bluuebunny/crossref_metadata_2025 huggingface dataset:
Widely Distributed Magnetoencephalography Spikes Related to the Planning and Execution of Human Saccades
Authors: Ioannides Andreas A. , Fenwick Peter B. C. , Liu Lichan
Published: August 2005

With sufficiently fast data sampling, ubiquitous sharp transients appear in magnetoencephalography (MEG) data. Initially, no known collective neuronal activity could explain MEG signal generation well above 100 Hz, so it was assumed that these transients were entirely composed of background electronic noise that could be eliminated by filtering and averaging. Recent studies at the cellular level provided evidence for synchronous synaptic input to dendrites and volleys of near-simultaneous action potentials. MEG studies have also identified high-frequency oscillations well above 200 Hz after averaging large number of somatosensory evoked responses. In this study, we searched for evidence of high-frequency neuronal activity in the raw MEG signal using the highest sampling rate available with our hardware. Two human subjects participated in three experiments using visual cues to define planning, preparation, and execution or inhibition of saccades. Tomographic analysis identified “MEG spikes” that were widely distributed across the cortex, cerebellum, and brainstem during cue presentations and saccades. Here we demonstrate how these MEG spikes can be recorded and localized in real time and show that task demands influence their properties. The MEG spikes were organized into feedforward and corollary discharge sequences that could, when combined with the slower activity-linked processing in discrete brain areas over long periods, lasting hundreds of milliseconds. Preparation for impending saccade began as soon as relevant information became available. Cues providing partial information initiated competing motor programs for as yet undecided future actions that were maintained until cues with new information resolved the uncertainty.
Chemosensory Selectivity of Output Neurons Innervating an Identified, Sexually Isomorphic Olfactory Glomerulus
Authors: Reisenman Carolina E. , Christensen Thomas A. , Hildebrand John G.
Published: August 2005

The antennal lobe (AL) of insects, like the olfactory bulb of vertebrates, is characterized by discrete modules of synaptic neuropil called glomeruli. In some insects (e.g., moths and cockroaches), a few glomeruli are sexually dimorphic and function in labeled lines for processing of sensory information about sex pheromones. Controversy still exists, however, about whether projection (output) neurons (PNs) of glomeruli in the main AL are also narrowly tuned. We examined this critical issue in the AL of the mothManduca sexta. We used intracellular recording and staining techniques to investigate the chemosensory tuning of PNs innervating an identifiable, sexually isomorphic glomerulus, G35, in the main AL. We found that the morphological features and chemosensory tuning of G35-PNs were nearly identical in females and males. G35-PNs responded to low concentrations of the plant-derived volatile compoundcis-3-hexenyl acetate (c3HA), but the sensitivity threshold of female PNs was lower than that of male PNs. The propionate and butyrate homologs of c3HA could evoke excitatory responses but only at moderate-to-high concentrations. Other plant volatiles did not evoke responses from G35-PNs. Moreover, PNs innervating glomeruli near G35 (in females) showed little or no response to c3HA. Female G35-PNs were hyperpolarized by (±)linalool, a compound that excites PNs in an adjacent glomerulus, thus providing evidence for lateral-inhibitory interactions between glomeruli. Our results show that PNs arborizing in an identified glomerulus in the main olfactory pathway are morphologically and physiologically equivalent in both sexes and have characteristic, limited molecular receptive ranges that are highly conserved across individuals.
Neonatal Infection-Induced Memory Impairment after Lipopolysaccharide in Adulthood Is Prevented via Caspase-1 Inhibition
Authors: Bilbo Staci D. , Biedenkapp Joseph C. , Der-Avakian Andre , Watkins Linda R. , Rudy Jerry W. , Maier Steven F.
Published: August 2005

We have reported that neonatal infection leads to memory impairment after an immune challenge in adulthood. Here we explored whether events occurring as a result of early infection alter the response to a subsequent immune challenge in adult rats, which may then impair memory. In experiment 1, peripheral infection withEscherichia colion postnatal day 4 increased cytokines and corticosterone in the periphery, and cytokine and microglial cell marker gene expression in the hippocampus of neonate pups. Next, rats treated neonatally withE. colior PBS were injected in adulthood with lipopolysaccharide (LPS) or saline and killed 1–24 h later. Microglial cell marker mRNA was elevated in hippocampus in saline controls infected as neonates. Furthermore, LPS induced a greater increase in glial cell marker mRNA in hippocampus of neonatally infected rats, and this increase remained elevated at 24 h versus controls. After LPS, neonatally infected rats exhibited faster increases in interleukin-1β (IL-1β) within the hippocampus and cortex and a prolonged response within the cortex. There were no group differences in peripheral cytokines or corticosterone. In experiment 2, rats treated neonatally withE. colior PBS received as adults either saline or a centrally administered caspase-1 inhibitor, which specifically prevents the synthesis of IL-1β, 1 h before a learning event and subsequent LPS challenge. Caspase-1 inhibition completely prevented LPS-induced memory impairment in neonatally infected rats. These data implicate IL-1β in the set of immune/inflammatory events that occur in the brain as a result of neonatal infection, which likely contribute to cognitive alterations in adulthood.
Association/Dissociation of a Channel–Kinase Complex Underlies State-Dependent Modulation
Authors: Magoski Neil S. , Kaczmarek Leonard K.
Published: August 2005

