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R Margreiter

Publications and source records attributed to R Margreiter.

At least 19 recordsLinked to original sources
PubMed2006

Non-invasive monitoring of kidney allograft rejection through IDO metabolism evaluation.

The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma (IFN-gamma) and via tryptophan depletion, suppresses adaptive T cell-mediated immunity in inflammation, host immune defense, and maternal tolerance. Its role in solid organ transplantation is still unclear. Therefore, we investigated the usefulness of IDO-mediated tryptophan catabolism in the evaluation of kidney allograft rejection. Blood, urine, and tissue samples were collected from 34 renal transplant patients without rejection and from nine patients with biopsy-confirmed episodes of acute rejection (n=12). Concentrations of kynurenine and tryptophan in serum and urine were analyzed by high-pressure liquid chromatography. Kynurenine to tryptophan ratio (kyn/trp) was calculated to estimate IDO activity. Immunostaining for IDO was performed on renal biopsies. Neopterin was assessed using radioimmunoassay. Kyn/trp and neopterin were detectable at low levels in serum of healthy volunteers and were increased in non-rejecting allograft recipients. Serum levels of kyn/trp were higher in recipients with rejection compared to non-rejectors as early as by day 1 post-surgery. Rejection episodes occurring within 13+/-5.9 days after transplantation were accompanied by elevated kyn/trp in serum (114+/-44.5 micromol/mmol, P=0.001) and urine (126+/-65.9 micromol/mmol, P=0.02) compared to levels during stable graft function. Kyn/trp correlated significantly with neopterin suggesting an IFN-gamma-induced increase in IDO activity. Immunostaining showed upregulation of IDO in rejection biopsies, localized in tubular-epithelial cells. Non-rejected grafts displayed no IDO expression. Acute rejection is associated with simultaneously increased serum and urinary kyn/trp in patients after kidney transplantation. Thus, IDO activity might offer a novel non-invasive means of immunomonitoring of renal allografts.

Acute Disease↗
PubMed2006

Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance.

AIMS: Pancreatic adenocarcinoma is an aggressive gastrointestinal malignancy with only a few long-term survivors even after radical surgery. Patients with ampullary cancer have a better prognosis but adjuvant therapy needs further improvement. Epithelial cell adhesion molecule (Ep-CAM) is strongly expressed in a variety of epithelial cancers and represents a promising target for immunological tumour therapy. Thus, the aim of this study was to investigate Ep-CAM expression and its potential prognostic impact in pancreatic and ampullary carcinomas. METHODS: Ep-CAM expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series of consecutive patients with pancreatic (n = 153) and ampullary cancer (n = 34). RESULTS: Ep-CAM overexpression was observed in 85 of 153 pancreatic cancer specimens (56%) and in 29 of 34 ampullary cancer samples (85%). Overall, Ep-CAM failed to be an independent prognostic marker. However, subgroup analyses showed that Ep-CAM overexpression correlated with shorter overall survival among patients with ampullary cancer and advanced stage pancreatic cancer. In the latter subgroup, survival gradually worsened with increasing Ep-CAM scores. Furthermore, in ampullary cancer, Ep-CAM overexpression was found to correlate with tumour stage. CONCLUSIONS: Ep-CAM overexpression was detectable in the majority of cases with pancreatic and ampullary cancer. Therefore, Ep-CAM represents an attractive target for immune-based therapeutic interventions in these tumour entities. However, the prognostic value of Ep-CAM overexpression remains undetermined.

Adenocarcinoma↗
PubMed2006

Infectious complications following 72 consecutive enteric-drained pancreas transplants.

