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神经精神药理学治疗药物监测共识指南:2017版

实用药物与临床 2022年第1期25卷 1-20页

作者： C.Hiemke N.Bergemann H.W.Clement A.Conca J.Deckert k.domschke G.Eckermann k.Egberts M.Gerlach C.Greiner G.Gründer E.Haen U.Havemann-Reinecke G.Hefner R.Helmer G.Janssen E.Jaquenoud G.Laux T.Messer R.M ssner M.J.Müller M.Paulzen B.Pfuhlmann P.Riederer A.Saria B.Schoppek G.Schoretsanitis M.Schwarz M.Silva Gracia B.Stegmann W.Steimer J.C.Stingl M.Uhr S.Ulrich S.Unterecker R.Waschgler G.Zernig G.Zurek P.Baumann 李文标(主译) 果伟(译) 贺静(译) 鲍爽(译) 路钊(译) 牛梦溪(译) 阮灿军(译) 臧彦楠(译) 王勇(译) 张玲(译) 刘辰庚(译) 李洁(译) 汤宜朗(审校) 王传跃(审校) 王刚(审校) Department of Psychiatry and Psychotherapy University Medical Center of MainzMainzGermany Institute of Clinical Chemistry and Laboratory Medicine University Medical Center of MainzMainzGermany kitzberg Hospitals Center for Psychosomatic Medicine and PsychotherapyBad MergentheimGermany Department of Child and Adolescent Psychiatry University of FreiburgFreiburgGermany Servizio Psichiatrico del Comprensorio Sanitario di Bolzano BolzanoItaly Department of Psychiatry Psychotherapy and PsychosomaticsUniversity Hospital of WürzburgGermany Department of Psychiatry and Psychotherapy Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany Psychiatric Hospital KaufbeurenGermany Department of Child and Adolescent Psychiatry Psychosomatics and PsychotherapyCenter of Mental HealthUniversity Hospital of WürzburgGermany Federal Institute for Drugs and Medical Devices(BfArM) BonnGermany Department of Psychiatry Psychotherapy and PsychosomaticsRWTH Aachen UniversityAachenand JARA–Translational Brain MedicineAachenGermany Clinical Pharmacology Department of Psychiatry and Psychotherapy and Department of Pharmacology and ToxicologyUniversity of RegensburgRegensburgGermany Department of Psychiatry and Psychosomatics University of G ttingenG ttingenGermany Psychiatric Hospital Vitos KlinikEichbergEltvilleGermany Center of Epilepsy BielefeldGermany Medical Laboratory Stein Limbach GroupM nchengladbachGermany Psychiatric Hospital K nigsfeldenBruggAargauSwitzerland Institute of Psychological Medicine Haag in OberbayernGermany Danuviuskliniken Psychiatric HospitalPfaffenhofenGermany Department of Psychiatry and Psychotherapy University of TübingenTübingenGermany Psychiatric Hospitals Oberberggruppe BerlinGermany Psychiatric Hospital Weisser Hirsch DresdenGermany Experimental Psychiatry Unit Department of Psychiatry1Medical University of InnsbruckInnsbruckAustria kbo-Isar-Amper klinikum München-Ost Psychiatric HospitalMunich-HaarGermany Department of

治疗药物监测(Therapeutic Drug Monitoring,TDM)通过定量测定和解释血药浓度以优化药物治疗。TDM着眼于药代动力学的个体差异,使个体化药物治疗成为可能。在精神病学和神经病学领域中,有可能明显获益于TDM的主要患者群体包括少年儿童... 详细信息

治疗药物监测(Therapeutic Drug Monitoring,TDM)通过定量测定和解释血药浓度以优化药物治疗。TDM着眼于药代动力学的个体差异,使个体化药物治疗成为可能。在精神病学和神经病学领域中,有可能明显获益于TDM的主要患者群体包括少年儿童、孕妇、老年患者、智障患者、药物滥用者、涉法精神病患者、已知或怀疑药代动力学异常的患者以及合并躯体疾病影响药代动力学的患者。常规剂量下治疗无效,用药依从性难以判断,药物耐受性不佳,以及可能存在药代动力学方面的药物-药物相互作用等情况都是治疗药物监测的典型指征。然而,只有将TDM充分整合到临床治疗过程中,才能发挥其优化药物治疗的潜在优势。为了向临床医生和实验室提供有效的TDM信息,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年发表了第一版《精神科治疗药物监测指南》。2011年进行了更新之后,现在再次更新。遵循新版指南,可能会改善神经精神药物治疗的效果,加快很多患者的康复,并降低医疗费用。

