• Deutsch
Login

Open Access

  • Home
  • Search
  • Browse
  • Publish
  • FAQ
Schließen
  • Collections
  • Universität Erlangen-Nürnberg
  • Nationallizenzen: Alle Beiträge sind mit Zustimmu...

Nationallizenzen 2010

Refine

Author

  • Rauch, Anita (4)
  • Amann, Kerstin (3)
  • Dötsch, Jörg (3)
  • Rascher, Wolfgang (3)
  • Rosanowski, Frank (3)
  • Uder, Michael (3)
  • Beckmann, Matthias W. (2)
  • Echardt, Kai-Uwe (2)
  • Eckardt, Kai-Uwe (2)
  • Hartner, Andrea (2)
+ more

Year of publication

  • 2010 (54)
  • 2009 (1)

Document Type

  • Article (55)

Language

  • English (53)
  • German (2)

Has Fulltext

  • yes (55)

Keywords

  • - (49)
  • Anemia (2)
  • Mammakarzinom (2)
  • Obesity (2)
  • Quality of life (2)
  • 5-Fluorouracil (1)
  • 5-Fluoruracil (1)
  • Acute ischemic stroke (1)
  • Acute myocardial infarction (1)
  • Acute phase protein (1)
+ more

Institute

  • Medizinische Fakultät -ohne weitere Spezifikation- (41)
  • Technische Fakultät -ohne weitere Spezifikation- (5)
  • Medizinische Fakultät (3)
  • Philosophische Fakultät und Fachbereich Theologie -ohne weitere Spezifikation- (3)
  • Rechts- und Wirtschaftswissenschaftliche Fakultät -ohne weitere Spezifikation- (2)
  • Naturwissenschaftliche Fakultät -ohne weitere Spezifikation- (1)

