Medical University of Graz

About: Medical University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Medicine. The organization has 5684 authors who have published 12349 publications receiving 417282 citations.

Piezo1 forms mechanosensitive ion channels in the human MCF-7 breast cancer cell line

Abstract: Mechanical interaction between cells – specifically distortion of tensional homeostasis-emerged as an important aspect of breast cancer genesis and progression. We investigated the biophysical characteristics of mechanosensitive ion channels (MSCs) in the malignant MCF-7 breast cancer cell line. MSCs turned out to be the most abundant ion channel species and could be activated by negative pressure at the outer side of the cell membrane in a saturable manner. Assessing single channel conductance (GΛ) for different monovalent cations revealed an increase in the succession: Li+ < Na+ < K+ ≈Rb+ ≈ Cs+. Divalent cations permeated also with the order: Ca2+ < Ba2+. Comparison of biophysical properties enabled us to identify MSCs in MCF-7 as ion channels formed by the Piezo1 protein. Using patch clamp technique no functional MSCs were observed in the benign MCF-10A mammary epithelial cell line. Blocking of MSCs by GsMTx-4 resulted in decreased motility of MCF-7, but not of MCF-10A cells, underscoring a possible role of Piezo1 in invasion and metastatic propagation. The role of Piezo1 in biology and progression of breast cancer is further substantiated by markedly reduced overall survival in patients with increased Piezo1 mRNA levels in the primary tumor.

The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)--quality of life during the first 4 months after fracture.

Abstract: The quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss. The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4 months after fracture based on the patients that have been thus far enrolled ICUROS. ICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18 months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire. The total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not. The findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.

Acquired von Willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: Rapid onset and fast recovery.

Abstract: Background Bleeding contributes to the high mortality of venovenous extracorporeal membrane oxygenation (vvECMO). The development of acquired von Willebrand syndrome (AVWS) has been identified as relevant pathology during ECMO. This study was performed to determine the onset of AVWS after implantation and the recovery of von Willebrand factor (VWF) parameters after explantation of ECMO in a large cohort of patients. Methods VWF parameters of 59 patients treated with vvECMO at a university ECMO center were obtained before ECMO implantation, during therapy, and after explantation. In a subgroup of patients, light transmission aggregometry of platelets and flow-cytometric quantification of platelet granule secretion were performed. Results All patients developed severe AVWS hours after implantation of vvECMO. After explantation, AVWS recovered within 3 hours in 60%, within 6 hours in 86%, and in all patients within 1 day. Aggregometry showed hypoaggregability of platelets after stimulation with ADP, ristocetin, collagen, and epinephrine. Flow-cytometric platelet analyses revealed severely reduced expression of CD62 and CD63. Conclusions All patients during vvECMO support rapidly develop AVWS and platelet dysfunction, resulting in severe impairment of coagulation. After explantation, AVWS overwhelmingly recovers within hours, resulting in a hypercoagulative state. These findings augment the need for novel extracorporeal technologies with reduced shear stress, and shift the emphasis for intense anti-coagulation during ECMO instead to a time-point after explantation.

Long‐term effects of weight‐reducing drugs in hypertensive patients

Abstract: All major guidelines for antihypertensive therapy recommend weight loss; anti-obesity drugs might be a helpful option. Objectives: Primary objectives: To assess the long-term effects of pharmacologically induced reduction in body weight with orlistat, sibutramine or rimonabant on: - all cause mortality - cardiovascular morbidity - adverse events Secondary objectives: - changes in systolic and/or diastolic blood pressure - body weight reduction Eight studies comparing orlistat or sibutramine to placebo fulfilled our inclusion criteria. No relevant studies investigating rimonabant for weight loss were identified. No study included mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of gastrointestinal side effects was consistently higher in orlistat treated vs. placebo treated patients. Most frequent side effects with sibutramine were dry mouth, constipation and headache. Patients assigned to weight loss diets, orlistat or sibutramine reduced their body weight more effectively than patients in the usual care/placebo groups. Blood pressure reduction in patients treated with orlistat was for systolic blood pressure (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg; 95%CI +1.4 to +4.9 mm Hg.