Other articles by Stephen Wigmore on PubMed

• Endogenous Lipoproteins Impact the Response to Endotoxin in Humans Critical Care Medicine. Jan, 2002  |   Pubmed ID: 11902267 To determine whether endogenous lipoproteins can abrogate the host response to lipopolysaccharide (LPS) in vivo.
• Living-related Liver Transplantation from the View of the Donor: a 1-year Follow-up Survey. Transplantation 2002; 73: 1799 Transplantation. Jun, 2002  |   Pubmed ID: 12084989
• Ethical Market in Organs. Defending the Indefensible? BMJ (Clinical Research Ed.). Oct, 2002  |   Pubmed ID: 12378729
• Establishing a Transplant Coordinator-led Living Kidney Donor Follow-up Clinic Progress in Transplantation (Aliso Viejo, Calif.). Jun, 2003  |   Pubmed ID: 12841521 The long-term risks of renal failure and hypertension are statistically low for living kidney donors as a group, but can have serious consequences for the individual.
• Insurance Issues in Living Kidney Donation Transplantation. Sep, 2003  |   Pubmed ID: 14508374
• To Biopsy or Not to Biopsy Transplantation. Sep, 2003  |   Pubmed ID: 14531395
• Incentives to Promote Organ Donation Transplantation. Jan, 2004  |   Pubmed ID: 14724458 The worldwide shortage of organs has led to the development of incentives to promote organ donation. These incentives vary widely in nature ranging from financial remuneration to preferential access to conditional donation. Such strategies to increase organ donation present a variety of ethical dilemmas challenging traditional concepts of justice and equity of access. In addition, there are legal and logistic considerations that must be discussed. The case is made that schemes using incentives to promote organ donation must meet the requirements of society for justice, equity of access, and avoidance of racial or other bias.
• Roux-en-Y Choledochojejunostomy is the Method of Choice for Biliary Reconstruction in Liver Transplantation for Primary Sclerosing Cholangitis Transplantation. Feb, 2004  |   Pubmed ID: 15084943 Opinion is divided regarding the optimal method of biliary reconstruction after liver transplantation for primary sclerosing cholangitis (PSC).
• Optimization of the Paired Enzyme Assay for Heme Oxygenase Activity Analytical Biochemistry. Sep, 2004  |   Pubmed ID: 15325310
• Management of Biliary Tract Complications After Orthotopic Liver Transplantation Clinical Transplantation. Dec, 2004  |   Pubmed ID: 15516238 Despite improved survival, biliary complications remain a significant cause of morbidity following orthotopic liver transplantation. The aim of this study was to review the incidence, treatment and optimum management pathway of biliary complications at the Scottish Liver Transplant Unit.
• Early Stress Protein Gene Expression in a Human Model of Ischemic Preconditioning Transplantation. Nov, 2004  |   Pubmed ID: 15599312 Intermittent clamping of the porta hepatis (PHC) is commonly performed during liver surgery to reduce blood loss and has been reported to precondition livers resulting in improved outcome after liver surgery (humans) and transplantation (animals). This study investigated the early expression of cytoprotective stress proteins during ischemia-reperfusion induced by PHC. Liver samples were taken before and after each event in a two-cycle ischemia-reperfusion protocol using 15 minutes of PHC followed by 5 minutes of reperfusion. Liver tissue was analyzed by real-time polymerase chain reaction for heme oxygenase (HO)-1 and heat shock protein (HSP)-70 mRNA expression. Extracted protein was analyzed by Western blot for HO-1, and HSP-70 and nuclear extracts were analyzed by DNA mobility shift assay for hypoxia inducible factor (HIF)-1alpha and heat shock factor (HSF)-1. Within minutes of PHC, significant increases in HO-1 mRNA expression were detected, and these were maintained throughout the protocol (P < 0.01). Protein expression of HO-1 (P < 0.03) and HO-1 activity (P < 0.05) were similarly increased between the start and end of ischemia- reperfusion (40 minutes). Binding of active HIF-1alpha to its consensus sequence was increased within 15 minutes of the start of the ischemia-reperfusion cycle. Although evidence of the transcriptionally active form of HSF-1 was detected at the same time point, this was not reflected in measurable changes in HSP-70 mRNA or protein. In conclusion, expression of the cytoprotective protein HO-1 is significantly up-regulated in the liver within minutes of PHC. It is likely that HO-1 contributes to the early protective effects of ischemic preconditioning.
• Non-paracetamol Drug-induced Fulminant Hepatic Failure Among Adults in Scotland European Journal of Gastroenterology & Hepatology. Feb, 2005  |   Pubmed ID: 15674093 This study details 30 cases of non-paracetamol drug-induced fulminant hepatic failure (NPDI-FHF) that have presented to the Scottish Liver Transplant Unit since 1992. Using the patients' case notes and a previously constructed database, the demographics of NPDI-FHF in Scotland were studied. The clinical and biochemical features, and the outcome of each individual case were also investigated.
• Prognostic Scoring in Colorectal Cancer Liver Metastases: Development and Validation Archives of Surgery (Chicago, Ill. : 1960). Feb, 2005  |   Pubmed ID: 15724001 A prognostic scoring system for colorectal cancer liver metastases that is derived from unselected patients referred for hepatic resection would improve the applicability and increase the accuracy of prognostication.
• The Utility of Laparoscopic Assessment in the Preoperative Staging of Suspected Hilar Cholangiocarcinoma Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. Apr, 2005  |   Pubmed ID: 15797226 The aim of this study was to review the role of laparoscopic assessment in the staging algorithm of suspected hilar cholangiocarcinoma and to identify factors highly likely to be associated with unresectable disease. Data prospectively collected between 1992 and 2003 were analyzed. Demographics, symptoms, preoperative radiologic staging, laparoscopic assessment, and final outcome were recorded. Yield was defined as the number of unresectable patients detected by laparoscopic assessment divided by the total number of patients undergoing laparoscopic assessment. Accuracy was defined as the number of unresectable patients detected by laparoscopic assessment divided by the total number of unresectable cases. Eighty-four patients underwent laparoscopic assessment for suspected hilar cholangiocarcinoma, of which 20 (23.8%) underwent resection. The yield from laparoscopy alone was 24.3% (20 of 82), which increased to 41.5% (35 of 82) with the addition of intraoperative ultrasound. The overall accuracy was 53.1% (35 of 66). The use of a preoperative radiologic staging system predicted the likelihood of unresectable disease (P=0.007). The use of laparoscopic assessment in the preoperative staging of patients with suspected hilar cholangiocarcinoma is justified given it will spare 42.2% of patients an unnecessary laparotomy. Accurate staging of cholangiocarcinoma remains a challenge, but the use of a preoperative radiologic staging system may help to stratify a patient's risk of unresectable disease.
