[Show abstract][Hide abstract] ABSTRACT: This study evaluated retention of the effect of a home-based, practitioner-initiated nutrition education model.
Children with elevated low-density lipoprotein (LDL) cholesterol levels were randomly assigned to one of two nutrition interventions or to an at-risk control group. Intervention effects were evaluated 3, 6, and 12 months postbaseline.
The parent-child autotutorial group demonstrated significant increases in knowledge and, along with the counseling group, decreases in total and saturated fat intake. Also, the autotutorial and counseling groups retained a majority of their initial LDL cholesterol decrease.
Knowledge of heart-healthful eating and dietary fat intake as well as dietary change can be affected and retained via home-based, practitioner-initiated nutrition interventions with hypercholesterolemic children, although some form of ongoing intervention may be necessary to produce lasting decreases in LDL cholesterol levels.
Full-text · Article · Mar 1998 · American Journal of Public Health
[Show abstract][Hide abstract] ABSTRACT: Breast tumors from post-menopausal women contain higher amounts of estradiol than would be predicted from levels circulating in plasma. This observation raised the hypothesis that tumors may synthesize estradiol in situ and increase their tissue estradiol levels via this mechanism. The key enzyme involved in tissue estrogen synthesis, aromatase, is present in breast tumors but, according to some investigators, not in sufficient concentration to be biologically meaningful. We postulated that foci of cells in breast tumors might contain high amounts of aromatase and this locally produced estrogen might act in a paracrine or autocrine fashion. To test this hypothesis, we utilized immunohistochemistry to localize the aromatase enzyme, an histological scoring system to quantitate it, and culture of isolated breast cells to demonstrate its potential regulation. In 26 archival breast tumors, 16 (62%) contained aromatase by radiometric assay. With the immunohistochemical method, we detected areas with staining in the stroma as well as tumor epithelial cells. Staining ranged from the intensity approaching that seen in placenta to levels just distinguishable from background. We adopted an histological scoring system (H-score) from that used to quantitate progesterone receptor levels in tissue and used it to quantitate aromatase activity. A higher histologic score was found in stromal spindle cells (13) than in tumor epithelial cells (4.8). The biochemical aromatase results correlated with the H-score of stromal but not epithelial cells. To further study stromal cells from tumors, we isolated stromal cells from breast tumors and the benign areas of breast distal to the tumor and grew them in culture. Addition of dexamethasone, phorbol esters, and cyclic AMP analogues stimulated aromatase enzyme and messenger RNA levels substantially. Use of aromatase enzyme inhibitors such as letrozole blocked estrogen production but did not alter aromatase message levels. Epithelial cells, whether nonmalignant or cancer derived, exhibited no regulation by dexamethasone, phorbol esters, or cAMP analogues. These data, taken together, suggest that stromal cells may be more important than epithelial cancer cells for estrogen production in breast tumors. The ability to stimulate aromatase activity substantially with various enhancers of aromatase provides further credence for an important biologic role of estrogen production in tumor tissue.
No preview · Article · Feb 1998 · Breast Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: As part of a program evaluating nutrition education for hypercholesterolemic children, a pediatric practice-based cholesterol screening program identified 261 3.9–9.9 year old children with elevated cholesterol levels (At-Risk). At baseline (before any intervention), the diets of these children were found to be relatively low in fat (29.7% calories as fat, and 11.2% as saturated fat). This is approaching recommended levels and is lower than has been reported for similar groups of children. To help evaluate potential influences upon the dietary intake of these At-Risk children, their diets were compared to the diets of children without elevated cholesterol levels (Not-At-Risk, n=81). The diets of the Not-At-Risk children were then compared to a group of children who had not completed cholesterol screening nor dietary intervention (not-screened, n=49). Three 24-hour dietary recalls were completed by telephone with each child at baseline and averaged. These recalls and subsequent comparisons showed that the only statistically significant differences between the groups were a lower caloric intake and fiber intake for the At-Risk group as compared to the Not-At Risk group. These results suggest that some groups of American children are consuming a diet with fat, saturated fat and cholesterol content closer to recommended levels than previously reported. In addition, participation in preventive health screening, such as a cholesterol screening program and being labelled as hypercholesterolemic, seemed to have little influence on the intake of fat, saturated fat or cholesterol.
