载Fe3O4液态氟碳纳米粒增强磁共振成像的实验研究

目的 制备载Fe₃O₄液态氟碳(Fe₃O₄-PFOB)纳米粒,并探讨其增强磁共振成像效果。方法 采用薄膜-超声法制备Fe₃O₄-PFOB纳米粒,并检测其理化性质。将24只健康SD大鼠随机分为3组:Fe₃O₄-PFOB纳米粒组(静脉注射Fe₃O₄-PFOB纳米粒)、PFOB纳米粒组(静脉注射PFOB纳米粒)及生理盐水组(静脉注射生理盐水)。对各组大鼠于处理后24 h行肝脏MR扫描。扫描完成后取出大鼠肝脏组织,进行HE及普鲁士蓝染色观察。 结果 所得样品为膜壳装载Fe₃O₄、中心包裹液态氟碳的纳米粒,呈球形,粒径(272.9±19.5)nm。注射Fe₃O₄-PFOB纳米粒24 h后,大鼠肝实质信号显著降低,肝脏-肌肉信号比明显减少,与其余两组比较差异均有统计学意义。普鲁士蓝染色可见Fe₃O₄-PFOB纳米粒组大鼠肝实质内有较多蓝色颗粒分布,其余两组染色阴性。HE染色各组大鼠肝脏均未见明显的形态学改变。结论 Fe₃O₄-PFOB纳米粒能有效增强磁共振成像效果,可以用作MRI阴性对比剂。     

载血卟啉单甲醚高分子纳米粒用于光声显像引导下声动力治疗:实验研究

目的 制备一种载血卟啉单甲醚（HMME）的多功能分子探针,评估其体外光声成像及声动力治疗（SDT）效果。方法 采用双乳化法制备载HMME的聚乳酸-乙醇酸（PLGA）纳米粒（HMME@PLGA）,观察纳米粒的基本表征和体外增强光声显像情况,通过流式细胞仪检测人乳腺癌MDA-MB-231细胞与HMME@PLGA共孵育后在超声辐照下产生活性氧的能力,并在细胞水平验证其SDT效果。结果 所制备的HMME@PLGA纳米粒大小均一,形态规则,平均粒径为（333.67±17.50）nm,表面电位为（-10.57±1.98）mV,包封率为75.62%,载药量为2.90%,浓度为1 mg/ml的纳米粒与人乳腺癌MDA-MB-231细胞共孵育24 h的细胞存活率为87.21%。随浓度增加,纳米粒光声信号逐渐增强。经超声辐照,HMME@PLGA纳米粒能使人乳腺癌MDA-MB-231细胞产生大量活性氧,并产生明显细胞毒性作用,使细胞大量死亡,Calcein-AM/PI染色呈红色荧光;通过吖啶橙染色观测到细胞溶酶体结构消失。结论 本研究成功制备了包裹HMME的高分子纳米粒,可实现体外光声成像引导下的SDT。     

一种产气超声/光声双模态纳米粒的制备及性质检测

目的 研制一种包碳酸氢铵溶液的脂质纳米粒,并观察其超声/光声成像效果。方法 采用薄膜水化法加挤出法制备脂质包裹碳酸氢铵溶液的纳米粒,光镜、电镜、激光粒径仪和电位检测仪检测纳米粒一般物理特性,并通过光声成像仪观察其超声/光声成像效果。结果 制备的纳米粒呈圆球形,形态规则,大小分布均匀,无明显聚集,平均粒径为(230.90±54.58)nm,电位为(-22.81±5.75)mV。碳酸氢铵纳米粒有超声/光声信号,双蒸水纳米粒无超声/光声信号。结论 成功制备包碳酸氢铵溶液脂质纳米粒,可用于超声及光声成像,为进一步体外、体内成像实验奠定了基础。     

携IR780碘化物液态氟碳纳米粒造影剂的制备及体外双模态成像

目的 制备携带IR780碘化物的液态氟碳纳米粒（IFNPs）,观察其体外超声/光声双模态成像效果。方法 以羟基端乳酸/羟基乙酸共聚物（PLGA-COOH）、IR780碘化物和全氟戊烷（PFP）为原料,采用双乳化法制备PLGA包裹的纳米粒IFNPs。以光学显微镜、共聚焦显微镜、透射电子显微镜及扫描电子显微镜检测其一般物理特性;以马尔文粒径分析仪分析其粒径大小、分布及表面电位;以紫外分光光度计测定IFNPs中IR780的包封率;观察IFNPs体外光声成像和超声成像的能力。结果 成功制备出IFNPs,其形态规则,大小均一,透射电子显微镜下表现为外壳黑色、内部灰白色的球形结构,扫描电子显微镜显示纳米粒表面光滑。IFNPs粒径为（241.87±3.47）nm,电位为（-0.766±0.096）mV,IR780包封率为（90.38±0.48）%。随IFNPs浓度增加,体外光声成像及超声成像效果均显著增强。结论 携带IR780碘化物的液态氟碳纳米粒造影剂制备成功,可用于体外超声/光声双模态成像。     

