Utility of frozen section in pediatric and adolescent malignant ovarian nonseminomatous germ cell tumors: A report from the children's oncology group.

PURPOSE: In adult women, most malignant ovarian tumors are epithelial in origin. The use of intra-operative frozen section to distinguish between benign and malignant histology is reliable in guiding operative decision-making to determine the extent of surgical staging required. Pediatric and adolescent patients with ovarian masses have a much different spectrum of pathology with most tumors arising from germ cell precursors. This review was undertaken to assess the concordance between the intra-operative frozen section and the final diagnosis as an aid to guide extent of surgical staging in a group of pediatric and adolescent patients with malignant ovarian germ cell tumors. METHODS: Records of patients aged 0 to 20 years with malignant ovarian germ cell tumors enrolled on Children's Oncology Group study AGCT0132 were reviewed. Pathology reports from patients who had both intra-operative frozen section diagnosis and final paraffin section diagnosis were compared using descriptive statistics. By inclusion criteria for the study, all patients had a final diagnosis of malignancy with required yolk sac tumor, choriocarcinoma or embryonal carcinoma histology. Available central review of pathology final paraffin section slides were compared with final institution pathology reports. RESULTS: Of 131 eligible patients with ovarian germ cell tumors, 60 (45.8%) had both intra-operative frozen section and final paraffin section diagnoses available. Intra-operative frozen section diagnoses were classified as: incorrect diagnosis of benign tumor (13.3%), confirmation of malignancy (61.7%), immature teratoma (16.7%), germ cell tumor not otherwise specified (5%) and no diagnosis provided (3.3%). Intra-operative frozen section was incorrect in 23 of 60 (38.3%) patients evaluated. Central pathology review was concordant with the final institution pathology diagnosis in 76.3% of patients. Central pathology review identified additional germ cell tumor components in 23.7% of patients. CONCLUSIONS: In pediatric and adolescent patients with a confirmed final diagnosis of ovarian germ cell malignancy, intra-operative frozen section diagnosis is not reliable to inform the extent of surgical staging required. Central review by an expert germ cell tumor pathologist provides important additional information to guide therapy.

Development of paediatric non-stage prognosticator guidelines for population-based cancer registries and updates to the 2014 Toronto Paediatric Cancer Stage Guidelines.

Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs.

Identification of testicular cancer driver genes by a cross-species comparative oncology approach.

BACKGROUND: Germ cell tumors arise in the testis, ovary, or extragonadal locations and have a wide range of histopathological and clinical presentations. The relative lack of animal models of germ cell tumors has impeded functional assessment of candidate driver genes. Previously, we described the development of testicular germ cell tumors in zebrafish carrying a mutation in bmpr1bb, a BMP family receptor, and demonstrated that human germ cell tumors have defects in BMP signaling. OBJECTIVE: To further credential the zebrafish model for studies of human germ cell tumor, and to elucidate conserved genetic programs underlying the development of germ cell tumor. MATERIALS AND METHODS: We used genetic techniques to ablate the germ cell lineage in developing fish and tested tumors for loss-of-heterozygosity of the wild-type allele of bmpr1bb. We performed comparative gene expression profiling of zebrafish and human germ cell tumors and carried out functional studies of selected genes. RESULTS: Ablation of germ cells completely prevents testis tumor formation in the fish, definitively establishing the germ cell origin of the tumors. Germ cell tumors in bmpr1bb heterozygous mutants retain the wild-type allele, indicating haploinsufficiency of bmpr1bb as the mechanism of tumor formation. Comparison of RNA-Seq and microarray data from human and zebrafish germ cell tumors revealed a unique overlapping signature shared by the zebrafish tumors with human seminomas, yolk sac tumors, and embryonal carcinomas. The most highly conserved gene set in this cross-species analysis included potential driver genes such as JUP, which we show to be essential for germ cell tumor cell growth. CONCLUSION: Our findings highlight the value of cross-species comparative oncology for the identification of candidate human cancer genes.

Risk of second malignant neoplasms in women and girls with germ cell tumors.

