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K Boudjema

Publications and source records attributed to K Boudjema.

At least 37 records · Page 2Linked to original sources
PubMed1998

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure. The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation. Sixty patients with chronic end-stage liver disease were included in a prospective randomized placebo-controlled study. NAC or the same volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Postoperative graft function was assessed by measurements of aminotransferases, prothrombin time, and monoethylglycinexylidide test over the 3 first postoperative days. Patient demographics were similar before the infusion of NAC or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen extraction ratio, and lactates were not different throughout the procedure. One hour after the revascularization of the hepatic artery, the oxygen extraction ratio by the liver was similar (17% +/- 7.6% v 17% +/- 6.2%) in both groups. Postoperative graft function was comparable within the 3 first postoperative days. This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease.

Acetylcysteine↗
PubMed1998

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Animals↗
PubMed1998

Efficacy of preconditioning with N-acetylcysteine against reperfusion injury after prolonged cold ischaemia in rats liver in which glutathione had been reduced by buthionine sulphoximine.

OBJECTIVE: To investigate the ability of N-acetylcysteine (NAC) to prevent cold ischaemic-reperfusion injury and improve hepatic integrity in a glutathione-depleted condition. DESIGN: Open laboratory study. SETTING: University hospitals, Japan and France. MATERIALS: 40 male Wistar rats. INTERVENTIONS: To produce a glutathione-depleted liver, buthionine sulphoximine (BSO) was injected intraperitoneally 2 hours before either NAC or 5% dextrose was infused 15 minutes before the liver was harvested. We used an isolated perfused rat liver model that had undergone prolonged hypothermic ischaemia, cold-storage for 48 hours and reperfusion for 120 minutes. MAIN OUTCOME MEASURES: Concentrations of hepatic enzymes released into samples of perfusate, concentration of adenosine triphosphate in liver tissue, concentrations of reduced and oxidized glutathione in perfusate, and bile production. RESULTS: The concentrations of the hepatocellular enzymes and oxidised glutathione in the perfusate samples were significantly reduced in the NAC group compared with the 5% dextrose group. Bile production improved significantly in the NAC group compared with the 5% dextrose group. The concentration of reduced glutathione in liver tissue was not increased by NAC. CONCLUSION: In a glutathione-depleted liver NAC prevented hepatic injury and improved liver integrity after a cold ischaemic-reperfusion injury, by acting not as a substrate for glutathione synthesis but as a direct free radical scavenger.

Acetylcysteine↗
PubMed1998

Augmentation of mitochondrial reduced glutathione by S-adenosyl-L-methionine administration in ischemia-reperfusion injury of the rat steatotic liver induced by choline-methionine-deficient diet.

We examined whether warm ischemia-reperfusion (I/R) damage of the rat steatotic liver can be reduced by administration of S-adenosyl-L-methionine (SAMe). We examined the effect of SAMe on the mitochondrial reduced-glutathione (GSH) pool. Sixty minutes of partial left lobar vascular clamping followed by 2 h of reperfusion were employed for a model of hepatic warm ischemia. Either 5% dextrose or SAMe was injected intraperitoneally 2 h before I/R in steatotic rats (S-D5% or S-SAMe group). Serum liver enzyme concentrations 2 h after reperfusion were significantly lower in the S-SAMe group than in the S-D5% group. The cytosolic and mitochondrial GSH concentrations after I/R were significantly higher in the S-SAMe group than in the S-D5% group (p < 0.05). The cytosolic and mitochondrial oxidized-glutathione/GSH ratios after I/R were significantly greater in the S-D5% group than in the S-SAMe group (p < 0.01). The adenosine triphosphate concentration was higher in the S-SAMe group than in the S-D5% group (p = 0.0515). These results show that hepatocellular and mitochondrial oxidative stress after I/R in the steatotic liver can be reduced by administration of SAMe. The results also show that mitochondrial function and hepatocellular integrity can be restored by administration of SAMe in steatotic rats.

Animals↗
PubMed1998

Metabolic capacities in cultured human hepatocytes obtained by a new isolating procedure from non-wedge small liver biopsies.

A new isolating procedure of human hepatocytes has been developed using two-step collagenase digestion by a non-perfusion procedure (NP) of non-wedge liver biopsies. 1. A yield of 2-7 x 10(6) hepatocytes/g liver, 52-95% viability and 13-75% attachment were obtained from liver biopsies weighing 6-60 g, comparable to that obtained when using the classical perfusion procedure (P) to isolate human hepatocytes from wedge liver samples of 50-150 g. 2. In culture, human hepatocytes obtained by NP remained attached to plastic for up to 5 days and displayed the usual morphological characteristics. Their metabolic capacities, assessed by liver-specific albumin and urea synthesis and by CYP-dependent and conjugation pathways, were equivalent to those of human hepatocytes obtained by P. In addition, they responded adequately to specific CYP inducers, demonstrating that they constitute a model in which human drug metabolism and toxicity studies can be performed.