关键词：抗凝药物妊娠期静脉血栓栓塞疾病抗抑郁药抗癫痫药抗帕金森病药抗精神病药血药浓度共识指南药物分析基因型分析神经药物遗传药理学药代动力学表型分析血浆药物浓度精神药物参考范围血清药物浓度治疗药物监测治疗窗

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神经精神药理学治疗药物监测共识指南:2017版

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实用药物与临床 2022年第2期25卷 97-118页

作者： C.Hiemke N.Bergemann H.W.Clement A.Conca J.Deckert k.domschke G.Eckermann k.Egberts M.Gerlach C.Greiner G.Gründer E.Haen U.Havemann-Reinecke G.Hefner R.Helmer G.Janssen E.Jaquenoud G.Laux T.Messer R.M ssner M.JMüller M.Paulzen B.Pfuhlmann P.Riederer A.Saria B.Schoppek G.Schoretsanitis M.Schwarz M.Silva Gracia B.Stegmann W.Steimer J.C.Stingl M.Uhr S.Ulrich S.Unterecker R.Waschgler G.Zernig G.Zurek P.Baumann 李文标(译) 果伟(译) 贺静(译) 鲍爽(译) 路钊(译) 牛梦溪(译) 阮灿军(译) 臧彦楠(译) 王勇(译) 张玲(译) 刘辰庚(译) 李洁(译) 汤宜朗(译) 王传跃(译) 王刚(译) Department of Psychiatry and Psychotherapy University Medical Center of MainzMainzGermany Institute of Clinical Chemistry and Laboratory Medicine University Medical Center of MainzMainzGermany kitzberg Hospitals Center for Psychosomatic Medicine and PsychotherapyBad MergentheimGermany Department of Child and Adolescent Psychiatry University of FreiburgFreiburgGermany Servizio Psichiatrico del Comprensorio Sanitario di Bolzano BolzanoItaly Department of Psychiatry Psychotherapy and PsychosomaticsUniversity Hospital of WürzburgGermany Department of Psychiatry and Psychotherapy Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany Psychiatric Hospital KaufbeurenGermany Department of Child and Adolescent Psychiatry Psychosomatics and PsychotherapyCenter of Mental HealthUniversity Hospital of WürzburgGermany Federal Institute for Drugs and Medical Devices(BfArM) BonnGermany Department of Psychiatry Psychotherapy and PsychosomaticsRWTH Aachen UniversityAachenand JARA–Translational Brain MedicineAachenGermany Clinical Pharmacology Department of Psychiatry and Psychotherapy and Department of Pharmacology and ToxicologyUniversity of RegensburgRegensburgGermany Department of Psychiatry and Psychosomatics University of G ttingenG ttingenGermany Psychiatric Hospital Vitos KlinikEichbergEltvilleGermany Center of Epilepsy BielefeldGermany Medical Laboratory Stein Limbach GroupM nchengladbachGermany Psychiatric Hospital K nigsfeldenBruggAargauSwitzerland Institute of Psychological Medicine Haag in OberbayernGermany Danuviuskliniken Psychiatric HospitalPfaffenhofenGermany Department of Psychiatry and Psychotherapy University of TübingenTübingenGermany Psychiatric Hospitals Oberberggruppe BerlinGermany Psychiatric Hospital Weisser Hirsch DresdenGermany Experimental Psychiatry Unit Department of Psychiatry1Medical University of InnsbruckInnsbruckAustria kbo-Isar-Amper klinikum München-Ost Psychiatric HospitalMunich-HaarGermany Department of