Background: While an elevated risk of second malignant neoplasms (SMNs) has been observed in men treated for germ cell tumors (GCTs), risk of SMNs have not been quantified in adult women or in girls treated for GCTs. Patients and methods: One-year survivors of primary GCTs diagnosed between January 1980 and December 2012 were identified from Surveillance, Epidemiology, and End Results (SEER 9) registries. Risk of SMNs was calculated using SEER*Stat. Results: Among 1507 patients, a total of 47 SMNs were identified. The overall risk of SMNs was not elevated in females overall or in females treated for GCT during adulthood although SMN sites (pancreas, soft tissue, bladder, kidney, and thyroid) and trends were comparable with those in men. There were too few childhood GCT cases with SMNs for further analysis. Conclusions: Unlike men, women treated for GCTs did not have a statistically significant elevated risk of SMNs [standardized incidence ratio = 1.11; 95% confidence interval (CI) = 0.81-1.47]. The fact that SMNs in women occur in sites similar to those observed in men indicate that long-term follow-up of a larger cohort of females treated for GCT is warranted.

Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls.

STUDY QUESTION: Is sugar-sweetened beverage (SSB) consumption associated with age at menarche? SUMMARY ANSWER: More frequent SSB consumption was associated with earlier menarche in a population of US girls. WHAT IS KNOWN ALREADY: SSB consumption is associated with metabolic changes that could potentially impact menarcheal timing, but direct associations with age at menarche have yet to be investigated. STUDY DESIGN, SIZE, DURATION: The Growing up Today Study, a prospective cohort study of 16 875 children of Nurses' Health Study II participants residing in all 50 US states. This analysis followed 5583 girls, aged 9-14 years and premenarcheal at baseline, between 1996 and 2001. During 10 555 person-years of follow-up, 94% (n = 5227) of girls reported their age at menarche, and 3% (n = 159) remained premenarcheal in 2001; 4% (n = 197) of eligible girls were censored, primarily for missing age at menarche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulative updated SSB consumption (composed of non-carbonated fruit drinks, sugar-sweetened soda and iced tea) was calculated using annual Youth/Adolescent Food Frequency Questionnaires from 1996 to 1998. Age at menarche was self-reported annually. The association between SSB consumption and age at menarche was assessed using Cox proportional hazards regression. MAIN RESULTS AND THE ROLE OF CHANCE: More frequent SSB consumption predicted earlier menarche. At any given age between 9 and 18.5 years, premenarcheal girls who reported consuming >1.5 servings of SSBs per day were, on average, 24% more likely [95% confidence interval (CI): 13, 36%; P-trend: <0.001] to attain menarche in the next month relative to girls consuming ≤2 servings of SSBs weekly, adjusting for potential confounders including height, but not BMI (considered an intermediate). Correspondingly, girls consuming >1.5 SSBs daily had an estimated 2.7-month earlier menarche (95% CI: -4.1, -1.3 months) relative to those consuming ≤2 SSBs weekly. The frequency of non-carbonated fruit drink (P-trend: 0.03) and sugar-sweetened soda (P-trend: 0.001), but not iced tea (P-trend: 0.49), consumption also predicted earlier menarche. The effect of SSB consumption on age at menarche was observed in every tertile of baseline BMI. Diet soda and fruit juice consumption were not associated with age at menarche. LIMITATIONS, REASONS FOR CAUTION: Although we adjusted for a variety of suspected confounders, residual confounding is possible. We did not measure SSB consumption during early childhood, which may be an important window of exposure. WIDER IMPLICATIONS OF THE FINDINGS: More frequent SSB consumption may predict earlier menarche through mechanisms other than increased BMI. Our findings provide further support for public health efforts to reduce SSB consumption. STUDY FUNDING/COMPETING INTERESTS: The Growing up Today Study is supported by grant R03 CA 106238. J.L.C. was supported by the Breast Cancer Research Foundation; Training Grant T32ES007069 in Environmental Epidemiology from the National Institute of Environmental Health Sciences, National Institutes of Health; and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. A.L.F. is supported by the American Cancer Society, Research Scholar Grant in Cancer Control. K.B.M. was supported in part by the National Cancer Institute at the National Institutes of Health (Public Health Service grants R01CA158313 and R03CA170952). There are no conflicts of interest to declare.

Adolescents' perceptions of social status: development and evaluation of a new indicator.

