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Biomedical subjects

F Gauthier

Publications and source records attributed to F Gauthier.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effectiveness of partial splenectomy in hereditary spherocytosis.

Total splenectomy eliminates the splenic destruction of erythrocytes with impaired deformability. However, concern has increased over the lifelong risk of overwhelming postsplenectomy infections in splenectomized patients, a risk reduced but not totally suppressed by appropriate prophylaxis. Partial splenectomy, as long as 80% to 90% of the enlarged spleen is removed and less than 25% of the normal spleen volume is retained, is a logical alternative, both preserving the phagocytic and immune function of the spleen and decreasing erythrocyte destruction. A 12-year experience has shown that subtotal splenectomy is efficient in decreasing hemolysis, although to a lesser extent than total splenectomy, with sustained results over years in most patients, and indirect evidence argues for the integrity of phagocytic function. Such a surgical procedure should be considered in transfusion-dependent infants with hereditary spherocytosis and in older patients with erythrocyte membrane defects, provided further follow-up confirms the experience of the past 12 years.

Humans↗
PubMed1997

Urgent liver transplantation for biliary atresia: the experience in Bicêtre.

According to French rules for cadaver organ sharing, children with biliary atresia (BA) complicated with acute necrosis (ALN) can be registered on the waiting list for liver transplantation (LT) in a special intermediate grade urgent code. Over a 7 years period, 100 children have been submitted to elective LT for BA and 15 to urgent LT. Urgent procedures accounted for 25% of LT for BA in patients aged 0-2 years and 67% (8/12) in patients under 1 year of age. Children actuarial survival at 1, 12 and 48 months was respectively 66%, 60% and 60% versus 92%, 86% and 85%, deaths occurring earlier in the urgent group. Graft actuarial survival at 1, 12 and 48 months were 60%, 53% and 53% versus 85%, 77% and 76% (p < 0.05), respectively. Outcome of children and grafts after LT is not significantly different in BA cases and in other urgent indications, excluding retransplantations. In a LT program based on cadaver organ donation, allocation of in an urgent registration code to children with BA and ALN offers them more than 50% chance to escape death and does not result in wasting of grafts.

Actuarial Analysis↗
PubMed1997

Determinants of life span after Kasai operation at the era of liver transplantation.

The aim of this work is to determine the influence of age, extrahepatic biliary lesions pattern (EHBP) and association to polysplenia syndrome (PS) on 10 years outcome of 164 patients with biliary atresia (BA) treated from 1984 to 1992 by initial Kasai operation (KO) and secondary liver transplantation (LT) when necessary. Actuarial crude survival without or after LT (CS), actuarial survival with native liver (NLS) and jaundice-free actuarial survival with native liver (JFS) were calculated from 1 to 10 years versus age (under/over 45 days), EHBP (favorable/ unfavorable) and PS (no/yes). Overall 10-year CS is 70%, overall 10-year NLS and JFS are 14%. In univariate analysis, age at KO under 46 days, favorable EHBP (BA with patent gallbladder, and/or cystic dilatation of extrahepatic bile duct, or BA restricted to choledocus), and absence of PS are significant determinants of a better outcome regarding CS, NLS and JFS. EHBP is more discriminant than age. Influence of PS in this series is redundant with that of EHBP since 11/11 patients with PS had unfavorable EHBP.

Age Factors↗
PubMed1996

Cystatins up-regulate nitric oxide release from interferon-gamma-activated mouse peritoneal macrophages.

