bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirement for the RIIβ Isoform of PKA, But Not Calcium-Stimulated Adenylyl Cyclase, in Visual Cortical Plasticity
Authors: Fischer Quentin S. , Beaver Christopher J. , Yang Yupeng , Rao Yan , Jakobsdottir Klara B. , Storm Daniel R. , McKnight G. Stanley , Daw Nigel W.
Published: October 2004

The cAMP-dependent protein kinase (PKA) signaling pathway plays a key role in visual cortical plasticity. Inhibitors that block activation of all PKA regulatory subunits (RIα,RIβ, RIIα, RIIβ) abolish long-term potentiation (LTP) and long-term depression (LTD)in vitroand ocular dominance plasticity (ODP)in vivo. The details of this signaling cascade, however, including the source of PKA signals and which PKA subunits are involved, are unknown. To investigate these issues we have examined LTP, LTD, and ODP in knock-out mice lacking either the two cortically expressed Ca2+-stimulated adenylyl cyclases (AC1 and AC8) or the predominant neocortical subunit of PKA (RIIβ). Here we show that plasticity remains intact in AC1/AC8-/- mice, whereas ODP and LTD, but not LTP, are absent in RIIβ-/- mice. We conclude that (1) plasticity in the visual cortex does not require the activity of known Ca2+-stimulated adenylyl cyclases, (2) the PKA dependence of ODP and LTD, but not LTP, is mediated by RIIβ-PKA, and (3) multiple isoforms of PKA contribute to LTD.
Retinotopic Organization and Functional Subdivisions of the Human Lateral Geniculate Nucleus: A High-Resolution Functional Magnetic Resonance Imaging Study
Authors: Schneider Keith A. , Richter Marlene C. , Kastner Sabine
Published: October 2004

Functional magnetic resonance imaging (fMRI) has provided intriguing insights into the topography and functional organization of visual cortical areas in the human brain. However, little is known about the functional anatomy of subcortical nuclei. Here, we used high-resolution fMRI (1.5 × 1.5 × 2 mm3) at 3 tesla to investigate the retinotopic organization of the human lateral geniculate nucleus (LGN). The central 15° of the visual field were mapped using periodic flickering checkerboard stimuli that evoked a traveling wave of activity. The contralateral visual hemifield was represented with the lower field in the medial-superior portion and the upper field in the lateral-inferior portion of each LGN. The horizontal meridian was significantly overrepresented relative to the vertical meridian. The fovea was represented in posterior and superior portions, with increasing eccentricities represented more anteriorly. The magnification of the fovea relative to the periphery was similar to that described for human primary visual cortex. The magnocellular regions of the LGN were distinguished based on their sensitivity to low stimulus contrast and tended to be located in its inferior and medial portions. Our results demonstrate striking similarities in the topographic organization of the macaque and human LGN and support accounts of a constant magnification from the retina through the cortex in both species.
Modulation Power and Phase Spectrum of Natural Sounds Enhance Neural Encoding Performed by Single Auditory Neurons
Authors: Hsu Anne , Woolley Sarah M. N. , Fremouw Thane E. , Theunissen Frédéric E.
Published: October 2004

We examined the neural encoding of synthetic and natural sounds by single neurons in the auditory system of male zebra finches by estimating the mutual information in the time-varying mean firing rate of the neuronal response. Using a novel parametric method for estimating mutual information with limited data, we tested the hypothesis that song and song-like synthetic sounds would be preferentially encoded relative to other complex, but non-song-like synthetic sounds. To test this hypothesis, we designed two synthetic stimuli: synthetic songs that matched the power of spectral-temporal modulations but lacked the modulation phase structure of zebra finch song and noise with uniform band-limited spectral-temporal modulations. By defining neural selectivity as relative mutual information, we found that the auditory system of songbirds showed selectivity for song-like sounds. This selectivity increased in a hierarchical manner along ascending processing stages in the auditory system. Midbrain neurons responded with highest information rates and efficiency to synthetic songs and thus were selective for the spectral-temporal modulations of song. Primary forebrain neurons showed increased information to zebra finch song and synthetic song equally over noise stimuli. Secondary forebrain neurons responded with the highest information to zebra finch song relative to other stimuli and thus were selective for its specific modulation phase relationships. We also assessed the relative contribution of three response properties to this selectivity: (1) spiking reliability, (2) rate distribution entropy, and (3) bandwidth. We found that rate distribution and bandwidth but not reliability were responsible for the higher average information rates found for song-like sounds.
Differential Control of Synaptic and Ectopic Vesicular Release of Glutamate
Authors: Matsui Ko , Jahr Craig E.
Published: October 2004