OBJECTIVE: Eliminating health disparities, including those that are a result of socioeconomic status (SES), is one of the overarching goals of Healthy People 2010. This article reports on the development of a new, adolescent-specific measure of subjective social status (SSS) and on initial exploratory analyses of the relationship of SSS to adolescents' physical and psychological health. METHODS: A cross-sectional study of 10 843 adolescents and a subsample of 166 paired adolescent/mother dyads who participated in the Growing Up Today Study was conducted. The newly developed MacArthur Scale of Subjective Social Status (10-point scale) was used to measure SSS. Paternal education was the measure of SES. Indicators of psychological and physical health included depressive symptoms and obesity, respectively. Linear regression analyses determined the association of SSS to depressive symptoms, and logistic regression determined the association of SSS to overweight and obesity, controlling for sociodemographic factors and SES. RESULTS: Mean society ladder ranking, a subjective measure of SES, was 7.2 +/- 1.3. Mean community ladder ranking, a measure of perceived placement in the school community, was 7.6 +/- 1.7. Reliability of the instrument was excellent: the intraclass correlation coefficient was 0.73 for the society ladder and 0.79 for the community ladder. Adolescents had higher society ladder rankings than their mothers (micro(teen) = 7.2 +/- 1.3 vs micro(mom) = 6.8 +/- 1.2; P =.002). Older adolescents' perceptions of familial placement in society were more closely correlated with maternal subjective perceptions of placement than those of younger adolescents (Spearman's rho(teens <15 years) = 0.31 vs Spearman's rho(teens 15 years) = 0.45; P <.001 for both). SSS explained 9.9% of the variance in depressive symptoms and was independently associated with obesity (odds ratio(society) = 0.89, 95% confidence interval = 0.83, 0.95; odds ratio(community) = 0.91, 95% confidence interval = 0.87, 0.97). For both depressive symptoms and obesity, community ladder rankings were more strongly associated with health than were society ladder rankings in models that controlled for both domains of SSS. CONCLUSIONS: This new instrument can reliably measure SSS among adolescents. Social stratification as reflected by SSS is associated with adolescents' health. The findings suggest that as adolescents mature, SSS may undergo a developmental shift. Determining how these changes in SSS relate to health and how SSS functions prospectively with regard to health outcomes requires additional research.

Comparing physical activity questionnaires for youth: seasonal vs annual format.

BACKGROUND: In large cohort studies of older children, self-report is the only practical way to assess physical activity. Assessing usual activity over the entire year is desirable, but children and adolescents may overestimate activities with high seasonal variability. Use of questionnaires in which individuals report each activity by season may improve accuracy. METHODS: A total of 6782 girls and 5110 boys, aged 9-14 years in 1996, completed self-administered activity questionnaires in 1996 and in 1997. In 1996, participants reported the average time spent in each of 17 activities during the previous 12 months; in 1997, we also asked for the average time spent in the previous year, but within each of the four seasons. RESULTS: Girls reported a median of 12.8 hours/week total activity in 1996 and 10.4 hours/week in 1997. For boys, the estimates were 15.5 hours/week and 13.4 hours/week, respectively. Girls and boys within 1-year age strata (e.g., comparison of 10-year olds in 1996 with 10-year olds in 1997) reported an average of 3.7 and 3.1 fewer hours per week, respectively, on the 1997 seasonal format versus the 1996 annual format questionnaire. In longitudinal analyses, the difference between the annual and the seasonal estimates was greater if participants did the activity in fewer seasons in 1997. CONCLUSIONS: In comparison to an annual format questionnaire, a seasonal format questionnaire may improve accuracy of self-report of physical activity by reducing over-reporting of activities in which pre-adolescents and adolescents engage in fewer seasons.

Risk of overweight among adolescents who were breastfed as infants.

