Effect of free radical scavenger (reduced glutathione) on PECAM expression in liver transplantation.
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Adenosine↗
Biomedical subjects
B R Davidson
Publications and source records attributed to B R Davidson.
In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver.
In vivo 31P magnetic resonance spectroscopy (MRS) provides direct biochemical information on hepatic metabolic processes. To assess in vivo changes in hepatic 31P MRS in liver transplant candidates, we studied 31 patients with cirrhosis of varying aetiology; 14 with compensated cirrhosis (Pugh's score < or = 7) and 17 with decompensated cirrhosis (Pugh's score > or = 8). Underlying cellular abnormalities were characterised using in vitro 31P MRS and electron microscopy. In vitro spectra were obtained from liver extracts, freeze-clamped at recipient hepatectomy, from all subjects. Electron microscopy of liver tissue was also performed in 17 cases. Relative to nucleotide triphosphates, elevations in phosphomonoesters and reductions in phosphodiesters were observed in vivo with worsening liver function. In vitro spectra showed elevated phosphoethanolamine and phosphocholine, and reduced glycerophosphorylethanolamine and glycerophosphorylcholine, mirroring the in vivo changes, but no distinction was noted between compensated and decompensated cirrhosis. With electron microscopy, functional decompensation was associated with reduced endoplasmic reticulum in parenchymal liver disease, but elevated levels in biliary cirrhosis. We conclude that in vivo spectral abnormalities in cirrhosis are consistent with alterations in phospholipid metabolism and quantity of endoplasmic reticulum. However, in individual patients the biopsy results do not always mirror in vivo findings.
Adult↗
Detection of small hepatocellular carcinomas in cirrhotic livers using iodised oil computed tomography.
BACKGROUND: The detection of hepatocellular cancers (HCC) is a major role of preoperative imaging in patients with end stage liver disease being considered for orthotopic liver transplantation (OLT). AIMS: To assess the sensitivity of iodised oil computed tomography (IOCT). PATIENTS AND METHODS: A prospective evaluation in 50 consecutive patients undergoing OLT included ultrasound scan, contrast enhanced CT, angiography (with intra-arterial injection of iodised oil), and a second CT (IOCT) 10 days later. Following transplantation the explant liver was serially sectioned for pathological evaluation. Soft tissue radiographs of the liver slices were used to match histological lesions with CT findings. RESULTS: Eleven patients were excluded due to protocol violations. Of the remaining 39, histological evaluation revealed no cancers in 33 explant livers, in keeping with negative preoperative imaging. Six explant livers contained 55 HCCs, 84% of which were less than 1 cm in diameter. Pretransplant IOCT detected 3/6 patients with cancer (50%) but only 7% of cancerous lesions. Ultrasound, contrast CT, and angiography each detected 2/6 patients with cancer and 4% of cancerous lesions. CONCLUSION: IOCT is an insensitive method for the detection of small HCCs in livers with advanced cirrhosis but in this study was slightly superior to ultrasound, CT, and angiography.
Carcinoma, Hepatocellular↗
Peritoneal seeding of pancreatic head carcinoma following percutaneous transhepatic drainage and stenting.
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Cholangiopancreatography, Endoscopic Retrograde↗
Prospective study of hepatobiliary scintigraphy and endoscopic cholangiography for the detection of early biliary complications after orthotopic liver transplantation.
