A pharmacokinetic model for factor VIII dosing during active haemorrhage in patients with haemophilia A

A theoretical one-compartment pharmacokinetic model is described, the aim of which is to guide factor VIII replacement therapy in patients with haemophilia A suffering from significant and ongoing haemorrhage. Based on our calculations, plasma factor VIII concentrations can decrease at a rapid rate even with non-severe blood loss.     

Help-seeking for intimate partner violence and forced sex in South Carolina

PURPOSE: In this population-based, random-digit-dial, cross-sectional survey, we assessed the lifetime victimization of intimate partner violence (IPV) and forced or coerced sex among 556 women and men in South Carolina, and the help-seeking behaviors of victims. RESULTS: Among women, 25.3% experienced IPV (sexual, physical, or emotional violence) compared with 13.2% of men. Although women were significantly more likely to report physical or sexual IPV (17.8%) than were men (4.9%), men (8.3%) were as likely as women (7.4%) to report perceived emotional abuse without physical or sexual IPV. One half of men and women with annual incomes <$15, 000 reported IPV. Among women experiencing physical or sexual IPV, 53% sought community-based or professional services for IPV; women with higher education levels and those experiencing more severe violence were most likely to seek services. CONCLUSIONS: These data show that IPV is common and that most victims do not receive services to address this violence.     

Escherichia coli thymidylate synthase expression protects human cells from the cytotoxic effects of 5-fluorodeoxyuridine more effectively than human thymidylate synthase overexpression

In this study, we compared the relative abilities of human thymidylate synthase (hTS) and Escherichia coli thymidylate synthase (eTS) expression to confer resistance to the cytotoxic effects of treatment with the TS inhibitor 5-fluorodeoxyuridine (FdUrd). G418-selected clones expressing either form of the protein were significantly more resistant than the lacZ-expressing clone, VALZ2, to FdUrd-induced cytotoxicity. Although eTS-expressing clones expressed 2- to 3-fold more TS protein than hTS-overexpressing clones, the representative eTS-expressing clone, VAEG8, and hTS-overexpressing clone, VAHGC, were equally sensitive to an FdUrd-induced loss of clonogenicity; in addition, a large fraction of either form of exogenously expressed TS appeared to be inactive in the intact cell. The clones differed, however, in their responses to leucovorin (LV). Although LV significantly enhanced FdUrd-induced TS inhibition, growth inhibition, and cytotoxicity in VAHGC cells, it had no effect on these parameters in VAEG8 cells. These results suggest that eTS may more efficiently confer resistance to FdUrd plus LV when expressed for the purposes of a "host protection" strategy in vivo.     

Psychological autopsy of completed suicide in children and adolescents

A psychological autopsy of 20 children and adolescents aged 12-19 years who had committed suicide and a matched-pair control group revealed that 85% of the victims and 18% of the control subjects had expressed suicidal ideation. A statistically significant number of the victims had a history of suicide threats (55%), suicide attempts (40%), drug or alcohol abuse (70%), antisocial behavior (70%), or inhibited personality (65%). Suicidal behavior of parents, relatives, or friends and a parental history of emotional problems and absence or abusiveness were also significant factors for the victims.