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R Margreiter

Publications and source records attributed to R Margreiter.

At least 37 records · Page 2Linked to original sources
PubMed2005

Lipid metabolism in renal transplant patients receiving tacrolimus/sirolimus combination therapy.

INTRODUCTION: The administration of sirolimus has been reported to be associated with high serum cholesterol and high triglyceride values. In a large prospective, multicenter 6-month study in renal transplantation, basic parameters of lipid metabolism (total serum cholesterol and triglycerides) were systematically assessed in patients who received tacrolimus/mycophenolate mofetil/steroids (Tac/MMF), tacrolimus/0.5 mg sirolimus (SIR)/steroids (Tac/0.5SIR) on tacrolimus/2 mg sirolimus/steroids (Tac/2SIR). METHODS: For purposes of analysis, lipid parameters were classified using the National Kidney Foundation Dyslipidemia Classification definitions. RESULTS: Complete sets of data at all visits (baseline, months 1, 3, and 6) were available for 211 Tac/MMF, 210 Tac/0.5SIR, and 203 Tac/2SIR patients. Total serum cholesterol in the Tac/MMF group was 193.4 at baseline and 202.9 mg/dL at month 6. Values increased from 196 mg/dL to 212.5 mg/dL in Tac/0.5SIR and from 200 mg/dL to 230.5 mg/dL in Tac/2SIR. Differences in parameters between treatment groups were statistically significant (P < .05). Serum triglycerides decreased from baseline to 6 months in Tac/MMF, increased from 176.3 mg/dL (baseline) to 191.4 mg/dL (6 months) in Tac/0.5SIR and from 203 mg/dL to 255.3 mg/dL in Tac/2SIR. Parameters differed significantly between Tac/0.5SIR versus Tac/2SIR at P = .0069, and between Tac/MMF versus Tac/2SIR at P = .0013. In the Tac/2SIR group 36.5% had "high" serum cholesterol and 8.3% had "very high" triglyceride levels at 6 months. CONCLUSION: Total serum cholesterol levels were relatively stable and serum triglycerides decreased between baseline and month 6 using a Tac/MMF regimen. Contrastingly, the Tac/SIR combinations led to increased total cholesterol values (at both sirolimus dose levels) and Tac/2SIR also led to increased triglyceride levels.

Cholesterol↗
PubMed2005

Islet isolation and GMP, ISO 9001:2000: what do we need--a 3-year experience.

Pancreatic islet cell isolation and transplantation has been performed for many years at several institutions. Although all institutions aim to produce high-quality islets, applied standards widely deviate from standards in the pharmaceutical industry. The legal situation within the European Union has changed requirements for setting up and running such a laboratory. The process is now clearly defined as a production of a pharmaceutical and therefore must be licensed by federal authorities. Analysis of workload for establishing an islet isolation program that fulfil GMP and ISO 9001 criteria including an estimation of costs and the impact of such a system on the isolation process. The definition of quality parameters and documentation is a central issue of all islet isolation laboratories. Therefore, GMP and ISO 9001:2000 do not add additional work per se. On the other hand, clear guidelines, a clear policy, working place descriptions, forms, checklists, and, particularly standard operating procedures, are instrumental for smooth functioning within the department. Collection of data such as errors, improvement measures, and preventive measures reduces subsequent costs. A clear definition of responsibilities minimizes organizational problems. Steering of inspection devices prevents bias errors and validating the processes clearly points out incorrect assumptions. Documentation helps to prove the correctness of the production at any time and is of use also for scientific evaluations. We strongly feel that GMP criteria are mandatory and together with an ISO 9001:2000 quality management system offers significant advantages for the process of islet isolation and a continuous improvement process.

Academies and Institutes↗
PubMed2005

"Real-time" assessment of human islet preparations with confocal live cell imaging.

