Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children.

UNLABELLED: We examined fat-independent associations of hormones with height and whole-body bone size and mineral content in 633 school children. IGF-1 and osteocalcin predict growth in height, while fat, osteocalcin, and in girls also, IGF-1 predict growth in bone size. Leptin and ghrelin are inversely associated with bone size in girls. INTRODUCTION: Obesity causes larger bone size and bone mass, but the role of hormones in this up-regulation of bone in obesity is not well elucidated. We examined longitudinal associations between baseline body fat mass (FM), and fat-independent fasting levels of ghrelin, adiponectin, leptin, insulin, insulin-like growth factor-I (IGF-1), osteocalcin, and intact parathyroid hormone, and subsequent changes in height and in whole-body height-adjusted bone area "BAheight" and size-adjusted bone mineral content "BMCsize" in 8- to 11-year-olds. METHODS: Analyses were carried out separately for boys (n = 325) and girls (n = 308) including data from baseline, 3 and 6 months from OPUS School Meal Study. RESULTS: In both sexes: gain in BAheight was positively associated with baseline FM (≥2.05 cm(2)/kg, both p ≤ 0.003). Furthermore, gain in height was positively associated with baseline IGF-1 (≥0.02 cm/ng/ml, p = 0.001) and osteocalcin (≥0.13 cm/ng/ml, p ≤ 0.009); and gain in BAheight was positively associated with baseline osteocalcin (≥0.35 cm(2)/ng/ml, p ≤ 0.019). In girls only, gain in BAheight was also positively associated with baseline IGF-1 (0.06 cm(2)/ng/ml, p = 0.017) and inversely associated with both baseline ghrelin (-0.01 cm(2)/pg/ml, p = 0.001) and leptin (-1.21 cm(2)/µg/ml, p = 0.005). In boys, gain in BMCsize was positively associated with osteocalcin (0.18 g/ng/ml, p = 0.030). CONCLUSIONS: This large longitudinal study suggests that in 8- to 11-year-old children, IGF-1 and osteocalcin predict growth in height, while FM, osteocalcin, and in girls also, IGF-1 predict growth in BAheight. Fat-independent inverse associations of leptin and ghrelin with BAheight in girls' are contrary to proposed growth-stimulating effects of leptin. Osteocalcin in boys predicts gain in BMCsize.

A fluorogenic complementation tool kit for interrogating lipid droplet-organelle interaction.

Contact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis upon metabolic demands. Detection of these contact sites at the nanometer scale over time in living cells is challenging. We developed a tool kit for detecting contact sites based on fluorogen-activated bimolecular complementation at CONtact sites, FABCON, using a reversible, low-affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic regulation.

A fluorogenic complementation tool kit for interrogating lipid droplet-organelle interaction.

Contact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis. Detection of these contact sites at nanometer scale over time in living cells is challenging. Here, we developed a tool kit for detecting contact sites based on Fluorogen-Activated Bimolecular complementation at CONtact sites, FABCON, using a reversible, low affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic switch.

Differences in the effects of school meals on children's cognitive performance according to gender, household education and baseline reading skills.

BACKGROUND/OBJECTIVES: We previously found that the OPUS School Meal Study improved reading and increased errors related to inattention and impulsivity. This study explored whether the cognitive effects differed according to gender, household education and reading proficiency at baseline. SUBJECTS/METHODS: This is a cluster-randomised cross-over trial comparing Nordic school meals with packed lunch from home (control) for 3 months each among 834 children aged 8 to 11 years. At baseline and at the end of each dietary period, we assessed children's performance in reading, mathematics and the d2-test of attention. Interactions were evaluated using mixed models. Analyses included 739 children. RESULTS: At baseline, boys and children from households without academic education were poorer readers and had a higher d2-error%. Effects on dietary intake were similar in subgroups. However, the effect of the intervention on test outcomes was stronger in boys, in children from households with academic education and in children with normal/good baseline reading proficiency. Overall, this resulted in increased socioeconomic inequality in reading performance and reduced inequality in impulsivity. Contrary to this, the gender difference decreased in reading and increased in impulsivity. Finally, the gap between poor and normal/good readers was increased in reading and decreased for d2-error%. CONCLUSIONS: The effects of healthy school meals on reading, impulsivity and inattention were modified by gender, household education and baseline reading proficiency. The differential effects might be related to environmental aspects of the intervention and deserves to be investigated further in future school meal trials.

Dark-adapted thresholds in children with histories of mild retinopathy of prematurity.

