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W O Bechstein

Publications and source records attributed to W O Bechstein.

At least 73 records · Page 4Linked to original sources
PubMed2000

Mechanisms of tolerance induction in second renal allografts of a chronic rejection model.

In a previous experiment we demonstrated the induction of tolerance by the allograft itself. In this model of weak histoincompatibility, second grafts of donor origin replacing chronically rejected first renal allografts were accepted long term. Additionally grafted donor-specific hearts functioned indefinitely while adoptive transfer experiments demonstrated the development of donor-specific transferable tolerance. In the current experiment we compared intragraft gene expression of chronically rejected first and tolerant second grafts by RT-PCR. Second renal allografts of donor origin (F-344) replaced first grafts 2, 4, 8, 12, and 16 weeks after the initial engraftment. No immunosuppression was used during second engraftment. Grafts were followed by serial proteinuria; morphological and immunohistological studies (APAAP/infiltrating cells, ICAM-1, MHC II expression) and competitive RT-PCR analyses (expressed as arbitary units AU/cDNA) for relevant cells and cytokines (CD-3, IFNgamma, IL-10, and IL-4) were assessed by the end of the observation period (16 weeks). Macrophages/monocytes (ED-1+) and T-cells (CD-5 and CD-4+) infiltrated first allografts in high numbers by 12 weeks associated with strong structural signs of chronic graft rejection (ca. 30% arterio- and glomerulosclerosis, tubular atrophy and interstitial fibrosis). Cellular infiltrates in second grafts were prominent, however significantly reduced, while histological changes were minor. At cDNA levels, CD-3 transcripts were elevated in second renal allografts performed 2, 4, and 8 weeks after the initial engraftment while comparable levels were observed when second engraftment was performed after 12 and 16 weeks. Analyses of relevant cytokines demonstrated a TH1/TH2 shift independent from the time interval between first and second engraftment. These results emphasize the role of alloresponsiveness for the development of chronic graft dysfunction. Mechanisms of tolerance induction in our model are associated with a distinct alloresponsive pattern. A crucial role for regulatory T-cells is suggested.

Animals↗
PubMed2000

Lamivudine as first- and second-line treatment of hepatitis B infection after liver transplantation.

Lamivudine and famciclovir have expanded therapeutical options for HBV infection after liver transplantation. First studies confirm good antiviral effects of both, but at present the major problem seems to be a rapid resistance formation in immunosuppressed patients. Thirty-four adult patients with HBV recurrence despite passive immunoprophylaxis and seven with de novo infection after orthotopic liver transplantation (OLT) were treated with 100-150 mg lamivudine daily. Patients were either treated directly after infection (n = 14) or after breakthrough of viral replication during an initial famciclovir therapy (n = 27). All patients except two responded to treatment with a reduction of serum HBV-DNA of over 50%. Thirty-one patients (76%) turned HBV-DNA-negative during lamivudine therapy. Viral breakthrough was observed in 14 of these patients after 4-13 months of treatment. A total of 17 patients (40%) remained HBV-DNA-negative for more than 12 months. Only nine patients eliminated HBsAg, of which four had and an HDV coinfection. None of the HBeAg-positive patients converted to anti-HBe. Most patients showed a prompt and significant reduction of aspartate aminotransferase (ALAT) levels. No severe complications occurred. Therefore, a safe and effective therapy of HBV infection after transplantation is possible with lamivudine. Viral replication is suppressed even in patients who revealed breakthrough during famciclovir therapy. Resistance formation as a major drawback occurred in one third of the patients within the first year of treatment.

2-Aminopurine↗
PubMed2000

Neurotoxicity of calcineurin inhibitors: impact and clinical management.

Between 10%-28% of patients who receive the immunosuppressant cyclosporine (CsA) experience some form of neurotoxic adverse event. Both sensorial motoric functions may be adversely affected, and thus patients present with a wide range of neurological and psychiatrical disorders. Mild symptoms are common and include tremor, neuralgia, and peripheral neuropathy. Severe symptoms affect up to 5 % of patients and include psychoses, hallucinations, blindness, seizures, cerebellar ataxia, motoric weakness, or leukoencephalopathy. Tacrolimus is associated with similar neurotoxic adverse events. Neurotoxicity may result in serious complications for some patients, particularly recipients of orthotopic liver transplants. Factors that may promote the development of serious complications include advanced liver failure, hypertension, hypocholesterolemia, elevated CsA or tacrolimus blood levels, hypomagnesemia, and methylprednisolone. Occipital white matter appears to be uniquely susceptible to the neurotoxic effects of CsA; injury to both the major and minor vasculature may cause hypoperfusion or ischemia and local secondary toxicity in the white matter. Calcineurin inhibition by CsA and tacrolimus alters sympathetic outflow, which may play a role in the mediation of neurotoxic and hypertensive adverse events. The symptoms of CsA- and tacrolimus-associated neurotoxicity may be reversed in most patients by substantially reducing the dosage of immunosuppressant or discontinuing these drugs. However, some patients have experienced permanent or even fatal neurological damage even after dose reduction or discontinuation. CsA-sparing and tacroli-mus-sparing drug regimens that use the immunosuppressant mycophenolate mofetil, which has no neurotoxic effects, may reduce the incidence and severity of neurotoxic adverse events while maintaining an adequate level of immunoisuppression.

