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Ponholzer A.,Danube Hospital | Gutjahr G.,Medical University of Vienna | Madersbacher S.,Danube Hospital
International Journal of Impotence Research | Year: 2010

Erectile dysfunction (ED) is linked to various cardiovascular risk factors and may therefore serve as a predictor of cardiovascular events. To gain further insight into this relationship, we reviewed all data regarding hospital admission for cardial or cerebral vascular disease that occurred until 2008 in a cohort of men who underwent a health investigation in 2001. Erectile function was assessed using the International Index of Erectile Function (IIEF-5) questionnaire. In total, 2506 men with a negative history of cardial or cerebral vascular disease were analysed. During the 6.5-year follow-up, 58 cardiovascular events (2.3%) occurred. Men without ED (IIEF-5 >22; n = 1636) at baseline developed a cardiovascular event in 1.9% (n = 32) as compared with 2.9% (52%; n = 26) in those with ED (IIEF-5 ≤22; n = 670). In contrast to age (hazard ratio (HR): 1.6; 1.2-1.8 for every decade), hypertension (HR: 1.88; 1.1-3.1) and diabetes (HR: 2.6; 1.2-5.8), ED was not an independent risk factor for a cardiovascular event. Although men with ED were at increased risk for future cardiovascular events, ED was not an age-independent predictor of cardiovascular events in our cohort. © 2010 Nature Publishing Group.

Kovacs G.G.,Medical University of Vienna | Milenkovic I.,Medical University of Vienna | Wohrer A.,Medical University of Vienna | Hoftberger R.,Medical University of Vienna | And 11 more authors.
Acta Neuropathologica | Year: 2013

Neurodegenerative diseases are characterised by neuronal loss and cerebral deposition of proteins with altered physicochemical properties. The major proteins are amyloid-β (Aβ), tau, α-synuclein, and TDP-43. Although neuropathological studies on elderly individuals have emphasised the importance of mixed pathologies, there have been few observations on the full spectrum of proteinopathies in the ageing brain. During a community-based study we performed comprehensive mapping of neurodegeneration-related proteins and vascular pathology in the brains of 233 individuals (age at death 77-87; 73 examined clinically in detail). While all brains (from individuals with and without dementia) showed some degree of neurofibrillary degeneration, Aβ deposits were observed only in 160 (68.7 %). Further pathologies included α-synucleinopathies (24.9 %), non-Alzheimer tauopathies (23.2 %; including novel forms), TDP-43 proteinopathy (13.3 %), vascular lesions (48.9 %), and others (15.1 %; inflammation, metabolic encephalopathy, and tumours). TDP-43 proteinopathy correlated with hippocampal sclerosis (p < 0.001) and Alzheimer-related pathology (CERAD score and Braak and Braak stages, p = 0.001). The presence of one specific variable (cerebral amyloid angiopathy, Aβ parenchymal deposits, TDP-43 proteinopathy, α-synucleinopathy, vascular lesions, non-Alzheimer type tauopathy) did not increase the probability of the co-occurrence of others (p = 0.24). The number of observed pathologies correlated with AD-neuropathologic change (p < 0.0001). In addition to AD-neuropathologic change, tauopathies associated well with dementia, while TDP-43 pathology and α-synucleinopathy showed strong effects but lost significance when evaluated together with AD-neuropathologic change. Non-AD neurodegenerative pathologies and their combinations have been underestimated, but are frequent in reality as demonstrated here. This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients. © 2013 Springer-Verlag Berlin Heidelberg.

