Showing papers by "Brian R. Davidson published in 2006"
TL;DR: The effect of brief remote ischaemia to the limb in reducing early liver warm IRI is determined.
Abstract: Background: Direct ischaemic preconditioning of the liver reduces ischaemia–reperfusion injury (IRI). Remote ischaemic preconditioning (RIPC) of a limb has been shown to reduce IRI to the heart. This study determined the effect of brief remote ischaemia to the limb in reducing early liver warm IRI. Methods: Twenty-eight male rabbits were allocated into four groups: sham operated, RIPC alone, IRI alone and RIPC + IRI. RIPC was induced in the leg with a tourniquet, before liver IRI, by three alternate cycles of 10 min ischaemia followed by 10 min reperfusion. Liver IRI was produced by total inflow occlusion for 25 min. Markers of liver injury, and systemic and hepatic haemodynamics were measured for 2 h after reperfusion. Results: At 2 h, IRI alone was associated with increased serum levels of aminotransferases, and reduced mean arterial blood pressure, hepatic blood flow and peripheral oxygen saturation. There was significant improvement in these variables in animals that had RIPC before liver IRI and hepatic venous nitrate/nitrite levels were also significantly greater. Conclusion: In this experimental model RIPC appeared to reduce liver IRI.
116 citations
TL;DR: In a cohort with a short waiting list time, only the largest nodule diameter, especially in the explant, predicted recurrence after LT independently of the number of nodules.
Abstract: Background.Recurrenceofhepatocellularcarcinoma(HCC)afterlivertransplantation(LT)remainsamajorcauseof post-LT death. Methods. To assess which preoperative and postoperative variables were related to recurrence of HCC after LT in patients with cirrhosis and HCC, we evaluated 96 patients with cirrhosis (74 with known HCC and 22 with incidental HCC) who survived more than 1 month after LT. Results. The median waiting list time was 36 days (range 1–370 days), and the median interval from detection to transplant was 180 days (range 14–1460 days). The size of largest nodule on imaging was strongly associated with recurrence (odds ratio 1.03; 95% confidence interval 0.99–1.06; P0.064) when transplantation was performed for knownHCC.Amongpostoperativevariables,onlythelargestnodulediameter(independentlyofthenumberofsmaller nodules)wasmultivariatelyassociatedwithrecurrence(oddsratio1.05;95%confidenceinterval1.01–1.08;P0.005). The best predictive cutoff was 35 mm in diameter, based on a receiver operating curve with 1-, 3-, and 5-year recurrence-free survival of 90%, 73%, and 49%, respectively, for patients with a nodule 35 mm in diameter or more compared with 96%, 93%, and 89% (P0.0005), respectively, for patients with smaller nodules. Conclusions. In our cohort with a short waiting list time, only the largest nodule diameter, especially in the explant, predicted recurrence after LT independently of the number of nodules. New proposals for increasing the diameter of the largest nodule as a selection criteria for LT do not agree with our data, which on the contrary indicate the optimal nodule diameter should be 35 mm or less.
75 citations
TL;DR: Tumour markers and CT should be used in combination in the follow-up of patients with resected colorectal liver metatases, including patients whose markers are normal at the time of initial liver resection.
Abstract: The aim of the study was to prospectively evaluate an intensive follow-up programme using serial tumour marker estimations and contrast-enhanced computed tomography (CT) of the chest and abdomen in patients undergoing potentially curative resection of colorectal liver metastases. Seventy-six consecutive patients having undergone potentially curative resections of colorectal liver metastases in a single unit were followed up with a protocol of 3 monthly carcinoembryonic antigen and carbohydrate antigen 19-9 estimations and contrast-enhanced spiral CT of the chest, abdomen and pelvis for the first 2 years following surgery and 6 monthly thereafter. The median period of follow-up was 24 months (range 18-60). Recurrent tumour was classed as early if within 6 months of liver resection. Thirty-seven of the 76 patients (49%) developed recurrence on follow-up. Nineteen recurrences were in the liver alone (51%), 16 liver and extrahepatic (43%) and two extrahepatic alone (6%). Of the 19 patients with isolated liver recurrence, eight developed within 6 months of liver resection none of which were resectable. Of the 11 recurrences after 6 months, five (45%) were resectable. Of the 37 recurrences, CT indicated recurrence despite normal tumour markers in 19 patients. Tumour markers suggested recurrence before imaging in 12 and concurrently with imaging in 6. In the 12 patients who presented with elevated tumour markers before imaging, there was a median lag period of 3 months (range 1-21) in recurrence being detected on further serial imaging. Seventeen patients who developed recurrence had normal tumour markers before initial resection of their liver metastases. Of these 17, 10 (58%) had an elevation of tumour markers associated with recurrence. Over a median follow-up of 2 years following liver resection, the use of CT or tumour markers alone would have failed to demonstrate early recurrence in 12 and 18 patients respectively. A combination of tumour markers and CT detected significantly more (P < 0.05) recurrence than either modality alone. Tumour markers and CT should be used in combination in the follow-up of patients with resected colorectal liver metatases, including patients whose markers are normal at the time of initial liver resection.
