Abstracts of staff publications
aFall 1996
Late Correction of Sagittal Synostosis in Children
Jay Pensler, Stanley Ciletti, Tadanori Tomita
From the Divisions of Plastic Surgery and Neurosurgery at the Northwestern University Medical School and Children’s Memorial Hospital, Chicago.
Plastic and Reconstructive Surgery 1996;97:1362–67
Twelve patients with sagittal synostosis underwent correction between 8 months and 8 years of age. The patients underwent expansion in the parietal region of 4 cm and had a reduction in length of 3 cm following dural plication. Average follow-up was 2.2 ± 0.8 years (mean ± SD). While optimal treatment for sagittal synostosis may be obtained in the first few months of life, late correction of sagittal synostosis may be obtained in a safe and effective manner.
Tumor Angiogenesis Correlates with Metastatic Disease, N-myc Amplification, and Poor Outcome in Human Neuroblastoma
Dafna Meitar, Susan Crawford, Alfred Rademaker, and Susan Cohn
From the Departments of Pediatrics and Pathology, Children’s Memorial Hospital; and the Biometry Section, Robert Lurie Cancer Center, Northwestern University Medical School, Chicago.
Journal of Clinical Oncology 1996;14:405–414
Purpose: To determine if the clinical outcome of children with neuroblastoma (NB) is correlated with the degree of tumor neovascularization and to assess the relationship of stage, N-myc copy number, and histology to angiogenesis.
Materials and Methods: The vascularity of primary untreated NB from 50 patients diagnosed at a single institution between 1984 and 1994 was evaluated. An image processor was used to analyze the tumor tissue area for each histologic slide of tumor, and a vascular index (VI) was calculated, where VI = total number of vessels/mm2
of tissue area. Tumors were classified histologically according to the criteria of Shimada et al (J Natl Cancer Inst 1984;73:405–416) and N-myc copy number was determined by Southern blot analysis.
Results: We found that higher VI (> 4.0) in NB strongly correlated with widely disseminated disease (P = 0.006) and poor survival (P < 0.0001). VI more than 4.0 was also statistically associated with N-myc amplification (P = 0.02) and unfavorable histology (P–0.02) Univariate analysis demonstrated that disease stage, tumor histology, and N-myc copy number were also predictive of outcome. Cox regression analysis showed that VI provided independent prognostic information.
Conclusion: Our studies indicate that angiogenesis may play an important role in determining the biologic behavior of NB. Antiangiogenic therapy may prove to be effective in the treatment of children with highly vascular, widely disseminated NB.
Inhaled Nitric Oxide for Children with Congenital Heart Disease and Pulmonary Hypertension
Ronald Curran, Constantine Mavroudis, Carl Backer, Michael Sautel, Vincent R. Zales, and David L. Wessel
From the Divisions of Cardiovascular-Thoracic Surgery and Cardiology, Children’s Memorial Hospital, and the Departments of Surgery and Pediatrics, Northwestern University Medical School, Chicago.
Annals of Thoracic Surgery 1995;60:1765–71
Background: Endothelium-derived nitric oxide (NO) is a potent vasodilator and a major mediator of pulmonary vascular tone.
Methods: Five infants underwent a trial of inhaled NO with hemodynamic monitoring in the operating room after atrioventricular canal repair. An additional 15 patients with congenital heart disease and refractory pulmonary hypertension were treated with inhaled NO for 1 day to 10 days postoperatively.
Results: In the 5 infants with atrioventricular canal, corrective surgical intervention and conventional therapy (hyperventilation, inspired oxygen fraction of 0.80, and inotropic agents) lowered mean pulmonary artery pressure from 49.5 ± 10.5 to 20.0 ± 2.2 mm HG (p < 0.001). Adding inhaled NO further decreased mean pulmonary artery pressure to 18.0 ± 2.8 mm Hg (p–not significant). Inhaled NO had no effect on ventricular function curves (inflow occlusion) in this group. In the 15 patients with refractory postoperative pulmonary hypertension, 11 had a favorable response to inhaled NO, with a decrease in mean pulmonary artery pressure from 30.9 ± 5.8 to 23.1 ± 5.4 mm Hg (p < 0.01) in 8 patients with pulmonary artery catheters.
