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1AGNP精神科治疗药物监测共识指南:2011显示文摘治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从'强烈推荐'到'可能有用'的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的'治疗参考浓度范围'和'剂量相关参考浓度范围'呈现给大家。本共识指南引入了'实验室警戒浓度'的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中获益。Hiemke C Baumann P Bergemann N Conca A Dietmaier O Egberts K Fric M Gerlach M Greiner C Gründer G Haen E Havemann-Reinecke U Jaquenoud Sirot E Kirchherr H Laux G Lutz UC Messer T Müller MJ Pfuhlmann B Rambeck B Riederer P Schoppek B Stingl J Uhr M Ulrich S Waschgler R Zernig G 李文标(译) 果伟(译) 阮灿军(译) 贺静(译) 汤宜朗(审校) 王传跃(审校) 2016实用药物与临床2016,19,10:37
2Extrahepatic complications to cirrhosis and portal hypertension: Haemodynamic and homeostatic aspects显示文摘In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitatingthe hepatorenal syndrome.Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.As a bridge to this treatment,knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs,antibiotics,drugs with specific effects on fibrogenesis and inflammation,and drugs that target specific receptors.S?ren M?ller Jens H Henriksen Flemming Bendtsen 2014World Journal of Gastroenterology2014,20,42:14
3血管紧张素Ⅱ2型受体的基因多态性(+1675G/A)对已接受治疗高血压患者的左心室肥大和左心室构型的作用显示文摘已有报道显示血管紧张素Ⅱ2型受体的基因多态性(AGTR2+1675G/A)与左心室肥大(left ventric-ular hypertrophy,LVH)相关。研究者检验这种基因多态性是否影响已按高血压治疗指南治疗的原发性高血压和心血管疾病患者的LVH和左心室构型参数。张玲玉 叶鹏 Huber M V ller H Jakob S Reibis R Do V Bol-brinker J Zergibel I Schmieder RE Treszl A Wegscheider K Kreutz R 2010中华高血压杂志2010,18,12:6
4National Forest Inventories capture the multifunctionality of managed forests in Germany显示文摘Background:Forests perform various important ecosystem functions that contribute to ecosystem services.In many parts of the world,forest management has shifted from a focus on timber production to multi-purpose forestry,combining timber production with the supply of other forest ecosystem services.However,it is unclear which forest types provide which ecosystem services and to what extent forests primarily managed for timber already supply multiple ecosystem services.Based on a comprehensive dataset collected across 150 forest plots in three regions differing in management intensity and species composition,we develop models to predict the potential supply of 13 ecosystem services.We use those models to assess the level of multifunctionality of managed forests at the national level using national forest inventory data.Results:Looking at the potential supply of ecosystem services,we found trade-offs(e.g.between both bark beetle control or dung decomposition and both productivity or soil carbon stocks)as well as synergies(e.g.for temperature regulation,carbon storage and culturally interesting plants)across the 53 most dominant forest types in Germany.No single forest type provided all ecosystem services equally.Some ecosystem services showed comparable levels across forest types(e.g.decomposition or richness of saprotrophs),while others varied strongly,depending on forest structural attributes(e.g.phosphorous availability or cover of edible plants)or tree species composition(e.g.potential nitrification activity).Variability in potential supply of ecosystem services was only to a lesser extent driven by environmental conditions.However,the geographic variation in ecosystem function supply across Germany was closely linked with the distribution of main tree species.Conclusions:Our results show that forest multifunctionality is limited to subsets of ecosystem services.The importance of tree species composition highlights that a lack of multifunctionality at the stand level can be compensated by managing forests at the landscape level,when stands of complementary forest types are combined.These results imply that multi-purpose forestry should be based on a variety of forest types requiring coordinated planning across larger spatial scales.Nadja K.Simons María R.Felipe-Lucia Peter Schall Christian Ammer Jürgen Bauhus Nico Blüthgen Steffen Boch François Buscot Markus Fischer Kezia Goldmann Martin M.Gossner Falk Hänsel Kirsten Jung Peter Manning Thomas Nauss Yvonne Oelmann Rodica Pena Andrea Polle Swen C.Renner Michael Schloter Ingo Schöning Ernst-Detlef Schulze Emily F.Solly Elisabeth Sorkau Barbara Stempfhuber Tesfaye Wubet Jörg Müller Sebastian Seibold Wolfgang W.Weisser 2021Forest Ecosystems2021,8,1:2
