Search PubMed⌕ Search

Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 361 records · Page 20Linked to original sources
PubMed1991

Procoagulant activity and tumor necrosis factor in rat hepatic allograft rejection.

We used a model of rat hepatic allograft rejection to evaluate levels of procoagulant activity and tumor necrosis factor during acute cellular rejection. ACI livers were transplanted into Lewis rats, and Lewis-to-Lewis isografts and unoperated animals served as controls. Animals were killed on days 1, 2, 3, 4, 5, 6, 7 and 9. Splenic mononuclear cells were obtained by Ficoll-Hypaque gradients. Collagenase perfusion, metrizamide gradients and centrifugal elutriation were used to isolate Kupffer cells. Procoagulant activity assay of the splenic and Kupffer cells was done using a one-step clotting assay. Tumor necrosis factor was assayed using an L929 cytotoxicity assay. Histological evidence of acute rejection began on the 4th postoperative day, and rats died by the 9th or 10th postoperative day. Splenic procoagulant activity was significantly elevated in rejecting rats on day 4 and remained elevated until death. In contrast, Kupffer-cell procoagulant activity was elevated over controls by day 3 and remained significantly elevated until death. The tumor necrosis factor levels were elevated from day 1 and remained so until death. The data indicate that procoagulant activity is synthesized both by peripheral monocytes and locally by Kupffer cells and that procoagulant activity and tumor necrosis factor levels rise during hepatic allograft rejection. Because procoagulant activity and tumor necrosis factor mediate immune functions that are postulated to be important in acute rejection (immune cell adherence, vascular thrombosis and delayed-type hypersensitivity), these elevations may contribute to the pathogenesis of acute rejection.

Animals↗
PubMed1991

Detection of complications after liver transplantation by technetium-99m mebrofenin hepatobiliary scintigraphy.

Fifty-five hepatobiliary scintigraphic studies using 99mTc-Mebrofenin were performed in 52 orthotopic liver transplant patients to evaluate suspected biliary complications, namely biliary extravasation and extrahepatic obstruction. Final diagnosis was made by analysis of the clinical course and other procedures. Three out of three studies of biliary leak and four out of five studies of biliary obstruction were detected. There were no false positives in either complication. The sensitivity, specificity and accuracy were 100, 100, 100% for ectravasation and 80, 100, 98% for obstruction, respectively. Hepatobiliary scintigraphy appears to be an accurate means of detecting biliary leak and obstruction associated with the transplanted liver.

Adolescent↗
PubMed1991

The spectrum of portal vein thrombosis in liver transplantation.

Thrombosis of the portal vein with or without patency of its tributaries used to be a contraindication to orthotopic liver transplantation (OLTX) until quite recently. Rapid progress in the surgical technique of OLTX in the last few years has demonstrated that most patients with portal vein thrombosis can be safely and successfully transplanted. Presented here is a series of 34 patients with portal vein thrombosis transplanted at the University of Pittsburgh since 1984. The various techniques used to treat various forms of thrombosis are described. The survival rate for this series was 67.6% (23 of 34 patients). Survival was best for patients who underwent phlebothrombectomy or placement of a jump graft from the superior mesenteric vein. The survival rate also correlated with the amount of blood required for transfusion during surgery. Overall it is concluded that a vast majority of the patients with thrombosis of the portal system can be technically transplanted and that their survival rate is comparable to that of patients with patent portal vein.

Anastomosis, Surgical↗
PubMed1991

Hepatic resection versus transplantation for hepatocellular carcinoma.

During the 10-year period (1980 to 1989), 76 patients with hepatocellular carcinoma (HCC) were treated by subtotal hepatic resection (HX) and 105 patients by orthotopic liver transplantation (TX) under cyclosporine-steroid therapy. Overall 1- to 5-year survival rates of the HX group were 71.1%, 55.0%, 47.2%, 37.2%, and 32.9%, respectively, and those of the TX group were 65.7%, 49.0%, 39.2%, 35.6%, and 35.6%, respectively. The survival rates after HX and after TX correlated well with pTNM stages and were similar in each stage between the two groups. However, when HCC was associated with cirrhosis of the liver, the survival rates after TX were significantly better than those after HX at each stage of pTNM classification. The tumor-recurrence rate was high both after HX (50%) and TX (43%), particularly in advanced stages of pTNM classification (60% or more). Twelve patients after HX and 13 patients after TX lived more than 5 years during this 10-year period. Fibrolamellar HCC and early stages of HCC were highly represented among the long-term survivors. Further improvement in survival rates depends on nonsurgical anti-cancer therapy before and/or after surgical removal of HCC.

Adolescent↗
PubMed1991

Hepatotrophic effects of FK506 in dogs.

Portacaval shunt (Eck fistula) in dogs causes hepatocyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this procedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of hepatocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506's efficacy for the treatment of chronic liver rejection. Also, the observations support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cytosolic binding sites of FK506, repatomycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.

Amino Acid Isomerases↗
PubMed1991

The clinical significance of the arterial ketone body ratio as an early indicator of graft viability in human liver transplantation.

