Abstracts of staff publications
aFall 1997
Potential in vitro activity of kutapressin against Epstein-Barr virus
Elaine Rosenfeld, Babak Salimi, Maurice R. G. O'Gorman, Carl Lawyer and Ben Z. Katz
From the Department of Pediatrics, Northwestern University Medical School, and Children's Memorial Hospital, Divisions of Infectious Diseases and Immunology, Chicago; and Schwarz Pharma, Mequou, Wis.
In vivo 1996;10:313–318
Background: Kutapressin (KU), a procine liver extract with bradykinin-potentiating effects but no vitamin B12 activity, has been used in the treatment of Herpes zoster. We examined a phenol-free preparation of this drug for in vitro activity against Epstein-Barr Virus (EBV).
Materials and Methods: Immortalization-inhibition assays were used to assess EBV infectivity. Mitogen stimulation and cell viability assays were used to assess kutapressin toxicity. Lytic replication assays and flow cytometry were used to assess the mechanism of drug activity.
Results: Seventy-five hundred mcg/ml of KU blocked the infection of 2 x 105
human umbilical cord mononuclear cells when added together with two strains of EBV (B95-8 and FF41). Doses as low as 250 mcg/ml were occasionally effective as well. Unlike acyclovir, KU does not inhibit viral DNA polymerase nor does it appear to compete with EBV as it binds to its receptor on the B-cell surface.
Conclusions: The mechanism whereby KU may inhibit EBV immortalization remains to be determined. KU, a drug which is safe in humans, deserves further study as an agent with potential to block EBV-induced immortaliztion of B-lymphocytes.
Monstrous, crablike hypertrophy of the cerebellar vermis and its relationship with Lhermitte-Duclos disease
Guillermo DeLeon, John Grant and Crystal Darling
From the Department of Pathology and Divisions of Neurosurgery and Neuroradiology, Children's Memorial Hospital and Northwestern University School of Medicine, Chicago.
Journal of Neurosurgery 1996;85:157–162
The case of an infant with a peculiar tumorous malformation of the cerebellum is described. The tumor apparently developed as an exophytic, hypertrophic sprout of the inferior vermis. It had a monstrous appearance resembling a crab, with a metameric body and multiple pairs of limbs attached to the folia of both cerebellar hemispheres. Histologically, the lesion was formed by poorly differentiated neuroepithelial cells without any evidence of organization into nuclei, cortex or fascicles. Clinically, the tumor behaved in an indolent manner and did not regrow after subtotal surgical resection. Because of its gross appearance and its biological behavior, this unusual hamartoblastomatous growth is readily distinguished from medulloblastoma. The morphology of the cerebellum in Lhermitte-Duclos disease is reviewed, and a new interpretation of its basic structure is proposed. This and other known types of cerebellar hypertrophy are different from the malformation in the present case.
Osteoblast-directed osteoclast metabolism from patients with premature coronal synostosis
Jay Pensler, Pravin-Kumar Patel and Craig Langman
Nephrology at Children's Memorial Hospital and Northwestern University School of Medicine, Chicago
Plastic and Reconstructive Surgery 1997;99:1518–1521
Osteoclasts were harvested from explants of five patients with premature unilateral coronal synostosis and plated on devitalized bovine bone wafers. The planar surface areas of resorption lacunae were quantitated by means of light microscopy and a digital imaging system. Osteoclasts isolated from involved regions of premature synostosis exhibited enhanced resorption when compared with osteoclasts isolated from noninvolved cranial bone in the same patients (P <0.05). When the involved osteoclasts were exposed to conditioned media from non-involved osteoblasts, the in vitro metabolism was reduced consistent with noninvolved osteoclasts. The results suggest there may be a primary cellular defect and that there appears to be a complex coupling between osteoblast and osteoclast function that may lead to sutural synostosis.
Adequacy of prenatal care utilization, maternal ethnicity, and infant birthweight in Chicago
James Collins, Jr., Stephen Wall and Richard David
From the Department of Pediatrics, Northwestern University Medical School, the Division of Neonatology, Children's Memorial Hospital, and the Department of Pediatrics, University of Illinois, Chicago.
