Search PubMed⌕ Search

Biomedical subjects

U Frei

Publications and source records attributed to U Frei.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cytotoxic effector molecule gene expression in acute renal allograft rejection: correlation with clinical outcome; histopathology and function of the allograft.

BACKGROUND: Cytotoxic effector molecule expression in human renal allograft biopsies has been closely associated with acute rejection. Here we studied whether intragraft expression of perforin, granzyme B, and Fas ligand correlates with long-term clinical outcome of acute rejection episodes. Furthermore, we examined the relation to histopathology and function of the allograft during rejection. METHODS: Twenty-two human renal biopsies were quantified for mRNA expression of perforin, granzyme B, Fas ligand, and Fas with reverse transcription-polymerase chain reaction. Expression levels were correlated with clinical outcome after 12 months, Banff rejection grades, and allograft function in the course of acute rejection. RESULTS: Only Fas ligand, but not perforin or granzyme B, showed significantly higher up-regulation in seven samples with therapy-resistant acute rejections versus eight samples with therapy-sensitive acute rejection. We found no relation between cytotoxic marker expression and Banff rejection grades or serum creatinine peak levels. CONCLUSIONS: Fas ligand may be useful as an early marker of therapy-resistant acute rejection. Cells that express Fas ligand but not classical soluble cytotoxic molecules might influence clinical outcome of acute rejection episodes.

Acute Disease↗
PubMed2001

Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1alpha in clear cell renal carcinomas.

The transcription factor hypoxia-inducible factor (HIF)-1 is an important mediator of hypoxic adaptation of tumor cells and controls several genes that have been implicated in tumor growth. Oxygen-dependent degradation of HIF-1alpha, the regulatory subunit, requires binding to the von Hippel Lindau (VHL) protein. Because functional inactivation of the VHL tumor suppressor gene occurs in up to 70% of clear cell renal carcinomas, we investigated whether this results in overexpression of HIF-1alpha and its target genes. Immunoblotting revealed increased expression of HIF-1alpha in 24 of 32 (75%) clear cell renal carcinomas but only 3 of 8 non-clear cell renal tumors. Somatic mutations of the VHL gene were detected only in clear cell renal carcinomas that overexpressed HIF-1alpha. None of the HIF-1alpha-negative tumors displayed a VHL mutation. The level of HIF-1alpha mRNA was not different between tumors and adjacent kidney tissue. Immunohistochemistry revealed distinct patterns of nuclear staining for HIF-1alpha, depending on histological type and overall abundance of HIF-1alpha. In those clear cell renal carcinomas that showed increased expression on immunoblots, HIF-1alpha was expressed in almost all cells. In the remaining clear cell and in non-clear cell tumors, staining was focal; these different patterns thus were compatible with genetic stabilization in contrast to microenvironmental stimulation of HIF-1alpha as the primary mechanism. The mRNA expression of two known target genes of HIF-1alpha, vascular endothelial growth factor and glucose transporter 1, increased progressively with increasing amounts of HIF-1alpha in tumor extracts. In addition, glucose transporter 1 protein levels correlated with HIF-1alpha abundance. In conclusion, the data provide in vivo evidence for a constitutive up-regulation of HIF-1alpha in the majority of clear cell renal carcinomas, which leads to more widespread accumulation of this transcription factor than hypoxic stimulation. These observations are most likely linked to functional inactivation of the VHL gene product. Increased expression of HIF-1alpha is associated with alterations in gene expression patterns that are likely to contribute to tumor phenotype and progression.

Adenocarcinoma, Clear Cell↗
PubMed2001

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↗
PubMed2001

[Combined liver and kidney transplantation: indications and long-term follow-up].

INTRODUCTION: In patients suffering from chronic liver and kidney disease combined liver-kidney transplantation is the only therapeutic option. However, in these patients, it is mandatory to distinguish between chronic and acute renal failure prior to transplantation, because acute renal failure may recover after successful liver transplantation. In this study we investigated the indications and results of this combined procedure. PATIENTS AND METHODS: We report on 27 patients who underwent liver and kidney transplantation. The underlying diseases were viral hepatitis (n = 12), polycystic liver and kidney disease (n = 9), primary hyperoxaluria (n = 4), and cryptogenic cirrhosis (n = 2) with end-stage renal disease due to glomerulonephritis, diabetic nephropathy or renal failure caused by nephrotoxicity of immunosuppressive therapy after liver transplantation. Nine patients had lymphocytotoxic antibodies and 5/27 patients had a positive crossmatch pretransplant. RESULTS: One patient died due to bleeding complications, two patients lost the kidney graft due to initial non-function or technical problems. The incidence of acute and steroid-resistant rejections was 60% and 20% in patients with a positive cross-match compared to 32% and 14% in negative cross-match transplants. Only two patients experienced a rejection episode of the kidney (3.7%). No hyperacute rejection of the kidney graft occurred. Long-term patients and graft survival was not impaired in the presence of a positive cross-match. The 1- and 5-year survival rates of patients who underwent combined transplantation was 97% and 93% versus 91% and 83% in patients with liver transplantation alone. CONCLUSION: Combined liver-kidney transplantation is a safe treatment for endstage liver and kidney disease even in the face of a positive cross-match.

