bluuebunny/crossref_metadata_2025 huggingface dataset:
Passive Transfer of Autoimmune Autonomic Neuropathy to Mice
Authors: Vernino Steven , Ermilov Leonid G. , Sha Lei , Szurszewski Joseph H. , Low Phillip A. , Lennon Vanda A.
Published: August 2004

Autoimmune autonomic neuropathy (AAN) is an acquired, often severe, form of dysautonomia. Many patients with AAN have serum antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (AChR). Rabbits immunized with a fusion protein corresponding to the N-terminal extracellular domain of the ganglionic AChR α3 subunit produce ganglionic AChR antibodies and develop signs of experimental AAN (EAAN) that recapitulate the cardinal autonomic features of AAN in man. We now demonstrate that EAAN is an antibody-mediated disorder by documenting sympathetic, parasympathetic, and enteric autonomic dysfunction in mice injected with rabbit IgG containing ganglionic AChR antibodies. Recipient mice develop transient gastrointestinal dysmotility, urinary retention, dilated pupils, reduced heart rate variability, and impaired catecholamine response to stress. The autonomic signs are associated with a reversible failure of nicotinic cholinergic synaptic transmission in superior mesenteric ganglia. Mice injected with IgG from two patients with AAN (of three tested) demonstrated a milder phenotype with evidence of urinary retention and gastrointestinal dysmotility. The demonstration that ganglionic AChR-specific IgG causes impaired autonomic synaptic transmission and autonomic failure in mice implicates an antibody-mediated pathogenesis for AAN. The antibody effect is potentially reversible, justifying early use of immunomodulatory therapy directed at lowering IgG levels and abrogating IgG production in patients with AAN.
Selective Gene Expression in Magnocellular Neurons in Rat Supraoptic Nucleus
Authors: Mutsuga Noriko , Shahar Tal , Verbalis Joseph G. , Brownstein Michael J. , Xiang Charlie C. , Bonner Robert F. , Gainer Harold
Published: August 2004

Oxytocin- and vasopressin-producing magnocellular neurons (MCNs) of the hypothalamo-neurohypophysial system are the only neuronal phenotypes present in the rat supraoptic nucleus (SON). Laser microdissection of the SON, extraction and T7-based amplification of its RNAs, and analysis of the resulting cDNAs by hybridization on a 35, 319 element DNA microarray have provided a detailed composite view of the gene expression profile of the MCNs. The genes expressed in the SON were compared with those expressed in a reference tissue consisting of total hypothalamus, and this “expression ratio” indicated which genes were preferentially expressed in the SON. Of the 26,000 unique genes on the array, 1385 were found to be expressed in the SON at levels more than two times greater than in the hypothalamus as a whole. Of these, 123 were expressed ≥3.4-fold higher in the SON versus hypothalamus. Most of these preferentially expressed genes were not previously known to be expressed in the MCNs. Quantitative and double-labelin situhybridization histochemistry was used selectively to confirm a number of these microarray observations and to evaluate the osmotic regulation and cell-specific expression of these genes, respectively.
Microtubule-Associated Protein 1B Controls Directionality of Growth Cone Migration and Axonal Branching in Regeneration of Adult Dorsal Root Ganglia Neurons
Authors: Bouquet Céline , Soares Sylvia , von Boxberg Ysander , Ravaille-Veron Michèle , Propst Friedrich , Nothias Fatiha
Published: August 2004

During development, microtubule-associated protein 1B (MAP1B) is one of the earliest MAPs, preferentially localized in axons and growth cones, and plays a role in axonal outgrowth. Although generally downregulated in the adult, we have shown that MAP1B is constitutively highly expressed in adult dorsal root ganglia (DRGs) and associated with central sprouting and peripheral regeneration of these neurons. Mutant mice with a complete MAP1B null allele that survive until adulthood exhibit a reduced myelin sheath diameter and conductance velocity of peripheral axons and lack of the corpus callosum. Here, to determine the function of MAP1B in axonal regeneration, we used cultures of adult DRG explants and/or dissociated neurons derived from thismap1b-/- mouse line. Whereas the overall length of regenerating neurites lacking MAP1B was similar to wild-type controls, our analysis revealed two main defects. First,map1b-/- neurites exhibited significantly (twofold) higher terminal and collateral branching. Second, the turning capacity of growth cones (i.e., “choice” of a proper orientation) was impaired. In addition, lack of MAP1B may affect the post-translational modification of tubulin polymers: quantitative analysis showed a reduced amount of acetylated microtubules within growth cones, whereas the distribution of tyrosinated or detyrosinated microtubules was normal. Both growth cone turning and axonal branch formation are known to involve local regulation of the microtubule network. Our results demonstrate that MAP1B plays a role in these processes during plastic changes in the adult. In particular, the data suggest MAP1B implication in the locally coordinated assembly of cytoskeletal components required for branching and straight directional axon growth.
Postnatal Management of Resolving Fetal Lung Lesions
Authors: Blau Hannah , Barak Asher , Karmazyn Boaz , Mussaffi Huda , Ben Ari Joseph , Schoenfeld Tommy , Aviram Micha , Vinograd Yitzchak , Lotem Yitzchak , Meizner Israel
Published: August 2004

Objectives. Lung lesions are increasingly diagnosed since the advent of routine prenatal ultrasound. These lesions seem to involute in 15% to 30% of cases. Postnatal evaluation is frequently limited, particularly when repeated ultrasound or initial chest radiographs are normal. As careful follow-up or resection may be required, accurate diagnosis is essential. The objective of this study was to determine whether prenatal lung lesions that seem to resolve are still present when evaluated more closely.

