306 research outputs found
DNA proves the Warrah was a wolf : and got to the Falklands unaided
No full textThe Falkland Islands hit the headlines at the beginning of November 2009, and for a
rather unusual reason. The DNA of the warrah, the extinct Falklands wolf, had been
sequenced and the results published in the scientific journal Current Biology. The
story clearly appealed to the UK Media and most newspapers ran it; typical was ‘How
scientists cracked puzzle of the Falklands wolf’ in The Independent for November 2nd
Der Wolf und die sieben Geißlein : eine Postkartenserie von Oskar Herrfurth und zwei Illustrationen von Ludwig Richter
No full textZu dem Volksmärchen "Der Wolf und die sieben Geislein" publiziert das Goethezeitportal die Postkartenserie des populären Malers Oskar Herrfurth (1862-1934) sowie Illustrationen von Ludwig Richter. Zur Lektüre laden ein die Texte des Volksmärchens in den Fassungen der Brüder Grimm und von Ludwig Bechstein
Identifying risk profiles in liver transplant candidates and implications for induction immunosuppression
No full textChanges in recipient and donor characteristics are redefining the role of induction in liver transplant recipients. Older recipients are more common, with greater concomitant comorbidity. Moderate or severe renal dysfunction is now estimated to affect 40% of liver transplant recipients. Donors are also becoming older, and other factors such as more frequent non-alcoholic fatty liver disease (NAFLD) compromise the quality of some grafts. Rejection rates are now relatively low (-10%) but some patients have a markedly increased risk such as younger recipients and those undergoing re-transplantation. Induction immunosuppression is associated with a significant reduction in rejection risk but due to various factors universal induction is not justified. Steroid-free therapy without induction increases the risk of biopsy-proven acute rejection (BPAR) but randomized trials have shown that induction with an interleukin-2 antagonist receptor (IL-2RA) agent or with rabbit antithymocyte globulin (rATG) maintains immunosuppressive efficacy in steroid-free regimens. Delayed calcineurin inhibitor (CNI) initiation (e.g. to days 4-5 post transplant) can prevent deterioration of renal function during the first year post-transplant, but requires induction with an IL-2RA agent or rATG to maintain early immunosuppressive efficacy.IL-2RA induction may be inadequate to ensure a low risk of rejection in a steroid-free regimen combined with delayed tacrolimus. Randomized trials of CNI withdrawal at month 1 post-transplant have only achieved an acceptable rate of BPAR when induction is administered. In terms of safety, an increased rate of infection does not seem to be a concern. The most recent large-scale analyses have not indicated any evidence for an increased risk of malignancy, or specifically post-transplant lymphoproliferative disease. In summary, the place of induction in the management of liver transplant patients is becoming established. Selective use in high-risk individuals to avoid graft rejection is still relevant, but the key rationale for induction is to facilitate steroid-sparing and CNI-sparing regimens to reduce long-term complications. (C) 2018 The Authors. Published by Elsevier Inc
Experimental approach and clinical analysis of factors influencing improvement of liver transplantation
No full textIm Falle irreversibler Leberschädigung, oder nicht behandelbarer metabolischer Erkrankungen der Leber gehört die Transplantation inzwischen zur Standardtherapie. Durch stetige Verbesserung der chirurgischen und anästhesiologisch-intensivmedizinischen Methoden können viele perioperative Komplikationen beherrscht werden.
Ein besonderes Problem stellt die kompensatorische arterielle Minderperfusion des
Transplantates bei portaler Hyperperfusion dar, auch Milzarteriensyndrom genannt. Dieses
entsteht entweder bei der Teillebertransplantation als Phänomen des zu kleinen Lebervolumens in Relation zum portalvenösen Einstrom, oder durch Splenomegalie mit konsekutiver portalvenöser Hyperperfusion bei der Ganzorgantransplantation. Über die hepatic arterial buffer response verstärkt sich dieser Effekt auf der Ebene der Lebersinusoide zusätzlich. Obwohl die präoperative Prädiktion des Effektes möglich ist, kann das Milzarteriensyndrom manchmal erst postoperativ diagnostiziert werden. Therapeutisch ist dann der interventionelle Verschluss der Arteria lienalis Mittel der Wahl. So kann die Optimierung der leberarteriellen Durchblutung komplikationsarm und langfristig erzielt werden.
Eine Alternative zur Ganzorgantransplantation, insbesondere bei metabolischen Erkrankungen, stellt die Leberzelltransplantation dar. Um das langfristige Anwachsen und Proliferieren der transplantierten Zellen zu optimieren, entwickelten wir ein Konzept zur Isolierung syngener Zellen aus erkrankten Lebern mit nachfolgender Transplantation. Wir etablierten zunächst die Isolierung humaner Hepatozyten aus erkrankten Explantaten. Diese Zellen konnten erfolgreich isoliert, charakterisiert und vorübergehend kühl gelagert werden, ohne ihr proliferatives Potential zu verlieren. Für die Weiterentwicklung dieser Idee führten wir im Rattenmodell die sequentielle Leber- und Leberzelltransplantation durch. Es gelang der Nachweis transplantierter syngener Hepatozyten bis 90 Tage nach kombinierter Leber- und Zell-Transplantation bei Ratten unter kontinuierlicher Immunsuppression.