No preview · Article · Aug 1997 · Nutrition Research
[Show abstract][Hide abstract] ABSTRACT: Food-frequency questionnaires are usually administered as a list of foods to be checked off by the respondent or interviewer. Techniques in which participants sort into categories cards on which names or pictures of foods are printed can also be used to assess food intake. Food-frequency scores were obtained from a five-category picture sort administered to 4643 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). This one-step (qualitative) assessment yielded significant associations in expected directions between frequency scores and sex, age, race or ethnicity, body mass index, and use of a special diet. In the two-step (semiquantitative) version of this instrument, an interviewer documented specific frequencies and portion-size information for the foods in each sorting category. A substudy of the two-step version with 96 CHS participants indicated relative validity similar to that of conventionally administered food-frequency questionnaires. The one-step version may be broadly applicable to situations in which general food-pattern data can be informative and cost and time limitations are great. When it is feasible, the two-step picture sort may offer certain methodologic advantages because respondents have a chance to change their responses and the format may simplify the cognitive-response task. Sorting or picture-sort procedures deserve systematic attention in research on dietary assessment methods.
Preview · Article · May 1997 · American Journal of Clinical Nutrition
[Show abstract][Hide abstract] ABSTRACT: The need to quantify agreement between two raters or two methods of measuring a response often arises in research. Kappa statistics (unweighted and weighted) are appropriate when the data are nominal or ordinal, whereas the concordance correlation coefficient is more appropriate when the data are measured on a continuous scale. We develop weighted product-moment and concordance correlation coefficients which are applicable for repeated measurements study designs. We consider two distinct situations in which the repeated measurements are paired or unpaired over time. We illustrate the methodology with examples comparing (1) two assays for measuring serum cholesterol, (2) two estimates of dietary intake, from a food frequency questionnaire and dietary recalls, and (3) two measurements of percentage body fat, from skinfold calipers and dual energy x-ray absorptiometry.
[Show abstract][Hide abstract] ABSTRACT: To assess the validity of a picture-sort approach to administering the National Cancer Institute food frequency questionnaire to older adults.
A picture-sort interview was conducted in each respondent's home. After the picture sort, a 24-hour recall interview was administered on the same occasion. Five additional in-home recall interviews were subsequently conducted at approximately 1-month intervals.
Forty-seven female and 49 male volunteers aged 66 to 100 years were recruited from among Cardiovascular Health Study participants from Maryland and North Carolina.
Estimates from the picture sort and the recall for intakes of macronutrients, cholesterol, fiber, and selected vitamins and minerals exclusive of supplements.
Comparison of means estimated by the two methods and correlation analyses were used. Correlations were adjusted under varied assumptions about the nature of the information contained in the six 24-hour recalls relative to respondents' usual intakes.
After correction for attenuation, Pearson correlation coefficients for macronutrients ranged from .41 for protein to .74 for saturated fat and cholesterol. For vitamins and minerals, correlations ranged from .26 for beta carotene to .62 for calcium.
Picture-sort estimates of mean nutrient intakes were comparable with estimates based on 24-hour recalls, and correlations with reference data were similar to those reported in the literature for conventionally administered food frequency questionnaires. This dietary assessment method may, therefore, offer a way to simplify or structure responses to improve ease of administration and increase respondents' liking for the interview without loss of data quality.