Although ion channels are regulated by protein kinases, it has yet to be established whether the behavioral state of an animal may dictate whether or not modulation by a kinase can occur. Here, we describe behaviorally relevant changes in the ability of a nonselective cation channel fromAplysiabag cell neurons to be regulated by protein kinase C (PKC). This channel drives a prolonged afterdischarge that triggers the release of egg-laying hormone and a series of reproductive behaviors. The afterdischarge is followed by a lengthy refractory period, during which additional bursting cannot be elicited. Previously, we reported that, in excised inside-out patches, the cation channel is closely associated with PKC, which increases channel activity. We now show that this channel–kinase association is plastic, because channels excised from certain neurons lack PKC-dependent modulation. Although direct application of PKC-activating phorbol ester to these patches had no effect, exposing the neurons themselves to phorbol ester reinstated modulation, suggesting that an absence of modulation was attributable to a lack of associated kinase. Furthermore, modulation was restored by pretreating neurons with either PP1 [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] or SU6656, inhibitors of Src tyrosine kinase, an enzyme whose Src homology 3 domain is required for channel–PKC association. Neurons that were stimulated to afterdischarge and had entered the prolonged refractory period were found to have more phosphotyrosine staining and less channel–PKC association than unstimulated neurons. These findings suggest that Src-dependent regulation of the association between the cation channel and PKC controls both the long-term excitability of these neurons and their ability to induce reproduction.
Chronic Enhancement of the Intrinsic Growth Capacity of Sensory Neurons Combined with the Degradation of Inhibitory Proteoglycans Allows Functional Regeneration of Sensory Axons through the Dorsal Root Entry Zone in the Mammalian Spinal Cord
Authors: Steinmetz Michael P. , Horn Kevin P. , Tom Veronica J. , Miller Jared H. , Busch Sarah A. , Nair Dileep , Silver Daniel J. , Silver Jerry
Published: August 2005

Peripherally conditioned sensory neurons have an increased capacity to regenerate their central processes. However, even conditioned axons struggle in the presence of a hostile CNS environment. We hypothesized that combining an aggressive conditioning strategy with modification of inhibitory reactive astroglial-associated extracellular matrix could enhance regeneration. We screened potential treatments using a model of the dorsal root entry zone (DREZ). In this assay, a gradient of inhibitory chondroitin sulfate proteoglycans (CSPGs) stimulates formation of dystrophic end bulbs on adult sensory axons, which mimics regeneration failurein vivo. Combining inflammation-induced preconditioning of dorsal root gangliain vivobefore harvest, with chondroitinase ABC (ChABC) digestion of proteoglycansin vitroallows for significant regeneration across a once potently inhibitory substrate. We then assessed regeneration through the DREZ after root crush in adult rats receiving the combination treatment, ChABC, or zymosan pretreatment alone or no treatment. Regeneration was never observed in untreated animals, and only minimal regeneration occurred in the ChABC- and zymosan-alone groups. However, remarkable regeneration was observed in a majority of animals that received the combination treatment. Regenerated fibers established functional synapses, as demonstrated electrophysiologically by the presence of an H-reflex. Two different postlesion treatment paradigms in which the timing of both zymosan and ChABC administration were varied after injury were ineffective in promoting regeneration. Therefore, zymosan pretreatment, but not posttreatment, of the sensory ganglia, combined with ChABC modification of CSPGs, resulted in robust and functional regeneration of sensory axons through the DREZ after root injury.
Induction of cAMP Response Element-Binding Protein-Dependent Medium-Term Memory by Appetitive Gustatory Reinforcement inDrosophilaLarvae
Authors: Honjo Ken , Furukubo-Tokunaga Katsuo
Published: August 2005

The fruit flyDrosophila melanogasterhas been successfully used as a model animal for the study of the genetic and molecular mechanisms of learning and memory. Although most of theDrosophilalearning studies have used the adult fly, the relative complexity of its neural network hinders cellular and molecular studies at high resolution. In contrast, theDrosophilalarva has a simple brain with uniquely identifiable neural networks, providing an opportunity of an attractive alternative system for elucidation of underlying mechanisms involved in learning and memory. In this paper, we describe a novel paradigm of larval associative learning with a single odor and a positive gustatory reinforcer, sucrose. Mutant analyses have suggested importance of cAMP signaling and potassium channel activities in larval learning as has been demonstrated with the adult fly. Intriguingly, larval memory produced by the appetitive conditioning lasts medium term and depends on bothamnesiacand cAMP response element-binding protein (CREB). A significant part of memory was disrupted at very early phase by CREB blockade without affecting immediate learning performance. Moreover, we also show that synaptic output of larval mushroom body neurons is required for retrieval but not for acquisition and retention of the larval memory, including the CREB-dependent component.
Accumulation of the Authentic Parkin Substrate Aminoacyl-tRNA Synthetase Cofactor, p38/JTV-1, Leads to Catecholaminergic Cell Death
Authors: Ko Han Seok , von Coelln Rainer , Sriram Sathya R. , Kim Seong Who , Chung Kenny K. K. , Pletnikova Olga , Troncoso Juan , Johnson Brett , Saffary Roya , Goh Eyleen L. , Song Hongjun , Park Bum-Joon , Kim Min Jung , Kim Sunghoon , Dawson Valina L. , Dawson Ted M.
Published: August 2005