• Serum Parathyroid Hormone-related Peptide is Associated with Systemic Inflammation and Adverse Prognosis in Gastroesophageal Carcinoma Cancer. May, 2005  |   Pubmed ID: 15800880 Parathyroid hormone-related peptide (PTHrP) is a tumor-derived circulating factor that has been associated with hypercalcemia of malignancy. The role of PTHrP as a prognostic indicator remains unclear. Studies suggest that it may function as a growth factor; and, recently, the ability of PTHrP to induce cytokine expression has been described. PTHrP also has been proposed as a procachectic factor. In this study, the authors investigated the prognostic value of PTHrP in patients who had gastroesophageal carcinoma without hypercalcemia and determined whether PTHrP was associated with systemic inflammation and adverse nutritional status.
• Systemic Inflammation, Cachexia and Prognosis in Patients with Cancer Current Opinion in Clinical Nutrition and Metabolic Care. May, 2005  |   Pubmed ID: 15809528 Cachexia remains an important cause of morbidity and mortality among cancer patients. The mechanisms underlying this syndrome remain unclear and are almost certainly multifactorial. Evidence from animal models suggests a compelling link between cachexia and inflammation, and a variety of pro-inflammatory cytokines play an integral role. This review summarizes current thinking relating to inflammation, cachexia and prognosis in cancer patients, with particular emphasis on studies relating to recent therapeutic advances.
• Higher Quality of Life in Living Donor Kidney Transplantation: Prospective Cohort Study Transplant International : Official Journal of the European Society for Organ Transplantation. Aug, 2005  |   Pubmed ID: 16008749 This prospective, longitudinal cohort study investigated the effect of donating or receiving a kidney on quality of life and relationship dynamics. Forty donors and 35 recipients from two UK transplantation centres completed the World Health Organisation quality of life questionnaire (WHOQOL) with additional questionnaires before, 6 weeks and one year after operation. Before donation the donor mean quality of life score in the physical domain was 18.8. This was significantly higher than the UK value for a healthy person of 16.4 (P < 0.001). Six weeks after operation, donor score reduced to UK normative levels however improved again at one year (17.7). Recipient mean physical domain score before was 11.4, significantly lower than the UK norm (P < 0.01), increasing to 16.0 one year after. Both donor (P < 0.009) and recipient (P < 0.05) experienced a significant improvement in their mutual relationship. Recipients expressed anxiety about the donor before operation. Donors were not concerned about living with one kidney. We concluded that living kidney donation has no detrimental effect on the physical or psychological well being of donors one year after donation. Transplantation results in a major improvement in quality of life for the recipient. Most donors would donate again, if this were possible.
• Febrile-range Temperature but Not Heat Shock Augments the Acute Phase Response to Interleukin-6 in Human Hepatoma Cells American Journal of Physiology. Gastrointestinal and Liver Physiology. May, 2006  |   Pubmed ID: 16339299 The relationship between the stress protein response and the acute phase response (APPR) was studied in human hepatoma cells to investigate the hierarchy of regulation of these survival responses. Huh-7 cells were subjected to heat treatment (febrile-range temperature 40 degrees C or heat shock 43 degrees C) followed by recovery at 37 degrees C in the presence or absence of IL-6 given either before or after heat treatment. The effects on total, fractional, and acute phase protein synthesis were then analyzed by metabolic labeling, ELISA, real-time PCR, Northern blot analysis, and activation of an alpha(1)-antitrypsin reporter plasmid. Cell energetics were studied under the same conditions using an index of mitochondrial activity and measurement of cellular ATP levels. Febrile-range temperature (40 degrees C) augmented acute phase protein production when cells had been pretreated with IL-6. Pretreatment of cells with IL-6 also prevented heat shock-induced suppression of alpha(1)-antichymotrypsin (ACT) but not transferrin. mRNA expression of ACT and alpha(1)-antitrypsin reporter activation studies was consistent with transcriptional regulation of these proteins. Expression of mRNA transcripts for transferrin was increased despite protein expression being reduced by heat shock. The effects of heat shock on acute phase protein synthesis can be modified by preincubation with IL-6, whereas addition of this ligand after heat treatment has no effect on the suppressive effect of heat on the APPR. The mechanism of this action appears to be transcriptionally regulated in the case of ACT, but in the case of transferrin, it may be mediated by another process such as posttranslational modification.
• Firefly Luciferase Terminally Degraded by Mild Heat Exposure: Implications for Reporter Assays Journal of Immunological Methods. Mar, 2006  |   Pubmed ID: 16443236 Luciferase reporter constructs are an accurate method of assessing gene promoter activity and vectors constitutively expressing luciferase are useful in quantifying transfection efficiency. Common methodologies for examining the induction of the heat shock (stress) response require exposure of cells transfected with luciferase-expressing vectors to a mild heat stress. Here we re-examine the under-recognised phenomenon that luciferase is exquisitely sensitive to small temperature changes. In cells subjected to mild heat exposure following transfection with both luciferase and beta-galactosidase reporter vectors, a marked reduction in luciferase activity was observed compared with beta-galactosidase activity. On exposing recombinant firefly luciferase to small increases in temperature in vitro, a time and temperature dependent decrease in luciferase activity was demonstrated. Loss of luciferase activity following mild heat exposure will result in misinterpretation of reporter activity. This vastly underappreciated effect is worthy of further emphasis and luciferase reporter vectors should be used with caution in protocols that involve exposure to temperatures outside the physiological range.
• Curcumin Induces Heme Oxygenase-1 in Hepatocytes and is Protective in Simulated Cold Preservation and Warm Reperfusion Injury Transplantation. Feb, 2006  |   Pubmed ID: 16495813 Preconditioning treatments hold significant potential for improving outcomes in solid organ transplantation. Protective phenotypes can be induced using certain drugs. Curcumin is a biologically active component of turmeric and has been reported to induce stress proteins in certain cell lines, leading to cell protection. This study investigates in detail the effect of curcumin on the stress-response in human hepatocytes, in particular its effect on heme oxygenase 1 (HO-1) and its cytoprotective effect. Pretreatment with curcumin protected hepatocytes in a model of oxidative injury and this protection was mediated through HO-1. In a model of cold preservation injury, curcumin pretreatment resulted in elevation of HO-1 throughout the cold storage and rewarming period, and was cytoprotective against oxidative injury. This is the first study to demonstrate that curcumin induces HO-1 in human hepatocytes, and that the protective effects of curcumin pretreatment may have clinical potential in hepatic transplantation.
• The Adaptive Response of the Reticuloendothelial System to Major Liver Resection in Humans Annals of Surgery. Apr, 2006  |   Pubmed ID: 16552202 To evaluate the contribution of the liver to total circulatory reticuloendothelial system (RES) phagocytosis capacity in patients undergoing liver resection and to compare it with values in end-stage chronic liver disease.
