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1.
Clinical features of hepatopulmonary syndrome in cirrhotic patients   总被引:4,自引:0,他引:4  
AIM:To evaluate the frequency,clinical andparaclinical features of hepatopulmonary syndrome(HPS)and to determine their predictive values in di-agnosis of this syndrome in patients in Iran.METHODS:Fifty four cirrhotic patients underwentcontrast enhanced echocardiography to detect intra-pulmonary and intracardiac shunts by two cardiolo-gists.Arterial blood oxygen,O_2 gradient(A-a)andorthodoxy were measured by arterial blood gas(ABG)test.The patients positive for diagnostic criteria ofHPS were defined as clinical HPS cases and thosemanifesting the intrapulmonary arterial dilation but noother criteria(arterial blood hypoxemia)were definedas IHPS cases.HPS frequency,sensitivity,positive andnegative predictive values of clinical and paraclinicalfeatures were studied.RESULTS:Ten(18.5%)and seven(13%)cases hadclinical and subclinical HPS,respectively.The mostcommon etiology was hepatitis B.Dyspnea(100%)and cyanosis(90%)were the most prevalent clinicalfeatures.Dyspnea and clubbing were the most sen-sitive and specific clinical features respectively.Nosignificant relationship was found between HPS andsplenomegaly,ascites,edema,jaundice,oliguria,andcollateral veins.HPS was more prevalent in hepatitisB.PaO_2<70 and arterial-alveolar gradient had thehighest sensitivity in HPS patients.Orthodoxy speci- ficity was 100%CONCLUSION:Clubbing with positive predictive val-ue(PPV)of 75% and dyspnea with negative predic-tive value(NPV)of 75% are the best clinical factorsin diagnosis of HPS syndrome.PaO_2<70 and P(A-a)O_2>30 and their sum,are the most valuable negativeand positive predictive values in HPS patients.  相似文献   

2.
目的 探讨基质金属蛋白酶(matrix metalloproteinase,MMP)-9基因启动子区多态性与乙型肝炎肝硬化的关系。方法应用PCR法和限制性片段长度多态性分析方法分别检测100例乙型肝炎肝硬化患者和124名正常对照者的MMP-9—1562C/T多态性,分析其基因型与乙型肝炎肝硬化发病风险相关性。结果 MMP-9—1562C/T多态性的基因型及等位基因频率在乙型肝炎肝硬化组和对照组间的分布差异无统计学意义(P〉0.05)。结论 MMP-9启动子1562位点基因多态性与乙型肝炎肝硬化易感无明显相关。  相似文献   

3.
目的测定急性冠状动脉综合征患者血浆基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9) 和组织金属蛋白酶抑制因子-1(tissue inhibitor metalloproteinase-1,TIMP-1)的变化,探讨MMP-9和TIMP-1 在急性冠状动脉综合征中的作用。方法急性冠状动脉综合征患者30例,稳定型心绞痛患者29例,正常对照17例,用酶联免疫法测定MMP-9和TIMP-1的血浆水平,血脂水平用比浊法测定。结果急性冠状动脉综合征组MMP.9(13±10)μg/L,TIMP-1(1.4±0.2)μg/L,MMP-9/TIMP-1(10±7);稳定型心绞痛组MMP-9 (2.2±0.5)μg/L,TIMP-1(0.7±0.4)μg/L和MMP-9/TIMP-1(3.2±2.0);正常对照组MMP-9(1.7±1.3)μg/L、 TIMP-1(0.6±0.4)μg/L和MMP-9/TIMP-1(5.2±0.9),急性冠状动脉综合征组与稳定型心绞痛组及对照组差异有统计学意义(P<0.01)。三组血脂水平差异无统计学意义。结论 MMP-9、TIMP-1和MMP-9/TIMP-1 在急性冠状动脉综合征患者中显著升高,他们有可能成为ACS患者易损斑块的预测指标。  相似文献   

4.
基质金属蛋白酶(MMPs)是细胞基质降解所必需的锌离子依赖性的内源性蛋白酶家族,是细胞外基质(ECM)的主要生理性调节物质,在基质成分合成和降解的过程中起着重要的作用。对血管系统的基质成分而言,最重要的MMPs是胶原酶和明胶酶。其中明胶酶-B(即MMP-9)在细胞外基质重塑中具有重要作用,在许多病理损伤方面,如冠状动脉粥样硬化斑块不稳定、心室重塑、心力衰竭进展及心血管疾病预后等中亦扮演着重要的角色。  相似文献   