Autosomal-recessive juvenile parkinsonism (AR-JP) is caused by loss-of-function mutations of the parkin gene. Parkin, a RING-type E3 ubiquitin ligase, is responsible for the ubiquitination and degradation of substrate proteins that are important in the survival of dopamine neurons in Parkinson's disease (PD). Accordingly, the abnormal accumulation of neurotoxic parkin substrates attributable to loss of parkin function may be the cause of neurodegeneration in parkin-related parkinsonism. We evaluated the known parkin substrates identified to date in parkin null mice to determine whether the absence of parkin results in accumulation of these substrates. Here we show that only the aminoacyl-tRNA synthetase cofactor p38 is upregulated in the ventral midbrain/hindbrain of both young and old parkin null mice. Consistent with upregulation in parkin knock-out mice, brains of AR-JP and idiopathic PD and diffuse Lewy body disease also exhibit increased level of p38. In addition, p38 interacts with parkin and parkin ubiquitinates and targets p38 for degradation. Furthermore, overexpression of p38 induces cell death that increases with tumor necrosis factor-α treatment and parkin blocks the pro-cell death effect of p38, whereas the R42P, familial-linked mutant of parkin, fails to rescue cell death. We further show that adenovirus-mediated overexpression of p38 in the substantia nigra in mice leads to loss of dopaminergic neurons. Together, our study represents a major advance in our understanding of parkin function, because it clearly identifies p38 as an important authentic pathophysiologic substrate of parkin. Moreover, these results have important implications for understanding the molecular mechanisms of neurodegeneration in PD.
The Site of a Motor Memory Shifts with Consolidation
Authors: Kassardjian Charles D. , Tan Yao-Fang , Chung Ji-Yeon J. , Heskin Raquel , Peterson Michael J. , Broussard Dianne M.
Published: August 2005

The basis for the consolidation of memory is a controversial topic, particularly in the case of motor memory. One view is that motor memory is transferred, partially or completely, to a new location during the consolidation process (“systems consolidation”). We investigated this possibility in a primitive motor system, the vestibulo-ocular reflex (VOR). In the simple circuitry of the VOR, there are relatively few possible storage sites for memory. We partially blocked excitatory neurotransmission in the cerebellar cortex of cats with the glutamate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). If CNQX was injected immediately after 60 min of rotation under conditions that induced a learned decrease in the gain of the VOR, gain was returned to its baseline value. Expression of the new memory could also be disrupted by rotation in darkness, suggesting that consolidation had not taken place; however, after learning had continued for 3 d, expression of the learned change was diminished only slightly by blockade and was unaffected by rotation in darkness. Our interpretation of these results is that learning may take place initially in the cerebellar cortex and that during consolidation, motor memories are converted to a more distributed representation that includes the cerebellar cortex and another site.
Dissociating Linguistic Processes in the Left Inferior Frontal Cortex with Transcranial Magnetic Stimulation
Authors: Gough Patricia M. , Nobre Anna C. , Devlin Joseph T.
Published: August 2005

Is the left inferior frontal cortex (LIFC) a single functional region, or can it be subdivided into distinct areas that contribute differently to word processing? Here we used transcranial magnetic stimulation (TMS) to investigate anterior and posterior LIFC when the meaning and sound of words were being processed. Relative to no stimulation, TMS of the anterior LIFC selectively increased response latencies when participants focused on the meaning of simultaneously presented words (i.e., synonym judgments) but not when they focused on the sound pattern of the words (i.e., homophone judgments). In contrast, the opposite dissociation was observed in the posterior LIFC, where stimulation selectively interfered with the phonological but not the semantic task. This double dissociation shows functionally distinct subdivisions of the LIFC that can be understood in terms of separable corticocortical connections linking the anterior LIFC to temporal pole regions associated with semantic memory and the posterior LIFC to temporoparietal regions involved in auditory speech processing.
Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission
Authors: Mameli Manuel , Zamudio Paula A. , Carta Mario , Valenzuela C. Fernando
Published: August 2005

Ethanol exposure during fetal development is a leading cause of learning disabilities. Studies suggest that it alters learning and memory by permanently damaging the hippocampus. It is generally assumed that this is mediated, in part, via alterations in glutamatergic transmission. Although NMDA receptors are presumed to be the most sensitive targets of ethanol in immature neurons, this issue has not been explored in the developing hippocampus. We performed whole-cell patch-clamp recordings in hippocampal slices from neonatal rats. Unexpectedly, we found that acute ethanol (10–50 mm) exposure depresses inward currents elicited by local application of exogenous AMPA, but not NMDA, in CA3 pyramidal neurons. These findings revealed a direct effect of ethanol on postsynaptic AMPA receptors. Ethanol significantly decreased the amplitude of both AMPA and NMDA receptor-mediated EPSCs evoked by electrical stimulation. This effect was associated with an increase in the paired-pulse ratio and a decrease in the frequency of miniature EPSCs driven by depolarization of axonal terminals. These findings demonstrate that ethanol also acts at the presynaptic level. ω-Conotoxin-GVIA occluded the effect of ethanol on NMDA EPSCs, indicating that ethanol decreases glutamate release via inhibition of N-type voltage-gated Ca2+channels. In more mature rats, ethanol did not affect the probability of glutamate release or postsynaptic AMPA receptor-mediated currents, but it did inhibit NMDA-mediated currents. We conclude that the mechanism by which ethanol inhibits glutamatergic transmission is age dependent and challenge the view that postsynaptic NMDA receptors are the primary targets of ethanol early in development.
Paired Motor Neuron–Muscle Recordings in Zebrafish Test the Receptor Blockade Model for Shaping Synaptic Current
Authors: Wen Hua , Brehm Paul
Published: August 2005

