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Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 289 records · Page 16Linked to original sources
PubMed1993

Liver transplantation for Alagille's syndrome.

Twenty-three children with Alagille's syndrome and end-stage liver disease underwent liver transplantation with cyclosporine and low-dose steroid immunosuppression. Two to 9 years (mean, 4.4 years) after surgery, 13 (57%) of the children were still alive, with normal liver function. Three of the fatalities were due to cardiovascular failure secondary to associated cardiopulmonary disease. Mortality was higher among patients who had more severe cardiac disease and patients who had previously undergone a Kasai procedure. Although it has a higher than average risk, liver transplantation can be efficacious in patients with Alagille's syndrome and end-stage liver disease.

Adolescent↗
PubMed1993

Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion.

The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half-life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1% of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate post-operative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment.

Adult↗
PubMed1993

Rat liver lipids during ex vivo warm and cold ischemia and reperfusion.

Rat livers were flushed and stored ex vivo in Krebs-Henseleit buffer at 37 degrees C for 3 hr or in University of Wisconsin solution at 2 degrees C for 48 hr. After this they were perfused with recirculated Krebs-Henseleit solution at 37 degrees C for 1 hr. Levels of phospholipids (PL), free fatty acids (FFA), and conjugated dienes were determined at various times during ischemia and after 1 hr of reperfusion. After 3 hr warm ischemia, total PL content decreased by about 30% primarily because of decreases in phosphatidylcholine and phosphatidylethanolamine. One hour of reperfusion normalized PL levels. Total PL content was unchanged up to 48 hr of cold ischemia because of offsetting alterations in levels of PL classes. FFA accumulation during warm ischemia was about half that during cold ischemia. Conjugated diene concentration increased fivefold during warm ischemia but was unchanged during cold ischemia. Low PL levels and FFA accumulation along with production of conjugated dienes suggest that lipid oxidation is a major mechanism of PL degradation during warm, but not cold, ischemia of the liver.

Animals↗
PubMed1993

Liver transplantation for type I and type IV glycogen storage disease.

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1-5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types I and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting.

Amylopectin↗
PubMed1993

The transplantation of gastrointestinal organs.

Over a period of 33 years, it has become possible to successfully transplant individual intra-abdominal viscera or combinations of these organs. The consequences have been, first, new information about the metabolic interrelations that the visceral organs have in disease or health; second, the addition of several procedures to the treatment armamentarium of gastrointestinal diseases; and third, a more profound understanding of the means by which all whole organ grafts are accepted.

Animals↗
PubMed1993

Intestinal transplantation in children under FK 506 immunosuppression.

Intestinal transplantation, solitary (n = 3) or in combination with the liver (n = 7), was performed in 10 pediatric patients with intestinal failure. The liver was only replaced if there was liver failure and portal hypertension. Immunosuppression was based on FK 506. Two patients died, one of graft-versus-host disease and one of lymphoproliferative disease. One patient as still in the intensive care unit 1 month posttransplantation due to perioperative complications. The function of the intestinal grafts in the remaining patients is normal. All nutrition and medications including immunosuppression are being administered enterally. This series indicates that small bowel transplantation, alone or in combination with the liver, is feasible in pediatric patients.

Child↗
PubMed1993

Effects of combined administration of FK 506 and the purine biosynthesis inhibitors mizoribine or mycophenolic acid on lymphocyte DNA synthesis and T cell activation molecule expression in human mixed lymphocyte cultures.

Our objective was to obtain new information on the in vitro antilymphocytic action of the cytokine synthesis inhibitor FK 506 and the purine biosynthesis inhibitors mycophenolic acid (MPA; the active moiety of RS61443) and mizoribine (MZB) when used alone or in combination. When added at the initiation of six-day human mixed lymphocyte cultures (MLC), FK 506, MPA or MZB exhibited dose-dependent inhibition of T-lymphocyte DNA synthesis. FK 506, however, was 100-fold more potent than MPA, and 10,000-fold more potent than MZB. Combination of FK 506 with either MPA or MZB, each at suboptional concentrations, produced no more than additive inhibitory effects on 3H thymidine incorporation. Two-colour flow cytometric analysis of lymphocytes revealed that none of the drugs affected cell surface activation molecule expression (CD25 = IL-2R 55 kD alpha-chain, HLA-DR or CD71 = transferrin receptor [TR]) on allostimulated CD4+ or CD8+ cells harvested at three days of culture. By day six, however, all three agents, at levels which markedly inhibited proliferation, suppressed the expression of activation markers on both CD4+ and CD8+ cells. Also at day six, inhibition of activation molecule expression on CD4+ cells was achieved with the combination of FK 506 and either MPA or MZB at concentrations which, on their own, were ineffective. These data provide new, additional information on the in vitro antilymphocytic action of FK 506, MPA and MZB when used alone and in combination.

Cells, Cultured↗
PubMed1993

Hepatic resection for cystic lesions of the liver.