No preview · Article · Mar 1996 · Journal of the American Dietetic Association
[Show abstract][Hide abstract] ABSTRACT: One hundred and twelve Caucasian girls, 11.9 +/- 0.5 years of age at entry, were randomized into a 24-month, double-masked, placebo-controlled trial to determine the effect of calcium supplementation on bone mineral content, bone area and bone density. Supplementation was 500 mg calcium as calcium citrate malate (CCM) per day. Controls received placebo pills, and compliance of both groups averaged 72%. Bone mineral content, bone mineral area and bone mineral density of the lumbar spine and total body were measured by dual energy X-ray absorptiometry (DXA). Calcium intake from dietary sources averaged 983 mg/day for the entire study group. The supplemented group received, on average, an additional 360 mg calcium/day from CCM. At baseline and after 24 months, the two groups did not differ with respect to anthropometric measurements, urinary reproductive hormone levels or any measurement of pubertal progression. The supplemented group had greater increases of total body bone measures: content 39.9% versus 35.7% (p = 0.01), area 24.2% versus 22.5% (p = 0.15) and density 12.2% versus 10.1% (p = 0.005). Region-of-interest analyses showed that the supplemented group had greater gains compared with the control group for bone mineral density, content and area. In particular, in the lumbar spine and pelvis, the gains made by the supplemented group were 12%-24% greater than the increases made by the control group. Bone acquisition rates in the two study groups were further compared by subdividing the groups into those with below- or above-median values for Tanner score and dietary calcium intake. In subjects with below-median Tanner scores, bone acquisition was not affected by calcium supplementation or dietary calcium level. However, the calcium supplemented subjects with above-median Tanner had higher bone acquisition rates than the placebo group with above-median Tanner scores. Relative to the placebo group, the supplemented group had increased yearly gains of bone content, area and density which represented about 1.5% of adult female values. Such increases, if held to adult skeletal maturity, could provide protection against future risk of osteoporotic fractures.
No preview · Article · Feb 1996 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: To assess the effects of a home-based, parent-child autotutorial (PCAT) dietary education program on the dietary knowledge, lipid consumption, and plasma low density lipoprotein-cholesterol (LDL-C) of 4- to 10-year-old children with elevated plasma LDL-C.
"At-risk" children (screening total cholesterol, (TC), exceeded 4.55 mmol/L and average LDL-C from two fasting samples was between 2.77 and 4.24 mmol/L for boys or 2.90 and 4.24 mmol/L for girls) were randomized to the PCAT program (N = 88), for dietary counseling with a registered dietitian (N = 86), or to an at-risk control group (N = 87). Dietary knowledge, diet, and LDL-C of these groups were assessed at baseline and after the educational period (3-month follow-up). The knowledge and diet of a not-at-risk (TC below 4.22 and 4.34 mmol/L for boys and girls, respectively) control group (N = 81) was also assessed and compared with that of the at-risk control group.
At the 3-month follow-up, the PCAT children's knowledge scores had increased three times more than those of the counseling and at-risk control groups (P < .001). Mean grams of total and saturated fat consumed by PCAT and counseling groups declined while that of the at-risk control group increased slightly; these differences were significant (P < .05). The mean LDL-C decline of the PCAT group was significantly different (P < .05) from the decline of the at-risk control group (0.26 vs 0.09 mmol/L), and approached significance (P = .07) when compared with that of the counseling group (0.26 vs 0.11 mmol/L). The at-risk control group's knowledge and diet did not differ from that of the not-at-risk group.
The PCAT program offers a mechanism for providing effective dietary education to children with elevated cholesterol and to their families.
