27 results on '"Rosenberger, C."'
Search Results
2. Hypoxia-inducible factor-2alpha-expressing interstitial fibroblasts are the only renal cells that express erythropoietin under hypoxia-inducible factor stabilization.
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Paliege A, Rosenberger C, Bondke A, Sciesielski L, Shina A, Heyman SN, Flippin LA, Arend M, Klaus SJ, and Bachmann S
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The adaptation of erythropoietin production to oxygen supply is determined by the abundance of hypoxia-inducible factor (HIF), a regulation that is induced by a prolyl hydroxylase. To identify cells that express HIF subunits (HIF-1alpha and HIF-2alpha) and erythropoietin, we treated Sprague-Dawley rats with the prolyl hydroxylase inhibitor FG-4497 for 6 h to induce HIF-dependent erythropoietin transcription. The kidneys were analyzed for colocalization of erythropoietin mRNA with HIF-1alpha and/or HIF-2alpha protein along with cell-specific identification markers. FG-4497 treatment strongly induced erythropoietin mRNA exclusively in cortical interstitial fibroblasts. Accumulation of HIF-2alpha was observed in these fibroblasts and in endothelial and glomerular cells, whereas HIF-1alpha was induced only in tubular epithelia. A large proportion (over 90% in the juxtamedullary cortex) of erythropoietin-expressing cells coexpressed HIF-2alpha. No colocalization of erythropoietin and HIF-1alpha was found. Hence, we conclude that in the adult kidney, HIF-2alpha and erythropoietin mRNA colocalize only in cortical interstitial fibroblasts, which makes them the key cell type for renal erythropoietin synthesis as regulated by HIF-2alpha. [ABSTRACT FROM AUTHOR]
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- 2010
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3. Experimental ischemia-reperfusion: biases and myths-the proximal vs. distal hypoxic tubular injury debate revisited.
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Heyman SN, Rosenberger C, Rosen S, Heyman, Samuel N, Rosenberger, Christian, and Rosen, Seymour
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Although the understanding of processes associated with hypoxic tubular cell injury has remarkably improved, controversies remain regarding the appropriateness of various animal models to the human syndrome of acute kidney injury (AKI). We herein compare available experimental models of hypoxic acute kidney damage, which differ both conceptually and morphologically in the distribution of tubular cell injury. Tubular segment types differ in their capacity to mount hypoxia-adaptive responses, mediated by hypoxia-inducible factors (HIFs), and in cell type-specific molecules shed into the urine, which may serve as early biomarkers for renal damage. These differences may be of value in the perception of the human AKI, its detection, and prevention. [ABSTRACT FROM AUTHOR]
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- 2010
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4. Adaptation to hypoxia in the diabetic rat kidney.
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Rosenberger, C., Khamaisi, M., Abassi, Z., Shilo, V., Weksler-Zangen, S., Goldfarb, M., Shina, A., Zibertrest, F., Eckardt, K.-U., Rosen, S., and Heyman, S. N.
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HYPOXEMIA , *CHRONIC kidney failure , *KIDNEY diseases , *DIABETES , *INSULIN , *SCIENTIFIC experimentation - Abstract
Hypoxia of the kidney in diabetes could predispose it to develop acute and chronic renal failure. To examine the relationship between renal hypoxia and renal failure, we measured hypoxia (as a pimonidazole adducts), hypoxia-inducible factors (HIFs), and a hypoxia target gene heme oxygenase-1. The studies were performed in rats with streptozotocin (STZ)-induced diabetes, Cohen diabetes sensitive rats, and during short-term artificial hyperglycemia in rats induced by intravenous glucose and octreotide. STZ-treated rats received insulin, the superoxide dismutase mimetic tempol, or contrast medium. Radiocontrast media causes hypoxia and HIF induction. Hypoxia, HIFs, and heme oxygenase were undetectable in controls, but transiently activated in STZ-treated and the Cohen diabetes sensitive rats. Different patterns of HIFs and pimonidazole were observed between the three models. Insulin abolished pimonidazole and HIF induction, whereas tempol lead to increased HIFs and heme oxygenase induction at similar levels of pimonidazole. When compared with control rats, STZ-treated rats exhibited more intense and protracted renal pimonidazole, with augmented hypoxia inducible factor production and reduced GFR following contrast media. Our data suggest that both regional hypoxia and hypoxia adaptation transiently occur in early stages of experimental diabetes, largely dependent on hyperglycemia or after contrast media. Tempol may augment the HIF response in diabetes.Kidney International (2008) 73, 34–42; doi:10.1038/sj.ki.5002567; published online 3 October 2007 [ABSTRACT FROM AUTHOR]
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- 2008
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5. Optimization-Based Image Segmentation by Genetic Algorithms.
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Chabrier, S., Rosenberger, C., Emile, B., and Laurent, H.
