我们承认日本促进科学协会 (KAKENHI 赠款至 [26893261])、Okinaka 医学研究纪念研究所 (对 KN) 以及日本卫生部、劳工和福利部 (TN) 提供的资助;Mrs. Kohichi 蒲田和 Atsushi 山在崎玉医科大学国际医学中心的病理学系, 为其组织化学和免疫组织化学染色提供了良好的帮助;以及 Dr. 塞尔索·阿莫林 e. 戈麦斯-桑切斯提供的小鼠单克隆 CYP11B2 抗体和大鼠单克隆 CYP11B1 抗体。

这项研究由崎玉医科大学国际医疗中心和横滨 Rosai 医院的机构审查委员会批准 (批准号: 16-093 和 26-38, 分别)。在手术前, 所有患者均获得书面同意. 
 1. 患者准备 <ol> <li> 在检查床上设置病人. </li>
	<li> 在手术过程中, 在上臂 (或左腿) 上放置一条静脉导管, 用于用药. </li>
	<li> 在适当的皮肤消毒和局部麻醉后, 将通路鞘插入右股静脉. </li>
	<li> 收集血液样本 (1 毫升) 从右股静脉 (外周血样本的管理前促). </li>
</ol> 2。导尿管 <ol> <li> ssAVS 右肾上腺电视 <ol> 插入任一导管与 mk 肾上腺-R 形状 (<li> 图 1A 和 1B ) 或导管与 mk X 形状 ( 图 1C )进入右肾上腺静脉 (雷夫), 如先前所报告的 15 , 16 , 收集血液样本 (1 毫升), 并取出导管 (右骑士样本前的管理促)。如果需要, 使用微导管. </li>
		<li> 为右肾上腺选择合适的父导管: 当和 #34; 下腔和 #34 的长径; 短于25毫米, 使用 MK 肾上腺-R。否则, 使用 MK x. </li>
		如果需要, <li> 重新定型父导管。
		<ol> <li> 基于 CT 图像, 塑造选定导管的宽度 ( 图 1A 或 1C 中的红色双向箭头) 以适合 #34; 下腔和 #34 的长直径; 15 (也请参阅案例 #1)和导管尖端的角度, 以适应和 #34; 修改了雷夫和 #34 的横向角度; 15 (也请参见案例 #1). </li>
			<li> 重新塑造导管, 同时将高温蒸汽从开水 (如电子水壶) 应用到导管。在其他地方 15 中描述了详细的过程. </li>
		</ol> </li> <li> 将父导管的尖端插入雷夫, 并以适当的角度 (雷夫的平均修改横向角度: 123.6 和 #176;) 15 和深度 (1-2 mm). 
		注: 准确的母导管放置是将微导管送至靶电视的关键. </li>
		<li> 操作母导管以改变导管尖端的方向, 以便瞄准其中一个正确的电视, 然后插入一个含盐水的微导管, 丝. 
		注: 推拉母导管会改变母导管的垂直角度, 即 当 3 d 型导管向脚部拉动时, 导管尖端向上, 而导管尖端则向下定向, 当导管被推挤 (参见案件 #1 下面)。一旦导管尖端插入雷夫出口的适当角度和深度, 微导管可以插入。这是重要的考官, 以防止病人的呼吸深度或垂直角度可能改变。上面所述的微导管插入丝到电视中. </li>
		<li> 用数字减影血管造影通过微导管进行造影, 少量生理盐水稀释 (1:1) 造影剂 (0.1-0.3 毫升; 普罗注射液), 轻轻冲洗。在血浆醛固酮浓度 (PAC) 和血浆皮质醇浓度 (PCC) 的测量中, 缓慢收集1毫升血液样本. </li>
		<li> 微导管稍稍向后拉, 用至少0.5 毫升盐水冲洗微导管线。在下一台电视上瞄准母导管提示. </li>
		<li> 对所有正确的电视重复步骤2.1.6 和 2.1.7. </li>
	</ol> </li> <li> ssAVS 左肾上腺电视 <ol> <li> 将 L 形导管 ( 图 2 ) 插入左肾上腺静脉 (LAV), 收集血液样本 (1 毫升), 并取出导管 (左骑士样本前管理促)。使用微导管. </li>
		<li> 放置父导管. 
		注意: 解剖上, 左肾上腺中央静脉与下膈静脉汇合, 静脉血流到 LAV 8 。因此, 要只收集左肾上腺组织的静脉血标本, 需要插入左肾上腺中央静脉, 即 , 在与膈下静脉合并前插入穴位, 这通常需要微导管, 甚至骑士。当进行肾上腺中央静脉造影, 类似于右侧, 这是重要的, 以确定左肾上腺电视, 特别是侧电视 (见和 #34; 案例 #2 作为一个例子, LAV-ssAVS 和 #34;)。使用 L 型导管的首选。部分 #1, #2, 和 #3 ( 图 2 ) 的导管适合下腔静脉, 肾静脉, 以及 LAV 的共同躯干, 从而允许部分 #3 稳定地坐在共同的躯干. </li>
		<li> 将微导管插入左侧肾上腺电视, 并从左电视收集血液样本。查看步骤 2.1.5-2.1.6 以上为一般程序的右肾上腺电视. 
		注: 微导管和丝 (与右 ssAVS 相同) 插入电视 (通常是上级-中位, 上侧和侧电视), 如下所述 #2 的情况下, 并收集血液样本. </li>
	</ol> </li> </ol> 3。注射后 <ol> <li> 注入200和 #181; 通过静脉线进行合成肾上腺皮质激素激素 (促、丸) g, 然后连续促50和 #181; g/分钟 </li>
	<li> 十五分钟后, 促注射, 再次执行骑士, 如上文所述, 和 ssAVS, 如步骤2.1 和2.2。收集1毫升血液. </li>
	<li> 从右股静脉采集血液样本 </li>
	<li> 卸下所有导管和通道鞘, 完成便秘后的骑士和 ssAVS 检查. 
	注: 有关一般肾上腺静脉取样技术的详细资料 (除3.2 的步骤外), 请参阅其他教科书或期刊 17 . </li>
</ol>

