bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitroglycerin can facilitate weaning of difficult-to-wean chronic obstructive pulmonary disease patients: a prospective interventional non-randomized study
Authors: Routsi Christina , Stanopoulos Ioannis , Zakynthinos Epaminondas , Politis Panagiotis , Papas Vassilios , Zervakis Demetrios , Zakynthinos Spyros 
Published: November 2010

Abstract
Introduction
Both experimental and clinical data give convincing evidence to acute cardiac dysfunction as the origin or a cofactor of weaning failure in patients with chronic obstructive pulmonary disease. Therefore, treatment targeting the cardiovascular system might help the heart to tolerate more effectively the critical period of weaning. This study aims to assess the hemodynamic, respiratory and clinical effects of nitroglycerin infusion in difficult-to-wean patients with severe chronic obstructive pulmonary disease.

Methods
Twelve difficult-to-wean (failed ≥ 3 consecutive trials) chronic obstructive pulmonary disease patients, who presented systemic arterial hypertension (systolic blood pressure ≥ 140mmHg) during weaning failure and had systemic and pulmonary artery catheters in place, participated in this prospective, interventional, non-randomized clinical trial. Patients were studied in two consecutive days, i.e., the first day without (Control day) and the second day with (Study day) nitroglycerin continuous intravenous infusion starting at the beginning of the spontaneous breathing trial, and titrated to maintain normal systolic blood pressure. Hemodynamic, oxygenation and respiratory measurements were performed on mechanical ventilation, and during a 2-hour T-piece spontaneous breathing trial. Primary endpoint was hemodynamic and respiratory effects of nitroglycerin infusion. Secondary endpoint was spontaneous breathing trial and extubation outcome.

Results
Compared to mechanical ventilation, mean systemic arterial pressure, rate-pressure product, mean pulmonary arterial pressure, and pulmonary artery occlusion pressure increased [from (mean ± SD) 94 ± 14, 13708 ± 3166, 29.9 ± 4.8, and 14.8 ± 3.8 to 109 ± 20mmHg, 19856 ± 4877mmHg b/min, 41.6 ± 5.8mmHg, and 23.4 ± 7.4 mmHg, respectively], and mixed venous oxygen saturation decreased (from 75.7 ± 3.5 to 69.3 ± 7.5%) during failing trials on Control day, whereas they did not change on Study day. Venous admixture increased throughout the trial on both Control day and Study day, but this increase was lower on Study day. Whereas weaning failed in all patients on Control day, nitroglycerin administration on Study day enabled a successful spontaneous breathing trial and extubation in 92% and 88% of patients, respectively.

Conclusions
In this clinical setting, nitroglycerin infusion can expedite the weaning by restoring weaning-induced cardiovascular compromise.
BRCA1-Associated Breast Cancers Present Differently From BRCA2-Associated and Familial Cases: Long-Term Follow-Up of the Dutch MRISC Screening Study
Authors: Rijnsburger Adriana J. , Obdeijn Inge-Marie , Kaas Reinoutje , Tilanus-Linthorst Madeleine M.A. , Boetes Carla , Loo Claudette E. , Wasser Martin N.J.M. , Bergers Elisabeth , Kok Theo , Muller Sara H. , Peterse Hans , Tollenaar Rob A.E.M. , Hoogerbrugge Nicoline , Meijer Sybren , Bartels Carina C.M. , Seynaeve Caroline , Hooning Maartje J. , Kriege Mieke , Schmitz Paul I. M. , Oosterwijk Jan C. , de Koning Harry J. , Rutgers Emiel J.T. , Klijn Jan G.M. 
Published: November 2010

