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Current protective strategies in liver surgery

World Journal of Gastroenterology 2010年第48期16卷 6098-6103页

作者： Kurinchi S Gurusamy Hector D Gonzalez brian r davidson HPB and Liver Transplantation Royal Free CampusUniversity College London Medical SchoolRoyal Free Hospital

During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (Ir) or Ir injury]. Modulation of Ir injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease Ir injury,genetic modulation of Ir injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces Ir injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease Ir injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.

关键词： Liver Hepatectomy Liver transplantation Ischemia-reperfusion injury Hypothermia Ischaemic preconditioning

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Molecular mechanisms of liver ischemia reperfusion injury:Insights from transgenic knockout models

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World Journal of Gastroenterology 2013年第11期19卷 1683-1698页

作者： Gourab Datta Barry J Fuller brian r davidson Liver Transplantation and Hepatobiliary Unit Division of Surgery and Interventional ScienceRoyal Free CampusUniversity College LondonRoyal Free Hampstead NHS Trust HospitalLondon NW 2QGUnited Kingdom

Ischemia reperfusion injury is a major obstacle in liver resection and liver transplantation *** the mechanisms of liver ischemia reperfusion injury(IrI) and developing strategies to counteract this injury will therefore reduce acute complications in hepatic resection and transplantation,as well as expanding the potential pool of usable donor *** initial liver injury is initiated by reactive oxygen species which cause direct cellular injury and also activate a cascade of molecular mediators leading to microvascular changes,increased apoptosis and acute inflammatory changes with increased hepatocyte *** adaptive pathways are activated during reperfusion that reduce the reperfusion *** involves a complex interplay between neutrophils,natural killer T-cells cells,CD4+ T cell subtypes,cytokines,nitric oxide synthases,haem oxygenase-1,survival kinases such as the signal transducer and activator of transcription,Phosphatidylinositol 3-kinases/Akt and nuclear factor κβ *** animals,particularly genetic knockout models,have become a powerful tool at elucidating mechanisms of liver ischaemia reperfusion injury and are complementary to pharmacological *** disruption of the protein at the genetic level is more specific and maintained than pharmacological inhibitors or stimulants of the same *** article reviews the evidence from knockout models of liver IrI about the cellular and molecular mechanisms underlying liver IrI.

关键词： Liver Ischemia/reperfusion Transgenic Knockout Nitric oxide synthase Haem oxygenase Mitogen-activated protein kinase T cell receptor

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Early acute kidney injury after liver transplantation: Predisposing factors and clinical implications

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World Journal of Hepatology 2017年第18期9卷 823-832页

作者： Suehana rahman Susan V Mallett brian r davidson royal Free Perioperative research Group Department of Anaesthesia Royal Free Hospital Royal Free NHS Foundation Trust Department of Surgery Royal Free Hospital Royal Free NHS Foundation Trust

To investigate the additional clinical impact of hepatic ischaemia reperfusion injury (HIrI) on patients sustaining acute kidney injury (AKI) following liver transplantation. METHODSThis was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation (OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT (> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration (CVVHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase (AST) within 24 h post-OLT was used as a surrogate marker for HIrI and severity was classified as minor (rate (1000-5000 IU/L) or severe (> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications (AKI and HIrI) alone and then as a combined outcome. rESULTSOut of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF and 70% sustained moderate or severe HIrI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively (P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIrI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIrI had a longer median time to extubation (P re length of stay (P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIrI was 89%, compared to 100% in the groups with either or neither complication (P = 0.049). CONCLUSIONHIrI has an important role in the devel

关键词： Hepatic ischaemia reperfusion injury Liver transplantation Perioperative care Acute kidney injury Marginal grafts

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Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury

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World Journal of Gastroenterology 2016年第33期22卷 7518-7535页

作者： Niteen Tapuria Sameer Junnarkar Mahmoud Abu-amara Barry Fuller Alexander M Seifalian brian r davidson Department of HPB Surgery and Liver transplantation Royal Free Hospital

AIM To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(rIPC) and modulation of *** Eight groups of animals were studied- Sham,ischemia reperfusion injury(IrI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,rIPC(remote ischemic preconditioning) + IrI group,remote ischemic preconditioning in sham(rIPC + Sham),PDTC + Ir(Pyridodithiocarbamate,HO donor),Zn PP + rIPC + IrI(Zinc protoporphyrin prior to preconditioning),Ir-24(45 min of ischemia followed by 24 h of reperfusion),rIPC+Ir-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. rESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic Ir were lower(P rison to rIPC and PDTC(HO inducer). rIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P reproduced the effects of rIPC in hepatic Ir. PDTC restored rBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of rBC in the rIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the rIPC group(9.46 ± 1.34). Zn PP in rIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in Ir injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in rIPC + Ir injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P reproducing the effects of rIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoida

关键词： reperfusion injury CINC Microcirculation Ischaemic preconditioning remote preconditioning Haemoxygenase

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三维三步MTT法肿瘤药敏试验与芬丹明B法的比较

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军医进修学院学报 2002年第3期23卷 170-172页

作者：王悦华蔡亚宁 brian r davidson 解放军总医院肝胆外科北京100853 北京佰师汇生物技术有限责任公司北京100039 伦敦大学皇家免费医院外科学系