载单宁酸铁和紫杉醇相变型纳米粒用于体外超声显像及治疗视网膜母细胞瘤

目的 制备可用于早期诊断和治疗视网膜母细胞瘤（Rb）的纳米粒，体外评价其超声显像和治疗效果。方法 制备载单宁酸铁（Fe^ⅢTA）和紫杉醇（PTX）并包裹全氟戊烷（PFP）的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒，检测其粒径、电位、电镜、吸光度、包封率、载药量等相关表征，评估808激光（1 W/cm²，5 min）辐照前后温度变化和超声信号改变，光镜下观察纳米粒相变情况。体外检测Fe^ⅢTA/PLGA/PFP纳米粒的生物安全性。设立空白对照组、激光组、Fe^ⅢTA/PLGA/PTX/PFP（FPTP）组、Fe^ⅢTA/PLGA/PTX/PFP+激光（FPTP+激光）组及不同浓度（0、0.250、0.500、1.000 g/L）FPTP+激光组，检测激光辐照5 min后各纳米粒组对肿瘤细胞的杀伤效果。结果 成功制备出Fe^ⅢTA/PLGA/PTX/PFP纳米粒，粒径（155.8±55.68）nm，电位（-27.3±5.14）mV，透射电子显微镜下见黑色Fe^ⅢTA外壳包裹核心灰白球形结构，PTX包封率（70.89±8.03）%，载药率（9.61±0.63）%。体外激光辐照FPTP纳米粒后温度上升与浓度呈正相关，B模式和造影模式超声信号也随浓度增加而增强。FPTP+激光组对Y79细胞的杀伤作用比空白对照组、激光组、FPTP组更强，并随浓度增加而增强。结论 成功制备出载单宁酸铁和紫杉醇的相变型纳米粒，具有良好的光热效应和超声显像效果，对Y79细胞有强杀伤作用，有望用于Rb实现诊疗一体。     

载印度墨水相变型光声/超声双模态造影剂的制备及体外显影

目的 制备一种新型的光声/超声双模态造影剂,观察其体外光致相变作用以及光声/超声显影效果。方法 采用多步乳化法 合成载印度墨水及全氟己烷(PFH)的高分子微球(i-PFH-PLGA),检测其基本理化性质、光致相变作用及体外增强光声及超声成像的显像效果。结果 制备的i-PFH-PLGA呈球型,平均粒径为(542.1±68.91)nm。经激光辐照后,显微镜下可观察到较多的i-PFH-PLGA纳米粒发生液气相转变产生微泡;体外光声成像实验显示,i-PFH-PLGA纳米粒可检测到明显的光声信号,且光声信号的强度随纳米粒浓度的增加而增强;体外超声成像实验显示,经激光照射后,i-PFH-PLGA纳米粒组回声强度较辐照前明显增强(P<0.05),而单纯的液态氟碳和印度墨水辐照前后回声强度未见明显改变。结论 成功制备出的载印度墨水和液态氟碳的双模态造影剂可用于体外光声/超声成像研究。     

靶向癌胚抗原载药纳米超声造影剂体外抑制卵巢癌细胞生长

目的 制备靶向癌胚抗原（CEA）载药相变型PLGA纳米粒（Ab-PTX-NPs）,探讨该纳米粒的体外寻靶及抑制肿瘤细胞生长的效能。方法 乳化溶剂挥发法联合碳二亚胺法制备靶向CEA载紫杉醇纳米粒（Ab-PTX-NPs）,采用马尔文粒径分析仪检测其粒径大小。采用高效液相色谱法检测紫杉醇包封率及载药量,恒温摇床透析法检测该纳米粒体外释药特征。激光共聚焦显微镜及流式细胞术观察该纳米粒体外寻靶情况,CCK-8试剂检测卵巢癌细胞存活率。结果 制备的Ab-PTX-NPs粒径为（397.70±99.95）nm,紫杉醇包封率及载药量分别为（67.26±4.15）%和（6.31±0.39）%。抗CEA单克隆抗体与纳米粒连接率为（92.74±5.75）%。共聚焦显微镜下观察到靶向组卵巢癌SKOV3细胞周围见较多造影剂黏附,流式细胞术测得靶向组细胞平均荧光强度明显高于其余各组（P<0.05）,CCK-8试剂法测得靶向组在24 h时,细胞存活率高于纯药组（P<0.05）,而低于无靶组（P<0.05）,当48 h时,靶向组与纯药组细胞存活率差异无统计学意义（P>0.05）。结论 成功制备靶向CEA载药相变型PLGA纳米粒,该纳米粒经低功率聚焦超声治疗仪（LIFU）致相变后可明显增强超声显影,且载药量高,释药快,靶向能力强。     