BACKGROUND: Biliary complications are a significant cause of morbidity and death after orthotopic liver transplantation (OLT). This study was a prospective evaluation of endoscopic retrograde cholangiography (ERC) and hepatobiliary scintigraphy (HBS), using 99mTc Mebrofenin, to detect early biliary complications following OLT. METHODS: One hundred consecutive patients who had OLT with a biliary duct-to-duct anastomosis were studied. Of these, 67 had both ERC and HBS performed within 30 days of OLT. Sensitivity, specificity and diagnostic accuracy of HBS in identifying biliary leak or stricture was calculated. RESULTS: Of the 67 cholangiographies performed 45 were normal. In 22 patients there was radiological evidence of a leak (n = 14) or stricture (n = 8) which required further intervention in nine and four patients respectively. The sensitivity and specificity of scintigraphy for the detection of biliary leak after transplantation was 50 and 79 per cent and for biliary stricture 62 and 64 per cent respectively. No patient with normal scintigraphy required biliary intervention. Only six of 14 patients with biliary leaks and two of 20 with strictures suggested by scintigraphy required intervention. If both ERC and HBS reported leak or stricture, the intervention rate was considerably higher at five of seven leaks and two of five strictures. CONCLUSION: This study suggests that scintigraphy is a useful screening test for biliary complications after OLT, ERC is only necessary if HBS is abnormal.
Adolescent↗
Liver resection.
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Carcinoma, Hepatocellular↗
Hepatic microcirculation during human orthotopic liver transplantation.
BACKGROUND: Laser Doppler flowmetry (LDF) can measure blood flow in the hepatic microcirculation. Adequate graft perfusion is essential to the outcome of organ transplantation and has not previously been measured during operation in liver transplant recipients. METHODS: LDF was carried out during operation in 22 human liver grafts after restoring portal vein and hepatic artery inflow. LDF readings were validated against liver blood flow with an electromagnetic flowmeter. Intraoperative haemodynamics and donor organ parameters known to influence graft function were correlated with LDF. RESULTS: There was a significant correlation (r = 0.96, P < 0.001) between hepatic perfusion determined with LDF and total liver blood flow measured by electromagnetic flowmetry. The perfusion measurements were reproducible with a coefficient of variation of 4 per cent. Mean(s.d.) hepatic perfusion increased significantly from baseline following venous reperfusion (17(6) versus 114(37) flux units, P < 0.001). Arterial revascularization resulted in a significant increase in mean(s.d.) perfusion (32(4)per cent, P = 0.02). There was a significant negative correlation between cold ischaemia time and graft perfusion (r = 0.48, P = 0.02; n = 22). CONCLUSION: LDF provides a reliable non-invasive method of monitoring liver graft blood flow perfusion during transplantation.
Constriction↗
Hepatic nucleotide triphosphate regeneration after hypothermic reperfusion in the pig model: an in vitro P-NMR study.
The aim of this study was to assess the possibility of regenerating nucleotide triphosphates (NTP) in the pig liver following its harvest and subsequent storage on ice. This study has used a pig model that allowed human donor liver retrieval techniques and methods of storage to be utilized. In vitro phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to evaluate the changes associated with phosphorus containing metabolites such as NTP, phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Po). During 4 hr storage NTP levels were reduced to undetectable levels but its regeneration was possible over a period of 2 hr of oxygenated hypothermic reperfusion. Resynthesized NTP reached values that were only 30% reduced from pre-harvest values. There was a corresponding reduction in Pi over the same period. Glycolytic intermediates, 3-phosphoglycerate and 2,3 diphosphoglycerate, both increased significantly during the period of storage and subsequently declined following hypothermic reperfusion. Cellular damage, indicated by the concentrations of glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE) was minimal during cold storage. However upon hypothermic reperfusion, concentrations of GPC and GPE reduced, indicating a degree of cellular damage caused by reperfusion. This study has shown for the first time that is possible to regenerate high energy phosphate nucleotides following a period of hypothermic reperfusion in a large, clinically related animal model. This technique warrants investigation clinically to improve the outcome of orthotopic liver transplantation. It also provides a method to study the effects of different preservation fluids and methods of storage and organ reperfusion.
2,3-Diphosphoglycerate↗
Strengths and weaknesses of laparoscopic and open mesh inguinal hernia repair: a randomized controlled experimental study.
