Biomedical subjects

Ulrich Theodor Hopt

Publications and source records attributed to Ulrich Theodor Hopt.

9 recordsLinked to original sources

PubMed2006

Targeting vascular endothelial growth factor pathway offers new possibilities to counteract microvascular disturbances during ischemia/reperfusion of the pancreas.

BACKGROUND: It is of crucial importance to explore new therapeutic strategies capable of combating or even preventing pancreatic graft failure after transplantation caused by ischemia reperfusion damage. So far, the role of the hypoxia induced mediator vascular endothelial growth factor (VEGF) upon pancreatic microcirculation has not been described. Therefore the aim of this study was to investigate its influence, using the novel tyrosinekinase inhibitor PTK787/ZK222584 (PTK/ZK), upon functional capillary density (FCD), leukocyte-endothelium interaction (LEI), and macromolecular permeability (P) of normal and postischemic pancreas tissue. METHODS: Sprague-Dawley rats were anesthetized and randomly assigned to five groups (n=7/group): (a) sham, (b) ischemia/reperfusion (I/R) control, (c) I/R and PTK/ZK treatment, (d) VEGF-superfusion, (e) VEGF-superfusion and PTK/ZK-treatment. A recently established method of digital dynamic intravital epifluorescence microscopy was used for evaluating the effective microvascular permeability together with FCD and LEI. RESULTS: Comparison between sham vs. I/R shows a significant upregulation of VEGF-expression followed by deterioration of microcirculation with decreased FCD, increased P and LEI. Treatment with PTK/ZK resulted in a significant decrease of P under conditions of superfusion with VEGF as well as I/R compared to corresponding groups without treatment. CONCLUSION: VEGF plays a crucial causative role involving an increase in permeability in normal as well as in postischemic pancreatitis via tyrosinkinase receptors. VEGF seems to be partly accountable for a deterioration of FCD and an upregulation of LEI via VEGF-tyrosinekinase receptor independent mechanisms. VEGF might be a promising potential therapeutic target in order to minimize edema formation caused by I/R and pancreatitis in pancreas transplantation.

Animals↗

PubMed2006

Living-donor kidney transplantation: the Freiburg experience.

BACKGROUND AND AIM: The objective of this study was to determine outcome after living-donor kidney transplantation in a single-center institution in Germany. MATERIALS AND METHODS: From 1976 to May 2005, a total of 298 living-donor kidney transplants were performed at the University of Freiburg. Most recipients (78.8%) were placed on cyclosporine, mycophenolate mofetil, and corticosteroids maintenance immunosuppression. Cox proportional hazard model was applied to analyze predictors for patient and graft survival. Mean follow-up was 5.3 years. RESULTS: According to Kaplan-Meier calculation, 1-, 5-, and 10-year patient survival was 98.6, 92.7, and 86.8%, respectively. Kidney function rate was 95.5, 82.8, and 67.9%, respectively. A 5-year graft function rate continued to increase from 79.5% in patients transplanted before 1996 to 83.6% in patients transplanted thereafter. In a Cox regression model recipient age above 50 years, duration of dialysis above 2 years and preexisting type 1 diabetes mellitus were associated with a decreased patient survival. Graft survival was mostly influenced by the type of immunosuppression and preexisting hypertension of the recipient. CONCLUSIONS: Our results demonstrate that living-donor kidney transplantation is a highly effective therapy for patients with end stage renal failure. Updates in immunosuppression, recipient selection, and operative technique may have contributed to the improved graft survival over the past three decades.

Adolescent↗

PubMed2006

Characterization of ischemia/reperfusion-induced gene expression in experimental pancreas transplantation.

BACKGROUND: The aim of this study was to identify genes that are differentially expressed in the early period after pancreatic cold ischemia/reperfusion (I/R) injury. METHODS: Grafts of isogeneic rat pancreaticoduodenal transplantation were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6-hour CIT; UW, 18-hour CIT; and physiologic saline solution, 6-hour CIT. Animals that did not receive transplants served as controls. At 2-hour reperfusion, grafts were removed and pancreatic RNA was isolated, pooled, and hybridized to Affymetrix RG-U34A arrays. Quantitative reverse-transcription polymerase chain reaction was used to confirm the results of microarray technology. RESULTS: A total of 49 genes were consistently upregulated (more than threefold) in all three groups of transplant recipient animals. Prominent genes include transcription factors; cytoskeletal factors; heat-shock proteins (e.g. Hsp27, Hsp90); molecules involved in inflammation (e.g. PAPIII), immunology, signal transduction, and translation; and genes that have not been associated with I/R injury so far (e.g. Best5). Messenger RNA levels of some genes were exclusively downregulated in response to the different conditions applied to the pancreatic grafts: Cybb, Reg3a, Per2, BMAL1, MAP, and Isl2. CONCLUSIONS: These results provide new insight in I/R-induced gene expression after experimental pancreas transplantation. The reported upregulation of heat shock proteins, Best5, and PAPIII may play a pathologic role in pancreatic cold I/R injury and could therefore provide a promising perspective for further investigations.

