Orthotopic liver transplantation is the most effective treatment for fulminant hepatic failure. As an alternative treatment, an efficient extracorporeal bioartificial liver should contain a large yield of functional hepatocytes with an immunoprotective barrier, for providing temporary adequate metabolic support to allow spontaneous liver regeneration or for acting as a bridge toward transplantation. Survival, proliferation, and functions of porcine hepatocytes were evaluated in primary cultures and after embedding in alginate beads, which were subsequently coated with a membrane made by a transacylation reaction between propylene glycol alginate and human serum albumin. Disruption of total pig livers by collagenase perfusion/recirculation allowed the obtention of up to 10(11) hepatocytes with a viability greater than 95%. Hepatocytes in conventional cultures or embedded in coated alginate beads survived for about 10 days, secreted proteins, particularly albumin, and maintained several phase I and II enzymatic activities, namely ethoxyresorufin-O-deethylase, oxidation of nifedipine to pyridine, phenacetin deethylation to paracetamol, glucuroconjugation of paracetamol, and N-acetylation of procainamide. Typical features of mitosis and [3H]thymidine incorporation indicated that porcine hepatocytes proliferated in both conventional cultures and alginate beads. The efficacy of the membrane surrounding alginate beads for protecting cells from immunoglobulins was tested by embedding HLA-typed human lymphocytes, which were subsequently incubated with specific anti-HLA immunoglobulin G and complement. These data show that large yields of porcine hepatocytes that are embedded in coated alginate beads remain functional and are isolated from large molecular weight molecules, such as immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver, containing xenogeneic hepatocytes, to treat acute liver disease in humans.
A dose of 3 mg.kg-1 of ropivacaine given as a single ilioinguinal/iliohypogastric nerve block in 1-12-year-old children provides satisfactory postoperative pain relief, and is well tolerated.
The ischemia-induced model of acute hepatic failure in pigs is reproducible and provides measurable clinical and biological features. A bioartificial liver containing alginate bead-entrapped hepatocytes improves the signs of encephalopathy in pigs with ischemia-induced acute hepatic failure, suggesting that the bioartificial liver can clear out toxic compounds that are released from necrotic livers.
After intermediate duration of anaesthesia administered to children for up to 90 min, isoflurane and sevoflurane allow recovery after approximatively the same lapse of time.
The goal of this double-blind prospective study was to compare the effect of a single injection versus multiple fractionated doses on the onset time and quality of motor and sensory block, obtained in 70 children anaesthetized with axillary block alone. The brachial plexus was identified with a peripheral nerve stimulator, and blocked with 0.5 ml.kg-1 of 1.5% lignocaine with adrenaline. In Group S (single injection), the total volume was injected after location of one nerve. In Group M (multiple fractionated doses), two nerves were located, including necessarily one nerve implicated in the surgical territory. Motor and sensory blocks were assessed according to Lanz's scale before surgery by a blinded observer. A block was considered complete if there was no feeling in at least three nerve territories at 30 min. No difference was found between groups for motor and sensory block quality. However the onset time of the block was faster after multiple fractionated doses (Group M, 25+/-7 min vs Group S, 29+/-4 min) and was faster in younger children (5-9 years: M=23+/-7 min vs S=28+/-5 min, 10-15 years: no difference). There was a significant difference in the quality of the sensory blockade of the musculocutaneous nerve: 18 versus 8 complete blocks, 10 versus 14 incomplete blocks, respectively for Group M versus Group S. No adverse effect was observed and analgesia was prolonged for more than 4 h. We can conclude that, unlike adults, fractionated doses in chilren bring no benefit to the quality of sensory and motor block. Selective block of the musculocutaneous nerve is recommended when a surgical procedure takes place in this territory.
The need for an alternative treatment to orthotopic liver transplantation for acute liver failure is a major issue, and systems capable of temporarily providing liver functions are being actively tested. Liver assist devices based on detoxication by dialysis or hemoperfusion through various membranes or cartridges proved to be inefficient because of their lack of metabolic function. An extracorporeal hybrid bioartificial liver might be an appropriate treatment, since it can provide liver-specific functions, maintain the patient alive, and allow spontaneous recovery of the patient's own liver or act as a bridge toward liver transplantation. Many devices have been proposed, including flat culture substrates, hollow-fiber bioreactors, or microcarriers, using xenogenic hepatocytes or hepatoma cell lines. Various drawbacks of these devices led us to attempt to develop a reliable extracorporeal bioartificial liver based on alginate bead-entrapped hepatocytes. This system was used successfully for the correction of the Gunn rat genetic defect, which results in lack of bilirubin conjugation. The development of this system for clinical purposes requires large yields of functional hepatocytes. We have isolated normal porcine hepatocytes by collagenase perfusion of the liver. Cells were immobilized in membrane-coated alginate gel beads, which were subsequently inoculated into a bioreactor. Porcine hepatocytes expressed liver-specific functions at high levels, particularly protein neosynthesis and enzymatic activities involved in detoxication and biotransformation processes. In addition, hepatocytes entrapped in coated alginate beads were isolated from immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver in human beings.
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