5.
Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma.   总被引:27,自引:0,他引:27  
Purpose Matrix metalloproteinases (MMPs) are known to play an important role in extracellular matrix remodeling during the process of tumor invasion and metastasis. However, little is known about their role in preinvasive lesions and early esophageal carcinomas.Method Immunohistochemical analysis of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinoma (ESCC) (58 cases) and paired distal normal esophageal tissues (44 cases) and correlated with clinicopathological parameters.Result Overexpression of MMP-2 and MMP-9 proteins was observed in 39 (67%) and 32 (55%) of the 58 ESCCs, respectively localized in tumor cell cytoplasm and stromal elements. Histological evaluation of hematoxylin- and eosin-stained 44 matched distal normal esophageal tissue sections revealed that 26 comprised of normal epithelium, while 15 tissues showed evidence of dysplasia and three tissues showed hyperplasia. Interestingly, 12 (80%) and 13 (87%) of these 15 dysplasias showed immunostaining for MMP-2 and MMP-9 proteins, respectively. Low levels of MMP-2 and MMP-9 were observed in 10 (38%) and 6 (23%) of 26 matched histologically normal esophageal tissues, respectively. Higher MMP-2 immunopositivity was observed in well and moderately differentiated SCCs in comparison with poorly differentiated tumors. The expression of MMP-2 was significantly reduced with the progressive de-differentiation of esophageal SCCs (P =0.03). Overexpression of MMP-2 and MMP-9 in dysplasia as well as SCC suggests that these alterations occur in early stages of esophageal tumorigenesis.Conclusion Increased levels of MMP-2 and MMP-9 proteins in ESCCs as compared to normal esophageal tissues suggest their association with esophageal tumorigenesis. Increased levels of these MMPs are observed in majority of dysplasias analyzed herein, indicating that these alterations may be early events in esophageal tumorigenesis. In-depth studies are warranted to determine their role in development and progression of esophageal cancer.  相似文献   

6.
目的探讨基质金属蛋白酶9(MMP-9)表达和活性与2型糖尿病(T2DM)大鼠大血管病变的关系。方法高脂饲料加小剂量链脲佐菌素(Streptozotocin,STZ)建立T2DM大鼠模型,0、4、8和12周末取大鼠主动脉。免疫组化和RT-PCR分别检测MMP-9蛋白和mRNA表达;含明胶的SDS-PAGE检测MMP-9的活性;病理图像分析主动脉相对病变面积。结果T2DM组主动脉病变逐渐加重,各时间点主动脉壁MMP-9表达及活性随病程延长而增加。结论T2DM大血管病变形成过程中伴有MMP-9表达和活性的变化,MMP-9在T2DM大血管病变的发生与发展过程中起一定作用。  相似文献   

7.
目的:研究基质金属蛋白酶-9(MMP-9)基因C1562T多态性与高血压颈动脉粥样硬化的相关性。方法:原发性高血压患者120例,测定受试者双侧颈动脉内-中膜厚度(IMT),IMT≥1.3mm认为存在粥样硬化斑块。依颈动脉有无粥样硬化分为颈动脉粥样硬化组、颈动脉正常组。用聚合酶链反应-限制性片段长度多态性分析法分析2组患者的MMP-9基因C1562T的多态性。结果:颈动脉粥样硬化组与颈动脉正常组CT TT基因型频率分别为28.8%、13.2%,差异有统计学意义(χ2=4.488,P=0.034),T等位基因与颈动脉粥样硬化发病密切相关(OR=2.092,95%CI:0.991~4.419,P=0.047)。结论:MMP-9T等位基因与高血压颈动脉粥样硬化密切相关,可能是其遗传标志。  相似文献   

