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Biomedical subjects

Pippa M Simpson

Publications and source records attributed to Pippa M Simpson.

At least 19 recordsLinked to original sources
PubMed2006

Estradiol protects against ethanol-induced bone loss by inhibiting up-regulation of receptor activator of nuclear factor-kappaB ligand in osteoblasts.

To investigate the effects of sex hormones on ethanol (EtOH)-induced bone loss, female Sprague-Dawley rats were fed control or EtOH-containing diets (12 g/kg/day) by intragastric infusion. After 3 weeks, rats receiving EtOH had significant decreases in tibial trabecular and total bone mineral density, induction of receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA expression, and enhanced bone resorption, all of which were prevented by treatment with 17beta-estradiol (E(2)). The addition of progesterone did not enhance the beneficial effect of E(2) alone. Consistent with our in vivo findings, EtOH stimulated RANKL mRNA expression in cultured primary osteoblasts, and this expression was blocked by 4-methylpyrazole. Acetaldehyde also induced RANKL expression. Class 1 alcohol dehydrogenase was found to be expressed and EtOH-inducible in cultured osteoblasts, whereas CYP2E1 was undetectable. We found that EtOH induced phosphorylation of extracellular signal-regulated kinase (ERK) and signal transducers and activators of transcription 3 (STAT3). E(2) and the mitogenactivated protein kinase kinase inhibitor 2'-amino-3'-methoxyflavone (PD98059) blocked ERK and STAT3 phosphorylation and blocked RANKL induction. Moreover, E(2) completely blocked EtOH-induced osteoclastogenesis in a primary osteoblast and osteoclast precursor coculture system. The E(2) effects were estrogen receptor-mediated. Therefore, E(2) prevents EtOH-induced bone loss by opposing the induction of RANKL mRNA in osteoblasts and ethanol-induced osteoclastogenesis, through opposing effects on sustained ERK signaling.

Animals↗
PubMed2006

Symptom profile and asthma control in school-aged children.

BACKGROUND: Children with poorly controlled asthma are at high risk of airway remodeling, sleep disruption, school absenteeism, and limited participation in activities. OBJECTIVE: To determine asthma prevalence and characterize disease severity and burden in school-aged children. METHOD: A case-finding study was conducted via a multiple-choice questionnaire and asthma algorithm. Items used for analysis include physician diagnosis of asthma, symptom severity, and health care utilization. The chi2 test was used to determine the significance of differences among cases. Logistic regression was used to evaluate the association of patient factors and asthma indicators. RESULTS: Of the 5,417 children surveyed, 1,341 (25%) were classified as being at risk of asthma. Of these asthma cases, 55% were positive by diagnosis and algorithm (active), 10% were positive per algorithm alone (suspected), and 35% were positive per diagnosis alone (nonactive). Only 14% of all asthma cases reported experiencing no respiratory symptoms (< 1% active, 2% suspected, and 40% nonactive) compared with 75% of noncases. Also, 75% of noncases reported never missing school compared with 19%, 33%, and 54% of active, suspected, and nonactive asthma cases. African American race, Medicaid enrollment, and male sex were independent predictors of asthma risk. Similarly, African American race, Medicaid enrollment, age, and persistent asthma were independent predictors of emergency department use among asthma cases. DISCUSSION: Prevalence of active symptoms suggestive of poor asthma control was extremely high among urban, minority children enrolled in Arkansas' largest public school district. Poor asthma control greatly affects quality of life, including school attendance and performance. Interventions should raise expectations and emphasize the importance of achieving asthma control.

Adolescent↗
PubMed2006

School-based asthma case finding: the Arkansas experience.

This population-based case-finding study sought to determine asthma prevalence and characterize disease severity and burden among school-aged children in the Little Rock School District. Asthma cases were identified by validated algorithm and parental report of asthma diagnosis. The overall response rate was low. Among schools with greater than 50% response rate, prevalence of physician-diagnosed asthma was comparable to other studies in public school settings. Prevalence of symptoms in cases identified as current is suggestive of poor asthma control. Improved systems for case identification of children with asthma are needed in schools. Efforts should focus on strategies to improve asthma control.

