Improving length-based weight estimates by adding a body habitus (obesity) icon.

BACKGROUND: Length-based dosing systems reduce errors associated with resuscitation drug dosing. Obese and thin children of the same length are dosed the same despite their different weights. METHODS: Length (height) and weight were measured in children after a body habitus icon assignment. Within each body habitus group, regression analysis was performed to generate a weight-estimation formula using body habitus and length (BHL). This BHL method was compared to the Broselow tape (BT). RESULTS: Height and weight data were plotted to obtain visual scattergrams. Logarithmic regression yielded higher correlation coefficients than standard linear regression. Within body habitus groups, BHL epinephrine dose estimates were more accurate than BT dose estimates using 0.01 mg/kg as a dosing standard. CONCLUSIONS: Adding body habitus information to the patient's length results in a more accurate weight estimate than length alone in children. The accuracy improvement is greater in children 3 years and older as compared to younger children.

Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions.

Although nonhomologous end-joining (NHEJ) deficiency has been shown to accelerate lymphoma formation in mice, its role in suppressing tumors in cells that do not undergo V(D)J recombination is unclear. Utilizing a tumor-prone mouse strain (ink4a/arf(-/-)), we examined the impact of haploinsufficiency of a NHEJ component, DNA ligase IV (Lig4), on murine tumorigenesis. We demonstrate that lig4 heterozygosity promotes the development of soft-tissue sarcomas that possess clonal amplifications, deletions, and translocations. That these genomic alterations are relevant in tumorigenesis is supported by the finding of frequent mdm2 amplification, a known oncogene in human sarcoma. Together, these findings support the view that loss of a single lig4 allele results in NHEJ activity being sufficiently reduced to engender chromosomal aberrations that drive non-lymphoid tumorigenesis.

Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice.

Aged humans sustain a high rate of epithelial cancers such as carcinomas of the breast and colon, whereas mice carrying common tumour suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. Among the many factors that may contribute to this species variance are differences in telomere length and regulation. Telomeres comprise the nucleoprotein complexes that cap the ends of eukaryotic chromosomes and are maintained by the reverse transcriptase, telomerase. In human cells, insufficient levels of telomerase lead to telomere attrition with cell division in culture and possibly with ageing and tumorigenesis in vivo. In contrast, critical reduction in telomere length is not observed in the mouse owing to promiscuous telomerase expression and long telomeres. Here we provide evidence that telomere attrition in ageing telomerase-deficient p53 mutant mice promotes the development of epithelial cancers by a process of fusion-bridge breakage that leads to the formation of complex non-reciprocal translocations--a classical cytogenetic feature of human carcinomas. Our data suggest a model in which telomere dysfunction brought about by continual epithelial renewal during life generates the massive ploidy changes associated with the development of epithelial cancers.