Pancreatic islet cell transplantation is a promising approach to restoring normoglycemia in diabetic patients. The outcome of islet transplantation is uncertain for two reasons: The quality of isolated islets is still poorly defined and the functional potential of transplanted islets is difficult to predict. Therefore, one of the primary challenges in islet transplantation is to identify and understand the changes taking place in islets after isolation and culture. Description of such changes in living islet cells offers insights not achievable by use of fixed-cell techniques. Three fluorescent dyes, dichlorodihydrofluorescein diacetate, tetramethylrhodamine methyl ester perchlorate (TMRM), and fluorescent wheat germ agglutinin, were used to assess either overall oxidative stress, time-dependent mitochondrial membrane potentials, or localization of oligosaccharides. Confocal microscopy was performed with a microlens-enhanced Nipkow disk-based confocal system mounted on an inverse microscope. We were able to show differences in the amount of oligosaccharides on the cell surface between endocrine and exocrine cells in freshly isolated human islet preparations. The study of the mitochondrial membrane potential via TMRM proved to be useful to early identification of damaged or stressed cells. Thus a combination of fluorescent dyes as subcellular markers, with a powerful live confocal imaging system may be of great value to isolation and culture.

Cell Survival↗
PubMed2005

A cluster of rotavirus enteritis in adult transplant recipients.

Diarrhea following solid organ transplantation is a common side effect of some immunosuppressive agents but can also be caused by many pathogens. An outbreak of rotavirus (RV) enteritis presenting with severe diarrhea in four solid organ recipients was analyzed. The first case was diagnosed in a 6-month-old liver recipient who was prehospitalized on a pediatric ward. Within 1 month, three adult patients (two liver, one renal recipient) presented with enteritis. During diarrhea a significant rise in tacrolimus levels was observed. One patient developed toxic megacolon with ulcerative colitis. Infections were self-limiting but led to secondary infectious complications and prolonged hospitalization. This is the first reported outbreak of RV enteritis in a multiorgan transplant unit involving adult patients. Although no fingerprinting or subtyping of the virus was performed we assume the child was the primary source. In transplant recipients presenting with diarrhea RV infection should be considered.

Aged↗
PubMed2005

Progression of macrovascular diseases is reduced in type 1 diabetic patients after more than 5 years successful combined pancreas-kidney transplantation in comparison to kidney transplantation alone.

Recent reports have demonstrated an improved cardiovascular outcome after simultaneous pancreas-kidney transplantation (SPKT) compared with kidney transplantation alone (KTA) in type 1 diabetic patients with end-stage renal disease. The purpose of this study was to determine the impact of SKPT and KTA on the progression of cerebrovascular disease (CVD), coronary heart disease (CHD) and peripheral vascular disease (PVD) 5 and 10 years after transplantation. Only patients with graft survival more than 5 years, were included in this study. In summary, 12 type 1 diabetic patients with SPKT and 10 diabetic subjects with KTA were evaluated. The immunosuppressive therapy was similar in both patient groups. The mean observation period was 124 (72-184) months in the SPKT group and 122 (64-216) months in the group with KTA. To investigate the vascular risk profile we examined mean HbA1c, blood pressure and lipid levels in both patient groups during the first 5 years (period I) and the second 5 years (period II) after transplantation (measurements at least at 3-month intervals). Additionally, we evaluated the prevalence of moderate (stage I-II) and severe (stage III-IV) macrovascular diseases prior as well as 5 and 10 years after transplantation. During period I the mean HbA1c-value was 5.7+/-0.4% in the group with SPKT versus 7.4+/-0.8% in the KTA group, and in period II 5.8+/-0.4% in the SPKT group versus 7.6+/-0.9% (P<0.001) in the patients with KTA. The cholesterol levels were approximately the same in both groups, the triglycerides were lower in the patients with SPKT than in the subjects with KTA with 1.3+/-0.4 vs. 2.2+/-0.9 mmol/l in period I, and 1.4+/-0.5 vs. 2.3+/-0.6 mmol/l in period II (P<0.05). The BP-values were similar in both groups. Five years after transplantation the prevalence of vascular diseases was not significantly different between both groups. During the following 5 years the prevalence of macrovascular diseases increased more in the KTA than in the SKPT group. After a mean observation period of 10 years the SKPT group showed a lower prevalence of vascular diseases (stage I-IV) with 41% CVD, 50% CHD and 50% PAV in comparison to the KTA group with a prevalence of 80% CVD, 90% CHD and 80% PAV), the difference was not statistically significant because of the small patient groups. The frequency of the vascular complications myocardial infarction (16% vs. 50%), stroke (16% vs. 40%) and amputations (16% vs. 30%) was in summary significant lower in the patients with SPKT than in the patients with KTA (P<0.05). In conclusion, while for the first 5 years after transplantation the progression of macroangiopathy in patients with SPKT and KTA was not significantly different, after a mean 10-year observation period the progression of macrovascular diseases was significantly lower in recipients with a functioning SPKT compared to patients with a KTA; this can be explained by a better vascular risk profile after SPKT. The 10-year patient survival was 83% in the SPKT group and 70% in patients with KTA.

