心肌缺血周负荷对兔心肌血管内皮生长因子表达的影响

目的：研究不同心肌缺血周负荷对兔心肌血管内皮生长因子（VEGF）表达的影响。方法：健康成年新西兰兔35只，体重2．2—2．5kg。根据不同的周缺血天数随机分为对照组、假手术组、3天，周组、5天，周组和7天，周组。将气囊梗阻器安装在冠状动脉左室支处，建立可控性心肌缺血模型。日缺血负荷为2min／h，2次，天，持续缺血刺激4周。取缺血区心肌观察形态学改变，并采用Western Blot方法检测缺血区和非缺血区心肌VEGF的表达水平。结果：①气囊充气后可以安全、有效地诱发心肌缺血。②与对照组和假手术组相比，缺血组左室支支配区心肌VEGF表达显著增高（P〈0．05）；各缺血亚组间VEGF表达差异无显著性意义（P〉0．05）。③假手术组心肌VEGF表达与对照组相比无明显变化（P〉0．05）。④左室支支配区心肌VEGF表达和冠状动脉侧支血流量（CCBn呈正相关（r=-0．775，P〈0．01）。结论：持续4周间断性心肌缺血可显著提高缺血区心肌VEGF表达，不同周缺血负荷对其表达无明显影响：缺血区心肌VEGF表达水平和CCBF相关。     

心肌缺血日负荷对冠状动脉侧支血流量的影响

目的:探讨心肌缺血日负荷对新西兰兔冠状动脉侧支血流量(CCBF)的影响。方法:健康成年新西兰兔34只,体重2.4±0.2kg。随机分为缺血组和假手术组,缺血组根据日缺血负荷分为2、4、6次/日亚组。将气囊梗阻器安装在冠状动脉左室支上,以建立间断性心肌缺血模型。气囊充气造成心肌缺血(2min/次,间隔1h),以各日缺血负荷持续4周。取缺血区心肌观察形态学改变;微球技术检测缺血区CCBF;取兔术前和首次缺血刺激前、后24h血清检测肌钙蛋白(cTn-I)。结果:4周间断性缺血刺激后,缺血组与假手术组相比,CCBF明显增加(P<0.05);各缺血亚组间CCBF差异无显著性意义(P>0.05)。各组缺血区心肌未见变性坏死灶,兔首次缺血刺激后24h血清肌钙蛋白无明显升高。结论:4周间断性心肌缺血对心肌无损伤,可促进缺血区CCBF增加;不同日缺血负荷对CCBF无明显影响。     

心肌周缺血频率对兔冠状动脉侧支循环生成的影响

目的观察不同的心肌周缺血频率对新两兰兔冠状动脉侧支生成影响。方法健康成年新西兰兔32只，体重2．0～2．5kg。于兔冠状动脉左室吏安装气囊梗阻器，制作间断性心肌缺血模型，缺血负荷为2min／h，2次／d，每次缺血2min后恢复血供，隔58min后行第二次缺血刺激，共4周。根据不同周缺血天数将实验动物随机分为假手1术组和3d／周、5d／周及7d／周缺血组。采用微球技术检测各组缺血和非缺血区心肌冠状动脉侧支循环血流（CCBF）变化，采州苏木素一伊红染色观察各组缺血区侧支循环的形态学改变，于术前和缺血刺激前、后24h进行血清肌钙蛋白的检测。结果3d／周、5d／周及7d／周的缺血刺激均可引起缺血区CCBF和毛细血管密度显著增加，组间比较，差异无统计学意义。缺血刺激后24h，血清肌钙蛋白无明显升高。结论每周3d、5d或7d，共4周的心肌缺血刺激均可显著促进心肌缺血区侧支生成，且不损伤心肌；高于每周3d的缺血频率不一定能进-步促进侧支的生成。     

