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Search Results: 1 - 10 of 297508 matches for " Fiegl J "
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Das psychosomatisch orientierte Gespr ch im Rahmen der Sterilit tsbehandlung - eine Quantifizierung der Gespr chsschwerpunkte und der therapeutischen Strategien
Kemeter P,Fiegl J
Journal für Fertilit？t und Reproduktion , 1999,
Abstract: Um einen besseren Einblick in unsere psychosomatisch orientierte Beratung bei unerfülltem Kinderwunsch zu bekommen, haben wir 69 Beratungsgespr che auf Band aufgezeichnet, abgeschrieben und analysiert. Jeder relevante Gespr chsinhalt erhielt einen Code für 5 Focus-Gruppen (Focus = Psychogener Ausl ser für Distress bzw. Symptome) und 3 Beratungsarten. Schlie lich wurde noch die Stimmung der Betroffenen am Ende des Gespr chs beurteilt und ein Code vergeben. Die folgenden diagnostischen Foci wurden gefunden (% Frau, % Mann): 1. Belastungen aus Umfeld, Lebenssituation und soziale Faktoren (92, 53); 2. Partnerschaftsprobleme (73, 65); 3. Biographische Faktoren (69, 23); 4. Psychodynamik (57, 39); 5. Stress der Behandlung (23, 17). An Beratung wurde eingesetzt (% Frau, % Mann): 1. Biologisch-medizinische Information (100, 86); 2. Psychotherapeutische Strategien (151, 86); 3. Trauerarbeit (49, 33). Die Stimmung am Ende des Gespr chs war bei Frauen und M nnern wie folgt: unver ndert (29, 21); erleichtert (32, 42); deutlich erleichtert (39, 37). Der statistische Vergeich der Stimmung bei Gespr chsende mit den diagnostischen Foci und den Behandlungsarten zeigte positive signifikante Zusammenh nge mit folgenden Parametern (Frau, Mann): 1. Umfeld, Lebenssituation, soziale Faktoren (p 0,01, p 0,05); 2. Partnerprobleme (p 0,01, p 0,05); 3. Psychotherapeutische Beratung (p 0,01, n.s.). Kein signifikanter Zusammenhang bestand zwischen der Stimmung am Ende der Beratung und dem Alter, der Diagnose, der Dauer des Kinderwunsches, der "unbefangenen Zeit", sowie der Entscheidung für oder gegen eine Behandlung mit assistierter Reproduktions-Technik (ART). Die Ergebnisse best tigen unsere Erfahrung mit der psychosomatisch orientierten Beratung bei unerfülltem Kinderwunsch, da man mit der Bearbeitung von psychischen Belastungen aus dem Umfeld, der Lebenssituation und der Partnerschaft - im Gegensatz zu solchen aus der Biographie und der Psychodynamik - am ehesten eine akute Erleichterung der Betroffenen erreicht. In der Mehrzahl der F lle genügt dazu eine Beratungsstunde. Der Langzeiteffekt mu durch eine Katamnese überprüft werden.
Psychosomatik und assistierte Reproduktion
Kemeter P,Fiegl J,Leeb K,Scholl T
Journal für Fertilit？t und Reproduktion , 2001,
Abstract: Nach unserem psychosomatischen Konzept hat die Berücksichtigung der bio-psycho-somatischen Zusammenh nge den gleichen Rang wie die ART. Dies wurde von unseren PatientInnen insoferne gewürdigt, als die meisten mit einer Beratung das Auslangen fanden, obwohl ihnen auch die ART angeboten wurde. Natürlich richtet sich die Behandlungsstrategie zun chst nach den organischen Befunden, l t aber die psychosozialen Einflu faktoren nie au er acht. Dies hat z. B. gro e Bedeutung für die Wahl des Behandlungszeitpunktes, für die Behandlungsumst nde, Behandlungspausen, sowie für etwaige Interventionen im psychosozialen Umfeld. Diese mehr personen- als schwangerschaftsorientierte Strategie soll die Kinderwunschproblematik entsch rfen und entlastend wirken. Die Tatsache, da etwa ein Viertel der Betroffenen in der Folge schwanger wurde, kann (auch) als Folge dieser Entlastung angesehen werden. Wenn man die doch deutlich h here Rate an gest rten Schwangerschaften (Aborte, EU) und Mehrlingsschwangerschaften nach ART bedenkt, so haben die spontan schwanger gewordenen PatientInnen, die sich, gestützt auf die Autorit t eines Reproduktionsmedizinischen Zentrums mehr auf die eigenen Ressourcen zur Gesundung verlassen haben, eindeutig gewonnen.
