A Phase 1/2, Dose-Escalation Trial of Deferasirox for the Treatment of Iron Overload in HFE-Related Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation >= 45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase >3x baseline and greater than the upper limit of normal range, and eight patients had serum creatinine >33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to <250 ng/mL. Conclusion: Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population

Aktive elektrisch und magnetisch gesteuerte supraleitende 3-Tor-Bauelemente auf Basis epitaktischer YBa_2Cu_3O_7- und Bi_2Sr_2CaCu_2O_8-Filme Abschlussbericht

At 4.2 K the obtained I_CR_n products of Josephson Junctions prepared on 45 , 36.8 and 24 bicrystal substrates are 0.1 mV, 0.7 mV and 1 mV, respectively. Raman-type Josephson contacts show the expected scaling of I_C with the barrier thickness, and I_CR_n products of 1 mV have been obtained at 4.2 K. The intrinsic Josephson effect in YBa_2Cu_3O_7_-_#delta#/PrBa_2Cu_3O_7_-_#delta# heterostructures and Bi_2Sr_2CaCu_2O_8_+_#delta# films could be investigated by means of the development of c-axis transport measurements in mesa-structures. In order to force the growth of Bi_2Sr_2CaCu_2O_8_+_#delta# films in orientations relevant for the construction of devices, vicinal SrTiO_3 (1 1 0) substrates were introduced. Thin films with dominant a-axis orientation were successfully prepared by using SrTiO_3 (1 0 0) substrates. By applying a gate voltage on Bi_2Sr_2Ca_n_-_1O_2_n_+_4_+_#delta# based MISFET structures, it was possible to modify the superconducting critical temperature by #DELTA#T_C/#DELTA#U_G_a_t_e#approx#1 KV. As a basis for non-volatile superconducting memory devices YBa_2Cu_3O_7_-_#delta#/BaTiO_3/Au heterostructures with ferroelectric remanent polarisation up to 1,25 #mu#C/cm"2 were prepared. (orig.)Die I_CR_n-Produkte der praeparierten Bi_2Sr_2Ca_2Cu_3O_1_0_+_#delta#-Josephson-Kontakte betrugen bei 4,2 K fuer Bikristallsubstrate mit 45 , 36,8 und 24 Korngrenzen 0,1 mV, 0.7 mV und 1 mV. Die praeparierten Rampen Josephson-Kontakte folgten der erwarteten Skalierung von I_C mit der Barrierendicke, und das I_CR_n-Produkt bei 4,2 K betrug 1 mV. Durch Untersuchung des c-Achsen Transports in Mesa-Strukturen konnte der intrinsische Josephson-Effekt in YBa_2Cu_3O_7_-_#delta#/PrBa_2Cu_3O_7_-_#delta#-Trilagen und -Uebergittern und Bi_2Sr_2CaCu_2O_8_+_#delta#-Filmen nachgewiesen werden. Um die fuer Bauelemente wichtige Filmverkippung in eine vorbestimmte Richtung zu erreichen, wurden erfolgreich vicinal geschnittene SrTiO_3 (1 1 0)-Substrate verwendet. Filme mit einem hohen Anteil an a-Achsen-orientiertem Bi_2Sr_2CaCu_2O_8_+_#delta# konnten auf SrTiO_3 (1 0 0)-Substraten praepariert werden. Durch Anlegen einer Gatespannung an eine MISFET-Struktur konnte die supraleitende Sprungtemperatur von Bi_2Sr_2Ca_n_-_1Cu_nO_2_n_+_4_+_#delta# um #DELTA#T_C/#DELTA#U_G_a_t_e#approx#1 K/V veraendert werden. Als Grundlage fuer nichtfluechtige supraleitende Speicherelemente wurden YBa_2Cu_3O_7_-_#delta#/BaTiO_3/Au-Heterostrukturen mit einer ferroelektrischen remanenten Polarisation von 1,25 #mu#C/cm"2 hergestellt. (orig.)Available from TIB Hannover: F98B1750+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

HTSL-Bauelemente fuer schnelle analoge und digitale Signalverarbeitung Abschlussbericht

Available from TIB Hannover: F98B897 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman