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PubMed2001

Risk of breast cancer in female flight attendants: a population-based study (Iceland).

OBJECTIVES: To study whether increased cancer risk, particularly of cancer types previously related to radiation, was found among cabin attendants, using employment time as a surrogate of exposure to cosmic radiation. METHODS: A cohort of 1690 cabin attendants, 158 men and 1532 women from the Icelandic Cabin Crew Association and two airline companies in Iceland, was established. Cancer sites were ascertained between 1955 and 1997 by follow-up in a cancer registry. The personal identification number of each subject was used in record linkage to population-based registers containing vital and emigration status, reproductive factors and histologically verified cancer diagnosis. Standardized incidence rates (SIR) of different cancer sites in relation to employment time and year of hiring were calculated, as well as predictive values of breast cancer risk for evaluating possible confounding due to reproductive factors. RESULTS: The total number of person-years was 27,148. Among the women, 64 cancers were observed whereas 51.63 were expected (SIR 1.2, 95% CI 1.0-1.6), and significantly increased risk for malignant melanoma (SIR 3.0, 95% CI 1.2-6.2) was found. Significantly increased risks of overall cancers (SIR 1.3, 95% CI 1.0-1.8) and breast cancer (SIR 1.6, 95% CI 1.0-2.4) were observed among the female cabin attendants when 15 years lag time was applied. Those hired in 1971 or later had the heaviest exposure to cosmic radiation at a young age and had significantly increased risk of overall cancer (SIR 2.8, 95% CI 1.4-4.9) and breast cancer (SIR 4.1, 95% CI 1.7-8.5). Predictive values calculated on the basis of reproductive factors among the cabin attendants and the population, and risk of breast cancer were 1.0 for parous vs. nulliparous, 1.0 for number of children, and 1.1 for age at birth of first child. CONCLUSION: The increased risk of breast cancer and malignant melanoma among cabin attendants seems to be occupationally related. The part played by occupational exposures, i.e. cosmic radiation, disturbance of the circadian rhythm, and electromagnetic fields or combination of these factors in the etiology of breast cancer among the cabin crew, is still a puzzle as confounding due to parity appears to be ruled out. The relationship between the sunbathing habits of the cabin crew and the increased risk of malignant melanoma needs to be clarified. There is also an urgent need to elucidate the importance of these findings for today's aviation.

Adult↗
PubMed2004

Assessing genetic association with human survival at multi-allelic loci.

Genetic variation plays an important role in natural selection and population evolution. However, it also presents geneticists interested in aging research with problems in data analysis because of the large number of alleles and their various modes of action. Recently, a new statistical method based on survival analysis (the relative risk model or the RR model) has been introduced to assess gene-longevity associations [Yashin et al. (1999) Am J Hum Genet 65: 1178-1193] which outperforms the traditional gene frequency method. Here we extend the model to deal with polymorphic genes or gene markers. Assuming the Hardy-Weinberg equilibrium at birth, we first introduce an allele-based parameterization on gene frequency which helps to cut down the number of frequency parameters to be estimated. We then propose both the genotype and allele-based parameterizations on risk parameters to estimate genotype and allelic relative risks (the GRR and ARR models). While the GRR model allows us to investigate whether the alleles are recessive, dominant or codominant, the ARR model further minimizes the number of parameters to be estimated. As an example, we apply the methods to empirical data on Renin gene polymorphism and longevity. We show that our models can serve as useful tools in searching for important genetic variations implicated in human aging and longevity.

Aging↗
PubMed2004

Twinning and the incidence of breast and gynecological cancers (United States).

Increasing epidemiological and experimental evidence indicates that the carcinogenic pathway in the breast and female reproductive organs is driven, at least in part, by factors associated with reproduction. We conducted a retrospective cohort study, comparing the risk of ovarian, breast, endometrial, and cervical cancers among women who had records of at least one twin pregnancy, compared with women who had given birth to only single children. Subjects were selected from the Utah Population Database, which consists of multiple linked datasets including genealogy, births and deaths and cancer registries. We used Poisson regression to calculate relative risks, adjusted for the number of pregnancies and the age of the mother at the birth of first and last children, with singleton mothers as the reference group in each case. The risks of breast and ovarian cancers did not differ between mothers of twins and mothers of single children. The risk of endometrial cancer was slightly lower in mothers of twins than in mothers of singleton children (RR = 0.90, 95% CI 0.67-1.21). Conversely the risk of cervical cancer was higher among twin mothers (RR = 1.78, 95% CI 0.88-3.52). This latter finding supports previous data suggesting that reproductive hormones act as cofactors in the etiology of cervical cancer.