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LITERATURE , *VERSIFICATION , *TECHNICAL specifications , *IMAGE processing , *IMAGING systems , *GENETIC algorithms , *DIGITAL images - Abstract
Many works in the literature focus on the definition of evaluation metrics and criteria that enable to quantify the performance of an image processing algorithm. These evaluation criteria can be used to define new image processing algorithms by optimizing them. In this paper, we propose a general scheme to segment images by a genetic algorithm. The developed method uses an evaluation criterion which quantifies the quality of an image segmentation result. The proposed segmentation method can integrate a local ground truth when it is available in order to set the desired level of precision of the final result. A genetic algorithm is then used in order to determine the best combination of information extracted by the selected criterion. Then, we show that this approach can either be applied for gray-levels or multicomponents images in a supervised context or in an unsupervised one. Last, we show the efficiency of the proposed method through some experimental results on several gray-levels and multicomponents images. [ABSTRACT FROM AUTHOR]
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- 2008
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6. Hypoxia-inducible factors and tubular cell survival in isolated perfused kidneys.
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Rosenberger, C., Rosen, S., Shina, A., Bernhardt, W., Wiesener, M. S., Frei, U., Eckardt, K.-U., and Heyman, S. N.
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HYPOXEMIA , *KIDNEY diseases , *TRANSCRIPTION factors , *URINARY organs , *PHOTOSYNTHETIC oxygen evolution - Abstract
Adaptation to hypoxic environment is conferred through hypoxia-inducible transcription factors (HIFs). We have previously shown that the HIF system is transiently activated in vivo in radiocontrast-induced acute renal failure, associated with profound hypoxia in the renal medulla. Medullary thick ascending limbs (mTALs), the most affected nephron segments in this model, were virtually unable to mount an adaptive HIF response. Here, we study correlations between oxygenation, HIF activation, and cell viability in a related ex vivo model, the isolated perfused rat kidney (IPK). In IPKs perfused with cell-free oxygenated medium, severe medullary hypoxic damage developed, affecting 42±9% of mTALs in the mid-inner stripe. HIF-1α tubular immunostaining was noted with a zonal and tubular pattern largely similar to our findings in vivo: in 34±3% of collecting ducts (CDs) within the mid-inner stripe and extensively in the papillary tip, whereas mTALs were all HIF-negative. In IPKs supplemented with RBCs (improved oxygen supply), mTAL damage was totally prevented and CDs’ HIF expression was attenuated (22±4%). By contrast, although measures designed to reduce medullary hypoxia by decreasing tubular reabsorptive activity (furosemide, ouabain, or high-albumin-non-filtering system) reduced mTAL damage, all paradoxically resulted in increased HIF expression in CDs (51±4%), and 17±3% of mTALs became immunostained as well. Our data confirm that CDs and mTALs have markedly different HIF responses, which correlate with their viability under hypoxic stress. mTALs transcriptional adaptation occurs within a narrow hypoxic range, and it appears that workload reduction can shift mTALs into this window of opportunity for HIF activation and survival.Kidney International (2006) 70, 60–70. doi:10.1038/sj.ki.5000395; published online 17 May 2006 [ABSTRACT FROM AUTHOR]
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- 2006
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7. Normotensive ischemic acute renal failure.
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Rosenberger C, Rosen S, Heyman SN, Bellomo R, Kellum JA, Bagshaw SM, and Abuelo JG
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- 2007
8. Cyclosporine A induces endothelin‐converting enzyme‐1: Studies in vivo and in vitro.
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Heyman, S. N., Abassi, Z., Rosenberger, C., Yaseen, H., Skarjinski, G., Shina, A., Mathia, S., Krits, N., and Khamaisi, M.
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KIDNEY failure , *HYPOXEMIA , *CYCLOSPORINE , *IN vitro studies , *PREPROENDOTHELIN , *VASOCONSTRICTION - Abstract
Abstract: Aim: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances the expression of endothelin‐1 (ET‐1) pro‐hormone (pre‐pro‐ET‐1), plausibly leading to a feed‐forward loop of renal vasoconstriction, hypoxia and enhanced synthesis of the potent vasoconstrictor ET‐1. Endothelin‐converting enzyme (ECE)‐1 cleaves big endothelin to generate endothelin (ET)‐1 and is upregulated by hypoxia via hypoxia‐inducible factor (HIF). We hypothesized that in addition to the direct induction of ET‐1 synthesis, CsA might also intensify renal ECE‐1 expression, thus contributing to enhanced ET‐1 synthesis following CsA. Methods: CsA was administered to Sprague Dawley rats (120 mg/kg/SC) for 4 days, and renal HIF and ECE‐1 expression were assessed with Western blots and immunostaining. Human umbilical vein endothelial cells (HUVEC) and proximal tubular cell line (HK‐2) were subjected to CsA, and ECE‐1 induction was evaluated using real‐time mRNA PCR and Western blots. Results: Cyclosporine A intensified renal parenchymal ECE‐1 expression in the rat kidney, particularly in distal nephron segments, along with renal hypoxia (detected by pimonidazole adducts) and HIF expression, in line with our recent observations showing episodic hypoxia in mice subjected to CsA. Furthermore, in cultured normoxic HUVEC and HK‐2 cells, CsA dose‐dependently induced both pre‐pro‐ET‐1 and ECE‐1 mRNA and protein expression, with enhanced ET‐1 generation. Conclusion: CsA induces ECE‐1 via both hypoxic and non‐hypoxic pathways. ECE‐1 may contribute to increased renal ET‐1 generation following CsA, participating in a feed‐forward loop of renal parenchymal hypoxia and ET synthesis. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study.
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Elsenbruch, S., Rosenberger, C., Enck, P., Forsting, M., Schedlowski, M., and Gizewski, E. R.