8.
目的探讨基质金属蛋白酶9(MMP-9)基因启动子C1562T多态性与老年冠心病(CHD)易感性的相关性。方法纳入2009年3月~2012年12月北京航天总医院年龄≥60岁的CHD患者168例作为CHD组,纳入同期健康体检者208例作为对照组。取外周血标本提取DNA,采用聚合酶链式反应-限制性内切酶片段长度多态性(PCR-RFLP)方法检测MMP-9基因启动子C1562T基因型,比较两组间MMP-9基因多态性频率分布的差异。结果 MMP-9基因启动子区C1562T多态性基因型和等位基因频率分布在CHD组和对照组之间差异有统计学意义(P0.05)。CHD组1562T等位基因频率明显高于对照组(20.8%vs.13.0%,P=0.004),携带T等位基因个体患冠心病的风险是C等位基因的3.97倍(OR=3.97)。不同临床类型的CHD患者在基因型及等位基因分布方面的差异无统计学意义(P0.05)。结论 MMP-9基因C1562T多态性与老年CHD的发生有关联,T等位基因可能是冠心病发病的遗传易感基因。  相似文献   

9.
目的探讨应用不同剂量阿托伐他汀短期治疗对急性冠脉综合征患者血清高敏C反应蛋白(hs—CRP)和基质金属蛋白酶-9(MMP-9)水平的影响。方法选择确诊的急性冠脉综合征患者63例,随机分为A组(22例,阿托伐他汀10mg/d)、B组(20例,阿托伐他汀20mg/d)和C组(21例,阿托伐他汀80mg/d),均于确诊后24小时内开始给药,其余用药按常规进行。所有患者均于服用阿托伐他汀前及服药后24小时、3天、7天采集静脉血,ELISA法测定血清hs—CRP和MMP-9水平。结果3组患者的临床基础资料比较无显著性差异;与治疗前比较服用阿托伐他汀3天后,C组血清hs—CRP和MMP-9水平明显减低(P〈0.05),而A、B两组虽有下降趋势,但差异无统计学意义;7天后,3组患者血清hs—CRP和MMP-9水平均明显降低(P〈0.05);C组患者血清hs—CRP和MMP-9水平明显低于A组和B组(P〈0.05);3组均未发现阿托伐他汀相关不良反应。结论急性冠脉综合征患者短期给予大剂量阿托伐他汀治疗可发挥其强大的抗炎作用,明显降低血浆hs—CRP和MMP-9水平。  相似文献   

10.
对肝肺综合征诊治的76例临床分析   总被引:2,自引:0,他引:2  
目的:探讨肝肺综合征(HPS)的临床特点及诊断方法,提高对其认识。方法:回顾性分析76例HPS患者的临床资料,并与无HPS的133例肝硬化患者在肺功能、血气分析等方面进行比较。结果:在HPS组中除4例为慢性酒精性肝损害基础上的急性药物性肝炎外,72例均为肝硬化患者。临床表现为呼吸困难、紫绀、杵状指及蜘蛛痣。据Child-Pugh分级标准,肝功能B级和C级者59例(77.6%),平均PaO2为(79.93±11.29)mm Hg(1 mm Hg=0.133 kPa),对照组为(92.48±13.53)mm Hg,2组比较有统计学意义(P0.01)。HPS组中76例中有48例直立性缺氧10%(63.1%)。不同门静脉内径、有无蜘蛛痣、不同肝功能分级的PaO2和SaO2值比较,均有统计学意义(P0.01)。影像学检查结果示肺内血管扩张。结论:肝肺综合征的发生与肝功能不全有明显的关系,该病患者常有呼吸困难、紫绀、杵状指、蜘蛛痣及直立性缺氧等典型表现,患者低氧血症发生率高,而肺功能存在弥散功能障碍,肺血管有明显的扩张。  相似文献   

11.
对肝肺综合征诊治的探讨   总被引:20,自引:0,他引:20  
目的提高对肝肺综合征(HPS)的认识。方法回顾性分析了6例HPS的临床资料,所有患者均经动态肺灌注显像检查。结果6例HPS的病因均为肝炎后肝硬化。除有肝病的临床表现外,还有进行性呼吸困难、紫绀(6/6)、杵状指(5/6)和低氧血症,平均动脉血氧分压为6.87kPa(1kPa=7.5mmHg),动脉血氧饱和度为85.2%。此外,还有立位性缺氧或平卧呼吸。6例患者经动态肺灌注显像均异常,有肺内血管扩张。结论有门脉高压、皮下蜘蛛痣和杵状指体征时,提示HPS的存在。早期诊断和治疗有助于缓解低氧血症,改善患者的预后。  相似文献   