• Face Transplantation: the View from Birmingham, England Southern Medical Journal. Apr, 2006  |   Pubmed ID: 16634264
• Insulin Induces Heme Oxygenase-1 Through the Phosphatidylinositol 3-kinase/Akt Pathway and the Nrf2 Transcription Factor in Renal Cells The FEBS Journal. Jun, 2006  |   Pubmed ID: 16704410 Heme oxygenase-1 catalyzes the breakdown of heme and is protective in models of kidney transplantation. In this study we describe the induction of heme oxygenase-1 mRNA and protein by insulin. Following treatment with insulin, a five-fold increase in heme oxygenase-1 mRNA and a four-fold increase in protein expression were observed in renal adenocarcinoma cells; insulin-induced heme oxygenase-1 expression was also demonstrated in mouse primary tubular epithelial cells. The induction of heme oxygenase-1 in renal adenocarcinoma cells was blocked by actinomycin D and cycloheximide and was abolished by the phosphatidylinositol 3-kinase inhibitor, LY294002, but not by the inactive analog LY303511. Overexpressing a dominant-negative form of Akt abrogated the heme oxygenase-1-inducing effects of insulin, whereas cells transfected with a constitutively active Akt construct demonstrated an increase in heme oxygenase-1 promoter activity and protein expression. The transcription factor NF-E2-related factor-2 was found to translocate to the nucleus following insulin treatment in a phosphatidylinositol 3-kinase-dependent manner. Pretreatment with NF-E2-related factor-2 small-interfering RNA abolished insulin-induced heme oxygenase-1 induction. Insulin was also found to activate the mitogen-activated protein kinase cascades p38 and extracellular signal-related kinase; however, inhibition of these pathways with SB202190 and PD98059 did not alter insulin-induced heme oxygenase-1 expression. Thus, insulin induces heme oxygenase-1 mRNA and protein expression in renal cells in a phosphatidylinositol 3-kinase/Akt and NF-E2-related factor-2-dependent manner.
• Interstitial Lactic Acidosis in the Graft During Organ Harvest, Cold Storage, and Reperfusion of Human Liver Allografts Predicts Subsequent Ischemia Reperfusion Injury Transplantation. Jul, 2006  |   Pubmed ID: 16858286 The impact of the process of liver transplantation on glucose metabolism in the graft was studied using microdialysis.
• Arginine and Urea Metabolism in the Liver Graft: A Study Using Microdialysis in Human Orthotopic Liver Transplantation Transplantation. Nov, 2006  |   Pubmed ID: 17130779 Arginine is an amino acid having a central role in the metabolism of urea and nitric oxide in the liver. We present our findings of the behavior of these metabolites during the process of transplantation of the liver.
• Is Death the Price of Tolerance? Transplantation. Dec, 2006  |   Pubmed ID: 17164709
• Host Cytokine Genotype is Related to Adverse Prognosis and Systemic Inflammation in Gastro-oesophageal Cancer Annals of Surgical Oncology. Feb, 2007  |   Pubmed ID: 17103073 Systemic inflammation has been linked with reduced survival in cancer, however, the role of the host cytokine genotype versus tumour phenotype in the generation of this response is not clearly established. This study examined the relationship between cytokine polymorphisms (IL-1beta 511, IL-6 174, IL-10 1082, TNFalpha 308 and LTalpha +252) and serum cytokine concentrations, serum CRP concentration and survival duration in patients with gastro-oesophageal malignancy.
• Curcumin Induces Heme Oxygenase 1 Through Generation of Reactive Oxygen Species, P38 Activation and Phosphatase Inhibition International Journal of Molecular Medicine. Jan, 2007  |   Pubmed ID: 17143561 Curcumin is a naturally occurring compound which is known to induce heme oxygenase 1 (HO-1), although the underlying mechanism has not been fully elucidated. This study investigates in detail the mechanism of HO-1 induction by curcumin in human hepatoma cells. There was increasing toxicity of curcumin at concentrations higher than 10 microM. Curcumin was found to induce HO-1 at doses of 10 to 25 microM. At both non-toxic and toxic doses, HO-1 induction was found to correlate with production of reactive oxygen species (ROS), suggesting a causative relationship. This was reinforced by the finding that pretreatment with the antioxidants N-acetylcysteine, vitamin E and catalase prevented HO-1 induction by curcumin. ROS production appeared to be mitochondrial in origin, and curcumin treatment resulted in depolarisation of the mitochondrial membrane potential. Nrf2 was induced by curcumin treatment, which was also partly ROS dependent. Using siRNA, Nrf2 was demonstrated to contribute to HO-1 induction. A panel of kinase inhibitors was used to examine the contribution of MAP kinases to the induction of HO-1 by curcumin. PKC and p38 MAPK activity are required for full induction of HO-1. Furthermore, curcumin also inhibited protein phosphatase activity. In conclusion, curcumin treatment results in ROS generation, activation of Nrf2 and MAP kinases and the inhibition of phosphatase activity in hepatocytes, and when curcumin is not administered in toxic doses, these multiple pathways converge to induce HO-1.
• Pretransplant Bilirubin Concentration Does Not Correlate with Early Reperfusion Injury Following Liver Transplantation Transplantation. Jan, 2007  |   Pubmed ID: 17220806
• De-repression of Heat Shock Transcription Factor-1 in Interleukin-6- Treated Hepatocytes is Mediated by Downregulation of Glycogen Synthase Kinase 3beta and MAPK/ERK-1 International Journal of Molecular Medicine. Mar, 2007  |   Pubmed ID: 17273789 Expression of inducible heat shock protein (HSP70) requires activation of heat shock transcription factor-1 (HSF-1). Recent evidence suggests that interleukin-6 (IL-6) can modify the response of HSF-1 to heat. We hypothesized that IL-6 would prime the HSP response by causing de-repression of HSF-1 resulting in augmented HSP expression in stressed cells. In this study we show that IL-6 has no direct effect on HSP70 expression at 37 degrees C but does augment HSP70 expression in response to heat. IL-6 treatment decreased active MAPK/pERK and glycogen synthase kinase 3beta (GSK3beta) expression and GSK3beta kinase activity. In IL-6-treated cells, monomeric HSF-1 accumulated in the cytoplasm and nucleus, bound DNA but was transcriptionally inactive. On exposure to heat shock this modified monomer assumed the transcriptionally active phenotype with trimerization and hyperphosphorylation evident. The increased induction of HSP70 in IL-6 and heat-treated cells was inhibited using PI3-kinase inhibitors or Akt inhibition and was HSF-1 dependent. IL-6, via the PI3-kinase/Akt pathway leads to inhibition of the repressive kinases MAPK/pERK and GSK3beta, and this converts inactive HSF-1 to an intermediate DNA-binding form augmenting transcriptional activation in the presence of a second stressor.
