J Pediatr

Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children.

Heubi JE. Barbacci MB. Zimmerman HJ.
Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
We compiled reports of acetaminophen hepatotoxicity after multiple overdoses from published cases, cases reported to the Food and Drug Administration, and cases from Children's Hospital Medical Center, Cincinnati, Ohio. Forty-seven children (age range, 5 weeks to 10 years) received 60 to 420 mg/kg/day for 1 to 42 days; 52% had received adult preparations of acetaminophen. The mean peak serum aspartate aminotransferase level was 10,225 IU/L (n = 45), and the mean serum alanine aminotransferase level was 7355 IU/L (n = 31), which were significantly higher (both p < 0.001) than the mean serum aspartate aminotransferase level of 3500 IU/L and alanine aminotransferase level of 3098 IU/L found in children (n = 12) with non-acetaminophen-associated hepatic failure. Serum acetaminophen levels for which an estimate of time from last dose could be calculated were available for 30 patients, of which 22 levels were greater than the toxic range described for acute ingestion. Twenty-four of 43 patients (55%) died, with an additional three surviving after orthotopic liver transplantation. Parents should be advised about the potential hepatotoxicity of acetaminophen when given to ill children in doses exceeding weight-based recommendations.

Predicting the duration of dependence on parenteral nutrition after neonatal intestinal resection.

Sondheimer JM. Cadnapaphornchai M. Sontag M. Zerbe GO.
University of Colorado Health Sciences Center, Department of Pediatrics, Denver, USA.
OBJECTIVE: To determine whether there are clinical or physical factors that could be used to predict the duration of dependence on parenteral nutrition (PN) in infants who have undergone resection of small intestine in the neonatal period. STUDY DESIGN: Medical records of 44 patients who had small intestinal resection as neonates from 1985 to 1996 and who were dependent on PN for at least 3 months were reviewed. Statistical evaluation of patient variables and their impact on duration of dependence on PN were determined by using the Cox Proportional Hazard model. RESULTS: Twenty-seven patients became independent of PN before the age of 36 months. Seven patients between 40 and 129 months of age are permanently dependent on PN. Outcome could not be determined in 10 patients, four of whom died of hepatic failure while still receiving PN and six of whom are still receiving PN but are younger than 36 months of age. Small bowel length after initial surgery and the percent of daily energy intake received by the enteral route at 12 weeks' adjusted age were significantly related to the duration of dependence on PN. Gestational age, presence of the ileocecal valve, and development of cholestasis were not significantly related. With the use of the Cox Proportional Hazards survival model, a formula was generated to allow estimation of the duration of dependence on PN. CONCLUSIONS: The duration of dependence on PN can be predicted at an early age in neonatal short bowel syndrome by using two patient variables: the length of residual small bowel after initial surgery and the percent of daily energy intake tolerated through the enteral route.

Home nebulizer use among patients with cystic fibrosis.

Rosenfeld M. Emerson J. Astley S. Joy P. Williams-Warren J. Standaert TA. Yim DL. Crist D. Thykkuttathil M. Torrence M. FitzSimmons S. Ramsey B.
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
OBJECTIVE: To describe current patterns of home nebulizer use among patients with cystic fibrosis. STUDY DESIGN: A population-based survey of home nebulizer practices among 227 patients with cystic fibrosis using nebulizers from 1993 to 1994 (Objective 1), and a prospective study of "typical" home use, including testing of performance and bacterial cultures in nebulizers after use, completed by 36 subjects (Objective 2). RESULTS: Objective 1: 85% of subjects reported using jet and 8% ultrasonic nebulizers (categories not mutually exclusive); 15% used unknown brands. Most jet nebulizers were disposable models, which were used for > 14 days by more than half the subjects. Mixing of medications in a single treatment (other than cromolyn and a bronchodilator) was reported by 28% of patients. Objective 2: no apparent deterioration in aerosol particle size or output rate of returned nebulizers compared with new units was observed. Staphylococcus aureus was cultured from 55% and Pseudomonas aeruginosa from 35% of returned nebulizers. Concordance between nebulizer and sputum cultures was poor. CONCLUSIONS: Although not generally tested for reusability, disposable nebulizers are generally used by patients for long periods. Medication mixing is common, although its effects on aerosol properties are unknown. Cystic fibrosis respiratory pathogens are frequently isolated from used nebulizers. Patient guidelines for home nebulizer use need to be established.

