Analysis of CD45RA- CD45RO+ "memory" T cells in patients after kidney, heart, and liver transplantation.
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Biomedical subjects
Publications and source records attributed to B Ringe.
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The main function of imaging procedures before liver transplantation is the exclusion of factors that may either constitute contraindications to surgery or necessitate a modification of the operation technique. Ultrasound and MRI are the modalities best suited for this purpose. After transplantation, imaging procedures are required mainly for diagnosis of and differentiation, in particular, between vascular and biliary complications, rejection, and infection, since these postoperative complications very often cannot be reliably differentiated on the basis of clinical and laboratory parameters alone. As vascular disturbances can vary widely in their presentation and can mimic other complications, duplex Doppler sonography plays a dominant role in clarification of the perfusion status of the graft. If infection is suspected, ultrasound generally has to be supplemented by other imaging procedures such as CT or MRI; if these techniques reveal suggestive lesions, a fine-needle aspiration is mandatory in most cases. Invasive procedures such as angiography or PTC are now applied only in selected cases, especially if an intervention is contemplated. Rejection cannot be reliably diagnosed by any of the imaging techniques and still requires biopsy.
Orthotopic liver transplantation (OLT) is frequently associated with systemic fibrinogenolysis and diffuse bleeding. At present antifibrinolytic treatment has not been initiated routinely in OLT. Therefore the influence of high dose aprotinin in OLT (2 million kallikrein inactivator units (KIU) given after induction of anesthesia followed by a 500,000 KIU/h infusion throughout the operation) on intraoperative blood loss and fibrinolysis was studied in 25 patients compared to 25 patients without aprotinin. The incidence of fibrinolysis shown in thrombelastography was 72% in the control group versus 16% in the aprotinin group. Oozing after reperfusion of the graft caused by severe fibrinolysis defined as a clot lysis index below 15% was only observed in the control group (42.8%). In contrast no significant difference was found between the groups in the course of fibrin and fibrinogen degradation product levels (FbDP, FgDP) although the mean concentrations of both parameters were evidently lower in the aprotinin treated patients. Levels of tissue-type plasminogen activator (t-PA) activity were initially high in both groups and peaked during and after the anhepatic period. After aprotinin there was a trend of lower t-PA levels which reached significance at the time of reperfusion (p less than 0.02). In both groups the course of thrombin antithrombin complex was in line with the variations of FbDP and FgDP. No correlation between thrombin formation and t-PA activity was found. Mean homologous blood requirement was reduced by 50% (5.6 +/- 4.0 vs. 11.2 +/- 8.6 units, p less than 0.005). The blood saving effect was more pronounced in the postanhepatic period (p less than 0.000001). In conclusion high dose aprotinin inhibits hyperfibrinolysis and reduces intraoperative homologous blood requirement. Therefore its routine use in OLT is recommended.
The aim of this study was to analyse the immunosuppressive contribution of cyclosporin metabolites in liver-grafted patients. Therefore the immunosuppressive potency of 17 metabolites, alone and in combination, was tested in human mixed lymphocyte cultures, and the results were correlated with metabolite blood levels in liver-grafted patients. Of the 17 metabolites tested only six highly lipophilic metabolites showed a detectable immunosuppressive activity of up to 10% of the activity of cyclosporin; the effect of combining metabolites was additive. For calculation of the in vivo activity, blood levels of seven major cyclosporin metabolites were determined in liver-grafted patients with normal liver function (group A, 43 episodes) and with severe hyperbilirubinaemia (group B, 66 episodes). Both patient groups had comparable levels of parent drug (122.9 +/- 17.4 vs. 111.1 +/- 23.5 ng/ml by HPLC) and similar blood levels of the highly lipophilic metabolites 17, 1 and 18. By contrast, blood levels of the less lipophilic metabolites 8, 9, 26 and 203-218 were substantially increased in group B (P less than 0.05). High overall metabolite blood levels in group B were also indicated by a non-specific monoclonal RIA (520 +/- 199 ng/ml for group A vs. 1318 +/- 407 ng/ml for group B). Despite the very high levels in group B, however, the overall contribution of the metabolites to immunosuppression was similar in both groups (12.6 +/- 5.0% for group A vs. 13.8 +/- 5.6% for group B). These findings indicate that, despite a marked accumulation of cyclosporin metabolites in patients with severe cholestatic liver dysfunction, their immunosuppressive contribution remains low.(ABSTRACT TRUNCATED AT 250 WORDS)
Liver resections are usually performed under occlusion of the hepatoduodenal ligament (Pringle manoeuvre) in order to limit operative blood loss. The maximal ischemic tolerance, although individually different, is generally accepted to be 60 min. Resections of centrally located tumors require precise preparation, sometimes combined with vascular reconstructions. In such cases a prolonged ischemic time is inevitable. A save prolongation of the ischemic tolerance could be useful for extensive liver resections. In an experimental study in pigs ischemic tolerance of the liver was studied under hypothermic protection with the HTK solution of Bretschneider during 2 and 3 h. Deterioration of liver function was compared with a warm ischemia during 2 h. Results showed significantly less serum transaminase activities and better hepatic blood flow (ICG test) after an ischemia under protection with the HTK solution compared to a warm ischemia during 2 h. A prolonged ischemia during 3 h under protection with the HTK solution was well tolerated. First clinical applications of hypothermic hepatic protection during resection were successful.