Calcineurin Inhibitors↗
PubMed2000

Arterial complications after liver transplantation.

From September 1988 through April 1998, 1,000 liver transplantations were performed on 911 patients. During the postoperative control examinations of 837 patients, we found 23 (2.74 %) with hepatic artery thromboses, 27 stenoses of the hepatic artery (3.22 %), and 6 aneurysms of the graft artery. Seventeen patients underwent retransplantation because of arterial complications. Depending on the clinical symptoms, we treated both the local situation as well as the resulting complications of inadequate arterial graft flow. The aneurysms were primarily treated surgically. The first choice of treatment of stenoses was balloon angioplasty. Early postoperative artery thromboses were also treated surgically by thrombectomy in selected cases. For the resulting biliary and local septic complications we preferred endoscopic and drainage procedures. Our clinical experiences have led us to find pretransplantation angiography recommendable, especially in the case of splanchnic artery stenoses, for bypassing from the aorta for arterial perfusion of the graft.

Adult↗
PubMed2000

Primary and secondary hepatic manifestation of neuroendocrine tumors.

BACKGROUND: In comparison with most other malignancies, in the treatment of metastatic neuroendocrine tumors one also has to consider endocrine symptoms and natural progression of disease. Since hepatic metastasis predominates and endocrine symptoms correlate with functional tumor mass, hepatic resection may improve prognosis or even cure patients. PATIENTS AND METHODS: We reviewed 41 consecutive patients with metastatic neuroendocrine tumors and four patients with primary hepatic disease presenting between 1989 and 1999. The neuroendocrine tumors were classified according to their origin, pattern of metastasis, endocrine activity, and histology. Operative therapy including hepatic resections of different extent, liver transplantation, and removal of the primary tumor was analyzed. The median survival after initial diagnosis and after hepatic resection were major parameters of outcome. RESULTS: There were 26 low-grade malignant, 12 high-grade malignant, 2 biphasically differentiated neuroendocrine carcinomas, and 5 pancreatic endocrine tumors. Hepatic resections were performed in 25 patients, resections of the primary tumor in 40 patients. The median survival after initial diagnosis was 49 months; 50.5 months in patients with hepatic resection versus 47 months in those with no liver surgery. CONCLUSION: Hepatic resection improved the outcome of patients with liver metastasis due to neuroendocrine tumors tendentiously but not significantly.

Adult↗
PubMed2000

Hepatoma of the liver--resection or transplantation?

INTRODUCTION: Despite recent advances with techniques of in situ tumor ablation, surgical therapy remains at present the mainstay in the treatment of primary hepatic malignancies. DISCUSSION: After an initial endeavor to establish liver transplantation as a treatment option, especially for unresectable liver tumors, 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 non-cirrhotics, have largely been abandoned or are still under debate, as with fibrolamellar carcinoma. Selection of patients suffering from hepatocellular carcinoma in cirrhosis for liver transplantation is still based on tumor 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 benefit.

Bile Duct Neoplasms↗
PubMed2000

Evidence for impaired glucose effectiveness in cirrhotic patients after liver transplantation.

To evaluate the impact of acute and chronic liver disease and single immunosuppression (cyclosporine A [CSA] or FK506) on insulin sensitivity and glucose effectiveness in liver-grafted patients, we performed a frequently sampled intravenous glucose tolerance test (FSIGTT) in nondiabetic patients after orthotopic liver transplantation (OLT) with acute liver failure ([ALF] group, n = 9, with CSA therapy), in patients after OLT with chronic liver disease (CSA group, n = 8; FK506 group, n = 8), and in 9 healthy control subjects. Insulin sensitivity and glucose effectiveness were determined by analyzing glucose and insulin data from the FSIGTT with Bergman's minimal model technique for glucose. The intravenous glucose tolerance index ([KG] ie, the slope of the regression of the logarithm of blood glucose concentration) was not different between the ALF group (2.17 +/- 0.16 min(-1)) and controls (2.29 +/- 0.13 min(-1)), but was lower (P < .05) in both groups with chronic liver disease (CSA group, 1.46 +/- 0.1; FK506 group, 1.61 +/- 0.11 min(-1)) compared with the ALF group (P < .05). A positive relation for the KG and glucose effectiveness was found in all liver-grafted patients and controls. Insulin sensitivity was not different between all liver-grafted patients and controls. The body mass index (BMI) was the overall determinant of insulin sensitivity in all groups. Single immunosuppressive therapy does not impair insulin sensitivity in liver-grafted patients. The lower glucose effectiveness in liver-grafted patients with chronic liver disease but not in patients after ALF points to a defect in the regulation of glucose-mediated glucose uptake in peripheral tissue.

Adult↗
PubMed2000

Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial.

The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.

Adult↗
PubMed2000

Venous complications after orthotopic liver transplantation.

