纳米级超声造影剂的研究进展

随着超声分子成像技术和生物纳米技术的迅猛发展,近年来出现了多种纳米级超声造影剂,包括纳米级脂质体造影剂、纳米级氟烷乳剂和纳米级微泡造影剂。本文就纳米级超声造影剂的研究背景、研究现状、现存的问题及发展前景做一综述。     

纳米级超声造影剂制备及成像的实验研究

目的 探讨纯度较高的纳米级超声微泡造影剂的理化性质及体内成像效果.方法 机械振荡法与低速离心法结合制备纳米级微泡,观察微泡形态,检测其平均粒径,并观察其增强正常兔肝显影的情况,并与微米级微泡造影剂进行比较.结果 光镜以及透射电镜观察,微泡呈圆形,分布均匀,无聚集现象.Zeta SIZIER 3000测定微泡粒径均值为623.4 nm,微泡表面电位均值1.3 mV.注射纳米级造影剂于新西兰大白兔体内能持续增强肝的显像效果,与微米级造影剂对比无明显差异.结论 纳米级的微泡造影剂大小合理,分布均匀,显像效果强,为下一步研制小型化靶向造影剂奠定了基础.     

自制纳米级超声微泡体外基本特性和肿瘤造影增强显影的实验研究

目的 探讨自制纳米级超声微泡的体内基本特性及体内造影增强显影效果.方法 机械振荡与低速离心法结合制备纳米级微泡,并对微泡粒径大小、分布、微观形态和稳定性进行研究.同时在裸鼠肝、肾及前列腺癌皮下移植瘤进行超声造影实验,与常规微米级造影剂对比造影效果.结果 所制备的微泡形态圆整,大小均一性较好,分布均匀无聚集,平均粒径(580.6±36.3)nm.该纳米级微泡能显著增强裸鼠肝肾及皮下移植瘤显影,与常规造影剂比较,不但增强强度相当,且显影时间显著延长.结论 自制纳米级超声微泡造影剂各项物理特性符合纳米级超声造影剂的要求,体内增强效果和稳定性较强,为下一步纳米级微泡在肿瘤显像和治疗中的应用提供实验依据.     

超声分子影像学研究进展

随着超声分子探针技术的兴起,超声分子成像成为当前医学影像学研究的热点之一.分子探针的设计是超声分子成像研究的重点和先决条件.靶向超声微泡(球)造影剂在分子影像中的研究、应用,愈来愈受到关注,而多学科的融合使其具有更大的发展空间.     

以HER2为靶点的靶向纳米级脂质微泡超声造影剂的制备及实验研究

目的 制备以HER2受体为靶点的靶向纳米级脂质微泡超声造影剂,并观察其体外寻靶能力及体外超声显像效果.方法 制备生物素化Herceptin单抗,检测其生物素化程度及生物学活性;薄膜水化-声振法制备生物素化纳米微泡,以生物素-亲和素为桥梁制备HER2为靶点的靶向纳米级脂质微泡超声造影剂,观察其对SKOV3卵巢癌细胞的体外寻靶能力及靶向结合的体外超声显像.结果 平均每分子Herceptin单抗可与16个生物素分子结合;与游离单抗相比,生物素化抗体的活性未见明显降低(P＞0.05).体外寻靶实验观察:靶向纳米微泡组SKOV3细胞表面有明显的红染纳米微泡与其牢固结合,沿细胞表面排列较规则;非靶向组SKOV3细胞表面未结合红染的纳米微泡.靶向纳米微泡体外超声显像:细胞爬片与靶向纳米微泡孵育后可明显增强超声显像效果,对照组均未见明显超声显像.结论 应用生物素-亲和素系统成功构建了以HER2为靶点的纳米级超声造影剂,与SKOV3细胞结合后有明显超声显像效果.     

纳米级超声微泡造影剂的制备及其性状的初步研究

目的制备适用于超声诊断的纳米级超声微泡造影剂,并对其性状进行初步研究。方法通过低速离心分级分离法制备纳米级的脂膜超声微泡,检测微泡大小形态、表面电位、粒径、分布,测试其与抗体结合情况,体外初步测试其增强显像效果。结果微泡呈圆形,分布均匀,粒径均值为623.4nm;微泡表面电位均值1.3mV,与抗体结合情况良好,体外初步测试能明显增强显像效果。结论通过低速离心分级分离法可以制备纯度较高的纳米级超声微泡,为超声造影剂的小型化和靶向性发展提供重要的工作平台。     

超声微泡造影剂的肿瘤靶向治疗研究进展

近几年,国内外着眼于靶向微泡造影剂的研究,利用超声波与微泡造影剂的相互作用及所产生的生物学效应,可实现微泡所携带的基因/药物等向目标组织的转移释放,介导肿瘤细胞的凋亡及肿瘤微血管的栓塞阻断等,从而起到靶向治疗的作用。随着各种兼具诊断治疗双重作用的超声探头和靶向微泡造影剂包括纳米级微泡造影剂的研制,以及对超声生物学效应的深入研究,超声微泡介导肿瘤靶向治疗将为临床肿瘤的治疗带来新的希望。     

靶向声学造影技术的研究现状与进展

超声造影剂 (ultrasoundcontrastagents ,UCA)是利用声波对气体反射比液体大近 10 0 0倍的原理 ,使用含气微泡后超声回声增强得到更高的对比分辨力 ,从而有利于疾病的诊断。至今 ,有关超声造影剂的研究已有近 3 0年的历史[1] 。过去几年中 ,靶向微泡的开发已取得可观进展。这种微泡对于靶向病变组织有一定亲和力 ,可以附着于某种疾病的特殊标记物 ,靶向微泡在病变组织的积聚可实现分子和细胞过程的无创性超声成像。本综述主要讨论靶向微泡分子成像的早期实验和对比增强超声分子成像具体应用的靶向方法。一、靶向炎症的对比超声成像血池中…     

纳米级分子靶向超声造影剂的制备及其体外肿瘤靶向性实验研究

目的制备针对肿瘤HER2分子的纯纳米粒径分子靶向超声造影剂,观测其理化特性,并在体外肿瘤细胞中验证其特异靶向性。方法利用改良的薄膜水化法直接制备纯纳米粒径微泡,鉴定其基本理化特性、形态学表现及体外超声造影成像效果;利用"亲和素-生物素法"构建"纳米微泡-Affibody",体外多种肿瘤细胞验证其特异靶向性,同时观察其稳定性。结果直接制备出了纯纳米级微泡,粒径为(498.7±55.0)nm,各项理化特性及超声成像效果良好;新构建的"纳米微泡-Affibody"在体外对多种HER2(+)肿瘤细胞具有特异靶向性。结论 "纳米微泡-Affibody"体外特异靶向性强,稳定性好,为进一步进行体内肿瘤分子靶向超声造影及抗肿瘤分子靶向治疗奠定了基础。     

纳米级造影剂在超声分子显像与靶向治疗中的研究进展

近年来，超声微泡类造影剂及其靶向技术已经在分子显像与靶向治疗领域取得了诸多研究成果。然而，由于微泡类造影剂直径为微米级，不能穿透血管内皮间隙，只能停留在血管内，发生血池内显影，因此限制了它们对血管外病变的探测能力。随着纳米技术与分子生物学的发展，另一类纳米级造影剂正日渐崛起，主要包括液态氟烷纳米粒／乳剂、具有声反射特性的脂质体等。这类造影剂以其分子小、穿透力强的突出特性，将有力地推动超声分子显像与靶向治疗向血管外领域拓展。     

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.     

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.     

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.     

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.