New immunosuppressive protocols and advanced surgical technique resulted in an improved outcome of pancreatic transplantation (PTx) with infection remaining the most common complication. Seventy-two enteric-drained whole PTxs performed at the Innsbruck University Hospital between September 2002 and October 2004 were retrospectively analyzed. Prophylactic immunosuppression consisted of either the standard protocol consisting of single bolus antithymocyteglobulin (ATG) (Thymoglobulin, Sangstat or ATG Fresenius) induction (9 mg/kg), tacrolimus (TAC), mycophenylate mofetil (MMF) and steroids (38 patients) or a 4-day course of ATG (4 mg/kg) tacrolimus and steroids with MMF (n = 19), or Sirolimus (n = 15). Perioperative antimicrobial prophylaxis consisted of Piperacillin/Tazobactam (4.5 g q 8 h) in combination with ciprofloxacin (200 mg q 12 h) and fluconazole (400 mg daily). Ganciclovir was used for cytomegalovirus (CMV) prophylaxis if donor was positive and recipient-negative. Patient, pancreas, and kidney graft survival at 1 year were 97.2%, 88.8%, and 93%, respectively, with no difference between the groups. All retransplants (n = 8) and single transplants (n = 8) as well as all type II diabetics and nine of 11 patients older 55 years received standard immunosuppression (IS). The rejection rate was 14% and infection rate 46% with no difference in terms of incidence or type according to the three groups. Severe infectious complications included intra-abdominal infection (n = 12), wound infection (n = 7), sepsis (n = 13), respiratory tract infection (n = 4), urinary tract infection (n = 12), herpes simplex/human herpes virus 6 infection (n = 5), CMV infection/disease (n = 7), post-transplant lymphoproliferative disorder (PTLD, n = 3), invasive filamentous fungal infection (n = 4), Clostridial/Rotavirus colitis (n = 1), and endocarditis (n = 1). All four patients in this series died of infectious complications (invasive aspergillosis n = 2) (one with Candida glabrata superinfection), invasive zygomycosis (n = 1), PTLD (n = 1). Five grafts were lost (vascular thrombosis n = 3, pancreatitis n = 1, noncompliance n = 1). Infection represented the most frequent complication in this series and all four deaths were of infectious origin. Better prophylaxis and management of infections now should be the primary target to be addressed in the field of pancreas transplantation.

Adult↗
PubMed2006

Tacrolimus combined with two different dosages of sirolimus in kidney transplantation: results of a multicenter study.

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.

Adult↗
PubMed2006

Status 5 years after bilateral hand transplantation.

Graft survival and function early after hand transplantation is good. It remains unknown, however, whether long-term survival is limited by chronic rejection. We here describe the clinical course and the status 5 years after bilateral hand transplantation with emphasis on immunosuppression (IS), function, morphology and graft vascular changes. Clinical observation, evaluation of hand function, skin biopsies, X-ray, ultrasound, angiography, CT angiography, electrophysiologic studies including compound motor and sensory action potentials (CMAP, CSAP) and somatosensory evoked potentials were performed and results recorded at regular intervals. Following reduction of IS one mild (grade II) rejection episode occurred at 4 years. Subsequently, skin histology remained normal and without signs of chronic rejection. Hand function continuously improved during the first 3 years and remained stable with minor improvement thereafter. CMAP and CSAP progressively increased during the observation period. Latencies of the cortical responses were prolonged but amplitudes were within normal range. Investigation of hand vessels revealed no signs of occlusion but showed revascularization of a primarily occluded right radialis artery. Motor and sensory function improved profoundly between years 1 and 5 after hand transplantation. No signs whatsoever of chronic rejection have been observed.

Angiography↗
PubMed2006

Tetrahydrobiopterin attenuates microvascular reperfusion injury following murine pancreas transplantation.

In this study we investigated the effect of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases, on ischemia-reperfusion injury (IRI) following murine pancreas transplantation. Pancreatic grafts were exposed to prolonged cold ischemia times (CIT) and different treatment regimens: normal saline (S), S + 16 h CIT, BH4 50 mg/kg + 16 h CIT. Nontransplanted animals served as controls. Graft microcirculation was analyzed by means of functional capillary density (FCD) and capillary diameters (CD) after 2 h reperfusion using intravital microscopy. Quantification of inflammatory responses (mononuclear infiltration) and endothelial disintegration (edema formation) was done by histology (hematoxylin and eosin), and peroxynitrite formation assessed by nitrotyrosine immunostaining. FCD was significantly reduced after prolonged CIT, paralleled by increased peroxynitrite formation as compared with controls (all p < 0.05). Microcirculatory changes correlated significantly with intragraft peroxynitrite generation (Spearman: r = -0.56; p < 0.01). Pancreatic grafts treated with BH4 displayed markedly higher FCD values (p < 0.01) and abrogated nitrotyrosine staining (p = 0.03). CD were not significantly different in any group. Histology showed increased inflammation, interstitial edema, hemorrhage, acinar vacuolization and focal areas of necrosis after 16 h CIT, which was diminished by BH4 administration (p < 0.01). BH4 treatment significantly reduces post-ischemic deterioration of microcirculation as well as histologic damage and might be a promising novel strategy in attenuating IRI following pancreas transplantation.