短暂缺血阈强度运动促进心肌侧支循环生成的机制

目的 在小型猪可控性心肌缺血动物模型上,观察短暂缺血阈强度运动促进缺血区冠状动脉侧支循环生成的机制.方法 选择健康广西巴马小型猪32头,钝缘支装上水囊缩窄器制作可控性心肌缺血动物模型,4周后行冠状动脉造影证实模型建立成功.实验动物随机分为假手术组、单纯缺血组和运动组.单纯缺血组通过缩窄器注水加压制造心肌缺血,每日2次,每次2 min,每周5 d,共8周;运动组除制造静息状态心肌缺血外,每天还进行平板训练30 min,其中包括2次缺血阈强度运动,每次2 min,每周训练5 d,共8周.假手术组不作任何干预.采用微球测定训练前、后缺血区相对心肌血流量(RMBF);采用Western-blot及Real-time RT-PCR法测定缺血心肌局部血管内皮细胞生长因子(VEGF)及其受体胎肝激酶-1(Flk-1)的蛋白及mRNA表达量;采用ELISA法测定血清肌钙蛋白含量以确定训练的安全性;应用电镜观察心肌细胞损伤情况.结果 运动组RMBF显著高于单纯缺血组及假手术组(均P＜0.01);单纯缺血组RMBF亦显著高于假手术组(P＜0.01).运动组VEGF及Flk-1的蛋白及mRNA表达量均显著高于单纯缺血组及假手术组(P＜0.05,P＜0.01).单纯缺血组的VEGF及Flk-1的蛋白及mRNA表达量均显著高于假手术组(P＜0.05).单纯缺血组及运动组训练后,血清肌钙蛋白与训练前相比无显著增加(均P＞0.05).光镜及电镜检查无明显异常.结论 小型猪可控性心肌缺血动物模型给予适宜短暂缺血阈强度运动,可通过缺血心肌局部VEGF及其受体Flk-1的上调安全有效地促进冠状动脉侧支循环生成.     

内皮祖细胞动员对兔生理性缺血训练促进远隔缺血心肌侧支生成的作用

摘要 目的：探讨血管内皮生长因子（VEGF）介导的内皮祖细胞（EPCs）动员在生理性缺血训练（PIT）促进远隔缺血心肌侧支循环生成过程中的作用。 方法：42只兔进行可控性心肌缺血造模,造模成功后随机分入以下6组：假手术组、单纯生理性缺血训练组、单纯心肌缺血组、生理性缺血训练组、阿托伐他汀组、雷帕霉素组。生理性缺血训练共4周,每次3min,间隔5min,每周训练5d,每天训练3次。实验终点时,处死动物取材,进行实验室检测：ELISA法检测外周血中VEGF含量;Western blot法检测缺血心肌中VEGF表达;流式细胞术检测外周血和缺血心肌中EPCs数量;微球技术检测缺血心肌侧支循环血流量。 结果：4周PIT后,VEGF含量在PIT组和PIT+组显著增加,与SO组、TO组和MI组相比,外周血和缺血心肌中VEGF含量在PIT组显著增加,结果具有显著性意义。PIT+组的EPCs数量在外周血和缺血心肌中均显著高于其他各组,PIT组与其他各组相比,外周血EPCs数量的差异同样具有显著性意义。冠状动脉侧支循环血流量（CCBF）和CCBF/冠状动脉血流量（CBF）在PIT+组和PIT组显著高于SO组、TO组和MI组。PIT-组的各项指标与SO组和TO组相比,差异均无显著性意义。EPCs数量的增加最高有43%可以被VEGF含量的增加解释,CCBF和CCBF/CBF的增加最高有90%可以被EPCs数量的增加解释。 结论：PIT可促进EPCs动员,通过其远隔效应归巢到缺血心肌生成侧支循环,改善冠脉血流,最终实现“生物搭桥”;通过促进和抑制EPCs,证实EPCs在PIT介导的缺血心肌侧支循环生成过程中具有重要作用。     

