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Rationale: Bronchopulmonary dysplasia (BPD) is a leading complication of preterm birth that affects infants born in the saccular stage of lung development at

Maternal infection-induced early pregnancy complications arise from perturbation of the immune environment at the uterine early blastocyst implantation site (EBIS), yet the underlying mechanisms remain unclear. Here, we demonstrated in a mouse model that the progression of normal pregnancy from days 4 to 6 induced steady migration of leukocytes away from the uterine decidual stromal zone (DSZ) that surrounds the implanted blastocyst. Uterine macrophages were found to be CD206+ M2-polarized. While monocytes were nearly absent in the DSZ, DSZ cells were found to express monocyte marker protein Ly6C. Systemic endotoxic lipopolysaccharide (LPS) exposure on day 5 of pregnancy led to: (1) rapid (at 2 h) induction of neutrophil chemoattractants that promoted huge neutrophil infiltrations at the EBISs by 24 h, (2) rapid (at 2 h) elevation of mRNA levels of MyD88, but not Trif, modulated cytokines at the EBISs, and (3) dose-dependent EBIS defects by day 7 of pregnancy. Yet, elimination of maternal neutrophils using anti-Ly6G antibody prior to LPS exposure failed to avert LPS-induced EBIS defects allowing us to suggest that activation of Tlr4-MyD88 dependent inflammatory pathway is involved in LPS-induced defects at EBISs. Thus, blocking the activation of the Tlr4-MyD88 signaling pathway may be an interesting approach to prevent infection-induced pathology at EBISs.

Lamellar bodies (LBs) are lysosome-related organelles (LROs) of surfactant-producing alveolar type 2 (AT2) cells of the distal lung epithelium. Trafficking pathways to LBs have been understudied but are likely critical to AT2 cell homeostasis given associations between genetic defects of endosome to LRO trafficking and pulmonary fibrosis in Hermansky Pudlak syndrome (HPS). Our prior studies uncovered a role for AP-3, defective in HPS type 2, in trafficking Peroxiredoxin-6 to LBs. We now show that the P4-type ATPase ATP8A1 is sorted by AP-3 from early endosomes to LBs through recognition of a C-terminal dileucine-based signal. Disruption of the AP-3/ATP8A1 interaction causes ATP8A1 accumulation in early sorting and/or recycling endosomes, enhancing phosphatidylserine exposure on the cytosolic leaflet. This in turn promotes activation of Yes-activating protein, a transcriptional coactivator, augmenting cell migration and AT2 cell numbers. Together, these studies illuminate a mechanism whereby loss of AP-3-mediated trafficking contributes to a toxic gain-of-function that results in enhanced and sustained activation of a repair pathway associated with pulmonary fibrosis.

Emerging evidence indicates that early life events can increase the risk for developing chronic obstructive pulmonary disease (COPD). Using an inducible transgenic mouse model for NF-κB activation in the airway epithelium, we found that a brief period of inflammation during the saccular stage (P3–P5) but not alveolar stage (P10–P12) of lung development disrupted elastic fiber assembly, resulting in permanent reduction in lung function and development of a COPD-like lung phenotype that progressed through 24 months of age. Neutrophil depletion prevented disruption of elastic fiber assembly and restored normal lung development. Mechanistic studies uncovered a role for neutrophil elastase (NE) in downregulating expression of critical elastic fiber assembly components, particularly fibulin-5 and elastin. Further, purified human NE and NE-containing exosomes from tracheal aspirates of premature infants with lung inflammation downregulated elastin and fibulin-5 expression by saccular-stage mouse lung fibroblasts. Together, our studies define a critical developmental window for assembling the elastin scaffold in the distal lung, which is required to support lung structure and function throughout the lifespan. Although neutrophils play a well-recognized role in COPD development in adults, neutrophilic inflammation may also contribute to early-life predisposition to COPD.