目的 :比较自创的三维三步MTT法 (3D3S MTT法 )与MTT法及芬丹明B法 (SrB法 )在肿瘤药敏试验中的价值。方法 :选用Hep G2、T 2 4和SKOV3三种细胞系和丝列霉素及阿霉素两种抗癌药 ,观察暴露于两种药物 3d后再培养不同时间 ,用上述三种方... 详细信息

目的 :比较自创的三维三步MTT法 (3D3S MTT法 )与MTT法及芬丹明B法 (SrB法 )在肿瘤药敏试验中的价值。方法 :选用Hep G2、T 2 4和SKOV3三种细胞系和丝列霉素及阿霉素两种抗癌药 ,观察暴露于两种药物 3d后再培养不同时间 ,用上述三种方法测定的药敏结果。MTT法与SrB法计算肿瘤生长抑制率 (%TGI)的公式均是 :%TGI =[1 At Ac]× 1 0 0 % ;根据自建的表达MTT代谢的数学模型 ,3D3S MTT法计算 %TGI的公式是 :%TGI =1 { [lnAmax ln(Amax At) ] [lnAmax ln(Amax Ac) ] } 1 b × 1 0 0 %。结果 :三种方法测定的药物剂量反应曲线均呈S型。MTT法测定的 %TGI要比SrB法和 3D3S MTT法测定的结果低 ,而MTT法测定的IC50 平均为SrB法和 3D3S MTT法测定结果的 3～ 5倍。而 3D3S MTT法测定的 %TGI及IC50 与SrB法测定的结果相近似。结论 :3D3S MTT法克服了MTT法测定肿瘤药敏所存在的 3～ 5倍的低估问题 ,与SrB法相比结果可靠。

关键词：三维三步MTT法肿瘤药敏试验芬丹明B法

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Literature review of the mechanisms of acute kidney injury secondary to acute liver injury

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World Journal of Nephrology 2022年第1期11卷 13-29页

作者： Esther Platt Enriko Klootwijk Alan Salama brian davidson Francis robertson Division of Surgery and Interventional Science University College LondonLondon NW32QGUnited Kingdom Department of renal Medicine University College LondonLondon NW32PFUnited Kingdom

People exposed to liver ischaemia reperfusion(Ir)injury often develop acute kidney injury and the combination is associated with significant morbidity and *** mediators released by the liver in response to Ir injury are the likely cause of acute kidney injury(AKI)in this setting,but the mediators have not yet been *** the mechanism of injury will allow the identification of therapeutic targets which may modulate both liver Ir injury and AKI following liver Ir injury.

关键词： Liver failure Liver transplantation Ischaemia-reperfusion injury Acute kidney injury Liver

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农业贸易改革——有利于澳大利亚大面积农业的改革措施

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经济资料译丛 2007年第1期 84-94页

作者： NeilAndrews BenjaminBuetre Alistair davidson Daniel McDonald FrankJotzo brian S．fisher 黄照影（译）不详厦门大学国际经济与贸易系 361005

澳大利亚的农业高度依赖于世界市场。澳大利亚相当部分的农产品是用于出口的，其农产品价格时刻反映世界市场的价格。全球农业政策的根本改革将会使世界市场的扭曲减少，在世界范围内提高农产品价格并为澳大利亚农民提供更多的贸易机会。

关键词：澳大利亚农业政策贸易改革农产品价格贸易机会

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围手术期患者的安全：正确的患者、正确的手术、正确的部位——一项多因素、跨部门的干预性研究

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麻醉与镇痛 2008年第4期4卷 1-6页

作者： Edna Zohar Yossi Noga Ehud davidson Margalit Kantor brian Fredman 周全红(译) 江伟(校) Departments of Anesthesiology Critical Care and Pain Management Hospital Administration Meir Medical Center Kfar Saba The Sadder School of Medicine Tel Aviv University Tel Aviv Israel 不详

背景为围手术期患者提供安全的环境非常重要。基于这一点，我们在围手术期实施了“患者安全第一”的政策。方法在干预性研究的第一阶段（2001—2002年），我们首先制定并实施干预性研究中组织和教育方面的内容。2003至2005年为研究的实... 详细信息

背景为围手术期患者提供安全的环境非常重要。基于这一点，我们在围手术期实施了“患者安全第一”的政策。方法在干预性研究的第一阶段（2001—2002年），我们首先制定并实施干预性研究中组织和教育方面的内容。2003至2005年为研究的实施阶段。根据我们的零忍受原则，在手术等候区内一旦发现患者的麻醉或手术准备工作中有重大差错，该患者就被送回病房（失败），并等到差错得到纠正后再进行手术。结果共有15856例患者参加了研究。在研究实施阶段的3年中，有112例患者被送回病房（0．71％）。与2003年的数据相比，2004年和2005年发生的重大错误明显减少，且有统计学意义（2003、2004和2005年的数据分别为1．04％、0．59％和0．49％）。而且，逐步逻辑回归方法分析结果显示，手术前准备不充分所致重大错误的发生率逐年下降，具有统计学意义（比值比=1．48，95％CI：1．16～1．87）。此外，在2003、2004和2005年中，各年的失败发生平均间隔时间分别为6．6、11．2和14．7天（P〈0．03）。最后，不仅患者手术前准备工作在研究期间有显著改善（P〈0．0001）；而且，使患者手术前准备工作评分为100％的可能性也有明显增加（P〈0．001）。结论教育和提高认识能减少围手术期的错误发生率。但是，即使有详细规划的制度，也无法达到无差错的环境。因此，检查和全面分析应该持续不断地进行。

关键词：围手术期干预性安全手术前准备手术准备回归方法间隔时间统计学

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