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IRRITABLE colon , *ANXIETY , *PAIN , *MAGNETIC resonance imaging , *OXYGENATORS , *PREFRONTAL cortex - Abstract
Objective To address the role of anxiety and depression symptoms in altered pain processing in irritable bowel syndrome (IBS). Design In this functional magnetic resonance imaging study, the blood oxygen level-dependent (BOLD) response to rectal distensions delivered at previously determined individual discomfort thresholds was assessed. Patients 15 female patients with irritable bowel syndrome (IBS) and with normal rectal pain thresholds, and 12 healthy women. Measures The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences in pain-induced brain activation with and without controlling for HADS scores were evaluated. Results Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively, as confounding variables led to a loss of significant group differences. Conclusions Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affective-motivational aspects of the pain response. [ABSTRACT FROM AUTHOR]
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- 2010
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10. Effects of psychological stress on the cerebral processing of visceral stimuli in healthy women.
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ROSENBERGER, C., ELSENBRUCH, S., SCHOLLE, A., DE GREIFF, A., SCHEDLOWSKI, M., FORSTING, M., and GIZEWSKI, E. R.
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PSYCHOLOGICAL stress , *WOMEN'S health , *MAGNETIC resonance imaging , *OXYGEN , *ANXIETY - Abstract
The aim of the study was to analyse effects of psychological stress on the neural processing of visceral stimuli in healthy women. The brain functional magnetic resonance imaging blood oxygen level-dependent response to non-painful and painful rectal distensions was recorded from 14 healthy women during acute psychological stress and a control condition. Acute stress was induced with a modified public speaking stress paradigm. State anxiety was assessed with the State-Trait-Anxiety Inventory; chronic stress was measured with the Perceived Stress Questionnaire. During non-painful distensions, activation was observed in the right posterior insular cortex (IC) and right S1. Painful stimuli revealed activation of the bilateral anterior IC, right S1, and right pregenual anterior cingulate cortex. Chronic stress score was correlated with activation of the bilateral amygdala, right posterior IC (post-IC), left periaqueductal grey (PAG), and right dorsal posterior cingulate gyrus (dPCC) during non-painful stimulation, and with activation of the right post-IC, right PAG, left thalamus (THA), and right dPCC during painful distensions. During acute stress, state anxiety was significantly higher and the acute stress – control contrast revealed activation of the right dPCC, left THA and right S1 during painful stimulation. This is the first study to demonstrate effects of acute stress on cerebral activation patterns during visceral pain in healthy women. Together with our finding that chronic stress was correlated wit the neural response to visceral stimuli, these results provide a framework for further studies addressing the role of chronic stress and emotional disturbances in the pathophysiology of visceral hyperalgesia. [ABSTRACT FROM AUTHOR]
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- 2009
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11. After Velvet, Iron….
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Rosenberger, C. and de Candole, J.
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ELECTIONS , *ECONOMIC reform , *POLITICAL parties , *POLITICAL participation ,SLOVAKIAN politics & government ,SLOVAKIAN history, 1945-1992 ,CZECHOSLOVAKIAN politics & government -- 1989-1992 - Abstract
This article deals with the outcome of the first multi-party elections in Czechoslovakia on June 5-6, 1992. The elections confirm that the two republics are heading in opposite and irreconcilable directions. In Czech lands, free-market reform parties won, but were eliminated by the nationalist Left in Slovakia. The only redeeming international reaction to the results of the elections came from Cuba. According to the Cuban newspaper "Trabajadores," Vladimir Meciar's Movement for a Democratic Slovakia is the only power in Czechoslovakia that is has the ability to stop economic reform and the privatization program of federal Finance Minister Vaclav Klaus.
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- 1992
12. Expression of hypoxia-inducible transcription factors in developing human and rat kidneys.
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Bernhardt, W. M., Schmitt, R., Rosenberger, C., Münchenhagen, P. M., Gröne, H. -J., Frei, U., Warnecke, C., Bachmann, S., Wiesener, M. S., Willam, C., and Eckardt, K. -U.
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HYPOXEMIA , *TRANSCRIPTION factors , *NEOVASCULARIZATION , *RENAL tubular transport , *BIOLOGICAL transport , *NEPHROLOGY - Abstract
Early kidney development is associated with the coordinated branching of the renal tubular and vascular system and hypoxia has been proposed to be a major regulatory factor in this process. Under low oxygen levels, the hypoxia-inducible transcription factor (HIF) regulates the expression of genes involved in angiogenesis, erythropoiesis and glycolysis. To investigate the role of HIF in kidney development, we analyzed the temporal and spatial expression of the oxygen regulated HIF-1α and -2α subunits at different stages of rat and human kidney development. Using double-staining procedures, localization of the HIF target geneproducts vascular endothelial growth factor (VEGF) and endoglin was studied in relation to HIFα. In both species, we found marked nuclear expression of HIF-1α in medullary and cortical collecting ducts and in glomerular cells. In contrast, HIF-2α was expressed in interstitial and peritubular cells podocytes of the more mature glomeruli. After completion of glomerulogenesis and nephrogenesis, HIF-1α and -2α were no longer detectable. The HIF-target gene VEGF colocalized with HIF-1α protein in glomeruli and medullary collecting ducts. HIF-2α colocalized with the endothelium-associated angiogenic factor, endoglin. Both HIFα isoforms are activated in the developing kidney in a cell-specific and temporally controlled manner, indicating a regulatory role of oxygen tension in nephrogenesis. HIF-1α seems to be primarily involved in tubulogenesis and HIF-2α in renal vasculogenesis. Both isoforms are found in glomerulogenesis, potentially having synergistic effects.Kidney International (2006) 69, 114–122. doi:10.1038/sj.ki.5000062 [ABSTRACT FROM AUTHOR]
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- 2006
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13. A comparative study of card-not-present e-commerce architectures with card schemes: What about privacy?