短暂缺血阈强度运动促进心肌侧支循环生成的机制

目的在小型猪可控性心肌缺血动物模型上,观察短暂缺血阈强度运动促进缺血区冠状动脉侧支循环生成的机制。 方法选择健康广西巴马小型猪32头,钝缘支装上水囊缩窄器制作可控性心肌缺血动物模型,4周后行冠状动脉造影证实模型建立成功。实验动物随机分为假手术组、单纯缺血组和运动组。单纯缺血组通过缩窄器注水加压制造心肌缺血,每日2次,每次2 min,每周5 d,共8周;运动组除制造静息状态心肌缺血外,每天还进行平板训练30 min,其中包括2次缺血阈强度运动,每次2 min,每周训练5 d,共8周。假手术组不作任何干预。采用微球测定训练前、后缺血区相对心肌血流量（RMBF）;采用Western-blot及Real-time RT-PCR法测定缺血心肌局部血管内皮细胞生长因子（VEGF）及其受体胎肝激酶-1（Flk-1）的蛋白及mRNA表达量;采用ELISA法测定血清肌钙蛋白含量以确定训练的安全性;应用电镜观察心肌细胞损伤情况。 结果运动组RMBF显著高于单纯缺血组及假手术组（均P<0.01）;单纯缺血组RMBF亦显著高于假手术组（P<0.01）。运动组VEGF及Flk-1的蛋白及mRNA表达量均显著高于单纯缺血组及假手术组（P<0.05,P<0.01）。单纯缺血组的VEGF及Flk-1的蛋白及mRNA表达量均显著高于假手术组（P<0.05）。单纯缺血组及运动组训练后,血清肌钙蛋白与训练前相比无显著增加（均P&rt;0.05）。光镜及电镜检查无明显异常。 结论小型猪可控性心肌缺血动物模型给予适宜短暂缺血阈强度运动,可通过缺血心肌局部VEGF及其受体Flk-1的上调安全有效地促进冠状动脉侧支循环生成。     

生理性缺血训练促进远隔缺血心肌侧支生成中内皮祖细胞的作用

摘要 目的：研究内皮祖细胞（EPCs）对生理性缺血训练（PIT）促进远隔缺血心肌侧支循环生成的影响。 方法：选择健康新西兰白兔雌雄不拘,体重（2.5±0.5）kg。冠状动脉左室支（LVB）安装特制水囊球,通过充放水制作可控性心肌缺血动物模型。休息1周后将实验动物随机分为6组：假手术组（SO）、单纯肢体缺血组（LIT）、单纯心肌缺血组（MI）、生理性缺血训练组（PIT）、EPCs促进剂组（Pro-EPCs）、EPCs抑制剂组（Inhi-EPCs）。SO组不做任何干预,LIT组进行双下肢缺血训练,MI组进行心肌缺血训练,PIT组生理性缺血训练,即心肌缺血同时进行双下肢缺血训练,Pro-EPCs组在PIT组基础上口服EPCs促进剂,Inhi-EPCs组在PIT组基础上口服EPCs抑制剂。训练4周后,取左室支支配区域心肌,采用微球法测定训练前、后缺血区心肌相对侧支循环血流量(RCBF);免疫组化法检测实验终点缺血区毛细血管密度（CD）。 结果：与实验前相比,MI组、PIT组RCBF值分别增加5.11、19.39（P＜0.05）。实验结束时,MI组、PIT组RCBF显著高于SO组和LIT组（P＜0.05）,PIT组高于MI组（P＜0.05）,SO组与LIT组无显著性差异（P＞0.05）。与PIT组比较,Pro-EPCs组RCBF明显增高（P＜0.05）,Inhi-EPCs组RCBF显著降低（P＜0.05）。CD结果与RCBF值类似。 结论：①生理性缺血训练可促进远隔缺血心肌侧支循环生成。②生理性缺血训练同时,正负向调节内皮祖细胞,可相应促进或抑制远隔缺血心肌侧支循环生成。EPCs是生理性缺血训练促进远隔缺血心肌侧支循环形成过程中的重要细胞机制。     