Adolescent↗
PubMed2006

The association of child and household food insecurity with childhood overweight status.

CONTEXT: The prevalence of childhood overweight status is increasing. Some have suggested that childhood overweight is associated with food insecurity, defined as limited or uncertain access to enough nutritious food. OBJECTIVES: The purpose of this work was to assess the association of household and child food insecurity with childhood overweight status. METHODS: The National Health and Nutrition Examination Survey 1999-2002 uses a stratified multistaged probability sample and collects a broad array of data from a nationally representative sample of US citizens. All children 3 to 17 years old in this sample are included in these analyses. We measured BMI categorized as at risk for overweight or greater (> or = 85%) or overweight (> or = 95%) and household and child food security/insecurity using the US Food Security Scale. RESULTS: When compared with children from food-secure households, children from food-insecure households were more likely to demonstrate significant associations with being at risk for overweight or greater in the following demographic categories: 12 to 17 years, girls, white, and in households with income < 100% and > 4 times the federal poverty level. Household food insecurity is associated with child overweight status in children aged 12 to 17, girls, and children who live in households with incomes > 4 times the federal poverty level. Child food insecurity demonstrated the same associations with being at risk for overweight or greater, as did household food insecurity, but associations were also seen in 3- to 5-year-old children, boys, and Mexican American children. Child food insecurity is significantly associated with child overweight status for children aged 12 to 17, girls, white children, and children in families with income < or = 100% poverty level. Controlling for ethnicity, gender, age, and family poverty index level, childhood food insecurity is associated with a child being at risk for overweight status or greater, but not overweight status. CONCLUSIONS: Household and child food insecurity are associated with being at risk for overweight and overweight status among many demographic categories of children. Child food insecurity is independently associated with being at risk for overweight status or greater while controlling for important demographic variables. Future longitudinal research is required to determine whether food insecurity is causally related to child overweight status.

Adolescent↗
PubMed2006

Assessing the reliability of amplified RNA used in microarrays: a DUMB table approach.

A certain minimal amount of RNA from biological samples is necessary to perform a microarray experiment with suitable replication. In some cases, the amount of RNA available is insufficient, necessitating RNA amplification prior to target synthesis. However, there is some uncertainty about the reliability of targets that have been generated from amplified RNA, because of nonlinearity and preferential amplification. This current work develops a straightforward strategy to assess the reliability of microarray data obtained from amplified RNA. The tabular method we developed, which utilises a Down-Up-Missing-Below (DUMB) classification scheme, shows that microarrays generated with amplified RNA targets are reliable within constraints. There was an increase in false negatives because of the need for increased filtering. Furthermore, this analysis method is generic and can be broadly applied to evaluate all microarray data. A copy of the Microsoft Excel spreadsheet is available upon request from Edward Bearden.

Benzothiazoles↗
PubMed2006

Spine bone densitometry in asthmatic children treated with high dose corticosteroids: correcting for racial discrepancies.

PURPOSE: Our hypothesis is that the use of standards based on Caucasian children will under-estimate the incidence of abnormal bone density in African American children. MATERIALS AND METHODS: Eighty-two African American and 80 Caucasian asthmatic children classified as high-dose inhaled corticosteroid users comprised the study population. Bone mineral density measurements were compared to reference standards, based on Caucasians, to calculate Z-values. Regression analysis was used to compare Z-values derived from the race-specific and Caucasian standards for 32 African American children. The derived regression analysis equation was then applied to the entire African American population to determine the incidence of abnormal bone density. RESULTS: The asthmatic Caucasian mean spine bone density was significantly less than the normal standards (p < .001), but the African American mean spine bone density was not, despite the high-dose steroid use. Using the Caucasian standards, Caucasians were significantly more likely to have abnormal bone density detected (p < 0.015). Regression analysis of the 32 children with available race specific standards resulted in the following equation: Z African American= Z Caucasian-0.86. The number of African Americans with abnormal bone density detected using the regression equation was not significantly different than the Caucasian children (p > 0.12). CONCLUSIONS: Asthmatic African Americans treated with high-dose inhaled corticosteroids had denser bones than Caucasians. Caucasian standards can be adjusted using a regression equation.

