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Biomedical subjects

V M Chinchilli

Publications and source records attributed to V M Chinchilli.

At least 37 records · Page 2Linked to original sources
PubMed2000

Longitudinal nutrient intake patterns of US adolescent women: the Penn State Young Women's Health Study.

PURPOSE: To use longitudinal nutrient intake data to determine whether dietary patterns remain consistent (or "track") as U.S. females progress from age 12 to 18 years. METHODS: Three-day diet records were collected at regular intervals over 6 years from participants in the Penn State Young Women's Health Study. Eighty-one subjects remained in the cohort during the study period. Tracking in body weight, in dietary intake of fat, sugar, iron, vitamin C, and in a total dietary score (TDS) was assessed using quartile-ranking analysis, year-to-year Pearson correlation analysis, and longitudinal linear analysis. RESULTS: Rank analysis revealed that subjects maintained their relative quartile positions for body weight throughout the study period, and year-to-year correlation coefficients for this variable were .93-.94. In contrast, rank and correlation analyses showed that the subjects did not track strongly with respect to any nutrient variable. Age 12 to 18 years correlation coefficients ranged from r = .04 for fat intake to r = .15 for the TDS. In longitudinal linear models, slopes differed in direction and significance across the original quartiles for nutrient intake, indicating varying dietary trends over time within the study population. CONCLUSIONS: Nutrient intake patterns do not track strongly throughout adolescence among U.S. females.

Adolescent↗
PubMed2000

The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma.

Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30. 5 +/- 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR. No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment.

Adolescent↗
PubMed2000

Adult female hip bone density reflects teenage sports-exercise patterns but not teenage calcium intake.

OBJECTIVE: To examine how cumulative teenage sports histories and time-averaged teenage calcium intake are related to total body bone mineral gain between ages 12 and 18 years and to proximal femur bone mineral density (BMD) at age 18 years. Design. Longitudinal. Setting. University Hospital and local suburban community in Central Pennsylvania. STUDY PARTICIPANTS: Eighty-one white females in the ongoing Penn State Young Women's Health Study. OUTCOME MEASURES: Total body and proximal femur (hip) bone measurements by dual energy radiograph absorptiometry; nutrient intakes, including calcium, from 33 days of prospective food records collected at regular intervals between ages 12 and 18 years; and self-reported sports-exercise scores between ages 12 and 18 years. RESULTS: Cumulative sports-exercise scores between ages 12 and 18 years were associated with hip BMD at age 18 years (r = .42) but were not related to total body bone mineral gain. Time-averaged daily calcium intake, which ranged from 500 to 1500 mg/day in this cohort was not associated with hip BMD at age 18 years, or with total body bone mineral gain at age 12 through 18 years. CONCLUSIONS: The amount of physical activity that distinguishes a primarily sedentary teenager from one who engages in some form of exercise on a nearly daily basis is related to a significant increase in peak hip BMD.

Adolescent↗
PubMed1999

A mixed effects model for the analysis of repeated measures cross-over studies.

A mixed effects model is developed for cross-over trials in which the response is measured repeatedly within each time period. Relative to previous work on repeated measures cross-overs, the methodology synthesizes two important features. First, our procedure eliminates preliminary testing for carry-over, defined loosely as the component of a response that is due to treatment in the preceding period. This is achieved by generalizing the methodology to cross-over designs in which preliminary testing for carry-over is unnecessary. We focus largely on 'simple' carry-over, that is, carry-over that lasts for exactly one period and is independent of the treatment administered in the period in which the carry-over occurs. However, we also illustrate a modification of the procedure for a repeated measures cross-over design which uses a more complicated model of carry-over. Second, the model allows both the between- and within-subject variance to differ among treatments. Conditions are described wherein closed-form (CF) solutions to the variance components as well as closed-form hypothesis tests of the treatment differences exist. Flexibility in the model is illustrated with an example in which inference based on the CF likelihood-based estimates of the variance, and estimates formed using an iterative routine (PROC MIXED) are compared.

Animals↗
PubMed1999

Effect of the potent aromatase inhibitor fadrozole hydrochloride (CGS 16949A) in postmenopausal women with breast carcinoma.

