Altered therapy schedules in postoperative treatment of patients with malignant gliomas

Results of altered therapy schedules obtained in postoperative treatment of 294 patients with malignant gliomas over last 20 years are presented. During this period 135 patients received Conventional Irradiation and Chemotherapy (CICH), 61 patients received Conventional Irradiation (CI), 59 patients received Split Course High Fractional Dose Irradiation (SCHFDI), and 39 patients received Twice a Day Accelerated Irradiation (TDAI). Actuarial survival rates at 2, 3 and 5 years were 19%, 7%, 0% respectively for patients treated with CICH, and they were 21%, 10%, 0% for CI group, 24%, 12%, 0% for SCHFDI option and 15%, 8%, 0% for TDAI schedule. According to the Cox proportional hazard model, only age was significant factor in prognosis.     

Response of recurrent glioblastoma and anaplastic astrocytoma to dibromodulcitol,BCNU and procarbazine

Twenty six (17 males) patients with glioblastoma (GBL), median age 55 years, median Karnofsky Index (KI) 70/100, and 11 patients (9 males) with anaplastic astrocytoma (AA), median age 56 years, median KI 70/100 were treated at recurrence with dibromodulcitol (DBD) 1400 mg/m² on day 1, BCNU 150 mg/m² on day 2, and procarbazine (PCZ) 150 mg/day on days 1 to 15. The course was repeated every 4 weeks, but was delayed or decreased by 25% according to hematological toxicity. Response to treatment was evaluated by the criteria of MacDonald et al. (J Clin Oncol 1990; 8: 1277–1280). All GBL-patients were followed until death. One patient with complete response (CR) survived one year, and 2 patients with partial response (PR) survived 1 and 3 years. Ten patients who stabilized (SD) survived 7.5 months, and 13 patients who progressed under chemotherapy had a median survival of 3.5 months. In AA-group 3 patients were alive at the time of the analyses. Six patients: 1 CR and 5 PR survived 6 to 40 + months. Two patients with SD survived 4 and 14 months. Three patients with progressive disease had a mean survived of less than 3 months. The response rate of 55% in AA was significantly higher (p=0.011) than the 12% response rate seen in GBL. We conclude that the regimen tested appears particularly promising in AA. The results in GBL are comparable to those obtained with a single nitrosourea, despite an increased but reversible toxicity.     

Guidelines for the administration of oral examinations

Practical oral examinations are considered an important and often a difficult part of medical school examinations. They represent an accurate and direct mean of assessing student's interaction with patients and their clinical and technical skills. This paper reviews an outline for the administration of oral examinations. The review is based on the medical literature detailed discussions with many senior examiners from different medical systems, and the author's personal experience. In summary, although examiner's judgment is crucial, some general rules remain important for fair and consistent evaluation of students. First, examiner's attitudes should be as friendly as possible with an objective aimed to assess student's medical competence and practical safety. Secondly, scoring should be based on a model answer or well-accepted medical practices for consistent rating. Finally, each examiner should give an independent score before discussing the final rating with the other examiners.     

Radiation effects in lymphocytes of children living in a Chernobyl contaminated region of Belarus