Absorptiometry, Photon↗
PubMed2005

Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats.

INTRODUCTION: High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity. METHOD: Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment. RESULTS: The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats. CONCLUSION: Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2005

Child health-related quality of life and household food security.

OBJECTIVE: To examine the association of household food insecurity with child self- or proxy-reported health-related quality of life (HRQOL). DESIGN: Cross-sectional telephone survey from January 1, 2000, through June 30, 2000. PARTICIPANTS: Three hundred ninety-nine children who live in 36 counties of the Delta region of Arkansas, Louisiana, and Mississippi. MAIN OUTCOME MEASURES: Household food insecurity status was measured using the US Household Food Security Scale. Child HRQOL was measured by the Pediatric Quality of Life Inventory, QL version 4.0. Analysis Summary statistics, linear and logistic regressions, incorporating survey weights, performed with SUDAAN version 8. RESULTS: Household food insecurity was significantly associated with total child HRQOL (P<.05) and physical function (P<.05), adjusted for child age, ethnicity, gender, and family income. Children aged 3 through 8 years in food insecure households were reported by parents to have lower physical function (P = .001), while children aged 12 through 17 years reported lower psychosocial function (P = .007). Black males in food insecure households reported lower physical function (P<.05) and lower total HRQOL (P<.05). CONCLUSIONS: Children who live in food insecure households have poorer HRQOL. The effect on physical or psychosocial function may differ by age, ethnicity, and gender. Food security should be considered an important risk factor for child health.

Adolescent↗
PubMed2005

Cytokines and toxicity in acetaminophen overdose.

Several cytokines have been reported to have hepatoprotective properties in animal models of acetaminophen toxicity. To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood samples were collected from patients following acute ingestions of acetaminophen. Samples for cytokine analysis were collected at the time of routine clinical monitoring in 111 patients (90 females; mean age 13.6 years). Plasma concentrations of interleukin 6, interleukin 8, interleukin 10, and monocyte chemoattractant protein 1 were analyzed by enzyme-linked immunosorbent assay. Patients were stratified by toxicity severity, defined by the maximal values of hepatic transaminase elevation. Levels of interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 were higher in patients with serum alanine aminotransferase > 1000 IU/L, and monocyte chemoattractant protein 1 had the strongest association with toxicity. Monocyte chemoattractant protein 1 values were higher in patients with greater delays in N-acetylcysteine treatment and in patients with higher values of prothrombin time. Monocyte chemoattractant protein 1 elevation in acetaminophen overdose may represent an innate, immunomodulary response of the liver to earlier events in the toxicity. An understanding of the role of cytokine responses in acetaminophen overdose may be relevant to the future development of new therapies for acetaminophen toxicity.

Acetaminophen↗
PubMed2004

Feeding of soy protein isolate to rats during pregnancy and lactation suppresses formation of aberrant crypt foci in their progeny's colons: interaction of diet with fetal alcohol exposure.