Animals↗
PubMed2005

Cortical motor activation patterns following hand transplantation and replantation.

We studied cortical activation patterns by functional MRI in a patient who received bilateral hand transplantation after amputation 6 years ago and in a patient who had received unilateral hand replantation within 2 hours after amputation. In the early postoperative period, the patient who had had the hand transplantation revealed strong activation of a higher motor area, only weak activation of the primary sensorimotor motor cortex and no activation of the primary somatosensory cortex. At 1-year follow-up, a small increase in primary sensorimotor motor cortex activation was observed. Activation of the primary somatosensory cortex was only seen at the 2 year follow-up. By contrast, after hand replantation, the activation pattern was similar to that of the uninjured hand within 6 weeks. This included activation of the primary sensorimotor motor cortex, higher motor areas and primary somatosensory cortex. Transplantation after long-standing amputation results in cortical reorganization occurring over a 2-year period. In contrast, hand replantation within a few hours preserves a normal activation pattern.

Adult↗
PubMed2005

Incidence of coronary heart disease and cardiac events in patients undergoing kidney and pancreatic transplantation.

One major cause of graft loss after kidney transplantation or simultaneous kidney and pancreas transplantation is death of the recipient due to cardiac events. Records of 261 patients who underwent sole kidney (group A) or combined kidney-pancreas transplantation (group B) were retrospectively analyzed. Patients were divided into groups with basic cardiac evaluation (chest X-ray, electrocardiogram) and patients with additional diagnostics [echocardiography, exercise stress test, myocardial perfusion test, and coronary angiography (CAG)]. The results of the performed CAGs were as follows: proven coronary artery disease (CAD) in 22 patients (12.43%) in group A and 37 patients (44.05%) in group B; stenosis of one main coronary artery of 70% or greater in 8.47% (group A) and 16.67% (group B) of the patients. Subsequent revascularization procedures were performed in 15 candidates (8.47%) of group A and 11 (13.10%) of group B. The incidence of posttransplant cardiac events (PCE) was lower in recipients in both groups who underwent additional cardiac evaluation. Late postoperative deaths were reported in 3.45% of kidney recipients with no additional evaluation (group A), in 2.06% of patients with further diagnostics (group A), and in only 1.19% of patients with invasive pretransplant evaluation (group B). Patients with known CAD and no further invasive diagnostics or subsequent revascularization are at great risk. PCE were observed in three of seven patients in this subgroup. Careful cardiac evaluation including echocardiography, exercise stress test, myocardial perfusion test, and CAG is associated with a low incidence of PCE.

Coronary Artery Bypass↗
PubMed2005

Excellent results with calcineurin inhibitor-free initial immunosuppression in old recipients of old kidneys.

The ever increasing demand for donor organs has forced transplant surgeons to liberalize selection criteria. To avoid initial nephrotoxicity to kidneys from donors over 65 years of age, immunosuppression was begun with an IL-2 receptor antibody, mycophenolate mofetil, and steroids in a total of 38 recipients over 65 years. Calcineurin inhibitors (CI) were added after sufficient graft function was reached. After a mean cold ischemia time of 14:01 hours and a delayed function rate of 31%, patient survival, graft survival, and serum creatinine were 97.4%, 94.7%, and 1.5 mg/dL at 1 and 92.1%, 92.1%, and 1.7 mg/dL at 2 years, respectively. Thus, excellent results can be achieved in old recipients of old donor kidneys with CI-free initial immunosuppression.

Adrenal Cortex Hormones↗
PubMed2005

In the search of potential human islet stem cells: is tetranectin showing us the way?

Pancreatic islet cell transplantation is a promising approach to restore the required mass of functional beta cells in diabetic patients as a means to achieve long-term normoglycemia. This therapy is, however, not yet widely used, in part because of the shortage of human islet cells. Gaining detailed knowledge of the physiological basis governing the processes of differentiation of pancreatic stem or progenitor cells and the mechanisms and molecules necessary for a successful engraftment of the transplanted cells into the liver is instrumental for the ambitious goal of engineering new pancreatic islets to cure type I diabetes. We describe the in vivo and in vitro localisation of tetranectin (TN) in human and murine islet cells. Similar to human islets, murine islets stain positive for tetranectin. The amount and localization of TN is influenced by different culture conditions. The ability of TN to bind plasminogen indicates that it may have a role in regulating pericellular proteolysis and proteolytic activation of latent forms of metalloproteinases and growth factors. Tetranectin may thereby play an important role in the survival of islets in the liver after islet transplantation. TN-positive cells can be isolated and maintained in culture after human islet isolation, thereby providing the possibility to further clarify its role and function in vivo as well as in the course of islet transplantation.