Adult↗
PubMed1998

Possible involvement of Von Willebrand factor in pancreatic graft thrombosis after kidney-pancreas transplantation: a retrospective study.

Early postoperative graft thrombosis remains the second cause of failure in pancreas transplantation. Thus, the aim of this study was to compare retrospectively coagulation and fibrinolysis in type I diabetic recipients of simultaneous kidney pancreas transplants having or not experienced thrombosis of their pancreatic graft. From December 1990 to August 1996, 30 simultaneous kidney pancreas transplants were performed in 30 uremic type I diabetic patients. Acute thrombosis of the pancreatic graft was observed among 6 patients (group A), whereas 24 did not develop thrombosis (group B) although 4 died from other causes. The control groups were composed of kidney transplant (group C) or haemodialysed (group D) non-diabetic patients, type I diabetics with HbA1C < 8% (group E) or > or = 8% (group F) who were not in end-stage renal failure and kidney transplant type I diabetic patients (group G). Beginning at least 6 months after transplantation, we analysed hemostatic factors (fibrinogen, thrombin, and prothrombin times), coagulation inhibitors (proteins C and S), fibrinolysis (plasminogen activator inhibitor) and endothelial cell abnormalities (Von Willebrand factor: VWf). Micro and macrovascular complications were evaluated on a score ranging from 0 to 12. Hemostatic factors, coagulation inhibitors and fibrinolysis were similar in groups A and B whereas VWf differed significantly in group A (3.49 +/- 0.93 IU/ml) as compared to group B (2.04 +/- 0.92 IU/ml) (p < 0.05). VWf was also significantly increased in group A relative to the control groups C, D, E, F, and G. The score of vascular complications was increased in groups A and B and significantly higher in group A (9 +/- 0.81 vs. 6.07 +/- 1.75) (p < 0.01), while a correlation (r = 0.812, p > 0.05) was observed between VWf levels and the severity of vascular complications. These results point out the possible involvement of VWf in the pathogenesis of pancreatic vein thrombosis in kidney-pancreas transplantation.

Adult↗
PubMed1998

[Treatments for hepatocellular carcinoma in cirrhosis : practical aspects].

Many treatments are able to eradicate or slow the progression of hepatocellular carcinoma in cirrhosis. All are described in this issue of Annales de Chirurgie. These various alternative mean that treatment can be adapted to different clinical situations determined by the patient's general state, the size of the liver tumour, its extrahepatic dissemination and the functional quality of the underlying liver parenchyma. Liver hepatic transplantation, offers a good chance of cure, provided it is reserved for patients in good general condition with a small hepatocellular carcinoma confined to the liver. This situation is increasingly frequent.

Carcinoma, Hepatocellular↗
PubMed1997

Long-term survival following resection of colorectal hepatic metastases. Association Française de Chirurgie.

AIM: The aim of this study was to analyse characteristics of patients who survived more than 5 years after liver resection of colorectal metastases. METHODS: A multicentre retrospective study collected 1818 patients who underwent curative resection of hepatic metastases between 1959 and 1991. Among the 747 patients operated on before 1987, 102 survived longer than 5 years, and were compared with patients who survived less than 5 years. RESULTS: Three risk factors proved independently significant in multivariate analysis between the two groups: serosa infiltration (P = 0.003), involvement of peritumoral lymph nodes around the primary colorectal tumour (P = 0.04), and a liver resection margin of less than 1 cm (P = 0.02). There was no significant difference for other parameters studied (location of primary tumour, location, number and size of metastases, type of resection). A trend towards a shorter survival of patients with increased carcinoembryonic antigen serum level was observed. CONCLUSION: Resection of colorectal hepatic metastases can provide long-term survival even in patients with poor prognostic factors. It seems justified to undertake resection of colorectal liver metastases whenever it may be performed safely as a curative treatment.

Carcinoembryonic Antigen↗
PubMed1997

Orthotopic liver transplantation with preservation of portocaval flow compared with venovenous bypass.

