Colleen Azen - Academia.edu (original) (raw)

Papers by Colleen Azen

Journal of the American Dietetic Association

Dietary intakes and blood phenylalanine levels of 125 10-year-old children with PKU are reported.... more Dietary intakes and blood phenylalanine levels of 125 10-year-old children with PKU are reported. Of those patients, 59 discontinued the special diet at 6 years, 16 discontinued at 8 years, 5 discontinued at 6 years but returned to the diet at 8 1/2 years, and 45 continued the diet to 10 years. Phenylalanine intake was determined by 2-day diet records. Blood phenylalanine concentrations revealed a lack of clear distinction between the diet groups; therefore, regression analysis was performed on the group as a whole. The analyses revealed significant relationships between blood phenylalanine levels from ages 6 to 10 years and each of the cognitive outcome variables, after the influences of parental IQ and the age at which treatment was initiated were controlled for. Intelligence test scores were also related to phenylalanine levels between ages 3 1/2 and 5 1/2 years. The findings suggest that dietary restriction of phenylalanine should continue in patients with PKU through at least 10 years of age.

PEDIATRICS

Objective. The Maternal PKU Collaborative Study (MPKUCS) was initiated in 1984 by the National In... more Objective. The Maternal PKU Collaborative Study (MPKUCS) was initiated in 1984 by the National Institute of Child Health and Human Development (NICHD). The purpose was to assess the efficacy of dietary restriction of phenylalanine in reducing morbidity in offspring of women with hyperphenylalaninemia (HPA). A contract was awarded to Childrens Hospital Los Angeles as the Coordinating Center to provide implementation of the research protocol, data collection, and analysis.

Molecular Genetics and Metabolism

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 28, 2015

The Clinical and Functional Translation of CFTR project (CFTR2) classified some cystic fibrosis t... more The Clinical and Functional Translation of CFTR project (CFTR2) classified some cystic fibrosis transmembrane conductance regulator (CFTR) gene variants as non-cystic fibrosis (CF)-causing. To evaluate this, the clinical status of children carrying these mutations was examined. We analyzed CF disease-defining variables over 2-6 years in two groups of California CF screen- positive neonates born from 2007 to 2011: (1) children with two CF-causing variants and (2) children with one CF-causing and one non-CF-causing variant, as defined by CFTR2. Children carrying non-CF-causing variants had significantly higher birth weight, lower immunoreactive trypsinogen and sweat chloride values, higher first year growth curves, and a lower rate of persistent Pseudomonas aeruginosa colonization compared to children with two CF-causing variants. The outcomes in children 2-6 years of age with the L997F, G576A, R1162L, V754M, R668C, R31C, and S1235R variants are consistent with the CFTR2 non-CF-causin...

The Journal of pediatrics, 2014

To determine whether additional supplementation of tryptophan (Trp) and tyrosine (Tyr) improve se... more To determine whether additional supplementation of tryptophan (Trp) and tyrosine (Tyr) improve serotonin and dopamine metabolism in individuals with phenylketonuria treated with large neutral amino acid (LNAA) tablets. Ten adult individuals with phenylketonuria participated in a randomized, double-blind, placebo-controlled cross-over study consisting of three 3-week phases: washout, treatment with LNAA tablets plus supplementation with either Trp and Tyr tablets or placebo, and LNAA tablets plus the alternate supplementation. An overnight protocol to measure blood melatonin, a serotonin metabolite in the pinealocytes, and urine 6-sulfatoxymelatonin and dopamine in first-void urine specimens was conducted after each phase. Serum melatonin and urine 6-sulfatoxymelatonin and dopamine levels were increased in the LNAA phase (LNAA plus placebo) compared with the washout phase. Serum melatonin and urine 6-sulfatoxymelatonin were not increased in the active phase (LNAA plus Trp + Tyr) comp...

Journal of inherited metabolic disease, 2002

During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a c... more During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjec...

The American journal of clinical nutrition, 1999

Low cobalamin concentrations and mild hyperhomocysteinemia are common in the elderly but ethnic d... more Low cobalamin concentrations and mild hyperhomocysteinemia are common in the elderly but ethnic differences have not been defined. Our objective was to determine the demographic characteristics of cobalamin deficiency in the elderly and its role in their hyperhomocysteinemia. We measured serum cobalamin, total homocysteine (Hcys), and methylmalonic acid (MMA) concentrations in 725 subjects >60 y old, and folate concentrations in 520 subjects. After exclusion of subjects taking cobalamin supplements or with renal insufficiency, high prevalences of low cobalamin (11.8%), high MMA (16.6%), and high Hcys (26.1%) concentrations were seen. Most cobalamin concentrations <140 pmol/L appeared to reflect deficiency because 78. 3% of them were accompanied by abnormal metabolites. Subjects with cobalamin concentrations of 140-258 pmol/L had significantly fewer metabolic abnormalities. A low cobalamin concentration and renal insufficiency were the strongest predictors of abnormal Hcys conc...

