支持Asthmatx，公司 Alair和Asthmatx Asthmatx，公司的注册商标。 Advair是葛兰素史克公司，公司的注册商标。 Symbicort是阿斯利康公司的注册商标。

1。简介： 哮喘是一种严重的公共卫生问题。目前的估计是，在美国20万人患有哮喘。每个在美国的一年，还有约13.6万不定期医生的办公室访问，急诊室180万，0.5万住院治疗，4000人死亡（NCHS 2005年）因哮喘。哮喘估计在美国每年的费用约为19.7亿美元。这个共包括5亿美元的间接费用，由于超过14.5万失去工作日内，美元和14.7亿美元的直接费用，如哮喘药，不定期医生诊所就诊，急诊和住院（美国肺脏协会2007）。 20多万美国人患有哮喘的10％被诊断为严重的哮喘。然而，这组严重哮喘是负责的与疾病相关的发病率不成比例。因此，这10％的最严重的哮喘患者负责大多数与哮喘有关的医疗负担，住院费用，急诊室参观，医生的办公室访问，和药物的使用（Cisternas等，2003）为代表的尽管可用的哮喘药物，严重哮喘的经验频繁和严重的症状，包括病情加重，可危及生命，需要紧急复苏措施，包括插管和机械通气患者，用高剂量正规治疗，直到气道阻塞可以得到缓解。病情加重，需要大量的医疗费用的医疗干预的结果和影响的病人和家属的生活质量。这反映了现有的治疗方案不能充分控制严重的疾病患者的哮喘严重哮喘的负担增加了。 2。病例报告： 典型的病人是40岁左右，有严重哮喘控制不佳的历史，尽管采取Advair，Symbicort的ICS + LABA的其他同等的组合，一天两次，仍经历因哮喘症状的日常活动困难。 支气管thermoplasty通常是在一家医院门诊支气管镜或胃镜套房或手术室管理。患者应接受支气管镜检查和bronchoscopist需要，以确保病人仍然是一个很好的候选人后，患者的选​​择标准概述如下的支气管thermoplasty稳定。在某些情况下，程序可以安全地执行在门诊的基础上，病人可以出院前一个较长的时期监察。在3.4以下的注意事项“一节所述的患者可能是这样的候选人。 3。病人选择： <ol><li> Alair支气管Thermoplasty系统是用于治疗重度持续性哮喘患者18岁及以上的哮喘没有得到很好的控制与吸入皮质类固醇和长效β受体激动剂表示。 </li><li>符合下列条件的病人不应该被视为： <ul><li>一个心脏起搏器，除颤器内部，或其他植入式电子装置的存在， </li><li>已知需要进行支气管镜检查，包括利多卡因，阿托品和苯二氮卓类药物的敏感性， </li><li>以前Alair系统治疗的患者不应该撤退在同一地区（S）。没有临床数据研究的安全性和/或重复治疗的有效性。 </li></ul></li><li>病人不应该被视为同时存在下列条件： <ul><li>主动呼吸道感染， </li><li>哮喘发作或改变剂量全身糖皮质激素对哮喘（向上或向下）在过去14天里， </li><li>已知的凝血功能障碍， </li><li>至于与其他支气管镜检查程序，患者的医师指导下的程序之前，应停止服用抗凝血剂，抗血小板药物，阿司匹林和非甾体抗炎药。 </li></ul></li><li>由于一个潜在的程序可能相关的不良事件的风险增加下列条件的患者时应注意。符合这些条件的患者没有关键性试验研究，并Alair此类患者的治疗的安全性尚未确定： <ul><li>后支气管扩张FEV1 &lt;65％。 </li><li>等呼吸道疾病，包括肺气肿，声带功能障碍，机械上呼吸道阻塞，囊性纤维化或阻塞性睡眠呼吸暂停失控。 </li><li>超过每12天喷的短效支气管扩张剂的使用支气管镜检查48小时内（不包括预防性使用锻炼）。 </li><li>超过每天10毫克的口服类固醇的使用，用于治疗哮喘。 </li><li>增加里SK为与支气管镜或麻醉相关的不良事件，如怀孕，胰岛素依赖型糖尿病，癫痫或其他重大合并症，如不受控制的冠状动脉疾病，急性或慢性肾功能衰竭，未控制的高血压，。 Alair系统应该只用于在不够稳定的患者接受支气管镜</li><li>用于治疗哮喘，气管插管或ICU入院前24个月内哮喘。 </li><li>在过去12个月以下的任何： <ul><li> 4个或更多的下呼吸道感染（LRTI） </li><li> 3个或更多的呼吸系统症状住院</li><li> 4个或更多的接触网脉冲哮喘发作</li></ul></li></ul></li></ol> 4。支气管Thermoplasty程序： <ol><li>在一天的过程中，bronchoscopist，需要重新评估，并确保病人仍然是一个很好的候选人为中度镇静下支气管thermoplasty。 </li><li>围程序的编写，包括3天的预防性管理的OCS（50毫克/ D）之前，日，手术后一天，以尽量减少后期程序炎症，和吸入支气管扩张剂和抗cholinergics抑制气道分泌物的应用。 </li><li>病人是适当的准备和温和的镇静作用下放置。外设静脉（IV）线和补充氧气通过口服或鼻导管（小于40％），建议适当的监测与温和的镇静作用，其中包括连续电气心脏监测，连续脉搏血氧饱和度，无创血压监测。