BACKGROUND: Fadrozole hydrochloride (CGS 16949A) is a highly potent, nonsteroidal aromatase inhibitor that significantly lowers estrogen levels in postmenopausal women and can be effective therapy for patients with advanced hormone-dependent breast carcinoma. Circulating estradiol, estrone, and estrone sulfate are reduced to undetectable levels within weeks of the initiation of therapy. Before this study, it was not known whether this decrease in serum estrogen levels results in altered parameters associated with cardiovascular disease. The authors examined the levels of several critical blood parameters that are important to cardiovascular risk for heart disease and thromboembolic disorders in patients treated with fadrozole. METHODS: Cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), antithrombin III, protein C, protein S, and fibrinogen were serially measured in 21 postmenopausal women with advanced breast carcinoma treated with various doses of fadrozole (1.8 mg/day, n=3; 2.0 mg/day, n=13; 4.0 mg/day, n=5) over 3-24 months (mean, 15.8 months). A repeated measure analysis of variance was applied to each cardiovascular variable to assess changes in the response over time. Analyses were performed separately for each dose group and were also pooled over the dose groups. RESULTS: There was no statistically significant change over time in lipid parameters, namely, total cholesterol (P=0.57), triglyceride (P=0.27), LDL (P=0.99), HDL (P=0.30), and VLDL (P=0.43), over the 24 months of therapy. There were also no significant changes in coagulation factors, namely, antithrombin III (P=0.41), protein C (P=0.49), or protein S (P=0.31), over the 24 months. However, an increase in fibrinogen that occurred over time did reach statistical significance (P=0.011). CONCLUSIONS: With the exception of acute phase reactant fibrinogen, this study did not identify an increase in parameters associated with cardiovascular disease in women treated with fadrozole, a potent aromatase inhibitor.

Aged↗
PubMed1999

Self-assessment of physical sexual maturation in boys and girls with delayed puberty.

We studied 49 boys and girls with delayed physical sexual maturation during treatment with sex steroids. We found significant agreements, but also some disagreements between physicians' and subjects' Tanner sexual maturity ratings. We found neither effects of treatment with sex steroids nor gender differences, comparing ratings between physicians and patients.

Adolescent↗
PubMed1999

Histopathology of the palmar beak ligament in trapeziometacarpal osteoarthritis.

Eighteen cadaver hands were studied to investigate the relationship between degeneration of the palmar beak ligament and articular disease of the trapeziometacarpal joint. Eight of 18 joints had chondromalacia alone; 10 contained areas of eburnation in the palmar aspect of the joint. Beak ligament degeneration correlated closely with the presence of articular degeneration; all joints with eburnation demonstrated frank detachment of the ligament from its metacarpal insertion site. Histologically, the collagen fibers of the beak ligament were disorganized at the metacarpal attachment. The normal insertional zone of fibrocartilage was often unrecognizable on the metacarpal side and, in more degenerative specimens, an intervening synovial recess appeared at the palmar beak of the metacarpal. The trapezial insertion of the beak ligament showed no degenerative change. Increasingly severe cartilage disease was associated with progressive and selective degeneration of the collagen framework of the beak ligament at its insertion onto the thumb metacarpal. These localized histopathologic findings further support the existence of an anatomically distinct intra-articular beak ligament essential to the normal function of the trapeziometacarpal joint and suggest an etiologic relationship to osteoarthritic disease.

Aged↗
PubMed1998

Body composition development of adolescent white females: the Penn State Young Women's Health Study.

