tbuckley/cabot-search huggingface dataset:
Parenteral Nutrition–Associated Hyperglycemia in Non–Critically Ill Inpatients Increases the Risk of In-Hospital Mortality (Multicenter Study)
Authors: Gabriel Olveira, María José Tapia, Julia Ocón, Carmen Cabrejas-Gómez, María D. Ballesteros-Pomar, Alfonso Vidal-Casariego, Carmen Arraiza-Irigoyen, Josefina Olivares, Maria del Carmen Conde-García, Álvaro García-Manzanares, Francisco Botella-Romero, Rosa P. Quílez-Toboso, Lucio Cabrerizo, Pilar Matia, Luisa Chicharro, Rosa Burgos, Pedro Pujante, Mercedes Ferrer, Ana Zugasti, Javier Prieto, Marta Diéguez, María José Carrera, Anna Vila-Bundo, Juan Ramón Urgelés, Carmen Aragón-Valera, Adela Rovira, Irene Bretón, Pilar García-Peris, Araceli Muñoz-Garach, Efren Márquez, Dolores del Olmo, José Luis Pereira, María C. Tous
Journal: Diabetes Care (2012)

Hyperglycemia may increase mortality in patients who receive total parenteral nutrition (TPN). However, this has not been well studied in noncritically ill patients (i.e., patients in the nonintensive care unit setting). The aim of this study was to determine whether mean blood glucose level during TPN infusion is associated with increased mortality in noncritically ill hospitalized patients.This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included prospectively, and data were collected on demographic, clinical, and laboratory variables as well as on in-hospital mortality.The study included 605 patients (mean age 63.2 ± 15.7 years). The daily mean TPN values were 1.630 ± 323 kcal, 3.2 ± 0.7 g carbohydrates/kg, 1.26 ± 0.3 g amino acids/kg, and 0.9 ± 0.2 g lipids/kg. Multiple logistic regression analysis showed that the patients who had mean blood glucose levels >180 mg/dL during the TPN infusion had a risk of mortality that was 5.6 times greater than those with mean blood glucose levels <140 mg/dL (95% CI 1.47-21.4 mg/dL) after adjusting for age, sex, nutritional state, presence of diabetes or hyperglycemia before starting TPN, diagnosis, prior comorbidity, carbohydrates infused, use of steroid therapy, SD of blood glucose level, insulin units supplied, infectious complications, albumin, C-reactive protein, and HbA1c levels.Hyperglycemia (mean blood glucose level >180 mg/dL) in noncritically ill patients who receive TPN is associated with a higher risk of in-hospital mortality.
Recipient iNOS but Not eNOS Deficiency Reduces Luminal Narrowing in Tracheal Allografts
Authors: Kanji Minamoto, David J. Pinsky
Journal: The Journal of Experimental Medicine (2002)

Chronic airway rejection is characterized by prolonged inflammation, epithelial damage, and eventual luminal obliterative bronchiolitis (OB). In cardiac allografts, the inducible nitric oxide synthase (iNOS) promotes acute rejection but paradoxically reduces neointimal formation, the hallmark of chronic rejection. The specific roles of NOS isoforms in modulating lymphocyte traffic and airway rejection are not known. Using a double lumen mouse tracheal transplant model, tracheal grafts from B10.A (allo) or C57BL/6J (iso) mice were transplanted into cyclosporine-treated wild-type (WT) iNOS−/− or endothelial NOS (eNOS)−/− recipients. OB was observed in WT tracheal allografts at 3 weeks (53 ± 2% luminal occlusion vs. 17 ± 1% for isografts, P &amp;lt; 0.05) with sites of obstructive lesion formation coinciding with areas of CD3+ CD8+ T cell–rich lymphocytic bronchitis. In contrast, allografts in iNOS−/− recipients exhibited reductions in local expression of proinflammatory chemokines and cytokines, graft T cell recruitment and apoptosis, and luminal obliteration (29 ± 2%, P &amp;lt; 0.05 vs. WT allografts). Recipient eNOS deficiency, however, suppressed neither chemokine expression, lymphocyte infiltration, nor airway occlusion (54 ± 2%). These data demonstrate that iNOS exacerbates luminal obliteration of airway allografts in contrast with the known suppression by iNOS of cardiac allograft vasculopathy. Because iNOS−/− airways transplanted into WT allograft hosts are not protected from rejection, these data suggest that iNOS expressed by graft-infiltrating leukocytes exerts the dominant influence on airway rejection.
Putative therapeutic targets in the treatment of visceral hyperalgesia
Authors: S Collins
Journal: Gut (2004)

