我院32例万古霉素血药浓度监测结果与临床疗效分析

目的评价我院32例患者万古霉素血药浓度监测结果与临床疗效分析,为临床合理用药提供参考。方法对我院2011年12月～2012年4月应用万古霉素并监测血药浓度的32例住院患者的临床资料（基础疾病、细菌学培养结果、用药情况、万古霉素血药谷浓度、疗效、肾功能情况等）进行统计、分析。结果细菌检出率53％,用药指征细菌学符合率31％。应用万古霉素的总有效率为69％,万古霉素血药浓度所测得谷值在10～20mg／L范围内者占25％,治疗后肾功能异常发生率为13％。结论32例应用万古霉素患者初次测得其血药浓度谷值在有效范围内的比例偏低,对老年患者需重视其血药浓度监测,并结合临床实际实现个体化给药。     

202例次万古霉素血药浓度监测与临床应用分析

目的 分析万古霉素血药浓度监测结果及临床应用情况,为临床合理用药提供参考。方法 采用反相-高效液相色谱法测定万古霉素血药浓度,对万古霉素血药浓度监测结果及相关用药信息进行比较分析。结果 万古霉素谷浓度监测202次,平均血药谷浓度（14.36±8.12）mg/L,浓度小于10 mg/L的有68例次（33.66%）,在10～20 mg/L的有100例次（49.51%）,大于20 mg/L的有34例次（16.83%）;肾功能正常与异常组间,血药谷浓度有显著性差异;用药前后,各项肾功能指标无显著性差异。结论 万古霉素个体差异大,需加强血药浓度监测;针对肾功能异常患者,临床医生和药师需审慎评估给药剂量;临床医生应根据血药浓度及时调整用药方案,实现个体化给药。     

某院117例患者去甲万古霉素血药浓度监测结果分析

摘要：目的:分析某院去甲万古霉素血药浓度的监测情况,为临床合理用药提供依据。方法:采用HPLC法测定去甲万古霉素的血药谷浓度和峰浓度,对117例去甲万古霉素血药浓度监测结果进行回顾性分析。比较不同谷浓度和峰浓度区间患者的分布,单因素方差分析考察性别、年龄和肾功能对血药浓度的影响,统计各浓度区间不良反应发生情况,并进行不良反应关联性评价。结果:117例患者中,去甲万古霉素血药谷浓度处于有效范围(10～20μg·ml-1)的占29. 06%（34/117）,处于有效峰浓度范围(20～40μg·ml-1)的占67. 52%（79/117）。平均血药谷浓度和峰浓度在不同年龄段人群间均存在显著差异（P<0. 05）,>75岁患者的血药谷浓度>20μg·ml-1和峰浓度>40μg·ml-1比例显著高于<60岁组和60～75岁组（P<0. 05）。不同性别患者血药浓度差异无统计学意义（P>0. 05）。肌酐清除率（Ccr）<40 ml·min-1组和Ccr 40～60 ml·min-1组患者的血药浓度均显著高于Ccr≥60 ml·min-1组（P<0. 05）,且易发生不良反应。总不良反应发生率14. 53%（17/117）,不良反应关联性评价结果为肯定14例,很可能2例,可能1例。结论:去甲万古霉素血药浓度个体差异大,年龄和肾功能对血药浓度影响显著,应常规进行血药浓度监测,特别应加强75岁以上老年人及肾功能损害患者的用药监护,保证临床用药的安全有效。     

老年患者万古霉素血药浓度分析及给药方案探讨

目的:对某院老年患者万古霉素血药浓度监测结果及对肾功能影响进行分析,并探讨给药方案的适宜性。方法:将符合入选标准的120例老年患者,按日剂量把给药方案分为4组,对万古霉素血清谷浓度以及治疗前后相关肾功能指标进行统计分析。结果:120例老年患者中,血药谷浓度监测结果在参考范围10~20 mg·L^-1的占41.67%,高于参考范围的占43.33%;轻度肾功能不全老年患者万古霉素给药方案为1g qd/0.5g q12h的仅占47.92%,给药方案为0.5g q8h或1g q12h的有近30%老年患者存在肾功能不全;万古霉素给药方案为1g q12h组,老年患者治疗前后内生肌酐清除率有统计学差异(P<0.05)。结论:老年患者使用万古霉素个体差异大,谨慎使用1g q12h的给药方案,给药方案需在血药谷浓度监测下进行调整。     

新指南建议的万古霉素血药谷浓度与疗效及肾功能的相关性分析

目的对新指南建议的万古霉素血药谷浓度与临床疗效及肾功能的相关性进行分析,为个体化给药提供参考。方法选择我院2013年1月至2015年1月收治的使用万古霉素治疗感染的患者78例,检测万古霉素的血药谷浓度,定期监测肾功能,对疗效进行评价,并记录不良反应发生情况。结果 78例患者中,有56例(71.79%)血药谷浓度为10~20 mg/L,临床总有效率为83.93%,3种谷浓度组(A组:5~10 mg/L,B组:10~15 mg/L,C组:15~20 mg/L)的疗效比较差异无统计学意义。三组患者中出现肾功能损伤的例数分别为0、2例(5.41%)、3例(15.79%),C组与A、B组比较差异有统计学意义。结论万古霉素治疗耐甲氧西林金黄色葡萄球菌等敏感菌引起的重症感染的临床疗效较好,其血药谷浓度>15 mg/L并不能提高临床疗效,反而会引起肾功能损害,因此在使用中应密切监测血药浓度。     

