高效液相色谱法检测氯丙嗪血药浓度

目的　建立反相高效液相色谱法检测抗精神病药氯丙嗪血药浓度。方法　采用惠普 110 0型高效液相色谱仪 ,原装进口BetaBasic C18分析柱 ,检测波长为 2 5 4nm ,柱温 4 0℃ ,甲醇、磷酸铵缓冲液为移动相 ,流速 1ml/min ,乙醚提取处理样本。以安定为内标。结果　批内、批间试验 :RSD <8 9% ;回收率 :92 0 %～ 99 4 %。最低检测限 :10ng。线性方程 :Y =3 9+132 9X ,r =0 9989,线性范围 :2 5～ 75 0ng/ml。结论　该方法快速、简便、正确 ,适合临床药物治疗时血药浓度的监测。     

氯氮平血浓度对白细胞的影响

作者对单用氯氮平治疗27例精神分裂症和1例精神发育迟滞伴发精神障碍的患者，作氯氮手血浓度和白细胞检测。患者均住院，无严重躯体疾病，不服任何升血药。以日本岛津LC－6A高效液们接紫外检测器（SPD－6AV）测定血清氯氟平浓度，批内和批问C．V％均＜10％。28例患者中出23例，女5例。年龄17～56（平均30土11）岁。服氯氟乎1、2、3周末剂员（mg／日）分别为2O3士73、3O3士95和32O士96；血浓度（ng／ml）分别yi346士2O9、548tri31ofi481士22O，白细胞总数（X10’／L）于疗前和疗后1、2、3周末分别为5．9士2．0、8．l土3．2、8．0士2．…     

脑脊液神经蛋白质对临床拟诊Creutzfeldt-Jakob病的早期诊断价值

目的探讨和比较数种神经蛋白质对Creutzfeldt—Jakob病（CJD）的早期诊断价值。方法对14例发病2个月内CJD取脑脊液，采用蛋白捕捉法和酶联免疫试验对总tau蛋白（t-tau）、磷酸化tau蛋白（p-tau）、t-tau蛋白与p-tau蛋白比值（t-tau／p—tau）、S-100β蛋白、14-3—3蛋白及14—3—2蛋白进行定量检测，同时设非CJD痴呆（OD，11例）和无痴呆（ND，18例）的对照组。结果（1）t-tau蛋白：CJD组、OD组和ND组分别是8295、300、161pg／ml。p-tau／t—tau值分别是0．0092、0．2258、0．2471。（2）S-100β蛋白：CJD组、OD组、ND组分别是1．576、0．639、0．239ng／ml。（3）14-3-3蛋白：CJD组、OD组、ND组分别是40．00、2．65、3．10ng／ml。（4）14-3-2蛋白：CJD组、OD组与ND组分别是48．43、14．00、20．50ng／ml。（5）t—taul〉500pg／ml为阈值点，敏感度为84．6％，特异度87．5％，p-tau无诊断意义；（6）S-100β蛋白≥1．626ng／ml为阈值点，敏感度为92．3％，特异度为83．8％；（7）14-3-3蛋白以≥9ng／ml为阈值点，敏感度为86．7％，特异度为86．4％；（8）14—3—2蛋白以≥24ng／ml为阈值点，其敏感度为78．6％，特异度为77．3％。结论脑脊液神经蛋白质检测对散发性Creutzfeldt—Jakob病的早期诊断有一定价值。     

经颈动脉灌注化疗治疗脑胶质瘤

目的研究脑胶质瘤术后经颈动脉灌注化疗的临床效果，探讨药物选择、给药途径及化疗时机等相关问题。方法对212例胶质瘤病人于术岳4～30d经颈动脉灌注盐酸尼莫司门2．5mg／kg，每周1次，3次为1个疗程，4～6周后行第2疗程治疗。结果显效(CR)39例，占18．8％；有效(PR)44例，占20．8％；微效(MR)59例，占27．8％；无变化(NC)61例，d／28．8％；恶化(PD)5例，占2．4％。中位生存期接近100周。结论经颈动脉灌注治疗脑胶质瘤具有疗效好、副作用小、简便、经济、病人愿意接受等诸多优点。     

