tbuckley/cabot-search huggingface dataset:
S28 Clinical predictors of admission in infants with acute bronchiolitis
Authors: M. Marlais, J. Evans, E. Abrahamson
Journal: Thorax (2010)

<h3>Introduction</h3> Bronchiolitis is a significant cause of acute morbidity in the first 12 months of life. A proportion of infants will be admitted to hospital and currently the decision to admit is based on clinical judgement alone. Research evidence identifying indicators for admission is scarce, there have been no studies assessing clinical predictors of admission in infants with bronchiolitis under the age of 12 months. <h3>Aim</h3> To determine which clinical features in the emergency department are able to predict the need for hospital admission in infants with acute bronchiolitis. <h3>Methods</h3> All infants presenting with acute bronchiolitis to one tertiary paediatric emergency department from April 2009 to March 2010 were included in this study. Inclusion criteria were a clinical diagnosis of bronchiolitis in an infant aged &lt;12 months. The case notes for each infant were reviewed and data on 29 potential clinical predictors were recorded. An exhaustive list of potential clinical predictors was devised through literature review. Institutional approval was obtained to perform this study. Logistic regression analysis was performed to determine which clinical features could predict admission. <h3>Results</h3> 449 infants presented with acute bronchiolitis during the study period (298 (66%) male, mean age 23±14.5 weeks). 163 (36%) infants were admitted to hospital. The main clinical features predictive of admission (mean for admitted group vs discharged group respectively) included: younger age at presentation (mean 17.9 weeks vs 26.4 weeks, p&lt;0.001), higher respiratory rate (mean 54.6 vs 46.9, p&lt;0.001), higher heart rate (mean 162.8 vs 147.7, p&lt;0.001), lower oxygen saturation (mean 96.4% vs 98.4%, p&lt;0.001), lower duration of symptoms (mean 2.9 days vs 4.9 days, p&lt;0.001), lower weight at presentation (mean 6196 g vs 7897 g, p&lt;0.001). The best single predictor of admission was oxygen requirement in the emergency department (OR 78.4 (95% CI 18.8 to 326.9), p&lt;0.001). <h3>Conclusion</h3> We have identified seven objective clinical parameters which can be used in the emergency department to predict which infants with bronchiolitis require admission to hospital. These data have been assimilated into a simple clinical risk score; further work is required to validate this scoring system and to assess its utility in supporting clinical decisions.
Perspectives of pediatricians and general practitioners on diagnosis and treatment of bronchiolitis
Authors: Carolina Constant, Manuel Magalhães, Maria Gabriela Andrade, Duarte Malveiro, Ines Azevedo, Eduarda Sousa, Rizério Salgado, Teresa Bandeira, Ricardo M. Fernandes
Journal: European Respiratory Journal (2014)

We assessed pediatricians9 (Peds) and general practitioners9 (GPs) perspectives on managing acute bronchiolitis (AB) and its concordance with a recent national guideline (NG).  The  ABBA  study was a Portuguese nationwide online survey with members of the Portuguese Society of Pediatrics and GPs9 mailing lists. Domains included diagnostic tests, treatments and hospital referral criteria, based on two clinical scenarios of AB severity (mild/moderate).  514 Peds and 165 GPs participated (59% specialists), 48% Peds and 44% GPs reported implementing the NG. Peds used diagnostic tests in  50%) of ≥1 bronchodilator was referred by 43% in mild and 78% in moderate AB (89% used a drug trial); salbutamol was the top choice [via spacer (40%), nebulised (32%)]. In moderate AB, frequent use of corticosteroids, adrenaline or hypertonic saline was reported by 33%, 21% and 20% Peds, respectively. The most used SpO 2  thresholds for initiating and discontinuing O 2  were 92% and 94%, respectively. Preferences of Peds between IV fluids, NG feeding were split at half. GPs referred to hospital 10% of mild and 93% of moderate AB, and up to 60% frequently used a bronchodilator. At their workplace, 34% did not have pulse oximetry and only 30% had spacers. Overall, NG recommendations were followed by 36% (diagnosis) and 12% (treatment) Peds; concordance was higher in those who reported implementing the NG (p  Management of AB is heterogeneous and diverges from the NG, particularly regarding treatment. Tailored strategies are needed to implement the NG at different levels of care.
Colour Transparencies for Teaching First Aid
Authors: A. W. Gardner
Journal: BMJ (1964)

