Browsing by Author "Ebert, Andreas"

This prospective, parallel-group, dose-escalation study evaluated the cardiac safety of trastuzumab (Herceptin((R))) plus epirubicin/ cyclophosphamide (EC) in women with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) and determined an epirubicin dose for further evaluation. HER2-positive patients received standard-dose trastuzumab plus epirubicin (60 or 90 mg/m(2))/cyclophosphamide (600 mg/m(2)) 3-weekly (EC60 + H, n = 26; EC90 + H, n = 25), for four to six cycles; 23 HER2-negative patients received EC alone (90/600 mg/m(2)) 3-weekly for six cycles (EC90). All patients underwent thorough cardiac evaluation. Two EC90 + H-treated patients experienced symptomatic congestive heart failure 4.5 and 6 months after the end of chemotherapy. One EC60 + H-treated patient experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) to < 50% 6 months after the end of chemotherapy. No such events occurred in control patients. Asymptomatic LVEF decreases of > 10% points were detected in 12 (48%), 14 (56%) and 5 (24%) patients treated with EC60 + H, EC90 + H, and EC90. Objective response rates with EC60 + H and EC90 + H were > 60%, and 26% for EC90 alone. These results indicate that trastuzumab may be combined with EC with manageable cardiotoxicity and promising efficacy. (C) 2004 Elsevier Ltd. All rights reserved.

Microstructures and textures of calcite mylonites from the Morcles nappe large-scale shear zone in southwestern Switzerland develop principally as a function of 1) extrinsic physical parameters including temperature, stress, strain, strain rate and 2) intrinsic parameters, such as mineral composition. We collected rock samples at a single location from this shear zone, on which laboratory ultrasonic velocities, texture and microstructures were investigated and quantified. The samples had different concentration of secondary mineral phases (< 5 up to 40 vol.%). Measured seismic P wave anisotropy ranges from 6.5% for polyphase mylonites (~ 40 vol.%) to 18.4% in mylonites with < 5 vol.% secondary phases. Texture strength of calcite is the main factor governing the seismic P wave anisotropy. Measured S wave splitting is generally highest in the foliation plane, but its origin is more difficult to explain solely by calcite texture. Additional texture measurements were made on calcite mylonites with low concentration of secondary phases (≤ 10 vol.%) along the metamorphic gradient of the shear zone (15 km distance). A systematic increase in texture strength is observed moving from the frontal part of the shear zone (anchimetamorphism; 280 °C) to the higher temperature, basal part (greenschist facies; 350–400 °C). Calculated P wave velocities become increasingly anisotropic towards the high-strain part of the nappe, from an average of 5.8% in the frontal part to 13.2% in the root of the basal part. Secondary phases raise an additional complexity, and may act either to increase or decrease seismic anisotropy of shear zone mylonites. In light of our findings we reinterpret the origin of some seismically reflective layers in the Grône–Zweisimmen line in southwestern Switzerland (PNR20 Swiss National Research Program). We hypothesize that reflections originate in part from the lateral variation in textural and microstructural arrangement of calcite mylonites in shear zones.