Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics

Introduction: In order to assess the significance of drug levels measured in intensive care medicine, clinical and forensic toxicology, as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. Therefore, it makes sense to offer a carefully referenced compilation of therapeutic and toxic plasma concentration ranges, as well as half-lives, of a large number of drugs and other xenobiotics for quick and comprehensive information. Methods: Data have been abstracted from original papers and text books, as well as from previous compilations, and have been completed with data collected in our own forensic and clinical toxicology laboratory. The data presented in the table and corresponding annotations have been developed over the past 20 years and longer. A previous compilation has been completely revised and updated. In addition, more than 170 substances, especially drugs that have been introduced to the market since 2003 as well as illegal drugs, which became known to cause intoxications, were added. All data were carefully referenced and more than 200 new references were included. Moreover, the annotations providing details were completely revised and more than 100 annotations were added. Results: For nearly 1,000 drugs and other xenobiotics, therapeutic ("normal") and, if data were available, toxic and comatose-fatal blood-plasma concentrations and elimination half-lives were compiled in a table. Conclusions: In case of intoxications, the concentration of the ingested substances and/or metabolites in blood plasma better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications, and to support forensic and clinical expert opinions

Digitoxin metabolism by rat liver microsomes.

Background: Malnutrition among hospitalized patients increases length of stay (LOS) and carries extra hospitalization costs. Objective: To review the impact of malnutrition on hospital LOS and costs in Europe. Methods: PubMed and Google Scholar search. All articles from January 2004 until November 2014 were identified. Reference lists of relevant articles were also manually searched. Results: Ten studies on LOS and nine studies on costs were reviewed. The methods used to assess malnutrition and to calculate costs differed considerably between studies. Malnutrition led to an increased LOS ranging from 2.4 to 7.2 days. Among hospitalized patients, malnutrition led to an additional individual cost ranging between 1640 V and 5829 V. At the national level, the costs of malnutrition ranged between 32.8 million V and 1.2 billion V. Expressed as percentage of national health expenditures, the values ranged between 2.1% and 10%. Conclusions: In Europe, malnutrition leads to an increase in LOS and in hospital costs, both at the individual and the national level. Standardization of methods and results reported is needed to adequately compare results between countries. © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved

Trypsin inhibition by macrocyclic and open-chain variants of the squash inhibitor MCoTI-II

MCoTl-I and MCoTl-II from the seeds of Momordica cochinchinensis are inhibitors of trypsin-like proteases and the only known members of the large family of squash inhibitors that are cyclic and contain an additional loop connecting the amino- and the carboxy-terminus. To investigate the contribution of macrocycle formation to biological activity, we synthesized a set of open-chain variants of MCoTl-II that lack the cyclization loop and contain various natural and non-natural amino acid substitutions in the reactive-site loop. Upon replacement of P1 lysine residue \#10 within the open-chain variant of MCoTl-II by the non-natural isosteric nucleo amino acid AlaG{[}beta-(guanin-9-yl)-L-alanine], a conformationally restricted arginine mimetic, residual inhibitory activity was detected, albeit reduced by four orders of magnitude. While the cyclic inhibitors MCoTl-I and MCoTl-II were found to be very potent trypsin inhibitors, with picomolar inhibition constants, the open-chain variants displayed an approximately 10-fold lower affinity. These data suggest that the formation of a circular backbone in the MCoTI squash inhibitors results in enhanced affinity and therefore is a determinant of biological activity

Entwicklung, Aufbau und Betrieb einer telemetrischen Plattform zur Therapieüberwachung am Beispiel der Hämophilie

Ubiquitäres Computing aufgrund von High-Speed-Internet und mobilen Geräten ermöglicht grundlegende neue Möglichkeiten für das Gesundheitswesen. Patienten mit seltenen chronischen Erkrankungen, die häufig weit entfernt vom medizinischen Behandlungszentrum leben, profitieren dabei besonders von der Telemedizin und dem Telemonitoring. Diese Arbeit beschreibt in diesem Zusammenhang unter anderem die Erfahrungen bei der Entwicklung, dem Test, der Implementierung und dem Betrieb einer telemetrischen Plattform am Beispiel der Hämophilie. Dabei stehen funktionale und nicht-funktionale Anforderungen bei der Entwicklung mobiler Anwendungen, die im Gesundheitswesen eingesetzt werden, im Fokus. Die Ergebnisse verdeutlichen einerseits die Barrieren, Herausforderungen und Anforderungen für die Entwicklung von telemetrischen Plattformen, andererseits dass die Verwendung von adäquater Technologie die Gesundheitskosten senken, Patienten sich schnell an Telemonitoring-Systeme gewöhnen und sich die Lebensqualität des Nutzers wesentlich erhöht

Ist das deutsche Modell der Unternehmensmitbestimmung überholt?

Die betriebliche Mitbestimmung in Deutschland ist nicht nur im Licht der Harmonisierung des europäischen Gesellschaftsrechts zum Streitpunkt geworden. Sie soll unter anderem auch ein Grund für die gegenwärtige wirtschaftliche Schwäche Deutschlands und die Zurückhaltung der Investoren sein. Im Gegensatz dazu vertritt Hubertus Schmoldt, IG Bergbau, Chemie, Energie, die Ansicht, dass das deutsche Modell der Mitbestimmung ein Standortvorteil sei, denn "diejenigen Unternehmen, die ihre Vorgehensweise intensiv mit den Arbeitnehmervertretern abstimmen, (sind) wesentlich weniger krisenanfällig und (überwinden) besser und schneller eingetretene Krisen". Prof. Dr. Walther Müller-Jentsch, Universität Bochum, widerspricht ebenfalls der oben genannten These, wobei er trotz der positiven Einschätzung der Unternehmensmitbestimmung Reformbedarf vor allem bei der Stärkung des Einflusses der Betriebsangehörigen sieht. Auch Dr. Wolfgang Jäger, Hans-Böckler-Stiftung, spricht sich für die Mitbestimmung aus.Mitbestimmung, EU-Recht, Standortwahl, Unternehmen, Gewerkschaft, Arbeitskräfte, Investition, Deutschland

Time Domain Ultrasonic Signal Characterization for Defects in Thin Unsurfaced Hardwood Lumber

One of the major users of thin, unsurfaced hardwood lumber is the pallet manufacturing industry. Almost all manufactured products spend part of their life cycle on a pallet during transportation. This makes pallets a critical component of both the transportation and manufacturing sectors of the economy. Many newly constructed wooden pallets, however, are not currently manufactured to deliver the best performance (strength, durability, and safety)—despite interest by pallet users and pallet manufacturers—because manual grading and sorting of parts is impractical due to processing speeds and volume, labor costs, and laborer skill. This paper describes initial work aiming to create an automated grading/sorting system for hardwood pallet parts using ultrasonic. Experiments were conducted on yellow-poplar (Liriodendron tulipifera, L.) and red oak (Quercus rubra, L.) deckboards using pressure-contact, rolling transducers in a pitch-catch arrangement. Sound and unsound knots, cross grain, bark pockets, holes, splits, and decay were characterized using six ultrasound variables calculated from the received waveforms. Our scanning system shows good data-collection repeatability, and scanning rate has little effect on the calculated variables. For each defect type, at least one ultrasonic variable demonstrated significant capability to discriminate between that defect and clear wood. Energy loss variables exhibited the greatest sensitivity to many defect types. Based on the empirical relationships identified in this study, we are now developing models to classify defects using ultrasonic signal characteristics. Scanning properties of the prototype apparatus suggest that it can readily be translated into a commercial product