<ol>
	<li>Funder, J. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Management+of+Primary+Aldosteronism:+Case+Detection,+Diagnosis,+and+Treatment:+An+Endocrine+Society+Clinical+Practice+Guideline.">The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.</a> J Clin Endocrinol Metab. 101 (5), 1889-1916 (2016).</li><li>Akehi, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Proposed+diagnostic+criteria+for+subclinical+Cushing's+syndrome+associated+with+adrenal+incidentaloma.">Proposed diagnostic criteria for subclinical Cushing's syndrome associated with adrenal incidentaloma.</a> Endocr J. 60 (7), 903-912 (2013).</li><li>Choi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=K++channel+mutations+in+adrenal+aldosterone-producing+adenomas+and+hereditary+hypertension.">K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension.</a> Science. 331 (6018), 768-772 (2011).</li><li>Beuschlein, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Somatic+mutations+in+ATP1A1+and+ATP2B3+lead+to+aldosterone-producing+adenomas+and+secondary+hypertension.">Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension.</a> Nat Genet. 45 (4), 440-444 (2013).</li><li>Scholl, U. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Somatic+and+germline+CACNA1D+calcium+channel+mutations+in+aldosterone-producing+adenomas+and+primary+aldosteronism.">Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism.</a> Nat Genet. 45 (9), 1050-1054 (2013).</li><li>Azizan, E. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Somatic+mutations+in+ATP1A1+and+CACNA1D+underlie+a+common+subtype+of+adrenal+hypertension.">Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension.</a> Nat Genet. 45 (9), 1055-1060 (2013).</li><li>Tamura, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Somatic+KCNJ5+mutation+occurring+early+in+adrenal+development+may+cause+a+novel+form+of+juvenile+primary+aldosteronism.">Somatic KCNJ5 mutation occurring early in adrenal development may cause a novel form of juvenile primary aldosteronism.</a> Mol Cell Endocrinol. 441, 134-139 (2017).</li><li>McLachlan, M. S., Roberts, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Demonstration+of+the+normal+adrenal+gland+by+venography+and+gas+insufflation.">Demonstration of the normal adrenal gland by venography and gas insufflation.</a> Br J Radiol. 44 (525), 664-671 (1971).</li><li>Nishikawa, T., Matsuzawa, Y., Saito, J., Omura, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Is+it+Possible+to+Extirpate+Cardiovascular+Events+in+Primary+Aldosteronism+After+Surgical+Treatment.">Is it Possible to Extirpate Cardiovascular Events in Primary Aldosteronism After Surgical Treatment.</a> Jpn Clin Med. 1, 21-23 (2010).</li><li>Nishikawa, T., Matsuzawa, Y., Saito, J., Omura, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Super-selective+ACTH-stimulated+adrenal+venous+sampling+can+simply+differentiated+bilateral+adrenal+hyperplasia+from+bilateral+adenomas+in+primary+aldosteronism.">Super-selective ACTH-stimulated adrenal venous sampling can simply differentiated bilateral adrenal hyperplasia from bilateral adenomas in primary aldosteronism.</a> , 35-36 (2009).</li><li>Nishimoto, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Case+Report:+Nodule+Development+From+Subcapsular+Aldosterone-Producing+Cell+Clusters+Causes+Hyperaldosteronism.">Case Report: Nodule Development From Subcapsular Aldosterone-Producing Cell Clusters Causes Hyperaldosteronism.</a> J Clin Endocrinol Metab. 101 (1), 6-9 (2016).</li><li>Miekos, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anatomical+basis+of+radiodiagnosis+of+the+adrenal+gland.">Anatomical basis of radiodiagnosis of the adrenal gland.</a> Int Urol Nephrol. 11 (3), 193-200 (1979).</li><li>Omura, M., Saito, J., Matsuzawa, Y., Nishikawa, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Supper-selective+ACTH-stimulated+adrenal+vein+sampling+is+necessary+for+detecting+precisely+functional+state+of+various+lesions+in+unilateral+and+bilateral+adrenal+disorders,+inducing+primary+aldosteronism+with+subclinical+Cushing's+syndrome.">Supper-selective ACTH-stimulated adrenal vein sampling is necessary for detecting precisely functional state of various lesions in unilateral and bilateral adrenal disorders, inducing primary aldosteronism with subclinical Cushing's syndrome.</a> Endocr J. 58 (10), 919-920 (2011).</li><li>Nishikawa, T., Omura, M., Saito, J., Matsuzawa, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Primary+aldosteronism:+comparison+between+guidelines+of+the+Japanese+and+the+US+Endocrine+Society.">Primary aldosteronism: comparison between guidelines of the Japanese and the US Endocrine Society.</a> Expert Rev. Endocrinol. Metab. 7 (6), 637-645 (2012).</li><li>Araki, T., Okada, H., Onishi, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Does+catheter+shape+influence+the+success+of+right+adrenal+venous+sampling?+The+interaction+of+catheter+shape+to+anatomical+factors+on+CT.">Does catheter shape influence the success of right adrenal venous sampling? The interaction of catheter shape to anatomical factors on CT.</a> Jpn J Radiol. 34 (11), 707-717 (2016).</li><li>Young, W. F., Stanson, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+are+the+keys+to+successful+adrenal+venous+sampling+(AVS)+in+patients+with+primary+aldosteronism?.">What are the keys to successful adrenal venous sampling (AVS) in patients with primary aldosteronism?.</a> Clin Endocrinol (Oxf). 70 (1), 14-17 (2009).</li><li>Harsha, A., Trerotola, S. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technical+aspects+of+adrenal+vein+sampling.">Technical aspects of adrenal vein sampling.</a> J Vasc Interv Radiol. 26 (2), 239 (2015).</li><li>Nishikawa, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+the+diagnosis+and+treatment+of+primary+aldosteronism--the+Japan+Endocrine+Society+2009.">Guidelines for the diagnosis and treatment of primary aldosteronism--the Japan Endocrine Society 2009.</a> Endocr J. 58 (9), 711-721 (2011).</li><li>Nishimoto, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immunohistochemistry+of+aldosterone+synthase+leads+the+way+to+the+pathogenesis+of+primary+aldosteronism.">Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism.</a> Mol Cell Endocrinol. , (2016).</li><li>Nishimoto, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adrenocortical+zonation+in+humans+under+normal+and+pathological+conditions.">Adrenocortical zonation in humans under normal and pathological conditions.</a> J Clin Endocrinol Metab. 95 (5), 2296-2305 (2010).</li><li>Funder, J. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Case+detection,+diagnosis,+and+treatment+of+patients+with+primary+aldosteronism:+an+endocrine+society+clinical+practice+guideline.">Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline.</a> J Clin Endocrinol Metab. 93 (9), 3266-3281 (2008).</li><li>Heitzer, E., Auer, M., Ulz, P., Geigl, J. B., Speicher, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circulating+tumor+cells+and+DNA+as+liquid+biopsies.">Circulating tumor cells and DNA as liquid biopsies.</a> Genome Med. 5 (8), 73 (2013).</li><li>Alix-Panabieres, C., Pantel, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+Applications+of+Circulating+Tumor+Cells+and+Circulating+Tumor+DNA+as+Liquid+Biopsy.">Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy.</a> Cancer Discov. 6 (5), 479-491 (2016).</li><li>Pinzani, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+circulating+tumor+cells+in+patients+with+adrenocortical+carcinoma:+a+monocentric+preliminary+study.">Detection of circulating tumor cells in patients with adrenocortical carcinoma: a monocentric preliminary study.</a> J Clin Endocrinol Metab. 98 (9), 3731-3738 (2013).</li><li>Pantel, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circulating+epithelial+cells+in+patients+with+benign+colon+diseases.">Circulating epithelial cells in patients with benign colon diseases.</a> Clin Chem. 58 (5), 936-940 (2012).</li><li>Chiu, L. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+differentially+expressed+microRNAs+in+human+hepatocellular+adenoma+associated+with+type+I+glycogen+storage+disease:+a+potential+utility+as+biomarkers.">Identification of differentially expressed microRNAs in human hepatocellular adenoma associated with type I glycogen storage disease: a potential utility as biomarkers.</a> J Gastroenterol. 49 (8), 1274-1284 (2014).</li><li>Nishimoto, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aldosterone-stimulating+somatic+gene+mutations+are+common+in+normal+adrenal+glands.">Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands.</a> Proc Natl Acad Sci U S A. 112 (33), E4591-E4599 (2015).</li></ol>