Exocytosis of synaptic vesicles occurs not only at synaptic active zones but also at ectopic sites. Ectopic exocytosis provides a direct and rapid mechanism for neurons to communicate with glia that does not rely on transmitter spillover from the synaptic cleft. In the cerebellar cortex the processes of Bergmann glia cells encase synapses between presynaptic climbing fiber varicosities and postsynaptic Purkinje cell spines and express both AMPA receptors and electrogenic glutamate transporters. AMPA receptors expressed by Purkinje cells and Bergmann glia cells are activated predominantly by synaptic and ectopic release, respectively, and therefore can be used to compare the properties of the two release mechanisms. We report that vesicular release differs at synaptic and ectopic sites in the magnitude of short-term plasticity and the proportions of Ca2+channel subtypes that trigger glutamate release. High-affinity glutamate transporter-mediated currents in Bergmann glia cells follow the rules of synaptic release more closely than the rules of ectopic release, indicating that the majority of glutamate is released from conventional synapses. On the other hand, ectopic release produces high-concentration glutamate transients at Bergmann glia cell membranes that are necessary to activate low-affinity AMPA receptors rapidly. Ectopic release may provide a geographical cue to guide Bergmann glia cell membranes to surround active synapses and ensure efficient uptake of glutamate that diffuses out of the synaptic cleft.
TheDrosophilaMetabotropic Glutamate Receptor DmGluRA Regulates Activity-Dependent Synaptic Facilitation and Fine Synaptic Morphology
Authors: Bogdanik Laurent , Mohrmann Ralf , Ramaekers Ariane , Bockaert Joël , Grau Yves , Broadie Kendal , Parmentier Marie-Laure
Published: October 2004

In vertebrates, several groups of metabotropic glutamate receptors (mGluRs) are known to modulate synaptic properties. In contrast, theDrosophilagenome encodes a single functional mGluR (DmGluRA), an ortholog of vertebrate group II mGluRs, greatly expediting the functional characterization of mGluR-mediated signaling in the nervous system. We show here that DmGluRA is expressed at the glutamatergic neuromuscular junction (NMJ), localized in periactive zones of presynaptic boutons but excluded from active sites. NullDmGluRAmutants are completely viable, and all of the basal NMJ synaptic transmission properties are normal. In contrast,DmGluRAmutants display approximately a threefold increase in synaptic facilitation during short stimulus trains. Prolonged stimulus trains result in very strongly increased (∼10-fold) augmentation, including the appearance of asynchronous, bursting excitatory currents never observed in wild type. Both defects are rescued by expression of DmGluRA only in the neurons, indicating a specific presynaptic requirement. These phenotypes are reminiscent of hyperexcitable mutants, suggesting a role of DmGluRA signaling in the regulation of presynaptic excitability properties. The mutant phenotypes could not be replicated by acute application of mGluR antagonists, suggesting that DmGluRA regulates the development of presynaptic properties rather than directly controlling short-term modulation.DmGluRAmutants also display mild defects in NMJ architecture: a decreased number of synaptic boutons accompanied by an increase in mean bouton size. These morphological changes bidirectionally correlate with DmGluRA levels in the presynaptic terminal. These data reveal the following two roles for DmGluRA in presynaptic mechanisms: (1) modulation of presynaptic excitability properties important for the control of activity-dependent neurotransmitter release and (2) modulation of synaptic architecture.
A Mouse Model of Classical Late-Infantile Neuronal Ceroid Lipofuscinosis Based on Targeted Disruption of the CLN2 Gene Results in a Loss of Tripeptidyl-Peptidase I Activity and Progressive Neurodegeneration
Authors: Sleat David E. , Wiseman Jennifer A. , El-Banna Mukarram , Kim Kwi-Hye , Mao Qinwen , Price Sandy , Macauley Shannon L. , Sidman Richard L. , Shen Michael M. , Zhao Qi , Passini Marco A. , Davidson Beverly L. , Stewart Gregory R. , Lobel Peter
Published: October 2004

Mutations in the CLN2 gene, which encodes a lysosomal serine protease, tripeptidyl-peptidase I (TPP I), result in an autosomal recessive neurodegenerative disease of children, classical late-infantile neuronal ceroid lipofuscinosis (cLINCL). cLINCL is inevitably fatal, and there currently exists no cure or effective treatment. In this report, we provide the characterization of the first CLN2-targeted mouse model for cLINCL. CLN2-targeted mice were fertile and apparently healthy at birth despite an absence of detectable TPP I activity. At ∼7 weeks of age, neurological deficiencies became evident with the onset of a tremor that became progressively more severe and was eventually accompanied by ataxia. Lifespan of the affected mice was greatly reduced (median survival, 138 d), and extensive neuronal pathology was observed including a prominent accumulation of cytoplasmic storage material within the lysosomal-endosomal compartment, a loss of cerebellar Purkinje cells, and widespread axonal degeneration. The CLN2-targeted mouse therefore recapitulates much of the pathology and clinical features of cLINCL and represents an animal model that should provide clues to the normal cellular function of TPP I and the pathogenic processes that underlie neuronal death in its absence. In addition, the CLN2-targeted mouse also represents a valuable model for the evaluation of different therapeutic strategies.
Differential Requirements for Semaphorin 3F and Slit-1 in Axonal Targeting, Fasciculation, and Segregation of Olfactory Sensory Neuron Projections
Authors: Cloutier Jean-François , Sahay Amar , Chang Ernie C. , Tessier-Lavigne Marc , Dulac Catherine , Kolodkin Alex L. , Ginty David D.
Published: October 2004