一旦建立静脉通路，并已应用于显示器，premedications可以管理病人在准备支气管thermoplasty。管理沙丁胺醇和格隆或阿托品等antisialogogue代理应在手术前至少30分钟。镇静管理四咪唑安定和芬太尼与局部麻醉的明智应用。 </li><li>支气管thermoplasty是使用该Alair系统。准备使用的设备和一个标准的凝胶型病人回路电极贴在病人提供一个完整的电路。 </li><li>支气管thermoplasty是一个标准的执行市售高频兼容灵活的支气管镜通过口腔或鼻腔的方法，和相应的应用局部麻醉。 bronchoscopist anesthetizes开始治疗前，后咽，声带和支气管树。下来航空公司bronchoscopist的收益，更多的局部麻醉剂是必要的。 </li><li>导航支气管镜治疗肺癌的地区和所有的目标航空公司在开始治疗前检查。该bronchoscopist计划的顺序气道段进行访问和处理，协助呼吸道地图。治疗计划是至关重要的彻底性，并最终成功的BT，有助于避免不足或过度治疗呼吸道。 </li><li>纤支镜导航到的第一个目标治疗部位，通常在最远端的气道有针对性的叶。 Alair导管引入通过支气管镜工作通道，并在所需的位置定位在呼吸道。在导管的尖端电极阵列扩大气道壁的接触和bronchoscopist激活射频控制器提供射频能量的组织。 </li><li>射频控制器提供低功耗，温度控制射频能量的气道，并自动终止后，完成的周期（约10秒）的能源供应。导管的一个单一的激活提供一个距离约5毫米（外露电极内的电极阵列的长度）射频能量。 bronchoscopist必须保持静态的联系，在这段时间内与目标5毫米部分，甚至在航空公司的潮式呼吸运动仍然。 </li><li>温度设定点，功率限制，交货时间是在射频控制器软件配置，而不​​是用户可调。 </li><li>映射的治疗计划，部署，从远端向正在接受治疗呼吸道的近端导管。 5毫米近端每个激活和随后激活后进行连续重叠，导管重新定位。这项技术是用来在所有可访问的航空公司远端主支气管和≥直径3mm的。 </li><li>一个系统化的方法，从远端到近端，工作有条不紊，从整个地区正在接受治疗的肺癌呼吸道气道建议，以确保所有访问的航空公司都只有一次仔细辨认和治疗。根据大小和解剖，范围约40-80能源的交货周期。 </li><li> BT是管理与不同地区在3个疗程每届会议期间接受治疗的肺癌（之一会话1下叶;第二次会议2叶;会议3双上肢叶）。每次治疗计划相距大约3个星期。对于上叶区域（通常在一个疗程一起处理），程序是完全相同以上，但需要额外的时间，因为它涉及到航行曲折的上呼吸道解剖，占地面积超过或者降低叶面积。根据病人的大小和解剖，进行一系列能源交货周期约为60-100。 </li><li>其次是病人在恢复室，肺功能，直到恢复到可接受的水平。这往往需要长达4小时，每个疗程。见程序后跟进部分获取更多细节。 </li></ol> 5。 POST程序追问： <ol><li>约4小时的观察和恢复/监测期内，每道工序。 </li><li>肺功能，呼吸音及出院前的生命体征（心率，血压，温度，呼吸频率，脉搏血氧饱和度）。 </li><li>放电如果，支气管扩张剂后FEV1≥80％的前置程序的价值和病人感觉良好。 </li><li>验证预防性使用强的松或相当于一天，每一个支气管镜。 </li><li>患者通过电话联系要求1天，2天，7天，以评估后的程序的状态。 </li><li>办公室在2至3周访问，以评估肺功能，并安排适当的后续支气管thermoplasty程序。 </li><li>后续改善哮喘状态长期监测的访问。 </li></ol> 6。结果： 哮喘干预研究2（AIR2）试用评估Alair支气管Thermoplasty系统的安全性和有效性。该项研究的数据提交给FDA，是该机构的批准一种治疗哮喘的新型设备的基础上。 AIR2数据还刊登在2010年1月15日，美国呼吸与危重病急救医学（AJRCCM）杂志的问题。试验表明Alair系统治疗，导致哮喘的质量，改善生活，以及在长期的后续以下临床意义的过假的好处： <ul><li>在哮喘发作减少32％ </li><li>在急诊室就诊的84％减少呼吸系统症状</li><li>在住院的73％减少呼吸系统症状</li><li>在天上班/上学或其他日常活动中因哮喘损失减少66％ </li></ul> 7。结论： 由Alair系统提供的支气管thermoplasty提供了一种新型的，基于过程的常规治疗难治的重症哮喘的治疗。肺病，过敏症，哮喘专家，以及呼吸治疗师应成为熟悉使用支气管thermoplasty此过程中患者的适当选择和管理。随机，对照临床试验日期支气管thermoplasty，已表现出显着改善的成果，是重要的我们的病人的生活质量，哮喘症状，需要糖皮质激素的严重恶化，失去工作/学校/其他日常活动天因哮喘，医疗利用率。与目前使用的药物治疗，需要每天使用管理症状，支气管thermoplasty提供持久的利益和整体控制哮喘的改善。