BRmTIsH 1513individual case is unimportant, however bad; the principle is clear.If the disciplinary procedure of the N.H.S. is to include the laying down of what is "good " or " bad " doctoring then I, for one.will require to see in the terms of service some pretty exhaustive and stringent definitions, and it may be that we shall have to abandon our present easy-going informal procedure that Dr. Dain spent so many years building up.-I am, etc.,
The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial
Authors: Andrew L Lux, Stuart W Edwards, Eleanor Hancock, Anthony L Johnson, Colin R Kennedy, Richard W Newton, Finbar JK O'Callaghan, Christopher M Verity, John P Osborne
Journal: The Lancet (2004)
HLA-Dw2: a genetic marker for human immune response to short ragweed pollen allergen Ra5. II. Response after ragweed immunotherapy.
Authors: D G Marsh, D A Meyers, L R Freidhoff, E Ehrlich-Kautzky, M Roebber, P S Norman, S H Hsu, W B Bias
Journal: The Journal of Experimental Medicine (1982)

After artificial immunization (immunotherapy) with ragweed antigens, specific immunoglobulin G (IgG) antibody (Ab) response to Ra5 was significantly associated with HLA-Dw2 (P less than 0.0001). From a total of 61 treated patients, all 22 Dw2+ subjects made good IgG Ab responses to Ra5 by year 2 of therapy (21 by year 1), even though 8 of them had no detectable IgG Ab and 9 had no detectable IgE Ab before therapy. The prevalence of IgG Ab response among 39 Dw2- subjects was markedly lower; only 11 (28%) responded well after 1-9 yr of therapy. Both by univariate and multivariate statistical analysis, Dw2 was also found to be strongly associated with the quantity of IgG Ab produced. In particular, both the strength and significance of the association between Dw2 and log[IgG Ab] response to Ra5 increased over a 3-yr period of ragweed therapy (P = 10(-9) by year 3). Multiple regression analysis also revealed a weak association with HLA-B13, which became apparent only after year 2 of therapy. Genetic hypotheses for these findings are discussed. In particular, the possibility of a second Ir gene, Ir-Ra5', separate from HLA-Dw2 and possibly located elsewhere in the genome, is considered.
Conditional FKBP12.6 Overexpression in Mouse Cardiac Myocytes Prevents Triggered Ventricular Tachycardia Through Specific Alterations in Excitation- Contraction Coupling
Authors: Barnabas Gellen, María Fernández-Velasco, François Briec, Laurent Vinet, Khai LeQuang, Patricia Rouet-Benzineb, Jean-Pierre Bénitah, Mylène Pezet, Gael Palais, Noémie Pellegrin, Andy Zhang, Romain Perrier, Brigitte Escoubet, Xavier Marniquet, Sylvain Richard, Fréderic Jaisser, Ana María Gómez, Flavien Charpentier, Jean-Jacques Mercadier
Journal: Circulation (2008)

Ca(2+) release from the sarcoplasmic reticulum via the ryanodine receptor (RyR2) activates cardiac myocyte contraction. An important regulator of RyR2 function is FKBP12.6, which stabilizes RyR2 in the closed state during diastole. Beta-adrenergic stimulation has been suggested to dissociate FKBP12.6 from RyR2, leading to diastolic sarcoplasmic reticulum Ca(2+) leakage and ventricular tachycardia (VT). We tested the hypothesis that FKBP12.6 overexpression in cardiac myocytes can reduce susceptibility to VT in stress conditions. We developed a mouse model with conditional cardiac-specific overexpression of FKBP12.6. Transgenic mouse hearts showed a marked increase in FKBP12.6 binding to RyR2 compared with controls both at baseline and on isoproterenol stimulation (0.2 mg/kg i.p.). After pretreatment with isoproterenol, burst pacing induced VT in 10 of 23 control mice but in only 1 of 14 transgenic mice (P<0.05). In isolated transgenic myocytes, Ca(2+) spark frequency was reduced by 50% (P<0.01), a reduction that persisted under isoproterenol stimulation, whereas the sarcoplasmic reticulum Ca(2+) load remained unchanged. In parallel, peak I(Ca,L) density decreased by 15% (P<0.01), and the Ca(2+) transient peak amplitude decreased by 30% (P<0.001). A 33.5% prolongation of the caffeine-evoked Ca(2+) transient decay was associated with an 18% reduction in the Na(+)-Ca(2+) exchanger protein level (P<0.05). Increased FKBP12.6 binding to RyR2 prevents triggered VT in normal hearts in stress conditions, probably by reducing diastolic sarcoplasmic reticulum Ca(2+) leak. This indicates that the FKBP12.6-RyR2 complex is an important candidate target for pharmacological prevention of VT.
Nitric Oxide Contributes to the Progression of Myocardial Damage in Experimental Autoimmune Myocarditis in Rats
Authors: Shigeru Ishiyama, Michiaki Hiroe, Toshio Nishikawa, Shinji Abe, Takashi Shimojo, Hiroshi Ito, Sakae Ozasa, Katsutoshi Yamakawa, Masunori Matsuzaki, Minhaz Uddin Mohammed, Hiroe Nakazawa, Takeshi Kasajima, Fumiaki Marumo
Journal: Circulation (1997)