Adolescent↗
PubMed1981

Postnatal development of absolute auditory thresholds in kittens.

Postnatal development of absolute auditory thresholds in the kitten was behaviorally measured from birth up to 1 mo of age. Unconditioned reactions to pure tones were observed for kittens up to Day 12, and conditioned responses were used for animals from Day 10 onward. At 1 day after birth, the first noticeable responses were obtained in 4 of 11 kittens at frequencies of .5-2 kHZ. At 2 days of age, 12 of 16 kittens responded. Thresholds remained high (above 100 dB SPL) up to the sixth day, but the range of behaviorally effective frequencies extended from .2 to 6 kHZ. All conditioned response thresholds at Day 10 and most at Day 12 were significantly lower than those measured by unconditioned reactions. From 10 days onward, all threshold curves showed a characteristic sensitivity optimum at 4 kHZ. For frequencies below 1 kHZ, maximum sensitivity was reached at Day 15; for frequencies up to 20 kHZ, at Day 20; and for even higher frequencies, at Day 30. At 1 mo of age, the frequency range is adultlike. The present behavioral results on developing acoustic function in the kitten closely followed structural maturation of the acoustic pathway and demonstrated limitations of the ability for acoustical communication during the first week of life.

Aging↗
PubMed1989

Oral contraceptives and breast cancer: results from an expanded case-control study.

The relationship between oral contraceptives and breast cancer was evaluated among 2,022 cases and 2,183 controls participating in a multicentre breast cancer screening programme. Ever use of oral contraceptives was not related to breast cancer risk (RR = 1.0, 95% CI 0.9-1.2), and no overall patterns of increasing or decreasing risks were observed according to the duration of use, or time since first or most recent use. Although we had no women with extended periods of oral contraceptive use early in life, no evidence of adverse effects attributable to short-term use before age 25, before first live birth or during the perimenopausal period were observed. Further, oral contraceptives did not interact with other breast cancer risk factors, except among those with a history of two or more breast biopsies (RR = 2.0). Analyses by stage of disease revealed that risk was related to the duration of oral contraceptive use: greater than or equal to 5 years use was associated with reduced risk for in situ cancer (RR = 0.59) and increased risks for invasive cancers (RR = 1.5 and 1.4 respectively for small and large lesions). These data suggest that oral contraceptive effects may vary by stage of disease, but provide no overall evidence of an association between oral contraceptives and breast cancer.

Adult↗
PubMed1990

Breast cancer and combined oral contraceptives: results from a multinational study. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

A collaborative, hospital-based case-control study was conducted at 12 participating centres in 10 countries. Based on data from personal interviews of 2,116 women with newly diagnosed breast cancer and 12,077 controls, the relative risk of breast cancer in women who ever used oral contraceptives was estimated to be 1.15 (1.02, 1.29). Estimated values of this relative risk based on data from three developed and seven developing countries were 1.07 (0.91, 1.26) and 1.24 (1.05, 1.47) respectively; these estimates are not significantly different (P = 0.22). Estimates for women under and over age 35 were 1.26 (0.95, 1.66) and 1.12 (0.98, 1.27), respectively, and these estimates are also not significantly different (P = 0.38). Risk was highest in recent and current users and declined with time since last use regardless of use. Risk did not increase with duration of use after stratifying on time since last use. Risk did not increase significantly with increasing duration of use before age 25 or before a first live birth. However, a relative risk of 1.5 that was of borderline statistical significance was observed in women who used oral contraceptives for more than 2 years before age 25. No single source of bias or confounding was identified that could explain the small increases in risk that were observed. Chance alone is also an unlikely explanation. The results could be due to a combination of chance and potential sources of bias, or they could represent a weak causal relationship.

Adult↗
PubMed1995

Reproductive and menstrual factors in relation to mammographic parenchymal patterns among perimenopausal women.

