Impact of aneurysm location on cardiopulmonary dysfunction after subarachnoid hemorrhage.

BACKGROUND: Cardiopulmonary dysfunction may occur after aneurysmal subarachnoid hemorrhage (SAH), but its characteristics have not been fully clarified. We investigated the impact of aneurysm location on systemic hemodynamics after SAH. METHODS: This multicenter prospective cohort study measured hemodynamic parameters in relation to aneurysm location in patients with SAH using a single-indicator transpulmonary thermodilution system (PiCCO) on days 1-14. RESULTS: Of 204 subjects enrolled, 58 had aneurysms of the anterior communicating artery (ACA), 61 of the middle cerebral artery (MCA), 57 of the internal carotid artery (ICA), and 28 of the vertebrobasilar artery (VA/BA). Patient characteristics were similar except for predominance of coiling in the VA/BA. Patients with ACA aneurysm had a lower systemic vascular resistance index (SVRI) in the acute phase and afterload mismatch (lower cardiac index [CI] and higher SVRI) in the spasm phase. Those with ICA aneurysm had a lower CI in the acute phase, and those with VA/BA aneurysm had a warm shock-like condition (higher CI and lower SVRI) in the spasm phase. Patients with MCA aneurysm showed no specific characteristics in CI and SVRI with a significant improvement in B-type natriuretic peptide. Extravascular lung water index was high independent of left cardiac dysfunction. In multivariate analysis, age and ACA were independently related to poor global ejection fraction after SAH. CONCLUSIONS: Aneurysm location affects cardiac output, vascular resistance, and pulmonary edema in biphasic fashion. Patient age and location of aneurysm in the ACA may be risk factors for cardiac failure after SAH.

Interleukin-5 and interleukin-10 are produced in central nervous system tumor cysts.

Interleukin-5 and interleukin-10, as important mediators of vascular permeability, contribute to the development of various pathologic effusions. However, little is known regarding the involvement of these two cytokines in the formation of cysts associated with central nervous system (CNS) tumors. Twenty-eight patients with various cystic CNS tumors were investigated for expression of interleukin-5 and interleukin-10 in cyst fluid and their matched cytokine receptors in tumor tissue. Interleukin-5 and interleukin-10 were detected in cyst fluid, and interleukin-5 concentration was significantly correlated with interleukin-10 concentration (r=0.508, p=0.006). Moreover, both receptors were also detectable in the tumor tissue specimens and high levels of expression were also found in perivascular cells. Therefore, the local production of interleukin-5 and interleukin-10 might be implicated in some types of cyst formation.

Molecular targeting of neuroblastoma with a novel p16INK4a transporter system.

Potential molecular targets in neuroblastoma include ALK mutations, p16 deletion and CDK2A mutations; however, targeted therapeutics have not been developed for these factors. We developed Wr-T, a new system for intracellular peptide and protein delivery with a 30-residue sequence that mediates molecule entrapment and intracellular permeability. Wr-T was used to introduce the p16INK4a functional peptide to restore the tumor suppressor function of p16INK4a. Introduction of Wr-T into rats with subcutaneous grafts of neuroblastoma produced an astonishing 75.6% tumor suppression (p<0.0005). Thus, the p16INK4a functional peptide can be introduced in low doses and, because it exists in vivo, it should produce fewer side-effects than standard chemotherapy. We suggest this system could be used for molecular-targeted peptides other than p16INK4a and should be pursued for further development.

Flow cytometric analysis for the mechanism of the new antineoplastic agent temozolomide in glioma cells.

Temozolomide (TMZ) has been accepted as a standard antitumor drug for glioma worldwide. Regarding its mechanism of action, there are quite a few analyses. In the present study, we investigated the cell-killing effect and mechanism of action of TMZ with flow cytometry using glioblastoma cell lines. Each cell line was divided into three groups: a control group, a low-dose TMZ group, and a high-dose TMZ group. On day 1, TMZ was added to each cell line. Then, we counted the numbers of cells on days 2, 3, 4, and 5; in U87MG, we counted the number of cells on days 8 and 9. Simultaneously, we performed flow cytometric analysis with single- and double-staining methods. Although results varied slightly depending on the cell line, with flow cytometric analysis we identified the G(0)G(1)-, S-phase block on days 2 through 4, at the beginning of TMZ administration. After that we identified the deviation of the G(2)M block over days 3 to 5. Dominant morphological changes observed in U87MG were confined to the nuclei, with positive TUNEL staining. Early S-phase block and then a G(2)M block were observed; consecutively, we could analyze these blocks with a double-staining method more clearly. The flow cytometric method is very effective in the analysis of the antitumor mechanism of each agent. On the basis of our analysis, more effective combined chemotherapy may be expected.

The intracranial pressure of the patients with mild form of craniosynostosis.

INTRODUCTION: While raised intracranial pressure (ICP) is a well recognized complication affecting children with syndromic craniosynostosis, certain percentage of the patients with non-syndromic craniosynostosis may have some problems related to increased ICP, such as developmental delay or visual problem. However, it is still not clear how many percent of and/or which types of craniosynostosis patients suffer from those symptoms, especially in older patients. OBJECTIVE: The aim of this study was to examine the ICP of older children with mild form of craniosynostosis to determine if any of them should be surgically treated. MATERIALS AND METHODS: We measured ICP before making the decision for surgical intervention. RESULTS: Twenty-five of thirty-six patients had raised ICP in our series. DISCUSSION: All of the 25 patients were treated surgically and followed-up after more than 1 year. All patients improved in some degree. Further investigations should be performed to determine what is the threshold for raised ICP in children.