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Shinji Uemoto

Publications and source records attributed to Shinji Uemoto.

64 records · Page 4Linked to original sources
PubMed2002

Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus.

BACKGROUND: The immunosuppressant tacrolimus shows poor and variable bioavailability following oral administration in clinical use. Recently, the hepatic and intestinal metabolisms, or first-pass effect, of tacrolimus have been suggested to be responsible for its bioavailability. In the present study, we investigated the respective contribution of the jejunum and ileum to the first-pass effect of tacrolimus in rats. METHODS: The metabolism of tacrolimus in everted sacs of the duodenum, jejunum, and ileum was examined. Tacrolimus was administered intravenously or intraintestinally to sham-operated, jejunum-resected, or ileum-resected rats. Blood samples were collected over a 240-min period, and whole-blood tacrolimus concentrations were measured by semiautomated microparticle enzyme immunoassay. The pharmacokinetic parameters of tacrolimus in each group were estimated. RESULTS: The metabolic activity of tacrolimus appeared to be the highest in the everted sacs of the duodenum. The bioavailability of tacrolimus in the jejunum- or ileum-resected rats was higher than that in sham-operated controls. On the other hand, the time to peak concentration in the jejunum-resected rats was about twofold slower than those in ileum-resected and sham-operated rats. CONCLUSIONS: These results suggested that the first-pass effect of tacrolimus in the small intestine shows regional differences and the extraction of tacrolimus in the small intestine consists of the amount of extraction in the jejunum and ileum. In addition, the ileum rather than the jejunum as a graft of segmental small bowel transplantation would be useful to avoid the adverse effects of tacrolimus.

Administration, Oral↗
PubMed2002

Subclinical central pontine myelinolysis following liver transplantation.

Central pontine myelinolysis (CPM) is a demyelinating disorder of unknown origin that almost exclusively affects the central portion of the basis pontis, and is one of the fatal neurological complications after liver transplantation. We describe two children with CPM detected incidentally after liver transplantation. To our knowledge, this is the first report of CPM diagnosed antemortem in children who had undergone liver transplantation. In our patients, there were no clinical manifestations associated with CPM. We conclude that, including silent cases such as our patients, CPM may be more prevalent than previously appreciated following liver transplantation.

Adolescent↗
PubMed2002

Refractory biliary leak from intrahepatic biliary-enteric anastomosis treated by selective portal vein embolization.

A 66-year-old woman underwent partial hepatectomy and pylorus-preserving pancreaticoduodenectomy for advanced Klatskin-type cholangiocarcinoma, and five intrahepatic biliary-enteric anastomoses were created. One anastomosis between the anterior-superior segmental bile duct and the jejunum developed a refractory biliary leak. Selective portal venous embolization with use of ethanol was performed in the anterior-superior portal branch to eliminate the production of bile by the target segment. The patient's clinical course was uneventful and the leak resolved after portal vein embolization.

Aged↗
PubMed2002

Hepatic copper concentration in children undergoing living related liver transplantation due to Wilsonian fulminant hepatic failure.

Liver transplantation is indicated for Wilson's disease (WD) patients having the fulminant form and end-stage liver failure. To evaluate whether living related liver transplantation (LRLT) can correct the copper metabolism in WD patients, we studied two children who underwent LRLT because of fulminant hepatic failure. They were 7 and 13 yrs old at the time LRLT was performed. Serum ceruloplasmin levels, serum copper levels, copper urine excretion, and hepatic copper concentrations were measured. Serum ceruloplasmin levels (16.7 +/- 1.2 mg/dL) and serum copper levels (67.0 +/- 1.4 microg/dL) were lower than the normal range after LRLT in case 1. In both patients, urinary copper excretion was reduced markedly after LRLT, but was not normalized (case 1, 191.2 +/- 182.2 microg/d; case 2, 140.0 +/- 156.7 microg/d). Hepatic copper concentrations were slightly elevated (case 1, 158.8 +/- 44.6 microg/g dry weight; case 2, 147.0 microg/g dry weight) after LRLT in both cases, but did not exceed 250 microg/g dry weight. LRLT is a curative procedure in Wilson's disease presenting fulminant hepatic failure or advanced cirrhosis. However, this study indicates that the conditions of copper metabolism in WD patients undergoing LRLT are similar to those in heterozygous genetic carriers. Because the living related donors are the parents who carry the abnormal gene, LRLT cannot completely restore the copper balance in WD patients.

