Diazepam metabolism in human foetal and adult liver

Summary Diazepam was metabolized by human foetal liver microsomes to N-desmethyldiazepam and N-methyloxazepam as early as the 13th week of gestation. The metabolic activity was lower than that of microsomes from adult human liver. Diazepam was shown mainly to be hydroxylated to N-methyloxazepam at substrate concentrations higher than 0.1 mM. Diazepam levels above 1.0 mM were inhibitory to the overall metabolic reaction. SKF 525-A inhibited diazepam metabolism by foetal liver microsomes at a concentration of 0.1 mM. The addition of diazepam to foetal and adult human liver microsomes resulted in a type II spectral change. Its inhibition by carbon monoxide indicated that biotransformation of diazepam was performed by the cytochrome P-450-linked mono-oxygenase system.     

Right-hemisphere dominance for the processing of sound-source lateralization.

Cortical processing of change in direction of a perceived sound source was investigated in 12 human subjects using whole-head magnetoencephalography. The German word "da" was presented either with or without 0.7 msec interaural time delays to create the impression of right- or left-lateralized or midline sources, respectively. Midline stimuli served as standards, and lateralized stimuli served as deviants in a mismatch paradigm. Two symmetrically linked dipoles fitted to the mismatch fields showed stronger moments in the hemisphere contralateral to the side of the deviant. The right dipole displayed equal latencies to both left and right deviants, whereas left dipole latencies were longer for ipsilateral than contralateral deviants. Frequency analysis between 20-70 Hz and statistical probability mapping revealed increased induced gamma-band activity at 53+/-2.5 Hz to both types of deviants. Right deviants elicited spectral amplitude enhancements in this frequency range, peaking at latencies of 160 and 240 msec. These effects were localized bilaterally over the angular gyri and posterior temporal regions. Coherence analysis suggested the existence of two separate interhemispheric networks. For left-lateralized deviants, both spectral amplitude enhancements at 110 and 220 msec and coherence increases were restricted to the right hemisphere. In conclusion, both mismatch dipole latencies at the supratemporal plane and gamma-band activity in posterior parietotemporal areas suggested a right hemisphere engagement in the processing of bidirectional sound-source shifts. In contrast, left-hemisphere regions responded predominantly to contralateral events. These findings may help to elucidate phenomena such as unilateral auditory neglect.     

Age of uptake of early cancer detection facilities by low-risk and high-risk patients with familial breast and ovarian cancer.

INTRODUCTION: Some 5-10% of all cases of breast cancer and ovarian cancer have a hereditary genesis. In the setting of an interdisciplinary cancer genetics clinic, a study of the age at which patients first take advantage of early cancer detection (ECD) facilities was conducted in order to assess the influence of familial risk on health issues. METHODS: The study included 556 women who fulfilled the inclusion criteria (IC) for genetic analysis of the BRCA1 and BRCA2 genes, as well as 205 who did not meet these criteria but attended the primary consultation. RESULTS: Consulters who met the inclusion criteria took advantage of nearly all methods of ECD at an earlier time than women who did not. A comparison of consulters with or without breast cancer showed that those without breast cancer participated in all methods of ECD at an earlier time. CONCLUSION: Methods of improving and increasing participation in ECD facilities, and of encouraging women who are at risk to start on such programs at a younger age, need to be discussed. In this study, familial risk already resulted in a younger age of uptake of ECD facilities.     

Zur Wirkung der Nicotinsäure bei Verschiedenen Anämien

Zusammenfassung Während in 2 Krankheitsfällen von perniziöser Anämie die Behandlung mit Nicotinsäure nicht zu sichtbaren Besserungen führte, gelang dies mit deutlichem Erfolg in einem Falle von perniciosaartiger Anämie bei Hiatushernie im Sinne einer Vermehrung der Erythrocyten von 2,3 auf 4,1 Mill. innerhalb von 10 Tagen und entsprechender Steigerung des Hämoglobingehaltes von 66 auf 82% in der gleichen Zeit.Theoretisch interessant ist, daß in allen behandelten 4 Fällen eine Blutreticulocytose von verschiedenen Ausmaßen eingetreten ist. Die Ausmaße waren am schwächsten bei dem letzten, am günstigsten reagierenden Falle.Zur Erklärung dieses Falles von Hiatushernie wird als Arbeitshypothese die Annahme erörtert, daß hier die Resorptionsfähigkeit des Magen-Darmtractus so weit herabgesetzt war, daß die in der Nahrung zur Verfügung stehenden Mengen an Nicotinsäure bzw. Nicotinsäureamid nicht in ausreichender Menge zur Resorption kamen. Nach Verbrauch des in der Leber nachgewiesenen Nicotinsäuredepots würde sich dieses dann im Sinne einer Anämie auswirken.Nicotinsäure und Nicotinsäureamid stehen mit der tierischen Nahrung in einer höchstwahrscheinlich völlig ausreichenden Menge zur Verfügung. Ob die Pflanzenkost, von Hefe, Reiskleie, Kohl- und roter Rübe abgesehen, nicotinsäurefrei ist, bleibt noch zu entscheiden.Die Arbeit wurde mit Mitteln der Deutschen Forschungsgemeinschaft durchgeführt.Eingegangen am 15. XII. 1938.     

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