Up-regulation of nitric oxide (NO) production by activated murine macrophages was observed during infection by Trypanosoma cruzi, the etiological agent of Chagas' disease. Cell infection by T. cruzi depends at least in part on cruzipain, a membrane-associated papain-related proteinase which is sensitive to inhibition by synthetic inhibitors of cysteine proteinases. Using the natural cysteine proteinase inhibitor chicken cystatin, a representative member of cystatin family 2, to investigate the effect of cruzipain on macrophage infection and NO release, we found that the inhibitor alone up-regulated NO release from interferon-gamma-activated macrophages. A 12-fold increase in NO production was observed in the presence of 1 microM chicken cystatin. This overproduction was concentration-dependent and could be detected at concentrations as low as 10 nM and remained in the presence of polymyxin B. Representative members of the other cystatin families, i.e. stefin B (family 1), T-kininogen, and its inhibitory domains (family 3), were also able to enhance NO production from interferon-gamma-activated macrophages. Neither E64, an irreversible inhibitor of cysteine proteinases, nor inhibitors of aspartyl and serine proteinases (aprotinin, pepstatin, and soybean trypsin inhibitor) enhanced NO production. Upon complexation with saturating amounts of reduced-alkylated papain, cystatins still remained active in increasing NO production, suggesting that the cystatin inhibitory site was not involved in the mechanism. The results demonstrate that members of all 3 cystatin families share another common property unrelated to their function of cysteine proteinase inhibitors, i.e. up-regulation of NO production, which biological significance remains to be elucidated.

Animals↗
PubMed1996

Inhibition of cathepsin B by its propeptide: use of overlapping peptides to identify a critical segment.

Ten overlapping 15-mer peptides (peptidyl amides) spanning the proregion of rat cathepsin B (residues 1p-60p) were constructed to identify minimal segments having inhibitory activity towards the mature enzyme, that could be used to develop a new generation of peptide-derived inhibitors specifically targeting the active site of the corresponding proteinase. Three synthetic peptides, containing the pentapeptide Leu-Cys-Gly-Thr-Val (residues 41p-45p) in their sequence, inhibited cathepsin B with Ki values in the micromolar range. Alkylation of the thiol group of Cys-42p of peptide PB8 (36p-50p) resulted in its rapid proteolytic degradation, suggesting that this residue is essential for inhibition. The inhibition constant was slightly improved (Ki = 2 microM) using a longer peptide (26p-50p) which was completely resistant to cleavage even after a prolonged incubation. Alkylation of its cysteinyl residue also resulted in rapid cleavage of the peptide chain. Peptides derived from the rat cathepsin B prosequence also inhibited human cathepsin B with similar Ki values. Unlike rat cathepsin B, which cleaves peptide PB8 at the G47p-G48p bond after prolonged incubation, the human enzyme cleaved both PB8 and PB11 at the Lys-40p-Leu-41p bond, in agreement with the different kinetic properties of these two proteinases. New probes with improved specificity for cysteine proteinases may therefore be designed based on the sequences of their propeptides.

Amino Acid Sequence↗
PubMed1996

Biotin-labelled peptidyl diazomethane inhibitors derived from the substrate-like sequence of cystatin: targeting of the active site of cruzipain, the major cysteine proteinase of Trypanosoma cruzi.

Biotin-labelled peptidyl diazomethane inhibitors of cysteine proteinases, based on the N-terminal substrate-like segment of human cystatin C, a natural inhibitor of cysteine proteinases, were synthesized. These synthetic derivatives were tested as irreversible inhibitors of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, to compare the kinetics of the inhibition of the parasite proteinase with that of the mammalian cathepsins B and L. The accessibility of the active sites of these proteinases to these probes was also investigated. The inhibition of cruzipain by Biot-LVG-CHN2 (where Biot represents biotinyl and L,V and G are single-letter amino acid residue abbreviations) and Biot-Ahx-LVG-CHN2 (where Ahx represents 6-aminohexanoic acid) was similar to that of unlabelled inhibitor. Biotin labelling of the inhibitor slowed the inhibition of both cathepsin B and cathepsin L. Adding a spacer arm (Ahx) between the biotin and the peptide moiety of the derivative increased the inhibition of cathepsin B but not that of cathepsin L. The discrimination provided by this spacer is probably due to differences in the topologies of the binding sites of proteinases, a feature that can be exploited to improve targeting of individual cysteine proteinases. Analysis of the blotted proteinases revealed marked differences in the accessibility of extravidin-peroxidase conjugate to the proteinase-bound biotinylated inhibitor. Cruzipain molecules exposed to Biot-LVG-CHN2 or Biot-Ahx-LVG-CHN2 were readily identified, but the reaction was much stronger when the enzyme was treated with the spacer-containing inhibitor. In contrast with the parasite enzyme, rat cathepsin B and cathepsin L treated with either Biot-LVG-CHN2 or Biot-Ahx-LVG-CHN2 produced no detectable bands. Papain, the archetype of this family of proteinases, was poorly labelled with Biot-LVG-CHN2, but strong staining was obtained with Biot-Ahx-LVG-CHN2. These findings suggest that optimized biotinylated diazomethanes might considerably improve their selectivity for the T. cruzi target enzyme.

