携VEGFR2靶向超声微泡在肾癌裸鼠模型中的显像研究

目的评价携血管内皮生长因子受体2(VEGFR2)抗体的靶向超声微泡在原位移植裸鼠肾癌模型中的显像效果。方法建立人肾透明细胞癌原位移植裸鼠模型,制备携VEGFR2抗体的靶向微泡(MBV)及携同型抗体IgG的对照微泡(MBC),每只裸鼠分别注射MBV及MBC(顺序随机,注射时间间隔30min)后行超声造影检查,比较注射两种微泡后10min内肿瘤的增强强度,并对肿瘤组织行VEGFR2免疫组化检测。结果超声造影示注射微泡后10s时两种微泡增强强度上升百分比比较差异无统计学意义,注射微泡后1,2,4,6,8,10min时MBV增强强度上升百分比明显高于MBC(P<0.05)。免疫组化显示肾肿瘤血管内皮VEGFR2高表达。结论应用携VEGFR2抗体的靶向微泡与肾癌新生血管内皮靶点特异性结合,能持续增强显像,可作为评价肿瘤新生血管及监测抗血管治疗疗效的重要分子成像方法。     

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.     

纳米级超声造影剂的技术进展

纳米级超声造影剂是指直径〈1000nm的超声造影剂。与微米级微泡相比,纳米造影剂粒径较小,渗透能力极强,可以通过血管内皮间隙,进行病变部位血管外显影。同时因为纳米系统具有一定的靶向能力,将纳米级造影系统与临床治疗相结合可以在肿瘤治疗方面表现出其特定的靶向治疗优势。现就纳米级超声造影剂的特征、国内外制备方法及研究前景进行总结。     

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.     

超声破坏靶向VEGFR2微泡治疗皮下结肠癌移植瘤的实验研究

目的 探讨靶向VEGFR2微泡结合超声辐照治疗结肠癌的效果.方法 将17只VEFGR2高表达的结肠癌皮下种植瘤Balb/C裸鼠模型分为三组:A组5只,为对照组,仅接受超声造影检查和假照;B组6只,空白脂质微泡结合超声辐照;C组6只,载靶向VEGFR2单抗的脂质微泡结合超声辐照,所有模型均用红色荧光蛋白标记.空化治疗前和空化后1周分别行超声造影和荧光摄片检查,测量肿块大小、荧光面积、荧光强度及血管密度,并进行比较.结果 治疗前裸鼠肿瘤长径、荧光面积、荧光强度及血管密度在各组间比较差异无统计学意义(P＞0.05);A组假照后肿瘤长径、荧光面积、荧光强度及血管密度均比假照前增加,差异有统计学意义(P＜0.05);B组辐照后荧光强度及血管密度均较空化前减小,差异有统计学意义(P＜0.05),而肿瘤长径和荧光面积差异不显著(P＞0.05);C组辐照后肿瘤长径、荧光面积、荧光强度及血管密度与辐照前比较均明显减小,差异有统计学意义(P＜0.01);治疗后A、B、C三组各参数两两比较差异有统计学意义(P＜0.05).结论 靶向VEGFR2脂质微泡能增强超声空化对结肠癌的治疗效果.     

携ICAM-1单抗超声造影剂体外评估兔腹主动脉内皮损伤实验研究

目的探讨携ICAM-1 单抗的超声造影剂评价血管内皮损伤的可行性及其价值.方法 FITC标记自制含氟碳声振白蛋白造影剂及携ICAM-1 单抗的靶向超声造影剂.新西兰大白兔8只,高脂饮食建立内皮损伤动物模型后,取兔腹主动脉做冰冻病理切片,随机分两组,分别滴加非靶向造影剂、靶向造影剂,比较两种微泡内皮分布情况及相应荧光染色度的差异.结果靶向造影剂组内皮黏附微泡明显增多,荧光染色较强.结论携ICAM-1 单抗的造影剂微泡可靶向黏附于损伤内皮,据此可评价早期内皮损伤.     