作者没有什么可透露的。

本文介绍了具有代表性的案例结果的 ssAVS 技术。病例 #1-2 例, 病例 #3 分别根据 ssAVS 结果进行手术治疗。此外, #1-3 病例的结果表明, ssAVS 样本中的类固醇激素浓度清楚地反映了上游肾上腺组织, 特别是肿瘤的激素活性, 推测是因为肿瘤血流是直接得到的。ssAVS 方法可能在鉴别肾上腺皮质病变 (例如, #1-2), 在明确诊断 IHA (如:如, 病例 #3) 和基础科学研究中发挥不可估量的作用, 以阐明pathophysiologies 肾上腺皮质疾病, 并发现新的生物标志物的这些疾病如下所述。
pa1、1821建议执行骑士通过计算侧比率 ([高 pac/pcc]/[低 pac/pcc]) 来鉴别 pa 的单侧肾上腺损伤。然而, 这种计算可能导致误诊时, 皮质醇产生的病变共存。可能的皮质醇产生腺瘤的情况下 #2 清楚地产生过量的皮质醇在右肾上腺, 和皮质醇生产左肾上腺被压制。重要的是要注意, 许多 apa 也产生过量的皮质醇, 因为他们经常表达的 CYP11B2 和 CYP11B120。骑士侧比率的另一个限制是, 它不能区分双边 apa 与特发性症 (例如, 案例 #3)。
此外, ssAVS 血液样本可能会大大促进激素过剩疾病的研究和治疗的进展。例如, 从腺瘤收集的 ssAVS 血液目录可能含有高浓度的循环肿瘤细胞及其 DNA22,23。以往的研究报告, 液体活检方法是临床有用的鉴别肾上腺皮质癌从腺瘤24和诊断良性腺瘤疾病25,26。为了证明这一概念, 目前正在尝试检测 APA 相关的突变, 包括使用 ssAVS 样本的KCNJ5和高性能的下一代排序器71119 ,27, 这可能有助于将来的 APA 治疗。液态活检细胞也可能为研究人员提供在 IHA 上进行分子分析的机会, 这是目前不可能的, 因为这种疾病不能通过手术治疗。除了液体活检方法外, 单纯的肿瘤流出样可能有助于代谢研究, 以识别新的类固醇生物标志物。
ssAVS 方法的关键技术步骤是: (i) 在中央肾上腺静脉造影中识别各支流静脉。(ii) 在静脉造影时, 使用少量造影剂 (0.1-0.3 毫升), 轻轻冲洗, 避免肾上腺出血。(iii) 轻轻地推进丝, 不需要太多的力, 以避免穿透支流静脉。(iv) 当肾上腺出血发生或怀疑时立即终止该方法。
选择父母导管对 ssAVS 的成功也是至关重要的。关于骑士的雷夫, 荒 et al. 最近报告了一个三维 (3 d) 型导管的用处, 3D 形状的15。带有 R 形 (图 1A和1B) 的导管和带有 X 形 (图 1C) 的导管可作为 ssAVS 3 d 型导管使用。荒 et al. 分析了一些解剖参数的基础上的 CT 表现, 关于成功率的 3 d 型导管15。在单变量分析中 (i) 较短的 "下腔静脉短径 (下)" (ii) 较大的 "长径比下腔静脉的短直径" (iii) 更小的 "雷夫的横向角度" (iv) 更小的 "修改过的横向角度雷夫", 和 (五) 较小的 "雷夫的垂直角与雷夫的成功率相关。在多变量分析中, 只有 (iv) 较小的 "改良横角雷夫" 是成功雷夫插管的独立预测因子。他们的结论是, 多变量分析的结果可能是由于在下腔静脉导管的稳定性;即, 3 d 型导管的宽度 (图 1A和1C中的红色双向箭头) 非常适合 "下腔静脉的长径", 从而稳定了这些导管。总的来说, 当 "下腔静脉的长径" 短于25毫米时, 使用 mk 肾上腺-R, 否则 mk x。
总的来说, ssAVS 的意义是: (一) 它对促进激素过剩疾病研究的贡献 (ii) 通过将激素产生性病变隔离到肾上腺段的水平 (见 #1) (iii.)通过收集纯肾上腺流出来促进对皮质醇过量的评估 (见案例 #2) (iv) 检测实际特发性症 (见案例 #3) (五) 它对推动新疗法的发展作出了贡献, 其中可能包括肾上腺的跨静脉节段消融术。因此, 如果按照本文所述, 任何 angiographer 可能成功地执行 ssAVS 协议, 除了骑士, 并有助于促进研究和治疗肾上腺激素过剩疾病。
ssAVS 与骑士经常在横滨 Rosai 医院和崎玉医学院为 PA 病人。在2014年10月和2015年9月之间, 两个 angiographers (公里和 SM) 对125例 (分别为78和47例) 进行了 ssAVS, 100% 的成功率和合理时间内 (58-130 分钟) 不需要手术的肾上腺破裂或血栓形成。在这种方法中, 一个额外的成本是发生的微导管 (10 倍的费用在日本比传统的导管) 和 PAC/PCC 测量的支流样品。然而, 考虑到该程序的临床和科学效益, 额外的费用是合理的, 至少在工业化国家。ssAVS 和双边肾上腺的一个边际限制是, 它可能无法治愈双边病变, 需要进行后续评估, 包括评估 PA 复发 (见案例 #1)。然而, 对单方面的 PA 案件也是如此。因此, 这些结果表明, 任何 angiographer 都能够按照本视频文章中提供的协议执行 ssAVS 的高成功率。为了促进ssAVS 方法在世界各地, 在横滨 Rosai 医院和玉崎医科大学始终提供实践培训。如果您对此方法感兴趣, 请随时与这些机构联系。

