Pediatrics

Sodium space and intravascular volume: dietary sodium effects in cystic fibrosis and healthy adolescent subjects.

Legris GJ. Dearborn D. Stern RC. Geiss CL. Hopfer U. Douglas JG. Doershuk CF.
St Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
OBJECTIVE. To assess the physiologic response to salt depletion in subjects with cystic fibrosis (CF) and control male adolescents for sodium balance, sodium space, and stimulation of the renin-angiotensin-aldosterone axis. DESIGN. Seven subjects with CF and six controls received a salt-replete (150 or 290 mmol NaCl per day) diet and then a salt-deplete (10 mmol NaCl per day) diet while in a clinical research center. RESULTS. Space maintenance: CF subjects responded to salt depletion with a greater weight loss than did controls (1.9 vs 0.8 kg) and a decrease in 24Na+ space, whereas controls maintained 24Na+ space. Paired (Na-deplete/Na-replete) blood volumes decreased in subjects with CF, but not in controls. Renin-angiotensin-aldosterone axis stimulation: During salt repletion, subjects with CF had significantly higher aldosterone values than did controls in the afternoon, but not at 7:00 AM. During salt depletion, plasma renin activity and aldosterone increased significantly more in subjects with CF than in controls (renin, 35 vs 13 ng/mL/hour [9.7 vs 3.6 ng.L-1 s-1]; aldosterone: 181 vs 101 ng/dL [5021 vs 2802 pmol/L]). Furthermore, the angiotensin antagonist saralasin increased renin much more in subjects with CF (154 vs 36 ng/mL per hour [43 vs 10 ng.L-1 s-1]). Vasomotor functions: Mean arterial pressure was decreased in subjects with CF on both diets and decreased significantly more with low salt only in subjects with CF. During salt depletion, subjects with CF showed enhanced orthostatic tolerance (less heart rate increase with standing) compared with controls, thus obscuring their volume loss. The blood pressure response to an acute infusion of saralasin suggested that in salt-replete subjects with CF, but not in controls, angiotensin receptors were functional in maintaining vascular tone. During salt depletion, angiotensin was more important for maintenance of blood pressure in subjects with CF than in controls, because the saralasin-induced drop in blood pressure was 20%, ie, close to shock levels, in subjects with CF, and only 6% in controls. CONCLUSION. The data suggest that patients with CF are so successful in compensating for volume depletion by vigorous activation of the renin-angiotensin system that salt depletion/dehydration cannot be recognized easily by routine clinical measurements, eg, capillary refill, serum sodium levels, or tachycardia.

Is the incidence of appendicitis reduced in patients with sickle cell disease?

Antal P. Gauderer M. Koshy M. Berman B.
Department of Pediatrics, Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, OH 44106-6019, USA.
BACKGROUND: Patients with sickle cell disease (SCD) often present with abdominal pain, usually attributable to vasoocclusion. Experience at a single institution suggested that appendicitis was a rare cause of abdominal symptoms in this population. OBJECTIVE: We sought to determine whether the incidence of appendicitis was significantly lower in patients with SCD than in the population at large. METHODS: A 17-year retrospective chart review was performed at Rainbow Babies and Children's Hospital, Cleveland, OH, to determine the approximate incidence of acute appendicitis (AA) in patients with SCD. In addition, we performed a statistical analysis comparing the incidence of AA among SCD patients enrolled in the Cooperative Study of Sickle Cell Disease with that in the general population. RESULTS: Only two patients with SCD with pathologically confirmed AA were identified among approximately 200 patients followed at our institution during a 17-year period ( approximately 3500 patient-years), yielding an incidence rate of 5.7 cases per 10 000 patient-years. Among 3765 patients with SCD enrolled in the Cooperative Study of Sickle Cell Disease followed for a mean of 5.3 years (19 886 patient-years), a maximum of 9 cases of AA were identified, yielding an incidence rate of 4.5 cases per 10 000 patient-years. Based on data from the National Hospital Discharge Survey of 1978 to 1981, the incidence rate of AA in the general population (0 to 44 years of age) is approximately 16 per 10 000 patient-years. Paired t test analysis demonstrated a highly significant difference (P < .001) when comparing the incidence of AA among patients enrolled in the Cooperative Study of Sickle Cell Disease and the population at large. CONCLUSION: AA is an unusual event in patients with SCD. The likelihood of developing appendicitis in SCD patients is less than one third of that for the population at large. Conservative therapy is warranted in the large majority of patients with SCD who present with acute abdominal pain. Surgical exploration is best limited to patients with clear evidence of potential surgical pathology or progressive findings during a period of observation. The biologic basis of our findings remains unknown.

Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage.