Adult↗
PubMed2001

Clinical and genetic analysis of Staphylococcus aureus nasal colonisation and exit-site infection in patients undergoing peritoneal dialysis.

Few data exist regarding the clonal identity of Staphylococcus aureus (SA) that colonises the nostrils and causes exit-site infections in peritoneal dialysis patients. Nasal and exit-site swabs were taken monthly from 41 patients undergoing peritoneal dialysis, and a genetic analysis of SA isolates was performed by pulsed-field-gel electrophoresis. When SA was identified at the exit-site, the clonal identity of nasal and exit-site isolates was demonstrated. In 50% of the SA carriers, nasal isolates were genetically constant over time; in the other 50% a change of colonising SA strains was observed. The risk of exit-site infection was identical in both groups.

Adult↗
PubMed2001

Synthesis of C-X-C and C-C chemokines by human peritoneal fibroblasts: induction by macrophage-derived cytokines.

Leukocyte accumulation during peritonitis is believed to be controlled by chemotactic factors released by resident peritoneal macrophages or mesothelial cells. Recent data indicate, however, that in many tissues fibroblasts play a key role in mediating leukocyte recruitment. We have therefore examined human peritoneal fibroblasts (HPFBs) for the expression and regulation of C-X-C and C-C chemokines. Quiescent HPFBs secreted monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 constitutively. This release could be dose-dependently augmented with the pro-inflammatory cytokines IL-1beta and tumor necrosis factor-alpha. Stimulated IL-8 production reached a plateau within 48 hours while MCP-1 continued to accumulate throughout 96 hours. Induction of IL-8 and MCP-1 synthesis by HPFBs was also triggered by peritoneal macrophage-conditioned medium. This effect was partly related to the presence of IL-1beta as demonstrated by IL-1 receptor antagonist inhibition. Pretreatment of HPFBs with actinomycin D or puromycin dose-dependently reduced cytokine-stimulated IL-8 and MCP-1 secretion, which suggested de novo chemokine synthesis. Indeed, exposure of HPFBs to IL-1beta and tumor necrosis factor-alpha produced a significant up-regulation of IL-8 and MCP-1 mRNA. This effect was associated with the rapid induction of nuclear factor-kappaB binding activity mediated through p65 and p50 subunits, and with a transient increase in the mRNA expression for RelB and inhibitory protein kappaB-alpha proteins. These data indicate that peritoneal fibroblasts are capable of generating large quantities of chemokines under a tight control of nuclear factor-kappaB/Rel transcription factors. Thus, peritoneal fibroblast-derived chemokines may contribute to the intraperitoneal recruitment of leukocytes during peritonitis.

Cells, Cultured↗
PubMed2001

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes.

BACKGROUND: International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS: Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

Adult↗
PubMed2001

Continuous measurements of renal perfusion in pigs by means of intravascular Doppler.

BACKGROUND: Changes in renal blood flow are considered to play a significant role in the induction and maintenance of kidney failure, but are difficult to monitor with currently available techniques. The objective was to validate renal flow measurements with Doppler guidewires and to apply this technique to assess dose and time dependency of the renal vascular effects of norepinephrine (NE). METHODS: In 10 anesthetized pigs, flow velocity in renal arteries (FVart) and veins (FVvein) and volumetric renal blood flow (VBF) were measured before and after intravenous bolus application of incremental doses of NE (2 to 200 microg). RESULTS: FVart curves exactly reflected the changes in VBF. Beat-to-beat analysis revealed a strong linear correlation over a mean VBF range of less than 0.05 to 0.35 L/min (median correlation coefficient with FVart, r = 0.998), and significant but less close relationships were also found between VBF and FVvein. Ten seconds after the administration of 200 microg NE, FVart dropped from 71 to 6 cm/sec and was 90% reversible after 48 seconds. Similarly, the renal vascular resistance temporarily rose from 988 to 13711 mm Hg. min/L. In contrast, NE-induced increases in systemic vascular resistance were on average a maximum of 1.5-fold but persisted for more than 60 seconds. CONCLUSIONS: Doppler flow measurements in the renal artery provide an excellent surrogate of volumetric blood flow, which may be useful for continuous monitoring of renal hemodynamics. The renal vasculature is more sensitive when compared with the systemic vasculature, but also appears to evoke more efficient counter-regulatory mechanisms in response to NE.