55 search hits

  • 1 to 20
  • 10
  • 20
  • 50
  • 100

Sort by

  • Year
  • Year
  • Title
  • Title
  • Author
  • Author
Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants (2010)
Griffin, Helen R. ; Töpf, Ana ; Glen, Elise ; Zweier, Christiane ; Stuart, A. Graham ; Parsons, Jonathan ; Peart, Ian ; Deanfield, John ; O'Sullivan, John ; Rauch, Anita ; Scambler, Peter ; Burn, John ; Cordell, Heather J. ; Keavney, Bernard ; Goodship, Judith A.
Background Tetralogy of Fallot (TOF) is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor TBX1. Objective To assess the contribution of common and rare TBX1 genetic variants to TOF. Design Rare TBX1 variants were sought by resequencing coding exons and splice-site boundaries. Common TBX1 variants were investigated by genotyping 20 haplotype-tagging SNPs capturing all the common variations present at the locus. Association analysis was performed using the program UNPHASED. Patients TBX1 exons were sequenced in 93 patients with non-syndromic TOF. Single nucleotide polymorphism analysis was performed in 356 patients with TOF, their parents and healthy controls. Results Three novel variants not present in 1000 chromosomes from healthy ethnically matched controls were identified. One of these variants, an in-frame 57 base-pair deletion in the third exon which removed 19 evolutionarily conserved residues, decreased transcriptional activity by 40% in a dual luciferase assay (p=0.008). Protein expression studies demonstrated that this mutation affected TBX1 protein stability. After correction for multiple comparisons, no significant associations between common genetic variants and TOF susceptibility were found. Conclusion This study demonstrates that rare TBX1 variants with functional consequences are present in a small proportion of non-syndromic TOF.
Disruption of ST5 is associated with mental retardation and multiple congenital anomalies (2010)
Göhring, Ina ; Tagariello, Andreas ; Endele, Sabine ; Stolt, Claus C. ; Ghassibe, Michaella ; Vikkula, Miika ; Winterpacht, Andreas ; FitzPatrick, David R. ; Rauch, Anita
Background The authors observed a patient with a cryptic subtelomeric de novo balanced translocation 46,XY.ish t(11;20)(p15.4;q13.2) presenting with severe mental retardation, muscular hypotonia, seizures, bilateral sensorineural hearing loss, submucous cleft palate, persistent ductus Botalli, unilateral cystic kidney dysplasia and frequent infections. Methods and Results Fluorescence in situ hybridisation mapping and sequencing of the translocation breakpoints showed that no known genes are disrupted at 20q13.2 and that ST5 (suppression of tumorigenicity 5; MIM 140750) is disrupted on 11p15.4. By quantitative PCR from different human tissues, the authors found ST5 to be relatively evenly expressed in fetal tissues. ST5 expression was more pronounced in adult brain, kidney and muscle than in the corresponding fetal tissues, whereas expression in other tissues was generally lower than in the fetal tissue. Using RNA in situ hybridisation in mouse, the authors found that St5 is expressed in the frontal cortex during embryonic development. In adult mouse brain, expression of St5 was especially high in the hippocampal area and cerebellum. Conclusion Hence, the authors suppose that ST5 plays an important role in central nervous system development probably due to disturbance of DENN-domain-mediated vesicle formation and neurotransmitter trafficking. Thus, these findings implicate ST5 in the aetiology of mental retardation, seizures and multiple congenital anomalies.
Comprehensive genotype–phenotype analysis in 230 patients with tetralogy of Fallot (2010)
Rauch, Ralf ; Hofbeck, Michael ; Zweier, Christiane ; Koch, Andreas ; Zink, Stefan ; Trautmann, Udo ; Hoyer, Juliane ; Kaulitz, Renate ; Singer, Helmut ; Rauch, Anita
Background Tetralogy of Fallot (ToF), the most frequent cyanotic congenital heart disease, is associated with a wide range of intra- and extracardiac phenotypes. In order to get further insight into genotype–phenotype correlation, a large cohort of 230 unselected patients with ToF was comprehensively investigated. Methods and results 230 patients with ToF were studied by karyotyping, comprehensive 22q11.2 deletion testing and sequencing of TBX1, NKX2.5 and JAG1, as well as molecular karyotyping in selected patients. Pathogenic genetic aberrations were found in 42 patients (18%), with 22q11.2 deletion as the most common diagnosis (7.4%), followed by trisomy 21 (5.2%) and other chromosomal aberrations or submicroscopic copy number changes (3%). Mutations in JAG1 were detected in three patients with Alagille syndrome (1.3%), while NKX2.5 mutations were seen in two patients with non-syndromic ToF (0.9%). One patient showed a recurrent polyalanine stretch elongation within TBX1 which represents a true mutation resulting in loss of transcriptional activity due to cytoplasmatic protein aggregation. Conclusion This study shows that 22q11.2 deletion represents the most common known cause of ToF, and that the associated cardiac phenotype is distinct for obstruction of the proximal pulmonary artery, hypoplastic central pulmonary arteries and subclavian artery anomalies. Atrioventricular septal defect associated with ToF is very suggestive of trisomy 21 and almost excludes 22q11.2 deletion. We report a further patient with a recurrent polyalanine stretch elongation within TBX1 and for the first time link TBX1 cytoplasmatic protein aggregation to congenital heart defects.
Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus (2010)
Fürnrohr, Barbara G. ; Wach, Sven ; Kelly, Jennifer A. ; Haslbeck, Martin ; Weber, Christian K. ; Stach, Christian M. ; Hueber, Axel J. ; Graef, Daniela ; Spriewald, Bernd M. ; Manger, Karin ; Herrmann, Martin ; Kaufman, Kenneth M. ; Frank, Summer G. ; Goodmon, Ellen ; James, Judith A. ; Schett, Georg ; Winkler, Thomas H. ; Harley, John B. ; Voll, Reinhard E.
Background: Heat shock proteins (Hsps) play a role in the delivery and presentation of antigenic peptides and are thought to be involved in the pathogenesis of multifactorial diseases. Objective: To investigate genes encoding cytosolic Hsp70 proteins for associations of allelic variants with systemic lupus erythematosus (SLE). Methods: Case–control studies of two independent Caucasian SLE cohorts were performed. In a haplotype-tagging single-nucleotide polymorphism approach, common variants of HspA1L, HspA1A and HspA1B were genotyped and principal component analyses were performed for the cohort from the Oklahoma Medical Research Foundation (OMRF). Relative quantification of mRNA was carried out for each Hsp70 gene in healthy controls. Conditional regression analysis was performed to determine if allelic variants in Hsp70 act independently of HLA-DR3. Results: On analysis of common genetic variants of HspA1L, HspA1A and HspA1B, a haplotype significantly associated with SLE in the Erlangen-SLE cohort was identified, which was confirmed in the OMRF cohort. Depending on the cohorts, OR ranging from 1.43 to 1.88 and 2.64 to 3.16 was observed for individuals heterozygous and homozygous for the associated haplotype, respectively. Patients carrying the risk haplotype or the risk allele more often displayed autoantibodies to Ro and La in both cohorts. In healthy controls bearing this haplotype, the amount of HspA1A mRNA was significantly increased, whereas total Hsp70 protein concentration was not altered. Conclusions: Allelic variants of the Hsp70 genes are significantly associated with SLE in Caucasians, independently of HLA-DR3, and correlate with the presence of autoantibodies to Ro and La. Hence, the Hsp70 gene locus appears to be involved in SLE pathogenesis.
Improvement of the cardiac marker N-terminal-pro brain natriuretic peptide through adjustment for renal function: a stratified multicenter trial (2010)
Luchner, Andreas ; Weidemann, Alexander ; Willenbrock, Roland ; Philipp, Sebastian ; Heinicke, Norbert ; Rambausek, Matthias ; Mehdorn, Uta ; Frankenberger, Burkhard ; Heid, Iris M. ; Echardt, Kai-Uwe ; Holmer, Stephan R.
Background: N-terminal-pro brain natriuretic peptide (NT-proBNP) is a useful cardiac marker that is also influenced by renal dysfunction. It was our objective to assess the relationship between NT-proBNP concentrations in plasma and worsening renal function, and to attempt adjustment of NT-proBNP for renal dysfunction in a prospective, stratified multi-center study. Methods: We stratified 203 male patients according to their cardiac status and the estimated glomerular filtration rate (eGFR). Cardiac disease was assessed by medical history, physical examination and standardized echocardiography. Patients were stratified according to the following: absence of cardiac history and abnormalities (control, CTRL, n=66), cardiac history without left ventricular hypertrophy (LVH) or left ventricular systolic dysfunction (LVD) (history, n=30), LVH without systolic dysfunction (LVH, n=68), and LVD [ejection fraction (EF) <40%, LVD, n=39]. Renal disease was stratified according to the eGFR: 15–30 mL/min (n=52), 31–75 mL/min (n=99), and >75 mL/min (n=52). Results: NT-proBNP was correlated with eGFR in the entire study population and for all levels of cardiac disease (all p<0.01). Regression analysis allowed adjustment of NT-proBNP for eGFR in a continuous manner, and this adjustment significantly improved the predictive value (receiver operating characteristic curve for symptomatic LVD from 0.80 to 0.86, p<0.01; sensitivity from 74% to 83% and specificity from 68% to 79%). Conclusions: NT-proBNP correlates inversely and significantly with eGFR throughout all levels of cardiac strata. We propose for the first time a continuous adjustment algorithm which markedly improves the predictive values of NT-proBNP in male patients with impaired renal function.