Adult↗
PubMed2004

Bilateral hand transplantation: bone healing under immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone.

PURPOSE: Little is known about bone healing after composite tissue transplantation that requires pharmacologic immunosuppression. Bone integration and callus development were assessed in bilateral hand transplantation. METHODS: In this study the course of callus development and callus maturation were assessed by color Doppler sonography and radiography in a double hand transplant and compared with forearm replantation. RESULTS: After hand transplantation, ingrowth of small vessels at the bone junction was observed at week 3, calcified callus became visible at month 4, and bone union was completed at month 11. A similar time course of bone integration was observed after replantation. Plating offered sufficient stability. A recipient periostal flap is thought to have improved blood supply and favored development and induction of callus. CONCLUSIONS: Bone healing after hand transplantation under immunosuppression with tacrolimus, mycophenolate mofetil, and prednisolone is identical to that after forearm replantation.

Amputation, Traumatic↗
PubMed2004

Aberrant tetranectin expression in human breast carcinomas as a predictor of survival.

AIMS: Tetranectin (TN), a plasminogen kringle 4 binding protein, is thought to play a prominent role in the regulation of proteolytic processes via binding to plasminogen. The aim of this study was to evaluate the expression of TN in human breast cancer and adjacent normal breast tissue and to determine the impact of this expression on survival. METHODS: A retrospective analysis was performed on 189 patients with breast cancer, with a median follow up time of 10.6 years. The expression of TN was assessed in tumour tissue and adjacent normal breast tissue by immunohistochemistry, and the prognostic relevance of its expression in tumour cells was evaluated. RESULTS: TN was highly expressed in connective tissue fibres surrounding normal breast epithelium, but not in normal epithelial cells. High expression of TN in tumour cells was found in 131 (69%) of the tumour samples. By western blot analysis, no significant difference in the amount and molecular weight of TN was seen between tumour tissue and normal tissue. Strong TN immunoreactivity in tumour tissue was predictive of poor disease free and tumour specific overall survival. By multivariate analysis, high TN expression in cancer cells was an independent prognostic factor for disease free and tumour specific overall survival. CONCLUSIONS: Our results demonstrate differential TN expression in normal and malignant breast tissue and a prognostic impact of TN protein expression in breast carcinoma tissue. These data suggest a possible role of TN in invasiveness and the metastatic spread of human breast cancer.

Adult↗
PubMed2004

[Pathology of small intestine transplantation].

Small bowel transplantation is being increasingly performed to treat patients with irreversible intestinal failure or short bowel syndrome. Worldwide approximately 100 transplantations are currently performed per year. Technical advances and new immunosuppressive strategies adopted during the last 10 years have significantly improved the quality of live and survival rate of the patients. The 5-year survival rate is currently around 60%. However, the procedure still bears significant live threatening risks. Mayor problems include surgical complications like anastomotic leakage or peritonitis, acute allograft rejection, systemic infection and in later stages loss of graft function due to chronic rejection. Acute rejection is common after intestinal transplantation. It may occur any time after transplantation and is seen in 50%-80% of the patients. The characteristic changes are enterocyte apoptosis in the crypts, cryptitis and mononuclear cell infiltration with activated lymphocytes. Severe cases may reveal ulcerations or even sloughing and widespread exfoliation of the epithelium and are almost invariably associated with graft loss. The histopathological abnormalities may be patchy and occur in grossly normal mucosa. Therefore, multiple biopsies should be generally sampled for histology. Acute rejection must be distinguished from infections in particular opportunistic viral infections caused by Cytomegalovirus (CMV) or Adenovirus as well as from Epstein-Barr virus-related B-lymphocyte proliferations. Differential diagnosis also includes preservation injury and ischemia resulting in damage of the mucosal surface epithelium. Long-term graft function and survival are now increasingly determined by chronic rejection. The hallmarks of chronic rejection are obliterative arteriopathy of mesenterial vessels and progressive fibrosis of the transplant including its mesentery.