Efficacy of oral versus intravenous N-acetylcysteine in acetaminophen overdose: results of an open-label, clinical trial.

Perry HE. Shannon MW.
Division of Emergency Medicine, Children's Hospital, Boston, Massachusetts, USA.
We compared the clinical course of pediatric patients (n = 25) with acetaminophen poisoning treated with an investigational intravenous preparation of N-acetylcysteine (IV-NAC) with that of historical control subjects (n = 29) treated with conventional oral NAC (O-NAC) therapy. Patients received IV-NAC for 52 hours; historical control subjects received O-NAC (72 hours). There were no significant intergroup differences between treatment groups in age (15.5 vs 15.9 years), gender (88% vs 90% female) or distribution of risk categories (probable risk, 12 vs 15; high risk; 13 vs 14). The peak prothrombin time was significantly higher in the IV-NAC group (14.2 vs 13.6 seconds; p = 0.048). Mean treatment delay was significantly longer in the IV-NAC group (14.4 vs 10.4 hours; p = 0.001). Hepatoxicity was noted in two (8.0%) patients in the IV-NAC treatment group and two (6.9%) patients in the O-NAC group. All patients recovered. Our results indicate that 52 hours of intravenous NAC is as effective as 72 hours of oral NAC.

Lysinuric protein intolerance masquerading as celiac disease: a case report.

Reinoso MA. Whitley C. Jessurun J. Schwarzenberg SJ.
Department of Pediatrics, University of Minnesota, Minneapolis, USA.
A 5 1/2-year-old boy presented with delayed growth, chronic diarrhea, and hypoproteinemia. Clinical presentation, initial laboratory data, and evaluation of an intestinal biopsy specimen suggested a diagnosis of celiac disease. Symptoms did not resolve on a gluten-free diet. The development of hyperammonemia prompted further studies that led to the diagnosis of lysinuric protein intolerance. Lysinuric protein intolerance, although a rare disorder, should be included in the differential diagnosis of conditions associated with intestinal villous atrophy.

Recombinant human erythropoietin for treatment of anemia of chronic disease in children with Crohns disease.

Dohil R. Hassall E. Wadsworth LD. Israel DM.
Division of Gastroenterology, University of British Columbia, Vancouver, Canada.
We evaluated the efficacy and safety of and compliance with rH-EPO (150 U/kg three times a week subcutaneously for up to 12 weeks) for treatment of anemia in childhood Crohn's disease (n = 4). The mean hemoglobin level before rH-EPO therapy was 109 gm/L (10.9 gm/dl) (range, 103 to 115 gm/L). The mean hemoglobin level in the three compliant children increased to 138 gm/L (13.8 gm/dl) after treatment. Response time for the correction of anemia ranged from 6 to 12 weeks (mean, 9.5 weeks). Resolution of symptoms of lethargy, poor appetite, and irritability occurred with correction of the anemia. The only adverse effect observed was transient local pain at the injection site.

Vertical transmission of hepatitis C virus infection: usefulness of viremia detection in HIV-seronegative hepatitis C virus-seropositive mothers.

Giacchino R. Tasso L. Timitilli A. Castagnola E. Cristina E. Sinelli N. Gotta C. Giambartolomei G. Moscatelli P. Picciotto A.
Department of Infectious Diseases G. Gaslini Children's Hospital, Genoa, Italy.
Seventy mother-newborn pairs were studied for hepatitis C viremia to evaluate the risk of vertical transmission of hepatitis C virus from human immunodeficiency virus-negative mothers. Forty-five mothers were hepatitis C virus-RNA positive: 4 to 45 children were positive at birth and during follow-up. The level of viremia plays an important role in vertical transmission.

Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis.