[Show abstract][Hide abstract] ABSTRACT: In situ synthesis of estrogens by breast cancer tissue provides a potential explanation for the high concentrations of estradiol in mammary neoplasms in postmenopausal women. A major metabolic pathway for estrogen biosynthesis is the conversion of androstenedione to estrone via the enzyme aromatase. Biochemical studies have demonstrated aromatase in tumor tissue, but at relatively low and not clearly biologically significant levels. The present study tested the hypothesis that tumor levels of aromatase, albeit low, could be biologically important if present in high concentrations in focal clusters of specific cell types. A pilot study used an immunohistochemical method in frozen sections of fresh breast tumors as an optimal means to detect aromatase. Twelve of 18 tumors contained aromatase-positive cells, some with highly intense staining. A follow-up study then attempted to precisely define the types of cells containing aromatase and correlate the immunohistochemical findings with biochemical aromatase activity. A modified H-score (histological scoring system) was used to semiquantitate the amount of aromatase staining in tumor epithelial, stromal spindle, stromal inflammatory, and normal breast epithelial cells. We found that immunohistochemical staining for aromatase predominated in stromal spindle cells with a median H-score of 13, whereas tumor epithelial, stromal inflammatory, and normal breast elements contained lesser amounts (median H-scores of 4.8, 0.03, and 0.5, respectively). The H-score for stromal spindle cells, but not those for other cell types, correlated highly with the biochemical aromatase assay (P < 0.01). Using a cut-off parameter estimated by a sensitivity/specificity (receiver operating curve) analysis, 62% of tumors were classified as aromatase positive based on stromal spindle cell staining. A similar number were also positive by biochemical assay, with concordance between the two methods of 77%. These observations provide substantial evidence for the presence of aromatase in human breast tumors, particularly in stromal spindle cells, and support the biological importance of aromatase for in situ production of estradiol.
No preview · Article · Aug 1994 · Journal of Clinical Endocrinology & Metabolism
[Show abstract][Hide abstract] ABSTRACT: FSH and/or LH deficiency in the second decade of life remains difficult to diagnose with testing at a single point in time because of the partial lack of hormone as well as the dynamic and inherently variable aspects of the pubertal process. A longitudinal study of gonadotropin excretion, therefore, was carried out in 78 normal boys and 157 male patients, aged 10-28 yr, with relative or absolute deficiencies of FSH and/or LH. Seven hundred and fifty-five timed urine samples were extracted with acetone, concentrated, and subjected to RIA. The results from patient groups with multiple tropic hormone deficiencies or isolated gonadotropin deficiency were clearly different from those of normal boys and individuals with constitutional delay in puberty. However, multiple samples obtained over a 2-yr period and, in selected cases, until the late teenage years may be required to diagnose gonadotropin deficiency in some patients, even using stringent predictive modeling criteria.
No preview · Article · Jun 1994 · Journal of Clinical Endocrinology & Metabolism
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls.
A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass.
Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry.
University hospital in a small town.
Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills.
Bone mineral density and bone mineral content of the lumbar spine and total body were measured by dual-energy x-ray absorptiometry and calcium excretion from 24-hour urine specimens.
Calcium intake from dietary sources averaged 960 mg/d for the entire study group. The supplemented group received, on average, an additional 354 mg/d of calcium. The supplemented group compared with the placebo group had greater increases of lumbar spine bone density (18.7% vs 15.8%; P = .03), lumbar spine bone mineral content (39.4% vs 34.7%; P = .06), total body bone mineral density (9.6% vs 8.3%; P = .05), and 24-hour urinary calcium excretion (90.4 vs 72.9 mg/d; P = .02), respectively.
Increasing daily calcium intake from 80% of the recommended daily allowance to 110% via supplementation with calcium citrate malate resulted in significant increases in total body and spinal bone density in adolescent girls. The increase of 24 g of bone gain per year among the supplemented group translates to an additional 1.3% skeletal mass per year during adolescent growth, which may provide protection against future osteoporotic fracture.
No preview · Article · Sep 1993 · JAMA The Journal of the American Medical Association
[Show abstract][Hide abstract] ABSTRACT: Urine concentrates assessed by RIA provide as sensitive a methodology for gonadotropin measurements as newly available immunofluorometric techniques. The ease of obtaining repeated, short-term (3-6hr), timed urine specimens and allowing the kidney to integrate for pulsatile secretion lends itself to distinguishing patients with gonadotropin deficiency from those with constitutional delay in adolescence. We have compared the rate of gonadotropin rise in males between the ages of 12-18 yrs. in 48 normal boys, 96 patients with constitutional delay, 19 patients with isolated gonadotropin deficiency, and 10 patients with multiple tropic hormone deficiency. A total of 511 specimens were analyzed by a longitudinal model that allowed for separate intercepts and linear slopes on log transformed data for each of the four diagnostic categories. For LH, the linear equation describing the constitutional group was log LH=0.6 + 0.32 x age (p<0.0001 for slope of line) but for the isolated hypogonadotropic patients was log LH=4.14 + 0.03 x age (p=0.74). Using a Bonferroni correction, the rate of hormone increase was markedly different for the constitutional delayed boys as compared to the hypogonadotropic patients (p=0.02). Similar findings existed for FSH. The model utilized provides a guide for determining the appropriate diagnosis for a patient with delayed adolescence who is followed for a year or more with sequential gonadotropin determinations. In conclusion, a separation of adolescent boys with hypogonadotropism from those who have constitutional delay can be made by following sequential urine gonadotropin determinations over a year or more.