Conclusions: These studies demonstrate that inhaled NO has minimal beneficial effect on pulmonary artery pressure or cardiac output in infants after repair of atrioventricular canal. Inhaled NO is effective in decreasing PAP postoperatively in select patients with congenital heart disease and pulmonary hypertension refractory to conventional therapeutic modalities.
Visualizing the Pediatric Airway: Three-Dimensional Modeling of Endoscopic Images
Michael Dunham and Rosalee N. Wolf
From the Division of Pediatric Otolaryngology, Northwestern University Medical School (MD), and the Department of Computer Science, DePaul University (RW), Chicago.
Annals of Otology, Rhinology & Laryngology 1996;105:12–17
Three-dimensional reconstruction of medical images has emerged as an important visualization tool for studying complex anatomy. These tools have found important applications in neurology and plastic surgery using computed tomography (CT) and magnetic resonance imaging (MRI) data. However, CT and MRI do not sufficiently delineate lesions of the pediatric airway. Inspection through the rod lens telescope remains the standard diagnostic method. A video recording of an endoscopic procedure is essentially a sequence of two-dimensional images captured as the telescope traverses the airway lumen. Using digitized endoscopic video recordings and computer graphics reconstruction techniques, we have developed a preliminary three-dimensional modeling system for the pediatric airway. A series of normal and abnormal telescopic airway examinations were video recorded. Serial sections were obtained by digitizing the video images at uniform intervals as the scope traversed the airway lumen between the vocal folds and the carina. The digitized images were calibrated and used to reconstruct the airway lumen in three dimensions. Classifying airway abnormalities according to the minimal cross-sectional area or with descriptive terms can be subjective and dependent on the endoscopist’s observational skills. We hope that this preliminary work will lead to more precise and understandable methods for representing complex airway lesions.
Detection of Bone Lesions in Langerhans Cell Histiocytosis: Complementary Roles of Scintigraphy and Conventional Radiography
A. Semih Dogan, James Conway, John Miller, David Grier, Manu Bhattathiry, and Craig Mitchell
From the Division of Nuclear Medicine, Children’s Memorial Hospital, Chicago, and the Division of Nuclear Radiology, Children’s Hospital Los Angeles, Los Angeles, California.
Journal of Pediatric Hematology/Oncology 1996;18(1):51–58
Purpose: This research was undertaken to determine the relative sensitivity of scintigraphic and radiographic bone survey examinations in detecting bone lesions in various regions of the skeleton in patients with a histopathologic diagnosis of Langerhans cell histiocytosis (LCH).
Patients and Methods: Radionuclide skeletal scintigraphy (RNSS) and x-ray skeletal surveys (XRSS) of 42 children with a histopathologic diagnosis of LCH were evaluated retrospectively.
Results: Of the 191 lesions detected in 42 patients, 36 (19%) were missed on RNSS and 55 (29%) missed on XRSS. Most of the missed lesions on RNSS were in the skull (26 of 36). XRSS also missed 13 skull lesions seen on RNSS. Most of the lesions missed on XRSS were in the ribs (20 of 30 rib lesions), whereas RNSS identified 29 of them. XRSS also missed 13 of 38 lesions in the spine and pelvis, while RNSS demonstrated all of them. Both modalities showed comparable sensitivity in the extremities.
Conclusion: RNSS has a greater value in detecting sites of bone involvement with LCH than reported previously. RNSS is more sensitive than XRSS in detecting histiocytic lesions in the ribs, spine and pelvis, and less sensitive in identifying lesions in the skull.
Nephrotic Syndrome Accompanying Familial Hemophagocytic Syndrome
Michael Braun, Richard Cohn, Morris Kletzel
From the Department of Pediatrics, Northwestern University Medical School and Children’s Memorial Hospital, Chicago.
Journal of Pediatric Hematology/Oncology 1996;18(2):195–197
Purpose: We describe the first reported case of familial hemophagocytic syndrome (FHS) with concurrent minimal change nephrotic syndrome (MCNS).
Patients and Methods: This is a case report of a 30-month-old girl who presented to Children’s Memorial Hospital with pancytopenia and heavy proteinuria.