The formation of precise stereotypic connections in sensory systems is critical for defining accurate internal representations of the external world; however, the molecular mechanisms underlying the formation of sensory maps are poorly understood. Here, we examine the roles of two structurally unrelated repulsive guidance cues, semaphorin 3F (Sema3F) and Slit-1, in olfactory sensory axon fasciculation, targeting, and segregation. Usingsema3F-/-mice, we show that Sema3F is critical for vomeronasal sensory neuron axonal fasciculation and for segregation of these sensory afferents from the main olfactory system; however, Sema3F plays only a minor role in targeting of apical vomeronasal neuron axons to the anterior accessory olfactory bulb (AOB). In addition, we show that Sema3F is required for lamina-specific targeting of olfactory sensory axons within the main olfactory system. In contrast to Sema3F, Slit-1 is dispensable for fasciculation of basal vomeronasal neuron axons but is critical for targeting these axons to the posterior AOB. These results reveal discrete and complementary roles for secreted semaphorins and slits in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections.
Physiological and Morphological Characterization of Dentate Granule Cells in the p35 Knock-Out Mouse Hippocampus: Evidence for an Epileptic Circuit
Authors: Patel Leena S. , Wenzel H. Jürgen , Schwartzkroin Philip A.
Published: October 2004

There is a high correlation between pediatric epilepsies and neuronal migration disorders. What remains unclear is whether there are intrinsic features of the individual dysplastic cells that give rise to heightened seizure susceptibility, or whether these dysplastic cells contribute to seizure activity by establishing abnormal circuits that alter the balance of inhibition and excitation. Mice lacking a functionalp35gene provide an ideal model in which to address these questions, because these knock-out animals not only exhibit aberrant neuronal migration but also demonstrate spontaneous seizures.

Extracellular field recordings from hippocampal slices, characterizing the input-output relationship in the dentate, revealed little difference between wild-type and knock-out mice under both normal and elevated extracellular potassium conditions. However, in the presence of the GABAAantagonist bicuculline, p35 knock-out slices, but not wild-type slices, exhibited prolonged depolarizations in response to stimulation of the perforant path. There were no significant differences in the intrinsic properties of dentate granule cells (i.e., input resistance, time constant, action potential generation) from wild-type versus knock-out mice. However, antidromic activation (mossy fiber stimulation) evoked an excitatory synaptic response in over 65% of granule cells from p35 knock-out slices that was never observed in wild-type slices. Ultrastructural analyses identified morphological substrates for this aberrant excitation: recurrent axon collaterals, abnormal basal dendrites, and mossy fiber terminals forming synapses onto the spines of neighboring granule cells. These studies suggest that granule cells in p35 knock-out mice contribute to seizure activity by forming an abnormal excitatory feedback circuit.
Listening to Dickinson
Authors: SHOPTAW JOHN
Published: October 2004

ABSTRACT Emily Dickinson's poetry survives in largely unpublished manuscript versions, which some take as finished poems, with all their scriptural features (lineation, variants, calligraphy) intended. This equation of poem with manuscript not only obscures some of Dickinson's most striking visual effects but also mutes her music. By listening to her rhythms, and by reading rather than just looking at her poems, Shoptaw recovers Dickinson's radically experimental metrical practice.
“The Philoctetes Problem” and the Poetics of Pastoral
Authors: ALPERS PAUL
Published: October 2004

ABSTRACT “The Philoctetes problem,” so named by Susan Stewart, concerns the limits of human expression: how can individual suffering be expressed in isolation from human listeners? This essay argues that the conventions and usages of pastoral poetry engage this problem and that because of the self-consciousness of pastoral, its poetics are pertinent to the expression of isolated suffering in other modes of poetry.
A Bugle, A Bell, A Stroke of the Tongue: Rethinking Music in Modern French Verse
Authors: BERGERON KATHERINE
Published: October 2004

ABSTRACT The synesthetic quality of timbre—referring to the “color” of an instrument or voice—held special appeal for French symbolist poets in the years before 1900. This essay explores the writings of Rimbaud and Mallarmé, as well as those of their younger disciples, to ponder the meaning of timbre, and what it might have to say about the “music” of French poetry. If the concept of timbre encourages us to hear a different kind of music in the poem, it also encourages us to rethink song. The essay concludes with a brief reflection on the poetic music produced by French composers of the same generation, in the form of mute and expressionless mélodies.
The Formal Rhythms of Mallarmé's Faun
Authors: CODE DAVID J.
Published: October 2004

ABSTRACT The eclogue L'Après-midi d'un faune has long been seen as a breakthrough to the mature “symbolist” phase of Mallarmé's oeuvre. Clichés about the “mystery” essential to symbolist poetic style have, however, forestalled rigorous analysis of the work's structure. Exposing a formal “rhythm” that draws the strophic sections into a pattern of virtual “folios and bifolios,” this article reads the faun eclogue as a secret model of “le Livre,” “the Book,” lodestar of Mallarmé's aesthetic project. In giving new focus to the work's pointed dialogue with classical Virgilian pastoral, this reading also draws on Benveniste's writings about linguistic subjectivity to understand its enactment, through the character of the faun, of an agonistic search for voiced presence.
Change in Recommendation Affects Influenza Vaccinations Among Children 6 to 59 Months of Age
Authors: Hemingway Celeste Ojeda , Poehling Katherine A.
Published: October 2004

Objective. To evaluate the impact of the 2002–2003 recommendation to “encourage when feasible” the influenza vaccine for healthy children 6 to 23 months of age.

Methods. A cross-sectional study of children who were 6 to 59 months of age and presented to a large, pediatric resident's continuity clinic or the affiliated acute care clinic in the summers of 2002 and 2003 was performed. The influenza vaccination status of children in the winter before enrollment and factors that influenced this status were determined by parental questionnaire.

