Search for a Susceptibility Locus to Tardive Dyskinesia

In order to find a genetic marker for vulnerability to tardive dyskinesia (TD), we looked for an association between vulnerability to TD and polymorphic sites in the gene loci encoding the dopamine D2 receptor (Nco I site), the dopamine D3 receptor (Bal I site), and the dopamine transporter (40-bp, tandem repeat polymorphism). No significant difference was observed in the allele and genotype frequencies of any of the polymorphic sites examined, when comparing psychiatric patients who were specifically vulnerable to TD (n = 49) and those who were not (n = 56). These results suggest that the polymorphic gene loci examined in the present study are unlikely to be of major aetiologic importance in the development of TD. © 1997 John Wiley & Sons, Ltd.     

Pharmacological Modification of Experimental Tardive Dyskinesia

Abstract Cebus apella monkeys subjected to chronic haloperidol administration develop neurologic disturbances very similar to neuroleptic-induced acute dystonia in human beings. After varying lengths of time, certain monkeys develop a prolonged dyskinetic syndrome resembling tardive dyskinesia (TD), as seen clinically. Two monkeys with signs of TD were given single intramuscular injections of various compounds with known effects on the catecholaminergic, cholinergic, serotoninergic and GABA-ergic neurotransmittor systems, and their effect on the TD signs were rated. Dopamine receptor blockers as well as cholinergics had an ameliorating effect on the symptoms. Some compounds known to activate the GABA system, including some benzodiazepines and the GABA-transaminase inhibitor amino-oxyacetic acid, also reduced the symptoms, as did the serotonin precursor L-5HTP. Results with serotonin antagonists were equivocal. It is concluded that dopamine receptor blockade, as well as increased activity within the GABA-ergic or cholinergic systems cause alleviation of TD. The findings are in agreement with earlier reports in man and thus seem to validate this primate model.     

Vitamin E Treatment in Tardive Dyskinesia

Sixteen patients with tardive dyskinesia were treated with vitamin E in an open trial of on–off–on design. Abnormal involuntary movement scale (AIMS) ratings were performed in every phase of the study. The patients exhibited a significant reduction in their mean AIMS score during vitamin E treatment. Thus, this finding may suggest a possible role for vitamin E in the treatment of tardive dyskinesia. © 1997 John Wiley & Sons, Ltd.     

氯硝西泮治疗持续性迟发性运动障碍

目的 探讨氯硝西泮对持续性TD的临床作用. 方法 对12例精神分裂症持续性TD患者加用小剂量氯硝西泮, 用AIMS、 TDRS、 TESS和BPRS, 随访半年, 进行前瞻性开放性研究. 结果 加服氯硝西泮前后自身对照比较 AIMS严重度分除加药第2周和第12周外, 差异均有显著性(P＜0.05), 4例患者(33.3%)加氯硝西泮后不自主运动明显改善, 未见反复. 结论小剂量氯硝西泮治疗部分持续性TD患者有一定疗效, 安全性较好.     

Association of the HSPG2 Gene with Neuroleptic-Induced Tardive Dyskinesia

Tardive dyskinesia (TD) is characterized by repetitive, involuntary, and purposeless movements that develop in patients treated with long-term dopaminergic antagonists, usually antipsychotics. By a genome-wide association screening of TD in 50 Japanese schizophrenia patients with treatment-resistant TD and 50 Japanese schizophrenia patients without TD (non-TD group) and subsequent confirmation in independent samples of 36 treatment-resistant TD and 136 non-TD subjects, we identified association of a single nucleotide polymorphism, rs2445142, (allelic p=2 × 10⁻⁵) in the HSPG2 (heparan sulfate proteoglycan 2, perlecan) gene with TD. The risk allele was significantly associated with higher expression of HSPG2 in postmortem human prefrontal brain (p<0.01). Administration of daily injection of haloperidol (HDL) for 50 weeks significantly reduced Hspg2 expression in mouse brains (p<0.001). Vacuous chewing movements (VCMs) induced by 7-week injection of haloperidol–reserpine were significantly infrequent in adult Hspg2 hetero-knockout mice compared with wild-type littermates (p<0.001). Treatment by the acetylcholinesterase inhibitor, physostigmine, was significantly effective for reduction of VCMs in wild-type mice but not in Hspg2 hetero-knockout mice. These findings suggest that the HSPG2 gene is involved in neuroleptic-induced TD and higher expression of HSPG2, probably even after antipsychotic treatment, and may be associated with TD susceptibility.     

Relationship between Tardive Dyskinesia and psychopathology in a group of schizophrenic patients attending a rehabilitation centre

Twenty-five of 76 patients suffering from chronic schizophrenia, treated in a rehabilitation centre, were found to have tardive dyskinesia (TD) according to the Tardive Dyskinesia Research Diagnostic Criteria (Schooler and Kane, 1982). Patients suffering from TD achieved significantly higher total scores on two subscales (affective flattening and blunting and avolition-apathy, respectively) of the Scale for the Assessment of Negative Symptoms. On the other hand, positive symptoms assessed by the Brief Psychiatric Rating Scale did not distinguish the two groups. Our findings support the idea that patients suffering predominantly from negative symptoms of schizophrenia may have a higher vulnerability for the development of TD than schizophrenic patients showing mainly positive symptoms.     

