Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children.

BACKGROUND: Knowledge regarding genetic influences on eating behaviours is expanding; yet less is known regarding contributions of epigenetic variation to appetitive traits and body mass index (BMI) in children. OBJECTIVE: The purpose of this study was to explore relationships between methylation at differentially methylated regions (DMRs) of imprinted genes (insulin-like growth factor 2/H19 and Delta-like, Drosophila, homolog 1/maternally expressed gene 3) using DNA extracted from umbilical cord blood leucocytes, two genetically influenced appetitive traits (food responsiveness and satiety responsiveness) and BMI. METHODS: Data were obtained from participants (N = 317; mean age = 3.6 years; SD = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were implemented to investigate the associations between DMRs of imprinted genes and BMI, and test whether this association was mediated by appetitive traits and birthweight and moderated by sex. RESULTS: Appetitive traits and birthweight did not mediate the relationship between methylation at DMRs. Increased insulin-like growth factor 2 DMR methylation was associated with higher satiety responsiveness. Higher satiety responsiveness was associated with lower BMI. Associations between methylation at DMRs, appetitive traits and BMI differed by sex. CONCLUSIONS: This is one of the first studies to demonstrate associations between epigenetic variation established prior to birth with appetitive traits and BMI in children, providing support for the need to uncover genetic and epigenetic mechanisms for appetitive traits predisposing some individuals to obesity.

Childhood somatic complaints predict generalized anxiety and depressive disorders during young adulthood in a community sample.

BACKGROUND: Children with somatic complaints are at increased risk for emotional disorders during childhood. Whether this elevated risk extends into young adulthood - and to which specific disorders - has rarely been tested with long-term prospective-longitudinal community samples. Here we test whether frequent and recurring stomach aches, headaches, and muscle aches during childhood predict emotional disorders in adulthood after accounting for childhood psychiatric and physical health status and psychosocial adversity. METHOD: The Great Smoky Mountains Study is a community representative sample with 1420 participants. Children/adolescents were assessed 4-7 times between ages 9-16 years. They were assessed again up to three times between ages 19-26 years. Childhood somatic complaints were coded when subjects or their parents reported frequent and recurrent headaches, stomach aches, or muscular/joint aches at some point when children were aged 9-16 years. Psychiatric disorders were assessed with the Child and Adolescent Psychiatric Assessment and the Young Adult Psychiatric Assessment. RESULTS: Frequent and recurrent somatic complaints in childhood predicted adulthood emotional disorders. After controlling for potential confounders, predictions from childhood somatic complaints were specific to later depression and generalized anxiety disorder. Long-term predictions did not differ by sex. Somatic complaints that persisted across developmental periods were associated with the highest risk for young adult emotional distress disorders. CONCLUSIONS: Children from the community with frequent and recurrent physical distress are at substantially increased risk for emotional distress disorders during young adulthood. Preventions and interventions for somatic complaints could help alleviate this risk.

The expression of cytokines and chemokines in the blood of patients with severe weight loss from anorexia nervosa: an exploratory study.

Anorexia nervosa (AN) is a serious, potentially life-threatening disorder characterized by severe weight loss, dysregulated eating, and often excessive exercise. While psychiatric illnesses such as depression are associated with increased levels of pro-inflammatory mediators, evidence for such disturbances in patients with AN has been less clear. In an exploratory study of possible disturbances in immune responses in AN, we assayed a panel of cytokines and chemokines in the blood of patients undergoing inpatient treatment, testing the hypothesis that metabolic disturbances in this disease would lead to a pattern of immune disturbances distinct from that of other psychiatric diseases. For this purpose, we evaluated patients by the Beck Depression Inventory-II (BDI-II) and the Eating Disorders Examination-Questionnaire and assessed cytokines and chemokines by enzyme-linked immunosorbent assays. Patients reported a moderate level of depression (mean BDI-II = 22.6) but exhibited few immunologic abnormalities of the kind associated with major depressive disorder [e.g., increased interleukin (IL)-6]; RANTES showed the most frequent elevations and was increased in 4 of the patients studied. Together, these findings suggest that features of AN such as loss of adipose tissue and excessive exercise may attenuate cytokine production and thus modulate the experience of illness that impacts on core features of disease.