Full-text · Article · May 1993 · Pediatric Research
[Show abstract][Hide abstract] ABSTRACT: Aromatase is present in human breast tumors and in breast cancer cell lines suggesting the possibility of in-situ estrogen production via the androstenedione to estrone and estradiol pathway. However, proof of the biologic relevance of aromatase in breast cancer tissue requires the demonstration that this enzyme mediates biologic effects on cell proliferation. Accordingly, we studied the effects of the aromatase substrate, androstenedione, on the rate of proliferation of wild-type and aromatase-transfected MCF-7 breast cancer cells. Androstenedione did not increase cell growth in wild-type MCF-7 cells which contained relatively low aromatase activity and produced 4-fold more estrone than estradiol. In contrast, aromatase-transfected cells contained higher amounts of aromatase, produced predominantly estradiol, and responded to androstenedione with enhanced growth. An aromatase inhibitor fadrozole hydrochloride, blocked the proliferative effects of androstenedione providing evidence for the role of aromatase in this process. As further evidence of the requirement for aromatase, cells transfected with the neomycin resistance expression plasmid but lacking the aromatase cDNA did not respond to androstenedione. These studies provide evidence that aromatase may have a biologic role for in-situ synthesis of estrogens in breast cancer tissue.
No preview · Article · Apr 1993 · The Journal of Steroid Biochemistry and Molecular Biology
[Show abstract][Hide abstract] ABSTRACT: Optimal synchronization of breast cancer cell proliferation by hormonal means may be limited by cellular heterogeneity in sensitivity to the multistep activation of growth following initial hormone binding to the receptor. We hypothesized that induced synchronous growth may be improved by combined manipulation of the polyamine (PA) pathway since we have previously shown that PAs are distal effectors of hormonal action on proliferation in breast cancer. To test our hypothesis, we induced an initial phase of hormone and PA depletion (castration plus administration of the PA synthesis inhibitor α-difluoromethylornithine) in rats bearing N-nitrosomethylurea induced mammary tumors. This was followed by transition phase of hormone repletion in the presence of α-difluoromethylornithine (to push the cells into the proliferative cascade up to the distal step controlled by PA) and finally a phase of hormone and PA repletion. Simultaneously, groups of rats were subjected to hormone/PA depletion/repletion individually. The effects of these manipulations on the labeling indices (LIs) of glandular, myoepithelial, and nonepithelial cells were estimated by autoradiography. The combined hormone/PA manipulation yielded the highest degree of synchronization with LIs of the glandular and myoepithelial cells being ∼2-fold over intact control after only 2 or 3 days of combined repletion. In contrast, hormone treatment alone restored the LIs of glandular cells only to control levels and minimally influenced those of myoepithelial cells. PA manipulation alone failed to affect the LIs of any cell type. Although the rate of tumor regrowth was highest with the combination treatment, the absolute tumor volumes did not differ significantly at the end of the repletion phase between the three regimens. These results indicate that combined hormone/PA manipulation provides the best "therapeutic window" (LI/tumor volume) for implementation of kinetically based cytotoxic chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Recent in vitro data suggest that at least some hormone-independent breast cancer cells exhibit increased polyamine biosynthesis and resistance to antipolyamine therapy. To address this issue under conditions of in vivo growth, we tested the antiproliferative effect of the polyamine synthetic inhibitor alpha-difluoromethyl-ornithine (DFMO) on hormone-dependent (MCF-7) and -independent (MDA-MB-231, BT-20) breast cancer cell lines growing in nude mice. We observed that DFMO significantly inhibited the growth of established tumors to a similar extent in all cell lines, even though tumor regression was only observed with MCF-7 cells. DFMO, while inhibiting E2-supported MCF-7 breast cancer growth, did not inhibit E2-stimulated progesterone receptor synthesis. Cellular levels of polyamines were highest in MCF-7 cells and lowest in the BT-20 cell line. Tumor content of spermidine was similarly suppressed by DFMO treatment in the 3 cell lines, while the spermine level was unaffected. Cellular putrescine levels were suppressed in MCF-7 and BT-20 cells. Administration of DFMO prior to implantation of fragments of MCF-7 or MDA-MB-231 tumors in nude mice significantly inhibited tumor development to a similar extent. The action of DFMO seemed to be predominantly tumoristatic since new tumors develop in some mice upon discontinuation of the drug. We conclude that the hormone-independent breast cancer cell lines tested do not exhibit increased polyamine biosynthesis or resistance to antipolyamine therapy when grown in vivo in nude mice.