12.
目的观察不同类型冠心病病人血清基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、组织基质金属蛋白酶抑制物-1(tissue-inhibitor of metalloproteinase-1,TIMP-1)和血管紧张素Ⅱ(anginotensinⅡ, AngⅡ)的血清浓度及相关关系,探讨急性冠状动脉综合征发病机制。方法冠心病病人分为急性心肌梗死组、不稳定心绞痛组(上述两组合称急性冠状动脉综合征组)和稳定心绞痛组,每组病人30例,另设健康对照组30例,比较各组间血清MMP-9、TIMP-1、MMP-9/TIMP-1和AngⅡ水平。结果急性心肌梗死组和不稳定心绞痛组血清MMP-9、MMP-9/TIMP-1和AngⅡ水平高于对照组,差异有统计学意义(P<0.01),但稳定心绞痛组血清MMP-9、TIMP-1、MMP-9/TIMP-1和AngⅡ水平与对照组比较差异无统计学意义(P> 0.05),急性冠状动脉综合征组病人血清MMP-9、MMP-9/TIMP-1与AngⅡ水平呈正相关(P<0.01)。结论血清MMP-9、MMP-9/TIMP-1和AngⅡ水平的增高与急性冠状动脉综合征相关,可作为评价冠状动脉粥样硬化斑块稳定性与病变严重程度的一个参考指标。  相似文献   

13.
目的:探讨在食管鳞癌EC-9706细胞中沉默CXCR4基因对MMP-9基因表达的影响,为阐明CXCR4基因在食管鳞癌侵袭转移中的作用提供实验依据.方法:化学合成2条靶向CXCR4基因的siRNA1和siRNA2,同时设立荧光标记阴性对照和空白对照.脂质体法转染入EC-9706细胞,荧光显微镜下观察转染效率.转染48h后,半定量RT-PCR检测各组细胞CXCR4和MMP-9基因mRNA表达的变化,Western blot检测各组细胞CXCR4和MMP-9基因蛋白表达的变化,侵袭小室检测各组细胞穿膜细胞数的变化,MTT检测各组细胞的A值.结果:与阴性对照和空白对照相比,转染CXCR4siRNA1和siRNA2组细胞CXCR4mRNA和蛋白的表达明显降低,差异具有统计学意义(P<0.05);同时与阴性对照和空白对照相比,转染CXCR4siRNA1和siRNA2组细胞MMP-9mRNA和蛋白的表达同样明显降低,差异具有统计学意义(P<0.05);转染CXCR4siRNA1和siRNA2组细胞穿膜细胞数与阴性对照和空白对照相比明显下降,差异具有统计学意义(P<0.05);MTT结果显示转染CXCR4siRNA1和siR...  相似文献   

14.
目的 探讨单核细胞基质金属蛋白酶-9(MMP-9)及组织型基质金属蛋白酶抑制物-1(TIMP-1)mRNA表达与急性冠脉综合征(ACS)之间的关系.方法 分离8例ACS、8例稳定性心绞痛(SAP)及8例对照循环血单核细胞,采用异硫氰酸胍-酚-氯仿抽提法提取总RNA,扩增目的 基因MMP-9及TIMP-1 mRNA.根据冠脉造影进行冠脉狭窄程度计分并测定血清ox-LDL水平.结果 ①ACS患者外周血单核细胞MMP-9 mRNA表达与对照组比较增加(P<0.05),而TIMP-1 mRNA表达在各组间无差异;②ACS组血清ox-LDL浓度高于SAP组及对照组(P<0.05),且SAP组高于对照组(P<0.05),③单核细胞MMP-9 mRNA表达与血清ox-LDL浓度正相关(r=0.458,P=0.024);而与冠脉狭窄计分(CSS)无相关性.结论 ACS患者外周血单核细胞MMP-9、TIMP-1 mRNA表达比例失衡,可能直接参与了不稳定斑块的形成及破裂.  相似文献   

