bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Detection of Imperforate Hymen Prevents Morbidity From Delays in Diagnosis
Authors: Posner Jill C. , Spandorfer Philip R.
Published: April 2005

Objective. Although it is detectable at all ages through inspection of the external genitalia, imperforate hymen (IH) is a diagnosis that is missed commonly. We hypothesized that children with late diagnoses (predefined as ≥8 years of age, chosen to reflect the timing of normal menarche) would be more likely to be symptomatic, undergo more diagnostic testing, and lack appropriate documentation in their medical records, compared with children with earlier diagnoses (ie, <8 years of age).

Methods. All patients with IH were identified through searches of 3 hospital databases with International Classification of Diseases, Ninth Revision, codes. The medical records of eligible subjects were reviewed by a single, blinded researcher. Comparisons were made between children diagnosed at younger versus older ages.

Results. A bimodal distribution of age at diagnosis was demonstrated; 43% (n = 10) of girls were diagnosed at <8 years of age, and 57% (n = 13) were diagnosed at ≥8 years of age. Among older girls, 100% were symptomatic (abdominal pain and/or urinary symptoms; duration of symptoms: 1–120 days), whereas 90% of cases in the younger group were detected incidentally. Documentation was lacking for breast development (77%), pubic hair development (69%), and menstrual history (46%) among the older girls. Older children were more likely to present symptomatically (odds ratio: 42.0; 95% confidence interval: 3.1–1965.7) and to undergo ancillary testing (odds ratio: 20.3; 95% confidence interval: 1.6–983.1).

Conclusions. Two distinct populations of girls with IH exist, ie, those diagnosed without symptoms at a young age and those not diagnosed until >8 years of age. By incorporating an examination of the external genitalia into their routine practice, clinicians caring for children can prevent the significant delays in diagnosis, misdiagnosis, and morbidity associated with the latter group.
Is Noncompliance Among Adolescent Renal Transplant Recipients Inevitable?
Authors: Feinstein Sofia , Keich Rami , Becker-Cohen Rachel , Rinat Choni , Schwartz Shepard B. , Frishberg Yaacov
Published: April 2005

Objective. To evaluate the prevalence of noncompliance and factors that influence poor adherence to immunosuppressive drug regimens among kidney transplant recipients.

Methods. We reviewed immunosuppressive drug compliance in 79 posttransplant patients. Patient self-report and low plasma calcineurin inhibitor levels served as indicators of noncompliance.

Results. The prevalence of noncompliance was found to be highest in adolescents who were responsible for their own medications and who underwent cadaveric kidney transplantation (CTx; 45.5%) and lower after living related transplantation (28.6%). There were no documented cases of noncompliance among any recipient of living unrelated (commercial) transplantation. Among 13 noncompliant patients, the first indication of “drug holiday” was low plasma calcineurin inhibitor levels in 11 children. Two additional children presented with acute rejection. In 7 patients, repeated episodes of “drug holidays” led to acute rejection later: 21.4 ± 13.2 months after the first decrease in plasma calcineurin inhibitor level had been recorded. All 9 patients who experienced acute rejection subsequently developed chronic rejection. In 4 patients, noncompliance did not influence graft function. Psychosocial factors that were associated with noncompliance included insufficient family support, low self-awareness caused by poor cognitive abilities, and denial.

Conclusions. The absence of cases of noncompliance in adolescents who underwent commercial living unrelated kidney transplantation suggests that although noncompliance is prevalent, it is not inevitable. Strategies to decrease noncompliance in young patients with chronic illnesses can be learned from the experience with transplant recipients. The general pediatrician has a central role in identifying and addressing the problem of noncompliance in adolescents with chronic disease.
Yield of Diagnostic Testing in Infants Who Have Had an Apparent Life-Threatening Event
Authors: Brand Donald A. , Altman Robin L. , Purtill Kerry , Edwards Karen S.
Published: April 2005

Objective. Many infants who have experienced an apparent life-threatening event (ALTE) seem normal by the time they reach the hospital. Nevertheless, they typically undergo an extensive evaluation to rule out serious underlying conditions. The purpose of the present investigation was to determine the yield of different diagnostic tests in helping to identify the cause of the ALTE.

Methods. We reviewed test results from a consecutive series of infants who were younger than 12 months and admitted to a tertiary care academic medical center between November 1996 and June 1999 after having experienced a sudden breathing irregularity, color change, or alteration in mental status or muscle tone. For each patient, we noted whether a given test was performed, whether the result was positive, and, if so, whether the test contributed to the diagnosis, that is, suggested or helped establish the cause. We also noted whether the initial history and physical examination contributed information that eventually led to the final diagnosis.

Results. A total of 243 patients met the enrollment criteria. Of the 3776 tests ordered, 669 (17.7%) were positive and 224 (5.9%) contributed to the diagnosis. Prompted by findings from the initial clinical assessment, the following tests proved useful in patients who had a contributory history and physical examination: blood counts, chemistries, and cultures; cerebrospinal fluid analysis and cultures; metabolic screening; screening for respiratory pathogens; screening for gastroesophageal reflux; chest radiograph; brain neuroimaging; skeletal survey; electroencephalogram; echocardiogram; and pneumogram. In the remaining patients, who had a noncontributory history and physical examination, only the following tests proved useful: screening for gastroesophageal reflux, urine analysis and culture, brain neuroimaging, chest radiograph, pneumogram, and white blood cell count. Broad evaluations for systemic infections, metabolic diseases, and blood chemistry abnormalities were not productive in these patients.