Amino Acid Sequence↗
PubMed1996

Investigation of the substrate specificity of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, through the use of cystatin-derived substrates and inhibitors.

A panel of intramolecularly quenched fluorogenic substrates containing the conserved QVVA and LVG inhibitory sequences of cystatin inhibitors was used to describe the specificity of the major cysteine proteinase of Trypanosoma cruzi (cruzipain or cruzain). This approach was based on the observations that: (1) cruzipain is strongly inhibited by chicken cystatin and rat T-kininogen, two representative members of cystatin families 2 and 3; (2) the QVVA- and LVG-containing substrates are specifically hydrolysed by papain-like proteinases; and (3) the cystatin-like motifs are similar to the proteolytically sensitive sequences in cruzipain that separate the pro-region and/or the C-terminal extension from the catalytic domain. Specificity constants (kcat/Km) were determined and compared with those of mammalian cathepsins B and L from rat liver lysosomes. Cruzipain and the mammalian proteinases cleaved cystatin-derived substrates at the same site, but their specificities differed significantly. Increased specificity for cruzipain was obtained by replacing amino acids at critical positions on both sides of the cleavage sites, especially at position P2'. The specificity constants (k(cat)/Km) obtained for the two substrates with a prolyl residue at P2' (O-aminobenzoyl-QVVAGP-ethylenediamine 2-4-dinitrophenyl and O-aminobenzoyl-VVGGP-ethylenediamine 2-4-dinitrophenyl) were about 50 times higher for cruzipain than for rat cathepsin L and about 100 times higher than for cathepsin B. Diazomethylketone derivatives, based on the non-prime sequence of cystatin-derived substrates, inhibited cruzipain irreversibly, but their inactivation rate constants were considerably lower than those for mammalian cathepsins B and L, confirming the importance of P' residues for cruzipain specificity.

Amino Acid Sequence↗
PubMed1996

[Sarcoidosis with hematologic involvement and hypogammaglobulinemia].

BACKGROUND: Hematological changes are uncommon in childhood sarcoidosis. CASE REPORT: Case 1. This patient developed severe hemolytic anemia associated with splenomegaly at the age of 11 months. A second episode of hemolysis was seen at the age of 6 years; it was associated with thrombocytopenia and hypogammaglobulinemia. A partial splenectomy permitted histological diagnosis of sarcoidosis that was confirmed by elevated angiotensin-converting enzyme level, and subsequently developement of pulmonary involvement. Case 2. This boy suffered from autoimmune hemolytic anemia and thrombocytopenia associated with splenomegaly at the age of 3 years. At the age of 7 years, he had splenomegaly, enlarged cervical and lomboaortic lymph nodes and hypogammaglobulinemia. Diagnosis of sarcoidosis was made from lymph nodes and spleen biopsies after splenectomy; the patient had increased angiotensin-converting enzyme concentration, and subsequently developed specific renal involvement. CONCLUSION: Association of hemolytic anemia, thrombocytopenia, hypogammaglobulinemia and splenomegaly should suggest the diagnosis of sarcoidosis and could be considered as part of the disease spectrum.