The transparent spinal cord and electrically compact fast muscle of zebrafish offer the first opportunity to perform simultaneous whole-cell patch-clamp recordings from both motor neuron and target skeletal musclein situ. Our paired recordings reveal the fastest reported kinetics for both spontaneous and evoked synaptic currents at any synapse and a large quantal size that facilitates the resolution of spontaneous synaptic currents. We used this preparation to test the recent proposal that open channel block of the acetylcholine receptor by acetylcholine modulates the kinetics and timing of transmission between nerve and muscle in larval zebrafish (Legendre et al., 2000). Contrary to the predictions of this model, we find similar delay and onset kinetics of synaptic current at positive and negative muscle membrane potentials, even after inhibition of acetylcholinesterase. In contrast, blockade of motor neuron K channels by 4-aminopyridine prolonged the action potential and introduced a significant delay and slowing of evoked synaptic currents, demonstrating our ability to measured altered transmitter release with this system. We conclude that the kinetics of neuromuscular synaptic currents in zebrafish is not governed by receptor block.
Grafts of Brain-Derived Neurotrophic Factor and Neurotrophin 3-Transduced Primate Schwann Cells Lead to Functional Recovery of the Demyelinated Mouse Spinal Cord
Authors: Girard Christelle , Bemelmans Alexis-Pierre , Dufour Noëlle , Mallet Jacques , Bachelin Corinne , Nait-Oumesmar Brahim , Baron-Van Evercooren Anne , Lachapelle François
Published: August 2005

Experimental studies provided overwhelming proof that transplants of myelin-forming cells achieve efficient remyelination in the CNS. Among cellular candidates, Schwann cells can be used for autologous transplantation to ensure robust remyelination of lesions and to deliver therapeutic factors in the CNS. In the present study, macaque Schwann cells expressing green fluorescent protein (GFP) were infected with human immunodeficiency virus-derived vectors overexpressing brain-derived neurotrophic factor (BDNF) or Neurotrophin 3 (NT-3), two neurotrophins that also modulate glial cell biology. The ability of transgenic Schwann cells to secrete growth factors was assessed by ELISA and showed 35- and 62-fold increases in BDNF and NT-3, respectively, in transduced macaque Schwann cell supernatants. Conditioned media of BDNF- and NT-3-transduced Schwann cells reduced Schwann cell proliferation and favored their differentiationin vitro. Transgenic cells were grafted in demyelinated spinal cords of adult nude mice. Two behavioral assays showed that NT-3- and BDNF-transduced Schwann cells promoted faster and stronger functional recovery than GFP-transduced Schwann cells. Morphological analysis indicated that functional recovery correlated with enhanced proliferation and differentiation of resident oligodendrocyte progenitors and enhanced oligodendrocyte and Schwann cell differentiation. Moreover, NT-3-transduced Schwann cells provided neuroprotection and reduced astrogliosis. These results underline the potential therapeutic benefit of combining neuroprotection and activation of myelin-forming cells to restore altered functions in demyelinating diseases of the CNS.
Lokalisierung mittels mengenbasierter nichtlinearer Filterung im Hyperraum (Localization Using Set-theoretic Nonlinear Filtering Methods)
Authors: Briechle Kai , Hanebeck Uwe D.
Published: September 2005

Moderne, leistungsfähige Verfahren zur Lokalisierung von Objekten haben in den letzten Jahren eine Vielzahl neuartiger technischer Anwendungen eröffnet. Die Mehrzahl dieser Lokalisierungsverfahren basiert auf Filterverfahren, mit welchen die Lage des zu lokalisierenden Objektes geschätzt wird. Dieser Artikel stellt ein neuartiges nichtlineares Filterverfahren vor, das die effiziente Behandlung nichtlinearer Filterprobleme ermöglicht. Es bietet sich damit für Lokalisierungsprobleme an, bei welchen mit herkömmlichen, linearisierenden Filterverfahren oft keine zufrieden stellenden Ergebnisse erzielt werden können. Die Leistungsfähigkeit des vorgestellten Verfahrens wird mit Anwendungen auf prototypische Lokalisierungsprobleme und einem Experiment zur Lokalisierung eines mobilen Roboters belegt.
Polynomiale Unterordnung und Dominanz rationaler Matrizen (Polynomial Subordination and Dominance of Rational Matrices)
Authors: Lampe Bernhard P. , Rosenwasser Efim N.
Published: September 2005

Beim Entwurf linearer Regelungssysteme im Frequenzbereich sind exakte (mathematische) Kürzungen gegenüber der Kompensation von Polen gegen Nullstellen zu unterscheiden. Die mathematischen Kürzungen müssen vorgenommen werden, da sonst real nicht existierende Bestandteile im Modell mitgeführt werden. Für Mehrgrößensysteme ist das eine komplizierte Aufgabe, zumal im Falle von durch Mess- oder Rundungsfehler verfälschten Modellen davon ausgegangen werden muss, dass Kürzungen erzwungen werden müssen. Die in diesem Artikel eingeführten Begriffe polynomialer Unterordnung und Dominanz erlauben es, solche Probleme einfacher zu lösen und verhelfen darüber hinaus zu einem tieferen Verständnis der Struktur von Mehrgrößen-Abtastsystemen, wie an einem Beispiel gezeigt wird.
Lower Limb Pain in a Preadolescent Population: Prognosis and Risk Factors for Chronicity—A Prospective 1- and 4-Year Follow-up Study
Authors: El-Metwally Ashraf , Salminen Jouko J. , Auvinen Anssi , Kautiainen Hannu , Mikkelsson Marja
Published: September 2005

Objective. To determine the short-term and long-term prognosis of preadolescent lower limb pain and to assess factors that contribute to pain persistence at 1-year follow-up and pain recurrence at 4-year follow-up.