Results. Of 245 and 329 children in the 2002 and 2003 study populations, influenza vaccinations increased from 7% to 18%, respectively. For healthy children 6 to 23 months of age, influenza vaccinations increased from 1% in 2002 to 17% in 2003 and accounted for most of the increase seen in the study population. Multivariate analysis revealed that the strongest predictor of pediatric influenza vaccination was parental recall of a physician recommendation (odds ratio: 39.3; 95% confidence interval: 17.3-89.4 in 2003). However, 65% of parents of high-risk children did not recall a physician recommendation despite the fact that the influenza vaccine was recommended for high-risk patients during both study years.

Conclusion. Concomitant with the 2002-2003 influenza vaccine recommendation for healthy children 6 to 23 months of age, influenza vaccinations for these children increased significantly. Because most children for whom the influenza vaccine was recommended were not vaccinated, physicians have the opportunity to increase the pediatric influenza vaccination rate by improving their recommendation strategies.
Social Smoking Among US College Students
Authors: Moran Susan , Wechsler Henry , Rigotti Nancy A.
Published: October 2004

Objective. Young smokers commonly identify themselves as “social smokers,” a pattern of smoking behavior that is poorly understood. We assessed the prevalence and correlates of social smoking among US college students.

Methods. Cross-sectional survey of a random sample of 10 904 students enrolled at 119 nationally representative US colleges in 2001.

Results. A total of 51% of 2401 current (past 30-day) smokers were social smokers. (To assess social smoking, students were asked, “In the past 30 days, do you smoke mainly when you are with people, mainly when you are alone, or do you smoke as often by yourself as with others?” Students who stated that they smoked mainly with others rather than alone or equally by themselves and others were defined as social smokers for this analysis.) Social smoking was independently associated with a lower frequency and intensity of tobacco use, less nicotine dependence, less intention to quit, and fewer recent quit attempts.

Conclusions. Social smoking is a distinct pattern of tobacco use that is common among college students and may represent a stage in the uptake of smoking.
Plagiocephaly and Brachycephaly in the First Two Years of Life: A Prospective Cohort Study
Authors: Hutchison B. Lynne , Hutchison Luke A.D. , Thompson John M.D. , Mitchell Ed A.
Published: October 2004

Objectives.Although referrals for nonsynostotic plagiocephaly (NSP) have increased in recent years, the prevalence, natural history, and determinants of the condition have been unclear. The objective of this study was to assess the prevalence and natural history of NSP in normal infants in the first 2 years of life and to identify factors that may contribute to the development of NSP.

Methods.Two hundred infants were recruited at birth. At 6 weeks, 4 months, 8 months, 12 months, and 2 years, the head circumference shape was digitally photographed, and head shape was quantified using custom-written software. At each age, infants were classified as cases when the cephalic index was ≥93% and/or the oblique cranial length ratio was ≥106%. Neck rotation and a range of infant, infant care, socioeconomic, and obstetric factors were assessed.

Results.Ninety-six percent of infants were followed to 12 months, and 90.5% were followed to 2 years. Prevalence of plagiocephaly and/or brachycephaly at 6 weeks and 4, 8, 12, and 24 months was 16.0%, 19.7%, 9.2%, 6.8%, and 3.3% respectively. The mean cephalic index by 2 years was 81.6% (range: 72.0%–102.6%); the mean oblique cranial length ratio was 102.6% (range: 100.1%–109.4%). Significant univariate risk factors of NSP at 6 weeks include limited passive neck rotation at birth, preferential head orientation, supine sleep position, and head position not varied when put to sleep. At 4 months, risk factors were male gender, firstborn, limited passive neck rotation at birth, limited active head rotation at 4 months, supine sleeping at birth and 6 weeks, lower activity level, and trying unsuccessfully to vary the head position when putting the infant down to sleep.

Conclusions.There is a wide range of head shapes in infants, and prevalence of NSP increases to 4 months but diminishes as infants grow older. The majority of cases will have resolved by 2 years of age. Limited head rotation, lower activity levels, and supine sleep position seem to be important determinants.
Cost-Effectiveness of Postnatal Home Nursing Visits for Prevention of Hospital Care for Jaundice and Dehydration
Authors: Paul Ian M. , Phillips Troy A. , Widome Mark D. , Hollenbeak Christopher S.
Published: October 2004

Objectives. (1) To describe the relationship between postnatal home nursing visitation and readmissions and emergency department (ED) visits for neonatal jaundice and dehydration in the first 10 days of life. (2) To evaluate the cost-effectiveness of providing home nursing visits after newborn discharge with specific attention to prevention of jaundice and dehydration that require hospital-based services.

Methods. A retrospective analysis of a financial database allowed for review of the discharge disposition and subsequent care for all neonates who were born at a single center from January 2000 through December 2002. Financial data reflect reimbursement values and costs of care from the payers’ perspective at the single center. We performed a deterministic cost-effectiveness analysis using a decision tree that reflected the costs and probabilities of infants in each particular health state after nursery discharge.

Results. A total of 73 (2.8%) of 2641 newborns who did not receive a home visit were readmitted to the hospital in the first 10 days of life with jaundice and/or dehydration compared with 2 (0.6%) of 326 who did receive a home visit. Similarly, 92 (3.5%) of 2641 newborns who were discharged without subsequent home nursing care had an ED visit for these reasons in the first 10 days of life compared with 0 (0%) of 326 who did have such a visit. Of infants who received a home visit, 324 (99.4%) of 326 did not require subsequent hospital services in this time period compared with 2497 (94.5%) of 2641 of those who did not receive a visit. After nursery discharge, the average cost per child who received a home health visit was $109.80 compared with $118.70 for each newborn who did not receive a visit. The incremental cost-effectiveness ratio of a routine home visit strategy compared with a no visit strategy was −$181.82.

