Randomised controlled trial of brief neonatal exposure to cows' milk on the development of atopy

OBJECTIVE: To determine the effect of brief early exposure to cows' milk on atopy in the first 2 years of life. DESIGN: Double blind, placebo controlled, randomised feeding intervention trial (Bokaal study). SETTING: Dutch midwifery practices. PARTICIPANTS: 1533 breast fed neonates. INTERVENTION: Exposure to cows' milk protein (n = 758) or a protein free placebo (n = 775) during the first 3 days of life. MAIN OUTCOME MEASURES: Clinical atopic disease and any positive radioallergosorbent (RAST) tests at 1 year of age. RESULTS: Atopic disease in the first year was found in 10.0% (cows' milk) v 9.3% (placebo) of the children, with a relative risk of 1.07; in the second year, atopic disease was found in 9.6% v 10.2%, respectively, with a relative risk of 0.94. Per protocol analysis showed similar results. Any RAST positive test was found in 9.4% (cows' milk) v 7.9% (placebo) of children, with a relative risk of 1.19. Stratified analysis for high family risk of allergy showed a doubled incidence of atopic disease but no effect from the intervention. CONCLUSION: Early and brief exposure to cows' milk in breast fed children does not increase the risk of atopic disease in the first 2 years.     

Early-life physical activity and postmenopausal breast cancer: effect of body size and weight change.

It is not yet known whether early-life physical activity reduces the risk of developing breast cancer. Subgroup analyses according to menopausal status and body mass may help clarify this association. Data from a population-based case-control study of female residents of Wisconsin, Massachusetts, Maine, and New Hampshire were used to examine associations between body mass and breast cancer risk. Cases (n = 4614) were identified by each state's tumor registry; controls (n = 5817) were randomly selected from population lists. Frequency of participation in strenuous physical activity when 14-22 years of age, weight at age 18 and 5 years before interview, height, and other factors were ascertained through structured telephone interviews. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression. Reductions in postmenopausal breast cancer risk associated with strenuous physical activity were greatest for women in the fourth quartile of body mass index at age 18; the OR for women with the highest activity frequency on average (> or =once/day) was 0.45 (95% CI = 0.26-0.79). Associations with frequency of activity also varied by weight change. Compared to women with no activity and little adult weight gain, frequent physical activity was associated with reduced postmenopausal breast cancer risk in women who had lost weight since age 18 (OR = 0.19, 95% CI = 0.05-0.70) or had gained little or modest amounts of weight (weight gain: first tertile, OR = 0.36, 95% CI = 0.05-0.85; second tertile, OR = 0.31, 95% CI = 0.14-0.66). Weighted MET score analyses yielded similar but less inverse results. These findings suggest that the reduced risk of postmenopausal breast cancer associated with frequent, early-life physical activity may be greatest in women who, over the adult years, either lost weight or gained only modest amounts.     

Definition and adjustment of Cesarean section rates and assessments of hospital performance.

BACKGROUND: Demand is growing for comparative data such as Cesarean section rates, but little effort has been made to develop either standardized definitions or risk adjustment approaches. OBJECTIVE: To determine to what extent a seemingly straightforward indicator like Cesarean section rate will vary when calculated according to differing definitions used by various performance measurement systems. DESIGN: Retrospective data abstraction of 200 deliveries per hospital. SETTING: Fifteen acute care hospitals including two from outside the USA. MEASUREMENTS: Four widely-used performance measurement systems provided specifications for their Cesarean section indicators. Indicator specifications varied on inclusion criteria (whether the population was defined using Diagnostic Related Groups or ICD-9-CM procedure codes or ICD-9-CM diagnosis codes) and risk-adjustment methods and factors. Rates and rankings were compared across hospitals using different Cesarean section indicator definitions and indicators with and without risk adjustment. RESULTS: Calculated Cesarean section rates changed substantially depending on how the numerator and denominator cases were identified. Relative performance based on Cesarean section rankings is affected less by differing indicator definitions than by whether and how risk adjustment is performed. CONCLUSIONS: Judgments about organizational performance should only be made when the comparisons are based upon identical indicators. Research leading to a uniform indicator definition and standard risk adjustment methodology is needed.     

Early life factors in relation to breast cancer risk in postmenopausal women.

We evaluated the role of early life factors in a large, population-based, case-control study of breast cancer risk in postmenopausal women. Case women in Massachusetts, New Hampshire, and Wisconsin were ascertained through state cancer registries; control women were randomly selected from drivers license lists (50-65 years of age) or Medicare beneficiary lists (65-79 years of age). Information concerning factors of interest was obtained through structured telephone interviews. Overall, 83% of eligible cases and 78% of eligible controls participated, and data from more than 2900 women were available for this analysis. We observed a weak J-shaped relationship between birth weight and breast cancer risk; the increased risk was not statistically significant for either the lowest or the highest birth weight. Parental smoking during the pregnancy was not associated with risk of breast cancer in the adult daughter. Breast cancer risk increased significantly with father's education (P = 0.01). Risk also increased with greater age of the mother at the time of the subject's birth (P = 0.04). The subject's birth rank was inversely associated with risk (P = 0.03), as was the number of older sisters (P = 0.03), but the number of older brothers, number of younger siblings, sibship gender ratio, and total sibship size were unrelated to risk. Overall, our results are consistent with previous studies and suggest that these early life factors have a modest influence on breast cancer risk in postmenopausal women.     

CORTICOSTEROIDS IN ESSENTIAL HYPERTENSION: MULTIPLE CANDIDATE LOCI AND PHENOTYPIC VARIATION

1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function. 2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics. 3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11β-hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine. 4. The genes encoding 11β-hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5’ regulatory regions from 11β-hydroxylase and 3’ coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition. 5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11-deoxycortisol/cortisol, consistent with reduced activity of 11β-hydroxylase in the zona fasciculata. 6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, remain to be studied.     

General deviance and psychological distress: impact of family support/bonding over 12 years from adolescence to adulthood

Comorbidity occurs within and across various domains of human pathology and may be diverse manifestations of a single, general dysfunction in early family support and bonding. Family socialisation, pseudomaturity, and self-derogation theories were tested using cross-sectional and 12-year prospective data from a community sample assessed in late adolescence (age 18) and again in adulthood (age 30). All of the hypotheses and expected findings received some support in the data analyses. these have confirmed that: (1) general deviance and psychological distress were significantly correlated for both men and women and therefore are overlapping and comorbid disorders; (2) both general distress and psychological distress were significantly predicted by family support/bonding in cross-sectional analyses for men and women; (3) family support/bonding fully accounted for the cross-sectional association between general deviance and psychological distress for men and substantially reduced the association between these constructs for the women; (4) over time family support/bonding reduced psychological distress for the women and general deviance for the men; (5) both theories of pseudomaturity and self-derogation explained many of the prospective effects from late adolescence into adulthood; (6) sexual involvement, although an indicator of general deviance, related negatively with indicators of psychological distress; (7) different patterns were evident for the developmental periods of adolescence compared with adulthood; and (8) many of the processes differed by sex. Copyright © 1997 Whurr Publishers Ltd.