Methods. We followed 24 cases of prenatally diagnosed lung lesions at our center, using repeated chest radiographs and chest computerized tomography (CT).

Results. Some lesions caused mild mediastinal shift, but none showed hydrops fetalis. In 7 cases, the last prenatal ultrasound was negative. In 15 cases, initial postnatal chest radiograph was normal and in only 4 of these, the lesion was seen on later chest radiographs. This apparently high rate of resolution was, however, misleading. In 22 of the 23 cases in which CT was performed, lung cysts or lobar overinflation was clearly demonstrated.

Conclusions. Apparent involution of lung lesions on serial prenatal ultrasounds or neonatal chest radiograph can be misleading. We strongly recommend repeated radiographs and chest CT for definitive diagnosis in all cases.
Current Treatment of Juvenile Rheumatoid Arthritis
Authors: Ilowite Norman T.
Published: August 2004

Prognostic factors in juvenile rheumatoid arthritis (JRA) include polyarticular onset, polyarticular disease course, and rheumatoid factor positivity; in the systemic onset subtype, persistence of systemic features at 6 months after onset confers a worse prognosis. Timely diagnosis and appropriate aggressive treatment of patients with poor prognostic features improve quality of life and outcome. After nonsteroidal anti-inflammatory drugs, methotrexate is the most commonly used second-line agent. However, approximately one third of patients do not respond to methotrexate adequately. Randomized, placebo-controlled, clinical trials in patients with JRA are few, but one such trial with the tumor necrosis factor inhibitor etanercept shows that this drug is effective and well-tolerated. Other recently approved agents for rheumatoid arthritis, including infliximab, leflunomide, celecoxib, and rofecoxib, have not been adequately studied in pediatric patients, and the role of these agents in children with JRA remains to be determined.
Report of the National Institute of Neurological Disorders and Stroke Workshop on Perinatal and Childhood Stroke
Authors: Lynch John Kylan , Hirtz Deborah G. , DeVeber Gabrielle , Nelson Karin B.
Published: August 2004

The National Institute of Neurological Disorders and Stroke and the Office of Rare Disorders sponsored a workshop on perinatal and childhood stroke in Bethesda, Maryland, on September 18 and 19, 2000. This was an international workshop to bring together experts in the field of perinatal and childhood stroke. Topics covered included epidemiology, animal models, risk factors, outcome and prognosis, and areas of future research for perinatal and childhood stroke. Stroke in infants and children is an important cause of morbidity and mortality and an emerging area for clinical and translational research. Currently, there is no consensus on the classification, evaluation, outcome measurement, or treatment of perinatal and childhood stroke. Pediatric stroke registries are needed to generate data regarding risk factors, recurrence, and outcome. The impact of maternal and perinatal factors on risk and outcome of neonatal stroke needs to be studied. This information is essential to identifying significant areas for future treatment and prevention.
Long-Term Ophthalmic Outcome of Low Birth Weight Children With and Without Retinopathy of Prematurity
Authors: O’Connor Anna R. , Stephenson Terence , Johnson Ann , Tobin Michael J. , Moseley Merrick J. , Ratib Sonia , Ng Yin , Fielder Alistair R.
Published: August 2004

Objective. A prospective study of retinopathy of prematurity (ROP) of 505 infants who weighed <1701 g at birth was undertaken in the mid-1980s. This cohort was traced at 10 to 12 years of age to determine how low birth weight alone and ROP might influence their ophthalmic outcome.

Methods. Outcome measures were 1) visual functions (visual acuity, contrast sensitivity, stereoacuity, perimetry, and color vision), 2) presence of strabismus, and 3), measurements of eye size and the dimensions of its components including refractive state. A total of 169 11-year-olds who were born at term were recruited as control subjects and examined under the same conditions.

Results. A total of 448 of the original cohort were traced, and 254 consented to a further examination. Compared with the control group, the follow-up cohort differed significantly with reduced visual functions and increased incidence of both myopia and strabismus. Compared with published data, eye size was smaller in the low birth weight cohort. To summarize the ophthalmic data, we defined ophthalmic morbidity as visual acuity below 0.0 log units or the presence of strabismus, myopia, color vision defect, or visual field defect. The rate of ophthalmic morbidity was 50.8% (n = 129/254) in the study cohort compared with 19.5% (n = 33/169) in the control group. The highest rate of ophthalmic morbidity was associated with severe ROP (stages 3/4), although those with no ROP had a less favorable outcome than the control group.

