Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings

The pharmacokinetics of a single oral dose of 6 mg perphenazine was studied in a group of six slow and six rapid hydroxylators of debrisoquin. Peak serum concentrations of perphenazine were significantly higher in slow hydroxylators than they were in rapid hydroxylators (2.4 +/- 0.6 versus 0.7 +/- 0.3 nmol/L, p less than 0.001). The AUC(0-12) was also higher in slow hydroxylators than it was in rapid hydroxylators (18.5 +/- 6.2 versus 4.5 +/- 2.5 nmol.L-1.hr, p less than 0.001). The data suggest that the disposition of the antipsychotic drug perphenazine covaries with polymorphic debrisoquin hydroxylation.     

Prospective comparison of novel dark blood late gadolinium enhancement with conventional bright blood imaging for the detection of scar

Background

Conventional bright blood late gadolinium enhancement (bright blood LGE) imaging is a routine cardiovascular magnetic resonance (CMR) technique offering excellent contrast between areas of LGE and normal myocardium. However, contrast between LGE and blood is frequently poor. Dark blood LGE (DB LGE) employs an inversion recovery T2 preparation to suppress the blood pool, thereby increasing the contrast between the endocardium and blood. The objective of this study is to compare the diagnostic utility of a novel DB phase sensitive inversion recovery (PSIR) LGE CMR sequence to standard bright blood PSIR LGE.

Methods

One hundred seventy-two patients referred for clinical CMR were scanned. A full left ventricle short axis stack was performed using both techniques, varying which was performed first in a 1:1 ratio. Two experienced observers analyzed all bright blood LGE and DB LGE stacks, which were randomized and anonymized. A scoring system was devised to quantify the presence and extent of gadolinium enhancement and the confidence with which the diagnosis could be made.

Results

A total of 2752 LV segments were analyzed. There was very good inter-observer correlation for quantifying LGE. DB LGE analysis found 41.5% more segments that exhibited hyperenhancement in comparison to bright blood LGE (248/2752 segments (9.0%) positive for LGE with bright blood; 351/2752 segments (12.8%) positive for LGE with DB; p?<?0.05). DB LGE also allowed observers to be more confident when diagnosing LGE (bright blood LGE high confidence in 154/248 regions (62.1%); DB LGE in 275/324 (84.9%) regions (p?<?0.05)). Eighteen patients with no bright blood LGE were found to have had DB LGE, 15 of whom had no known history of myocardial infarction.

Conclusions

DB LGE significantly increases LGE detection compared to standard bright blood LGE. It also increases observer confidence, particularly for subendocardial LGE, which may have important clinical implications.

     

Disposition of single oral doses of E-10-hydroxynortriptyline in healthy subjects, with some observations on pharmacodynamic effects

The active and major metabolite of nortriptyline (NT), E-10-hydroxynortriptyline (E-10-OH-NT), was taken orally as the hydrogen maleate in single doses by nine healthy subjects. The doses (10 to 100 mg) were completely absorbed, as shown by the high urinary recovery of 86.1% +/- 9.9%. Of the given dose, 51.2% +/- 8.7% was recovered as conjugated E-10-OH-NT and 23.9% +/- 4.3% was recovered as unchanged compound. The plasma t1/2 of E-10-OH-NT was 8.0 +/- 1.2 hours and total plasma clearance was 47.5 +/- 10.3 L/hr. The rate of elimination varied little between individuals. There was no indication of dose-dependent elimination. The mean apparent volume of distribution was 7.7 +/- 2.1 L/kg. Single oral doses of 50 mg E-10-OH-NT significantly increased the plasma levels of norepinephrine in both the supine and standing positions (P less than 0.01). Pulse rate increased in the standing but not the supine position. These effects might result from inhibition of neuronal uptake of norepinephrine by E-10-OH-NT. Coupled with its low affinity for muscarinic receptors, these kinetic and pharmacodynamic features of E-10-OH-NT call for further phase I studies.     

亲属活体肾移植18例报告

目的：总结亲属活体肾移植的临床经验，以期提高该技术的安全性及疗效。方法：选择2005—11／2006—12解放军第一七五医院收治的亲属活体肾移植患者18例，均知情同意。受体均为慢性肾小球肾炎；供体年龄24-74岁，17例有血缘关系，另一例为妻子供肾。均行经腰开放手术取肾，左侧供肾15例，右侧供肾3例。术后受体采用环孢素A＋霉酚酸酯＋激素三联低剂量免疫抑制剂方案。结果：①所有供体在术后10d左右出院，均无严重并发症且肾功能正常。②16例受体均在术后1-3d内移植肾功能恢复正常，另2例因供肾迷走血管损伤在术后5d左右血肌酐下降到200μmol／L，1个月左右稳定在160μmol／L。1例他克莫司仅服0．5-0．75mg／d，于术后5个月出现急性排斥反应。1例术后2个月出现环孢素A急性肾毒性（血药浓度谷值为343μg，L）。2例出现药物性肝炎。结论：亲属活体肾移植术较为安全，排斥反应少，结果满意。免疫抑制剂宜采用低剂量方案。     