Graft Rejection↗
PubMed2003

Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival.

Recent studies have demonstrated cyclooxygenase 2 (COX-2) overexpression in various human malignancies, especially in breast cancer, where COX-2 turned out to be a predictor of poor survival. To evaluate the relation of COX-2 and Ep-CAM overexpression and its prognostic significance, we performed a retrospective study on 212 breast cancer patients with a median follow-up time of 10.5 years. Overexpression of COX-2 in tumour tissue samples was assessed by immunohistochemistry. COX-2 overexpression was found in 48.6% of the tumour samples and was predictive for poor disease-free and overall survival. Univariate analysis revealed a strong correlation between COX-2 and Ep-CAM overexpression (P=0.009). Concurrent COX-2 and Ep-CAM overexpression was present in 21.7% of tumour specimens and had an additive negative impact on disease-free and overall survival. Determination of both tumour markers should help in guiding new therapeutic strategies in patients with invasive breast cancer.

Adult↗
PubMed2003

Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer.

Matrix metalloproteinases (MMPs) have been implicated in ovarian cancer progression. Among them, MMP-8 that degrades type I collagen may play a crucial role. The aim of our study was to determine MMP-8 expression and regulation in ovarian cancer and its association with other MMPs and tissue inhibitors of metalloproteinases (TIMPs). Tissue microarrays (TMAs) containing tissue cylinders from 302 patients were used for immunohistochemical studies. In addition, MMP-8 expression in vitro was analysed by a specific immunoassay and PCR-analysis. MMP-7 (81%), MMP-8 (95%), MT3-MMP (100%), TIMP-2 (100%), and TIMP-3 (96%) were expressed in all the OVCAs, but the staining intensities varied. MMP-3 (6%), MMP-9 (57%) and TIMP-1 (43%) expressions were more rarely detected. Only MMP-8 expression levels correlated with tumour grade (P<0.01), tumour stage (P<0.01), and a poor prognosis (P<0.05). MMP-8 protein and gene expression in vitro was found to be significantly upregulated by interleukin-1beta (IL-1beta, P<0.01). The data indicate that MMP-8 overexpression in OVCAs is regulated by IL-1beta and that pro-inflammatory cytokines may promote the invasive potential of ovarian cancer.

Adult↗
PubMed2003

Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10850 comparing modified radical mastectomy with tumorectomy plus tamoxifen.

We have examined the outcome of older patients with operable breast cancer treated in a randomised trial by either standard surgery or less extensive surgery and tamoxifen. There were 236 participants aged >/=70 years, randomised to either modified radical mastectomy MRM (n=120) or wide local excision (WLE) and tamoxifen (T) 20 mg daily (n=116). Survival curves were estimated using the Kaplan-Meier method and multivariate analyses were performed using Cox's proportional hazards model. Endpoints were survival and time to first relapse or progression, loco-regional progression, time to distant progression and progression-free survival. No significant difference was seen in terms of progression-free survival, but there were significantly more loco-regional relapses in the WLE+T group. In contrast, there were more distant metastases in the MRM group, but with a similar overall survival in both groups. The results of this trial give cautious support for the use of WLE+T for selected older women.

Age Factors↗
PubMed2003

Heparanase-1 gene expression in normal, hyperplastic and neoplastic prostatic tissue.

