Conversion of twice-daily tacrolimus to once-daily tacrolimus formulation in stable pediatric kidney transplant recipients: pharmacokinetics and efficacy.

The pharmacokinetics, efficacy and safety of once-daily tacrolimus formulation (Tac-OD) were assessed in 34 stable pediatric kidney transplant recipients. Enrolled patients received their dose of twice-daily tacrolimus formulation (Tac-BID) on study Days 0 through 7. On the morning of study Day 8, the total daily doses for patients were converted to Tac-OD on a 1:1 basis and maintained on a once-daily morning dosing regimen. Tacrolimus pharmacokinetic profiles were obtained on study Days 7, 14 and 28 (after dose adjustment). Although the mean C0 concentrations (4.10 ± 1.16-3.53 ± 1.10 ng/mL, p = 0.004), and AUC0-24 (151.8 ± 41.6-129.8 ± 39.3 ng h/mL, p < 0.001) were decreased significantly after a 1:1 based conversion, there was high interindividual variability. The dose of Tac-OD was decreased in 26.5% and increased in 44.1% of patients. The resultant tacrolimus dose and pharmacokinetic profiles on study Day 28 were comparable to those on Day 7. There were no serious adverse events. In conclusion, Tac-BID can be safely converted to Tac-OD in stable pediatric kidney transplant patients with the heightened therapeutic drug monitoring. Effects of drug conversion on the cardiovascular risk factors, neurological side effects and adherence should be further evaluated.

Spinal cord neurons are vulnerable to rapidly triggered kainate neurotoxicity in vitro.

Initial studies found glutamate injury to murine spinal cultures (14-17 days in vitro) to reflect contributions of both NMDA and AMPA/kainate receptors. Subsequent experiments found the spinal cultures to be more sensitive than cortical cultures to injury from prolonged low level kainate exposures, and, unlike cortical cultures, to be significantly damaged by relatively brief (30-60 min) kainate exposures. This rapidly triggered kainate damage to spinal neurons is Ca(2+)-dependent. Also, more than 40% of spinal neurons (in comparison to about 15% of cortical neurons) are subject to kainate-activated Co2+ uptake (Co2+(+) neurons), a histochemical technique that labels neurons with Ca(2+)-permeable AMPA/kainate channels. These spinal Co2+(+) neurons are very sensitive to Ca(2+)-dependent kainate injury, and show greater kainate-induced elevations in intracellular Ca2+ concentrations ([Ca2+]i) than other spinal neurons during low level kainate exposures. Thus, the heightened vulnerability of spinal neurons to kainate toxicity may at least in part reflect the large proportion that possess Ca2+ permeable AMPA/kainate channels, permitting receptor activation to trigger rapid Ca2+ influx and overwhelm the cells Ca2+ homeostatic capabilities.

Infantile gastrointestinal hemangioma as a cause of chronic anemia.

Gastrointestinal hemangiomas, though rare, can be an important source of GI bleeding in infants. In the past, diagnosis has been hampered by a lack of reliable methods. With the recent advent of selective mesenteric angiography, the suspected diagnosis can be readily confirmed. Surgical resection remains the definitive therapy; steroid therapy has produced conflicting results.