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Biomedical subjects

A R Müller

Publications and source records attributed to A R Müller.

At least 19 recordsLinked to original sources
PubMed2004

Expression of E-selectin and its transcripts during intestinal ischemia-reperfusion injury in pigs.

BACKGROUND: Ischemia-reperfusion injury (IRI) can result in severe organ dys- or nonfunction. Interaction of leukocytes and endothelial cells mediated by E-selectin appears to be a key step for disturbed microcirculation. Therefore we studied gene and protein expression as well as localization of E-selectin during intestinal IRI. METHODS: Intestinal tissue samples were obtained from extracorporeal perfused intestines (cold ischemia time [CIT] 2 or 20 hours, each n = 5) and additionally in intestinal transplanted pigs (CIT 2 or 20 hours, each n = 1). Mucosal damage was graded according to the Chiu classification. E-selectin mRNA was determined by PCR and quantitative RT-PCR. Localization of E-selectin mRNA was performed by in situ hybridization and of the protein by immunohistochemistry. RESULTS: Histologically, mucosal damage occurred during reperfusion and was earlier and more severe after 20 hours of CIT. E-selectin mRNA expression was detected by PCR already after laparotomy and was elevated after reperfusion. Interestingly, mRNA expression was already increased after 20 hours of CIT. E-selectin mRNA was localized to the luminal surface of muscular, submucosal, and mucosal endothelial cells and the protein was detected on submucosal arterial endothelium as early as 2 hours after reperfusion. CONCLUSION: Prolongation of CIT results in more severe mucosal damage during reperfusion, which is associated with protein expression of E-selection that might be used as a marker for activated endothelial cells. Increased E-selectin mRNA at end of 20 hours of CIT might indicate a preactivated state of endothelial cells potentially triggered by bacterial translocation or products.

Animals↗
PubMed2004

Kinetics and localization of interleukin-2, interleukin-6, heat shock protein 70, and interferon gamma during intestinal-rerfusion injury.

BACKGROUND: Intestinal ischemia-reperfusion injury (IRI) represents an exaggerated inflammatory cascade with a complex pathophysiology. IL-2, IL-6, HSP70, and INF-gamma are mediators of the inflammatory process. Therefore, we investigated their kinetics and localization during intestinal IRI. METHODS: Pig intestinal specimens were obtained during cold preservation (cold ischemia time 2 hours) and extracorporeal perfusion. Mucosal damage was graded according to the Chiu classification. MRNA expression was determined by Northern blot (IL-2, IL-6, IFN-gamma) or by quantitative RT-PCR (IL-6, HSP70) and localized by in situ hybridization. RESULTS: Histologically, mucosal damage occurred during reperfusion. Expression of IL-2 mRNA was up-regulated after HTK perfusion and was highest at the start and 7 hours after reperfusion. Expression of IL-6 mRNA increased at 2 hours after reperfusion and HSP70 at 3 hours after reperfusion. IFN-gamma mRNA was expressed after HTK perfusion, with expression of this cytokine increasing to 1 hour after the start of reperfusion, and decreasing thereafter. IL-2 mRNA was localized to endothelial cells (EC) and leukocytes and in close relation to ganglion cells (GC): IL-6 mRNA in EC, smooth muscle cells (SMC), and GC: HSP70 mRNA in EC and SMC; and IFN-gamma mRNA in leukocytes. CONCLUSION: IL-2, IL-6, HSP70, and INF-gamma are parameters of early mRNA expression during intestinal IRI. EC, SMC, leukocytes, and GC have been identified as sources of transcripts that might afford potential targets for intervention strategies to attenuate IRI.

Animals↗
PubMed2004

[Consensus-recommendations for sirolimus in liver transplantation].

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

Drug Therapy, Combination↗
PubMed2003

Clinical extracorporeal hybrid liver support--phase I study with primary porcine liver cells.

The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.

Adolescent↗
PubMed2003

[Small bowel transplantation - current status and initial results].

During the last years, clinical small bowel transplantation has significantly improved. This is especially true for isolated small bowel transplantation with success rates of 80 % 1-year patient survival. Currently, approximately 100 small bowel transplantations are performed per year worldwide. In Germany, small bowel transplantation is still rare, because of the high risk for the development of acute rejection and rejection-associated complications. This includes peritonitis and sepsis as well as over-immunosuppression-associated infections. Due to improvements in immunosuppression, the incidence of acute rejection decreased from about 85 % below 25 %. Half of the patients will receive a combined liver-small bowel graft due to TPN (total parenteral nutrition)-associated liver cirrhosis. Although the combined procedure has immunological advantages, complication rates are high and patient survival is significantly lower (ca. 50 % at 1 year). Next to bacterial, fungal, and atypic infections, which are frequently associated with rejection and other complications, CMV and EBV infections are of significant interest. This is of special importance for EBV infections, since all PTLD (lymphoproliferative disease) after small bowel transplantation are EBV-associated so far. Viral infections should be monitored and preemptive therapy using ganciclovir or foscavir will be initiated. Of the 800 patients transplanted so far, 50 % are still alive up to 15 years. Of these, more than 80 % are off parenteral nutrition, in good healths, with good quality of live.