Purpose The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation carriers and first results on survival. Patients and Methods Women with higher than 15% cumulative lifetime risk (CLTR) of breast cancer were screened with biannual clinical breast examination and annual mammography and magnetic resonance imaging (MRI). Participants were divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR). Results Our update contains 2,157 eligible women including 599 mutation carriers (median follow-up of 4.9 years from entry) with 97 primary breast cancers detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was superior to that of mammography for invasive cancer (77.4% v 35.5%; P < .00005), but not for ductal carcinoma in situ. Results in the BRCA1 group were worse compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis ≤ 1 cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%) and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%), respectively, and 100% in the familial groups (n = 43). Conclusion Screening results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was high in all risk groups.
Fluorouracil Induces Myocardial Ischemia With Increases of Plasma Brain Natriuretic Peptide and Lactic Acid but Without Dysfunction of Left Ventricle
Authors: Jensen Søren Astrup , Hasbak Philip , Mortensen Jann , Sørensen Jens Benn 
Published: November 2010

Purpose Fluorouracil (FU) is a cornerstone of colorectal cancer treatment; however, it has clinical and subclinical influence on the heart. This study aimed to clarify the pathophysiology, risk factors, and long-term effects of FU cardiotoxicity. Patients and Methods The study prospectively accrued colorectal cancer patients (n = 106) completely resected and adjuvantly treated with FU and oxaliplatin according to the FOLFOX4 regimen (infusional FU, folinic acid, and oxaliplatin). Serial measurements were made of systolic and diastolic features of the left ventricle by radionuclide ventriculography, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), lactic acid, and ECG before chemotherapy, immediately after a treatment infusion, and at follow-up 2 weeks after cessation of the intended 12 treatment courses and were further evaluated by multivariate regression analysis that included cardiovascular history and its risk factors. Results In the entire cohort, NT-proBNP significantly increased from baseline 14.5 ± 3.2 pmol/L (mean ± standard error) to 28.3 ± 5.3 pmol/L during FU therapy (P < .001). Nine patients (8.5%) with cardiotoxicity had significantly higher NT-proBNP of 55.3 ± 40.8 pmol/L compared with 25.4 ± 4.1 pmol/L in those without (P < .001). In multivariate analysis, the FU-induced rise of NT-proBNP was significantly higher in females (P < .001). Plasma lactic acid significantly increased from baseline (1.3 ± 0.1 mmol/L to 1.8 ± 0.1 mmol/L) during FU therapy (P < .001). Left ventricular ejection fraction at baseline of 0.66 ± 0.01 remained unchanged at 0.65 ± 0.01 during FU therapy and 0.66 ± 0.01 at follow-up (P = .4). Conclusion FU therapy generally induces myocardial neuroendocrine changes with increasing plasma NT-proBNP and lactic acid but without long-term dysfunction of the left ventricle. The usability of NT-proBNP as a predictive marker for FU cardiotoxicity remains to be clarified.
Phase III Trial Comparing Oral S-1 Plus Carboplatin With Paclitaxel Plus Carboplatin in Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Oncology Group Study
Authors: Okamoto Isamu , Yoshioka Hiroshige , Morita Satoshi , Ando Masahiko , Takeda Koji , Seto Takashi , Yamamoto Nobuyuki , Saka Hideo , Asami Kazuhiro , Hirashima Tomonori , Kudoh Shinzoh , Satouchi Miyako , Ikeda Norihiko , Iwamoto Yasuo , Sawa Toshiyuki , Miyazaki Masaki , Tamura Kenji , Kurata Takayasu , Fukuoka Masahiro , Nakagawa Kazuhiko 
Published: November 2010

Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm. Conclusion Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.
Plasma Transforming Growth Factor α and Amphiregulin Protein Levels in NCIC Clinical Trials Group BR.21
Authors: Addison Christina L. , Ding Keyue , Zhao Huijun , Le Maître Aurélie , Goss Glenwood D. , Seymour Lesley , Tsao Ming-Sound , Shepherd Frances A. , Bradbury Penelope A. 
Published: November 2010

