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Biomedical subjects

D Houssin

Publications and source records attributed to D Houssin.

At least 109 records · Page 6Linked to original sources
PubMed1994

Organ xenografting between rodents: an evolutionary perspective.

Rejection times of heart xenografts in several donor-recipient combinations including the guinea pig, rat, hamster, and mouse are examined in light of the paleontological history of rodents and the resulting phylogenetic distances between taxa. This multidisciplinary review at the molecular, chromosomal and morphological levels suggests that xenograft rejection time is inversely proportional to the time divergence or phylogenetic distance, and that the binomial terminology concordant/discordant does not reflect the amplitude of phylogenetic distances.

Animals↗
PubMed1994

Liver function improvement following increased portal blood flow in cirrhotic rats.

BACKGROUND/AIMS: Liver microcirculation in cirrhosis is characterized by development of intrahepatic shunts and capillarization of sinusoids secondary to cell necrosis and deposition of new collagen, resulting in both decreased drug elimination and increased vascular resistance with portal hypertension. The aim of this study was to examine the effects of increased portal blood flow on hepatic microcirculation and drug elimination in 13 perfused livers from cirrhotic rats. METHODS: Intrahepatic resistance was assessed under basal conditions (21.2 +/- 0.3 mL/min) and 1 hour after doubling the flow (41.6 +/- 1.0 mL/min). A multiple indicator dilution technique was used at both flow rates to measure sinusoidal volume, albumin and sucrose extravascular volumes, and cellular water volume. Hepatic elimination of labeled taurocholate and propranolol was also measured, and the recovery of 15-microns microspheres was used to evaluate large intrahepatic shunts. RESULTS: After doubling the flow, intrahepatic resistance decreased by 31%. Sinusoidal and extravascular volume increased significantly without a change in microsphere recovery. However, there was a marked increase in taurocholate and propranolol elimination by cirrhotic livers. Moreover, during high flow, significant correlations were found between changes in albumin extravascular volume and taurocholate and propranolol elimination. CONCLUSIONS: Increased portal blood flow in cirrhotic rats induces a decrease in intrahepatic resistance without changes in intrahepatic shunting and improves drug elimination by the liver without deleterious effects on hepatocyte viability.

Animals↗
PubMed1994

The influence of cold ischemia time on biliary complications following liver transplantation.

Biliary complications are a continuing source of morbidity and mortality following orthotopic liver transplantation. The results of 100 whole-liver allografts performed in 92 adult patients were reviewed to determine whether cold ischemia time and preservation injury influenced both the incidence and type of biliary complications. Mean cold ischemia time was 10.2 +/- 0.5 h (range 3.6-19). Eighteen patients (19.6%) developed 25 biliary complications: there were eight anastomotic leaks, eight anastomotic strictures, six non-anastomotic strictures, two cystic duct mucoceles, and one biliary fistula following T-tube removal. Despite the high rate of reoperative surgery (68%), no death was attributable to biliary complications. Neither cold ischemia time nor early graft function influenced the rate of biliary complications or strictures of either type. Furthermore, an analysis of different factors revealed no predisposing effect of the pre-operative status of the recipient, type of biliary reconstruction, blood requirement, vascular complications, rejection or cytomegalovirus infection on the incidence of biliary complications or strictures. Only chronic rejection could be singled out as a risk factor for non-anastomotic strictures (p = 0.05). These results suggest that prolonged cold ischemia time does not seem to affect the rate or type of biliary complications following orthotopic liver transplantation. In view of these data, there is no clear reason to reconsider prolonged cold ischemia up to 15 h in University of Wisconsin solution, as it has transformed liver transplantation from an emergency operation to a semi-elective procedure and allows longer back-table preparation for graft reduction of splitting.

Adolescent↗
PubMed1994

Portal pumping: a new perspective for treatment of variceal hemorrhage and liver failure in end-stage cirrhosis?

In end-stage cirrhosis complicated by variceal hemorrhage, attempts to reduce portal pressure by treatments such as portosystemic shunts also decrease sinusoidal perfusion and risk impairing liver function. It has been suggested that encouraging portal flow to pass through the cirrhotic liver by mechanical action could cause a decrease in distal (splanchnic) portal pressure on one hand, and improve liver function on the other. The aim of this work was to evaluate the hemodynamic and functional effects of a 30-min pump-driven increase in portal blood flow through the liver of patients with end-stage cirrhosis before the anhepatic phase of liver transplantation. Basel portal flow (800 +/- 270 ml.min-1) was increased two fold (n = 10) or four fold (n = 9). When the flow was doubled, splanchnic portal pressure decreased 17.9 +/- 11.3% (from 31.8 +/- 5.3 to 26.0 +/- 5.8 mmHg, n = 10; p < 0.001); when flow was increased four fold, splanchnic portal pressure decreased 39.2 +/- 15.4% (from 32.8 +/- 5.0 to 19.9 +/- 6.0 mmHg, n = 9; p < 0.001). The comparison of indocyanine green clearance between basal and doubled portal flow demonstrated an increase of 32.1 +/- 26.9% (n = 5; p = 0.053). Histological analysis demonstrated sinusoidal dilatation in three out of ten livers. These results, as well as previous studies using isolated perfused cirrhotic rat or human livers, suggest that portal pumping should be explored as a treatment for certain sclerotherapy-resistant cirrhotic patients, with variceal hemorrhage and liver failure.