Hahn JS. Berquist W. Alcorn DM. Chamberlain L. Bass D.
Departments of Neurology and Neurological Sciences, Pediatrics, and Ophthalmology Stanford University School of Medicine Packard Children's Hospital at Stanford Stanford, CA 94305-5235, USA.
OBJECTIVE: Wernicke encephalopathy (WE) is an acute neurologic disorder characterized by a triad of ophthalmoplegia, ataxia, and mental confusion. WE is attributable to thiamine (vitamin B1) deficiency. Beriberi is the systemic counterpart of thiamine deficiency and often manifests in cardiovascular collapse. WE is usually associated with alcoholism and malnutrition. It has also been seen in people with gastrointestinal diseases with malabsorption. Patients who have received total parenteral nutrition (TPN) without proper replacement of thiamine have also developed WE. Since November 1996, there has been a shortage of multivitamin infusion (MVI). Many patients who were on chronic TPN with MVI ceased to receive the MVI and were converted to an oral form of the multivitamin. As a result, there have been several reports of children and adults on TPN who have developed WE as a result of thiamine deficiency. With this case report, we bring to attention the association of the MVI shortage and WE. Early diagnosis of WE is important, because if it is treated with thiamine in the acute stages, the neurologic and cardiovascular abnormalities can be reversed. CASE REPORT: We report a 20-year-old female patient with Crohn's disease who developed WE as a result of thiamine deficiency. She had Crohn's disease since age 9 years and was on chronic TPN. Two months before admission, MVI was discontinued in the TPN because of the shortage of its supply. An oral multivitamin tablet was substituted instead. She was admitted to the hospital for persistent vomiting. In the hospital, she continued to receive TPN without MVI, but continued taking an oral multivitamin preparation. Two weeks after admission, she developed signs of WE including diplopia, ophthalmoplegia, nystagmus, and memory disturbance. She also developed hypotension that was thought to be caused by beriberi. She was treated with 50 mg of intravenous thiamine. Within hours of the intravenous thiamine, her hypotension resolved. The day after the infusion, she no longer complained of diplopia, and her ophthalmoplegia had improved dramatically. Magnetic resonance imaging showed several areas of abnormally high signal on T2-weighted images in the brainstem, thalamus, and mamillary bodies. The topographic distribution of these changes was typical of WE. After 2 months, her mental status and neurologic status had recovered completely. CONCLUSION: WE and thiamine deficiency should be considered in all patients with malabsorption, malnutrition, and malignancies. WE from thiamine deficiency can occur as a result of cessation of MVI in the TPN infusion. Even if an oral multivitamin preparation is given instead of MVI, patients with malabsorption may not absorb thiamine adequately. Prompt diagnosis of WE is important because it is potentially fatal and readily treatable with thiamine supplementation. Early recognition of WE may be more difficult in children, because the classic triad of symptoms may not develop fully. Magnetic resonance imaging may be useful in these cases to confirm the diagnosis of WE. Because the shortage of MVI is expected to be a long-term, there are likely to be more cases of WE in the pediatric population of TPN-dependent children. Because there is no shortage of intravenous thiamine, it should be administered with TPN even if MVI is not available.

Risky behavior in teens with cystic fibrosis or sickle cell disease: a multicenter study.

Britto MT. Garrett JM. Dugliss MA. Daeschner CW Jr. Johnson CA. Leigh MW. Majure JM. Schultz WH. Konrad TR.
University of North Carolina, Chapel Hill, USA.
OBJECTIVE: To determine the prevalence and age of onset of common risky behaviors such as smoking and sexual activity in teens with cystic fibrosis and those with sickle cell disease and to compare their behaviors with those of adolescents in the general population. DESIGN: Survey. SETTING: All five major pediatric tertiary care centers in North Carolina (study participants with sickle cell disease or cystic fibrosis) and North Carolina public schools (comparison population). PARTICIPANTS: Three hundred twenty-one adolescents with cystic fibrosis or sickle cell disease aged 12 to 19 years (mean age, 15.6 years; 49% female). Demographically matched comparison teens for each group were selected from 2760 in-school adolescents (mean age, 16.0 years; 51% female). MAIN OUTCOMES MEASURES: Prevalence of tobacco and marijuana use, alcohol use, sexual intercourse, sexually transmitted diseases, seat belt use, weapon carrying, and age of onset of these behaviors. RESULTS: Chronically ill teens reported significantly less lifetime and current use of tobacco, marijuana, and alcohol; less sexual intercourse; less weapon carrying, less drunk driving, and more seat belt use than their peers. Nonetheless, 21% of the teens with cystic fibrosis and 30% of those with sickle cell disease had smoked; sexual intercourse was reported by 28% and 51%, respectively. Age of onset of these behaviors was frequently older for the chronically ill teens. CONCLUSION: Teens with cystic fibrosis or sickle cell disease took more potentially damaging health risks than might be expected, although the prevalence was lower than reported by their peers. Future longitudinal studies should examine the relationships between chronic illness, physical and psychosocial maturation, and risky behavior. Screening for psychosocial issues, including risky behaviors, should be incorporated into the routine health care of chronically ill teens.