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Plateaux, A., Lacharme, P., Vernois, S., Coquet, V., and Rosenberger, C.
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COMPARATIVE studies , *PRIVACY , *ELECTRONIC commerce , *ACCURACY , *DATA science - Abstract
Internet is increasingly used for card-not-present e-commerce architectures. Several protocols, such as 3D-Secure, have been proposed in the literature by card schemes or academics. Even if some of them are deployed in real life, these solutions are not perfect considering data security and user's privacy. In this paper, we present a comparative study of existing solutions for card-not-present e-commerce solutions. We consider the main security and privacy trends of e-payment in order to make an objective comparison of existing solutions. This comparative study illustrates the need to consider privacy in deployed e-commerce architectures. This has never been more urgent with the recent release of the new specifications of 3D-secure. [ABSTRACT FROM AUTHOR]
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- 2018
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14. Myoglobin facilitates angiotensin II-induced constriction of renal afferent arterioles.
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Liu, Z. Z., Mathia, S., Pahlitzsch, T., Wennysia, I. C., Persson, P. B., Lai, E. Y., Högner, A., Xu, M. Z., Schubert, R., Rosenberger, C., and Patzak, A.
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Vasoconstriction plays an important role in the development of acute kidney injury in rhabdomyolysis. We hypothesized that myoglobin enhances the angiotensin II (ANG II) response in afferent arterioles by increasing superoxide and reducing nitric oxide (NO) bioavailability. Afferent arterioles of C57Bl6 mice were isolated perfused, and vasoreactivity was analyzed using video microscopy. NO bioavailability, superoxide concentration in the vessel wall, and changes in cytosolic calcium were measured using fluorescence techniques. Myoglobin treatment (10−5 M) did not change the basal arteriolar diameter during a 20-min period compared with control conditions. NG-nitro-l-arginine methyl ester (l-NAME, 10−4 M) and l-NAME + myoglobin reduced diameters to 94.7 and 97.9% of the initial diameter, respectively. Myoglobin or l-NAME enhanced the ANG II-induced constriction of arterioles compared with control (36.6 and 34.2%, respectively, vs. 65.9%). Norepinephrine responses were not influenced by myoglobin. Combined application of myoglobin and l-NAME further facilitated the ANG II response (7.0%). Myoglobin or l-NAME decreased the NO-related fluorescence in arterioles similarly. Myoglobin enhanced the superoxide-related fluorescence, and tempol prevented this enhancement. Tempol also partly prevented the myoglobin effect on the ANG II response. Myoglobin increased the fura 2 fluorescence ratio (cytosolic calcium) during ANG II application (10−12 to 10−6 M). The results suggest that the enhanced afferent arteriolar reactivity to ANG II is mainly due to a myoglobin-induced increase in superoxide and associated reduction in the NO bioavailability. Signaling pathways for the augmented ANG II response include enhanced cytosolic calcium transients. In conclusion, myoglobin may contribute to the afferent arteriolar vasoconstriction in this rhabdomyolysis model. [ABSTRACT FROM AUTHOR]
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- 2017
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15. Cyclosporin a induces renal episodic hypoxia.
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Fähling, M., Mathia, S., Scheidl, J., Abramovitch, R., Milman, Z., Paliege, A., Peters, H., Persson, P. B., Heyman, S. N., and Rosenberger, C.
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CYCLOSPORINE , *HYPOXIA-inducible factors , *KIDNEY physiology , *NEPHROTOXICOLOGY , *KIDNEYS , *MAGNETIC resonance imaging - Abstract
Aim Cyclosporin A (CsA) causes renal toxicity. The underlying mechanisms are incompletely understood, but may involve renal hypoxia and hypoxia-inducible factors (Hifs). We sought for hypoxia and Hif in mouse kidneys with CsA-induced toxicity, assessed their time course, Hif-mediated responses and the impact of interventional Hif upregulation. Methods Mice received CsA or its solvent cremophore for up to 6 weeks. Low salt diet (Na+↓) was given in combination with CsA to enhance toxicity. We assessed fine morphology, renal function, blood oxygen level-dependent magnetic resonance imaging under room air and following changes in breathing gas composition which correlate with vascular reactivity, pimonidazole adducts (which indicate O2 tensions below 10 mmHg), Hif- α proteins, as well as expression of Hif target genes. Stable Hif upregulation was achieved by inducible, Pax8-rt TA-based knockout of von Hippel-Lindau protein (Vhl- KO), which is crucial for Hif- α degradation. Results Cyclosporin A transiently increased renal deoxyhaemoglobin (R2*). Augmented vascular reactivity was observed at 2 h, but decreased at 24 h after CsA treatment. Na+↓/CsA provoked chronic renal failure with tubular degeneration and interstitial fibrosis. Nephron segments at risk for injury accumulated pimonidazole adducts, as well as Hif- α proteins. Remarkably, Hif target gene expression remained unchanged, while factor-inhibiting Hif (Fih) was enhanced. Na+↓/CsA/Vhl- KO aggravated morpho-functional outcome of chronic renal CsA toxicity. Conclusions Cyclosporin A provokes episodic hypoxia in nephron segments most susceptible to chronic CsA toxicity. Fih is upregulated and likely blocks further Hif activity. Continuous tubular Hif upregulation via Vhl- KO worsens the outcome of chronic CsA-induced renal toxicity. [ABSTRACT FROM AUTHOR]
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- 2017
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16. Adaptive response to hypoxia and remote ischaemia pre-conditioning: a new hypoxia-inducible factors era in clinical medicine.