• Outcomes After Identical and Compatible Orthotopic Liver Transplantation for Fulminant Hepatic Failure: a Single Center Experience in UK Transplant International : Official Journal of the European Society for Organ Transplantation. Aug, 2007  |   Pubmed ID: 17343687 To analyze the outcomes between identical and compatible liver transplantation (OLT) for fulminant hepatic failure (FHF) from September 1984 to November 2005. The patients were divided in three groups; group 1 (identical), group 2 (compatible) and group 3 (incompatible), according to the donor-recipient blood type matching. We analyzed several outcomes regarding mortality, patient and graft survival, incidence of acute graft rejection during the first postoperative month (30 days), incidence of biliary complications and indications of re-transplantation. We also analyzed the relationship of Coomb's positive test with postoperative hemolysis to all the above mentioned factors. During the study period, 168 males and 112 females underwent their first OLT for FHF, with 37.1% overall mortality and 42.1% overall graft failure rate. The results between group 1 (203 patients) and group 2 (73 patients) were comparable. A statistically significant difference was recorded in 1 year and overall graft survival between group 1 and group 2 (P = 0.049 and log-rank = 0.035 respectively). Coomb's positive test did not influence the outcomes. OLT in FHF can be safely carried out whether the donor organs are identical or compatible. Hemolysis (Coomb's positive test) after identical or compatible OLT does not influence the outcomes.
• Negative Regulation of Soluble Flt-1 and Soluble Endoglin Release by Heme Oxygenase-1 Circulation. Apr, 2007  |   Pubmed ID: 17389265 Preeclampsia is characterized clinically by hypertension and proteinuria. Soluble Flt-1 (sFlt-1; also known as soluble vascular endothelial growth factor receptor-1 [VEGFR-1]) and soluble endoglin (sEng) are elevated in preeclampsia, and their administration to pregnant rats elicits preeclampsia-like symptoms. Heme oxygenase-1 (HO-1) and its metabolite carbon monoxide (CO) exert protective effects against oxidative stimuli. Thus, we hypothesized that HO-1 upregulation may offer protection against preeclampsia by inhibiting sFlt-1 and sEng release.
• Effect of High-fat Enteral Nutrition on Hepatocyte Injury in Response to Hemorrhagic Shock in the Rat World Journal of Surgery. Aug, 2007  |   Pubmed ID: 17566822 High-fat enteral nutrition reduces the inflammatory response following hemorrhagic shock in the rat.
• The Use of Marginal Heart Beating Donor Livers for Transplantation in the United Kingdom Transplantation. Jul, 2007  |   Pubmed ID: 17627240 This study investigated the use of deceased heart-beating donor livers offered for transplantation during a 10-year period, during which there has been an increasing disparity between organ supply and demand in the United Kingdom.
• Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection World Journal of Surgery. Oct, 2007  |   Pubmed ID: 17668263 Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection.
• A New Approach to Isolation and Culture of Human Kupffer Cells Journal of Immunological Methods. Sep, 2007  |   Pubmed ID: 17692868 Macrophages are a diverse population of cells that are able to adapt to specific tissue environments. Kupffer cells are liver resident macrophages and form the largest population of fixed tissue macrophages. Their isolation offers an exciting opportunity to study this subpopulation of uniquely adapted cells. However existing Kupffer cell isolation techniques are tedious and are still largely based on enzymatic digestion to liberate tissue macrophages from the closely associated surrounding tissue. Isolation techniques have continually evolved over the last 3 decades but are neither easily applicable nor user friendly. This is highlighted by a review of current literature which will show that there is a scarcity of published studies employing human Kupffer cells. The other difficulty with Kupffer cells and some other populations of macrophages in culture is the strong tenacity with which they adhere to solid substrate and their resistance to conventional sub-culture dissociation agents. The difficulty with cell dissociation has previously required cells to be grown in suspension culture. This has been achieved by culturing macrophages in Teflon bags but unfortunately this deprives cells of the maturation signals generated by adherence. In this article we have upped the ante by describing a 'user friendly' method for Kupffer cell isolation and new culture techniques that allow Kupffer cells to be grown in adherency whilst at the same time circumventing the difficulties posed by the adherence of these unique cells.
• Effect of Major Liver Resection on Hepatic Ureagenesis in Humans American Journal of Physiology. Gastrointestinal and Liver Physiology. Nov, 2007  |   Pubmed ID: 17717046 Changes in hepatic ureagenesis following major hepatectomy are not well characterized. We studied the relation between urea synthesis and liver mass before and after major hepatectomy in humans. Fifteen patients scheduled for resection of malignancies in otherwise healthy livers were studied. Pre- and postoperative liver volume was assessed by computerized tomography-volumetry. During surgery, a primed, continuous infusion of [(13)C]urea was administered intravenously, and arterial blood samples were obtained hourly. Indocyanine green clearance was determined before and after resection. Seven patients underwent major hepatectomy, and eight patients underwent minor [
• Liver Volumetry Plug and Play: Do It Yourself with ImageJ World Journal of Surgery. Nov, 2007  |   Pubmed ID: 17726630 A small remnant liver volume is an important risk factor for posthepatectomy liver failure and can be predicted accurately by computed tomography (CT) volumetry using radiologic image analysis software. Unfortunately, this software is expensive and usually requires support by a radiologist. ImageJ is a freely downloadable image analysis software package developed by the National Institute of Health (NIH) and brings liver volumetry to the surgeon's desktop. We aimed to assess the accuracy of ImageJ for hepatic CT volumetry.
• Immune-mediated Liver Injury Seminars in Liver Disease. Nov, 2007  |   Pubmed ID: 17979072 Diseases with different pathogeneses share common pathways of immune-mediated injury. Autoreactive T cells destroy hepatocytes or cholangiocytes in autoimmune disease and virus-specific T cells destroy infected hepatocytes in viral hepatitis. In these conditions, antigen-specific mechanisms can be implicated but immune-mediated injury is central to diseases where there is a less-defined role for specific antigens. In all these diseases, "bystander cells" activated by the local microenvironment rather than a specific antigen are major players and amplify effector responses by recruiting natural killer and natural killer T cells, macrophages, neutrophils, eosinophils, and even platelets. Immune-mediated liver injury is driven by repeated cycles of inflammation and damage sustained by continuing recruitment, retention, and survival of effector leukocytes within the inflamed liver. These processes depend on complex interactions involving epithelial cells, stromal cells, and leukocytes shaped by the local cytokine microenvironment. Understanding these interactions will elucidate the pathogenesis of liver disease and suggest new therapies.
• Expression and Functional Consequences of Oestrogen and Progesterone Receptors in Human Insulinomas Endocrine-related Cancer. Dec, 2007  |   Pubmed ID: 18045959 The expression of steroid receptors by tumours offers a therapeutic advantage if functionally responsive to exogenous hormones. Insulinomas represent a highly symptomatic group of pancreatic tumours and the steroid receptor status of these tumours is poorly understood. The object of the study was to characterise the sex steroid receptor status of human insulinomas and to investigate whether sex steroids alter insulin expression therein. At our tertiary referral University Hospital, archival and prospective tissues from 25 insulinoma patients collected over 14 years were analysed for oestrogen receptor-alpha (ERalpha), oestrogen receptor beta (ERbeta) and progesterone receptor (PR) expression. Tissue explants of insulinoma and control pancreatic tissue from two new insulinoma patients were cultured and treated with oestrogen and progesterone and insulin expression measured by RT-PCR and ELISA. The main outcome measures were established before data collection and included sex steroid receptor status of tumours and insulin expression in fresh tissue in response to exogenous sex steroids. PR was expressed in 24 out of 25, ERalpha in 10 out of 25 and ERbeta in 21 out of 25 insulinomas. In fresh insulinoma cultures, insulin expression was increased by oestrogen or progesterone, whereas no significant effect was observed in adjacent pancreatic tissue. This study demonstrates widespread expression of sex steroid receptors on human insulinoma tissue and provides in vitro evidence of functionality with increased expression of insulin by insulinoma explants in response to exogenous oestrogen or progesterone. Confirmation of these results may provide a therapeutic mechanism for reducing symptomatic insulin secretion by receptor blockade.