Reproducibility of 24-hour intraesophageal pH monitoring in pediatric patients.

Mahajan L. Wyllie R. Oliva L. Balsells F. Steffen R. Kay M.
Section of Pediatric Gastroenterology and Nutrition, Cleveland Clinic Foundation, OH 44195, USA.
OBJECTIVE: Despite the widespread use of 24-hour intraesophageal pH monitoring for evaluation of gastroesophageal reflux in infants and children, there is little published information regarding the reproducibility of ambulatory pH studies in this patient population. The purpose of our study was to evaluate the reproducibility of 24-hour intraesophageal pH monitoring in pediatric patients. METHODS: We prospectively investigated 26 patients with symptoms suggestive of gastroesophageal reflux (14 females and 12 males) ranging in age from 1 month to 18 years (mean, 9.2 years). The patients underwent extended intraesophageal pH monitoring over two consecutive 24-hour periods. RESULTS: Data analysis revealed that the overall reproducibility of ambulatory 24-hour pH monitoring is only 69% (r = 0.32). Eight of 26 patients had conflicting results on day 1 compared with results on day 2. Of the 8 patients with conflicting results on day 1 versus day 2, 5 had normal studies on day 1, but demonstrated pathologic reflux on day 2. Thus, the false-negative rate for day 1 was 19.2%. The kappa statistic calculated for the total time the pH was abnormal was 0.32, with values < 0.4 representing poor correlation. Spearman correlation coefficients indicated that the percentage of time with pH < 4 (r = 0.64) and the number of reflux episodes (r = 0.71) per 24-hour period are the most reproducible pH parameters. CONCLUSION: The reproducibility of 24-hour intraesophageal pH monitoring in the pediatric population is suboptimal. The investigation should be extended or repeated if the result does not correlate with the patient's clinical history.

Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome.

Carlsson A. Axelsson I. Borulf S. Bredberg A. Forslund M. Lindberg B. Sjoberg K. Ivarsson SA.
Department of Pediatrics, University of Lund, University Hospital, Malmo, Sweden.
OBJECTIVE: This study was undertaken to investigate the prevalence of celiac disease in children and adolescents with Down syndrome. MATERIAL AND METHODS: Forty-three children and adolescents with Down syndrome were screened for IgA-antigliadin antibodies (AGA) and IgA-antiendomysium antibodies (EMA). Patients found to be either AGA- or EMA-positive were investigated further with intestinal biopsy. RESULTS: None of the 43 patients had known celiac disease at entry into the study; 37% (16/43) were found to have AGA levels above normal, and 16% (7/43) to be EMA-positive. Of the 15 patients who underwent biopsy, 8 manifested villous atrophy. Villous atrophy was present in all 7 of the EMA-positive patients, whereas the villi were normal in 7 of the 13 AGA-positive patients who underwent biopsy. CONCLUSIONS: EMA is a good immunologic marker for use in screening for celiac disease, and screening is justified in patients with Down syndrome.

Lung volume, pulmonary vasculature, and factors affecting survival in congenital diaphragmatic hernia.

Thibeault DW. Haney B.
Department of Pediatrics, Children's Mercy Hospital, University of Missouri-Kansas City School of Medicine 64108, USA.
OBJECTIVES: There is a wide variation in published mortality from congenital diaphragmatic hernia (CDH). The prevailing opinion is that this variation is related directly to the degree of pulmonary hypoplasia. Our aim was to test the hypothesis that other factors are important for outcome. The specific objectives of this study were: 1) to quantitate the degree of lung hypoplasia and pulmonary arterial wall thickness in infants eligible for, and treated with, extracorporeal membrane oxygenation (ECMO), using postmortem analysis of lung DNA, wet lung weight, lung volume, and vessel morphometrics; 2) to correlate the degree of lung hypoplasia and vascular changes with functional tests of oxygenation and estimated right ventricular systolic pressures (RVSP); 3) to determine the minimum lung volume necessary for survival; and 4) to determine contributory clinical factors as potential causes of death in ECMO-treated infants with CDH. METHODOLOGY: We retrospectively analyzed all 90 infants with CDH admitted consecutively over a 9-year period to a children's hospital with an ECMO program. Infants were categorized as lived or died, with or without ECMO. Indication for ECMO was an evolving process; however, in general, it was the therapy of last resort for pulmonary insufficiency. Clinically, the single best oxygenation index before ECMO or CDH repair while on conventional ventilation, and serial echocardiograms before, during, and after ECMO, were obtained. Twelve of 14 infants dying with ECMO and 6 of 12 without ECMO had postmortem examinations. Lung volume, DNA content, wet weights, and arterial wall thickness at the level of alveolar ducts were measured in both lungs. Postmortem morphometric findings were correlated with in vivo tests of cardiopulmonary function and contributory clinical factors in mortality. RESULTS: Sixty-three percent of all infants with CDH and 61% of ECMO-treated infants lived. All infants with CDH requiring ECMO had elevated RVSP/systolic systemic blood pressure ratios before ECMO (0.98 +/- 0.24). Eighty-eight percent of ECMO-treated infants with CDH decreased this ratio to < 0.5 within 14 days, regardless of lung size. However, infants dying with normal ratios still had increased arterial wall thickness and muscle in both lungs. In infants whose lung volume, DNA, and weight were > 45% of values predicted for age-matched controls, the oxygenation index ranged from 4 to 29, significantly less than that in infants with values < 45% of predicted values (range, 25 to 133). We speculate that eight infants with lung volumes > 45% of that for controls died from potentially preventable surgical and medical complications. CONCLUSION: A minimum lung volume of 45% of the value predicted from age-matched controls is required for survival in ECMO-treated infants. The RVSP/systolic systemic blood pressure ratio can be reduced with ECMO to < 0.5 in the majority of infants, even with lung volumes inadequate for survival. We speculate that 9% of infants with adequate lung volume were potentially survivable, but died of medical and surgical complications.

