Biomedical subjects
D Houssin
Publications and source records attributed to D Houssin.
[Pediatric liver transplantation and related live donor. Technical and ethical considerations].
With improved results of liver transplantation, the number of candidates is increasing. However the scarcity of suitable grafts from cadaveric donors remains a limitation. In spite of the use of full size or reduced size grafts or partial grafts from split livers, some children still die while waiting for liver transplantation. We describe a successful orthotopic liver transplantation in a 10 months old female using the left lateral lobe (segments II and III) from her 27 years old father. The child suffered from biliary atresia, her condition was deteriorating with intractable ascites and increasing jaundice. The father asked us to give a part of his own liver to his daughter. The concept of this innovative therapy had already been submitted to a research-ethics consultation which gave us favorable conclusions. After careful donor evaluation, the left lateral lobe was harvested on July 22, 1992, including the left hepatic artery, left portal vein and left hepatic vein; hepatic artery for segment IV, which arose from the right structures, was preserved, The graft was immediately transplanted orthotopically after recipient total hepatectomy with inferior vena cava preservation. Cold ischemia time was 1 hour and 45 minutes, revascularization of the graft was homogeneous from the very beginning and its early function was excellent. Thirteen days after the operation, the donor was discharged in good condition. The child was reoperated at day 9 for a small biliary leak originating from the cut surface of the liver. After resolution of an episode of rejection and an intra-abdominal abscess, the child was discharged in good health with normal liver function 1 month post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
[Single-stage resection of at least 6 liver segments in cases of liver tumors].
Seven partial liver resections of at least six hepatic segments (five extended left hepatectomies, also called left trisegmentectomies, and two subtotal hepatectomies) were performed for tumor (of malignant nature in 6 cases). Six of seven patients were admitted for liver transplantation and one for liver resection. These procedures were performed under total vascular exclusion of the liver in six cases (with a veno-venous bypass in two cases) and with the Pringle maneuver in one case. Postoperative liver function was satisfactory in six cases whereas one patient died of hepatic failure on the tenth postoperative day. There was one bile duct stricture at eight months, after extended left hepatectomy. Four patients survived more than one year, three with hepatic tumor recurrence and one with distant metastases. Two patients were still alive, one after fourteen months with tumor recurrence in the liver, the other after seventeen months. In selected cases, partial hepatic resection of more than six segments can be performed for very large tumors. In cases of malignant tumors, a short period of survival with good quality of life can be offered to these patients.
[Budd-Chiari's syndrome with caval membranous web treated by liver transplantation].
In this paper, the case of a 30 year-old Asiatic man with a Budd-Chiari syndrome secondary to a caval membranous web, associated with cirrhosis is presented. After unsuccessful percutaneous dilatation, liver transplantation associated with membranotomy treated the venous obstacle and ensured satisfactory recovery. Orthotopic liver transplantation is the most effective treatment in this setting.
[Evolution of delta bilirubin/conjugated bilirubins ratio in serum after live transplantation].
Serum delta-bilirubin measured in relationship to total bilirubin could be a liver function test in hepatobiliary diseases and even a marker of early rejection after liver transplantation. Delta-bilirubin bound to albumin constitutes with mono and diglucuroconjugates, conjugated bilirubins. We determined the delta-bilirubin/conjugated bilirubins ratio and studied its value in various complications in 16 liver recipients. The results were compared with alanine aminotransferase activity and prothrombin index. Hyperbilirubinemia and a delta-bilirubin/conjugated bilirubins ratio lower than 40% were observed initially. After 15 days, the delta-bilirubin/conjugated bilirubins ratio evolved differently according to the functional state of the graft, which allowed to distinguish three patient groups: in patients with good graft function, the ratio increased regularly to reach 65% or more on the 30th day; in patients with dysfunctional episodes, the ratio was always less than or equal to 40% and did not increase after the 15th day; in other patients, the ratio was lower than 40% and dropped suddenly before death. After liver transplantation, the delta-bilirubin/conjugated bilirubins ratio may be a simple liver function marker. Alone, however, it cannot be used to assess acute rejection.
