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D Houssin

Publications and source records attributed to D Houssin.

At least 127 records · Page 7Linked to original sources
PubMed1994

Extrafascial hyper-reduction of the hepatic graft.

The technique and limits of graft reduction in orthotopic liver transplantation (OLT) are not well-defined, especially for small recipients. To reduce the hepatic graft to the left lateral segment (segments II and III), the authors have used an extrafascial hepatectomy without any dissection of the hepatic hilum. Among 165 pediatric OLT, 22 procedures using such hyper-reduced hepatic grafts were performed upon 21 children of median age 2.6 years between 1988 and 1992. These 22 hyper-reduced hepatic grafts were transplanted orthotopically with conservation of the inferior vena cava of the recipient. The three-year patient survival rate was 66 percent (80 and 50 percent for those patients undergoing elective and emergent procedures, respectively). The main postoperative complications were: primary graft nonfunction (n = 1), arterial complications (n = 2), portal vein thrombosis (n = 1), intra-abdominal bleeding (n = 2) and biliary complications (n = 2). This technique is useful in instances of a large size discrepancy between the donor and recipient. However, it does not increase per se the absolute number of hepatic grafts available for transplantation.

Adolescent↗
PubMed1994

Partial hepatic resection for ischemic graft damage after liver transplantation: a graft-saving option?

BACKGROUND: Intrahepatic biliary strictures or parenchymal infarcts may occur after liver transplantation as a complication of ischemic damage to the graft. In some selected cases the lesions appear to be confined to a part of the liver. We report our experience with partial graft resection in this setting. METHODS: From January 1984 to December 1991, 286 liver transplantations were performed in 257 recipients. Seven patients, three children and four adults, underwent partial hepatectomy 3 to 218 weeks after liver transplantation of a full-size graft. The clinical presentation included septic parenchymal infarcts (n = 4) and nonanastomotic biliary strictures (n = 3) complicating (n = 5) artery thrombosis or not (n = 2). There were four left hepatectomies, two left lobectomies, and one right hepatectomy. In four instances partial hepatectomy was performed after failed attempt at biliary reconstruction (n = 2) or arterial revascularization (n = 2). Partial graft resection was performed extrafascially without Pringle's maneuver and mobilization of the remnant liver to preserve its vascularization. RESULTS: No surgical complications occurred, and none of the patients experienced acute hepatic failure during the postoperative period. All patients were discharged home 10 to 96 days (median, 23 days) after liver resection. Two patients had recurrent ischemic cholangitis. One patient underwent successful regrafting for recurrent Budd-Chiari syndrome; one patient died of tumor recurrence. Six patients were alive with a follow-up ranging from 12 to 45 months. CONCLUSIONS: These results suggest that partial graft resection is a safe and graft-saving option after liver transplantation in selected patients with localized ischemic damage of the graft.

Adult↗
PubMed1994

Augmentation of portal blood flow improves function of human cirrhotic liver.

In cirrhotic livers, the intrahepatic resistance is increased and drug elimination and portal transhepatic flow are decreased. The aim of our work was to study the effect of a twofold increase in portal blood flow during 2 hr on the hemodynamic parameters, drug elimination and hepatic viability in eight isolated perfused human cirrhotic livers. Using an oxygenated recirculating system with independent arterial and portal flows, we perfused livers with Kreb's buffer bicarbonate solution, bovine serum albumin (20 gm.L-1) and human red blood cells (hematocrit 20%). The flow was maintained at a basal level of 0.713 +/- 0.19 L/min for 1 hr and then increased and maintained for 2 hr at twice the basal flow. Portal pressure-portal flow curve slopes were linear (27.04 +/- 21.06 mm Hg.L-1 x min; range = 6.43 to 60.8) and correlated with intrahepatic resistance during the basal-flow period (r = 0.87, p < 0.01). Parameters registered during the basal- and high-flow periods were compared by use of Student's t test: portal pressure increased from 23.5 +/- 7 to 37.3 +/- 16.7 mm Hg (p < 0.05); arterial pressure increased from 80.3 +/- 19 to 103.5 +/- 26 mm Hg (p < 0.005); hepatic artery flow resistance increased 31.9% (from 690.1 +/- 218 to 899.4 +/- 269 mm Hg.L-1 x min; p < 0.005); indocyanine green clearance increased by 28.2% (from 86.0 +/- 58.3 to 109.2 +/- 74.8 ml.min-1 x kg liver-1; p < 0.04). No significant differences were observed in enzyme release, biliary flow (n = 5) and oxygen consumption. Histological examinations demonstrated sinusoidal dilatations in six of eight cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Regression of established macroscopic liver metastases after in situ transduction of a suicide gene.