Journal of the National Medical Association 1997; 89,198–203
This study examines the extent to which the Adequacy of Prenatal Care Utilization Index explains the racial disparity in infant birthweight. A stratified analysis was performed on all African-American, Mexican-American, and non-Latino white singleton infants born in Chicago, Illinois, between 1982 and 1983. This older cohort was chosen to avoid the confounding effect of cocaine associated with its increased local availability after 1985. The adequacy of prenatal care utilization varied by race and place of residence. However, in moderate-income areas (median family annual income $20,001 to $30,000), the African-American birthweight disadvantage persisted among infants born to mothers who received adequate and adequate-plus prenatal care. Similarly, although race-specific term (gestational age>37 weeks) low birthweight rates declined as prenatal care usage rose, the position of African-Americans relative to Mexican-Americans and whites was essentially unchanged. These findings indicate that maternal race or some factor closely related to it affects pregnancy outcome regardless of the adequacy of prenatal care utilization.
Patterns and correlates of supervision in child pedestrian injury
Karen Wills, Katherine Christoffel, John Lavigne, Robert Tanz, Joseph Schofer, Mark Donovan, Kristin Kalangis, and the Kids ‘N' Cars Research Team
From Loyola University (KW), Children's Memorial Hospital and Northwestern University Medical School (KC, JL, RT, MD, KK, Kids ‘N' Cars Research Team), Chicago, IL
Journal of Pediatric Psychology 1997;22:89–104
Described supervision in 142 child pedestrian injuries (PI), based on presence and proximity of supervisors and/or peers. Children (5–12 years), families, sites, and PI events were described via record reviews, interviews, questionnaires, and site investigation. Supervision of PI victims varied with family size and cohesion, and with children's age, self-help skills, nearness to home, and activity (playing or journey). Peer presence was associated with more impulsive behavior among supervised (but not among unsupervised) PI victims. Definitions of supervision parameters offered here can aid research on the complex relationship between supervision and PI risk.
The prognostic value and significance of serial bone scintigraphy in Legg-Calvé-Perthes disease
Audrey Tsao, Luciano Dias, James Conway and Philip Straka
From the Department of Orthopaedic Surgery, University of Mississippi Medical Center, Jackson, and the Divisions of Orthopaedic Surgery and Nuclear Medicine, Children's Memorial Hospital, Chicago.
Journal of Pediatric Orthopaedics 1997;17:230-239
We reviewed 44 consecutive patients treated for Legg-Calvé-Perthes disease who underwent serial technetium 99m diphosphonate bone scintigraphy. The average follow-up was 4.4 years. The bone-scintigraphy classification characterizes the A pathway by early lateral column formation not seen in the B pathway. Pathway A had 20 hips. The average age at presentation was 6.1 years. At last follow-up, this group had an average Mose classification of 1.2 and Catterall score of 2.4, without any patient having 'head-at-risk" signs or requiring operative treatment. Pathway B had 20 hips. The average age at presentation was 5.8 years. At last follow-up, this group had an average Mose classification of 5.2, a Catterall score of 3.5, and 18 patients had head-at-risk signs, with 11 requiring operative treatment. Our bone-scintigraphy classification preceded the radiographic head-at-risk signs by an average of 3 months, allowing earlier treatment and correlated with subsequent femoral head involvement.
Prevalence of symptoms of gastroesophageal reflux during infancy
Suzanne Nelson, Edwin Chen, Gina Syniar, Katherine Christoffel
From the Divisions of Gastroenterology (SN, GN) and General Academic Pediatrics (KC), Department of Pediatrics, and the Statistical Sciences nd Epidemiology Programs (EC), Northwestern University and Children's Memorial Medical Center, Chicago.
Archives of Pediatric Adolescent Medicine 1997;151:569–572
Objectives: To determine the prevalence of symptoms associated with overt gastroesophageal (GER) during the first year of life, to describe when most infants outgrow these symptoms, and to assess the prevalence of parental reports of various symptoms associated with GER and the percentages of infants who have been treated forGER.