载单宁酸铁及二氢卟吩纳米粒用于光声成像及杀伤视网膜母细胞瘤Y79细胞

目的 制备载单宁酸铁(Fe^Ⅲ TA)及二氢卟吩(Ce6)纳米粒,观察其用于光声(PA)成像及杀伤视网膜母细胞瘤(RB)Y79细胞的价值。方法 制备Fe^Ⅲ TA/PLGA/Ce6纳米粒并检测其特性,观察其体内、体外PA成像能力及对人源性RB Y79细胞的杀伤能力。结果 成功制备的Fe^Ⅲ TA/PLGA/Ce6纳米粒基本特性良好,光热稳定性优异,用于实时PA成像效果较好。纳米粒浓度越高,经808 nm激光辐照后样品升温幅度越大。各种浓度纳米粒对人视网膜色素上皮细胞均无明显细胞毒性。于Y79细胞中加入纳米粒后,荧光强度随时间延长而增高;激光组(Y79细胞+激光辐照)、Fe^Ⅲ TA/PLGA/Ce6组(Y79细胞+纳米粒)、Fe^Ⅲ TA/PLGA/Ce6+激光组(Y79细胞+纳米粒+激光辐照)及空白对照组(Y79细胞)于Y79细胞内的活性氧产量百分比分别为28.01%、55.41%、42.74%及26.57%。Fe^Ⅲ TA/PLGA/Ce6纳米粒及激光辐照共同作用可使Y79细胞大量凋亡。结论 成功制备的Fe^Ⅲ TA/PLGA/Ce6纳米粒用于PA成像效果较好;用于光热治疗联合化学动力疗法可有效杀伤体外Y79细胞。     

诊疗一体化胶质瘤靶向纳米粒增效声动力治疗及多模态显像：体外实验研究

目的 制备胶质瘤靶向诊疗一体化纳米粒,观察体外多模态显像及对U87细胞主动靶向能力和增效声动力治疗（SDT）效果。方法 以双乳化法制备载IR780和全氟戊烷（PFP）纳米粒（IR780-PFP@PLGA）,验证其体外光声（PA）/超声（US）/荧光（FL）多模态显像能力;以细胞计数试剂盒（CCK-8）检测细胞毒性,激光共聚焦显微镜观察其主动靶向能力,通过单线氧荧光探针（SOSG）检测法、JC-1染色法、2'',7''-二氯荧光黄双乙酸盐（DCFH-DA）染色法、钙黄绿素/碘化丙啶（Calcein-AM/PI）双染及CCK-8评价其增效SDT效果。结果 所制备IR780-PFP@PLGA呈圆形,形态规则,粒径均匀,平均（240.67±1.30） nm,表面电位（-9.50±0.06） mV,IR780包封率（92.03±0.42）%;经激光辐照后其PA和FL信号强度呈浓度依赖性,经低强度聚焦超声（LIFU）辐照后表现出良好US对比度成像能力和较强U87细胞靶向能力,并呈活性氧（ROS）浓度依赖。于U87细胞中检出大量ROS,线粒体膜电位明显降低,细胞毒作用明显。结论 成功构建的IR780-PFP@PLGA不仅可用于PA/US/FL多模态显像并具有良好体外寻靶能力,还可通过声致相变（ADV）增强SDT疗效,有望用于多模态成像指导下早期诊断和靶向精准治疗脑胶质瘤并评估疗效。     

载盐酸阿霉素液态氟碳脂质体对乳腺癌治疗效果

目的 制备一种载盐酸阿霉素（DOX）和液态氟碳（PFH）脂质体（Lip-PFH-DOX）,探讨Lip-PFH-DOX纳米粒增强超声显影及对人乳腺癌MAD-MB-231细胞治疗效果。方法 采用薄膜水化法及声振法技术制备Lip-PFH-DOX纳米粒。检测Lip-PFH-DOX纳米粒的形态、粒径、电位、包封率。通过低强度聚焦超声促使纳米粒发生相变并使其破裂,通过高效液相色谱法检测不同时间点药物释放情况。检测该纳米粒对人乳腺癌MDA-MB-231的细胞毒性作用,观察细胞凋亡情况。建立裸鼠人乳腺癌MDA-MB-231模型,经尾静脉注射适量纳米粒,以低强度聚焦超声辐照,观察肿瘤部位增强超声表现。结果 成功制备载DOX和PFH的脂质体,其粒径（340.81±68.54）nm,电位（-17.72±7.66）mV,药物包封率（86.80±2.55）%。透射电镜下可观察其内部成功包载药物,光镜下可见脂质体大小均匀,可发生相变。Lip-PFH-DOX在48 h时DOX释放率达40.05±3.22,当Lip-PFH-DOX纳米粒浓度为100 μg/ml,孵育48 h时,细胞存活率为45.00%,且出现大量凋亡细胞。Lip-PFH-DOX纳米粒在低强度超声辐照后可以明显增强体内超声显影。结论 本研究成功制备了包裹DOX和PFH纳米粒,可实现体内外超声显影,同时可对MAD-MB-231细胞产生杀伤作用。     

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.