The relationship between mammographic patterns and reproductive and menstrual factors was examined in 3640 Norwegian women, aged 40-56 years, participating in the Third Tromsö study conducted in 1986-87. Epidemiological data were obtained from questionnaires. The mammograms were categorised into five groups. This categorisation is based on anatomic-mammographic correlations, following three-dimensional (thick slice technique) histopathologic-mammographic comparisons, rather than simple pattern reading. Patterns 1-3 were combined into a low-risk group and patterns 4 and 5 into a high-risk group for analysis. Women who had more than four children were 90% less likely to have a high-risk pattern than nulliparous women (OR = 0.09, 95% CI 0.04-0.16) controlling for age, weight, height and menopausal status. Furthermore, those who first gave birth over 34 years of age were more than twice as likely to have a high-risk pattern than those giving birth in their teens (OR = 2.37, 95% CI 1.23-4.56) adjusting for parity. Among post-menopausal women, age at menarche was negatively (P for trend = 0.015) and late age at menopause positively (P for trend = 0.072) related to high-risk patterns. Among premenopausal women, age at menarche was positively related to high-risk patterns (P for trend = 0.001). Also, menopausal status rather than age was associated with high-risk patterns. These findings support the opinion that reproductive and menstrual factors are involved in determining the mammographic parenchymal pattern among perimenopausal women.

Adult↗
PubMed2000

Maternal report of attention deficit hyperactivity disorder symptoms in preschool children.

Two hundred and fifty-three mothers were surveyed regarding attention deficit hyperactivity disorder (ADHD) symptoms in their preschool children (aged 2-6 years). Twenty-four children (9.5%) met DSM-IV criteria (criterion A only) for ADHD based solely on parent report. Mean ratings of the three core symptoms of ADHD (hyperactivity, impulsivity, and inattentiveness) were in the mid-range on a 1-7 point scale, with mothers indicating their children were most likely to be impulsive. Positive parental endorsement of the 18 individual DSM-IV symptoms of ADHD ranged from 4% for 'loses things necessary for tasks', to 28.4% for 'is on the go or acts as if driven by a motor'. Males and children of less-educated parents were more likely to receive endorsement of ADHD symptoms. There were no differences with respect to age of the child or birth order (first vs later born). Global ratings of hyperactivity and inattentiveness predicted overall ratings of ADHD but when classification rates were examined, high global ratings were not predictive of diagnosis. These results lend support to the notion that relying solely on parents' verbal reports of isolated ADHD symptoms may lead to over-identification of the disorder. Thus, using full DSM-IV diagnostic criteria and including standardized behaviour rating scales across multiple informants and settings, is recommended.

Age Distribution↗
PubMed2002

Differential expression of phospholipase D1 in the developing retina.

Expression patterns of phospholipase D1 (PLD1) in the developing rat retina were investigated using immunocytochemistry and Western blot analysis and compared with the expression patterns of glutamine synthetase. PLD1 immunoreactivity appeared first in a few neuroblasts in the middle of the mantle zone of the primitive retina by embryonic (E) day 13. PLD1-immunoreactive primitive ganglion cells were characterized in the ganglion cell layer by E17. Faint immunoreactivity at E17 profiled radially orientated cells and this pattern appeared up to postnatal (P) day 7. In the ganglion cell layer at P3, displaced amacrine cells and ganglion cells were classified. At P5, presumptive horizontal cells and amacrine cells were identified. By P7, a thin outermost layer of newly formed segments of the photoreceptor cells was also PLD1 immunoreactive. PLD1 immunoreactivity at P8 was limited to radial Müller cells and the outer segment layer of the photoreceptor cells, and the expression pattern was conserved to adulthood. Western blot analysis showed relatively high amounts of PLD1 protein at E17 and P3, a decrease at P7, and moderate amounts from P8 onward. Co-expression of PLD1 with glutamine synthetase in the retina appeared first after birth in differentiating neurons and in Müller cells by P8; thereafter the pattern was maintained. The expression pattern of the PLD1 during development of the retina suggests that PLD1 plays important roles in glutamate-associated differentiation of both specific neurons and radial glial cells, and in glutamate-mediated cellular signalling in Müller cells.

Aging↗
PubMed1998

Facilitated diagnosis of the contiguous gene syndrome: tuberous sclerosis and polycystic kidneys by means of haplotype studies.

Tuberous sclerosis (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are genetically heterogeneous diseases. The major gene for ADPKD (PKD1) lies adjacent to the TSC2 gene on chromosome 16p13. Some reports in the literature referred to an unusual presentation of TSC with enlarged cystic kidneys at birth, but it was not until the localization of the TSC2 and PKD1 genes that it was possible to analyze the interaction between both genes. We describe a case of a child with TSC and enlarged cystic kidneys. The study of genetic marker segregation in the family pointed to the presence of a deletion involving the 3' region of PKD1. A further study of the region showed a deletion of 40 kb involving both PKD1 and TSC2. We suggest that an additive or synergistic effect between PKD1 and TSC2 may cause this renal phenotype. A contiguous gene syndrome involving PKD1 and TSC2 should be suspected in children with TSC and enlarged polycystic kidneys at birth. The first approach to identify a deletion of both genes could be the analysis of the segregation of PKD1 and TSC2 markers in the family.