实验性脑积水脑能量代谢的研究

1．建立脑积水模型：重10～15kg成年健康雄性脑室正常20条杂种狗，随机分为对照组、诱导后3d、8d、4个月4组，各5条。速眠新肌注全麻，穿刺枕大池，注入无菌25％高岭土悬浊液0．3ml／kg诱导脑积水，CT检查证实。     

不同剂量盐酸纳洛酮治疗急性脑梗死的疗效观察

目的探讨应用不同剂量的盐酸纳洛酮治疗急性脑梗死效果。方法随机将急性脑梗死惠者分成3组，对照组用5％GS250ml加血栓通注射液，维生素类和神经保护剂治疗；另两组则加用不同剂量的纳洛酮加入NS250ml内静滴治疗，连用10d；大剂量组：加纳洛酮4．0—8．0mg／d；小剂量组：加纳洛酮1．2～2．0mg／d。结果大剂量组总有效率82．5％，小剂量组总有效率73．3％，都明显高于对照组的53．3％。而且大剂量组显效率60．O％，明显高于小剂量组的39．3％。结论用纳洛酮治疗急性脑梗死安全性好，使用时应及早、足量和持续用药。     

6-羟多巴胺损毁的大鼠纹状体内多巴胺排空与左旋千金藤啶碱引起的旋转关系(英文)

用高效液相－电化学检测器和旋转计数方法检测6－羟多巴胺（6－hydroxydopamine，6－OHDA）损毁大鼠纹状体多巴胺（dopamine，DA)排空与旋转的关系。D1/D2混合性激动剂阿扑吗啡（apomorphine，APO，0．2mg/kg，iP）可使33只大鼠中的20只出现旋转．其中15只旋转强度＞5次／分钟，平均为12．l±5．8次／分钟。D1选择性激动剂SKF38393、D2选择性激动剂LY171555有类似APO的作用。然而，左旋千金藤啶碱（（-）－stepholidine,SPD)仅使14只大鼠出现旋转，其中6只旋转＞5次/分钟，平均为6．41±1．3次/分钟。33只损毁大鼠健测纹状体DA合量平均为9．9±1．1μg/g湿组织，损侧为2．8±2．9μg/g湿组织。旋转＞5次／分钟的大鼠，其健侧和损侧纹状体内DA含量分别为10．1±0．8和0．3±0．1μg/g湿组织。说明纹状体内DA排空程度与旋转行为有密切关系。当损侧纹状体排空小于51％时．APO不能引起任何旋转，而SPD的阈值为88．2％。APO、SKF38393、LY171555和SPD引起＞5次／分钟的旋转，分别需要损侧纹状体内DA排空达96±4％，94±4％，95±4％和98±2％以上。     

甲亢性周期性麻痹94例临床分析

目的：探讨甲亢性周期性麻痹(TPP)的临床特点。方法：对94例TPP临床资料进行回顾性分析和总结。结果：中国北方人TPP发生率占同期住院甲亢患者的5．8％，男女比例93：1，21～40岁为发病高峰年龄，肌无力发作期97．6％(80／82)的病例血钾低于正常。结论：中国北方人住院甲亢患者了PP发生率为5．8％，98．9％7PP为男性青年；低钾性周期性麻痹是其最常见临床类型。     