<ol>
	<li>Castro, M., Musani, A., Mayse, M., Shargill, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bronchial+thermoplasty:+a+novel+technique+in+the+treatment+of+severe+asthma.">Bronchial thermoplasty: a novel technique in the treatment of severe asthma.</a> Ther Adv Respir Dis. 4 (2), 101-116 (2010).</li><li>Castro, M., Rubin, A. S., Laviolette, M., Fiterman, J., De Andrade, L. M., Shah, P. L., Fiss, E., Olivenstein, R., Thomson, N. C., Niven, R. M., Pavord, I. D., Simoff, M., Duhamel, D. R., McEvoy, C., Barbers, R., ten Hacken, N. H. 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C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+pearls+for+bronchial+thermoplasty.">Clinical pearls for bronchial thermoplasty.</a> J Bronchol. 14, 115-123 (2007).</li><li>Pavord, I. D., Cox, G., Thomson, N. C., Rubin, A. S., Corris, P. A., Niven, R. M., Chung, K. F., Laviolette, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+and+efficacy+of+bronchial+thermoplasty+in+symptomatic,+severe+asthma.">Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma.</a> Am J Respir Crit Care Med. 176 (12), 1185-1191 (2007).</li><li>Cox, G., Thomson, N. C., Rubin, A. S., Niven, R. M., Corris, P. A., Siersted, H. C., Olivenstein, R., Pavord, I. D., McCormack, D., Chaudhuri, R., Miller, J. D., Laviolette, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asthma+control+during+the+year+after+bronchial+thermoplasty.">Asthma control during the year after bronchial thermoplasty.</a> N Engl J Med. 356 (13), 1327-1337 (2007).</li><li>Wilson, S. R., Cox, G., Miller, J. D., Lam, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+assessment+after+bronchial+thermoplasty:+the+patient's+perspective.">Global assessment after bronchial thermoplasty: the patient's perspective.</a> Journal of Outcomes Research. 10, 37-46 (2007).</li><li>Cox, G., Miller, J. D., McWilliams, A., Fitzgerald, J. M., Lam, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bronchial+thermoplasty+for+asthma.">Bronchial thermoplasty for asthma.</a> Am J Respir Crit Care Med. 173 (9), 965-969 (2006).</li><li>Brown, R. H., Wizeman, W., Danek, C., Mitzner, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+bronchial+thermoplasty+on+airway+distensibility.">Effect of bronchial thermoplasty on airway distensibility.</a> Eur Respir J. 26 (2), 277-282 (2005).</li><li>Brown, R. H., Wizeman, W., Danek, C., Mitzner, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+evaluation+of+the+effectiveness+of+bronchial+thermoplasty+with+computed+tomography.">In vivo evaluation of the effectiveness of bronchial thermoplasty with computed tomography.</a> J Appl Physiol. 98 (5), 1603-1606 (2005).</li><li>Miller, J. D., Cox, G., Vincic, L., Lombard, C. M., Loomas, B. E., Danek, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+prospective+feasibility+study+of+bronchial+thermoplasty+in+the+human+airway.">A prospective feasibility study of bronchial thermoplasty in the human airway.</a> Chest. 127 (6), 1999-2006 (2005).</li><li>Danek, C. J., Lombard, C. M., Dungworth, D., Cox, G., Miller, J. D., Biggs, M. J., Keast, T., Loomas, B. E., Wizeman, W. J., Hogg, J. C., Leff, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+in+airway+hyperresponsiveness+to+methacholine+by+the+application+of+RF+energy+in+dogs.">Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs.</a> J Appl Physiol. 97, 1946-1953 (2004).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> National Center for Health Statistics (NCHS). , (2005).</li><li>Cisternas, M. G., Blanc, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comprehensive+study+of+the+direct+and+indirect+costs+of+adult+asthma.">A comprehensive study of the direct and indirect costs of adult asthma.</a> J Allergy Clin Immunol. 111 (6), 1212-1218 (2003).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Trends in asthma morbidity and mortality. , (2007).</li></ol>