CONTEXT: Overweight during adolescence predicts short- and long-term morbidity as well as obesity in adulthood. The prevalence of overweight among adolescents is high and continues to increase. Physiological and behavioral mechanisms and preliminary epidemiologic data suggest that breastfeeding could lower the risk of subsequent obesity in adolescence. OBJECTIVE: To examine the extent to which overweight status among adolescents is associated with the type of infant feeding (breast milk vs infant formula) and duration of breastfeeding. DESIGN, SETTING, AND SUBJECTS: Survey of 8186 girls and 7155 boys, aged 9 to 14 years, who are participants in the Growing Up Today Study, a nationwide cohort study of diet, activity, and growth. In the fall of 1996 we mailed a questionnaire to each of the subjects, and in the spring of 1997, we mailed a supplemental questionnaire to their mothers, who are participants in the Nurses' Health Study II. MAIN OUTCOME MEASURE: Overweight status defined as body mass index exceeding the 95th percentile for age and sex from US national data. RESULTS: In the first 6 months of life, 9553 subjects (62%) were only or mostly fed breast milk, and 4744 (31%) were only or mostly fed infant formula. A total of 7186 subjects (48%) were breastfed for at least 7 months while 4613 (31%) were breastfed for 3 months or less. At ages 9 to 14 years, 404 girls (5%) and 635 boys (9%) were overweight. Among subjects who had been only or mostly fed breast milk, compared with those only or mostly fed formula, the odds ratio (OR) for being overweight was 0.78 (95% confidence interval [CI], 0.66-0.91), after adjustment for age, sex, sexual maturity, energy intake, time watching television, physical activity, mother's body mass index, and other variables reflecting social, economic, and lifestyle factors. Compared with subjects who had been breastfed for 3 months or less, those who had been breastfed for at least 7 months had an adjusted OR for being overweight of 0.80 (95% CI, 0.67-0.96). Timing of introduction of solid foods, infant formula, or cow's milk was not related to risk of being overweight. CONCLUSION: Infants who were fed breast milk more than infant formula, or who were breastfed for longer periods, had a lower risk of being overweight during older childhood and adolescence.

Cost-effectiveness of screening for colorectal cancer in the general population.

CONTEXT: A recent expert panel recommended that persons at average risk of colorectal cancer (CRC) begin screening for CRC at age 50 years using 1 of several strategies. However, many aspects of different CRC screening strategies remain uncertain. OBJECTIVE: To assess the consequences, costs, and cost-effectiveness of CRC screening in average-risk individuals. DESIGN: Cost-effectiveness analysis from a societal perspective using a Markov model. SUBJECTS: Hypothetical subjects representative of the 50-year-old US population at average risk for CRC. SETTING: Simulated clinical practice in the United States. MAIN OUTCOME MEASURES: Discounted lifetime costs, life expectancy, and incremental cost-effectiveness (CE) ratio, compared used 22 different CRC screening strategies, including those recommended by the expert panel. RESULTS: In 1 base-case analysis, compliance was assumed to be 60% with the initial screen and 80% with follow-up or surveillance colonoscopy. The most effective strategy for white men was annual rehydrated fecal occult blood testing (FOBT) plus sigmoidoscopy (followed by colonoscopy if either a low- or high-risk polyp was found) every 5 years from age 50 to 85 years, which resulted in a 60% reduction in cancer incidence and an 80% reduction in CRC mortality compared with no screening, and an incremental CE ratio of $92,900 per year of life gained compared with annual unrehydrated FOBT plus sigmoidoscopy every 5 years. In a base-case analysis in which compliance with screening and follow-up is assumed to be 100%, screening more often than every 10 years was prohibitively expensive; annual rehydrated FOBT plus sigmoidoscopy every 5 years had an incremental CE ratio of $489,900 per life-year gained compared with the same strategy every 10 years. Other strategies recommended by the expert panel were either less effective or cost more per year of life gained than the alternatives. Colonoscopy every 10 years was less effective than the combination of annual FOBT plus sigmoidoscopy every 5 years. However, a single colonoscopy at age 55 years achieves nearly half of the reduction in CRC mortality obtainable with colonoscopy every 10 years. Because of increased life expectancy among white women and increased cancer mortality among blacks, CRC screening was even more cost-effective in these groups than in white men. CONCLUSIONS: Screening for CRC, even in the setting of imperfect compliance, significantly reduces CRC mortality at costs comparable to other cancer screening procedures. However, compliance rates significantly affect the incremental CE ratios. In this model of CRC, 60% compliance with an every 5-year schedule of screening was roughly equivalent to 100% compliance with an every 10-year schedule. Mathematical modeling used to inform clinical guidelines needs to take into account expected compliance rates. JAMA. 2000;284:1954-1961.