The herpes simplex virus type 1 thymidine kinase (HSV1-TK) converts nontoxic nucleoside analogs such as ganciclovir into phosphorylated compounds that act as chain terminators and specifically kill dividing cells. This property could be exploited for the treatment of tumors that are made up of rapidly dividing cells invading a nonproliferating tissue. For this purpose, specific expression of the suicide gene into dividing tumor cells can be further targeted by using retroviral-mediated gene transfer. We investigated whether the direct intratumoral transduction of a suicide gene might induce the elimination of malignant solid tumors. Rats with established macroscopic liver metastases were given an intratumoral injection of packaging cells producing either HSV1-TK- or lacZ-expressing recombinant retroviral particles. All rats were next treated with ganciclovir. A dramatic regression of the tumor volume was observed in the HSV1-TK-treated animals. The residual tumors were mostly made up of a massive fibrotic reaction, with the mean cancer cell mass being reduced approximately 60-fold compared to controls. In some animals, the residual tumors were devoid of cancer cells. This treatment efficacy appears in part due to a "bystander effect" in which phosphorylated ganciclovir could be transferred from cell to cell and to an active local immune reaction evidenced by massive infiltration of the tumors by macrophages and both CD4+ and CD8+ lymphocytes. This efficient therapeutic approach might be an ultimate treatment for disseminated liver metastases in humans and could also be applied to treatment of a large variety of solid tumors.

Animals↗
PubMed1993

[Hepatocellular carcinoma on cirrhosis. Resection or transplantation].

In cirrhotic patients who develop hepatocellular carcinoma the only hope of prolonged survival is surgery. A review of the literature was carried out in order to determine precisely the indications for surgical treatment and the choice between liver resection and transplantation. With a low post-operative mortality rate, the survival rate 3 years after liver resection is almost 50 percent. The most favourable cases are tumours smaller than 5 cm, uninodular and well encapsulated, but intrahepatic recurrences are almost constant at 5 years. Liver transplantation does not improve the long-term survival. Its best indications are the same as those of liver resection. Because of graft scarcity and rapid tumoral progress in patients on the waiting list, liver transplantation must be reserved for unstable cirrhosis. In the other situations, liver resection must be considered in priority.

Carcinoma, Hepatocellular↗
PubMed1993

Controlled liver splitting for transplantation in two recipients: technique, results and perspectives.

A technique of controlled liver splitting for transplantation in two recipients is proposed, based on a full anatomical assessment of the graft including arteriography and cholangiography on the back-table. Using eight livers, 16 patients received a graft: right liver (eight patients), left lobe (four) or left liver (four). Twelve patients required urgent or very urgent transplantation. Anatomical assessment of the graft demonstrated a portal bifurcation in all cases, a common trunk of the left and middle hepatic veins in five, a right biliary duplication in three and duplication of the left branch of the middle hepatic artery in one. After revascularization of the graft, bleeding was greater in patients with a right graft, particularly if the middle hepatic vein had been ligated. The main postoperative complications were hepatic artery thrombosis (four cases), biliary complications (four), portal vein thrombosis (two), haematoma (two) and abscess (two). No primary non-function of the graft was observed. The postoperative survival rate was 75 per cent. The four patients in whom transplantation was not considered urgent are still alive. The immediate survival rate of the grafts was 69 per cent. These results compare favourably with those in the literature. In spite of the technical, logistical and ethical problems raised by this technique, the results suggest that controlled liver splitting for transplantation in two recipients may in the future significantly improve the feasibility of liver transplantation.

Adolescent↗
PubMed1993

Cytochromes P-450 in human hepatocyte plasma membrane: recognition by several autoantibodies.

