Effect of cryopreservation on the morphology of blastocysts of the ferret Mustela eversmanni

PURPOSE: We describe a practical, reliable, efficient dose-finding design for cytotoxic drugs applied in a multi-institutional setting. METHODS: The continual reassessment method (CRM) was modified for use in phase I trials conducted through the New Approaches to Brain Tumor Therapy (NABTT) Consortium. Our implementation of the CRM uses (1) a simple dose-toxicity model to guide data interpolation, (2) groups of three patients to minimize calculations and stabilize estimates, (3) investigators' clinical knowledge or opinion in the form of data to make the process easier to understand, and (4) a flexible computer program and interface to facilitate calculations. RESULTS: The modified CRM was used in two dose-finding trials of 9-aminocamptothecin in patients with newly diagnosed and recurrent glioblastoma who were taking anticonvulsant medication. The CRM located the maximum tolerated dose (MTD) efficiently in both trials. Compared to conventional designs, the CRM required slightly more than half the number of patients expected, did not greatly overshoot the MTD (i.e. no patients were treated at dangerously high doses), and did not underestimate the MTD. CONCLUSIONS: Our experience demonstrates the feasibility of implementing this design in multi-institutional trials and the possibility of performing dose-finding studies that require fewer patients than conventional methods.     

East European gene pool and diseases in the rural population of European Russia

New data on the association of the state of health and the disease incidence with the gene pool were obtained in the East European population. The second principal component (PC2.G, 11.4% of the total variance) of the geographic variation in the gene pool (100 alleles of 34 loci) showed a distinct latitudinal dependence corresponding to the natural zonality of Eastern Europe. This was also characteristic of the first principal component (PC1.M, 75.6% of the total variance) of the geographic variation in the disease incidence (i.e., the number of all new cases diagnosed in out-patient clinics per year) in the rural population. The disease incidence decreased from the south-southeast to the north-northwest in European Russia. The coefficient of the geographic pairwise correlation between PC2.G and PC1.M was r = 0.945; their specific correlation remained high (r = 0.864), even after a correction for the effects of age composition and heterozygosity. Thus, an insignificant variation in the gene pool was shown to significantly affect the geographic distribution of disease incidence in the East European population of Russia (eta 2 = 0.892). A correlation of mapped geographic distributions of PC1.M and PC2.G in the modern population with those of the principal components of the geographic variation of the late Paleolithic material culture in Eastern Europe was analyzed. The origin of the latitudinal zonality of the modern gene pool was dated back to the late Pleistocene-early Holocene. A conclusion was made that diseases that affected reproduction and lethality in the Paleolithic population still represent a mechanism of the gene pool's adaptation to the natural zonality of the environment. The latitudinal zonality of disease incidence, which was characteristic of the ancient population, is conserved in the today's population, owing to the gene pool.     

Transportation of cytotoxic liposomes to malignant cells using a carbohydrate determinant

A method of the synthesis of lipophilic glycoconjugates (vectors) on the basis of polyethyleneglycol-containing detergent was proposed. It has been shown by flow cytofluorometry that fluorescent labeled liposomes equipped with beta-galactosyl conjugate are bound human leukosis HL-60 cells more effectively than liposomes embedded with the beta-glucosyl conjugate or vector-free liposomes. A new lipid derivative of antitumor drug rubomycin (daunorubicin), N-(rac-1,2-dioleoylglycero-3-oxalyl)rubomycin (RubDG) has been synthesized. Liposomes loaded with RubDG and equipped with galactosyl vector showed higher cytotoxic activity in vitro against HL-60 cells than analogous unvectored liposomes or liposomes bearing glucosyl conjugate.     

Energy and angular sensitivity of the S2010 dosimeter

Based on the requirements to x-ray equipment and its modern characteristics, the authors validate the 5-130 keV range for radiation registration in radiation control of x-ray examination rooms. Experimentally derived graphic representation of the sensitivity of S2010 dosimeter in this energy interval shows that the error of measurements of radiation less than 26 keV is exceedingly over 25%, recorded in the certificate. Experimentally determined angular anisotropy for the 109Cd radiation shows that a corporal angle of 0.04 pi sr corresponds to a relative sensitivity of 0.8. The narrow aperture of the pickup necessitates its careful orientation during measurements. The proper background of the dosimeter is 0.05 mR/h in the 4 to 14 keV range and 0.01 mR/h in the 14 to 140 keV range with the external background equal to 1.5 microR/h.     

Cold-induced anesthesia under a tourniquet during amputation of the lower limbs in old patients

The technic of cold anesthesia under a tourniquet is described, and an analysis of 26 operated patients is given. The anesthesia was always a success. A complication was observed in one case (after inadequate application of a tourniquet chill and tachycardia were noted). A conclusion is made on certain advantages of cold anesthesia under a tourniquet in high amputation of the lower extremities in patients with manifest senile changes in the respiratory and cardiovascular systems.