Epigenotyping in Peripheral Blood Cell DNA and Breast Cancer Risk: A Proof of Principle Study
Martin Widschwendter, Sophia Apostolidou, Elke Raum, Dietrich Rothenbacher, Heidi Fiegl, Usha Menon, Christa Stegmaier, Ian J. Jacobs, Hermann Brenner
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002656
Abstract: Background Epigenetic changes are emerging as one of the most important events in carcinogenesis. Two alterations in the pattern of DNA methylation in breast cancer (BC) have been previously reported; active estrogen receptor-α (ER-α) is associated with decreased methylation of ER-α target (ERT) genes, and polycomb group target (PCGT) genes are more likely than other genes to have promoter DNA hypermethylation in cancer. However, whether DNA methylation in normal unrelated cells is associated with BC risk and whether these imprints can be related to factors which can be modified by the environment, is unclear. Methodology/Principal Findings Using quantitative methylation analysis in a case-control study (n = 1,083) we found that DNA methylation of peripheral blood cell DNA provides good prediction of BC risk. We also report that invasive ductal and invasive lobular BC is characterized by two different sets of genes, the latter particular by genes involved in the differentiation of the mesenchyme (PITX2, TITF1, GDNF and MYOD1). Finally we demonstrate that only ERT genes predict ER positive BC; lack of peripheral blood cell DNA methylation of ZNF217 predicted BC independent of age and family history (odds ratio 1.49; 95% confidence interval 1.12–1.97; P = 0.006) and was associated with ER-α bioactivity in the corresponding serum. Conclusion/Significance This first large-scale epigenotyping study demonstrates that DNA methylation may serve as a link between the environment and the genome. Factors that can be modulated by the environment (like estrogens) leave an imprint in the DNA of cells that are unrelated to the target organ and indicate the predisposition to develop a cancer. Further research will need to demonstrate whether DNA methylation profiles will be able to serve as a new tool to predict the risk of developing chronic diseases with sufficient accuracy to guide preventive measures.
Epigenetic variability in cells of normal cytology is associated with the risk of future morphological transformation
Andrew E Teschendorff, Allison Jones, Heidi Fiegl, Alexandra Sargent, Joanna J Zhuang, Henry C Kitchener, Martin Widschwendter
Genome Medicine , 2012, DOI: 10.1186/gm323
Abstract: We analyzed DNA methylation (DNAm) profiles of over 27,000 CpGs in cytologically normal cells of the uterine cervix from 152 women in a prospective nested case-control study. We used statistics based on differential variability to identify CpGs associated with the risk of transformation and a novel statistical algorithm called EVORA (Epigenetic Variable Outliers for Risk prediction Analysis) to make predictions.We observed many CpGs that were differentially variable between women who developed a non-invasive cervical neoplasia within 3 years of sample collection and those that remained disease-free. These CpGs exhibited heterogeneous outlier methylation profiles and overlapped strongly with CpGs undergoing age-associated DNA methylation changes in normal tissue. Using EVORA, we demonstrate that the risk of cervical neoplasia can be predicted in blind test sets (AUC = 0.66 (0.58 to 0.75)), and that assessment of DNAm variability allows more reliable identification of risk-associated CpGs than statistics based on differences in mean methylation levels. In independent data, EVORA showed high sensitivity and specificity to detect pre-invasive neoplasia and cervical cancer (AUC = 0.93 (0.86 to 1) and AUC = 1, respectively).We demonstrate that the risk of neoplastic transformation can be predicted from DNA methylation profiles in the morphologically normal cell of origin of an epithelial cancer. Having profiled only 0.1% of CpGs in the human genome, studies of wider coverage are likely to yield improved predictive and diagnostic models with the accuracy needed for clinical application.The ARTISTIC trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821.It has been proposed that epigenetic variation may contribute to the risk of complex genetic diseases like cancer and that differential exposure to environmental risk factors may underlie much of this variation [1,2]. Consistent with this view, a recent study has shown that regi
The Dynamics and Prognostic Potential of DNA Methylation Changes at Stem Cell Gene Loci in Women's Cancer
Joanna Zhuang,Allison Jones,Shih-Han Lee,Esther Ng,Heidi Fiegl,Michal Zikan,David Cibula,Alexandra Sargent,Helga B. Salvesen,Ian J. Jacobs,Henry C. Kitchener,Andrew E. Teschendorff ,Martin Widschwendter