Conclusions. For many tests used in the evaluation of an ALTE, the likelihood of a positive result is low and the likelihood of a contributory result is even lower. Estimates of diagnostic yield derived from the present investigation can help clinicians maximize the productivity and efficiency of their evaluation.
Use of Volume Expansion During Delivery Room Resuscitation in Near-Term and Term Infants
Authors: Wyckoff Myra H. , Perlman Jeffrey M. , Laptook Abbot R.
Published: April 2005

Objective. To characterize use of volume infusion (VI) for infants who are ≥34 weeks' gestational age and receive intensive cardiopulmonary resuscitation (CPR; defined as >1 minute of positive-pressure ventilation and chest compressions, with or without the administration of medications) in the delivery room and are admitted to the NICU.

Methods. A retrospective review of a resuscitation registry between January 1999 and June 2001 was conducted.

Results. Of 37 972 infants, 23 received CPR, including 13 with VI. Ten of 13 received VI for persistent bradycardia despite CPR, and only 3 of 13 received VI for suspicion of hypovolemia with poor perfusion. More VI versus no VI infants had Apgar scores ≤2 at 5 and 10 minutes. VI versus no VI infants had lower cord arterial pH, had higher arterial partial pressure of carbon dioxide, had larger base deficit, required longer CPR, and required more epinephrine. On admission to the NICU, VI versus no VI infants had lower blood pressure and larger base deficit over the first 2 hours but did not differ in arterial pH, arterial partial pressure of carbon dioxide, heart rate, mortality, or use of additional VI or buffer.

Conclusions. VI is rarely given for overt hypovolemia and more often for asphyxiated infants who are slow to respond to intensive CPR. Persistent postnatal hypotension in VI infants suggests that other factors, eg, myocardial dysfunction, may be important contributors to lack of response to CPR.
The Role of Endogenous Opioids in Mediating Pain Reduction by Orally Administered Glucose Among Newborns
Authors: Gradin Maria , Schollin Jens
Published: April 2005

Objective. It has been demonstrated clearly that sweet-tasting solutions given before a painful intervention can reduce pain among newborns. There is no fully accepted explanation for this effect, but activation of endogenous opioids has been suggested as a possible mechanism. The aim of this study was to obtain deeper knowledge of the underlying mechanism by investigating whether administration of an opioid antagonist would reduce the effect of orally administered glucose at heel stick among term newborns.

Design. A randomized, placebo-controlled, double-blind trial with a validated, neonatal, pain-rating scale.

Participants. The trial included 30 term newborns undergoing heel stick, who were assigned randomly to 1 of 2 groups, ie, group I, with naloxone hydrochloride (opioid antagonist) 0.01 mg/kg administered intravenously before oral administration of 1 mL of 30% glucose, or group II, with a corresponding amount of placebo (saline solution) administered intravenously before oral administration of glucose.

Outcome Measures. Pain-related behavior during blood sampling was measured with the Premature Infants Pain Profile. Crying time and heart rate were also recorded.

Results. The 2 groups did not differ significantly in Premature Infant Pain Profile scores during heel stick. The median crying time during the first 3 minutes was 14 seconds (range: 0–174 seconds) for the naloxone group and 105 seconds (range: 0–175 seconds) for the placebo group. There was no significant difference in heart rate between the 2 groups.

Conclusion. Administration of an opioid antagonist did not decrease the analgesic effect of orally administered glucose given before blood sampling.
Risk Factors for and Outcomes of Bloodstream Infection Caused by Extended-Spectrum β-Lactamase–Producing Escherichia coli and Klebsiella Species in Children
Authors: Zaoutis Theoklis E. , Goyal Monika , Chu Jaclyn H. , Coffin Susan E. , Bell Louis M. , Nachamkin Irving , McGowan Karin L. , Bilker Warren B. , Lautenbach Ebbing
Published: April 2005

Objective. The increasing prevalence of infections caused by extended-spectrum β-lactamase–producing Escherichia coli and Klebsiella species (ESBL-EK) has become a growing concern in the hospitalized patient population. Previous studies on risk factors for infection with ESBL-EK have mainly focused on adult populations, and these findings may not be relevant among the pediatric population that experiences a unique set of health care exposures and underlying conditions. The objective of this study was to define the risk factors and outcomes associated with ESBL-EK bloodstream infections in children.

Methods. We conducted a nested case-control study using data from the Children's Hospital of Philadelphia from May 1, 1999, to September 30, 2003. Eligible patients were identified from the hospital database of microbiology laboratory records. All patients with ESBL-EK bloodstream infections were compared to a random sample of patients with non–ESBL-EK bloodstream infections. Risk factors analyzed included prior antimicrobial use, comorbid conditions, and demographic characteristics. Pulsed-field gel electrophoresis was performed to determine genetic relatedness of the ESBL-EK isolates.