Adolescent↗
PubMed2002

A successful liver transplantation for refractory hepatic veno-occlusive disease originating from cord blood transplantation.

An 11-month-old boy with acute lymphoblastic leukemia (ALL) underwent umbilical cord blood transplantation (CBT) from an unrelated donor after a first complete remission. Despite the prophylactic use of low molecular weight heparin, prostaglandin E1 and ursodeoxycholic acid, hepatic veno-occlusive disease (VOD) occurred on the 29th day after CBT. Furthermore, neither defibrotide nor antithrombin-III improved the hepatic coma and coagulopathy due to the hepatic VOD. On the 42nd day after CBT, he underwent living related liver transplantation (LRLT) with a left lateral segment graft from his father. He received tacrolimus for the prevention of rejection and graft-vs.-host disease (GVHD) and also received aggressive antifungal and antiviral prophylaxis. Although he showed signs of acute rejection on postoperative days 5 and 10, the postoperative course was uneventful in general. At present, 17 months after LRLT, the patient shows stable liver function and no signs of either GVHD or a relapse of ALL. In conclusion, LRLT can be seen as a feasible option for the treatment of a hepatic VOD after CBT, though aggressive prophylaxis for infection and the anticipation of acute rejection are of importance.

Cord Blood Stem Cell Transplantation↗
PubMed2002

Duct-to-duct biliary reconstruction in living donor liver transplantation utilizing right lobe graft.

OBJECTIVE: To assess the feasibility and safety of duct-to-duct biliary anastomosis for living donor liver transplantation (LDLT) utilizing the right lobe. SUMMARY BACKGROUND DATA: Biliary tract complications remain one of the most serious problems after liver transplantation. Roux-en-Y hepaticojejunostomy has been a standard procedure for biliary reconstruction in LDLT with a partial hepatic graft. However, end-to-end choledochocholedochostomy is the technique of choice for biliary reconstruction and yields a more physiologic bilioenteric continuity than can be achieved with Roux-en-Y hepaticojejunostomy. The authors performed right lobe LDLT with end-to-end duct-to-duct biliary anastomosis, and this study assessed retrospectively the relation between the manner of reconstruction and complications. METHODS: Between July 1999 and December 2000, 51 patients (11-67 years of age) underwent 52 right lobe LDLTs with duct-to-duct biliary reconstruction and remained alive more than 1 month after their transplantation. Interrupted biliary anastomosis was performed for 24 transplants and the continuous procedure was used for 28. A biliary tube was inserted downward into the common bile ducts through the recipient's cystic duct in 16 transplants (cystic drainage), or a biliary stent tube was pushed upward into the anastomosis through the cystic duct in four transplants (cystic stent), or upward into the anastomosis through the wall of the common bile duct in 31 transplants (external stent). RESULTS: Biliary anastomotic procedures consisted of 34 single end-to-end anastomoses, 11 double end-to-end anastomoses, and 7 single anastomoses for double hepatic ducts. Overall, 5 patients developed leakage (9.6%) and 12 patients suffered stricture (23.0%). For biliary anastomosis with interrupted suture, the incidence of stricture was significantly higher in the cystic drainage group (53.3%, 8/15) than in the stent group consisting of cystic stent and external stent (0%, 0/8). While the respective incidences of leakage and stricture were 20% and 53.3% for intermittent suture with a cystic drainage tube (n = 15), they were 7.7% and 15.4% for a continuous suture with an external stent (n = 26). There was a significant difference in the incidence of stricture. CONCLUSIONS: Duct-to-duct reconstruction with continuous suture combined with an external stent represents a useful technique for LDLT utilizing the right lobe, but biliary complications remain significant.

Adolescent↗
PubMed2002

C3435T polymorphism in the MDR1 gene affects the enterocyte expression level of CYP3A4 rather than Pgp in recipients of living-donor liver transplantation.