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002517
Abstract: Aberrant DNA methylation is an important cancer hallmark, yet the dynamics of DNA methylation changes in human carcinogenesis remain largely unexplored. Moreover, the role of DNA methylation for prediction of clinical outcome is still uncertain and confined to specific cancers. Here we perform the most comprehensive study of DNA methylation changes throughout human carcinogenesis, analysing 27,578 CpGs in each of 1,475 samples, ranging from normal cells in advance of non-invasive neoplastic transformation to non-invasive and invasive cancers and metastatic tissue. We demonstrate that hypermethylation at stem cell PolyComb Group Target genes (PCGTs) occurs in cytologically normal cells three years in advance of the first morphological neoplastic changes, while hypomethylation occurs preferentially at CpGs which are heavily Methylated in Embryonic Stem Cells (MESCs) and increases significantly with cancer invasion in both the epithelial and stromal tumour compartments. In contrast to PCGT hypermethylation, MESC hypomethylation progresses significantly from primary to metastatic cancer and defines a poor prognostic signature in four different gynaecological cancers. Finally, we associate expression of TET enzymes, which are involved in active DNA demethylation, to MESC hypomethylation in cancer. These findings have major implications for cancer and embryonic stem cell biology and establish the importance of systemic DNA hypomethylation for predicting prognosis in a wide range of different cancers.
Fallbericht: Becken-Beinvenenthrombose bei kongenitaler Aplasie der Vena cava inferior
Schierl M,Fiegl N,Gunek-Zalodek S,Trnka H
Zeitschrift für Gef？？medizin , 2009,
Abstract:
Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development
Allison Jones equal contributor,Andrew E. Teschendorff equal contributor,Quanxi Li equal contributor,Jane D. Hayward,Athilakshmi Kannan,Tim Mould,James West,Michal Zikan,David Cibula,Heidi Fiegl,Shih-Han Lee,Elisabeth Wik,Richard Hadwin,Rupali Arora,Charlotte Lemech,Henna Turunen,P？ivi Pakarinen,Ian J. Jacobs,Helga B. Salvesen,Milan K. Bagchi,Indrani C. Bagchi,Martin Widschwendter
PLOS Medicine , 2013, DOI: 10.1371/journal.pmed.1001551
Abstract: Background Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. Conclusions HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary
Continuously assessed right ventricular end-diastolic volume as a marker of cardiac preload and fluid responsiveness in mechanically ventilated cardiac surgical patients
Christoph Wiesenack, Christoph Fiegl, Andreas Keyser, Sven Laule, Christopher Prasser, Cornelius Keyl
Critical Care , 2005, DOI: 10.1186/cc3503
Abstract: We studied 21 patients undergoing elective coronary artery bypass grafting. After induction of anesthesia, hemodynamic parameters were measured simultaneously before (T1) and 12 min after volume replacement (T2) by infusion of 6% hydroxyethyl starch 200/0.5 (7 ml/kg) at a rate of 1 ml/kg per min.The volume-induced increase in thermodilution-derived stroke volume index (SVITD) was 10% or greater in 19 patients and under 10% in two. There was a significant correlation between changes in CEDV index and changes in SVITD (r2 = 0.55; P < 0.01), but there were no significant correlations between changes in CVP, PCWP and LVEDA index, and changes in SVITD. The only variable apparently indicating fluid responsiveness was LVEDA index, the baseline value of which was weakly correlated with percentage change in SVITD (r2 = 0.38; P < 0.01).An increased cardiac preload is more reliably reflected by CEDV index than by CVP, PCWP, or LVEDA index in this setting of preoperative cardiac surgery, but CEDV index did not reflect fluid responsiveness. The response of SVITD following fluid administration was better predicted by LVEDA index than by CEDV index, CVP, or PCWP.Accurate evaluation of cardiac performance and preload status, and assessment of fluid responsiveness are important goals in the treatment of critically ill patients. Despite the current controversy surrounding the usefulness of and risks associated with the pulmonary artery catheter (PAC) [1,2], the PAC remains more frequently used for monitoring and is preferred over transesophageal echocardiography (TEE) by cardiovascular anaesthesiologists [3]. However, it has been demonstrated that PAC-derived filling pressures are of little help when making decisions regarding adequate volume therapy. Nevertheless, the majority of intensive care unit (ICU) physicians use filling pressures in their decision making regarding volume replacement to improve hemodynamics. This accentuates the need for reliable indicators of fluid responsiv