Methods. A 1- and 4-year follow-up was conducted of a population-based 10- and 12-year old cohort of schoolchildren with lower limb pain at baseline

Results. Of the baseline students with lower limb pain, 32% reported pain persistence at 1-year follow-up and 31% reported pain recurrence at 4-year follow-up. Vigorous exercise was the only statistically significant predictor of lower limb pain persistence at 1-year follow-up (odds ratio [OR]: 2.43; 95% confidence interval [CI]: 1.16–5.05), whereas at 4-year follow-up (at adolescence), hypermobility was predictive of pain recurrence (OR: 2.93; 95% CI: 1.13–7.70). Traumatic lower extremity pain had a 50% lower risk for pain recurrence compared with nontraumatic pain (OR: 0.48; 95% CI: 0.19–0.92).

Conclusion. Trauma-induced lower extremity pain in preadolescents has a favorable long-term natural course. Children’s involvement in vigorous exercise predicts short-term outcome of lower limb pain, whereas hypermobile children have a worse long-term prognosis.
Clinical and Demographic Factors Associated With Urinary Tract Infection in Young Febrile Infants
Authors: Zorc Joseph J. , Levine Deborah A. , Platt Shari L. , Dayan Peter S. , Macias Charles G. , Krief William , Schor Jeffrey , Bank David , Shaw Kathy N. , Kuppermann Nathan ,   for the Multicenter RSV-SBI Study Group of the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics
Published: August 2005

Objective. Previous research has identified clinical predictors for urinary tract infection (UTI) to guide urine screening in febrile children <24 months of age. These studies have been limited to single centers, and few have focused on young infants who may be most at risk for complications if a UTI is missed. The objective of this study was to identify clinical and demographic factors associated with UTI in febrile infants who are ≤60 days of age using a prospective multicenter cohort.

Methods. We conducted a multicenter, prospective, cross-sectional study during consecutive bronchiolitis seasons. All febrile (≥38°C) infants who were ≤60 days of age and seen at any of 8 pediatric emergency departments from October through March 1999–2001 were eligible. Clinical appearance was evaluated using the Yale Observation Scale. UTI was defined as growth of a known bacterial pathogen from a catheterized specimen at a level of (1) ≥50000 cfu/mL or (2) ≥10000 cfu/mL in association with a positive dipstick test or urinalysis. We used bivariate tests and multiple logistic regression to identify demographic and clinical factors that were associated with the likelihood of UTI.

Results. A total of 1025 (67%) of 1513 eligible patients were enrolled; 9.0% of enrolled infants received a diagnosis of UTI. Uncircumcised male infants had a higher rate of UTI (21.3%) compared with female (5.0%) and circumcised male (2.3%) infants. Infants with maximum recorded temperature of ≥39°C had a higher rate of UTI (16.3%) than other infants (7.2%). After multivariable adjustment, UTI was associated with being uncircumcised (odds ratio: 10.4; bias-corrected 95% confidence interval: 4.7–31.4) and maximum temperature (odds ratio: 2.4 per °C; 95% confidence interval: 1.5–3.6). Factors that were reported previously to be associated with risk for UTI in infants and toddlers, such as white race and ill appearance, were not significantly associated with risk for UTI in this cohort of young infants.

Conclusions. Being uncircumcised and height of fever were associated with UTI in febrile infants who were ≤60 days of age. Uncircumcised male infants were at particularly high risk and may warrant a different approach to screening and management.
Isolated Sulfite Oxidase Deficiency: A Case Report With a Novel Mutation and Review of the Literature
Authors: Tan Wen-Hann , Eichler Florian S. , Hoda Sadaf , Lee Melissa S. , Baris Hagit , Hanley Catherine A. , Grant P. Ellen , Krishnamoorthy Kalpathy S. , Shih Vivian E.
Published: September 2005

Isolated sulfite oxidase deficiency is a rare but devastating neurologic disease that usually presents in early infancy with seizures and alterations in muscle tone. Only 21 cases have been reported in the literature. We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life. Plasma total homocysteine was not detectable. Urinary sulfite, thiosulfate, and S-sulfocysteine levels were elevated. The patient began a low-methionine and low-cysteine diet and was treated with thiamine and dextromethorphan. However, he became increasingly microcephalic and was severely developmentally delayed. Mutation analysis of the sulfite oxidase gene revealed that the patient was homozygous for a novel 4-base pair deletion, and both of his parents were found to be heterozygous carriers of the same deletion. We reviewed the clinical, biochemical, neuroradiologic, and neuropathologic features in all published cases of isolated sulfite oxidase deficiency. Seizures or abnormal movements were prominent features in all cases. Developmental delays were reported in 17 cases. Ectopia lentis was detected in 9 cases. Clinical improvement with dietary therapy was seen in only 2 patients, both of whom presented after the age of 6 months and had relatively mild developmental delays. Plasma or urinary S-sulfocysteine levels were elevated in all cases. Urinary sulfite was detected in all except 1 case. Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency. The main alternative in the differential diagnosis of isolated sulfite oxidase deficiency is molybdenum cofactor deficiency.
Preventable Adverse Events in Infants Hospitalized With Bronchiolitis
Authors: McBride Sarah C. , Chiang Vincent W. , Goldmann Donald A. , Landrigan Christopher P.
Published: September 2005

Objective. To determine the incidence of preventable adverse events (AEs) and near misses (NMs) among infants hospitalized for bronchiolitis at a pediatric tertiary care hospital and the impact of these errors on hospital length of stay (LOS).