Agammaglobulinemia↗
PubMed1996

Spontaneous perforation of the biliary tract in infancy: a series of 11 cases.

Eleven patients presenting with spontaneous perforation of the biliary tract were treated at Bicêtre Hospital between 1971 and 1993. Three groups were individualised, each with a different pattern of local presentation: generalised biliary peritonitis (n = 2), localised biliary peritonitis (n = 4), secondary biliary stenosis (n = 5). In each case, cholestatic jaundice developed after a postnatal symptom-free interval. Ten patients were operated on. Perforation was located in the cystic duct (n = 2), at the junction of the cystic and hepatic ducts (n = 4), in the common hepatic duct (n = 1) or common bile duct (n = 1). The site of perforation was no longer identifiable in two cases with stenosis. A cholecystectomy was performed in the 2 cases with cystic duct perforation; in the cases of lesions of the main duct, either simple external biliary drainage (n = 3) or biliary reconstruction (n = 5) was carried out. Postoperative complications included bile leak (n = 2), ascending cholangitis (n = 1), portal vein thrombosis (n = 2). Five patients were submitted to further surgery including biliary revision (n = 3), porto-systemic shunt (n = 1), and other procedures (n = 2). One infant died from postoperative sepsis; 2 were lost to follow-up, one of which probably did not survive; 4 are alive and well. Late sequelae are present in 4 children: portal hypertension (n = 1), mild residual bile duct dilatation without cholestasis (n = 1), and mild to moderate liver fibrosis (n = 2). Prompt diagnosis and appropriate treatment should improve the prognosis of this rare condition.

Bile Duct Diseases↗
PubMed1996

Homology modelling of rat kallikrein rK9, a member of the tissue kallikrein family: implications for substrate specificity and inhibitor binding.

The rat kallikrein rK9 is one of the six members of the rat tissue kallikrein family isolated to date. It is 84% identical to rK2 (tonin), and both proteinases are thought to have vasoconstrictive properties. Recently we have shown that rK9 and rK2 have distinct substrate specificities and sensitivities to inhibitors, despite their similar sequences. Unlike all other mammalian kallikrein-related proteinases, rK9 is resistant to inhibition by aprotinin. We have developed a 3-D model of rK9, based on the known X-ray structures of rK2, porcine kallikrein and bovine trypsin, to identify the structural features underlying this functional diversity. The final rK9 model is structurally similar to rK2, but variable regions surrounding the active site differ quite markedly from the reference proteins. The kallikrein loop, which differs from that in porcine kallikrein by a seven-residue insertion, has been generated de novo and subjected to simulated annealing to assess its influence on the restricted substrate specificity of these proteinases. The proposed conformation of the specificity pocket in rK9 differs from that of other serine proteinases, but it can still accommodate both aromatic and basic amino acid side chains at the substrate P1 position, thus explaining the dual chymotrypsin and trypsin-like activity of rK9. The electrostatic potentials of rK9 and aprotinin were calculated using the finite difference Poisson-Boltzmann method. They indicated a large positive region near the active site of rK9 not found in related proteinases because of positively charged residues at positions 61 and 65 in rK9. They generate a positive region, which overlaps a positive region in aprotinin, and may prevent aprotinin binding. A single mutation in aprotinin is suggested that might allow kallikrein rK9 inhibition by aprotinin. This model contributes significantly to our understanding of the structure-function relationships among proteinases of the tissue kallikrein family.

Amino Acid Sequence↗
PubMed1996

[Prenatal detection of a cyst in the liver hilum. Interpretation for an adequate treatment].