Single-agent pegylated liposomal doxorubicin (PLD) in the treatment of metastatic breast cancer: results of an Austrian observational trial
Michael Fiegl, Brigitte Mlineritsch, Michael Hubalek, Rupert Bartsch, Ursula Pluschnig, Günther G Steger
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-373
Abstract: 129 consecutive patients with advanced breast cancer, of whom the majority had been massively pretreated, received PLD as monotherapy within licensed approval, for which efficacy and toxicities were documented.In a routine therapy setting, PLD was administered in a slightly reduced dose (median, 40 mg/m2 per cycle). Response rate (complete and partial remission) was 26%, and stable disease was observed in 19% of patients. Progression-free (PFS) and overall survival (OS) were 5.8 months and 14.2 months, respectively. There was no difference in terms of response and PFS, no matter if patients had already received anthracycline treatment. Interestingly, PFS proved similar regardless whether PLD was administered as palliative therapy in first, second or third line. Furthermore, PFS and OS were similar in patients with response or stable disease, underscoring the view that disease stabilization is associated with a profound clinical benefit. The most common side effects reported were palmar-plantar erythrodysesthesia (17%), exanthema (14%) and mucositis (12%).Efficacy and toxicity data in these "real life" patients permit the conclusion that PLD is a valuable option in the treatment of advanced breast cancer even in heavily pretreated patients.There are numerous systemic therapeutic options available for the tailored treatment of metastatic breast cancer. In addition, therapeutic antibodies and small molecules increasingly complement the therapeutic range of instruments. The choice of systemic therapy follows accepted guidelines (1) but remains largely based on individual factors (2). In case instant response is required, such as rapidly progressive, threatening disease or massive symptoms, combination cytostatic therapy is usually administered; more often, however, monotherapy is the method of choice for patients in whom a long-term stabilization of metastatic disease is the objective. Thus, different therapies can be applied in sequence over a long period of metastatic
The impact of sample storage time on estimates of association in biomarker discovery studies
Karl G Kugler, Werner O Hackl, Laurin AJ Mueller, Heidi Fiegl, Armin Graber, Ruth M Pfeiffer
Journal of Clinical Bioinformatics , 2011, DOI: 10.1186/2043-9113-1-9
Abstract: In the laboratory experiment levels of two serum markers measured at sample collection and again in the same samples after approximately ten years in storage increased by 15%. For a 15% increase in marker levels over ten years, odds ratios (ORs) of association were significantly underestimated, with a relative bias of -10%, while for a 15% decrease in marker levels over time ORs were too high, with a relative bias of 20%.Biases in estimates of parameters of association need to be considered in sample size calculations for studies to replicate markers identified in exploratory analyses.Using specimens, including serum, plasma or tumor tissue, from biobanks is attractive for biomarker studies, as samples are readily available. For example, archived patient tissue specimens from prospective clinical trials can be used for establishing the medical utility of prognostic or predictive biomarkers in oncology [1]. Convenience samples from clinical centers and hospitals may be of use in biomarker discovery studies. The National Cancer Institute maintains a website http://resresources.nci.nih.gov webcite that lists human specimen resources available to researchers, including specimens and data from patients with HIV-related malignancies, a repository of thyroid cancer specimens and clinical data from patients affected by the Chernobyl accident, normal and cancerous human tissue from the Cooperative Human Tissue Network (CHTN) and blood samples to validate blood-based biomarkers for early diagnosis of lung cancer. However, freezing specimens over long periods of time can alter levels of some of their components [2] causing decreases or increases in marker concentrations [3-5]. Among other factors, storage temperature [6-8] and storage time [3,9,10] are known to impact frozen samples. Thus, even in carefully collected and stored samples time alone can alter marker levels.Our work was motivated by a biomarker discovery study at the Medical University of Innsbruck that aims to id
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