Optical Multi-Sensor Metrology for Extruded Profiles (2010)
Weckenmann, Albert ; Bernstein, Johannes
Nowadays the process-control of concave extruded profiles is a measuring task with rising requirements. A novel optical bi-sensorial measurement system – consisting of a shadow- and a light-section-system – as well as suitable methods of analysis for in-line inspection are presented. The proposals help to ensure the product quality on a higher level than before. The combination of dimensional accuracy and data-density leads to excellent results. Extruded profiles are semi-finished products (from steel, brass, aluminum, synthetics…) which are appointed for wide applications in technical products. For monitoring and controlling the parts in-line adequately, today often the shading technology is used. It detects – neglecting the profiles coat in measurement range – with high precision the dimension of the objects shadow orthographically to the axis of illumination. As a matter of fact, concave and local areas cannot be recorded. Alternatively, light-section-systems can measure concave zones and undercut zones but do not comply with the required accuracy. The combination of accuracy and data-density qualifies the mentioned multi-sensor metrology for realizing a maximum of efficiency in process control what ensures product quality and less defective goods. The optical multi-sensor measurement system has to be calibrated and aligned to detect the same surface zone despite of high refresh rates and optical resolutions. The metered characteristics will be coordinate transformed to extrinsic world-coordinates for evaluating form deviations of complex parts. An appropriate user-interface enables to re-calculate measurement objects in-line and evaluate the conformity of the part consequently. Finally the real length information assists to influence the process control. After a successful test in the laboratory the results will be proved in production to the target: measurement uncertainty of better than 0.1 mm at every profile.
Orientierung endoskopischer Bilder: Rektifizierung durch Schwerkraft (2010)
Höller, Kurt ; Schneider, Armin ; Jahn, Jasper ; Gutierrez, Javier ; Wittenberg, Thomas ; Meining, Alexander ; Delius, Stefan von ; Hornegger, Joachim ; Feußner, Hubertus
Ein nach wie vor ungelöstes Problem in der endoskopischen Chirurgie (insbesondere mit Hilfe von flexiblen Video-Endoskopen) ist das Fehlen eines stabilen Horizonts der endoskopischen Bilder auf dem Monitor. Mit unserem „Endoscopy with the New Dimension of Orientation (ENDOrientation)“-Ansatz kann eine Korrektur der Bildverdrehung, sogar in der nicht-starren interventionellen Endoskopie (insbesondere NOTES) mit einem 3 mm schmalen dreiachsigen MEMS-Beschleunigungssensor realisiert werden, der an der Spitze des Endoskops positioniert wird. Dieser Sensor misst den Anteil der Erdanziehungskraft auf jede der drei orthogonalen Achsen. Nach einer initialen Kalibrierung und zeitlichen Filterung dieser drei Datenströme kann der Rotationswinkel direkt ermittelt werden. Die erreichbare Abtastrate liegt dabei deutlich über der gewöhnlichen Videoframe-Rate von 25 Hz, die Genauigkeit der Rotationserkennung liegt bei etwa einem Grad. Die Aufrichtung des Endoskopbildes in Relation zu einem stabilen Horizont wird in Echtzeit über eine digitale Rotation des analogen Endoskopie-Video-Signals ermöglicht. Die Verbesserungen und Vorteile wurden in Tierversuchen evaluiert. Die Koordination und Führung mehrerer Instrumente zugleich wurde bei endoskopischen Bildern mit stabilisiertem Horizont als deutlich intuitiver beurteilt. Die ermittelten Arbeitsschrittzeiten und Bewegungspfade stützten diese Beobachtung eindeutig.
Imaging Studies in Metastatic Urogenital Cancer Patients Undergoing Systemic Therapy: Recommendations of a Multidisciplinary Consensus Meeting of the Association of Urological Oncology of the German Cancer Society (2010)
Heidenreich, Axel ; Albers, Peter ; Classen, Johannes ; Graefen, Markus ; Geschwend, Jürgen ; Kotzerke, Jörg ; Krege, Susanne ; Lehmann, Jens ; Rohde, Detlef ; Schmidberger, Heinz ; Uder, Michael ; Zeeb, Hajo
Introduction: Imaging studies are an integral and important diagnostic modality to stage, to monitor and follow-up patients with metastatic urogenital cancer. The currently available guidelines on diagnosis and treatment of urogenital cancer do not provide the clinician with evidence-based recommendations for daily practice. Objectives: To develop scientifically valid recommendations with regard to the most appropriate imaging technique and the most useful time interval in metastatic urogenital cancer patients undergoing systemic therapy. Methods: A systematic literature review was performed searching MedLine, Embase and Web of Science databases using the terms prostate, renal cell, bladder and testis cancer in combination with the variables lymph node, lung, liver, bone metastases, chemotherapy