Chromosomes, Human, Pair 16↗
PubMed1986

[Risk factors for breast cancer and their use in early detection. Results of a case control study].

Doubtful and established breast cancer risk factors were checked in a case/control study. Multivariate analysis with the logistical regression approach resulted in a usable separation of the cases from the controls on the basis of the five dichotimized variables: age at birth of first child, family history, Quetelet index, breast complaints, and a behavior score. On the basis of probability, the risk patterns were summarized in six risk categories, and a maximum 70-fold risk was thus established. The proportion of incidence represented by the risk groups was then estimated from distribution in the control group. Approx. 5% of new cases originate in 30% of the female population aged under 30, but approx. 51% originate in a mere 10%. Hence it is logical to use risk factors for early detection based on risk.

Adult↗
PubMed2002

The atopic dog as a model of peanut and tree nut food allergy.

BACKGROUND: Animal models are needed that mimic human IgE-mediated peanut and tree nut allergy. Atopic dogs have been previously used in a model of food allergy to cow's milk, beef, wheat, and soy, with the demonstration of specific IgE production and positive oral challenges similar to those seen in human subjects. OBJECTIVE: We sought to sensitize dogs to peanut, walnut, and Brazil nut and to assess whether sensitization is accompanied by clinical reactions and whether there is cross-reactivity among the different preparations. METHODS: Eleven dogs were sensitized subcutaneously by using an established protocol with 1 microg each of peanut, English walnut, or Brazil nut protein extracts in alum first at birth and then after modified live virus vaccinations at 3, 7, and 11 weeks of age. The dogs were sensitized to other allergens, including soy and either wheat or barley. Intradermal skin tests, IgE immunoblotting to nut proteins, and oral challenges were performed with ground nut preparations. RESULTS: At 6 months of age, the dogs' intradermal skin test responses were positive to the nut extracts. IgE immunoblotting to peanut, walnut, and Brazil nut showed strong recognition of proteins in the aqueous preparations. Each of the 4 peanut- and the 3 Brazil nut-sensitized dogs and 3 of the 4 walnut-sensitized dogs reacted on oral challenge with the corresponding primary immunogen at age 2 years. None of the peanut-sensitized dogs reacted clinically with walnut or Brazil nut challenges. One of the walnut-sensitized dogs had delayed (overnight) vomiting to Brazil nut. CONCLUSIONS: On the basis of measurements of the mean amount of allergen eliciting a skin test response in dogs, the hierarchy of reactivity by skin testing is similar to the clinical experience in human subjects (peanut > tree nuts > wheat > soy > barley). Cross-reactivity, which was not apparent between soy and peanut or tree nuts or between peanut and tree nuts, was slight between walnut and Brazil nut. The results give further support to the dog as a model of human food allergy.

Animals↗
PubMed2001

Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study.

OBJECTIVE: We sought to determine risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum. STUDY DESIGN: We performed a population-based case-control study. All Olmsted County, Minnesota, residents with a first lifetime deep vein thrombosis or pulmonary embolism during pregnancy or post partum from 1966 to 1990 were identified (N = 90). Where possible, a resident without deep vein thrombosis or pulmonary embolism was matched to each patient by date of the first live birth after the patient's child. The medical records of all remaining patients and all control subjects were reviewed for >25 baseline characteristics, which were tested as risk factors for deep vein thrombosis or pulmonary embolism. RESULTS: In multivariate analysis smoking (odds ratio, 2.4) and prior superficial vein thrombosis (odds ratio, 9.4) were independent risk factors for deep vein thrombosis or pulmonary thrombosis during pregnancy or post partum. CONCLUSION: Venous thromboembolism prophylaxis may be warranted for pregnant women with prior superficial vein thrombosis. Smoking cessation should be recommended, especially during pregnancy and the postpartum period.

Bed Rest↗
PubMed2002

The relationship among demographics, reproductive characteristics, and intimate partner violence.

