Experimental model of pediatric asphyxial cardiopulmonary arrest in rats.

Objective: Develop a clinically relevant model of pediatric asphyxial cardiopulmonary arrest in rats.

Design: Prospective interventional study.

Setting: University research laboratory.

Association between chromosome 1p and 19q loss and outcome in pediatric malignant gliomas: results from the CCG-945 cohort.

Background: Results of recent molecular studies on malignant gliomas in adults showed that deletions within the short arm of chromosome 1 and/or the long arm of chromosome 19 identified a prognostically favorable subgroup of tumors that often respond to conventional chemotherapy. To determine if this association applies to pediatric malignant gliomas, we examined the correlation between 1p and 19q deletions and outcome in the cohort derived from the Children's Cancer Group study 945, the largest randomized trial of such tumors completed to date.

Methods: Archival histopathologic material yielded tissue of sufficient quality and quantity for genotyping in 121 specimens.

The influence of central review on outcome associations in childhood malignant gliomas: results from the CCG-945 experience.

To examine the influence of the pathology review mechanism on the results of analyses of therapeutic efficacy and biological prognostic correlates for pediatric high-grade gliomas, we evaluated the effects of using single-expert review or consensus review, as alternatives to institutional classification, in determining outcome results of a large randomized trial. The study group was the randomized cohort of Children's Cancer Group study 945, which compared efficacy of 2 chemotherapy regimens adjuvant to surgery and radiation. Trial eligibility required institutional histopathologic diagnosis of high-grade glioma.

Molecular abnormalities and correlations with tumor response and outcome in glioma patients.

Molecular analysis approaches hold promise to refine the management of patients with malignant gliomas. An important step in the application of these techniques to guide clinical decision-making involves transitioning these approaches from the research setting into the clinical diagnostic arena, using methods that can be performed rapidly and reliably on surgically obtained tumor specimens. Many centers have begun this process for the detection of chromosome 1p and 19q deletions in oligodendroglial neoplasms.

Impact of proliferation index on outcome in childhood malignant gliomas: results in a multi-institutional cohort.

Objective: Prognoses of pediatric high-grade gliomas are unpredictable, even when clinical and histological factors are taken into account. In preliminary studies with an institutional cohort of pediatric high-grade gliomas, we observed a strong association between outcome and proliferation index, as assessed by immunolabeling with the MIB-1 antibody. To determine whether this marker could provide prognostically useful information independent of tumor histology, we examined the prognostic usefulness of this marker in the multi-institutional cohort of Children's Cancer Group Study 945, the largest group of childhood high-grade gliomas analyzed to date.

Age and TP53 mutation frequency in childhood malignant gliomas: results in a multi-institutional cohort.

Malignant astrocytoma is one of the most deadly primary central nervous system tumors. Although significant progress has been made in understanding the molecular pathways that lead to the development of these tumors in adults, comparatively little analysis has been done in childhood astrocytomas, which are less common and have a more favorable prognosis. Our previous studies of an institutional cohort of children with malignant gliomas suggested the existence of distinct molecular pathways of tumorigenesis in younger versus older children, based on the finding of a high frequency of TP53 mutations in tumors from children >3 years of age at diagnosis, compared with those from younger children.

Can succinylcholine be abandoned?

The elective use of succinylcholine in anesthesia has largely been abandoned because of unwanted side effects. Alternatives now exist for short, intermediate, or long elective surgical procedures. NMBDs are frequently used only to facilitate tracheal intubation; rapacuronium fills an important niche particularly for a short elective case (e.

Inhibition of Ras and related guanosine triphosphate-dependent proteins as a therapeutic strategy for blocking malignant glioma growth: II--preclinical studies in a nude mouse model.

Objective: Preliminary studies have demonstrated that the Ras family and related guanosine triphosphate-dependent proteins are overactivated in malignant gliomas and that inhibition of the activation of such proteins, by blockade of their post-translational processing, reduces tumor cell growth in vitro. The current study evaluates the utility of this therapeutic strategy in vivo, using preclinical glioma model systems.

Methods: We examined the efficacy against U-87 human malignant glioma cells, in both subcutaneous and intracranial nude mouse models, of selective peptidomimetic inhibitors of farnesyltransferase (FTI-276) and geranylgeranyltransferase (GGTI-297), which are involved in critical steps in the post-translational processing of Ras and related guanosine triphosphate-dependent proteins.

Pure endotoxin does not pass across the intestinal epithelium in vitro.

Numerous reports suggest that endotoxin (LPS) may play a central role in triggering the inflammatory cascade that leads to the systemic inflammatory response syndrome. Although conditions that promote bacterial translocation in vivo may also facilitate direct translocation of LPS, the exact mechanisms by which LPS crosses the intestinal barrier to reach the systemic circulation are unknown. This study was designed to determine whether pure endotoxin could pass across injured rat ileal mucosa in the Ussing chamber.

Inhibition of Ras and related G-proteins as a therapeutic strategy for blocking malignant glioma growth.

Objective: Preliminary studies have demonstrated that the Ras family and related guanosine 5'-triphosphate-dependent proteins (G-proteins) are overactivated in malignant gliomas and may function as indirect mediators of glial transformation initiated by deregulated upstream signaling elements. We postulated that inhibiting the activation of such proteins might represent a promising strategy for blocking the aberrant proliferation of these tumors.

Methods And Results: Accordingly, we examined the therapeutic efficacy against malignant glioma cells in vitro of a series of selective peptidomimetic inhibitors of farnesylation (FTI-277) and geranylgeranylation (GGTI-286 and GGTI-298), which are critical steps in the post-translational processing (prenylation) of these proteins.

Follow-up of children with shunted hydrocephalus.

In order to determine if routine yearly evaluations of children with shunted hydrocephalus were likely to diagnose shunt malfunction, we reviewed the medical records of the last 100 children who had such routine evaluations. Only 4 children had symptoms that were potentially referable to malfunction; none were subsequently found to have malfunction and no child had signs of malfunction. We also reviewed the medical records of the last 100 children who had shunt revisions to determine if any of them were diagnosed during routine follow-up examinations.

Transmucosal passage of bacteria across rat intestinal epithelium in the Ussing chamber: effect of nutritional factors and bacterial virulence.

Transmucosal passage of bacteria across the intestine, the essential and prerequisite step for bacterial translocation, cannot be effectively studied using in vivo models of translocation. We have adapted the Ussing chamber into a fresh, sterile organ culture system that can facilitate the study of bacterial-epithelial interactions. Intestinal membranes were mounted in the Ussing chamber and perfused with a solution rich in putative mucosal micronutrients.