BACKGROUND: Anti-cytochrome P-450 autoantibodies are present in several forms of autoimmune hepatitis. The possibility that cytochromes P-450 are present in the plasma membrane of human hepatocytes was examined. METHODS: (1) Plasma membranes with microsomal contamination < 1%, as judged from the activities of glucose-6-phosphatase and NADH-cytochrome c reductase, were prepared. (2) After exposure of uncut, fixed hepatocytes to antibodies, immunofluorescence and immunoperoxidase studies were performed. RESULTS: (1) The specific content of cytochrome P-450 in plasma membrane was 9% of that in microsomes. Plasma membranes showed NADPH-cytochrome c reductase and mono-oxygenase activities; immunoblots showed the presence of cytochromes P-450 1A2, 2C, 2D6, 2E1, and 3A4; cytochromes P-450 1A2, 2D6, and 2C were also recognized by anti-liver microsome and anti-liver/kidney microsome type 1 and type 2 autoantibodies, respectively. (2) Immunofluorescence and immunoperoxidase labeling of the plasma membrane was observed with the three auto-antibodies and with anti-cytochrome P-450 1A2, 2C, 2E1, or 3A4. CONCLUSIONS: It is concluded that cytochromes P-450 are present and functional in the plasma membrane of human hepatocytes and that anti-cytochrome P-450 autoantibodies recognize epitopes expressed on the outer surface.

Autoantibodies↗
PubMed1993

Augmented portal flow in the isolated perfused cirrhotic rat liver: a haemodynamic and morphological study.

1. Isolated perfused cirrhotic rat livers were used to study the effects of an increase in portal perfusion pressure and portal flow on the microcirculation and viability of the hepatocytes. Cirrhosis was induced by CCl4, and Krebs-Ringer bicarbonate buffer solution was used as the perfusate. Portal perfusion pressures were increased incrementally between 25 and 45 cm H2O. The viability of the livers was assessed and histological studies were performed under light and electron microscopy. 2. An increase in portal perfusion pressure induced an increase in hepatic flow in all the experiments (P < 0.05). Hepatic flow was 2.52 ml min-1g-1 of liver (SD 0.67; n = 5) at basal pressure compared with 4.19 ml min-1g-1 of liver (SD 0.93; n = 5) and 5.91 ml min-1g-1 of liver (SD 0.63; n = 5) when pressures were raised to 25 and 45 cmH2O, respectively. Portal perfusion pressure and hepatic flow were correlated (r = 0.908; P < 0.001; n = 30). 3. Production of the enzyme alanine aminotransferase (EC 2.6.1.2) increased significantly from 5.69i.u. ml-1min g-1 of liver (SD 3.62; n = 5) to 23.53i.u. ml-1min g-1 of liver (SD 16.7; n = 5) when the perfusion pressure was raised from baseline to 30 cmH2O. In all the cases the porto-caval gradient of enzyme production was within the normal range. No correlation existed between the release of enzyme and portal perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

In situ retrovirus-mediated gene transfer into dog liver.

Dogs were used as a large animal model to assess the feasibility and safety of a surgical method for gene transfer into hepatocytes in vivo. This method, which we previously described in rats, consists of a partial hepatectomy aimed at inducing liver regeneration, followed by the selective in situ perfusion of the remnant liver parenchyma with a retrovirus preparation. Isolation of the liver was obtained by clamping the afferent and efferent blood vessels, a procedure that prevented retroviral vector dissemination and genetic modification of nonhepatic organs. A helper-free retrovirus vector encoding beta-galactosidase targeted to the nucleus was perfused in the liver of 5 golden retriever dogs. Volumes up to 1,650 ml of fresh or concentrated vector stocks were perfused and the procedure was well tolerated. Gene transfer, observed in 3 of 5 treated dogs when documented on liver biopsy fragments obtained at day 4, involved 0.15-0.6% hepatocytes and persisted at equivalent levels at the time of sacrifice, 6 weeks later. No propagation of the vector to other tissues was detected. These observations suggest that the selective perfusion of the regenerating liver might be considered an alternative to liver transplantation for the treatment of certain severe genetic liver disorders, or for the delivery of a therapeutic protein into the serum.

Animals↗
PubMed1993

Target antigens of hyperacute xenogeneic rejection in the rat to guinea pig to rat discordant combinations.