OBJECTIVE: Our purpose was to examine the associations between demographics and reproductive characteristics on the occurrence of intimate partner violence (IPV) in young women. STUDY DESIGN: An anonymous questionnaire was completed by 727 women between 14 and 26 years old who were seen in the family planning clinics in southeast Texas between March 1997 and February 1998 and who reported a current spouse or partner. Subjects completed a standardized measure of violence perpetrated by a partner and provided information on demographics and reproductive characteristics. Separate logistic regression analyses were used to analyze factors associated with physical and verbal violence. RESULTS: Significant and positive associations with physical violence were found for race, employment, and parity (> or =1); risk of verbal abuse included employment, history of sexual abuse, and inconsistent condom and prescription contraceptive use. Protective factors for physical violence included education level, use of hormonal methods of contraception or condoms at last intercourse, and older age at first intercourse and at first childbirth; protection from verbal assault included dual contraceptive use, as well as barrier and hormonal contraception at last intercourse. CONCLUSION: Different patterns of risk emerge between physical and verbal assault among young women seen in a publicly funded family planning clinic. Minority parous women with limited education, early onset of sexual activity, and who report no contraception use at last intercourse appear to be at highest risk for reporting physical violence, whereas history of sexual victimization, early sexual activity, and younger age at first child birth elevates risk for verbal abuse.

Adolescent↗
PubMed1993

The effect of undernutrition in the early postnatal period on skeletal muscle tissue.

Guinea-pigs were undernourished from birth by first, cross-fostering in groups of six (in pairs for control animals) and then by feeding a diet of 60% of ad lib. intake from 2 to 6 weeks. The changing characteristics of muscle fibre types in the biceps brachii and soleus muscles were monitored by histochemistry. Undernutrition appeared to delay maturation of muscle fibres. Fibre cross-sectioned area was reduced in all fibres of the 60% of ad lib. intake group. Fibres of the biceps brachii were more affected than those of the soleus. Fibre area vulnerability was partly associated with a high relative growth rate in biceps brachii at this time. Total protein content in the semitendinosus muscle was depressed in the undernourished group compared with the control group. DNA concentrations were initially higher in the control group but decreased in both groups to similar levels by 6 weeks. RNA concentration increased up to 5 weeks in the control group and then decreased, but decreased after 2 weeks in the undernourished group.

Animals↗
PubMedDate not supplied

Acute effects of total suspended particles and sulfur dioxides on preterm delivery: a community-based cohort study.

The acute effects of air pollution on preterm delivery were examined in a prospective cohort in Beijing, China. From early pregnancy until delivery in 1988, we followed all registered pregnant women who lived in four residential areas of Beijing. Information for both mothers and infants was collected. Daily air pollution and meteorological data were obtained independently. The sample for analysis included 25,370 resident women who gave first live births in 1988. Multiple linear regression and logistic regression were used to estimate the effects of air pollution on gestational age and preterm delivery (i.e., < 37 wk), with adjustment for outdoor temperature and humidity, day of the week, season, maternal age, gender of child, and residential area. Very high concentrations of ambient sulfur dioxide (mean = 102 micrograms/m3, maximum = 630 micrograms/m3) and total suspended particulates (mean = 375 micrograms/m3, maximum = 1 0003 micrograms/m3) were observed in these areas. There was a significant dose-dependent association between gestational age and sulfur dioxide and total suspended particulate concentrations. The estimated reduced duration of gestation was .075 wk (12.6h) and .042 wk (7.1 h) for each 100-micrograms/m3 increase in sulfur dioxide and total suspended particulates 7-d lagged moving average, respectively. The adjusted odds ratio for preterm delivery was 1.21 (95% CI = 1.01-1.46) for each in micrograms/m3 increase in sulfur dioxide, and was 1.10 (95% CI = 1.01-1.20) for each 100-micrograms/m3 increase in total suspended particulates. In addition, the gestational age distribution of high-pollution days was more skewed toward the left tail (i.e., very preterm and preterm), compared with low-pollution days. We concluded that high levels of total suspended particulates and sulfur dioxide, or of a more complex pollution mixture associated with these pollutants, appear to contribute to excess risk of preterm delivery in this population. Further work need to be carried out, with more detailed information on personal exposure and effect modifiers.

Adult↗
PubMed1998

Fertility in The Netherlands as an expected value process and developmental readiness.

In this 2-wave panel study, the decision to have children was examined in the context of Feather's (1982) expectancy-value model among a representative sample of 288 childless Dutch adults aged 18-30 years. The effects of 2 indicators of developmental readiness (age and duration of relationship) were also explored. It was expected that (a) the likelihood of having a baby would increase as a function of intentions, evaluations of being childless, and expected rewards of having children and (b) developmental readiness would be positively related to whether respondents had children at the 2nd wave of the study. Structural equation modeling was used. The results largely supported expectations. Developmental readiness affected fertility both directly and indirectly via the expected rewards of having children.

Adolescent↗

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