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Heyman, S. N., Leibowitz, D., Mor ‐ Yosef Levi, I., Liberman, A., Eisenkraft, A., Alcalai, R., Khamaisi, M., and Rosenberger, C.
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ISCHEMIA , *HYPOXEMIA , *CELL metabolism , *NEOVASCULARIZATION , *ERYTHROPOIESIS - Abstract
Transient ischaemia leads to tolerance to subsequent protracted ischaemia. This 'ischaemia pre-conditioning' results from the induction of numerous protective genes, involved in cell metabolism, proliferation and survival, in antioxidant capacity, angiogenesis, vascular tone and erythropoiesis. Hypoxia-inducible factors ( HIF) play a pivotal role in this transcriptional adaptive response. HIF prolyl hydroxylases ( PHDs), serving as oxygen sensors, control HIF α degradation. HIF-mediated ischaemic pre-conditioning can be achieved with the administration of PHD inhibitors, with the attenuation of organ injury under various hypoxic and toxic insults. Clinical trials are currently under way, evaluating PHD inhibitors as inducers of erythropoietin. Once their safety is established, their potential use might be further tested in clinical trials in various forms of acute ischaemic and toxic organ damage. Repeated transient limb ischaemia was also found to attenuate ischaemic injury in remote organs. This 'remote ischaemic pre-conditioning' phenomenon ( RIP) has been extensively studied recently in small clinical trials, preceding, or in parallel with an abrupt insult, such as myocardial infarction, cardiac surgery or radiocontrast administration. Initial results are promising, suggesting organ protection. Large-scale multi-centre studies are currently under way, evaluating the protective potential of RIP in cardiac surgery, in the management of myocardial infarction and in organ transplantation. The mechanisms of organ protection provided by RIP are poorly understood, but HIF seemingly play a role as well. Thus, Inhibition of HIF degradation with PHD inhibitors, as well as RIP (in part through HIF), might develop into novel clinical interventions in organ protection in the near future. [ABSTRACT FROM AUTHOR]
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- 2016
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17. Chronic activation of vasopressin V2 receptor signalling lowers renal medullary oxygen levels in rats.
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Dietrich, A., Mathia, S., Kaminski, H., Mutig, K., Rosenberger, C., Mrowka, R., Bachmann, S., and Paliege, A.
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VASOPRESSIN regulation , *PHYSIOLOGICAL transport of oxygen , *BRATTLEBORO rat , *DESMOPRESSIN , *HYPOXIA-inducible factor 1 , *GENE expression , *RENAL papilla , *PHYSIOLOGY - Abstract
Aim In the present study, we aimed to elucidate the effects of chronic vasopressin administration on renal medullary oxygen levels. Methods Adult Sprague Dawley or vasopressin-deficient Brattleboro rats were treated with the vasopressin V2 receptor agonist, desmopressin (5 ng/h; 3d), or its vehicle via osmotic minipumps. Immunostaining for pimonidazole and the transcription factor HIF-1α (hypoxia-inducible factor-1α) were used to identify hypoxic areas. Activation of HIF-target gene expression following desmopressin treatment was studied by microarray analysis. Results Pimonidazole staining was detected in the outer and inner medulla of desmopressin-treated rats, whereas staining in control animals was weak or absent. HIF-1α immunostaining demonstrated nuclear accumulation in the papilla of desmopressin-treated animals, whereas no staining was observed in the controls. Gene expression analysis revealed significant enrichment of HIF-target genes in the group of desmopressin-regulated gene products ( P = 2.6*10−21). Regulated products included insulin-like growth factor binding proteins 1 and 3, angiopoietin 2, fibronectin, cathepsin D, hexokinase 2 and cyclooxygenase 2. Conclusion Our results demonstrate that an activation of the renal urine concentrating mechanism by desmopressin causes renal medullary hypoxia and an upregulation of hypoxia-inducible gene expression. [ABSTRACT FROM AUTHOR]
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- 2013
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18. Parametrization of an image understanding quality metric with a subjective evaluation
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Hemery, B., Laurent, H., Emile, B., and Rosenberger, C.