Design: Cross-sectional survey.
Setting: Nineteen Pediatric Practice Research Group practices in the Chicago, Ill. area (urban, suburban and semirural).
Participants: A total of 948 parents of healthy children 13 months old and younger.
Intervention: None.
Main Outcome Measure: Reported frequency of regurgitation.
Results: Regurgitation of at least 1 episode a day was reported in half of 0- to 3-month-olds. This symptom decreased to 5% at 10 to 12 months of age (p<.001). Peak reported regurgitation was 67% at 4 months; the prevalence of symptoms decreased dramatically from 61% to 21% between 6 and 7 months of ages. Infants with at least 4 episodes daily of regurgitation showed a similar patter (p<.001). Peak regurgitation reported as a "problem" was most often seen at 6 months (23%); this prevalence decreased to 14% at 7 months of age. Parental perception that regurgitation was a problem was associated with the frequency and volume of regurgitation, increased crying and fussiness, reported discomfort with spitting up, and frequent back arching. Reported treatment for regurgitation included a change in formula in 8.1%, thickened feedings in 2.2%, termination of breast-feeding in 1.1%, and medication in 0.2%.
Conclusions: Complaints of regurgitation are common during the first year of life, peaking at 4 months of age. Many infants "outgrow" overt GER by 7 months and most by 1 year. Parents view this symptom as a problem more often than medical intervention is given.
Clinical evaluation of a rapid diagnostic screen (URISCREEN) for bacteriuria in children
Lane Palmer, Ingrid Richards, and William Kaplan
From the Division of Urology, Children's Memorial Hospital, Northwestern University Medical School, Chicago.
The Journal of Urology 1997;157:654–657
Purpose
: We assessed clinical use of the URISCREEN (Bard, Covington, Georgia) test for detecting significant bacteriuria in children and compared it to standard quantitative culture.
Materials and Methods: URISCREEN detects catalase in urine samples, reflecting the presence of at least 50,000 colony-forming units per ml. Or 10 somatic cells per high power field. Catheterized urine specimens from 200 consecutive children scheduled to undergo urodynamic evaluation were tested by URISCREEN and quantitative culture methods. Sensitivity, specificity, positive and negative predictive values, and accuracy were determined.
Results: Of these specimens there were 22 false-positive and 16 false-negative URISCREEN results. Sensitivity was 65.2%, specificity 85.7%, positive predictive value 57.7%, negative predictive value 89.2% and overall accuracy 81%.
Conclusions: URISCREEN is a rapid screen for bacteriuria. However, the high false-negative rate limits clinical use in the pediatric urological patient for whom detecting infection is essential.
Management considerations for treating vesicoureteral reflux in children with solitary kidneys
Lane Palmer, Greg Andros, Max Maizels, William Kaplan and Casimir Firlit
From the Division of Urology, Children's Memorial Hospital/Northwestern University Medical School, Chicago.
Pediatric Urology 1997;49:604–608
Objectives: To evaluate the management approach for vesicoureteral reflux (reflux) into a solitary kidney.
Methods: Outcomes of all children with solitary kidneys and reflux managed between 1981 and 1996 were reviewed. Solitary kidneys were documented by nuclear renography and ultrasonography; reflux was graded after cystography. Management consisted of observation and antimicrobial prophylxis or surgery by ureteroneocystostomy or subureteric injection of polytetrafluoroethylene (STING). Follow-up ranged from 3 months to 14 years and included serial cystography, sonography and serum creatinine measurement.
Results: Twenty-one patients with a median follow-up of 26 months were identified. Etiologies included contralateral renal agenesis (14 children), multicystic dysplastic kidney (5 children), or nonfunctioning ureteropelvic junction obstruction (2 children). Low-grade (I to II) reflux was identified in 6 children and high grade (III to V) was identified in 15. Reflux resolved in 20 patients. Five children with low-grade reflux were managed without surgery and demonstrated reflux resolution after a mean of 20.5 months. Renal function deteriorated in only 1 child. Ureteroneocystostomy was performed in 13 children with grades III to V reflux, and STING was performed in 1 child with grade II reflux. Every surgical patient maintained stable renal function and was infection-free during a mean follow-up of 56 months. Management by observation in 2 children with grades IV to V reflux resulted in spontaneous resolution in one and stable grade IV in the other.