2.2剂量相关参考浓度范围对于TDM结果的解释,除了治疗参考浓度范围外还有另一个浓度范围,即所谓的剂量相关参考浓度范围。治疗参考浓度范围的应用是药效动力学问题,而剂量相关参考浓度范围的运用是药代动力学问题。后者比较的是测得的... 详细信息

2.2剂量相关参考浓度范围对于TDM结果的解释,除了治疗参考浓度范围外还有另一个浓度范围,即所谓的剂量相关参考浓度范围。治疗参考浓度范围的应用是药效动力学问题,而剂量相关参考浓度范围的运用是药代动力学问题。后者比较的是测得的药物浓度与理论预期药物浓度范围。参照药代动力学研究,优先考虑没有合并用药或药物基因组异常的患者群(“正常”患者),在日维持剂量(Daily maintenance dose,D m)、给药间隔(Dosing interval,d i)、总清除率(Total clearance,CL)和生物利用度(Bioavailability,F)已知情况下,某种药物在某个“正常”患者体内的预期平均稳态浓度(Average steady-state concentration,C av)可通过下面的公式计算。

关键词：治疗药物监测药效动力学给药间隔维持剂量生物利用度药物浓度药代动力学合并用药

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Clinical outcome and predictors of survival after TIPS insertion in patients with liver cirrhosis

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World Journal of Gastroenterology 2012年第37期18卷 5211-5218页

作者： Hauke S Heinzow Philipp Lenz Michael khler Frank Reinecke Hansjrg Ullerich Wolfram domschke Dirk Domagk Tobias Meister Department of Medicine B University of Muenster Institute of Radiology University of Muenster Department of Medicine Ⅱ Helios Albert-Schweitzer-Hospital

AIM:To determine the clinical outcome and predictors of survival after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation in cirrhotic patients. METHODS:Eighty-one patients with liver cirrhosis and consequential portal hypertension had TIPS implantation (bare metal) for either refractory ascites (RA) (n= 27) or variceal bleeding (VB) (n = 54). Endpoints for the study were:technical success, stent occlusion and stent stenosis, rebleeding, RA and mortality. Clinical records of patients were collected and analysed. Baseline characteristics [e.g., age, sex, CHILD score and the model for end-stage liver disease score (MELD score), underlying disease] were retrieved. The kaplan-Meier method was employed to calculate survival from the time of TIPS implantation and comparisons were made by log rank test. A multivariate analysis of factors influencing survival was carried out using the Cox proportional hazards regression model. Results were expressed as medians and ranges. Comparisons between groups were performed by using the Mann-Whitney Utest and the χ 2 test as appropriate. RESULTS:No difference could be seen in terms of age, sex, underlying disease or degree of portal pressure gradient (PPG) reduction between the ascites and the bleeding group. The PPG significantly decreased from 23.4 ± 5.3 mmHg (VB) vs 22.1 ± 5.5 mmHg (RA) before TIPS to 11.8 ± 4.0 vs 11.7 ± 4.2 after TIPS implantation (P = 0.001 within each group). There was a tendency towards more patients with stage CHILD A in the bleeding group compared to the ascites group (24 vs 6, P = 0.052). The median survival for the ascites group was 29 mo compared to > 60 mo for the bleeding group (P = 0.009). The number of radiological controls for stent patency was 6.3 for bleeders and 3.8 for ascites patients (P = 0.029). kaplan-Meier calculation indicated that stent occlusion at first control (P = 0.027), ascites prior to TIPS implantation (P = 0.009), CHILD stage (P = 0.013), MELD score (P = 0.001

关键词： TIPS 预测因子临床疗效肝硬化患者 Cox回归模型压力梯度毫米汞柱

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Role of receptor tyrosine kinases in gastric cancer: New targets for a selective therapy

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World Journal of Gastroenterology 2006年第21期12卷 3297-3305页

作者： JC Becker C Müller-Tidow H Serve W domschke T Pohle Department of Medicine B University of Münster D-48129 MünsterGermany Department of Medicine A University of Münster D-48129 MünsterGermany

受体酷氨酸家族 ases (RTk ) 象表皮的生长因素受体家庭那样包括增长和变形传播参予肿瘤形成的几步。几已知的 RTk 起来在是主要的胃的癌症调整了定制的治疗的目标。仅仅初步的数据然而，在使用上存在当前临床上可得到的药象在胃的癌症... 详细信息