OBJECTIVE: To obtain simultaneous and longitudinal measures of height, weight, total body bone mineral content, total body bone mineral density, percentage of body fat, lean body mass, and body mass index in healthy white females between the ages of 11 and 18 years. DESIGN: A longitudinal, observational study. SETTING: University medical center in a small city. STUDY PARTICIPANTS: At initiation in 1990, 112 premenarchal, healthy girls were enrolled. Results presented in this report are based on measurements made on the 82 participants who remained in the study in 1996 and for whom we had comprehensive measurements. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry was used to obtain measurements of total body bone mineral content, total body bone mineral density, percentage of body fat, and lean body mass every 6 months for the first 4 years of the study and yearly thereafter. RESULTS: The mean age for peak velocity and peak accumulation for each measurement was as follows: height, 11 1/2 and 17 1/2 years, respectively; weight, 11 1/2 and 17 1/2 years; body mass index, 11 1/2 and 17 1/2 years; percentage of body fat, 11 1/2 and 13 1/2 years; lean body mass, 12 and 17 1/2 years; total body bone mineral content, 13 1/2 and 17 1/2 years; and total body bone mineral density, 13 1/2 and 17 1/2 years. CONCLUSIONS: Among a healthy population of white females, the age of peak velocities for height, weight, body fat, and lean body mass occur at 11 1/2 to 12 years. Thus, peak soft-tissue velocities precede hard-tissue velocities by about 2 years, with peak accumulation of all tissue components being reached, on average, by age 17 1/2 years.

Absorptiometry, Photon↗
PubMed1998

The effect of sex hormone replacement therapy on behavior problems and moods in adolescents with delayed puberty.

OBJECTIVE: The objective of this clinical study was to determine the effects of sex steroids on behavior and mood in adolescents with hypogonadism. STUDY DESIGN: The experimental design consisted of a randomized, double-blind, placebo-controlled, crossover trial lasting for 21 months. The study group consisted of 39 boys and 16 girls recruited from a pediatric endocrine clinic for delayed puberty. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks, alternating with placebo, at 3 dose levels approximating early, middle, and late pubertal amounts. The Child Behavior Checklist, Youth Self Report, Differential Emotion Scale, and Daily Mood Diary were administered after each placebo and treatment period to ascertain the effect of sex steroids on self- and parent-reported behavior problems and moods. RESULTS: The data demonstrated only one significant treatment effect, namely, an increase in withdrawn behavior problems during administration of low-dose estrogen in girls. There were no consistent sex differences. CONCLUSION: These results demonstrate that administered testosterone or estrogen has minimal effects on behavior problems or mood in adolescents.

Adolescent↗
PubMed1998

Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids.

BACKGROUND: Allergic rhinitis (AR) is a frequent disease affecting up to 20% of the population. AR causes a hypersensitivity reaction, which results in inflamed nasal mucosa and nasal congestion. Negative pressure generated during inspiration in the nasal airway secondary to nasal congestion may lead to nasal collapse, airway obstruction, and an increased number of sleep microarousals. Sleep disturbances and microarousals can detrimentally affect daytime energy levels, mood, and daytime function. It is unknown whether treatment directed to reduce congestion may reduce these microarousals, sleep problems, and, consequently, associated daytime fatigue. OBJECTIVE: We sought to determine whether reducing nasal congestion with nasal steroids will reduce sleep complaints and daytime sleepiness. METHOD: We enrolled 20 subjects in a double-blind, placebo-controlled study using Balaam's Design. Patients were treated with topical nasal corticosteroids or placebo. Subjective data were collected by use of a daily diary, which focused on nasal symptoms, sleep, and daytime sleepiness. RESULTS: The results demonstrated that nasal congestion and subjective sleep improved significantly in the topical corticosteroid-treated subjects but not in the placebo group. Sleepiness improved, but not significantly (p = 0.08). CONCLUSION: Often, people with perennial allergies may attribute their daytime fatigue to causes such as the side effects of medications, when in fact, the fatigue may be a result of nasal congestion and associated sleep fragmentation. Decreasing nasal congestion with nasal steroids may improve sleep, daytime fatigue, and the quality of life of patients with AR.

Administration, Topical↗
PubMed1998

Fruit consumption, fitness, and cardiovascular health in female adolescents: the Penn State Young Women's Health Study.