Conclusion. This study shows that low birth weight children are at increased risk of visual impairments compared with children who are born at full term. Visual impairments are associated with low birth weight per se and severe ROP. Regressed mild ROP is only a risk factor for strabismus. The functional significance of these deficits is largely unknown.
Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?
Authors: Offit Paul A. , Quarles Jessica , Gerber Michael A. , Hackett Charles J. , Marcuse Edgar K. , Kollman Tobias R. , Gellin Bruce G. , Landry Sarah
Published: August 2004

Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant’s immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant’s immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant’s ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago.
An Integrated Approach to the Diagnosis and Prospective Management of Partial Ornithine Transcarbamylase Deficiency
Authors: Scaglia Fernando , Zheng Qiping , O’Brien William E. , Henry Joseph , Rosenberger Judy , Reeds Peter , Lee Brendan
Published: August 2004

Ornithine transcarbamylase deficiency (OTCD) is the most common inherited urea cycle disorder, and is transmitted as an X-linked trait. Female OTCD heterozygotes exhibit wide clinical severities, ranging from being apparently asymptomatic to having the profound neurologic impairment observed in affected males. However, clinical and laboratory diagnosis of partial OTCD during asymptomatic periods is difficult, and correlation of phenotypic severity with either DNA mutation and/or in vitro enzyme activity is imprecise. Provocative testing, including protein load and allopurinol challenge used in the diagnosis of OTCD females, is not without risk and subject to both false positives and negatives. Although definitive when successful, DNA-based diagnosis is unable to detect mutations in all cases. We have previously used the ratio of isotopic enrichments of [15N]urea/[15N]glutamine (15N-U/G) derived from physiologic measurements of ureagenesis by stable isotope infusion as a sensitive index of in vivo urea cycle activity. We have now applied this method in combination with traditional biochemical testing to aid in the diagnosis of a symptomatic OTCD female in whom mutation in the ornithine transcarbamylase (OTC) gene was not found. The 15N-U/G ratio in this patient showed that she had severe reduction of in vivo urea cycle activity on par with affected male subjects. This was correlated with partially deficient OTC activity in her liver, degree of orotic aciduria, and history of suspected recurrent hyperammonemic episodes before age 3. The measurement of in vivo urea cycle activity in combination with traditional biochemical indices optimizes a diagnostic approach to the at-risk partial OTCD patient, especially in those in whom molecular testing is unproductive. Together they contribute to the risk versus benefit considerations regarding the pursuit of medical therapy versus surgical, ie, orthotopic liver transplantation (OLT) therapy. The decision to resort to OLT in females with partial OTC activity is controversial, requiring consideration of phenotypic severity, failure of medical therapy, access to tertiary care centers experienced in the management of acute hyperammonemia, and social factors. In this patient, the use of in vivo and in vitro measures of urea cycle activity in conjunction with a consideration of her clinical history and medical-social situation led to a decision for OLT.
Infective Endocarditis Successfully Treated in Extremely Low Birth Weight Infants With Recombinant Tissue Plasminogen Activator
Authors: Marks Kyla A. , Zucker Nili , Kapelushnik Joseph , Karplus Michael , Levitas Aviva
Published: August 2004

Increased survival of extremely low birth weight infants depends on the use of indwelling catheters. These catheters expose the infant to the risk of thrombus formation and line infection. When intracardiac thromboses become infected, the entity is indistinguishable from infective endocarditis and exposes the infant to prolonged sepsis and risk of disseminated infected emboli. Despite prolonged antiinfective therapy and removal of the infected line, resolution of the sepsis and dissolution of the vegetations is frequently not achieved. We describe 2 cases of infective endocarditis in extremely low birth weight infants successfully treated with recombinant tissue plasminogen activator in addition to prolonged antiinfective therapy. Blood cultures became sterile and vegetations disappeared within days of commencing treatment, and there were no systemic complications. A literature search detailed in the article confirms the poor outcome associated with infectious endocarditis in preterm infants. Tissue plasminogen activator may play an important role when standard care has failed.
Multiple-Birth Infants at Higher Risk for Development of Deformational Plagiocephaly: II. Is One Twin at Greater Risk?
Authors: Littlefield Timothy R. , Kelly Kevin M. , Pomatto Jeanne K. , Beals Stephen P.
Published: August 2004

Objective. In part 1 of this investigation, we demonstrated that children of multiple birth pregnancies are at higher risk for development of deformational plagiocephaly. In the current investigation, we explore whether certain prenatal and postnatal risk factors predispose one twin over the other by examining the occurrence and severity of plagiocephaly in both discordant (only 1 affected) and concordant (both affected) twin pairs.

Methods. Throughout 1999, we obtained detailed medical histories on 140 sets of twins who had presented for treatment at 1 of 9 treatment centers across the United States. The study cohort consisted of 46 concordant and 94 discordant twin pairs (a total of 280 study participants). Information about prenatal and postnatal history of each infant was obtained through detailed review of the children’s medical records as well as analysis of a patient database maintained on all infants who receive treatment. Follow-up interviews were performed to verify the information recorded and to obtain additional information about the child who had not received treatment (if appropriate) or use of reproductive assistance (fertility drugs, intracytoplasmic sperm injection, etc) that had not been previously recorded. Statistical analyses were performed to assess the effects of prenatal and postnatal risk factors (in utero position, in utero orientation, birth weight, neck involvement, sleeping position) with respect to which infant was affected in the discordant twin pairs and to which infant was more severely affected in the concordant twin pairs.

Results. Statistical analyses of both discordant and concordant twin pairs demonstrated that the lower in utero infant was significantly more likely to be affected (χ2 = 17.391). In addition, the more severely affected infant was significantly more likely to have some form of neck involvement (torticollis, neck tightness; χ2 = 46.380), as well as have been carried in a vertex position (χ2 = 7.408). Conversely, neither sleeping position nor gender was found to be associated with development of plagiocephaly.