44 citations
TL;DR: In this paper, the authors present the mechanisms by which thiols act as antioxidants and signalling molecules and the experimental and clinical evidence regarding their role in liver I/R injury with a particular emphasis on liver reperfusion.
Abstract: Thiol-containing compounds have an essential role in many biochemical reactions due to their ability to be easily oxidised and then quickly regenerated. Main representatives are glutathione, lipoic acid and thioredoxin which are synthesised de novo in mammalian cells. N-acetylcysteine and Bucillamine are synthetic thiols which have been administered in experimental and clinical studies for treatment of conditions associated with oxidative stress. Ischemia and reperfusion (I/R) injury is characterised by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. I/R occurs in a variety of clinical settings such as liver resection, organ transplantation, haemorrhagic shock with fluid resuscitation, heart surgery, myocardial infarction followed by reperfusion and laparoscopic surgery. In these circumstances, the administration of antioxidant agents such as thiols, could provide protection from the harmful effects of I/R injury. However, the ability of thiol compounds to reduce free radicals is associated with the formation of thiyl radicals and the rate and efficiency of removal of thiyl radicals has a critical effect on antioxidant or prooxidant actions of thiols in the cells. The aim of this review is to present the mechanisms by which thiols act as antioxidants and signalling molecules and the experimental and clinical evidence regarding their role in I/R injury with a particular emphasis on liver I/R. The current evidence suggests that thiols ameliorate I/R injury and that their clinical significance should be further evaluated in large scale randomised clinical trials.
39 citations
TL;DR: A poor preoperative clinical status in conjunction with a suboptimal graft was associated with PSIC after OLT, and acute liver failure, older age, and higher levels of serum sodium and serum potassium were all associated with a reduced likelihood of developing PSIC in the first month.
33 citations
TL;DR: Pre-resection chemotherapy does not impair the function or culture integrity of hepatocytes isolated at the time of liver resection and phase II enzymes was not adversely affected by pre-operative chemotherapy.
30 citations
TL;DR: Glycine is currently being used experimentally, in human liver transplant recipients and has been shown to be beneficial in animal models of ischemia-reperfusion injury (IRI) in liver and several other organs, with special reference to the liver.
Abstract: Glycine is a non-essential amino acid which is cheap, easily available and relatively non-toxic. It is composed of a single carbon attached to an amino and a carboxyl group, with a molecular weight of 75. It is involved in the production of bile, nucleic acids, porphyrins and creatine phosphate. It is part of the normal human diet and is used clinically, as an irrigant solution in urological and gynaecological procedures. Glycine has broad spectrum anti-inflammatory, cytoprotective and immunomodulatory properties whose therapeutic role has largely been un-investigated. Since the demonstration of its cytoprotective effect on hypoxic cultured renal tubule cells, further research has established its mechanism of anti-inflammatory action, which depends on stimulation of glycine sensitive chloride channel receptors on the cell membrane. The mechanism of non-specific cytoprotective effect which is present even in chloride and calcium free media is not clear. However glycine is currently being used experimentally, in human liver transplant recipients and has been shown to be beneficial in animal models of ischemia-reperfusion injury (IRI) in liver and several other organs. This review addresses the properties of glycine, its mechanism of action and its role in modulating IRI with special reference to the liver, with the aim of stimulating translational research into the potential role of glycine as a pharmaceutical agent.
30 citations
TL;DR: It is found that large amounts of nitric oxide are generated during the late phase of liver I/R injury and that the beneficial effects of N-acetylcysteine are associated with reduced levels of nitrous oxide, which is a good example of a common pathogenesis.
2 citations