Alveolar type II (AT2) epithelial cells are uniquely specialized to produce surfactant in the lung and act as progenitor cells in the process of repair after lung injury. AT2 cell injury has been implicated in several lung diseases, including idiopathic pulmonary fibrosis and bronchopulmonary dysplasia. The inability to maintain primary AT2 cells in culture has been a significant barrier in the investigation of pulmonary biology. We have addressed this knowledge gap by developing a three-dimensional (3D) organotypic coculture using primary human fetal AT2 cells and pulmonary fibroblasts. Grown on top of matrix-embedded fibroblasts, the primary human AT2 cells establish a monolayer and have direct contact with the underlying pulmonary fibroblasts. Unlike conventional two-dimensional (2D) culture, the structural and functional phenotype of the AT2 cells in our 3D organotypic culture was preserved over 7 days of culture, as evidenced by the presence of lamellar bodies and by production of surfactant proteins B and C. Importantly, the AT2 cells in 3D cocultures maintained the ability to replicate, with approximately 60% of AT2 cells staining positive for the proliferation marker Ki67, whereas no such proliferation is evident in 2D cultures of the same primary AT2 cells. This organotypic culture system enables interrogation of AT2 epithelial biology by providing a reductionist in vitro model in which to investigate the response of AT2 epithelial cells and AT2 cell–fibroblast interactions during lung injury and repair.

Loss of secretory IgA is common in the small airways of patients with chronic obstructive pulmonary disease and may contribute to disease pathogenesis. Using mice that lack secretory IgA in the airways due to genetic deficiency of polymeric Ig receptor (pIgR-/- mice), we investigated the role of neutrophils in driving the fibrotic small airway wall remodeling and emphysema that develops spontaneously in these mice. By flow cytometry, we found an increase in the percentage of neutrophils among CD45+ cells in the lungs, as well as an increase in total neutrophils, in pIgR-/- mice compared with wild-type controls. This increase in neutrophils in pIgR-/- mice was associated with elastin degradation in the alveolar compartment and around small airways, along with increased collagen deposition in small airway walls. Neutrophil depletion using anti-Ly6G antibodies or treatment with broad-spectrum antibiotics inhibited development of both emphysema and small airway remodeling, suggesting that airway bacteria provide the stimulus for deleterious neutrophilic inflammation in this model. Exogenous bacterial challenge using lysates prepared from pathogenic and nonpathogenic bacteria worsened neutrophilic inflammation and lung remodeling in pIgR-/- mice. This phenotype was abrogated by antiinflammatory therapy with roflumilast. Together, these studies support the concept that disruption of the mucosal immune barrier in small airways contributes to chronic obstructive pulmonary disease progression by allowing bacteria to stimulate chronic neutrophilic inflammation, which, in turn, drives progressive airway wall fibrosis and emphysematous changes in the lung parenchyma.

Rationale: Antenatal factors, such as chorioamnionitis, preeclampsia, and postnatal injury, are associated with an increased risk for bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) after preterm birth. IGF-1 (insulin-like growth factor-1) is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown. Objectives: To evaluate whether postnatal treatment with rhIGF-1 (recombinant human IGF-1)/BP3 (binding peptide 3) improves lung growth and prevents PH in two antenatal models of BPD induced by intraamniotic exposure to endotoxin (ETX) or sFlt-1 (soluble fms-like tyrosine kinase 1), and in a postnatal model due to prolonged hyperoxia. Methods: ETX or sFlt-1 were administered into the amniotic sac of pregnant rats at Embryonic Day 20 to simulate antenatal models of chorioamnionitis and preeclampsia, respectively. Pups were delivered by cesarean section at Embryonic Day 22 and treated with rhIGF-1/BP3 (0.02–20 mg/kg/d intraperitoneal) or buffer for 2 weeks. Study endpoints included radial alveolar counts (RACs), vessel density, and right ventricular hypertrophy (RVH). Direct effects of rhIGF-1/BP3 (250 ng/ml) on fetal lung endothelial cell proliferation and tube formation and alveolar type 2 cell proliferation were studied by standard methods in vitro. Measurements and Main Results: Antenatal ETX and antenatal sFlt-1 reduced RAC and decreased RVH in infant rats. In both models, postnatal rhIGF-1/BP3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased lung endothelial cell and alveolar type 2 cell proliferation. Conclusions: Postnatal rhIGF-1/BP3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP3 treatment may provide a novel strategy for the prevention of BPD in preterm infants.