Journal of inherited metabolic disease, 1998

This study assesses the impact of prenatal and postnatal factors in maternal phenylketonuria (PKU... more This study assesses the impact of prenatal and postnatal factors in maternal phenylketonuria (PKU). The Dubowitz Neurological Assessment of the Preterm and Full-term Newborn Infant was administered within the first 8 days of life to 56 offspring of women with PKU and 45 controls. Follow-up testing of the maternal PKU offspring at age 1 year consisted of the Bayley Scales of Infant Development and the Receptive-Expressive Emergent Language Scale (REEL). In addition, the Home Observation for Measurement of the Environment (HOME Scale) was given. Birth weight was lower (z = 2.0, p = 0.045), birth length was lower (z = 2.1, p = 0.03) and birth head circumference was smaller (z = 3.5, p = 0.0005) in the maternal PKU offspring than in the control infants. Examiners rated 29% of the maternal PKU offspring and 9% of the control infants abnormal (Fisher's exact test, p = 0.01). At 1 year of age, 19% of the maternal PKU offspring attained a Bayley Developmental Quotient (DQ) and a score o...

The American journal of clinical nutrition, 1996

Serum cobalamin concentrations are frequently low in the elderly but the cause is often not appar... more Serum cobalamin concentrations are frequently low in the elderly but the cause is often not apparent. Because oral contraceptives have been associated with low cobalamin concentrations in young women, we compared hormone use with cobalamin status in elderly women to determine whether it could account for their unexplained low cobalamin concentrations. Thirty-eight of the 111 women had abnormal cobalamin status (defined by low cobalamin, elevated methylmalonic acid, and/or elevated homocysteine concentrations) and 73 had normal status. There was no difference in hormone use between the two groups: 7 (18.4%) of the 38 cobalamin-deficient subjects used estrogens compared with 20 (27.4%) of the 73 control subjects. No differences in hormone use were apparent either when analysis was confined to abnormal serum cobalamin concentrations alone. Similarly, the 27 women taking hormones and the 84 women not taking hormones did not have significantly different serum cobalamin or serum total hom...

CNS Spectrums, 2014

To evaluate the effects of tetrahydrobiopterin (BH4) on maladaptive behavior in patients with phe... more To evaluate the effects of tetrahydrobiopterin (BH4) on maladaptive behavior in patients with phenylketonuria (PKU). In an effort to determine if BH4 has any effects on the central nervous system, we studied 10 individuals with PKU and measurable maladaptive behaviors for 1 year. Behavioral assessments using the Vineland Adaptive Behavior Scales-Second Edition and a PKU Behavior Checklist were obtained at baseline, 6 months, and at the end of the study. Biochemical measures including plasma amino acids were obtained quarterly, and phenylalanine (Phe) and tyrosine (Tyr) were obtained monthly. Out of the 10 subjects, 2 were responders to BH4, as determined by a blood Phe reduction &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;30%. While blood Phe in the 8 nonresponders did not change significantly throughout the study, their Tyr levels were significantly higher at 6 months (p=0.012), but not at 12 months (p=0.23). By the end of the study, 8 subjects exhibited fewer maladaptive behaviors on the components of the Vineland Maladaptive Behavior Index, and all 10 had lower total scores on the PKU Behavior Checklist. These findings suggest that there may be direct effects of BH4 on the central nervous system, independent of lowering blood Phe.

SpringerPlus, 2013

Optimal care for breast cancer patients undergoing aromatase inhibitor (AI) treatment is ensured ... more Optimal care for breast cancer patients undergoing aromatase inhibitor (AI) treatment is ensured when estradiol (E2) levels are adequately suppressed. To assess treatment efficacy accurately, it is important to measure the serum E2 levels using a well validated assay method with high sensitivity and specificity. This translates into the urgent need to evaluate various E2 immunoassay kits, which are frequently used in hospital settings to measure E2 serum levels in patients undergoing AI treatment, so clinicians obtain accurate and reliable measurements allowing appropriate clinical decision making. Our objective was to evaluate the performance of different commercially available and commonly used E2 immunoassay kits regarding measurement of E2 levels in the serum of postmenopausal breast cancer patients treated with AIs, in comparison to a highly accurate and reliable mass spectrometry assay. Clinical and demographic data were obtained from 77 postmenopausal breast cancer patients w...

