Lonnie C. Roy

Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less.

OBJECTIVE. Ductus arteriosus (DA) closure occurs within 96 hours in >95% of neonates >1500 g in birth weight (BW). The prevalence and postnatal age of spontaneous ductal closure in neonates ≤1000 g in BW (extremely low birth weight [ELBW] neonates) remain unclear, as does the incidence of failure to close with indomethacin. Therefore, we prospectively examined the prevalence, postnatal age, and clinical variables associated with spontaneous DA closure, occurrence of persistent patent DA, and indomethacin failure in ELBW neonates. METHODS. Neonates delivered at Parkland Memorial Hospital from February 2001 through December 2003 were studied. Those with congenital heart defects or death <10 days postnatally were excluded. Echocardiograms were performed 48 to 72 hours postnatal and every 48 hours until 10 days postnatally. RESULTS. We studied 122 neonates with BW of 794 ± 118 (SD) g and estimated gestational age (EGA) of 26 ± 2 weeks. Spontaneous permanent DA closure occurred in 42 (34%) neonates at 4.3 ± 2 days postnatally, with 100% closure by 8 days. These neonates were more mature, less likely to have received antenatal steroids or have hyaline membrane disease (HMD; 52% vs 79%), and more likely to be growth restricted (31% vs 5%) and delivered of hypertensive women. Using regression analysis, EGA and absence of antenatal steroids and HMD predicted ductal closure. Ten (8%) neonates with early DA closure reopened and required medical/surgical closure. Eighty neonates had persistent patent DA; 7 were surgically ligated, and 5 remained asymptomatic, with 4 of 5 closing after 10 days postnatally. Sixty-eight (85%) received indomethacin at 6.2 ± 4 days postnatally; 41% failed therapy and had no distinguishing characteristics. CONCLUSIONS. Spontaneous permanent DA closure occurs in >34% of ELBW neonates and is predicted by variables related to maturation, for example, EGA and an absence of HMD, whereas indomethacin failure could not be predicated.

Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis

A subset of Spitz nevi poses substantial diagnostic difficulty, even among experts, due to its resemblance to malignant melanoma. These lesions are termed atypical Spitz nevi/tumors and there is currently a lack of objective criteria for predicting their biologic behavior. We compared the expression of Ki-67, p21, and fatty acid synthase by immunohistochemistry in 10 atypical Spitz nevi, 28 typical Spitz nevi, 19 compound melanocytic nevi and 18 invasive malignant melanomas. There was a progressive increase in fatty acid synthase cytoplasmic expression with statistically significant differences observed between Spitz nevi and atypical Spitz nevi (P=0.003) and between atypical Spitz nevi and malignant melanoma (P<0.050). Ki-67 nuclear staining was lower in both typical and atypical forms of Spitz lesions than in malignant melanoma (P<0.001). The degree of P21 nuclear expression in atypical Spitz nevi was not significantly different than in Spitz nevi, but was significantly greater than expression in conventional nevi and approached significance after multiple comparisons corrections for malignant melanoma. Thus, a high level of P21 expression makes a tumor more likely to be a typical or atypical Spitz nevus than a malignant melanoma, especially when coupled with a low Ki-67 index and weak expression of fatty acid synthase. These immunohistochemical observations support the concept that atypical Spitz nevi are distinct lesions of borderline biologic behavior residing between Spitz nevi and malignant melanoma. The study also compared a large array of histologic features of 16 cases of typical Spitz nevi in children with 12 typical Spitz nevi in adults. The adult lesions were significantly more likely to be intradermal and to display dermal fibroplasia, but were histologically similar to their pediatric counterparts in all other respects.

Differential Recruitment of Dendritic Cells and Monocytes to Respiratory Mucosal Sites in Children with Influenza Virus or Respiratory Syncytial Virus Infection