Conclusions. The results of this investigation strongly support an in utero cause of plagiocephaly and demonstrate that intrauterine positioning may play a prominent role in determining both the occurrence and severity of deformational plagiocephaly in twins. These findings confirm that the lower in utero infant is at increased risk for the development of plagiocephaly, likely resulting from the more restrictive intrauterine environment encountered during the later part of the pregnancy.
Social Factors Associated With Prolonged Hospitalization Among Diabetic Children
Authors: Keenan Heather T. , Foster Carol M. , Bratton Susan L.
Published: August 2004

Objective. To determine social factors associated with increased risk of hospital admission from diabetic ketoacidosis (DKA) or diabetic coma as well as risk of prolonged hospital stay.

Methods. A cohort of all children (≤21 years) with type 1 diabetes mellitus (DM) in the National Inpatient Sample admitted for DKA or diabetic coma during 1996 or 1997 was conducted. Patients’ age, race, gender, and insurance coverage were identified. Length of stay and charges were examined; prolonged length of stay was defined as ≥7 days.

Results. A total of 8443 children with a primary hospital diagnosis of DKA and 123 children with type 1 DM and coma were identified; 55% of the children were girls, 32% were nonwhite, 29% received Medicaid insurance, and 33% resided in areas of poverty. Children with prolonged hospital stay were significantly more likely to be of nonwhite race (odds ratio [OR]: 2.0; 95% confidence interval [CI]: 1.6–2.5), to receive Medicaid insurance (OR: 1.4; 95% CI: 1.1–1.7), to live in areas of poverty (OR: 1.3; 95% CI: 1.1–1.7), and to be of younger age.

Conclusions. When compared with state census data, nonwhite and poor children were more likely to be admitted with complications of DM and to have significantly prolonged and expensive hospital stays. These children should be targeted for intensive diabetes education and outpatient medical support both to improve their health and potentially to decrease total health care costs.
Centers for Disease Control and Prevention 2000 Growth Charts for the United States: Improvements to the 1977 National Center for Health Statistics Version
Authors: Ogden Cynthia L. , Kuczmarski Robert J. , Flegal Katherine M. , Mei Zuguo , Guo Shumei , Wei Rong , Grummer-Strawn Laurence M. , Curtin Lester R. , Roche Alex F. , Johnson Clifford L.
Published: August 2004

Objective. To present a clinical version of the 2000 Centers for Disease Control and Prevention (CDC) growth charts and to compare them with the previous version, the 1977 National Center for Health Statistics (NCHS) growth charts.

Methods. The 2000 CDC percentile curves were developed in 2 stages. In the first stage, the empirical percentiles were smoothed by a variety of parametric and nonparametric procedures. To obtain corresponding percentiles and z scores, we approximated the smoothed percentiles using a modified LMS estimation procedure in the second stage. The charts include of a set of curves for infants, birth to 36 months of age, and a set for children and adolescents, 2 to 20 years of age.

Results. The charts represent a cross-section of children who live in the United States; breastfed infants are represented on the basis of their distribution in the US population. The 2000 CDC growth charts more closely match the national distribution of birth weights than did the 1977 NCHS growth charts, and the disjunction between weight-for-length and weight-for-stature or length-for-age and stature-for-age found in the 1977 charts has been corrected. Moreover, the 2000 CDC growth charts can be used to obtain both percentiles and z scores. Finally, body mass index-for-age charts are available for children and adolescents 2 to 20 years of age.

Conclusion. The 2000 CDC growth charts are recommended for use in the United States. Pediatric clinics should make the transition from the 1977 NCHS to the 2000 CDC charts for routine monitoring of growth in infants, children, and adolescents.
Central Precocious Puberty in Girls: An Evidence-Based Diagnosis Tree to Predict Central Nervous System Abnormalities
Authors: Chalumeau Martin , Chemaitilly Wassim , Trivin Christine , Adan Luis , Bréart Gérard , Brauner Raja
Published: August 2004

Objective. To identify predictors of central precocious puberty (CPP) that reveal central nervous system (CNS) abnormalities in girls with CPP.

Methods. A retrospective cohort study was conducted of all girls younger than 8 years with breast development related to CPP, seen between 1982 and 2000, in a university pediatric hospital in Paris, France. For a pilot population (186 idiopathic, 11 revealing CNS abnormalities), the accuracy of the Lawson Wilkins Pediatric Endocrine Society recommendations were evaluated. Potential clinical, radiological, and biological predictors of CNS abnormalities were assessed by univariate and multivariate analyses. A diagnosis tree aiming for 100% sensitivity for the detection of CNS abnormalities was constructed and was tested on a validation population (39 idiopathic, 3 revealing CNS abnormalities).

Results. Applying the Lawson Wilkins Pediatric Endocrine Society recommendations, 2 of 11 girls with CPP that revealed CNS abnormalities would not have been considered to require brain imaging. Independent predictors of CNS abnormalities were age at onset of puberty <6 years (adjusted odds ratio [AOR]: 6.7; 95% confidence interval [CI]: 1.5–29), lack of pubic hair at diagnosis (AOR: 7.7; 95% CI: 1.8–33), and estradiol >110 pmol/L (AOR: 4.1, 95% CI: 1.0–17). The diagnosis tree that was constructed on the basis of these predictors had 100% sensitivity and 56% specificity for the validation population.