Pediatrics, 2003

The aim of the present study was to examine to what extent maternal and offspring phenylalanine h... more The aim of the present study was to examine to what extent maternal and offspring phenylalanine hydroxylase (PAH) genotypes in conjunction with maternal IQ and dietary control during pregnancy are related to cognitive development in offspring of women with phenylketonuria (PKU). PAH gene mutations were determined in 196 maternal PKU subjects and their offspring. The women were grouped according to PAH genotype, which predicts the metabolic phenotype (severe PKU, mild PKU, and mild hyperphenylalaninemia [MHP]). IQ was determined in both the mothers (Wechsler Adult Intelligence Scale-Revised at >18 years) and their children (Wechsler Intelligence Scale for Children-Revised at > or = 6-7 years of age). According to PAH genotypes, 62% of the women exhibited severe PKU, 19% exhibited mild PKU, and 19% exhibited MHP. Maternal IQ increased, and the assigned phenylalanine (Phe) levels decreased with decreasing severity of PAH genotype. In offspring of mild maternal PKU, multiple regre...

Journal of Vascular Nursing, 2014

The standard of care is to obtain a noninvasive blood pressure (NIBP) measurement from the right ... more The standard of care is to obtain a noninvasive blood pressure (NIBP) measurement from the right upper arm. However, in the pediatric population it is common practice to take blood pressure (BP) measurements from the calf/upper ankle. Nurses commonly take calf NIBPs for many reasons, but there is little evidence to support calf BPs as a reliable site for BP measurement. Furthermore, there is conflicting evidence. Some studies suggest no difference between the calf and the upper arm BPs, whereas others conclude great variability between the two. The purpose of this study was to demonstrate the reliability of calf BPs, by showing no difference between brachial and calf BP measurements in neonates and infants #1 year old. From July 2008 to December 2008, a convenience sample of 52 subjects admitted to the Neonatal and Infant Critical Care Unit were enrolled into the study. Limb selection was not randomized. Three BPs were taken from the arm and 3 BPs were taken from the calf. Data were analyzed using a mixed analysis of variance (P = 0.05). The difference was not significant for systolic (P = 0.6159) or mean BP (P = 0.1298), but it was significant for diastolic (P = 0.0263). The authors concluded that these results support the current practice of bedside nurses and contribute to the limited knowledge on this topic. Because there was a difference in the diastolic BPs, further investigation is needed.

Pediatric Cardiology, 2014

Few studies have examined the role that small for gestational age (SGA) status plays in postopera... more Few studies have examined the role that small for gestational age (SGA) status plays in postoperative outcomes for low-birth-weight (LBW) infants with congenital heart disease (CHD). This study aimed to examine the effect of SGA status, gestational and chronologic age, and weight on differences in morbidities and mortalities during the immediate postoperative hospitalization period. The charts of infants with CHD weighing less than 2.5 kg who underwent operative repair during the neonatal period between 2004 and 2011 were reviewed. Infants with an isolated patent ductus arteriosus were excluded from the study. Data on hospital morbidities and mortality before discharge were collected. The study identified 136 LBW infants with a diagnosis of CHD. Among the 74 infants who underwent surgery and had complete chart records, the SGA infants had a higher gestational age at birth (36.8 vs. 32.3 weeks; p \ 0.0001). The SGA and non-SGA infants did not differ in terms of survival to discharge or immediate postoperative outcomes. A lower weight at surgery was significantly associated with an increased risk of postoperative infection. In contradistinction, an older postnatal age at surgery was associated with an increased risk of preoperative infection (p \ 0.0001). Additionally, lower gestational age at birth was associated with home oxygen use, higher tracheostomy rates, and discharge with a gastrostomy tube. Small for gestational age status played no protective role in the outcome for LBW infants after primary surgery for CHD. A weight of 2.4 kg or greater at the time of surgery was associated with lower rates of postoperative infections. Greater duration of time between birth and surgery was associated with a greater risk of preoperative infection. A gestational age of 32 weeks or more at birth was associated with decreased morbidities, which could influence obstetric management.