PURPOSE: To test the hypothesis that rod-mediated visual thresholds at 10 degrees eccentricity are elevated in children with histories of mild retinopathy of prematurity (ROP). METHODS: Dark-adapted thresholds for detection of 50 msec, 2 degrees diameter spots at a 10 degrees eccentric site, and at a peripheral reference site, 30 degrees eccentric, were measured in 20 children with a history of mild ROP and known courses of refractive development. Ten myopic control subjects also were tested. The thresholds of the ROP and control subjects were compared. RESULTS: Six of the subjects with ROP had elevated thresholds at the 10 degrees site. High myopia had been present since age 18 months or younger in each of the six. The thresholds of all other subjects with ROP, whose courses of refractive development had been toward emmetropia, and the control subjects with myopia were normal. In subjects with ROP, the association of early, persistent high myopia and an elevated threshold at 10 degrees was significant (chi 2 = 20; P < 0.01). Among the subjects with ROP, refractive error and axial length were correlated. CONCLUSIONS: ROP or factors causing ROP appear to alter rod-mediated retinal function. The association of abnormal rod-mediated sensitivity and refractive development suggests that rod-mediated retinal function is involved in the regulation of eye growth in children with a history of mild ROP.

Expression of CYP6B1 and CYP6B3 cytochrome P450 monooxygenases and furanocoumarin metabolism in different tissues of Papilio polyxenes (Lepidoptera: Papilionidae).

The CYP6B1 and CYP6B3 cytochrome P450 monooxygenases in the midgut of the black swallowtail participate in the metabolism of toxic furanocoumarins present in its host plants. In this study, biochemical analyses indicate that the fat body metabolizes significant amounts of the linear furanocoumarins bergapten and xanthotoxin after larvae feed on xanthotoxin. Northern analyses of the combined CYP6B1/3 transcript expression patterns indicate that transcripts in this P450 subfamily are induced in the midgut and fat body by xanthotoxin. Semi-quantitative RT-PCR analyses of individual CYP6B1/CYP6B3 mRNAs indicate that CYP6B1 transcripts are induced by xanthotoxin in all tissues examined and that CYP6B3 transcripts are induced in the fat body only. These results indicate that the fat body participates in the P450-mediated metabolism of excess furanocoumarins unmetabolized by the midgut. Although transcripts of both genes were detected and CYP6B1 transcripts were induced by xanthotoxin in the integument, furanocoumarin metabolism was not detected. Comparison of these P450 promoters with the promoters of alcohol dehydrogenase genes expressed in the fat bodies of several Drosophila species suggest that the xanthotoxin inducibilities of these P450 genes in fat bodies are regulated by elements other than those modulating expression of Adh genes.

Optic nerve hypoplasia with good visual acuity and visual field defects: a study of children of diabetic mothers.

Seventeen children, born of severely diabetic mothers, exhibited segmental optic nerve hypoplasia with normal visual acuity and altitudinal or sector field defects corresponding to the hypoplastic areas of the disc. This is the first group of patients with optic nerve hypoplasia in which a possible cause has been identified. Optic nerve hypoplasia is neither a rare abnormality usually associated with serious central nervous system defects, nor is it always accompanied by decreased visual acuity.

Spontaneous absorption of the lens in the congenital rubella syndrome.

Seven eyes in five patients with the congenital rubella syndrome have shown partial or complete absorption of a cataractous lens without surgical intervention. The rare occurrence of spontaneous lens absorption should not be a reason for delaying the early removal of dense bilateral cataracts in this condition.

The rod photoreceptors in retinopathy of prematurity: an electroretinographic study.

OBJECTIVE: To test the hypothesis that the more severe the acute phase retinopathy of prematurity (ROP) was in the preterm weeks, the more severely compromised is rod photoreceptor function after the ROP has resolved. METHODS: Electroretinographic (ERG) responses were recorded from 25 dark-adapted children (ages 2.5 months' postterm to 14 years) categorized by maximum, acute phase ROP (None to Very Severe). From the ERG a-wave "S," a sensitivity parameter for the rod photoreceptor response, and R(mp3), the saturated amplitude of the rod photoreceptor response were calculated using a model of the activation of rod phototransduction. The patients' results were compared with those of healthy controls (n = 71). RESULTS: Among those in the None, Mild, Moderate, and Severe categories, both S and R(mp3) varied significantly with severity of acute phase ROP. In the Very Severe category, ERG responses were too attenuated to calculate S and R(mp3). CONCLUSIONS: The rod photoreceptors must be involved in ROP. The more severe the acute phase ROP, the more severe is the compromise of the processes involved in the activation of phototransduction in the rods.

Reduced association between the Ii blood group and congenital cataracts in white patients.

