Chemotherapy with the "8 in 1" protocol for malignant brain tumors in children: a population-based study in Finland

We evaluated the outcome of 68 children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol in Finland from 1986 to 1993, comparing 5-year survival rates with those for a historical control group (from 1975 to 1985). For all malignant brain tumors, overall survival was 43% (vs 28% in the control group; P <0.05), and progression-free survival (PFS) was 43% (vs 23%; P <0.05). For medulloblastoma and primitive neuroectodermal tumor, survival was 63% (vs 35%; P <0.05), and the corresponding PFS was 59% (vs 35%; P = 0.15). For high-grade glioma, both the survival rate and the PFS were 27% (vs 17%; P = NS). Thus the outcome was significantly better for our "8 in 1" -treated patients than for the historical controls, especially among the children with primitive neuroectodermal tumor and medulloblastoma. In contrast, those with high-grade gliomas and brain stem tumors seem to have received little benefit; different, more effective treatments are needed for these patients.     

Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin

G protein-coupled receptor kinases (GRKs) are implicated in the homologous desensitization of G protein-coupled receptors. Six GRK subtypes have so far been identified, named GRK1 to GRK6. The functional state of the GRKs can be actively regulated in different ways. In particular, it was found that retinal rhodopsin kinase (GRK1), but not the ubiquitous betaARK1 (GRK2), can be inhibited by the photoreceptor-specific Ca2+-binding protein recoverin through direct binding. The present study was aimed to investigate regulation of other GRKs by alternative Ca2+-binding proteins such as calmodulin (CaM). We found that Gbetagamma-activated GRK2 and GRK3 were inhibited by CaM to similar extents (IC50 approximately 2 microM), while a 50-fold more potent inhibitory effect was observed on GRK5 (IC50 = 40 nM). Inhibition by CaM was strictly dependent on Ca2+ and was prevented by the CaM inhibitor CaMBd. Since Gbetagamma, which is a binding target of Ca2+/CaM, is critical for the activation of GRK2 and GRK3, it provides a possible site of interaction between these proteins. However, since GRK5 is Gbetagamma-independent, an alternative mechanism is conceivable. A direct interaction between GRK5 and Ca2+/CaM was revealed using CaM-conjugated Sepharose 4B. This binding does not influence the catalytic activity as demonstrated using the soluble GRK substrate casein. Instead, Ca2+/CaM significantly reduced GRK5 binding to the membrane. The mechanism of GRK5 inhibition appeared to be through direct binding to Ca2+/CaM, resulting in inhibition of membrane association and hence receptor phosphorylation. The present study provides the first evidence for a regulatory effect of Ca2+/CaM on some GRK subtypes, thus expanding the range of different mechanisms regulating the functional states of these kinases.     

Analysis of unsteady flow of blood conveying iron oxide nanoparticles on melting surface due to free convection using Casson model

Iron oxide nanoparticles have great importance in future biomedical applications because of their intrinsic properties, such as low toxicity, colloidal stability, and surface engineering capability. So, blood containing iron oxide nanoparticles are used in biomedical sciences as contrast agents following intravenous administration. The current problem deals with an analysis of the melting heat transfer of blood consisting iron nanoparticles in the existence of free convection. The principal equations of the problem are extremely nonlinear partial differential equations which transmute into a set of nonlinear ordinary differential equations by applying proper similarity transformations. The acquired similarity equalities are then solved numerically by Runge‐Kutta Felhsberg 45th‐order method. The results acquired are on the same level with past available results. Some noteworthy findings of the study are: the rate of heat transfer increases as the Casson parameter increases and also found that the temperature of the blood can be controlled by increasing or decreasing the Prandtl number. Hence, we conclude that flow and heat transfer of blood have significant clinical importance during the stages where the blood flow needs to be checked (surgery) and the heat transfer rate must be controlled (therapy).     

Management of thyroid carcinoma invading the aerodigestive tract

OBJECTIVES: To evaluate approaches to thyroid carcinoma invading the aerodigestive tract, with particular attention to well-differentiated carcinomas. STUDY DESIGN: Retrospective review of experience with thyroid carcinoma invading the aerodigestive tract over a 20-year period at a tertiary referral hospital. METHODS: The medical records of all patients with a diagnosis of thyroid cancer treated at Emory University Hospital, Atlanta, Georgia, from 1977 through 1997 were reviewed. Multiple clinical variables were analyzed including treatment, development of recurrence, and survival. Survival and time to local recurrence were determined by Kaplan-Meier analysis, and statistical comparisons were made using log-rank analysis. RESULTS: Five hundred thirty-six cases were identified; 28 patients (5.2%) were identified with invasive disease involving the aerodigestive tract. Histologic findings at the time of invasion included 15 well-differentiated (WD) carcinomas and 13 poorly differentiated (PD) carcinomas. Eight of the 28 patients (5 WD, 3 PD) underwent surgical resection of some portion of the aerodigestive tract with curative intent. Ten patients (8 WD, 2 PD) underwent incomplete resection with tumor left adjacent to aerodigestive tract structures. All patients undergoing incomplete resection developed local recurrence. Six required salvage resection, as opposed to no recurrences in WD carcinomas following complete resection (P = .01). Survival at 5 years for WD carcinomas undergoing complete resection versus initial incomplete resection was 100% versus 50%, respectively (P = .27). CONCLUSION: Review of our experience shows that complete resection of thyroid carcinoma invading the aerodigestive tract can offer prolonged palliation, improved local control, and the opportunity for cure in selected patients.     

Phenol-degrading denitrifying bacteria in wastewater sediments

The simultaneous determination of amino and organic acids in plant tissue extracts using capillary gas chromatography is described. Plant leaves were extracted in 5% (w/v) perchloric acid and neutralized extracts were purified using C18 cartridges. The amino and organic acids in purified extracts were then converted to tert-butyldimethylsilyl (TBDMS) derivatives prior to separation and detection by capillary gas chromatography (GC) with flame ionization detection. Conditions required for optimal derivatization were investigated. Amino and organic acids were readily converted to their TBDMS derivatives using N-methyl-N-tert-butyldimethylsilyltrifluoroacetamide in dimethylformamide solvent 1:6 (v/v) with an average recovery of 90% and a reproducibility of about 5%. The characteristic [M-57] and [M-159] fragment ion of the TBDMS derivatives was confirmed using GC-MS. The proposed method was demonstrated by the determination of amino and organic acids in extracts of Acacia and Eucalyptus leaves, where detection limits were 1-20 ng.