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Biomedical subjects

P Neuhaus

Publications and source records attributed to P Neuhaus.

At least 73 records · Page 4Linked to original sources
PubMed2004

Course and treatment of recurrent Hepatitis C after liver transplantation.

Hepatitis C virus (HCV) related liver cirrhosis is the most common indication for orthotopic liver transplantation (OLT) in most transplant centers. However, recurrence of hepatitis C-infection after OLT in HCV positive patients is almost universal. Severity of graft hepatitis increases during the long term follow-up and up to 30% of patients develop severe graft hepatitis and cirrhosis. This led to decreased patient and graft survival in HCV positive patients. A number of variables like genotype, donor age, rejection treatment, cytomegalo-virus disease and liver retransplantation for HCV recurrence have shown to be associated with early and severe graft hepatitis. Prophylactic or therapeutic regimens which alter the course of disease in HCV positive patients are not established yet, and with longer follow-up the prevalence of HCV-related graft failure is likely to increase. New immunosuppressive regimens and anti-viral treatment with ribavarin in combination with pegylated interferon a have to be investigated to reduce the complications of HCV recurrence in the future.

Antiviral Agents↗
PubMed2003

Focal overexpression of insulin-like growth factor 2 by hepatocytes and cholangiocytes in viral liver cirrhosis.

Insulin-like growth factor (IGF)-2 is overexpressed in hepatocellular carcinoma and accompanying dysplastic lesions. IGF-2 signalling is mediated through IGF-1 receptor (IGF-1R), while mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF-2R) controls pericellular levels of free IGF-2. We studied, by in situ hybridisation and immunohistology, 18 liver specimens with cirrhosis of different aetiology without neoplastic or dysplastic lesions. Immunohistology was also performed for insulin receptor IGF-1R and IGF-binding proteins 3 and 4. High focal levels of IGF-2 RNA were found in some hepatocytes of all livers with HBV- or HCV-induced cirrhosis (n=10), but in only one of the cirrhoses with nonviral aetiology (n=8). IGF-2 was overexpressed in biliary duct epithelial cells in one case. Compared with noncirrhotic liver, all cirrhotic specimens showed reduced hepatocellular expression of M6P/IGF-2R protein, which contrasted with enhanced expression in perisinusoidal cells. Immunostaining for the other antigens did not reveal significant differences. Upregulation of IGF-2 in some hepatocytes may lead to high focal IGF-2 levels sufficient to saturate local IGF-2 binding capacities, and may result in an increased susceptibility to cellular dedifferentiation and, ultimately, liver cancer. Downregulation of hepatocellular M6P/IGF-2R and upregulation of IGF-2 seem to be early events in hepatocarcinogenesis prior to the appearance of morphologically distinct dysplastic lesions. Elevated focal IGF-2 transcript levels may therefore indicate an increased risk for hepatocellular and cholangiocellular carcinomas.

Bile Ducts↗
PubMed2003

[Innovations in liver surgery through transplantation from living donors].

Living-donor liver transplantation was introduced into clinical practice in the early 1990s. At first the results were unsatisfactory, but today's results after living donation are as good as those obtained after conventional liver transplantation with full-sized organs. With minimally invasive diagnostic methods, it is now possible to determine the quality of potential donor livers and exclude focal lesions and anatomical variants which influence the strategy of organ retrieval procedures. Donor liver resection is done without hilar occlusion after determining the anatomical variants of the bile system (especially for right lobes) and localizing of the course of the middle hepatic vein. Microsurgical techniques are used for reconstruction of the biliary system and hepatic vessels. Living-donor liver transplantation allows us to investigate the complex changes after liver resection. The surgical techniques and pathophysiological postoperative changes can be adapted unconventionally to complex oncological liver resections. Therapeutic optimization and better risk management are becoming possible for liver resections.

Bile Ducts↗
PubMed2003

Quality of life of living donors before and after living donor liver transplantation.

Living donor liver transplantation (LDLT) is becoming an established method for treatment of terminal liver disease in adults. After resection of the right hepatic lobe, postoperative complications can arise in healthy donors, and even individual cases of death have been recorded. There remains, however, little research on the psychosocial aspects in living donors before and after LDLT. Using the WHOQOL questionnaire, this prospective study investigates the quality of life (QoL) in a sample of 28 living donors, including the relationship between postoperative complications and QoL before and 6 months after donation. Before LDLT, the donor QoL is high, above that of the general healthy population. After LDLT, a significant reduction in the QoL appears in the areas of "physical health" and "living conditions." Nevertheless, the QoL remains above the level of the general population. Only two donors showed general QoL values below those of the general population. The postoperative complications had no significant influence on the QoL after transplantation. The high QoL of donors following LDLT indicates a positive psychosocial outcome for the majority of donors, irrespective of donation-related complications. Additional psychosocial studies will be necessary to disclose predictors for an unfavorable psychosocial outcome following LDLT.