原发性醛 (PA) 和亚临床库欣氏综合征 (SCS) 的情况下, 肾上腺自主产生过量的醛固酮和皮质醇, 分别。在成人中, PA 主要由醛固酮产生腺瘤 (APA) 或特发性症 (IHA)1引起, 而 SCS 主要是由皮质醇产生的腺瘤2引起的。离子通道/泵基因中的体细胞突变, 包括钾通道、内整流亚科 J、成员 5 (KCNJ5), 已在 apa 中被识别, 并与自主醛固酮生成有关3,4,5,6. 家族性症类型 1-3 是 PA 的稀有类型, 而类型3是由KCNJ5生殖细胞变异3引起的。一个新类型的少年 PA 的情况下, 这大概是由于遗传嵌的正常和KCNJ5突变的肾上腺皮质细胞, 最近被确定为7。在少年 PA 的情况下, 肾上腺皮质由正常部分和增生性醛固酮产生的损害, 与正常部分被识别的小说 ' 选择性 ' 肾上腺静脉取样 (ssAVS, 也称为节段性肾上腺静脉取样) 方法的描述。ssAVS 方法允许这种双边 PA 患者手术治疗的双边肾上腺, 同时保留正常部分7。
肾上腺静脉取样最初报告在 1971年8时, 计算机断层扫描 (CT) 尚未开发。在 "常规" 肾上腺静脉取样 (骑士), 导管插入两个肾上腺中央静脉, 血液样本收集。因此, 骑士只适用于判断 pa 的侧, 而不用于确定双边 pa 的手术选择。Kohzoh 牧 (本文作者) 在横滨 Rosai 医院开发了 ssAVS 方法, 以调查 PA7、8、9的其他外科治疗选项, 10,11, 这对 SCS 也很有用, 如情况 #2 (请参见代表性结果) 中所述。
在 ssAVS, 血液样本收集的小肾上腺支流静脉 (电视: 较小的上游分支肾上腺中央静脉) 使用专门的分裂尖端微导管9。右侧和左侧肾上腺通常有三条支流静脉, 即在右侧肾上腺中的上级、侧面和下位电视以及左侧肾上腺中的中位、上侧和侧电视。这些电视12之间的连接很少被识别。因此, ssAVS 能够识别一个特定的肾上腺段 (s) 不产生醛固酮在一个受影响的肾上腺, 从而允许双侧肾上腺手术在双边 PA, 同时保留不影响肾上腺段 (s)。此外, ssAVS 方法也适用于少年 pa 等新型 pa 的病理生理学研究 (如上述7) 和双侧 APA13、14。由于对双边 PAs 的治疗和对其发病机制的说明至关重要, 其中可能包括 "特发性" 症, 因此建议在全世界范围内 ssAVS, 因此, 本文提供了有关方法的详细描述。

<table border="0" cellpadding="0" cellspacing="0" width="1000">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:303px;">CX-Catheter EII with the MK Adrenal-R shape</td>
			<td style="width:143px;">Silux co.</td>
			<td style="width:164px;">GA-E5F-MK1-60S</td>
			<td style="width:391px;">3D catheter for right adrenal venous sampling</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">CX-Catheter EII with the MK X shape</td>
			<td>Silux co.</td>
			<td>GA-E5F [MK-X] 60S</td>
			<td>3D catheter for right adrenal venous sampling</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Aqua V3 guidewire</td>
			<td>Formec co.</td>
			<td>HS8616H</td>
			<td>guidewire for the micro-catheter</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Gold Crest Micro-Catheter</td>
			<td>Goldcrest Medic Inc.</td>
			<td>KCV29S1S-OM</td>
			<td>micro-catheter for superselective adrenal venous sampling</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">CX catheter-UII with the MK ADRENAL-L shape</td>
			<td>Silux co.</td>
			<td>GA-US5F [MK-3] B65S</td>
			<td>3D catheter for left adrenal venous sampling</td>
		</tr>
	</tbody>
</table>

a novel method: super-selective adrenal venous sampling

原发性醛 (PA) 和亚临床库欣氏综合征 (SCS) 的情况下, 肾上腺自主产生过量的醛固酮和皮质醇, 分别。传统的肾上腺静脉取样 (骑士) 方法收集来自肾上腺中心静脉的血样, 并可用于鉴别单侧病变 (s) 中过剩激素的侧, 如 PA 病例所示。在骑士队, 血浆皮质醇浓度 (PCCs) 被用来正常化血浆醛固酮浓度 (PACs)。一种新的 "选择性" 肾上腺静脉取样 (ssAVS) 的方法是利用微导管, 收集血液样本从肾上腺支流静脉 (电视)。ssAVS 样本中的 PACs 不需要 PCC 正常化, 因为样本含有有限数量的全身静脉血, 如果有的话。ssAVS 方法可以在两个肾上腺中检测到节段性病变, 这可能由双侧肾上腺, 从而保留无损伤段 (s)。右和左肾上腺通常有三电视,即, 右肾上腺的上位、侧、下位电视以及左侧肾上腺中的中位、上侧和侧电视。在 ssAVS 方法中, 需要特定的母导管和处理它们的技术, 并在此描述。此外, 三例 PA 的 ssAVS 结果提出: 双侧醛固酮产生腺瘤 (apa) (病例 #1), 左 APA 和右侧可能产生的皮质醇分泌腺瘤 (病例 #2), 和特发性症, 其中双边肾上腺段产生过量的醛固酮 (病例 #3)。ssAVS 方法是不难的专家 angiographers, 因此, 建议在全球范围内治疗 PA 的情况下, 骑士不代表一个可行的外科治疗选项。