[Resection of hepatocellular carcinomas. Analysis of prognostic factors of a multicenter series of 153 patients].
In order to identify the prognostic factors of the resection of hepatocellular carcinoma, the results of 153 resections performed between January 1984 and December 1988 in 18 French centers were analysed. Cirrhosis was present in 76% of the patients. Among the postoperative complications (61%), the most frequent were ascites (35.3%) and liver failure (19%). Operative mortality was 20%. One-, 3- and 5-year survival rates were 52.7, 30.1, and 17.9%, respectively. The survival rate was significantly higher in patients with a curative resection, Pugh's class A or with a tumor less than 3 centimeters in diameter. After curative resection, actuarial survival rates without recurrence were 65, 24.4, and 16.7% after, 1, 3, and 4 years respectively. In this case, the survival rate was significantly related to the number of resected nodules and the size of the tumor but not to the presence of a capsule surrounding the tumor.
Study of the target antigens of hyperacute xenogeneic rejection in discordant combinations.
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Relationship between human natural anti-A, anti-B alloantibodies and anti-pig xenoantibodies.
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Prolonged survival of guinea pig-to-rat heart xenografts using repeated low doses of cobra venom factor.
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OKT3 prophylaxis in liver transplant patients: a European and Australian multicenter, prospective controlled trial.
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Partial hepatic resection following liver transplantation.
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Study of the toxicity of various concentrations of 2-3-butanediol in the isolated perfused rat liver.
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[Superacute xenogenic rejection: attempted treatment with anti-idiotypic antibodies].
Heart xenotransplantation in the guinea-pig to rat model, a highly discordant combination, is invariably followed by a hyperacute rejection of the graft. Preformed IgMs were shown to be responsible for the destruction of the graft by stimulating the complement cascade. We tried to inhibit preformed antibodies, before transplantation, by inducing anti-idiotypic antibodies using autologous Fab' mu specific for guinea-pig endothelial cells. This treatment seems to exert a neutralizing effect on xenogeneic hyperimmunization, against guinea-pig endothelial cells but not against preformed anti-guinea-pig antibodies.
Lack of correction of acquired heparin cofactor II deficiency in patients with liver failure after successful orthotopic liver transplantation.
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Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse.
Cell-mediated immunity is impaired during cholestasis, and there is evidence that bile acids play a role in this immune defect. Ursodeoxycholic acid (UDCA), which corrects the immunological abnormalities observed in primary biliary cirrhosis, could counter the detrimental effects of the endogenous bile acids. Accordingly, we assessed the respective effects of cholestasis, chenodeoxycholic acid (CDCA), and UDCA, using mixed lymphocyte culture as a model of allogeneic immune response. CDCA induced a dose-dependent inhibition of the proliferative response (0-150 mumol/L). Mononuclear cells obtained from bile duct-ligated mice had a normal immunostimulatory effect, whereas responder cells obtained from such animals showed a profoundly impaired proliferative response, suggesting that responder T cels are the main target of the cholestasis-induced immune defect. Supplementation of cultures with exogenous interleukins partially compensated for the inhibitory effect of 25 mumol/L CDCA, but not for that of 50 mumol/L CDCA, suggesting that impaired secretion of interleukins is not the only factor involved in the effect of bile acids. In contrast to CDCA, UDCA had no inhibitory effect on the allogenic immune response at concentrations of up to 50 mumol/L.
Liver transplantation: the challenges of the 1990s.