BACKGROUND Influenza virus and respiratory syncytial virus (RSV) are among the most common viruses causing infections of the lower respiratory tract in young children. Although there are important differences in the immunopathogenesis of these 2 viral pathogens, little is known about how they affect antigen-presenting cells in children with acute infections. METHODS To characterize the immune cells that are mobilized to the respiratory tract by influenza virus and RSV, we analyzed nasal wash and blood samples obtained from children hospitalized with acute respiratory infections. RESULTS Influenza virus and RSV mobilize immune cells, including myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), to the nasal mucosa. Patients with influenza virus infection had greater numbers of mDCs, pDCs, and monocytes in nasal wash samples than did patients with RSV infection. The frequencies of respiratory tract and blood T cell subsets were not affected by infection with influenza virus or RSV. Monocyte chemoattractant protein-1 concentrations in nasal wash samples were significantly increased in patients with influenza virus infection but not in those with RSV infection. RANTES (regulated on activation, normally T cell expressed and secreted) concentrations were increased only in the blood of patients with influenza virus infection. CONCLUSIONS Infection with influenza virus or RSV mobilizes antigen-presenting cells to the respiratory tract. The differences in antigen-presenting cell numbers and cytokine concentrations suggest that there are distinctive, early immune responses to these 2 viruses.

A comparison of the influence of hospital-trained, ad hoc, and telephone interpreters on perceived satisfaction of limited English-proficient parents presenting to a pediatric emergency department

Background: Latinos are the fastest growing minority group in the United States with a significant percentage of this population having limited English proficiency. Objective: To determine whether mode of interpretation influences satisfaction of limited English-proficient parents presenting to a tertiary care pediatric emergency department. Design: One hundred eighty parents of patients presenting to a pediatric emergency department were surveyed after receiving services from one of the following interpreters: hospital-trained, ad hoc, or telephone. An English-proficient comparison group of 60 parents of any ethnicity was also surveyed (total N = 240). Results: Parents were significantly more satisfied (P < 0.001) with hospital-trained interpreters. While no significant difference was found in overall visit satisfaction, there were significant differences in several other outcome variables. When hospital-trained interpreters were used, parents were significantly more satisfied (P < 0.001) with their physicians and nurses. With regard to the ability to communicate with pediatric emergency department personnel, parents using hospital-trained interpreters averaged significantly higher scores (P < 0.001) than the telephone group. Quality-of-care scores were significantly higher (P < 0.001) for parents assigned to hospital-trained interpreters than for the other forms of interpretation. English-proficient parents scored highest in the following categories: ability to communicate, quality of care, and overall visit satisfaction. Parents using hospital-trained interpreters scored higher than English-proficient parents when questioned about physician and nursing satisfaction. Conclusion: Hospital-trained interpreters are a valuable and needed resource to facilitate communication with limited English-proficient patients and families. Other interpretation services are useful but have limitations.

Fatty acid synthase expression in cutaneous melanocytic neoplasms.

Mammalian fatty acid synthase is a multifunctional enzyme complex involved in de novo synthesis of saturated fatty acids, and inhibitors of fatty acid synthase are being evaluated as potential therapeutic agents. Increased fatty acid synthase expression has been demonstrated in subsets of malignancies, including colon, breast, endometrium, prostate and ovarian carcinomas, and recently malignant melanomas. We evaluated the immunohistochemical expression of fatty acid synthase in 155 cutaneous melanocytic lesions. They included 30 congenital nevi, 19 compound nevi, 40 Spitz nevi, 48 primary melanomas, and 18 metastatic melanomas. Fatty acid synthase expression was stronger in malignant melanomas in comparison to conventional nevi and Spitz nevi, and was the highest for metastatic melanoma. Of the primary malignant melanomas, mean fatty acid synthase scores were significantly greater for Clark levels IV and V compared to Clark levels I and II (P<0.001). In addition, melanomas with Breslow thickness 0.75–1.50 mm and >1.50 mm showed significantly higher mean fatty acid synthase scores compared with those with Breslow thickness <0.75 mm (P=0.013 and <0.001, respectively). Of interest, congenital melanocytic nevi also showed strong fatty acid synthase expression, similar to that seen in metastatic melanoma. This may represent persistence of or regression to a fetal phenotype since normal fetal tissues are known to express high levels of fatty acid synthase.