我院41例万古霉素血药浓度监测与临床用药分析

目的:评价我院万古霉素血药浓度监测及其临床应用情况。方法:采用回顾性调查方法,对我院2005年11月～2008年12月应用万古霉素并监测血药浓度的41例住院患者的临床资料(基础疾病、细菌学培养结果、万古霉素血药浓度值、疗效、肾功能情况等)进行统计、分析。结果:我院住院患者应用万古霉素的总有效率为65.0%;万古霉素血药浓度所测得峰值<25mg.L-1者占62.7%,谷值<5mg.L-1者占55.2%;治疗后肾功能异常发生率为12.2%。结论:我院住院患者万古霉素应用量和血药浓度均偏低,需重视其血药浓度监测并结合临床实际,实现个体化给药。     

利奈唑胺血药浓度监测结果及影响因素分析

摘要：目的:对我院利奈唑胺血药浓度监测结果进行分析,探讨利奈唑胺血药浓度的影响因素。方法:回顾性收集2019年2月～2020年6月我院符合纳入标准住院患者的相关信息,采用单因素及多因素回归分析利奈唑胺血药谷浓度的影响因素。结果:73例患者中利奈唑胺平均血药谷浓度为（6.54±2.31）μg·ml-1,在参考范围内的占34.2%,低于参考范围的占12.3%,高于参考范围的占53.4%;单因素分析结果显示老年患者和肾功能不全患者利奈唑胺血药谷浓度高于非老年患者及肾功能正常患者（P＜0.05）;多因素分析结果显示利奈唑胺谷浓度随ALT和肌酐清除率的升高而降低。结论:利奈唑胺血药浓度个体差异大,肾功能不全患者进行血药浓度监测可能有助于降低不良反应发生风险。     

我院万古霉素临床合理使用评价及血药浓度监测分析

目的:为万古霉素临床合理使用提供参考。方法:收集我院2015年1月-2016年6月使用万古霉素的299例患者的病历资料,对用药情况、用药合理性、病原学检查结果、万古霉素血药浓度、疗效、不良反应等指标进行统计分析。结果:我院住院患者应用万古霉素多为治疗用药,且以经验性治疗用药为主(90.30%);用药前样本送检率为61.82%,有52例(28.42%)患者检出特异病原菌。万古霉素用药不合理的有69例(23.08%),均为药物浓度不适宜。万古霉素血药浓度监测率为43.33%,谷浓度维持在10~20mg/L的占40.00%;治疗有效率为79.39%;治疗后急性肾损伤的发生率为5.41%。结论:我院住院患者应用万古霉素前样本送检率和血药浓度监测率均偏低,有效血药谷浓度的患者比例亦低。医院应加强万古霉素的应用管理,促进临床个体化用药。     

万古霉素个体化给药辅助决策系统在烧伤患者中的应用

摘要：目的:评价个体化给药辅助决策系统PharmVan、Smart Dose和“万古霉素剂量推荐和血药浓度预测系统”（G系统）在预测烧伤患者万古霉素血药谷浓度中的临床效用。方法:回顾性分析2018年10月～2021年1月上海交通大学医学院附属瑞金医院烧伤科收治的97例使用万古霉素治疗且进行血药浓度监测的烧伤患者临床资料。使用PharmVan、Smart Dose和G系统预测万古霉素血药谷浓度,比较血药谷浓度预测值与实测值的差异,以评价3种个体化给药辅助决策系统对烧伤患者万古霉素血药谷浓度的预测效能。结果:PharmVan对烧伤患者万古霉素血药谷浓度的预测值与实测值无统计学差异（P=0.187）,但预测误差绝对值（APE）＞30%。Smart Dose和G系统万古霉素血药谷浓度的预测值与实测值差异有统计学意义（P=0.021和P＜0.001）,且APE＞30%,说明Smart Dose与G系统万古霉素血药谷浓度的预测值与实测值无相关性。单因素分析发现,肌酐清除率与PharmVan预测万古霉素血药谷浓度的准确性呈显著相关（P=0.027）,随着肌酐清除率增加,PharmVan的绝对预测误差呈增加趋势（P=0.012）。多因素Logistic回归分析显示,肌酐清除率＞130 ml·min-1时,PharmVan对万古霉素血药谷浓度的预测能力差[优势比（OR）=3.997,95%置信区间（CI）:1.032,15.478,P=0.045]。ROC曲线分析显示,肌酐清除率构建的ROC曲线对应的ROC曲线下面积（AUC）为0.626,95%CI:0.510,0.741,P=0.036,当肌酐清除率大于106.07 ml·min-1时,PharmVan预测万古霉素血药谷浓度不准确的风险增加,其敏感度为71.9%,特异度为52.5%。结论:PharmVan对肌酐清除率大于106.07 ml·min-1的烧伤患者预测万古霉素血药谷浓度不准确的风险增加。Smart Dose和G系统不适用于烧伤患者万古霉素血药谷浓度的预测,提示需要建立适合中国烧伤患者的群体药物动力学模型。     

123例万古霉素血药浓度监测及临床用药分析

目的 通过分析123例患者万古霉素血药浓度的监测结果,为临床合理用药提供参考.方法 采用回顾性调查方法,对本院2010年1 月～2011 年1 月应用万古霉素并监测血药浓度的123 例住院患者的临床资料(基础疾病、细菌学培养结果 、万古霉素血药浓度值、疗效、肾功能情况等)进行统计、分析.结果 本院住院患者应用万古霉素的总有效率为69.11%;万古霉素血药浓度所测得峰值＜ 30 μg/mL者占60.18%,＜ 10 μg/mL者占13.85%;治疗后肾功能异常发生率为12.20%.结论 本院住院患者万古霉素应用量和血药浓度均偏低,需重视其血药浓度监测并结合临床实际,实现个体化给药.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.