and molecular therapy, and the search terms computed tomography, magnetic resonance imaging and positron emission tomography were applied. A total of 11,834 records were retrieved from all databases. The panel reviewed the records to identify articles with the highest level of evidence using the recommendation of the US Agency for Health Care Policy and Research. Conclusions: Contrast-enhanced computed tomography remains the standard imaging technique for monitoring of pulmonary, hepatic and lymph node metastases. Bone scintigraphy is still the most widely used imaging technique for the detection and follow-up of osseous lesions. For clinical trials it might be replaced by either PET-CT or MRI of the skeletal axis. Response assessment for patients treated with cytotoxic regime is best performed by the RECIST/WHO criteria; treatment response to molecular triggered therapy is best assessed by CT evaluating decrease in tumor size and density. Cross-sectional imaging studies for response assessment might be obtained after each 2 cycles of systemic therapy to early stratify responders from nonresponders.
A New Method for Measuring the Dynamic Shape Change of Platelets (2010)
Kraus, Max-Joseph ; Strasser, Erwin F. ; Eckstein, Reinhold
Background: Platelet shape change is a dynamic process that has been classified in different types. Exact documentation of platelet structure needs an improved method of measuring platelet shape. Methods: 10 l of platelet-rich plasma (PRP) from anticoagulated whole blood (3.2% buffered sodium citrate 0.105 mol/l) was put onto a glass slide covered with a cover slip. By use a of dark field light microscope connected with a CMOSCamera a photographic snap-shot was taken after 5 and 30 min. Diameter of platelets and length of filopodia were measured with a self-developed plugin for ImageJ software. Statistic calculation was performed with Excel WinSTAT Microsoft software. Results: We showed a swelling of the granulomer from 2.06 ± 0.56 m to 2.33 ± 0.59 m (p < 0.05), a reduction of pseudopodia (2.10 ± 0.94 vs. 1.78 ± 1.04 m; p < 0.05) in conjunction with an increase of hyalomer diameter from 3.29 ± 0.83 to 3.50 ± 0.85 m (p < 0.05), and an increase of pseudopodia length from 2.68 ± 1.45 m to 3.67 ± 1.79 m (p < 0.005) in conjunction with an increase of hyalomer diameter from 6.58 ± 1.91 m to 7.94 ± 1.87 m (p < 0.05). Conclusion: We revealed and documented a dynamic change of platelet size and filopodia structure in PRP. This method allows an exact analysis of platelet size and surface structures.
Fluorescein-Aided Confocal Laser Endomicroscopy of the Lung (2010)
Fuchs, Florian S. ; Zirlik, Sabine ; Hildner, Kai ; Frieser, Markus ; Ganslmayer, Marion ; Schwarz, Stephan ; Uder, Michael ; Neurath, Markus F.
Background: There are only few reports about confocal laser endomicroscopy (CLE) for pulmonary imaging. In these studies, in contrast to gastrointestinal endoscopy, CLE was performed without fluorescein. Objectives: The aim of the present study was to evaluate the value of fluorescein usage for CLE of the lung. Methods: Fluorescein-aided CLE was performed in 15 consecutively recruited patients and in 4 young healthy volunteers with a miniprobe during flexible bronchoscopy. Before and after intravenous administration of fluorescein, central airways and alveolar structures were evaluated. Results: Fluorescein administration did not permit imaging of epithelial cells in the central airways. In the lung periphery, alveolar walls and partially macrophages could be seen in native imaging, as expected. After administration of fluorescein, alveoli were almost filled with foam in areas with normal lung tissue. The origin of this foam was shown to be artificial. Furthermore, in patients with pathologies of the lung parenchyma, dark neoplastic and inflammatory cells adjacent to the alveolar walls were identified. No relevant side effects of fluorescein administration could be observed. Conclusions: Fluorescein-aided CLE of the lung appeared to be safe and well tolerated. While the lack of staining of cells in the central airways was a major limitation, it permitted analysis of the lung interstitium and alveolar space and thus emerges as a new approach for the in vivo analysis of interstitial lung diseases.
Mutational Activation of FGFR3 is Not Involved in the Development of Prostate Cancer (2010)
Koufou, Stella ; Lunz, Jens-Claudio ; Borchardt, Albert ; Keck, Bastian ; Kneitz, Burkhard ; Gaisa, Nadine T. ; Hafner, Christian ; Giedl, Christian ; Rau, Tilman T. ; Rogler, Anja ; Wieland, Wolf F. ; Hartmann, Arndt ; Stoehr, Robert