15.
目的:观察红霉素对4-羟基壬烯醛(4-HNE)刺激的气道上皮细胞基质金属蛋白酶2(MMP-2)、MMP-9、环氧合酶2(COX-2)和活化蛋白-2(AP-2)表达的影响。方法 Western blot 检测红霉素(5μmol/L)预孵育不同时间(24、36、48 h)后4-HNE(10μmol/L 作用4 h)刺激的气道上皮细胞MMP-2、MMP-9、COX-2和 AP-2蛋白表达的变化。结果红霉素预孵育36 h 和48 h 后明显抑制4-HNE刺激的气道上皮细胞 MMP-2、MMP-9、COX-2合成,明显抑制4-HNE 刺激的气道上皮细胞核转录因子 AP-2的激活,与红霉素未预孵育组相比,差异具有统计学意义(P <0.05)。结论红霉素可明显抑制4-HNE 刺激的气道上皮细胞 MMP-2、MMP-9、COX-2表达,其机制可能和抑制核转录因子 AP-2的激活有关。  相似文献   

16.
目的:观察急性冠状动脉综合征(ACS)患者血浆白三烯B4(LTB4)与基质金属蛋白酶-9(MMP-9)水平的变化及其相关性,探讨其在ACS中可能的临床意义。方法:采用酶联免疫吸附法(ELISA)测定65例ACS患者以及20例健康对照人群(对照组)血浆LTB4和MMP-9的水平,以全自动生化分析仪测定血脂水平和C反应蛋白(CRP),并比较LTB4与MMP-9、血脂以及CRP的相关性。结果:ACS患者LTB4水平在急性心肌梗死(AMI)和不稳定型心绞痛(UAP)组分别为(112.77±22.59),(86.94±14.81)ng/L,显著高于对照组[(40.5±8.85)ng/L,P<0.01)],且AMI组高于UAP组(P<0.05)。LTB4与MMP-9的水平显著正相关(r=0.875,P<0.01),与CRP正相关(r=0.641,P<0.01),与TG正相关(r=0.469,P<0.01),与HDL-C负相关(r=-0.370,P<0.01)。结论:ACS患者血浆LTB4和MMP-9水平增高,LTB4可能与MMP-9以及CRP构成炎症网络并参与脂质代谢紊乱,导致动脉粥样斑块不稳定而成为ACS的危险信号。  相似文献   

17.
用酶联免疫吸附方法(ELISA)检测糖尿病脑梗死组、非糖尿病脑梗死组、糖尿病非脑梗死组、健康对照组的基质金属蛋白酶9(MMP-9)、组织基质金属蛋白酶抑制物1(TIMP-1)的水平.结果 显示糖尿病脑梗死组MMP-9、TIMP-1水平明显明显高于其他3组(P<0.05),提示其可能在糖尿病脑梗死发病过程中有重要作用.  相似文献   

18.
肝肺综合征患者降钙素基因相关肽及内皮素含量检测   总被引:3,自引:0,他引:3  
目的 肝肺综合征 (HPS)的发生与血循环或肺内扩张 /收缩血管物质失衡密切相关。检测HPS患者血浆中降钙素基因相关肽 (CGRP)和内皮素 (ET)含量 ,以探讨它们在HPS发病中的作用。方法 选择经肺灌注扫描及血气分析诊断的HPS患者 16例 ,无HPS的肝硬化患者 30例 ,用放射免疫分析法测定其血浆CGRP、ET含量 ,同时以 15名健康献血员作为对照。结果 HPS组血浆CGRP[(6 5± 15 )pg/ml]、ET[(78± 2 1) pg/ml]显著高于肝硬化组 [(5 1± 15 ) pg/ml,(6 0± 14 ) pg/ml,P <0 .0 1],也显著高于对照组 [(32± 12 ) pg/ml,(36± 11)pg/ml,P <0 .0 1];肝硬化组与正常对照组比较差异也有显著性(P <0 .0 1)。线性相关分析显示 ,HPS组患者血浆CGRP及ET含量与动脉血氧分压呈显著负相关 ,与肺内分流率大小无关。结论 HPS患者血浆CGRP、ET含量增高 ,其增高可能与HPS肺内血管扩张和动脉血氧分压下降有关。  相似文献   