Background Excess amounts of NO produced by an inducible NO synthase (iNOS) in response to cytokines may be cytotoxic and can be destructive to tissue. We investigated the role of NO in the development of myocardial damage and the effects of aminoguanidine (AG), an inhibitor of iNOS, on experimental autoimmune myocarditis in rats. Methods and Results Autoimmune myocarditis was induced in 20 Lewis rats by injection of porcine cardiac myosin. Ten of the 20 rats were administered AG. The severity of myocarditis was evaluated by measuring the size of myocarditic lesion and serum levels of CK-MB. Serum NO levels were determined using the Cd/Cu method. Tissue specimens were immunohistochemically examined for iNOS and nitrotyrosine. Histopathological study revealed extensive myocardial destruction and massive inflammatory cell infiltration in AG-untreated rats but only focal mononuclear cell infiltration in AG-treated rats. The mean percent areas of inflammatory lesions in the untreated and treated rats were 56±13% and 3±2%, respectively ( P &lt;.001). NO levels were 102±23 and 25±9 IU/L, respectively ( P &lt;.01). CK-MB levels were 68±13 and 16±13 nmol/L, respectively ( P &lt;.01). Superoxide production as measured with an ex vivo monitoring system was also significantly decreased in the treated rats. Nitrotyrosine relating to the generation of peroxynitrite was detected through immunostaining in the inflammatory lesions of untreated rats but not in those of treated rats. Conclusions Excess amounts of NO produced by iNOS appear to contribute to the progression of myocardial damage in myocarditis. AG may prove to be useful in the treatment of myocarditis.
Suppression of Hypoxia-Inducible Factor 2α Restores p53 Activity via Hdm2 and Reverses Chemoresistance of Renal Carcinoma Cells
Authors: Andrew M. Roberts, Ian R. Watson, Andrew J. Evans, David A. Foster, Meredith S. Irwin, Michael Ohh
Journal: Cancer Research (2009)

p53 mutations are rarely detected in clear cell renal cell carcinoma (CCRCC), but, paradoxically, these tumors remain highly resistant to chemotherapy and death receptor-induced death. Here, we show that the accumulation of hypoxia-inducible factor 2alpha (HIF2alpha), a critical oncogenic event in CCRCC following the loss of von Hippel-Lindau (VHL) tumor suppressor protein, leads to Hdm2-mediated suppression of p53. Primary CCRCC specimens exhibiting strong hypoxic signatures show increased levels of activated nuclear phospho-Hdm2(Ser(166)), which is concomitant with low p53 expression. The abrogation of Hdm2-p53 interaction using the small-molecule Hdm2 inhibitor nutlin-3 or the downregulation of HIF2alpha via HIF2alpha-specific short hairpin RNA or wild-type VHL reconstitution restores p53 function and reverses the resistance of CCRCC cells to Fas-mediated and chemotherapy-induced cell death. These findings unveil a mechanistic link between HIF2alpha and p53 and provide a rationale for combining Hdm2 antagonists with chemotherapy for the treatment of CCRCC.
Receptor-Mediated Antigen Uptake and its Effect on Antigen Presentation to Class II-Restricted T Lymphocytes
Authors: A Lanzavecchia
Journal: Annual Review of Immunology (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Differential Enzyme Targeting As an Evolutionary Adaptation to Herbivory in Carnivora
Authors: Graeme M Birdsey, Jackie Lewin, Andrew A Cunningham, Michael W Bruford, Christopher J Danpure
Journal: Molecular Biology and Evolution (2004)

