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Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 559 records · Page 31Linked to original sources

Indications for pediatric liver transplantation.

Two hundred fifty pediatric (less than 18 years of age) patients underwent orthotopic liver transplantation because of end-stage liver disease and were given combination therapy with cyclosporine and prednisone. The most common indications for transplantation in decreasing order of frequency were biliary atresia, inborn errors of metabolism, and postnecrotic cirrhosis. The 5-year actuarial survival for the entire group was 69.2%. Age and diagnosis did not influence survival. Infections were the most common cause of death, followed by liver failure and cerebrovascular accident. The impact of retransplantation on survival depends on the indication. The survival is better when retransplantation is carried out after rejection than because of technical complications, and the latter has a better survival than does primary graft nonfunction. The difference in survival among these groups is statistically significant. The quality of life for 164 of 173 survivors is good to excellent; only nine children are currently experiencing medical problems. A persistent problem in pediatric transplantation is the scarcity of small donors.

Adolescent↗

Liver transplantation before 1 year of age.

Since 1981, 20 infants younger than 1 year of age received 26 orthotopic liver transplants. Immunosuppression was with cyclosporine and corticosteroids. Thirteen (65%) of the recipients were discharged from the hospital. To date, 12 (60%) of the 20 recipients are surviving, with follow-up of 1 to 56 months (average 14 months). The 5-year actuarial survival is 53.8%. The allograft liver function in the majority of surviving infants is excellent. The predominant causes of mortality were primary nonfunction of the allograft (three patients) and sepsis (three). Major morbidity was caused by hepatic artery thrombosis (five patients), gastrointestinal complications (six), biliary tract complications (five), and bacterial and viral infections (13). Six patients underwent retransplantation; three of these six survived. Results could be improved by prevention of hepatic artery thrombosis, by decreasing the incidence of sepsis, and by procurement of more and better suited pediatric donors.

Actuarial Analysis↗

Liver transplantation today.

In summary, liver transplantation has truly come of age. To put things in perspective, the recipient waiting list at the University of Pittsburgh never includes fewer than 200 suitable candidates, and it continues to grow in spite of the fact that we are now doing essentially one transplant per day. There are many excellent transplant centers throughout the United States and Europe, the only limiting factor being the supply of donors. Orthotopic liver transplantation is now covered by most major health insurance carriers, and some form of government coverage is anticipated for the indigent. As the supply of donors increases with aggressive education programs, the need for transplantation centers will also increase. However, this should not be uncontrolled growth. Mandatory training in transplantation surgery will surely be required as a prerequisite to the establishment of transplant centers in the future. The field of organ transplantation is the newest and most dynamic in medicine today. The results are encouraging and acceptable and offer the only hope to many persons dying of end-stage organ failure. With improvements in immune modulation at hand, organ transplantation will soon become a commonplace procedure offering a completely normal life expectancy.

Graft Rejection↗

Complications of venous reconstruction in human orthotopic liver transplantation.

In 313 consecutive recipients of 393 orthotopic liver grafts, there were 51 (16.3%) and nine (2.9%) patients who had pre-existing portal vein and inferior vena cava abnormalities, respectively. These abnormalities required adjustments in the transplant operation and were a source of morbidity and mortality. The incidence of thrombosis of the reconstructed portal vein was 1.8%. Only three (0.8%) vena caval thromboses were seen after 393 liver replacements. Venous stenoses or disruptions were rare. Six women with the Budd-Chiari syndrome had liver replacement. Although this disorder is a veno-occlusive disease, five of the recipients achieved prolonged survival, only one had recurrence of disease, and three are alive after 2-6 years.

Adolescent↗

Prolongation of pig-to-dog renal xenograft survival by modification of the inflammatory mediator response.