Rivlin J. Lerner A. Augarten A. Wilschanski M. Kerem E. Ephros MA.
Department of Pediatrics, Carmel Medical Center, Haifa, Israel.
We report four patients with cystic fibrosis and fulminant Clostridium difficile-associated colitis: two died, and one required hemicolectomy. Three of four patients carried the N1303K mutation. Severe and fatal C. difficile colitis can occur in cystic fibrosis patients, possibly with a genotype-specific predilection (i.e., N1303K/other). Because cystic fibrosis patients may have a wide spectrum of gastrointestinal symptoms, disease caused by C. difficile must be considered when these patients have acute abdominal pain, diarrhea, or severe leukocytosis.

Comparison of the clinical manifestations of cystic fibrosis in black and white patients.

Year 1998
Hamosh A. Fitz-Simmons SC. Macek M Jr. Knowles MR. Rosenstein BJ. Cutting GR.
Department of Pediatrics and Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA.
No large-scale studies of the incidence or disease severity of cystic fibrosis (CF) in black patients have been reported to date. In this study, the CF Foundation National Patient Registry was used to establish new incidence figures and to compare the clinical status of U.S. black (n = 601) and white patients (n = 17,755) with CE Results indicate that the incidence of CF is approximately 1 in 3,200 white and 1 in 15,000 black live births in the United States. Black patients with CF are currently, and were at diagnosis, younger and have poorer nutritional status and pulmonary function than white patients with CF. Fewer have meconium ileus, but more have distal intestinal obstruction syndrome. To control for genotype, each black deltaF508 homozygote (n = 47) was compared with four age- and sex-matched white deltaF508 homozygotes. Only the difference in nutritional status remained. The deltaF508 mutation is associated with higher levels of meconium ileus than other genotypes, independent of race. In conclusion, the clinical manifestations of CF are similar in black and white patients except for poorer nutritional status in black patients, which appears to be independent of age and genotype.

Relationship between socioeconomic status and disease severity in cystic fibrosis.

Year 1998
Schechter MS. Margolis PA.
Department of Pediatrics, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157, USA.
OBJECTIVE: This study was carried out to evaluate whether patients with cystic fibrosis (CF) who are socioeconomically disadvantaged, have a different outcome than higher-income patients. Medicaid insurance coverage was used as a proxy of low family income. STUDY DESIGN: A cross-sectional analysis was performed on a group of patients younger than 21 years of age seen at the University of North Carolina CF Center in 1994. RESULTS: The difference in median age at diagnosis for Medicaid (132 days) and non-Medicaid (177 days) patients was not statistically significant (p = 0.17). Medicaid patients' mean maximum percent predicted forced expiratory volume in 1 second for the year was 11.6% less than that of the non-Medicaid group (p = 0.01); this difference was constant across age. Medicaid patients averaged 0.8 more admissions for the year (p < 0.01) and 8.8 more days (p < 0.01) in the hospital but received the same amount of outpatient intravenous therapy. They also had 1.20 more outpatient visits to the center during the year (p = 0.02). CONCLUSIONS: Medicaid patients with CF have worse lung function and require more treatment for pulmonary exacerbations than their more advantaged counter-parts. This difference appears to begin early in life, does not increase with age, and is not explained by inadequate access to outpatient specialty care or delayed diagnosis. Other explanations such as inadequate access to primary care, poor adherence to prescribed regimens, or greater exposure to pollutants (e.g., environmental tobacco smoke) are speculative.

Enteral nutrition for patients with cystic fibrosis: comparison of a semi-elemental and nonelemental formula.

