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Biomedical subjects

F Mühlbacher

Publications and source records attributed to F Mühlbacher.

At least 37 records · Page 2Linked to original sources

Thrombopoietic cytokines and reversal of thrombocytopenia after liver transplantation.

OBJECTIVES: Thrombopoietin (TPO), the key regulator of platelet production, is mainly produced by the liver and reduced expression of TPO could cause thrombocytopenia in liver cirrhosis. Reversal of thrombocytopenia by orthotopic liver transplantation seems to be mediated through an increase in TPO plasma levels after transplantation, but other cytokines with thrombopoietic activity could augment the actions of TPO on post transplant platelet recovery. DESIGN: Measurement of thrombopoietic cytokines before and for 14 days post liver transplantation in a cohort of thrombocytopenic liver transplant patients. METHODS: TPO, interleukin-3 (IL-3), IL-6, and IL-11 plasma levels as well as peripheral platelet count were analysed in thrombocytopenic patients with liver disease undergoing orthotopic liver transplantation (17 patients) and followed for 14 days after the intervention. RESULTS: Before liver transplantation, TPO plasma levels were undetectable and IL-3, IL-6, and IL-11 levels were normal. Sixteen out of 17 patients showed a significant rise of TPO levels within 2 days after transplantation, with a peak between days 4 and 6, while IL-3 and IL-6 levels did not show a significant rise. IL-11 levels remained normal. Platelet counts were significantly higher than pretransplantation levels by day 14 post transplantation. CONCLUSION: Restitution of normal TPO production by liver replacement seems to be of key importance for reversal of thrombocytopenia in liver disease. The early acting thrombopoietic factor IL-3 and the late acting factors IL-6 and IL-11 do not play a major role for recovery of peripheral platelet count after orthotopic liver transplantation.

Analysis of Variance↗

Apoptosis of tubular epithelial cells in donor kidney biopsies predicts early renal allograft function.

Acute renal failure (ARF) is a serious complication in the early postoperative period after kidney transplantation. In an effort to identify subjects at risk, several donor-, recipient-, and procedure-related factors have been studied. Because no morphologic parameter predictive of delayed graft function has been identified to date, this study was conducted to determine whether the number of apoptotic cells in donor biopsies obtained before engraftment is predictive of the development of posttransplant ARF. Donor biopsies of patients with "biopsy-proven" acute tubular damage but no signs of rejection (n = 23) showed significantly higher counts of apoptotic tubular epithelial cells when compared to patients with immediate transplant function (n = 44) or early rejection (n = 22). In all groups, a significantly higher percentage of apoptotic cells was found in the distal compared to the proximal tubule. The expression of bcl-2 and proliferating cell nuclear antigen was not different among the groups. Late allograft function was not affected by early ARF as serum creatinine values were similar in all three groups after 6 mo. These data suggest that the number of apoptotic renal tubular epithelial cells in donor biopsies before engraftment is predictive of the early postoperative course in patients undergoing kidney transplantation.

Acute Kidney Injury↗

[Liver transplantation in acute liver failure].

Acute hepatic failure is characterized by jaundice and hepatic encephalopathy within eight weeks after the onset of disease. Although acute hepatic failure is a rare occurrence, its rapid progression and high mortality (50 to 90%, depending on the etiology of disease) necessitate immediate intervention. In the absence of causal therapy, orthotopic liver transplantation is currently the only definitive and effective means of treating acute hepatic failure in Europe, acute hepatic failure accounts for 11% of all liver transplantations. At the University department of transplantation surgery in Vienna a total of 27 patients with acute hepatic failure underwent 31 liver transplantations in the last 10 years (1.1.1987 to 31.12.1996). Twenty (74%) of the 27 patients survived the acute event and were discharged from hospital in good general condition after a median postoperative stay of 25 days (range 14-81 days). Seven patients (26%) died between the first and 34th postoperative day (median 26 days) in the intensive care unit, although all potential modern options of intensive care and surgery were used. The causes of death were irreversible cerebral edema (n = 3), multiple organ failure due to bacterial sepsis (n = 3) and uncontrollable haemolysis (n = 1). With a 3-year graft survival rate of 70% the 3-year patient survival rate was 74%. A retrospective analysis of our patients revealed that the postoperative graft function and the incidence of re-transplantation were significant prognostic factors (p < 0.05) for survival following orthotopic liver transplantation for acute hepatic failure. In the absence of further prognostically relevant preoperative indices and in consideration of the potentially fulminant progression of disease, we strongly recommend that any patient, in whom acute hepatic failure is suspected, is immediately transferred to a specialized center with experience both in the conservative treatment of acute hepatic failure and emergency liver transplantation.

