for a standard technique for measuring the single-breath carbon monoxide diffusing capacity (transfer factor)
Authors: E Rosenberg
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

"The 1995 update of recommendations for a standard technique for measuring the single-breath carbon monoxide diffusing capacity (transfer factor)." American journal of respiratory and critical care medicine, 154(3), pp. 827–828
Abstract 3303: BRAF activation induces cellular transformation and senescence and down-regulates SOX2 in human neural stem cells: a model of pilocytic astrocytoma
Authors: Eric H. Raabe, Kah Suan Lim, Xing-Gang Mao, Eli Bar, Alan Meeker, Ulf Kahlert, Jaroslaw Maciaczyk, Guido Nikkhah, Charles G. Eberhart
Journal: Cancer Research (2011)

Abstract In pilocytic astrocytomas, the primary molecular alteration is BRAF activation occurring via gene duplication/fusion or V600E point mutation. To investigate the mechanisms by which BRAF activation leads to transformation, BRAF V600E was introduced into cortical and cerebellar human fetal neural stem and progenitor cells. Overexpression of BRAF V600E did not lead to increases in cellular proliferation compared to controls, but did promote colony forming ability in soft agar. However, after initially growing well, BRAF V600E expressing cells subsequently showed decreased proliferation as compared to control cells, though they remained viable visually. Because constitutive BRAF activation in melanocytes usually leads to cellular senescence, with only rare lesions progressing to melanoma, we examined if senescent markers were induced in our system. Overexpression of BRAF V600E led to an increase in markers of oncogene-induced senescence, such as acidic beta-galactosidase and p16. FISH analysis revealed no differences in telomere length in BRAF over-expressing cells compared to GFP-transduced control cells, indicating that this phenotype was not due to telomere shortening. The pattern of initial transformation followed by senescence is similar to the frequently indolent course of pilocytic astrocytoma, suggesting that overexpressing constitutively active BRAF in human neural stem and progenitor cells phenocopies the behavior of this tumor. To further investigate the mechanism of oncogene-induced senescence, we examined SOX2 expression. This human somatic cell reprogramming factor is an important neurodevelopmental gene and is known to prevent the induction of cellular senescence. However, the functional role of SOX2 in gliomas is poorly understood. We found that although SOX2 was expressed in control GFP transduced neurospheres, high-level expression of BRAFV600E led to downregulation of SOX2 in association with senescence. Our data support the concept that BRAF oncogene-induced senescence plays a role in the pathobiology of pilocytic astrocytoma, and suggest that modulation of SOX2 may play an important role in this process. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3303. doi:10.1158/1538-7445.AM2011-3303
Rules for distinguishing toxicants that cause type I and type II narcosis syndromes.
Authors: G D Veith, S J Broderius
Journal: Environmental Health Perspectives (1990)

Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.
TCT-817 Clinical and hemodynamic results of mitral balloon valvuloplasty in patients with mitral stenosis complicated by pulmonary hypertension
Authors: Ricardo Sarmiento, Rodrigo I. Blanco, Gerardo I. Gigena, Jorge Lax, Federico Blanco, Jorge Szarfer, Juan I. Gagliardi, Alejandro I. García Escudero, Miguel Riccitelli
Journal: Journal of the American College of Cardiology (2014)
The Evolution of Departments of Medicine
Authors: Robert G. Petersdorf
Journal: New England Journal of Medicine (1980)

Departments of medicine have grown from small, professorial, hospital-based units to large, multi-institutional organizations. Their growth is analyzed from the perspectives of teaching, graduate training, research, patient care, and organization. Research-oriented departments of medicine are heavily dependent on federal funds, and this dependence has profound implications for all aspects of a department's function. The job of the chairman has become progressively more difficult, and a rapid turnover of chairmen has resulted. The major reasons for a chairman's distress are the excessive expectations placed on him. Some possible remedies to make the chairman's lot easier include better managerial help, improved fiscal support, and alternative forms of organization. Departments of medicine must improve their planning processes if they are to survive in the 1980's.
New obesity mediator is discovered
Authors: D. Josefson
Journal: BMJ (1998)

Scientists at the University of Texas have uncovered a new hormonal cascade that is concerned with the regulation of feeding behaviour. The discovery may eventually lead to new drug treatment for obesity, diabetes, and cachexia.