Objective: The mutational constitutive activation of FGFR3 has been discovered in several malignancies but only limited data on FGFR3 mutations in prostate cancer are available. Most recently, activating FGFR3 mutations were described as being associated with low-grade prostate tumors. Therefore, we investigated the FGFR3 mutation status in a comprehensive series of prostate tumors. Methods: 102 archival formalin- fixed paraffin-embedded prostate tumors of patients treated with radical prostatectomy [with a low-grade subgroup (Gleason score ^ 6) of 29 patients] as well as 29 incidental prostate tumors [low-grade tumors (Gleason score ^ 6); n = 22] and 16 benign prostatic hyperplasia samples obtained by transurethral resection of the prostate were investigated. After microdissection and DNA isolation, all FGFR3 mutation hotspots discovered in human malignancies were analyzed using the SNaPshot © approach or restriction fragment length polymorphism (RFLP) analysis. Results: All cases could successfully be analyzed by SNaPshot; 80 cases were investigated using RFLP. No mutation in FGFR3 could be detected in any of the analyzed cases. Conclusion: The most recently reported FGFR3 mutations in low-grade prostate tumors could not be verified in our series. There were also no mutations in prostate tumors from patients with concomitant bladder tumors as reported previously. These data suggest that the mutational activation of FGFR3 plays no important role in prostate carcinogenesis, which is in accordance with previous studies performed on smaller tumor cohorts.
Neue Daten zum Pankreaskarzinom (2010)
Fietkau, Rainer ; Heinemann, Volker ; Oettle, Helmut ; Trudo Knoefel, Wolfram ; Tannapfel, Andrea
Beim Pankreaskarzinom zeigt sich eine auffällige Diskrepanz zwischen der angegebenen R0-Resektionsrate und dem klinischen Langzeitergebnis. Deshalb erscheint es notwendig, hier zusätzliche Parameter zu finden, die besseren prognostischen Wert besitzen. Auffällig ist die innerhalb der Studien unterschiedliche Anwendung der R-Klassifikation. Wichtig erscheint, die Standards der histopathologischen Aufarbeitung zu überprüfen und zu der klassischen R-Klassifikation zurückzukehren, gegebenenfalls entsprechend den Erfahrungen beim Rektumkarzinom einen «zirkumferentiellen Resektionsrand» einzuführen. Um ein optimales Langzeitüberleben zu erzielen, ist ein Abstand zwischen Tumor und Resektionsrand von >1,0 oder gar >1,5 mm erforderlich. Zu wenige Patienten mit Gefäßinvasion werden operativ saniert, obwohl die Infiltration der Pfortader und der Vena mesenterica superior nach den S3-Leitlinien kein Ausschlusskriterium ist. Mit «High-Volume»-Pankreaszentren könnte eine Qualitätsverbesserung erreicht werden. Der Stellenwert der Radiochemotherapie (RCT) in der perioperativen Situation wird derzeit in mehreren großen Studien überprüft. Die adjuvante Chemotherapie ist Standard und im klinischen Alltag etabliert.
Efficacy and Safety of Irinotecan-Based Chemotherapy for Advanced Colorectal Cancer outside Clinical Trials: An Observational Study (2010)
Moehler, Markus ; Ababneh, Younes ; Verpoort, Karl ; Schmidt, Burghard ; Musch, Reinhard ; Soeling, Ulrike ; Maintz, Christoph ; Siebler, Jürgen ; Schimanski, Carl C. ; Galle, Peter R. ; Fahlke, Jörg
Background: This prospective observational study in typical community-based outpatient clinics evaluated the efficacy and toxicity of weekly and biweekly irinotecan-based chemotherapies and their compatibility depending on age. Methods: 601 patients with advanced or metastatic colorectal cancer receiving first-, second-, or third-line irinotecanbased therapy were regularly analyzed for response and toxicity until the end of therapy. Results: The median age was 65 (28–87) years, approximately one-third of the patients were ≥70 years old. Of all patients, 405 were treated weekly and 68 biweekly. Median overall survival (OS) for first-line therapy was 26.5 months for the <70-year-old patients and 19.4 months for the ≥70-year-old patients. Toxicities were moderate in all groups. Tumor growth control rates (TCR) and median time to progression (TTP) were marginally better for patients <70 years old. Median TTP was 9.9 months in first-line therapy, 9.8 months after adjuvant therapy, 7.7 months in second-line, and 6.4 months in third-line therapy. Conclusions: Toxicity and response data from this observational study clearly confirm the positive results from previous clinical studies and show a slight advantage in efficacy for the <70-year-old patients.
Cost-Effectiveness Analysis of Anastrozole versus Tamoxifen in Adjuvant Therapy for Early-Stage Breast Cancer – a Health-Economic Analysis Based on the 100-Month Analysis of the ATAC Trial and the German Health System (2010)
Lux, Michael P. ; Wöckel, Achim ; Benedict, Agnes ; Buchholz, Stefan ; Kreif, Noémi ; Harbeck, Nadia ; Kreienberg, Rolf ; Kaufmann, Manfred ; Beckmann, Matthias W. ; Jonat, Walter ; Hadji, Peyman ; Distler, Wolfgang ; Raab, Guenther ; Tesch, Hans ; Weyers, Georg ; Possinger, Kurt ; Schneeweiss, Andreas
Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a significantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen.