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IMAGE analysis , *IMAGE retrieval , *ALGORITHMS , *PATTERN perception , *LOCALIZATION (Mathematics) , *IMAGE processing - Abstract
Abstract: Image understanding has many real industrial applications (video-monitoring, image retrieval, etc.). Given an image and an associated ground truth, it is possible to quanjpgy the quality of understanding results provided by different algorithms or parameters. To this end, it is necessary to take into account many factors for each object in the image: localization and recognition errors and under or over-detection of objects. In order to define an evaluation metric for quanjpgying the quality of an image understanding result, we have to set, as for example, the weights of each kind of error in the global score. For a correct parameters setting of an evaluation metric we defined previously, we conducted a subjective evaluation of image understanding results involving many experts in image processing. We present in this paper the developed method and analyze the obtained results to weight the various errors in an appropriate way. We show the benefit of this kind of study to define the correct parameters of the metric in order to have a judgment as reliable the one provided by experts. Experimental results on many images from the PASCAL VOC Challenge show the good behavior of this metric compared to the human judgment. [Copyright &y& Elsevier]
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- 2013
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19. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rt TA-based deletion of von Hippel- Lindau protein.
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Mathia, S., Paliege, A., Koesters, R., Peters, H., Neumayer, H.‐H., Bachmann, S., and Rosenberger, C.
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HYPOXIA-inducible factors , *LABORATORY mice , *VON Hippel-Lindau disease , *IMMUNOHISTOCHEMISTRY , *HISTOLOGY , *ERYTHROPOIETIN , *NEOVASCULARIZATION - Abstract
Aim Von Hippel- Lindau protein ( VHL) provides the degradation of hypoxia-inducible factor ( HIF). Tetracycline-induced, Pax8-rt TA-based knockout of VHL ( VHL- KO) affects all renal tubules and periportal hepatocytes and leads to sustained upregulation of HIF. Here, we study the phenotype of VHL- KO in both organs, the time course of changes, and long-term morpho-functional outcome. Methods Mice with doxycycline-induced VHL- KO and controls ( CON) were followed for up to 9 months. Systemic and tissue parameters were evaluated using clinical chemistry, histology, immunohistochemistry, RT- PCR and in situ hybridisation. Results At day 3 following VHL- KO, substantial abundance of HIF-1α and -2α was detected in the nuclei of hepatocytes and renal tubular epithelia. Hypoxia, induced by bleeding anaemia, did not further augment HIF signal. Erythropoietin mRNA was detectable in hepatocytes but not in the kidney. Vascular endothelial growth factor mRNA was upregulated in kidney but not in liver. At day 7 following VHL- KO, the renal capillary density was enhanced, reaching its maximum at day 14. Blood haemoglobin increased constantly up to day 28 (23.3 vs. 15.8 g dL−1, VHL-KO vs. CON). Thereafter, it was kept within the normal range by weekly blood collections. Pathological changes were absent from kidney and liver 9 months after VHL-KO. Conclusions Inducible, Pax8-rt TA-based deletion of VHL leads to organ-specific expression of epithelial HIF and erythropoietin in liver and kidney without causing pathological changes. Uniform, maximal and sustained HIF activation along the renal tubule may serve to study the potential benefits of hypoxia adaptation in experimental renal injury. [ABSTRACT FROM AUTHOR]
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- 2013
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20. Mood, working memory and brain activity during experimental human endotoxemia
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Kullmann, J.S., Grigoleit, J.S., Rosenberger, C., Engler, H., Wolf, O.T., Oberbeck, J.R., Schedlowski, M., and E.R. Gizewski
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- 2010
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21. Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders.
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Elsenbruch S, Kotsis V, Benson S, Rosenberger C, Reidick D, Schedlowski M, Bingel U, Theysohn N, Forsting M, Gizewski ER, Elsenbruch, Sigrid, Kotsis, Vassilios, Benson, Sven, Rosenberger, Christina, Reidick, Daniel, Schedlowski, Manfred, Bingel, Ulrike, Theysohn, Nina, Forsting, Michael, and Gizewski, Elke R
- Abstract
This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
22. Towards a sensor for detecting human presence and characterizing activity
- Author
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Benezeth, Y., Laurent, H., Emile, B., and Rosenberger, C.
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DETECTORS , *CAMERAS , *ENERGY management , *BUILDING operation management , *ENVIRONMENTAL engineering , *HEATING , *VENTILATION , *ENERGY consumption , *ARCHITECTURE & energy conservation - Abstract
Abstract: In this paper, we propose a vision-based system for human detection and activity analysis in indoor environment. The developed presence sensor is based on video analysis, using a static camera. Composed of three main steps, the first one consists in change detection using a background model updated at different levels to manage the most common variations of the environment. Second, a moving objects tracking, based on interest points, is performed. Third, in order to know the nature of the various objects that could be present in the scene, multiple cascades of boosted classifiers are used. The validation protocol, defined by the industrial partners involved in the CAPTHOM project focusing among other things on “Energy Management in Building”, is then detailed. Three applications integrated into the CAPTHOM project illustrate how the developed system can help in collecting useful information for the building management system. Occupancy detection and people counting as well as activity characterization and 3D location extend to a wide variety of buildings technology research areas such as human-centered environmental control including heating adjustment and demand-controlled ventilation, but also security and energy efficient buildings. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
23. Diabetes and radiocontrast media increase endothelin converting enzyme-1 in the kidney.
- Author
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Khamaisi, M., Raz, I., Shilo, V., Shina, A., Rosenberger, C., Dahan, R., Abassi, Z., Meidan, R., Lecht, S., and Heyman, S. N.