Heparanase-1 (Hpa-1) has been implicated in tumour invasion and metastasis. In the present study, we evaluated the clinicopathological significance of Hpa-1 mRNA expression in prostate cancer and non-cancerous prostatic tissue by one-step polymerase chain reaction (PCR) of laser microdissected prostatic gland cells. In addition, cell type-specific expression of Hpa-1 mRNA in prostatic tissue was analysed by in situ hybridisation. Hpa-1 mRNA expression was found in 50% of normal and 40% of hyperplastic prostatic tissue. In situ hybridisation showed that Hpa-1 mRNA was strongly expressed in prostate gland cells. Of the 26 prostate carcinomas tested, 42% were positive for Hpa-1 mRNA. However, in non-cancerous prostatic tissue, Hpa-1 mRNA was significantly more often expressed than in less differentiated or more invasive prostate cancers (P<0.05). In situ hybridisation revealed only focal Hpa-1 mRNA expression in the neoplastic gland cells. Hpa-1 mRNA expression in the tumours significantly correlated with tumour differentiation and tumour stage (P<0.05). Our data indicate that Hpa-1 gene expression may be lost during dedifferentiation of prostatic gland cells.

Adult↗
PubMed2003

Percutaneous portal vein embolisation in preparation for extended hepatic resection of primary nonresectable liver tumours.

BACKGROUND: In patients with malignant primary and secondary liver tumours or proximal bile duct carcinoma radical surgery is superior to all other therapeutic modalities in terms of survival and quality of life. Radical resection, however, often requires the removal of a large amount of liver parenchyma, resulting in a marked reduction of functional liver tissue with the risk of liver failure. AIM: Preoperative partial portal vein embolisation induces hypertrophy of the controlateral liver and thereby increases the safety of extended liver resections. PATIENTS AND METHODS: Between January 1997 and February 2001 we applied this strategy in 19 patients with primary and secondary nonresectable hepatobiliary malignancies, in whom the estimated amount of the remnant liver was < or =25% of the liver volume. RESULTS: The increase in volume ranged between 7 and 245%. Radical extended liver resection was performed in 13 patients (68%) without mortality. After a mean observation time of 22 months patient survival was 19 months with six tumour-related deaths during the second year after surgery. The remaining seven patients are alive and well with tumour recurrence in one. CONCLUSION: Preoperative partial portal vein embolisation allows more patients with previously unresectable liver tumours to benefit from a potentially curative resection.

Biliary Tract Neoplasms↗
PubMed2003

Metabolic consequences of functional complexes of mitochondria, myofibrils and sarcoplasmic reticulum in muscle cells.

Regulation of mitochondrial respiration both by endogenous and exogenous ADP in the cells in situ was studied in isolated and permeabilized cardiomyocytes, permeabilized cardiac fibers and 'ghost' fibers (all with a diameter of 10-20 micro m) at different (0-3 micro moll(-1)) free Ca(2+) concentrations in the medium. In all these preparations, the apparent K(m) of mitochondrial respiration for exogenous ADP at free Ca(2+) concentrations of 0-0.1 micro moll(-1) was very high, in the range of 250-350 micro moll(-1), in contrast to isolated mitochondria in vitro (apparent K(m) for ADP is approximately 20 micro moll(-1)). An increase in the free Ca(2+) concentration (up to 3 micro moll(-1), which is within physiological range), resulted in a very significant decrease of the apparent K(m) value to 20-30 micro moll(-1), a decrease of V(max) of respiration in permeabilized intact fibers and a strong contraction of sarcomeres. In ghost cardiac fibers, from which myosin was extracted but mitochondria were intact, neither the high apparent K(m) for ADP (300-350 micro moll(-1)) nor V(max) of respiration changed in the range of free Ca(2+) concentration studied, and no sarcomere contraction was observed. The exogenous-ADP-trapping system (pyruvate kinase + phosphoenolpyruvate) inhibited endogenous-ADP-supported respiration in permeabilized cells by no more than 40%, and this inhibition was reversed by creatine due to activation of mitochondrial creatine kinase. These results are taken to show strong structural associations (functional complexes) among mitochondria, sarcomeres and sarcoplasmic reticulum. Inside these complexes, mitochondrial functional state is controlled by channeling of ADP, mostly via energy- and phosphoryl-transfer networks, and apparently depends on the state of sarcomere structures.

Adenosine Diphosphate↗