Amylase and lipase measurements in paediatric patients with traumatic pancreatic injuries

INTRODUCTION Pancreatic injuries occur in up to 10% of paediatric patients who suffer blunt trauma. Initial amylase and lipase measurements have not been helpful as a screening tool to detect pancreatic injuries. However, one primarily adult study suggests that a delayed measurement may be useful. MATERIALS AND METHODS A retrospective chart review was conducted of patients admitted to a Level I paediatric trauma centre from April 1996 to November 2006 with traumatic pancreatic injuries. RESULTS The trauma database identified 51 patients with traumatic pancreatic injuries. Inclusion and exclusion criteria were met by 26 patients. Patients with initial amylase and lipase levels measured greater than 2h post-injury were more consistently elevated compared to those patients who had levels measured at 2h or less post-injury. There was a significant association between time of measurement and an increased amylase level (p=0.012). No significant association was found for lipase measurements (p=0.178). DISCUSSION AND CONCLUSIONS In children with blunt pancreatic injury, elevated serum amylase levels were seen in a significantly higher percentage of patients with initial measurements at greater than 2h post-injury compared to those measured at 2h or less. Lipase measurements demonstrated a similar trend. Delayed amylase and lipase measurements may be helpful to detect pancreatic injuries, but further study is needed.

Results of an inner-city school-based asthma and allergy screening pilot study: a combined approach using written questionnaires and step testing

BACKGROUND A questionnaire alone may not be an adequate screening tool for asthma. OBJECTIVE To determine whether an asthma questionnaire used in combination with an exercise step test is better than a questionnaire alone in screening for asthma in children and to evaluate the validity of a rhinitis questionnaire in determining atopy. METHODS The International Study of Asthma and Allergies in Childhood (ISAAC) asthma core questionnaire was used to screen for asthma in 307 inner-city first through third graders. All children who had scores consistent with a diagnosis of asthma underwent step testing, as did a subset of children who had negative overall scores. All children who had inconsistent asthma scores and step test results underwent methacholine challenge testing. The same 307 children underwent rhinitis screening and children who had one or more positive responses on the ISAAC rhinitis questionnaire underwent skin testing as did a subset of children who had all negative responses. RESULTS Three hundred of 307 asthma and rhinitis questionnaires were returned. Twenty-eight children (9%) had global asthma scores that were considered to be positive (5 or above). Twenty-four of these children underwent step testing as did 34 randomly selected children who had negative global asthma scores. Thirty-one (91%) of the 34 children who had negative global asthma scores had negative step tests. Similarly, 20 of 24 children (83%) of the children who had positive global asthma scores had negative step tests. Only 4 children who had positive global asthma scores were step test-positive or had reversible airway obstruction at baseline. Using a positive methacholine challenge as the gold standard for establishing bronchial hyperresponsiveness, the global asthma score derived from the eight-item ISAAC asthma questionnaire yielded a sensitivity of 64%, a specificity of 11%, a positive predictive value of 47%, and a negative predictive value of 20%. Comparing the six-item ISAAC rhinitis questionnaire results to the gold standard, skin test reactivity, the questionnaire yielded a sensitivity of 76%, a specificity of 21%, a positive predictive value of 56%, and a negative predictive value of 40%. CONCLUSIONS Step testing was not useful as a screening tool for asthma. In addition, the ISAAC asthma questionnaire may not be a good asthma screening tool for inner-city pediatric populations, especially if the form is self-administered. Investigators should first validate both the ISAAC asthma and rhinitis screening questionnaires in the particular population to be studied before widespread asthma and allergy screening efforts are initiated using these tools.

Echocardiographic predictors of symptomatic patent ductus arteriosus in extremely-low-birth-weight preterm neonates

Objective:Identify echocardiographic parameters at ⩽4 day postnatal that predict the subsequent need for closure of a clinically significant patent ductus arteriosus (sPDA) in extremely-low-birth-weight neonates (ELBW).Study Design:Serial echocardiograms obtained in 115 ELBW at ⩽10 day postnatal were examined to estimate PDA size using the PDA:left pulmonary artery (LPA) diameter ratio: ⩾1 indicated a large PDA, <1 but ⩾0.5 moderate, and <0.5 small. Sensitivity, specificity, and positive predictive values (PPV) were determined for ELBW <27 weeks and ⩾27 weeks gestational age.Result:Neonates with moderate to large PDA at ⩽4 day had 15-times greater likelihood of requiring treatment for sPDA than those with a small PDA (95% confidence interval (CI): 5.6–41). Sensitivity, specificity and PPV of the PDA:LPA at <27 weeks was 80, 86 and 92%, respectively.Conclusion:A moderate to large PDA determined from the PDA:LPA ratio at ⩽4 day postnatal identifies neonates <27 week gestation who subsequently require closure of a PDA.