OBJECTIVE: The purpose of this study was to report the authors' experience with hepatic resection for cystic lesions of the liver. SUMMARY BACKGROUND DATA: Past experience with aspiration, sclerosing therapy, internal drainage, fenestration, and marsupialization are of limited value. Hepatic resection has evolved into a safe operation over the last two decades. METHODS: A retrospective study of 44 patients with various cystic lesions of the liver (polycystic disease, 2; solitary or multiple congenital cysts, 19; biliary cystadenoma, 6; cystadenocarcinoma, 3; squamous cell carcinoma, 3; Caroli's disease, 5; and hydatid cyst, 6) was performed. RESULTS: After 7 trisegmentectomies, 24 lobectomies, 6 left lateral segmentectomies, and 7 nonanatomical hepatic resections, only 1 operative death occurred in a Jehovah's Witness. Symptomatic relief was complete and permanent in all of the patients with benign congenital or parasitic hepatic cysts, except for the two patients with polycystic disease of the liver. One of the 3 patients with adenocarcinoma and 3 patients with squamous cell carcinoma of the cyst wall died of tumor recurrence between 3 and 14 months after hepatic resection. CONCLUSIONS: Hepatic resection is safe and effective for cystic lesions of the liver. Symptomatic relief is complete and permanent after hepatic resection, except in cases of diffuse polycystic disease of the liver. Liver transplantation should be considered for diffuse polycystic disease of the liver when the symptoms are extremely severe.

Adult↗
PubMed1993

Graft-versus-host disease after brown Norway-to-Lewis and Lewis-to-Brown Norway rat intestinal transplantation under FK506.

In LEW rats treated daily with variable doses of FK506 for 14 days and weekly thereafter, successful intestinal transplantation from fully allogeneic BN donors never was complicated by fatal GVHD. In contrast, with LEW-to-BN transplantation, rejection was difficult to control and GVHD developed after the end of the daily treatment. However, FK506 in high daily doses continued after the initial 14-day course could prevent this GVHD or even reverse it after allowing its onset. Further experiments did not clarify why the BN rat was an "easy" donor and "difficult" recipient. In unaltered animals the lymphocyte population of normal LEW rats had a higher proportion of T cells, fewer B cells, and a lower CD4:CD8 ratio than normal BN rats. However, one-way MLR reactions of the BN and LEW combinations were generally similar in either direction and not affected differently by the addition of FK506 to the medium. The two-way lymphocyte traffic from graft to host lymphoid organs and vice versa also was similar with BN-to-LEW and LEW-to-BN models. The BN rat may be a useful tool to investigate inadequately explained mechanisms of GVHD.

Animals↗
PubMed1993

Pediatric liver transplantation. History, recent innovations, and outlook for the future.

Pediatric liver transplantation has advanced remarkably over the past three decades. One-year survival has progressively increased to nearly 90% in patients transplanted for most forms of liver disease. Parallel advances in organ procurement, operative technique, immunosuppression, and infection control are responsible for improved patient survival. Among the most important advances are use of the University of Wisconsin (UW) organ preservation solution, the employment of venovenous bypass and/or "piggyback" operative technique, the development of cyclosporine A (CyA) and FK506, and the emergence of acyclovir, ganciclovir, foscarnet, and alpha interferon to combat life-threatening viral infections. The current organ shortage is being addressed by "cutdown" liver transplantation, "split liver" transplantation, and living-related donations. The next decade is likely to see advances in multi-visceral transplantation, induction of chimerism by simultaneous bone marrow-solid organ transplantation, and performance of cross-species xenografting.

Child↗
PubMed1993

Contrast examination of the small bowel in patients with small-bowel transplants: findings in 16 patients.

OBJECTIVE: The purpose of this study was to describe the findings on contrast examinations of the gastrointestinal tract in patients with small-intestinal transplants. SUBJECTS AND METHODS: Sixteen consecutive adult transplant recipients received a total of 17 allografts: eight isolated small-bowel, six small-bowel and liver, and three multivisceral (stomach, duodenum, pancreas, small-bowel, liver). Grafts included the entire mesenteric small bowel. Gastrointestinal contrast studies were done in asymptomatic patients according to protocol and in patients having clinical indications for examination. Median time from transplantation to examination was 78 days (range, 5-768 days). Seventy-five gastrointestinal contrast examinations were performed: 53 upper gastrointestinal and small-intestinal series, 12 upper gastrointestinal series, eight enteroclyses, and two water-soluble contrast enemas. Radiographs were analyzed for postsurgical anatomy, integrity of anastomoses, allograft radiologic appearance, small-bowel transit time, and rate of gastric emptying. RESULTS: Usual postsurgical anatomy included native-to-donor duodenojejunal, jejunojejunal, and gastrogastric anastomoses and donor-to-native ileocolonic and ileoileal anastomoses. No anastomotic complications were found. Leaks at native duodenal and colonic stumps resulted in a duodenocutaneous fistula and an abscess, respectively. Moderate to marked thickening of mucosal folds consistent with edema was present in nine allografts (53%) and 11 (17%) of 66 upper gastrointestinal and small-intestinal examinations, primarily in the early postoperative period. Chronic loss of allograft mucosal folds developed in four grafts in three patients; pathologic diagnoses included acute and chronic rejection and enteric infection; a jejunocutaneous fistula developed in one such patient. Transit times of barium through the small intestine ranged from 0.2 to 17.8 hr (median, 2 hr). Self-limited delayed gastric emptying was present in 14 patients (88%) and 32 (60%) of 54 upper gastrointestinal and small-intestinal examinations. CONCLUSION: Gastrointestinal contrast examinations in recipients of small-bowel transplants are useful for assessing graft anatomy, enteric anastomoses, and gastrointestinal motor function. Most intestinal grafts showed normal caliber and mucosal pattern and exhibited active peristalsis. Abnormal findings included self-limited postoperative edema of graft mucosal folds, chronic loss of the mucosal folds due to rejection and/or enteric infection, delayed gastric emptying that improved with time, leaks from native duodenal and colon stumps, and a jejunocutaneous fistula in a failing graft. Small-intestinal transit times were similar to those observed in patients not receiving transplants, although there was wide variation.

Adult↗