Size does matter--age-related weight estimation in "tall n' thin" and "tiny n' thick" children and a new habitus-adapted alternative to the EPLS-formula.

AIM OF THE STUDY: Weight in kilograms is a required parameter in the emergency medical care of children. In emergent situations, obtaining an accurate weight is often not possible. In such situations, weight can be estimated by using an age-dependent formula such as the EPLS-formula (age in years+4)×2. As recently recognized for emergency tapes, the habitus of the child has a major influence on weight estimation. In this study, the performance of various age-dependent formulas is to be investigated, with special regard to children demonstrating non-normal growth. METHODS: The performance of various formulas for weight estimation in children growing along the 5th, 50th, and 95th percentile is investigated based on a mathematical model compared to the WHO and CDC reference percentiles using ICC and Bland-Altman methods. Additionally, a new formula for children demonstrating non-normal growth is derived by regression analysis and tested: f×age in years+6 with the factor f being 2 for "tall n' thin", 3 for normal and 4 for "tiny n' thick" children. RESULTS: All previously published formulas lack precision when applied to children outside the 50th percentile. The new habitus-adapted formula shows a better performance for children growing along the 5th or 95th percentile. CONCLUSIONS: The new formula provides enhanced precision in weight estimation and can help in reducing, e.g. drug dosing errors. It should be used for weight estimation in children demonstrating non-normal weight development and in situations when superior methods such as weighing or habitus-adapted emergency tapes are not applicable.

O6-methylguanine-DNA-methyltransferase (MGMT) gene therapy targeting haematopoietic stem cells: studies addressing safety issues.

As haematopoietic stem cell gene therapy utilizing O(6)-methylguanine-DNA-methyltransferase has reached the clinical stage, safety-related questions become increasingly important. These issues concern insertional mutagenesis of viral vectors, the acute toxicity of pre-transplant conditioning protocols and in vivo selection regimens as well as potential genotoxic side effects of the alkylating drugs administered in this context. To address these questions, we have investigated toxicity-reduced conditioning regimens combining low-dose alkylator application with sublethal irradiation and have analysed their influence on engraftment and subsequent selectability of transduced haematopoietic stem cells. In addition, a strategy to monitor the acute and long-term genotoxic effects of drugs with high guanine-O(6) alkylating potential, such as chloroethylnitrosoureas or temozolomide is introduced. For this purpose, assays were implemented which allow an assessment of the generation and fate of primary drug-induced adducts as well as their long-term effect on chromosomal integrity at the single cell level.