星形细胞瘤生物学行为特征及机理探讨

目的：阐明星形细胞瘤生物学行为特征及形成机理。方法：①根据CT影像学对52例星形细胞瘤瘤周水肿厚度进行分级：一级：<20mm；二级：20～40mm；三级：>40mm。②电镜对照观察6例瘤体、水肿区和正常脑组织的血脑屏障超微结构。③光镜观察3例瘸体及水肿组织的连续切片。④免疫组化方法检测52例星形细胞瘤、18例瘤周水肿组织、11例腔质增生的p53、CerbB-2/neu、PCNA表达，结果：①水肿级别与瘤体及水肿区的血脑屏障改变程度呈正相关；瘤体及水肿组织连续切片可见瘤体各8部位分化不一致；水肿区可见瘤细胞最润，水肿越明显．浸润越明显．水肿不明显，未见瘤细胞浸润。②星形细胞瘤p53、CerbB-2／neu、PCNA异常表达率分别为46．2%（24／52)、38．5％(20/52)和77％（40/52)；瘤周水肿组织分别为：44．4％（8/18)、0和72．2％(13/18)。与正常组织对比P值分别为：00169、0．044和<0．001；00251、1和0．003。其表达率与病理级别、分化程度、水肿分级有关。病理Ⅲ、Ⅳ级阳性率80％(16/20)、40％(8／20)、100％(20/20)；Ⅱ级：33.3％(8/24)、50％(12/24)、83.3％(20/24)；Ⅰ级阳性率均为0，Ⅰ与Ⅱ比P值为：0.1522、0．0302、0；Ⅰ与Ⅲ、Ⅳ比P值为：0．0002、0.0628、0；Ⅱ与Ⅲ、Ⅳ比P值为：0．0199、0．5071、0．1651。水肿一级阳性率：0、0、14．2％（1/7)。二级：31.6％(6/19)、31.6％(6/19)、68．4％(13/19)：三级：69.2％(18／26）、53．8％(14／26)、100％(26/26)，一级与二级比P值为：0.1456、0．1456、0.0261；一级与三级比：0.0015、0.026、0；二级与三级比：0．001239、0.1376、0．0084。FCNA表达与CerbB-2/neu表达无一致性．P>005，③11例胶质增生有1例显示p53表达，CerbB-2／neu、PCNA无表达，随访3年，病变复发。术后病理诊断星形细胞瘤Ⅱ级，同时CerbB-2，neu表达，PCNA高指数，瘤周出现水肿。结论；①水肿的产生与p53、CerblB-2/neu、PCNA异常表达引起瘤体、瘤周血脑屏障改变有关，而肿瘤侵袭与水肿有关。水肿区是瘤细胞侵袭扩散实际范围．其增生的胶质细胞也具有恶性表型。②p53、CerbB-2／neu、PCNA异常表达与肿瘤发生发展有关，可作为肿瘤恶性程度及预后指标，p53主要影响肿瘤的分化。p53对预测早期癌症有帮助。③肿瘤起动基因可能来自分化调节基因，而肿瘤的异常分化又可能引发其它相关的异常表达，构成肿瘤发生发展的多击中过程，作在此基础上，提出肿瘤生物学行为所遵守的可能法则。     

HPLC检测红细胞内氯氮平浓度

采用反相ＨＰＬＣ紫外检测法测定红细胞内氯氮平浓度。批内及批间回收率为９７．０８～１０２．１０％，ＣＶ为２．０４～３．４６％，最低检测浓度６１．２ｎｍｏｌ／Ｌ。本法操作简便，准确性高。经间接换算法验证，相对偏差〈３．６％。     

高效液相色谱法测定血清氯氮平药物浓度

目的 建立一种简便、快速、灵敏的反相高效液相色谱(HPLC)紫外检测法测定血清氯氮平药物浓度.方法 选用C18柱,波长254nm,移动相为甲醇∶乙腈∶水∶正丁胺∶冰乙酸(16∶36.5∶47.5∶0.5∶1,调PH8.0),流速1.0ml/min,以乙醚为萃取液.结果 氯氮平保留时间为(3.74±0.02)min,日内...     

Analysis of glutamine, glutamate, pyroglutamate, and GABA in cerebrospinal fluid using ion pairing HPLC with positive electrospray LC/MS/MS

A simple and sensitive method for the separation and quantitation of glutamine, glutamate, pyroglutamate, and gamma-aminobutyric acid (GABA) in cerebrospinal fluid (CSF) is presented. The method utilizes ion pairing with heptafluorobutyric acid (HFBA) to achieve HPLC separation with detection by positive ESI LC/MS/MS. The method does not require extraction or derivatization, utilizes a heavy labeled internal standard for each analyte, and allows for rapid throughput with a 5 min run time. The method was developed with particular attention taken to prevent conversion between analytes known to occur under certain conditions. The lower limit of quantitation is 7.8 ng/ml for all analytes, and the intra-day and inter-day accuracy (%RE) and precision (%R.S.D.) are defined for all analytes. The method was developed as a sensitive, selective, and robust method to investigate the excitatory and inhibitory neurotransmitters (glutamate and GABA) as biomarkers in drug development.     

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

Background

The effect of reactive oxygen species (ROS) on platelet function in coronary heart disease (CHD) is complex and poorly defined. Platelet aggregation studies in healthy volunteers have demonstrated contrasting results when platelets are exposed to ROS. We investigated the effect of ROS on whole blood aggregation (WBA) and the endothelial cell-platelet interaction in patients with CHD.