短暂缺血阈强度运动对冠脉侧支循环生成的作用

目的:在小型猪可控性心肌缺血动物模型上,观察适宜短暂缺血阈强度运动对缺血区冠脉侧支循环生成的作用。方法:钝缘支装上水囊缩窄器。4周后,冠脉造影证实可控性心肌缺血动物模型建立。随机分为3组:假手术组(SO)、单纯缺血组(PI)、运动组(ET)。PI组通过缩窄器注水加压产生心肌缺血2次/天,每次2min;ET组除以上静息状态心肌缺血外,还需每天平板训练30min,其中包括2次每次2min的缺血阈强度运动。PI及ET组每周训练5d,共8周。SO组不作任何干预。微球测定训练前后缺血区相对心肌血流量(RMBF);免疫组化Ⅷ染色测定毛细血管密度(CD);电镜及光镜检查心肌细胞损伤情况。结果:ET组CD显著高于PI组(P<0.01)及SO组(P<0.01);PI组CD亦显著高于SO组(P<0.01)。RMBF的结果类似于CD。光镜及电镜检查无明显异常。结论:在小型猪可控性心肌缺血动物模型上,适宜短暂缺血阈强度运动可以安全有效地促进冠脉侧支循环生成。     

心肌缺血损伤小型猪模型内关穴位埋针后血管新生及成纤维细胞生长因子mRNA和蛋白的表达

背景：血管生成及成纤维细胞生长因子与心肌缺血损伤后修复关系密切,针刺内关防治心肌缺血损伤的机制是否与此有关尚不清楚。目的：观察内关穴位埋针对心肌缺血损伤小型猪血管新生及成纤维细胞生长因子基因和蛋白表达的影响。方法：将32只小型猪随机分为4组,采用左冠状动脉前降支结扎法建立心肌缺血模型,假手术组穿线但不结扎,内关组和膈俞组分别在造模的基础上进行内关、膈俞穴埋针治疗,模型组和假手术组不进行任何干预。结果与结论：免疫组织化学染色显示小型猪经冠脉结扎后心肌毛细血管密度降低（P〈0.01）,内关、膈俞穴埋针治疗7d,损伤心肌组织毛细血管密度增加（P〈0.05或P〈0.01）,内关组优于膈俞组（P〈0.05）;Real time PCR和Western blot检测显示小型猪经冠脉结扎后心肌组织成纤维细胞生长因子mRNA和蛋白表达量显著增高（P〈0.05或P〈0.01）,内关和膈俞穴位埋针治疗均可上调成纤维细胞生长因子mRNA和蛋白表达量,以内关埋针效果最明显（P〈0.05）。揭示内关、膈俞穴位埋针均可通过上调成纤维细胞生长因子mRNA和蛋白的表达,增加心肌毛细血管密度,改善缺血心肌的损伤,且内关优于膈俞。     

缺血负荷对家兔冠状动脉固有侧支循环开放的影响

目的:观察不同缺血负荷对冠状动脉固有侧支循环开放程度和开放持续时间的影响。方法:家兔49只,体重(2.5±0.5)kg,冠状动脉左室支穿线阻断,制作心肌缺血模型,逐级设定不同缺血时间和缺血频率。采用微球技术定量检测冠状动脉侧支循环血流(CCBF)。以心电图和肉眼所见心肌颜色变化作为心肌缺血和再灌注的判断标准。实验终止时取支配区和正常心肌组织检测微球,并取支配区心肌和结扎段血管观察形态学改变。结果:①病理观察:阻断8min和20min组见心肌细胞变性,未见心肌坏死和血栓形成。②局部血流在阻断0—2min呈增加趋势,2min时明显增加(P<0.05),阻断至4、5、8、10、20min不再进一步增加,呈现下降趋势。③局部血流在阻断2min后再灌注即刻较阻断前明显增加(P<0.05),至2min时回落到阻断前基础水平(P>0.05)。④反复3次阻断2min后(分别间隔5min,10min和30min)CCBF的增加不产生进一步变化(P>0.05)。结论:家兔冠状动脉固有侧支循环的最大开放需要至少2min缺血刺激,侧支开放维持时间不超过2min。缺血负荷的进一步增加不能提高侧支循环开放程度和持续时间。     

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.