Thaler R.,Hanusch Hospital | Spitzer S.,Hanusch Hospital | Karlic H.,Ludwig Boltzmann Research Institute | Berger C.,Danube Hospital | And 2 more authors.
Biochemical Pharmacology | Year: 2013

There is growing evidence that aminobisphosphonates like ibandronate show anticancer activity by an unknown mechanism. Biochemically, they prevent posttranslational isoprenylation of small GTPases, thus inhibiting their activity. In tumor cells, activated RAS-GTPase, the founding member of the gene family, down-regulates the expression of the pro-apoptotic gene FAS via epigenetic DNA-methylation by DNMT1. We compared ibandronate treatment in neoplastic human U-2 osteosarcoma and in mouse CCL-51 breast cancer cells as well as in the immortalized non-neoplastic MC3T3-E1 osteoblastic cells. Ibandronate attenuated cell proliferation in all cell lines tested. In the neoplastic cells we found up-regulation of caspases suggesting apoptosis. Further we found stimulation of FAS-expression as a result of epigenetic DNA demethylation that was due to down-regulation of DNMT1, which was rescued by re-isoprenylation by both geranylgeranyl-pyrophosphate and farnesylpyrophosphate. In contrast, ibandronate did not affect FAS and DNMT1 expression in MC3T3-E1 non-neoplastic cells. Data suggest that bisphosphonates via modulation of the activity of small-GTPases induce apoptosis in neoplastic cells by DNA-CpG-demethylation and stimulation of FAS-expression. In conclusion the shown epigenetic mechanism underlying the anti-neoplastic activity of farnesyl-transferase-inhibition, also explains the clinical success of other drugs, which target this pathway. © 2012 Elsevier Inc.

Weber T.,Danube Hospital | Wagner T.,Danube Hospital | Neumann K.,Franklin University | Deusch E.,Hanuschkrankenhaus
Pediatric Critical Care Medicine | Year: 2015

Objective: To predict fluid responsiveness by noninvasive methods in a pediatric critical care population. Design: Prospective observational clinical trial. Setting: PICU in a tertiary care academic hospital. Patients: Thirty-one pediatric patients aged from 1 day to 13 years under mechanical ventilation and on catecholamine support. Interventions: We tested three noninvasive methods to predict fluid responsiveness: an esophageal Doppler system (CardioQ), a pulse contour analysis algorithm system (LiDCOrapid), and respiratory variations in vena cava inferior diameter. Stroke volume index was measured by transthoracic echocardiography before and after fluid challenge to determine fluid responders. Infusion of 10 mL/kg hydroxyethylstarch 130/0.4. Measurements and Main Results: Predictability of fluid responsiveness was only found in Doppler peak velocity of descending aortal blood flow. Increased peak velocity with reduction after fluid bolus was predictive for nonresponding to IV fluid challenge. Sensitivity and specificity of peak velocity were 69% and 73%, respectively. The cut point was set at 135.5 cm/s. The lower the Doppler peak velocity, the higher was the probability for a fluid response. Neither stroke volume variations nor respiratory variations in vena cava inferior diameter during mechanical ventilation were useful in predicting fluid responsiveness in this pediatric patient population. None of the children had abdominal hypertension measured by bladder pressure. Conclusions: Dynamic preload variables such as stroke volume variation or respiratory variations in vena cava inferior diameter may not be useful for predicting fluid responsiveness in certain pediatric patient populations. Esophageal Doppler peak velocity was predictive of fluid responsiveness where a target value of more than 135,5 cm/s may be a signal to terminate further fluid challenges. This target value may be different in different age groups, as esophageal Doppler peak velocity varies with age. Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

Jungwirth S.,Ludwig Boltzmann Research Institute | Zehetmayer S.,Medical University of Vienna | Hinterberger M.,Ludwig Boltzmann Research Institute | Tragl K.H.,Ludwig Boltzmann Research Institute | And 2 more authors.
International Psychogeriatrics | Year: 2012