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.     

微泡双重击破效应对裸鼠HepG2肿瘤微血管的损伤作用

目的 研究微泡双重击破效应对裸鼠HepG2移植肿瘤微血管的损伤作用以及对血流灌注的阻断作用.方法 28只皮下荷人类肝癌HepG2肿瘤的裸鼠随机分为3组,超声微泡组经静脉推注脂质微泡0.1 ml并联合空化治疗仪辐照肿瘤3 min,单纯超声组以等量生理盐水代替微泡,单纯微泡组推注微泡时进行超声假照.各组肿瘤治疗前后行超声造影检查,分析肿瘤造影的峰值强度及曲线下面积,最后获取肿瘤标本行光镜观察.结果 超声微泡组肿瘤造影的峰值强度百分比由(26.9±10.9)％下降至(8.2±5.8)％,曲线下面积由1210.4±823.1下降至291.6±255.2,差异有统计学意义(P＜0.05);但两对照组肿瘤治疗前后造影峰值强度及曲线下面积变化均无显著差异.病理观察发现超声微泡组肿瘤血管内皮细胞肿胀、血管断裂,组织间隙内出血、水肿.结论 微泡双重击破效应可造成裸鼠HepG2肿瘤微血管物理损伤和血流灌注显著下降.     

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。     

超声辐照联合微泡转染短发卡状重组质粒诱导裸鼠宫颈癌移植瘤凋亡的研究

目的探讨超声辐照联合微泡对靶向存活素的短发卡状重组质粒（survivin—shRNA）的转染增效作用及其安全性,分析其凋亡诱导效应和增殖抑制作用。方法将荷人宫颈癌（Hela）裸鼠18只随机分为3组,每组6只。1组：质粒＋超声辐照组,注入质粒溶液后予以超声辐照;2组：质粒＋微泡＋超声辐照组,注入质粒及微泡复合物后辐照;对照组：不予任何处理。对组织样本行冰冻切片、组织学检查、转染率检测。采用免疫组化SABC法检测移植瘤增殖细胞核抗原（PCNA）及survivin蛋白在各组肿瘤标本中的表达,测定凋亡指数（AI）和增殖指数（PI）。结果2组的移植瘤内荧光表达率显著高于对照组、1组（P〈0．01）;裸鼠其他器官组织中未观察到基因表达,且未观察到明显的组织损伤;PCNA及survivin蛋白表达下降,AI明显升高,PI明显减少,与对照组及1组比较差异均有统计学意义（P〈0．05）。结论超声辐照联合微泡能显著增强基因转染效率,无明显副作用,联合Survivin—shRNA能明显诱导裸鼠体内肿瘤凋亡,抑制细胞增殖。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Prospects for the control of neglected tropical diseases by mass drug administration

The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In spite of this and other striking successes, mass drug administration programs are faced with major challenges resulting from suboptimal coverage and lack of efficacy. At current suboptimal coverage rates, programs may need prolongation for an extended period, increasing costs and undermining sustainability. Community participation through health education and information appears to be crucial to improve coverage and to achieve sustainability. Implementation of complementary measures, such as vector control, improved hygiene and environmental sanitation, are important to further control transmission and to prevent re-emergence of the infection and, again, may only be achieved effectively through community-based initiatives. To reduce costs and to relieve pressure on the health system, combining neglected tropical disease programs in areas where diseases coexist and integration with existing control programs for malaria, tuberculosis and HIV/AIDS is advocated. The risk of developing drug resistance is of particular concern in view of the lack of alternative drugs, and reduced treatment efficacy due to emerging resistance is evident for the soil-transmitted helminths and onchocerciasis. Given the risk for the development of drug resistance and the need for a high degree of participation, close attention should be paid to the monitoring of the coverage and efficacy of the different program components.     