Journal of the Society for Gynecologic Investigation, 1998

PEDIATRICS, 1999

To examine the relationship of phenylalanine hydroxylase (PAH) genotypes to biochemical phenotype... more To examine the relationship of phenylalanine hydroxylase (PAH) genotypes to biochemical phenotype and cognitive development in maternal phenylketonuria (PKU). PAH gene mutations were examined in 222 hyperphenylalaninemic females enrolled in the Maternal PKU Collaborative Study (MPKUCS). A total of 84 different mutations were detected, and complete genotype was obtained in 199 individuals. Based on previous knowledge about mutation-phenotype associations, 78 of the mutations could be assigned to one of four classes of severity (severe PKU, moderate PKU, mild PKU, and mild hyperphenylalaninemia [MHP]). Then, 189 MPKUCS subjects were grouped according to the various combinations of mutation classifications. The sample sizes were large enough for statistical testing in four groups with at least one mutation that completely abolishes enzyme activity. These patients are considered functionally hemizygous. The biochemical phenotype predicted from the genotype in functionally hemizygous patients was related significantly to the assigned phenylalanine level. Cognitive performance (IQ) was also significantly related to genotype. The IQ of PAH-deficient mothers with a severe PKU mutation in combination with a MHP mutation or a mild PKU mutation was 99 and 96, respectively, whereas the IQ of PKU mothers with two severe PKU mutations or with one severe and one moderate PKU mutation was 83 and 84, respectively. Of the patients with PKU, 92% had been treated during childhood. Those who were untreated or treated late had lower than average IQ scores for their group of mutation combinations. Females with moderate or mild PKU who were treated early and treated for >6 years showed IQ scores 10 points above average for their group. The reproductive outcome in maternal phenylketonuria is dependent on prenatal metabolic control and postnatal environmental circumstances. Both factors depend on the intellectual resources of the mother with PKU. The significant relationship among genotype, biochemical phenotype, and cognitive performance observed in the present study is of importance for the development of an optimal strategy for future treatment of females with PKU who plan pregnancy.

Obstetrical & Gynecological Survey, 1994

ABSTRACT

Obesity, 2010

Ghrelin and peptide YY (PYY) stimulate hunger and satiety, respectively. The physiology of these ... more Ghrelin and peptide YY (PYY) stimulate hunger and satiety, respectively. The physiology of these hormones during normal meal intake remains unclear. The present study was designed to compare the responses of these two hormones to meal intake between lean and obese Hispanic adolescents. Ten obese and seven lean Hispanic youth, aged 11-14 yr, consumed two mixed meals, one small and one large, during which plasma measurements of active and total ghrelin and total PYY were obtained. Obese subjects tended to consume more calories during the small meal than lean subjects, although this did not reach statistical significance. Intake of the small meal significantly suppressed active ghrelin and stimulated PYY levels in the lean subjects, and these changes were further accentuated by the large meals. In obese subjects, the suppression of active ghrelin and stimulation of PYY by caloric intake were blunted. Interestingly, a paradoxical stimulation of active ghrelin levels was noted during the small meals in both lean and obese subjects. This stimulation was not seen during the larger meals in lean subjects, but remained present in the obese subjects. Thus, mealrelated changes in active ghrelin and PYY are blunted in obese as compared to lean Hispanic subjects. This blunting could contribute to the development or worsening of obesity.

Molecular Genetics and Metabolism, 2000

Maternal phenylketonuria (PKU) syndrome results in multiple congenital anomalies in the offspring... more Maternal phenylketonuria (PKU) syndrome results in multiple congenital anomalies in the offspring, usually consisting of microcephaly, intrauterine growth retardation, dysmorphology, and congenital heart disease. Pregnancies treated preconceptionally with a phenylalanine-restricted diet and control of maternal blood phenylalanine levels within the recommended range result in normal offspring. However, in this 15-year study, several significant factors resulted in microcephaly in 27% of the offspring, and 7% exhibited serious congenital heart disease. These results occurred chiefly in women with mean IQ scores of 83 associated with low socioeconomic status and decreased educational achievement. Another important factor associated with suboptimal control of blood phenylalanine levels during pregnancy was the fact that most pregnancies were not carefully planned and occurred in women off dietary treatment with phenylalanine-restricted products. These results indicate that greater effort must be developed to assist women with PKU in remaining on diet during their reproductive years. It appears that continued adherence to the diet, resulting in normal maternal intelligence, is an important contribution to improved fetal development.

Mental Retardation and Developmental Disabilities Research Reviews, 1999

The incidence of congenital heart disease was found to be 7.5% from 414 offspring born to women w... more The incidence of congenital heart disease was found to be 7.5% from 414 offspring born to women with phenylketonuria in the National Collaborative Study for Maternal Phenylketonuria (MPKU). Nutrient intake was studied in a subset of 22 offspring with congenital heart disease. The infants with congenital heart disease were divided into two groups, those whose mothers consumed greater than 50% of the recommended dietary allowance (RDA) for protein and those who had consumed less than 50% of the RDA for protein during the pregnancy. The subjects were further categorized based on the blood phenylalanine of the mother of less than or greater than 10 mg/dl during the first eight weeks of gestation. All of the women who produced offspring with congenital heart disease had blood phenylalanine concentrations greater than 10 mg/dl during the first eight weeks of gestation. A Fisher's Exact test showed that there were a significantly greater number of offspring born to women who had low protein intake (p Ͼ 0.0013). Stepwise analysis indicated first trimester variables that discriminate infants with congenital heart disease. These variables included dietary intake of protein, blood phenylalanine from weeks 4-8 of gestation, dietary fat intake, the initial blood phenylalanine concentration, and intake of vitamin B 12 . An Odds ratio showed that intake of vitamin B 12 was a predictor of congenital heart disease among treated women with PKU.