5The β-lactam antibiotic, ceftriaxone, dramatically improves survival, increases glutamate uptake and induces neurotrophins in stroke显示文摘Christa Th?ne-Reineke Christian Neumann Pawel Namsolleck Kristin Schmerbach Maxim Krikov Jan H Schefe Kristin Lucht Heide H?rtnagl Michael Godes Susanne Müller Kay Rumschüssel Heiko Funke-Kaiser Arno Villringer U Muscha Steckelings Thomas Unger 2008Journal of Hypertension2008,,12:2
6Chronic hepatitis C:Treat or wait? Medical decision making in clinical practice显示文摘AIM:To analyzes the decision whether patients with chronic hepatitis C virus (HCV) infection are treated or not.METHODS:This prospective cohort study included 7658 untreated patients and 6341 patients receiving pegylated interferon α2 a/ribavirin,involving 434 physicians/institutions throughout Germany (377 in private practice and 57 in hospital settings).A structured questionnaire had to be answered prior to the treatment decision,which included demographic data,information about the personal life situation of the patients,anamnesis and symptomatology of hepatitis C,virological data,laboratory data and data on concomitant diseases.A second part of the study analyzes patients treated with pegylated interferon α2a.All questionnaires included reasons against treatment mentioned by the physician.RESULTS:Overall treatment uptake was 45%.By multivariate analysis,genotype 1/4/5/6,HCV-RNA ≤ 520 000 IU/mL,normal alanine aminotransferase (ALT),platelets ≤ 142 500/μL,age > 56 years,female gender,infection length > 12.5 years,concomitant diseases,human immunodeficiency virus co-infection,liver biopsy not performed,care in private practice,asymptomatic disease,and unemployment were factors associated with reduced treatment rate.Treatment and sustained viral response rates in migrants (1/3 of cohort) were higher than in German natives although 1/3 of migrants had language problems.Treatment rate and liver biopsy were higher in clinical settings when compared to private practice and were low when ALT and HCV-RNA were low.CONCLUSION:Some reasons against treatment were medically based whereas others were related to fears,socio-economical problems,and information deficits both on the side of physicians and patients.Claus Niederau Dietrich Hüppe Elmar Zehnter Bernd Mller Renate Heyne Stefan Christensen Rainer Pfaff Arno Theilmeier Ulrich Alshuth Stefan Mauss 2012World Journal of Gastroenterology2012,18,12:2
7Cre-loxP-mediated gene replacement:a mouse strain producing humanized antibodies显示文摘Zou Y R Müller W Gu H 1994Curr Biol1994,4,12:1
8显示文摘MüLLER A REUTER H DILLINGER S 1995Angew Chem Int Ed Eng1995,34,:1
9DNA vaccination of pigs with open reading frame 1-7 of PRRS virus显示文摘Barfoed A M Blixenkrone-Mφller M Jensen M H 2004Vaccine2004,22,2728:1
10Differential diagnosis of suprasellar tumors in children 显示文摘Warmuth-Metz M Genkow AK Mu'ller H 2004Klin Paediatr2004,216,6:1
11Evolution of magnetic domain structures and coercivity in high-performance SmCo 2:17-type permanent magnets显示文摘Gutfleisch O Müller K H Khlopkov K 2006Acta Materialia2006,54,4:1
12Involvement of chemokine receptors in breast cancer metastasis显示文摘Müller A Homey B Soto H 0,,6824:1
13Cylindrical polymer brushes显示文摘Zhang M Müller A H E 2005Journal of Polymer Science Part A: Polymer Chemistry2005,43,16:1