Relation of childhood diet and body size to menarche and adolescent growth in girls.

Adolescent growth and development may be affected by factors such as dietary intake and body size from much earlier in childhood. In a longitudinal study of 67 Caucasian girls in Boston, Massachusetts, data were collected prospectively from birth during the 1930s and 1940s. Heights and weights were measured semiannually, and dietary history interviews were conducted with mothers. Stepwise linear regression methods were used to seek factors which best predicted age at menarche, adolescent peak height growth velocity, and the age at which peak growth velocity occurred. Girls who consumed more (energy-adjusted) animal protein and less vegetable protein at ages 3-5 years had earlier menarche, and girls aged 1-2 years with higher dietary fat intakes and girls aged 6-8 years with higher animal protein intakes became adolescents with earlier peak growth. Controlling for body size, girls who consumed more calories and animal protein 2 years before peak growth had higher peak growth velocity. These findings may have implications regarding adult diseases whose risks are associated with adolescent growth and development factors.

Association of adolescent cigar use with other high-risk behaviors.

OBJECTIVES: To describe the association of cigar use with use of cigarettes, smokeless tobacco, and alcohol among adolescents; and to examine the association of self-esteem, physical activity, and use of tobacco promotional items with cigar use. METHODS: A cross-sectional study of 7104 girls and 5499 boys 10 to 15 years of age in 1997. Data were collected from self-report questionnaires. RESULTS: The prevalence of cigar use increased with age among both girls and boys. Among 11-year-olds, only 1% of girls and 3% of boys had used a cigar, whereas among 15-year-olds, 11% of girls and 25% of boys had used a cigar. Cigar users were much more likely than nonusers to have experimented with cigarettes (girls, odds ratio [OR]: 23.6; 95% confidence interval [CI]: 17.2-32.3; boys, OR: 21.3; 95% CI: 17.1-26.6), smokeless tobacco (girls, OR: 7.5; 95% CI: 4. 5-12.4; boys, OR: 13.0; 95% CI: 9.8-17.4), and alcohol (girls, OR: 6. 6; 95% CI: 4.8-9.1; boys, OR: 6.8; 95% CI: 5.3-8.8). There was a strong association between cigar use and binge drinking, especially among boys (girls, OR: 11.6; 95% CI: 7.9-16.9; boys, OR: 34.8; 95% CI: 19.4-62.3). Cigar users reported more hours of weekly physical activity than did nonusers. Additionally, cigar users were more likely to report high social self-esteem and to possess a tobacco promotional item. CONCLUSIONS: Adolescents who use cigars are more likely to use other tobacco products and alcohol, to report high social self-esteem, and to possess tobacco promotional items. Health care professionals and teachers should include cigar use in discussions with adolescents addressing substance use.

Activity, dietary intake, and weight changes in a longitudinal study of preadolescent and adolescent boys and girls.

OBJECTIVE: To examine the role of physical activity, inactivity, and dietary patterns on annual weight changes among preadolescents and adolescents, taking growth and development into account. STUDY DESIGN: We studied a cohort of 6149 girls and 4620 boys from all over the United States who were 9 to 14 years old in 1996. All returned questionnaires in the fall of 1996 and a year later in 1997. Each child provided his or her current height and weight and a detailed assessment of typical past-year dietary intakes, physical activities, and recreational inactivities (TV, videos/VCR, and video/computer games). METHODS: Our hypotheses were that physical activity and dietary fiber intake are negatively correlated with annual changes in adiposity and that recreational inactivity (TV/videos/games), caloric intake, and dietary fat intake are positively correlated with annual changes in adiposity. Separately for boys and girls, we performed regression analysis of 1-year change in body mass index (BMI; kg/m(2)). All hypothesized factors were in the model simultaneously with several adjustment factors. RESULTS: Larger increases in BMI from 1996 to 1997 were among girls who reported higher caloric intakes (.0061 +/-.0026 kg/m(2) per 100 kcal/day; beta +/- standard error), less physical activity (-.0284 +/-.0142 kg/m(2)/hour/day) and more time with TV/videos/games (.0372 +/-.0106 kg/m(2)/hour/day) during the year between the 2 BMI assessments. Larger BMI increases were among boys who reported more time with TV/videos/games (.0384 +/-.0101) during the year. For both boys and girls, a larger rise in caloric intake from 1996 to 1997 predicted larger BMI increases (girls:.0059 +/-.0027 kg/m(2) per increase of 100 kcal/day; boys:.0082 +/-.0030). No significant associations were noted for energy-adjusted dietary fat or fiber. CONCLUSIONS: For both boys and girls, a 1-year increase in BMI was larger in those who reported more time with TV/videos/games during the year between the 2 BMI measurements, and in those who reported that their caloric intakes increased more from 1 year to the next. Larger year-to-year increases in BMI were also seen among girls who reported higher caloric intakes and less physical activity during the year between the 2 BMI measurements. Although the magnitudes of these estimated effects were small, their cumulative effects, year after year during adolescence, would produce substantial gains in body weight. Strategies to prevent excessive caloric intakes, to decrease time with TV/videos/games, and to increase physical activity would be promising as a means to prevent obesity.