Low-dose ketamine Efficacy in pediatric sedation

Objectives: Intravenous (IV) ketamine has gained widespread use in the emergency department (ED) for procedural sedation. The most commonly recommended starting dose is 1.5 mg/kg. We examined whether lower doses of ketamine in the range of 0.5 to 1.0 mg/kg could successfully sedate pediatric patients. Methods: We retrospectively reviewed quality assurance data of patients sedated with IV ketamine in a pediatric ED. Patients were administered 0.02 mg/kg of IV atropine, 0.05 mg/kg of IV midazolam, and then 0.5 mg/kg of IV ketamine. Additional aliquots of 0.25 to 0.5 mg/kg of ketamine were given as necessary, to a maximum of 2.0 mg/kg. Efficacy of sedation was assessed after every dose by pediatric emergency medicine attendings or fellows. Results: Seventy-two patients had quality assurance forms completed. The total ketamine dose administered ranged from 0.5 to 2 mg/kg. Adequate procedural sedation was obtained for 70 (97%) of 72 patients. Forty-four percent of patients required 0.75 mg/kg or less of ketamine to obtain adequate initial sedation; 25% of subjects required only 0.5 mg/kg; 43% of patients required 1.0 mg/kg of IV ketamine. We found that 88% of our patients could be successfully sedated at initial doses of 1 mg/kg or less. Conclusions: Our study suggests a potential role for low-dose IV ketamine in the range of 0.5 to 1.0 mg/kg for pediatric procedural sedation. Most pediatric ED patients can be successfully sedated with 1 mg/kg of ketamine.

Reliability and validity of the Pediatric Intensity Level of Therapy (PILOT) scale : A measure of the use of intracranial pressure-directed therapies

Objective:To test the reliability and validity of the Pediatric Intensity Level of Therapy (PILOT) scale, a novel measure of overall therapeutic effort directed at controlling intracranial pressure (ICP) in the setting of severe (Glasgow Coma Scale of ≤ 8) pediatric traumatic brain injury (TBI). Design:Case-control study via retrospective review of medical records. Setting:Tertiary-care, university-based children’s hospital intensive care unit. Patients:Randomly selected patients ≤18 yrs old admitted to the intensive care unit in 2002–2003 with severe TBI (cases: group 1, n = 27), mild–moderate TBI (control: group 2, n = 30), extracranial trauma (control: group 3, n = 29), or nontraumatic illnesses (control: group 4, n = 27). Interventions:None. Measurements and Main Results:A 38-point scale was developed to quantify daily ICP-directed therapeutic effort. All currently recommended therapies are represented. Demographic and physiologic data were collected on all patients. A total of 24 of 27 patients with severe TBI received ICP-directed therapy; three did not because of judgments of futility. No control patients received ICP-directed therapy. The PILOT scale score was assessed for the first 7 days posttrauma or postadmission. Interrater reliability was 0.91 (intraclass correlation coefficient) and intrarater reliability was 0.94. The highest PILOT scale scores were in patients with severe TBI (11.7 ± 5.6 vs. 1.3 ± 1.7 vs. 2.0 ± 2.1 vs. 1.9 ± 1.8 for groups 1, 2, 3 and 4, respectively [mean ± sd]; p < .001 by analysis of variance/Bonferroni). Patients with severe TBI who received ICP-directed therapy had higher PILOT scale scores (12.6 ± 5.3 vs. 5.0 ± 3.0, p = .001) than those who did not. Pearson’s correlation coefficients of mean PILOT scale scores with measures of injury severity, outcome, and ICP were as follows: Glasgow Coma Scales score, −0.73 (p < .001); overall Injury Severity Score, 0.37 (p < .001); Injury Severity Score (head component only), 0.53 (p < .001); 6-month Glasgow Outcome Scale, −0.26 (p = .006); ICP burden (hours per day with ICP above treatment threshold), 0.59 (p = .002); and mean ICP, 0.41 (p = .044). Conclusions:The PILOT scale score can be obtained retrospectively and has good reliability. It can discriminate patients receiving ICP-directed therapy, even among patients with severe TBI, and correlates with measures of injury severity, outcome, and ICP in an expected way. Thus, it seems to be a valid measure of the use of ICP-directed therapy, although prospective, multiple-center validation is recommended.