The bioavailability of structurally unrelated drugs is limited by active secretion via the multidrug resistance gene (MDR1) product P-glycoprotein (Pgp) from enterocyte into lumen as well as intestinal metabolism by cytochrome P450 IIIA4 (CYP3A4). In the present study, we analyzed whether genetic polymorphism of the MDR1 had some influence on the intestinal expression levels of Pgp and CYP3A4 and the tacrolimus concentration/dose ratio over the first postoperative days in recipients of living-donor liver transplantation (LDLT). Genotyping assays were performed for the major 10 polymorphisms in the MDR1 gene by the polymerase chain reaction-restriction enzyme length polymorphism method. The allele frequencies of variations at five positions were almost comparable with those in the former studies in Caucasians and Japanese, but there was no variation at the other five positions. Although no polymorphism correlated with the intestinal expression of MDR1 mRNA or the tacrolimus concentration/dose ratio in the LDLT recipients, the C3435T polymorphism significantly affected the intestinal expression level of CYP3A4 mRNA as follows; 3435C/C>3435C/T (P < 0.05 vs. 3435C/C)>3435T/T (P < 0.01 vs. 3435C/C). Therefore, the identified polymorphisms including C3435T in the MDR1 gene were indicated to have no influence on the intestinal expression level of Pgp or the tacrolimus concentration/dose ratio in the recipients of LDLT. On the other hand, the C3435T polymorphism of MDR1 was suggested to correlate with the enterocyte expression of CYP3A4 rather than Pgp linking unknown genetic variation in CYP3A4 gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Diagnosis of inflammatory pseudotumor of the liver.

Inflammatory pseudotumor (IPT) is a rare benign tumor of unknown origin, it has the appearance of a malignant tumor but has a benign histology and clinical course. Therefore, we studied five patients with IPT of the liver to determine what examination can aid in its diagnosis. Five cases of inflammatory pseudotumor of the liver were analyzed. All patients were examined by echography, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography (ERC) and angiography to diagnose the liver tumor. In all patients echography and CT scan showed a similar appearance while MRI showed a variable pattern. In two patients ERC showed a stenotic image of intra-hepatic bile ducts. In the angiographic study, the arterial phase in three patients showed a hypervascular tumor and in one patient, a hypovascular tumor. Vascular abnormality was presented in one patient. Similarly, portography in four patients showed some abnormality. We performed ultrasonography-guided percutaneous needle biopsy in two patients in order to diagnose IPT. Histological examinations of two patients were consistent with IPT. The other three patients underwent surgical treatment for a cholangiocellular carcinoma or abscess. It is difficult to diagnose IPT of the liver exclusively with an image examination. Ultrasonography-guided percutaneous liver biopsy should be performed in order to diagnose IPT by histology.

Aged↗
PubMedDate not supplied

Impact of venous drainage on regeneration of the anterior segment of right living-related liver grafts.

The effect of additional venous reconstruction on morphologic and functional regeneration of the anterior segment of right-lobe liver grafts was compared among three groups according to graft type: right liver graft without the middle hepatic vein (MHV) or MHV tributaries (n=7), with MHV tributaries (n=25) and with the MHV (n=10). Whole graft volume (GV) and anterior segment volume (ASV) were estimated from CT scans and post-operative laboratory data and daily ascitic fluid volume were examined. Peak GV in each group was reached two or three wk after surgery. The ASV/GV ratios of the grafts with the MHV or MHV tributaries were higher than those of grafts without additional venous reconstruction. However, the asparate aminotransferase and ascitic fluid volume values in the group that received grafts with MHV tributaries were higher than in the group that received grafts with the MHV in the same period. Although rapid enlargement of the anterior segment of right-lobe grafts with MHV tributaries occurred in the early post-operative period, complete functional liver regeneration may not occur even after additional tributary reconstruction. These results suggest that the selection of right-lobe grafts with the MHV is more beneficial for recipients, as long as donor safety is protected and that as many MHV tributaries as possible should be reconstructed in right-lobe grafts without MHV.

Adolescent↗