Adolescent↗

Underlying disease as a predictor for rejection after liver transplantation.

BACKGROUND: As significantly more patients die of infection than of rejection after liver transplantation, we have to conclude that overimmunosuppression is common. Our analysis was performed to investigate underlying disease as an appropriate parameter for individually reduced immunosuppression. DESIGN: A consecutive series of patients receiving primary liver transplantation was analyzed with regard to acute rejection. SETTING: Department of transplantation surgery in a university hospital. PATIENTS AND METHODS: From 1988 to 1995, 252 patients received liver transplantation for posthepatitic cirrhosis, alcoholic cirrhosis, cholestatic disease, or hepatoma and were analyzed in a univariate and multivariate manner. MAIN OUTCOME MEASURE: The influence of various underlying diseases on the incidence of acute rejection. RESULTS: The estimated risk for freedom from acute rejection and analysis of cumulative rates of acute rejection stratified by group showed significant differences between the groups, except for alcoholic and posthepatitic cirrhosis. Severity of acute rejection episodes, as assessed by the need for rescue therapy, was similar in both univariate analysis and cumulative rates for alcoholic and posthepatitic cirrhosis. As expected, patients with cholestatic disease exhibited a significantly increased requirement for rescue therapy. For patients with hepatoma, a low incidence of initial and a high rate of repeated rescue therapy were observed. The varying immunological behavior within this group may have influenced both expansion of the tumor and severity of acute rejection. Multivariate analysis of potential risk factors identified underlying disease as a variable of independent prognostic significance for acute rejection and the need to receive rescue therapy. CONCLUSION: These results indicate the importance of taking the original disease into consideration where immunosuppressive therapy is concerned.

Acute Disease↗

Management of lymphoceles after kidney transplantation.

Post-transplant lymphoceles (LC) may lead to impaired graft function. Treatment modalities include fine-needle aspiration, percutaneous drainage, and surgical internal drainage. Recently, laparoscopic fenestration has been performed with good results, but experience is still limited. Between January 1991 and August 1996, 919 kidney transplantations were performed in 876 patients at our department. There were 745 first, 133 second, 30 third, 9 fourth, and 2 fifth operations. Sixty-three symptomatic LCs were detected in 62 patients (6.8%) after 39 +/- 31 days. In 44% of the cases, graft function was impaired; in 29% hydronephrosis was documented and in 6% infection of the LC. Forty-five of the 62 patients with LC (73%) had histologically proven rejection. Thirty-five of the 63 LCs were drained percutaneously, 20 LCs were internally drained by open surgery, and 8 LCs were drained by laparoscopy. In 14 of the 47 patients (30%) with primary percutaneous drainage, LC recurred; infection occurred in 17%. Twelve of these patients underwent surgery. One surgical redrainage was necessary after open fenestration. No conversion or complication was noted in the laparoscopy group. We conclude that surgery for post-transplant lymphoceles is safe and effective. We favor the laparoscopic technique in selected patients.

Adult↗

Preoperative TNM-classification is a better prognostic indicator for recurrence of hepatocellular carcinoma after liver transplantation than albumin mRNA in peripheral blood. Liver Transplant Oncology Group.