Adult↗
PubMed2002

[Living donor liver transplantation of the right liver lobe between adults].

BACKGROUND AND OBJECTIVE: Adult living donor liver transplantation has been established in an increasing number of transplant centres during the last few years. Donor safety and risks are important criteria influencing the further development. We report our experience with 43 adult-to-adult right lobe living donor liver transplantations. METHODS: 43 patients (mean age: 49,8 +/- 16,0 years; f:m = 14:29) with end-stage liver disease received a right lobe liver graft from an adult living donor (mean age: 42,4 +/- 13,4 years; f:m = 27:16) between December 1999 and December 2001. An approval by the local ethics committee was obtained prior to the start of the programme and each donation. RESULTS: None of the donors experienced fatal or long-term complications. The rate of surgical complications in donors (biliary leakage, bleeding) was 9 %. Actuarial recipient survival was 93 % after three months and 88 % after one year. Five patients had to be re-transplanted. Thus the actuarial 1-year graft survival was 79 %. Biliary complications occurred in 14 % of all recipients. CONCLUSION: According to our experience, living donor liver transplantation of the right hepatic lobe is a safe and effective procedure. Especially for patients in acute and chronic liver failure, who otherwise would have died on the waiting list, this approach offers a life-saving option.

Adult↗
PubMed2002

[Acute liver failure following the use of ecstasy (MDMA)].

The use of "ecstasy" (Methylenedioxymethamphetamine) as a recreational drug is increasing in europe since the 1980's. Aside intended psychological effects the use of ecstasy can be followed by symptoms of intoxication; complications include toxic hepatic damage up to acute hepatic failure. This case-report is about a 17-year old female patient who regularly used "ecstasy" over a six-month period. Two days after the last use of "ecstasy", she reported to her general practitioner with nausea, vomiting, abdominal pain and jaundice. Within 10 days the patient developed acute liver failure. With criteria for liver transplantation fulfilled she was listed for orthotopic liver transplantation of high urgency which was carried out only one day later. Histological examination of the explanted liver showed evidence for a toxic fulminant hepatitis. After transplantation the patient made a full recovery and was released from hospital on day 26 after transplantation. At the first control after six months the patient was in good physical and nutritional condition, serological parameters were normal and ultrasound examination of the transplanted liver was unremarkable. The ethiopathology of "ecstasy"-induced hepatotoxicity, which can occur dose-independently with a symptom-free period from days to weeks after ingestion is not yet fully understood. Possible mechanisms of hepatic damage include influence of MDMA on body temperature regulation, harmful effects of the substance or further components of the "ecstasy"-tablets on the liver cell or a genetic vulnerability of some individuals against amphetamines and amphetamine derivates. There are no parameters existing which could predict the course and severity of "ecstasy"-induced hepatopathy. Especially in young patients with symptoms of hepatic damage frequent controls of clinical status and relevant laboratory parameters are of great importance. Patient transfer to a specialised centre should follow as early as possible; at the latest, when coagulopathy occurs.

Adolescent↗
PubMed2002

Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after liver transplantation minimizes HBV recurrence rates unless evolution of pretransplant lamivudine resistance.

BACKGROUND: Survival rates of hepatitis B patients after liver transplantation improved significantly by introduction of passive immunoprophylaxis. Due to viral escape mutations recurrence still occurs, but recently a combination prophylaxis with hepatitis B immunoglobuline plus lamivudine is evaluated in transplant centers in terms of a further reduction of recurrence rates. PATIENTS AND METHODS: Between 1996 and 2000 a postoperative combination prophylaxis with HBIg and lamivudine was initiated in 44 HBsAg positive liver transplant recipients. In total 14 patients were HBV-DNA negative and 30 were HBV-DNA positive at the time of evaluation. In 22 HBV-DNA positive patients a pre-operative lamivudine treatment (150 mg/die) was started. Five of them developed pre-transplant lamivudine resistance with high viral replication (mean HBV-DNA prior to transplantation 728 +/- 219 pg/ml). In all patients passive immunoprophylaxis was started in the anhepatic phase with application of 10.000 units hepatitis B immunoglobuline. It was continued after seroconversion to HBsAg negativity with an aimed titer of more than 100 U/l and only stopped in case of HBV recurrence. Lamivudine was also continued indefinitely after liver transplantation. RESULTS: Overall recurrence rate in the 44 patients, including retransplantations and patients with pretransplant lamivudine resistance, was 11.5 % under combination prophylaxis. Recurrence was seen only in one of 39 patients (2.6 %) without preoperative lamivudine resistance, in contrast 4 out of 5 patients (80 %) with pre-existing lamivudine resistance suffered from early hepatitis B recurrence. The single patient without preoperative lamivudine resistance, who developed recurrence was pre-transplant HBV-DNA negative without lamivudine treatment, but a postoperative seroconversion to negative HBsAg could not be achieved. The overall 3 year patient survival rate was 91 % in the study population. One patient, who was retransplanted with preoperative lamivudine resistance, died 4.5 months after retransplantation due to hepatitis B recurrence and sepsis, three other patients died for reasons not related to hepatitis B recurrence. Combination prophylaxis was well tolerated in all patients and no severe side effects were observed. CONCLUSION: Combination prophylaxis with hepatitis B immunoglobulin and lamivudine is safe and highly effective in prevention of HBV recurrence after liver transplantation, even in case of positive viral replication. In accordance with the results of other centers it should therefore be the standard regimen. However it fails in the majority of patients with preoperative evolution of YMDD mutations, in which the optimal management has to be determined yet. To minimize preoperative resistance formation universal preoperative antiviral treatment of HBV-DNA positive patients should be replaced by individualized indication for preoperative treatment.