Family dinner and diet quality among older children and adolescents.

CONTEXT: The proportion of children eating dinner with their families declines with age and has decreased over time. Few data exist concerning the nutritional effect of eating family dinner. OBJECTIVE: To examine the associations between frequency of eating dinner with family and measures of diet quality. DESIGN: Cross-sectional. SETTING: A national convenience sample. PARTICIPANTS: There were 8677 girls and 7525 boys in the study, aged 9 to 14 years, who were children of the participants in the ongoing Nurses' Health Study II. MAIN OUTCOME MEASURES: We collected data from a self-administered mailed survey, including food and nutrient intakes from a validated semiquantitative food frequency questionnaire. Main outcome measures included servings per day of selected foods and food groups, daily intakes of selected macronutrients and micronutrients, and frequency of multivitamin use. RESULTS: Approximately 17% of participants ate dinner with members of their family never or some days, 40% on most days, and 43% every day. More than half of the 9-year-olds ate family dinner every day, whereas only about one third of 14-year-olds did so. In age- and sex-adjusted logistic regression models, the odds ratios associated with a frequency of family dinner of most days compared with never or some days, or every day compared with most days, were as follows: for eating at least 5 servings per day of fruits and vegetables, 1.45 (95% confidence interval [CI], 1.37-1.53); for eating any fried foods away from home, 0.67 (95% CI, 0.64-0.70); and for drinking any soda, 0.73 (95% CI, 0.66-0.80). Multiple linear regression showed that an increased frequency of family dinner was also associated with substantially higher intake of several nutrients, including fiber, calcium, folate, iron, vitamins B6, B12, C, and E; lower glycemic load; and lower intake of saturated and trans fat as a percentage of energy. We observed little or no effect on intakes of whole dairy products, red meat, or snack foods. Patterns were similar for boys and girls. CONCLUSIONS: Eating family dinner was associated with healthful dietary intake patterns, including more fruits and vegetables, less fried food and soda, less saturated and trans fat, lower glycemic load, more fiber and micronutrients from food, and no material differences in red meat or snack foods.

Weight concerns, weight control behaviors, and smoking initiation.

OBJECTIVE: To examine the cross-sectional relationships between weight concerns, weight control behaviors, and initiation of tobacco use among youths. STUDY DESIGN: Smoking status, weight concerns, and weight control behaviors were assessed in a cross-sectional sample of 16 862 children, 9 to 14 years of age, in 1996. Logistic regression was used to examine the relationship between weight concerns, weight control behaviors, and early stages of smoking initiation (precontemplation, contemplation, and experimentation). All analyses were adjusted for age, body mass index, and known predictors of initiation. RESULTS: Approximately 9% of participants had experimented with cigarettes, and 6% were contemplating cigarette smoking. Contemplation of tobacco use was associated with misperception of being overweight (boys: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.10-2.48), unhappiness with appearance (girls: OR, 2.05; 95% CI, 1.48-2.84; boys: OR, 1.60; 95% CI, 1.05-2. 42), and a tendency to change eating patterns around peers (girls: OR, 2.87; 95% CI, 2.28-3.62; boys: OR, 1.83; 95% CI, 1.25-2.66). Experimentation with cigarettes was associated with daily exercise to control weight among boys (OR, 1.92; 95% CI, 1.07-3.43) and with monthly purging (OR, 2.54; 95% CI, 1.27-5.07) and daily dieting among girls (OR, 1.79; 95% CI, 1.09-2.96). CONCLUSIONS: Our findings suggest that, among both girls and boys, contemplation of smoking is positively related to weight concerns. Experimentation seems to be positively related to weight control behaviors. It is important for both pediatricians and comprehensive school health programs to address healthy methods of weight maintenance and to dispel the notion of tobacco use as a method of weight control.