Sepsis disproportionately affects the very old and the very young. IL-1 signaling is important in innate host defense but may also play a deleterious role in acute inflammatory conditions (including sepsis) by promulgating life-threatening inflammation. IL-1 signaling is mediated by two distinct ligands: IL-1α and IL-1β, both acting on a common receptor (IL-1R1). IL-1R1 targeting has not reduced adult human sepsis mortality despite biologic plausibility. Because the specific role of IL-1α or IL-1β in sepsis survival is unknown in any age group and the role of IL-1 signaling remains unknown in neonates, we studied the role of IL-1 signaling, including the impact of IL-1α and IL-1β, on neonatal murine sepsis survival. IL-1 signaling augments the late plasma inflammatory response to sepsis. IL-1α and not IL-1β is the critical mediator of sepsis mortality, likely because of paracrine actions within the tissue. These data do not support targeting IL-1 signaling in neonates.

The developing neonate is exposed to a plethora of antigens and must evolve innate and adaptive immune responses to combat pathogenic microorganisms and at the same time, develop tolerance to self-antigens and commensal microbes. While some components of the immune system are functionally at par with adults, immaturity in others may result in a state of immunodeficiency in the neonate. This chapter highlights the qualitative and quantitative differences in distribution and function of leukocyte populations that together shape the immune responses in the fetus, neonate and the adult. Knowledge of these differences may enable a better understanding of the inherent susceptibility of the neonate to various infections.

Wnt/β-catenin signaling is necessary for normal lung development, and abnormal Wnt signaling contributes to the pathogenesis of both bronchopulmonary dysplasia (BPD) and idiopathic pulmonary fibrosis (IPF), fibrotic lung diseases that occur during infancy and aging, respectively. Using a library of human normal and diseased human lung samples, we identified a distinct signature of nuclear accumulation of β-catenin phosphorylated at tyrosine 489 and epithelial cell cytosolic localization of β-catenin phosphorylated at tyrosine 654 in early normal lung development and fibrotic lung diseases BPD and IPF. Furthermore, this signature was recapitulated in murine models of BPD and IPF. Image analysis of immunofluorescence colocalization demonstrated a consistent pattern of elevated nuclear phosphorylated β-catenin in the lung epithelium and surrounding mesenchyme in BPD and IPF, closely resembling the pattern observed in 18-week fetal lung. Nuclear β-catenin phosphorylated at tyrosine 489 associated with an increased expression of Wnt target gene AXIN2, suggesting that the observed β-catenin signature is of functional significance during normal development and injury repair. The association of specific modifications of β-catenin during normal lung development and again in response to lung injury supports the widely held concept that repair of lung injury involves the recapitulation of developmental programs. Furthermore, these observations suggest that β-catenin phosphorylation has potential as a therapeutic target for the treatment and prevention of both BPD and IPF.

Alveolar epithelial cell (AEC) dysfunction underlies the pathogenesis of pulmonary fibrosis in Hermansky-Pudlak syndrome (HPS) and other genetic syndromes associated with interstitial lung disease; however, mechanisms linking AEC dysfunction and fibrotic remodeling are incompletely understood. Since increased macrophage recruitment precedes pulmonary fibrosis in HPS, we investigated whether crosstalk between AECs and macrophages determines fibrotic susceptibility. We found that AECs from HPS mice produce excessive MCP-1, which was associated with increased macrophages in the lungs of unchallenged HPS mice. Blocking MCP-1/CCR2 signaling in HPS mice with genetic deficiency of CCR2 or targeted deletion of MCP-1 in AECs normalized macrophage recruitment, decreased AEC apoptosis, and reduced lung fibrosis in these mice following treatment with low-dose bleomycin. We observed increased TGF-β production by HPS macrophages, which was eliminated by CCR2 deletion. Selective deletion of TGF-β in myeloid cells or of TGF-β signaling in AECs through deletion of TGFBR2 protected HPS mice from AEC apoptosis and bleomycin-induced fibrosis. Together, these data reveal a feedback loop in which increased MCP-1 production by dysfunctional AECs results in recruitment and activation of lung macrophages that produce TGF-β, thus amplifying the fibrotic cascade through AEC apoptosis and stimulation of fibrotic remodeling.

Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18-null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G(+) myeloid cells, and blocking IL-17A reduced IL-18-potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18-mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis.

