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Showing papers by "Brian R. Davidson published in 2005"


Journal ArticleDOI
TL;DR: This review has 2 aims: to highlight the clinical significance of liver ischemia‐reperfusion injury, the underlying mechanisms and the main pathways by which the antioxidants function, and to describe the new developments that are ongoing in antioxidant therapy.

215 citations


Journal ArticleDOI
TL;DR: Results suggest that duodenal bile crystal analysis (involving both calcium bilirubinate and cholesterol crystals) may be a useful technique for the investigation of patients with ‘idiopathic’ pancreatitis.
Abstract: Duodenal bile crystal analysis for the detection of gallstones was assessed in 26 patients with acute pancreatitis of known aetiology (11 attributable to gallstones and 15 to alcohol) and in 37 patients without a history of acute pancreatitis (21 with gallstones and 16 without). The sensitivity was 64–67 per cent and the specificity was 94–100 per cent in these groups. Analysis of duodenal bile from 14 patients with ‘idiopathic’ pancreatitis revealed calcium bilirubinate crystals (but not cholesterol crystals) in 5 patients (36 per cent). Gallstones were confirmed at cholecystectomy in three of these patients and also in one other patient who had a gallstone on a ‘late’ ultrasound examination but was negative for crystals. Thus 29 per cent of the original ‘idiopathic’ group had gallstones confirmed. Gallstone analysis showed that pigment stones were present in 7 of 31 (23 per cent) non-pancreatitis controls compared with 9 of 13 (69 per cent) pancreatitis patients (P = 0·0048). These results suggest that duodenal bile crystal analysis (involving both calcium bilirubinate and cholesterol crystals) may be a useful technique for the investigation of patients with ‘idiopathic’ pancreatitis.

93 citations


Journal ArticleDOI
TL;DR: A safe alternative to endobiliary methods is percutaneous fine‐needle aspiration cytology; this yields a diagnosis in about half of patients presenting with obstructive jaundice and an imaged mass lesion.
Abstract: Over the past 20 years, bile aspiration at endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography has been developed for cytological diagnosis of biliary tract stricture. This safe and specific test has allowed a diagnosis to be reached before or without operation in about one-third of malignancies of the pancreas or biliary tree. The recent development of biliary brush cytology has produced better results. An endobiliary biopsy forceps is now available that may allow safe sampling of lesions causing extrinsic compression of the biliary tract. An endobiliary aspiration cytology needle has been produced that may permit non-ulcerating lesions to be diagnosed. A safe alternative to endobiliary methods is percutaneous fine-needle aspiration cytology; this yields a diagnosis in about half of patients presenting with obstructive jaundice and an imaged mass lesion.

77 citations


Journal ArticleDOI
TL;DR: Endoscopic sphincterotomy is now the first choice treatment for surgical complications of hepatic hyd atid disease open to the biliary tree, as well as the drainage procedure of choice in patients with cholangitis due to hydatid disease.
Abstract: Communication with the biliary tree is the most common complication of hydatid disease of the liver and up to a few years ago surgery was the only way to treat it successfully. The introduction of endoscopic sphincterotomy represented a great advance in the management of this disease. We report the results obtained with this technique in ten patients after surgical treatment of hepatic hydatid disease open to the biliary tree. The results were satisfactory in all cases, with no morbidity or mortality. Endoscopic sphincterotomy is now the first choice treatment for surgical complications of hepatic hydatid disease open to the biliary tree, as well as the drainage procedure of choice in patients with cholangitis due to hydatid disease.

63 citations


Journal ArticleDOI
TL;DR: In this paper, the authors identify the isoforms responsible for the generation of cytoprotective NO during liver ischemic preconditioning (IPC) in Sprague-Dawley rats.
Abstract: This study was undertaken to identify nitric oxide synthase (NOS) isoforms responsible for the generation of cytoprotective NO during liver ischemic preconditioning (IPC). Sprague-Dawley rats were subjected to 45 min lobar ischemia followed by 2 h reperfusion. L-arginine or Nomega-nitro-L-arginine methyl ester (L-NAME) was administered to stimulate or block NO synthesis. Study groups (n=6) had 1) sham laparotomy, 2) ischemia reperfusion (IR), 3) IPC with 5 min ischemia and 10 min reperfusion before IR, 4) L-arginine before IR, or 5) L-NAME + IPC before IR. Liver function tests, nitrite + nitrate (NOx) and plasma amino acids were analyzed. The endothelial cell and inducible isoforms of NOS (eNOS and iNOS) were identified using immunohistochemistry and Western blotting. Both IPC and L-arginine treatment increased NOx (P<0.05) and improved serum liver enzymes (P<0.05) when compared with IR. These effects were prevented by L-NAME. Hepatic vein NOx was significantly higher than circulating NOx. iNOS expression was absent within the groups. The preconditioned livers were associated with up-regulation of eNOS expression and also increased L-arginine levels. The effects of L-arginine administration were similar to those evident following IPC. Thus, cytoprotective NO generation during IPC of the liver was a result of increased eNOS expression and increased L-arginine substrate availability.