The researchers identified centrally acting neuropeptides and their associated receptors, which they named orexin A and B and OX-1R and OX-2R respectively ( Cell 1998; 92:573-83). The orexins are produced in the lateral hypothalamus, an area of the brain known to be concerned with the sensation …
Antitumor and Anti-inflammatory Effects of Trabectedin on Human Myxoid Liposarcoma Cells
Authors: Giovanni Germano, Roberta Frapolli, Matteo Simone, Michele Tavecchio, Eugenio Erba, Samantha Pesce, Fabio Pasqualini, Federica Grosso, Roberta Sanfilippo, Paolo G. Casali, Alessandro Gronchi, Emanuela Virdis, Eva Tarantino, Silvana Pilotti, Angela Greco, Manuela Nebuloni, Carlos Maria Galmarini, Juan Carlos Tercero, Alberto Mantovani, Maurizio D'Incalci, Paola Allavena
Journal: Cancer Research (2010)

Inflammatory mediators present in the tumor milieu may promote cancer progression and are considered promising targets of novel biological therapies. We previously reported that the marine antitumor agent trabectedin, approved in Europe in 2007 for soft tissue sarcomas and in 2009 for ovarian cancer, was able to downmodulate the production of selected cytokines/chemokines in immune cells. Patients with myxoid liposarcoma (MLS), a subtype characterized by the expression of the oncogenic transcript FUS-CHOP, are highly responsive to trabectedin. The drug had marked antiproliferative effects on MLS cell lines at low nanomolar concentrations. We tested the hypothesis that trabectedin could also affect the inflammatory mediators produced by cancer cells. Here, we show that MLS express several cytokines, chemokines, and growth factors (CCL2, CCL3, CCL5, CXCL8, CXCL12, MIF, VEGF, SPARC) and the inflammatory and matrix-binder protein pentraxin 3 (PTX3), which build up a prominent inflammatory environment. In vitro treatment with noncytotoxic concentrations of trabectedin selectively inhibited the production of CCL2, CXCL8, IL-6, VEGF, and PTX3 by MLS primary tumor cultures and/or cell lines. A xenograft mouse model of human MLS showed marked reduction of CCL2, CXCL8, CD68+ infiltrating macrophages, CD31+ tumor vessels, and partial decrease of PTX3 after trabectedin treatment. Similar findings were observed in a patient tumor sample excised after several cycles of therapy, indicating that the results observed in vitro might have in vivo relevance. In conclusion, trabectedin has dual effects in liposarcoma: in addition to direct growth inhibition, it affects the tumor microenvironment by reducing the production of key inflammatory mediators.
Glaucoma: genes, phenotypes, and new directions for therapy
Authors: Bao Jian Fan, Janey L. Wiggs
Journal: Journal of Clinical Investigation (2010)

Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative. This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible.
Neural tube defects and periconceptional folic acid in England and Wales: retrospective study Commentary: Food should be fortified with folic acid
Authors: R. A Kadir, C. Sabin, B. Whitlow, E. Brockbank, D. Economides, E. Alberman, J. M Noble
Journal: BMJ (1999)

The risks of a first occurrence and a recurrence of neural tube defects have been shown to be reduced by periconceptional folic acid supplementation-that is by taking folic acid from 3 months before conception to 3 months after conception. 1 2 The Expert Advisory Group in the United Kingdom recommended in 1992 that women who were trying to conceive should take 0.4 mg folic acid per day. 3 We assessed whether there had been any change in the incidence of neural tube defects since this recommendation was made.
Human hepatic cancer stem cells are characterized by common stemness traits and diverse oncogenic pathways
Authors: Jens U. Marquardt, Chiara Raggi, Jesper B. Andersen, Daekwan Seo, Itzhak Avital, David Geller, Yun-Han Lee, Mitsuteru Kitade, Agnes Holczbauer, Matthew C. Gillen, Elizabeth A. Conner, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Hepatology (2011)