Conclusion. The identification of girls who have CPP and require cerebral imaging seems possible on the basis of validated, simple, and reproducible predictors: age and estradiol. However, this process needs to be tested on other populations.
Neonatal Antibody Titers Against Varicella-Zoster Virus in Relation to Gestational Age, Birth Weight, and Maternal Titer
Authors: van der Zwet Wil C. , Vandenbroucke-Grauls Christina M.J.E. , van Elburg Ruurd M. , Cranendonk Anneke , Zaaijer Hans L.
Published: August 2004

Objective. Varicella-zoster virus (VZV) can cause severe disease in premature neonates. The fetus receives protective maternal VZV-immunoglobulin G (IgG) mainly in the third trimester of pregnancy. Therefore, premature neonates are considered at risk for VZV infection. Administration of varicella-zoster immunoglobulin (VZIG) within 96 hours after exposure effectively prevents severe illness in susceptible patients. The objectives of this study were to define the major determinants of the neonatal VZV-IgG titer and to determine the half-life of transplacentally acquired VZV-IgG. Guidelines provided by the Centers for Disease Control and Prevention for the use of VZIG in (premature) neonates were evaluated.

Methods. VZV-IgG titers were measured in sera of 221 neonates and 43 mothers using a quantitative enzyme-linked immunosorbent assay. In 27 neonates, VZV-IgG titers were followed for up to 14 weeks.

Results. In a linear regression model, the maternal antibody titer was the major determinant of the neonatal titer (β = 0.89); gestational age was only of minor importance (β = 0.18). The median half-life of VZV-IgG in neonates was 25.5 days (range: 14.6–76.0 days). In the first weeks of life, major fluctuations of the VZV-IgG titer occurred in >50% of the neonates. The predictive value of Centers for Disease Control and Prevention guidelines for identification of neonates who should receive VZIG in case of exposure to VZV was poor: positive and negative predictive values were 0.80 and 0.43, respectively.

Conclusions. The neonatal VZV-IgG titer is predominantly predicted by the maternal VZV-IgG titer, whereas birth weight and gestational age are much less predictive than previously reported.
Gastroesophageal Reflux and Apnea of Prematurity: No Temporal Relationship
Authors: Peter Corinna S. , Sprodowski Nadine , Bohnhorst Bettina , Silny Juri , Poets Christian F.
Published: August 2004

Objective. A relationship between gastroesophageal reflux (GER) and apnea of prematurity (AOP) has long been suspected but is difficult to prove because most GER in this age group is nonacidic and thus undetectable by pH monitoring, the current standard for GER detection. The new multiple intraluminal impedance (MII) technique allows pH-independent reflux detection via changes in impedance caused by a liquid bolus inside the esophagus. We used this technique to investigate whether there is a temporal relationship between GER and AOP and whether GER occurs predominantly before a cardiorespiratory (CR) event.

Methods. Nineteen infants with AOP (median gestational age at birth: 30 weeks; range: 24–34; age at study: 26 days [13–93]) underwent 20 6-hour recordings of MII, breathing movements, nasal airflow, electrocardiogram, pulse oximeter saturation, and pulse waveforms. MII signals were analyzed, independent of CR signals, for reflux episodes (RE), defined as a fall in impedance in at least the 2 most distal channels. CR signals were analyzed for CR events, ie, apneas of ≥4-second duration, desaturations to ≤80%, and falls in heart rate to ≤100/min. A temporal relationship between an RE and a CR event was considered present if both commenced within 20 seconds of each other.

Results. There were 2039 apneas (median: 67; range: 10–346), 188 desaturations (6; 0–25), 44 bradycardias (0; 0–24), and 524 RE (25; 8–62). The frequency of apnea occurring within ± 20 seconds of an RE was not significantly different from that during reflux-free epochs (0.19/min [0.00–0.85] vs 0.25/min [0.00–1.15]); the same was true for desaturations and bradycardias. Also, RE occurred similarly often within 20 seconds before as after an apnea (2; 0–14 vs 1; 0–17). A minority of apneas (3.5%) was associated with an RE reaching the pharyngeal level; of these, significantly more (45 vs 26; median: 1; 0–10 vs 1; 0–7) occurred after rather than before an RE.

Conclusion. Both CR events and GER were common in these infants but, with few exceptions, did not seem to be temporally related.
Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency: Clinical Presentation and Follow-Up of 50 Patients
Authors: den Boer Margarethe E. J. , Wanders Ronald J. A. , Morris Andrew A. M. , IJlst Lodewijk , Heymans Hugo S. A. , Wijburg Frits A.
Published: August 2004

Objectives. To assess the mode of presentation, biochemical abnormalities, clinical course, and effects of therapy in patients of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.

Background. LCHAD deficiency is a rare, autosomal recessive inborn error of fatty acid oxidation. Although case reports and small series of patients have been published, these may not give a true picture of the clinical and biochemical spectrum associated with this disorder. To improve the early recognition and management of this potentially lethal disorder, we have reviewed a large cohort of LCHAD-deficient patients.

Methods. A questionnaire was sent to the referring physicians of 61 unselected patients with LCHAD deficiency diagnosed in our center. The standardized questionnaire requested information about the clinical signs and symptoms at presentation, the clinical history, family history, pregnancy, biochemical parameters at presentation, treatment, and clinical outcome.