60 citations


Journal ArticleDOI
TL;DR: The performances of the one‐ and three‐factor systems were marginally better than that of the five‐factor system; the one-factor system, however, had the advantage of simplicity.
Abstract: Three clinicobiochemical systems have been proposed for predicting gallstones in acute pancreatitis based on one, three and five factors respectively, but have not been compared in a single prospective study. System 1 is based on the serum transaminase alone; system 2 uses alkaline phosphatase and bilirubin in addition to transaminase; and system 3 involves female gender, age, amylase and alkaline phosphatase in addition to transaminase. Over the 4-year period 1983-86, 368 patients with 391 episodes of acute pancreatitis had clinicobiochemical analysis within 48 h. Of these episodes, 220 were related to gallstones (56 per cent), 62 to alcohol (16 per cent) and 109 to other aetiologies or were idiopathic (28 per cent). Significant differences were found between the biliary and non-biliary groups with respect to sex (139 versus 59 women, P less than 0.002), age (65 +/- 17 versus 52 +/- 19 years, P less than 0.0001) and serum amylase (6041 +/- 6335 versus 4546 +/- 3990 units/l, P less than 0.0001), alkaline phosphatase (257 +/- 225 versus 141 +/- 137 units/l, P less than 0.0001), alanine transaminase (221 +/- 227 versus 72 +/- 119 units/l, P less than 0.0001) and bilirubin (40 +/- 39 versus 24 +/- 30 mumol/l, P = 0.0001). The sensitivity and specificity was 75 per cent and 74 per cent for the one-factor system, 74 per cent and 78 per cent for the three-factor system and 62 per cent and 80 per cent for the five-factor system. The predictive value of a positive result was 78.8 per cent, 81.5 per cent and 80.1 per cent and of a negative result 69.4 per cent, 70.1 per cent and 62.3 per cent for the three systems respectively. The performances of the one- and three-factor systems were marginally better than that of the five-factor system; the one-factor system, however, had the advantage of simplicity.

55 citations


Journal ArticleDOI
TL;DR: NAC administration decreased the extent of I/R injury in the steatotic liver, particularly during the late phase of reperfusion, as indicated by ALT serum activity, and decreased the oxidation of DHR to RH.
Abstract: Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the aim of the present study was to evaluate the in vivo effect of NAC ( N -acetylcysteine) on hepatic function in the early and initial late phase of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits were fed a high-cholesterol (2%) diet. The control group ( n =6) underwent lobar liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group receiving NAC ( n =6), an intravenous infusion of NAC was administered prior to and during the 6 h reperfusion period. Systemic and hepatic haemodynamics were monitored continuously. ALT (alanine aminotransferase) activity and bile production were measured. NMR spectroscopy was used to analyse bile composition. Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of production of reactive oxygen and nitrogen species. Moderate centrilobular hepatic steatosis was demonstrated by histology. The results showed that NAC administration significantly improved portal flow, hepatic microcirculation, bile composition and bile flow after 5 h of reperfusion. NAC administration was also associated with less hepatocellular injury, as indicated by ALT serum activity, and decreased the oxidation of DHR to RH. In conclusion, NAC administration decreased the extent of I/R injury in the steatotic liver, particularly during the late phase of reperfusion. Abbreviations: ALT, alanine aminotransferase; DHR, dihydrorhodamine; I/R, ischaemia/reperfusion; LDF, laser Doppler flowmeter; MABP, mean arterial blood pressure; NAC, N-acetylcysteine; PC, phosphatidylcholine; RH, rhodamine; RNS, reactive nitrogen species; ROS, reactive oxygen species; TSP, sodium 3-(trimethylsilyl)-[2,2,3,3-2H4]-1-propionate; THBF, total hepatic blood flow

54 citations


Journal ArticleDOI
TL;DR: In this pilot study, NAC administered during donor operation did not show a protective effect on I/R injury or on acute cellular rejection.