To determine the impact of cerebellar hemorrhage (CH) on mortality and adverse neurodevelopmental (ND) outcome rates in extremely preterm infants admitted to a tertiary neonatal unit. A total of 1120 eligible infants (

Background Communication of children's weight status and targeted counseling by pediatricians may change parental perceptions or child dietary and physical activity behaviors. The aim of this study was to determine whether accuracy of parental perception of children's weight status and reports of related behaviors changed following a brief pediatrics resident intervention. Methods Parents (N = 115) of children aged 4 to 12 years enrolled in Medicaid completed baseline questionnaires with providers about prior communication of weight status and/or body mass index (BMI), perceptions of their children's weight, and children's dietary and physical activity behaviors, and children were weighed and measured. Trained residents used a toolkit to communicate weight status to parents (via color-coded BMI charts) and counseled about mutually chosen healthy behaviors. Questionnaires were repeated at 1 and 3 months, and measurements were repeated for children with BMI ≥85%. Results At baseline, 42% of parents of overweight children believed their children were at healthy weight. Most (n = 96; 83%) parents completed 1-month questionnaires, and 56% completed 3-month follow-up questionnaires. Improvements in fruit and vegetable consumption, sweet drinks, unhealthy snacks, frequency of restaurant food, lower-fat milk, and screen time occurred among both overweight and healthy weight children. There were also increases in discussions with providers about weight/BMI and parental accuracy of overweight assessment. Conclusions Parent accuracy of weight status and short-term childhood dietary and physical activity behavior changes improved following resident pediatrician use of a toolkit to support communication of weight status and counseling. Further research needs to determine whether accurate parental perception motivates improved behavior change or healthier BMI trajectories.

Objective. Neonates with congenital heart disease (CHD) frequently require prompt intervention to improve outcomes and limit morbidities. We sought to determine the time to identification for infants with serious CHD admitted to the State of Alabama's neonatal cardiovascular center and to identify types of cardiac lesions associated with an earlier vs. later diagnosis. Design/Setting. Medical record review of all infants admitted to Alabama's cardiovascular referral center over a 3-year period. Patients. Neonates with serious CHD admitted for medical/surgical care. Results. In total, 178 neonates were identified with serious CHD. Of these, 146 (82%) were identified postnatally. Thirty-two (21%) of the postnatally detected infants were identified after initial discharge from the hospital. Neonates with aortic arch anomalies presented at a median age of 7 days. Conclusion. Identification of infants with serious CHD, especially those with aortic arch anomalies is frequently delayed. These findings support the need for improved methods to detect CHD in the newborn.

PURPOSE: The purpose of this study was to estimate the prevalence of dementia in individuals 65 years of age and older in the state of South Carolina using capture-recapture methodology. METHODS: We linked data from the Department of Mental Health admissions, inpatient admissions, and emergency room visits. Separate log-linear models were used to obtain estimates of the underascertainment-corrected prevalence of dementia in twelve age-gender-race subgroups, which were summed to estimate the prevalence of dementia in the total population. RESULTS: We found an overall prevalence of dementia of 14% in South Carolina for persons 65 years of age and older using capture-recapture methodology. This estimate of persons with dementia is 25% higher than the identified cases of dementia in the South Carolina Alzheimer's Disease Registry (10.5%). CONCLUSIONS: Although capture-recapture methods are prone to limitations, they can be used to more accurately estimate the prevalence of dementia in a geographic area.

BACKGROUND: Adult mammalian cardiac myocytes are generally assumed to be terminally differentiated; nonetheless, a small fraction of cardiac myocytes have been shown to replicate during ventricular remodeling. However, the expression of Replication Factor C (RFC; RFC140/40/38/37/36) and DNA polymerase δ (Pol δ) proteins, which are required for DNA synthesis and cell proliferation, in the adult normal and hypertrophied hearts has been rarely studied. METHODS: We performed qRT-PCR and Western blot analysis to determine the levels of RFC and Pol δ message and proteins in the adult normal cardiac myocytes and cardiac fibroblasts, as well as in adult normal and pulmonary arterial hypertension induced right ventricular hypertrophied hearts. Immunohistochemical analyses were performed to determine the localization of the re-expressed DNA replication and cell cycle proteins in adult normal (control) and hypertrophied right ventricle. We determined right ventricular cardiac myocyte polyploidy and chromosomal missegregation/aneuploidy using Fluorescent in situ hybridization (FISH) for rat chromosome 12. RESULTS: RFC40-mRNA and protein was undetectable, whereas Pol δ message was detectable in the cardiac myocytes isolated from control adult hearts. Although RFC40 and Pol δ message and protein significantly increased in hypertrophied hearts as compared to the control hearts; however, this increase was marginal as compared to the fetal hearts. Immunohistochemical analyses revealed that in addition to RFC40, proliferative and mitotic markers such as cyclin A, phospho-Aurora A/B/C kinase and phospho-histone 3 were also re-expressed/up-regulated simultaneously in the cardiac myocytes. Interestingly, FISH analyses demonstrated cardiac myocytes polyploidy and chromosomal missegregation/aneuploidy in these hearts. Knock-down of endogenous RFC40 caused chromosomal missegregation/aneuploidy and decrease in the rat neonatal cardiac myocyte numbers. CONCLUSION: Our novel findings suggest that transcription of RFC40 is suppressed in the normal adult cardiac myocytes and its insufficient re-expression may be responsible for causing chromosomal missegregation/aneuploidy and in cardiac myocytes during right ventricular hypertrophy.