Bacterial meningitis: an update of new treatment options

The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure <20 mmHg (in particular, external ventriculostomy, osmotherapy and temporary hyperventilation) were effective in a case–control study. Although many experimental approaches were protective in animal models, none of them has been proven effective in patients. Antibiotics, which are bactericidal but do not lyse bacteria, and inhibitors of matrix metalloproteinases or complement factor C5 appear the most promising therapeutic options. At present, vaccination is the most efficient method to reduce disease burden. Palmitoylethanolamide appears promising to enhance the resistance of the brain to infections.     

Prise en charge des entorses externes de cheville : étude clinique préliminaire sur l’efficacité du dispositif Myolux™

Ankle sprains are the most common injury of the musculoskeletal system and are associated with significant societal and economic impacts. It has been proven that classical therapeutic strategies may not be effective in preventing recurrent injuries: the recurrence rates reported in the literature can reach 73%. In order to provide an effective rehabilitation solution, a destabilizing orthosis was developed. This device is equipped with a mechanical articulator reproducing the subtalar mechanics and placed under the heel. In this paper, we present the main results of a preliminary clinical study conducted between 2004 and 2007. All subjects included in this study were treated with the abovementioned orthosis during 10 rehabilitation sessions of 30 minutes each. Data show a relatively low recurrence rate of 12% for the overall population. Moreover, it's of primary importance to note that this satisfactory ratio is largely reduced (3% of recurrence rate) for the 29 patients who performed one training session per month after the 10th initial rehabilitation sessions. Hence, the destabilizing orthosis appears to be an effective solution to prevent recurrent ankle sprains. However, joint protection requires long-term and regular training sessions. This result has motivated the development of a similar device allowing patients to perform training sessions at home. Finally, data obtained in this study are promising awaiting the final results of the comparative, multicentric and independent clinical trials currently managed by the Hospices Civils de Lyon.     

Imaging choices in occult hip fracture

Background: Hip fracture is a common injury, with an incidence rate of > 250,000 per year in the United States. Diagnosis is particularly important due to the high dependence on the integrity of the hip in the daily life of most people. Objectives: In this article we review the literature focused on hip fracture detection and discuss advantages and limitations of each major imaging modality. Discussion: Plain radiographs are usually sufficient for diagnosis as they are at least 90% sensitive for hip fracture. However, in the 3–4% of Emergency Department (ED) patients having hip X-ray studies who harbor an occult hip fracture, the Emergency Physician must choose among several methods, each with intrinsic limitations, for further evaluation. These methods include computed tomography, scintigraphy, and magnetic resonance imaging. Conclusion: We present an evidence-based algorithm for the evaluation of a patient suspected to have an occult hip fracture in the ED. Also outlined are future directions for research to distinguish more effective techniques for identifying occult hip fractures.     

Systematic Reviews Published in the April 2012 Issue of the Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD but monthly online. The April 2012 issue (second DVD for 2012) contains 5045 complete reviews, 2182 protocols for reviews in production, and 17,084 short summaries of systematic reviews published in the general medical literature. In addition, there are citations of 674,000 randomized controlled trials, and 15,400 cited papers in the Cochrane methodology register. The health technology assessment database contains just over 11,000 citations. One hundred and seventeen new reviews have been published in the last 3 months of which 12 have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 6.186. Readers are encouraged to access the full report for any articles of interest as only a brief commentary is provided.     

Platelets,thrombosis, coagulation,and atherosclerosis

When I first got the invitation to join a medical delegation going to Moldova, I thought for a moment that our destination was the fictional country in the old Marx Brothers movie Duck Soup. On further checking, it turns out that entertaining place was called Freedonia. I now know that Moldova is indeed a real country, bordered on the west by Romania and on the other three sides by the Ukraine. It is a proud country, rich with traditions, and its people are warm, giving, eager to learn ways to improve their healthcare system, and deeply appreciative of our attempts to help them in the task.