The effect of the home environment on physical activity and dietary intake in preschool children.

BACKGROUND: The effects of the home environment on child health behaviors related to obesity are unclear. PURPOSE: To examine the role of the home physical activity (PA) and food environment on corresponding outcomes in young children, and assess maternal education/work status as a moderator. METHODS: Overweight or obese mothers reported on the home PA and food environment (accessibility, role modeling and parental policies). Outcomes included child moderate-vigorous PA (MVPA) and sedentary time derived from accelerometer data and two dietary factors ('junk' and healthy food intake scores) based on factor analysis of mother-reported food intake. Linear regression models assessed the net effect (controlling for child demographics, study arm, supplemental time point, maternal education/work status, child body mass index and accelerometer wear time (for PA outcomes)) of the home environment on the outcomes and moderation by maternal education/work status. Data were collected in North Carolina from 2007 to 2011. RESULTS: Parental policies supporting PA increased MVPA time, and limiting access to unhealthy foods increased the healthy food intake score. Role modeling of healthy eating behaviors increased the healthy food intake score among children of mothers with no college education. Among children of mothers with no college education and not working, limiting access to unhealthy foods and role modeling reduced 'junk' food intake scores whereas parental policies supporting family meals increased 'junk' food intake scores. CONCLUSIONS: To promote MVPA, parental policies supporting child PA are warranted. Limited access to unhealthy foods and role modeling of healthy eating may improve the quality of the child's food intake.

Classification of eating disturbance in children and adolescents: proposed changes for the DSM-V.

Childhood and adolescence are critical periods of neural development and physical growth. The malnutrition and related medical complications resulting from eating disorders such as anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified may have more severe and potentially more protracted consequences during youth than during other age periods. The consensus opinion of an international workgroup of experts on the diagnosis and treatment of child and adolescent eating disorders is that (a) lower and more developmentally sensitive thresholds of symptom severity (e.g. lower frequency of purging behaviours, significant deviations from growth curves as indicators of clinical severity) be used as diagnostic boundaries for children and adolescents, (b) behavioural indicators of psychological features of eating disorders be considered even in the absence of direct self-report of such symptoms and (c) multiple informants (e.g. parents) be used to ascertain symptom profiles. Collectively, these recommendations will permit earlier identification and intervention to prevent the exacerbation of eating disorder symptoms.

Classification of child and adolescent eating disturbances. Workgroup for Classification of Eating Disorders in Children and Adolescents (WCEDCA).

OBJECTIVE: : The purpose of this article is to summarize major conceptual and clinical variables related to age-appropriate and developmentally appropriate classification of eating problems and disorders in children and adolescents. METHOD: A review of current classifications and related literature in child development is provided. Problems with current classification schemes are identified and discussed. RESULTS: Current classifications are inadequate to address the clinical and research needs of children and adolescents with eating disturbances and disorders. CONCLUSION: A range of possible changes in classification strategies for eating disorders in children and adolescents are described.

A group parent-training program: a novel approach for eating disorder management.

OBJECTIVE: To describe the rationale, development, and preliminary acceptability of a Group Parent Training Program (GPT) as an alternative approach for the treatment of adolescent eating disorders. METHOD: Sixteen families participated in a 16-session group treatment. After four months, parents were administered a treatment satisfaction questionnaire. RESULTS: Parent response to the intervention was positive. All parents indicated GPT was essential for the management of their child, improved general parenting skills, improved their own self-care, and decreased the burden they experienced as a result of managing their child's illness. DISCUSSION: Given the magnitude of task demands placed on a family for the management of adolescent eating disorders, there is the need for the development of effective intervention strategies that ease the stress of illness management for parents. Preliminary satisfaction data from GPT are promising and argue for a more systematic test of this intervention.

Prenatal diagnosis of Shone's syndrome: parental counseling and clinical outcome.