Results. Questionnaires on 50 patients (82%) were returned and included in this study. The mean age of clinical presentation was 5.8 months (range: 1 day-26 months). Seven (15%) of the patients presented in the neonatal period. Thirty-nine patients (78%) presented with hypoketotic hypoglycemia, the classical features of a fatty acid oxidation disorder. Eleven patients (22%) presented with chronic problems, consisting of failure to thrive, feeding difficulties, cholestatic liver disease, and/or hypotonia. In retrospect, most (82%) of the patients presenting with an acute metabolic derangement also suffered from a combination of chronic nonspecific symptoms before the metabolic crises. Mortality in this series was high (38%), all dying before or within 3 months after diagnosis. Morbidity in the surviving patients is also high, with recurrent metabolic crises and muscle problems despite therapy.

Conclusions. LCHAD deficiency often presents with a combination of chronic nonspecific symptoms. Early diagnosis is difficult in the absence of the classical metabolic derangement. Survival can be improved by prompt diagnosis, but morbidity remains alarmingly high despite current therapeutic regimes.
Heparin-Induced Thrombocytopenia-Associated Thrombosis in Pediatric Intensive Care Patients
Authors: Schmugge Markus , Risch Lorenz , Huber Andreas R. , Benn Anne , Fischer Joachim E.
Published: August 2004

Background. Heparin-induced thrombocytopenia (HIT), a well-known side effect of heparin therapy, occurs in 1% to 5% of adults exposed to heparin. Of those, about 29% to 88% develop thrombosis. Most data on HIT-associated thrombosis in children are confined to anecdotal reports.

Objective. To determine the incidence of HIT-associated thrombosis in heparin-exposed children.

Methods. We performed a retrospective cohort study on all patients admitted to our pediatric intensive care unit between August 1996 and January 1999. Patients who received heparin for ≥5 days were eligible. Within these patients, we identified all cases of radiologically confirmed thrombosis. Cases of thrombosis were reviewed for fulfillment of clinical HIT criteria. HIT-associated thrombosis was confirmed serologically by determination of levels of antibodies against heparin/platelet factor 4 complexes.

Results. Of 1950 children admitted during the study period, 612 were exposed to heparin for ≥5 days. Thrombosis occurred in 57 patients (9.3%). Plasma samples were available for 38 cases, of which 14 satisfied clinical HIT-criteria. Calculated incidence rate for HIT-associated thrombosis: 2.3%, (95% confidence interval: 1.3%–3.9%, for patients exposed to heparin ≥5 days). Nine patients suffered from venous, 2 patients from arterial, and 3 had combined arterial and venous thrombosis. None of the 14 patients died or underwent amputation. Six patients had heparin and platelet factor 4-complex antibody levels above the cutoff level for adults. The remaining 8 patients had significantly higher antibody levels than a matched control group.

Conclusion. Compared with that reported for adults, HIT-associated thrombosis in pediatric intensive care unit patients has a similar incidence but a less severe outcome.
Hepatobiliary Disease in Neonatal Lupus: Prevalence and Clinical Characteristics in Cases Enrolled in a National Registry
Authors: Lee Lela A. , Sokol Ronald J. , Buyon Jill P.
Published: August 2004

Objective. To extend the information base on the hepatobiliary manifestations of neonatal lupus erythematosus (NLE) with regard to frequency of occurrence, clinical characteristics, and outcome.

Methods. Review of records from the Research Registry for Neonatal Lupus.

Results. Nineteen (9%) of 219 patients who had NLE and were enrolled in a national registry had probable or possible NLE hepatobiliary disease. In 16 cases, hepatobiliary disease occurred in addition to cardiac or cutaneous NLE. In 3 cases, hepatobiliary disease occurred as the sole clinical manifestation of NLE. Three clinical variants of hepatobiliary disease were observed: 1) severe liver failure present during gestation or in the neonatal period, often with the phenotype of neonatal iron storage disease; 2) conjugated hyperbilirubinemia with mild or no elevations of aminotransferases, occurring in the first few weeks of life; and 3) mild elevations of aminotransferases occurring at approximately 2 to 3 months of life. The prognosis for the children in the last 2 categories is excellent.

Conclusions. Hepatobiliary disease is a relatively common finding in NLE and can be the sole clinical manifestation of NLE. Clinicians should be aware of the broad range of hepatobiliary disease that may occur in children with NLE.
Increased Prevalence of Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator in Children With Chronic Rhinosinusitis
Authors: Raman Vidya , Clary Randall , Siegrist Karen L. , Zehnbauer Barbara , Chatila Talal A.
Published: August 2004

Objective. Chronic rhinosinusitis results in significant morbidity in the pediatric population; however, no predisposing factor is found in many cases. Cystic fibrosis (CF) is a recognized cause of chronic rhinosinusitis. Although the carrier frequency for CF ranges from 3% to 4% in the general white population, the prevalence of mutations in the CF transmembrane conductance regulator (CFTR) among children with chronic rhinosinusitis is unknown. Our objective was to study the frequency of CFTR mutations among children with chronic rhinosinusitis.