The fetal lung vasculature forms in tandem with developing airways. Whereas saccular airway morphogenesis is arrested in bronchopulmonary dysplasia (BPD), the potential vascular phenotype in BPD at this stage of development is less well-understood. As inflammation increases the risk of BPD and induces arrest of saccular airway morphogenesis, we tested the effects of Escherichia coli LPS on fetal mouse lung vascular development. Injecting LPS into the amniotic fluid of Tie2- lacZ endothelial reporter mice at embryonic day 15 stimulated angiogenesis in the saccular stage fetal lung mesenchyme. LPS also increased the number of endothelial cells in saccular stage fetal mouse lung explants. Inflammation appeared to directly promote vascular development, as LPS stimulated pulmonary microvascular endothelial cell angiogenesis, cell migration, and proliferation in vitro. Whereas LPS did not increase expression of VEGF, angiopoietin-1 (Ang-1), Tie2, fetal liver kinase-1 (Flk-1), fms-like tyrosine kinase-1 (Flt-1), PDGFA, PDGFB, heparin-binding EGF-like growth factor (HB-EGF), or connective tissue growth factor (CTGF), LPS did stimulate the production of the angiogenic CC chemokines macrophage inflammatory protein-1α (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1). Both MIP-1α and MCP-1 increased angiogenesis in fetal mouse lung explants. In addition, inhibitory antibodies against MIP-1α and MCP-1 blocked the effects of LPS on fetal lung vascular development, suggesting these chemokines are downstream mediators of LPS-induced angiogenesis. We speculate that an inflammation-mediated surge in angiogenesis could lead to formation of aberrant alveolar capillaries in the lungs of patients developing BPD.

This pilot investigation assesses whether barriers to children's healthy eating and physical activity reported by parents on a newly developed brief pediatric obesity screening and counseling tool are related to healthy eating and physical activity behaviors. The sample included parents of 115 Medicaid-enrolled children in a general pediatric clinic. Of 10 barriers, 7 were statistically associated with parent-reported behaviors with odds ratios (ORs) ranging from 0.6 to 9.4. Relationships remained significant when child characteristics were controlled in the analysis. Although additional testing is needed, the tool provides clinicians with an approach to identify barriers and behaviors for targeted counseling.

The obesity epidemic confronts the pediatrician every day in the office. Pediatricians should help curb the epidemic through prevention and the usual pediatric primary care tasks of screening, communication and anticipatory counseling. This review highlights findings from recent literature to guide office-based prevention of obesity in children.More and more, children and society feel the effects of the obesity epidemic; prevention efforts need to begin earlier. Pediatricians' efforts to screen help identify at-risk children who may benefit from early lifestyle changes. The identification of overweight children also helps foster the appropriate work up of comorbidities. Pediatricians' communication of weight trajectories, which includes techniques like motivational interviewing, may help parents to adopt behavioral prescriptions. Pediatricians should focus on promoting breastfeeding, limiting television, increasing physical activity and reducing sugar-sweetened beverages. New tools used in the training setting show promising results.Pediatricians must focus efforts on preventing childhood overweight, while awaiting effective treatment options for this chronic illness with its many associated morbidities. Such prevention involves sensitively communicating early body mass index screening results to parents and helping them to adopt key behavioral changes in diet and physical activity.