BACKGROUND/AIM: Survival after orthotopic liver transplantation for hepatocellular carcinoma is limited by a high rate of tumor recurrence. A polymerase chain reaction assay based on the detection of albumin mRNA expression in peripheral blood for detection of hematogenous micrometastasis of hepatocellular carcinoma has been described, which may help to select candidates for orthotopic liver transplantation. METHODS: The prognostic value of a highly sensitive nested reverse transcription-polymerase chain reaction assay was evaluated in comparison with the TNM-classification of the International Union against Cancer in a population of liver transplant candidates. RESULTS: Eighty patients with liver disease and 42 control patients were evaluated. Six of 21 patients with hepatocellular carcinoma and 11 of 59 patients with other diseases of the liver were positive for albumin reverse transcription-polymerase chain reaction, making this assay an indicator of ongoing liver damage without absolute specificity for hepatocellular carcinoma. Twelve patients with hepatoma were followed after liver transplantation and seven of those patients had a tumor recurrence within 12 months. Six of these patients with recurrence had International Union against Cancer stage IV A tumors preoperatively, while only one of them was positive for albumin reverse transcription-polymerase chain reaction before transplantation. Only one patient with a stage I to III tumor had a recurrence within 12 months. CONCLUSIONS: Detection of albumin mRNA in peripheral blood by reverse transcription-polymerase chain reaction seems to be an unreliable marker for assessing hematogenous spread of hepatocellular carcinoma. With International Union against Cancer stage IV A being a much better predictor of tumor recurrence, the practical value of albumin mRNA reverse transcription-polymerase chain reaction for patient selection in liver transplant candidates seems to be very limited.

Adult↗

Haemophilus parainfluenzae liver abscess after successful liver transplantation.

Haemophilus parainfluenzae was isolated from a bile specimen and from an aspirate of a liver abscess in a 58-year-old liver-transplanted woman that was indicative of an invasion of the graft by an ascending route. Drug therapy, immunosuppression, rejection therapy, and Roux-en-Y choledochojejunostomy may have contributed to the septic course. Interdisciplinary cooperation was instrumental in diagnosis and successful management in this case.

Bile↗

Hepatic perfusion after liver transplantation: noninvasive measurement with dynamic single-section CT.

PURPOSE: To compare hepatic perfusion values after orthotopic liver transplantation with those in healthy volunteers. MATERIALS AND METHODS: Dynamic single-section computed tomography (CT) of the liver was performed in 50 participants, including 30 study patients who had undergone orthotopic liver transplantation and had no clinical evidence of postoperative complications (mean age, 53.7 years) and 20 healthy volunteers (control subjects) (mean age, 59.0 years). CT scans were obtained at a single level to include the liver, spleen, aorta, and portal vein. Scans were obtained over 88 seconds (one baseline scan followed by 16 scans every 2 seconds and, then, eight scans every 7 seconds) beginning with the injection of 40 mL of contrast agent (flow rate, 10 mL/sec). On each CT scan, the attenuation of these organs was measured in regions of interest to provide time-attenuation curves. From these data, the arterial, portal venous, and total perfusion of the liver were calculated, and the hepatic perfusion index was assessed. RESULTS: In control subjects and study patients, respectively, mean arterial hepatic perfusion was 0.16 and 0.25 mL/min/mL (P = .001 [two-tailed paired Student t test]), mean portal venous perfusion was 1.22 and 1.26 mL/min/mL, mean total liver perfusion was 1.38 and 1.50 mL/min/mL (difference not significant), and the mean hepatic perfusion index was 0.12 and 0.16 (P = .002). CONCLUSION: Arterial hepatic perfusion was significantly increased after orthotopic liver transplantation, but differences in portal venous and total liver perfusion were not significant. Dynamic single-section CT might also help evaluate hepatic vascular complications, chronic transplant rejection, and hepatic perfusion in liver cirrhosis.

Adult↗

Simultaneous heart and kidney transplantation as treatment for end-stage heart and kidney failure.