Background: Clinical subtypes of mild cognitive impairment (MCI) were assigned as potential prodromes to various types of dementia. Amnestic MCI (aMCI) is said to have a high likelihood of progressing to Alzheimer's dementia (AD) and non-amnestic MCI (naMCI) subtypes are assumed to have a higher likelihood of progressing to non-AD dementia. The aim of this study was to investigate the prognostic accuracy of aMCI and naMCI for the development of AD, vascular dementia (VaD), and mixed dementia. Methods: In this longitudinal study, 487 subjects without dementia (cognitively healthy: n = 387; MCI cases: n = 115) aged 75 years at baseline, who participated in a population-based cohort study (Vienna Transdanube Aging study), were available for analysis. The observation period was 90 months. The diagnoses of the clinical MCI subtypes were made according to common criteria. The outcome (AD, VaD, mixed dementia) was described for both MCI subtypes. Diagnostic values of aMCI and naMCI according to incident AD, VaD, and mixed dementia were determined. Results: AD was the most common type of dementia following both MCI subtypes. Participants with aMCI were more likely to progress to AD than participants with naMCI. The proportion of incident VaD and mixed dementia did not differ concerning the MCI subtypes. The positive predictive value for both MCI subtypes was low (range: 1%-46%), whereas the negative predictive value was high (range: 86%-99%). Conclusions: The increased risk of clinical MCI subtypes for a particular type of dementia could only be confirmed for aMCI and incident AD. © 2012 International Psychogeriatric Association.

Hinterberger M.,Ludwig Boltzmann Research Institute | Fischer P.,Ludwig Boltzmann Research Institute | Fischer P.,Danube Hospital
Journal of Neural Transmission | Year: 2013

Folate is necessary for DNA and mtDNA integrity and via folate/B12-dependent methionine cycle for methylation of multiple substrates (epigenetic DNA and enzymes) and methylation of homocysteine. During embryogenesis, folate deficiency is a risk factor for neural tube defects and late in life for cognitive decline and Alzheimer's dementia (AD). It induces several Alzheimer pathomechanisms like oxidative stress, Ca++ influx, accumulation of hyperphosphorylated tau and β-amyloid. But impact of folic acid supplementation on prevention or delay of dementia is a matter of debate. Six out of seven randomized controlled trials (RCT) with B vitamin intervention periods between 2 and 5.4 years reported about cognitive benefits in the supplemented groups mainly for those subjects with high homocysteine or low folate levels at baseline. This review tries to demonstrate the connection between folate deficiency and AD, analyses selected epidemiologic studies and RCT on folate/B12/homocysteine with long-observation periods (≥2 years RCT; ≥4 years observational) and attempts to find explanations for the controversy in literature like short follow-up, heterogeneity of subjects concerning age, recruitment, baseline cognition, inclusion criteria and probably "misleading"(not representative for the past) folate/B12/homocysteine levels due to not reported short-term use of multivitamins or food-fortification. Population-based studies - epidemiologic and interventional - starting in the fourth decade would provide the best information about the impact of folate on later development of AD. Mandatory folate fortification areas will be important future field studies for - like neural tube defects - hopefully declining AD incidence and disproving safety concerns. © 2012 Springer-Verlag.

Mossaheb N.,Medical University of Vienna | Zehetmayer S.,Medical University of Vienna | Jungwirth S.,Ludwig Boltzmann Research Institute | Weissgram S.,Ludwig Boltzmann Research Institute | And 4 more authors.
Journal of Clinical Psychiatry | Year: 2012

Objective: To investigate whether specific symptoms of major depression are associated with later development of possible or probable Alzheimer's dementia. Method: The analysis is part of the Vienna Transdanube Aging Study, a prospective, community-based cohort study of all 75-year-old inhabitants of 2 Viennese districts. Current depressive symptoms were captured with a DSM-IV-TR-based questionnaire. Diagnosis of possible or probable Alzheimer's dementia was performed according to criteria by the National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The baseline sample included 437 not-demented and not previously depressed individuals. At 60-month follow-up, 65 of the remaining 296 subjects had possible or probable Alzheimer's dementia. The primary outcome measure was the probability of diagnosis of Alzheimer's dementia related to baseline depressive symptoms. Baseline data were collected between May 2000 and December 2002; 60-month follow-up data were collected between June 2005 and February 2008. Results: 10.8% of those who were diagnosed with possible or probable Alzheimer's dementia at 60-month follow-up had shown loss of interest versus 2.2% in the nondemented group. The analysis showed a significant association of loss of interest only with the later occurrence of possible or probable Alzheimer's dementia (adjusted P value <.05, OR = 5.27 [95% CI, 1.62-17.2], area under the receiver operating characteristic curve = 0.541). The specificity of this symptom in predicting Alzheimer's dementia was 97.8, and the sensitivity was 10.4. Conclusions: Of 9 symptoms of depression, only loss of interest was associated with the development of Alzheimer's dementia over a period of 5 years in a sample of 75-year-old not-demented, never-depressed subjects, suggesting that depressive symptoms in the elderly are mostly symptoms of genuine depression. © Copyright 2012 Physicians Postgraduate Press, Inc.