作者在AIR2审判，关键的临床研究支持Alair支气管Thermoplasty系统FDA批准的临床调查。

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		<th>Material Name</th>
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		<th>Catalogue Number</th>
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<td>Standard diagnostic High Frequency Fiberoptic Bronchoscope</td>
<td>&nbsp;</td>
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<td>minimum 2.0 mm working channel</td>
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<td>Alair Radio Frequency Controller</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
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<td>Alair Bronchial Thermoplasty Catheter</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
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<td>Gel Type Patient Return Electrode</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Continuous vital signs monitoring</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>heart rate, blood pressure, temperature, respiratory rate, pulse oximetry</td>
</tr>
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<td>Local Anesthetic: Lidocaine 1-2% (jelly and solution)</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
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<td>Sedatives: Midazolam and Fentanyl</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
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<td>Antiemetics: ondanestron or like</td>
<td>&nbsp;</td>
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<td>Anticholinergic drying agent: Atropine or Glycopyrrolate</td>
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<td>Prednisone</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>3 days before, day of and day after procedure</td>
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<td>Albuterol nebulizer</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
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<td>Peripheral IV line</td>
<td>&nbsp;</td>
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<td>&nbsp;</td>
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<td>Supplemental oxygen</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>less than 40% via oral or nasal cannula</td>
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<tr>
<td>Pulmonary Function Testing with Body Plethysmography</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Lung Map or procedure form for planning and recording of treatment</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>		</tbody>
		</table>
		</div>

