A new method for orthotopic rat liver transplantation with arterial cuff anastomosis to the recipient common hepatic artery.
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Biomedical subjects
Publications and source records attributed to R A Krom.
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We conducted a pilot study to assess the feasibility and efficacy of postdilution hemofiltration (PDHF) in the management of acute hepatic failure. From January 1984 through May 1986, we encountered seven patients with acute hepatic failure and entered these consecutive patients in the study; three had non-A, non-B hepatitis and one each had type B hepatitis, fulminant Wilson's disease (hepatolenticular degeneration), acute allograft (liver) failure, and acute fatty liver of pregnancy. Two of these seven patients were unable to undergo PDHF because of a precarious hemodynamic status. Of the five patients treated with PDHF, four had amelioration of hepatic encephalopathy; in two of these patients, a close temporal relationship was noted between the improvement and the procedure. Four patients had appreciable thrombocytopenia related to PDHF and bleeding complications. Our preliminary results support a possible role for PDHF as a temporary artificial liver support system for patients with acute hepatic failure.
Among the first 52 recipients of primary liver allografts with follow-up of 2 weeks or greater, 6 patients had biopsy-confirmed vanishing bile duct syndrome (VBDS) and required retransplantation. Five of these six patients had positive lymphocyte crossmatches. Of the 46 remaining liver transplant recipients, 11 had positive crossmatches. Thus, the incidence of VBDS was 5/16 in recipients with a positive crossmatch and 1/36 in recipients with a negative crossmatch. The positive-crossmatch group was significantly more likely to develop VBDS than the negative-crossmatch group (P less than 0.004, log rank test). Additional HLA studies comparing degree of donor-recipient mismatch at the various HLA loci showed no significant difference between the groups for class I disparity. However, class II mismatch was of borderline significance (P less than 0.056). When evaluated individually, the DQ mismatch (P less than 0.04) appeared to be more important than the DR mismatch (P = NS). Our data suggest that a positive lymphocyte crossmatch and a class II mismatch, in particular HLA DQ disparity, may play an important role in the pathogenesis of VBDS.
We found splenic artery aneurysms in 6 of 71 consecutive patients who underwent orthotopic liver transplantation at the Mayo Clinic. The incidence of splenic artery aneurysms in cirrhotic patients with portal hypertension was 10%. Five of the aneurysms were found in patients suffering from chronic active hepatitis, whereas no aneurysms were encountered in patients with primary sclerosing cholangitis or primary biliary cirrhosis. One patient ruptured a splenic artery aneurysm shortly after liver transplantation, and 1 patient developed an aneurysm 3 months after transplantation. We recommend coeliac angiography to be performed prior to liver transplantation, and if splenic artery aneurysms are found, ligation of the splenic artery should be performed at the time of transplantation to prevent possible rupture.
Twelve liver and 5 kidney transplant recipients with severe cytomegalovirus infection were treated with Ganciclovir (7.5 mg/kg/day, intravenously). Ten were evaluable (compatible clinical picture, organ involvement shown histopathologically or by culture, viremia, and absence of concomitant infection). All 17 patients were studied for adverse drug side effects. A total of 9 evaluable patients survived the infection; 1 died during treatment due to infection or drug toxicity. A death 19 days after completion of treatment was due to unrelated causes. Patients became afebrile after 2-9 days (mean, 5.3 days) of treatment. Liver function improved, pulmonary infiltrates cleared, and hypoxemia reversed during therapy. Viremia ceased during therapy in 9 patients; asymptomatic viruria persisted or recurred in 6 of 7 patients studied. No relapses occurred during follow-up (7-17 months; mean, 13 months). Transient neutropenia and thrombocytopenia occurred in 3 and 1 patients, respectively. Ganciclovir appears promising for treatment of severe CMV infection in patients with kidney or liver transplants.
Despite the occurrence of serious side effects, the use of cyclosporin A after organ transplantation has increased because of its ability to effectively suppress allograft rejection. Its use in the treatment of ophthalmic disease has also recently increased. Central nervous system toxicity due to cyclosporin A is a significant but apparently clinically reversible side effect. A liver transplant patient in whom cortical blindness from profound neurotoxicity was the initial presentation is described. Neurologic abnormalities, including cortical blindness, resolved completely after discontinuation of cyclosporin A. However, pathologic studies performed 8.5 months after the initial transplant revealed residual central nervous system demyelination.
In 1983, a Danish female with primary biliary cirrhosis underwent orthotopic liver transplantation (OLT). The transplantation took place in Groningen under a Danish-Dutch cooperation, at this writing, and more than four years after transplantation, the patient is still alive. The quality of her life has been dramatically improved, making possible her return to work. Liver tests, liver function, and biopsies are normal and without signs of development of primary biliary cirrhosis in the transplanted liver. Liver transplantation is now frequently performed at several centres throughout the world with an increasing success rate. In Scandinavia, centres have been established in Norway, Finland, and Sweden, whereas in Denmark the organisation of a programme for liver transplantation is still being discussed. Because of the extremely high costs, liver transplantation has to be approved medically and politically, and the brain death criteria have to be accepted before it can be considered as a generally accepted modality of treatment.