Conclusions. A home nursing visit after newborn nursery discharge is highly cost-effective for reducing the need for subsequent hospital-based services.
Neonatal Brain Magnetic Resonance Imaging Before Discharge Is Better Than Serial Cranial Ultrasound in Predicting Cerebral Palsy in Very Low Birth Weight Preterm Infants
Authors: Mirmiran Majid , Barnes Patrick D. , Keller Kathy , Constantinou Janet C. , Fleisher Barry E. , Hintz Susan R. , Ariagno Ronald L.
Published: October 2004

Objective. To compare the value of serial cranial ultrasound (US) with a single magnetic resonance imaging (MRI) before discharge in very low birth weight preterm infants to predict cerebral palsy (CP).

Methods. Infants who weighed <1250 g at birth and were <30 weeks' gestational age underwent conventional brain MRI at near term (36–40 weeks' postmenstrual age) using 1.5 Tesla MRI scanner. Sagittal and axial T1 and T2 fluid attenuated inversion recovery and gradient recalled echo images were obtained. Cranial US was also obtained at least twice during the first 2 weeks of life. MRI and US images were interpreted by 2 independent radiologists, who were masked to clinical outcome, and scored as follows: category 1, no abnormality; category 2, subependymal hemorrhage or mineralization; category 3, moderate to severe ventriculomegaly; category 4, focal parenchymal abnormality with or without ventriculomegaly. For the purpose of this study, 1 and 2 were categorized as “normal,” and 3 and 4 were categorized as “abnormal.” The infants were assessed at a mean age of 20 and 31 months using the Amiel-Tison standardized neurodevelopmental examination.

Results. The sensitivity and specificity of MRI for predicting CP were 71% and 91% at 20 month and 86% and 89% at 31 months, respectively. The sensitivity and specificity of US for predicting CP were 29% and 86% at 20 months and 43% and 82% at 31 months.

Conclusions. As a predictor of outcome for CP, MRI at near-term in very low birth weight preterm neonates is superior to US. However, both US and MRI demonstrate high specificity.
Apparent Diffusion Coefficient in the Posterior Limb of the Internal Capsule Predicts Outcome After Perinatal Asphyxia
Authors: Hunt Rod W. , Neil Jeffrey J. , Coleman Lee T. , Kean Michael J. , Inder Terrie E.
Published: October 2004

Objective. Predicting long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) is a difficult task. Magnetic resonance imaging, particularly diffusion imaging, holds promise in this regard as it is more sensitive to brain injury than any other available imaging modality. Previous studies have suggested that abnormal signal intensity in the posterior limb of the internal capsule (PLIC), detectable on inversion-recovery T1-weighted imaging, is a strong predictor of outcome. The aim of this study was to assess the relationship between apparent diffusion coefficient (ADC) values from the PLIC, measured by diffusion imaging, and neuromotor outcome in term infants with HIE.

Methods. Twenty-eight term infants with a clinical diagnosis of HIE underwent magnetic resonance imaging as soon as practicable after birth (mean age: 5.6 days), including diffusion-weighted imaging, from which ADC values in the PLIC were measured. Motor outcome was assessed in 12 of 16 survivors.

Results. The ADC value in the PLIC was significantly associated with survival in term infants with HIE. For survivors, the mean ADC value in the PLIC was 0.89 ± 0.17 μm2/ms, whereas the mean ADC value for nonsurvivors was 0.75 ± 0.17 μm2/ms (t = 2.25). Among survivors, the ADC value in the PLIC was also associated with neuromotor outcome (F = 5.60).

Conclusion. The ADC value in the PLIC is an indicator of ischemic injury and may be of use as an objective prognostic marker for infants with HIE.
The Mortality Index for Neonatal Transportation Score: A New Mortality Prediction Model for Retrieved Neonates
Authors: Broughton Simon J. , Berry Andrew , Jacobe Stephen , Cheeseman Paul , Tarnow-Mordi William O. ,   and Neonatal Intensive Care Unit Study Group, Greenough Anne
Published: October 2004

Objective. To develop a mortality prediction score for retrieved neonates based on the information given at the first telephone contact with a retrieval service.

Methods. Data from the New South Wales Newborn and Pediatric Emergency Transport Service database were examined. Analysis was performed with the results for 2504 infants (median gestational age: 36 weeks; range: 24–43 weeks) who were <72 hours of age at the time of referral and whose outcome (neonatal death or survival) was known. The study population was divided randomly into 2 halves, the derivation and validation cohorts. Univariate analysis was performed to identify variables in the derivation cohort related to neonatal death. The variables were entered into a multivariate logistic regression analysis with neonatal death as the outcome. Receiver operator characteristic (ROC) curves were constructed with the regression model and data from the derivation cohort and then the validation cohort. The results were used to generate an integer-based score, the Mortality Index for Neonatal Transportation (MINT) score. ROC curves were constructed to assess the ability of the MINT score to predict perinatal and neonatal death.

Results. A 7-variable (Apgar score at 1 minute, birth weight, presence of a congenital anomaly, and infant’s age, pH, arterial partial pressure of oxygen, and heart rate at the time of the call) model was constructed that generated areas under ROC curves of 0.82 and 0.83 for the derivation and validation cohorts, respectively. The 7 variables were then used to generate the MINT score, which gave areas under ROC curves of 0.80 for both neonatal and perinatal death.