Year 1998
Erskine JM. Lingard CD. Sontag MK. Accurso FJ.
Department of Pediatrics, University of Colorado School of Medicine and The Children's Hospital, Denver, USA.
OBJECTIVE: To determine whether differences in tolerance and absorption of fat and nitrogen exist between a semi-elemental nutritional formula without enzyme replacement and a nonelemental formula with enzyme replacement. STUDY DESIGN: Sixteen patients (eight girls and eight boys) with cystic fibrosis, 4 to 20 years of age (12+/-1.3, mean +/- SEM), who were pancreatic insufficient completed two 6-day regimens of nocturnal continuous enteral feedings offered in random order. Forty-four percent of the total daily energy was consumed as enteral tube feedings, and the remaining oral dietary intake remained constant throughout the study. Seventy-two-hour fecal collections from each study period were analyzed for total fat, long-chain fatty acids (LCFAs), medium-chain fatty acids (MCFAs), and nitrogen. RESULTS: Fat absorption was 80.2%+/-2.9% and 82.3%+/-3.1% (p = 0.58) for the semi-elemental and nonelemental formulas, respectively. Similarly, the coefficient of absorption of LCFAs was 69.5%+/-4.5% and 79.6%+/-3.4% (p = 0.30) for the semi-elemental and nonelemental formulas. Malabsorption of MCFAs contributed minimally to total fat malabsorption. There was no difference between formulas for MCFA or for nitrogen absorption, 83.7%+/-1.9% and 87.4%+/-1.4%, p = 0.48. All patients tolerated all feedings, and weight gained was 1.8+/-0.3 kg with no difference in weight gain between the trials. CONCLUSION: A nonelemental formula, with enzyme replacement, is absorbed as well as a predigested formula in patients with CF who are pancreatic insufficient.

Do infants with cystic fibrosis need a protein hydrolysate formula? A prospective, randomized, comparative study.

Year 1998
Ellis L. Kalnins D. Corey M. Brennan J. Pencharz P. Durie P.
Research Institute and the Department of Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
OBJECTIVES: We compared the nutritional benefits of a protein hydrolysate and a conventional infant formula in infants newly diagnosed with cystic fibrosis (CF). STUDY DESIGN: Twenty-three infants with CF (

Omeprazole in infants with cimetidine-resistant peptic esophagitis.

Year 1998
Alliet P. Raes M. Bruneel E. Gillis P.
Department of Pediatrics, Virga Jesse Hospital, Hasselt, Belgium.
Twelve neurologically normal infants (age 2.9+/-0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine (in addition to positioning, cisapride, and Gaviscon) were treated with omeprazole, 0.5 mg/kg once a day, for 6 weeks. The effectiveness of omeprazole was evaluated in all infants by clinical assessment and endoscopy before and after treatment and by 24-hour gastric pH monitoring during treatment in seven infants. Omeprazole therapy led to a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity.

Pulmonary function in hospitalized infants and toddlers with cystic fibrosis.

Year 1998
Clayton RG Sr. Diaz CE. Bashir NS. Panitch HB. Schidlow DV. Allen JL.
Department of Pediatrics, Temple University School of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, USA.
In older children with cystic fibrosis (CF), well-documented improvements in lung function occur during hospitalization for treatment of pulmonary exacerbations. OBJECTIVES: (1) To test the hypothesis that improvement in lung function occurs in infants and toddlers hospitalized because of CF pulmonary exacerbations. (2) To compare changes in lung function measured during forced expiratory flow and tidal breathing. STUDY DESIGN: Seventeen infants and toddlers with CF were evaluated at the beginning and end of hospitalization by the rapid thoracic compression technique to yield maximal flow at forced residual capacity. Tidal mechanics were measured by the esophageal balloon technique to yield lung conductance and compliance. RESULTS: Lung function improved during the course of hospitalization. The greatest change was observed in measurements of maximal flow at functional residual capacity (.VmaxFRC), increasing from 38.5% +/- 6% predicted (mean +/- SEM) to 59.8% +/- 6% at the end (p < 0.005). Lung conductance (GL) increased from 60% +/- 6% to 78% +/- 8% (p < 0.02); lung compliance (CL) increased from 66% +/- 5% to 75% +/- 5% (p < 0.03). The degree of improvement of .VmaxFRC, GL, and CL was related to baseline measurements; those with poorer pulmonary function at baseline had the greatest degree of improvement during hospitalization. CONCLUSION: Assessments of airflow obstruction from measurements of .VmaxFRC and GL do not necessarily demonstrate similar findings in a given infant with CF, perhaps because these two techniques measure different physiologic properties. Changes in .VmaxFRC may best reflect the predominant pathophysiology of lung disease in infants and toddlers with CF.

Long-term growth and development in children after home parental nutrition.