The management of abdominal pain remains a major challenge for clinicians despite an explosion of knowledge regarding the physiology and pathophysiology of sensory neural circuits. Initial progress was made in the field of somatic pain and this provided broad hypotheses that could be tested in the field of visceral pain. The major advances in our understanding of basic mechanisms underlying visceral pain originated in the urinary tract and have been applied to the gut. As yet, this increased understanding of enteric sensory physiology has yet to generate new effective treatments for abdominal pain. This review addresses novel insights into peripheral mechanisms underlying visceral hyperalgesia and their applicability to the development of novel therapeutic approaches to the treatment of chronic abdominal pain.
Endothelial function and myocardial infarction
Authors: K Bhagat
Journal: Cardiovascular Research (1998)

Time for primary review 34 days 

Several standard risk factors are now recognised for the development of coronary disease and a modulation of some of these factors has been shown to decrease the incidence and recurrence of coronary events [1–3]. Mortality in coronary disease is directly related to the number of diseased vessels, the presence of left ventricular dysfunction, and an ischaemic response on treadmill exercise testing. However, our ability to prognosticate based on an understanding of ischaemia or angiography still remains very poor. Furthermore, it is recognised that traditional antianginal therapy does not significantly alter prognosis; angioplasty does not prevent myocardial infarction or death on follow up and although by-pass surgery may decrease subsequent mortality in certain sub-groups, it has not been shown to decrease the future incidence of myocardial infarction [4, 5].

At least one important reason for this unpredictability is that acute ischaemic events, particularly myocardial infarction, are unrelated to stenosis severity [6–8]. Acute coronary events, which include a diagnosis of unstable angina, acute myocardial infarction and some cases of sudden cardiac death, are usually related to a sudden disruption or fissure of an atherosclerotic plaque with the formation of thrombus that partially occludes (unstable angina) or completely occludes (myocardial infarction or sudden death) the coronary vessel. Serial angiographic studies performed prior to and following an acute event, or angiographic studies performed early after myocardial infarction, indicate that the underlying plaque responsible for unstable angina and myocardial infarction was usually less than 50% narrowed prior to the acute event [6, 9]. Moreover, these lesions would be unlikely to cause ischaemia if looked for using ambulatory monitoring (a means to establish the total ischaemic burden). A recent angiographic study suggests that the positive correlation between the number of severely diseased arteries and coronary mortality … 

* Tel.: 00 44 171 209 6616; Fax: 00 44 171 813 2846; E-mail: k.bhagat@ucl.ac.uk
Cellular basis for blunted volume expansion natriuresis in experimental nephrotic syndrome.
Authors: J P Valentin, C Qiu, W P Muldowney, W Z Ying, D G Gardner, M H Humphreys
Journal: Journal of Clinical Investigation (1992)

Experimental nephrotic syndrome results in sodium retention, reflecting, at least in part, an intrinsic defect in renal sodium handling in the distal nephron. We studied the relationships among plasma atrial natriuretic peptide (ANP) concentration, sodium excretion (UNaV), and urinary cyclic GMP excretion (UcGMPV) in vivo, and the responsiveness of isolated glomeruli and inner medullary collecting duct (IMCD) cells to ANP in vitro, in rats with adriamycin nephrosis (6-7 mg/kg body weight, intravenously). 3-5 wk after injection, rats were proteinuric and had a blunted natriuretic response to intravenous infusion of isotonic saline, 2% body weight given over 5 min. 30 min after onset of the infusion, plasma ANP concentrations were elevated in normals and were even higher in nephrotics. Despite this, nephrotic animals had a reduced rate of UcGMPV after the saline infusion, and accumulation of cGMP by isolated glomeruli and IMCD cells from nephrotic rats after incubation with ANP was significantly reduced compared to normals. This difference was not related to differences in binding of 125I-ANP to IMCD cells, but was abolished when cGMP accumulation was measured in the presence of 10(-3) M isobutylmethylxanthine or zaprinast (M&B 22,948), two different inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Infusion of zaprinast (10 micrograms/min) into one renal artery of nephrotic rats normalized both the natriuretic response to volume expansion and the increase in UcGMPV from the infused, but not the contralateral, kidney. These results show that, in adriamycin nephrosis, blunted volume expansion natriuresis is associated with renal resistance to ANP, demonstrated both in vivo and in target tissues in vitro. The resistance does not appear related to a defect in binding of the peptide, but is blocked by PDE inhibitors, suggesting that enhanced cGMP-PDE activity may account for resistance to the natriuretic actions of ANP observed in vivo. This defect may represent the intrinsic sodium transport abnormality linked to sodium retention in nephrotic syndrome.
MODIFICATION OF THE PATHOGENICITY OF PSEUDORABIES VIRUS BY ANIMAL PASSAGE
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1933)

