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Biomedical subjects

W O Bechstein

Publications and source records attributed to W O Bechstein.

At least 37 records · Page 2Linked to original sources

[Morbidity following simultaneous pancreas/kidney transplantation].

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) is still associated with the highest rate of morbidity among solid organ transplantations. Although improved long-term survival following SPK has been proven in IDDM patients, a further decrease in morbidity would be desirable. METHODS: A retrospective, single-center study was performed to investigate the morbidity following SPK and to compare the results to kidney transplantation alone (KTA). Parameters included the rates of relaparotomies, septic complications (urinary tract infection, wound infection, pneumonia), and graft function. RESULTS: Between September 2000 and August 2001, 99 patients underwent transplantation (34 SPK, 63 KTA, 2 pancreas transplants alone). Relaparotomies were performed in six SPK patients (17.6%), mostly due to complications related to the pancreatic graft (n=5). Three reoperations (4.8%) were necessary in KTA patients (p=0.085). Septic complications occurred more often in SPK than in KTA patients (55.9% vs 30.2%, p<0.05). This difference resulted from the high rate of wound infections in SPK patients (35.3%). No intra-abdominal infection or sepsis occurred in any patient. There was one hospital death in SPK and KTA patients, respectively. The rejection rate was similar in SPK (17.6%) and KTA (12.7%, p=0.72). At discharge 91.2% of SPK patients were insulin free and 97.1% free of dialysis. At discharge 96.8% of KTA patients were free of dialysis. CONCLUSION: SPK is still associated with a higher morbidity (relaparotomies, septic complications) than KTA, although life-threatening complications were rare. There was no increased mortality following SPK.

Adult↗

[Early detection of colorectal tumors: CT or MRI?].

Cancer screening is currently offered for the organs breast, prostate, cervix and colorectum. With progressing technique in computerized tomography (CT) and magnetic resonance imaging (MRI) the colorectum can be increasingly better assessed. Because in CT and MRI also other organs are imaged with the colorectum, a colorectal screening automatically becomes a multiorgan screening. CT and MRI protocols designed for early detection of colorectal tumors are presented and discussed with regard to monoorganscreening (in CT: low dose, no i.v. contrast) and multiorganscreening (in CT: diagnostic dose for neighboured organs with i.v. contrast). More information under http://www.multiorganscreening.org.

Colonic Polyps↗

The immunosuppressive drug mycophenolate mofetil impairs the adhesion capacity of gastrointestinal tumour cells.

Immunosuppression correlates with the development and recurrence of cancer. Mycophenolate mofetil (MMF) has been shown to reduce adhesion molecule expression and leucocyte recruitment into the donor organ. We have hypothesized that MMF might also prevent receptor-dependent tumour dissemination. Therefore, we have investigated the effects of MMF on tumour cell adhesion to human umbilical vein endothelial cells (HUVEC) and compared them with the effects on T cell-endothelial cell interactions. Influence of MMF on cellular adhesion to HUVEC was analysed using isolated CD4+ and CD8+ T cells, or WiDr colon adenocarcinoma cells as the model tumour. HUVEC receptors ICAM-1, VCAM-1, E-selectin and P-selectin were detected by flow cytometry, Western blot or Northern blot analysis. Binding activity of T cells or WiDr cells in the presence of MMF were measured using immobilized receptor globulin chimeras. MMF potently blocked both T cell and WiDr cell binding to endothelium by 80%. Surface expression of the endothelial cell receptors was reduced by MMF in a dose-dependent manner. E-selectin mRNA was concurrently reduced with a maximum effect at 1 microm. Interestingly, MMF acted differently on T cells and WiDr cells. Maximum efficacy of MMF was reached at 10 and 1 microm, respectively. Furthermore, MMF specifically suppressed T cell attachment to ICAM-1, VCAM-1 and P-selectin. In contrast, MMF prevented WiDr cell attachment to E-selectin. In conclusion, our data reveal distinct effects of MMF on both T cell adhesion and tumour cell adhesion to endothelial cells. This suggests that MMF not only interferes with the invasion of alloactivated T cells, but might also be of value in managing post-transplantation malignancy.

CD4-Positive T-Lymphocytes↗

[Transplantation and outcome quality].

Organ transplants are procedures which require intensive personal and material resources. The results of organ transplants have continuously improved during recent decades. International data bases (registries) have documented the continuous evolution of organ transplantation. On the basis of the German Transplant Law guidelines for "Requirements regarding quality control for procedures related to organ procurement and transplantation" have been formulated by the German Medical Chamber. Thus, monitoring of outcome quality will become a requirement for all German transplant centers. In this paper, the guidelines for the different organ transplants (kidney, pancreas, liver, heart, lung) are discussed as well as quality control for living donor transplantation. Studies from the USA and Europe demonstrated volume-outcome relationships in organ transplantation. In addition, in kidney transplantation a centre-effect could be demonstrated which influences outcome more than the immunological match between donor and recipient. The introduction of required quality control may have far reaching consequences for the future structure of organ transplantation in Germany.