Methods and Results

ROS generated by xanthine and xanthine oxidase caused a concentration-dependent inhibition of WBA in blood from healthy donors and patients with CHD. In patients with CHD, 100 μM xanthine and 100 mU/ml xanthine oxidase inhibited WBA in response to 3 μg/ml collagen by 28.9% (95% CI 15.9%-41.8%, p < 0.001) and in response to 5 μM ADP by 36.0% (95% CI 9.6%-62.4%, p = 0.005). Using nitrotyrosine expression, platelets isolated from patients with CHD were found to be susceptible to peroxynitrite damage. The addition of 1 × 10⁵ cultured endothelial cells inhibited WBA in response to 3 μg/ml collagen by 31.2% (95% CI 12.2%-50.2%, p < 0.05) and in response to 5 μM ADP by 31.6% (95% CI 2.5-60.7%, p < 0.05). Addition of xanthine and xanthine oxidase did not alter this effect, however pre-treatment of endothelial cells with a nitric oxide synthase inhibitor (L-NAME) partly reversed the inhibition.

Conclusion

ROS inhibit WBA in blood from patients with CHD. Whilst endothelial cells also inhibit WBA, the effect is attenuated by L-NAME, suggesting that nitric oxide is likely to remain an important protective mechanism against thrombosis in CHD.     

Microbore liquid chromatography with UV detection to study the in vivo passage of compound 21, a non-peptidergic AT₂ receptor agonist, to the striatum in rats

A microbore liquid chromatography method coupled to UV detection was developed and validated in order to monitor the passage of compound 21 (C21), a non-peptide angiotensin II type 2 receptor agonist, to the striatum of rats. For this purpose, sampling from the striatum was performed using the in vivo microdialysis technique. Separations were performed on a C₁₈ microbore (1 mm i.d.) column using gradient elution. The retention time for C21 was found to be 6.3 min. The calibration curve was linear between 10 and 200 ng/ml with a correlation coefficient ≥0.999. The limit of detection and the limit of quantification were 3 and 10 ng/ml respectively. The intra-day and the inter-day precision (RSD%) ranged between 0.5 and 4.6% with an average recovery of 101.5 ± 10.0% (mean ± SD, n = 15). In vivo experiments were performed on rats to measure the concentration of C21 in striatal dialysates after intraperitoneal (10 or 50 mg/kg) or intravenous injection (10 mg/kg or 20 mg/kg) of C21 and suggest minimal passage of the compound to the striatum.     

血管内治疗后循环动脉瘤（附24例分析）

目的总结后循环动脉瘤的血管内治疗经验。方法回顾性分析采用血管内栓塞治疗24例后循环动脉瘤的临床资料。入院时Hunt-Hess分级：0级3例,Ⅰ级8例,Ⅱ级6例,Ⅲ级5例,Ⅳ级2例。支架辅助弹簧圈栓塞4例,单纯弹簧圈栓塞20例。结果动脉瘤达致密栓塞（99%～100%）13例,大部分栓塞（90%～98%）8例,部分栓塞（〈90%）3例。随访6～22个月,平均9.2个月;GOS5分16例,4分5例,3分2例,2分1例,无再出血发生。结论血管内栓塞是后循环动脉瘤安全而有效的治疗方法。     

Assessment of the performances of AcuStar HIT and the combination with heparin-induced multiple electrode aggregometry: A retrospective study

Background

Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods.

Objectives

We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis.

Methods

Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n = 81). The clinical diagnosis was established by analysing in a standardized manner the patient’s medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference.

Results

Using the recommended thresholds (1.00 AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89 AU, HIT-Ab: 9.41 AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed.

Conclusion

Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV.     

免架测量定位排空器治疗高血压性脑内血肿

采用脑内血肿排空器及颅骨钮技术.以 CT片为依据免架测量定位行高血压性脑内血肿排空治疗Ⅲ例共112次;壳核区83例.丘脑4例.皮质下20例.小脑2例.胼胝体膝、纵裂各1例: 体积21～50ml 51例51～100 ml 42例.101～150 ml12例.>150ml 4例.以上共有27例同时破入脑室;2例小脑血肿<20ml.排空率>81%者73次、61%～80%者29次,51%～60%者10次: 手术病死率按病情统计.Ⅲ级为3%.Ⅳ级为12. 5%.Ⅴ级为69;Ⅲ、Ⅳ级合计为9.2%.Ⅲ、Ⅳ、Ⅴ级合计为16.2% 病死率按手术与发病时间分别统计为6h内含者62.5%.7～12h者25%.13～24h者10%.2～3d者11.6%.4～14d者11%.76例术后随访2～6O个月.2例呈植物状态.17例因其它原因死亡,57例恢复良好.     