The increasing shortage in allografts has led to a renewed interest in xenogeneic transplantation. Discordant combinations are characterized by hyperacute rejection partly due to the presence of natural antixenogeneic antibodies in the recipient. The aim of this work was to characterize the target antigens, using 2 discordant models. In the rat into guinea pig model, analysis of organ homogenates by immunoblotting revealed numerous bands. Some of these bands were organ specific, whereas others, namely in the 55-kDa region, were detected in liver, heart, lung, and kidney. Using membrane extracts of liver cells or of aortic endothelial cells, only bands of 55 kDa were revealed. No band could be seen using extracts of isolated hepatocytes. Two bands of 55 kDa disappeared after preabsorption of guinea pig sera on the various rat tissue homogenates, suggesting that they represent xenoantigens common to these tissues. In order to investigate the in vivo relevance of these 55-kDa antigens, isolated rat livers were perfused with decomplemented guinea pig sera. Eluates revealed one single print of 55 kDa on rat tissue homogenates. Finally, preincubation of rat mononuclear cells with various xenogeneic sera did not inhibit the binding of mAb specific for rat class I or class II MHC antigens, suggesting that the latter are not recognized by natural xenoantibodies. In the guinea pig to rat model, the antigens detected had a molecular mass ranging from 95 to 110 kDa. Absorption and perfusion experiments also showed that these antigens were common to various tissues and involved in the binding of rat natural antibodies ex vivo. In conclusion, our results indicate that rat xenoantigens of about 55 kDa are recognized by guinea pig natural antibodies, while guinea pig xenoantigens of 95-110 kDa are bound by rat natural antibodies. These antigens are common to liver, heart, lung, and kidney, are borne by endothelial cells, and cannot be found on hepatocytes.

Acute Disease↗
PubMed1993

Cyclosporine-induced stimulation of the renin-angiotensin system after liver and heart transplantation.

To analyze the status of the renin-angiotensin system in hypertensive transplant recipients on cyclosporine, we prospectively explored 21 cardiac (CTR: 52 +/- 8.2 yr) and 12 liver (LTR: 45 +/- 10 yr) transplant recipients on a normal salt diet with 19 normotensive controls in the same age range. Systolic and diastolic blood pressure was measured in the supine and standing positions. Renal function was assessed by serum creatinine values, and 24-hr urinary sodium and potassium excretion were recorded. Plasma renin activity (PRA), active renin, total renin, angiotensinogen, aldosterone, and cortisol plasma levels were simultaneously determined. Results were expressed as mean +/- SD, and between-group differences were compared using variance analysis. Supine blood pressure (+/- SD) was 158 +/- 15/103 +/- 8.4 in CTR and 155 +/- 21.4/102 +/- 11.7 mmHg in LTR. Serum creatinine was higher in CTR (159 +/- 52 mumol/L) than in LTR (117 +/- 24.7, P < 0.05) and values in both groups were above controls (83 +/- 14.1, P < 0.05). Urinary sodium excretion tended to be lower in transplant recipients (59 +/- 42 mmol/L) for CTR and 44 +/- 36.7 in LTR than in healthy controls (117 +/- 24.7 mmol/L). Supine and upright PRA values tended to be higher in hypertensive transplant recipients than in healthy volunteers, although not significantly. Supine active renin was significantly higher in CTR (47 +/- 42 pg/ml) and in LTR (44 +/- 29.8 pg/ml) than in normal subjects (17 +/- 4.8 pg/ml, P < 0.05). Total renin levels in CTR (supine: 716 +/- 357 pg/ml) and in LTR (supine: 647 +/- 365 pg/ml) were 3- to 4-fold higher than in controls (supine: 207 +/- 69 pg/ml) (P < 0.05), as were inactive renin levels (P < 0.01). Active renin was effectively correlated with PRA (P < 0.001) and with total renin (P < 0.001) in the supine and in the upright position. Plasma aldosterone was almost within the normal range in CTR and in LTR, and it did not correlate with PRA values. Plasma angiotensinogen levels were normal in LTR (1032 +/- 226 ng/ml) but were significantly lower in CTR (938 +/- 216 ng/ml, P < 0.05). Cortisol plasma levels were lower in both CTR (7 +/- 4.4 micrograms/L) and LTR (6 +/- 1.9 micrograms/L) than in healthy controls (11 +/- 4 micrograms/L, P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗
PubMed1993

[Principles and technique of multiorgan procurement for transplantation].

On the basis of own experience from many years and literature model principles are presented of multiorgan obtaining (MOO) for transplantation. The paper describes the general principles of MOO and the basic elements of the technique of obtaining the heart, liver, and kidneys. The main purpose of the publication is to present the problems of MOO to wider circles of doctors in the context of striving to a unification of obtaining methods on the basis of the widely accepted European model.

Europe↗