The current problems in protecting the health of the population in the oil- and gas-producing regions of Tyumen Province

A socioeconomic and medicodemographic analysis of modern problems related to population health protection in the oil and gas extraction regions of Tyumen Province has been carried out under conditions of radical reconstruction of the national economy. Changes in the parameters of natural migration of the population for each year over a period of 1991 to 1995 are followed up, and specific features of the migration processes, effects of socioeconomic and medical factors on the health status of individual population groups, rates of increment in the number of disabled subjects, and population mortality from various causes analyzed. The authors discuss the status of public health services and offer measures for improving their efficacy in the above regions.     

Interpretation of simulation studies for efficient estimation of population pharmacokinetic parameters

OBJECTIVE: To develop new approaches for evaluating results obtained from simulation studies used to determine sampling strategies for efficient estimation of population pharmacokinetic parameters. METHODS: One-compartment kinetics with intravenous bolus injection was assumed and the simulated data (one observation made on each experimental unit [human subject or animal]), were analyzed using NONMEM. Several approaches were used to judge the efficiency of parameter estimation. These included: (1) individual and joint confidence intervals (CIs) coverage for parameter estimates that were computed in a manner that would reveal the influence of bias and standard error (SE) on interval estimates; (2) percent prediction error (%PE) approach; (3) the incidence of high pair-wise correlations; and (4) a design number approach. The design number (phi) is a new statistic that provides a composite measure of accuracy and precision (using SE). RESULTS: The %PE approach is useful only in examining the efficiency of estimation of a parameter considered independently. The joint CI coverage approach permitted assessment of the accuracy and reliability of all model parameter estimates. The phi approach is an efficient method of achieving an accurate estimate of parameter(s) with good precision. Both the phi for individual parameter estimation and the overall phi for the estimation of model parameters led to optimal experimental design. CONCLUSIONS: Application of these approaches to the analyses of the results of the study was found useful in determining the best sampling design (from a series of two sampling times designs within a study) for efficient estimation of population pharmacokinetic parameters.     

Membrane fusion induced by 11-mer anionic and cationic peptides: a structure-function study

We recently demonstrated that an amphipathic net-negatively charged peptide consisting of 11 amino acids (WAE 11) strongly promotes fusion of large unilamellar liposomes (LUV) when anchored to a liposomal membrane [Pecheur, E. I., Hoekstra, D., Sainte-Marie, J., Maurin, L., Bienvenue, A., and Philippot, J. R. (1997) Biochemistry 36, 3773-3781]. To elucidate a potential relationship between peptide structure and its fusogenic properties and to test the hypothesis that specific structural motifs are a prerequisite for WAE-induced fusion, three 11-mer WAE-peptide analogues (WAK, WAEPro, and WAS) were synthesized and investigated for their structure and fusion activity. Structural analysis of the synthetic peptides by infrared attenuated total reflection spectroscopy reveals a distinct propensity of each peptide toward a helical structure after their anchorage to a liposomal surface, emphasizing the importance of anchorage on conveying a secondary structure, thereby conferring fusogenicity to these peptides. However, whereas WAE and WAK peptides displayed an essentially nonleaky fusion process, WAS- and WAEPro-induced fusion was accompanied by substantial leakage. It appears that peptide helicity as such is not a sufficient condition to convey optimal fusion properties to these 11-mer peptides. Studies of changes in the intrinsic Trp fluorescence and iodide quenching experiments were carried out and revealed the absence of migration of the Trp residue of WAS and WAEPro to a hydrophobic environment, upon their interaction with the target membranes. These results do not support the penetration of both peptides as their mode of membrane interaction and destabilization but rather suggest their folding along the vesicle surface, posing them as surface-seeking helixes. This is in striking contrast to the behavior observed for WAE and WAK, for which at least partial penetration of the Trp residue was demonstrated. These results indicate that subtle differences in the primary sequence of a fusogenic peptide could induce dramatic changes in the way the peptide interacts with a bilayer, culminating in equally drastic changes in their functional properties. The data also reveal a certain degree of sequence specificity in WAE-induced fusion.     

Rapid molecular diagnosis of erythropoietic protoporphyria among Swiss patients

Erythropoietic protoporphyria (EPP) is an autosomal dominant inherited disorder with incomplete penetrance. It is caused by partial deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. Measurement of protoporphyrin concentrations in red cells and feces, although sufficient for diagnosis of symptomatic EPP patients, fails to detect asymptomatic gene carriers. We have developed a molecular diagnostic procedure for rapid and reliable screening of five known mutations in the ferrochelatase gene among Swiss EPP patients in a single denaturing gradient gel electrophoresis (DGGE) gel.     

Corneal opacities in Gaucher disease

PURPOSE: To describe the corneal findings in a variant of Gaucher disease. METHODS: Case report. In an 18-year-old man, ophthalmic and general clinical evaluation, and enzymatic and molecular genetics studies were performed. RESULTS: Diffuse, well-defined, small, linear, or dotlike corneal opacities were observed through, out the posterior two thirds of the corneal stroma in both eyes. The patient had calcific valvular heart disease. Enzymatic and ultrastructural studies were consistent with Gaucher disease. Analysis of the glucocerebrosidase gene disclosed homozygosity for a D409H mutation. CONCLUSION: Corneal opacities are a distinguishing ocular feature of the variant of Gaucher disease associated with the D409H mutation and with calcific cardiac disease.     

Phase transformation behavior in a multipurpose dental casting gold alloy during continuous heating

Phase transformation in a multipurpose dental casting gold alloy during continuous heating was studied by electrical resistivity measurements, hardness tests, X-ray diffraction and scanning and transmission electron microscopy. The behavior can be explained by the following reaction sequences in the nodule: ₁(FCC) + ₂ (L1₂) ₁(fcc) + ₂(L1₂) + (L1₀), where fcc is face centred cubic. A discontinuous precipitation with very fine nodules contributed to the hardening and the growth produced the softening. This multipurpose gold alloy is characterized by the introduction of a PtZn ordered phase with L1₀ structure instead of a CuAu I phase.     

Immunological studies of patients with asbestosis. I. Studies of cell-mediated immunity

A variety of cancers have been documented in patients exposed to asbestos dust. Since a deranged immune system may play a r?le in cancer development, the general level of immunocompetence was studied in a group of twenty-six patients with radiographically defined asbestosis, who might be at risk of developing asbestos-related neoplasms. Statistical comparisons were made with a comparable control group. A disproportionate number of the patients displayed cutaneous energy to certain recall antigens and to 2,4-dinitrochlorobenzene. In vitro studies of cellular immunity, as evaluated by phytohaemagglutinin-induced proliferative and cytotoxicity assays, showed significantly lower values amongst the patient group. Serum inhibitors of mitogen-induced lymphocyte transformation were also detected in several of the patients. The possible significance of these findings is discussed.     

Weight and lymphocyte content of the female rat's thymus following first mating

Eleven groups, each of ten Sprague-Dawley female rats, were sacrificed at 12 to 13 weeks of age; one group of virgins, the others at two-day intervals during the first ten days after either inbred or outbred mating. Observations were made on thymus weight, total white cell count, and thymic white cell density. Compared with the virgin group no significant differences were observed in the thymic weight at any stage after either inbred or outbred mating. In contrast the total white cell counts were significantly greater than the virgin count on the second postcoital day after both inbred and outbred mating. These increased total counts were maintained until the end of the observation period and were associated with significant increases in the thymic white cell densities. These observations suggest that mating and implantation initiate and sustain a mechanism of lymphocyte accumulation in the rat thymus.