Postanalytical external quality assessment of blood glucose and hemoglobin A1c: an international survey

BACKGROUND: Diabetes mellitus (DM) is diagnosed and monitored worldwide by blood glucose (BG) and glycohemoglobin A(1c) (HbA(1c)) testing, respectively. Methods for quality assessment of clinician interpretations of changes in these laboratory results have been developed. This study uses survey responses from general practitioners (GPs) in different countries to investigate possible differences in interpretation of results, as well as the feasibility of performing international postanalytical external quality assessment surveys (P-EQAS). METHODS: GPs recruited from 7 countries received questionnaires requesting interpretation of changes in a potentially diagnostic capillary BG result and an HbA(1c) value obtained during monitoring of a patient with type 2 DM. GPs were asked to estimate clinically significant differences between 2 consecutive laboratory results [critical difference (CD)/reference change value] for both BG and HbA(1c). The CDs reported by GPs were used to calculate the analytical variation (CV(a)), which was taken as the quality specification for analytical imprecision. Participants received national benchmarking feedback reports after the survey. RESULTS: The study included responses from 2538 GPs. CDs in BG results showed the same pattern and were comparable among countries. Calculated median CV(a) values would be possible to attain at 80% confidence but not at the conventional 95% confidence. For HbA(1c), the same pattern was shown across countries, but with lower changes considered true when HbA(1c) increased than when it decreased. Despite the consistent pattern, variations among GPs were considerable in all countries. CONCLUSIONS: Assessments of CDs for BG and HbA(1c) were similar internationally, and quality specifications for these analytes based on clinicians' opinions are therefore interchangeable among countries. International P-EQAS may contribute to a more rational use of laboratory services and clinical guidelines.     

不同孔径纳米羟基磷灰石人工骨修复兔桡骨缺损效果比较

目的:纳米级的羟基磷灰石材料与人体内组织成分更为相似,具有更佳的生物性能。评价不同孔径的多孔纳米羟基磷灰石人工骨的骨缺损修复能力,从而筛选出适合的孔径以达到骨传导功能与生物力学性能的良好统一。方法:实验于2005-10/2006-10在深圳市第二人民医院中心实验室完成。①实验材料:纳米羟基磷灰石人工骨以硝酸钙和磷酸二氢铵为原料,采用溶胶-絮凝法制备粉体,运用压力成型、木模成型和浸渍成型分别制得孔隙分布均匀的孔径分别为50～150μm、100～250μm和300～500μm的多孔纳米羟基磷灰石人工骨。②实验动物:雄性新西兰大白兔60只随机分为植入50～150μm孔径材料组、植入100～250μm孔径材料组、植入300～500μm孔径材料组、空白对照组,每组15只。实验过程中对动物处置符合动物伦理学要求。③实验方法:制备双侧桡骨骨缺损动物模型,然后用3种不同孔径的纳米羟基磷灰石人工骨材料植入骨缺损处进行修复,空白对照组不植入任何材料。④实验评估:术后4,8和12周分别行大体标本观察、X射线片观察、扫描电镜观察及生物力学测试,比较各组材料修复骨缺损的能力。结果:实验动物均进入结果分析。①X射线片检查结果:术后4周、8周、12周,植入100～250μm孔径材料组X射线评分高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。②生物力学检测结果:术后4周、8周、12周,植入100～250μm孔径材料组生物力学强度高于植入50～150μm,300～500μm孔径材料组,差异有显著性意义(P<0.05)。③扫描电镜观察结果:植入100～250μm孔径材料组成骨效果明显优于植入50～150μm,300～500μm孔径材料组和空白对照组。结论:纳米羟基磷灰石人工骨具有良好的成骨能力,但其骨修复能力受孔径因素的影响,孔径100～250μm的纳米羟基磷灰石人工骨材料成骨能力较好。     

Guidelines for setting up an external quality assessment scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting.

Blood smear analysis is a well-known technique in medical laboratories. The clinical relevance of this analysis and its interpretation are very important. Consequently, monitoring of laboratory performance by an external quality assessment scheme is strongly recommended. This article represents a very practical guidance document for External Quality Assessment Scheme (EQAS) organizers for setting up blood smear schemes. In the first part of the guidelines, the Hematology Working Group of the European External Committee for External Quality Assurance Programmes in Laboratory Medicine (EQALM) published practical information for the preparation of blood smears for use in an EQAS. Part II focuses on aspects such as survey preparation, statistical evaluation and reporting, and describes particular details for organizing blood morphology EQA surveys by means of virtual microscopy.     