Adolescent↗
PubMed1994

Liver transplantation for end-stage liver disease associated with alpha-1-antitrypsin deficiency in children: pretransplant natural history, timing and results of transplantation.

Alpha-1-antitrypsin deficiency is an inborn metabolism error which can cause emphysema and liver disease. As regards the pathophysiology of liver disease, this deficiency is poorly understood, and it is also not known why only a small proportion of Pi ZZ individuals progress towards cirrhosis and liver failure. Since there is no specific therapy for end-stage liver disease associated with alpha-1-antitrypsin deficiency, patients are considered candidates for liver transplantation. In this paper, the natural history of 16 children who underwent liver transplantation is reviewed. Fourteen patients had neonatal cholestasis as a first symptom of the disease and hepatosplenomegaly was present in all children by the age of 12 months. In 11 children, jaundice recurred, always with liver function deterioration. Two patients had a histological paucity of interlobular bile ducts and required early transplantation due to rapid progression of liver failure. At the time of pretransplant assessment, all the patients in this study had portal hypertension and seven of them had experienced at least one episode of gastrointestinal bleeding. One child had moderate intrapulmonary shunts with hypoxemia, but the others had normal spirometry and blood gases. There was no other extrahepatic complication of alpha-1-antitrypsin deficiency. Eighteen orthotopic liver transplantations were performed in 16 patients. One patient died 8 days after retransplantation due to graft necrosis. Fifteen patients (94%) were alive after a median follow-up of 22 months with an excellent quality of life, normal serum alpha-1-antitrypsin levels and without evidence of liver disease recurrence or pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1994

[Immuno-hematologic aspects of xenotransplantation].

The main barrier to pig organ xenograft in humans, is the hyperacute rejection, which is provoked by the fixation of human xenoantibodies on the graft endothelial cells, and by complement activation. Because pig red blood cells and endothelial cells carry common xenogeneic epitopes, human anti-pig xenoantibodies can be detected and titered by pig red blood cells direct agglutination. Individuals of AB blood group have lower anti-pig hemagglutinins titers than those of other blood groups. Anti-A and anti-B alloantibodies do not agglutinate pig red blood cells. The anti-B (and not the anti-A) alloantibodies can be adsorbed on pig red blood cells. A linear B type 2 epitope recognized by human natural antibodies has been previously described on pig cells. If the role of xenoantibodies is prominent in the rejection of pig organ xenografts in humans, the role of alloantibodies remains to be precise.

ABO Blood-Group System↗
PubMed1994

Orthotopic liver transplantation in children with chronic liver disease and severe hypoxemia.

Liver transplantation has been considered until recently as an absolute contraindication in hypoxemic patients. We report our experience in nine patients who had orthotopic liver transplantation between June 1986 and June 1992. These patients had cirrhosis-related hypoxemia with intrapulmonary shunting (IPS). The arterial oxygen pressure (PaO2) on room air ranged from 47 to 78 mmHg. OLT resulted in resolution of hypoxemia and closure of IPS in five patients whose hypoxemia was higher than 60 mmHg, and in death for the remaining four patients who had severe hypoxemia (PaO2 < 60 mmHg). We conclude that hypoxemia is no longer a contraindication to liver transplantation. Patients having PaO2 levels higher than 60 mmHg should have OLT as soon as possible before reaching lower levels of PaO2, and combined lung-liver transplantation or heart-lung-liver transplantation should be discussed in patients with severe hypoxemia (PaO2 < 60 mmHg).

Adolescent↗
PubMed1994

Hyperacute xenograft rejection in the swine-to-human donor-recipient combination. In vitro analysis of complement activation.

