tbuckley/cabot-search huggingface dataset:
Diagnostic Performance of Coronary Angiography by 64-Row CT
Authors: Julie M. Miller, Carlos E. Rochitte, Marc Dewey, Armin Arbab-Zadeh, Hiroyuki Niinuma, Ilan Gottlieb, Narinder Paul, Melvin E. Clouse, Edward P. Shapiro, John Hoe, Albert C. Lardo, David E. Bush, Albert de Roos, Christopher Cox, Jeffery Brinker, João A.C. Lima
Journal: New England Journal of Medicine (2008)

The accuracy of multidetector computed tomographic (CT) angiography involving 64 detectors has not been well established.We conducted a multicenter study to examine the accuracy of 64-row, 0.5-mm multidetector CT angiography as compared with conventional coronary angiography in patients with suspected coronary artery disease. Nine centers enrolled patients who underwent calcium scoring and multidetector CT angiography before conventional coronary angiography. In 291 patients with calcium scores of 600 or less, segments 1.5 mm or more in diameter were analyzed by means of CT and conventional angiography at independent core laboratories. Stenoses of 50% or more were considered obstructive. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate diagnostic accuracy relative to that of conventional angiography and subsequent revascularization status, whereas disease severity was assessed with the use of the modified Duke Coronary Artery Disease Index.A total of 56% of patients had obstructive coronary artery disease. The patient-based diagnostic accuracy of quantitative CT angiography for detecting or ruling out stenoses of 50% or more according to conventional angiography revealed an AUC of 0.93 (95% confidence interval [CI], 0.90 to 0.96), with a sensitivity of 85% (95% CI, 79 to 90), a specificity of 90% (95% CI, 83 to 94), a positive predictive value of 91% (95% CI, 86 to 95), and a negative predictive value of 83% (95% CI, 75 to 89). CT angiography was similar to conventional angiography in its ability to identify patients who subsequently underwent revascularization: the AUC was 0.84 (95% CI, 0.79 to 0.88) for multidetector CT angiography and 0.82 (95% CI, 0.77 to 0.86) for conventional angiography. A per-vessel analysis of 866 vessels yielded an AUC of 0.91 (95% CI, 0.88 to 0.93). Disease severity ascertained by CT and conventional angiography was well correlated (r=0.81; 95% CI, 0.76 to 0.84). Two patients had important reactions to contrast medium after CT angiography.Multidetector CT angiography accurately identifies the presence and severity of obstructive coronary artery disease and subsequent revascularization in symptomatic patients. The negative and positive predictive values indicate that multidetector CT angiography cannot replace conventional coronary angiography at present. (ClinicalTrials.gov number, NCT00738218.)
Cystic dystrophy of the gastric and duodenal wall developing in heterotopic pancreas: an unrecognised entity.
Authors: J F Flejou, F Potet, G Molas, P Bernades, P Amouyal, F Fekete
Journal: Gut (1993)

Ten patients in whom cystic dystrophy developed in a heterotopic pancreas of the duodenal (nine patients) or gastric (one patient) wall are reported. All were young or middle aged white men, only two of whom were alcoholic. The symptoms were caused by intestinal or biliary stenosis, or both, secondary to the inflammation and fibrosis. Only endosonography provided strong evidence for the diagnosis in three patients. All patients underwent surgery: a pancreaticoduodenectomy was performed in eight patients. The surgical specimen showed cystic lesions of the gut wall, occurring in inflammatory and fibrous heterotopic pancreatic tissue. The pancreas proper was normal in all patients. It is suggested that cystic dystrophy is an uncommon and serious complication of heterotopic pancreas. Similar cases associated with chronic pancreatitis of the pancreas have been observed and it is suggested that this process could be responsible for some of the chronic pancreatitis encountered in young, non-alcoholic patients.
Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome
Authors: Christian Drosten, Stephan Günther, Wolfgang Preiser, Sylvie van der Werf, Hans-Reinhard Brodt, Stephan Becker, Holger Rabenau, Marcus Panning, Larissa Kolesnikova, Ron A.M. Fouchier, Annemarie Berger, Ana-Maria Burguière, Jindrich Cinatl, Markus Eickmann, Nicolas Escriou, Klaus Grywna, Stefanie Kramme, Jean-Claude Manuguerra, Stefanie Müller, Volker Rickerts, Martin Stürmer, Simon Vieth, Hans-Dieter Klenk, Albert D.M.E. Osterhaus, Herbert Schmitz, Hans Wilhelm Doerr
Journal: New England Journal of Medicine (2003)