• Living Donor Kidney Transplantation Southern Medical Journal. Dec, 2007  |   Pubmed ID: 18090958
• Coculture of Human Liver Macrophages and Cholangiocytes Leads to CD40-dependent Apoptosis and Cytokine Secretion Hepatology (Baltimore, Md.). Feb, 2008  |   Pubmed ID: 17999420 In the vanishing bile duct syndromes (VBDS), primary biliary cirrhosis and chronic allograft rejection, cholangiocyte apoptosis is associated with sustained macrophage infiltration of the liver, suggesting that these cells may mediate tissue damage and contribute to bile duct destruction. We have previously reported that activation of CD40 on cholangiocytes with either soluble CD154 or cross-linking monoclonal antibody to CD40 induces apoptosis in vitro. We have now developed a novel primary human cell coculture model and used it to investigate (1) how macrophages kill cholangiocytes; (2) how paracrine cell interactions can shape the local cytokine milieu within the liver. We report that lipopolysaccharide (LPS) and interferon (IFN) induce sustained expression of CD154 on liver-derived macrophages (LDM) in vitro. Coculture of activated LDM expressing high levels of CD154 (CD40 ligand) with human cholangiocytes resulted in (1) CD40-dependent secretion of proinflammatory cytokines; (2) apoptosis of cholangiocytes that was abolished by antagonistic antibodies directed against human CD40 or human CD154.
• Polyarteritis Nodosa, Presenting As Life-threatening Gastrointestinal Hemorrhage in a Liver Transplant Recipient Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Feb, 2008  |   Pubmed ID: 18236387 This unique case reports the first recorded episode in the medical literature of vasculitis post-liver transplantation, presenting as life-threatening gastrointestinal hemorrhage. A 52-year-old Caucasian woman underwent orthotopic liver transplantation (OLT) for autoimmune cirrhosis complicated by hepatoma and portal vein thrombosis. Late hepatic artery thrombosis led to a second liver graft. Following recovery from an episode of acute rejection, the patient presented with large volume hematemesis, melena, and hemochezia (passage of fresh blood from the rectum). Following upper and lower gastrointestinal endoscopy and surgery, angiography illustrated the presence of polyarteritis nodosa (PAN), which was successfully treated with high-dose steroid therapy. Gastrointestinal hemorrhage is an unusual presentation of vasculitis, especially PAN. The occurrence of this phenomenon post-OLT, in the presence of immunosuppression is previously unreported.
• Intrahepatic Complement Activation, Sinusoidal Endothelial Injury, and Lactic Acidosis Are Associated with Initial Poor Function of the Liver After Transplantation Transplantation. Mar, 2008  |   Pubmed ID: 18337666 Changes in glucose metabolism in the liver during transplantation have been recently described using microdialysis. Here, these findings are correlated with histopathologic, immunohistochemical, and ultrastructural changes in liver.
• Defining Surgical Complications World Journal of Surgery. Jun, 2008  |   Pubmed ID: 18368446
• Application of Portsmouth Modification of Physiological and Operative Severity Scoring System for Enumeration of Morbidity and Mortality (P-POSSUM) in Pancreatic Surgery World Journal of Surgical Oncology. 2008  |   Pubmed ID: 18400108 Pancreatoduodenectomy (PD) is associated with high incidence of morbidity and mortality. We have applied P-POSSUM in predicting the incidence of outcome after PD to identify those who are at the highest risk of developing complications.
• Heat Shock Protein 90-binding Agents Protect Renal Cells from Oxidative Stress and Reduce Kidney Ischemia-reperfusion Injury American Journal of Physiology. Renal Physiology. Aug, 2008  |   Pubmed ID: 18562631 Heat shock proteins (Hsps) are protective in models of transplantation, yet practical strategies to upregulate them remain elusive. The heat shock protein 90-binding agent (HBA) geldanamycin and its analogs (17-AAG and 17-DMAG) are known to upregulate Hsps and confer cellular protection but have not been investigated in a model relevant to transplantation. We examined the ability of HBAs to upregulate Hsp expression and confer protection in renal adenocarcinoma (ACHN) cells in vitro and in a mouse model of kidney ischemia-reperfusion (I/R) injury. Hsp70 gene expression was increased 30-40 times in ACHN cells treated with HBAs, and trimerization and DNA binding of heat shock transcription factor-1 (HSF1) were demonstrated. A three- and twofold increase in Hsp70 and Hsp27 protein expression, respectively, was found in ACHN cells treated with HBAs. HBAs protected ACHN cells from an H2O2-mediated oxidative stress, and HSF1 short interfering RNA was found to abrogate HBA-mediated Hsp induction and protection. In vivo, Hsp70 was upregulated in the kidneys, liver, lungs, and heart of HBA-treated mice. This was associated with a functional and morphological renal protection from I/R injury. Therefore, HBAs mediate upregulation of protective Hsps in mouse kidneys which are associated with reduced I/R injury and may be useful in reducing transplant-associated kidney injury.
• The Gut Does Not Contribute to Systemic Ammonia Release in Humans Without Portosystemic Shunting American Journal of Physiology. Gastrointestinal and Liver Physiology. Oct, 2008  |   Pubmed ID: 18703642 The gut is classically seen as the main source of circulating ammonia. However, the contribution of the intestines to systemic ammonia production may be limited by hepatic extraction of portal-derived ammonia. Recent data suggest that the kidney may be more important than the gut for systemic ammonia production. The aim of this study was to quantify the role of the kidney, intestines, and liver in interorgan ammonia trafficking in humans with normal liver function. In addition, we studied changes in interorgan nitrogen metabolism caused by major hepatectomy. From 21 patients undergoing surgery, blood was sampled from the portal, hepatic, and renal veins to assess intestinal, hepatic, and renal ammonia metabolism. In seven cases, blood sampling was repeated after major hepatectomy. At steady state during surgery, intestinal ammonia release was equaled by hepatic ammonia uptake, precluding significant systemic release of intestinal-derived ammonia. In contrast, the kidneys released ammonia to the systemic circulation. Major hepatectomy led to increased concentrations of ammonia and amino acids in the systemic circulation. However, transsplanchnic concentration gradients after major hepatectomy were similar to baseline values, indicating the rapid institution of a new metabolic equilibrium. In conclusion, since hepatic ammonia uptake exactly equals intestinal ammonia release, the splanchnic area, and hence the gut, probably does not contribute significantly to systemic ammonia release. After major hepatectomy, hepatic ammonia clearance is well preserved, probably related to higher circulating ammonia concentrations.