BACKGROUND: The aim of the present analysis was to define the role of simultaneous heart and kidney transplantation (HNTX) using organs from the same donor by evaluation of clinical strategy and achieved outcome compared with a reference group of concurrently single heart transplant (HTX) and kidney transplant (NTX) recipients. Compared with other organ combinations (pancreas-kidney, heart-lung), HNTX has been performed infrequently and is reported mainly as case records in the literature. Because of expansion of recipient selection criteria for HTX and NTX, the number of patients requiring simultaneous replacement of both organs is increasing. METHODS: Six HNTX recipients, three of them suffering from long-standing type I diabetes, received transplants between September 1990 and March 1996 and were analyzed in terms of clinical and immunological demographics and outcome. They were compared with 379 HTX and 769 NTX recipients operated upon within this period. RESULTS: Survival for HNTX is 100% with a mean follow-up of 32.7+/-21.1 months. Cold ischemic time of the kidney was significantly shorter for HNTX than for NTX (6.5+/-1.0 hr vs. 22.1+/-6.8 hr, P<0.005). Although HNTX patients received HLA-unmatched grafts, no rejection of the kidney has been observed to date. There was no difference for rejection of the heart in HNTX compared to HTX recipients. CONCLUSIONS: Satisfying results are obtained by HNTX and justify the use of two organs for one recipient. The favorable immunological behavior of the kidney despite use of HLA-unmatched grafts is most probably explained by higher immunosuppression and short cold ischemic time, although a combination effect cannot be excluded.

Adult↗

Improvement of cardiac output and liver blood flow and reduction of pulmonary vascular resistance by intravenous infusion of L-arginine during the early reperfusion period in pig liver transplantation.

BACKGROUND: The release of liver arginase after orthotopic liver transplantation (OLT) causes a deficiency of L-arginine and nitrite in the plasma. This deficiency is possibly related to pulmonary hypertension and reduced hepatic blood flow, which are commonly observed in the immediate reperfusion period. The aim of this study was to evaluate the impact of L-arginine supplementation on metabolic and hemodynamic parameters during liver reperfusion after OLT in pigs. METHODS: Thirteen pig OLTs (control group, n=6; arginine group, n=7) were performed by a standard technique. Cold ischemic time was 20 hr. L-Arginine was infused at a dosage of 500 mg/kg body weight into the donor pigs (30 min before liver explantation) and also into the recipients (over a period of 3 hr from the beginning of the reperfusion period). At the end of the experimental study, the pigs were killed with an overdose of potassium. RESULTS: In the control group, liver revascularization increased plasma arginase concentrations (+615%) and reduced plasma levels of L-arginine (-87%), nitrite (-82%), and nitrate (-53%). Infusion of L-arginine increased plasma levels of L-arginine from 94+/-21 micromol/L to 1674+/-252 micromol/L (P<0.001), L-ornithine from 46+/-8 micromol/L to 2215+/-465 micromol/L (P<0.001), and L-citrulline from 58+/-8 micromol/L to 116+/-34 micromol/L (P<0.001), but had no effect on plasma levels of nitrite and nitrate. Administration of L-arginine in the donor pigs did not produce any systemic or organ-specific hemodynamic alterations. Infusion of L-arginine into the recipient pigs improved cardiac performance (increase in heart rate [+61%, P=0.017] and cardiac index [+53%, P=0.005], reduction in pulmonary capillary wedge pressure [-54%, P=0.014]). Moreover L-arginine infusion increased oxygen consumption (+65%, P=0.003), reduced pulmonary vascular resistance index (P=0.001), stimulated portal venous blood flow (P=0.014), and elevated body temperature during the reperfusion period (P=0.007). CONCLUSIONS: From these data, we conclude that the infusion of L-arginine during OLT improves the hemodynamic performance of the heart, lung, and liver.

Animals↗

[Definition and evaluation of a documentation standard for intensive care medicine: the ASDI(Working Group for Standardization of a documentation system for Intensive care medicine) pilot project].