Clinical Competence↗

[Model construction for reperfusion of the isolated pig liver].

In recent years thermal ablation of liver tumors as a minimally invasive method became a promising alternative to conventional strategies such as chemotherapy or resection of liver tissue. Thereby an electrode is placed inside the tumor delivering energy in the form of high frequency current into the target volume to achieve and maintain a tissue temperature between 60 and 100 degrees C. Cells exposed to this thermic stress undergo coagulation necrosis and are irreversibly damaged. To protect vital liver structures from heat, it is necessary to develop an online temperature monitoring system. An experimental setup perfusing isolated pig livers under physiological conditions with 0.9% NaCl solution was established to develop and evaluate the measuring technique.

Animals↗

[Development of primary malignancies after liver and kidney transplantation and the treatment approach].

Primary malignancy after solid organ transplantation has a more than three-fold incidence compared to the normal population. Causes are intensity and duration of immunosuppression, pre-operatively undetected, occult malignancy or pre-cancerous lesions in the recipient, direct or indirect tumor transmission via the transplant and environmental factors. Measures for prevention comprise antiviral treatment of individuals at risk for primary EBV-infection and prevention of sun exposure. Early detection follows general medical guidelines and, in addition, selective screening of certain risk groups of patients. Treatment of solid tumors follows established guidelines of professional working parties. Post-transplant lymphoproliferative disorders can often be treated with anti-CD antibody (rituximab). Antiproliferative immunosuppressants like rapamycin may seem promising with regard to a possibly reduced incidence of de-novo malignancy in the future.

Humans↗

[Intensive care treatment of post-traumatic liver failure].

Liver failure following trauma or surgery is associated with a mortality of between 15-->50%, depending on the extent of the operation, pre-operative functional impairment of the liver as well as the occurrence of concomitant infectious disease. The liver can be the source as well as the target of posttraumatic liver failure (PLF). PLF can be caused by a reduction of liver perfusion due to hypotension, catecholamines or increased intraabdominal pressure. Further contributing factors include prolonged parenteral nutrition, endotoxemia, and potentially hepatotoxic drugs (sedatives, anticonvulsive drugs, antibiotics etc.). PLF is mostly associated with MOF. The Child classification and the APACHE score may predict prognosis before surgery and serum bilirubin levels thereafter. Prevention and therapy is based on treatment of shock and tissue hypoxia. It should be accompanied by appropriate diagnostic measures and followed by an aggressive medical and surgical approach.

APACHE↗

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↗

Prospective randomized trial to assess the value of preemptive oral therapy for CMV infection following liver transplantation.

BACKGROUND: With the development of sensitive tests to detect cytomegalovirus (CMV) viremia, preemptive approaches become a reasonable alternative to general CMV prophylaxis. We performed a randomized trial comparing pp65-antigenemia guided preemptive therapy using oral ganciclovir with symptom-triggered intravenous ganciclovir treatment. METHODS: Eighty-eight of 372 liver transplant recipients developed antigenemia early after orthotopic liver transplantation. Twenty-eight symptomatic patients with antigenemia were excluded from randomization and treated with intravenous ganciclovir. Sixty pp65-antigen-positive asymptomatic patients were randomized to receive either oral ganciclovir 3x1 g/day for 14 days (group 1) or no preemptive treatment (group 2). Patients that developed CMV disease were treated with intravenous ganciclovir 2x5 mg/kg body weight for 14 days. The high-risk (Donor+/Recipient-) patients were equally distributed in the two study groups. RESULTS: Three of 30 (10%) patients on oral ganciclovir developed mild to moderate CMV disease compared with 6/30 (20%) patients in the control group. In the Donor+/Recipient- patients, the incidence of CMV disease was 1/6 and 3/7. All disease episodes resolved after intravenous treatment. The 1- and 3-year patient and organ survival was the same in the study groups and in the patients with or without CMV infection. No deaths related to CMV occurred. CONCLUSIONS: The positive predictive value of pp65-antigenemia for the development of CMV disease was very low, and, in 28/88 patients (32%), antigenemia did not precede symptoms. Therefore, pp65-antigenemia is of limited value in deciding on the timing and need for ganciclovir therapy after liver transplantation.

Administration, Oral↗

Significance of a T-lymphocytotoxic crossmatch in liver and combined liver-kidney transplantation.