案例 #1 (YRPA #3472)
案例 #1 是一个 46 year-old 的女性。当她33岁的时候, 她在当地医院住院治疗严重高血压合并低钾血症 (血清钾 1.8 [正常范围: 3.5-5.9] 当量/升)。她被诊断为根据血液测试结果 (PAC 320 [35.7-240] pg/毫升, PRA 和 #60; 0.1 [0.3-2.9] ng/毫升/小时)。CT 显示双侧肾上腺皮质腺瘤 (数据不可用)。在骑士之后 (数据不可用), 她接受了左肾上腺, 但她的 PA 坚持了。第一次手术后十三年 (46 岁), 她被称为横滨 Rosai 医院评估 PA。身体检查是正常的, 除了高身体质量索引 (29.3 [和 #60; 25] 公斤或 m2)。实验室测试是正常的, 除了非常高的 PAC (1490 pg/毫升) 和非常低血清 K (2.2 当量/升)。她的 PAC 是非常高 (2550 [截止: 和 #60; 60] pg/毫升), 甚至4小时后, 2 升盐水 (盐水输液测试), 表明她有严重的 PA。腹部 CT 扫描显示22毫米右侧肾上腺肿瘤 (图 3A)。
骑士和 ssAVS 在刺激下进行了合成肾上腺皮质激素激素 (ACTH)。基于 CT "下腔静脉的长径" (图 3A中红色虚线的长度) 和 "修改过的雷夫的横向角度" (图 3A中红色和蓝色虚线之间的较大角度) 分别为 28 mm 和145度。导管的 "宽度" 和 "尖角" 与 X 形状 (图 1C) 前重塑以适合下腔静脉和雷夫, 详见15。插管进入雷夫的出口很快就完成了, 没有任何困难。右肾上腺静脉造影显示, 侧电视明显扩大 (粉红色箭头在图 3B) 在其分支机构概述了肿瘤的形状, 表明大量的血液从腺瘤流出到这台电视机里。在证实其静脉造影 (图 3C) 后, 插入了一根微导管, 并从侧电视采集血液样本。通过拉动和推导管, 微导管很容易插入到上、下位电视中进行静脉造影 (图 3D和3E), 随后进行取样。
在中央静脉和侧电视的 PAC 是非常高的 (42.2万 pg/毫升和 58.8万 pg/毫升, 分别; 正常范围和 #60; 1.4万 pg/毫升为两个18), 建议肿瘤是一个 APA (图 3C, 表 1)。在高级和下位电视的 PAC 分别为 8230 pg/毫升和 12600 pg/毫升 (图 3D和3E), 这表明这些电视是从正常的肾上腺组织中采集血液的。在中央静脉, 高级电视, 侧电视和下位电视的 PCC 水平相似 (1110 µg/dl, 1150 µg/dl, 1050 µg/dl, 和1080µg/dl, 分别), 表明皮质醇的生产是均匀的整个肾上腺皮质包括肿瘤轴承部分。因此, 通常用于骑士数据分析的 pac/PCC 值与骑士和 ssAVS 的 pac 值是一致的。她接受了部分肾上腺的正常部分。病理检查发现肾上腺皮质腺瘤 (t 在图 3F), 表达醛固酮合成酶 (CYP11B2) 在许多细胞 (t 在图 3G) 和类固醇11β羟化酶 (CYP11B1, 皮质醇合成酵素) 在少量的单元格 (T 在图 3H中), 确认了 APA19、20的诊断。在毗邻正常肾上腺, 虽然 CYP11B2 没有表达的透明球状, 这可能是由于低循环肾素, CYP11B1 表达的透明束和透明网状 (N 在图 3H), 表明皮质醇生产正常。这些病理结果的 APA 和抑制 CYP11B2 表达在相邻的正常肾上腺组织是一致的 ssAVS 结果 (表 1)。手术后, 她的血压 (114/62 柱), 以及 PAC 和 PRA 在她的外周血 (52 pg/毫升和 0.8 ng/毫升/小时, 分别) 正常化没有任何降压药物。
案例 #2 (YRPA #4119)
案件 #2 是 59 year-old 男性与高血压, 因为他是45岁。CT 在例行体检中偶然发现了双侧肾上腺结节, 这是增强的对比培养基 (图 4A)。他被转介到横滨 Rosai 医院, 进一步评估高血压和肾上腺结节。体检正常, 没有明显的 Cushingoid 特征。血液测试正常, 包括 PCC (7.6 [6.2-18.0] µg/dL), ACTH (20.8 [7.2-63.3] pg/毫升), 和 PAC (201 pg/毫升), 除了 PRA (和 #60; 0.2 ng/毫升/小时) 和血清钾 (3.0 当量/升)。盐水灌注试验显示高 PAC (374 pg/毫升)。PCC 在下午11点和在隔夜管理以后1毫克地塞米松是6.8 和 7.2 (切断: 5 和≤1.8) µg/dL, 分别。因此, 他被诊断为 PA 与 SCS2,18。
为了确定哪个肿瘤是导致过量激素分泌的原因, 骑士与 ssAVS 是在合成促肾上腺皮质激素刺激下进行的。左肾上腺静脉造影使用微导管通过导管与 L 形 (图 2) 确定了典型的高级中位数 (图 4B中的黄色箭头)、上级侧 (红色箭头) 和侧电视 (粉红色箭头)。中位电视有一个短的装填瑕疵, 大概归结于腺瘤 (绿色箭头在图 4B)。值得注意的是, 微导管的头部 (图 4B中的黑色箭头) 被放置在肾上腺中央静脉内, 然后与膈下静脉合并, 从而使侧电视的成像通畅。在丝, 微导管插入到上级中位 (静脉造影是不可用的) 和上级侧 (图 4C) 电视的静脉造影和样本收集。横向电视与垂直合并了中央静脉, 这是一个典型的发现。微导管及其丝的尖端被弯曲并插入侧电视, 采集血液样本。如 #1 的情况所述, 骑士从雷夫和 ssAVS 从右上电视 (红色箭头在图 4E), 侧面电视 (粉红色箭头) 的下游肿瘤, 和劣质电视 (黄色箭头) 也执行。
在骑士和 ssAVS 的数据分析中, 使用了 pac 和 pcc 值, 而不是 pac/pcc 值, 因为 pcc 的值在右边和左边的电视中明显变化 (中值和分范围: 分别为99.6 和 70.3-577.5 µg/dL),表 1)。PAC 在左肾上腺中央静脉高 (94800, #60; 1.4万] pg/毫升), 并在左上-中位电视是非常高的 (30.4万 pg/毫升: 3.2 倍, 在中央静脉), 表明左肾上腺肿瘤是损害 PA 负责。然而, PAC 在左上侧和侧面电视是低的 (分别2060和 2240 pg/毫升), 建议他们收集血液从肿瘤部分。左中央静脉的 PCC 上位电视、上侧电视和侧电视 (74.7 µg/dl、87.1 µg/dl、75.7 µg/dl、54.1 µg/dl 分别) 明显低于 #1, 表明皮质醇生产在整个左肾上腺皮质包括肿瘤由于过量的皮质醇生产从右肾上腺, 如下所述。关于右肾上腺 PAC 在右中央静脉 (5190 pg/毫升,即, 在正常范围内和 #60; 1.4万) 和侧电视 (5300 pg/毫升) 高于那些在高级和劣质电视 (1710 和 2180 pg/毫升, 分别),建议右瘤产生少量醛固酮。右侧电视 (1050 µg/dl) 的 PCC 明显高于右侧电视 (112 µg/dl)、右下电视 (420 µg/dl) 和左电视, 这表明右肾上腺肿瘤产生过量的皮质醇 (即皮质醇产生腺瘤) 和引起的 SCS。为了治疗 PA, 患者接受了正确的部分肾上腺, 正常化他的高血压 (136/82 柱没有药) 和 PAC (50 pg/毫升) 手术后3天。病理检查确定了一个肾上腺皮质腺瘤 (t 在图 4F), 表示 CYP11B2 (t 在图 4G), 但不是 CYP11B1 (t 在图 4H), 确认诊断 APA。相邻的正常肾上腺没有表达 CYP11B1 (N 在图 4H), 这表明皮质醇生产被抑制, 由于可能的皮质醇产生腺瘤在相反的一侧。这些病理结果的腺瘤和相邻的肾上腺组织是一致的 ssAVS 的结果 (表 1)。SCS 目前没有治疗, 因为它没有引起高血压或糖耐量受损2。
总的来说, 在 #1 和 #2 的情况下, ssAVS 方法清楚地显示出节段肾上腺激素的产生, 不仅对醛固酮, 而且对皮质醇, 并使这些患者的手术治疗。
案例 #3 (YRPA #8243)
病例 #3 是一名50岁的 year-old 女性, 自48岁以来因严重高血压而头晕。一个高 PAC 到 PRA 比率 ([131 pg/毫升]/[0.3 ng/毫升/小时] = 436.7, [截止: 和 #60; 200]18) 建议她有 PA。她被转到横滨 Rosai 医院进一步评估高血压。体检是正常的身体质量指数 (23.4 公斤/米2)。血液检查正常, 包括 PAC (183 pg/毫升) 和 PRA (0.4 ng/毫升/小时)。盐水灌注试验显示微高 PAC (66 [截止: 和 #60; 60] pg/毫升)18, 表明她有轻度 PA。一个高 PAC 到 PRA 比率 ([146 pg/毫升]/[0.4 ng/毫升/小时] = 365 [截止: 和 #60; 200]) 后, 卡托普利的管理确认她有 PA (卡托普利挑战测试)18。CT 检测无明显肾上腺腺瘤 (图 5A)。为了确定醛固酮产生的肾上腺段 (s), 骑士与 ssAVS 进行了综合促肾上腺皮质激素刺激。在骑士队, PAC 或 PCC 在右和左中央静脉是 ([57600 pg/毫升]/[901 µg/dl] = 63.9) 和 ([1.8万 pg/毫升]/[389 µg/dl] = 46.3), 分别表明, 她有双边 PA (侧比率 = 1.4, 截止: 和 #60; 2.618, 表 1)。在右 ssAVS, PAC 在高级电视 (#1 在图 5B) 中, 中位电视 (#2)、侧电视 (#3) 和下位电视 (#4) 分别为 59100 pg/毫升、66400 pg/毫升、57300 pg/毫升、45400 pg/毫升。在左 ssAVS, PAC 在高级中值电视 (#1 在图 5C) 中, 上位电视 (#2)、侧电视 (#3) 和下位电视 (#4) 分别为 43900 pg/毫升、19600 pg/毫升、2.3万 pg/毫升、36900 pg/毫升。因此, PAC 超过 1.4万 pg/毫升, 在整个双边电视, 表明案件 #3 是真正的 IHA。她目前正接受皮质受体拮抗剂的治疗。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/55716/55716fig1.jpg"> 
图 1:用于右骑士的导管.(A和B)导管的正面和侧面视图分别为 R 型。(C) 导管与 X 形状的正面视图。由图 1A和1C中的双向箭头表示的长度适合骑士的 "下腔静脉的长直径"15 。<a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55716/55716fig1large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/55716/55716fig2.jpg"> 
图 2:左骑士用导管.导管的正面观点与 L 形状。部分 #1、#2 和 #3 在图中分别适合下膈静脉和 LAV 的下腔、肾静脉和共同躯干, 让部分 #3 稳定地坐在共同的树干上。<a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55716/55716fig2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/55716/55716fig3v4.jpg"> 
图 3:CT, 静脉造影, ssAVS, 组织学切除肾上腺 #1.(A) 对比度增强 CT。红色虚线的长度表示 "下腔静脉的长直径"15。红色和蓝色虚线之间的较大夹角表示 "雷夫的修正横向角"s = "xref" > 15。下腔静脉;Ao, 主动脉;孩子, 肾脏;T 肿瘤( B) 右肾上腺静脉造影。红色、黄色和粉红色箭头分别表示上级、侧面和劣质电视。( C、D、和E) 分别为侧向 (lat)、上级 (inf) 和劣质电视的静脉造影图像。粉红色、红色和黄色箭头指向的黑点表示微导管头。(F) 经切除的肾上腺皮质肿瘤 (T) 和相邻的肾上腺 (N) 的苏木素和曙红染色。(G和H)醛固酮合成酶 (CYP11B2: 缩写为 B2 在图中) 和类固醇11β羟化 (CYP11B1: B1) 的串行部分, 在图 3F。在 A 和 F H 中的刻度线分别表示1厘米和1毫米。<a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55716/55716fig3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/55716/55716fig4.jpg"> 
图 4:CT, 静脉造影, ssAVS, 组织学切除肾上腺 #2.(A) 造影增强 CT. 下腔静脉;Ao, 主动脉;左肾上腺皮质肿瘤;右肾上腺皮质肿瘤(B) 左肾上腺静脉造影。黄色、红色和粉红色箭头分别显示中位、上侧和侧电视。静脉造影采用微导管, 其头部由一个黑色箭头表示。绿色箭头表示一个短的填补缺陷大概由于腺瘤。(C和D)分别进行外侧 (lat) 和侧向 (拉特) 电视的静脉造影图像。红色和粉红色箭头表示微导管头 (图 4C中的黑点和4D,分别)。值得注意的是, 在图 4B和数字 4C - 4D中, 同样的彩色箭头显示了相同的电视部分, 尽管中值电视的造影在图 4B中由黄色箭头表示, 但不可用。(F) 经切除的肾上腺皮质肿瘤 (T) 和相邻的肾上腺 (N) 的苏木素和曙红染色。(G和H)醛固酮合成酶 (CYP11B2: 缩写为 B2 在图中) 和类固醇11β羟化 (CYP11B1: B1) 的串行部分, 在图 4F。在 A 和 F H 中的刻度线分别表示1厘米和0.5 毫米。<a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55716/55716fig4large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/55716/55716fig5.jpg"> 
图 5: CT 和静脉造影在 ssAVS 病例 #3.(A) 造影增强 CT. Rt, 它表示肾上腺。(B) 右肾上腺静脉造影。数字1、2、3和4与红色箭头表示上级, 中位, 横向和劣质电视. ( C) 左肾上腺静脉造影。数字1、2、3和4带有红色箭头, 表示中位、上侧、上侧和高级侧电视. 刻度线 = 1 厘米 (A)。<a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55716/55716fig5large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Table 1" src="/files/ftp_upload/55716/55716table1v2.jpg"> 
表 1: 骑士和 ssAVS 案件数据 #1-3.<a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55716/55716table1v2large.jpg" target="_blank">请单击此处查看此表的较大版本.</a>

