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1.
Characteristics of hyperparathyroid states in the Canadian multicentre osteoporosis study (CaMos) and relationship to skeletal markers 下载免费PDF全文
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Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma
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Jennifer C. Sasaki Ashley Allemang Steven M. Bryce Laura Custer Kerry L. Dearfield Yasmin Dietz Azeddine Elhajouji Patricia A. Escobar Albert J. Fornace Jr Roland Froetschl Sheila Galloway Ulrike Hemmann Giel Hendriks Heng-Hong Li Mirjam Luijten Gladys Ouedraogo Lauren Peel Stefan Pfuhler Daniel J. Roberts Véronique Thybaud Jan van Benthem Carole L. Yauk Maik Schuler 《Environmental and molecular mutagenesis》2020,61(1):114-134
In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc. 相似文献
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Baher Husain Christian Kuehne Christian Waydhas Ulrike Lewan Claudia Ose Dieter Nast-Kolb Steffen Ruchholtz 《European Journal of Trauma》2006,32(6):548-554
Abstract
Background: Does there exist a difference in the outcome of severely injured children and severely injured healthy adults?
Methods: The data of 1,566 severely injured patients, treated between May 1998 and December 2002 in our emergency department of the
University Essen/Germany, were analyzed. Patients with an injury severity score (ISS) > 24 were included in the present study.
Patients younger as 18 (17) years were located to the children group c. Patients aged 18 and up to the age of 54 were included
in the adult group a.
Results: Fifty-four children and 252 adults met the selection criteria. ISS and the Glasgow coma scale (GCS) before intubation were
not statistically different in both groups. Seriously injured children stayed significantly shorter on the intensive care
unit, required significantly less ventilator days. Furthermore, the incidence of single organ failure (SOF) and multiple organ
failure (MOF) was significantly lower in the children group. Mortality in the children group (29.6%) was lower than that in
the adult group (33.7%). There was no death due to MOF in the children group as compared to 2.4% (n = 6) in the adults.
Conclusion: The incidence of SOF and MOF was significantly lower in the children group although there was no difference in ISS, GCS and
injury patterns. The prognosis of severely injured children was found to be better than those of adults. Moreover, there was
no death due to MOF in the children group. 相似文献
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Pharmacokinetics and pharmacodynamics of benazepril hydrochloride in patients with major proteinuria
Ch. Schweizer G. Kaiser W. Dieterle J. Mann 《European journal of clinical pharmacology》1993,44(5):463-466
Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o.The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients.Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients.In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage. 相似文献