Surgical treatment of gastroesophageal reflux in children: a combined hospital study of 7467 patients.

Fonkalsrud EW. Ashcraft KW. Coran AG. Ellis DG. Grosfeld JL. Tunell WP. Weber TR.
Department of Surgery,UCLA School of Medicine, Los Angeles, California 90095, USA.
OBJECTIVE: To review retrospectively the combined clinical experience with the surgical treatment of persistently symptomatic gastroesophageal reflux (SGER) in childhood from seven large children's surgery centers in the United States. DESIGN: During the past 20 years, 7467 children

Proteolysis associated with insulin resistance in cystic fibrosis.

Hardin DS. LeBlanc A. Lukenbaugh S. Para L. Seilheimer DK.
Department of Pediatrics, University of Texas Health Science Center, Houston, Texas.
OBJECTIVE: We hypothesized that patients with cystic fibrosis (CF) have higher rates of protein breakdown than normal volunteers and that the infusion of insulin would result in less suppression of proteolysis. Methods. Using [1-C]leucine and a three-step hyperinsulinemic euglycemic clamp, we measured rates of leucine appearance in 29 adult CF patients and 18 matched-control volunteers. The CF patients were characterized by oral glucose tolerance testing and clinical status scoring. RESULTS: The CF patients had significantly increased proteolysis when compared with that of controls (CF, 123 +/- 28 micromol/kg/h; controls, 71 +/- 15 micromol/kg/h) and rates of proteolysis were significantly different between CF patients with impaired glucose tolerance and diabetes and those CF patients with normal glucose tolerance. Suppression of proteolysis by insulin was less in all CF subgroups than in the controls at peripheral insulin levels of 16 and 29 microU/mL. At peripheral insulin levels of 100 microU/mL, there was no difference in insulin suppression of proteolysis between CF patients and controls. Importantly, basal rates of proteolysis had an inverse relationship with clinical status in CF patients (r = -.76). CONCLUSIONS: Our findings indicate that proteolysis is higher in adult CF patients than in controls and that CF patients exhibit resistance to the anabolic effects of insulin on proteolysis. Most significantly, our findings indicate that basal rates of proteolysis inversely correlate with clinical status in CF.

QT interval in children and infants receiving cisapride.

Levine A. Fogelman R. Sirota L. Zangen Z. Shamir R. Dinari G.
Division of Gastroenterology and Nutrition, the Division of Cardiology, Schneider Children's Medical Center of Israel, Tel Aviv University Sackler School of Medicine, Petah Tikva, Israel.
OBJECTIVES: Life-threatening arrhythmias and prolonged QT interval have been reported in adults and children using cisapride, a medication structurally similar to procainamide. Premature infants have reduced activity of cytochrome p-450, the system responsible for metabolism of cisapride, which could lead to QT prolongation. Therefore, we prospectively studied premature infants and children receiving cisapride to analyze the effect of prolonged cisapride therapy on QT interval. DESIGN: Premature infants in a neonatal intensive care unit and children seen at a pediatric gastroenterology clinic in a tertiary care hospital had electrocardiography-analyzed and -corrected QT interval measured before cisapride (0.8/mg/kg per day) therapy, and again after 1 month of therapy. If baseline electrocardiography was not performed initially, it was obtained after cessation of therapy. RESULTS: A total of 30 children participated in the study. Mean corrected QT interval was similar at baseline and at 1 month after therapy. Significant QT prolongation was not found, and no adverse effects were recorded. CONCLUSIONS: Corrected QT interval during prolonged cisapride therapy at 0.8 mg/kg per day appears to be similar for premature infants and children. An inherent trend toward QT prolongation was not detected in either group. In the absence of other risk factors that alter cisapride metabolism or predispose to arrhythmia, cisapride may be safe for use in premature infants as well as in children. Additional studies are needed to confirm these data.