Association Study Indicates a Protective Role of Phosphatidylinositol-4-Phosphate-5-Kinase against Tardive Dyskinesia

Background:

Tardive dyskinesia is a disorder characterized by involuntary muscle movements that occur as a complication of long-term treatment with antipsychotic drugs. It has been suggested to be related to a malfunctioning of the indirect pathway of the motor part of the cortical-striatal-thalamic-cortical circuit, which may be caused by oxidative stress-induced neurotoxicity.

Methods:

The purpose of our study was to investigate the possible association between phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) function and tardive dyskinesia in 491 Caucasian patients with schizophrenia from 3 different psychiatric institutes in West Siberia. The Abnormal Involuntary Movement Scale was used to assess tardive dyskinesia. Individuals were genotyped for 3 single nucleotide polymorphisms in PIP5K2A gene: rs10828317, rs746203, and rs8341.

Results:

A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene (rs10828317) and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related.

Conclusions:

We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.     

Impact of a Pharmacist-Driven MRSA Nasal PCR Protocol on Pneumonia Therapy

Background:Methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) testing can rapidly detect MRSA colonization via nasopharyngeal swab. With a high negative predictive value for MRSA pneumonia, this test may help minimize the duration of anti-MRSA therapy and associated adverse drug events. Objective: This study aimed to evaluate the impact of a pharmacist-initiated MRSA nasal PCR protocol on pneumonia therapy. Methods: This retrospective, quasi-experimental study evaluated adult patients with pneumonia before and after the implementation of a pharmacist-initiated MRSA nasal PCR protocol. The primary outcome of this study was to compare duration of anti-MRSA therapy between the Pre-PCR group and PCR group. Secondary comparisons included duration of antipseudomonal therapy, time from intravenous (IV) to oral interchange, and clinical outcomes. Results: In total, 210 patients (Pre-PCR: n = 138, PCR: n = 72) were included. The MRSA nasal PCR result was negative for 63 patients (87.5%), and 56 (88.9%) vancomycin orders were discontinued within 24 hours of the negative result. The mean duration of vancomycin therapy was significantly shorter in the PCR group (2.5 vs 1.4 days, P < .001) as well as duration of IV therapy (5 vs 3.9 days, P = .003). There was no difference between groups in duration of antipseudomonal therapy (P = .425), acute kidney injury (AKI; P = .332), 30-day readmission (P = .137), or 30-day mortality (P = .179). Conclusion and Relevance: A pharmacist-driven MRSA nasal PCR protocol significantly decreased the duration of anti-MRSA therapy and IV antibiotics in patients with pneumonia. These findings add to the relatively small body of literature supporting pharmacist-initiated rapid diagnostic testing and follow-up.     

惠州市职业病防治院“阳光用药”监察工作的成效评价

目的:通过阳光用药监察系统监测电子处方药品使用情况,结合处方点评制度、基本药物制度、抗菌药物分级使用制度及医疗质量监控制度,评价在构筑公立医院医德医风长效监察机制方面所取得的成效。方法:抽取2013年—2015年3年度电子处方,分析处方用药的规范性和合理性,以及分析抗菌药物、基本药物使用情况和患者平均次就诊治疗用药品费用。结果:2015年与2013年相比,处方合格率提升4.26%,门诊基本药物使用率增至56%,住院基本药物使用率增加3倍,门诊抗菌药物使用率降低36%,住院抗菌药物使用率降低8%,门诊用药均次药费降低15%,住院用药均次药费降低8%。结论:处方用药监察工作进一步提高了处方书写和药品使用的合理性,为降低医疗成本,预防医疗腐败,推动优质医疗管理和服务质量起到了积极的作用。     

浅议省级药品不良反应监测与评价专家库的建设与管理

药品不良反应专家咨询是协助各级药品不良反应监测中心开展药品安全性监测与评价的基础,省级药品不良反应监测与评价专家库的建设及管理是做好专家咨询的保证。本文通过分析专家库的建立及管理方法,旨在建立科学、合理的专家库发挥省级药品不良反应监测与评价工作的技术支撑作用。     

Tardive Tourette-like syndrome: a systematic review

Tardive Tourette syndrome is characterized by the occurrence of multiple motor and vocal tics in patients on long-term neuroleptic, antiepileptic medication or stimulants, and was first reported by Golden in 1974 and was given its name in 1980 by Steven Stahl who linked it to tardive dyskinesia. The Medline was searched with the combination of the words 'tardive' or 'induced' or 'late' and 'Tourette' or 'Tourettism' and 375 papers were indentified; 42 of them were judged to be relevant. Forty-one cases were identified, caused by antipsychotics, antiepileptics, stimulants and other medication. A number of treatment options are reported in the literature but no systematic study of the syndrome has been done yet.     