Soy protein isolate (SPI) in the diet may inhibit colon tumorigenesis. We examined azoxymethane (AOM)-induced aberrant crypt foci (ACF) in male rats in relation to lifetime, pre-weaning, or post-weaning dietary exposure to SPI and also within the context of fetal alcohol exposure. Pregnant Sprague Dawley rats were fed AIN-93G diets containing casein (20%, the control diet) or SPI (20%) as the sole protein source starting on gestation day 4 (GD 4). Progeny were weaned on postnatal day (PND) 21 to the same diet as their dams and were fed this diet until termination of the experiment at PND 138. Rats received AOM on PND 89 and 96. Lifetime (GD 4 to PND 138) feeding of SPI led to reduced frequency of ACF with 4 or more crypts in the distal colon. Progeny of dams fed SPI only during pregnancy and lactation or progeny fed SPI only after weaning exhibited similarly reduced frequency of large ACF in distal colon. Number of epithelial cells, in the distal colon, undergoing apoptosis was unaffected by diet. SPI reduced weight gain and adiposity, but these were not correlated with fewer numbers of large ACF. Lifetime SPI exposure similarly inhibited development of large ACF in Sprague Dawley rats whose dams were exposed to ethanol during pregnancy. In summary, feeding of SPI to rat dams during pregnancy and lactation suppresses numbers of large ACF in their progeny, implying a long-term or permanent change elicited by the maternal diet. Moreover, results support the use of ACF as an intermediate endpoint for elucidating effects of SPI and its biochemical constituents in colon cancer prevention in rats.

Journal Article↗
PubMed2004

Proximity of residence to trichloroethylene-emitting sites and increased risk of offspring congenital heart defects among older women.

BACKGROUND: Previous studies suggest that trichloroethylene (TCE) is a selective cardiac teratogen. We tested the hypothesis that the odds of maternal residence close to TCE-emitting sites would be greater among infants with congenital heart defects (CHDs) than among infants without CHDs. METHODS: We conducted a case-control study of 4025 infants, identified from hospital and birth records, born from 1997 to 1999 to Milwaukee, Wisconsin mothers. A geographic information system was used to calculate distances between maternal residences and TCE sites. We used classification tree analysis to determine appropriate values by which to dichotomously categorize mothers by TCE exposure (exposed: residence within 1.32 miles of at least one TCE site) and age (older: >/=38 years), and logistic regression to test for CHD risk factors. RESULTS: The proportion of mothers who were both older and had presumed TCE exposure was more than six-fold greater among case infants than among control infants (3.3% [8/245] versus 0.5% [19/3780]). When adjusted for other variables, CHD risk was over three-fold greater among infants of older, exposed mothers compared to infants of older, nonexposed mothers (adjusted OR, 3.2; 95% CI, 1.2-8.7). Older maternal age, alcohol use, chronic hypertension, and preexisting diabetes were each associated with CHDs (adjusted ORs, 1.9, 2.1, 2.8, 4.1; 95% CIs, 1.1-3.5, 1.1-4.2, 1.2-6.7, 1.5-11.2, respectively), but residence close to TCE sites alone was not. CONCLUSIONS: Our findings suggest that maternal age and TCE exposure interact to increase CHD risk, although the mechanism by which this occurs is unknown. A prospective study is underway to confirm this finding.

Adult↗
PubMed2004

Validation of a noninvasive blood pressure monitoring device in normotensive and hypertensive pediatric intensive care patients.

OBJECTIVE: To evaluate the performance and to define limitations of a noninvasive blood pressure monitoring device in the critically ill pediatric population. METHOD: Patients were included in the study if they were admitted to the Pediatric Intensive Care Unit, were between the ages of 1 month and 18 years with wrist circumferences of > or =10 cm, and had an indwelling arterial line. Patients were excluded if their systolic blood pressure differed by > or =7.5% between their upper extremities. The measurements were collected simultaneously with those from an arterial line by a computer interfaced with the noninvasive blood pressure monitoring system and the patient's monitor. Heart rates were calculated from the recorded pulse waveforms of the arterial lines. Comparison analyses were performed via bias and precision plots of the blood pressure and heart rate data in addition to calculation of Pearson's correlation coefficients and concordance correlation coefficients. As a nonparametric method of comparison, the proportion of measurements that differed by greater than 10% was calculated. Results. Blood pressures and heart rates of 20 patients between the ages of 12 months and 17 years were monitored by a noninvasive blood pressure monitor for 30 min per patient. This data collection resulted in 2015 data points for each blood pressure and heart rate for comparison of methods. Concordance correlation coefficients were the following: systolic blood pressure, 0.93; diastolic blood pressure, 0.93; mean blood pressure, 0.94; and heart rate, 0.85. CONCLUSIONS: The noninvasive blood pressure monitor is capable of producing an accurate blood pressure measurement every 12-15 heartbeats in addition to providing a pulse waveform and digital display of the heart rate. Our study showed good agreement between the methods in the normotensive and hypertensive critically ill pediatric population with a wrist circumference limitation defined at > or =11 cm.