Animals↗
PubMed2005

Infectious complications limit the outcome of liver transplantation in medical urgency code 2 patients.

The Organ shortage has caused an accumulation of acutely decompensated patients listed as medical urgency code 2 (MUC 2) (United network for Organ Sharing 2) while awaiting liver transplantation. Between June 1997 and June 2003, 22 of 360 liver transplantation patients (6%) were listed as MUC 2. Prophylactic immunosuppression consisted of calcineurin inhibitor-based drug therapy, using antithymocyte globulin or interleukin-2 receptor antagonist induction in 64%. The overall perioperative infection rate was 50%, and the rejection rate was 23%. We observed 7 episodes of oral or genital herpes simplex virus lesions; 2 patients (both with cytomegalovirus-mismatched transplants) developed cytomegalovirus disease, and another 5 patients received ganciclovir for preemptive therapy or prophylaxis. Two patients developed pneumonia: 5, sepsis that originated in 4 cases from a contaminated central venous line; and 1 methicillin-resistant endocarditis, which resulted in Staphylococcus aureus lethal outcome. After a median follow up of 3 years, 1 patient underwent a repeat transplantation procedure and 6 patients had died, 4 of them from infectious complications. Liver transplantation of MUC 2-listed patients may result in acceptable results similar to those of MUC 3 and MUC 4 categories.

Adult↗
PubMed2005

Impact of steroid withdrawal on metabolic parameters in a series of 112 enteric/systemic-drained pancreatic transplants.

BACKGROUND: New immunosuppressive protocols and advanced surgical techniques have brought major improvements in pancreas transplantation outcomes. Steroid withdrawal might have a beneficial long-term effect on metabolic parameters. METHODS: We retrospectively analyzed 112 enteric-drained pancreas transplants (PTx) performed between March 1997 and October 2001. Prophylactic imunosuppression consisted of ATG induction, tacrolimus, MMF, and steroids. RESULTS: Actuarial patient, pancreas, and kidney graft survivals at 1 year were 96.4%, 86.7%, and 95.3%, respectively. The 5-year pancreatic graft survival was 77%. In addition to four patients who died with functioning grafts, eight grafts were lost due to intraabdominal infection; ten due to rejection; and the remaining three, due to other complications. One-year follow-up was available for 89 patients, Including 22 (25%) withdrawn from steroids. Significantly lower median serum cholesterol values were measured among patients off steroids (158 mg/dL [range 135 to 231 mg/dL] versus 188 mg/dL [range 91 to 278 mg/dl]; P = .005). In contrast, the difference in triglycerides did not reach statistical significance; that is, at last follow-up, at a median of 41.3 months posttransplant, 64 patients (70% of the available study population) were off steroids. Cessation of steroids resulted in significantly lower cholesterol (median 176 mg/dL [range 101 to 229 mg/dL] versus 196 mg/dL [range 107 to 339 mg/dL]; P = .047) and triglyceride values (median 74 mg/dL [range 34 to 299 mg/dL] versus 98 mg/dL [range 47 to 565 mg/dL]; P = .008), but had no impact on rejection rate, serum creatinine and urea, HbA(1c), or fasting blood glucose levels. CONCLUSIONS: Steroid withdrawal after pancreatic transplantation can be performed in the majority of cases without risking an immunologic complication, but it seems to be associated also with the benefit of improved lipid metabolism.

Adult↗
PubMed2005

Improved attainment of NKF classified lipid target levels after conversion from cyclosporine to tacrolimus in renal graft recipients.

