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從臨床血液動力學到基礎代謝體學探討肝臟器官移植

為了解決aesculon醫學的問題，作者蔡欣怡 這樣論述：

指導教授推薦書……………………………………………………口試委員審定書……………………………………………………誌謝………………………………………………………………… iii中文摘要……………………………………………………………. vABSTRACT………………………………………………………… viiABBREVIATION………………………………………………….. ixChapter 1 Introduction on Liver Transplantation......................... 11.1 Types of Liver Tra

nsplantation……………………………... 21.1.1 De Novo Malignancies after Liver Transplantation from Taiwan’s Database……………………………. 41.1.2 Cardiovascular Disease Risks after Liver Transplantation from Taiwan’s Database……………. 71.2 Selection Criteria on Recipient……………………………... 101.3 Selectio

n Criteria on Living Donor………………………… 121.4 Intraoperative Monitoring and Management……………….. 141.4.1 Arterial Waveform Monitoring –FloTrac…………… 161.4.2 Electrical Velocimetry Monitoring System - Aesculon™………………………………………….. 181.5 Primary Graft Dysfunction…………………………………. 24Cha

pter 2 Introduction to Instrumentation in Metabolomic Analysis…………………………………………………………….. 272.1 Metabolomics……………………………………………….. 272.2 Nuclear Magnetic Resonance Spectroscopy……………………………………………………. 292.3 Mass Spectrometry…………………………………………. 312.4 Data Analysis……………………………………………….. 34Chapter

3 A Lipidomic Study of Early Allograft Dysfunction In Living Donor Liver Transplantation……………………………... 383.1 Methods and Materials……………………………………… 403.1.1 Patient Selection……………………………………… 403.1.2 Blood Samples……………………………………….. 413.1.3 NMR analysis of the plasma…………………………. 413.1.4 Liqui

d Chromatography coupled with Mass Spectrometry based Lipidomic…………………………….. 433.1.5 Ultra-performance liquid chromatography (UPLC)-based amino acid measurement…………………... 453.1.6 Statistical analysis……………………………………. 463.2 Results………………………………………………………. 473.2.1 Demographics and Clinical Dat

a…………………….. 473.2.2 Change in circulatory amino acid profiles in recipients with EAD……………………………………….. 483.2.3 Changes in NMR plasma profiles in recipients with EAD………………………………………………………… 483.2.4 Changes in circulatory lipid profiles in recipients with EAD………………………………………………………… 493.2.5 Dis

criminative ability of potential biomarkers for EAD and in-hospital mortality…………………………… 493.2.6 External validation of lipidomic profiling as prediction of EAD, long hospital stay and in-hospital mortality……………………………………………………. 503.3 Discussion……….………………………………………….. 513.3.1 Amino Acid………………

………………………...… 513.3.2 Lipids…………………………………………………. 523.3.3 Bilirubin……………………………………………… 55Chapter 4 Conclusion........................................................................ 56Chapter 5 Future Perspectives…………………………………... 59Chapter 6 Figures…………………………………………………. 60Figure 1. Flowchar

t of organ transplant recipients during 1996-201.. 60Figure 2. Flowchart of organ transplant patients during 1996-2011... 61Figure 3. Cumulative probability of any kind of vascular diseasefrom years after organ transplant…………………………………….62Figure 4. Cumulative probability of cardiovascular disease fro

myears after organ transplant…………………………………………..63Figure 5 Cumulative probability of cerebrovascular disease fromyears after organ transplant…………………………………………..64Figure 6. Cumulative probability of peripheral vascular disease fromyears after organ transplant…………………………………………..65Figure 7. Cumulative pro

bability of deep vein thrombosis fromyears after organ transplant………………………………………….66Figure 8. Modified formula of cardiac output analyses for theFloTrac algorithm…………………………………………………… 67Figure 9. Bland-Altman plot for COEv and COPAC………………… 68Figure 10. Four-quadrant plot for comparing changes in COEv

andCOPAC……………………………………………………………….69Figure 11. Schematic of the electrospray ionization process………... 70Figure 12. Flow diagram of the patient selection, allocation andanalysis……………………………………………………………… 71Figure 13. 1H NMR plasma profile model………………………….. 72Figure 14. 1H NMR plasma profile model………………

………….. 73Figure 15. Plasma samples analyzed by LC-MS in electrospraypositive ion mode, comparing EAD and nonEAD recipients inOPLS-DA plot……………………………………………………… 74Figure 16. Plasma samples analyzed by LC-MS in electrospraypositive ion mode, comparing EAD and nonEAD recipients in 75S-plot……………………………………

……………………………Figure 17. Plasma samples analyzed by LC-MS in electrospraypositive ion mode, comparing EAD and nonEAD recipients by classpermutation analysis………………………………………………… 76Figure 18. Prediction of early allograft dysfunction in study cohort... 77Figure 19. Prediction of long hospital stay in stud

y cohort…………. 78Figure 20. Prediction of all-cause in-hospital mortality in studycohort…………………………………………………………….......79Figure 21. Prediction of early allograft dysfunction in validationcohort………………………………………………………………...80Figure 22. Prediction of long hospital stay in validation cohort…….. 81Figure 23

. Prediction of all-cause in-hospital mortality in validationcohort ………………………………………………………………..82Figure 24. Schematic illustration of metabolic disturbancesassociated with poor outcomes of liver transplants………………… 83Chapter 7 Tables………………………..………………………….. 84Table 1. Risk of malignancies in liver tran

plant recipients………….. 84Table 2. Risk of vascular disease in liver transplant recipients……... 86Table 3. Summary of clinical data for living donor livertransplantation recipients……………………………………………. 87Table 4. Biochemical data for the patients before and after livertransplantation……………………………………………………

….88Table 5. Concentrations of amino acids at T6 in study group………. 90Table 6. A List of metabolites that discriminated the EAD from thenon-EAD groups …………………………………………………….91Table 7. Receiver operating characteristic (ROC) curve analysis forindividual metabolites in study and validation group……………….