Adolescent↗
PubMed2004

Characteristics of children with asthma who are enrolled in a Head Start program.

BACKGROUND: Asthma is an increasing public health concern that disproportionally affects children. In 1998, the Centers for Disease Control identified children aged 0 to 4 years as the "driving force" behind climbing rates of asthma-related emergency department visits and hospitalizations. Despite the significant asthma burden in preschool children, few studies characterize this population. OBJECTIVE: This study identifies and characterizes children at risk for asthma who are enrolled in a local Head Start program. METHODS: Caregivers of 368 children aged 3 to 5 years who were identified by using an asthma survey were recruited. Data were collected on demographics, health care use and access, medication use, symptoms, and trigger exposure. Exposure to tobacco smoke was determined by urinary cotinine and allergen sensitization by skin prick test. RESULTS: At baseline, 64% of the children had more than 1 emergency department visit for asthma in their lifetime, whereas 31% had more than 1 visit in the previous 6 months. Caretakers reported smoking in 37% of households with cotinine exceeding 20 ng/mg in 27% of the sample. Twenty-one percent reported symptoms consistent with intermittent asthma, and 79% reported symptoms consistent with persistent asthma. Forty-five percent of the children reported nighttime symptoms more than 1 night per week. Seventy-one percent had positive test results for more than 1 allergen, and 42% had positive test results for more than 3 allergens. Only 32% of children with persistent asthma had both rescue and controller medications. CONCLUSION: Children with asthma enrolled in a Head Start program have significant environmental tobacco smoke exposure, are highly atopic and symptomatic, and do not receive appropriate medication treatment. Overall, children in the study had poor asthma control. This high-risk group could benefit from case management programs.

Black or African American↗
PubMed2004

Hospital survival of very-low-birth-weight neonates from 1977 to 2000.

OBJECTIVE: To determine patterns of survival for very low birth weight (VLBW, birth weight 501 to 1500 g) neonates over 23 years. STUDY DESIGN: Data for 4873 VLBW neonates born from 1977 to 2000 were divided into five epochs. The primary outcome was survival to hospital discharge. Birth weight-specific survival rates were estimated by race and gender for each epoch. Presence of comorbidities and congenital anomalies, delivery mode, and provision of artificial ventilation were investigated to determine whether they could explain observed survival patterns. RESULTS: From 1977 to 1995, survival increased from 50.2% to 81.0% as the proportion of VLBW neonates receiving artificial ventilation rose from 59.0% to 80.9%. Survival was unchanged between 1990 to 1995 and 1996 to 2000. Black females maintained a survival advantage over the entire study period. Survival improved for neonates with congenital anomalies over time, but had little impact on race/gender survival patterns. Survival patterns also could not be explained by comorbidity status, delivery mode, or access to artificial ventilation. CONCLUSION: The survival advantage of VLBW black females persists and remains unexplained.

Congenital Abnormalities↗
PubMed2004

Household food insecurity is associated with adult health status.