Hepatitis C virus infection. American Academy of Pediatrics. Committee on Infectious Diseases.

Year 1998

No information.
Hepatitis C virus (HCV) has become the most significant cause of chronic liver disease of infectious etiology in the United States. The recognition that HCV can be transmitted perinatally or through blood transfusions warrants particular attention by the pediatrician. The American Academy of Pediatrics recommends screening infants born to HCV-infected mothers and persons with risk factors for HCV infection such as injection drug use, transfusion of >/= 1 U of blood or blood products before 1992, or hemodialysis should be screened for anti-HCV. Also, persons who received clotting factor concentrates before 1987, when effective inactivation procedures were introduced, also should be screened. Guidelines for counseling families of HCV-infected children are provided.

Helicobacter pylori and abdominal symptoms: a population-based study among preschool children in southern Germany.

Year 1998
Bode G. Rothenbacher D. Brenner H. Adler G.
Department of Internal Medicine I, University of Ulm, Ulm, Germany.
OBJECTIVE: To determine the relation of Helicobacter pylori infection with gastrointestinal symptoms in a healthy population-based sample of children. DESIGN: Population-based cross-sectional study of preschool children. SETTING: Screening examination for school fitness by physicians of the Public Health Service in Ulm, a city with 100 000 inhabitants in southern Germany. PARTICIPANTS: One thousand two hundred one preschool children. MAIN OUTCOME MEASURES: Infection status was determined by 13C-urea breath test. Information on gastrointestinal symptoms was collected from children's parents by a standardized questionnaire and integrated into a symptom score. Results. Nine hundred forty-five children participated in the study (response rate, 79%). Overall, 127 children (13.4%) were infected. H pylori infection was not positively related to specific gastrointestinal symptomatology. Infected children had even fewer symptoms when compared with uninfected children. CONCLUSIONS: Our results indicate that H pylori infection in children is mostly asymptomatic and not associated with specific gastrointestinal symptoms.

The collaborative UK ECMO (Extracorporeal Membrane Oxygenation) trial: follow-up to 1 year of age.

Year 1998

No information.
OBJECTIVE: To evaluate the clinical effectiveness of neonatal extracorporeal membrane oxygenation (ECMO), in terms of mortality and morbidity, in the treatment of cardiorespiratory failure in term infants. METHODS: The criteria for trial entry were: an oxygenation index of >40 or arterial partial pressure of carbon dioxide (PaCO2) >12 kPa for at least 3 hours; gestational age at birth of 35 completed weeks or more; a birth weight of 2 kg or more;

Long-term outcome after neonatal meconium obstruction.

Year 1998
Fuchs JR. Langer JC.
Department of Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
OBJECTIVE: It is unclear whether children with cystic fibrosis (CF) who present with neonatal meconium ileus have a different long-term outcome from those presenting later in childhood with pulmonary complications or failure to thrive. We examined a cohort of patients with meconium ileus, and compared their long-term outcome with children who had CF without meconium ileus and neonates who had meconium obstruction without CF (meconium plug syndrome). STUDY DESIGN: Comparative study using retrospective and follow-up interview data. PATIENTS: Group 1 consisted of 35 surviving CF patients who presented with meconium ileus between 1966 and 1992. Two control groups were also studied: 35 age- and sex-matched CF patients without meconium ileus (group 2), and 12 infants presenting with meconium plug syndrome during the same time period (group 3). OUTCOME MEASURES: Pulmonary, gastrointestinal, nutritional, and functional status were reviewed, and surgical complications were recorded. RESULTS: Mean follow-up was 12.6 +/- 6, 12.6 +/- 6, and 9. 3 +/- 4 years in groups 1, 2, and 3, respectively. Patients without CF (group 3) demonstrated better growth and functional status, and had a lower incidence of pulmonary and gastrointestinal problems. Although the presence of meconium ileus among CF patients was associated with an earlier diagnosis, there were no significant differences between groups 1 and 2 with respect to hepatobiliary, nutritional, functional, or respiratory status. Meconium ileus was associated with a higher risk of meconium ileus equivalent (20% vs 6%), although this difference was not statistically significant. Long-term surgical complications (adhesive small bowel obstruction and blind loop syndrome) were seen in 27% of children with meconium ileus; there were no long-term surgical complications in groups 2 or 3, because these infants did not have any neonatal surgical procedures. Children presenting with complicated meconium ileus had a higher rate of long-term surgical complications than those with uncomplicated meconium ileus (36% vs 17%), and those managed with resection or enterostomy had more complications than those treated by enterotomy and lavage (33% vs 0%). CONCLUSIONS: Long-term outcome is similar in CF patients who present with meconium ileus and those who do not, except for a slightly higher incidence of meconium ileus equivalent, and a significantly higher rate of surgical complications. The risk of surgical complications is highest in those presenting with complicated meconium ileus and those undergoing resection or enterostomy. Patients with meconium obstruction who do not have CF have an excellent long-term prognosis. This information will be useful in counseling the families of infants presenting with neonatal meconium obstruction.

