The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration-clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM. Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants.     

Complications in laparoscopic myomectomy

Background An increasing number of patients with fibroids wish to retain their uterus without improving fertility. We evaluated the rate of complications in our teaching hospital and its association with patients’ age. Methods Chart records of 351 patients were evaluated according to patients’ age. Results A total of 654 fibroids were removed. Mean size of fibroids was 5.3 cm; mean duration of surgery was 113.2 min. Blood transfusion was necessary in one patient. The intraoperative complication rate was 2.6% and postoperative complications occurred in 5.7% of patients. Sonographic evaluation showed a hyperechogenic scar in 29.2%. A total of 57.1% pregnancies ended in term infants. No uterine rupture was reported. As a sign of contentment, 87% of patients would choose the same procedure again. Indication for myomectomy in elder women was more often associated with uncertain sonographic findings due to intraligamentary localization. Conclusion Morbidity was low. Age had no impact. Laparoscopic myomectomy can be offered to all women.     

Zur Frage der Geburtsauslösung durch Serotonin

Ohne ZusammenfassungHerrn Prof. Dr. Dr.E. Werle zum 60. Geburtstag gewidmet.     

人胰岛素基因逆转录病毒旋转感染Phoenix细胞的表达

目的:观察新构建人胰岛素基因逆转录病毒表达载体(pM54)在Phoenix和HepG2等细胞的表达情况。方法:1)脂质体法转染pM54质粒进入pT67、Phoenix和3T3细胞系;2)用新构建质粒的父本质粒p54和pCMVβGal质粒做转染基因对照;3)制备转染后细胞培养拟逆转录病毒上清液;4)旋转感染Phoenix及HepG2细胞;5)ELISA法检测转染、感染后上清液INS含量。结果:ELISA法检测证实感染细胞培养上清液中含较高水平目的蛋白INS的表达。对照结果均为阴性。结论:人胰岛素基因逆转录病毒介导旋转感染Phoenix等细胞,目的蛋白INS获得了预期的表达。实验为基因治疗或基因结合干细胞治疗糖尿病的进一步相关研究提供了重要数据。     

Effect of silibinin and vitamin E on restoration of cellular immune response after partial hepatectomy

Our aim was to study the antioxidant and immunomodulatory effect of silibinin and vitamin E on the early postoperative course in rats that had undergone a partial hepatectomy (PHX). Male Wistar rats that were treated with silibinin (50 mg/b.w.kg i.p.) and/or vitamin E (500 mg/b.w.kg p.o.) were randomised to undergo 70% PHX. At 72 h after operation, Concanavalin A (Con-A) induced lymphocyte proliferation, and lipopolysaccharide (LPS) induced interleukin-1 (IL-1) mitogenicity and tumour necrosis factor-alpha (TNF-alpha) cytotoxicity were measured in the spleen. In addition, total free radical scavenger capacity of the liver was analysed. In PHX animals, Con-A induced lymphocyte proliferation was significantly decreased, and both LPS induced IL-1 and TNF-alpha activity were significantly increased as compared to Sham treated animals. Treatment with silibinin and vitamin E synergistically restored both lymphocyte proliferation (P<0.01) and cytokine activity (P<0.001) in PHX animals. In addition, silibinin and vitamin E synergistically (P<0.001) restored total hepatic free radical scavenger capacity as well as serum levels of AST and gammaGT, that were all markedly decreased in PHX animals. Our results suggest that preoperative treatment with silibinin and/or vitamin E modulates the cellular immunoresponse and restores impaired liver function following PHX, presumably through their antioxidant capacity. This may explain their beneficial effects on the postoperative course of liver repair.     

Intelligence and development in Aarskog syndrome

AIM: To test the hypothesis that overall intelligence quotient (IQ) is decreased in patients with Aarskog syndrome. METHODS: 21 boys under 17 years of age with a confirmed clinical diagnosis of Aarskog syndrome were assessed using the Griffiths mental development scales and the British ability scales. RESULTS: IQ ranged from 68 to 128 and followed a normal distribution. CONCLUSION: This study does not support the hypothesis that Aarskog syndrome is associated with a lowering of mean IQ.