OBJECTIVES: A comparison of data from different intensive care units (ICUs) needs standardized documentation. In this study the ASDI documentation standard for intensive care was tested in clinical practice. Goal of the study was to evaluate parameters and functionality required for a national, interdisciplinary documentation system for intensive care. DESIGN: 13 ICUs participated in a 4-week trial using the provided program for documentation of all admitted patients during the observation period. In addition, a questionnaire was distributed to the unit coordinators. RESULTS: 376 patients were documented in 1591 patient days. Valid SAPS II scores were found in only 29% of the discharged patients (39.1 +/- 15.5 points). Time needed for data entry exceeded preset limits (ten minutes per patient and day) in 38% of the cases. All participants affirmed the necessity of a documentation standard for intensive care, giving quality control and cost analysis as the most important reasons. CONCLUSION: The ASDI data set fitted existing needs very closely. Only 7 out of 122 parameters (5.7%) were found to be superfluous and thus removed. Measures to reduce documentation effort to the default limits were a) a new, date orientated concept for manual recording, b) rede-sign of the user interface with new, user friendly data entry possibilities, and c) the integration of statistical analysis and reports in the documentation system. The revised data set represents a broad-based consensus, which seems to be well-suited as foundation for the national quality assurance program.

Adolescent↗

[Transplantation today].

Purpose of this review is, to highlight key issues in transplantation medicine today and to summarise basic information on current state of perfused organ transplantation. There is special emphasis on ethical and legal considerations with regard to living donor transplantation, brain death concept, donor consent and organ allocation. Transplantation frequencies and the impact of whole organ transplantation on the treatment concept for patients with end stage organ disease is heavily dependent on donor and organ availability. Organ donor rate of 25 to 30 donors per million inhabitants per year seems to yield sufficient organ supply for patients on renal replacement therapy. 15 to 20 liver transplantations per million inhabitants per year, my be sufficient, to cover the need of organs for non malignant end stage liver diseases. This frequency may be achieved by increasing donor rates and employing "split techniques", where one liver is used for two recipients. One year graft survival in kidney transplantation can be expected to be between 85 and 90%, one year patient survival in heart and liver transplantation can be expected to be beyond 80%. The risk of organ failure is highest in the first year, long term results are dependent on incidence of chronic rejection, comorbidity of the patient and original disease. Patient- and/or graft loss after the first year is in the order of 1 to 5%. Whole organ transplantation for kidneys, hearts and livers are considered routine procedures, lung transplantation is reaching standard phase, pancreas and combined pancreas kidney transplantation is well established technically, but its indication is still controversial.

Ethics, Medical↗

Is inadequate thrombopoietin production a major cause of thrombocytopenia in cirrhosis of the liver?

BACKGROUND/AIMS: Thrombocytopenia secondary to cirrhosis of the liver and portal hypertension is a well-known complication of advanced stage liver disease, but theories about the underlying pathogenetic mechanisms, mostly centering on splenic sequestration and destruction of platelets, have failed to solve the problem so far. METHODS: Peripheral platelet count and thrombopoietin levels in human plasma were measured in 28 patients with cirrhosis of the liver. Seven of those patients underwent orthotopic liver transplantation and five patients portal decompression by transjugular intrahepatic portosystemic shunt. Thrombopoietin plasma levels were followed for 14 days after the interventions. RESULTS: No measurable thrombopoietin was detectable in the plasma of 28 thrombocytopenic patients with cirrhosis of the liver, in contrast to thrombocytopenic patients without liver disease. Seven of these patients with cirrhosis underwent orthotopic liver transplantation, resulting in a rise of thrombopoietin levels within 2 days after transplantation. The rise in platelet number followed with a mean lag of 6 days, and shortly thereafter, thrombopoietin levels returned to levels below the limit of detection. Five patients with thrombocytopenia, who underwent only decompression of portal hypertension, showed no rise in either thrombopoietin levels or platelet count. CONCLUSIONS: Thrombocytopenia associated with liver disease may at least in part be attributable to inadequate thrombopoietin production in the failing liver.

Humans↗