Animals↗

PubMed2006

Kidney transplantation with concomitant unilateral nephrectomy: a matched-pair analysis on complications and outcome.

BACKGROUND: We sought to determine the impact of kidney transplantation with simultaneous unilateral nephrectomy on perioperative morbidity and patient and graft survival. METHODS: From January 1990 to May 2004, 75 kidney transplantations with simultaneous unilateral nephrectomy (group NE+) were performed at the University of Freiburg. Of these, 49 had polycystic kidney disease. Patients of group NE+ were matched with 75 kidney transplants without nephrectomy (group NE-). Immunosuppressive maintenance therapy in both groups was based on cyclosporine A, mycophenolate mofetil or azathioprine, and prednisone. Mean follow up was 4.1 yrs (range 0.3-11.7 yrs). RESULTS: Patient survival rate at 1 and 5 yrs was 95% and 84% versus 95% and 93% in group NE+ and NE-, resp. (P=0.56). Accordingly, kidney function rate was 85% and 74% in group NE+ versus 89% and 79% in group NE- (P=0.89). Perioperative (90 days) mortality rate in group NE+ was 1.3% and 2.7% in group NE- (P=0.56). Perioperative surgical complications were similar in both groups. CONCLUSIONS: Kidney transplantation with concomitant unilateral nephrectomy has no negative impact on patient or graft survival and is associated with a reasonable morbidity rate.

Adolescent↗

PubMed2005

Risk factors for the intermediate outcome of morbid obesity after laparoscopically placed adjustable gastric banding.

BACKGROUND: The overall long-term results of medical treatment for morbid obesity are poor. Surgery is the only treatment option to obtain long-term weight reduction. Analysis of risk factors for treatment success of laparoscopically placed gastric banding (LGB) has not been available until now. METHODS: Prospective study with 99 patients with LGB between January 1997 and July 2003. The parameters assessed as risk factors included onset of obesity, feeling of postprandial satiety, and initial body mass index (BMI). RESULTS: Median follow-up was 36 months (3 to 72). Independent prognostic factors of excess body weight reduction (>25%) were for the first postoperative year: onset of obesity as an adolescent (relative risk [RR] 0.21), an initial BMI <45 kg/m(2) (RR 4.76), and a BMI between 45.1 and 50 kg/m(2) (RR 3.23). After the second year, independent prognostic factors were as follows: feeling of postprandial satiety (RR 5.26) and an initial BMI <45 kg/m(2) (RR 3.03). CONCLUSION: LGB is suitable to achieve intermediate weight reduction in patients with morbid obesity. To obtain the best results, patients should be treated before they achieve a BMI >45 kg/m(2). Additionally a postprandial feeling of satiety after LGB is mandatory for good long-term results.

Adult↗

PubMed2005

Serous cystadenocarcinoma of the pancreas: management of a rare entity.

Whereas mucinous cystadenomas of the pancreas are considered premalignant, serous cystadenomas are believed to remain benign. We present a case of an 80-year-old woman with a primary tumor of the pancreas that was histologically classified as serous cystadenocarcinoma. Because preoperatively available criteria that determine malignancy in serous lesions are lacking, observation is the preferred option in serous cystadenomas. Operating every serous lesion is not justified. Reviewing all reports of serous cystadenocarcinomas that have been published to date, we are providing recommendations for the management of this rare entity.

Aged, 80 and over↗

PubMed2004

Long-term follow-up of 78 simultaneous pancreas-kidney transplants at a single-center institution in Europe.

