Late formation and prolonged differentiation of the Moon inferred from W isotopes in lunar metals.

The Moon is thought to have formed from debris ejected by a giant impact with the early 'proto'-Earth and, as a result of the high energies involved, the Moon would have melted to form a magma ocean. The timescales for formation and solidification of the Moon can be quantified by using 182Hf-182W and 146Sm-142Nd chronometry, but these methods have yielded contradicting results. In earlier studies, 182W anomalies in lunar rocks were attributed to decay of 182Hf within the lunar mantle and were used to infer that the Moon solidified within the first approximately 60 million years of the Solar System. However, the dominant 182W component in most lunar rocks reflects cosmogenic production mainly by neutron capture of 181Ta during cosmic-ray exposure of the lunar surface, compromising a reliable interpretation in terms of 182Hf-182W chronometry. Here we present tungsten isotope data for lunar metals that do not contain any measurable Ta-derived 182W. All metals have identical 182W/184W ratios, indicating that the lunar magma ocean did not crystallize within the first approximately 60 Myr of the Solar System, which is no longer inconsistent with Sm-Nd chronometry. Our new data reveal that the lunar and terrestrial mantles have identical 182W/184W. This, in conjunction with 147Sm-143Nd ages for the oldest lunar rocks, constrains the age of the Moon and Earth to Myr after formation of the Solar System. The identical 182W/184W ratios of the lunar and terrestrial mantles require either that the Moon is derived mainly from terrestrial material or that tungsten isotopes in the Moon and Earth's mantle equilibrated in the aftermath of the giant impact, as has been proposed to account for identical oxygen isotope compositions of the Earth and Moon.

Rapid accretion and early core formation on asteroids and the terrestrial planets from Hf-W chronometry.

The timescales and mechanisms for the formation and chemical differentiation of the planets can be quantified using the radioactive decay of short-lived isotopes. Of these, the (182)Hf-to-(182)W decay is ideally suited for dating core formation in planetary bodies. In an earlier study, the W isotope composition of the Earth's mantle was used to infer that core formation was late (> or = 60 million years after the beginning of the Solar System) and that accretion was a protracted process. The correct interpretation of Hf-W data depends, however, on accurate knowledge of the initial abundance of (182)Hf in the Solar System and the W isotope composition of chondritic meteorites. Here we report Hf-W data for carbonaceous and H chondrite meteorites that lead to timescales of accretion and core formation significantly different from those calculated previously. The revised ages for Vesta, Mars and Earth indicate rapid accretion, and show that the timescale for core formation decreases with decreasing size of the planet. We conclude that core formation in the terrestrial planets and the formation of the Moon must have occurred during the first approximately 30 million years of the life of the Solar System.

Novel oestrogen sulfamates: a new approach to oral hormone therapy.

Sulfamate substitution at the C-3 position of the steroid skeleton leads to orally active prodrugs of ethinyloestradiol, oestradiol, oestrone, oestriol and probably many other natural or synthetic steroidal oestrogens. These compounds have higher systemic, but reduced hepatic, oestrogenic activity than their parent steroids. The release of the parent oestrogen results from the passage of the sulfamates in the erythrocyte compartment through the liver and the systemic hydrolysis of the sulfamate ester. Sulfamates may be used to generate natural oestrogens, oestradiol and other oestrogens for different types of oral oestrogen therapy, e.g., as oestriol for hindered oestrogen or as 17-alpha oestradiol for 'non-feminising' oestrogen. Oestradiol sulfamate J995 is currently in the initial stages of clinical testing. It has per se no oestrogen receptor affinity or oestrogenic activity in vitro, i.e., is inactive without hydrolysis. Its oral uterotropic activity in rats is approximately 100-times higher than that of oestradiol, its hepatotropic activity, however, is only 2- to 3-fold higher than oestradiol. Oral oestradiol sulfamate treatment should, therefore, reduce the hepatic side-effects seen with conventional oral hormone therapy, while at the same time lead to full stimulation of the uterus and the vagina, and suppression of gonadotropin. In the rat, orally administered oestradiol is effectively extracted from the portal vein and excreted via the bile. In contrast, oestradiol sulfamate is present in the circulation at high concentrations, up to 30% of the dose. Initially, 98% of this is found in the erythrocyte compartment and only 2% in the plasma. Significant oestradiol levels in the blood are recorded during the depletion of this pool. Pharmacokinetic and toxicological studies reveal complete excretion of the compound and its metabolites. No toxic effects have been seen in rats and cynomolgus monkeys at any dose, in spite of the compound's distinct oestrogenicity. The evaluation of genotoxicity also yielded negative results.

[Results of allogenic and autologous bone marrow transplantation in children with acute myeloid leukemia]. / Ergebnisse der allogenen und autologen Knochenmarktransplantation bei Kindern mit akuter myeloischer Leukämie.

We report on our experience of bone marrow transplantation (BMT) in children with acute myeloblastic leukaemia (AML) and high risk of relapse (initial WBC greater than 20 x 10(9)/l, FAB M 5, M 6, M 7). 32 children were grafted between november 1982 and october 1991 at the Children's Hospital of the University of Jena. Two patients underwent an allogenous BMT in relapse and died from progressive disease. In 13 children an allogeneic BMT was performed in first complete remission. One patient relapsed, two patients died from severe acute graft-versus-host disease, and two patients died from encephalopathy and cardiomyopathy. Eight of the 13 patients are living and well 18 months to eight and a half year after BMT. Seventeen patients received an autologous (unpurged) BMT. Four of them relapsed four to seven months after BMT. The disease free survival (DFS) for the 29 patients grafted in remission was 0.65. There was no statistical significant difference in DFS between patients with allogeneic and autologous BMT. We conclude that in children with AML and high risk for relapse BMT offers a real chance for better survival. Autologous BMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.

[Therapy of acute myeloid leukemia in children--results of the AML II/87 multicenter study]. / Therapie der akuten myeloischen Leukämie bei Kindern--Ergebnisse der multizentrischen Therapiestudie AML II/87.

Fifty seven patients entered the cooperative study AML II/87 of the working group "Pediatric Hematology and Oncology" of East Germany. Two patients with initial hyperleukocytosis died prior therapy. 13 patients died within the first 4 weeks of therapy, 3 patients did not respond to therapy, and one patient is not yet in remission. 38 patients (70%) attained a complete remission. 15 patients get a bone marrow transplantation in first CR (10 autologous BMT without purging, 5 allogenous BMT). 12 of them are living and well 3 to 34 months after BMT. 9 of the 23 patients under chemotherapy relapsed, one patient is lost to follow up. 13 patients are living in continuous complete remission. The life table probabilities 48 months after the start of the protocol are 0.43 for disease free survival (DFS) and 0.60 for event free interval (EFI). The respective results of the former protocol AML I/82 were 0.34 for DFS and 0.47 for EFI.