bronchial thermoplasty:  a novel therapeutic approach to severe asthma

支气管thermoplasty是一个重度持续性哮喘，在精确控制的方式提供热能的气道壁，以减少过度的气道平滑肌的非药物的过程。减少气道平滑肌，降低到收缩航空公司的能力，从而减少哮喘发作的频率。支气管thermoplasty Alair系统交付和执行三个门诊手术访问，预定相距约三个星期。第一个过程将右下肺叶的航空公司，第二把左下肺叶航空公司和第三次和最后的程序将在双方上叶航空公司。毕竟三个程序进行支气管thermoplasty治疗完成。 支气管thermoplasty是在与温和的镇静作用下病人支气管镜检查。所有可访问的航空公司远端主支气管与右肺中叶外，3至10毫米，直径，下支气管镜可视化处理。连续和非重叠激活设备的使用，从远端到近端沿气道的长度，并系统地从气道气道，如前面所述。虽然概念简单明了，实际执行的支气管thermoplasty是相当复杂的，单一叶治疗程序的时间往往是大大长于常规支气管镜检查期间遇到的。因此，支气管thermoplasty应被视为一个复杂的介入性支气管镜，目的是为有经验的bronchoscopist。最佳病人的管理是在任何复杂和持续时间较长的支气管镜检查程序的关键。本文讨论了细致的病人选择的重要性，患者准备，病人管理，手术时间，术后护理和跟进，以确保安全，支气管thermoplasty。 支气管thermoplasty预计，通过提供长期的哮喘控制和改善与哮喘有关的严重哮喘患者的生活质量的补充哮喘保养药物。此外，支气管thermoplasty已经证明，以减少的严重恶化（哮喘发作）呼吸系统症状的急诊室参观，并从工作，学校和其他日常活动中因哮喘失去。

Watch this Scientific Journal Video about Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma at JoVE.com

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

支气管thermoplasty是一个重度持续性哮喘，在精确控制的方式提供热能的气道壁，以减少过度的气道平滑肌的非药物的过程。减少气道平滑肌，降低到收缩航空公司的能力，从而减少哮喘发作的频率。

支气管Thermoplasty：严重哮喘的一种新的治疗方法

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

bronchial-thermoplasty-a-novel-therapeutic-approach-to-severe-asthma

Research

JoVE Journal

Medicine

31.7K 次观看.  Virginia Hospital Center. 支气管thermoplasty是一个重度持续性哮喘，在精确控制的方式提供热能的气道壁，以减少过度的气道平滑肌的非药物的过程。减少气道平滑肌，降低到收缩航空公司的能力，从而减少哮喘发作的频率。

视频: Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Vascular Occlusion Training for Inclusion Body Myositis: A Novel Therapeutic Approach

Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy. It is known to produces remarkable muscle weakness and to greatly compromise function and quality of life. Moreover, clinical practice suggests that, unlike other inflammatory myopathies, the majority of IBM patients are not responsive to treatment with immunosuppressive or immunomodulatory drugs to counteract disease progression1. Additionally, conventional resistance training programs have been proven ineffective in restoring muscle function and muscle mass in these patients2,3. Nevertheless, we have recently observed that restricting muscle blood flow using tourniquet cuffs in association with moderate intensity resistance training in an IBM patient produced a significant gain in muscle mass and function, along with substantial benefits in quality of life4. Thus, a new non-pharmacological approach for IBM patients has been proposed. Herein, we describe the details of a proposed protocol for vascular occlusion associated with a resistance training program for this population.

The present article presents the details pertaining to the application of resistance training associated to vascular occlusion in IBM patients.

血管闭塞包涵体肌炎培训：一种新的治疗方法

Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy. It is known to produces remarkable muscle weakness and to greatly compromise ...