The diagnosis assigned to a cystic collection of liver hilum (CCLH) detected by means of prenatal ultrasonography is usually that of choledochal cyst (CC) thus carrying a good prognosis. The aim of this work is to state more precisely the significance of such CCLH, from a review of our experience. Files of children treated in our institution for either CC or biliary atresia (BA) with bile duct cysts have been screened for prenatal detection of CCLH. From 1985 to 1994, seven children have been referred to our institution, all after birth, all after prenatal detection of CCLH between 22 and 38 weeks of pregnancy (median = 33 weeks). Postnatal diagnosis, established by means of percutaneous cholangiography, was CC in 5 children without any evidence of cholestasis, and BA in 2 children with alcoholic stools and hepatomegaly. The 5 CC patients have been submitted to successful surgery at age 16 days to 10 months. The 2 BA patients have been operated at age 23 and 111 days, the latter unfortunately with gross cirrhosis and portal hypertension. An accurate prenatal diagnosis had been done by previous investigators only in 3 of the 7 cases, all 3 being CC cases. A review of the literature confirms that prenatal detection of a CCLH occurs mostly during the 3rd trimester of pregnancy and that of the postnatal diagnosis is almost always CC. Nevertheless the diagnosis of BA, requiring an early surgical procedure is also possible. We recommend that prenatal detection of a CCLH should result at least in referring the baby soon after birth to a team skilled in hepatobiliary pathology.

Common Bile Duct↗
PubMed1995

Liver transplantation in children with Alagille syndrome--a study of twelve cases.

Cholestasis associated with Alagille syndrome may, in a few cases, be extremely severe and result in major impairment in the quality of life during early childhood and end up in cirrhosis eventually. We report the results of liver transplantation in 12 children with a severe hepatic form of Alagille syndrome. All children presented with cholestatic jaundice from birth, peculiar facies, stenosis of the peripheral pulmonary artery, and posterior embryotoxon; butterfly-like vertebrae were present in 9 children. At the time of transplantation (mean age 7 years 10 months) refractory pruritus was present in 9 children, xanthoma in 11, and height and weight retardation in 11. Total serum bilirubin ranged from 116 to 322 mumol/L and total serum cholesterol from 3.5 to 29 mmol/L. Systolic right ventricular pressure was moderately raised (36 to 48 mmHg) in 5 children; mean creatinine clearance was 99 ml/min/1.73 m2. Histologic examination of the removed livers showed cirrhosis, severe annular fibrosis, and moderate portal fibrosis in 4 children each. Follow-up in the 11 survivors has ranged from 14 months to 5 1/2 years. All lead normal lives. Pruritus and xanthomas disappeared. Increase in height was observed in 8 of the 10 survivors who had growth retardation prior to transplantation. School level is normal in 4 (median age at LT: 5 yr 9 mo) and below normal in 6 (median age at OLT: 9 yr 9 mo). Liver function tests are normal in 10 children. Mean creatinine clearance is 101 ml/min/1.73 m2. These results indicate that the quality of life can be considerably improved after liver transplantation in children with a severe hepatic form of Alagille syndrome and suggest that it could be carried out before these children attend elementary school.

Alagille Syndrome↗
PubMed1995

Inhibition of U-937 membrane-associated cathepsin G by GP120 (IIIB) and V3 loop-derived peptides from several strains of HIV-1.

A cell surface-associated cathepsin G has been reported to be a possible complementary factor for HIV-1 infection of U-937 cells. The effect of recombinant gp120 (IIIB) and a series of V3 loop peptides derived from the sequence of different strains of HIV on the activity of U-937 cathepsin G was assayed. The sequence on the N-terminal side of the highly conserved GPGRAF V3 loop segment was required for interaction with cathepsin G. The inhibition was stable for several hours and there was no cleavage of the peptides derived from the HIV-1(IIIB) strain. Recombinant gp120 (IIIB) also remained uncleaved after incubation with cathepsin G for 3 h, but some cleavage occurred, generating 2 fragments (50 kDa and 70 kDa), after 16 h. Linear peptides derived from HIV-1 Mal, ELI, MN, CDC4 and SF162 strains, and consensus V3 peptides all had inhibitory properties towards cathepsin G, although they were significantly cleaved after one hour. The cleavage site was at the carboxy-terminus of Tyr323 which is conserved in all these HIV-1 strains but not in HIV-1(IIIB). There was no cleavage at the Arg residue of the GPGRAF sequence, whatever the V3 peptide sequence, the amount of proteinase, or the incubation time. We conclude that the inhibition of membrane-associated cathepsin G of U-937 cells by the gp120 V3 loop of HIV-1 does not occur via a Kunitz-type mechanism, and that the proteinase-V3 loop interaction does not result in a significant cleavage of the V3 loop, though it has been suggested that this event is required for the entry phase of the virus.