Conclusions: Reflux into the solitary functioning kidney may be managed by the same strategies used to manage unilateral reflux in children with two normally functioning kidneys: low-grade reflux by observation/chemoprophylaxis until spontaneous resolution occurs, and higher grades by surgery to protect renal function; however, chemoprophylaxis and serial imaging may be used until well-defined indications for surgery are satisfied. Renal function should be monitored diligently.
How rational is the crossmatching of blood in a pediatric emergency department?
Jacqueline Grupp-Phelan and Robert R. Tanz
From the Divisions of Pediatric Emergency Medicine (JG-P) and General Academic Pediatrics (RT), Children's Memorial Hospital and the Department of Pediatrics, Northwestern University Medical School, Chicago.
Archives of Pediatrics and Adolescent Medicine 1996;150:1140–1144
Objective: To determine if typed and crossmatched blood ordered in a pediatric emergency department (ED) is actually used for transfusion and if some ordering patterns are not cost-effective.
Design: Retrospective medical record review. Emergency department records and blood bank logs were reviewed daily to identify patients who had a type and crossmatch (T&C) ordered; inpatient records were then reviewed. A priori diagnostic and patient care categories were determined. Physicians and nurses providing care were unaware of the study.
Setting: An inner-city, tertiary care, pediatric trauma center ED.
Patients: A consecutive sample of ED patients who had a T&C ordered from October 1, 1993, through January 31, 1994.
Main Outcome Measures: Outcome measures included age, general category of diagnosis, number of units of blood crossmatched and transfused within 7 days, hemoglobin concentration in the ED, surgical procedures in the operating room, and hospital charges for typed and crossmatched blood. For trauma patients, the Pediatric Trauma Score was recorded. The crossmatch-to-transfusion (C/T) ratio was calculated for each diagnostic category (the typical C/T ratio for US hospitals is 2). We calculated a new ratio, the patient-to-transfusion (P/T) ratio, to correct for the transfusion of numerous units of blood in a few patients.
Results: Two hundred eighty-two patients had 468 U of blood typed and crossmatched. Fifty-six patients received a total of 110 U of blood. The mean hemoglobin concentration was 81 g/L for patients who received a transfusion and 117 g/L for patients who did not receive a transfusion (P<.001). The C/T ratio for all patients was 4.3. The P/T ratio for all patients was 5.3. Sixty-four surgery patients had 78 U of blood typed and crossmatched; 1U of blood was transfused to 1 patient, yielding a C/T ratio of 78 and a P/T ratio of 64. Ninety-one units of blood were typed and crossmatched for 38 major trauma patients; 20 U of blood were transfused to 2 patients, 19 U were transfused to 1 patient with a Pediatric Trauma Score of 4, and 1 U was transfused to a patient with a Pediatric Score of 7. The C/T ratio for major trauma patients was 4.6, and the P/T ratio was 19. Forty-five children with ventriculoperitoneal shunt problems had 51 U of blood typed and cross-matched, but no blood was transfused. Children with sickle cell disease had a C/T ratio of 2.2 and a P/T ratio of 3.3; those with cancer diagnoses had a C/T ratio of 1.6 and a P/T ratio of 1.3. During the 4-month study period, the hospital charged $84,726 for these T&Cs. The charge for T&Cs never used for transfusion was $65,643.
Conclusions: Most typed and crossmatched units of blood ordered in our pediatric ED were never used for transfusion. The C/T and P/T ratios were high for many diagnostic categories, suggesting inefficient blood ordering and patient management. Transfusions were uncommon in children with the following problems: ventriculoperitoneal shunt malfunction, virtually all surgical diagnoses, cancer with a hemoglobin concentration greater than 105 g/L, and trauma patients with a Pediatric Trauma Score of greater than 7.