OBJECTIVE: To describe a series of fetuses diagnosed as having Shone's syndrome, which includes four cardiac defects and for which there is a wide variety of clinical presentations, surgical treatments and outcomes, and to discuss the counseling strategy. METHODS: We reviewed retrospectively the records of four babies who were suspected prenatally to have Shone's syndrome. RESULTS: The mean age at diagnosis was 27.5 (range, 22-35) weeks. A small left ventricle, mitral and aortic annulus and ascending aorta were detected in three cases. In three fetuses there was an abnormal mitral valve apparatus and in two fetuses a sub-aortic membrane was detected. Coarctation of the aorta was an impending diagnosis in three babies. Following counseling, all parents decided to continue the pregnancy to term. Echocardiographic evaluation was performed soon after birth. The mean mitral valve annulus diameter was 8.2 (range, 7-10) mm, and that of the aortic valve annulus was 6 (range, 5-7) mm. The aortic valve was bicuspid in all babies with an additional sub-aortic membrane in two babies. Doppler ultrasound examination revealed high-velocity flow through the mitral valve in three babies; two of them had a parachute mitral valve. Coarctation repair was performed in two babies during the first week of life. One patient underwent mitral valvuloplasty followed by later mitral valve replacement. All patients were alive after a mean of 7.8 (range, 3.3-10.5) years' follow-up. CONCLUSION: When counseling families regarding fetal Shone's syndrome, it is important to emphasize the wide variety of clinical presentations and possible outcomes. Differentiation between hypoplastic left ventricle and Shone's complex is crucial and may influence the physician's attitude, the presentation of the case to the family and the family's final decision.

Psychosocial variables associated with binge eating in obese males and females.

OBJECTIVE: This study tested a psychosocial model of binge eating symptoms in obese men and women. Predictor variables included depression, dietary restraint, self-esteem, weight cycling, history of teasing, body dissatisfaction, and neuroticism. METHOD: Participants (N = 808) completed a packet of self-report questionnaires. RESULTS: Weight cycling, teasing about weight and shape, body dissatisfaction, negative affect, and dietary restraint comprised the best fitting models (original and cross-validation) for binge eating in women and men. These variables explained 61-72% of the variance in symptoms of binge eating in the samples of men and 70% of the variance in the samples of women. Although the male and female models were mostly similar, notable differences between them were found. DISCUSSION: The variables that comprise these etiological models should be considered in the development of prevention programs for obese binge eaters. Longitudinal studies, however, are needed to examine these etiological paths and to test for causal relationships.

The role of tissue plasminogen activator in the successful treatment of infected cardiac thrombus in children.

Infected cardiac thrombus is rare in children, with antibiotic or antifungal agents used as the first line of treatment. Persistence is an indication for surgical intervention. We describe two children who were treated successfully with a combination of antibiotic and antithrombotic agents. Use of antithrombotic agents promotes degeneration of fibrin, thus reducing the mass and facilitating the diffusion of the antibiotic and/or antifungal agents.

Body image assessment for obesity (BIA-O): development of a new procedure.

OBJECTIVE: A new measure of body image, named the body image assessment for obesity (BIA-O) was developed and tested for reliability and validity in a sample of 1,209 adult men and women. Separate BIA-O procedures were developed for men and women. Current, ideal and reasonable body image estimates of Caucasian and African-American men and women were compared. METHOD: Figural stimuli of males and females were developed for body sizes ranging from very thin to very obese in 18 increments. Participants selected figures that represented estimates of current, ideal and reasonable (a body size that could be maintained over time) body size. Some participants (n=641) also completed two measures of body dissatisfaction in a test of the validity of the BIA-O as a measure of body dissatisfaction. A sample of 77 participants was administered the BIA-O on two occasions to test the test-retest reliability of the BIA-O. RESULTS: The reliability of the BIA-O was supported by test-retest reliability coefficients which ranged from 0.65 to 0.93. Concurrent validity of the discrepancy between current and ideal and current and reasonable body size estimates was supported by positive correlations with two measures of body dissatisfaction. The BIA-O body size estimates of Caucasians and African-Americans, controlled for age and BMI, were compared. As BMI increased, Caucasian men and women were found to select larger current body size estimates in comparison to African-Americans. DISCUSSION: The reliability and validity of the BIA-O were supported. Greater body size dissatisfaction in obese Caucasians, relative to African-Americans of the same size, may be a function of biased estimates of current body size.

Maintenance of androdioecy in the freshwater shrimp, Eulimnadia texana: estimates of inbreeding depression in two populations.