科研

医学

A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and acquired diseases. Apart from congenital or inherited abnormalities with the requirement for long-term expression of the delivered gene, several non-inherited perinatal conditions, where short-term gene expression or pharmacological intervention is sufficient to achieve therapeutic effects, are considered as potential future indications for this kind of approach. Candidate diseases for the application of short-term prenatal therapy could be the transient neonatal deficiency of surfactant protein B causing neonatal respiratory distress syndrome1,2 or hyperoxic injuries of the neonatal lung3. Candidate diseases for permanent therapeutic correction are Cystic Fibrosis (CF)4, genetic variants of surfactant deficiencies5 and &alpha;1-antitrypsin deficiency6.
Generally, an important advantage of prenatal gene therapy is the ability to start therapeutic intervention early in development, at or even prior to clinical manifestations in the patient, thus preventing irreparable damage to the individual. In addition, fetal organs have an increased cell proliferation rate as compared to adult organs, which could allow a more efficient gene or stem cell transfer into the fetus. Furthermore, in utero gene delivery is performed when the individual's immune system is not completely mature. Therefore, transplantation of heterologous cells or supplementation of a non-functional or absent protein with a correct version should not cause immune sensitization to the cell, vector or transgene product, which has recently been proven to be the case with both cellular and genetic therapies7.
In the present study, we investigated the potential to directly target the fetal trachea in a mouse model. This procedure is in use in larger animal models such as rabbits and sheep8, and even in a clinical setting9, but has to date not been performed before in a mouse model. When studying the potential of fetal gene therapy for genetic diseases such as CF, the mouse model is very useful as a first proof-of-concept because of the wide availability of different transgenic mouse strains, the well documented embryogenesis and fetal development, less stringent ethical regulations, short gestation and the large litter size.
Different access routes have been described to target the fetal rodent lung, including intra-amniotic injection10-12, (ultrasound-guided) intrapulmonary injection13,14 and intravenous administration into the yolk sac vessels15,16 or umbilical vein17. Our novel surgical procedure enables researchers to inject the agent of choice directly into the fetal mouse trachea which allows for a more efficient delivery to the airways than existing techniques18.

We developed a novel surgical approach for intratracheal administration of bioactive agents into the mouse fetus. The delivery route is more efficient in targeting the fetal mouse lungs than the commonly used intra-amniotic injection. This procedure has to date not been described in a mouse model.

一种新的手术方法气管内注射生物活性剂在胎鼠模型

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and ...

A Contusion Model of Severe Spinal Cord Injury in Rats

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is described to obtain a consistent model of severe SCI. Use of a stereotactic frame and computer controlled impactor allows for creation of reproducible injury. Hypothermia and urinary tract infection pose significant challenges in the post-operative period. Careful monitoring of animals with daily weight recording and bladder expression allows for early detection of post-operative complications. The functional results of this contusion model are equivalent to transection models. The contusion model can be utilized to evaluate the efficacy of both neuroprotective and neuroregenerative approaches.

A contusion model of severe spinal cord injury is described. Detailed pre-operative, operative and post-operative steps are described to obtain a consistent model.

挫伤模型脊髓严重损伤的保护作用

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

Angiogenesis in the Ischemic Rat Lung

The adult lung is perfused by both the systemic bronchial artery and the entire venous return flowing through the pulmonary arteries. In most lung pathologies, it is the smaller systemic vasculature that responds to a need for enhanced lung perfusion and shows robust neovascularization. Pulmonary vascular ischemia induced by pulmonary artery obstruction has been shown to result in rapid systemic arterial angiogenesis in man as well as in several animal models. Although the histologic assessment of the time course of bronchial artery proliferation in rats was carefully described by Weibel 1, mechanisms responsible for this organized growth of new vessels are not clear. We provide surgical details of inducing left pulmonary artery ischemia in the rat that leads to bronchial neovascularization. Quantification of the extent of angiogenesis presents an additional challenge due to the presence of the two vascular beds within the lung. Methods to determine functional angiogenesis based on labeled microsphere injections are provided.

The lung is perfused by both the systemic bronchial artery and pulmonary arteries. In most lung pathologies, it is the smaller systemic vasculature that shows robust neovascularization. Cessation of pulmonary blood flow promotes brisk bronchial angiogenesis. We provide surgical details of inducing left pulmonary artery ischemia that promotes bronchial neovascularization.

在缺血大鼠肺的血管生成

The  adult lung is perfused by both the systemic bronchial artery and the entire  venous return flowing through the pulmonary arteries. In most lung ...