Results. Thirty-five cases and 105 control subjects were included in the study. The median age among the cases was 2 years (interquartile range: 0–11), compared with 1 year (interquartile range: 0–8) among control subjects. Patients with ESBL-EK infections were 5.8 times (95% confidence interval: 1.9–17.7) more likely to have had exposure to an extended-spectrum cephalosporin in the 30 days before infection than those with non–ESBL-EK infections. Other independent predictors of ESBL-EK infection were being female, infection with a Klebsiella species, and steroid use in the 30 days before infection. All ESBL-EK isolates were susceptible to carbapenem antibiotics. Pulsed-field gel electrophoresis analysis revealed that the ESBL-EK isolates were polyclonal. Although a substantially higher proportion of children with ESBL-EK died (in-hospital mortality: 36% vs 13%), this difference was not statistically significant.

Conclusions. Receipt of extended-spectrum cephalosporins in the 30 days before infection by an Escherichia coli or Klebsiella species is significantly associated with having an ESBL-EK infection in hospitalized children. Curtailed use of cephalosporins among high-risk groups may reduce the occurrence of ESBL-EK infections. Future studies on identifying high-risk children and investigating the impact of curtailed third-generation cephalosporin use to limit additional emergence of ESBL-EK infections should be undertaken.
Variation in Inpatient Diagnostic Testing and Management of Bronchiolitis
Authors: Christakis Dimitri A. , Cowan Charles A. , Garrison Michelle M. , Molteni Richard , Marcuse Edgar , Zerr Danielle M.
Published: April 2005

Objectives. We know little about the variation in diagnosis and management of bronchiolitis. The objectives of this study were (1) to document variations in treatment and diagnostic approaches, lengths of stay (LOSs), and readmission rates and (2) to determine which potentially modifiable process of care measures are associated with longer LOSs and antibiotic usage.

Methods. We used the Pediatric Health Information System, which includes demographic, diagnostic, and detailed patient-level data on 30 large children's hospitals. We examined infants who were younger than 1 year and hospitalized for bronchiolitis (October 2001–September 2003). Multivariate analysis of variance was used to determine whether the variance in the outcomes was hospital related after controlling for other covariates. Linear regression was used to model predictors of increased LOS. Logistic regression was used to model antibiotic usage. Analyses were stratified by age group (<3 months and 3–11 months).

Results. A total of 17397 patients were included in the analysis. The mean LOS was 2.97 days; 72% of patients received chest radiographs, 45% received antibiotics, and 25% received systemic steroids. The mean LOS varied considerably across hospitals (range: 2.40–3.90 days), and hospital remained a significant contributor to LOS variation after controlling for our covariates. Variations in the use of diagnostic tests and medications as well as readmission rates also existed and also remained significant after controlling for covariates. The factors associated with the greatest increases in LOS in the regression analyses included higher severity scores and use of antibiotics, bronchodilators, and corticosteroids. The strongest predictors of antibiotic use in the logistic regression analyses were higher severity scores and receipt of a blood or cerebrospinal fluid culture. Receiving a chest radiograph was a significant predictor of antibiotic use in older but not younger infants.

Conclusions. Considerable, unexplained variation exists in the inpatient management of bronchiolitis. The development of national guidelines and controlled trials of new therapies and different management approaches are indicated.
Prenatal Risk Factors for Severe Retinopathy of Prematurity Among Very Preterm Infants of the Australian and New Zealand Neonatal Network
Authors: Darlow Brian A. , Hutchinson Jolie L. , Henderson-Smart David J. , Donoghue Deborah A. , Simpson Judy M. , Evans Nicholas J. ,   on behalf of the Australian and New Zealand Neonatal Network
Published: April 2005

Objective. To identify prenatal and perinatal risk factors for clinically severe (stage 3 or 4) retinopathy of prematurity (ROP).

Methods. Data were collected prospectively as part of the ongoing Australian and New Zealand Neonatal Network audit of high-risk infants (birth weight of <1500 g or gestational age [GA] of <32 weeks) admitted to a level III neonatal unit in Australia or New Zealand. Prenatal and perinatal factors to 1 minute of age were examined for the subset of infants with GA of <29 weeks who survived to 36 weeks’ postmenstrual age and were examined for ROP (n = 2105). The factors significantly associated with stage 3 or 4 ROP were entered into a multivariate logistic regression model.

Results. Two-hundred three infants (9.6%) had stage 3 or more ROP. Prematurity was the dominant risk factor, with infants with GA of <25 weeks having 20 times greater odds of severe ROP than infants with GA of 28 weeks. Birth weight for GA also had a “dose-response” effect; the more growth-restricted infants had greater risk, with infants below the 3rd percentile of weight for GA having 4 times greater odds of severe ROP than those between the 25th and 75th percentiles. Male gender was also a significant risk factor (odds ratio: 1.73; 95% confidence interval: 1.25–2.40).

Conclusions. These data, for a large, essentially population-based cohort, suggest that factors related to the degree of immaturity, intrauterine growth restriction, and male gender contribute to severe ROP.
Primary and Secondary Nocturnal Enuresis: Similarities in Presentation
Authors: Robson Wm. Lane M. , Leung Alexander K.C. , Van Howe Robert
Published: April 2005

Objective. To determine the differences or similarities in the clinical presentation between patients with primary and secondary nocturnal enuresis.