Androdioecy is an uncommon form of reproduction in which males coexist with hermaphrodites. Androdioecy is thought to be difficult to evolve in species that regularly inbreed. The freshwater shrimp Eulimnadia texana has recently been described as both androdioecious and highly selfing and is thus anomalous. Inbreeding depression is one factor that may maintain males in these populations. Here we examine the extent of "late" inbreeding depression (after sexual maturity) in these clam shrimp using two tests: (1) comparing the fitness of shrimp varying in their levels of individual heterozygosity from two natural populations that differ in overall genetic diversity; and (2) specifically outcrossing and selfing shrimp from these same populations and comparing fitness of the resulting offspring. The effects of inbreeding differed within each population. In the more genetically diverse population, fecundity, size, and mortality were significantly reduced in inbred shrimp. In the less genetically diverse population, none of the fitness measures was significantly lowered in selfed shrimp. Combining estimates of early inbreeding depression from a previous study with current estimates of late inbreeding depression suggests that inbreeding depression is substantial (delta = 0.68) in the more diverse population and somewhat lower (delta = 0.50) in the less diverse population. However, given that males have higher mortality rates than hermaphrodites, neither estimate of inbreeding depression is large enough to account for the maintenance of males in either population by inbreeding depression alone. Thus, the stability of androdioecy in this system is likely only if hermaphrodites are unable to self-fertilize many of their own eggs when not mated to a male or if male mating success is generally high (or at least high when males are rare). Patterns of fitness responses in the two populations were consistent with the hypothesis that inbreeding depression is caused by partially recessive deleterious alleles, although a formal test of this hypothesis still needs to be conducted.

Duration of illness predicts outcome for bulimia nervosa: a long-term follow-up study.

OBJECTIVE: The purpose of this study was to investigate long-term outcome and prognosis in a bulimic and subthreshold bulimic sample. METHOD: In a follow-up study, 44 patients diagnosed with bulimia nervosa and subthreshold bulimia nervosa were contacted after an average follow-up period of 9 years. RESULTS: Results revealed that 72.7% (n = 32) of the participants were recovered at the time of follow-up. An investigation of prognostic variables showed that good outcome was associated with a shorter duration of illness, which was defined as the time between onset of symptoms and first treatment intervention. If participants were initially treated within the first few years of the illness, the probability of recovery was above 80%. However, if they were initially treated 15 years or more after the onset of the illness, the probability of recovery fell below 20%. DISCUSSION: This finding suggests that early identification of bulimia nervosa may be a very important factor in preventing a chronic eating disorder.

Successful non-surgical treatment of Candida tropicalis endocarditis with liposomal amphotericin-B (AmBisome).

Fungal endocarditis in children is most commonly a complication of palliative or curative surgery for congenital heart disease, rheumatic valvulitis and prolonged indwelling central venous and umbilical catheters. We describe here the case of a 3-y-old patient with chronic diarrhoea and prolonged total parenteral alimentation who developed severe C. tropicalis endocarditis and was treated successfully using a liposomal preparation of amphotericin-B (AmBisome) without surgical intervention.

Congenital dyserythropoietic anemia type I presenting as persistent pulmonary hypertension of the newborn.

Congenital dyserythropoietic anemia (CDA) is a rare group of inherited bone marrow disorders characterized by anemia with ineffective erythropoiesis. We report 3 siblings from a family known to have CDA type I who presented with persistent pulmonary hypertension of the newborn (PPHN). We suggest that the diagnosis of CDA type I should be considered in any neonate with PPHN and anemia.

Surgical management of tetralogy of Fallot in the first year of life.

