Contraception and abortion attitudes and practices of Western Ukraine women.

OBJECTIVES: To assess the attitudes and practices of contraceptive behaviors of Western Ukraine women. METHODS: A survey of 500 women in the Oblast was conducted to assess their knowledge, attitudes and practices on a variety of health topics. Convenience sampling was used to access the subjects in 16 different towns/villages in nine rayons throughout the Oblast. Respondents were asked more than 100 questions pertaining to their knowledge, attitudes and practices on a variety of health topics, including stress, contraception, breast health, sexually transmitted diseases, parity, abortion, nutrition, alcohol and tobacco use, domestic violence, and depression and mental health. RESULTS: Of married women, 44% (112/256) would terminate their pregnancy while 56% (144/256) said they would keep their baby. Of unmarried women, 35% (31/88) would abort while 65% (57/88) would keep their baby. A large proportion of married women (82%; 222/271) and unmarried women (70%; 52/74) did not use condoms at all. CONCLUSION: These results suggest lack of birth control education and contribution to poor protection from sexually transmitted infections. Higher abortion practices may also play a role in the infertility issues that Ukrainian women currently face.

Patterns of morphological discrimination in selected human tarsal elements.

A suite of measurements was collected from the talus, calcaneus, navicular, and cuboid of humans from Southern China, Victorian Britain, Roman Britain, and Zulu tribes people from the Republic of South Africa. Univariate and multivariate statistical analyses of dimensions of individual foot bones revealed subtle but distinct patterns of morphological discrimination on the basis of sex and size on the one hand, and geographical relationships on the other. These differences are largely expressed in the first three canonical variates of the multivariate analyses: the first axis expresses both sex and size differences, and the second and third, geographical group differences. Confirmation of morphological patterns obtained from individual multivariate analyses was provided by an integrated analysis of the four tarsal elements together. However, the integrated analysis also gave larger separations with discriminations along different axes. Thus the three geographical groups (Zulus, Southern Chinese, and the two British groups together) were separated by first and third variates. The discrimination of sex and size differences was found in the second axis, mirroring what was found in the first axes of the individual studies. This axis reversal implies that in examining all bones together, there is enough redundant information about sex and size in each individual bone that they are relegated to a second axis. It likewise implies that the data referring to geographic discriminations provided by each individual bone are not redundant; they sum in the integrated analysis, and therefore contribute to the overall analysis to a greater extent, with increased clarity.

Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin.

Cytochrome P450 (CYP) 2C9 is the principal enzyme responsible for the metabolism of numerous clinically important drugs. Two polymorphic alleles CYP2C9*2 and CYP2C9*3 have been documented which affect the metabolism and clinical toxicity of drugs such as phenytoin, warfarin, glipizide, and tolbutamide. The present study reports the first example of a null polymorphism in CYP2C9. This mutation dramatically affects the half-life and clinical toxicity of phenytoin. The study subject was a female African-American presented to the emergency department with phenytoin toxicity evidenced by mental confusion, slurred speech, memory loss and the inability to stand. She exhibited extremely poor clearance of phenytoin with an elimination half-life of approximately 13 days. Genotyping studies demonstrated that the patient did not possess any known variant CYP2C9 alleles. Phenytoin is metabolized to a minor extent by the polymorphic CYP2C19, but this individual did not possess any variant CYP2C19 alleles. Sequencing studies revealed that the individual was homozygous for a new CYP2C9 allele (CYP2C9*6) with the deletion of an adenine at base pair 818 of the cDNA. The clearance of phenytoin in this individual is estimated to be approximately 17% of that observed in normal patients. The frequency of this allele was 0.6% (95% confidence limits of 0.1 to 3.5%) in 79 African-Americans and 0% (95% confidence limits of 0 to 1.1%) in 172 Caucasians. The study also demonstrates the severe clinical consequences to patients with a null mutation in CYP2C9 after treatment with normal doses of phenytoin.

Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele.

Genetic polymorphisms in the cytochrome P450 (CYP) family are widely known to contribute to interindividual differences in the pharmacokinetics of many drugs. Several alleles for the CYP2C9 gene have been reported. Individuals homozygous for the Leu359 variant (CYP2C9*3) have been shown to have significantly lower drug clearances compared with Ile359 (CYP2C9*1) homozygous individuals. A male Caucasian who participated in six bioavailability studies in our laboratory over a period of several years showed extremely low clearance of two drugs: phenytoin and glipizide (both substrates of CYP2C9), but not for nifedipine (a CYP3A4 substrate) and chlorpheniramine (a CYP2D6 substrate). His oral clearance of phenytoin was 21% of the mean of the other 11 individuals participating in the study, and his oral clearance of glipizide, a second generation sulfonylurea structurally similar to tolbutamide, was only 188% of the mean of the other 10 individuals. However, his oral clearance of nifedipine and chlorpheniramine did not differ from individuals in other studies performed at our laboratories. An additional blood sample was obtained from this individual to determine if he possessed any of the known CYP2C9 or CYP2C19 allelic variants that would account for his poor clearance of the CYP2C9 substrates (phenytoin and glipizide) compared with the CYP3A4 (nifedipine) and CYP2D6 (chlorpheniramine) substrates. The results of the genotype testing showed that this individual was homozygous for the CYP2C9*3 allele and did not possess any of the known defective CYP2C19 alleles. This study establishes that the Leu359 mutation is responsible for the phenytoin and glipizide/tolbutamide poor metabolizer phenotype.