Methods. A total of 170 patients with nocturnal enuresis were assessed at a busy tertiary care pediatric voiding dysfunction clinic at the University of Oklahoma Health Sciences Center. Patients with primary nocturnal enuresis (PNE) were compared with patients with secondary nocturnal enuresis (SNE) for a variety of clinical features, including gender, age when first voiding on their own, age on presentation, infrequent voiding, frequent voiding, urgency, daytime wetting, nocturia, urinary tract infection, constipation, vesicoureteral reflux, attention-deficit/hyperactivity disorder, uroflow results, and ultrasound evidence of a postvoid residual.

Results. The only significant difference between the patients with PNE and those with SNE was in the prevalence of constipation. Constipation was significantly associated with PNE (74.59% vs 57.54%; odds ratio: 2.17; 95% confidence interval: 1.07–4.41). When adjusted for a history of constipation, the age at which a child began to void on his or her own became statistically significant. Patients with SNE started to void on their own at 2.13 years (SD: 0.61), an average of 0.22 years earlier than those with PNE, who started to void on their own at 2.35 years.

Conclusions. PNE and SNE likely share a common pathogenesis. Symptoms of daytime voiding dysfunction are common in patients with PNE and SNE. Daytime voiding habits might influence how the central nervous system responds at night to a full or contracting bladder.
Lengths of Stay and Costs Associated With Children's Hospitals
Authors: Merenstein Dan , Egleston Brian , Diener-West Marie
Published: April 2005

Objective. Because of the unique mission of freestanding children's hospitals, higher costs have generally been accepted; however, increasing health care costs and the impetus for outcomes data demand more accountability. For common diagnoses, with respect to quality care indicators, length of stay (LOS), and total charges, we propose to compare freestanding children's hospitals and other hospitals. Our hypothesis is that, for similar diagnoses, freestanding children hospitals will have longer LOSs and higher costs than other hospitals.

Methods. Data were analyzed from the Healthcare Cost and Utilization Project Kids' Inpatient Database 2000. Encounters qualified for evaluation when 1 of the top 3 discharge codes was consistent with pneumonia, gastroenteritis, respiratory syncytial virus, dehydration, or asthma. Our outcomes were LOS and total charges per hospital admission; hospitals were categorized as children's hospitals and nonchildren's hospitals. We adjusted for the following potential confounders: number of diagnoses, insurance information, patient age in years, race of patient, admission source, procedures, teaching status of hospital, and hospital location. Because of the right skew of the outcomes, our primary analyses consisted of robust median regression; to support our final models, we also performed sensitivity analyses.

Results. Of 252262 total inpatient encounters, 24322 met the inclusion criteria. There were 3408 encounters from 23 different freestanding children's hospitals and 20914 encounters from 1749 nonchildren's hospitals. Freestanding children's hospitals provided care to a higher risk population with more children transferred from other hospitals, a higher percentage of minorities, increased number of co-diagnoses, and a higher percentage on Medicaid. There was no statistically significant difference in LOS by hospital type. However, there was a significant difference in total costs, with the median cost of an admission at freestanding children's hospitals $1294 more per hospitalization than at nonchildren's hospitals, after adjusting for confounders.

Conclusion. We found no significant difference in median LOS among freestanding children's hospitals and nonchildren's hospitals, but freestanding children's hospitals had higher total charges per admission, even after adjusting for differences in population characteristics. Additional studies are needed to elucidate whether these increased costs result in better health outcomes or are simply attributable to other characteristics of children's hospitals, in which not all patients may benefit.
Estimated Impact of Competing Policy Recommendations for Age of First Dental Visit
Authors: Jones Kari , Tomar Scott L.
Published: April 2005

Objective. To compare levels of dental utilization and untreated dental decay among children aged 1 to 3 years that are likely to occur under 2 potential guidance policies: (1) pediatricians refer all toddlers to dentists for screening (consistent with American Academy of Pediatric Dentistry and the American Dental Association recommendations; DENT), and (2) pediatricians receive training in caries risk assessment, screen toddlers, and refer at-risk children to dentists (consistent with American Academy of Pediatrics recommendations; PED).

Methods. Using decision analysis, we estimated the impact of PED and DENT assuming alternately unlimited dental capacity for Medicaid-insured patients and fixed Medicaid dental capacity.

Results With unlimited capacity, if DENT were implemented, then dental utilization is estimated to increase from 27% under the status quo to 65% and untreated decay to decrease from a mean of 0.60 surfaces to 0.52 surfaces per child. If PED were implemented, then dental utilization and untreated decay would decrease from status quo levels to an estimated 11% and 0.47 surfaces, respectively, assuming that diagnostic sensitivity and specificity both equaled 1; they would decrease to 13% and 0.53 surfaces, respectively, if sensitivity equaled 0.76 and specificity equaled 0.95. With fixed capacity, under DENT, untreated decay is estimated to increase to 0.63 surfaces because low-risk private-pay patients would crowd out at-risk Medicaid-insured children, whereas under PED, untreated decay would still be less than under the status quo.