The pathogenesis of hyperacute renal rejection consists of a nonspecific effector cascade that invokes most of the components of a typical acute inflammatory response. Platelet-activating factor (PAF) represents the most recent and perhaps the most significant mediator and promoting agent of this phenomenon. These studies evaluated SRI 63-441, a novel, synthetic, and the most potent PAF receptor antagonist available, alone and in combination with other prostanoids, for their ability to influence this response and to prolong renal xenograft survival and function in a model of pig-to-dog heterotransplantation. Inhibition of PAF by SRI 63-441 alone, at the dosage and schedule used in these experiments, did not significantly prolong xenograft survival or function. However, the combination of SRI 63-441 with either prostacyclin (PGI2) or prostaglandin E1 (PGE1) infusion demonstrated significant synergism, and resulted in a 6-9-fold increase in kidney survival and a 3-20-fold increase in urine output. Neither PGI2 nor PGE1 infusions alone significantly influenced this xenograft model. Electromagnetic flow studies demonstrated significantly delayed diminution in renal artery blood flow in the combination-treated animals. Serial and end-stage histologic examination of kidneys receiving combination therapy demonstrated a delayed onset of the pathologic deterioration and an overall amelioration of the entire process. These studies demonstrate that significant abrogation of a rapid and violent form of hyperacute rejection can be achieved solely by the pharmacologic manipulation of the inflammatory mediator response.

Alprostadil↗

Biliary tract complications in human orthotopic liver transplantation.

The results of 393 consecutive orthotopic liver transplants in 313 patients were reviewed to determine the incidence of primary biliary tract complications. There were 52 biliary tract complications in 393 grafts (13.2%), and 5 directly related deaths. Choledochojejunostomy over an internal stent to a Roux-en-Y limb of proximal jejunum (RYCJ-S) was the most frequently used technique (175 cases) and the most successful with only 9 technical failures (5.2%). Choledochocholedochostomy over a T tube (CC-T) was used in 159 cases and was successful in all but 20 cases (12.6%). Other methods of reconstruction were associated with high failure rates or technical complexity that do not justify their use. Biliary leak and obstruction were the most common complications. Leakage after CC-T at the T tube exit site was usually directly repaired, but anastomotic leakage required conversion to RYCJ-S. Obstruction may be relieved by percutaneous balloon dilatation but definitive treatment also usually required conversion to RYCJ-S. The most common complication after RYCJ-S is functional obstruction by a retained stent, which has a low morbidity but may necessitate surgical removal. Anastomotic leaks, which occurred in 2 cases, were successfully managed by revision of the choledochojejunostomy.

Adult↗

Monoclonal antibody therapy with ciclosporin and steroids in nonmatched cadaveric renal transplants.

Thirty-six ciclosporin-prednisone-treated recipients of nonmatched cadaver renal allografts were given a course of Orthoclone OKT3 monoclonal antibody for steroid-resistant cell-mediated rejection. Although side effects were common, only 2 patients had to be withdrawn from therapy and there were no deaths related to therapy. Twenty-three (63.9%) allografts were rescued with OKT3 therapy and 21 (58.3%) of the grafts have continued to function well. We conclude that OKT3 is an effective agent for the treatment of steroid-resistant cell-mediated rejection and that rebound rejection can be prevented in most patients if adequate therapy with ciclosporin-prednisone is maintained.

Adolescent↗

Biopharmaceutical aspects of FK-506.

FK is a potent immunosuppressive agent. FK can be analyzed in biologic fluids by EIA. The oral absorption of FK is rapid but variable in dogs. After intramuscular administration, FK is slowly and continuously absorbed. FK is primarily eliminated by metabolism. Less than 1% of the administered dose is excreted in the bile or the urine. After chronic intramuscular administration FK inhibits drug metabolism. Monitoring of FK levels in plasma is essential for the proper interpretation of efficacy and toxicity studies.

Administration, Oral↗

Orthotopic liver transplantation in dogs receiving FK-506.

Ten dogs that survived the perioperative events of liver transplantation were treated with 1 mg/kg/d oral FK. Eight of the recipients lived for at least 1 month postoperatively, and seven are still alive with normal hepatic function after 35 to 65 days. The consistency and good quality of results with this difficult transplant preparation using FK, in spite of its rumored great toxicity in dogs, have highlighted the importance of further developing the drug.

