The effect of a single dose of human chorionic gonadotropin at proestrus on embryonic mortality, fetal growth and gestation length in the rat

The noxious effect of a single dose of 20 IU human chorionic gonadotropin (hCG) given at proestrus on embryonic and fetal survival as well as on fetal weight was studied. Fetal survival varied between 43.6 and 67.6%; the mortality rate was highest before implantation. The surviving fetuses of rats treated with hCG between days 17 and 20 of pregnancy weighed significantly less than controls. Embryonic mortality and fetal growth retardation could be prevented by giving anti-hCG monoclonals 28 or 45 h after hCG administration, but not when anti-hCG was given 69 or 93 h after hCG. 5 IU hCG did not induce embryonic or fetal mortality. On the other hand, 80 IU hCG increased the mortality to 100%; this was entirely due to preimplantation loss. It is speculated that due to a long metabolic half-life of hCG, the steroid metabolism is disturbed, causing implantation failure and/or delay of implantation. By day 21 of pregnancy, however, the fetuses of the hCG-treated rats had made up greatly for the growth retardation; they were born after a similar gestation length and with a similar birth weight as the pups of control rats.     

Effect of doxorubicin exposure on cell-cycle kinetics of human leukemia cells studied by bivariate flow cytometric measurement of 5-iodo-2-deoxyuridine incorporation and DNA content

Cell kinetics of two human leukemic cell lines, Molt-4 and K562, following a 2-h exposure to doxorubicin, were studied. DNA flow cytometry provided static information that for both cell lines a dose-dependent accumulation occurred at the G2 + M compartment that disappeared in time. Kinetic information was provided by time-monitoring cells labeled with 5-iodo-2-deoxyuridine (IdUrd) by two-parameter flow cytometry, analyzing the IdUrd label and the DNA content. The cell-cycle time (Tc) of exponentially growing Molt-4 cells was determined to be 20 h. Twenty-four hours after a 2-h exposure to 0.25 micrograms/ml doxorubicin, the Tc had increased to 23 h; following exposure to 1.0 micrograms/ml, it increased to 33 h. Cell kinetics of K562 cells following doxorubicin exposure were monitored in time up to 4 days. The average Tc of exponentially growing K562 cells was determined to be 24.7 h. Twenty-four hours following 2-h exposure to 0.25 or 0.5 micrograms/ml doxorubicin, the Tc were determined to be 28 and 32 h, respectively. After an additional 2 days, the Tc were both determined to be 24 h. The dose-dependent, reversible cell-cycle delay that persisted at least 48 h should be taken into account as an additional mode for decrease of a (tumor) cell population doubling time after exposure to doxorubicin.     

Sumatriptan nasal spray in the acute treatment of migraine in adolescents and children

About 4-10% of children and adolescents suffer from migraine. In the last few years, several studies have been performed to assess the efficacy and safety of triptans for the acute treatment of migraine in children and adolescents. Only sumatriptan nasal spray has been approved for the treatment of acute migraine with or without aura in adolescents aged 12-17 years in Europe. This review describes the results of the studies with sumatriptan nasal spray that have been performed in children and adolescents, including a study performed in the Netherlands.     

In vivo and in vitro pharmacokinetic differences between four structurally closely related anthracyclines in hematopoietic cell subtypes in humans

Minor differences in chemical structure of adriamycin (ADM), 4'-epiadriamycin (E-ADM), daunomycin (DNM), and 4-demethoxydaunomycin (D-DNM) lead to large differences between cellular and plasma pharmacokinetic parameters in vivo, as well as in cellular drug handling. Anthracyclines accumulated in cells to several hundred-fold the plasma concentration. Half-lives, as well as the ratio of parent drug/metabolite, differed markedly. The slopes of the in vivo cellular concentration-time curves after the end of the bolus injection resembled the efflux curves observed after a 5-min exposure in vitro. In vivo, the area under the cellular concentration-time curve (AUCc) for equimolar dosages was largest for ADM and smallest for D-DNM. In vitro however, cellular drug levels and AUCc were highest for D-DNM, followed by DNM, E-ADM, and ADM. Final cellular drug concentrations were 300-2500 times the medium concentration, with clearly higher values observed after the 360-min exposure. Minor structural differences were related to considerable variations in cellular drug handling, with different patterns in vivo and in vitro. These studies point to difficulties occurring in the in vitro experimental studies of in vivo pharmacokinetic properties of anthracyclines and stress the need for direct determination of target cell drug concentrations in vivo, in the search for the understanding of cell drug handling-related mechanisms of action of the anthracyclines.     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.     

Brachytelephalangic chondrodysplasia punctata in an extremely premature infant

We report on 3 sibs (2 males and one female) with sensorineural deafness. The presence of ovarian dysgenesis in the girl suggested a diagnosis of Perrault syndrome. In addition our patients have a sensory polyneuropathy and amelogenesis imperfecta. Two of the patients have mild mental retardation, fine choreatic movements, and dyspraxia. It is discussed whether these findings are part of a separate clinical entity or should be included within the spectrum of the Perrault syndrome. © 1994 Wiley-Liss, Inc.