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Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 469 records · Page 26Linked to original sources
PubMed1990

Overview of FK506 in transplantation.

FK506 is a potent immunosuppressive agent which is undergoing clinical testing in liver, kidney, heart, and bone marrow transplantation. It has been shown to effectively prevent and reverse ongoing rejection in these models. From the outset, FK506 was used with low-dose steroids to treat 110 primary liver, 30 heart, and 66 kidney graft recipients. FK506 was also used in the setting of complications related to CsA or to ongoing chronic or acute rejection. One hundred seventy-three liver, 21 kidney, 10 heart, and 11 bone marrow recipients were converted to FK506 and low-dose steroids, from a combination of CsA, steroids, and/or Aza. A randomized, prospective trial comparing FK506 with CsA in primary liver transplantation has verified the lower incidence of rejection and greater ease in treating rejection episodes, with fewer adverse effects. In summary, FK506 has proven to be an effective baseline immunosuppressive agent, as well as a dose-adjustable agent for the treatment of rejection.

Anti-Bacterial Agents↗
PubMed1990

[Effects of mesna (2-mercaptoethane sodium sulfonate) in children with malignant disease receiving oxazaphosphorine chemotherapy].

We studied the efficacy of mesna as a protectant for urotoxicity in pediatric patients receiving chemotherapy including oxazaphosphorines. Nineteen patients with malignant diseases (5 neuroblastoma, 3 acute lymphocytic leukemia, 4 acute non-lymphocytic leukemia, 2 non-Hodgkin lymphoma, 3 osteosarcoma and 2 rhabdomyosarcoma) were treated with a total of 106 courses of therapy between June of 1986 and May of 1989. Of these, no gross hematuria were seen. Microhematuria transiently occurred only in 2 courses (5%) of 1 patient (2%). These data indicated that mesna was highly effective for urotoxicity of oxazaphosphorines without any side effects, especially in pediatric patients.

Bone Neoplasms↗
PubMed1990

Liver transplantation in the treatment of primary liver cancer.

One hundred and fifteen patients underwent orthotopic liver transplantation (OLT) for primary liver malignancy. Overall survivals of these patients were significantly lower than those of patients with non-malignant diseases (5-year survival rates 37% and 65%, respectively). Hepatocellular carcinoma (HCC) was the most common malignancy among our patients (n = 80). Fibrolamellar HCC (n = 9) was associated with better survival than non-fibrolamellar HCC (N = 71) among the lesions greater than or equal to 5 cm in diameter. More frequent recurrence was noted in patients with large tumors (greater than or equal to 5 cm), multiple tumors, and gross vascular involvement. A significant lower survival rate was observed in patients with bile duct cancer (n = 19) than in those with HCC or epithelioid hemangioendothelioma (n = 8). Careful patient selection and effective adjuvant anti-cancer therapy are needed to improve the results of OLT for primary liver malignancy.

Carcinoma, Hepatocellular↗
PubMed1990

The hepatotropic influence of cyclosporine.

The effect of cyclosporine on liver regeneration has been investigated in 25 dogs that underwent an end-to-side portacaval shunt (Eck fistula) followed by 4 days continuous infusion of the drug into the left branch of the portal vein. Three different cyclosporine infusion rates were used: 0.06, 0.6, and 4.0 mg/kg/day. Control animals received the intravenous vehicle of cyclosporine at the same rate as the treated animals; a second control group received insulin, 0.42 units/kg/day. Hepatocyte 3H-thymidine-labeled mitoses (index of hyperplasia) and hepatocyte volume (index of hypertrophy) were studied in the left (infused) and right (control) lobes in each animal. Cyclosporine vehicle had no measurable effect on hepatocytes that suffered typical atrophy and moderate increase in mitotic index after the Eck fistula. Cyclosporine infusion stimulated cell renewal significantly and restored hepatocyte size in the infused lobes with a dose-response relation. Similar positive effects were observed in the right (nonperfused) lobes, although they were less than those in the left (infused) lobes. This was because of an unmistakable spillover of cyclosporine from the infused lobes, especially in the large-dose group. No sign of hepatotoxicity was detected at any cyclosporine infusion rate. Cyclosporine has a remarkable hepatotropic effect that may be helpful in the context of liver transplantation.

Animals↗
PubMed1990

Rejection of multivisceral allografts in rats: a sequential analysis with comparison to isolated orthotopic small-bowel and liver grafts.