Die Analyse des langfristigen Transplantationserfolges fokussierte sich auf Patienten mit PSC. Zum einen konnte gezeigt werden, dass bei 55% der Patienten nach 12,1 Jahren biliäre Komplikationen, Organverlust, oder Tod auftraten und männliches Geschlecht einen Risikofaktor darstellt. Zum anderen wurde der Einfluss der Immunsuppression auf die Progression der CED untersucht, die bei den meisten Patienten mit PSC besteht. Hier zeigte sich ein positiver Einfluss der Immunsuppression auf den Verlauf der CED im Vergleich zu einer nicht-transplantierten Kontrollgruppe. Insbesondere die kombinierte Immunsuppression mit Mycophenolat-Mofetil war mit anhaltender Remission der CED vergesellschaftet.In case of irreversible liver failure or metabolic liver disease transplantation is the only curative treatment option. Following continuous improvement of surgical technique, anesthesia and intensive care many perioperative complications can be managed successfully.
The splenic artery syndrome, meaning portal hyperperfusion of the transplant liver with consecutively diminished arterial perfusion signifies a serious problem. It either results from extensive liver surgery, termed the small-for-size syndrome, or from splenomegaly with consecutive portal hyperperfusion after liver transplantation. The hepatic arterial buffer response aggravates this effect in the sinusoidal space. Although preoperative diagnostics may predict the splenic artery syndrome, it sometimes is diagnosed postoperatively. Interventional occlusion of the splenic artery is an uncomplicated standardized therapy leading to optimized arterial perfusion.
Liver cell transplantation signifies an alternative approach, especially in patients with metabolic diseases. In order to improve long-term engraftment and proliferation of transplanted cells we developed the isolation of syngeneic cells from diseased livers with consecutive transplantation. We established isolation of human hepatocytes from diseased explanted organs. These cells were successfully isolated and characterized and underwent cold-storage without losing their proliferative capacity in culture. In order to proof our hypothesis we established combined allogeneic liver and syngeneic liver cell transplantation in a rat model. Transplanted hepatocytes could be detected up to 90 days after combined liver and liver cell transplantation in rats under continuous immunosuppression.
Analyses of long-term outcome after liver transplantation focused on patients with PSC. Up to 55% of patients develop biliary complications, organ loss or death 12.1 years after transplant with male gender as risk-factor in multi-variate analysis. Also, influence of immunosuppression on evolution of CED in patients with PSC was examined. In this cohort, immunosuppression had a positive impact on progression of CED compared with controls without organ-transplantation. Especially immunosuppression including Myophenolat-Mofetil was linked with continuing remission of CED.
Altogether, various clinical aspects of perioperative and long-term improvement of liver transplantation were analyzed. The development of syngeneic liver cell transplantation my represent an alternative to minimize complications of continuous immunosuppression
Comparison of the collagen haemostat Sangustop(R) versus a carrier-bound fibrin sealant during liver resection; ESSCALIVER-study
No full textBackground: Haemostasis in liver surgery remains a challenge despite improved resection techniques. Oozing from blood vessels too small to be ligated necessitate a treatment with haemostats in order to prevent complications attributed to bleeding. There is good evidence from randomised trials for the efficacy of fibrin sealants, on their own or in combination with a carrier material. A new haemostatic device is Sangustop(R). It is a collagen based material without any coagulation factors. Pre-clinical data for Sangustop(R) showed superior haemostatic effect. This present study aims to show that in the clinical situation Sangustop(R) is not inferior to a carrier-bound fibrin sealant (Tachosil(R)) as a haemostatic treatment in hepatic resection. Methods: This is a multi-centre, patient-blinded, intra-operatively randomised controlled trial. A total of 126 patients planned for an elective liver resection will be enrolled in eight surgical centres. The primary objective of this study is to show the non-inferiority of Sangustop(R) versus a carrier-bound fibrin sealant (Tachosil(R)) in achieving haemostasis after hepatic resection. The surgical intervention is standardised with regard to devices and techniques used for resection and primary haemostasis. Patients will be followed-up for three months for complications and adverse events. Discussion: This randomised controlled trial (ESSCALIVER) aims to compare the new collagen haemostat Sangustop(R) with a carrier-bound fibrin sealant which can be seen as a "gold standard" in hepatic and other visceral organ surgery. If non-inferiority is shown other criteria than the haemostatic efficacy (e.g. costs, adverse events rate) may be considered for the choice of the most appropriate treatment. Trial Registration: NCT0091861
RANDOMIZED MULTICENTER STUDY OF CETUXIMAB PLUS FOLFOX OR PLUS FOLFIRI IN NEOADJUVANT TREATMENT OF NON-RESECTABLE COLORECTAL LIVER METASTASES (CELIM-STUDY)
No full textProgression Free and Overall Survival After Neoadjuvant Treatment of Colorectal Liver Metastases With Cetuximab Plus FOLFOX or FOLFIRI - Results of the CELIM Study
No full textPrescribing and monitoring of tacrolimus in primary therapy following kidney transplantation
No full textPrescribing and monitoring of tacrolimus in primary therapy following kidney transplantation
No full textRANDOMIZED MULTICENTER STUDY OF CETUXIMAB PLUS FOLFOX OR PLUS FOLFIRI IN NEOADJUVANT TREATMENT OF NON-RESECTABLE COLORECTAL LIVER METASTASES (CELIM-STUDY)
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