Methods. We studied 143 infants with bronchiolitis, ages 0 to 12 months, admitted from December 2002 to April 2003. Using prospective chart review and staff reports, we captured medical errors and AEs. Each event was classified as a (1) preventable AE, (2) nonpreventable AE, (3) intercepted NM, (4) nonintercepted NM, or (5) error with little or no potential for harm.

Results. Of 143 patients, 15 (10%) suffered an AE or NM. The incidence of preventable AEs was 10 per 100 admissions. We found a higher incidence of preventable AEs and NMs among critically ill patients (CIPs) compared with non-CIPs (68 vs 5 per 100 admissions, respectively), making the absolute risk of an AE or NM 14 times more likely in CIPs. Mean LOS was significantly longer for CIPs with at least 1 AE (9.1 ± 8.8 days) than for CIPs without AEs (2.9 ± 1.5 days). Mean LOS was not significantly different between non-CIPs who did (3.8 ± 2.6 days) and did not (4.2 ± 5.0 days) experience an AE.

Conclusions. Preventable AEs occur frequently among patients admitted for bronchiolitis, especially those who are critically ill. CIPs who suffer AEs during their hospitalization have longer hospital LOSs. Future studies should investigate error-prevention strategies with a focus on those patients with severe disease.
Exercise With and Without an Insulin Pump Among Children and Adolescents With Type 1 Diabetes Mellitus
Authors: Admon Gil , Weinstein Yitzhak , Falk Bareket , Weintrob Naomi , Benzaquen Hadassa , Ofan Ragina , Fayman Gila , Zigel Levana , Constantini Naama , Phillip Moshe
Published: September 2005

Background. The use of insulin pumps is becoming a popular technique for insulin delivery among patients with type 1 diabetes mellitus (T1DM), but there is no consensus regarding the guidelines for proper pump use during exercise.

Objective. To investigate the physiologic responses and risk of hypoglycemia among children and adolescents with T1DM when exercising with the pump on (PO) (50% of the basal rate) or pump off (PF).

Methods. Ten subjects with T1DM (6 female subjects and 4 male subjects), 10 to 19 years of age, performed prolonged exercise (40–45 minutes) on a cycle ergometer ∼2 hours after a standard breakfast and an insulin (Lispro) bolus. Complex carbohydrates (20 g) were provided before and after the exercise. Each patient exercised once with PO and once with PF, in a randomized, crossover (single-blind) manner. During exercise and 45 minutes of recovery, subjects were monitored for cardiorespiratory, metabolic, and hormonal responses. Blood glucose concentrations were recorded for 24 hours after exercise, with a continuous glucose monitoring system, to document late hypoglycemic events.

Results. During exercise, blood glucose concentrations decreased by 59 ± 58 mg/dL (mean ± SD: 29 ± 24%) with PF and by 74 ± 51 mg/dL (35.5 ± 18%) with PO (not significant). No significant differences were found in cortisol, growth hormone, or noradrenaline levels between PO and PF. There were no differences in cardiorespiratory parameters, blood lactate concentrations, or free fatty acids concentrations between pump modes. Hypoglycemic events during exercise were asymptomatic and occurred for 2 subjects with PO and 2 with PF. Nine subjects had late hypoglycemia after PO, compared with 6 after PF (not significant).

Conclusions. We found no advantage for subjects with either PO or PF during exercise, and we noted that late hypoglycemia was more common than hypoglycemia during exercise. However, PO was associated with a trend of increased risk for late hypoglycemia. We recommend that the pump be removed or turned off during prolonged exercise and that blood glucose concentrations be monitored for several hours after exercise, regardless of the pump mode.
A Randomized Clinical Trial of the Management of Esophageal Coins in Children
Authors: Waltzman Mark L. , Baskin Marc , Wypij David , Mooney David , Jones Dwight , Fleisher Gary
Published: September 2005

Context. Children frequently ingest coins. When lodged in the esophagus, the coin may cause complications and must either be removed or observed to pass spontaneously.

Objectives. (1) To compare relatively immediate endoscopic removal to a period of observation followed by removal when necessary and (2) to evaluate the relationship between select clinical features and spontaneous passage.

Design/Setting. Randomized, prospective study of children <21 years old who presented to an emergency department with esophageal coins in the esophagus. Exclusion criteria were (1) history of tracheal or esophageal surgery, (2) showing symptoms, or (3) swallowing the coin >24 hours earlier. Children were randomized to either endoscopic removal (surgery) or admission for observation, with repeat radiographs ∼16 hours after the initial image.

Outcome Measures. Proportion of patients requiring endoscopic removal, length of hospital stay, and the number of complications observed.