BackgroundAbstractThe severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent.MethodsClinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques.ResultsA novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)–based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated.ConclusionsThe novel coronavirus might have a role in causing SARS.
Much debated controversies of diffuse low-grade gliomas
Authors: Gelareh Zadeh, Osaama H. Khan, Michael Vogelbaum, David Schiff
Journal: Neuro-Oncology (2015)

See the article by Duffau and Taillandier, on pages 332–342. Duffau and colleagues present a comprehensive and provocative review of the concepts of surgical and medical management of adult diffuse low-grade gliomas (DLGG). The review takes a very strong position, which will likely generate debate and stimulate much discussion regarding the establishment of guidelines for care of patients with DLGG. Here we provide a counterpoint to summarize the perspectives on observation and delayed intervention in management of DLGG. The management of DLGG remains controversial, as the level of evidence to support best practices is not conclusive, and as a result, there is variation in practice patterns for individual patients who present with DLGG. The principal controversies include: the necessary components of the diagnostic workup; the role of a “wait-and-see” strategy; following patients based on their clinical status and imaging alone; and the nature and goals of surgical intervention. Following initial treatment decisions, postoperative management issues include but are not limited to: role of imaging, role of repeat surgery, adjuvant treatment, and follow-up. Although we have a better understanding of the isocitrate dehydrogenase – mutant, glioma cytosine/ phosphate/guanine island methylator phenotype–positive subclass of DLGG, there are further biological signatures that will likely distinguish DLGG into subgroups, which will impact the outcome, extent and timing of tumor progression, as well as
Cross-talk between LPA1 and Epidermal Growth Factor Receptors Mediates Up-regulation of Sphingosine Kinase 1 to Promote Gastric Cancer Cell Motility and Invasion
Authors: Dai Shida, Xianjun Fang, Tomasz Kordula, Kazuaki Takabe, Sandrine Lépine, Sergio E. Alvarez, Sheldon Milstien, Sarah Spiegel
Journal: Cancer Research (2008)

Abstract Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lysophospholipid mediators of diverse cellular processes important for cancer progression. S1P is produced by two sphingosine kinases, SphK1 and SphK2. Expression of SphK1 is elevated in many cancers. Here, we report that LPA markedly enhanced SphK1 mRNA and protein in gastric cancer MKN1 cells but had no effect on SphK2. LPA also up-regulated SphK1 expression in other human cancer cells that endogenously express the LPA1 receptor, such as DLD1 colon cancer cells and MDA-MB-231 breast cancer cells, but not in HT29 colon cancer cells or MDA-MB-453 breast cancer cells, which do not express the LPA1 receptor. An LPA1 receptor antagonist or down-regulation of its expression prevented SphK1 and S1P3 receptor up-regulation by LPA. LPA transactivated the epidermal growth factor receptor (EGFR) in these cells, and the EGFR inhibitor AG1478 attenuated the increased SphK1 and S1P3 expression induced by LPA. Moreover, down-regulation of SphK1 attenuated LPA-stimulated migration and invasion of MNK1 cells yet had no effect on expression of neovascularizing factors, such as interleukin (IL)-8, IL-6, urokinase-type plasminogen activator (uPA), or uPA receptor induced by LPA. Finally, down-regulation of S1P3, but not S1P1, also reduced LPA-stimulated migration and invasion of MKN1 cells. Collectively, our results suggest that SphK1 is a convergence point of multiple cell surface receptors for three different ligands, LPA, EGF, and S1P, which have all been implicated in regulation of motility and invasiveness of cancer cells. [Cancer Res 2008;68(16):6569–77]
Effects of quinidine sulfate on the balance among active and passive cellular properties that comprise the electrophysiologic matrix and determine excitability in sheep Purkinje fibers.
Authors: M F Arnsdorf, G J Sawicki
Journal: Circulation Research (1987)