Increasing breastfeeding rates to reduce infant illness at the community level.

Year 1998
Wright AL. Bauer M. Naylor A. Sutcliffe E. Clark L.
Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, USA.
OBJECTIVE: Although breastfeeding is associated with lower rates of a variety of infant illnesses, skeptics have suggested that much of the association is attributable to confounding, even after appropriate statistical adjustment. This article utilizes a novel design to investigate changes in infant illness at the community level after a successful breastfeeding promotion program. METHODS: In this population-based cohort study, the medical records of all infants born in one Navajo community the year before a breastfeeding promotion program (n = 977) and the year during the intervention (n = 858) were reviewed. Outcomes assessed include changes after the intervention in: proportion breastfeeding and/or breastfeeding exclusively; incidence of common infant illnesses in the first year of life; and feeding-group specific incidence of illness. RESULTS: The proportion of women breastfeeding exclusively for any period of time increased from 16.4% to 54.6% after the intervention. The percent of children having pneumonia and gastroenteritis declined 32. 2% and 14.6%, respectively, after the intervention. Feeding-group specific rates of these illnesses were unchanged, indicating that the decline observed was attributable to the increased proportion of infants breastfeeding. In contrast, rates of croup and bronchiolitis increased after the intervention among those fed formula from birth, suggesting a viral epidemic which was limited to those never exclusively breastfed. Finally, sepsis declined in both formula-fed and breastfed infants after the intervention, suggesting that other factors affected this illness outcome after the intervention. CONCLUSIONS: Increasing the proportion of exclusively breastfed infants seems to be an effective means of reducing infant illness at the community level. The experimental design suggests that the increased incidence of illness among minimally breastfed infants is causally related to lack of breast milk, rather than being attributable to confounding.

Buccal cell DNA mutation analysis for diagnosis of cystic fibrosis in newborns and infants inaccessible to sweat chloride measurement.

Year 1998
Parad RB.
Division of Newborn Medicine (Joint Program in Neonatology), Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
OBJECTIVES: To assess the application of DNA-based cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis as a primary cystic fibrosis (CF) diagnostic test in preterm and term newborns and infants for whom the quantitative pilocarpine iontophoresis test (QPIT) cannot be used. DESIGN: Retrospective survey. SETTING: DNA Diagnostic Laboratory, Children's Hospital, Boston, Massachusetts. Buccal cell DNA samples were received from inpatients, outpatients, and three neonatal intensive care units. OUTCOME MEASURE: Detection of at least 1 of 12 CFTR mutations. PATIENTS: Between November 1, 1992, and April 30, 1994, 28 newborns and infants under 12 months of age at risk for CF had CFTR DNA mutation analysis performed because a sweat chloride (SC) value could not be obtained. QPIT was either not performed (infant weight

Management of acute gastroenteritis in children in Israel.

Year 1998
Shamir R. Zahavi I. Abramowich T. Poraz I. Tal D. Pollak S. Dinari G.
Division of Gastroenterology and Nutrition, Schneider Children's Medical Center of Israel, Tel-Aviv University, Sackler School of Medicine, Petah Tikva, Israel.
OBJECTIVE: Diarrheal diseases are a major cause of morbidity and mortality worldwide. Guidelines about the use of oral rehydration solutions (ORS) and dietary management of acute gastroenteritis (GE) were recently revised and published by the American Academy of Pediatrics (AAP). Study aims were to examine Israeli pediatricians' knowledge and implementation of the revised AAP guidelines, the effect of medical school (Israeli versus foreign medical graduates) on the physicians' practice, and the effect of the type of practice (community vs hospital-based) on the management of gastroenteritis. METHODS: A multiple-choice, written questionnaire was distributed at two pediatrics annual meetings. RESULTS: A total of 87 pediatricians completed the questionnaire. They were aware of 73% of the current AAP guidelines and followed 60% of the guidelines. Most pediatricians (83%) use ORS for treatment of dehydration in GE, but 60% of pediatricians believe that full-strength feeds are inappropriate in the presence of GE, and 67% of them do not recommend full-strength formulas. In addition, 37% of the pediatricians stop feeding temporarily in the presence of GE, in contrast to the 1996 AAP guidelines. There were no differences in knowledge and management practices among pediatricians graduating in Israel, Europe, or the United States, and no differences between pediatricians working in an ambulatory setting or in a hospital. CONCLUSIONS: Pediatricians in Israel, regardless of country of origin, medical school, or place of practice, are aware of the correct use of ORS but do not follow nutritional practices recommended recently by the AAP. These findings suggest that steps for implementing the guidelines are needed in Israel and most probably worldwide.