Results: This patient presented with anemia, neutropenia, thrombocytopenia, hypertriglyceridemia, and proteinuria. A brother died at 2 months of age with similar findings. A bone marrow biopsy demonstrated histiocyte proliferation with marked erythrophagocytosis, consistent with FHS. Treatment was begun with corticosteriods and VP–16. The patient developed worsening peripheral edema and hypoalbuminemia, with heavy proteinuria. After one month of therapy with persistence of heavy proteinuria, a renal biopsy was performed, the results of which were consistent with MCNS.
Conclusion: this is the first reported case of FHS with coincident MCNS.
Hepatitis C Infection in Children Who Received Extracorporeal Membrane Oxygenation
Suzanne Nelson and Maureen Jonas
From the Center for Childhood Liver Disease, Combined Program in Gastroenterology, Children’s Hospital, Boston, Massachusetts. (Nelson is now at Children’s Memorial in Chicago.)
Journal of Pediatric Surgery 1996;31(5):644–648
Objective: To determine the prevalence of antibody to hepatitis C virus (HCV) in a cohort of neonates who received extracorporeal membrane oxygenation (ECMO) therapy, and to determine risk factors associated with seropositivity.
Design: Eighty-three patients who had been treated with ECMO as neonates (from August 1986 through January 1992) at Children’s Hospital, Boston, were tested for antibodies to HCV. The medical records were reviewed, and information regarding neonatal history was obtained. Anti-HCV seronegative and seropositive children were compared using univariate and multivariate analyses.
Results: Seven patients (8%) were anti-HCV seropositive. Of the seven seropositive children, four (57%) currently have ALT values of more than 1.5 times the upper limit of normal; only five of the 52 (9.6%) seronegative patients have values this high (P < 0.001). Patients in the seropositive group had received blood screened by "surrogate markers" (6 of 50) or by ELISA–1 anti-HCV testing (1 of 33). Significant differences between the seropositive and seronegative patients were found with respect to the aminotransferase and bilirubin levels during the initial ECMO hospitalization. The last ALT value before discharge was the only significant predictor of HCV infection in the multivariate model.
Conclusion: Neonates treated with ECMO are at risk for the development of HCV infection. Neonates who received blood products from donors screened by surrogate markers or ELISA–1 anti-HCV testing should be considered at risk. Neonates who had an abnormal ALT value at the time of discharge are most likely to be anti-HCV seropositive.
Gun Storage Patterns in US Homes With Children
Yvonne Senturia, Katherine Kaufer Christoffel, Mark Donovan
From the Children’s Memorial Hospital, Northwestern University Medical School, Chicago.
Archives of Pediatric and Adolescent Medicine 1996;150:265–269
Objective: To describe gun storage patterns in gun-owning families with children.
Design: Survey of parents attending participating offices.
Settings: Twenty-nine urban, suburban, and rural pediatric practices in Chicago, Ill.; New Jersey; Houston, Tex.; Utah; Georgia; Iowa; and South Carolina.
Subjects: Parents of children attending offices for well- or sick-child care.
Selection Procedure: Consecutive sample of families seen during the 1-week study period.
Measurements and Analyses: Logistic regression models were constructed to identify sociodemographic factors associated with keeping guns loaded.
Results: Of 5233 surveys, 1682 (32%) indicated ownership of at least one powder firearm. Of the gun-owning families, 61% reported at least one gun unlocked, and 15% reported at least one gun loaded. Rifles were more often stored unlocked (62% rifles vs 52% handguns, P < 0.001, z = 4.60; two-proportion z-test), but handguns were more likely to be kept loaded (3% rifles vs 27% handguns, P < 0.001). Seven percent of gun-owning families reported at least one gun unlocked and loaded (handguns 12 times more likely than rifles). Only 30% of households reported all guns stored unloaded and locked up. The best-fit logistic regression model for keeping a gun loaded identified four predictor variables: owning a gun for self-protection, work-related gun ownership, owning a handgun, and no men in the home.
Conclusions: Because most gun-owning families store guns loaded, unlocked, or both, anticipatory guidance should address gun storage in all such families. Interventions designed to alter the way work guns are dealt with after work, and to provide safe and effective means of self-protection might affect these storage patterns.