Watch this Scientific Journal Video about A Novel Method: Super-selective Adrenal Venous Sampling at JoVE.com

A Novel Method: Super-selective Adrenal Venous Sampling

' 超选择性 ' 肾上腺静脉取样 (ssAVS, 也称为节段性肾上腺静脉取样: sAVS) 是使用微导管来鉴别肾上腺段 (s) 产生过多的激素。本文对 ssAVS 技术进行了描述, 并对肾上腺节段性病变进行了 ssAVS 鉴定, 并探讨了 ssAVS 在今后肾上腺研究中的应用价值。

一种新的方法: 超选择性肾上腺静脉取样

Primary aldosteronism (PA) and subclinical Cushing&#39;s syndrome (SCS) are conditions in which the adrenal glands autonomously produce excessive amounts ...

a-novel-method-super-selective-adrenal-venous-sampling

Nanyang Technological University

Research

JoVE Journal

Medicine

23.2K 次观看.  Nerima Hikarigaoka Hospital. ' 超选择性 ' 肾上腺静脉取样 (ssAVS, 也称为节段性肾上腺静脉取样: sAVS) 是使用微导管来鉴别肾上腺段 (s) 产生过多的激素。本文对 ssAVS 技术进行了描述, 并对肾上腺节段性病变进行了 ssAVS 鉴定, 并探讨了 ssAVS 在今后肾上腺研究中的应用价值。