Cystic fibrosis: when should high-resolution computed tomography of the chest Be obtained?

Year 1998
Santamaria F. Grillo G. Guidi G. Rotondo A. Raia V. de Ritis G. Sarnelli P. Caterino M. Greco L.
Department of Pediatrics, Federico II University, Naples, Italy.
OBJECTIVE: To provide indications for high-resolution computed tomography (HRCT) of the chest in patients with cystic fibrosis (CF). DESIGN: We compared the HRCT and conventional chest radiography (CCR) scores and assessed their correlation with clinical scores and pulmonary function tests. SETTING: Department of Pediatrics, Federico II University, Naples, Italy. SUBJECTS: A total of 30 patients with CF 6.75 to 24 years of age. RESULTS: CCR scores correlated highly with HRCT (r = -0.8) and clinical (r = 0.5) scores, whereas total HRCT scores were not related to clinical scores. Of all the specific HRCT findings, only bronchiectasis appeared related significantly to the clinical score (r = 0.6). Most pulmonary function tests were related to CCR and total HRCT scores, but not to HRCT scoring of specific changes. Forced vital capacity and CCR scores appeared the best predictors of the HRCT score (multiple R = 0.58 and 0.79, respectively). In patients with mild lung disease, HRCT detected bronchiectasis and air trapping in 57% and 71% of the cases, respectively. In patients with more abnormal chest radiographs, bronchiectasis and air trapping were demonstrated on HRCT in all cases. CONCLUSIONS: These findings suggest that HRCT of the chest is most useful in the identification of early lung abnormalities in patients with CF with mild respiratory symptoms, whereas for established disease, CCR is still the first-line imaging technique. The advantage of detecting early changes on CT imaging awaits additional confirmation, at least until early therapeutic interventions affecting significantly the final outcome of the disease are demonstrated. In patients with advanced disease, HRCT may be useful in the evaluation of specific lung changes when more aggressive treatment such as chest surgical interventions is indicated. Given the cost of the procedure and the high radiation dosage compared with CCR, a careful assessment of the cost:benefit ratios of HRCT is strongly recommended in CF.

Point mutation in exon 12 of the receptor tyrosine kinase proto-oncogene RET in Ondine-Hirschsprung syndrome.

Year 1998
Sakai T. Wakizaka A. Matsuda H. Nirasawa Y. Itoh Y.
Department of Biochemistry, Kyorin University School of Medicine, Tokyo, Japan.
A 5-year-old girl with congenital central hypoventilation syndrome associated with Hirschsprung's disease (Ondine-Hirschsprung syndrome) representing a missense mutation in exon 12 of the receptor tyrosine kinase (RET) proto-oncogene is reported. Using a direct sequencing technique, genomic DNA obtained from the patient's peripheral leukocytes was analyzed for its nucleotide sequences in all 20 exons of the RET proto-oncogene, seven regions of the 1st to the 7th exon of the endothelin-B receptor gene and endothelin 3 gene, including sequences corresponding to proteolytic cleavage sites. The analysis revealed that adenine at the 2116th base in the 12th exon in the RET proto-oncogene was substituted by guanine, supposedly resulting in a mutation of Thr 706 to Ala. No other mutational change was observed in the gene examined in this case. Mutation analysis has not been described previously on the gene in this disease complex. Mutation in this case might impair the maturation of the tyrosine kinase protein and subsequently cause neurocristopathy supposedly originating from the neural crest.

Incidence and prevalence of neutralizing antibodies to the common adenoviruses in children with cystic fibrosis: implication for gene therapy with adenovirus vectors.

