Ciprofloxacin does not impair the elimination of diazepam in humans

The pharmacokinetics of a single iv dose of 10 mg diazepam and the renal excretion of its metabolites resulting from N-demethylation and C-3-hydroxylation were investigated in 10 healthy volunteers when diazepam was administered alone and on day 3 of administration of the fluoroquinolone ciprofloxacin (500 mg twice per day). No significant changes in the diazepam half-life, its volume of distribution, the total body clearance, or the renal clearance were observed. In addition, the renal excretion of the metabolites desmethyldiazepam, 3-hydroxydiazepam (temazepam), and 3-hydroxydesmethyldiazepam (oxazepam) were not altered by ciprofloxacin co-medication. These data demonstrate that in a 500 mg twice per day oral dosage, ciprofloxacin does not influence the metabolic clearance of diazepam in young healthy volunteers.     

Ärztliche Fehleroffenbarung – Strafrechtliche Strategien für postinvasive Arzt-Patientengespräche

Ohne Zusammenfassung     

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Views of Dutch general practitioners about premenstrual symptoms: A qualitative interview study

BackgroundGeneral practitioners (GPs) encounter women suffering from premenstrual symptoms. Often women with premenstrual problems experience little understanding from GPs. Views of GPs will influence their approach to these women and their care. Insight into these views is lacking but could help in designing educational programmes for GPs.ObjectivesTo explore the views of Dutch GPs towards aetiology, diagnostic process, and preferred treatment of premenstrual symptoms.MethodsIn 2017, we conducted a qualitative, semi-structured, interview survey among 27 GPs, varying in age, gender, and practice setting.ResultsImportant themes emerged from the interviews: ‘no need for a symptom diary,’ ‘PMS defined as illness’ exclusively in case of disruption of normal functioning, and ‘symptomatic treatment’ as preferred approach. Most GPs considered PMS to be a physiological phenomenon, with taking history as an adequate diagnostic tool. Almost all GPs regarded a normal cyclical hormonal cycle as causal; many also mentioned the combination with personal sensitivity. Some pointed to a dividing line between physiological condition and illness if women could not function normally in daily life. Lastly, the approach GPs preferred was focussing on relieving symptoms of individual patients. In addition to explaining the hormonal cycle and lifestyle advice, all GPs advocated oral contraceptives, and if necessary psychological support. GPs expressed negative feelings about prescribing antidepressants.ConclusionGPs considered physiological changes and personal sensitivity as aetiological factors. We recommend more training to improve GPs knowledge and more insight into the burden of women with PMS. A symptom diary is an essential diagnostic tool for GPs.