In an open, prospective, multicenter study, stable renal graft recipients were converted to tacrolimus because of cyclosporine-related side effects. Seventy-five patients were switched primarily because of hyperlipidemia. After the switch to tacrolimus, mean total cholesterol was reduced by 15% at month 6. One hundred seventy-seven additional patients were switched primarily for other indications: hypertrichosis, gingival hyperplasia, and arterial hypertension, and these symptoms also improved after the switch. In this analysis, serum lipid levels were categorized according to a modified standard classification of lipid parameters for renal transplant patients (published by the NKF Work Group). The aim was to estimate the proportion of patients reaching normal lipid levels after the conversion to tacrolimus therapy. In patients with primary indication hyperlipidemia, the proportion with normal cholesterol levels increased significantly from 5.6% at baseline to 37.5% at month 6 (P < .05). For LDL cholesterol, the increase was from 54.1% at baseline to 64.9% at month 6, and for triglycerides the improvement was from 25.4% to 33.8%. HDL cholesterol levels remained stable. Similar changes of lipid parameters were also observed in the subgroups of patients converted to tacrolimus primarily because of other indications. After conversion from cyclosporine to tacrolimus, a significantly higher proportion of stable renal graft recipients reached normal total cholesterol levels. For LDL cholesterol and triglycerides, a trend for normalization was observed. Thus, the improvement of serum lipid levels resulted for many patients in a change to a better level class and improved or normalized their cardiovascular risk parameters.

Cholesterol, LDL↗
PubMed2005

Successful management of recurrent Epstein-Barr virus-associated multilocular leiomyosarcoma after cardiac transplantation.

BACKGROUND: In contrast to Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorders (PTLD), EBV-associated leiomyomatous tumors have thus far only rarely been described. CASE REPORT: Two years after heart transplantation with ATG induction, cyclosporine (CsA; trough levels of 250 ng/mL)-based triple drug immunosuppression), a 23-year-old patient developed a small round lesion within the left lateral liver segment. The patient underwent ultrasound-guided biopsy followed by liver resection. Histological and immunohistological examination showed a leiomyosarcoma. In situ hybridization using EBV-specific EB endoplasmic reticulum-RNA showed an intensive signal in almost all tumor cells. The tumor stained for EB nuclear antigen (EBNA)-2-protein. Immunosuppression was drastically reduced, namely, CsA levels <100 ng/dL, prednisolone 5 mg, azathioprine withdrawn, and antiviral chemotherapy initiated with 10 days of IV gancyclovir and acyclovir followed by oral famcyclovir. During the follow-up, anti-EBV-IgM, anti-early antigen antibodies, and anti-EBNA antibodies were continuously monitored excluding significant EBV replication. Eighteen months post-liver resection, and high-resolution computed tomography scan demonstrated two paravertebral tumors. These lesions and a small nodule at the left ankle were resected revealing identical leiomyosarcomata. Immunosuppression was further reduced (CsA levels 75 ng/dL) and famcyclovir maintenance therapy started. Nevertheless, 2 years later the patient again developed tumor recurrence (perirectal, liver, and right adrenal gland); the tumors were surgically removed. The therapy was switched to Rapamycin and famcyclovir was continued. Three years after the last surgical intervention, the patient is well and recurrence-free. CONCLUSION: Long-term survival in patients with posttransplant EBV-associated leiomyosarcoma can be achieved by combined surgical intervention, reduction of immunosuppression, switch to Sirolimus, and antiviral chemotherapy.

Acyclovir↗
PubMed2005

Kaposi sarcoma in solid organ transplant recipients: a single center report.

BACKGROUND: Human herpes virus (HHV8) is associated with Castleman's disease, primary effusion lymphoma, and the Kaposi's sarcoma (KS). PATIENTS AND METHODS: Among 3815 solid organ transplants performed at our center between 1977 and 2003, five patients (0.1%) were identified with KS. RESULTS: There were one cardiac, one liver, and three renal allograft recipients of median age of 52 (range 38 to 60) years, three of whom were females. Three patients were of Italian and one of Turkish descent; only one patient was a native Austrian. The onset of the disease was 2.0, 7.5, 7.8, 9.4 months, and 22 years posttransplant. Diagnosis of KS was based in all cases on histology. The heart recipient developed a tumor on the planta pedis; one renal recipient, on both legs. The liver and the two remaining renal recipients presented with disseminated disease. Treatment in all cases consisted of reduction in immunosuppression, together with surgery (n = 1), chemotherapy (n = 1), or irradiation (n = 2). Furthermore, immunosuppression was switched in two cases from Tacrolimus to Sirolimus. In the liver recipient a complete response was achieved; he died, however, due to noncompliance followed by graft failure. One renal recipient died without evidence of recurrent disease from myocardial infarction. The cardiac and two renal recipients are alive between 4 months and 17 years with well-functioning grafts and no evidence of recurrent disease. DISCUSSION: HHV8-associated lesions seem to be extremely rare in the Central European transplant population. Nevertheless, awareness of KS is important for early diagnosis and optimal treatment.

Adult↗