Conclusions. Implementing PED will decrease untreated decay under most plausible scenarios, whereas switching to DENT will increase the burden of disease if Medicaid dental capacity is limited.
Preventing Abusive Head Trauma Among Infants and Young Children: A Hospital-Based, Parent Education Program
Authors: Dias Mark S. , Smith Kim , deGuehery Kathy , Mazur Paula , Li Veetai , Shaffer Michele L.
Published: April 2005

Objective. Abusive head injuries among infants (shaken infant or shaken impact syndrome) represent a devastating form of child abuse; an effective prevention program that reduces the incidence of abusive head injuries could save both lives and the costs of caring for victims. We wished to determine whether a comprehensive, regional, hospital-based, parent education program, administered at the time of the child's birth, could be successfully implemented and to examine its impact on the incidence of abusive head injuries among infants <36 months of age.

Methods. All hospitals that provide maternity care in an 8-county region of western New York State participated in a comprehensive regional program of parent education about violent infant shaking. The program was administered to parents of all newborn infants before the infant's discharge from the hospital. The hospitals were asked to provide both parents (mothers and, whenever possible, fathers or father figures) with information describing the dangers of violent infant shaking and providing alternative responses to persistent infant crying and to have both parents sign voluntarily a commitment statement (CS) affirming their receipt and understanding of the materials. Program compliance was assessed by documenting the number of CSs signed by parents and returned by participating hospitals. Follow-up telephone interviews were conducted with a randomized 10% subset of parents, 7 months after the child's birth, to assess parents' recall of the information. Finally, the regional incidence of abusive head injuries among infants and children <36 months of age during the program (study group) was contrasted with the incidence during the 6 preceding years (historical control group) and with statewide incidence rates for the Commonwealth of Pennsylvania during the control and study periods, using Poisson regression analyses with a type I error rate of 0.05.

Results. During the first 5.5 years of the program, 65 205 CSs were documented, representing 69% of the 94 409 live births in the region during that time; 96% of CSs were signed by mothers and 76% by fathers/father figures. Follow-up telephone surveys 7 months later suggested that >95% of parents remembered having received the information. The incidence of abusive head injuries decreased by 47%, from 41.5 cases per 100 000 live births during the 6-year control period to 22.2 cases per 100000 live births during the 5.5-year study period. No comparable decrease was seen in the Commonwealth of Pennsylvania during the years 1996–2002, which bracketed the control and study periods in western New York State.

Conclusions. A coordinated, hospital-based, parent education program, targeting parents of all newborn infants, can reduce significantly the incidence of abusive head injuries among infants and children <36 months of age.
Infection Control Policies and Hospital-Associated Infections Among Surgical Patients: Variability and Associations in a Multicenter Pediatric Setting
Authors: Zerr Danielle M. , Garrison Michelle M. , Allpress Amanda L. , Heath Joan , Christakis Dimitri A.
Published: April 2005

Background. Hospital-associated infections are an important cause of patient morbidity and death. Little is known about the variability of infection rates and infection control practices among pediatric hospitals.

Methods. This cross-sectional study was performed with the Pediatric Health Information System database, which includes demographic and diagnostic data for 35 freestanding, noncompeting, children's hospitals, and with data from a survey of the hospitals, which yielded additional information on infection control policies and practices. Patients undergoing elective surgical procedures were included in this study.

Results. Of the 35 eligible hospitals, 31 (89%) chose to participate in the survey component of this study. A total of 48278 patients met the inclusion criteria for the study; 2.3% of these patients had respiratory infections and 0.8% had gastrointestinal infections. The frequency of patients diagnosed with respiratory or gastrointestinal infections varied considerably among the hospitals and ranged from <1% to 6%. Certain infection control processes also varied among the hospitals during the study period. For instance, of the 31 hospitals, 12 monitored hand hygiene, 19 had administrative support of hand hygiene, and 16 had alcohol hand gel present for the entire study period. The presence of alcohol hand gel for the entire study was strongly and independently associated with lower odds of gastrointestinal infections (adjusted odds ratio: 0.64; 95% confidence interval: 0.49-0.85).

Conclusions. Hospitals should support the use of alcohol hand gel, with the aim of decreasing hospital-associated infection rates.
Short- and Long-Term Beneficial Effects of a Combined Dietary–Behavioral–Physical Activity Intervention for the Treatment of Childhood Obesity
Authors: Nemet Dan , Barkan Sivan , Epstein Yoram , Friedland Orit , Kowen Galit , Eliakim Alon
Published: April 2005

Background. Obesity has become the most common pediatric chronic disease in the modern era. Early prevention and treatment of childhood and adolescent obesity is mandated. Surprisingly, however, only a minor fraction of obese children participate in weight reduction interventions, and the longer-term effects of these weight-reduction interventions among children have not been elucidated.

Objective. To examine prospectively the short- and long-term effects of a 3-month, combined dietary-behavioral-physical activity intervention on anthropometric measures, body composition, dietary and leisure-time habits, fitness, and lipid profiles among obese children.

Methods. In this randomized prospective study, 24 obese subjects completed the 3-month intervention and were compared with 22 obese, age- and gender-matched, control subjects.

