A novel amphibian tier 2 testing protocol: a 30-week exposure of Xenopus tropicalis to the antiandrogen flutamide.

In 1996, the U.S. Congress mandated the development of a screening program for endocrine-disrupting chemicals (EDCs) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs. For that reason, a tier 2 testing protocol using Xenopus (Silurana) tropicalis and a 30-week, flow-through exposure to the antiandrogen flutamide from stage 46 tadpoles through sexually mature adult frogs were developed and evaluated in this pilot study. The endpoints for this study included measurements of frog body lengths and weights, liver weights, ovary/egg mass weights, testicular and ovarian histopathology, plasma vitellogenin levels, and notes on any abnormalities observed at necropsy. Increasing exposure concentrations to flutamide caused significant increases in frogs with no recognizable gonadal tissue and increased body and liver weights in male frogs, whereas the body lengths and weights decreased significantly in female frogs. Important issues must be resolved before a tier 2 amphibian assay can be further developed and validated, including the establishment of baseline values in the controls for the parameters under study; the maintenance, measurement, and timing of exposure concentrations; and the development of additional biomolecular markers of effect. This study demonstrated the feasibility of conducting long-term EDC exposure studies using X. tropicalis.

Relationship between sperm characteristics and hormonal parameters in normal couples.

OBJECTIVE: To examine the relationships between hormone profiles and semen analysis measures and fertility in the male partners of presumed normal couples. DESIGN: Prospective clinical study. SETTINGS: Healthy volunteers in an academic research environment. PATIENT(S): One hundred forty-five reproductive age couples without known risk factors for infertility and who had discontinued contraception to achieve pregnancy completed this component of this study. Each couple was followed for < or =12 menstrual cycles while they attempted to conceive. INTERVENTION(S): Semen quality measures for the first ejaculates were obtained at the start of the study along with a single blood sample. Levels of FSH, bioactive FSH, inhibin B, LH, and T were measured for each man. MAIN OUTCOME MEASURE(S): Semen analysis, FSH, inhibin B, LH, T, and clinical pregnancy. RESULTS: Significant positive relationships were observed between the two measures of FSH as well as between both of the FSH measures and LH. Follicle-stimulating hormone as measured by RIA was significantly negatively correlated with inhibin B. Inhibin B showed a marginally significant negative correlation with LH, and LH and T had a marginally significant positive correlation. Inhibin B increased significantly, and both measures of FSH activity showed significant decreases, with increasing levels in several semen quality measures. There was no significant relationship between the measured hormones and the pregnant and nonpregnant groups or time to pregnancy. CONCLUSION(S): These results contribute additional information on the utility of reproductive hormone measurements for predicting semen quality in couples without known reduced fertility.

Cognitive research enhances accuracy of food frequency questionnaire reports: results of an experimental validation study.

OBJECTIVE: To test whether changing a food frequency questionnaire (FFQ) on the basis of cognitive theory and testing results in greater accuracy. Accuracy was examined for 4 design issues: a) Grouping: asking about foods in a single vs multiple separate questions; b) different forms of a food: asking consumption frequency of each form of a food (eg, skim, 2%, whole milk) vs a nesting approach--asking frequency of the main food (eg, milk) and proportion of times each form was consumed; c) additions (eg, sugar to coffee): asking independent of the main food vs nested under the main foods; d) units: asking frequency and portion size vs frequency of units (eg, cups of coffee). DESIGN: Participants in two randomly assigned groups completed 30 consecutive daily food reports (DFRs), followed by 1 of 2 FFQs that asked about foods consumed in the past month. One was a new, cognitively-based National Cancer Institute (NCI) Diet History Questionnaire; the other was the 1992 NCI-Block Health Habits and History Questionnaire. SUBJECTS/SETTING: 623 participants, age range 25 to 70 years, from metropolitan Washington, DC. Statistical analyses performed Accuracy was assessed by comparing DFR and FFQ responses using categorical (percent agreement) and continuous (rank order correlation, discrepancy scores) agreement statistics. RESULTS: Grouping: accuracy was greater using separate questions. Different forms of food: accuracy was greater using nesting. Additions: neither approach was consistently superior; accuracy of the addition report was affected by accuracy of the main food report. Units: both approaches were similarly accurate. CONCLUSIONS: Accuracy of FFQ reporting can be improved by restructuring questions based on cognitive theory and testing.

Performance of a food-frequency questionnaire in the US NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health Study.

OBJECTIVE: We evaluated the performance of the food-frequency questionnaire (FFQ) administered to participants in the US NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health Study, a cohort of 566 404 persons living in the USA and aged 50-71 years at baseline in 1995. DESIGN: The 124-item FFQ was evaluated within a measurement error model using two non-consecutive 24-hour dietary recalls (24HRs) as the reference. SETTING: Participants were from six states (California, Florida, Pennsylvania, New Jersey, North Carolina and Louisiana) and two metropolitan areas (Atlanta, Georgia and Detroit, Michigan). SUBJECTS: A subgroup of the cohort consisting of 2053 individuals. RESULTS: For the 26 nutrient constituents examined, estimated correlations with true intake (not energy-adjusted) ranged from 0.22 to 0.67, and attenuation factors ranged from 0.15 to 0.49. When adjusted for reported energy intake, performance improved; estimated correlations with true intake ranged from 0.36 to 0.76, and attenuation factors ranged from 0.24 to 0.68. These results compare favourably with those from other large prospective studies. However, previous biomarker-based studies suggest that, due to correlation of errors in FFQs and self-report reference instruments such as the 24HR, the correlations and attenuation factors observed in most calibration studies, including ours, tend to overestimate FFQ performance. CONCLUSION: The performance of the FFQ in the NIH-AARP Diet and Health Study, in conjunction with the study's large sample size and wide range of dietary intake, is likely to allow detection of moderate (> or =1.8) relative risks between many energy-adjusted nutrients and common cancers.