BACKGROUND: In contrast to kidney transplants a positive crossmatch is no contraindication for liver transplantation (OLT). In liver transplantation, antibody mediated rejections are rarely reported and a liver graft is suspected to have protective effects for kidney grafts when transplanted simultaneously. The aim of this study was to evaluate the effect of a positive crossmatch on outcome after OLT and combined liver and kidney transplantation (CLKTx). METHODS: We analyzed retrospectively the impact of a positive crossmatch on graft survival and rejection episodes after OLT (793pats) and CLKTx (18pats, 2.2%). Immunosuppression consisted of either Cyclosporine- or Tacrolimus-based regimens. RESULTS: A total of 50/811 (6%) of patients had a positive crossmatch, 45/793 (5.6%) with liver transplantation alone and 5/18 (28%) of patients with CLKTx. Follow-up ranged from 1 to 122.5 months (median 45.8 months). One- and 5-year graft survival rates of liver transplants alone with a positive crossmatch were 89.6% and 75.3%, respectively and were 88% and 77.5% in crossmatch negative recipients. Additionally, the incidence of acute and steroid-resistant rejection (44% and 15.5%) was not significantly increased in patients with a positive crossmatch when compared with patients with a negative crossmatch (38% and 19%). None of the patients with a positive crossmatch and CLKTx underwent a hyperacute-rejection episode after transplantation, and kidney graft survival 100%. CONCLUSIONS: In conclusion, a positive crossmatch is no contraindication for OLT and CLKTx. Furthermore, not having to wait for results of donor/recipient crossmatching can shorten cold ischemia time and may improve the clinical outcome.

Adult↗

Comparison of famciclovir and lamivudine in the long-term treatment of hepatitis B infection after liver transplantation.

BACKGROUND: Preliminary results of short-term famciclovir and lamivudine therapy in patients with hepatitis B virus (HBV) infection after liver transplantation revealed promising results. In a retrospective study the efficacy of long-term treatment with these substances was compared. METHODS: A total of 53 HBV-infected adults (48 reinfections and 7 de novo infections) received antiviral treatment. A total of 32 of these patients were treated with famciclovir 3x500 mg, 20 of them were later switched to lamivudine. Fourteen patients received lamivudine, 150 mg/day orally, as first line therapy and 7 patients after failure of famciclovir-prophylaxis. Follow-up time was 8 to 62 months (mean 35 months). Response to therapy (HBV-DNA negative) was compared using Kaplan-Meier estimates. Potential influence factors (HBV-DNA and HBeAg pretransplant, HDV coinfection, pretreatment with famciclovir and immunosuppression) on treatment response were analyzed by log. Rank test (univariate); then a multivariate analysis (Cox multiple stepwise regression model) was applied. RESULTS: A total of 19 and 76% of the patients treated with famciclovir and lamivudine resp. became HBV-DNA negative; 0 and 24% HBsAg negative. Lamivudine was also effective as second line therapy. In a multivariate analysis of all 73 treatment courses, lamivudine treatment and HDV-coinfection were significant factors for better treatment response; regarding only the lamivudine group, negative HBeAg pretransplant was significant. Viral breakthrough after prolonged treatment occurred in 55% (lamivudine) to 80% (famciclovir) of treatment courses but was only accompanied by mild hepatitis. CONCLUSIONS: Lamivudine and famciclovir are potent drugs for the treatment of HBV-infection after liver transplantation. The antiviral capacity of lamivudine is superior even after pretreatment with famciclovir but after prolonged treatment viral breakthrough is often observed.

2-Aminopurine↗

Portal vein angioplasty using a transjugular, intrahepatic approach for treatment of extrahepatic portal vein stenosis after liver transplantation.

Symptomatic portal vein stenosis is an uncommon complication after liver transplantation. Portal vein angioplasty has been successfully established for treatment of portal vein stenosis using mesenteric or percutaneous, transhepatic approaches. We herein report on a patient who suffered from variceal bleeding due to portal hypertension 3 months after liver transplantation. After successful endoscopic sclerotherapy, an extrahepatic portal vein stenosis was diagnosed, and portal vein angioplasty was considered as primary therapeutic option. Instead of mesenteric or percutaneous, transhepatic approaches, we adopted a transjugular, intrahepatic access to introduce a 14-mm balloon catheter into the portal vein. Using this technique, angioplasty was successfully performed. After intervention, no further episodes of variceal bleeding occurred. We favour the transjugular, intrahepatic technique for portal vein angioplasty because it does not require general anesthesia, in contrast to the mesenteric approach, and it reduces the risk of intra-abdominal bleeding, compared to the percutaneous, transhepatic approach.

Angioplasty↗