Results. At 3 months, there were significant differences in changes in body weight (−2.8 ± 2.3 kg vs 1.2 ± 2.2 kg), BMI (−1.7 ± 1.1 kg/m2 vs −0.2 ± 1.0 kg/m2), body fat percentage (from skinfold tests; −3.3 ± 2.6% vs 1.4 ± 4.7%), serum total cholesterol level (−24.6 ± 15.1 mg/dL vs 0.8 ± 18.7 mg/dL), low-density lipoprotein cholesterol level (−23.3 ± 15.2 mg/dL vs −3.7 ± 17.3 mg/dL), and fitness (215 ± 107 seconds vs 50 ± 116 seconds) in the intervention group versus the control group. After a 1-year follow-up period, there were significant differences between the intervention group (n = 20) and the control group (n = 20) in body weight (0.6 ± 6.0 kg vs 5.3 ± 2.7 kg), BMI (−1.7 ± 2.3 kg/m2 vs 0.6 ± 0.9 kg/m2), and body fat percentage. There was a significant increase in leisure-time physical activity among the intervention participants, compared with a decrease among the control subjects.

Conclusions. Our data demonstrate the short- and longer-term beneficial effects of a combined dietary-behavioral-physical activity intervention among obese children. These results highlight the importance of multidisciplinary programs for the treatment of childhood obesity and emphasize their encouraging long-term effects.
The Pediatrician’s Role in Community Pediatrics
Authors:   Committee on Community Health Services
Published: April 2005

This policy statement reaffirms the pediatrician’s role in community pediatrics. It offers pediatricians a definition of community pediatrics and provides a set of specific recommendations that underscore the critical nature of this important dimension of the profession.
Providing Care For Immigrant, Homeless, and Migrant Children
Authors:   Committee on Community Health Services
Published: April 2005

This policy statement, which replaces the retired statements “Health Care for Children of Immigrant Families” (1997) and “Health Needs of Homeless Children and Families” (1996), is a broader discussion and addresses not only immigrant but also homeless and migrant child populations. It provides pediatricians with the necessary framework for addressing underserved children: those who face substantial barriers that limit access to appropriate health care services. This statement supports a community-based approach to health care delivery to ensure that underserved children have a medical home.
Guiding Principles for Pediatric Hospitalist Programs
Authors:   Section on Hospital Medicine
Published: April 2005

Pediatric hospitalist programs have become increasingly popular recently, emulating the growth and success of adult hospitalist programs. This statement provides an overview of hospitalist programs, factors influencing their growth, and their expected benefits. Six guiding principles for the establishment of pediatric hospitalist programs are identified in this statement concerning voluntary referrals; local design; minimum physician-training requirements; arrangement for appropriate follow-up; communication among primary care physicians, subspecialists, and hospitalists; and data collection and outcome measurements.
Use of Performance-Enhancing Substances
Authors:   Committee on Sports Medicine and Fitness
Published: April 2005

Performance-enhancing substances include dietary supplements, prescription medications, and illicit drugs. Virtually no data are available on the efficacy and safety in children and adolescents of widely used performance-enhancing substances. This statement is intended to provide a generalized but functional definition of performance-enhancing substances. The American Academy of Pediatrics strongly condemns the use of performance-enhancing substances and vigorously endorses efforts to eliminate their use among children and adolescents.
Association of the serotonin transporter promoter polymorphism with smoking behavior among adolescents
Authors: Gerra G. , Garofano L. , Zaimovic A. , Moi G. , Branchi B. , Bussandri M. , Brambilla F. , Donnini C.
Published: April 2005

Serotonin transporter promoter polymorphism (5‐HTTLPR) genotype was previously found associated with smoking behavior, difficulty in quitting smoking, and nicotine addiction; with non‐replicated findings and contrasting results. Aim of the present study was to evaluate the possible association between 5‐HTTLPR genotype and smoking behavior among adolescents, in relationship with psychological characteristics. Two hundred and ten Caucasian high school students (aged 14–19 years); 103 non‐smokers, who have never smoked nicotine; and 107 tobacco smokers have been genotyped. Aggressiveness levels and temperamental traits were measured in both smokers and non‐smokers, respectively, utilizing Buss–Durkee Hostility Inventory (BDHI) and Cloninger Three‐Dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short–short (SS) genotype frequency was significantly higher among smokers compared with non‐smokers (P = 0.023). The odds ratio for the SS genotype versus the long–long (LL) genotype frequency was 1.17 [95% CL (0.30–2.05)], when smokers were compared with non‐smokers. The SS genotype frequency was significantly higher among heavy smokers with early onset, compared with moderate smokers with late onset (P = 0.042). BDHI irritability scores, NS scores at TPQ, and school failure frequency were significantly higher in smokers than in non‐smokers. Multivariate model‐fitting analysis evidenced a significantly greater relationship of genotype with irritability levels (BDHI scores) (0.34, P < 0.001) and temperament traits (NS scores) (0.36, P < 0.001), than with school performance (rate of school under‐achievements) (0.18, P < 0.05) and nicotine smoking (number of cigarettes) (0.24, P < 0.01). Accordingly, factor‐analysis showed that gene polymorphism contributes more directly to BDHI scores and NS scores (0.73; 0.71) than to smoking behavior and school under‐achievement (0.54; 0.51). Our data suggest that a decreased expression of the gene encoding the 5‐HTT transporter, due to “S” promoter polymorphism, may be associated with smoking behavior among adolescents and increased risk to develop nicotine dependence, possibly in relationship to personality traits, temperamental characteristics, and school under‐achievements.© 2005 Wiley‐Liss, Inc.
Neural tube closure and neural tube defects: Studies in animal models reveal known knowns and known unknowns
Authors: Wallingford John B.
Published: April 2005