Many extremely preterm infants continue to suffer from bronchopulmonary dysplasia, which results from abnormal saccular-stage lung development. Here, we show that fibroblast growth factor-10 (FGF-10) is required for saccular lung development and reduced in the lung tissue of infants with bronchopulmonary dysplasia. Although exposure to bacteria increases the risk of bronchopulmonary dysplasia, no molecular target has been identified connecting inflammatory stimuli and abnormal lung development. In an experimental mouse model of saccular lung development, activation of Toll-like receptor 2 (TLR2) or Toll-like receptor 4 (TLR4) inhibited FGF-10 expression, leading to abnormal saccular airway morphogenesis. In addition, Toll-mediated FGF-10 inhibition disrupted the normal positioning of myofibroblasts around saccular airways, similar to the mislocalization of myofibroblasts seen in patients with bronchopulmonary dysplasia. Reduced FGF-10 expression may therefore link the innate immune system and impaired lung development in bronchopulmonary dysplasia.

To assess the incidence, treatment, and follow-up of iron deficiency in children seen in a tertiary hospital, a retrospective chart review was performed in 2002 of 364 consecutive children screened for iron deficiency with free erythrocyte protoporphyrin and hemoglobin. Sixty-five of the 352 children studied (18.5%) were iron-deficient and 19 patients (5.4%) were anemic. Eighty percent of the affected children were treated with iron, and only 25% had follow-up blood testing done. Iron deficiency is common in children younger than 2 years of age. Whether or not the children had anemia, treatment and follow-up were less than optimal.

A 6-year-old female presented to her local emergency room with a history of vomiting and fever. She had had 20-30 episodes of emesis over the previous 2 days and an acute onset of abdominal distension and also gave a 1-day history of fever to 101°F. Two weeks before her ER visit she had had a spica cast placed because of a right femur fracture resulting from a motor vehicle accident. Her medical history was significant for Schwartz-Jampel syndrome, type 1. She demonstrated the following characteristics of this syndrome: mild developmental delay, skeletal muscle abnormalities including muscle weakness and stiffness, short stature, small mouth, flat nose, short neck, muscular hypertrophy, and stiffness in her wrists and fingers. Both Tegretol® (started at 3 years of age) and Dilantin® (begun at 5 years of age) had controlled her muscle stiffness. She had had no difficulty related to her spica cast until 2 days before her visit to the ER. On presentation to the ER, her abdomen was so distended that the anterior portion of her spica cast needed to be removed. Laboratory findings included the following: elevated concentrations of amylase (488 mu/mL) and lipase (761 U/dL), a peripheral white cell count of 28,900/cm3 with 87% segmented polys, therapeutic concentrations of Tegretol® and DilantinO, and normal results from liver function tests: aspartate aminotransferase (AST): 47 mU/mL; alanine

Objectives: To describe a pediatric resident telephone triage system in a tertiary hospital and to determine its relevance to telephone experience in general pediatric practice. Design: An analysis of 514 telephone calls from parents of continuity clinic patients made to pediatric residents. The evaluation included: chief complaint, disposition of call, age of patient, and level of training of the resident answering the call. A comparison was made with published information about a private-practice telephone triage system. Setting: Pediatric continuity clinic, Medical College of Georgia, Augusta. Patients: Children registered in the pediatric resident continuity clinic at the Medical College of Georgia. Results: The 13 most frequent reasons for calling were some of the most common problems seen in pediatric practice. The disposition of calls was as follows: 272 (53%) were given telephone advice alone, 119 (23%) were offered an appointment for the next day, and 123 (24%) were advised to come to the emergency department immediately. Disposition did not vary with residency level. Both chief complaints and disposition of calls were similar to those reported in a private-practice nurse triage system. Conclusions: Answering telephone calls in a residency telephone triage system, when combined with a curriculum that includes next-day monitoring, feedback from a preceptor, and seminar discussions focused on telephone management situations, is a valuable training experience and is relevant for residents going into private pediatric practice. Arch Pediatr Adolesc Med. 1997;151:1254-1257

Free erythrocyte protoporphyrin (FEP) and hemoglobin (Hgb)concentrations were tested in 790 children in a private pediatric office; results were compared to those obtained in 1984. Only 16 children (2%) had abnormal FEPs in 1990 compared to 76 children (9.6%) in the earlier study. The mean FEP in the normal group also decreased significantly in each age group studied. The hemoglobin concentrations were not significantly different in most of the age groups studied. Screening for iron deficiency in our pediatric practice by determining hemoglobin and FEP concentrations had a much lower yield in 1990 than in 1984.