The prevalence of household food security, which reflects adequacy and stability of the food supply, has been measured periodically in the United States and occasionally in high-risk groups or specific regions. Despite a plausible biological mechanism to suggest negative health outcomes of food insecurity, this relation has not been adequately evaluated. This study was conducted in the Lower Mississippi Delta region to examine the association between household food insecurity and self-reported health status in adults. A two-stage stratified cluster sample representative of the population in 36 counties in the Delta region of Arkansas, Louisiana, and Mississippi was selected using list-assisted random digit dialing telephone methodology. After households were selected and screened, a randomly selected adult was interviewed within each sampled household. Data were collected to measure food security status and self-reported mental, physical, and general health status, using the U.S. Food Security Survey Module and the Short Form 12-item Health Survey (SF-12). Data were reported on a sample of 1488 households. Adults in food-insecure households were significantly more likely to rate their health as poor/fair and scored significantly lower on the physical and mental health scales of the SF-12. In regression models controlling for income, gender, and ethnicity, the interaction between food insecurity status and race was a significant predictor of fair/poor health and lower scores on physical and mental health. Household food insecurity is associated with poorer self-reported health status of adults in this rural, high-risk sample in the Lower Mississippi Delta.

Adult↗
PubMed2004

Alcohol dehydrogenase 2*3 affects alterations in offspring facial morphology associated with maternal ethanol intake in pregnancy.

BACKGROUND: Ethanol intake during pregnancy alters offspring facial morphology. However, significant variation that may be due to genetic diversity in ethanol metabolizing enzymes occurs. The alcohol dehydrogenase 1B*3 (ADH1B*3) allele is protective for offspring developmental outcome after maternal alcohol drinking in pregnancy and may explain the spectrum of facial morphology. METHODS: Faces of infants with known ADH1B genotype, whose mothers' ADH1B genotypes and ethanol intake were determined during pregnancy, were photographed using uniform procedures. Photographs were scanned and the inner canthal distance, palpebral fissure length, and distance from the bridge of the nose to the bottom of the upper lip were measured by an investigator who was blinded to genotype and ethanol exposure. RESULTS: Among 247 photographed infants, each facial measurement varied >2-fold. Median absolute ethanol daily intake was 0.5 oz among mothers who reported drinking in the periconceptional period (N = 173) and 0.17 oz among mothers who reported drinking before the first prenatal visit (N = 62). Controlling for the amount of maternal ethanol intake just before the first prenatal visit and infant sex, the three-way interaction among the absence of a maternal and offspring ADH1B*3 allele and the presence of ethanol consumption just before the first prenatal visit was associated with smaller facial measurements (p = 0.002, MANCOVA). CONCLUSIONS: These are the first observations of a significant gene-environment interaction explaining variation in facial morphology associated with ethanol use in pregnancy. This positive effect of ADH1B*3 is consistent with its known positive effect on offspring birth weight and developmental outcome after in utero ethanol exposure.

Adolescent↗
PubMed2003

Treatment-seeking inpatient cocaine abusers show hypothalamic dysregulation of both basal prolactin and cortisol secretion.

Cocaine causes neuroendocrine aberrations in cocaine abusers with pituitary stress hormone secretion providing a window to the stress system in the brain. Substance abusers and control participants were hormonally profiled for 3 weeks. Abusers showed significant basal elevations in prolactin in week 1 with normalization over the 3 weeks. No differences in prolactin secretion were seen with either thyrotropin-releasing hormone stimulation or L-dopa suppression testing. Basal afternoon cortisol secretion was significantly elevated during weeks 1 and 2 comparing abusers to controls. Elevated afternoon cortisol secretion is a sensitive indicator of central stress activation. These results point to the hypothalamus, not the pituitary gland, as being primarily altered in cocaine withdrawal. The data demonstrate that both the dopamine-prolactin and hypothalamic-pituitary-adrenal (HPA) axes are affected during cocaine cessation. As medications are developed to modulate activation of a dysfunctional stress system, future therapeutic studies of substance abuse, withdrawal, craving and relapse should employ more sophisticated tests of hypothalamic pituitary function, especially the HPA axis, as this information may be a guide in the diagnosis and predict clinical responses.

Adult↗