Amino Acid Sequence↗
PubMed1995

Pro-rat atrial natriuretic peptide-mimicking peptides as substrates for rat kallikreins rK2 (tonin) and rK9.

Investigation of the substrate specificity of rat tissue kallikreins has shown the importance of an extended site of interaction, and that the proform of rat natriuretic peptides, pro-ANP, could be a substrate for two members of the family, rK2 (tonin) and rK9 (Moreau et al. (1992) J. Biol. Chem. 267, 10045-10051). Synthetic peptide substrates that reproduce the sequence of rat pro-ANP in the region of the activation sites were used to further assess the specificity of these two proteinases. Peptides 95-107 (AGPRSLRRSSCFG) and 91-107 (RALLAGPRSLRRSSCFG) of the rat pro-ANP sequence, which include all the cleavage sites for generating natriuretic peptides (R98, R101, R102), were synthesized and assayed as kallikrein substrates. Despite their homology, the two peptides had different susceptibilities to cleavage by rK2 and rK9. Peptide 91-107 was rapidly and specifically cleaved by both kallikreins, with a single cleavage site at the R98-S99 bond, which is the primary cleavage site in pro-ANP for generating ANP[1-28]. The kcat/Km values were 289,000 M-1 s-1 for rK2 and 39,000 M-1 s-1 for rK9. The N-terminally truncated peptide (95-107) was also cleaved at that bond by both proteinases, but far less rapidly than peptide 91-107, and additional cleavages appeared at secondary sites i.e those generating atriopeptin III (R101) and auriculin (R102) in rat pro-ANP. A commercial fluorogenic tetrapeptide substrate reproducing the sequence of rat pro-ANP was slowly hydrolysed under the same conditions. The kinin-releasing kallikrein rK1 did not cleave synthetic peptides at the R98-S99 bond, further demonstrating the different specificities of tissue kallikreins. The results indicate that residues in positions P5 to P8 with respect to the cleavage site in the substrate, are essential for the substrate binding and specificity of kallikreins rK2 and rK9. They also show that long peptide substrates should be used to identify biological substrates of kallikreins from the investigation of their kinetic properties. The biological significance of pro-ANP processing by these proteinases, remains, however, to be proven.

Amino Acid Sequence↗
PubMed1995

Substrate specificity of tissue kallikreins: importance of an extended interaction site.

The contribution of an extended interaction site in tissue kallikreins to their substrate specificity was investigated using peptides of increasing length and with different amino acids in positions P5 and P6. These substrates were constructed from a consensus dodecapeptide sequence (VASPFRSYDLDA) deduced from the hydrolysis of short synthetic peptide substrates, and from the identification of the cleavage sites in reduced-pyridylethylated lysozyme by 6 rat tissue kallikreins. Though the specificity constant kcat/Km generally increases with increasing the peptide substrate length on its N-terminal end, individual residues at P4-P6 may specifically alter this value for specific kallikreins. A seryl residue at P4 induces a 20-fold decrease in the specificity constant with rK2 and rK9, but it slightly improves this value for rK1 and rK10. A tryptophan in P6 is unfavourable for both rK1 and rK2 but not for rK9 and rK10, whereas a negatively charged residue has a negative effect for all four kallikreins. This demonstrates the importance of an extended interaction site in kallikreins, and suggests that the differing specificities of individual kallikreins are partly due to the presence of proteinase subsites which accommodate residues remote from the scissile bond in the substrate. These sites could be located in variable loops that surround the kallikrein active sites, and correspond to regions of lower structural similarity. Molecular modeling studies indicate that loop 4 may contribute to the P4-P7 specificity of kallikreins.