Thrombocytopenia occurs in postoperative liver transplant patients, with platelet counts reaching a nadir on the third postoperative day. Significant bleeding episodes are not uncommon during the first five days postoperatively when platelet counts are low. This thrombocytopenia may be the result of platelet sequestration in the newly grafted liver. The sequestration phenomenon does not appear to be on the basis of antiplatelet antibody activity. Further work defining the time course of this organ sequestration and evaluating the possible release of previously sequestered platelets back into the circulation need to be done. Also, it may be productive to study medications known to inhibit platelet activation (ie, cyclooxygenase inhibitors, prostacyclin, and calcium channel blockers) with the intent of interrupting platelet adhesiveness-sequestration at the time of recirculation of the newly grafted liver.
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We describe severe central nervous system (CNS) toxicity, manifested by confusion, cortical blindness, quadriplegia, seizures, and coma, associated with cyclosporine treatment in three patients undergoing liver transplantation. CT and magnetic resonance studies disclosed a severe, diffuse disorder of the white matter. All side effects and radiographic findings were reversed with discontinuation or a reduction in the dose of cyclosporine. We also observed an inverse association between CNS side effects and total serum cholesterol levels after transplantation. A retrospective analysis of 54 liver transplantations performed in 48 patients revealed that 13 patients had symptoms of CNS toxicity associated with the use of cyclosporine. These patients' total serum cholesterol levels in the first week after transplantation were reduced as compared with those in patients without symptoms (mean +/- SE, 94 +/- 4 mg per deciliter vs. 132 +/- 6, or 2.44 +/- 0.10 mmol per liter vs. 3.43 +/- 0.16). We conclude that cyclosporine therapy for immunosuppression in liver transplantation may cause a syndrome of encephalopathy, seizures, and white-matter changes and that this is most likely to occur in patients with low total serum cholesterol levels after transplantation.
A detailed coagulation and thromboelastographic study was done on the first 50 liver transplantation procedures performed at the Mayo Clinic between March 1985 and June 1986. Most of the patients suffered from primary sclerosing cholangitis, primary biliary cirrhosis, or chronic active hepatitis. Seven patients required a second liver transplantation, and six patients died, none intraoperatively. Most of the patients had distorted hemostatic mechanisms preoperatively, as would be expected because the liver generates most of the clotting factors. The outstanding exception was factor VIII, which was usually in the high-normal range or even more elevated. Substantial deterioration of coagulation factors occurred regularly during reperfusion of the donor liver. In some instances, this trend was corrected within 1 hour, but platelet counts continued to decrease, and some coagulation factors rebounded only partially. Because thromboelastographic tracings are quickly available to the liver transplant team and because they tend to forewarn of impending hemostatic problems, we believe that thromboelastography is a reasonably effective procedure for monitoring coagulation during liver transplantation.
Monoclonal antibodies were used to identify T-helper cells (TH) and T-suppressor/cytotoxic cells (TS/C) in biopsy specimens obtained 7, 21, 90, 180, and 365 days postoperatively, and during episodes of graft dysfunction, from 34 consecutive liver transplant patients treated with cyclosporine and steroids. Rejection was diagnosed by the presence of appropriate laboratory and light microscopic findings and at least 8 weeks of follow-up to exclude other causes of graft dysfunction. Four immunohistologic patterns were seen--no labeled cells (No), only lobular TS/C, only portal TH, and a portal mixture of TH and TS/C (mix). Of 36 specimens with the No or only lobular TS/C pattern, 29 were not associated with rejection. Of the 39 specimens with the portal TH or portal Mix pattern, 33 were associated with a rejection episode. In addition, in nine specimens from patients with no biochemical or routine histologic evidence of rejection, the presence of portal TH or a portal mix indicated immunologic rejection 5 days to 5 weeks before biochemical and routine histologic evidence of it was manifested. Immunohistologic labeling appears to be an early indicator of liver allograft rejection.
In 20 adult patients undergoing orthotopic liver transplantation (OLT), we studied longitudinally for the first 3 weeks after OLT the composition of bile with regard to differences between surviving and non-surviving patients and between patients with more or less rejection and the relation between bile and serum concentrations. The analyzed biliary components were bilirubin, cholesterol, bile acids, phospholipids, copper, iron, glucose, urea, creatinine, ammonia, protein, sodium, potassium, chloride, pH, bicarbonate, calcium and phosphate. After the 1st day the composition of bile was often different from reference values. In most patients deviations of the hepatic excretion function were found. Especially, a sharp fall was noticed in the biliary concentrations of cholesterol and copper. The composition of bile was not helpful in predicting the histologic degree of rejection or the ultimate outcome of the patients. Changes in bile glucose, electrolyte, urea, and creatinine concentrations were positively related to serum concentrations. We conclude that for the compounds analyzed the composition of bile after OLT is not only influenced by the state of the liver but also by the overall metabolic state of the patient.