Purpose To evaluate the prognostic and predictive significance of plasma levels of the epidermal growth factor receptor (EGFR) ligands, transforming growth factor α (TGF-α) and amphiregulin, in patients with non–small-cell lung cancer (NSCLC) enrolled in NCIC Clinical Trials Group BR.21 comparing erlotinib with placebo. Patients and Methods TGF-α and amphiregulin were assessed retrospectively by enzyme-linked immunosorbent assay from available prospectively collected baseline plasma samples in 565 of 731 BR.21 patients. Cutoff points were determined for both amphiregulin (low, < 10 pg/mL; high, ≥ 10 pg/mL) and TGF-α (low, ≤ 12 pg/mL; high, > 12 pg/mL) using a graphical method. Cox regression models were used to correlate biomarker data and baseline characteristics with outcomes including overall (OS) and progression-free survival (PFS). Results High TGF-α and amphiregulin were associated with poorer performance status (P = .06 and P < .0001, respectively) and no prior platinum therapy (P = .06 and P = .02, respectively). High amphiregulin was also associated with anemia (P = .001), increased lactate dehydrogenase (P = .03), ever-smokers (P = .04), and non-Asian ethnicity (P = .001). Patients on the placebo arm with high amphiregulin had poorer OS than patients with low amphiregulin (hazard ratio [HR] = 1.88; 95% CI, 1.34 to 2.64; P = .0002), which remained significant in multivariate analysis. Amphiregulin levels did not predict for benefit from erlotinib (interaction P = .87). Conversely, TGF-α levels did not have prognostic significance, but high TGF-α predicted lack of benefit from erlotinib compared with low TGF-α (TGF-α low, OS HR = 0.66; 95% CI, 0.54 to 0.81; P < .0001; high, OS HR = 1.32; 95% CI, 0.73 to 2.39; P = .36; interaction P = .04). Conclusion High baseline amphiregulin is a poor prognostic factor, whereas high baseline TGF-α predicts for lack of benefit from erlotinib in advanced NSCLC.
Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration
Authors: Karschner Erin L , Darwin W David , Goodwin Robert S , Wright Stephen , Huestis Marilyn A 
Published: November 2010

BACKGROUNDSativex®, a cannabis extract oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction.METHODSCannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board–approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L.RESULTSNine cannabis smokers completed all 5 dosing sessions. Significant differences (P &lt; 0.05) in maximum plasma concentrations (Cmax) and areas under the curve from 0–10.5 h postdose (AUC0→10.5) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in Cmax, time to maximum concentration or in the AUC0→10.5 between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively.CONCLUSIONThese data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.
Targeted Massively Parallel Sequencing of Maternal Plasma DNA Permits Efficient and Unbiased Detection of Fetal Alleles
Authors: Liao Gary JW , Lun Fiona MF , Zheng Yama WL , Chan KC Allen , Leung Tak Y , Lau Tze K , Chiu Rossa WK , Lo YM Dennis 
Published: November 2010

BACKGROUND
Massively parallel sequencing has recently been used in noninvasive prenatal diagnosis. The current costs of this technology are still relatively expensive, however, and sample throughput is still relatively low when it is used as a molecular diagnostic tool. Rather than nonselectively sequencing the genome, target enrichment provides a logical approach for more efficient and cost-effective massively parallel sequencing because it increases the proportion of informative data from the targeted region(s). Existing applications of targeted sequencing have mainly been qualitative analyses of genomic DNA. In this study, we investigated its applicability in enriching selected genomic regions from plasma DNA and the quantitative performance of this approach.

METHODS
DNA was extracted from plasma samples collected from 12 pregnant women carrying female fetuses. The SureSelect Target Enrichment System (Agilent Technologies) was used to enrich for exons on chromosome X. Plasma DNA libraries with and without target enrichment were analyzed by massively parallel sequencing. Genomic DNA samples of the mother and fetus for each case were genotyped by microarray.

RESULTS
For the regions targeted by the enrichment kit, the mean sequence coverage of the enriched samples was 213-fold higher than that of the nonenriched samples. Maternal and fetal DNA molecules were enriched evenly. After target enrichment, the coverage of fetus-specific alleles within the targeted region increased from 3.5% to 95.9%.