Complications involving the portal vein or the vena cava, are rare after orthotopic liver transplantation. We report on the incidence and treatment of venous complications following 1000 orthotopic liver transplantations in 911 patients. Twenty-six of the adult patients (2.7%) suffered from portal complications after transplantation, whereas complications of the vena cava were observed in only 17 patients (1.8%). Technical problems or recurrence of the underlying disease (e.g. Budd-Chiari syndrome) accounted for the majority of complications of the vena cava, whereas alteration of the vessel wall or splenectomy during transplantation could be identified as important risk factors for portal vein complications. In patients undergoing modification of the standard end-to-end veno-venous anastomosis of the portal vein due to pathological changes of the vessel wall, complications occurred in 8.3%, whereas only 2.4% of patients who received a standard anastomosis of the portal vein experienced complications of the portal vein. Furthermore, splenectomy during transplantation was also associated with an increased incidence of portal vein complications (10.5 vs. 2.2% in patients without splenectomy). Treatment was dependent on the signs and symptoms of the patients, and varied considerably between patients with portal vein complications and patients suffering from complications of the vena cava. Complications of the vena cava led to retransplantation in about one-third of the patients, whereas in patients with occlusion of the portal vein, retransplantation was necessary in only 15%, and more than half of the patients suffering from portal vein complications did not require any treatment at all. Usually, treatment of patients with portal vein complications only became necessary when additional complications such as arterial occlusion or bile duct injuries occurred.

Adult↗
PubMed2000

[Imaging of intra-arterial hepatic port catheter systems by power-doppler sonography using contrast media--preliminary results].

AIM: This study was designed to determine whether intra-arterial hepatic port catheter systems can be adequately detected by contrast-enhanced power-Doppler sonography. METHOD: 15 patients with a liver port system were investigated before chemotherapy. Examinations were performed with short bolus injections of the contrast medium Levovist in addition to angiographic imaging. RESULTS: Liver port systems were easily detected by the contrast-enhanced power-Doppler method. In 11 out of 15 patients a correct flow of the contrast medium via the port system was seen with both examination methods. One partially occluded hepatic artery was not identified by power-Doppler despite correct flow of the contrast fluid. In one of three patients showing an incorrect flow of the contrast medium the blood circulated primarily through the splenic artery due to a dislocation of the catheter tip. Circulation through both the hepatic and the splenic arteries was shown in a second patient and an occluded right hepatic artery was demonstrated in a third. All these findings were observed with both examination techniques. CONCLUSION: Power-Doppler sonography provides a reliable image of the port catheter system. This method can be used as a follow-up procedure to determine the state of arterial hepatic circulation during chemotherapy.

Aged↗
PubMed2000

[Therapy of recurrent hepatitis B infection after liver transplantation. A retrospective analysis of 200 liver transplantations based on hepatitis B associated liver diseases].

BACKGROUND: Before introduction of passive immunoprophylaxis and new antiviral nucleoside analogues the course of hepatitis B recurrence after liver transplantation could hardly be influenced. The result was a inferior graft survival. In the present retrospective analysis of the efficacy of hepatitis B therapy after liver transplantation was analysed retrospectively. PATIENTS AND METHODS: Between 1988 and 1998 in total 179 patients were transplanted due to hepatitis B related liver failure at our centre. All patients received passive immunoprophylaxis with hepatitis B immunoglobulin. In case of reinfection after 1993 an antiviral therapy with famciclovir 1500 mg daily was initiated (n = 26), since 1996 lamivudine (100-150 mg daily) was used (n = 12). In case of viral breakthrough under famciclovir treatment or prophylaxis therapy was switched to lamivudine (n = 22). In case of ineffectiveness of lamivudine an antiviral combination therapy with lamivudine and interferon (n = 4) or lamivudine and famciclovir (n = 4) was initiated. Before availability of antiviral agents or in case of viral breakthrough in total 12 patients were retransplanted due to acute or chronic reinfection. RESULTS: With passive immunoprophylaxis reinfection rate was 33%, 43% and 44% after 1, 3 and 5 years respectively. Without antiviral treatment 52% of patients died within the first year after reinfection. Antiviral therapy with lamivudine or famciclovir improved the one year survival after reinfection to 79%. Suppression of viral replication was more effective with lamivudine. Under lamivudine 26 patients (76%) became HBV-DNA negative, 9 patients HBsAg negative (26%). In contrast no patient became HBsAg negative during famciclovir therapy. Lamivudine was effective also after famciclovir breakthrough in 94% of patients. In case of lamivudine resistant reinfection viral replication could be suppressed with an antiviral combination therapy up to negative HBV-DNA in the hybridization assay. Severe side effects were not observed during any of the antiviral therapies. The graft survival after retransplantation for hepatitis B reinfection was 42% and 25% after one and 3 years. CONCLUSION: Whereas it is generally accepted, that passive immunoprophylaxis lowers the reinfection rate it could be shown in the present study, that antiviral treatment lowers mortality of hepatitis B reinfection. The major problem of lamivudine and famciclovir is viral resistance formation. In this case an antiviral combination therapy might be useful, whereas retransplantation for hepatitis B reinfection should be considered carefully due to inferior graft survival rates.

2-Aminopurine↗