Purpose of Study Prenatal exposure to inflammation increases the risk of bronchopulmonary dysplasia (BPD) in preterm infants. In a fetal mouse lung model, lipopolysaccharide (LPS) decreased distal airway branching, which may contribute to BPD pathology. In a candidate gene approach, we tested if LPS decreased expression of FGF-10, a master regulator of branching morphogenesis. We hypothesized that decreased FGF-10 expression could lead to defective distal airway branching. Methods E16 fetal mouse lung explants were cultured for up to 72 hours. Distal airway branching was measured by counting the number of distal airways per explant area. Fetal mouse lung mesenchymal cells were also isolated and cultured. Gene expression was measured by real time PCR. Results We measured decreased FGF-10 gene expression in LPS-treated fetal lung explants (55% of control, p Conclusion LPS decreased FGF-10 expression and altered gene expression along the FGF-10 signaling pathway. Decreased FGF-10 expression may identify a mechanism by which innate immunity can contribute to BPD.

Introduction Severe congenital cardiovascular malformation (CCVM) occurs in 1 to 2 per 1000 live births. The outlook for newborns with CCVM has improved considerably, but these malformations still contribute morbidity and mortality in this age group particularly with delays in recognition and treatment. Aim To determine the prevalence of late referral for infants with serious congenital cardiac anomalies. Methods All neonates with CCVM admitted to Alabama9s regional cardiovascular referral center from January 1, 1989 to June 30, 2004 were eligible for study. Demographic data and time of referral for cardiovascular evaluation were collected prospectively and maintained in a database. Medical records of a subset of these infants, admitted from January 1 to August 20, 2004, were reviewed retrospectively. Information on type of cardiac lesion, time of diagnosis, and various demographic variables was obtained. Infants with patent ductus arteriosus or ventricular septal defect as the only cardiac diagnosis were not included. Referral was considered late if it occurred after 2 days of age. Results During the 15-year study period, 2390 infants were admitted with CCVM. 726 (30%) were referred for care after 2 days of age. During the study year, 2004, 59 infants were referred with CCVM. Overall, 19 infants (32%) were diagnosed after postnatal day 2. The figure shows the proportion of early and late referrals in study year 2004 for each cardiac diagnosis. Conclusion More than 30% of infants with serious CCVM were referred for diagnosis and treatment after the second postnatal day. The high proportion of infants in whom diagnosis of CCVM is delayed underscores the need for earlier detection and referral.

Congenital dyserythropoietic anemia is characterized by ineffective erythropoiesis and increased numbers of multinucleated red cell precursors in the marrow. This syndrome has been subclassified on the basis of morphologic differences in the red cell precursors. Type I is characterized by megaloblastoid erythropoiesis and macrocytosis; Type II, by normoblastic multinuclearity and normocytosis; and Type III, by frequent giant multinucleated erythroblasts and macrocytes. Type II is further distinguished from the other types by serologic and ultrastructural abnormalities. The patient presented in this report does not fit any of the above categories; her red cells are similar to Type II congenital dyserythropoietic anemia cells, but no characteristic ultrastructural or serologic abnormalities are present. It is suggested that this patient may represent an additional variant of congenital dyserythropoietic anemia, Type IV.

stream or (2) altered bowel mucosa may have allowed enteric organisms to invade the bloodstream, resulting in secondary sepsis. Neither of our patients had intravenous fluid infusing at a single site for more than 48 hours. Maki and associates ~ noted that only one of 535 patients receiving intravenous fluid therapy through scalp vein needles developed septicemia. It seems improbable that our two patients developed Klebsiella sepsis secondary to scalp vein needles. There were no other concurrent cases of Klebsiella sepsis while either of the two patients was hospitalized. Alternately, shigellae may disrupt the bowel mucosa and allow the penetration of other enteric bacteria. Haltalin and Nelson :~ suggested this as the explanation for secondary Aerobacter sepsis complicating shigellosis in three of their patients. Our two patients, as did those patients of Haltalin and Nelson, had initial improvement and then developed a secondary fever. Blood cultures obtained during the secondary fever revealed septicemia. Secondary temperature elevation rarely occurs during Shigella dysentery and should serve as a marker for a possibly serious complication of Shigella dysentery or intravenous fluid therapy. Blood cultures should be obtained in the event of a secondary fever so that gramnegative sepsis might be recognized quickly and appropriately treated.

Postsplenectomy sepsis is a serious problem with high morbidity and high mortality. Surgical alternatives to total splenectomy are being sought. This paper describes two cases where, after splenectomy, some splenic tissue was either reimplanted or was left in situ and remains functional.