Pseudorabies virus, Iowa strain ("mad itch"), after passage through guinea pig brain, fails to produce infection in guinea pigs when injected subcutaneously unless enormous doses are employed. Such virus is still pathogenic for rabbits when given subcutaneously and for rabbits and guinea pigs intracerebrally. Comparison of the amounts of virus present in the brains of rabbits and guinea pigs following fatal cerebral infection shows that the latter contain, per gram, only approximately one-tenth the amount of virus in the former. Comparing the resistance of the two species to subcutaneously administered pseudorabies virus it has been found that rabbits are approximately 100 times more susceptible than guinea pigs. Over and above the working of these two factors, guinea pig passage appears to achieve some actual attenuation of virus when tested by subcutaneous inoculation into guinea pigs.
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
Authors: José Baselga, Mario Campone, Martine Piccart, Howard A. Burris, Hope S. Rugo, Tarek Sahmoud, Shinzaburo Noguchi, Michael Gnant, Kathleen I. Pritchard, Fabienne Lebrun, J. Thaddeus Beck, Yoshinori Ito, Denise Yardley, Ines Deleu, Alejandra Perez, Thomas Bachelot, Luc Vittori, Zhiying Xu, Pabak Mukhopadhyay, David Lebwohl, Gabriel N. Hortobagyi
Journal: New England Journal of Medicine (2011)

Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity.In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed.Baseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confidence interval [CI], 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001).Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials.gov number, NCT00863655.).
A Tumor-Targeted and Conditionally Replicating Oncolytic Adenovirus Vector Expressing TRAIL for Treatment of Liver Metastases
Authors: Pavel Sova, Xiao-Wei Ren, Shaoheng Ni, Kathrin M Bernt, Jie Mi, Nancy Kiviat, André Lieber
Journal: Molecular Therapy (2004)

We have constructed a new capsid-modified adenovirus (Ad) vector that specifically replicates in tumor cells and expresses TNF-related apoptosis-inducing ligand (TRAIL). The Ad capsid contains short-shafted fibers derived from Ad serotype 35, which allow for efficient infection of malignant tumor cells, and largely avoids innate toxicity after intravenous application. Replication-dependent homologous recombination in Ad genomes was used to achieve tumor-specific expression of Ad E1a (to mediate viral replication) and TRAIL (to mediate apoptosis and enhance release of progeny virus from infected cells). We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer. Both in vitro and in vivo tumor models showed efficient intratumoral spread of this vector. In a model for metastatic colon cancer, tail vein infusion of Ad5/35.IR-E1A/TRAIL resulted in elimination of preestablished liver metastases. Intravenous injection of this vector caused a transient elevation of serum glutamic pyruvic transaminase in tumor-bearing mice, which we attributed to factors released from apoptotic tumor cells. Liver histology analyzed at day 14 after virus injection did not show signs of hepatocellular damage. This new oncolytic vector represents a potentially efficient means for gene therapy of metastatic cancer.
Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells
Authors: Myrna L. Ortiz, Vinit Kumar, Anna Martner, Sridevi Mony, Laxminarasimha Donthireddy, Thomas Condamine, John Seykora, Stella C. Knight, George Malietzis, Gui Han Lee, Morgan Moorghen, Brianna Lenox, Noreen Luetteke, Esteban Celis, Dmitry Gabrilovich
Journal: The Journal of Experimental Medicine (2015)

Evidence links chronic inflammation with cancer, but cellular mechanisms involved in this process remain unclear. We have demonstrated that in humans, inflammatory conditions that predispose to development of skin and colon tumors are associated with accumulation in tissues of CD33+S100A9+ cells, the phenotype typical for myeloid-derived suppressor cells in cancer or immature myeloid cells (IMCs) in tumor-free hosts. To identify the direct role of these cells in tumor development, we used S100A9 transgenic mice to create the conditions for topical accumulation of these cells in the skin in the absence of infection or tissue damage. These mice demonstrated accumulation of granulocytic IMCs in the skin upon topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting in a dramatic increase in the formation of papillomas during epidermal carcinogenesis. The effect of IMCs on tumorigenesis was not associated with immune suppression, but with CCL4 (chemokine [C-C motif] ligand 4)-mediated recruitment of IL-17–producing CD4+ T cells. This chemokine was released by activated IMCs. Elimination of CD4+ T cells or blockade of CCL4 or IL-17 abrogated the increase in tumor formation caused by myeloid cells. Thus, this study implicates accumulation of IMCs as an initial step in facilitation of tumor formation, followed by the recruitment of CD4+ T cells.
Simultaneous sensitivity to fragrances
Authors: D.A. Buckley, D.A. Basketter, C.K. Smith Pease, R.J.G. Rycroft, I.R. White, J.P. McFadden
Journal: British Journal of Dermatology (2006)