[Show abstract][Hide abstract] ABSTRACT: Bone mass accretion during puberty appears to be critical in the development of peak bone mass, which, in turn, is believed to be a major determinant of osteoporosis risk. Although genetics may be the primary determinant of peak bone mass, modifiable secondary factors, such as nutrition and hormone exposure, may significantly affect bone mass accretion during the second decade of life. As part of a longitudinal study of major determinants of bone development during puberty, we obtained cross-sectional measurements from 112 premenarchal caucasian females (mean +/- SD age, 11.9 +/- 0.49 yr at study entry). Total body bone mineral density (TBBMD) and total body bone mineral content (TBBMC) were measured by dual energy x-ray absorptiometry and compared to anthropometric, pubertal development, urinary steroid and gonadotropin levels, and nutrient intake. An integrated estrogen exposure index was developed and used to evaluate the cumulative effect of circulating estrogen levels on both development. Compared to normative reference data for adults, our subjects possessed 90% of adult height, 68% of adult weight, 83% of adult TBBMD, and 53% of TBBMC. The strongest combined predictors of prepubertal TBBMD and TBBMC were body weight, followed by height and pubertal development. Urinary estradiol levels were positively correlated with dietary intake of iron and vitamin B6.
No preview · Article · Sep 1992 · Journal of Clinical Endocrinology & Metabolism
[Show abstract][Hide abstract] ABSTRACT: The mechanism by which transforming growth factor-alpha (TGF-alpha) stimulates breast cancer cell proliferation is largely unknown. Furthermore, its potential role as an autocrine effector of estradiol-17 beta (E2)-stimulated growth of hormone-dependent mammary tumors remains controversial. Transient changes in phosphatidylinositol (PI) turnover have been demonstrated in several tissues in response to growth factors. In these experiments, we tested the effects of TGF-alpha and E2 on PI metabolism in three MCF-7 breast cancer cell sublines (MCF-7B, MCF-7I, and MCF-7J). Although TGF-alpha was mitogenic in MCF-7I and MCF-7J cells, PI hydrolysis was stimulated by the growth factor only in the MCF-7I cells. In addition, the TGF-alpha effect was relatively modest, ranging from 23% to 42%. E2 effects on PI turnover were tested in the MCF-7B cells, which were the most sensitive to the proliferative effect of the hormone. E2 did not stimulate PI hydrolysis, whether or not the cells were labelled in the presence of the hormone. On the other hand, E2 did seem to stimulate de novo synthesis of phosphatidylinositol and induce activation of PI kinases. These results demonstrate that TGF-alpha-stimulated PI hydrolysis is modest and cell type dependent. At least under certain conditions, PI metabolism is not involved in the proliferative effects of TGF-alpha (MCF-7J) or E2 (MCF-7B). The role of increased PI synthesis in E2-stimulated MCF-7 cell growth remains to be established.
No preview · Article · Feb 1992 · Breast Cancer Research and Treatment