Year 1998
Piedra PA. Poveda GA. Ramsey B. McCoy K. Hiatt PW.
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
OBJECTIVE: Defining the infection rate and prevalence of the common adenoviruses (Ads) in cystic fibrosis (CF) children may aid in formulation of strategies for gene therapy with Ad vectors. We undertook this study to determine the incidence and prevalence of infection with the common Ads in children with CF. METHODOLOGY: Thirty newly diagnosed CF children mean age 1.1 years (Group 1), 48 CF children mean age 4.6 years (Group 2), and 47 mothers of CF children (Group 3) were followed for a mean of 13 months. Group 4 consisted of 33 adult volunteers seen once. Throat and stool specimens for virus culture, and blood samples were obtained every 3 months from CF children in Group 1. Blood samples from CF children (Group 2) and their mothers (Group 3) were obtained every 6 months, and once from adults in Group 4. Neutralizing antibody to Ad serotypes 1 through 7 (Ad 1 to Ad 7) was evaluated with a microneutralization assay. RESULTS: Five (16.7%) CF children in Group 1 were culture-positive for an Ad; 4 of these CF children developed a fourfold or greater rise in antibody titer. Ad 3 infection occurred frequently based on serology; seronegative (< 3.5 log 2) CF children had a higher infection rate compared with seropositive CF children (7/11 vs 1/34). The prevalence of neutralizing antibodies in CF children in order of decreasing frequency was 91.1% to Ad 3, 37.5% to Ad 2, 27.1% to Ad 1, 26.1% to Ad 7, 16.7% to Ad 5, 8.5% to Ad 4, and 2.0% to Ad 6. The neutralizing antibody titers in seropositive CF children were comparable to those in adults except to Ad 3, which was significantly greater in mothers of CF children. CONCLUSIONS: CF children had a normal antibody response after Ad infection, preexisting antibody may protect against reinfection and antibody prevalence was low to the common Ads.

Proarrhythmia associated with cisapride in children.

Year 1998
Hill SL. Evangelista JK. Pizzi AM. Mobassaleh M. Fulton DR. Berul CI.
Division of Pediatric Cardiology, Floating Hospital for Children, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
BACKGROUND: Cisapride is a prokinetic agent that facilitates gastrointestinal motility and is widely used for the treatment of gastroesophageal reflux disease (GERD) in adults and children. However, reports of ventricular proarrhythmia have been noted in patients taking cisapride, particularly in conjunction with other drugs that may inhibit hepatic metabolism of cisapride via the cytochrome P450 3A4 system. OBJECTIVE: We designed a prospective, blinded study to evaluate the effect of cisapride on ventricular repolarization in children with GERD. METHODS: We analyzed the electrocardiograms (ECGs) from 35 children (age 0.4 to 18 years, mean 5.2 years) including measurement of the resting QT interval (QTc), JT interval (JTc), as well as QT and JT interlead dispersion markers. Data from these patients were compared with ECGs from a control group of 1000 normal children. RESULTS: Eleven (31%) of 35 patients receiving cisapride had a prolonged QTc (> or = 450 ms). The JTc was prolonged > or = 360 ms in 16 of 35 patients (46%). The mean QTc in the cisapride group was 428 +/- 35 ms and mean JTc was 336 +/- 35 ms. An increased QT or JT dispersion (> 70 ms) was seen in only 3 of 35 children. Of the 11 children with QTc prolongation, 2 had documented torsades de pointes ventricular tachycardia. Both patients were taking cisapride concomitantly with a macrolide antibiotic. All other patients were treated with either cisapride alone or in conjunction with other GERD agents, such as ranitidine or omeprazole. CONCLUSIONS: Cisapride may cause prolongation of ventricular repolarization in children. There does not appear to be increased heterogeneity of repolarization or delayed depolarization in this small sample. The proarrhythmia may be exacerbated by medications that inhibit cytochrome P450 3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum clearance. ECG intervals should be monitored in children maintained on cisapride, particularly when used in combination with other known QT-prolonging medications.

The Internet as a source for current patient information.

Year 1998
McClung HJ. Murray RD. Heitlinger LA.
Division of Gastroenterology, Department of Pediatrics, Ohio State University College of Medicine and Public Health, and Columbus Children's Hospital, Columbus, OH 43205, USA.
OBJECTIVE: The purpose of this study was to assess the quality of information a lay person could obtain from Internet (Net) sources regarding the treatment of childhood diarrhea. It also afforded an opportunity to evaluate the awareness and compliance of the general medical community with the American Academy of Pediatrics (AAP) guidelines on the management of acute diarrhea. METHODS: This was a prospective, open, observational, literature review performed with a computer workstation and medical library. The AAP practice parameter on the management of acute gastroenteritis in young children was selected as the current standard by which to judge all other documents. The Net was searched, and all documents retrievable from the first 300 references were evaluated for compliance with current recommendations on the management of diarrhea in children. RESULTS: Of 60 articles published by traditional medical sources, only 12 (20%) conformed to current AAP recommendations for treatment of children. The source of the information, even if from a major academic medical center, did not improve the likelihood of compliance. CONCLUSIONS: As demonstrated by information supplied on World Wide Web sites by traditional medical sources, recommendations for the treatment of acute diarrhea show a low percentage of concurrence with the AAP guidelines. Major medical institutions, schools, and hospitals need to devise ways to carefully monitor and establish quality control of what is being distributed from their home pages. Patients must be warned about the voluminous misinformation available on medical subjects on the Net.