Conventional liver transplantation requires cross-clamping of the hepatic pedicle and inferior vena cava, leading to severe hemodynamic and metabolic disturbances, usually attenuated by the use of venovenous bypass. A more recent surgical technique, piggyback with temporary portocaval shunting, preserves both caval and portal blood flows. The aim of this study was to compare the two methods prospectively. Forty-four patients with chronic liver disease were studied. Local anatomic conditions guided the surgeon to choose the easiest way to remove the native liver. Anesthetic management was standardized. Hemodynamic and metabolic changes were assessed by use of routine tests at specific periods. Graft function was evaluated by measurement of aminotransferases and monoethylglycinexylidide (MEGX) test 12, 24, 48, and 72 hours postoperatively. Conventional liver transplantation with venovenous bypass was performed in 26 patients, and the piggyback with temporary portocaval shunting was performed in 15 patients. ANOVA showed that cardiac output and systemic oxygen delivery were better maintained before revascularization in the piggyback group. Metabolic changes were comparable, and hyperfibrinolytic activity was detected in both groups. Graft function was comparable and satisfactory within the 3 first postoperative days. Piggyback with temporary portocaval shunting provided better intraoperative hemodynamics and tissue oxygenation than liver transplantation with venovenous bypass.

Adult↗
PubMed1997

Early assessment of transplanted liver function: lignocaine clearance test (MEGX).

The purpose of this study was to assess the value of lignocaine biotransformation into monoethylglycinexylidide (MEGX) and conventional liver function tests in the early post-operative period as an indicator of graft function and as a diagnostic tool for complications after hepatic transplantation. Monoethylglycinexylidide formation, plasma bilirubin, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), factor V index (FVI) and prothrombin time index (PTI) were measured in 71 patients undergoing 80 liver transplantations respectively at 12 (T1), 24 (T2), 48 (T3) and 72 h (T4) after liver graft revascularization. Patients were divided into two group according to the post-operative outcome. Patients with favourable outcome (n = 59) had significantly higher monoethylglycinexylidide synthesis, higher factor V index and prothrombin time index plasma concentrations, lower bilirubin, ASAT and ALAT plasma concentration (P < 0.0001 at T2 and T3) than those with complicated time course (n = 21). Monoethylglycinexylidide synthesis was the best discriminant of a favourable outcome, whereas bilirubin and ALAT concentrations were associated with complications (bilirubin for primary non function [PNF], ALAT for acute rejection). Thus, the combination of parameters at T2 was a very efficient predictor of primary non function, acute rejection and an uncomplicated time course.

Anesthetics, Local↗
PubMed1997

The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet.

Abundant fat in the liver has been implicated in poor outcome after liver transplantation or liver surgery, but the reasons for this association are still unclear. The aim of the present study was to examine mechanisms that may be involved in hepatic dysfunction after ischemia-reperfusion (I/R) of the steatotic rat liver. Steatosis was produced by a choline-methionine-deficient (CMDD) diet. In the first experiment, isolated perfused rat livers, subjected to 24-hour cold storage followed by 120-minute reperfusion, were used to investigate hypothermic I/R injury of the steatotic rat liver. In the second experiment, livers were subjected to 60-minute partial left lobar vascular clamping to allow study of normothermic I/R injury. In the first experiment, compared with normal nonsteatotic liver, steatotic livers showed significantly greater injury, as assessed by amounts of hepatic enzymes released into the perfusate, bile production, the concentrations of reduced glutathione (GSH) in the perfusate, as well as in the livers themselves, and electron microscopic findings of sinusoidal microcirculatory injury. The addition of N-acetylcysteine (NAC), a precursor of glutathione, to the liver before cold storage significantly improved these parameters in steatotic livers. The second experiment showed that, compared with nonsteatotic livers, steatotic livers had lower concentrations of GSH and impaired rates of bile production. There was also evidence of increased oxidative stress in polymorphonuclear leukocytes (PMNLs) in liver or peripheral blood of rats with fatty livers. An anti-rat intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody inhibited neutrophil infiltration into pericentral sinusoids and improved these parameters in the steatotic rats. We conclude that sinusoidal microcirculatory injury is involved in hypothermic I/R injury, that oxidative stress produced by PMNLs is involved in normothermic I/R injury, and that NAC and anti-rat ICAM-1 monoclonal antibody restore liver integrity in I/R injury.

Acetylcysteine↗
PubMed1997

[An original case of simultaneous cardiac, pancreatic and renal transplantation. Results over 6 years].

Combined transplantation is actually performed on specific and rare indications. We are presenting here the results of a combined heart-kidney and pancreatic graft. It was performed in a patient presenting an idiopathic cardiomyopathy in end-stage failure and a post-diabetic nephropathy on dialysis. Today, organs function is quite satisfactory with a 6 year follow-up. Only one isolated heart rejection episode was observed at the 15th post-operative day. The patient has recovered a full-time professional activity at one year. This successful graft was obtained by an "homogeneous multiorgan approach" during all the pre-peri and postoperative time.

Adult↗