Not all members of the order Carnivora are carnivorous. Some are omnivorous, and a few, such as the giant panda, Ailuropoda melanoleuca, are almost exclusively herbivorous. Although a number of adaptations to increased plant-eating are recognized within Carnivora, few have been studied at the molecular level. One molecular adaptation to diet that is spread widely across Mammalia is the differential intracellular targeting of the intermediary metabolic enzyme alanine:glyoxylate aminotransferase (AGT), which tends to be mitochondrial in carnivores, peroxisomal in herbivores, and both mitochondrial and peroxisomal in omnivores. In the present study, we have analyzed the targeting of AGT in Carnivora in relation to species' natural diets. We show not only that there has been an adaptive shift in AGT targeting from the mitochondrion toward the peroxisome as diets have shifted from being mainly carnivorous to ones that are more omnivorous and herbivorous but also that in one lineage, namely that of the giant panda, there is evidence for positive selection pressure at the molecular level on the AGT mitochondrial targeting sequence to decrease its efficiency, thereby allowing more AGT to be targeted to the peroxisomes.
Octreotide in the treatment of refractory diarrhoea and intestinal fistulae.
Authors: M J Farthing
Journal: Gut (1994)

Persistent, refractory diarrhoea continues to be an important clinical problem. The mechanisms involved are associated with reduced intestinal absorption and increased intestinal secretion. Reduced intestinal absorption can result from small intestinal resection or from disorders in which there is damage to the small intestine. Motility disorders may also impair absorptive function. The rationale for using octreotide in refractory diarrhoea, intestinal motility disorders, and fistulae relates to its ability to promote intestinal absorption and inhibit gastric, pancreatic, and intestinal secretion. Several clinical studies in patients with short bowel syndrome have reported a reduction of intestinal output in patients taking octreotide compared with controls. Additionally, a number of studies have shown that octreotide improves secretory diarrhoea resulting from neuroendocrine tumours, intestinal infections in AIDS patients, and intestinal graft v host disease. Octreotide may be of use in patients suffering from intestinal motility disorders such as those associated with systemic sclerosis. Octreotide may also be of value in promoting closure of gastrointestinal and pancreatic fistulae.
Contrasting Histories of G6PD Molecular Evolution and Malarial Resistance in Humans and Chimpanzees
Authors: Brian C. Verrelli, Sarah A. Tishkoff, Anne C. Stone, Jeffrey W. Touchman
Journal: Molecular Biology and Evolution (2006)

Although mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene result in several blood-related diseases in humans, they also confer resistance to malarial infection. This association between G6PD and malaria was supported by population genetic analyses of the G6PD locus, which indicated that these mutations may have recently risen in frequency in certain geographic regions as a result of positive selection. Here we characterize nucleotide sequence variation in a 5.2-kb region of the G6PD locus in a population sample of 56 chimpanzees, as well as among 7 other nonhuman primates, to compare with that in humans in determining whether other primates that are impacted by malaria also exhibit patterns of G6PD polymorphism or divergence consistent with positive selection. We find that chimpanzees have several amino acid variants but that the overall pattern at G6PD in chimpanzees, as well as in Old and New World primates in general, can be explained by recent purifying selection as well as strong functional constraint dating back to at least 30–40 MYA. These comparative analyses suggest that the recent signature of positive selection at G6PD in humans is unique.
Effect of nicotine on gastric mucosal blood flow and acid secretion.
Authors: A Sonnenberg, N Husmert
Journal: Gut (1982)