The authors have identified a white patient with the red blood cell phenotype i, who also has congenital cataracts. However, in comparison with the strong association in Japanese patients between congenital cataracts and the i phenotype, the overall incidence of cataracts in white people with the i phenotype (three of ten people have congenital cataracts) is much lower. In addition, the authors studied the blood of 31 white patients with congenital cataracts and found no patients with the i phenotype. Thus, a close link between genes for these traits does not appear in most white patients with i red blood cell phenotypes.

Molecular detection and differentiation of deletions in band 13q14 in human retinoblastoma.

Five cloned DNA segments within or adjacent to human chromosome band 13q14 were mapped by a combination of in situ hybridization and DNA dosage blotting. The DNA was isolated from human retinoblastoma patients with deletions varying in size and precise location. One of these deletions occurred in mosaic form, requiring T-cell cloning to obtain cells uniformly containing the deletion and useful for blotting. Regions of overlap between the intervals on chromosome #13 deduced for each probe from the two different mapping methods permitted a more precise location for each, from which a physical ordering of these five probes could be obtained. This ordered set of probes constitutes the start of a grid spanning band 13q14 of potential use in the diagnosis and understanding of human retinoblastoma.

Keratoconus and acute hydrops in mentally retarded patients with congenital rubella syndrome.

Four patients with the congenital rubella syndrome had keratoconus and evidence of acute or previous corneal hydrops. All four of the patients vigorously rubbed and poked their eyes. The keratoconus and acute corneal hydrops in these patients probably resulted from chronic traumatizing mannerisms common in other patients with mental retardation and are not specific for the congenital rubella syndrome.

Cycloplegic refractions of premature infants.

Cyclopentolate refractions of 146 premature infants disclosed higher incidences of myopia and anisometropia than those reported for full-term infants. Also, more than 70% of the premature infants had I diopter or more of astigmatism; 83% of the astigmatism was against-the-rule. Infants with shorter gestational periods had more severe myopia and astigmatism. Infants born very prematurely should undergo follow-up refractions to determine whether they retain refractive errors large enough to interfere with visual function.

Cycloplegic refractions in infants and young children.

We studied groups of normal infants and infants with amblyopia and esoropia to determine the incidence of infantile astigmatism. Under cycloplegia, 19% of normal infants had astigmatism; this was at least twice the incidence in adults, but less than one-hale that found by noncycloplegic refractions of infants. During the first three postnatal years the incidence of astigmatism and distributions of spherical equivalents and anisometropia did not distinguish normal patients from most of those with esotropia and amblyopia.

A stereotactic radiation therapy device for retinoblastoma using a noncircular collimator and intensity filter.

The proximity of the lens to the retina makes the treatment of retinoblastoma a challenge for external beam radiation therapy. The approximately 1 mm separation between the posterior edge of the lens and the anterior region of the retina causes a trade-off between coverage of the entire retina and excessive dose to the lens. A stereotactic, LINAC based, lens sparing technique for treating retinoblastoma is presented. The technique uses noncoplanar arcs with the lens at isocenter. A special noncircular collimator blocks the lens but it also causes the dose distribution to vary across the retina. A fluence modulation filter is used to reduce the dose inhomogeneity across the target. The resulting dose distribution is roughly hemispheric, providing both anterior coverage of the retina and lens blocking unlike conventional techniques. The method used to develop the collimator and filter assembly is presented. Dosimetry of the assembly was carried out using radiochromic film, and the results were entered in a treatment planning system. The dose distribution as measured in a phantom is provided and compared to calculations.

The course of myopia in children with mild retinopathy of prematurity.

The courses of spherical equivalent in patients (n = 62) who had mild, non-cicatricial retinopathy of prematurity (ROP), and in those without a history of ROP (n = 25) were modeled as a linear function of age; an exponential model was also considered. A few (n = 5) without ROP have abnormal courses characterized by hyperopia in early infancy; none have poor acuity. Although the majority of patients with ROP have courses indistinguishable from those of term born controls, 27 (43.5%) have abnormal courses, most of which are toward myopia. Optotype acuities were significantly poorer among the ROP patients with abnormal than normal refractive courses. Thus abnormal refractive development and acuity deficits are associated in eyes that have had mild ROP.

Management of orbital subperiosteal abscess in children.