Expression of Neuropeptide Y, Omentin and Visfatin in Visceral and Subcutaneous Adipose Tissues in Humans: Relation to Endocrine and Clinical Parameters (2010)
Barth, Stephanie ; Klein, Peter ; Horbach, Thomas ; Dötsch, Jörg ; Rauh, Manfred ; Rascher, Wolfgang ; Knerr, Ina
Objective: We aimed at exploring the expression of neuropeptide Y (NPY), omentin and visfatin in adipose tissues of adults along with clinical parameters and hormones. Methods: We included 168 adult patients (31 surgical obese patients and 31 surgical controls, 76 non-surgical obese patients, 30 non-surgical controls). We measured plasma NPY (by radioimmunoassay), cortisol (with an electrochemiluminescence immunoassay) and urinary cortisol metabolites (by gas chromatography/ mass spectrometry). Expression of NPY, omentin and visfatin in subcutaneous and visceral adipose tissue specimens of the surgical patients was quantified using real-time PCR. Results: NPY was detectable in adipose tissue specimens and, like plasma NPY concentrations, comparable between groups. Omentin gene expression was higher in visceral than in subcutaneous adipose tissues (p < 0.0001). Visfatin expression was lower in the subcutaneous tissue of obese patients compared with controls (p < 0.05). Cortisol was lower in obese adults compared with controls (136.5 ± 74.1 vs. 162.2 ± 56.1 ng/ml; p < 0.05), cortisol metabolites were comparable between groups. Conclusion: In our obese adults, plasma NPY levels and the glucocorticoid measures were not elevated. Even though the expression of NPY, omentin and visfatin was comparable between obese individuals and controls, we have to consider differences in the total production rate of adipose tissue-derived factors.
Prevalence of Allelic Loss at TP53 in Endometrial Carcinomas (2010)
Semczuk, Andrzej ; Schneider-Stock, Regine ; Szewczuk, Wiktor
Alterations within the TP53 tumor suppressor belong to the most common genetic features reported in various human neoplasms, including endometrial cancer. In this article, the prevalence of allelic loss at the TP53 locus in primary human endometrial carcinomas (ECs) is discussed. Furthermore, we reviewed the role of allelic imbalance at 17p13.1 in metastatic human ECs on the basis of a literature review and on recently published data ascertained by our laboratory staff.
Dopamine D4 Receptor Exon III Polymorphism, Adverse Life Events and Personality Traits in a Nonclinical German Adult Sample (2010)
Reiner, Iris ; Spangler, Gottfried
Personality and temperament embrace a wide area of both psychological and behavioral processes which are also based on disposition. A functional polymorphism in exon III of the dopamine D4 receptor gene (DRD4) has been a highly suspect genetic marker for personality in spite of ambiguous results. The present study aimed to further elucidate the relationship between DRD4, negative life events and personality in a representative nonclinical sample. Hundred sixty-seven Germans completed the NEO Five-Factor Inventory, the Tridimensional Personality Questionnaire and the California Adult Q-Sort. A factor analysis revealed 3 factors: emotional stability, social orientation and impulsivity. DNA from buccal cells was genotyped for the DRD4 variable-number tandemrepeat exon III polymorphism with respect to presence versus absence of the DRD4 7-repeat allele. Adverse life events were assessed by means of the Adverse Life Events Scale. Men carrying the DRD4 7-repeat allele were more impulsive than those without. Male 7-repeat carriers were more emotionally instable than others, but only when they experienced a large amount of negative life events. No genotypepersonality relationships were found for women. The results indicate gender-specific influences of the DRD4 gene on human behavior and invite researchers to further investigate gene-environment correlations on personality traits.
Pituitary Surgery for Cushing’s Disease (2010)
Buchfelder, Michael ; Schlaffer, Sven
In this article, the present status of neurosurgical operations for Cushing’s disease is briefly reviewed. Transsphenoidal surgery is considered the treatment of choice in most patients with Cushing’s disease once the diagnosis has been established. In a considerable proportion of patients, even sophisticated imaging does not directly depict the tiny micro adenoma. The search for the tumor is technically difficult, particularly when the sella turcica is small, the dura vascularized and the sphenoid sinus poorly pneumatized. Thus, even in expert hands, microadenomas cannot always be identified intraoperatively. Usually, a selective adenomectomy is attempted, preserving pituitary functions. There is a huge variation of surgical outcomes reported. As an estimate, a remission rate of some 75% can be expected 5 years after surgery. Almost all data available to date derive from microsurgical operations. Unfortunately, even in patients who initially remit, recurrences may occur. Low postoperative serum cortisol levels and