Caroline L.S. George

Surfactant-Associated Protein A Provides Critical Immunoprotection in Neonatal Mice

ABSTRACT The collectins surfactant-associated protein A (SP-A) and SP-D are components of innate immunity that are present before birth. Both proteins bind pathogens and assist in clearing infection. The significance of SP-A and SP-D as components of the neonatal immune system has not been investigated. To determine the role of SP-A and SP-D in neonatal immunity, wild-type, SP-A null, and SP-D null mice were bred in a bacterium-laden environment (corn dust bedding) or in a semisterile environment (cellulose fiber bedding). When reared in the corn dust bedding, SP-A null pups had significant mortality (P < 0.001) compared to both wild-type and SP-D null pups exposed to the same environment. The mortality of the SP-A null pups was associated with significant gastrointestinal tract pathology but little lung pathology. Moribund SP-A null newborn mice exhibited Bacillus sp. and Enterococcus sp. peritonitis. When the mother or newborn produced SP-A, newborn survival was significantly improved (P < 0.05) compared to the results when there was a complete absence of SP-A in both the mother and the pup. Significant sources of SP-A likely to protect a newborn include the neonatal lung and gastrointestinal tract but not the lactating mammary tissue of the mother. Furthermore, exogenous SP-A delivered by mouth to newborn SP-A null pups with SP-A null mothers improved newborn survival in the corn dust environment. Therefore, a lack of SP-D did not affect newborn survival, while SP-A produced by either the mother or the pup or oral exogenous SP-A significantly reduced newborn mortality associated with environmentally induced infection in SP-A null newborns.

Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responses

Background Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early‐life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease.

Long-Term Use of Ventricular Assist Device as a Bridge to Recovery in Acute Fulminant Myocarditis

We report the successful long-term use of a left ventricular assist device (Berlin EXCOR) as a bridge to recovery in a patient with fulminant parvovirus B19 myocarditis. The use of this device allowed time for myocardial recovery, avoiding the need for cardiac transplantation.

Maternal surfactant protein A influences the immunoprotective properties of milk in a murine model

Background:Maternal surfactant protein A (SP-A), a collectin with innate immune system function, is critical to newborn mouse survival preventing bacterial peritonitis associated with a nonhygienic environmental exposure. We hypothesized that SP-A improves newborn survival by optimizing milk immunoprotection.Methods:Regional (lung) and systemic (milk and serum) immunologic responses to a novel antigen, 2,4-dintirophenyl keyhole limpet hemocyanin (DNP-KLH), and to a nonhygienic environment were evaluated in wild-type (WT) and SP-A null murine dams. Cross-fostering pups assessed the impact of milk on newborn survival.Results:Maternal SP-A optimized antigen-specific milk secretory IgA (sIgA) production following the DNP-KLH exposure. Milk total and environment-specific sIgA production was not dependent on maternal SP-A in the nonhygienic exposure. At baseline, SP-A null milk contained physiologically meaningful increases in two proinflammatory cytokines compared with WT milk. The lack of SP-A plus the nonhygienic environmental exposure synergistically increased the number of proinflammatory cytokines contained in milk. Finally, the SP-A null genotype decreased pup survival during a nonhygienic environmental exposure.Conclusion:Maternal SP-A impacts milk sIgA and cytokine content, and is associated with improved newborn health.

Endotoxin inhalation alters lung development in neonatal mice.

BACKGROUND Childhood asthma is a significant public health problem. Epidemiologic evidence suggests an association between childhood asthma exacerbations and early life exposure to environmental endotoxin. Although the pathogenesis of endotoxin-induced adult asthma is well studied, questions remain about the impact of environmental endotoxin on pulmonary responsiveness in early life. METHODS We developed a murine model of neonatal/juvenile endotoxin exposures approximating those in young children and evaluated the lungs inflammatory and remodeling responses. RESULTS Persistent lung inflammation induced by the inhalation of endotoxin in early life was demonstrated by the influx of inflammatory cells and pro-inflammatory mediators to the airways and resulted in abnormal alveolarization. CONCLUSIONS Results of this study advance the understanding of the impact early life endotoxin inhalation has on the lower airways, and demonstrates the importance of an experimental design that approximates environmental exposures as they occur in young children.

Vascular Channel Mimicking a Skull Fracture

A 15-month-old boy was referred for magnetic resonance imaging to evaluate macrocephaly. The magnetic resonance imaging demonstrated a small subacute left parietal subdural hematoma (Figure 1, A). The medical history was significant for delivery at 32 weeks gestation, no prenatal care, prenatal illicit drug exposure, several cutaneous hemangiomas below the neck in different phases of evolution, and foster care placement since 1 month of age. Additional medical evaluation included a head computed tomography with 3-dimensional reconstruction, which identified only a right frontal bone defect interpreted as a fracture (Figure 2; available at www.jpeds.com). Because of the skull and intracranial findings without a history of trauma, an evaluation for physical abuse was completed. A skeletal survey was significant for a longitudinal irregularity within the right frontal bone (Figure 1, B). Re-evaluation of the head computed tomography clarified the skull defect as a diploic vein tracking within the bone causing the calvarial deformity (Video; available at: www.jpeds.com). Skull defects, sometimes described as pseudofractures, include variation in suture formation and neurovascular channels. Cranial suture variations have been reported as child abuse mimics. Enlarged diploic veins and emissary veins (collateral pathways connecting dural sinuses to the external jugular circulation) are usually normal variants and can mimic fractures in adults. These skull veins have not been identified as a cause of pediatric pseudofractures or abuse mimics, to our knowledge. The American Academy of Pediatrics has published guidelines for age appropriate evaluation for occult injuries. Prompt identification and evaluation of sentinel injuries of abuse is important due to associated morbidity and mortality. Equally important is the correct identification of mimics of abuse. These complex cases need an interdisciplinary approach to help differentiate fractures from pseudofractures. Thus, vascular variants must be differentiated from skull fractures for accurate diagnosis and care. ■