Complement activation is central to the rejection of discordant xenografts. In order to assess the respective roles of direct and alternative pathways, an in vitro model of hyperacute rejection in the swine-to-human donor-recipient combination was designed, using a complement-dependent cytotoxicity test with swine endothelial cells in culture as targets, and fresh human serum as the source of xenogeneic antibodies and complement. The cytotoxic activity of the sera was evaluated by a colorimetric assay using (3-[4,5-dimethyldiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT). Pure human serum lysed 58 +/- 5% of swine endothelial cells. Selective inhibition of the direct pathway by adding EGTA to the serum reduced cytolysis to 51 +/- 2% (P < 0.01 versus normal serum). Similarly, when using C1q-deficient human sera, only 37 +/- 7% of swine endothelial cells were killed (P < 0.001 versus normal serum). When the alternative pathway was selectively inhibited by heating for 20 min at 50 degrees C, the lytic activity of human serum dropped to 42 +/- 5% (P < 0.001 versus normal serum). Factor B-deficient human serum could only lyse 42 +/- 10% of porcine endothelial cells (P < 0.001 versus normal serum). Syngeneic normal swine serum and heat-inactivated serum were not cytotoxic. Mixing serum with deficient direct pathway and serum with deficient alternative pathway restored the cytotoxicity to normal levels. Similarly, the cytotoxic activity of deficient serum supplemented with purified C1q or factor B at physiological concentrations reached that of normal human serum. In this model of in vitro hyperacute rejection, both pathways of complement activation are involved, suggesting that regimens designed to inhibit hyperacute rejection of swine xenografts into humans should take into account the dual activation of complement in this donor-recipient combination.

Acute Disease↗
PubMed1994

[Training of surgeons for laboratory research].

A degree in surgical research has been set up in 1986 in France. It includes a one-year full time work in a research laboratory, and seminars (one to three days long, each). General surgical research objectives are gathered in a first seminar. Then, candidates select one among four optional subjects: biomaterials-artificial organs, transplantation, oncology, and neurosciences. Two prerequisites are necessary in order to register. The first is to write a research project according to standardized rules, and the second is to attend two seminars, one dealing with scientific communication and the other with methodology in clinical research. A nation-wide valid Academic degree is delivered to candidates who pass an oral presentation of their research report and who attended all seminars according to the optional subject that they selected. From 1986 to 1993, 434 students attended the formation. They came from different regions of France, proving the nation-wide characteristic of the degree, and some from foreign countries. Seminars were held in different French University towns. An increasing number of students become Ph.D.

Education, Medical, Graduate↗
PubMed1994

Fatal hemobilia after liver graft biopsy in a transplanted child.

Severe hemobilia after liver transplantation is a rare complication. We report one case of fatal hemobilia resulting from arterio-biliary fistula after a liver graft needle biopsy in a 7-year-old girl transplanted with a reduced-size graft. Arterial reconstruction was performed by an iliac conduit implanted in the aorta. The diagnosis of hemobilia was made by angiography but the hemorrhage could not be controlled by selective embolization of the bleeding arterial branch. The patient died from early and massive recurrent bleeding before surgery. The prevention of iatrogenic hemobilia and current therapeutic strategies are discussed.

Angiography↗
PubMed1994

[Ascites after liver transplantation in children].

The objective of this study, based on a series of 148 transplants performed in 131 children, was to evaluate the frequency, complications and predisposing factors of ascites occurring after liver transplantation (LT). The diagnosis of post-LT ascites was defined as a drainage rate greater than 25 ml/kg/day (or- > 500 ml/day) persisting for at least 72 hours after removal of the drains. Among the 123 transplants analysed, 31 (25.2%) were complicated by ascites (group I). Group II consisted of 92 LT without ascites. This ascites was predominantly lymphocytic (669 +/- 1,104/mm3), rich in proteins (32 +/- 13 g/l), with a low triglyceride concentration. The mean duration of ascites was 25 +/- 19 days. Complications of ascites included: infection of ascitic liquid (35%), respiratory complications (65%), parietal complications (50%), consumption coagulopathy (35%), functional renal failure (Creat > 130 mumol/l, 35%). There were 9 deaths (29%) in group I versus 8 in group II (p < 0.02). The predictive factors, pre-LT, of postoperative ascites included: serum bilirubin > 300 mumol/l (p < 0.02); PT < 30% (p < 0.05); and serum albumin < 30 g/l (p < 0.05). Intraoperative factors favouring the development of ascites were end-to-side cavo-caval implantation of the graft when it was reduced (p < 0.02) and a volume of transfused blood after unclamping greater than 60 ml/kg (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Perspectives of liver replacement: consideration of the uniqueness of the human liver].

The feasibility of liver replacement is currently dominated by the problems of availability of liver transplants. This has led to the development of surgical techniques allowing the use, in children, of a transplant derived from an older donor, whose volume is reduced by partial hepatectomy. Transplant sharing techniques have also been developed allowing the same donor organ to be used in two recipients. Despite the negative aspects of this approach, some teams have also been forced to develop liver transplantation in children using a living related donor. With the possibility of a growing shortage of transplants, research is underway in the field of heterologous transplantation, i.e. interspecies transplantation. Control of rejection is currently the principal obstacle in this context and is a long way from being completely resolved.

Ethics↗