93Table 8. Demographic details from the validation population……… 94Table 9. Biochemical details from the validation study population… 95Chapter 8 References…….………………………………………... 96Appendix……………………………………………………………. 112List of FiguresFigure 1. Flowchart of organ transplant recipients during 1996-201..

60Figure 2. Flowchart of organ transplant patients during 1996-2011... 61Figure 3. Cumulative probability of any kind of vascular diseasefrom years after organ transplant…………………………………….62Figure 4. Cumulative probability of cardiovascular disease fromyears after organ transplant…………………………………………..63Fi

gure 5 Cumulative probability of cerebrovascular disease fromyears after organ transplant…………………………………………..64Figure 6. Cumulative probability of peripheral vascular disease fromyears after organ transplant…………………………………………..65Figure 7. Cumulative probability of deep vein thrombosis fromyears after or

gan transplant………………………………………….66Figure 8. Modified formula of cardiac output analyses for theFloTrac algorithm…………………………………………………… 67Figure 9. Bland-Altman plot for COEv and COPAC………………… 68Figure 10. Four-quadrant plot for comparing changes in COEv andCOPAC……………………………………………………………….69Figure 11. Sche

matic of the electrospray ionization process………... 70Figure 12. Flow diagram of the patient selection, allocation andanalysis……………………………………………………………… 71Figure 13. 1H NMR plasma profile model………………………….. 72Figure 14. 1H NMR plasma profile model………………………….. 73Figure 15. Plasma samples analyzed by LC-M

S in electrospraypositive ion mode, comparing EAD and nonEAD recipients inOPLS-DA plot……………………………………………………… 74Figure 16. Plasma samples analyzed by LC-MS in electrospraypositive ion mode, comparing EAD and nonEAD recipients inS-plot………………………………………………………………… 75Figure 17. Plasma samples analyzed by LC

-MS in electrospraypositive ion mode, comparing EAD and nonEAD recipients by classpermutation analysis………………………………………………… 76Figure 18. Prediction of early allograft dysfunction in study cohort... 77Figure 19. Prediction of long hospital stay in study cohort…………. 78Figure 20. Prediction of all-cause

in-hospital mortality in studycohort…………………………………………………………….......79Figure 21. Prediction of early allograft dysfunction in validationcohort………………………………………………………………...80Figure 22. Prediction of long hospital stay in validation cohort…….. 81Figure 23. Prediction of all-cause in-hospital mortality in

validationcohort ………………………………………………………………..82Figure 24. Schematic illustration of metabolic disturbancesassociated with poor outcomes of liver transplants………………… 83List of TablesTable 1. Risk of malignancies in liver tranplant recipients………….. 84Table 2. Risk of vascular disease in liver transplant

recipients……... 86Table 3. Summary of clinical data for living donor livertransplantation recipients……………………………………………. 87Table 4. Biochemical data for the patients before and after livertransplantation……………………………………………………….88Table 5. Concentrations of amino acids at T6 in study group………. 90Table 6.

A List of metabolites that discriminated the EAD from thenon-EAD groups …………………………………………………….91Table 7. Receiver operating characteristic (ROC) curve analysis forindividual metabolites in study and validation group……………….93Table 8. Demographic details from the validation population……… 94Table 9. Bio

chemical details from the validation study population… 95

非侵入性與傳統血流動力監測 於急重症休克病患之研究

為了解決aesculon醫學的問題，作者彭瑞炆 這樣論述：

中文摘要休克是一急性的綜合症。在這種狀態下，全身有效血流量減少，微循環出現障礙，導致重要的生命器官缺血缺氧。即是身體器官需氧量與得氧量失調。休克是內、外、 婦、 兒以及急診科常見的急性危急重症。根據文獻，休克的定義為各種強烈致病因素作用於機體，使其循環功能急劇減退，組織微循環灌注嚴重不足，以致重要生命器官機能減退以及代謝嚴重障礙的全身性重症病理過程。本研究針對中部某家大型醫學中心具有25張床的外科綜合加護病房做回溯性研究分析40個病例，以非侵入性血流動力監視儀與臨床醫師利用傳統的診斷做分析，以決定這兩者的相關性。休克的在每個類型中有許多病因，目前在重症監護病房中，血液動力學監測可分為傳統的侵

入性血液動力學監測以及新一代非侵入性血液動力學監測。唯有血液動力學變化是監測和區分休克的最佳選擇；血液動力學以明確前負荷、心收縮和後負荷提供臨床醫生參考，進而優化治療休克的患者。經由本研究的結果顯示，未來可以以非侵入性血流動力監視儀作為心因性休克及非心因性休克的快速鑑別診斷，搶救患者治療的黃金時期。