受体酷氨酸家族 ases (RTk ) 象表皮的生长因素受体家庭那样包括增长和变形传播参予肿瘤形成的几步。几已知的 RTk 起来在是主要的胃的癌症调整了定制的治疗的目标。仅仅初步的数据然而，在使用上存在当前临床上可得到的药象在胃的癌症的背景的 trastuzumab， cetuximab， bevacizumab， gefitinib， erlotinib，和 imatinib 那样。现出症状之前的潜的数据建议他们的使用的一个潜在的好处，特别在有“常规”的抑制细胞的联合治疗。这评论象新途径和药一样在癌症治疗关于他们的使用总结当前的知识优化治疗成功。

关键词：受体酪氨酸激酶胃癌治疗方法

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Reduced expression of Ca^(2+)-regulating proteins in the upper gastrointestinal tract of patients with achalasia

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World Journal of Gastroenterology 2006年第37期12卷 6002-6007页

作者： Harald Fischer Judith Fischer Peter Boknik Ulrich Gergs Wilhelm Schmitz Wolfram domschke Jan W konturek Joachim Neumann Medizinische klinik und Poliklinik B Universittsklinikum Mnster 48129 Mnster Germany Institut fr Pharmakologie und Toxikologie Universittsklinikum Mnster 48149 Mnster Germany Institut fr Pharmakologie und Toxikologie Martin-Luther-Universitt Halle-Wittenberg 06112 Halle (Saale) Germany klinik fr Innere Medizin/Gastroenterologie Elbe Klinikum Stade 21682 Stade Germany

AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profi les of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed. RESULTS: SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were signif icantly reduced in patients with achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus mightbe of lesser importance for regulation of SERCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.

关键词：基因表达弛缓不能食管疾病肌集钙蛋白

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Intraductal ultrasound substantiates diagnostics of bile duct strictures of uncertain etiology

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World Journal of Gastroenterology 2013年第6期19卷 874-881页

作者： Tobias Meister Hauke S Heinzow Carina Woestmeyer Philipp Lenz Josef Menzel Torsten kucharzik Wolfram domschke Dirk Domagk Department of Medicine B University of Münster Department of Medicine Ⅱ HELIOS AlbertSchweitzer University Teaching Hospital Department of MedicineⅡ Klinikum IngolstadtD-85049 IngolstadtGermany Department of Medicine University Teaching Hospital Lüneburg

AIM:To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile ***:A patient cohort with bile duct strictures of unknown etiology was examined by ***,specificity and accuracy rates of IDUS were calculated relating to the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo *** of the endosonographic report allowed drawing conclusions with respect to the T and N staging in 147 *** staging was compared to the postoperative histopathological staging data allowing calculation of sensitivity,specificity and accuracy rates for T and N *** endoscopic retrograde cholangio-pancreatography and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160,Olympus,Ltd.,Tokyo,Japan).All procedures were performed under conscious sedation (propofol combined with pethidine) according to the German *** IDUS,a 6 F or 8 F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co.,Tokyo,Japan).RESULTS:A total of 397 patients (210 males,187 females,mean age 61.43 ± 13 years) with indeterminate bile duct strictures were *** hundred and sixty-four patients were referred to the department of surgery for operative exploration,thus surgical histopathological correlation was available for those *** of 264 patients,174 had malignant disease proven by surgery,in 90 patients benign disease was *** these patients decision for surgical exploration was made due to suspicion for malignant disease in multimodal diagnostics (computed tomography scan,endoscopic ultrasound or magnetic resonance imaging).Twenty benign bile duct strictures were misclassified by IDUS as malignant while 14 patients with malignant strictures were initially misdiagnosed by IDUS as benign resulting in s

关键词： Intraductal ultrasound Bile duct strictures Accuracy

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Ileal gallstone obstruction:Single-balloon enteroscopic removal

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World Journal of Gastrointestinal Endoscopy 2010年第9期2卷 321-324页

作者： Hauke Sebastian Heinzow Tobias Meister Johannes Wessling Wolfram domschke Hansjoerg Ullerich Department of Medicine B University of Muenster Department of Radiology University of Muenster

Gallstone-induced ileus is a rare complication of *** localization of gallstones impacted in the small bowel,especially in the ileum,prevents access by conventional endoscopy in most cases,the mainstay of treatment remains *** invention of double-and single-balloon enteroscopy has added much to the ability of imaging the small bowel and enables endoscopically directed ***,for the first time,we report a successful endoscopic calculus removal via peroral single-balloon enteroscopy in an 81-year-old woman suffering from gallstone ileus of the ileum.