Multivisceral isografts and allografts were transplanted to Lewis rats, and the histopathologic changes were studied in the liver, intestine, and other constituent organs. Rats receiving isografts had indefinite survival with maintenance of weight. With multivisceral allografts (from Brown-Norway donors), the intestinal component was rejected more severely than the companion liver and with about the same severity as when intestinal transplantation was performed alone. Intestinal rejection in either circumstance was a lethal event, causing death in 10 to 12 days. The earliest (by day 4) and most intense cellular rejection was in the Peyer's patches and mesenteric lymph nodes. This was associated with or followed by cryptitis, epithelial cell necrosis, focal abscess formation, mural necrosis, and eventual perforation. Liver allografts transplanted alone or as part of multivisceral grafts also had histopathologic evidence of rejection, but this was self-limiting and spontaneously reversible when the liver was transplanted alone. Thus the Achille's heel of multivisceral grafts is the intestinal component that is not protected by the presence of the liver in the organ complex. Better immunosuppression should permit successful experimental and clinical transplantation of such grafts.

Animals↗
PubMed1990

Analysis of surgical complications after 397 hepatic transplantations.

The results of 397 consecutive orthotopic hepatic transplantations in 333 recipients were reviewed. One or more surgical complications developed in 172 of 323 patients (55 per cent), excluding ten intraoperative deaths. The six month mortality rate among the patients with surgical complications (55 of 172; 32 per cent) was statistically higher than that among patients without such complications (16 of 151; 11 per cent) (p less than 0.001; chi-square, 58.36). Surgical complications included exploratory laparotomy for bleeding or infection in 74 (22 per cent), reconstruction of the bile duct for biliary obstruction or leakage in 55 (17 per cent), external biliary drainage for biliary leakage in four (1 per cent), tracheostomy in 80 (24 per cent), thoracotomy in 12 (4 per cent) and splenectomy in seven (2 per cent). The incidence of biliary obstruction (16 per cent mortality rate) and leakage (48 per cent mortality rate) was 18 per cent (34 of 193) and 2 per cent (four of 193) each after choledochocholedochostomy, which was 3 per cent (five of 187) and 9 per cent (17 of 187) each after choledochojejunostomy. Biliary obstruction (16 per cent mortality rate) was more common after choledochocholedochostomy (p less than 0.005; chi-square, 23.01), whereas the incidence of more serious biliary leakage (48 per cent mortality rate) was higher after choledochojejunostomy (p less than 0.005; chi-square, 8.97). It is concluded that orthotopic hepatic transplantation remains an unforgiving extensive surgical procedure, in which choledochocholedochostomy remains the first-choice reconstruction of the biliary tract because of its lower mortality.

Adult↗
PubMed1990

Evolution of hepatitis B virus liver disease after hepatic replacement. Practical and theoretical considerations.

The morphologic evolution of hepatitis B virus (HBV) liver disease in 45 hepatic allograft recipients who were HBV surface-antigen positive (HBs-Ag+) at the time of liver replacement and who survived for more than 60 days was studied by routine histologic and immunocytochemical analysis of serial pathology specimens. The findings in these patients were compared to a control group of 30 individuals who were immune to the HBV (anti-HBs antibody positive), but required hepatic replacement for other reasons. Eight of the forty-five (18%) HBsAg-positive patients have no serologic evidence of HBV reinfection after transplantation. All 37 remaining patients are reinfected; 21 (47%) developed chronic active hepatitis and/or cirrhosis, 3 (7%) developed submassive necrosis, and 6 (14%) developed chronic lobular hepatitis. One patient lost her graft to chronic rejection, despite reinfection with the B virus. Four other patients (9%) developed a chronic carrier state. No long-term follow-up biopsies were available in the remaining two patients. The histologic features associated with dysfunction related to recurrent HBV infection evolved from an acute to chronic phase and were similar to hepatitis B seen in nonallografted livers. Furthermore HBV-related lesions could be separated from rejection using routine histology alone. The only exception to this conclusion was the occurrence of a peculiar HBV-related lesion in two recipients, described herein. Immunohistochemical analysis demonstrated the presence of viral antigens in almost all cases. Hepatic inflammation also was commonly present during HBV disease and consisted mostly of accessory cells and T lymphocytes. Analysis of the effect of major histocompatibility complex matching revealed no clear association between the number of class I or II matches or mismatches and the development, or pattern, of active hepatitis in the allograft. Peculiar pathologic alterations in several of the biopsies and failed allografts after HBV reinfection suggests that, under special circumstances, the B virus may be cytopathic.

