Biomedical subjects

Peter Neuhaus

Publications and source records attributed to Peter Neuhaus.

166 records · Page 10Linked to original sources

PubMedDate not supplied

Long-term results of mycophenolate mofetil as part of immunosuppressive induction therapy after liver transplantation.

BACKGROUND: The addition of mycophenolate mofetil (MMF) to the induction protocol resulted in a lower incidence of rejection episodes. However, the question whether MMF should be administered in combination with tacrolimus or cyclosporine has not been answered yet. In our study, we report on the long-term results of triple induction therapy after orthotopic liver transplantation (OLT), consisting of MMF and low-dose corticosteroids, in combination with either tacrolimus or cyclosporine. METHODS: Between March 1996 and April 1997, 120 consecutive patients, who underwent OLT at our institution, were enrolled in this study. Of these patients, 80 received triple induction therapy consisting of cyclosporine and MMF (40) or tacrolimus and MMF (40), in combination with low-dose corticosteroids, whereas the remaining 40 patients served as 'MMF-free' control group receiving dual induction therapy with tacrolimus and corticosteroids. Besides the eight-yr follow-up of patient and graft survival, clinical data were also reviewed for episodes of rejection and infection. Additionally, the early post-operative pharmacokinetics of mycophenolic acid (MPA, immunological active metabolite of MMF) were evaluated. RESULTS: Long-term results provided higher patient and graft survival after tacrolimus/MMF-based induction therapy than after cyclosporine/MMF-based induction therapy. However, the tacrolimus-based control protocol yielded similar results and, therefore, no significantly superior effect was observed when MMF was added. The same observation was made for incidence of rejection and infection episodes. AUC and C(max) of MPA increased in combination with tacrolimus compared with cyclosporine. CONCLUSIONS: Although pharmacological synergy between tacrolimus and MMF was observed, MMF showed no significant beneficial effects in the immunosuppressive induction protocol, neither in combination with tacrolimus nor with cyclosporine.

Cyclosporine↗

PubMedDate not supplied

Impaired psychosocial outcome of donors after living donor liver transplantation: a qualitative case study.

Adult-to-adult living donor liver transplantation (LDLT) of the right hepatic lobe has been developing into an established therapy for treating pre-terminal liver diseases. There is little experience available on the psychosocial outcome of living donors. The aim of this first qualitative case study was to investigate the patterns for impaired psychosocial outcome in donors after LDLT. Donor hepatectomies were performed in 30 donors at the Charité Berlin. Six months after surgery, the six of the 30 donors with negative moods and physical complaints in psychometric monitoring were examined. The post-operative interviews were transcribed and analysed using current qualitative research methods. These six donors (20%) reported various unspecific complaints and psychological conflicts. Sadness was expressed about organ rejection and death of the recipient. Anxieties about the recipient and their own health were verbalized. Disappointment and anger refer to the experience that they were not as fully appreciated by the medical system and their social environment as expected. The negative emotions of donors with impaired psychosocial outcome could be related to a decrease in self-esteem in the post-operative course. Adequate medical and psychological treatment opportunities for these donors should be provided.

Adult↗

PubMedDate not supplied

Three-dimensional co-culture of primary human liver cells in bioreactors for in vitro drug studies: effects of the initial cell quality on the long-term maintenance of hepatocyte-specific functions.

In vitro culture models that employ human liver cells could be potent tools for predictive studies on drug toxicity and metabolism in the pharmaceutical industry. A bioreactor culture model was developed that permits the three-dimensional co-culture of liver cells under continuous medium perfusion with decentralised mass exchange and integral oxygenation. We tested the ability of the system to support the long-term maintenance and differentiation of primary human liver cells. The effects of the initial cell quality were investigated by comparing cultures from resected, non-preserved liver with cultures from liver graft tissue damaged by long-term preservation. In cultures originating from non-preserved liver, protein and urea synthesis, glucose metabolism, and cytochrome (CYP450) activities were stable over the 2-week culture period, with maximal activities at the end of the first week in culture. Enzyme induction led to increased 7-ethoxyresorufin O-deethylase activities of up to 20 times the basal value. In cultures from preservation-damaged liver, recovery of metabolic activities was detected during bioreactor culture. After two weeks, most biochemical parameters approached those of cultures from non-preserved human liver. Light microscopy demonstrated the three-dimensional reorganisation of hepatocytes and non-parenchymal cells in co-culture. Long-term maintenance, and even the regeneration of specific functional activities of human liver cells, can be achieved in the bioreactor. This could facilitate the introduction into the pharmaceutical industry of in vitro drug testing with primary human liver cells.

Albumins↗

PubMedDate not supplied

Gene therapy in colon cancer cells with a fiber-modified adenovector expressing the TRAIL gene driven by the hTERT promoter.

BACKGROUND: Repeated administration of adenoviral vectors can lead to cell resistance, probably because of the initial coxsackie-adenovirus receptor (CAR). Modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence can overcome resistance. We constructed an adenoviral vector with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter (designated Ad/TRAIL-F/RGD), and tested its antitumor activity in 5 colon carcinoma cell lines. MATERIALS AND METHODS: Colon cancer cells were infected with Ad/CMV-GFP (vector control), Ad/gTRAIL (positive control) and Ad/TRAIL-FIRGD. PBS was used as a control. Cell viability was determined by proliferation assay. Cell-cycle analysis and quantification of Caspase-8 and TRAIL were used to identify apoptosis. RESULTS: Treatment with Ad/TRAIL-F/RGD resulted in significantly less cell viability, increased Caspase-8 and TRAIL activity, and a greater apoptotic fraction than treatment with PBS or Ad/CMV-GFP. CONCLUSION: The adenoviral vector Ad/TRAIL-F/RGD could become a potent therapeutic agent for the treatment of colon carcinoma.

Adenoviruses, Human↗