Conclusion. Data collected at the first telephone contact by the referring hospital with a regionalized transport service can identify neonates at the greatest risk of dying.
Nephrotic Syndrome Complicating α-Glucosidase Replacement Therapy for Pompe Disease
Authors: Hunley Tracy E. , Corzo Deyanira , Dudek Martha , Kishnani Priya , Amalfitano Andrea , Chen Yuan-Tsong , Richards Susan M. , Phillips John A. , Fogo Agnes B. , Tiller George E.
Published: October 2004

We report a patient with Pompe disease who developed reversible nephrotic syndrome during prolonged, high-dose, experimental, enzyme replacement therapy with recombinant human acid α-glucosidase (rhGAA). Because of the development of antibodies to rhGAA and concomitant clinical decline, escalating doses of rhGAA were administered as part of an experimental immune tolerance regimen. Histologic evaluation of kidney tissue revealed glomerular deposition of immune complexes containing rhGAA itself, in a pattern of membranous nephropathy. To our knowledge, this is the first reported case of nephrotic syndrome occurring during enzyme replacement therapy. The nephrotic syndrome gradually resolved after the rhGAA dose was decreased, indicating that decreasing the antigenic load can ameliorate glomerular immune complex deposition associated with enzyme replacement in a highly sensitized patient.
Behavioral Outcomes and Evidence of Psychopathology Among Very Low Birth Weight Infants at Age 20 Years
Authors: Hack Maureen , Youngstrom Eric A. , Cartar Lydia , Schluchter Mark , Taylor H. Gerry , Flannery Daniel , Klein Nancy , Borawski Elaine
Published: October 2004

Objective. Information on the mental health of very low birth weight (VLBW; <1500 g) children in young adulthood is sparse. We thus sought to examine gender-specific behavioral outcomes and evidence of psychopathology in a cohort of VLBW young adults at 20 years of age.

Methods. We compared a cohort of 241 survivors among VLBW infants who were born between 1977 and 1979 (mean birth weight: 1180 g; mean gestational age at birth: 29.7 weeks), 116 of whom were men and 125 of whom were women, with 233 control subjects from the same population in Cleveland who had normal birth weights (108 men and 124 women). Young adult behavior was assessed at 20 years of age with the Achenbach Young Adult Self-Report and the Young Adult Behavior Checklist for parents. In addition, the young adults and parents completed the ADHD Rating Scale for Adults. Gender-specific outcomes were adjusted for sociodemographic status.

Results. VLBW men reported having significantly fewer delinquent behaviors than normal birth weight (NBW) control subjects, but there were no differences on the Internalizing, Externalizing, or Total Problem Behavior scales. Parents of VLBW men reported significantly more thought problems for their sons than did parents of control subjects. VLBW women reported significantly more withdrawn behaviors and fewer delinquent behavior problems than control subjects. Their rates of internalizing behaviors (which includes anxious/depressed and withdrawn behaviors) above the borderline clinical cutoff were 30% versus 16% (odds ratio: 2.2; 95% confidence interval [CI]: 1.2-4.1). Parents of VLBW women reported significantly higher scores for their daughters on the anxious/depressed, withdrawn, and attention problem subscales compared with control parents. The odds ratios for parent-reported rates above the borderline-clinical cutoff among women for the anxious/depressed subscale was 4.4 (95% CI: 1.4-13.5), for thought problems was 3.7 (95% CI: 1.2-11.6), and for attention problems was 2.4 (95% CI: 1.0-5.5). There were no differences in the young adult self-report of attention-deficit/hyperactivity disorder (ADHD). Parents of VLBW men reported higher mean scores on the attention subtype of ADHD but not higher rates of ADHD.

Conclusion. The increase in psychopathology among VLBW survivors in young adulthood indicates a need for anticipatory guidance and early intervention that might help to prevent or ameliorate potential psychopathology.
Externalizing Problem Behaviors and Headache: A Follow-up Study of Adolescent Finnish Twins
Authors: Virtanen Ruut , Aromaa Minna , Koskenvuo Markku , Sillanpää Matti , Pulkkinen Lea , Metsähonkala Liisa , Suominen Sakari , Rose Richard J. , Helenius Hans , Kaprio Jaakko
Published: October 2004

Objective.To examine the association of teacher- and parent-rated behavior with headache in a prospective follow-up study of adolescent Finnish twins.

Methods.Questionnaire data were collected during 1995–2001 from a nationwide sample of Finnish families of 11-year-old twins who were born 1983–1987 (n = 5393) and again at age of 14. Psychological factors were measured by using parents’ and teachers’ ratings of a 37-item multidimensional rating instrument at the ages of 11 and 14.

Results.At age 11, headache frequency (5 categories) was associated with total scales of externalizing and internalizing problem behaviors and adaptive behaviors, assessed by parents, but only with externalizing problem behaviors assessed by teachers. Results were similar at age 14. The incidence of at least monthly headache between the ages of 11 and 14 years was predicted by externalizing problem behaviors and 2 subscales of adaptive behaviors: constructiveness and poor compliance. In twin pairs discordant for headache, externalizing and internalizing problem behaviors were more common among headache sufferers than among headache-nonsufferers. Headache-discordant monozygotic co-twins confirmed the association of externalizing problem behaviors with headache.