19.
高压氧治疗肝肺综合征大鼠的实验研究   总被引:1,自引:0,他引:1  
李宁  郝建宇  庞宝森  刘福佳 《肝脏》2007,12(2):103-107
目的 研究高压氧治疗对大鼠肝肺综合征(HPS)的作用.方法 采用胆总管结扎术(CBDL)制备HIS动物模型.44只雄性SD大鼠随机分为4组:假手术对照组(Sham组)8只、单纯造模组(CBDL5w组)12只、治疗1周组(HBOT1w组)12只、治疗2周组(HBOT2w组)12只.两治疗组在造模成功后送入高压氧舱治疗,分别治疗1周和2周.Sham组和CBDL5w组大鼠在术后5周,HBOT1w组和HBOT2w组在治疗结束后,进行血气分析、肝功能以及血清一氧化氮(NO)、内皮素-1(ET-1)浓度检测,肝、肺病理检查,并使用激光多普勒血流仪检测肝、肺微循环.结果 CBDL5w组大鼠肝功能检测中ALB降低,ALT、AST、ALP、γ-GT、TBIL及TBA均升高,血气分析中PaO2降低,PA-aO2增大,与Sham组相比均有显著差异(P<0.01),且病理检查CBDL5w组大鼠的肝脏组织可见胆汁性肝纤维化表现,肺组织可见肺毛细血管扩张、充血,证实HPS大鼠模型制成;同时与Sham组相比,CBDL5w组大鼠血清NO及ET-1浓度均升高(P<0.01),肝脏毛细血管血流量降低(P<0.01),肺脏毛细血管血流量增大(P<0.01).经高压氧治疗后,HBOT1w组大鼠与CBDL5w组相比,以上指标均好转(P<0.01).HBOT2w组大鼠与CBDL5w组相比,除血清NO水平和肺脏毛细血管血流量无统计学差异(P>0.05)外,其余指标的差异有显著性意义(P<0.01).结论 高压氧治疗大鼠HPS可通过降低血清NO、ET-1浓度,提高组织氧含量及改善肝、肺微循环等,有效改善肝、肺功能及病理,且治疗前期效果更好.  相似文献   

20.
BACKGROUND/AIMS: The use of transesophageal contrast echocardiography (TOCE) in the diagnosis of intrapulmonary vascular dilatation (IVD) and hepatopulmonary syndrome (HPS) needs to be studied. We tested the specificity of TOCE using traditional criteria and the value of a new method based on TOCE, a grading scale and a selected contrast. METHODS: 1) Several solutions were tested and two were selected: 20% mannitol and 0.9% saline. 2) 71 cirrhotic patients and 20 controls were studied. Left atrium opacification with contrast was classified into 6 degrees by TOCE. Mild and significant IVD were considered in relation to results in controls. Patients were studied with saline and mannitol-TOCE. Results were compared to transthoracic contrast echocardiography (TTCE), to gas exchange abnormalities and to Child class. RESULTS: The reproducibility of TOCE grading was excellent, (Kappa >0.9). IVD detection using TTCE, mannitol-TOCE and saline-TOCE was 29.5%, 55% (25% mild and 30% significant), and 45% (38% mild and 7% significant), respectively. The best agreement with TTCE (reference method) was obtained with mannitol-TOCE, using significant IVD as the cut point. By this criterion, 18% reached the criteria of HPS using TTCE and 22% using mannitol-TOCE. Patients with IVD by TTCE had non-significant changes in gas exchange determinations. Patients with significant IVD by saline TOCE had lower mean PaO2 levels (67.3+/-14 vs. 79.5+/-11 mm Hg, p<0.05) than patients without IVD. Patients with significant IVD by mannitol TOCE had higher mean AaPO2 (29.3+/-14 vs. 19.7+/-9 mm Hg; p<0.005) and lower mean PaCO2 levels (30.1+/-4.4 vs. 33.4+/-4.8 mm Hg; p<0.05) than patients without IVD. Severity of IVD by TOCE correlated to Child class (r = 0.43; p<0.001). CONCLUSIONS: The presence of contrast in the left atrium cannot be a criterion of IVD when TOCE is used. Our semi-quantitative scale has proved to be feasible and reproducible, presenting a good agreement with TTCE, and has shown better correlation with gas exchange abnormalities and Child class. Saline TOCE appears to be more specific in the detection of hypoxemic patients with IVD, but mannitol TOCE adds sensitivity.  相似文献   

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