Reproducibility and validity of maternal recall of pregnancy-related events.

We assessed the reproducibility and validity of a questionnaire that asks mothers to recall pregnancy-related events from thirty or more years ago. Among 146 women who completed the questionnaire twice, responses were highly reproducible for pre-pregnancy height and weight (r = 0.95), pregnancy complications (r = 0.74), substance use (r = 0.80), preterm delivery (r = 0.82), birthweight (r = 0.94), and breastfeeding (r = 0.89). Among 154 women whose questionnaire responses were compared to data collected during their pregnancies, recall was highly accurate for height (r = 0.90), pre-pregnancy weight (r = 0.86), birthweight (r = 0.91), and smoking (sensitivity = 0.86, specificity = 0.94). These findings suggest that long-term maternal recall is both reproducible and accurate for many factors related to pregnancy and delivery.

Adolescence and breast carcinoma risk.

BACKGROUND: Breast carcinoma risk may be modified by early life factors, including physical growth and development, diet, and life-style factors of preadolescence and adolescence, as well as genetic factors. METHODS: The authors tested their hypothesis that adolescent growth and development are related to breast carcinoma incidence by evaluating 65,140 women who participated in the Nurses' Health Study. During 16 years of follow-up, 806 women were diagnosed with breast carcinoma prior to menopause, and another 1485 were diagnosed after menopause. Because adolescent growth was not directly observed in this cohort, the peak height growth velocity for each participant was estimated by using a model from another longitudinal study. Finally, Cox proportional hazards regression models were used to study associations between breast carcinoma incidence and adolescent factors in the Nurses' Health Study. RESULTS: Later menarche (relative risk [RR] = 0.52 for > or =15 vs. < or =11 years) and more body fatness at age 10 years (RR = 0.60 for fattest vs. leanest) were associated with a decreased risk of premenopausal breast carcinoma. The risk of postmenopausal breast carcinoma was lower for girls with later menarche (RR = 0.80), more body fat at age 10 years (RR = 0.72), and shorter adult height (RR = 1.29 for > or =67 vs. < or =62 inches). Higher peak height growth velocity, derived from these 3 variables, was associated with increased risk of both premenopausal (RR = 1.31 for highest vs. lowest quintile) and postmenopausal (RR = 1.40) breast carcinoma. These analyses controlled for birth cohort, other possible risk factors from the adolescent period, and family history. These associations persisted after controlling for age at the birth of a first child, parity, adult adiposity, and age at menopause. Post-hoc analyses suggested that, although childhood body fatness was associated with lower risk, increasing body fatness between ages 10 and 20 years was not protective against either premenopausal or postmenopausal breast carcinoma. CONCLUSIONS: Earlier menarche, extremely lean body mass at age 10 years, and taller adult height were predictive of elevated breast carcinoma risk. The same three factors were also predictive of higher peak growth velocities during adolescence, lending credence to the hypothesis that more rapid adolescent growth may increase the risk of breast carcinoma development.

Overweight, weight concerns, and bulimic behaviors among girls and boys.