Conclusions.The frequency of adolescents’ headache is predicted by psychological factors, especially by externalizing problem behaviors. This seems to be independent of genetic or familial influences on behavior and headache. Behavioral problems may be a sign of worsening of headache or vice versa.
Habitual Snoring, Intermittent Hypoxia, and Impaired Behavior in Primary School Children
Authors: Urschitz Michael S. , Eitner Steffen , Guenther Anke , Eggebrecht Esther , Wolff Judith , Urschitz-Duprat Pilar M. , Schlaud Martin , Poets Christian F.
Published: October 2004

Objectives. Sleep-disordered breathing is associated with impaired behavior and poor academic performance in children. We aimed to determine the extent of behavioral problems in snoring children, clarify the role of intermittent hypoxia, and test the reversibility of impaired behavior and poor academic performance.

Methods. In 1144 children, habitual snoring (HS; snoring frequently or always) and impaired behavior were assessed using parental questionnaires. Intermittent hypoxia (ie, presence of ≥5 arterial oxygen desaturations by ≥4% or ≥1 desaturation to ≤90%) was investigated with pulse oximetry. Poor academic performance (grade 4–6 on a 6-point scale in mathematics, science, or spelling) was based on the last school report. HS, impaired behavior, and academic performance were reevaluated after 1 year. Adjusted odds ratios (ORs) were calculated using unconditional logistic regression.

Results. HS was significantly associated with hyperactive (OR: 2.4) and inattentive behavior (OR: 4.0), daytime tiredness (OR: 7.1), and sleepiness (OR: 2.6–4.8). These associations were independent of intermittent hypoxia. HS was also significantly associated with bad conduct (OR: 2.8), emotional symptoms (OR: 5.5), and peer problems (OR: 9.7). At follow-up, hyperactive and inattentive behavior but not academic success had significantly improved in children in whom HS had ceased.

Conclusions. We suggest that impaired behavior is a key feature of HS independent of intermittent hypoxia and improves when HS ceases.
Severe Infantile Hypercalcemia Associated With Williams Syndrome Successfully Treated With Intravenously Administered Pamidronate
Authors: Cagle Andrew P. , Waguespack Steven G. , Buckingham Bruce A. , Shankar R. Ravi , DiMeglio Linda A.
Published: October 2004

Infantile hypercalcemia occurs in ∼15% of children with Williams syndrome (WS) and is typically not clinically severe. We report on 3 children with WS (confirmed with fluorescent in situ hybridization probes) who presented with severe symptomatic hypercalcemia. The first patient's severe hypercalcemia resolved with traditional therapies, whereas the subsequent 2 patients were treated with intravenously administered pamidronate after traditional measures proved only partially successful. Besides asymptomatic mild hypocalcemia, there were no complications resulting from pamidronate administration. We conclude that WS-associated hypercalcemia can be quite severe and symptomatic and that it can be successfully and safely treated with intravenously administered bisphosphonate in some cases.
Limits of the HEDIS Criteria in Determining Asthma Severity for Children
Authors: Cabana Michael D. , Slish Kathryn K. , Nan Bin , Clark Noreen M.
Published: October 2004

Objective. Although the Health Plan Employer Data Information Set (HEDIS) is a common method for evaluating the quality of asthma care, its accuracy in characterizing persistent asthma in children is unknown. The objective of this study was to compare the assessment of asthma severity (persistent vs nonpersistent asthma) using the HEDIS criteria versus clinical criteria using National Heart, Lung, and Blood Institute (NHLBI) guidelines.

Methods. In a cross-sectional study, we analyzed baseline data from interviews with the parents of 896 children who had asthma and participated in a randomized controlled trial. Patients had an active clinical diagnosis of asthma, were between 2 and 12 years of age, and had no other pulmonary diseases. Patients had persistent asthma by parent report according to the HEDIS criteria when, within the last year, they had 1 asthma inpatient admission or emergency department visit or 4 asthma medication dispensing events, or 4 outpatient asthma visits and at least 2 asthma medication dispensing events. Patients had persistent asthma by parent report according to the NHLBI criteria when, within the last 2 months, they had nighttime asthma symptoms >2 nights/mo or daytime asthma symptoms >2 days/wk. We calculated the sensitivity of each HEDIS criterion, separately and then combined, using the NHLBI criteria as a gold standard.

Results. On the basis of HEDIS criteria, 656 (73%) patients had persistent asthma, compared with 338 (38%) using NHLBI criteria. Although the HEDIS criteria for persistent asthma were fairly sensitive (0.89), they were not very specific (0.70). For children without daily controller medications (n = 346), the sensitivity was even lower (0.45), but the specificity was similar (0.68). We found that the test characteristics were fairly consistent across different age group strata (2–4, 5–9, and 10–12 years of age).

Conclusions. HEDIS criteria used to determine the quality of asthma care should be interpreted with caution. Although the criteria for persistent disease—used to determine which children require daily controller medications—are fairly sensitive, they are not very specific and include children who may not require such medications.
Follow-up After a Pediatric Emergency Department Visit: Telephone Versus E-Mail?
Authors: Goldman Ran D. , Mehrotra Shruti , Pinto Tanya R. , Mounstephen William
Published: October 2004

Objective.The Internet has become in recent years an unlimited source of health-related information and revolutionized health information access. Follow-up after an emergency department (ED) visit is important for continuity of care but is difficult to achieve. We conducted this study to determine whether e-mail could become a method for a follow-up contact after leaving the pediatric ED.