• Tissue-resident Macrophages Protect the Liver from Ischemia Reperfusion Injury Via a Heme Oxygenase-1-dependent Mechanism Molecular Therapy : the Journal of the American Society of Gene Therapy. Jan, 2009  |   Pubmed ID: 19002167 Kupffer cells are the resident macrophage population of the liver and have previously been implicated in the pathogenesis of hepatic ischemia-reperfusion injury (IRI). Kupffer cells are the major site of expression of hepatic heme oxygenase-1 (HO-1), which has been shown to have anti-inflammatory actions and to protect animals and cells from oxidative injury. Kupffer cells and circulating monocytes were selectively ablated using liposomal clodronate (LC) in the CD11b DTR mouse before induction of hepatic ischemia. Kupffer cell depletion resulted in loss of HO-1 expression and increased susceptibility to hepatic IRI, whereas ablation of circulating monocytes did not affect IRI phenotype. Targeted deletion of HO-1 rendered mice highly susceptible to hepatic IRI. In vivo, HO-1 deletion resulted in pro-inflammatory Kupffer cell differentiation characterized by enhanced Ly6c and MARCO (macrophage receptor with collagenous structure) expression as well as decreased F4/80 expression, mirrored by an expansion in immature circulating monocytes. In vitro, HO-1 inhibition throughout macrophage differentiation led to increased cell numbers, and pro-inflammatory Ly6c+ CD11c- F4/80- phenotype. These data support a critical role for tissue-resident macrophages in homeostasis following ischemic injury, and a co-dependence of HO-1 expression and tissue-resident macrophage differentiation.
• Choledochoduodenostomy As an Alternative to Choledochojejunostomy in Liver Transplantation World Journal of Surgery. May, 2009  |   Pubmed ID: 19234741
• Cancer Cachexia is Associated with the IL10 -1082 Gene Promoter Polymorphism in Patients with Gastroesophageal Malignancy The American Journal of Clinical Nutrition. Apr, 2009  |   Pubmed ID: 19244371 The genetic predisposition of the host to local or systemic inflammation may contribute to the effect of cancer cachexia.
• The Utilization of Liver Transplantation in the Management of Acute Liver Failure: Comparison Between Acetaminophen and Non-acetaminophen Etiologies Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Jun, 2009  |   Pubmed ID: 19479803 Liver transplantation (LT) may be life-saving in severe acute liver failure (ALF). The aim of this study was to compare the utilization of LT in acetaminophen and non-acetaminophen ALF. Between 1992 and 2006, 469 patients with ALF were admitted, and 104 underwent LT. Acetaminophen was the most common etiology, but LT proceeded more frequently in the non-acetaminophen cohort (acetaminophen: 45/326 patients received LT, 13.8%; non-acetaminophen: 59/143 patients received LT, 41.3%; P < 0.01). A retrospective analysis of the individual steps in the management of patients revealed more ALF patients in the non-acetaminophen cohort fulfilled the King's College Hospital poor prognostic criteria (non-acetaminophen: 91/143, 63.6%; acetaminophen: 165/326, 50.6%; P < 0.01), more patients had contraindications to LT in the acetaminophen cohort (acetaminophen: 99/165, 60%; non-acetaminophen: 21/91, 23.1%; P < 0.01), and survival on the LT waiting list was reduced in the acetaminophen cohort (acetaminophen: 45/66, 68.2%; non-acetaminophen: 59/70, 84.3%; P < 0.05). Post-LT survival was similar in the 2 groups. An analysis of cohorts admitted in 1993-1996 and 2002-2005 revealed that LT proceeded less commonly in acetaminophen ALF in the later cohort (1993-1996: 16/99 LT, 16.2%; 2002-2005: 4/81 LT, 5%; P < 0.01) in comparison with the non-acetaminophen cohort, in which transplantation proceeded more commonly in the later cohort (1993-1996: 11/34 LT, 32.4%; 2002-2005: 24/49 patients, 49.0%; P < 0.01). This was due to an increase in the number of patients with psychiatric contraindications to transplantation (predominantly resistant and severe alcohol dependence). In conclusion, at all decision steps between admission and emergency LT, LT is favored in non-acetaminophen patients, and nonoperative management is favored in acetaminophen ALF patients.
• C-Jun Terminal Kinase-2 Gene Deleted Mice Overexpress Hemeoxygenase-1 and Are Protected from Hepatic Ischemia Reperfusion Injury Transplantation. Aug, 2009  |   Pubmed ID: 19667931 Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 transcription factor system. We hypothesized that this would lead to induction of hemeoxygenase-1 (HO-1) and confer protection from hepatic ischemia reperfusion injury.
• Clinical Practice Guidelines for the Management of Atypical Haemolytic Uraemic Syndrome in the United Kingdom British Journal of Haematology. Jan, 2010  |   Pubmed ID: 19821824 Atypical haemolytic uraemic syndrome (aHUS) is associated with a poor prognosis with regard to survival at presentation, recovery of renal function and transplantation. It is now established that aHUS is a disease of complement dysregulation with mutations in the genes encoding both complement regulators and activators, and autoantibodies against the complement regulator factor H. Identification of the underlying molecular abnormality in an individual patient can now help to guide their future management. In these guidelines we make recommendations for the investigation and management of aHUS patients both at presentation and in the long-term. We particularly address the role of renal transplantation alone and combined liver-kidney transplantation.
• Web-based Image Transmission: a Novel Approach to Aid Communication in Split Liver Transplantation Clinical Transplantation. Jan-Feb, 2010  |   Pubmed ID: 19878514 Split liver transplantation (SLT) is technically demanding and requires good communication between transplant centers. The recipient surgeon receiving a shipped split liver needs detailed information on allocation of inflow and outflow vessels. We describe the first use of an image transmission system to facilitate SLT.
• Reduction in Bile Leaks Following Adult Split Liver Transplant Using a Fibrin-collagen Sponge: A Pilot Study Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. Mar, 2010  |   Pubmed ID: 19913466 Bile leaks are a frequent complication of adult split liver transplantation. We compared surgical complications in patients who had the cut surface of the donor liver treated with a patch to those in whom the cut surface of the liver was treated with fibrin glue.
• Practical Barriers to Delivering Autologous Bone Marrow Stem Cell Therapy As an Adjunct to Liver Resection Stem Cells and Development. Feb, 2010  |   Pubmed ID: 19954303 Liver resection has been associated with significant morbidity and mortality due to hepatic dysfunction or hepatic failure in the postoperative period. Autologous bone marrow stem cell (BMSC) therapy may offer the potential to enhance hepatic regeneration in this setting, perhaps increasing the safety of the procedure. Preclinical models and initial translational studies have suggested that autologous BMSC administration can facilitate hepatic regeneration following both acute and chronic liver disease. While translational studies have begun in chronic hepatic disease, translation to hepatic surgical indications has been limited. This review explores the practical barriers currently restricting the delivery of autologous stem cell therapies to enhance hepatic regeneration following liver resection including selection of cell type, cell isolation, therapy delivery, trial design, and assessment of efficacy.