BACKGROUND: The objective of this study was to determine the long-term results after simultaneous pancreas-kidney transplantation (SPK) at a single-center institution in Europe. PATIENTS AND METHODS: Seventy-eight consecutive patients with insulin-dependent diabetes mellitus and end-stage nephropathy were followed for a median of 7 years after SPK. Immunosuppressive protocol consisted of cyclosporine A, azathioprine, prednisone, and antithymocyte globulin. Multivariate Cox proportional hazard model was used to investigate the impact of different putative risk factors on long-term patient survival. Health-related quality of life was assessed by a validated questionnaire (SF-36). RESULTS: Patient survival at 5 and 10 years was 81% and 67%, respectively. Pancreas function rate was 73% and 60% and kidney function 67% and 44%, respectively. In multivariate analysis, preexisting myocardial infarction (relative risk [RR] 5.1, 95% confidence interval [CI] 1.5-16.6) and amputation (RR 3.7, 95% CI 1.1-12.9) were strongly associated with a diminished long-term patient survival. Analysis of patients with long-term functioning pancreas and kidney grafts revealed excellent results for quality of life posttransplant that were comparable with average scores of the normal German population. CONCLUSIONS: This series representing the largest experience with long-term follow-up in Europe confirms an excellent long-term survival and an exceptional quality of life after SPK.

Adult↗

PubMed2004

Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation.

Brief periods of warm ischemia and subsequent short reperfusion before either long-term cold or warm ischemic insult (ischemic preconditioning, IPC) have proven to ameliorate ischemia/reperfusion (I/R) injury in various organs, such as the liver and lung. The aim of this study was to examine the effect of IPC on pancreatic cell apoptosis and microcirculatory impairments in experimental pancreas transplantation. Male Lewis rats served as donors and recipients of heterotopic syngeneic pancreaticoduodenal transplantation. Recipient animals were divided into two experimental groups: group Tx (n=7) received grafts without IPC, group Tx&IPC received grafts with IPC. Animals that had not undergone transplantation but whose pancreata had been exteriorized served as controls (n=5). All pancreatic grafts were preserved in University of Wisconsin solution for 6 h at 4 degrees C. IPC was induced by interruption of the arterial blood flow for 10 min followed by 10 min of reperfusion. One and two hours after reperfusion, graft microcirculation was assessed by means of intravital microscopy (IVM). Rats were immediately killed after the second measurement and DNA breaks of acinar cells were detected by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end-labelling (TUNEL) assay and gel electrophoresis (laddering). The apoptotic index (AI) was defined as the number of apoptotic cells per high-power field. Analysis of both groups of transplanted grafts showed a significant decrease in functional capillary density (FCD) and a significant increase in leukocyte sticking to postcapillary venules (LAV) at 1 h and 2 h of reperfusion, compared with animals that had not undergone transplantation ( P<0.01). In parallel, AI was significantly increased in transplanted grafts compared to the controls ( P<0.01). Grafts subjected to IPC showed no significant differences, neither for FCD nor LAV, at both time points if compared with grafts of group Tx. However, IPC resulted in a significant increase in AI ( P<0.05). We can conclude that IPC has no effect on pancreatic microcirculation but enhances acinar cell apoptosis in experimental pancreas transplantation. These results indicate that IPC might increase I/R injury after pancreatic cold ischemia.

Animals↗

PubMed2004

Brain death impairs pancreatic microcirculation.

Brain death (BD) influences the quality of donor grafts in transplantation. To evaluate the impact of BD on pancreas grafts, we investigated the influence of BD on the microcirculation and histology of the pancreas in a rat model of explosive BD. A group of Wistar rats (n=7), rendered brain dead by inflating an intracranially inserted Fogarty catheter was compared with controls (CO) using intravital epifluorescence-microscopy over 4 h after BD induction; functional capillary density (FCD), leukocyte adherence (AL) in post-capillary venules, histology and pancreatic enzymes were investigated. Four hours after BD, FCD decreased (333 +/- 11 vs. baseline 444 cm/cm2 +/- 5 SEM; p<0.01) and showed lower values than CO (388 +/- 9 p<0.01). In BD, AL was increased (628 cells/mm2 +/- 110 SEM vs. baseline 123 +/- 32, and vs. CO 180 +/- 33; p<0.001). BD caused increased histological damage (CO 1.6 score-points +/- 0.7 SD vs. BD 8.3 +/- 7.1; p<0.05). Amylase was higher in BD (p<0.05) but did not reach pathological values. We show for the first time that BD causes relevant changes in pancreatic microcirculation, histology and leukocyte endothelial interaction which might have a serious impact on the function of grafts. New strategies for preventing this damage are therefore highly desirable in order to improve the outcome of pancreas transplantation.

Amylases↗