Height, weight, and cardiovascular effects of stimulants on children with brain tumors.

INTRODUCTION: Children with brain tumors may develop inattention, slow processing, and hypersomnia. Stimulant medications improve these problems, but their effect on growth, heart rate, and blood pressure (BP) are inadequately explored. PROCEDURE: We retrospectively studied children with brain tumors treated at our institution that had data available for 1 year pre and 2 years on stimulant treatment. Tumor location, gender, radiation treatment (RT), age at RT, drug type, and hormone therapy were variables of interest. RESULTS: We identified 65 children (35 males) that fulfilled eligibility criteria. Focal RT was utilized in 58; 11 additionally had whole brain RT; and seven received no RT. Thirty were treated for hypersomnia and inattention, eight for hypersomnia alone, and rest for inattention. Modafinil was the first drug in 18 (27.7%), and methylphenidate in the others. Forty-seven (72.3%), 45 (69.2%), and 49 (75.4%) were on thyroxine, cortisone, and growth hormones, respectively. There was no difference in pre- and post-stimulant body mass index (BMI), heart rate, and BP. There was also no difference between modafinil and methylphenidate groups. Rate of height acquisition slowed on stimulants (P = .0096). Thyroxine treatment correlated with increase in BMI after stimulants (P = .04). Younger age (P = .0003) and higher prestimulant BMI (P = .0063) correlated with increased heart rate on stimulants, while higher age at RT (P =.016) correlated with elevated systolic BP on stimulants. No associations were found with height acquisition and diastolic BP. CONCLUSION: Stimulants are well tolerated by children with brain tumors that are appropriately managed for endocrine deficiencies, but may reduce the trajectory of height attainment.

A novel synthetic peptide vector system for optimal gene delivery to bone marrow stromal cells.

A 23-amino acid, bifunctional, integrin-targeted synthetic peptide was evaluated for ex vivo gene delivery to rabbit bone marrow stromal cells (BMSCs). The peptide (K)(16)GRGDSPC consists of an amino terminal domain of 16 lysines for electrostatic binding of DNA, and a 7-amino acid integrin-binding domain at the carboxyl terminal. PcDNA3-EGFP plasmids were transfected into BMSCs by (K)(16)GRGDSPC and the positive cells gave out a bright green fluorescence. High levels of gene delivery of pcDNA3-TGF-beta1 plasmids were obtained with 2 to 4 microg/ml DNA concentration, with (K)(16)GRGDSPC at an optimal peptide: DNA w/w ratio of 3:1, with a required exposure time of more than 4 h but shorter than 24 h for BMSC exposure to the peptide/DNA complexes with completely absent serum in the initial stage; with 100 microM chloroquine and at least 8 h exposure for BMSC exposure to chloroquine; with a fusogenic peptide at an optimal (K)(16)GRGDSPC/DNA/fusogenic peptide w/w ratio of 3:1:5; and with Lipofectamine 2000 at an optimal (K)(16)GRGDSPC/DNA/Lipofectamine 2000 w/w ratio of 3:1:2 at a constant DNA concentration of 2 microg/ml. Chloroquine, the fusogenic peptide and Lipofectamine 2000 all significantly promoted gene delivery, but chloroquine was more effective than the fusogenic peptide and had obvious synergistic effects with Lipofectamine 2000. Under optimal conditions, TGF-beta1 gene was transfected into BMSCs without observable toxicity, and the stable expression was examined by RT-PCR and Western blot analysis. The stable transgenic cells showed obvious bands. This novel synthetic peptide, providing a new way for the use of polylysine and RGD motif in DNA vector system, is potentially well suited to ex vivo gene delivery to BMSCs for experimental and clinical applications in the field of bone tissue engineering.