CONCLUSIONS
Targeted sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles at genomic regions of interest and is a powerful method for measuring the proportion of fetal DNA in a maternal plasma sample.
A polymorphism in the 5’ UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients
Authors: Crovella Sergio , Segat Ludovica , Amato Annalisa , Athanasakis Emmanouil , Bezzerri Valentino , Braggion Cesare , Casciaro Rosaria , Castaldo Giuseppe , Colombo Carla , Covone Angela Elvira , De Rose Virginia , Gagliardini Rolando , Lanzara Carmen , Minicucci Laura , Morgutti Marcello , Nicolis Elena , Pardo Francesca , Quattrucci Serena , Raia Valeria , Ravazzolo Roberto , Seia Manuela , Stanzial Valentino , Termini Lisa , Zazzeron Laura , Cabrini Giulio , Gasparini Paolo 
Published: November 2010

Abstract

Background: The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.–52G>A, c.–44C>G and c.–20G>A) in the 5’ untranslated region (5′ UTR) of the β defensin 1 (DEFB1) gene and the CF pulmonary phenotype.

Methods: Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan® allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42).

Results: For the c.–20G>A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.–20G>A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients.

Conclusions: Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype.
Emotion und Gedächtnis
Authors: Hahn Alois 
Published: November 2010

Zusammenfassung
Ausgehend von der Annahme, dass alle geäußerte Emotion ein Resultat soziokultureller Prägung ist, ergibt sich, dass Emotionen historisch variabel sind, da sie zum kulturellen Fundus einer jeweiligen Gesellschaft gehören. Analog zum Wortschatz einer Sprache lassen sich je gesellschaftsspezifische Gefühlslexika mit größerem oder kleinerem Gefühlsschatz bilden, in denen die Emotionen mit ihren dinglichen Korrelaten aufgelistet bzw. umgekehrt die Dinge mit ihren emotionalen Konnotationen eingetragen sind (Tod/Angst; Mutter/Liebe). Als Momente kreativer Vollzüge sind Gefühle darüber hinaus auf ein habituelles Gedächtnis angewiesen, wobei hier aber die erfahrenen Emotionen nicht als vorgestellte Vergangenheit, sondern als fortdauernde Wirkung präsent sind (Kondensation im Sinne Luhmanns). Die sinnhafte Konstitution und Gestaltung einer Situation bedarf eben auch der sie interpretierenden Emotionen. Zum Gefühlshaushalt von Gesellschaften gehört auch ihre je differenzielle Normierung sowohl in normativer Hinsicht (moralisch, kognitiv, kathektisch) wie auch auf der Ebene situations-, rollen- und kontextspezifischer Orientierung im Sinne der Parsons′schen Pattern Variables, so dass man auf diese Weise den gesamten Rollenhaushalt einer Gesellschaft danach rubrizieren könnte, je nachdem, welche Bedeutung je-weils Affekte haben und wie legitim ihr Ausdruck ist.
A Spatial and Perspective Change Theory of the Difference Between Sympathy and Empathy
Authors: Berthoz Alain , Thirioux Bérangère 
Published: November 2010

Abstract
Empathy is a multicomponent faculty of the human brain which is funda-mental for social interactions.Understanding its behavioural, cognitive, emotional neural mechanisms and pathology is a major interdisciplinary challenge..Here we propose, in relation with a modern conception of the Philosophical tradition of Phenomenology and a primary role of cognitive embodiement, a new theory in which we give an important although not exclusive, role to the brain mechanisms which also are involved in spatial cognition: we show, that there is a basic difference between *sympathy* and *empathy*. Whether sympathy is akin to emotional contagion and does not require the siubject to adopt the point of view of others, empathy requires a dynamic and complex manipulation of spatial reference frames. We give an example of an experiment using virtual reality in which a subject interacts with an artificial tight rope walker and discuss also the possible interindividual differences, and gender differences, in the different strategies used by subjects to have an empathic relationship.
Die Ruinanz als Grundbewegtheit des Faktischen und die Wurzeln der Seinsfrage. Zu Heideggers Verständnis der Fundamentalontologie als Daseinsanalyse
Authors: Malisardi Francesco 
Published: November 2010