Quinidine is the most commonly used drug for the chronic treatment of ventricular arrhythmias, but it may be arrhythmogenic. Much information exists concerning quinidine's effects on active properties in cardiac tissues, but virtually nothing is known of its effects on passive properties. We studied the effects of quinidine, in a clinically relevant concentration, on the balance among active and passive cellular properties that comprise the electrophysiologic matrix that determines cardiac excitability. The multiple microelectrode method of intracellular-current application and transmembrane voltage recording was used in sheep Purkinje fibers to determine strength-duration and constant current-voltage relations as well as cable properties. A rapid, on-line computerized data analysis system tracked in time the alterations in the active and passive properties relevant to excitability. In normal fibers at [K+]o = 5.4 mM, quinidine increased cardiac excitability as manifested by a decrease in the current required to attain threshold and/or a downward shift in strength- and charge-duration relations by altering passive properties despite a depressed sodium system and a slowed conduction velocity. During washout, excitability and passive properties remained altered despite a return of descriptive action potential parameters such as the resting potential, the maximum rate of rise of phase 0, overshoot, and the action potential duration to or nearly to normal. At [K+]o = 8.0 mM, quinidine could either increase or decrease excitability; net excitability depends on the balance between altered passive properties and the depressed sodium system. The results explain, in part, the antiarrhythmic actions and arrhythmogenic potential of quinidine. The data for quinidine and other antiarrhythmic drugs are interpreted in terms of the electrophysiologic matrix, which we believe has important advantages over traditional hierarchical classifications.
SAT0598-HPR Valued Life Activities: Swedish Version (VLA-SWE) with Cultural Adaptation, ICF Linkage and Psychometric Testing
Authors: M. Björk, M. Thyberg, E. Waltersson, B. Stenström, P. Katz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Disability is an important outcome in rheumatoid arthritis (RA). The Valued Life Activity scale (VLA) comprises a wide range of life activities deemed to be important by the individual, ranging from self-care to leisure activities. Thereby VLA takes the patients´ priorities into account and includes activities in which disability may occur early. <h3>Objectives</h3> Translation, cultural adaptation including linkage to the International Classification of Functioning, Disability and Health (ICF) and psychometric testing of the VLA scale in Swedish patients with RA. <h3>Methods</h3> The VLA, developed by Katz et al (1) was translated and culturally adapted to a Swedish version, the VLA-swe. As a part of this, both the VLA and VLA-swe were linked to the ICF according to linking rules (2). 737 RA patients(73% women)aged 18 - 80 (mean age 62 years) were recruited from the Swedish Rheumatology Quality Registry (SRQ). The average disease duration was 16 years. Data for disease activity (DAS28), activity limitations (HAQ) and life satisfaction (LiSat11) were registered and patients completed the VLA-swe. Internal consistency was assessed with Cronbach's alpha and item statistics. To establish construct validity VLA-swe was correlated to DAS28, HAQ and LiSat11. <h3>Results</h3> The conceptual similarity between the VLA-swe and the original VLA was high when linked to the ICF: in 29 of the 33 items the ICF codes tallied exactly with each other and the remaining differed only slightly. Each of the 9 ICF activity/participation domains was represented in one or more items. The internal consistency was excellent for the VLA-swe (0.97) and alpha coefficients did not improve after omitting any of the 33 items. The correlations between the single items and the total VLA-swe score varied between r=0.57 and r=0.84. Scores of the VLA-swe correlated strongly with the HAQ (r=0.87), moderately with the LiSat11 (r=-0.61) and weakly with the DAS28 (r=0.38), as expected. <h3>Conclusions</h3> The VLA-swe is culturally adapted and validated, and addresses a broad range of ICF activity/participation domains. Since both the patients´ preferences and ICF concepts of disability are taken into account, it is a useful complement to traditional measures, such as the HAQ, which measure activity limitations only. <h3>References</h3> Katz P, Morris A, Yelin E. Prevalence and predictors of disability in valued life activities among individuals with rheumatoid arthritis. Ann Rheum Dis 2006;65:763e9. Cieza A, Geyh S, Chatterji S, Kostanjsek N, Ustun B, Stucki G. ICF linking rules: an update based on lessons learned. J Rehabil Med 2005;37:212-218. <h3>Disclosure of Interest</h3> None Declared
Blood loss after partial gastrectomy
Authors: I. M. Baird, D. R. Sutton
Journal: Gut (1972)