Results. Among 168 children who presented with esophageal coins lodged in the esophagus, 81 were eligible. Of those eligible, 60 enrolled, 20 refused consent, and 1 was not approached. In the observation group, 23 of 30 (77%) children required endoscopy compared with 21 of 30 (70%) in the surgical group. Total hospital length of stay was longer in the randomized-to-observation group compared with the randomized-to-surgery group (mean: 19.4 [SD: ±8.0] hours vs 10.7 [SD: ±7.1] hours, respectively). There were no complications in either group. Spontaneous passage occurred at similar rates in both groups (23% vs 30%). Spontaneous passage was more likely in older patients (66 vs 46 months) and male patients (odds ratio: 3.7; 95% confidence interval: 0.98–13.99) and more likely to occur when the coin was in the distal one third of the esophagus (56% vs 27% [95% confidence interval: 1.07–5.57]).

Conclusions. Because 25% to 30% of esophageal coins in children will pass spontaneously without complications, treatment of these patients may reasonably include a period of observation, in the range of 8 to 16 hours, particularly among older children and those with distally located coins.
End-of-Life Decisions in Newborns: An Approach From the Netherlands
Authors: Verhagen A. A. E. , Sauer P. J. J.
Published: September 2005

End-of-life decisions in newborns with incurable conditions are especially difficult for pediatricians if they regard the group of stable infants with a hopeless prognosis, not dependent on technology. If a life full of severe and sustained suffering that cannot be relieved by any other means is expected, deliberate ending of life can be an acceptable choice in the Netherlands under very strict conditions. To increase the quality of the decision-making process and facilitate the mandatory reporting of life-ending procedures, a set of medical and legal guidelines (the Groningen protocol) was made in our institution in collaboration with the district attorney. This protocol serves as a tool to bring newborn euthanasia under a regime of effective control. This article describes the present approach to life-ending measures in newborns in the Netherlands and gives an overview of the protocol.
A Clinical Decision Rule to Identify Children at Low Risk for Appendicitis
Authors: Kharbanda Anupam B. , Taylor George A. , Fishman Steven J. , Bachur Richard G.
Published: September 2005

Objective. Computed tomography (CT) has gained widespread acceptance in the evaluation of children with suspected appendicitis. Concern has been raised regarding the long-term effects of ionizing radiation. Other means of diagnosing appendicitis, such as clinical scores, are lacking in children. We sought to develop a clinical decision rule to predict which children with acute abdominal pain do not have appendicitis.

Methods. Prospective cohort study was conducted of children and adolescents who aged 3 to 18 years, had signs and symptoms suspicious for appendicitis, and presented to the emergency department between April 2003 and July 2004. Standardized data-collection forms were completed on eligible patients. Two low-risk clinical decision rules were created and validated using logistic regression and recursive partitioning. The sensitivity, negative predictive value (NPV), and negative likelihood ratio of each clinical rule were compared.

Results. A total of 601 patients were enrolled. Using logistic regression, we created a 6-part score that consisted of nausea (2 points), history of focal right lower quadrant pain (2 points), migration of pain (1 point), difficulty walking (1 point), rebound tenderness/pain with percussion (2 points), and absolute neutrophil count of >6.75 × 103/μL (6 points). A score ≤5 had a sensitivity of 96.3% (95% confidence interval [CI]: 87.5–99.0), NPV of 95.6% (95% CI: 90.8–99.0), and negative likelihood ratio of .102 (95% CI: 0.026–0.405) in the validation set. Using recursive partitioning, a second low-risk decision rule was developed consisting of absolute neutrophil count of <6.75 × 103/μL, absence of nausea, and absence of maximal tenderness in the right lower quadrant. This rule had a sensitivity of 98.1% (95% CI: 90.1–99.9), NPV of 97.5% (95% CI: 86.8–99.9), and negative likelihood ratio of 0.058 (95% CI: 0.008–0.411) in the validation set. Theoretical application of the low-risk rules would have resulted in a 20% reduction in CT.

Conclusions. Our low-risk decision rules can predict accurately which children are at low risk for appendicitis and could be treated safely with careful observation rather than CT examination.
Obesity, Shame, and Depression in School-Aged Children: A Population-Based Study
Authors: Sjöberg Rickard L. , Nilsson Kent W. , Leppert Jerzy
Published: September 2005

Objectives. To investigate whether there is an association between adolescent obesity and depression in a nonclinical population and whether psychosocial and economic status and subjective experiences of shame (defined as experiences of being degraded or ridiculed by others) may account for such an association.

Method.We examined associations between self-reported body mass index (BMI) and depression, controlling for gender, shame, parental employment, parental separation, and economy. The study was performed on a sample of 4703 adolescents (71% of the target population of 15- and 17-year-old students in 1 Swedish County) who answered the Survey of Adolescent Life in Vestmanland 2004.

Results.Obesity was significantly related to depression and depressive symptoms among 15- and 17-year-olds. Obesity was also significantly related to experiences of shame. All significant association between BMI grouping and depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition disappeared when shaming experiences, parental employment, and parental separation were controlled for. Adolescents who reported many experiences of shame had an increased risk (odds ratio: 11.3; confidence interval: 8.3–14.9) for being depressed.