PURPOSE: To investigate cytogenetic and mutational effects in lymphocytes from individuals chronically exposed to radiation from the Chernobyl catastrophe. MATERIALS AND METHODS: Nine years after the Chernobyl accident (1986), peripheral blood lymphocytes from 20 Kalinkovichi children (age 10-15) and 10 Minsk children (age 10-17) were analysed for genetic damage by several assays. Radiation damage in exposed children was investigated in descendants of progenitor cells that were irradiated during a short period immediately after the accident. In the time-span between the accident and blood sampling the cells were also irradiated chronically by internal radiation originating from ingested radionuclides and, to a smaller extent, by external radiation from radionuclides. The parameters measured in whole blood smears were the frequency of micronucleated mononucleated lymphocytes and binucleated lymphocytes with nucleoplasmic bridges and associated micronuclei. Cultures of cytokinesis-blocked lymphocytes were used to analyse mononuclear and binuclear cells for the presence of micronuclei, also cell killing effects. A colony assay was used to study induction of recessive mutations in the HPRT gene. RESULTS: The analysis of whole-blood smears indicated a doubling of the frequency of micronuclei per 100 mononuclear lymphocytes in exposed children compared with unirradiated children. Small numbers of binucleated lymphocytes with nucleoplasmic bridges and associated micronuclei were found in blood smears from exposed children. Analysis of cytokinesis-blocked cultures indicated in mononuclear cells of exposed children a statistically significant increase in the frequency of micronuclei. When the same parameters were studied in binucleated cells there was no difference between exposed and unexposed children. Results of the dye-exclusion assay showed a four-fold increase in the percentage of dead cells between exposed and unexposed children. There was no evidence for induction of HPRT mutations in exposed children. CONCLUSION: These results indicate that the frequently advocated procedure of simply analysing micronuclei in cytokinesis-blocked binucleated lymphocytes can result in an underestimate of genetic damage induced by radiation accidents. Biodosimetric studies should therefore employ a battery of assays for the detection of several types of genetic damage in different generations of lymphocytes.     

Development and characterisation of a head calibration phantom for in vivo measurements of actinides.

The investigation of actinides' internal contamination in human body makes use of a variety of techniques. In large scale screening the technique of "in vivo" evaluation of bone 241Am burden via the determination of the nuclide activity in the skull is often used. For this purpose, adequate calibration procedures and standard phantoms are needed. The present paper summarises the studies and technical procedures followed for the development of a calibration phantom based on a commercial Alderson angiographic head in which a set of 24 241Am point sources were embedded. A theoretical study was first carried out, at the ENEA Institute for Radiation Protection, using the MCNP4-B Monte Carlo code to determine the point source distribution that closely approximates a homogeneous bone contamination. The numerical models were also used to evaluate the resulting degree of approximation. The point sources were prepared at the ENEA National Metrology Institute for ionising radiation quantities and were traceable to the Italian national standard of radionuclide activity. The sources were prepared by quantitatively dispensing a liquid solution onto a plastic disc. The activity of each source was checked by gamma-ray spectrometry and the reproducibility of the activity values was determined. Each source was then placed in the optimum position in the skull, given by the Monte Carlo modelling, by a precision mechanical device. The phantom was finally used to calibrate a whole body counter operating at the ENEA Institute for Radiation Protection. The paper reports the main theoretical and experimental aspects of this work, and also discusses the results of the first calibrations.     

In situ and immunocytochemical localization of E-FABP mRNA and protein during neuronal migration and differentiation in the rat brain

The present study compares the temporal-spatial expression and tissue localization of the rat epidermal type fatty acid binding protein (E-FABP) (DA11/C-FABP/S-FABP/LEBP/KLBP) in the developing rat central nervous system (CNS). In situ hybridization (ISH) and immunocytochemistry (ICC) studies demonstrate that mRNA E-FABP and protein are expressed at high levels during neurogenesis, neuronal migration, and terminal differentiation. Migrating pyramidal cells in the cerebral cortex, Purkinje cells and deep nuclear neurons in the cerebellum, and neurons in the olfactory bulb and retina exhibited a strong E-FABP-like immunoreactivity (E-FABP-LI) throughout the entire process of differentiation and migration. The levels of E-FABP mRNA and protein were dramatically higher in prenatal and early postnatal neurons, as compared to adult neurons. The E-FABP antibody immunoreacted with growing neurites, and nuclear and cytoplasmic regions of neurons. The intracellular multiregional pattern of localization of E-FABP and its differential temporal expression during development, are consistent with its proposed role in transporting long chain free fatty acids and/or other hydrophobic ligands during neuronal differentiation and axon growth.