37 citations


Journal ArticleDOI
TL;DR: In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis and may have important clinical implications in liver surgery and transplantation.
Abstract: IPC (ischaemic preconditioning) may protect the steatotic liver, which is particularly susceptible to I/R (ischaemia/reperfusion) injury. Hepatic steatosis was induced in Sprague-Dawley rats with a high-cholesterol (2%) diet for 12 weeks after which rats were subjected to I/R (ischaemia/reperfusion; 45 min of lobar ischaemia followed by 2 h of reperfusion). Rats were divided into three study groups (n=6 each) receiving: (i) sham laparotomy alone, (ii) I/R, and (iii) IPC (5 min of ischaemia, followed by 10 min of reperfusion) before I/R. Hepatic extra- and intra-cellular oxygenation and HM (hepatic microcirculation) were measured with near-infrared spectroscopy and laser Doppler flowmetry respectively. Plasma liver enzymes and hepatic tissue ATP were measured as markers of liver injury. Histology showed moderate-grade steatosis in the livers. At the end of 2 h of reperfusion, I/R significantly decreased extra- and intra-cellular oxygenation concomitant with a failure of recovery of HM (21.1+/-14.4% of baseline; P<0.001 compared with sham animals). IPC increased intracellular oxygenation (redox state of the copper centre of cytochrome oxidase; P<0.05 compared with rats receiving I/R alone) and flow in HM (70.9+/-17.1% of baseline; P<0.001 compared with rats receiving I/R alone). Hepatocellular injury was significantly reduced with IPC compared with I/R injury alone (alanine aminotransferase, 474.8+/-122.3 compared with 5436.3+/-984.7 units/l respectively; P<0.01; aspartate aminotransferase, 630.8+/-76.9 compared with 3166.3+/-379.6 units/l respectively; P<0.01]. In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis. These data may have important clinical implications in liver surgery and transplantation.

34 citations



Journal ArticleDOI
TL;DR: This technique was evaluated in 16 patients with colorectal tumours with the 111In‐labelled monoclonal antibody ICR2 which recognizes the tumour‐associated epithelial membrane antigen (EMA) and the uptake of radiolabelled antibody was higher in EMA‐expressing cancers than in those not expressing the target antigen.
Abstract: Radiation detectors may allow the intraoperative localization of small cancer deposits following administration of radiolabelled tumour-associated antibodies. This technique was evaluated in 16 patients with colorectal tumours (14 cancers, one adenoma, one lipoma) with the 111In-labelled monoclonal antibody (MAb) ICR2 which recognizes the tumour-associated epithelial membrane antigen (EMA). At operation counting was carried out (3 x 20 s per site) using a hand-held radiation probe over the primary lesions and any palpable lymph nodes in the mesocolon. The tumour to normal colon (T/NC) ratio of counts recorded at operation was more than 1.5:1 in eight of the 14 patients with cancer (mean(s.d.), 1.54(0.41):1) and 0.91:1 and 1.06:1 respectively in the two patients with benign tumours. Node to normal colon ratios were higher in lymph nodes containing metastases. The uptake of radiolabelled antibody (T/NC ratio) was higher in EMA-expressing cancers than in those not expressing the target antigen (mean(s.d.), 2.45(0.65):1 versus 1.40(0.20):1, P = 0.019). An abdominal tumour model was also developed. Radioactively filled containers of 0.5-10 ml representing tumour deposits were suspended in a tank of 111In solution representing the background activity found in normal tissues. The ratio of radioactivity in the 'tumour' to that of background varied from 2:1 to 8:1. The 'tumour' was considered to be detectable if the mean counts recorded over the 'tumour' exceeded the mean of counts recorded over background by three standard deviations. At a ratio of 2:1 only 'tumours' greater than 5 ml could be detected with a sodium iodide probe and those over 10 ml could be detected with a cadmium telluride (CdTe) probe. At a ratio of 8:1, 'tumours' of 0.5 ml could be detected with either probe. At all ratios and counting periods the NaI probe was more sensitive than the CdTe.

Journal ArticleDOI
TL;DR: A retrospective study was carried out of children undergoing Nissen fundoplication and pyloroplasty for the correction of gastro‐oesophageal reflux of mentally retarded children, finding the ‘normal’ children gained weight postoperatively whereas the ’retarded’ group did not.
Abstract: A retrospective study was carried out of children undergoing Nissen fundoplication and pyloroplasty for the correction of gastro-oesophageal reflux. Twenty children (thirteen males, seven females) aged 8 months to 12 years underwent surgery over a 10 year period. Forty per cent were mentally retarded. Presentation was failure to thrive in 19 (95 per cent), recurrent vomiting in 18 (90 per cent) and haematemesis in 14 (70 per cent). Four children had Barrett's oesophagus. There were no operative or perioperative mortalities. Follow-up (mean period 3 years, 9 months) revealed no further symptoms of reflux. The ‘normal’ children gained weight postoperatively whereas the ‘retarded’ group did not. Adhesion obstruction (10 per cent) was the major late postoperative complication. Regression of Barrett's epithelium was noted endoscopically. ‘Gas-bloat’ syndrome, a major complication following fundoplication, was not encountered.

Journal ArticleDOI
TL;DR: The case of a young adult with NF1, having a unique concurrence of plexiform neurofibroma involving the liver with an ampullary NET, is presented and step by step the management in a specialist centre is discussed.
Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, with variable clinical manifestations and unpredictable course, associated with an increased incidence of various tumours. Plexiform neurofibromas are hallmark lesions of NF1; they are slow-growing tumours, which account for substantial morbidity, including disfigurement and functional impairment, and may even be life-threatening. Neuroendocrine tumours (NETs), a rare diverse group of neoplasms, are occasionally associated with neurofibromatosis. Pancreatic NETs are tumours with an incidence of less than 1/100 000 population/year and complex patterns of behaviour, which often need complicated strategies for optimal management. We present the case of a young adult with NF1, having a unique concurrence of plexiform neurofibroma involving the liver with an ampullary NET, and we discuss step by step the management in a specialist centre.

Journal ArticleDOI
TL;DR: The aim of the study was to determine the value of radioisotope bone scans in the preoperative staging of patients with hepatopancreatobiliary (HPB) cancer.
Abstract: Background: The aim of the study was to determine the value of radioisotope bone scans in the preoperative staging of patients with hepatopancreatobiliary (HPB) cancer. Methods: Bone scanning was performed as part of a routine staging protocol in 402 consecutive patients with HPB cancer over a period of 5 years. Patients with positive bone scans underwent coned radiography, computed tomography with review on bone windows, or a bone biopsy. Bone scans were reviewed along with staging investigations, surgical and histological findings. Patients were followed for a minimum of 6 months. Results: There were 171 patients with colorectal liver metastases, 106 with suspected pancreatic cancer, 47 with hepatocellular cancer, 52 with gallbladder cancer or cholangiocarcinoma, and 26 with other types of HPB cancer. Bone scans were negative in 377 patients (93·8 per cent) and positive in 25 patients (6·2 per cent). Of the 25 positive scans, 16 were falsely positive as a result of degenerative bone disease. Of nine patients with a true-positive bone scan, four had locally irresectable disease and four distant metastases. In only one patient did the bone scan result alone influence the decision to resect the HPB cancer. Overall sensitivity was 100 per cent, specificity 95·9 per cent, positive predictive value 36·0 per cent and negative predictive value 100 per cent. Conclusion: Bone scanning should not be included in the routine staging protocol for HPB cancer. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Journal Article
TL;DR: In liver transplants patients with an end-to-end choledochostomy with a t-tube, endoscopic biliary stenting allows an early removal of the T tube, with few complications.
Abstract: AIM: Duct to duct anastomosis in orthotopic liver transplant (OLT) patients have been traditionally performed with a t-tube in place for 3 to 6 months. Following removal of the t-tube a high incidence of biliary leakage has been reported. METHODS: Prospective study to evaluate the role of endoscopic biliary stenting to facilitate early and uncomplicated t-tube removal. All patients with duct to duct biliary anastomosis who had a t-tube in situ, from January 1998 to December 2002 were included in this study. RESULTS: There were 29 patients eligible for the study. Eight patients were not included due to early death. A protocol t-tube cholangiogram was performed in all patients, (median 12 days; range 4-47 days) followed by an endoscopic stent insertion (median 37 days; range 20-55 days). The stent was removed later (median 84 days; range 45-133 days). All complications related to the procedure were noted. Stent insertion was successful in all cases. In 2 patients a second endoscopic retrograde cholangiopancreatography (ERCP) was necessary, either because of failure to cannulate the papilla or to reposition the stent. There was a patient who presented a biliary leak due to stent displacement requiring a laparotomy. There were two further biliary leaks, one of them in an asymptomatic patient, which were managed conservatively. In addition 1 patient developed a mild case of postERCP pancreatitis. CONCLUSIONS: In liver transplants patients with an end-to-end choledochostomy with a t-tube, endoscopic biliary stenting allows an early removal of the T tube, with few complications.