There are no objective data available on the relative strengths of inguinal hernia repairs. The aim of this randomized controlled study was to measure th force required to disrupt laparoscopic and open mesh repairs in a porcine model. Eleven pigs had inguinal hernia repair following randomization to an open mesh group (n = 5) or a transabdominal preperitoneal laparoscopic group (n = 6). Four weeks after operation the pigs were killed and the pelvic girdles were mounted in a test jig on a mechanical testing machine. The applied disruption forces were measured and recorded. Mean(s.d.) force required to disrupt the normal inguinal canal (n = 11) was 68.6(30.1) N with no difference between groups. The open mesh repair required 110.3(41.4) N and the laparoscopic mesh 220.0(95.2) N. Both open and laparoscopic mesh repairs were stronger than the normal side (P < 0.03). The laparoscopic mesh repair was stronger than the open mesh repair (P = 0.04). This model provides a standardized method for mechanically testing inguinal hernia repairs in pigs. It confirms that both open and laparoscopic mesh hernia repairs are stronger than the non-herniated normal side at 4 weeks after operation. Laparoscopic mesh repair is stronger than open mesh repair. The weakest points of the repairs correlate well with those identified in clinical reports.
Animals↗
Duct-to-duct biliary reconstruction following liver transplantation for primary sclerosing cholangitis.
The biliary complications in patients undergoing biliary reconstruction by duct-to-duct (D-D) anastomosis or with a Roux-en-Y loop (RL) at the time of liver transplantation for primary sclerosing cholangitis (PSC, 16 D-D, 10RL) or primary biliary cirrhosis (PBC, 31 D-D, 1 RL) were reviewed and compared. Patients were followed up for a mean period of 32 months. Extrahepatic biliary strictures occurred in 18.7%, 10% and 9.7% of DD-PSC, RL-PSC and DD-PBC patients, respectively, leaks in 6.2%, 20% and 6.4% DD-PSC, RL-PSC and DD-PBC patients, respectively (P = NS). Four intrahepatic biliary abnormalities developed in the PSC group. Duct-to-duct anastomosis did not significantly increase the risk of stricture formation or bile leaks in PSC patients compared to PBC patients. We conclude that duct-to-duct biliary reconstruction following liver transplantation for PSC is satisfactory unless the distal common bile duct is strictured.
Adolescent↗
Human liver cancer cells and endothelial cells incorporate iodised oil.
Iodised oil (lipiodol) administered via the hepatic artery localises selectively in primary liver cell cancers (hepatocellular carcinomas or HCCs) for prolonged periods and has been used as a vehicle for cytotoxic agents. Despite clinical use, the mechanism of lipiodol retention by tumours has remained unclear, embolisation of oil droplets in the tumour vasculature being the prevailing hypothesis. We have investigated the role of tumour and endothelial cells in lipiodol retention. Human liver tumour (Hep G2) cells and human umbilical vein endothelial cells in culture were exposed to lipiodol. Light microscopy using selective silver impregnation stains and transmission electron microscopy revealed lipiodol incorporation by both cell types, probably by pinocytosis. This was not associated with cellular injury in terms of cell lysis, cell replication or radio-labelled leucine uptake. Histological analysis of 24 HCCs either surgically resected or discovered incidentally at liver transplantation (with prior arterial injection of lipiodol) revealed vesicles of lipiodol in the cytoplasm of tumour cells and endothelial cells lining tumour vessels. Thus, lipiodol is likely to deliver cytotoxic agents directly into tumour cells and endothelial cells, both in vitro and in vivo. This may also apply to other lipids and to other human tumours. These findings have significant therapeutic implications.
Carcinoma, Hepatocellular↗
Detection and widespread distribution of Chlamydia pneumoniae in the vascular system and its possible implications.