Animals↗

Heterotopic heart transplantation in the rat receiving FK-506 alone or with cyclosporine.

In rats, FK significantly prolonged heterotopic heart graft survival over a wide dose range when given for 2 weeks starting on the day of the operation. Brief courses of FK for one to four days preoperatively, and especially beginning four days postoperatively, allowed long subsequent survival of heart grafts in otherwise untreated recipients. The seeming acceptance of the grafts with postoperative FK treatment was largely but not exclusively donor specific when tested eight days after the last FK dose by second grafts from the same donor v third-party donor grafts. FK in minimally therapeutic doses was synergistic with suboptimal doses of CyA.

Abdomen↗

OKT4 epitope deficiency in a patient with acute myeloblastic leukemia.

The association of OKT4 epitope deficiency and acute myeloblastic leukemia (M1 by FAB) in a 12-year-old girl is reported. The patient's peripheral lymphocytes lacked the antigen identified by the OKT4 monoclonal antibody, but showed normal OKT4A and Leu-3a reactivity. Functional studies of the lymphocytes revealed normal responses to mitogens, but slightly reduced helper T cell function. The patient responded well to antileukemia chemotherapy and has been in remission for 30 months. The possible link between OKT4 epitope deficiency and the pathogenesis of AML is discussed.

Antibodies, Monoclonal↗

Glucose metabolism during liver transplantation in dogs.

Arterial and hepatic venous blood levels of glucose were studied in 12 dogs during orthotopic liver transplantation performed under ketamine anesthesia without exogenous glucose administration. During the early part of surgery, arterial blood glucose levels were stable: 161 +/- 12 mg/dl (mean +/- SEM) after laparotomy and 183 +/- 16 mg/dl 5 min before the anhepatic stage. During the anhepatic stage, arterial blood glucose levels decreased progressively to 135 +/- 9 and 88 +/- 8 mg/dl, 5 min in the anhepatic stage and 5 min before reperfusion of the graft liver, respectively (P less than 0.05). Reperfusion of the graft liver resulted in an increase in arterial glucose levels to 206 +/- 17 and 240 +/- 24 mg/dl, 5 and 30 min after reperfusion, respectively (P less than 0.05). Hepatic venous blood glucose levels increased after reperfusion (405 +/- 37 and 346 +/- 41 mg/dl, 5 and 30 min after reperfusion, respectively) and were significantly higher than in arterial blood (P less than 0.05). Arterial plasma insulin, measured in five animals, did not change significantly during the procedure, whereas plasma glucagon levels, stable during the preanhepatic and anhepatic stages, increased steadily after reperfusion of the graft liver, from 66.1 +/- 14.2 to 108.4 +/- 38.1 pg/ml (P less than 0.05). This study shows that in dogs with ketamine anesthesia mild hypoglycemia occurs during the anhepatic stage of liver transplantation without exogenous glucose administration followed by hyperglycemia on reperfusion of the graft liver, possibly secondary to the release of glucose from the donor liver.

Analysis of Variance↗

Thymic localization of gallium-67 in pediatric patients with lymphoid and nonlymphoid tumors.

To determine the significance of 67Ga localization in the thymus of children, 142 67Ga photoscans from 45 children with various tumors were studied. Sixty-nine photoscans were taken for 17 cases of lymphoma, 73 photoscans were made for 28 cases of nonlymphoid tumors. Thymic localization of 67Ga was positive in 16 (36%) of the 45 patients and in 30 (21%) of the 142 photoscans. Positive thymus scans were seen in five (29%) of the 17 cases of lymphoma and 11 (39%) of the 28 solid tumors. The positive incidence was highest (90%) in ages 1-2 yr old. Of the eight grade 2 (strong positive) patients, the thymus in one case of Hodgkin's disease was diagnosed as malignant and the other seven solid tumor cases were nonmalignant. Most of the latter seven cases became positive after beginning of treatment (surgery and/or chemotherapy). Although the precise mechanism is not well understood, thymic localization of 67Ga may represent immunologic response to tumors, especially in infants with nonlymphoid neoplasms.

Child↗