Methods.Over a 2-month period, parents who had a telephone line and e-mail access and whose child was discharged from the ED at the Hospital for Sick Children in Toronto were randomized to receive an e-mail or a telephone follow-up. Main outcome measure was the response rates by parents to the telephone or e-mail.

Results.A total of 265 (79%) of the 337 families who were approached had Internet access, and the majority (75%) check e-mails at least once a day. Eighty-seven percent (85 of 98) and 53% (53 of 100) of the families who were contacted by telephone or e-mail, respectively, were reached within an average of 17 and 46 hours, respectively. Fourteen percent of families from the study population were unreachable either by telephone or by e-mail. Most (57%) parents who did not respond to the e-mail did not check or did not remember reading the e-mail or had trouble with access. Ten percent of the e-mails were undeliverable.

Conclusions.The telephone is better than e-mail as a follow-up channel with families of children who visit the pediatric ED. The main reason for not responding to e-mails is “technical problems.” E-mail could be a mean for follow-up contact for part of our patient population, especially for nonurgent purposes.
Features of Invasive Staphylococcal Disease in Neonates
Authors: Healy C. Mary , Palazzi Debra L. , Edwards Morven S. , Campbell Judith R. , Baker Carol J.
Published: October 2004

Objective. Most clinical descriptions of invasive staphylococcal disease (ISD) in neonates date from before the mid-1980s, when neonatal viability and intensive care differed substantially from current standards. We aimed to describe the contemporary incidence, clinical features, and outcome of infants with ISD in a neonatal intensive care unit.

Methods. A retrospective cohort study was conducted of infants who had ISD and were in the neonatal intensive care unit of the Woman's Hospital of Texas, Houston, from January 2000 to June 2002. Confirmed ISD was defined as clinical sepsis and Staphylococcus aureus (SA) isolated from ≥1 blood culture (BC) or a sterile body site excluding urine or coagulase-negative staphylococci (CoNS) isolated from ≥2 BC or from 1 BC and a sterile body site. Probable ISD was defined as CoNS isolated from 1 BC or a sterile body site for which clinical and laboratory data review by 3 infectious disease specialists indicated that antimicrobial treatment was appropriate. Confirmed and combined confirmed plus probable cases were analyzed.

Results. A total of 149 episodes (83 confirmed [39 SA, 44 CoNS], 66 probable) in 137 infants (mean gestational age [GA]: 27.6 weeks [22.4–36.4]; mean birth weight: 981 g [350–2995]) were reviewed. Four (3%) infants had early-onset infection (2 SA, 2 CoNS). Median age at infection onset was similar (17 days SA; 18 days CoNS). Intravascular catheters (IVC) were in situ in a minority of infants with ISD episodes (38% SA, 43% CoNS). CoNS more than SA infections were associated with very low birth weight (<1500 g), lower GA, a history of more IVCs and concurrent total parenteral nutrition, but IVC and parenteral nutrition days were similar. By multivariate analysis correcting for birth weight and complications of prematurity, hypoxia at the time of sepsis evaluation was significantly associated with CoNS and hypotension with SA infections; other clinical features were similar. Methicillin-resistant SA caused 8% of SA infections. Among bacteremic infants, SA more frequently than CoNS involved ≥2 sites. Overall, SA had more focal complications (primarily bone and joint) than CoNS, resulting in a 2- to 3-fold higher SA-associated morbidity rate. Mortality directly attributable to either organism was similar (5% SA; 5% confirmed, 3% confirmed/probable CoNS).

Conclusion. CoNS ISD occurred in smaller, more premature infants than SA and was IVC associated in a minority of cases. Hypoxia and hypotension were the only presenting features that differentiated CoNS and SA. SA-associated morbidity was substantial, but SA infection carried no greater risk of death (5%) than CoNS.
Respiratory Syncytial Virus Hospitalizations Among American Indian and Alaska Native Infants and the General United States Infant Population
Authors: Holman Robert C. , Curns Aaron T. , Cheek James E. , Bresee Joseph S. , Singleton Rosalyn J. , Carver Karen , Anderson Larry J.
Published: October 2004

Objective. To determine the burden of respiratory syncytial virus (RSV) disease among American Indian (AI) and Alaska Native (AN) infants, by examining RSV-associated hospitalizations.

Methods. Infant hospitalizations from 1997 through 2001 with RSV listed as a diagnosis were selected by using Indian Health Service/tribal hospital discharge data for AIs/ANs and National Hospital Discharge Survey data for the general US population.

Results. In 2000–2001, RSV disease was listed as a diagnosis for 14.4% of all AI/AN infant hospitalizations, with bronchiolitis attributable to RSV infection (12.2%) being among the top 5 listed diagnoses. The rate of RSV-specific hospitalizations was 34.4 hospitalizations per 1000 infants for AI/AN infants and 27.4 hospitalizations per 1000 births for the general US infant population. The hospitalization rates for AI/AN infants living in the Alaska and Southwest regions (70.9 and 48.2 hospitalizations per 1000 infants, respectively) were much higher than the overall rate for US infants.

Conclusions. RSV infection is one of the leading causes of hospitalization among all infants in the United States, and AI/AN infants living in the Southwest and Alaska regions are at especially high risk for hospitalizations associated with RSV infection. Development of vaccines, antiviral agents, and other strategies to prevent RSV disease could yield substantial public health benefits.