Six male and three female patients previously iron deficient after a partial gastrectomy were investigated using a whole body counter to measure their percentage <sup>59</sup>Fe retention. No significant difference in iron loss between postgastrectomy patients and controls was found in the majority of subjects over a study which lasted from 175 to 225 days. The detection of increased free iron loss requires a more sensitive double isotope faecal recovery method. Two patients developed acute bleeding during the study and the whole body counter provided clinically useful data on blood loss. If patients develop gastrointestinal blood loss after partial gastrectomy either a recurrent ulcer or a site of blood loss elsewhere (eg, in the lower bowel) should be excluded.
Further observations on the gastric secretory depressant in human gastric juice
Authors: P. B. Rowe, B. H. Fenton, D. Beeston
Journal: Gut (1964)

A gastric secretory depressant ;gastrone' has been previously found in normal gastric juice. These studies show that it is present in the neutralized gastric juice and is not destroyed by peptic digestion in one hour, indicating that this factor is not a protein and would be consistent with the view that it is related to the mucopolysaccharides in gastric juice.
Fatal head injury from boxing: a case report from Greece: Figure 1
Authors: C Constantoyannis, M Partheni
Journal: British Journal of Sports Medicine (2004)

The case is described of a fatal injury to a young amateur boxer. The number of deaths from boxing have decreased in recent years. However, new rules devised to promote safety, such as limitation of the number of rounds, mandatory use of safety head guards, and better medical control during the match, seem to be of limited value in preventing severe head injuries from boxing.
Impairment of autonomically mediated heart rate control in patients with cardiac dysfunction.
Authors: R E Goldstein, G D Beiser, M Stampfer, S E Epstein
Journal: Circulation Research (1975)

Patients with cardiac disorders have defective parasympathetic control of heart rate. To evaluate the possibility of similar changes in sympathetic control of heart rate, we compared reflex chronotropic responses to 80 degree upright tilt and nitroglycerin-induced hypotension in 31 cardiac patients and 7 normal individuals before and after partial parasympathetic blockade with atropine. Tilting revealed an attenuation of the normal heart rate increase in patients; the magnitude of this defect was greatest in patients with more severe symptoms (class III) and evidence of left ventricular dysfunction (the heart rate increase averaged 25 plus or minus 3 beats/min in normal subjects, 12 plus or minus 2 beats/min in class I-II patients, and 7 plus or minus 1 beats/min in class III patients). Class III symptoms due to mechanical causes (mitral stenosis), however, were not associated with this defect. A marked reduction in heart rate rise with hypotension was seen only in those class III patients without mitral stenosis (0.4 plus or minus 0.1 beats min-minus 1 mm Hg-minus 1 vs. 3.0 plus or minus 0.5 beats min-minus 1 mm Hg-minus 1 in normal subjects). This abnormality also persisted after atropine administration, thus confirming a defect in the sympathetic as well as the parasympathetic component of baroreceptor-mediated reflex heart rate control in patients with cardiac dysfunction. Infusions of isoproterenol produced equivalent rises in heart rate in patients and normal individuals, excluding a reduction in beta-receptor responsiveness as a cause of impaired sympathetic influence. Norepinephrine depletion, however, is a well-recognized concomitant of cardiac failure. It is possible that the reduction in sympathetically mediated heart rate responses results in part from depletion of the sympathetic neurotransmitter.
INHIBITION OF PHOSPHORYLATION OF GLUCOSE IN MOUSE BRAINS BY VIRUSES AND ITS PREVENTION BY PREPARATIONS OF DIPHOSPHOPYRIDINE NUCLEOTIDE
Authors: E. Racker, I. Krimsky
Journal: The Journal of Experimental Medicine (1946)

1. Inhibition of glucose utilization in homogenates of brains of mice infected with poliomyelitis virus (Lansing strain) is reported. The inhibition occurs with glucose, or fructose-6-phosphate as substrate. No inhibition occurs in the presence of hexosediphosphate. 2. Brain homogenates of mice infected with the Theiler FA strain of mouse encephalomyelitis virus show inhibition ranging between 45 and 85 per cent (average 73 per cent). 3. Purified preparations of the Lansing and the Theiler FA strain invariably inhibit glycolysis when added to homogenates of normal mouse brain. A similar, but much less consistent inhibition is provoked by adding high concentrations of non-neurotropic viruses (influenza A and tobacco mosaic virus) to normal mouse brains. 4. The magnitude of inhibition caused by the purified virus is a function of the virus concentration and depends on temperature and time of incubation of the virus-brain mixture. 5. The inhibition of glycolysis in the brains of mice infected with Theiler FA virus and in normal brain-Theiler FA virus mixtures is prevented by the addition of preparations of DPN and glucose.
Activator protein 1 transcription factor fos-related antigen 1 (fra-1) is dispensable for murine liver fibrosis, but modulates xenobiotic metabolism
Authors: Sebastian C. Hasenfuss, Latifa Bakiri, Martin K. Thomsen, Rainer Hamacher, Erwin F. Wagner
Journal: Hepatology (2013)

The Activator Protein 1 (AP-1) transcription factor subunit Fos-related antigen 1 (Fra-1) has been implicated in liver fibrosis. Here we used loss-of-function as well as switchable, cell type-specific, gain-of-function alleles for Fra-1 to investigate the relevance of Fra-1 expression in cholestatic liver injury and fibrosis. Our results indicate that Fra-1 is dispensable in three well-established, complementary models of liver fibrosis. However, broad Fra-1 expression in adult mice results in liver fibrosis, which is reversible, when ectopic Fra-1 is switched off. Interestingly, hepatocyte-specific Fra-1 expression is not sufficient to trigger the disease, although Fra-1 expression leads to dysregulation of fibrosis-associated genes. Both opn and cxcl9 are controlled by Fra-1 in gain-of-function and loss-of-function experiments. Importantly, Fra-1 attenuates liver damage in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine-feeding cholestatic liver injury model. Strikingly, manipulating Fra-1 expression affects genes involved in hepatic transport and detoxification, in particular glutathione S-transferases. Molecular analyses indicate that Fra-1 binds to the promoters of cxcl9 and gstp1 in vivo. Furthermore, loss of Fra-1 sensitizes, while hepatic Fra-1 expression protects from acetaminophen-induced liver damage, a paradigm for glutathione-mediated acute liver failure. Conclusion: These data define a novel function of Fra-1/AP-1 in modulating the expression of detoxification genes and the adaptive response of the liver to bile acids/xenobiotic overload. (Hepatology 2014;58:261–273)
Plasma protein profiling in alpha-1-antitrypsin deficiency
Authors: Helen Stone, Douglas Ward, Robert Stockley
Journal: European Respiratory Journal (2011)

Introduction: Alpha-1-antitrypsin deficiency (ATD) results in an imbalance of proteases and antiproteases with proteolytic destruction of lung parenchyma, and subsequently early onset emphysema. We hypothesised changes in plasma peptides/proteins would be detectable and could provide potential biomarkers to predict a response to treatment in patients with ATD receiving augmentation therapy.

Methods: Mass spectrometry was used to identify proteolytic fragments in plasma following neutrophil activation by ionophore or the addition of neutrophil elastase (NE). 72 paired plasma samples from the EXACTLE trial, taken at baseline and 6 months, were subsequently analysed using weak cation exchange beads and MALDI-TOF-MS, to determine whether any of the protein fragments generated in vitro were present in clinical samples and changed significantly in response to augmentation.

Results: Following neutrophil activation or the addition of NE to plasma 325 peptides from 32 proteins were identified. 207 peptide peaks were detected in the spectra of the EXACTLE patients. T Tests were performed to determine whether or not the peak intensities of the peptides changed with treatment. Of these, 12 were significantly different in the treatment group, yet unchanged in the placebo group. The most significant of these had a p value of 2.08E-05.

Conclusion: Changes in the plasma peptidome can be found in patient plasma after the addition of calcium ionophore and NE. Some of these changes can be detected in plasma pre/post augmentation. We aim to use more in depth proteomic approaches to further characterise changes in the plasma peptidome, and determine clinical utility as a guide to monitoring and treatment in ATD.