比较两种制备载紫杉醇超声微泡的方法

目的 比较能被超声击破的两种载紫杉醇超声微泡的制备方法,并评价其理化性质以及超声散射强度.方法 用单纯紫杉醇法Ⅰ号和三醋酸甘油酯溶解法Ⅱ号分别制备载紫杉醇脂质超声微气泡,测定其包封率、载药量、粒径大小、分布和Zeta电位、pH值,并行超声击破试验及兔VX2皮下肿瘤显像试验. 结果两种微泡显像无明显差异,可被低能量超声击破,但Ⅱ号(加入三醋酸甘油酯)脂质微泡较Ⅰ号(常规冷冻干燥法制备)载药微泡粒径显著减小[(1.07±0.38)μm vs(2.79±0.41)μm,P<0.01],表面电位增高[(19.10±0.32)mV vs (-5.90±0.21)mV,P<0.01],包封率和载药量显著增高[(95.00±1.22)% vs (36.10±4.74)%,P<0.01;(5.60±0.11)% vs (0.50±0.04)%, P<0.01]. 结论 三醋酸甘油酯溶解法制备的Ⅱ号微泡在局部药物释放中具有更大的应用价值.     

载诺帝脂质微泡的制备及特性的实验研究

目的 制备载诺帝(去甲二氢愈创木酸)脂质微泡并测定其包封率、载药量及观察其体内超声显像效果.方法 采用机械振荡法制备载诺帝脂质微泡,测定其粒径大小、分布和Zeta电位、包封率、载药量;超声造影观察其在兔肝内的显像效果.结果 载药脂质微泡的浓度为(2.53±0.52)×109个/ml,粒径为(2.61±0.32)μm,Zeta电位为+(17.52±2.04)mV;脂质微泡诺帝的包封率(27.1±2.01)%,载药量为(10.9±0.90)%;微泡经外周静脉注射后,兔肝可见良好、持续的增强显像效果.结论 采用机械振荡法可以成功制备携带诺帝的脂质微泡,微泡可以通过肺血管床,符合静脉注射要求,在家兔体内获得了良好的显像效果.     

冷冻干燥法制备载紫杉醇脂质微泡的实验研究

目的 探讨冷冻干燥法制备载紫杉醇脂质微泡的可行性,并对其质量和安全性进行评价.方法 采用冷冻干燥法制备携带紫杉醇的脂质微泡,在光学显微镜和荧光显微镜下观察其形态、大小以及紫杉醇在微泡上的定位,用血球计数板、激光粒度分析仪和pH计测定其浓度、粒径及分布、表面电位、pH值,通过反相高效液相色谱法检测包封率,锥虫蓝排斥试验观察载紫杉醇脂质微泡对血管平滑肌细胞的毒性作用.结果 载紫杉醇脂质微泡的粒径为2～10μm,平均粒径(2.79±0.14)μm,浓度为(7～8)×109/mL,表面电位为(-5.9±0.21)mV,pH值为5.54±0.18,包封率为(36.1±4.74)%,对血管平滑肌细胞无毒性作用.结论 采用冷冻干燥法可成功制备携带紫杉醇的脂质微泡,其粒径大小符合静脉注射要求,体外细胞毒性试验证实该载药脂质微泡的安全性.     

载药脂质微气泡的制备及其应用

目的制备载紫杉醇脂质微气泡并测定其包封率、载药量、药物释放及观察其体内超声显像效果。方法制备载紫杉醇脂质微气泡,测定其包封率,载药量,粒径大小、分布和Zeta电位;观察苏丹黑对脂质微气泡的染色,以及超声辐照后苏丹黑的释放情况;观察辐照后载药脂质微气泡各层溶液药物的释放;并观察其在小鼠肝内的显像效果。结果载药脂质微气泡的浓度为2.3×109~3.5×109/ml,粒径范围为90%以上2~6μm,平均粒径为2.95μm。脂质微气泡紫杉醇的包封率大于90%,载药量为(26.5±0.7)%;Zeta电位为-(21.8±1.1)mV;苏丹黑染色后光镜下可见微气泡壁被染成黑色,超声辐照后微气泡稀释液变黑,并且超声辐照载药脂质微泡溶液后,上层和中间层的药物释放明显增加;静脉注射此载药微气泡后,小鼠肝可见良好、持续的增强显像效果。结论采用机械振荡法制备的紫杉醇脂质微气泡,包封率和载药量均较高,粒径分布好,体内显像效果好,超声辐照能促使微泡中的药物释放,有望实现实时监控下的体内定点靶向给药。     

载10-羟基喜树碱脂质超声微泡的处方制备及一般特性研究

目的 研究载10-羟基喜树碱(HCPT)脂质超声微泡的处方制备工艺,筛选出最佳处方制备载药微泡,研究微泡的一般特性及显影效果,并检测微泡的药物包封率和载药量.方法 以机械振荡法制备载HCPT脂质超声微泡;采用正交试验优选处方;采用紫外分光光度法和反相高效液相色谱法测定微泡的包封率和载药量;在光学显微镜下计数并观察微泡的外观和分布情况;以马尔文激光粒径测量仪测量微泡粒径大小和Zeta电位;观察并比较微泡经60Co射线灭菌前后其外观、形态、平均粒径和包封率的改变;并观察微泡在兔肝脏的增强显影效果.结果 以最佳处方制备的载10-羟基喜树碱(2 mg)微泡的药物包封率为86.70%,载药量为21.70%;浓度为(3.07±0.58)×109/ml,粒径范围为(1.10±0.20)μm,平均粒径为1.10 μm;Zeta电位为-(3.90±0.80)mV;超声定向辐照微泡后,药物吸光度值明显增加;经60Co射线灭菌后观察微泡形态、平均粒径及包封率无明显变化;静脉注射此载药微泡后,兔肝脏超声显影持续增强.结论 采用机械振荡法制备的载HCPT脂质微泡,包封率和载药量较高,粒径分布均匀,体内显影效果好,有望实现实时监控下的体内定点靶向给药,为进一步研究奠定了基础.     

载多西紫杉醇脂质微泡超声造影剂的制备及其性质

目的 制备载多西紫杉醇脂质微泡并测定性质及观察其体内显像效果.方法 制备载多西紫杉醇脂质微泡,测定粒径、包封率等性质;观察60Co射线灭菌前后微泡性质的差异,观察超声辐照后载药微泡药物的释放,并观察其对兔VX2肝癌的显像效果.结果 载多西紫杉醇微泡的浓度为2.2×109～3.2×109个/ml;粒径分布范围为473.4～706.6 nm,平均粒径为623.1 nm;微泡的包封率为70%以上,载药量为(17.5±0.8)%;Zeta电位为-(3.1±0.9)mV;超声辐照微泡溶液后,药物可释放;静脉注射此微泡后,兔肝实质见良好、持续的增强显像,肝癌病灶可见明显的"快进快出"显影表现.结论 载多西紫杉醇脂质微泡包封率较高,性质较佳,体内显像效果好,提高了超声在肝癌等肿瘤诊断中的价值,超声辐照能促使微泡中的药物释放,有望在实时监控下体内定点靶向给药,实现对肿瘤的靶向治疗.     

载血卟啉脂质微泡的制备及一般特性的实验研究

目的 制备一种载声动力药物的脂质超声微泡并测定其包封率、粒径大小、观察其体内超声显像效果.方法 采用机械振荡的方法制备载血卟啉的脂质超声微泡,用荧光分光光度仪测定其包封率,用倒置显微镜及马尔文激光粒径测量仪测量粒径大小、分布和Zeta电位;观察60Co射线灭菌前后造影剂外观、形态、浓度和平均粒径的改变,并观察其在兔肝内的显像效果.结果 载药脂质微泡的浓度为(3.24±0.79)×109/ml,粒径范围为1.5～5.3μm,平均粒径为(2.84±0.4)μm;脂质载血卟啉(1mg)微泡的包封率为(30.25±4.45)%;Zeta电位为-(15.4±2.4)mV.经60℃射线灭菌后观察微泡形态、粒径及包封率无明显变化,其平均粒径大小及包封率分别为(2.24±0.3)μm,(27.39±2.91)%.静脉注射此载药微泡后,小鼠肝脏可见良好、持续的增强显像效果.结论 采用机械振荡法制备的载血卟啉脂质微泡,包封率较高,粒径分布均一,体内显像效果好,有望实现实时监控下的体内定点靶向给药.     

载紫杉醇靶向超声脂质微泡对于卵巢癌细胞体外存活率的实验研究

目的制备一种载紫杉醇的靶向相变型纳米级超声造影剂,并评价其一般特性。方法薄膜水化法、乳化法制备载紫杉醇的非靶向相变型脂质纳米粒(PTX-LNP),通过生物素-亲和素法将生物素化的促黄体生成素释放激素(LHRH)连接于非靶向相变型脂质纳米粒制备载紫杉醇的LHRH靶向相变型脂质纳米粒(PTX-LNP-LHRH),于观察室温下PTX-LNP-LHRH的形态,载药量及包封率,致人卵巢癌OVCAR3细胞的凋亡率。结果 PTX-LNP-LHRH的平均粒径为(303±57.76)nm,载药量及包封率分别为(13.37±0.95)%和(80.72±5.19)%,OVCAR3细胞的存活率随各组培养时间延长而下降。空白微球组的细胞存活率均90%。提示该组对细胞活性影响较小。而靶向组联合低强度聚焦超声组(PTX-LNP-LHRH+LIFU)的细胞存活率最低,与其他实验组比较,差异具有统计学意义(P0.05)。结论成功制备外接LHRH的载药微泡,并且不影响紫杉醇的载药量及包封率,靶向造影剂组的卵巢癌细胞凋亡率显著增高,且差异均具有统计学意义(P0.05)。     