转染SV40永生化基因对正常成人肝细胞生长特性的影响

背景：生物型人工肝采用猪肝细胞或肝癌细胞作为移植物来源存在动物源性疾病和致瘤性的担心,而正常成人肝细胞也具有一定的局限性。 目的：通过检测转染前、后正常成人肝细胞的活率、生长曲线和细胞周期的变化,了解转染SV40永生化基因对正常成人肝细胞生长特性的影响。 方法：培养不同时间的正常人肝细胞和永生化正常成人肝细胞,采用胎盘蓝染色和AO-PI染色,于培养后1~8 d采用MTT染色法计数细胞活率;用MTT比色法测定细胞的A值并绘制生长曲线;采用流式细胞术检测细胞的生长周期。 结果与结论：3种染色法检测显示两种细胞的活率为95%~99%,存活率无明显差异。转染前、后的两种正常成人肝细胞的生长曲线无明显差异,均在培养 3~5 d时呈指数型生长,但转染后正常成人肝细胞较转染前增殖略快。采用流式细胞术测得的两种肝细胞的细胞周期：转染后肝细胞S期细胞占65.64%,G0~G1期细胞占34.36%,G2期细胞占0%;转染前肝细胞S期占21.27%,G0~G1期细胞占62.64%,G2期细胞占12.09%,提示转染后肝细胞的S期细胞明显增多,增殖能力增强。转染SV40永生化基因的正常成人肝细胞较转染前细胞的增殖活力增高,存活率无明显差异,提示转染后细胞增殖能力更强。     

Development of a radioimmunoassay for oxytocin and measurement of oxytocin in the spinal cord and brain of rats

A specific radioimmunoassay for oxytocin and its application to measurements of the contents of oxytocin in the spinal cord and several regions of the brain of rats are described. Antiserum to oxytocin was produced in rabbits immunized with synthetic oxytocin - bovine serum albumin conjugate emulsified in complete Freund's adjuvant. Oxytocin was labelled with ¹²⁵I by the chloramine T method, and the labelled hormone was purified by gel filtration on a Sephadex G-25 column. The double antibody method was used for separation of antibody-bound oxytocin from free oxytocin. The range of the assay was 5–1000 μIU/ml, and the cross-reactivities with arginine- and lysine-vasopressin were less than 0.1%. The intra- and inter-assay coefficients of variation were 3.0–5.1% and less than 11.3%, respectively, and the mean recovery rate was 102.5%.

Each segment of the spinal cord was found to contain oxytocin, but the content in the lumbosacral segment (1040 ± 196 μIU/mg protein) was significantly higher than those in the cervical and thoracic segments (370 ± 98 and 650 ± 140 μIU/mg protein, respectively). Significant amounts of oxytocin were also found in extrahypothalamic regions of the brain, such as the midbrain, pons and medulla oblongata.     

Intramuscular Absorption of Carbamazepine in Rhesus Monkeys

The intramuscular absorption characteristics of carbamazepine were investigated in a group of six chair-adapted rhesus monkeys from three parenteral formulations [A:100 mg/ml of carbamazepine in PEG-400; B:50 mg/ml of carbamazepine in PEG-400; and C:50 mg/ml of carbamazepine in a PEG-400-Tween-80 mixture (9:1)]. The absolute bioavailability was determined by administering formulations A or B intravenously. The kinetic profiles obtained after intramuscular administration suggested biphasic absorption in the majority of animals: an initial rapid absorption phase yielding peak concentrations in less than 1 hr followed by a slower phase where absorption was probably rate limiting. The absolute bioavailability was 38% from formulation A, 81% from formulation B and 82% from formulation C. In two of four cases, Tween-80 eliminated the rate-limiting absorption phase. The data suggest that an intramuscular formulation of carbamazepine with acceptable bioavailability may be feasible.