关键词： Gallstone ileus Small bowel obstruction Single-balloon enteroscopy Cholelithiasis

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胰胆管系统的管内超声

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德国医学 1999年第3期16卷 158-160页

作者： J.Menzel W.domschke J.W.konturek A.Gillessen E.Foerster 张林 Medizinische klinik und Poliklinik B der Universitt Albert-Schweitzer-Str.33D-48149MünsterGermany 同济医科大学附属同济医院

内超声检查可以直接发现包括肝门区的胆道狭窄。尽管病例有限,显示出很高的特异性、敏感性和正确性。虽然胆管壁的厚度不是鉴别胆道良性或恶性疾病的标准,无痛性黄疸是胰腺肿瘤和胆管肿瘤主要的临床症状。大多数情况下在确诊胰腺癌时已... 详细信息

内超声检查可以直接发现包括肝门区的胆道狭窄。尽管病例有限,显示出很高的特异性、敏感性和正确性。虽然胆管壁的厚度不是鉴别胆道良性或恶性疾病的标准,无痛性黄疸是胰腺肿瘤和胆管肿瘤主要的临床症状。大多数情况下在确诊胰腺癌时已不能手术,预后差,5年生存率<5％。同样,当胆道癌得到诊断时也很少能经手术切除,1年生存率20％,5年生存率3％。

关键词：胰胆管疾病胰胆管内超声波诊断

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A typical presentation of a rare cause of obscure gastrointestinal bleeding

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World Journal of Gastrointestinal Endoscopy 2011年第2期3卷 40-45页

作者： Stefan Reuter Dominik Bettenworth Sren Torge Mees Jrg Neumann Torsten Beyna Wolfram domschke Johannes Wessling Hansjrg Ullerich Department of Internal Medicine D University Hospital Münster Albert-Schweitzer Str. 33 Münster 48149 Germany Department of Internal Medicine B University Hospital Münster Albert-Schweitzer Str. 33 Münster 48149 Germany Department of General and Visceral Surgery University Hospital Münster Albert-Schweitzer Str. 33 Münster 48149 Germany Gerhard Domagk Institute of Pathology University Hospital Münster Albert-Schweitzer Str. 33 Münster 48149 Germany Department of Radiology University Hospital Münster Albert-Schweitzer Str. 33 Münster 48149 Germany

A 52-year-old white woman had suffered from intermittent gastrointestinal (GI) bleeding for one year. Upper GI endoscopy, colonoscopy and peroral doubleballoon enteroscopy (DBE) did not detect any bleeding sour ce, suggesting obscure GI bleeding. However, in video capsule endoscopy a jejunal ulceration without blee ding signs was suspected and this was endoscopically conf irmed by another peroral DBE. After transfusion of packed red blood cells, the patient was discharged from our hospital in good general *** weeks later she was readmitted because of another episode of acute bleeding. Multi-detector row computed tomography with 3D reconstruction was performed revealing a jejunal tumor causing lower gastrointestinal bleeding. The patient underwent exploratory laparotomy with partial jejunal resection and end-to-end jejunostomy for reconstruction. Histological examination of the specimen confirmed the diagnosis of a low risk gastrointestinal stromal tumor (GIST). Nine days after surgery the patient was discharged in good health. No signs of gastrointestinal rebleeding occurred in a followup of eight months. We herein describe the comp lex presentation and course of this patient with GIST and also review the current approach to treatm ent.

关键词： Gastrointestinal stromal tumor Gastrointestinal neoplasms Gastrointestinal hemorrhage Computed tomography

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