Early Diagnosis of Usher Syndrome in Infants and Children
Nancy Young, Marilyn Mets, Timothy Hain
Divisions of Pediatric Otolaryngology(NY) and Ophthalmology (MM), Children’s Memorial Hospital, and the Departments of Otolaryngology—Head and Neck Surgery (NY, TH), Ophthalmology (MM), and Neurology, Northwestern University Medical School, Chicago.
American Journal of Otology 1996;17:30–34
The electroretinogram (ERG) is the only test currently available that has the potential to identify patients with Usher syndrome before onset of fundoscopic and visual abnormalities. The ERG is a noninvasive technique that can diagnose retinitis pigmentosa via measurement of corneal-retinal potentials. Forty-seven children with bilateral severe to profound sensorineural hearing loss were evaluated. Usher syndrome was diagnosed in five children, all of whom subsequently underwent cochlear implantation. We have found that accurate diagnosis of Usher syndrome in infants and young children is possible via ERG. Benefits of early diagnosis include timely counseling regarding genetic issues, educational and vocation placement, and cochlear implantation. For this reason we recommend that all newly identified children with bilateral severe to profound sensorineural hearing loss undergo ERG testing.
Postoperative Apnea in Former Preterm Infants after Inguinal Herniorrhaphy
Charles Cote, Alan Zaslavsky, John J. Downes, C. Dean Kurth, Leila Welborn, Louise O. Warner, Shobha V. Malviya
From the Department of Anesthesiology, Children’s Memorial Hospital, Chicago.
Anesthesiology 1995;82(4):809–822
Background: Controversy exists as to the risk for postoperative apnea in former preterm infants. The conclusions of published studies are limited by the small number of patients.
Methods: The original data from eight prospective studies were subject to a combined analysis. Only patients having inguinal herniorrhaphy under general anesthesia were included; patients receiving caffeine, regional anesthesia, or undergoing other surgical procedures were excluded. A uniform definition for apnea was used for all patients. Eleven risk factors were examined: gestational age, postconceptual age, birth weight, history of respiratory distress syndrome, bronchopulmonary dysplasia, neonatal apnea, necrotizing enterocolitis, ongoing apnea, anemia, and use of opioids or nondepolarizing muscle relaxants.
Results: Two hundred fifty-five of 384 patients from eight studies at four institutions fulfilled study criteria. There was significant variation in apnea rates and the location of apnea (recovery room and postrecovery room) between institutions (P< 0.001). There was considerable variation in the duration and type of monitoring, definitions of apnea, and availability of historical information. The incidence of detected apnea was greater when continuous recording devices were used compared to standard impedance pneumography with alarms or nursing observations. Despite these limitations, it was determined that: (1) apnea was strongly and inversely related to both gestational age (P = 0.0005) and postconceptual age (P < 0.0001); (2) an associated risk factor was continuing apnea at home; (3) small-for-gestational-age infants seemed to be somewhat protected from apnea compared to appropriate- and large-for-gestational-age infants; (4) anemia was a significant risk factor, particularly for patients > 43 weeks’ postconceptual age; (5) a relationship to apnea with history of necrotizing enterocolitis, neonatal apnea, respiratory distress syndrome, bronchopulmonary dysplasia, or operative use of opioids and/or muscle relaxants could not be demonstrated.
Conclusions: The analysis suggests that, if it is assumed that the statistical models used are equally valid over the full range of ages considered and that the average rate of apnea reported across the studies analyzed is accurate and representative of actual rates in all institutions, the probability of apnea in non-anemic infants free of recovery-room apnea is not less than 5%, with 95% statistical confidence until postconceptual age was 48 weeks with gestational age 35 weeks. This risk is not less than 1%, with 95% statistical confidence, for that same subset of infants, until postconceptual age was 56 weeks with gestational age 32 weeks or postconceptual age was 54 weeks and gestational age 35 weeks. Older infants with apnea in the recovery room or anemia also should be admitted and monitored. The data do not allow prediction with confidence up to what age this precaution should continue to be taken for infants with anemia. The data were insufficient to allow recommendations regarding how long infants should be observed in recovery. There is additional uncertainty in the results due to the dramatically different rates of detected apnea in different institutions, which appear to be related to the use of different monitoring devices. Given the limitations of this combined analysis, each physician and institution must decide what is an acceptable risk for postoperative apnea.