视频: A Novel Method: Super-selective Adrenal Venous Sampling

Electrolytic Inferior Vena Cava Model (EIM) of Venous Thrombosis

Animal models serve a vital role in deep venous thrombosis (DVT) research in order to study thrombus formation, thrombus resolution and to test potential therapeutic compounds (1). New compounds to be utilized in the treatment and prevention of DVT are currently being developed. The delivery of potential therapeutic antagonist compounds to an affected thrombosed vein has been problematic. In the context of therapeutic applications, a model that uses partial stasis and consistently generates thrombi within a major vein has been recently established. The Electrolytic Inferior vena cava Model (EIM) is mouse model of DVT that permits thrombus formation in the presence of continuous blood flow. This model allows therapeutic agents to be in contact with the thrombus in a dynamic fashion, and is more sensitive than other models of DVT (1). In addition, this thrombosis model closely simulates clinical situations of thrombus formation and is ideal to study venous endothelial cell activation, leukocyte migration, venous thrombogenesis, and to test therapeutic applications (1). The EIM model is technically simple, easily reproducible, creates consistent thrombi sizes and allows for a large sample (i.e. thrombus and vein wall) which is required for analytical purposes.

Electrolytic Inferior Vena Cava Model EIM of Venous Thrombosis

The electrolytic induction of endothelial activation to the internal surface of the Inferior Vena Cava results in venous type thrombus formation due to endothelial activation and partial blood stasis, two components of Virchow's triad.

电解下腔静脉静脉血栓形成的模型（EIM）

Animal models serve a vital role in deep venous thrombosis (DVT) research in order to study thrombus formation, thrombus resolution and to test potential ...

科研

医学

Method for Novel Anti-Cancer Drug Development using Tumor Explants of Surgical Specimens

The current therapies for malignant glioma have only palliative effect. For therapeutic development, one hurdle is the discrepancy of efficacy determined by current drug efficacy tests and the efficacy on patients. Thus, novel and reliable methods for evaluating drug efficacy are warranted in pre-clinical phase. In vitro culture of tumor tissues, including cell lines, has substantial phenotypic, genetic, and epigenetic alterations of cancer cells caused by artificial environment of cell culture, which may not reflect the biology of original tumors in situ. Xenograft models with the immunodeficient mice also have limitations, i.e., the lack of immune system and interspecies genetic and epigenetic discrepancies in microenvironment. Here, we demonstrate a novel method using the surgical specimens of malignant glioma as undissociated tumor blocks to evaluate treatment effects. To validate this method, data with the current first-line chemotherapeutic agent, temozolomide (TMZ), are described.


We used the freshly-removed surgical specimen of malignant glioma for our experiments. We performed intratumoral injection of TMZ or other drug candidates, followed by incubation and analysis on surgical specimens. Here, we sought to establish a tumor tissue explant method as a platform to determine the efficacy of novel anti-cancer therapies so that we may be able to overcome, at least, some of the current limitations and fill the existing gap between the current experimental data and the efficacy on an actual patient's tumor. This method may have the potential to accelerate identifying novel chemotherapeutic agents for solid cancer treatment.

Here, we established a method for drug efficacy testing with surgical specimens of brain tumors, termed &#x201C;tumor explant method&#x201D;. With this method, we can evaluate drug efficacy without breaking the microenvironment of solid tumors. To validate reliability of this method, we describe representative data with our glioma specimen treated with the current first-line chemotherapeutic agent, temozolomide.

新型抗癌药物使用手术标本肿瘤植的发展方法


The current therapies for malignant glioma have only palliative effect. For therapeutic development, one hurdle is the discrepancy of efficacy determined ...

Femoral Arterial and Venous Catheterization for Blood Sampling, Drug Administration and Conscious Blood Pressure and Heart Rate Measurements

In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically implanted catheters permit a researcher to effectively and humanely administer substances, perform repeated blood sampling and assists in conscious direct measurements of blood pressure and heart rate. Once the catheter is implanted long-term sampling is possible. Patency and catheter life depends on multiple factors including the lock solution used, flushing regimen and catheter material. This video will demonstrate the methodology of femoral artery and venous catheterization of the rat. In addition the video will demonstrate the use of the femoral venous and arterial catheters for blood sampling, drug administration and use of the arterial catheter in taking measurements of blood pressure and heart rate in a conscious freely-moving rat. A tether and harness attached to a swivel system will allow the animal to be housed and have samples taken by the researcher with minimal disruption to the animal. To maintain patency of the catheter, careful daily maintenance of the catheter is required using lock solution (100 U/ml heparinized saline), machine-ground blunt tip syringe needles and the use of syringe filters to minimize potential contamination. With careful aseptic surgical techniques, proper catheter materials and careful catheter maintenance techniques, it is possible to sustain patent catheters and healthy animals for long periods of time (several weeks).

Chronic catheterization of blood vessels in the rat is often required for administration of substances, obtain blood sample over a period of time or for direct conscious blood pressure measurements. Femoral arterial catheterization of the rat and corresponding measurements of blood pressure in the conscious animal will be demonstrated.

股动脉和静脉导管采血，药品监督管理局和意识的血压和心率测量

In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically ...

A Novel Vertebral Stabilization Method for Producing  Contusive Spinal Cord Injury

Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing reliable cervical SCI is difficult due to lack of satisfactory methods of vertebral stabilization. The conventional method to stabilize the spine is to suspend the rostral and caudal cervical spine via clamps attached to cervical spinous processes. &#160;However, this method of stabilization fails to prevent tissue yielding during the contusion as the cervical spinal processes are too short to be effectively secured by the clamps (Figure 1). &#160;Here we introduce a new method to completely stabilize the cervical vertebra at the same level of the impact injury. &#160;This method effectively minimizes movement of the spinal column at the site of impact, which greatly improves the production of consistent SCIs. &#160;We provide visual description of the equipment (Figure 2-4), methods, and a step-by-step protocol for the stabilization of the cervical 5 vertebra (C5) of adult rats, to perform laminectomy (Figure 5) and produce a contusive SCI thereafter. &#160;Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS impactor device, this vertebral stabilization technique can be applied to other regions of the spinal cord, or be adapted to other SCI devices. &#160;Improving spinal cord exposure and fixation through vertebral stabilization may be valuable for producing consistent and reliable injuries to the spinal cord. &#160;This vertebral stabilization method can also be used for stereotactic injections of cells and tracers, and for imaging using two-photon microscopy in various neurobiological studies.

Vertebral stabilization is necessary for minimizing variability, and for producing consistent experimental spinal cord injuries.&#160; Using a customized stabilizing apparatus in conjunction with the NYU/MASCIS impactor device, we have demonstrated here the proper equipment and procedure for generating reproducible hemi-contusive cervical (C5) spinal cord injuries in adult rats.

一种新的椎稳定制备方法挫伤脊髓损伤

Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing ...