Amino Acid Sequence↗
PubMed1995

Conserved cystatin segments as models for designing specific substrates and inhibitors of cysteine proteinases.

Peptide segments derived from consensus sequences of the inhibitory site of cystatins, the natural inhibitors of cysteine proteinases, were used to develop new substrates and inhibitors of papain and rat liver cathepsins B, H, and L. Papain hydrolyzed Abz-QVVAGA-EDDnp and Abz-LVGGA-EDDnp at about the same rate, with specificity constants in the 10(7) M-1 sec-1 range; cathepsin L also hydrolyzes both substrates with specificity constants in the 10(5) M-1 sec-1 range due to lower k(cat) values, with the Km's being identical to those with papain. Only Abz-LVGGA-EDDnp was rapidly hydrolyzed by cathepsin B, and to a lesser extent by cathepsin H. Peptide substrates that alternate these two building blocks (LVGGQVVAGAPWK and QVVAGALVGGAPWK) discriminate the activities of cathepsins B and L and papain. Cathepsin L was highly selective for cleavage at the G-G bond of the LVGG fragment in both peptides. Papain and cathepsin B cleaved either the LVGG fragment or the QVVAG fragment, depending on their position within the peptide. While papain was more specific for the segment located C-terminally, cathepsin B was specific for that in N-terminal position. Peptidyl diazomethylketone inhibitors based on these two sequences also reacted differently with papain and cathepsins. GlcA-QVVA-CHN2 was a potent inhibitor of papain and reacted with papain 60 times more rapidly (k + 0 = 1,100,000 M-1 sec-1) than with cathepsin L, and 220 times more rapidly than with cathepsin B. Cathepsins B and L were preferentially inhibited by Z-RLVG-CHN2. Thus cystatin-derived peptides provide a valuable frame-work for designing sensitive, selective substrates and inhibitors of cysteine proteinases.

Amino Acid Sequence↗
PubMed1995

Liver retransplantation in children.

Between January 1988 and December 1993, 132 children received 154 orthotopic liver transplantation (OLT) at Bicêtre Hospital (France). Among them, 18 children underwent two and 2 children underwent three transplants (retransplant rate; 15.2%). Retransplantations were classified into three groups according to the interval between both OLTs: 1 (< 7 days, n = 8), 2 (8 days to 6 months, n = 10) and 3 (> 6 months, n = 4). Each group was compared with a control group whose grafts survived more than 1 week. There were no significant differences regarding age (35 +/- 49, 23 +/- 13, and 33 +/- 15 versus 49 +/- 41 months), cold ischemic time (566 +/- 105, 470 +/- 144, and 476 +/- 58 versus 455 +/- 110 minutes) and reduced size graft ratio (62.5%, 60%, and 75%, versus 58.3%). The causes of graft failure included primary nonfunctioning liver (PNF, n = 8) all in group 1 cases, biliary complications associated with hepatic artery thrombosis (HAT, n = 10; group 2, 6; group 3, 4), chronic rejection (n = 3; group 2, 1; group 3, 2) and three others (uncontrollable acute rejection, fulminant hepatitis, and secondary dysfunction, all in the group 2). The authors were unable to detect the cause of PNF. The overall survival rate after retransplantation was 62.5%, 60.0% and 75%, respectively. To reduce the rate of retransplants and improve the prognosis after OLT, further investigation into the cause of PNF, refinements in the anastomotic technique of the hepatic artery, and also early treatment of HAT are some of the goals to be achieved.

Adolescent↗