Animals↗
PubMed2001

Platelet activation through triathlon competition in ultra-endurance trained athletes: impact of thrombin and plasmin generation and catecholamine release.

The aims of this study were to evaluate whether platelets are activated during strenuous exercise in healthy athletes. Also, to determine the impact of plasmin and thrombin activity and catecholamine release. Previous studies have shown activation of the hemostatic system after competitive exercise, but platelet activation was thought to be absent in trained athletes. The impact of thrombin and other potent platelet activators is still a matter for debate. We examined 30 healthy triathletes during a triathlon competition. Flow cytometric detection of CD62p (P-selectin) was used to measure in vivo activation of platelets. Platelet-leukocyte aggregates were also determined. Thrombin concentration was assessed by the thrombin-antithrombin III complex (TAT) and the fibrinolytic state was characterised by the plasmin-alpha2-antiplasmin complex (PAP). Catecholamines were measured by means of high-pressure liquid chromatography. CD62p rose from baseline (2.3%) to 3.4% and was still elevated after 2 hours (3.1%, p = 0.0133). Platelet-leukocyte aggregates were elevated 30 min after exercise (4.3 % vs 3.6%) and decreased significantly after 60 min (2.9 %, p = 0.008). TAT increased from 3.9 microg/l to 8.3 microg/l after competition and to 5.4 microg/l 2 hours later (p < 0.001). PAP increased 10-fold from 350 microg/l to 3,267 microg/l after the triathlon and was still elevated after 2 hours (1,074 microg/l, p<0.001). No linear correlation was found between the hemostatic markers, catecholamines and platelet activation. Platelets, coagulation and fibrinolysis are activated by competitive exercise in athletes, whereby fibrinolytic changes are pronounced. Mechanisms of platelet activation during exercise include phenomena other than plasmatic hemostatic factors and catecholamines.

Adult↗
PubMed2001

Removal of contrast media by different extracorporeal treatments.

BACKGROUND: Although the capability of extracorporeal treatments after administration of contrast media to prevent radiocontrast-induced nephropathy is controversial, haemodialysis is performed in many institutions after radiographic procedures. There are conflicting reports on the efficacy of different dialysers and treatment modalities to remove contrast media. METHODS: We compared the contrast medium-removing ability of different extracorporeal treatments in a randomized trial. Thirty-nine patients on chronic renal-replacement therapy or with chronic renal failure were randomized to receive low-flux haemodialysis (Low-HD, n=10), high-flux haemodialysis (High-HD, n=10), online haemodiafiltration (HDF, 10 litre substitution, n=10) and online haemofiltration (HF, 18 litre substitution, n=9) after administration of contrast medium during routine radiological procedures. Plasma concentrations of contrast medium (iopromide or iomeprol) were measured by energy-dispersive X-ray fluorescence analysis. RESULTS: The extraction ratio for contrast media was 0.64+/-0.1 for Low HD (P<0.05 vs. High-HD and vs. HDF), 0.74+/-0.1 for High-HD (P<0.05 vs. HF), 0.81+/-0.1 for HDF (P<0.05 vs HF), and 0.62+/-0.1 for HF. Mean extracorporeal plasma clearances were 82+/-2 for Low-HD (P<0.05 vs. High-HD and vs HDF), 100+/-2 for High-HD, 115+/-4 for HDF (P<0.05 vs. HF), and 86+/-5 ml/min for HF. CONCLUSIONS: We conclude that HDF and High-HD remove contrast media more effectively than Low-HD and HF during the time of each treatment session. However, whether this is also true for the overall elimination of contrast media by these different procedures needs to be addressed in future studies, by a precise assessment of the drug time course after the session.

Angiography↗
PubMed2001

Trends and perspectives in pancreas and simultaneous pancreas and kidney transplantation.

Pancreas transplantation is still the best option to achieve normoglycaemia and insulin independence in patients with type I diabetes. As a result of improvements in surgical techniques, immunosuppression and patient selection, one year survival rates of 95, 83, and 88% for patient, pancreas, and kidney survival, respectively, are reported for patients with simultaneous pancreas and kidney transplantation. The main goals for the future are to reduce postoperative morbidity, to identify the relevant indications for single pancreas transplantation, to adopt the best surgical technique for individual patients' needs (bladder versus enteric drainage with or without portal venous delivery of insulin), and to develop immunosuppressive strategies with low nephrotoxic and diabetogenic potential.

Graft Rejection↗