Methods. Fifty-eight white children who were from the St Louis metropolitan area and had chronic rhinosinusitis, none of whom satisfied diagnostic criteria for CF, underwent sweat testing and genotyping for CFTR mutations using an assay that detects 90% of mutations seen in this ethnic group.

Results. Seven of the 58 patients (12.1%) tested harbored CFTR mutations as compared with the expected rate of 3% to 4% in this ethnic group. Five patients had the ΔF508, 1 had the R117H, and 1 had the I148T mutation. Only 1 of the 7 children had a borderline abnormal sweat test. Two of the 58 patients experienced recurrent Pseudomonas aeruginosa rhinosinusitis, and both were ΔF508 heterozygotes. Three other children with no detectable CFTR mutation had borderline elevated sweat-test results. The CFTR intron 8 5T polymorphism was found at a frequency comparable to that reported for the general population.

Conclusion. There is an increased occurrence of CFTR mutations in children who have chronic rhinosinusitis and do not meet diagnostic criteria for CF, usually in the setting of a normal sweat chloride. These results suggest a role for CFTR mutations in predisposition to chronic rhinosinusitis.
Group A Streptococcus Spinal Epidural Abscess During Varicella
Authors: Quach Caroline , Tapiero Bruce , Noya Francisco
Published: August 2004

Multiple complications of varicella have been described. Musculoskeletal complications (osteomyelitis, septic arthritis, and necrotizing fasciitis) as well as neurologic complications (ataxia, encephalitis, and transverse myelitis) are well-known. We describe the cases of 2 children, ages 18 months and 5 years, who were admitted recently to 2 pediatric hospitals in Montreal with a resolving varicella, abdominal and lumbar pain, and a refusal to walk and in whom a diagnosis of epidural abscess caused by group A streptococcus (GAS) was established. No previous case of epidural abscess caused by GAS in the context of varicella has been reported. Epidural abscesses are rare in pediatrics and are caused mainly by hematogenous spread of Staphylococcus aureus. The diagnosis in pediatrics is challenging because it is rare and does not present as classically as in adults. The prognosis is related to the presence of neurologic deficits before surgery and to the rapidity with which the diagnosis and the intervention are made. These cases highlight a new clinical association in children of epidural abscess caused by GAS and varicella. An early clinical diagnosis requires a high index of suspicion when back or abdominal pain with or without neurologic signs and symptoms occurs during or soon after varicella.
Partial Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency as the Unsuspected Cause of Renal Disease Spanning Three Generations: A Cautionary Tale
Authors: Augoustides-Savvopoulou Persephone , Papachristou Fotis , Fairbanks Lynette D. , Dimitrakopoulos Kostas , Marinaki Anthony M. , Simmonds H. Anne
Published: August 2004

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an X-linked defect of purine metabolism. Clinical manifestations are usually related to the degree of enzyme deficiency: complete HPRT deficiency (Lesch-Nyhan syndrome) presenting with severe neurologic or renal symptoms, or partial HPRT deficiency (Kelley-Seegmiller syndrome) manifesting as a gout-urolithiasis syndrome. A 3-generation kindred is described in which the recognition of partial HPRT deficiency in 2 adolescent male siblings presenting with uric acid lithiasis led to the diagnosis in 2 maternal uncles already in renal failure of unknown cause. This report highlights the importance of clinical awareness leading to early diagnosis, appropriate diagnostic methodology, and therapy of a treatable inherited disorder of purine metabolism for the prevention of renal failure.
Philosophic Objection to Vaccination as a Risk for Tetanus Among Children Younger Than 15 Years
Authors: Fair Elizabeth , Murphy Trudy V. , Golaz Anne , Wharton Melinda
Published: August 2004

Objectives. Although safe and effective vaccines are available to protect against tetanus in the United States and vaccination rates are high, cases of tetanus among children continue to occur. The objectives of this article are to describe reported cases of tetanus in children in the United States and to identify the reasons for lack of protection against tetanus.

Methods. We reviewed all cases of tetanus in children <15 years of age that were reported to the National Notifiable Diseases Surveillance System from 1992 through 2000. Cases were defined by physician diagnosis. We verified the information in the case reports with state and local health departments.

Results. From 1992 through 2000, 15 cases of tetanus in children <15 years of age were reported from 11 states. Twelve cases were in boys. Two cases were in neonates <10 days of age; the other 13 cases were in children who ranged in age from 3 to 14 years. The median length of hospitalization was 28 days; 8 children required mechanical ventilation. There were no deaths. Twelve (80%) children were unprotected because of lack of vaccination, including 1 neonate whose mother was not vaccinated. Among all unvaccinated cases, objection to vaccination, either religious or philosophic, was the reported reason for choosing not to vaccinate.

Conclusion. The majority of recent cases of tetanus among children in the United States were in unvaccinated children whose parents objected to vaccination. Parents who choose not to vaccinate their children should be advised of the seriousness of the disease and be informed that tetanus is not preventable by means other than vaccination.
Mediators of the Association Between Age of First Sexual Intercourse and Subsequent Human Papillomavirus Infection
Authors: Kahn Jessica A. , Rosenthal Susan L. , Succop Paul A. , Ho Gloria Y. F. , Burk Robert D.
Published: August 2004

Objective. Previous studies have demonstrated that early age of first sexual intercourse is associated with human papillomavirus (HPV) infection. The objective of this study was to identify a set of risk behaviors and partner characteristics that mediate the association between age of first sexual intercourse and subsequent HPV infection in adolescent and young adult women.