The vertebrate central nervous system is a hollow structure that develops first as a flat sheet of cells and subsequently rolls into a tube during embryogenesis. Failure of this rolling process, called neural tube closure, results in a class of common human birth defects called neural tube defects. The cellular and molecular mechanisms governing neural tube closure have been studied extensively in animal models, but much remains to be elucidated. In this review, I will highlight recent progress in understanding neural tube closure mechanisms and how these studies can inform our search for the genes that underlie human neural tube defects. Supplementary material for this article can be found on the American Journal of Medical Genetics (Part C) website (http://www.mrw.interscience.wiley.com/suppmat/1552‐4868/suppmat/2005/135/v135.1.wallingford.html) © 2005 Wiley‐Liss, Inc.
Ventral abdominal wall dysmorphogenesis of Msx1/Msx2 double‐mutant mice
Authors: Ogi Hidenao , Suzuki Kentaro , Ogino Yukiko , Kamimura Mika , Miyado Mami , Ying Xu , Zhang Zunyi , Shinohara Masanori , Chen Yiping , Yamada Gen
Published: April 2005

Msx1 and Msx2 genes encode the homeodomain transcription factors. Several gene knockout mice and expression studies suggest that they possess functionally redundant roles in embryogenesis. In this study, we revealed that Msx1 and Msx2 were expressed during ventral body wall formation in an overlapping manner. Msx1/Msx2 double‐mutant mice displayed embryonic abdominal wall defects with disorganized muscle layers and connective tissues. These findings indicate that Msx1 and Msx2 play roles in concert during embryonic ventral abdominal wall formation. © 2005 Wiley‐Liss, Inc.
Immunolocalization of chick periostin protein in the developing heart
Authors: Kern Christine B. , Hoffman Stanley , Moreno Ricardo , Damon Brook J. , Norris Russell A. , Krug Edward L. , Markwald Roger R. , Mjaatvedt Corey H.
Published: April 2005

The process that cardiac cushions undergo to form the mature septa and valves of the adult heart is poorly understood. Periostin is an extracellular molecule that is expressed during cushion mesenchyme formation and throughout valvulogenesis. Once thought to be an osteoblast‐specific factor, studies have shown this molecule is antiosteogenic. We have produced an antibody to chicken periostin and examined periostin's localization in the developing avian heart. This antibody recognized proteins from chick heart lysates around 90 kD molecular weight as predicted from the chick periostin mRNA and other periostin orthologs. Periostin immunolocalization was first evident as fibrous strands in the cushion mesenchyme. At HH25, periostin was detected on the basal surface of the trabecular endothelium and also on the endocardial epithelium of the atrioventricular cushion. We hypothesize that periostin may function in the organization of extracellular matrix molecules, providing cues necessary for attachment and spreading during the epithelial‐to‐mesenchymal transitions of the endocardial epithelium. Enhanced secretion of periostin in the region of delamination may directly or indirectly promote change in the myocardium that precedes or mediates delamination of the leaflet. At later stages of development (HH34‐38), periostin was seen predominantly in the fibrous regions of the heart, such as the left atrioventricular valve (LAV), annulus, cardiac skeleton, and adventitia. We propose that periostin is induced by sheer stress and may be an essential molecular component for structures of the heart that undergo mechanical stress or tension during the cardiac cycle. © 2005 Wiley‐Liss, Inc.
Fractionation of bovine serum albumin and monoclonal antibody alemtuzumab using carrier phase ultrafiltration
Authors: Wan Yinhua , Ghosh Raja , Hale Geoff , Cui Zhanfeng
Published: April 2005

Protein transmission and hence selectivity of separation can be significantly affected by solution pH and ionic strength in protein fractionation using ultrafiltration. Using parameter scanning ultrafiltration, the transmission of bovine serum albumin (BSA) and monoclonal antibody alemtuzumab (Campath‐1H) through 300 kDa polyethersulfone (PES) ultrafiltration membranes were studied over a range of pH and salt concentrations, with focus on the likely conditions for achieving “reverse selectivity,” i.e., obtaining purified alemtuzumab (∼155 kDa) in the permeate. Experimental results demonstrate that the reverse selectivity could be obtained by manipulating the operating conditions such as the solution pH, ionic strength, permeate flux, and system hydrodynamics. With a two‐stage batch ultrafiltration process under suitable conditions, the monoclonal antibody alemtuzumab with a purity of >98% was obtained in the permeate from a feed solution initially containing 0.50 g/l each of BSA and alemtuzumab. Further purity can be expected by selecting more suitable membranes and optimizing operating conditions. © 2005 Wiley Periodicals, Inc.
Transient gene expression in HEK293 cells: Peptone addition posttransfection improves recombinant protein synthesis
Authors: Pham P.L. , Perret S. , Cass B. , Carpentier E. , St‐Laurent G. , Bisson L. , Kamen A. , Durocher Y.
Published: April 2005