14Assessment of tobacco heating system 2.4 on osteogenic differentiation of mesenchymal stem cells and primary human osteoblasts compared to conventional cigarettes显示文摘BACKGROUND Cigarette smoking(CS)is the most common method of consuming tobacco.Deleterious effects on bone integrity,increased incidence of fractures,and delayed fracture healing are all associated with CS.Over 150 of the 6500 molecular species contained in cigarette smoke and identified as toxic compounds are inhaled by CS and,via the bloodstream,reach the skeletal system.New technologies designed to develop a reduced-risk alternative for smokers are based on electronic nicotine delivery systems,such as e-cigarettes and tobacco heating systems(THS).THS are designed to heat tobacco instead of burning it,thereby reducing the levels of harmful toxic compounds released.AIM To examine the effects of THS on osteoprogenitor cell viability and function compared to conventional CS.METHODS Human immortalized mesenchymal stem cells(n=3)and primary human preosteoblasts isolated from cancellous bone samples from BG Unfall Klinik Tübingen(n=5)were osteogenically differentiated in vitro with aqueous extracts generated from either the THS 2.4“IQOS”or conventional“Marlboro”cigarettes for up to 21 d.Cell viability was analyzed using resazurin conversion assay(mitochondrial activity)and calcein-AM staining(esterase activity).Osteogenic differentiation and bone cell function were evaluated using alkaline phosphatase(AP)activity,while matrix formation was analyzed through alizarin red staining.Primary cilia structure was examined by acetylatedα-tubulin immunofluorescent staining.Free radical production was evaluated with 2’,7’-dichlorofluoresceindiacetate assay.RESULTS Our data clearly show that THS is significantly less toxic to bone cells than CS when analyzed by mitochondrial and esterase activity(P<0.001).No significant differences in cytotoxicity between the diverse flavors of THS were observed.Harmful effects from THS on bone cell function were observed only at very high,non-physiological concentrations.In contrast,extracts from conventional cigarettes significantly reduced the AP activity(by two-fold)and matrix mineralization(four-fold)at low concentrations.Additionally,morphologic analysis of primary cilia revealed no significant changes in the length of the organelle involved in osteogenesis of osteoprogenitor cells,nor in the number of ciliated cells following THS treatment.Assessment of free radical production demonstrated that THS induced significantly less oxidative stress than conventional CS in osteoprogenitor cells.CONCLUSIONTHS was significantly less harmful to osteoprogenitor cells during osteogenesisthan conventional CS. Additional studies are required to confirm whether THS isa better alternative for smokers to improve delays in bone healing followingfracture.Romina H Aspera-Werz Sabrina Ehnert Monja Müller Sheng Zhu Tao Chen Weidong Weng Johann Jacoby Andreas K Nussler 2020World Journal of Stem Cells2020,12,8:1
15显示文摘Melsheimer A Seegar M Kronmüller H 1999J Magn Magn Mater1999,202,:1
16显示文摘MüLLER A KRICKEMEYER E BOGGE H 1997Angew Chem Int Ed Eng1997,36,:1
17Issues in pharmacokinetics and pharmacodynamics of anti-infective agents:distribution in tissue显示文摘Müller M dela Pea A Derendorf H 2004Antimicrob Agents Chemother2004,48,:1
18Wnt/β-catenin and Bmp signals control distinct sets of transcription factors in cardiac progenitor cells显示文摘KLAUS A M(U)LLER M SCHULZ H 2012Proc Natl Acad Sci U S A2012,109,10:1
19查看详情显示文摘(O)zyürek Z Komber H Gramm S Schmaljohann D Müller A H E Voit B 0,,10:1
20Nanosuspensions as a new approach for the formulation for the poorly soluble drug tarazepide显示文摘Jacobs C Kayser O Müller R H 0,,2:1
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