The Goeckerman Regimen for the Treatment of Moderate to Severe Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2-3% of the population. The Goeckerman regimen consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). Goeckerman therapy is extremely effective and relatively safe for the treatment of psoriasis and for improving a patient's quality of life. In the following article, we present our protocol for the Goeckerman therapy that is utilized specifically at the University of California, San Francisco. This protocol details the preparation of supplies, administration of phototherapy and application of topical tar. This protocol also describes how to assess the patient daily, monitor for adverse effects (including pruritus and burning), and adjust the treatment based on the patient's response. Though it is one of the oldest therapies available for psoriasis, there is an absence of any published videos demonstrating the process in detail. The video is beneficial for healthcare providers who want to administer the therapy, for trainees who want to learn more about the process, and for prospective patients who want to undergo treatment for their cutaneous disease.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. The Goeckerman regimen, formulated for the treatment of psoriasis, consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). The following protocol is for the administration of Goeckerman therapy for the treatment of moderate-to-severe psoriasis.

Goeckerman方案用于治疗中度至重度牛皮癣

Psoriasis is a  chronic, immune-mediated inflammatory skin disease affecting approximately 2-3%  of the population. The Goeckerman regimen consists of ...

A Novel Approach for the Administration of Medications and Fluids in Emergency Scenarios and Settings

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or intraosseous routes, but in many patients, particularly in the emergency or critical care settings, these routes are often unavailable or time-consuming to access. A novel device is now available that offers an easy route for administration of medications or fluids via rectal mucosal absorption (also referred to as proctoclysis in the case of fluid administration and subsequent absorption). Although originally intended for the palliative care market, the utility of this device in the emergency setting has recently been described. Specifically, reports of patients being treated for dehydration, alcohol withdrawal, vomiting, fever, myocardial infarction, hyperthyroidism, and cardiac arrest have shown success with administration of a wide variety of medications or fluids (including water, aspirin, lorazepam, ondansetron, acetaminophen, methimazole, and buspirone). Device placement is straightforward, and based on the observation of expected effects from the medication administrations, absorption is rapid. The rapidity of absorption kinetics are further demonstrated in a recent report of the measurement of phenobarbital pharmacokinetics. We describe here the placement and use of this device, and demonstrate methods of pharmacokinetic measurements of medications administered by this method.

This study presents a novel device that offers an easy route to quickly provide medications and fluids in patients with limited or difficult IV access. This small-diameter device is placed in the distal third of the rectum, allowing for ongoing medication and fluids administration.

应急方案和设置药物和液体管理的新方法

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or ...

A Component-resolved Diagnostic Approach for a Study on Grass Pollen Allergens in Chinese Southerners with Allergic Rhinitis and/or Asthma

Sensitization to grass pollen imposes a global risk for allergic airway diseases. Although prevention relies on local investigation of the pollen allergens, data on this topic are limited in southern China. Any available data were obtained by self-report questionnaires, skin prick tests, and total or specific IgE tests using crude extracts. For many reasons, these methods are unreliable. Serum sIgE reactivity to Bermuda grass, Timothy grass, and Humulus scandens allergens in a cohort of patients from Greater Guangzhou (southern China&#39;s largest city and its outskirts) with allergic rhinitis and/or asthma were examined using a fully-automated immunoassay analyzer as a component-resolved diagnostics (CRD) tool.
For the first time, a considerably high prevalence of Bermuda grass sIgE positivity was demonstrated in Chinese southerners with allergic rhinitis and/or asthma. In these patients, a subtle prevalence of sensitization to Timothy grass and Humulus scandens was also noted, which may arise from cross-reactivity, as the latter two are not common in the region. This was also supported by the detection of allergen components.
Fully-automated immunoassay analyzers may offer satisfactory consistency between regions, laboratories, and institutions and over time. The automaticity of the instrument may enable a standardized detection that would not have been readily revealed before the advent of CRD.
This is a study that uses a CRD approach to investigate sensitization to grass pollen allergens in southern China. It adds to current evidence in the literature. Future studies are needed to validate these findings. However, although CRD is a useful tool, the findings made with the fully-automated immunoassay analyzer should not substitute for other laboratory investigations, clinical evaluations, and physician expertise.

This work describes a protocol that uses a component-resolved approach to study sensitization to grass pollen allergens in a cohort of patients from southern China with allergic rhinitis and/or asthma.

中国南方与过敏性鼻炎和/或哮喘的花粉过敏原研究的成分分析诊断方法

Sensitization to grass pollen imposes a global risk for allergic airway diseases. Although prevention relies on local investigation of the pollen ...

Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization and for minimizing organ damage resulting from prolonged extracorporal circulation. The goal of this paper was to demonstrate a fully functional and clinically relevant model of cardiopulmonary bypass in a mouse. We report on the device design, perfusion circuit optimization, and microsurgical techniques. This model is an acute model, which is not compatible with survival due to the need for multiple blood drawings. Because of the range of tools available for mice (e.g., markers, knockouts, etc.), this model will facilitate investigation into the molecular mechanisms of organ damage and the effect of cardiopulmonary bypass in relation to other comorbidities.

This paper describes how to perform cardiopulmonary bypass in mice. This novel model will facilitate the investigation of the molecular mechanisms involved in organ damage.

小鼠体外循环模型: 一种新方法

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization ...

A Novel Approach to Overcome Movement Artifact When Using a Laser Speckle Contrast Imaging System for Alternating Speeds of Blood Microcirculation

The laser speckle contrast imager (LSCI) provides a powerful yet simple technique for measuring microcirculatory blood flow. Ideal for blood dynamic responses, the LSCI is used in the same way as a conventional Laser Doppler Imager (LDI). However, with a maximum skin depth of approximately 1 mm, the LSCI is designed to focus on mainly superficial blood flow. It is used to measure skin surface areas of up to 15 cm x 20 cm. The new technique introduced in this paper accounts for alternating speeds of microcirculations; i.e. both slow and fast flow flux measurement using the LSCI. The novel technique also overcomes LSCI&#39;s biggest shortcoming, which is high sensitivity to artifact movement. An adhesive opaque patch (AOP) is introduced for satisfactory recording of microcirculatory blood flow, by subtracting the LSCI signal from the AOP from the laser speckle skin signal. The optimal setting is also defined because the LSCI is most powerful when flux changes are measured relative to a reference baseline, with blood microcirculatory flux expressed as a percentage change from the baseline. These changes may be used for analyzing the status of the blood flow system.

This study introduces a novel technique for the measurement and analysis of alternating speeds of blood microcirculation in a single experiment using a laser speckle contrast imager.

用激光散斑对比成像系统克服运动伪影的新方法血液微循环的交替速度

The laser speckle contrast imager (LSCI) provides a powerful yet simple technique for measuring microcirculatory blood flow. Ideal for blood dynamic ...

Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological pathways impair the inflammation response, resulting in delayed wound healing. Impaired wound healing frequently occurs in patients with diabetes leading to unfavorable outcomes such as amputation. Hence, dressings having beneficial effect in promoting burn wound repair are needed. However, studies on burn wound treatment are limited due to lack of proper animal models. Our previous study demonstrated wound-healing performance in rat and swine models using a minimally invasive surgical technique. This study aimed to demonstrate a swine model of severe burn injury that eliminates wound contraction and more closely approximates the human processes of re-epithelialization and new tissue formation. This protocol provides a detailed procedure for creating consistent burn wounds and examining the wound-healing performance under the treatment of an experimental dressing in a swine model. Six burn wounds were created symmetrically on the dorsum, which were covered with a clinical dressing composed of four layers: an inner contact layer of experimental materials, an inner intermediate layer of waterproof film, an outer intermediate layer of gauze, and an outer layer of adhesive plaster. Upon the completion of experiments, wound closure, wound area, and Vancouver Scar Scale score were examined. The samples of skin resected from each animal post-sacrifice were histologically prepared and stained using hematoxylin and eosin staining. Antibacterial activity of each dressing in the context of wound healing was also examined. The application of the clinical dressing to the wounds in swine model mimics the biological processes of human wound healing with respect to the processes of epithelialization, cellular proliferation, and angiogenesis. Therefore, this swine model provides an easy-to-learn, cost-effective, and robust method to assess the effect of clinical dressings in severe burn injury.

To closely mimic the mode of burn injuries requires the interplay between clinical observation and studies in animal models. In this study, a swine model of severe burn injury was established to assess an experimental dressing in physiological and pathophysiological settings.

猪临床敷料评价模型中的严重烧伤

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological ...