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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
2Association between thyroid function and gallstone disease显示文摘AIM: To investigate those associations using data of the population-based Study of Health in Pomerania.METHODS: A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis.RESULTS: There were 385 persons (10.3%) with low (<0.3 mIU/L), 3 321 persons (88.6%) with normal and 43 persons (1.2%) with high serum TSH levels (>3 mIU/L).The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis (OR 3.77; 95%-CI 1.06-13.41; ,P<0.05). zAlso among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH (OR 1.40; 95%-CI 0.96-2.02; P = 0.07). In the female population, no such relation was identified.CONCLUSION: There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis.Henry Vlzke Daniel M Robinson Ulrich John 2005World Journal of Gastroenterology2005,11,35:8
3Batch methanogenic fermentation experiments of wastewater from a brown coal low-temperature coke plant显示文摘Coke plant effluents with high contents of organic compounds are mainly treated by biological aerobic fermentation after physical pre-treatment.In this study,a brown coal condensate wastewater from a low temperature coking process was fermented under methanogenic conditions in discontinuous experiments.By this fermentation,acetate,propionate,and the main polyphenolic compounds(catechol,resorcinol and hydroquinone) were degraded to a level below the detection limit.The COD was reduced by 72% with a residual concentration of 2.1 g/L.This anaerobic fermented wastewater had a residual BOD 5 of 0.66 g/L and 2.2 L CH4 were formed per litre of wastewater.An abiotic pre-treatment for this wastewater with air had a negative effect on the COD reduction and decrease of colour on the methanogenic fermentation due to the autoxidation of polyphenolic compounds to humic-like compounds.This study showed that methanogenic fermentations in the treatment sequence of brown coal coking wastewaters could reduce energy consumption for aeration in further treatment processes and had the potential for a better effluent quality due to a less formation of recalcitrant humic-like compounds.Peter Kuschk Ulrich Stottmeister Yong-Jun Liu Arndt Wiessner Matthias Kǎistner Roland-Amo Mǔller 2010Journal of Environmental Sciences2010,22,2:7
4CaMKII in cerebral ischemia显示文摘神经原上的 Ischemic 侮辱触发引起 Ca 导致 neuronal 房间死亡(excitotoxicity ) 的 2+ 超载的过多的、病理学的 glutamate 版本。Ca 2+/calmodulin (凸轮) 依赖者蛋白质 kinase II (CaMKII ) 是位于 neuronal 粘性下面并且学习的生理的有刺激性的 glutamate 信号的一个主要调停人。Glutamate 刺激在 T286 触发 CaMKII 的 autophosphorylation,使 kinase 成为 “ 的一个过程; autonomous”(从 Ca 2+ 刺激的部分活跃的独立人士) 并且那为 synaptic 的形式被要求粘性。最近的研究为侮辱以后的 neuroprotection 作为潜在的药目标也建议了自治 CaMKII 活动,在在 neuronal 文化的 glutamate 侮辱以后并且在在 vivo 的焦点的服的局部缺血以后。然而, CaMKII 和凸轮 kinase 家庭的另外的成员在 neuronal 死亡和幸存的规定被含有。这里,我们在 excitotoxicity 和服的局部缺血讨论过去的调查结果和凸轮 kinase 功能的可能的机制,与 CaMKII 和它的规定的一个焦点。Steven J COULTRAP Rebekah S VEST Nicole M ASHPOLE Andy HUDMON K Ulrich BAYEF 2011Acta Pharmacologica Sinica2011,32,7:6
5Selective conversion of syngas to propane over ZnCrO_x-SSZ-39 OX-ZEO catalysts显示文摘Oxide-Zeolite(OX-ZEO) bifunctional catalyst design concept has been exemplified in several processes to direct conversion syngas to value-added chemicals and fuels such as mixed light olefins, ethylene, aromatics and gasoline.Herein we demonstrate that the product can be steered toward liquefied petroleum gas(LPG) with a selectivity up to 89% in hydrocarbons especially propane selectivity reaching 80% at CO conversion of 63% using ZnCrOx-H-SSZ-39 catalyst.Interestingly, the quantity of the acid sites of SSZ-39 does not influence obviously the hydrocarbon distribution but the strength is crucial for selective formation of propane.This finding provides an alternative route of LPG synthesis from a variety of carbon resources via syngas.Gen Li Feng Jiao Dengyun Miao Yong Wang Xiulian Pan Toshiyuki Yokoi Xiangju Meng Feng-Shou Xiao Andrei-Nicolae Parvulescu Ulrich Müller Xinhe Bao 2019Journal of Energy Chemistry2019,28,9:6
6Resin infiltration of deproteinised natural occlusal subsurface lesions improves initial quality of fissure sealing显示文摘The aim of this ex vivo study was to evaluate the infiltration capability and rate of microleakage of a low-viscous resin infiltrant combined with a flowable composite resin(RI/CR) when used with deproteinised and etched occlusal subsurface lesions(International Caries Detection and Assessment System code 2). This combined treatment procedure was compared with the exclusive use of flowable composite resin(CR) for fissure sealing. Twenty premolars and 20 molars revealing non-cavitated occlusal carious lesions were randomly divided into two groups and were meticulously cleaned and deproteinised using Na OCl(2%). After etching with HCl(15%), 10 premolar and 10 molar lesions were infiltrated(Icon/DMG; rhodamine B isothiocyanate(RITC)-labelled) followed by fissure sealing(G-?nial Flo/GC; experimental group, RI/CR). In the control group(CR), the carious fissures were only sealed. Specimens were cut perpendicular to the occlusal surface and through the area of the highest demineralisation(DIAGNOdent pen, Ka Vo). Using confocal laser-scanning microscopy, the specimens were assessed with regard to the percentage of caries infiltration, marginal adaption and internal integrity. Within the CR group, the carious lesions were not infiltrated. Both premolar(57.9% ± 23.1%) and molar lesions(35.3% ± 22.1%) of the RI/CR group were uniformly infiltrated to a substantial extent, albeit with significant differences(P = 0.034). Moreover, microleakage(n = 1) and the occurrence of voids(n = 2) were reduced in the RI/CR group compared with the CR group(5 and 17 specimens,respectively). The RI/CR approach increases the initial quality of fissure sealing and is recommended for the clinical control of occlusal caries.Andrej M Kielbassa Ina Ulrich Rita Schmidl Christoph Schuller Wilhelm Frank Vanessa D Werth 2017International Journal of Oral Science2017,9,2:4
7Lactobacilli,bifi dobacteria and E.coli nissle induce pro-and anti-inflammatory cytokines in peripheral blood mononuclear cells显示文摘AIM: To investigate whether the stimulation of peripher- al blood mononuclear cells (PBMNC) with the cell debris and cell extraction of different probiotic strains is similar or species specifi c. METHODS: Three strains of bifi dobacteria, 4 strains of lactobacilli, and E. coli nissle were sonicated and centri- fuged in order to divide them into cell extract and cell debris. PBMNC were separated by density gradient and incubated for 36 h with either the cell debris or the cell extract of single strains of probiotic bacteria in doses from 102 to 108 CFU/mL. Cell supernatants were taken and interleukin (IL)-10, IL-1β, and tumor necosis factor (TNF)-α were determined by ELISA. RESULTS: Depending on the species super-family, the strains had different stimulation patterns. Except for both L. casei strains, the cell extract of bifidobacteriaand lactobacilli had less stimulating capacity than cell debris, whereas the cell extract of E. coli nissle had simi- lar stimulating properties to that of the cell debris of the strain and significantly more stimulating capacity than that of bifi dobacteria and lactobacilli. The cell debris of bifi dobacteria stimulated more cytokine release than the cell debris of lactobacilli. The cell debris of lactobacilli did not have a stimulating capacity when lower concentra- tions were used. Neither cell extraction nor cell debris had an inhibitory effect on the production of the tested cytokines by stimulated PBMNC. CONCLUSION: The incubation of probiotic strains, which have been used in clinical trials for inflammatory diseases, with immunocompetent cells leads to different species specifi c reactions. High IL-10 response to cell de- bris of bifi dobacteria and E. coli nissle can be found. This corresponds to positive effects of bifi dobacteria and E. coli nissle in clinical trials for inflammatory bowel disease compared to negative outcomes obtained with lactoba- cilli.Ulf Helwig Karen M Lammers Fernando Rizzello Patricia Brigidi Verena Rohleder Elisabetta Caramelli Paolo Giochetti Juergen Schrezenmeir Ulrich R Foelsch Stefan Schreiber Massimo Campieri 2006World Journal of Gastroenterology2006,12,37:3
8Nerve Growth Factor and Artemin Are Paracrine Mediators of Pancreatic Neuropathy in Pancreatic Adenocarcinoma显示文摘Güralp O. Ceyhan Karl-Herbert Sch?fer Annika G. Kerscher Ulrich Rauch Ihsan Ekin Demir Mustafa Kadihasanoglu Carolin B?hm Michael W. Müller Markus W. Büchler Nathalia A. Giese Mert Erkan Helmut Friess 2010Annals of Surgery2010,,5:2
9Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace显示文摘Ulrich F?rstermann Thomas Münzel 2006Circulation2006,,13:2
10Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12显示文摘AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral(DAA) treatment with respect to sustained virological response(SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting.METHODS Two hundred and sixty patients treated with SOF combination partners PR(n = 51), R(n = 10), SMV(n = 30), DCV(n = 81), LDV(n = 73), or 3D(n = 15).144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were postliver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3.RESULTS Two hundred and forty/256(93.7%) patients achieved SVR12(m ITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/n L, 88% post-liver transplantation, 95% for GT1 a, 93% for GT1 b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10(P < 0.0001), liver cirrhosis(P = 0.005) at baseline. In Interferonfree treatment GT3 had significantly lower SVR rates than GT1(P = 0.016). Side effects were mild. CONCLUSION Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into 'real-world'. Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/n L and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.Christoph R Werner Julia M Schwarz Daniel P Egetemeyr Robert Beck Nisar P Malek Ulrich M Lauer Christoph P Berg 2016World Journal of Gastroenterology2016,22,35:2
11Neural invasion in pancreatic cancer: A mutual tropism between neurons and cancer cells显示文摘Güralp O. Ceyhan Ihsan Ekin Demir Burak Altintas Ulrich Rauch Gerald Thiel Michael W. Müller Nathalia A. Giese Helmut Friess Karl-Herbert Sch?fer 2008Biochemical and Biophysical Research Communications2008,,3:2
12Safe and Early Discharge After Colorectal Surgery Due to C-Reactive Protein: A Diagnostic Meta-Analysis of 1832 Patients显示文摘Rene Warschkow Ulrich Beutner Thomas Steffen Sascha A. Müller Bruno M. Schmied Ulrich Güller Ignazio Tarantino 2012Annals of Surgery2012,,2:2
13Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature显示文摘Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.Stefan Schlabe Kathrin van Bremen Souhaib Aldabbagh Dieter Glebe Corinna M Bremer Tobias Marsen Walter Mellin Veronica Di Cristanziano Anna M Eis-Hübinger Ulrich Spengler 2018World Journal of Hepatology2018,10,7:2
14Differential toxicity and environmental fates of hexachlorocyclohexane isomers显示文摘Willett K L Ulrich E M Hites R A 1998Environ Sci Technol1998,32,15:2
15Voxel-based analyses of magnetization transfer imaging of the brain in hepatic encephalopathy显示文摘AIM: To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI).METHODS: Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging. They gave institutional-review-board-approved written consent. Magnetization transfer ratio (MTR) maps were generated from MTI. We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxelbased evaluation.RESULTS: The MTR of grey and white matter was lower in subjects with more severe HE. Changes were found in patients with cirrhosis without neurological defi cits in the basal ganglia and bilateral white matter. The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE. Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98, P = 0.0001].CONCLUSION: The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE.Falk R Miese Hans-Jrg Wittsack Gerald Kircheis Arne Holstein Christian Mathys Ulrich Mdder Mathias Cohnen 2009World Journal of Gastroenterology2009,15,41:2
16A vital sugar code for ricin toxicity显示文摘Jasmin Taubenschmld Johannes Stadlmann Markus Jost Tove Irene Klok.k Cory D Rillahan Andreas Leibbrandt Karl Mechtler James C Paulson Julian Jude Johannes Zuber Kirsten Sandvig Ulrich Elling Thorsten Marquardt Christian Thiel Christian Koerner Josef M Penninger 2017Cell Research2017,27,11:2
17Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism显示文摘AIM:To investigate if and how the proinflammatory cytokine interferon γ(IFNγ) affects ghrelin expression in mice.METHODS:The plasma concentration of ghrelin,andgastric ghrelin and somatostatin expression,were examined in wild-type mice and mice infected with Helicobacter pylori(H.pylori).Furthermore,ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth.To study the effect of IFNγ alone,mice were given a subcutaneous infusion of IFNγ for 7 d.Finally,the influence of IFNγ and somatostatin on the ghrelin promoter was characterized.RESULTS:H.pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration.Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models.Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations.Finally,we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ.CONCLUSION:Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression.IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.Jesper AB Strickertsson Kristina BV DΦssing Anna JM Aabakke Hans-Olof Nilsson Thomas VO Hansen Ulrich Knigge Andreas Kjr Torkel Wadstrm Lennart Friis-Hansen 2011World Journal of Gastroenterology2011,17,26:2
18Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells显示文摘Katharina Timper Dalma Seboek Michael Eberhardt Philippe Linscheid Mirjam Christ-Crain Ulrich Keller Beat Müller Henryk Zulewski 2006Biochemical and Biophysical Research Communications2006,,4:2
19Chronic 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
20Stroke prevention technology for patients with non-valvular AF-wordwide experience with the new watchman LAA system显示文摘Sick PB Ulrich M Hauptmann C 2006J Am Coll Cardiol2006,47,:1
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