Among the worldwide accepted indications for liver transplantation, inherited metabolic disorders play an increasing role. In some paediatric centres this indication runs second after extrahepatic biliary atresia. The aim of liver transplantation in inherited metabolic disorders is twofold: the first is to save a patient's life, the second is to accomplish phenotypic and functional cure of his disease. These aims may be achieved in disorders presenting with cirrhosis, hepatoma, life-threatening progression or failure of other organs with preserved liver function. The timing of liver transplantation has become easier with development of surgical techniques of reduced-size donor livers. These techniques enable the performance of liver transplantation with ABO blood group compatible organs of almost any size if indicated either by deterioration of liver function or impending complications such as hepatoma or life-threatening progression. In comparison with other indications such as extrahepatic biliary atresia, postnecrotic liver cirrhosis or acute liver failure, the results of transplantation in patients with inherited metabolic disorders seem to be better, reaching up to 78-95% actuarial 1-year survival rates. However, lifelong immunosuppressive therapy is necessary. This seems to be acceptable even in disorders with only partial liver function defects.
In the early postoperative period after liver transplantation a possible neurotropic side effect of middle-chain triglycerides used for total parenteral nutrition (TPN) was evaluated by EEG and Glasgow Coma Scale. Group I: no fat for TPN; Group II: 0.7 g/kg body weight (BW) and day, of MCT/LCT emulsion; Group III: 1.5 g/kg BW and day, of MCT/LCT emulsion. Only on postoperative day 5/6 significant differences in distribution of background activity in the EEG were seen between Group I and II. Patients in Group I showed more pathological EEG patterns (Mann-Whitney-U-test p less than 0.05). Per discriminant analysis an influence of applicated fatty acids on the registered background activity could be excluded. Instead an underlying rejection of the graft in 7 of 10 patients could be made responsible for deterioration of the EEG pattern. Following the presented data a negative neurotropic effect of MCT/LCT emulsions in the described dosages can be negated.
Detailed haemostatic changes were investigated during eight liver transplantations. The patients were divided into two groups; group 1 had minor operative bleeding (four cases) and group 2 had major bleeding (four cases). Group 2 had lower levels of platelets, fibrinogen, factor V (FV), and alpha 2-antiplasmin than group 1, and the thromboelastography showed fibrinolysis. In both groups, plasma tissue-plasminogen activator levels rose slightly. After revascularization of the graft liver, reductions in the values of PT, fibrinogen, FV and FVII were noted, along with a prolongation of the PTT and an increase in thrombin-antithrombin III complex levels. Plasma levels of protein C, protein S, antithrombin III, and plasminogen remained relatively stable throughout the operation. These results show that the preceding fibrinolysis and subsequent superimposed activation of the clotting system are the main causes of coagulopathy during liver transplantation, which correlate with the amount of operative haemorrhage and the abnormalities found in haemostatic tests.
Episodes of graft dysfunction are frequently observed after liver transplantation and can be due to different causes requiring specific therapy. In this study the usefulness and reliability of liver transplant aspiration cytology (TAC) for differential diagnosis of liver graft dysfunction is assessed. Out of more than 1500 TACs performed, 292 TACs, taken during episodes of liver dysfunction due to retrospectively defined causes, were analyzed. Immune activation and parenchymal damage in the aspirates were determined cytologically. In 63 episodes of acute rejection, marked immune activation was present in aspirate but not in blood, with varying degrees of hepatocyte damage and cholestasis. No or only minimal immune activation was observed in 86 cases of toxic, ischemic, or septic liver damage, but considerable parenchymal damage and cholestasis were observed. In 3 cases of hepatitis slight-to-moderate immune activation with large granular lymphocytes was found in the aspirate, while 17 cases of viral infection presented with slight-to-moderate immune activation in aspirate and blood. After successful treatment the cytologic patterns normalized, except when the cause of liver dysfunction persisted. Moreover, typical patterns of parenchymal changes were found for preservation damage of the liver (n = 108), fatty degeneration (n = 3), obstructive cholestasis (n = 5), and acute arterial ischemia (n = 2). One case of moderate subcapsular hematoma was the only complication observed (less than 0.1%). Thus, liver TAC is an easy, safe, and clinically useful method for differential diagnosis of liver graft dysfunction. In particular, differentiation between acute rejection and nonimmunologic causes of dysfunction is very reliable, but hepatitis and viral infections also present distinctive patterns in liver TAC.
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Heart transplantation was performed in a 24-year-old man suffering from dilated cardiomyopathy who was also infected with hepatitis B virus and had not yet seroconverted. Most likely due to the immunosuppression, the hepatitis exacerbated and soon led to hepatic dystrophy and precoma. In this phase of congruent rejection of the heart transplant, liver transplantation was performed. During the procedure the patient had stable circulatory parameters and a reduced cardiac output. The heart rate and cardiac output stabilized after release of the anastomosis of the hepatic vessels. The patient survived for 6 months and died at home with signs of a myocardial infarction.
Liver transplantation opens the view on the border lines of medicine. Its performance requires great surgical and anaesthesiological experiences. Based on the authors' own experience the selection of liver donors and the indications for liver transplantations are pointed out. Special pathophysiological aspects of liver transplantation as well as the anaesthesiological procedure and the intensive care in the early postoperative period are described. The results of liver transplantation can be improved by further research on preservation of explanted organs, early recognition of complications after transplantation and immunological suppression.
As hepatic transplantation becomes more successful, there is increasing demand on noninvasive methods for studying graft dysfunction during the postoperative period. Duplexsonography now is a routine investigation with the possibility of quantitative description of changes in hepatic blood flow during graft dysfunction. Serial quantitative doppler measurements of hepatic artery, portal vein and hepatic veins were obtained in 20 adult patients during hospitalisation after transplantation and retrospective correlated to clinical datas. The resistive index of hepatic artery was maximal elevated in the initial period after graft reperfusion. There was no correlation with acute rejection. The angle independent damping index (minimum frequency shift/maximum frequency shift) calculated for portal- and hepatic vein showed significant changes during acute rejection, chronic rejection and cholangitis.
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