机械振荡法制备激肽原酶载药微泡的实验研究

目的:探讨机械振荡法制备激肽原酶载药微泡的最佳参数。方法:机械振荡法制备激肽原酶载药微泡,利用不同的振荡时间,激肽原酶与微泡不同的混合比例,检测载药微泡的携带率、激肽原酶的效价、载药微泡的粒径及粒径分布、浓度、pH值、包封率。结果:振荡时间在45 s,载药微泡携带率最高,为(93.46±1.7)%。激肽原酶与微泡混合比在4∶1的条件下,激肽原酶效价最高且达到合格标准。载药微泡的表面电位为(-56.47±8.23)mV,平均粒径为(13.2±7.3)μm,粒径范围为6~20μm,浓度为(6~7)×108/mL,pH值为(6.20±0.01),包封率为(52.5±0.8)%。结论:采用机械振荡法可成功制备激肽原酶载药微泡,该载药微泡药物携带率高,稳定性较好,且能维持良好的药物效价。     

载竹红菌素脂质微泡的制备及对兔VX2肝肿瘤的显影实验

目的 制备一种载光动力药物的脂质超声微泡,测定物理特性,并观察其对兔VX2肝肿瘤的显影效果及过程.方法 采用机械振荡的方法 制备载竹红菌素脂质微泡,并测定其粒径大小、分布、Zeta电位和包封率、稳定性及超声辐照后药物释放情况.采用不同超声模式观察微泡在兔VX2肝肿瘤的显像效果及过程.结果 载药微泡的粒径为(1052.4±322.7)nm,Zeta电位为 (21.1±7.4)mV,包封率为(88.1±4.6)%,超声辐照能够促使微泡释放药物,对兔VX2肝肿瘤的显影效果好.结论 载竹红菌素脂质微泡包封率高、微泡能够释放药物、显像好,符合理想的药物载体,为实时监控下的体内定位光动力治疗疾病提供了一种新的思路.     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.     

手转胎头术失败的原因与分娩结局临床分析

目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4％(55/72)]明显高于成功组[31.7％(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3％(42/72)]高于成功组[38.1％ (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9％ (28/72)]高于成功组[23.8％(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大＜6 cm、胎头位于坐骨棘上及宫口开大8～10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1％(44/72)]高于成功组[38.9％(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2％(52/72)]明显高于成功组[34.1 ％(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.     

Evidence-Based Pain Management and Palliative Care in Issue Four for 2009 of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly. Issue 4 for 2009 contains 4027 complete reviews, 1906 protocols for reviews in production, and 11447 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 600,000 randomized controlled trials, and 12,200 cited papers in the Cochrane methodology register. The health technology assessment database contains over 7500 citations. This edition of the Library contains 90 new reviews, of which 19 have potential relevance for practitioners in pain and palliative medicine.     

Wie zuverlässig sind Angaben zu nichtentzündlichen ausgedehnten Schmerzen?

ZusammenfassungFragestellung Es wurde geprüft, wie sich der Differenziertheitsgrad zweier Schmerzmessmethoden auf Angaben zur Ausgedehntheit klinischer Schmerzen auswirkt. Zugleich wurde der Referenzzeitraum variiert, über den die Patienten berichten sollten.Methode Erfasst wurde der Einfluss zu Lasten der Befragungsdifferenziertheit durch den Vergleich zweier Körperschema-Bildvorlagen. Drei Referenzzeiträume (Schmerz aktuell, letzte Woche, letztes halbes Jahr) wurden vorgegeben.Ergebnisse Patienten mit ausgedehnten Schmerzen gaben bei differenzierter Befragung um so mehr Schmerzen an, je weiter die Schmerzen zurück lagen und je größer der Berichtszeitraum war. Patienten mit gelenknahen Schmerzen gaben bei hoch differenzierter Befragung weniger ausgedehnte Schmerzen in der Vergangenheit an als bei globaler Einschätzung. Patienten mit Rückenschmerzen berichteten bei differenzierter Befragung zum aktuellen Schmerz über weniger ausgedehnte Schmerzen als bei globaler Befragung.Schlussfolgerung Die Angaben zur Schmerzausdehnung variieren vor allem bei Patienten mit ausgedehnten Schmerzen in Abhängigkeit von der Differenziertheit der Befragung. In diesen Fällen ist die Wahrscheinlichkeit erhöht, dass sich die Beschwerdesymptomatik zumindest teilweise erst in der Reaktion auf die situativen Befragungsbedingungen konstituiert und daher nicht auf andere Befragungsbedingungen generalisiert werden kann.