Conclusions.There is a significant statistical association between adolescent obesity and depression. Effects of experiences of shame, parental separation, and parental employment explain this association. These results suggest that clinical treatment of obesity may sometimes not just be a matter of diet and exercise but also of dealing with issues of shame and social isolation.
Worse Quality of Life for Children With Newly Diagnosed Attention-Deficit/Hyperactivity Disorder, Compared With Asthmatic and Healthy Children
Authors: Escobar Rodrigo , Soutullo Cesar A. , Hervas Amaia , Gastaminza Xavier , Polavieja Pepa , Gilaberte Inmaculada
Published: September 2005

Objective. To evaluate the quality of life (QOL) of untreated children with newly diagnosed attention-deficit/hyperactivity disorder (ADHD), compared with asthmatic and healthy children.

Methods. This prospective, case-control study included a group of 120 children, 6 to 12 years of age, with newly diagnosed ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Subjects were matched according to age, gender, and health care area with 2 control groups, ie, 93 asthmatic children and 120 healthy children. Sociodemographic characteristics and Child Health Questionnaire scores were collected.

Results. The QOL of children with ADHD was rated worse than that of asthmatic or healthy children for most Child Health Questionnaire domains. The greatest differences were found in behavior, social limitations attributable to physical problems, emotional impact on parents, and family activities. Almost every psychosocial domain was more affected in comparison with asthmatic children and both psychosocial and physical domains in comparison with healthy children.

Conclusions. ADHD interferes with the daily lives of children, parents, and families even more than asthma, primarily in areas related to psychosocial functioning, although evidence of impaired physical functioning also emerged. Delays in recognition, assessment, and management of ADHD may affect negatively the QOL of those children.
Are Language Barriers Associated With Serious Medical Events in Hospitalized Pediatric Patients?
Authors: Cohen Adam L. , Rivara Frederick , Marcuse Edgar K. , McPhillips Heather , Davis Robert
Published: September 2005

Objective. Language barriers may lead to medical errors by impeding patient-provider communication. The objective of this study was to determine whether hospitalized pediatric patients whose families have language barriers are more likely to incur serious medical errors than patients whose families do not have language barriers.

Methods. A case-control study was conducted in a large, academic, regional children's hospital in the Pacific Northwest. Case patients (n = 97) included all hospitalizations of patients who were younger than 21 years and had a reported serious medical event from January 1, 1998, to December 31, 2003. Control patients (n = 475) were chosen from hospitalizations without a reported serious medical event and were matched with case patients on age, admitting service, admission to intensive care, and date of admission. The main exposure was a language barrier defined by self- or provider-reported need for an interpreter. Serious medical events were defined as events that led to unintended or potentially adverse outcomes identified by the hospital's quality improvement staff.

Results. Fourteen (14.4%) of the case patients and 53 (11.2%) of the control patients were assigned an interpreter during their hospitalization. Overall, we found no increased risk for serious medical events in patients and families who requested an interpreter compared with patients and families who did not request an interpreter (odds ratio: 1.36; 95% confidence interval: 0.73–2.55). Spanish-speaking patients who requested an interpreter comprised 11 (11.3%) of the case patients and 26 (5.5%) of the control patients. This subgroup had a twofold increased risk for serious medical events compared with patients who did not request an interpreter (odds ratio: 2.26; 95% confidence interval: 1.06–4.81).

Conclusions. Spanish-speaking patients whose families have a language barrier seem to have a significantly increased risk for serious medical events during pediatric hospitalization compared with patients whose families do not have a language barrier.
Decline in the Prevalence of Spina Bifida and Anencephaly by Race/Ethnicity: 1995–2002
Authors: Williams Laura J. , Rasmussen Sonja A. , Flores Alina , Kirby Russell S. , Edmonds Larry D.
Published: September 2005

Objective. In an effort to reduce the occurrence of neural tube defects (NTDs), folic acid fortification of US enriched grain products was authorized by the Food and Drug Administration in March 1996 and required by January 1998. Fortification has been shown to result in an important decline in the prevalence of spina bifida and anencephaly in the general US population; however, fortification's impact on specific racial/ethnic groups has not been well described. We sought to characterize the decline in the prevalence of spina bifida and anencephaly among specific racial/ethnic groups during the transition to mandatory folic acid fortification in the United States.

Methods. Data from 21 population-based birth defects surveillance systems were used to examine trends in prevalence of spina bifida and anencephaly for specific racial/ethnic groups for the years 1995–2002. These years were divided into 3 periods: prefortification, optional fortification, and mandatory fortification. Race/ethnicity was defined as Hispanic, non-Hispanic white, and non-Hispanic black. Prevalence ratios were calculated for each racial/ethnic group by dividing the prevalence from the mandatory fortification period by the prevalence in the prefortification period.

Results. The study included data on 4468 cases of spina bifida and 2625 cases of anencephaly. The prevalence of spina bifida and anencephaly was highest among Hispanic births, followed by non-Hispanic white births, with the lowest prevalence among non-Hispanic black births. Significant declines in spina bifida and anencephaly were observed among Hispanic births and non-Hispanic white births. The prevalence ratio for non-Hispanic black births was of borderline significance for spina bifida and was not significant for anencephaly.

Conclusions. The results of this study suggest that folic acid fortification is associated with significant decreases in the prevalence of spina bifida and anencephaly among non-Hispanic white and Hispanic births. The magnitude of the reduction was similar between these 2 groups and was more pronounced for spina bifida than for anencephaly. The decline in the prevalence of spina bifida and anencephaly among non-Hispanic black births did not reach statistical significance. Efforts to increase folic acid consumption for the prevention of NTDs in pregnancies among women of all races/ethnicities should be continued, and studies to identify and elucidate other risk factors for NTDs are warranted.