Hammerer P.,Academic Hospital Braunschweig | Madersbacher S.,Danube Hospital
BJU International | Year: 2012

It is >70 years since the responsiveness of symptomatic metastatic prostate cancer to androgen deprivation was first demonstrated. Since those pivotal studies, progress in hormonal therapy of prostate cancer has been marked by several important developments and the availability of various androgen-suppressing agents. Treatment guidelines have continued to evolve with clinical and therapeutic progress, but androgen-deprivation therapy (ADT) remains the standard of care for non-localised prostate cancer. Because of the long-term experience (>20 years) and wealth of evidence from the large number of clinical trials, the luteinizing hormone-releasing hormone (LHRH) agonists are currently the main forms of ADT. Treatment strategies should be adapted to the individual patient in terms of timing, duration and choice of agent. Prostate cancer remains the most common type of cancer in men and the development of castration-resistant disease seems inevitable, which together drive the clear and continuing need for new, effective agents for ADT to be used alongside the LHRH agonists. © 2012 BJU INTERNATIONAL.

Bock P.,Danube Hospital | Lanz U.,Danube Hospital | Kroner A.,Danube Hospital | Grabmeier G.,Danube Hospital | Engel A.,Danube Hospital
Clinical Orthopaedics and Related Research | Year: 2010

Background: The Scarf osteotomy was described as a technique to correct a metatarsus primus varus in primary hallux valgus surgery, but it is unclear whether the technique could correct recurrent hallux valgus when an initial procedure failed to provide any or an adequate lateral displacement of the metatarsal head. Questions/purposes: We asked whether the Scarf osteotomy could reduce pain, improve the AOFAS score, reduce the deformity, and prevent further recurrence when used as a revision procedure. Patients and Methods: Of 41 patients (45 feet) we treated for failed initial operations, we retrospectively reviewed 35 (39 feet) who underwent a Scarf osteotomy. We administered a VAS for pain and the AOFAS score preoperatively and postoperatively. Preoperative and postoperative radiographs were taken to assess the hallux valgus angle [HVA] and intermetatarsal angle [IMA]. The minimum followup was 24 months (mean, 42 months; range, 24-89 months). Results: The mean VAS for pain improved from 5.9 to 0.4 points. The mean AOFAS score improved from 56 to 90 points. The radiographic evaluation showed improvement of the mean HVA from 30° to 8° and improvement of the IMA from 13° to 4°. Complications included one asymptomatic recurrence with a 20°-HVA, one overcorrection with a 3°-varus deformity, and pain attributable to irritation caused by screws in five patients. Conclusions: As a revision procedure the Scarf osteotomy clinically and radiographically corrected recurrent hallux valgus recurrence in most patients. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. © 2010 The Association of Bone and Joint Surgeons®.

Katzenschlager R.,Danube Hospital
European Neurological Review | Year: 2012

Continuous delivery of dopaminergic drugs is an important treatment strategy to delay or reverse motor complications in Parkinson's disease (PD). Subcutaneous apomorphine (APO) infusion has been shown (in uncontrolled studies) to significantly reduce 'off' time and dyskinesia duration and severity, and long-term data show the beneficial effects persist for several years. There is some evidence that the maximum antidyskinetic effect of APO infusion may be attained when oral medications are reduced or discontinued, making monotherapy an important clinical goal. Recent studies demonstrate possible positive effects of APO infusion on the non-motor symptoms of PD. However, more trials are needed to assess the neuropsychiatric effects of this treatment. Moreover, randomised controlled trials are needed to compare APO infusion with best medical treatment and with other invasive treatments such as levodopa/carbidopa intestinal gel infusion and deep brain stimulation. © TOUCH BRIEFINGS 2012.

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