- Subjects
- *
ENDOCRINE diseases , *CARBOHYDRATE intolerance , *MESSENGER RNA , *BLOOD plasma , *ANTINEOPLASTIC antibiotics , *IMMUNOHISTOCHEMISTRY - Abstract
Plasma endothelin-1 levels rise in diabetes and after exposure to contrast media suggesting a role in progressive diabetic and acute radiocontrast nephropathies. Here we studied individual and combined effects of streptozotocin-induced diabetes and contrast media on renal endothelin converting enzyme-1 levels in the rat. In vivo, medullary (but not cortical) endothelin converting enzyme protein gradually increased 4 to 5-fold following the induction of diabetes or after the administration of contrast media but rose 15-fold when diabetic rats were given contrast media. Changes in mRNA expression paralleled those of the protein. Immunohistochemistry confirmed that increased tubular and endothelial cell endothelin converting enzyme-1 were most pronounced in the medulla. In vitro, endothelin-1 levels increased 3-fold following incubation of endothelial cells with media high in glucose or with contrast and 4-fold with their combination. Endothelin converting enzyme-1 protein and mRNA expression changed in a similar pattern while prepro endothelin-1 mRNA increased with each insult but not in an additive way. Our study shows that diabetes and contrast media up-regulate renal medullary endothelin converting enzyme-1 expression and synthesis.Kidney International (2008) 74, 91–100; doi:10.1038/ki.2008.112; published online 2 April 2008 [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
24. Development of Kaposi's sarcoma under sirolimus-based immunosuppression and successful treatment with imiquimod.
- Author
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Babel, N., Eibl, N., Ulrich, C., Bold, G., Sefrin, A., Hammer, M. H., Rosenberger, C., and Reinke, P.
- Subjects
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KAPOSI'S sarcoma , *RAPAMYCIN , *IMMUNOSUPPRESSION , *TUMORS , *IMMUNOLOGICAL deficiency syndromes - Abstract
Kaposi's sarcoma (KS) is a vascular neoplasm typically observed in the immunocompromised patient populations, such as acquired immunodeficiency syndrome or transplant patients. KS can appear simultaneously at multiple sites as red to purple, maculo-papular or nodular cutaneous lesions sometimes showing a visceral extension. Sirolimus, an immunosuppressive agent with potent antitumor activity, has been effective in combating post-transplant KS. However, an aggressive regimen of immunosuppression for therapy of severe acute rejection episodes may abolish the antitumor effects of sirolimus. The following is a description of KS development under immunosuppressive therapy with sirolimus, and the successful treatment of KS lesions utilizing the topical application of imiquimod 5% cream, an immune response modifier. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
25. Induction of pre-transplant Epstein–Barr virus (EBV) infection by donor blood transfusion in EBV–seronegative recipients may reduce risk of post-transplant lymphoproliferative disease in adolescent renal transplant patients: report of two cases
- Author
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Babel, N., Gabdrakhmanova, L., Hammer, M., Rosenberger, C., Oppert, M., Volk, H.-D., and Reinke, P.
- Subjects
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LYMPHOPROLIFERATIVE disorders , *IMMUNOLOGICAL deficiency syndromes , *EPSTEIN-Barr virus diseases , *TRANSPLANTATION of organs, tissues, etc. , *BLOOD transfusion , *CELL proliferation , *HEALTH care rationing - Abstract
Background: Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication following organ transplantation. The greatest risk is seen in Epstein–Barr virus (EBV)-seronegative patients receiving allografts from EBV-seropositive donors. We demonstrate a new approach of pre-transplant prophylaxis of EBV-related PTLD, suggesting that, prior to living-related renal transplantation, blood transfusion from an EBV-seropositive donor to an EBV-seronegative recipient could induce primary EBV infection in the recipient, developing EBV immunity and decreasing risk of PTLD. Methods: Recipients underwent weekly donor-specific blood transfusion (3 × 100 mL) before transplantation. EBV-mRNA expression, viral load, serological tests, and clinical signs of EBV infection were assessed following blood transfusion. Results: We explored a new approach in 2 young EBV-seronegative renal allograft recipients. Both patients developed primary EBV infection following blood transfusion before transplantation and showed symptom-free seroconversion post-transplantation without persistent EBV activation. There were no signs of PTLD during 5-year follow-up. Conclusions: A new effective and inexpensive approach is suggested for development of EBV immunity and probably for prophylaxis of EBV-associated PTLD. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
26. A dual role of miR‐22 in rhabdomyolysis‐induced acute kidney injury.
- Author
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Mathia, S., Rudigier, L. J., Kasim, M., Kirschner, K. M., Persson, P. B., Eckardt, K.‐U., Rosenberger, C., and Fähling, M.