The effects of an intravenous infusion of nicotine at a dose of 2 . 5, 5 . 0, 7 . 5, or 10 . 0 micrograms kg-1h-1 on pentagastrin-stimulated gastric mucosal blood flow and acid secretion were investigated in eight healthy male non-smokers. Each dose was tested in two males. Gastric neutral red clearance served as a measure of mucosal blood flow. Nicotine reduced volume secretion, acid secretion, and neutral red clearance in a dose dependent manner. In five healthy male smokers smoking of five cigarettes per two hours induced similar changes to the intravenous infusion of 5 micrograms kg-1h-1 nicotine. As volume secretion was inhibited more than neutral red clearance, it is concluded that nicotine increases blood supply to the gastric mucosa relatively to the reduced gastric secretion. Nicotine is either not associated with the development of peptic ulcers, or it exerts its ulcerogenic action via other mechanisms than change of acid secretion and gastric mucosal blood flow.
The Maltese cross: A new simplistic model for memory
Authors: Donald E. Broadbent
Journal: Behavioral and Brain Sciences (1984)

Abstract This paper puts forward a general framework for thought about human information processing. It is intended to avoid some of the problems of pipeline or stage models of function. At the same time it avoids the snare of supposing a welter of indefinitely many separate processes. The approach is not particularly original, but rather represents the common elements or presuppositions in a number of modern theories. These presuppositions are not usually explicit, however, and making them so reduces the danger of slipping back into earlier modes of thought. The key point is to distinguish between persisting representations and the processes that translate one representation into another. Various classes or groups of persisting representations can be distinguished by the experimental treatments that interfere with them. In particular, there now seem to be several kinds of short-term or temporary storage, different from each other as well as from longterm memory; the translating processes also have several different modes or kinds. A particularly important aspect of the current position is that a model of this general type no longer requires some external agent to direct and control long sequences of behaviour.
Randomized, Double-Blind, Placebo-Controlled Phase IIB Trial of the Cyclooxygenase Inhibitor Ketorolac as an Oral Rinse in Oropharyngeal Leukoplakia
Authors: James L. Mulshine, Jane C. Atkinson, Robert O. Greer, Vassiliki A. Papadimitrakopoulou, Carter Van Waes, Susan Rudy, Jack W. Martin, Seth M. Steinberg, David J. Liewehr, Ingalill Avis, R. Ilona Linnoila, Stephen Hewitt, Scott M. Lippman, Robin Frye, Paul F. Cavanaugh
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia. Experimental Design: 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists. Results: The patients included 67% males, 11% non-Caucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms. Conclusion: Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted.
Tralokinumab for moderate-to-severe UC: a randomised, double-blind, placebo-controlled, phase IIa study
Authors: Silvio Danese, Janusz Rudziński, Wolfgang Brandt, Jean-Louis Dupas, Laurent Peyrin-Biroulet, Yoram Bouhnik, Dariusz Kleczkowski, Peter Uebel, Milan Lukas, Mikael Knutsson, Fredrik Erlandsson, Mark Berner Hansen, Satish Keshav
Journal: Gut (2014)

<h3>Objective</h3> Interleukin-13 (IL-13) has been implicated as a key driver of UC. This trial evaluates the efficacy and safety of tralokinumab, an IL-13-neutralising antibody, as add-on therapy in adults with moderate-to-severe UC despite standard treatments. <h3>Design</h3> Non-hospitalised adults with UC (total Mayo score ≥6) were randomised to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks for 12 weeks. The primary end point was the rate of clinical response at week 8. Secondary efficacy end points included clinical remission and mucosal healing rates at week 8 and changes in total Mayo score, total modified Riley score, partial Mayo score and disease activity markers. <h3>Results</h3> Clinical response rate was 38% (21/56) for tralokinumab vs 33% (18/55) for placebo (p=0.406). Clinical remission rate was 18% (10/56) vs 6% (3/55) (p=0.033) and mucosal healing rate was 32% (18/56) vs 20% (11/55) (p=0.104) for tralokinumab vs placebo. Changes to week 8 in total Mayo score and total modified Riley score were similar for tralokinumab and placebo (least-squares mean difference between groups: −0.49 (p=0.394) and 0.25 (p=0.449), respectively). Partial Mayo score at week 4 was lower with tralokinumab than placebo (least-squares mean difference between groups: −0.90 (p=0.041)). No consistent patterns were observed for disease activity markers. Tralokinumab had an acceptable safety profile. <h3>Conclusions</h3> Add-on therapy with tralokinumab did not significantly improve clinical response. However, the higher clinical remission rate with tralokinumab than placebo suggests that tralokinumab may benefit some patients with UC. Tralokinumab was well tolerated. <h3>Trial registration number</h3> ClinicalTrials.gov number: NCT01482884.