Evaluation of the Effectiveness of Sugammadex for Verapamil Intoxication

Previous studies have shown that medications from the cyclodextrin family bind to verapamil. The aim of our study was to determine whether sugammadex could bind to verapamil and prevent the cardiovascular toxicity of that drug. Twenty‐eight sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, the animals were treated with a bolus of either 16 mg/kg, 100 mg/kg or 1000 mg/kg sugammadex. The control group was treated with an infusion without sugammadex. The heart rate and respiratory rate were monitored, and an electrocardiogram was recorded. The primary end‐point was the time to asystole. The verapamil infusion continued until the animals arrested. The asystole time for the S16 group was significantly longer compared to those for the control and S1000 groups (p < 0.05). The asystole time for the S1000 group was significantly shorter than those for all of the other groups (p < 0.05). Reflecting these data, there was a near doubling of the mean lethal dose of verapamil from 13.57 mg/kg (S.D. ±8.1) in the saline‐treated rats to 22.42 mg/kg (S.D. ±9.9) in the sugammadex 16 group (p < 0.05). However, for the sugammadex 1000 group, the mean lethal dose was found to be 6.28 ± 1.11 mg/kg. This dose is significantly lower than those for all of the other groups (p < 0.05). We found that treatment with 16 mg/kg sugammadex delayed verapamil cardiotoxicity in rats. However, 1000 mg/kg sugammadex accelerated verapamil cardiotoxicity in rats. Further studies must be conducted to investigate the interaction between verapamil and sugammadex.     

药品不良反应监测数据库信息标准化建设

目的：促进广东省药品不良反应自发呈报系统数据库的信息标准化建设，对2002年4月28日～2007年7月10日收集的42255条数据进行规范化整理。方法：结合第15版新编药物学与MCDEX药物临床信息参考（2006），对数据库中的6万多条的药物通用名称进行规范化整理。结合WHO的不良反应术语集和ICD-10疾病系统分类，规整42255条药品不良反应记录。结果：建立了5407个药物通用名称规则名，形成4031个药物通用名称标准名。建立了8715个不良事件名称规则名，形成2332个不良事件名称标准名。建立的规则库能自动完成新入库病例的80％的规范化工作。结论：数据标准化将不规范的习惯用语转化成标准化信息，为数据利用如信号检测和数据挖掘提供了基础。     

发作性运动障碍误诊分析

目的探讨发作性运动障碍的临床特点及误诊原因,减少误诊发生.方法对误诊误治的5例发作性运动障碍临床资料进行回顾性分析.结果5例早期分别误诊为癫痫.小舞蹈病、短暂性脑缺血发作.结论医生对本病认识不足是误诊的主要原因,提高认识,仔细分析病情,是减少误诊的关键.     

对住院医师进行抗菌药物临床应用培训效果评价

目的：评价理论与互动相结合式抗菌药物培训效果,探索住院医师更易接受的培训方式,为更好执行《抗菌药物临床应用管理办法》提供参考。方法：对沧州市人民医院新入职住院医师进行理论与互动相结合式培训,比较培训前后抗菌药物考试成绩,在培训前后分别进行问卷调查,内容包括住院医师是否接受过抗菌药物培训、抗菌药物培训的必要性、对抗菌药物基础知识和法律法规的了解程度、培训满意度、哪种培训方式更容易接受等。结果：共83名新入职医师参加培训,回收有效试卷及调查问卷各76份。培训前平均成绩为（67.70±14.13）分,培训后为（94.54±4.84）分,较培训前平均提高39.65%（P < 0.01）。与单纯理论授课式、互动式培训相比,93.42%医师表示更容易接受二者相结合的培训模式,满意度为100%。结论：通过理论与互动相结合式抗菌药物培训,住院医师对抗菌药物认知水平明显提高,理论与互动相结合式抗菌药物培训更容易被住院医师接受。     

Evaluation of a Noninvasive Method for Monitoring Percutaneous Absorption of Lidocaine in Vivo

The pharmacodynamic measurement of in vivo skin penetration of lidocaine was explored with an instrument used in dentistry to determine tooth pulp vitality. The instrument delivers a low-current, pulsatile electrical waveform of increasing intensity with time. The readings, which are reproducible, are in arbitrary units on a scale of 0–80. Testing of naive sites showed variation as a function of location, even over relatively small distances. The response at a marked site over a 12-hr period generally was consistent in five subjects. Following intradermal administration of 1 or 2% lidocaine hydrochloride injection in one subject, the instrument reached its maximum value within 2 min. This was followed by a sustained plateau and then a gradual falloff of the effect. Topical formulations containing 5% lidocaine base and corresponding blank formulations were applied under occlusion within Hilltop chambers to intact skin on the forearms of human volunteers for 3 hr. While the response to a 40% propylene glycol formulation was not significantly different from the corresponding control, a cream exhibited slow development of profound anesthesia that lasted for several hours following chamber removal.     

治疗药物监测中Access数据库的应用

目的:建立治疗药物监测数据管理系统,实现个体化给药。方法:在Windows平台用Access建立治疗药物监测数据库,综合管理患者的血药浓度、用药情况及临床检验等数据。结果与结论:该数据库数据处理方便,存储信息量大,查询快捷,为临床药学工作提供了有力的支持。