OBJECTIVE: To assess the prevalence rates and correlates of overweight, concern with weight, and bulimic behaviors. METHOD: A survey was completed by a population-based sample of 16,114 boys and girls aged 9 to 14 years. RESULTS: Although fewer girls (19%) than boys (26%) were overweight, more girls (25% versus 22%) perceived themselves as overweight (p < .001). The proportion of girls reporting trying to lose weight increased with age (p < .001). The prevalence of binge eating at least monthly increased with age among the girls, but remained stable among the boys. The prevalence of purging was low (< or = 1%) and comparable between genders until age 13. Among the 13- and 14-year-olds, girls were significantly more likely than boys to report using laxatives or vomiting to control weight (p < or = .001). Purging was independently positively associated with stage of pubertal development (girls: odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.6-2.7; boys: OR = 1.5, 95% CI 1.0-2.2) and overweight (girls: OR = 1.9, 95% CI 1.2-3.0; boys: OR = 2.7, 95% CI 1.4-5.1). CONCLUSIONS: Misperception of being overweight and concern with weight were common. Purging was a very rare behavior, but increased with pubertal development. Among the girls, the prevalence increased sharply around the onset of adolescence.

Validation of a youth/adolescent food frequency questionnaire.

BACKGROUND: To address limited longitudinal nutrition data on children and adolescents, a self-administered food frequency questionnaire was designed for older children and adolescents. Initially, the Youth/Adolescent Questionnaire (YAQ) was developed and demonstrated to be reproducible. This study was conducted to evaluate its validity. METHODS: The form was administered twice to a sample of 261 youths (ages 9 to 18) at an approximate interval of 1 year (1993-1994), and three 24-hr dietary recalls were collected during this period. Pearson correlation coefficients were calculated on nutrient data. RESULTS: Validity was first evaluated by comparing the average of the three 24-hr recalls to the average of the two YAQs. Similar mean nutrients were found by both methods. Correlation coefficients between the mean energy-adjusted nutrients computed by the two methods ranged from 0.21 for sodium to 0.58 for folate. After correction for within-person error, the average correlation coefficient was 0.54, similar to that found among adults. CONCLUSION: A simple self-administered questionnaire completed by older children and adolescents can provide nutritional information about this age group.

Physical activity and reduced risk of colon cancer: implications for prevention.

This paper reviews the consistency of the relation between increased physical activity and reduced risk of colon cancer, estimates the potential prevention benefit from increasing population levels of physical activity, and considers social strategies to increase activity levels. The published literature was reviewed systematically and supplemented by MEDLINE searches through March 1997. Studies that reported a measure of physical activity and outcomes of colon cancer or colorectal cancer were included. We excluded the first report of a study that was expanded subsequently by extended follow-up, and any study that did not report the methods for measurement of physical activity. Data were extracted including details on study size, methods of classifying physical activity, and outcomes. A consistent inverse relation was observed such that increased physical activity was associated with reduced risk of colon cancer. About a 50 percent reduction in incidence was observed among those with the highest level of activity across numerous studies that used different measures of activity (occupational or leisure-time activity). This association persisted in studies using multivariate analyses to control for diet and other known or suspected risk factors for colon cancer. Risk reduction was attenuated in those studies that combined colon and rectal cancer. This review indicates that greater attention should be placed on social strategies to increase physical activity as a means of preventing colon cancer.

Identification and characterisation of a human calmodulin-stimulated phosphodiesterase PDE1B1.

A cDNA encoding a calmodulin-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE) was isolated from a human brain cDNA library. The cDNA, designated HSPDE1B1, encoded a protein of 536 amino acids that shared 96% sequence identity with the bovine "63 kDa" calmodulin-stimulated PDE. The recombinant protein had cyclic nucleotide phosphodiesterase activity that was stimulated approximately 2-fold by Ca2+/calmodulin and preferred cGMP as substrate. In addition, the enzymatic activity of HSPDE1B1 was inhibited by phosphodiesterase inhibitors with potencies similar to that displayed toward the bovine PDE1 enzymes: IBMX approximately equal to 8-methoxymethyl-IBMX > vinpocetine approximately equal to zaprinast > cilostamide > rolipram. HSPDE1B1 mRNA was found predominantly in the brain. Lower mRNA levels were found in heart and skeletal muscle. In situ hybridisation of brain revealed expression of HSPDE1B1 predominately in neuronal cells of the cerebellum, hippocampus and caudate. The HSPDE1B1 gene was mapped to human chromosome 12. A partial genomic sequence of HSPDE1B1 was isolated and shown to contain two splice junctions that are conserved in the rat PDE4 and the Drosophila dunce genes.