- Subjects
- *
KIDNEY injuries , *HYPOXEMIA , *RHABDOMYOLYSIS , *INTERFERON gamma release tests , *CARCINOGENESIS - Abstract
Aim: In acute kidney injury (AKI), regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia‐inducible factor (HIF) is limited. Here, we studied miR‐22, a potential HIF repressor, in normal kidneys, as well as in rhabdomyolysis‐induced AKI, a condition where miR‐22 is up‐regulated. Methods: AKI in mice was provoked by IM injection of glycerol. Tissue homogenates were processed to determine the levels of candidate RNAs and proteins, as well as global gene expression profiles. Reporter assays quantified in vitro miR‐22 activity and its modulation by mimic or inhibitor molecules, under normoxia or hypoxia (1% O2) respectively. In vivo, anti–miR‐22 molecules were applied to normal mice or prior to induction of AKI. Renal outcome was assessed by measuring plasma creatinine, plasma urea and the levels of the injury markers Kim‐1 and Ngal. Results: Renal miR‐22 is inducible by hypoxia and represses hypoxia‐inducible factor (HIF). Specific inhibition of miR‐22 regulates 1913 gene transcripts in kidneys controls and 3386 in AKI, many of which are involved in development or carcinogenesis. Specific inhibition of miR‐22 up‐regulates tissue protective HIF target genes, yet renal function and injury markers are unchanged or worsened. Conclusions: miR‐22 is a HIF repressor constitutively expressed in the adult kidney and up‐regulated in AKI. Specific inhibition of miR‐22 is efficient in vivo and profoundly affects renal gene expression in health and disease, including up‐regulation of HIF. However, the net effect on rhabdomyolysis‐induced AKI outcome is neutral or even negative. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
27. Hemodialysis (HD) Patients Profit from Complete Anemia Correction and Modern Heart Failure Therapy.
- Author
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Hampl, H., Hennig, L., Gogoll, L., Rosenberger, C., and Riedel, E.
- Subjects
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ANEMIA , *PHYSIOLOGICAL transport of oxygen , *HEART failure , *HEART diseases , *DISEASE risk factors - Abstract
Objective: Myocardial oxygen (O2) consumption is the highest of all organs (4.5 mMol O2 /min/kg), and anemia considerably impairs oxygen delivery. Anemia diminishes the O2 supply to the heart significantly, since the suffered heart has a higher requirement for O2. We postulate that HD patients with both anemia and severe preexisting cardiac diseases would benefit from complete correction of anemia and modern therapy of heart failure. Methods: Between II / 1997 and III / 2004 we recruited consecutively 204 HD patients (91f, 113 m, mean age 68, time on dialysis range 1/2-36 years) into our single ambulatory care center. Cardiac risk factor assessment: coronary artery disease (CAD) (N = 24), dilated cardiomyopathy (DCM) (N = 40), severe arterial hypertension (≥BP 200 /90 mmHg) (N = 16), severe valve diseases (N = 24), ejection fraction (EF) ≤45-55% (N = 50), ≤35-45% (N = 58), ≤35% (N = 10) ≤ 20% (N = 3), atrium septum defect (ASD) (N = 2), heart-lung-liver transplantation (N = 4, EF ≤ 45%), concentric (N = 80) and excentric (N = 56) LVH, arterial fibrillation (N = 22), pace maker carriers (N = 8). Clinic: NYHA stages: II (N = 67), III (N = 33), IV (N = 7), Therapeutic strategy containing: Predialytic HCO3 ≥ 23 mMol /l and haemoglobin 13.5(f)-14.5 (m) g/dl, target BP ≤ 130/80mmHg. Combination treatment of statines, β-blockers, ACE-inhibitors, AT1-receptor blockers, Clonidin, aldosterone antagonists, close control of hydration, serum albumin (≥3.5 g/dl), heart rate (60-70/min.), calcium/phosphate product (≤5.5 mMol/l). Serial echocardiographies were performed every 3-6 months by the same cardiologist (small dialysis interval). Results: Based on initial left ventricular mass index (LVMI g/m², normal 110-130 f/m) 4 groups were defined. Significant values are given as average and standard deviations (before/after). Use of paired student t-test. LVMI-values (g/m²): Group 1: 68 patients (33.3%) without LVH remained stable (105 ± 18.0 to 98 ± 18, p < 0.05). Group 2: 72 patients (35.3%) with moderate LVH experienced total regression (162 ± 33 to 115 ± 17, p ≤ 0.01). Group 3: 36 patients (17.6%) with severe LVH were significantly improved, but to date not normalized (210 ± 43 to 167 ± 30, p < 0.01). Group 4: had to be divided: 9 patients (4.4%) worsened (158 ± 29 to 222 ± 57, p < 0.01) and 19 patients (9.3%) with unchanged high values (203 ± 34 to 206 ± 37, n.s.). This group did not respond to therapeutic efforts in consequence of CAD, progressive valve diseases (cardiologic intervention refused by patients) and severe DCM. Total 2-year mortality of all patients was 23.2%, cardiac mortality was only 11.6% compared to the international cardiac mortality of about 50%. Clinic: NYHA 2, 3 could be normalized or significantly improved. Conclusions: Our data show in contrast to Beserab et al (N Engl J of Med 1998;339:584) that especially in HD patients with pre-existing cardiovascular comorbidity total anaemia correction leads to a significantly improved cardiac condition and lower risk of mortality. Unalterable a modern heart failure therapy is necessary to diminish the effect of neurohormonal stimulation (adrenergic and RAA-system) which is caused by anemia and arterial hypertension. However, LVH develops over a long period of time; therefore, regression may take equally as long (in average: concentric 23.2/eccentric 24.1 months). [ABSTRACT FROM AUTHOR]
- Published
- 2004
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