异硫氰酸荧光素标记动态观察天花粉蛋白对黑色素瘤B16细胞的损伤

目的:应用异硫氰酸荧光素标记天花粉蛋白,在激光共聚焦显微镜下直接观察天花粉蛋白进入黑色素瘤B16细胞的动态过程并分析其对黑色瘤B16细胞的损伤作用。方法:实验于2003-08/2004-08在南通大学神经再生重点实验室完成。将常规传代培养的黑色素瘤B16细胞用胰酶消化,以5×109个/L的浓度种植于24孔培养板。将天花粉蛋白、异硫氰酸荧光素-天花粉蛋白、异硫氰酸荧光素-牛血清白蛋白分别加入培养细胞中,终浓度为50mg/L,同时加入等量生理盐水作为正常对照组,每组再分别设3,6,12h不同孵育时间组。异硫氰酸荧光素标记天花粉蛋白后,利用激光共聚焦显微镜观察异硫氰酸荧光素-天花粉蛋白进入细胞的过程及其荧光强度,CCK-8细胞毒性实验评估各组细胞存活率、并用单细胞凝胶电泳及hoechst33258染核观察天花粉蛋白对黑色素瘤B16细胞致DNA损伤作用。结果:①终浓度50mg/L的异硫氰酸荧光素-天花粉蛋白孵育3h时已经进入黑色素瘤细胞,6h时进入细胞量达到最高,12h时已轻度下降,各时间点比较差异有统计学意义(P<0.01)。异硫氰酸荧光素-天花粉蛋白组与异硫氰酸荧光素-牛血清白蛋白组荧光强度差异有显著性(P<0.01)。②终浓度50mg/L异硫氰酸荧光素-天花粉蛋白、天花粉蛋白孵育黑色素瘤细胞3,6h后利用单细胞电泳和Hoechst33258染色未观察到核形态的变化;但孵育6h后CCK-8细胞毒性实验显示活细胞数量明显下降;孵育12h后出现DNA损伤的特征性彗星尾现象,并观察到明显的核浓缩和边集现象,出现特征性凋亡小体。结论:孵育6h时天花粉蛋白进入细胞量最多,但并没有明显的细胞DNA损伤的作用,而孵育12h时产生明显的细胞毒作用和凋亡的发生。     

上海市0～6岁小儿佝偻病的现状调查

目的:了解上海市小儿佝偻病的现状及影响因素。方法:2005年春季以整群和分层随机抽样法抽取上海市部分城区0～6岁小儿821名,采取问卷调查方法了解小儿的生活环境、饮食习惯、户外活动、营养状况、既往疾病史及母亲的妊娠情况等。佝偻病的诊断以1996年国家卫生部颁布的"婴幼儿佝偻病防治方案"为诊断标准。结果:取得完整有效资料769名,其中男童396名,女童373名;集居儿童456名,散居儿童313名。①小儿佝偻病患病率为17.3%(133/769),其中男童患病率为17.4%、女童为17.2%。②佝偻病与喂养方式(母乳喂养的患病率为13.0%、混合喂养的患病率为17.5%、人工喂养的患病率为25.2%)、鱼肝油添加(按时添加维生素D的患病率为13.5%、偶加或未加维生素D的患病率为32.5%)、居住环境(居住在市区的患病率为23.6%、居住在郊区的患病率为10.6%;集居儿童患病率为13.8%、散居儿童患病率为22.4%)、户外活动时间(经常户外活动的患病率为12.9%、偶尔户外活动的患病率为31.8%)、反复呼吸道感染(小儿有反复呼吸道感染的患病率为26.9%、无反复呼吸道感染的患病率为12.9%)、母孕期缺钙(母孕期有缺钙的患病率为33.2%、无缺钙的患病率为12.0%)等因素有关(P<0.01)。结论:上海市小儿佝偻病患病率有上升趋势。影响因素与城市环境污染、母乳喂养减少、年轻父母科学育儿知识缺乏等有关。     

Guidelines for blood smear preparation and staining procedure for setting up an external quality assessment scheme for blood smear interpretation. Part I: Control material.

Blood smear analysis is a well known technique in medical laboratories. Clinical relevance of this analysis and its interpretation are very important. Consequently, monitoring of laboratory performance by an external quality assessment scheme is strongly recommended. Most starting external quality organizers set up a scheme for clinical chemistry. Due to a lack of guidance documents, many organizers are reluctant to offer a hematology scheme. This article aims to be a very practical guidance document for external quality assessment organizers for the set up of blood smear schemes.