The partitioning of phosphoramide mustard and its aziridinium ions among alkylation and P-N bond hydrolysis reactions

NMR (1H and 31P) and HPLC techniques were used to study the partitioning of phosphoramide mustard (PM) and its aziridinium ions among alkylation and P-N bond hydrolysis reactions as a function of the concentration and strength of added nucleophiles at 37 degrees C and pH 7.4. With water as the nucleophile, bisalkylation accounted for only 10-13% of the product distribution given by PM. The remainder of the products resulted from P-N bond hydrolysis reactions. With 50 mM thiosulfate or 55-110 mM glutathione (GSH), bisalkylation by a strong nucleophile increased to 55-76%. The rest of the PM was lost to either HOH alkylation or P-N bond hydrolysis reactions. Strong experimental and theoretical evidence was obtained to support the hypothesis that the P-N bond scission observed at neutral pH does not occur in the parent PM to produce nornitrogen mustard; rather it is an aziridinium ion derived from PM which undergoes P-N bond hydrolysis to give chloroethylaziridine. In every buffer studied (bis-Tris, lutidine, triethanolamine, and Tris), the decomposition of PM (with and without GSH) gave rise to 31P NMR signals which could not be attributed to products of HOH or GSH alkylation or P-N bond hydrolysis. The intensities of these unidentified signals were dependent on the concentration of buffer.     

A simplified in vivo drug sensitivity test for malaria in the field

Using a derivative of the plasmid pBR322 we have tested the dimer catastrophe hypothesis of plasmid instability. Most of the theory was confirmed by our observations, but our data suggest that some of the quantitative aspects need modification. In a recF strain of Escherichia coli we estimated the difference in loss rate between the plasmid in the monomeric and the dimeric state to be a factor of 13-14 and the difference in the loss rate between the plasmid in the monomeric and the trimeric state to be a factor of 14-50. We were able to confirm that plasmid oligomers were heterogeneously distributed within a rec+ population, but we were unable to detect any pronounced difference in the level of growth inhibition exerted by the plasmid when in the monomeric, dimeric, or trimeric state. This leaves open the question as to whether runaway plasmid multimerization was prevented (i) by a small correlation between the inhibition of growth and the 'multimeric status' of the plasmid, (ii) by intramolecular homologous recombination, or (iii) whether the process of runaway multimerization is too slow to be recognized within the duration of the experiments, i.e. 200 generations of growth.     

Selective termination and elective reduction in twin pregnancies: 10 years experience at a single centre

Selective termination is employed in multifetal pregnancies, in the presence of an abnormal fetus, in order to improve the prognosis of the normal fetuses. The term elective reduction is used to describe reduction in twin pregnancies for maternal medical conditions, psychological, or socioeconomic reasons. The purpose of this study was to evaluate the factors that influence outcome in such pregnancies. Eighty-two twin pregnancies underwent selective termination (n = 59) or elective reduction (n = 23) over a 10-year period. Early procedures, performed < or = 14 weeks (n = 31), had a pregnancy loss of 9.7% and a mean procedure-to-loss interval of 4.1 +/- 2.8 weeks; mean birthweight was 3299 +/- 395 g in survivors, with a mean gestational age at delivery of 38.4 +/- 2.3 weeks. In comparison, procedures performed > 14 weeks (n = 51) had a pregnancy loss of 7.8%, with a procedure-to-loss interval of 1.2 +/- 0.6 weeks. Mean birthweight was 2577 +/- 999 g, with a mean gestational age at delivery of 35.7 +/- 5 weeks. In conclusion, outcomes were more favourable among patients who underwent a first trimester procedure. The slight increase in pregnancy loss may be attributed to a higher than expected rate of spontaneous abortions in the first trimester, as manifested by the higher procedure-to-loss interval after a first trimester procedure. These facts underscore the importance of early detection of fetal abnormalities in twin pregnancies by ultrasonography and chorionic villus sampling.     

Selective ventricular and coronary denervation (author's transl)

A technique for selective ventricular denervation is described and functional documentation of the effectiveness of this method is presented. Further evidence is presented to demonstrate that selective ventricular denervation interrupts the alpha-adrenergic coronary vasoconstriction fibers and significantly decreases the myocardial oxygen demands during sympathetic nerve stimulation.