AIMS: To attempt to detect Chlamydia pneumoniae DNA in atheromatous vascular tissue. METHODS: A modification of an existing polymerase chain reaction (PCR) assay and immunofluorescence staining with a monoclonal antibody directed against C pneumoniae were used to detect C pneumoniae. Specimens from 32 patients undergoing abdominal aortic aneurysm repair were examined. Vascular tissue, ostensibly normal, from six liver transplant donors was also examined for comparison. Altogether, 43 vessels from these 38 subjects (age range 36-85 years) were examined. RESULTS: C pneumoniae was detected in 11 (44%) of 25 aortas, five (55%) of nine iliac arteries, two (40%) of five femoral arteries, and one of two iliac veins. Immunofluorescence staining supported positive PCR results in three of 12 cases in which it was used. Overall, C pneumoniae was detected in the arteries of 14 (44%) of the patients undergoing vascular surgery and three (50%) of the donors. CONCLUSIONS: This study is the first in the UK in which C pneumoniae organisms have been found in atherosclerotic vessels and the tendency for the organisms to be present most often in such vessels exhibiting chronic inflammatory changes suggests that a search for them in various forms of arteritis may also be rewarding.
Adult↗
Massive colonic haemorrhage from a solitary caecal varix.
A 51 year old lady with chronic active hepatitis presented with massive lower gastrointestinal tract bleeding. Angiography demonstrated a solitary varix in the caecum which was found at laparotomy to be entering the bowel wall at the site of adhesion from a previous appendicectomy. The portal pressure was found to be raised. A right hemicolectomy stopped the blood loss, but she subsequently died of liver failure. Solitary colonic varices associated with adhesions are extremely rare and their optimal management has not been established.
Appendectomy↗
Cirrhosis of the human liver: an in vitro 31P nuclear magnetic resonance study.
Human livers with histologically proven cirrhosis were assessed using in vitro 31P NMR spectroscopy. Spectra were compared with those from histologically normal livers and showed significant elevations in phosphoethanolamine (PE) and phosphocholine (PC) and significant reductions in glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC). There were no significant differences in spectra from livers with compensated and decompensated cirrhosis. These results help to characterise the alterations in membrane metabolism in cirrhosis of the liver.
Ethanolamines↗
Drain-site herniation of the appendix.
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Adult↗
An underlying mechanism for improved liver preservation with a combined histidine-lactobionate-raffinose flush solution.
In previous experimental liver transplant studies, it was possible to extend cold ischaemic time (CIT) by using a flush/storage solution combining histidine, lactobionate and raffinose (HLR). In this study, energy metabolism, glycolytic substrate (glucose) and anaerobic end-product (lactate) were examined in rat liver over 24 h of cold storage to determine the mechanism of action of the HLR solution. In livers subjected to simple flush and storage with the HLR solution, levels of ATP and ADP were considerably higher than livers stored with modified UW throughout 24 h of storage; at 4 h of storage, ATP and ADP levels were 1.1 and 3.1 mumol/g for HLR solution versus 0.18 and 0.81 mumol/g for UW solution. Total adenylate contents (TA = ATP + ADP + AMP) also remained 1-2 mumol/g higher in HLR-treated livers than those preserved in UW; TA values ranged from 3.8 to 5.7 mumol/g. Glucose increased to 20-35 mumol/g by 10-24 h of storage (similar to the UW group). Lactate rose to almost twice that in livers stored in UW; total lactate accumulation was approximately 10.0 mumol/g. This study demonstrated that the combined HLR solution is able to prolong the maximum 'safe' CIT by increasing anaerobic metabolism and consequently preserving liver energetics. The second part of the experiment examined the effect of continuous perfusion (with/without O2) over the 1st h of cold ischaemia. Under current methods of liver flushing and excision, the 1st h of cold storage may be the critical time of metabolic 'adjustment' since most of the pH and ATP changes occur during this period.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine↗
Assessment of pancreatic duct damage following trauma: is endoscopic retrograde cholangiopancreatography the gold standard?
A 12-year-old girl was admitted as an emergency with blunt pancreatic trauma. Computed tomography (CT) showed an intact pancreas. She failed conservative treatment. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated division of the pancreatic duct at the neck of pancreas. At laparotomy, however, there was complete necrosis of the pancreatic head. She recovered well following enteric drainage of the body of pancreas. CT and ERCP are considered the optimal imaging for pancreatic trauma but the findings may be misleading.
Child↗