• The Management of an Accessory or Replaced Right Hepatic Artery During Multiorgan Retrieval: Results of an Angiographic Study Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Jun, 2010  |   Pubmed ID: 20517908 In the presence of anatomical variants such as an accessory or replaced (A/R) right hepatic artery (RHA), a conflict of interest can arise during organ retrieval between liver and pancreatic teams. This angiographic study examines the anatomy of the inferior pancreaticoduodenal artery (IPDA), its relation to the A/R RHA, and the implications for the use of livers and pancreases from multiorgan donors. Gastrointestinal angiograms performed in our institution for unrelated indications were reviewed, and the relevant arteries, their diameters, the distances between origins, the time at which variants were found, and the blood supply to relevant solid organs were recorded. A review of 122 angiograms identified 100 patients in whom both the superior mesenteric artery (SMA) and the celiac axis were cannulated synchronously; these patients composed our study cohort. The IPDA was identified in 95% of the cases. There were 8 patients with a replaced RHA and 4 with an accessory RHA. In all 12, the IPDA had an SMA origin; 3 of these shared a common origin with the A/R RHA on the SMA. In the rest, the mean distance between them was 29 mm (range = 17.8-48.3 mm). All anomalous arteries found were segmental vessels. In conclusion, the A/R RHA incidence in our series was 12%, and no case had an IPDA originating from the A/R RHA. Separate accessory RHA and IPDA origins potentially allow an uncompromised accessory RHA (with its Carrel patch) without risk of prejudice to the pancreatic graft if retrieval is accurately performed. Rarely (3%), there is a common origin between the A/R RHA and the IPDA, and back-bench reconstruction would be required to allow the use of both the liver and pancreas.
• Increasing Donor Body Weight to Prevent Small-for-size Syndrome in Living Donor Liver Transplantation World Journal of Surgery. Oct, 2010  |   Pubmed ID: 20533035
• Editorial Policy on Clinical Transplantation Articles from the People's Republic of China World Journal of Surgery. Aug, 2010  |   Pubmed ID: 20549209
• Prospects for Stem Cell Transplantation in the Treatment of Hepatic Disease Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Jul, 2010  |   Pubmed ID: 20583084 Stem cell therapy has the potential to provide a valuable adjunct to the management of hepatic disease. Preclinical studies have demonstrated a range of endogenous repair processes that can be exploited through stem cell therapy. Initial translational studies have been encouraging and have suggested improved liver function in advanced chronic liver disease and enhanced liver regeneration after portal vein embolization. This article reviews the potential for stem cell therapies to enhance hepatic regeneration in acute and chronic hepatic disease and is based on a MEDLINE and PubMed search for English language articles investigating mechanisms of hepatic regeneration and delivery of cell therapies. Two main mechanisms of potential stem cell therapy delivery have emerged: (1) a direct contribution to the functional hepatocyte population with embryonic, induced pluripotent, or adult stem cells and (2) the promotion of endogenous regenerative processes with bone marrow-derived stem cells. Bioartificial hepatic support systems may be proven to be an effective method of using ex vivo differentiated hepatocytes and be indicated as a bridging therapy to definitive surgery in acute liver failure. The administration of bone marrow-derived stem cells may enhance liver regeneration in chronic liver disease after portal vein embolization and could facilitate regeneration after partial hepatic resection. Ultimately, the most appropriate hepatic disease targets for stem cell therapies will become apparent as mechanisms of stem involvement in hepatic regeneration are further elucidated.
• What Defines 'cure' After Liver Resection for Colorectal Metastases? Results After 10 Years of Follow-up HPB : the Official Journal of the International Hepato Pancreato Biliary Association. May, 2010  |   Pubmed ID: 20590894 During the last two decades, resection of colorectal liver metastases (CLM) in selected patients has become the standard of care, with 5-year survival rates of 25-58%. Although a substantial number of actual 5-year survivors are reported after resection, 5-year survival rates may be inadequate to evaluate surgical outcomes because a significant number of patients experience a recurrence at some point.
• Hepatic Resection for Metastatic Endometrioid Carcinoma HPB : the Official Journal of the International Hepato Pancreato Biliary Association. Aug, 2010  |   Pubmed ID: 20662792 The role of hepatic resection for gynaecological tumours is not well defined as evidence on the subject is lacking. This article describes a tertiary hepatopancreatobiliary unit's experience with hepatic resection for liver metastases from endometrioid primaries.
• Current Challenges in Liver Transplantation Following Donation After Cardiac Death Transplantation. Nov, 2010  |   Pubmed ID: 20881663 There is a resurgence of interest in liver transplantation using donation after cardiac death (DCD) donor livers. Careful donor and recipient selection can result in excellent outcomes, but injury to the biliary system remains a serious challenge to DCD liver transplantation. This mini review addresses the current challenges to DCD liver transplantation.
• Heme Oxygenase System in Hepatic Ischemia-reperfusion Injury World Journal of Gastroenterology : WJG. Dec, 2010  |   Pubmed ID: 21182221 Hepatic ischemia-reperfusion injury (IRI) limits access to transplantation. Heme oxygenase-1 (HO-1) is a powerful antioxidant enzyme which degrades free heme into biliverdin, free iron and carbon monoxide. HO-1 and its metabolites have the ability to modulate a wide variety of inflammatory disorders including hepatic IRI. Mechanisms of this protective effect include reduction of oxygen free radicals, alteration of macrophage and T cell phenotype. Further work is required to understand the physiological importance of the many actions of HO-1 identified experimentally, and to harness the protective effect of HO-1 for therapeutic potential.
• Prospective Volumetric Assessment of the Liver on a Personal Computer by Nonradiologists Prior to Partial Hepatectomy World Journal of Surgery. Feb, 2011  |   Pubmed ID: 21136056 A small remnant liver volume is an important risk factor for posthepatectomy liver failure. ImageJ and OsiriX® are both free, open-source image processing software packages. The aim of the present study was to compare ImageJ and OsiriX® in performing prospective computed tomography (CT) volumetric analysis of the liver on a personal computer (PC) in patients undergoing major liver resection.
• Liver Resection for Colorectal Metastases in Presence of Extrahepatic Disease: Results from an International Multi-institutional Analysis Annals of Surgical Oncology. May, 2011  |   Pubmed ID: 21136180 Hepatic resection for colorectal liver metastasis (CLM) with concomitant extrahepatic disease (EHD) is a controversial topic. We sought to evaluate the long-term outcome of patients undergoing liver resection for CLM in presence of EHD and identify factors associated with prognosis.
• Impact of Concomitant Arterial Injury on the Outcome of Laparoscopic Bile Duct Injury American Journal of Surgery. Feb, 2011  |   Pubmed ID: 21266217 Concomitant injury to the bile duct and hepatic artery is an increasingly recognized complication of laparoscopic cholecystectomy (LC). The impact of a concomitant arterial injury in patients with a bile duct injury (BDI) remains debatable. Early reports described a high incidence of septic complications, difficulty of biliary repair, and increased the risk of recurrent stricture.