a long-lasting adrenocortical insufficiency seem to be factors associated with a favorable long-term outcome. When no distinct microadenoma can be identified intraoperatively, partial or even total hypophysectomy has been suggested. However, the outcome of these procedures is less favorable than with selective resec- tions of distinct adenomas. Less than 10% of pituitary adenomas associated with Cushing’s disease are macroadenomas. These also bear a less favorable outcome than microadenomas. Only for selected patients with mainly extrasellar tumor localizations are craniotomies recommended. A close cooperation with the endocrinologist is mandatory for a neurosurgeon operating on patients with Cushing’s disease, namely for the pre- and perioperative care and for long-term follow-up.
Effects of Adrenomedullin on the Glomerular Adrenomedullin System in a Rat Model of Anti-Thy1 Glomerulonephritis (2009)
Geissler, Bettina ; Plank, Christian ; Hartner, Andrea ; Amann, Kerstin ; Struwe, Friedrich G. ; Hilgers, Karl F. ; Rascher, Wolfgang ; Dötsch, Jörg
Background: Adrenomedullin (ADM) has antiproliferative effects on glomerular mesangial cells. The study was performed to determine changes in glomerular gene expression of the ADM system by ADM treatment in anti-Thy1 glomerulonephritis (GN). Methods: GN in rats was induced by injecting anti-Thy-1 antibody. To show the effect of ADM treatment, rats received ADM from day 3 to day 6 of GN. Supplemental rats were sacrificed on day 3, 7 and 14 of GN to show the expression pattern of adrenomedullin and its receptors. Glomeruli were prepared by sieving or laser-assisted microdissection. Expression of ADM, calcitonin receptor-like receptor (CLR), receptor activity-modifying proteins (RAMP) 1–3, CD34, Thy1 and nephrin was analyzed using real-time PCR. Results: During GN a reduction of CLR and RAMP 2 + 3 expressions was detected on days 3, 7 and 14, while RAMP 1 rose. ADM mRNA decreased on days 3 and 7. Thy1 expression as a surrogate of mesangial cell number was downregulated during GN. A significant reduction of CD34 expression, as a surrogate for endothelial cell number, was detected on day 7. A tendency towards reduction of nephrin gene expression, as a surrogate for number of podocytes, was seen. The administration of ADM during GN did not change the expression on Thy1, CD34 or nephrin. The results were similar for microdissected and sieved glomeruli. In ADM-treated GN animals ADM gene expression rose compared to untreated GN animals on day 6. These effects were detected both in sieved and microdissected glomeruli. ADM administration did not change the expression of the receptors. Conclusion: The downregulation of adrenomedullin during GN at the gene level can be improved by ADM application.
An Epidemiological Study of Hemodialysis Patients Based on the European Fresenius Medical Care Hemodialysis Network: Results of the ARO Study (2010)
Francisco, Angel L. M. ; Kim, Joseph ; Anker, Stefan D. ; Belozeroff, Vasily ; Canaud, Bernard ; Chazot, Charles ; Drüeke, Tilman, B. ; Eckardt, Kai-Uwe ; Floege, Jürgen ; Kronenberg, Florian ; Macdougall, Iain C. ; Marcelli, Daniele ; Molemans, Bart ; Passlick-Deetjen, Jutta ; Schernthaner, Guntram ; Stenvinkel, Peter ; Wheeler, David C. ; Fouqueray, Bruno ; Aljama, Pedro
Background/Aims: ARO, an observational study of hemodialysis (HD) patients in Europe, aims to enhance our understanding of patient characteristics and practice patterns to improve patient outcome. Methods: HD patients (n = 8,963) from 134 Fresenius Medical Care facilities treated between 2005 and 2006 were randomly selected from 9 European countries (Czech Republic, France, Hungary, Italy, Poland, Portugal, Spain, Slovak Republic and Slovenia) and Turkey. Information was captured on demographics, comorbidities, medications, laboratory and dialysis parameters, and outcome. Results: Patients were followed for 1.4 8 0.7 years. Wide variation by country was observed for age, sex and diabetes as a cause of chronic kidney disease. Cardiovascular disease was present in 73% of patients. Dialysis parameters were homogeneous across countries. Arteriovenous fistulas were frequently used (73%). More incident patients had hemoglobin ! 11 g/dl than prevalent patients (50 vs. 33%, respectively). Phosphatemia and intact parathyroid hormone were similar between incident and prevalent patients (4.7 8 1.2 mg/dl and 190 vs. 213 ng/l, respectively). Medication use varied widely by country. In total, 5% of patients underwent renal transplantation. Overall death rate was 124/1,000 pa- tient-years. Conclusion: ARO revealed differences in HD practice patterns and patient characteristics in the 10 participating countries. Future ARO studies will fill gaps in the knowledge about the care of European HD patients.
  • 1 to 20

DINI-Zertifikat 2013     DINI-Zertifikat 2016     Members of COAR OPUS4 Logo

  • Contact
  • Imprint
  • Sitelinks