An enormous increase in liver transplantation has been observed over the last decade since it now represents a suitable therapeutic option for patients with end-stage liver disease. The overall one-year survival rate is about 75% for adults and 85% for children, when fulminant hepatic failure and malignancies are excluded. Such improvements in both survival and quality of life are due to many concurrent factors: better timing and selection; development of the UW solution for liver preservation; improvement in operative management including surgical technique, veno-venous bypass and cell-saver; progress in intensive care management of immunosuppressed patients. Nevertheless, the increasing demand for livers is now confronting the transplant teams with organ shortage, for which the introduction of graft reduction, hepatic biparition and living-related donation will contribute to alleviate the scarcity of donors. As a consequence of the increasing number of long-term survivors, greater efforts are now being directed towards the long-term outcome after liver transplantation: disease recurrence, the need for permanent immunosuppression and the quality of rehabilitation will become the challenges of the 1990s before reaching the next step towards multiple organ transplantation.
The role of natural IgM in the hyperacute rejection of discordant heart xenografts.
The mechanism of xenograft hyperacute rejection in discordant species combinations remains controversial. The purpose of this work was to study the role of natural antibodies in the hyperacute rejection of guinea pig hearts transplanted into rats, a highly discordant combination. This study was conducted in vitro, ex vivo, and in vivo. The endothelial cells of the graft being the first targets damaged in the process of hyperacute rejection, the binding of rat natural antibodies to guinea pig endothelial cells was studied by immunofluorescence. The study was carried out in vitro on guinea pig endothelial cells in culture, and ex vivo on isolated guinea pig hearts perfused with either rat serum or immunoglobulins or immunoglobulin fragments bearing the antigen-binding site. In vitro and ex vivo, rat natural IgM were found to bind specifically to guinea pig endothelial cells, since IgM fragments bearing the antigen-binding site (Fab mu and Fab' mu) could be detected on these cells. IgM fragments were able to inhibit the fixation of native IgM molecules. In contrast, rat IgG only bound to endothelial cells through Fc portions. Thus rat natural IgM might play a role in hyperacute rejection by binding to the graft endothelial cells and triggering the complement cascade activation. In order to test the role of natural IgM in vivo, isolated guinea pig hearts were first perfused with rat Fab' mu, which inhibit the binding of IgM and are unable to activate the complement cascade. These hearts were then transplanted into Lewis rats. The rejection time of Fab' mu-perfused guinea pig hearts was prolonged compared with hearts perfused with buffer or IgG F(ab')2. Therefore, in the guinea pig to rat combination, preventing the binding of the recipient's natural IgM to the graft endothelium delays the hyperacute rejection. In addition, natural IgM are likely to play a greater role than natural IgG.
In vitro bronchial hyperresponsiveness after lung transplantation in the rat.
In this study, we examined the effect of unilateral lung transplantation on in vitro responses of bronchial smooth muscle to electrical field stimulation (EFS) and exogenous acetylcholine (ACh). In syngeneic Lewis rats, we compared the contractile responses of the left hilar transplanted bronchus with that of the nontransplanted right bronchus and the left and right bronchi from control and sham-operated animals. Atropine-sensitive bronchial contraction to EFS was greater on left transplanted than on right nontransplanted bronchi at all frequencies and voltages used. In control and sham-operated animals, contractile responses to EFS were identical on left and right sides and similar to the responses of the right nontransplanted bronchus of the lung transplant recipient. Concentration-response curves to exogenous ACh were similar on transplanted and all control bronchi. Intramural cholinergic nerve cell bodies reactive for acetylcholinesterase were present in the transplanted bronchus. We conclude that EFS-induced cholinergic contraction of rat bronchial smooth muscle is enhanced after lung transplantation. Enhancement is not a result of medication, inflammation, or rejection, absent from our syngeneic transplant, or of upregulation of muscarinic post-junctional receptors because the response to exogenous ACh was normal. Hence, an increased release of ACh from cholinergic nerve terminals may occur, due either to hyperexcitability of postganglionic parasympathetic nerves or to loss of inhibitory mechanism resulting from interruption of neural connections with the central nervous system.