Journal Article Simultaneous sensitivity to fragrances Get access D.A. Buckley, D.A. Buckley Contact Dermatitis Clinic, St John's Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. *Safety and Environmental Assurance Centre, Unilever Colworth Laboratory, Sharnbrook, Bedford MK44 1LQ, U.K D.A. Buckley, Department of Dermatology, Great Western Hospital, Swindon SN3 688, U.K. E‐mail: dbuckley@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar D.A. Basketter, D.A. Basketter Contact Dermatitis Clinic, St John's Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. *Safety and Environmental Assurance Centre, Unilever Colworth Laboratory, Sharnbrook, Bedford MK44 1LQ, U.K Search for other works by this author on: Oxford Academic Google Scholar C.K. Smith Pease, C.K. Smith Pease Contact Dermatitis Clinic, St John's Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. *Safety and Environmental Assurance Centre, Unilever Colworth Laboratory, Sharnbrook, Bedford MK44 1LQ, U.K Search for other works by this author on: Oxford Academic Google Scholar R.J.G. Rycroft, R.J.G. Rycroft Contact Dermatitis Clinic, St John's Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. *Safety and Environmental Assurance Centre, Unilever Colworth Laboratory, Sharnbrook, Bedford MK44 1LQ, U.K Search for other works by this author on: Oxford Academic Google Scholar I.R. White, I.R. White Contact Dermatitis Clinic, St John's Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. *Safety and Environmental Assurance Centre, Unilever Colworth Laboratory, Sharnbrook, Bedford MK44 1LQ, U.K Search for other works by this author on: Oxford Academic Google Scholar J.P. McFadden J.P. McFadden Contact Dermatitis Clinic, St John's Institute of Dermatology, St Thomas’ Hospital, London SE1 7EH, U.K. *Safety and Environmental Assurance Centre, Unilever Colworth Laboratory, Sharnbrook, Bedford MK44 1LQ, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 5, 1 May 2006, Pages 885–888, https://doi.org/10.1111/j.1365-2133.2006.07170.x Published: 01 May 2006 Article history Accepted: 13 November 2005 Published: 01 May 2006
Gene regulatory networks in plants: learning causality from time and perturbation
Authors: Gabriel Krouk, Jesse Lingeman, Amy Marshall Colon, Gloria Coruzzi, Dennis Shasha
Journal: Genome biology (2013)

The goal of systems biology is to generate models for predicting how a system will react under untested conditions or in response to genetic perturbations. This paper discusses experimental and analytical approaches to deriving causal relationships in gene regulatory networks.
Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome
Authors: J.W. Song, S-B. Hong, C-M. Lim, Y. Koh, D.S. Kim
Journal: European Respiratory Journal (2010)

Although acute exacerbation of idiopathic pulmonary fibrosis (IPF) has become well recognised, the reported incidence and outcomes are highly variable, and risk factors are unknown. The aim of this study was to estimate the incidence, risk factors and impact of acute exacerbations, and other known causes of rapid deterioration. This was a retrospective review of 461 patients with IPF (269 cases were biopsy-proven). The median follow-up period was 22.9 months. Rapid deterioration requiring hospitalisation occurred in 163 (35.4%) patients, with multiple episodes in 42 patients. Acute exacerbation was the most frequent cause (55.2%), followed by infection. The 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low forced vital capacity (FVC) were significant risk factors. The in-hospital mortality rate was 50.0%, and the 1- and 5-yr survival rates from the initial diagnosis were 56.2 and 18.4%, respectively. Acute exacerbation was a significant predictor of poor survival after the initial diagnosis, along with increased age, low FVC and diffusing capacity of the lung for carbon monoxide, and steroid use with or without cytotoxic therapy. 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low FVC were risk factors. Acute exacerbation had a serious impact on the overall survival of the patients with IPF.
Investigation of the anti-inflammatory properties of hydroxypyridinones.
Authors: S D Hewitt, R C Hider, P Sarpong, C J Morris, D R Blake
Journal: Annals of the Rheumatic Diseases (1989)

Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the chelators competed successfully for iron with apotransferrin, and some removed up to 34% of iron from ferritin. The best anti-inflammatory effects were achieved with the most hydrophilic chelators and those which chelated iron most avidly. Activity was dependent on dose. The route of administration was also an important factor with lower affinity chelators. This work introduces a range of simple bidentate iron chelators, which under certain conditions exceed desferrioxamine in their iron scavenging abilities, and some of which, in this simple animal model, approach indomethacin in their anti-inflammatory capabilities.