• Effectiveness of Epidural Analgesia Following Open Liver Resection HPB : the Official Journal of the International Hepato Pancreato Biliary Association. Mar, 2011  |   Pubmed ID: 21309939 Epidural analgesia is often considered the reference standard for pain relief following major abdominal surgery; however, the provision of analgesia in the context of liver surgery raises unique challenges. This study investigated the effectiveness of analgesia and the postoperative course of patients who did or did not receive epidural analgesia following liver resection.
• Paid Organ Donation Annals of the Royal College of Surgeons of England. Apr, 2011  |   Pubmed ID: 21477428
• Can Serotonin Agonists Unlock Age-dependent Failure of Liver Regeneration? Journal of Hepatology. Dec, 2011  |   Pubmed ID: 21741345
• Is There a Role for Extracorporeal Liver Support As a Bridge to Liver Transplantation in Acute Liver Failure? Transplantation. Oct, 2011  |   Pubmed ID: 21989274
• Study on the Feasibility of Provision of Distance Learning Programmes in Surgery to Malawi The Surgeon : Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland. Dec, 2011  |   Pubmed ID: 22041645 Medical educational opportunities and resources are considerably limited in the developing world. The expansion of computing and Internet access means that there exists a potential to provide education to students through distance learning programmes. This study investigated the feasibility of providing distance learning course in surgery in Malawi. The study investigated the user requirements, technical requirements and Internet connections in two teaching hospitals in Malawi. In addition the appropriateness of current course material from the Edinburgh Surgical Sciences Qualification to Malawi trainees was assessed. The study found a high degree of interest from Malawian trainees in distance learning. The provision of basic science modules such as anatomy and physiology and the ability to access journals were considered highly desirable. The current ESSQ course would require extensive re-modelling to make it suitable to an African trainee's requirements. Internet speeds remain slow and access is currently expensive. There is considerable interest in distance learning programmes in Malawi but access to them is limited partly because of slow and expensive Internet access. Understanding the needs of trainees in countries such as Malawi will allow better direction of educational aid and resources to support surgical training.
• Factors in Perioperative Care That Determine Blood Loss in Liver Surgery HPB : the Official Journal of the International Hepato Pancreato Biliary Association. Apr, 2012  |   Pubmed ID: 22404261 Excessive blood loss during liver surgery contributes to postoperative morbidity and mortality and the minimizing of blood loss improves outcomes. This study examines pre- and intraoperative factors contributing to blood loss and identifies areas for improvement.
• Hospital Volume and Patient Outcomes After Cholecystectomy in Scotland: Retrospective, National Population Based Study BMJ (Clinical Research Ed.). 2012  |   Pubmed ID: 22623634 To define associations between hospital volume and outcomes following cholecystectomy, after adjustment for case mix using a national database.
• The Role of Heat Shock Protein 90 in Modulating Ischemia-reperfusion Injury in the Kidney Expert Opinion on Investigational Drugs. Oct, 2012  |   Pubmed ID: 22876854 Kidney transplantation is the gold standard treatment for end-stage renal disease. Ischemia-reperfusion injury (IRI) is an unavoidable consequence of the transplantation procedure and is responsible for delayed graft function and poorer long-term outcomes. AREAS COVERED: Pharmacological induction of heat shock protein (Hsp) expression is an emerging pre-conditioning strategy aimed at reducing IRI following renal transplantation. Hsp90 inhibition up-regulates protective Hsps (especially Hsp70) and potentially down-regulates NF-κB by disruption of the IκB kinase (IKK) complex. However, the clinical application of Hsp90 inhibitors is currently limited by their toxicity profile and the exact mechanism of protection conferred is unknown. Toll-like receptor 4 (TLR4) is a further regulator of NF-κB and recent studies suggest TLR4 plays a dominant role in mediating kidney damage following IRI. The full interaction of Hsps with TLRs is yet to be delineated and whether TLR4 signalling can be targeted by Hsp90 inhibition in IRI remains uncertain. EXPERT OPINION: Pharmacological pre-conditioning by Hsp90 inhibition involves direct treatment to the kidney donor and/or organ, which aims to reduce injury prior to the onset of ischemia. The major challenges going forward are to establish the exact mechanism of protection offered by these drugs and the investgiation of less toxic analogues that could be safely translated into human studies.
• Randomized Clinical Trial of Local Infiltration Plus Patient-controlled Opiate Analgesia Vs. Epidural Analgesia Following Liver Resection Surgery HPB : the Official Journal of the International Hepato Pancreato Biliary Association. Sep, 2012  |   Pubmed ID: 22882198 Epidural analgesia is recommended for the provision of analgesia following major abdominal surgery. Continuous local anaesthetic wound infiltration may be an effective alternative. A prospective randomized trial was undertaken to compare these two methods following open liver resection. The primary outcome was length of time required to fulfil criteria for discharge from hospital.
• Ischemic Preconditioning in the Liver is Independent of Regulatory T Cell Activity PloS One. 2012  |   Pubmed ID: 23185394 Ischemic preconditioning (IPC) protects organs from ischemia reperfusion injury (IRI) through unknown mechanisms. Effector T cell populations have been implicated in the pathogenesis of IRI, and T regulatory cells (Treg) have become a putative therapeutic target, with suggested involvement in IPC. We explored the role of Treg in hepatic IRI and IPC in detail. IPC significantly reduced injury following ischemia reperfusion insults. Treg were mobilized rapidly to the circulation and liver after IRI, but IPC did not further increase Treg numbers, nor was it associated with modulation of circulating pro-inflammatory chemokine or cytokine profiles. We used two techniques to deplete Treg from mice prior to IRI. Neither Treg depleted FoxP3.LuciDTR mice, nor wildtyoe mice depleted of Tregs with PC61, were more susceptible to IRI compared with controls. Despite successful enrichment of Treg in the liver, by adoptive transfer of both iTreg and nTreg or by in vivo expansion of Treg with IL-2/anti-IL-2 complexes, no protection against IRI was observed.We have explored the role of Treg in IRI and IPC using a variety of techniques to deplete and enrich them within both the liver and systemically. This work represents an important negative finding that Treg are not implicated in IPC and are unlikely to have translational potential in hepatic IRI.
• Systematic Review and Meta-analysis of Haemostatic and Biliostatic Efficacy of Fibrin Sealants in Elective Liver Surgery Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. Apr, 2013  |   Pubmed ID: 23086450 Fibrin sealants are frequently used in liver surgery to achieve intraoperative haemostasis and reduce post-operative haemorrhage and bile leak. This meta-analysis aimed to review the haemostatic and biliostatic capacity of fibrin sealants in elective liver surgery.
• Unexpectedly Low Variation in Liver Ischemia Preconditioning Study Journal of Surgical Oncology. May, 2013  |   Pubmed ID: 23677689