Biomedical subjects

Oliver Drognitz

Publications and source records attributed to Oliver Drognitz.

12 recordsLinked to original sources

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↗

PubMed2006

Persistent normoglycemia in the streptozotocin-diabetic rat by syngenic transplantation of islets isolated from a single donor with Liberase.

OBJECTIVES: Enzymatic digestion of donor pancreas is a vital step in islet isolation process. Recently, human and large mammalian islet isolation has been improved by Liberase. However, there are no data to show the improvement of rat islet isolation with Liberase. We hypothesized that commercially available Liberase has variable activities from batch to batch and that a short culture period might improve the function of isolated islets in vivo. We therefore isolated islets with Liberase and cultured them for a short period before transplantation to reverse diabetes in a syngenic rat model. METHODS: Islets of high inbred Lewis rats were isolated with Liberase, purified by discontinuous density gradients, hand-picked, and cultured at 37 degrees C for 24 hours. The same batch of Liberase was used for all experiments in this study. Freshly isolated and cultured islets were implanted intraportally into rats rendered diabetic by streptozotocin. RESULTS: In this study, we were not able to reverse diabetes by syngenic transplantation of freshly isolated islets from 2 donors with Liberase in the rat model. Surprisingly, for the first time, we successfully achieved normoglycemia for more than 100 days in the diabetic rats by syngenic transplantation of the cultured islets isolated with Liberase. These normoglycemic diabetic rats showed normal glucose tolerance curves. Histologic examination of the livers of the islet recipients revealed intact islets, with numerous well-granulated insulin-containing cells and only few glucagon-expressing cells. In islets of the recipients' pancreata, the remaining native islets consisted mainly of glucagon-expressing cells, with few insulin-expressing cells in the center. CONCLUSIONS: We conclude that Liberase isolation followed by a short culture period may be a good substitute for collagenase in rats. Islet culture before transplantation can promote the success of single-donor-single-recipient islet transplantation to reverse diabetes in the rat model.

Animals↗

PubMed2006

ABO-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab: a single center experience.

BACKGROUND: For years ABO-incompatible kidney transplantations were preferentially performed in Japanese centers. In order to overcome the increased risk of humoral rejections, patients were treated with multiple sessions of plasmapheresis, intensified immunosuppressive therapy and splenectomy before transplantation. Despite good long-term results regarding patient and organ survival rates, increased morbidity during the early post-transplant period prevented a broad application of this method. Recently, a new protocol including the anti-CD20-antibody (Ab) rituximab and blood group-specific immunoadsorption instead of splenectomy and plasmapheresis was published with excellent short-term results. METHODS: From April 2004 to September 2005, 11 patients were prepared for ABO-incompatible transplantation. All patients received 375 mg/m2 rituximab intravenous 3 to 4 weeks before transplantation. Immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and prednisone and was started at least 7 days before transplantation. Intravenous immunoglobulins (0.5 g/kg) were administered the day before transplantation. Immunoglobulin G (IgG)-anti-A or -B Ab titers before starting immunoadsorption treatment ranged between 1 : 4 and 1 : 1024. Immunoadsorption treatment was started in parallel with immunosuppressive medication and was continued until the anti-A or anti -B Ab titers (IgG and IgM) were lowered to the aimed pre-transplant threshold of <1 : 8. During the early postoperative period, additional immunoadsorption treatments were performed, if the titers increased again above 1 : 8 (days 0 to 7) or 1 : 16 (days 8 to 14), respectively. RESULTS: Transplantation could be conducted in eight of 11 patients (two females, six males, mean recipient age 52+/-11 yr). The mean follow-up was 7.0 months (range 4 to 17). The blood group constellation was A1 to 0 in four cases, A2 to 0 in two cases, B to A in one case, and A1 to B in another case, respectively. On average, each patient received seven immunoadsorption treatments. All transplants showed primary function and no humoral rejections occurred. Three of our 11 patients showed rapid increases of isoagglutinin titers after each immunoadsorption treatment and thus could not be transplanted. One patient died 4 months after transplantation with a functioning graft due to sepsis secondary to pseudomembranous enterocolitis. The mean creatinine value of the remaining seven patients now is 1.6 mg/dl. SUMMARY: The use of antigen-specific immunoadsorption and an immunosuppressive regimen consisting of a conventional triple immunosuppressive therapy has shown excellent short-term results. The immunoadsorption treatment using antigen-specific columns is highly effective and even patients with high isoagglutinin titers can be transplanted. This protocol is an option for end-stage renal disease patients who have no blood group-compatible donor.

ABO Blood-Group System↗

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↗

PubMed2004

Effects of organ preservation, ischemia time and caspase inhibition on apoptosis and microcirculation in rat pancreas transplantation.

This study was undertaken to examine the impact of ischemia-reperfusion (I/R) injury on microcirculation and apoptosis in experimental pancreas transplantation. Pancreatic grafts were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6-h CITs (group U6); UW, 18-h CITs (group U18); normal saline, 6-h CITs (group S6); and normal saline, 6-h CITs with Z-Asp-2,6-dichlorobenzoyloxymethylketone (pan-caspase inhibitor; group S6 & CI). Nontransplanted animals served as controls. At 1- and 2-h reperfusion microcirculation was assessed by means of intravital microscopy. Apoptosis was detected by in situ nick end-labeling method (TUNEL) at 2-h reperfusion. Deterioration of microcirculation was lowest in group U6 and highest in groups S6 and S6 & CI compared with controls. The apoptotic index (cells per high power fields) of groups U6, U18 and S6 correlated well with functional capillary density (r=- 0,70, p < 0.0001) and leucocyte sticking (r= 0,69, p < 0.0001) at 1-h reperfusion. Caspase inhibition had no impact on microcirculation but significantly reduced AI compared with group S6 (p < 0.001). These data suggest that pancreatic I/R injury-induced apoptotic cell death well predicts the extent of [corrected] microcirculatory impairment. Caspase inhibition might be a promising strategy in reducing I/R injury in pancreas transplantation.