Adult↗
PubMed2003

Plastic reconstruction of an extended corrosive injury of the posterior tracheal wall with an autologous esophageal patch.

We report on a patient with an extended corrosive injury of the posterior tracheal wall and left-sided tracheo-esophageal fistula after severe inhalative trauma. Resection of the fistula and necrotic tissue was followed by reconstruction of the posterior tracheal wall with an esophageal patch. Interposition of the stomach was performed to restore upper gastro-intestinal continuity. Revision was necessary due to an anastomotic insufficiency and a recurrent fistula between the trachea and the esophago-gastrostomy on the left side. The stomach was resected and the fistula was covered with a sternocleidomastoideus muscle flap. Several weeks later interposition of the right hemicolon was performed to establish the gastro-intestinal tract and the patient recovered completely, thereafter.

Adult↗
PubMed2003

Correlation of intimal hyperplasia development and shear stress distribution at the distal end-side-anastomosis, in vitro study using particle image velocimetry.

Low shear areas at the distal anastomosis of peripheral bypasses are thought to promote neointimal hyperplasia. In this study we evaluated the fluid dynamic environment at the distal anastomosis of peripheral bypasses by means of a new method for in vitro flow visualization and quantitative velocity field measurement. A silastic model of a distal end-side anastomosis was attached to a mock circulation loop driven by an artificial heart. High resolution velocity fields were measured by means of particle image velocimetry (PIV). The velocity vector data were used to calculate vorticity omega, strain rates ex, shear rates h and shear stresses tau. Two separations and a stagnation zone were identified by means of flow visualization. Measured velocities inside the three zones were significantly lower than in the high velocity mainstream. Calculated shear rates and shear stresses inside the zones were significantly lower than human wall shear rates. At the transition between the effective mainstream and the boundary layers high vorticity and compressive strain fields existed, indicating the presence of high shear forces. The locations of these areas corresponded to the well known zones of intimal hyperplasia. The high resolution shear stress analysis supports the low shear theory of intimal hyperplasia development. A wall diversion angle greater than 6 degrees leads to flow separation and presumed IH promotion until high shear transition areas are reached.

Anastomosis, Surgical↗
PubMed2003

Local haemodynamics and shear stress in cuffed and straight PTFE-venous anastomoses: an in-vitro comparison using particle image velocimetry.

OBJECTIVES: To use particle image velocimetry (PIV) to study the haemodynamics and shear stress associated with cuffed and straight PTFE-venous anastomoses. METHODS: Silastic models of a straight and cuffed (Venaflo) PTFE-venous anastomoses were attached to a pulsatile flow 'Berlin Heart' circuit filled with glycerine/water and hollow glass tracer spheres. Instantaneous velocity fields were obtained PIV and shear rates and patterns calculated from frame-by-frame analysis. RESULTS: A high velocity jet struck the anastomotic 'floor' and was deflected toward the venous outflow. Shear stresses near the floor were significantly higher, in the straight anastomosis. Sites of high shear stress correlated well with the known sites of intimal hyperplasia. CONCLUSIONS: A cuffed anastomosis type may be favourable in terms of local haemodynamics so enhancing the long-term patency of PTFE-venous grafts.

Anastomosis, Surgical↗
PubMed2003

Technique of bile duct reconstruction and management of biliary complications in right lobe living donor liver transplantation.

From December 1999 to January 2002, 50 right lobe living donor liver transplantations were performed. The donor operations included an intraoperative cholangiography to elicit variations in bile duct anatomy. The biliary reconstruction was done whenever possible as an end-to-end microanastomosis of the donor right hepatic duct with the recipient's bile duct. As a result of the early segmental branching of the donor biliary tree, two segment bile ducts had to be anastomosed in 20 patients and three segment bile ducts in three patients. In 12 patients, a Roux-en-Y hepaticojejunostomy was performed. All anastomoses were drained externally. We observed two leakages at the resection surface which could be treated successfully by an external drainage. Six leaks occurred at the site of end-to-end biliary anastomoses. Twice the problem could be conservatively solved placing a stent percutaneously. In two patients a hepaticojejunostomy was performed after a bile duct necrosis. In two patients with an anastomotic leak, occurring 3 d, respectively, 3 month after the original transplantation, the bile duct could be directly reconstructed over a T-tube. Two anastomotic stenoses were observed, one in combination with a leak treated by percutaneous stent implantation and the second, 3 month after transplantation which was treated surgically. Biliary reconstruction after living donor liver transplantation requires microsurgical techniques and can be performed as a direct end-to-end anastomosis in most cases. Biliary complications were treated by percutaneous drainage or surgical revision in all cases.