Arterial ketone body ratio (AKBR) was measured sequentially in 84 liver transplantations (OLTx). These transplantation procedures were classified into 3 groups with respect to graft survival and patient condition at the end of the first month (Group A, the grafts survived longer than 1 month with satisfactory patient condition; Group B, the grafts survived longer than 1 month but the patients were ICU-bound; Group C, the grafts were lost and the patients died or underwent re-OLTx). In Group A, the AKBR was elevated to above 1.0 by the second postoperative day. In Group B, the AKBR was elevated to above 0.7 but stayed below 1.0 during this period. In Group C, the AKBR remained below 0.7 longer than 2 days after operation. Although conventional liver function tests showed significant increases in Groups B and C as compared with Group A, they were less specific in predicting ultimate graft survival.

Adolescent↗
PubMed1991

Effect of cold ischemia time on the early outcome of human hepatic allografts preserved with UW solution.

Five hundred ninety-three cadaveric livers were used for primary liver transplantation between October 24, 1987, and May 19, 1989. The grafts were procured with a combined method, using in situ cooling with cold electrolyte solution and backtable flushing with UW solution. The mean cold-ischemia time was 12.8 (range 2.4-34.7) hr. The cases were divided into 5 groups according to the cold-ischemia time: group 1: less than 10 hr (n = 223); group 2: 10-14 hr (n = 188); group 3: 15-19 hr (n = 101); group 4: 20-24 hr (n = 52); and group 5: greater than or equal to 25 hr (n = 29). There was no difference between the 5 groups in 1-year patient survival, highest SGOT in first week after operation, and SGOT and total bilirubin during the first month after operation. However, with a logistic regression model, the retransplantation rate (P = 0.001) and primary nonfunction rate (P = 0.006) significantly rose as cold-ischemia time increased, meaning that the equivalency of patient survival was increasingly dependent on aggressive retransplantation.

Adenosine↗
PubMed1991

The effect of graft function on FK506 plasma levels, dosages, and renal function, with particular reference to the liver.

Plasma FK506 was studied in 49 liver, 13 heart, 3 double-lung or heart-lung, and 21 kidney recipients. The levels were correlated with the drug doses used, kidney function, and liver function. In all varieties of recipients, there was an early rise in the FK506 plasma levels that occurred at the time of intravenous administration of the drug. At the same time or shortly after, there were increases in serum creatinine that were transitory except in liver recipients with continuing suboptimal graft function. The quality of hepatic function dominated all aspects of FK506 management in the liver recipients. Those who received well-functioning grafts could be given about the same drug doses as recipients of kidneys and the thoracic organs. Liver recipients with defective grafts had astronomical rises in plasma FK506, a high incidence of renal failure, and probably increased neurotoxicity. In kidney transplant recipients, the FK506 plasma levels and doses were essentially the same in patients with prompt versus delayed renal function. These studies have highlighted the necessity, first, of close pharmacologic monitoring of patients who are given FK506 in the presence of abnormal liver function, and second, of using smaller intravenous induction doses than in past practice.

Adolescent↗
PubMed1991

Treatment for stage III-IV neuroblastoma patients: initial response to chemotherapy evaluated by biochemical parameters.

Fourteen patients with stage III-IV neuroblastoma were treated with alternating combination chemotherapy consisting of (a) VP16/cisplatin and (b) doxorubicin/vincristine/cyclophosphamide. The initial response to induction chemotherapy, especially to VP16/cisplatin was evaluated by determining t 1/2 for urinary vanillylmandelic acid (VMA), homovanillic acid and serum neuron specific enolase (NSE). The period prior to normalization of these parameters was also determined. The patients could be classified as 7 rapid responders, with less than 3 weeks of t 1/2 VMA, or t 1/2 NSE, and 7 slow responders longer than 4 weeks of t 1/2 VMA. An analysis of the data indicates that an initial rapid response correlated with subsequent high complete response rate, but did not necessarily predict better prognosis in these patients.

Abdominal Neoplasms↗
PubMed1991

In-vitro interaction of a novel immunosuppressant, FK 506, and antacids.

The effect of selected antacids on the amount of FK 506 in solution in simulated gastric juice has been studied. FK 506 (2.5 mg) was incubated in 100 mL simulated gastric fluid (SGF) with the equivalent of 500 mg of various antacids. The addition of Mylanta and Tums resulted in 14 and 30% loss of FK 506, respectively, in 24 h; 98% loss was observed in 12 h in the presence of Mag-Ox; 100% loss was observed in the presence of magnesium oxide powder in 2 h. The loss of FK 506 from these solutions appears to be due to a pH mediated degradation of FK 506. The addition of aluminium hydroxide gel USP (Roxane) to the FK 506 solution resulted in a 35% loss within 2 min but no further loss was noted for 24 h, indicative of adsorption of FK 506. These results suggest that until additional in-vivo studies are carried out, it is prudent not to dose FK 506 and antacids at the same time to avoid potential interactions.

Antacids↗
PubMed1991

One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults.

An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration.

Adult↗
PubMed1991

The question of FK 506 nephrotoxicity after liver transplantation.

Formal studies have not been published on the nephrotoxicity of FK 506 when the drug was used from the outset. This kind of information was sought in 101 recipients of primary livers, 24 hearts, and 3 double lungs or heart-lung. Perioperative renal dysfunction was commonly seen, which appeared to be related to FK 506 doses and plasma levels, particularly when the drug was given IV. This was reversible. Late renal function has been generally satisfactory in all three cohorts of patients, and the incidence of hypertension has been low. The therapeutic index of FK 506 is a good one, as revealed by these observations in patients whose most notable achievement was a low mortality.

Anti-Bacterial Agents↗