Adult↗
PubMed2002

[Influence of probiotics and fibre on the incidence of bacterial infections following major abdominal surgery - results of a prospective trial].

INTRODUCTION: Early enteral nutrition with fibre and probiotics has been effective in preventing bacterial translocation and is therefore expected to reduce the incidence of postoperative bacterial infections. PATIENTS AND METHODS: In a prospective randomized trial including 172 patients following major abdominal surgery or liver transplantation, the incidence of bacterial infections was compared in patients receiving either a) conventional parenteral or enteral nutrition, b) enteral nutrition with fibre and lactobacillus plantarum 299 or c) enteral nutrition with fibre and heat inactivated lactobacilli (placebo). Liver transplant recipients were also treated with selective bowel decontamination (SBD). Routine laboratory parameters, nutritional parameters and the cellular immune status were measured preoperatively and on postoperative days 1, 5 and 10. RESULTS: Patients were comparable regarding preoperative ASA-classification, Child-Pugh classification of cirrhosis, operative data and immunosuppression. The incidence of bacterial infections after liver, gastric oder pancreas resection was 31 % in the conventional group a) compared to 4 % in the lactobacillus-group b) and 13 % in the placebo-group c). In the analysis of 95 liver transplant recipients, 13 % group b)-patients developed infections compared to 48 % group a)-patients and 34 % group c)-patients. The difference between groups a) and b) was statistically significant in both cases. In addition, the duration of antibiotic therapy was significantly shorter in the lactobacillus-group. Cholangitis and pneumonia were the most frequent infections and enterococci the most frequently isolated bacteria. Fibre and lactobacilli were well tolerated in most cases. CONCLUSION: Fibre and probiotics could lower the incidence of bacterial infections following major abdominal surgery in comparison to conventional nutrition with or without SBD. With this new concept, costs can be reduced by shortening the duration of antibiotic therapy and sparing SBD.

Adult↗
PubMed2001

Preoperative antiviral treatment and postoperative prophylaxis in HBV-DNA positive patients undergoing liver transplantation.

BACKGROUND: Despite passive immunoprophylaxis a significant number of patients, especially if hepatitis B virus (HBV) DNA is positive prior to transplantation, develop HBV recurrence. This number might be reduced by lowering viral replication pretransplant with antiviral agents and by postoperative combination of antiviral agents and passive immunoprophylaxis. PATIENTS AND METHODS: A total of 74 HBV-DNA positive patients who underwent liver transplantation between 9/88 and 4/00 were analyzed retrospectively. Before lamivudine or famciclovir were available, in total 40 patients did not receive any preoperative antiviral therapy. Since 11/93, 17 patients were treated with famciclovir 1500 mg daily, after 4/96 17 patients with lamivudine 150 mg daily prior liver transplantation. Posttransplant all patients received passive immunoprophylaxis aiming at a titer of more than 100 U/liter. In the 34 patients with preoperative antiviral therapy an additional prophylaxis with the respective antiviral agent was applied. RESULTS: Under preoperative famciclovir and lamivudine 30 and 71% of patients became HBV-DNA negative, respectively. Actuarial reinfection rate 2 years after liver transplantation was 48% without antiviral prophylaxis, which was not statistically different from 55% under perioperative famciclovir therapy. In contrast only 18% developed HBV recurrence under perioperative lamivudine treatment. During both antiviral regimens neither pre nor posttransplant severe side effects were observed. CONCLUSION: Perioperative application of famciclovir is not recommendable, whereas lamivudine seems to lower recurrence rates significantly. Whether the observed effect is due to pre- or postoperative application remains to be addressed in further studies. In addition the long-term course has to be awaited.

2-Aminopurine↗