Animals↗

PubMed2003

Postoperative oral glucose tolerance and stimulated insulin secretion: a predictor of endocrine graft function more than 10 years after pancreas-kidney transplantation.

BACKGROUND: After pancreas transplantation, endocrine function is determined by the insulin secretory capacity of the transplanted pancreas. The authors evaluated the predictive value of postoperative oral glucose tolerance test (OGTT) and stimulated insulin secretion on long-term endocrine function. METHODS: Forty-one patients after pancreas-kidney transplantation with systemic venous drainage were studied. Patients were categorized to have normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) (World Health Organization criteria: NGT, <7.8 mM; IGT, 7.8-11.1 mM 120 min after glucose intake) and high or low total insulin secretion. Mean follow-up of graft function and patient outcome was 10.2+/-0.5 years after OGTT. RESULTS: Patients with IGT had grafts with a longer ischemia time and a significantly worse urine amylase excretion as compared with patients with NGT. Using Kaplan-Meier survival analysis, patients with NGT had better long-term pancreatic function as compared with IGT in the follow-up after performing the first OGTT (mean, 10.9+/-0.2 vs. 8.8+/-0.9 years of graft function; P=0.02), but there was no difference in patient survival and kidney graft function. Also, high insulin secretion predicted significantly longer pancreas graft function as compared with low insulin secretion (P=0.04). CONCLUSIONS: Although IGT does not lead to poorer long-term patient survival and kidney graft function, it does predict compromised long-term endocrine function of the transplanted pancreas. Therefore, postoperative OGTT are useful tools for identification of patients at risk of long-term endocrine graft failure after pancreas transplantation.

Adult↗

PubMed2003

Endotoxin preconditioning in pancreatic ischemia/reperfusion injury.

OBJECTIVES: Prospective organ donors are exposed to various stress types. The effect of endotoxin pretreatment (ETX) on pancreatic ischemia/reperfusion injury (IRI) is unclear. We investigated, using a rat model of pancreatic IRI of an in situ isolated pancreatic tail segment, the effect of ETX on postischemic microcirculation and organ damage. METHODS: Twenty-four hours before pancreatic dissection, either intraperitoneal application of ETX (1 mg/kg in 0.9% NaCl) or saline only (control) was performed. Two-hour normothermic ischemia of the pancreatic tail was induced by clamping the splenic vessels and was followed by a reperfusion period of 2 hours. Microcirculatory parameters were measured by intravital epifluorescence microscopy [functional capillary density (FCD), adherent leukocytes (ALs), and histology]. The presented data represent the mean +/- SEM/SD as appropriate. RESULTS: ETX pretreatment caused a significantly greater decrease in FCD (497 +/- 6 cm/cm2 baseline versus 326 +/- 15 cm/cm2 2 hours of reperfusion) compared with controls (498 +/- 8 versus 258 +/- 15 cm/cm2) 2 hours after reperfusion (P < 0.01). Two hours after reperfusion, ALs were significantly decreased in ETX animals compared with controls (ETX: 141 +/- 37 versus 273 +/- 36 cells/mm2, P < 0.05). Histologic damage was less in ETX (6.4 score points +/- 0.32 versus 8.8 +/- 0.33 control, P < 0.05). CONCLUSION: ETX preconditioning decreases microcirculatory deterioration caused by IRI by means of less loss of nutritive tissue perfusion, decrease in ALs, and less histologic damage. This indicates a protective effect of ETX preconditioning in pancreatic IRI.

Animals↗

PubMed2002

Celiac axis stenosis in pancreatic head resection for chronic pancreatitis.

BACKGROUND AND AIMS: To determine the outcome of pancreatic head resection for chronic pancreatitis in the presence of celiac axis stenosis or occlusion we analyzed the blood supply of the upper abdominal organs in 11 patients before and after surgery. PATIENTS AND METHODS: Between March 1994 and April 2000 we performed 145 pancreatic head resections for chronic pancreatitis. Preoperatively 11 patients showed celiac axis stenosis at angiography. All 11 patients underwent duplex ultrasonography postoperatively and 8 had magnetic resonance angiography during follow-up. RESULTS: In two cases division of the median arcuate ligament was performed to reestablish hepatic artery blood flow. No further revascularization procedures of the celiac axis were necessary. Postoperative duplex ultrasonography and magnetic resonance angiography showed normal blood flow in five patients. Four patients still had an occlusion or a significant celiac axis stenosis, and two had a stenosis only during expiration. At follow-up nine patients were completely free of abdominal pain (82%), and all had gained weight postoperatively, ranging from 5 to 16 kg. CONCLUSIONS: Our data suggest that celiac axis stenosis infrequently causes complications in pancreatic head resection for chronic pancreatitis and therefore does not represent a contraindication for this procedure. Nevertheless the hepatopedal blood flow must be confirmed by palpation or duplex ultrasonography after pancreatic head resection in these patients.

Celiac Artery↗