The objective of this study was to compare the relations among nutrient intake, fitness, serum antioxidants, and cardiolipoprotein profiles in female adolescents. The study design was a cross-sectional analysis of the Penn State Young Women's Health Study. The present study was performed with the entire cohort (n = 86) when they were 17.1+/-0.5 y (x+/-SD) of age. Primary measurements included cardiolipoprotein indexes, serum antioxidants, nutrient intakes, aerobic fitness, and percentage body fat. The cohort was stratified by estimated maximal oxygen uptake (VO2max) measurements and by percentage body fat. The fifth quintile by estimated VO2max had significantly lower percentage body fat, higher athletic scores, higher fruit intake, lower total serum cholesterol, and lower ratios of total serum cholesterol to HDL cholesterol than members of the first quintile. When the members of the first and fifth quintiles by percentage body fat were compared, the first quintile had significantly lower weight, lower body mass index, higher estimated VO2max, higher athletic scores, lower ratios of total serum cholesterol to HDL cholesterol, and higher fruit, carbohydrate, and fiber intakes. Correlation analyses performed with the data for the entire cohort showed fruit consumption to be positively correlated with estimated VO2max, and predicted VO2max to be positively correlated with circulating beta-carotene and alpha-tocopherol. This study provided evidence that the positive associations of exercise and fruit consumption with cardiovascular health apply to female adolescents as well as to adults.

Adipose Tissue↗
PubMed1998

Effects of estrogen or testosterone on self-reported sexual responses and behaviors in hypogonadal adolescents.

The purpose of this study was to investigate the effects of administration of sex steroids on self-reported sexual responses and behaviors in hypogonadal adolescents. We used a randomized, double blind, placebo-controlled, cross-over, clinical trial as the experimental design. The subjects were 39 boys and 16 girls with delayed puberty. We treated girls with oral conjugated estrogen and boys with testosterone enanthate in 3 dose levels intended to simulate early, middle, and late pubertal levels. We administered a modification of the Udry sexual behavior questionnaire after each 3-month placebo and treatment period to detect the effect of sex steroids on self-reported sexual behaviors and responses. We employed a strict intent to treat statistical analytical model. The data showed significant effects of the administration of testosterone to boys causing increases in nocturnal emission and touching behaviors at the mid- and high doses. No other treatment effects on sexual behaviors or responses were seen in boys. For girls, there was a significant increase in necking caused by the administration of estrogen only at the late pubertal dose. No other treatment effects on sexual behaviors or responses were seen in girls. We noted some gender differences for thinking about sex, sexual "turn-on," and the nature of sexual behavior. The administration of physiological doses of sex steroids to boys or girls with delayed puberty have few effects on sexual behaviors and responses.

Adolescent↗
PubMed1997

Enhanced anti-proliferative activity of the combination of tamoxifen plus HER-2-neu antibody.

HER-2/neu overexpression has been associated with poor prognosis in human breast cancer. Many of these cancers are also ER-positive. A logical therapeutic approach for patients who are ER-positive and overexpress HER-2/neu may be to block both the ER and the HER-2/neu pathways. In our study, we used both the MTT tetrazolium dye assay and 3H-thymidine incorporation to measure the effects of the anti-estrogen Tamoxifen or the 4D5 anti-HER-2/neu antibody alone or in combination on the growth of BT474 human breast cancer cells which express ER and overexpress HER-2/neu. We found an enhanced inhibitory effect on cell proliferation with the combination of Tamoxifen and the antibody compared to that seen by either agent alone. This simultaneous interruption of both the ER and the HER-2/neu pathways may be relevant in the clinical treatment of patients who are both ER-positive and overexpress HER-2/neu.

Antibodies, Monoclonal↗
PubMed1997

The multivariate assessment of bioequivalence.

We propose an approach for comparing directly the reference and test blood concentration x time profiles of subjects in a bioequivalence trial under a crossover design. We compare the test and reference profiles via the construction of two regions, namely, an acceptable region based on the reference profile and another region based on reflecting the test profile about the reference profile. Also, we describe how to construct these regions if the assay for measuring the concentration has a lower limit of detection and how to adjust the reference and test concentrations of the n subjects participating in a bioequivalence trial. If the test and reference formulations are bioequivalent, then the area displaced by the latter region should be less than the area displaced by the acceptable region. Therefore, we construct a ratio of these areas for each subject. Then we calculate upper confidence limits for quantiles, either under theassumption of lognormality or based on a bootstrapping algorithm, to investigate population and/or individual bioequivalence.

Cross-Over Studies↗