Epigenetic mechanisms play critical roles in stem cell biology by maintaining pluripotency of stem cells and promoting differentiation of more mature derivatives. If similar mechanisms are relevant for the cancer stem cell (CSC) model, then epigenetic modulation might enrich the CSC population, thereby facilitating CSC isolation and rigorous evaluation. To test this hypothesis, primary human cancer cells and liver cancer cell lines were treated with zebularine (ZEB), a potent DNA methyltransferase-1 inhibitor, and putative CSCs were isolated using the side population (SP) approach. The CSC properties of ZEB-treated and untreated subpopulations were tested using standard in vitro and in vivo assays. Whole transcriptome profiling of isolated CSCs was performed to generate CSC signatures. Clinical relevance of the CSC signatures was evaluated in diverse primary human cancers. Epigenetic modulation increased frequency of cells with CSC properties in the SP fraction isolated from human cancer cells as judged by self-renewal, superior tumor-initiating capacity in serial transplantations, and direct cell tracking experiments. Integrative transcriptome analysis revealed common traits enriched for stemness-associated genes, although each individual CSC gene expression signature exhibited activation of different oncogenic pathways (e.g., EGFR, SRC, and MYC). The common CSC signature was associated with malignant progression, which is enriched in poorly differentiated tumors, and was highly predictive of prognosis in liver and other cancers.Epigenetic modulation may provide a tool for prospective isolation and in-depth analysis of CSC. The liver CSC gene signatures are defined by a pernicious interaction of unique oncogene-specific and common stemness traits. These data should facilitate the identifications of therapeutic tools targeting both unique and common features of CSCs.
Studies of the Retinal Circulation with Fluorescein
Authors: C. T. Dollery, J. V. Hodge, M. Engel
Journal: BMJ (1962)

An account is given of five former professional boxers, four of whom developed a chronic cerebral disorder in later life.Two (Cases I and 5) were both locally considered to be punch-drunk.However, the former had an absent septum pellucidum and the other was an alc-oholic.Necropsy in the latter showed foci of softening in the cerebral and cerebellar cortex.Two (Cases 2 and 3) suffered from cerebral atrophy.Both had cavum septi pellucidi, and in one (Case 2) the leaves of the septum seemed to be perforated.One (Case 4) was not physically disabled, but his behaviour was violent, his cerebrospinal fluid protein was raised (60 mg./100 ml.), and air encephalography suggested that there was a perforation in his septum pellucidum.The possible relationship between, these lesions and boxing is discussed.There is a paucity of pathological observations of the so-called punch-drunk syndrome, but before the existence of the sy-ndrome is denied, as in some quarters it has been, follow-up studies of former professional boxers will be necessary.
Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways
Authors: D. Woodrow Benson, G. Michael Silberbach, Ann Kavanaugh-McHugh, Carol Cottrill, Yizhong Zhang, Steve Riggs, Octavia Smalls, Mark C. Johnson, Michael S. Watson, J.G. Seidman, Christine E. Seidman, John Plowden, John D. Kugler
Journal: Journal of Clinical Investigation (1999)

Heterozygous mutations in NKX2.5, a homeobox transcription factor, were reported to cause secundum atrial septal defects and result in atrioventricular (AV) conduction block during postnatal life. To further characterize the role of NKX2.5 in cardiac morphogenesis, we sought additional mutations in groups of probands with cardiac anomalies and first-degree AV block, idiopathic AV block, or tetralogy of Fallot. We identified 7 novel mutations by sequence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardiac disease in nearly a quarter of affected individuals, as well as atrial septal defect and ventricular septal defect. Ventricular septal defect was associated with tetralogy of Fallot or double-outlet right ventricle in 3 individuals. Ebstein’s anomaly and other tricuspid valve abnormalities were also present. Mutations in human NKX2.5 cause a variety of cardiac anomalies and may account for a clinically significant portion of tetralogy of Fallot and idiopathic AV block. The coinheritance of NKX2.5 mutations with various congenital heart defects suggests that this transcription factor contributes to diverse cardiac developmental pathways.
Balloon dilation of the papilla after sphincterotomy: rescue therapy for difficult bile duct stones
Authors: S. Attasaranya, S. Sherman
Journal: Endoscopy (2007)

Endoscopic papillary balloon dilation (EPBD) for removal of bile duct stones was first described in a series of nine patients by Staritz et al. in 1982 [1]. Later on, in the 1990s, with the emerging concept of preservation of the sphincter of Oddi, numerous studies reported on the use of EPBD (mainly using an 8-mm dilation balloon) as an alternative to biliary endoscopic sphincterotomy for the treatment of bile duct stones. More widespread use of EPBD has subsequently been limited, however, because of what appears to be a significant risk of pancreatitis [2] [3] [4]. In addition, it has been shown that more endoscopic retrograde cholangiopancreatography sessions and more frequent use of mechanical lithotripsy are required with EPBD in order to achieve a comparable success rate to that achievable by standard therapy with biliary endoscopic sphincterotomy [5] [6] [7]. One recent series from Japan involving 1000 patients undergoing EPBD (using balloons up to 8 mm in size) showed that lithotripsy was required for complete bile duct clearance in 77 % of the 328 patients who had stones measuring 10 mm or more but in only 6 % of the 672 patients with smaller stones [8].