Graft Rejection↗
PubMed1989

FK 506 for liver, kidney, and pancreas transplantation.

FK 506 was given for immunosuppression in 14 liver recipients. The drug was used in the first 10 cases because the recipients under conventional immunosuppression had rejection, nephrotoxicity, or both. This salvage therapy was successful in 7 of the 10 attempts. 2 of the 10 patients in the original salvage group as well as 4 new patients underwent fresh orthotopic liver transplantation under FK 506 plus low-dose steroids from the outset. None of these 6 patients had rejection although 1 with preexisting cor pulmonale and coronary atherosclerosis died of a myocardial infarction. In addition, 2 of the 14 liver recipients were given cadaveric kidneys, either from the same donor or from a different donor, and a third was given a pancreas as well as a kidney from the liver donor. There were no rejections of the kidney and pancreas grafts, and serious side-effects were not encountered.

Administration, Oral↗
PubMed1989

Endotoxaemia, pulmonary complications, and thrombocytopenia in liver transplantation.

Plasma endotoxin was measured in 64 patients undergoing primary liver replacement. Endotoxin concentrations increased during the anhepatic phase of the operations, and remained high for several days. Although the severity of endotoxaemia did not correlate with duration of the anhepatic phase, there was a correlation between endotoxaemia and the need for perioperative platelet transfusions, ventilator dependency postoperatively, and one-month case-fatality.

Adult↗
PubMed1989

Transplantation of multiple abdominal viscera.

Two children with the short-gut syndrome and secondary liver failure were treated with evisceration and transplantation en bloc of the stomach, small intestine, colon, pancreas, and liver. The first patient died perioperatively, but the second lived for more than 6 months before dying of an Epstein-Barr virus-associated lymphoproliferative disorder that caused biliary obstruction and lethal sepsis. There was never evidence of graft rejection or of graft-vs-host disease in the long-surviving child. The constituent organs of the homograft functioned and maintained their morphological integrity throughout the 193 days of survival.

Animals↗
PubMed1989

Extended preservation of human liver grafts with UW solution.

The fate of 185 cadaveric liver homografts preserved for four to 24 hours with University of Wisconsin (UW) solution was compared with that of 180 grafts preserved for three to 9 1/2 hours with conventional Euro-Collins solution. Although the average preservation time of the UW-preserved livers was almost twice as long as that of the Euro-Collins-preserved livers, the UW-preserved grafts survived at a higher rate; permitted equal patient survival; and had a lower rate of primary nonfunction, a reduced need for retransplantation, and a lower rate of hepatic artery thrombosis. There was no correlation between the time of preservation of UW-preserved grafts up to 24 hours and liver function abnormalities in the first postoperative week. In contrast, livers preserved with Euro-Collins solution for more than five hours had significantly increased perturbations of hepatic function tests. The potential revolutionary effect of the UW solution on liver transplantation is described herein.

Cause of Death↗
PubMed1989

Biliary tract complications in orthotopic adult liver transplantation.

In a series of orthotopic liver transplantations performed between April and August 1987 at the University of Pittsburgh, the monofilament absorbable suture polyglyconate was compared with a braided absorbable suture, polyglactin 910, for its biliary complication rate over a 6-month postoperative period. Complications that were suture-related (obstruction or leak from the anastomotic site) occurred in 1 of 21 transplantations in the polyglyconate group compared with 8 of 26 in the polyglactin 910 group (p = 0.02). Even though the patient sample was relatively small, it appears that the type of suture used for the biliary anastomosis directly correlates with the outcome. A larger patient trial could confirm these initial results.

Anastomosis, Surgical↗
PubMed1989

Liver transplantation for primary biliary cirrhosis.

Liver transplantation is an effective treatment for PBC. The Pittsburgh experience is reported, with 1- and 5-year survival of 75.62% and 70.71%, respectively. Recurrence of PBC, when it occurs, has not been of clinical significance. Transplantation markedly improves chances for survival, an advantage that is demonstrable in all of the risk groups. Rehabilitation is achieved after transplantation in approximately 90% of the patients. Some clinical variables are associated with a poorer outcome and indicate the need for earlier treatment.

Aged↗