Gene expression by large‐scale transfection of mammalian cells is becoming an established technology for the fast production of milligram and even gram amounts of recombinant proteins (r‐proteins). However, efforts are still needed to optimize production parameters in order to maximize volumetric productivities while maintaining product quality. In this study, transfection efficiency and volumetric productivity following transient gene expression in HEK293 cells were evaluated using green fluorescent protein (GFP) and human placental secreted alkaline phosphatase (SEAP) as reporter genes. We show that a single pulse of peptones (protein hydrolysates) to the cultures performed in a low serum (1%, v/v) and in serum‐free medium results in a significant increase in volumetric protein productivity. Sixteen peptones from different sources were tested and almost all of them showed a positive effect on r‐protein production. This effect, however, is time‐ and concentration‐dependent. By using Tryptone N1 (a casein peptone, TN1) to feed the cultures at 24 h posttransfection (hpt), a 2‐fold increase in volumetric SEAP productivity was obtained 5 days posttransfection. This effect was shown to be equal to that obtained when the culture was fed with a supplementary 4% (v/v) of serum. The positive effect of TN1 on protein production was also demonstrated with Tie2 protein ectodomain produced in serum‐free medium. HPLC analysis of amino acids consumption/production during control batch and TN1 pulse culture showed some major differences in amino acid metabolism when using TN1 pulse. Asparagine, glycine, histidine, threonine, leucine, and valine show accumulation in the medium over the cultivation period instead of being consumed as observed in unfed sample (except for asparagine, which remained unchanged). Isoleucine, tyrosine, methionine, and phenylalanine all remained unchanged or slightly fluctuated in TN1‐fed culture after the feeding pulse, while they were all steadily consumed in the control run. The relative abundance of SEAP's mRNA suggests that the improvement in protein yield results both from an increase of the translational activity and transcription efficiency. Further understanding of mechanisms by which amino acids/peptides regulate transcriptional and translational machinery in mammalian cells should facilitate the design of new strategies for the improvement of r‐protein production by large‐scale transfection. © 2005 Government of Canada.
High‐yield retroviral production using a temperature‐modulated two‐stage operation
Authors: Kwon Young Jik , Peng Ching‐An
Published: April 2005

For clinical trials, large amounts of high‐titer retroviral supernatants are required. However, retroviral concentration is relatively low compared with other viral vectors. Moreover, less than half of retroviral vectors suspended in a collected supernatant are infectious because of their short half‐lives. In this study, a culture medium of ecotropic retrovirus‐producing GP+E86/LNCX cells in tissue culture dishes was circulated through a reservoir, which was arranged with an incubator or ice‐bath stage. Titers determined from the retroviral supernatant circulated through an ice‐cold reservoir increased for a week from the beginning of retroviral production, while the titers from static production with circulation through the 37°C reservoir reached a plateau after 3 days of retroviral production. After 5 days, 10 times more infectious retroviruses were obtained by circulating and keeping the majority of supernatant longer in the cold reservoir than in the production vessel at 37°C in comparison with the number collected from the static tissue culture dish without circulating the culture medium. Furthermore, the concentration of transduction inhibitors in the supernatant was decreased along with the retardation of retroviral decay at low temperature. The two‐stage operation developed in this study should be easily applied to large‐scale bioreactors for mass production of high‐titer retroviral supernatants. © 2005 Wiley Periodicals, Inc.
Localization of receptors in lipid rafts can inhibit signal transduction
Authors: Lim Kwang‐il , Yin John
Published: April 2005

Processes of cell survival, division, differentiation, and death are guided by the binding of signal molecules to receptors, which activates intracellular signaling networks and ultimately elicits genetic, biochemical, or biomechanical responses within the cell. While intracellular mechanisms for these processes have been well studied, little attention has been given to the role extracellular ligand transport and binding may play in signal initiation. Recent studies have found that the localization of receptors in lipid rafts is critical for the functions of many signaling pathways. By concentrating membrane components, rafts may promote essential interactions for signaling. Lipid rafts can also have negative effects on signaling, but mechanisms remain elusive. We propose that raft‐mediated receptor clustering can reduce signaling by prolonging the diffusion of ligands to their receptors. We quantify this effect using a simple diffusion‐limited binding model that accounts for the spatial distribution of lipid rafts and receptors on the cell surface. We find that receptor clustering can reduce the apparent rate of receptor binding by up to 80%, consistent with observed increases in epidermal growth factor (EGF) binding by up to 100% following disruption of lipid rafts (Pike and Casey 2002 Biochemistry 41:10315–10322; Roepstorff et al. 2002 J Biol Chem 277:18954–18960). Failure to account for the effects of receptor clustering on rates of ligand binding can skew the interpretation of current methods of cancer diagnosis and treatment. Finally, we discuss how the activation of particular signaling pathways can change over time, depending, in part, on the overall level and spatial distribution of the receptors. © 2005 Wiley Periodicals, Inc.