Adolescent↗
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

Coexpression of p21(WAF1/CIP1) in adenovirus vector transfected human primary hepatocytes prevents apoptosis resulting in improved transgene expression.

Replication-deficient adenovirus (Ad vector) is one of the most effective gene transfer systems. However, its employment in human gene therapy trials is hampered by Ad vector associated cytotoxicity and induction of apoptosis of the infected cells. Here, we identify one underlying mechanism as uncoupling of S phase and mitosis of the cell cycle leading to apoptosis and decline of transgene expression. Moreover, we demonstrate a strategy to avoid Ad vector associated cytotoxicity and induction of apoptosis in human primary hepatocytes by coinfection of Ad vector carrying the cDNA of choice and the cell cycle regulator p21(WAF1/CIP1) (p21). In addition, animal experiments were performed using Ad vector directed coexpression of p21 and human alpha 1-antitrypsin. As serum analysis of alpha 1-antitrypsin after Ad vector mediated gene transfer to the liver of mice revealed, this strategy resulted also in the improvement of transgene expression by two orders of magnitude. These data suggest that coexpression of p21 and Ad vector carrying a therapeutic gene may be a promising strategy to avoid cytotoxicity and induction of apoptosis leading to improved safety in human gene therapy.

Adenoviridae↗
PubMed2003

Review article: liver transplantation for hepatocellular carcinoma.

Despite recent advances in techniques of in situ tumour ablation, surgical therapy remains at present the mainstay treatment for primary hepatic malignancies. After an initial endeavour in the establishment of liver transplantation as a treatment option, in particular for unresectable liver tumours, only a few indications, for example early hepatocellular carcinoma in cirrhosis, are currently agreed upon. Other indications, such as peripheral cholangiocarcinoma and hepatocellular carcinoma in noncirrhotics have largely been abandoned or are still under debate, as is the case with fibrolamellar carcinoma. The selection of patients suffering from hepatocellular carcinoma in cirrhosis for liver transplantation is still based on tumour size and node number, because the current state of diagnostic imaging fails to reliably predict the most important prognostic parameter: vascular infiltration. Other selection criteria are under investigation. Studies on multimodal therapy are also underway but have not yet demonstrated a clear benefit.

Carcinoma, Hepatocellular↗
PubMed2003

[Accuracy of the CT-estimated weight of the right hepatic lobe prior to living related liver donation (LRLD) for predicting the intraoperatively measured weight of the graft].

PURPOSE: Due to the shortage of cadaver donors, living related liver donation (LRLD) has emerged as an alternative to cadaver donation. The expected graft weight is one of the main determinants for donor selection. This study investigates the accuracy of preoperatively performed CT-volumetry to predict the actual weight of the right liver lobe graft. MATERIALS AND METHODS: In a prospective study the weight of the right hepatic lobe was calculated by volumetric analysis based on CT in 33 patients (21 females, 12 males, mean age 42.1 years, median age 41 years) prior to living related liver donation. Graft weight was calculated as the product of CT-based graft volume and 1.00 g/ml (the approximated density of healthy liver parenchyma). The calculated weight was compared with the intraoperatively measured weight of the harvested right hepatic lobe. The difference was used to determine a correction factor for estimating the actual graft weight. RESULTS: Based on the assumption of a parenchymal density of 1.00 g/ml, the preoperatively estimated graft weight (mean 980 g +/- 168 g) deviated +33 % from the intraoperatively measured right hepatic lobe weight (mean 749 g +/- 170 g). By reducing the preoperatively predicted weight of the right hepatic lobe with a correction factor of 0.75, the actual graft weight can be calculated. CONCLUSION: Preoperative estimation of the weight of the right hepatic lobe based on CT of living related liver donors predicts the weight of the right lobe graft with sufficient accuracy by applying a single correction factor. Intraoperative fluid loss (i.e., blood, bile) from the harvested liver as well as variations in parenchymal density may contribute to the observed preoperative overestimation of the actual graft volume by CT-based volumetry.

Adult↗
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↗