OBJECTIVES: To present guidelines for the management of an orbital subperiosteal abscess (SPA) in children and to assess the efficacy and safety of transnasal endoscopic drainage of an orbital SPA. SETTING: Tertiary care children's hospital. PATIENTS: Nineteen patients treated for an SPA between July 1997 and December 1999. The age of the patients ranged from 17 months to 14 years (mean, 6 years). The male-female ratio was 10:9. Treatment modalities included transnasal endoscopic drainage (n = 11), external drainage (n = 3), and intravenous antibiotics alone (n = 5). RESULTS: Bilateral pansinusitis was the most common cause. All patients received an initial trial of intravenous antibiotics. Based on the Fisher exact test, no statistically significant differences were detected for age, sex, presence of gaze restriction, and radiographic findings. Based on multiple logistic regression, degree of proptosis was the only significant multivariate predictor of surgery (P =.003). The estimated probability of surgery was 6% when there was no proptosis, and 92% for 2 mm of proptosis. The location of the SPA determined the route of surgical drainage. Eleven patients with a medially based SPA underwent drainage via the transnasal endoscopic approach, and 3 with a superior SPA underwent drainage externally. The external approach was associated with a longer hospital stay (median, 7 days) than either the endoscopic or the intravenous antibiotic approach (median, 5 days).

Endoscopic dacryocystorhinostomy in children.

BACKGROUND: Persistent nasolacrimal duct obstruction (NLDO) often requires treatment by probing, intubation, or balloon dacryoplasty. Refractory cases have been managed by external dacryocystorhinostomy (DCR), which leaves a scar; however, this procedure is generally avoided in young children. Endoscopic DCR has been successfully performed in adults and described in children. We report the success of this procedure in a series of pediatric patients. METHODS: A retrospective review of all endoscopic lacrimal procedures performed in a 3-year period was undertaken. Seventeen children (22 ducts) with persistent NLDO after at least one failed probing, with or without silicone tube placement, underwent endoscopic DCR. Follow-up ranged from 6 to 36 months, and success was defined as resolution of tearing and discharge by follow-up clinical evaluation and by parental history. RESULTS: All but 2 patients (88%) with NLDO showed complete resolution of tearing and discharge. These 2 patients had recurrent symptoms after the Crawford tubes were removed and required revision endoscopic DCR. No complications from this procedure were noted. CONCLUSIONS: Endoscopic DCR is a safe and effective means of treating persistent NLDO in infants and young children when simple probing, intubation, or balloon procedures have failed. The team ophthalmology-otolaryngology endoscopic approach provides a highly successful alternative for patients with a persistent distal obstruction that might otherwise require an external procedure.

Extracorporeal membrane oxygenation causing asymmetric vasculopathy in neonatal infants.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass therapy used in term or near-term infants with severe cardiorespiratory disorders not responsive to conventional intensive care interventions. An ECMO-associated retinal vasculopathy has been described with little reference to the specific condition of the patient. We examined the eyes of 91 infants who underwent ECMO treatment. An assessment was made of the following: (1) when retinal changes occurred, (2) whether there was a particular systemic disorder or ECMO approach associated with these retinal findings, and (3) whether there may be ocular sequelae from this development. METHODS: Ninety-one neonates were treated with ECMO for meconium aspiration syndrome (MAS), primary persistent pulmonary hypertension of the newborn, sepsis, congenital diaphragmatic hernia (CDH), respiratory distress syndrome (RDS), and blood aspiration. Venoarterial bypass was performed in 73 patients. The remaining 18 patients underwent venovenous bypass. Ophthalmologic examinations were performed during bypass in 6 infants and within 3 weeks of ECMO in the remainder. RESULTS: Asymmetric retinopathy (left eye > right eye) was discovered in six infants with CDH and in one infant with RDS within a 2-week period after bypass, demonstrating venous tortuosity with or without intraretinal hemorrhages. One infant treated for MAS had a left eye intraretinal hemorrhage only. All patients with the noted retinal changes underwent venoarterial cannulation. Six of 9 patients with CDH had retinal findings noted compared with 1 of 10 patients with RDS and 1 of 35 patients with MAS. CONCLUSION: Because we were able to examine infants while they were receiving ECMO or shortly after termination of bypass, asymmetric vasculopathy was found in a greater percentage of our patients compared with a similar large case series. ECMO-associated retinal vasculopathy appeared to disproportionately occur in those patients with CDH who underwent venoarterial bypass. Further study of retinal vascular changes in patients with CDH should be performed to assess long-term effects.

The natural course of congenital obstruction of the nasolacrimal duct.

In order to establish the rate of spontaneous resolution of congenital obstruction of the nasolacrimal duct, 50 infants, referred from a local pediatric group practice over a period of five years, were followed from the time of first symptoms until 8 to 13 months of age. Among the 50 infants, 65 nasolacrimal ducts were blocked and 58 ducts in 44 patients opened spontaneously. Only seven ducts in six patients required probing for relief of the obstruction. During the same period another seven patients from various referral sources were seen because of noninflammatory swelling of the lacrimal sac at birth. These patients were also found to have nasolacrimal duct obstruction, but early surgical intervention was required in six of the seven patients to relieve the distention of the sac.