A Novel Application of Musculoskeletal Ultrasound Imaging

Ultrasound is an attractive modality for imaging muscle and tendon motion during dynamic tasks and can provide a complementary methodological approach for biomechanical studies in a clinical or laboratory setting. Towards this goal, methods for quantification of muscle kinematics from ultrasound imagery are being developed based on image processing. The temporal resolution of these methods is typically not sufficient for highly dynamic tasks, such as drop-landing. We propose a new approach that utilizes a Doppler method for quantifying muscle kinematics. We have developed a novel vector tissue Doppler imaging (vTDI) technique that can be used to measure musculoskeletal contraction velocity, strain and strain rate with sub-millisecond temporal resolution during dynamic activities using ultrasound. The goal of this preliminary study was to investigate the repeatability and potential applicability of the vTDI technique in measuring musculoskeletal velocities during a drop-landing task, in healthy subjects. The vTDI measurements can be performed concurrently with other biomechanical techniques, such as 3D motion capture for joint kinematics and kinetics, electromyography for timing of muscle activation and force plates for ground reaction force. Integration of these complementary techniques could lead to a better understanding of dynamic muscle function and dysfunction underlying the pathogenesis and pathophysiology of musculoskeletal disorders.

We describe a new ultrasound-based vector tissue Doppler imaging technique to measure muscle contraction velocity, strain and strain rate with sub-millisecond temporal resolution during dynamic activities. This approach provides complementary measurements of dynamic muscle function and could lead to a better understanding of mechanisms underlying musculoskeletal disorders.

肌肉骨骼超声成像的一种新应用

Ultrasound is an attractive modality for imaging muscle and tendon  motion during dynamic tasks and can provide a complementary methodological  approach ...

A Novel Clinical Grade Isolation Method for Human Kidney Perivascular Stromal Cells

Mesenchymal Stromal Cells (MSCs) are tissue homeostatic and immune modulatory cells that have shown beneficial effects in kidney diseases and transplantation. Perivascular Stromal Cells (PSCs) share characteristics with bone marrow MSCs (bmMSCs). However, they also possess, most likely due to local imprinting, tissue-specific properties and play a role in local tissue homeostasis. This tissue specificity may result in tissue specific repair, also within the human kidney. We previously showed that human kidney PSCs (kPSCs) have enhanced kidney epithelial wound healing whereas bmMSCs did not have this potential. Moreover, kPSCs can ameliorate kidney injury in vivo. Therefore, kPSCs constitute an interesting source for cell therapy, particularly for kidney diseases and renal transplantation. Here we show the detailed isolation and culture method for kPSCs from transplant-grade human kidneys based on whole-organ perfusion of digestive enzymes via the renal artery and enrichment for the perivascular marker NG2. In this way, large cell quantities can be obtained that are suitable for cellular therapy.

Here we present a novel clinical grade isolation and culture method for kidney Perivascular Stromal Cells (kPSCs) based on whole organ perfusion with digestive enzymes and NG2-cell enrichment. With this method, it is possible to acquire sufficient cell numbers for cellular therapy.

人类肾脏血管周围间质细胞新型临床分级分离方法

Mesenchymal Stromal Cells (MSCs) are tissue homeostatic and immune modulatory cells that have shown beneficial effects in kidney diseases and ...

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 ...

'Boden Food Plate': Novel Interactive Web-based Method for the Assessment of Dietary Intake

Different methods can be used in research to assess dietary intake, many of which are still paper-based. Written estimated food diaries are often utilized in clinical trials, despite being a burden for both study participants and researchers. This method requires participant literacy, it is time consuming, labor intensive, and can easily lead to under-reporting. With advancements in technology, there is a growing interest in electronic diaries that automate the dietary assessment process. These are focused on improving accuracy, reducing both time and cost and providing users with a visual and more enjoyable experience. The methodology presented here aimed to validate the &#39;Boden Food Plate&#39;, a novel web-based platform for self-recording of food and drink items, compared to a traditional estimated food diary. The application was also rated on a satisfaction scale by study participants using a paper-based questionnaire. Sixty-seven participants completed the dietary measures on both the three-day electronic and paper food diaries. For the analysis, only dietary data completed at both study time points (baseline and week six) was utilized. Despite small mean differences between dietary data collection methods, Bland Altman analysis showed fairly wide 95% limits of agreement between the electronic platform and the written estimated food diary and there were few cases which did not fall within the 95% confidence intervals. Overall, participants found the electronic food diary to be more fun than the paper method and as easy to use as hard copy diaries. The new platform has potential as a self-recording tool for the collection of dietary data, particularly when utilized in clinical trial settings. However, further validation studies are needed to improve the validity of this novel electronic dietary data collection tool.

The &#39;Boden Food Plate&#39; is an electronic food diary designed to be an interactive and fun method to collect dietary intake using visual depictions. The purpose of this study was to validate the web-based application against a traditional three-day estimated food diary method.

"食品板块": 一种新的基于交互式 Web 的膳食摄入量评估方法

Different methods can be used in research to assess dietary intake, many of which are still paper-based. Written estimated food diaries are often utilized ...

Veno-Venous Extracorporeal Membrane Oxygenation in a Mouse

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for acute as well as end-stage lung diseases. With the increase in clinical demand and prolonged use of ECMO, procedural optimization and prevention of multi-organ damage are of critical importance. The aim of this protocol is to present a detailed technique of veno-venous ECMO in a non-intubated, spontaneously breathing mouse. This protocol demonstrates the technical design of the ECMO and surgical steps. This murine ECMO model will facilitate the study of pathophysiology related to ECMO (e.g., inflammation,bleeding and thromboembolic events). Due to the abundance of genetically modified mice, the molecular mechanisms involved in ECMO-related complications can also be dissected.

Here we present a protocol describing the technique of veno-venous extracorporeal membrane oxygenation (ECMO) in a non-intubated, spontaneously breathing mouse. This murine model of ECMO can be effectively implemented in experimental studies of acute and end-stage lung diseases.

小鼠静脉内膜氧化术

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for ...

The Dyspepsia Educational Tool As a Novel Aid in Dyspepsia Management

Digital educational tools have a well-established role in current healthcare. In particular, disorders that are managed non-pharmacologically benefit from this development, as it enables patient engagement in self-management. Dyspepsia is a condition thought to arise from gastric and duodenal perturbations, brain-gut axis disturbances, and dietary factors. Behavioral interventions are a major part of dyspepsia treatment, hence patient engagement and motivation through education is essential. Protocols that describe the development process of such educational tools are scarce. We provide a methodology describing development of a dyspepsia educational tool. Assessment of users' needs is the first step, followed by a literature search. The content is developed based on the main themes and entered into a content management system, to build the program. Final adjustments are made after a pilot test of the tool. The presented protocol can be used as a guide for development of a digital dyspepsia educational tool or as a tool for similar situations.

This protocol describes the development process of a digital dyspepsia educational tool. Assessment of unmet needs and literature, content development, and building of the tool are presented. The methodology can be used as a guide for future development of digital educational tools.

消化不良教育工具作为消化不良管理中的一种新帮助

Digital educational tools have a well-established role in current healthcare. In particular, disorders that are managed non-pharmacologically benefit from ...