Zusammenfassung
Der Ausdruck Ruinanz, die Grundbewegtheit faktischen Lebens, wird von Heidegger im Wintersemester 1921/22 im Rahmen der Vorlesung Phänomenologische Interpretationen zu Aristoteles. Einführung in die Phänomenologische Forschung verwendet. Danach gebraucht er den Ausdruck nie wieder. Er war sich vermutlich weder damals noch später bewusst, dass das, was er dabei war zu entwerfen, d.h. eine neue Begrifflichkeit für ein neues Verständnis des Zugangs zum Sein, vieles dieser frühen Intuition zu verdanken hatte. Das Gleiche scheint auch für die meisten Heidegger-Interpretatoren zu gelten. Im Ausdruck Ruinanz verbirgt sich ein Erklärungspotential, wie man es schwer anderswo bei Heidegger findet. Was in der Ruinanz geschieht, ist so selbstverständlich, dass es nicht zum Ausdruck kommen kann.
Als Möglichkeitsbedingung aller Verständlichkeit und Unverständlichkeit gilt hier das Faktische: das, was der Spaltung in Erkenntnisobjekt und Erkennendem ontologisch vorausgeht. Insofern ist hier auch zu erfahren, ob das Dasein wirklich den eigenen Schatten nicht überspringen kann, d.h., ob es genau in dieser Unmöglichkeit verstehensmäßig ein- und dasselbe ist wie das Sein.
Motus, Meute, Meuterei: Formen wüster Bewegung
Authors: Sardinha Diogo 
Published: November 2010

Zusammenfassung
Die Vorstadtkrawalle werden auf französisch oft als émeutes bezeichnet. Dieses Wort bewahrt die Spur seines lateinischen Ursprungs, die an die Vorstellung einer Bewegung (motus) geknüpft ist, mischt dem aber einen entschieden gewalttätigen Unterton bei. Nach diesem Beispiel, erkennt das Deutsche den etymologischen Zusammenhang des Worts Meuterei mit dem lateinischen motus. Anhand von diesen Prämissen und vom Beispiel der Unruhen in Frankreich versucht dieser Beitrag zu beweisen, dass der Aufstand als politische Situation nicht durch den Aufeinanderprall unterschiedlicher Identitäten gekennzeichnet wird, vielmehr durch den Zusammenstoß eines Willens zur Identität (Polizei, Organisation) mit einer Macht, die einem Fluss gleicht und die eine stetige und entfesselte Bewegung ist.
Körper und Bewegung in der Frauenmystik. Die Entmächtigung des Körpers, die Macht der Imagination und die Schrift
Authors: Kasten Ingrid 
Published: November 2010

Zusammenfassung
In allen mystischen Religionen steht das Streben nach der Vereinigung von Gott und Mensch, nach der unio mystica, im Zentrum. In der christlich-abendländischen Tradition wird dieser Vorgang als eine Abstiegs- oder eine Aufstiegsbewegung vorgestellt. Von diesen gegenläufigen Bewegungsmodellen ausgehend, fragt die Studie, wie sie in einer frauenmystischen Dichtung des 13. Jahrhunderts, in Das fließende Licht der Gottheit Mechthilds von Magdeburg, produktiv gemacht werden. Es zeigt sich, dass die Bewegungsstruktur zwischen Gott und Mensch von beiden Modellen bestimmt ist, wobei eine enge Wechselbeziehung zwischen der Stimme Gottes, der Materialität des Körpers und der Materialität der Schrift imaginiert wird. Das in der christlichen Tradition vielfach antagonistisch gedachte Verhältnis von Leib und Seele wird dabei dynamisiert und der (weibliche) Körper als Medium der Kommunikation mit Gott aufgewertet.