Methods. Female university students completed surveys and underwent HPV testing every 6 months for up to 3 years. HPV-positive participants were matched to HPV-negative participants (252 pairs, total N = 504). Associations were examined between risk behaviors/partner characteristics and both age of first sexual intercourse and HPV infection. Those variables associated with either age of first sexual intercourse or HPV infection were entered into a generalized estimating equation (to account for the matched study design) modeling the association between age of first sexual intercourse and HPV infection.

Results. Mean age of first sexual intercourse was 16.7 (±1.8) years, and early age of first sexual intercourse was associated significantly with HPV infection (β = −0.20; odds ratio: 0.82; 95% confidence interval: 0.74–0.90). The association was mediated by number of sexual partners in the past 6 months, history of sexually transmitted infection, alcohol and drug use related to sexual behaviors, and partner’s number of sexual partners.

Conclusion. A set of behavioral risk factors and partner characteristics partially mediate the association between age of first sexual intercourse and subsequent HPV infection.
Religious/Spiritual Coping in Childhood Cystic Fibrosis: A Qualitative Study
Authors: Pendleton Sara M. , Cavalli Kristina S. , Pargament Kenneth I. , Nasr Samya Z.
Published: August 2004

Objective. To understand the role of religiousness/spirituality in coping in children with cystic fibrosis (CF).

Methods. Participants were a convenience sample of 23 patients with CF, ages 5 to 12 years, and their parent(s) in an ambulatory CF clinic. The design was a focused ethnography including in-depth interviews with children and parent(s), children’s drawings, and self-administered written parental questionnaires. Analysis used grounded theory.

Results. Main outcome measures were participants’ views on religion/spirituality in coping with illness. Data included 632 quotes organized into 257 codes categorized into 11 themes. One overarching domain emerged from analysis of the 11 themes: Religious/Spiritual Coping, composed of 11 religious/spiritual coping strategies.

Conclusions. Children with CF reported a variety of religious/spiritual coping strategies they nearly always associated with adaptive health outcomes. A preliminary conceptual framework for religious/spiritual coping in children with CF is presented. More study is needed to assess how variability in age, disease type, disease severity, religious/spiritual preference, and religious/spiritual intensity affect religious/spiritual coping in children with chronic illness. Future studies should also investigate whether physician attention to religious/spiritual coping could assist patients in coping with CF and strengthen the doctor-patient relationship.
Infant Weight Gain and Childhood Overweight Status in a Multicenter, Cohort Study
Authors: Stettler Nicolas , Zemel Babette S. , Kumanyika Shiriki , Stallings Virginia A.
Published: August 2004

Objective. To determine whether a rapid rate of weight gain in early infancy is associated with overweight status in childhood.

Design. Prospective, cohort study from birth to age 7 years.

Setting. Twelve sites across the United States.

Participants. Twenty-seven thousand, eight hundred ninety-nine (27 899) eligible participants born at full term between 1959 and 1965.

Main Outcome Measure. Overweight status at age 7 years, defined by a body mass index above the 95th percentile of the Centers for Disease Control and Prevention reference data.

Results. In the 19 397 participants with complete data (69.6%), the prevalence of overweight status at age 7 years was 5.4%. The rate of weight gain during the first 4 months of life (as 100 g/month) was associated with being overweight at age 7 years, after adjustment for several confounding factors: odds ratio: 1.38; 95% confidence interval: 1.32–1.44. This association was present in each birth weight quintile, and remained significant after adjustment for the weight attained at age 1 year (odds ratio: 1.17; 95% confidence interval: 1.11–1.24).

Conclusions. A pattern of rapid weight gain during the first 4 months of life was associated with an increased risk of overweight status at age 7 years, independent of birth weight and weight attained at age 1 year. These findings may lead to new hypotheses regarding the cause of childhood obesity, which may contribute to our understanding of this increasing public health problem in the United States.
Risk Factors for Severe Respiratory Syncytial Virus Infection Among Alaska Native Children
Authors: Bulkow Lisa R. , Singleton Rosalyn J. , Karron Ruth A. , Harrison Lee H. ,   the Alaska RSV Study Group
Published: August 2004

Objective. The incidence of hospitalization for respiratory syncytial virus (RSV) infection among Alaska Native children is much higher than among non-Native populations in the United States. We conducted this study to better understand factors associated with hospitalization attributable to RSV infection in this high-risk population.

Design. Case-control study, including collection of cord blood for RSV-neutralizing antibody measurement.

Setting. Remote region of southwest Alaska served by 1 regional hospital and 2 referral hospitals.

Subjects. Case-patients identified through surveillance for RSV infection and matched control subjects without acute respiratory infection hospitalization.

Results. Breastfeeding was associated with a lower risk of RSV hospitalization (odds ratio: 0.34), whereas underlying medical conditions (primarily prematurity) were associated with increased risk (odds ratio: 6.25). Environmental factors associated with a higher risk of hospitalization included household crowding (4 or more children in the household and crowding index ≥2). The level of maternal RSV-neutralizing antibody was not associated with the risk of hospitalization.

Conclusions. In this region with extremely high risk of RSV hospitalization, several measures, such as encouraging breastfeeding and reducing household crowding, could reduce the risk of hospitalization attributable to RSV.