BACKGROUND: The surgical approach to tetralogy of Fallot (TOF) continues to evolve and now many centers favor early repair for TOF. METHODS: Our experience includes 82 consecutive patients less than 1 year old with TOF (n = 74) and TOF with pulmonary atresia (n = 8) who were operated on between January 1992 and March 1998. Mean age at repair was 5.2 +/- 1.2 months and mean weight was 4.5 +/- 0.4 kg. Seven patients (anomalous left anterior descending artery [n = 1], pulmonary atresia with hypoplastic pulmonary arteries [n = 6]), underwent palliative procedures in the neonatal period followed by complete repair. Forty-nine patients (59%) were symptomatic (severe cyanosis or hypoxic spells), and 33 patients (41%) were asymptomatic. A combined transatrial-transpulmonary approach was employed in 28 patients (34%), and transannular patch or conduit for reconstruction of the right ventricular outflow tract (RVOT) was required in 54 patients (66%). The mean Nakata index was 160 +/- 25 mm2/m2. RESULTS: There were no hospital deaths. Mean post-repair peak right ventricular/systemic pressure ratio was 0.48 +/- 0.1. There were no late deaths or reoperations during a mean follow-up of 23 +/- 5 months. All patients are currently asymptomatic and in New York Heart Association class 1. Postoperative evaluation by two-dimensional and Doppler echocardiography or cardiac catheterization showed minimal pulmonary artery stenosis with a mean pressure gradient of 15 +/- 6 mm Hg across the RVOT. CONCLUSIONS: Our experience suggests that early repair of TOF can yield excellent results and initial palliation does not preclude early complete repair.

Acute dilated cardiomyopathy and central nervous system toxicity following propranolol intoxication.

OBJECTIVE: We report a case of a 16-year-old boy who developed central nervous system (CNS) depression and acute dilated cardiomyopathy following ingestion of 3200 mg of propranolol in a suicide attempt. Early echocardiographic findings were the only sign of cardiac toxicity. DESIGN: A case report. SETTING: Pediatric intensive care unit of a teaching hospital. RESULTS: This child developed significant acute dilated cardiomyopathy and severe CNS depression 2 hours after ingesting 3200 mg of propranolol. The child was treated with gastric lavage, activated charcoal, and mechanical ventilation. Following the echocardiographic findings, treatment with isoprenaline hydrochloride and glucagon were given intravenously. Echocardiographic examination 12 hours following treatment showed normal left ventricular size and function. No change in pulse rate or blood pressure was reported on admission and during his hospitalization. DISCUSSION: In the early stages of propranolol and other lipophilic beta-blocker intoxication, severe CNS depression can develop in the absence of clinical signs of cardiac toxicity. Early echocardiographic evaluation is important and may prevent delay in diagnosis and treatment of cardiac toxicity.

Successful radiofrequency ablation in a 3-month-old baby with permanent junctional reciprocating tachycardia: a new era in the treatment of incessant life-threatening arrhythmias in infants.

We report our experience in treating a 3-month-old baby with accessory atrioventricular pathway by radiofrequency (RF) ablation. The baby was discovered to have incessant supraventricular tachycardia at 4 weeks of age. At that time, two-dimensional echocardiography showed dilated cardiomyopathy. Multiple direct current shocks and multipharmaceutical treatment failed to restore sinus rhythm. Electrophysiology study showed the presence of posteroseptal accessory pathway. Immediately after delivery of two RF pulses, successful ablation of the accessory pathway and complete atrioventricular (AV) block with good junctional escape rhythm were observed. Normal rhythm and AV conduction subsequently returned and all medical treatment was discontinued. To our best knowledge, this is the first case of successful treatment with RF ablation in early infancy.

Abnormal coronary perfusion in experimental scorpion envenomation.

Perfusion defects and left ventricular dilation after experimental scorpion envenomation were evaluated in five dogs. Left Left ventricular dilation was observed in three dogs and right ventricular dilation in one other, in scans immediately after envenomation. Perfusion defects were inferred from scans in four dogs. The data are strongly suggestive of coronary hypoperfusion, and the mechanics of abnormal coronary flow after scorpion envenomation are discussed.

Cardiac abnormalities in the Bardet-Biedl syndrome: echocardiographic studies of 22 patients.

The Bardet-Biedl syndrome is an autosomal recessive disorder of polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and renal involvement. A high incidence of congenital and acquired heart disease was reported in the former "Laurence-Moon-Biedl-Bardet" syndrome. However, since the establishment of the Bardet-Biedl syndrome as a separate clinical entity, cardiac involvement has not been evaluated in this disorder. We have performed echocardiographic studies on 22 patients with the Bardet-Biedl syndrome from three extended, highly inbred Bedouin families. In addition to previously reported congenital heart defects we have observed hypertrophy of the interventricular septum and dilated cardiomyopathy. Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow-up of patients with Bardet-Biedl syndrome.