Year 1998
Leonberg BL. Chuang E. Eicher P. Tershakovec AM. Leonard L. Stallings VA.
Department of Clinical Nutrition, The Children's Hospital of Philadelphia, Pennsylvania 19104-4399, USA.
Growth and development after the cessation of prolonged parenteral nutrition (PN) has not been fully evaluated. Growth, body composition, and nutritional and developmental status were documented in nine children (five boys, four girls) 2 to 6 years old (mean 4.9 +/- 1.0 years) who had previously received long-term PN (mean 14.6 +/- 11.4 months). PN had been discontinued in all subjects for at least 6 months (mean 3.4 +/- 1.4 years); they were receiving oral feedings only. One subject had a significantly low height-for-age, and another had a low percent ideal body weight; five subjects had low total body fat. Serum vitamin A was low in six subjects. Seventy-two-hour fecal fat analysis was abnormal in two of eight subjects. Abnormal bone mineral density was present in four of nine subjects. Psychomotor development was normal in all nine subjects. Two had functional difficulties in swallowing. One or more abnormalities were present in all nine subjects. These findings suggest that children who require prolonged PN in early life are at risk for abnormalities in growth and nutritional status in later childhood; they require long-term dietary, growth, and nutritional monitoring.

Growth status in children with cystic fibrosis based on the National Cystic Fibrosis Patient Registry data: evaluation of various criteria used to identify malnutrition.

Year 1998
Lai HC. Kosorok MR. Sondel SA. Chen ST. FitzSimmons SC. Green CG. Shen G. Walker S. Farrell PM.
Department of Pediatrics, University of Wisconsin School of Medicine, Madison 53792, USA.
OBJECTIVES: The objectives of this study were to determine growth status and to identify malnutrition with various anthropometric indicators in children with cystic fibrosis (CF) based on cross-sectional analysis of the 1993 National CF Patient Registry data. METHODS: Heights and weights of 13,116 children with CF were evaluated with percentile, percent of reference median, Z-score, and percent ideal weight-for-height based on National Center for Health Statistics/Centers for Disease Control growth references. Malnutrition was defined by four criteria: (1) height-for-age

Nutrition intervention for weight gain in cystic fibrosis: a meta analysis.

Year 1998
Jelalian E. Stark LJ. Reynolds L. Seifer R.
Brown University School of Medicine, Providence, Rhode Island, USA.
OBJECTIVES: A meta analysis of the literature on treatment approaches to malnutrition in cystic fibrosis (CF) was conducted to evaluate the effectiveness of oral supplementation, enteral nutrition, parenteral nutrition, and behavioral intervention on weight gain before and after treatment. STUDY DESIGN: Eighteen studies were reviewed: four behavioral, six supplement, five enteral nutrition, and three parenteral nutrition. RESULTS: The weighted effect size for weight gain was large for each intervention: 1.51 behavioral, 1.62 oral, 1.78 enteral, and 2.20 parenteral intervention. All interventions produced a large effect for weight gain in patients with CF. A univariate analysis of variance indicated no significant difference among the four interventions, F(3, 17) = 0.87, p > 0.05. Effect size for calorie intake was also evaluated when data were available (N = 7 studies), yielding a sample size of three behavioral, two enteral, and two oral supplement studies. Analysis of variance indicated a significant effect for treatment, F(2,4) = 13.34, p < 0.05, with post hoc analysis indicating that the behavioral intervention had a greater effect size for calorie intake than oral supplement. CONCLUSIONS: All interventions were effective in producing weight gain in patients with CF. Behavioral intervention appeared to be as effective in improving weight gain in patients with CF as more invasive medical procedures. These findings support continued research on nutrition intervention with patients with CF including controlled clinical trials of the interventions and long-term follow-up on the impact of nutrition on disease progression.

Acute pulmonary exacerbation is not associated with increased energy expenditure in children with cystic fibrosis.

Year 1998
Stallings VA. Fung EB. Hofley PM. Scanlin TF.
The Cystic Fibrosis Center, Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, 19104, USA.
OBJECTIVE: The objective of this study was to document alterations in resting energy expenditure (REE), energy intake, and body composition that occur during admission for management of a pulmonary exacerbation in children with cystic fibrosis. STUDY DESIGN: A prospective study of 14 children with cystic fibrosis (8 male, 12.5 +/- 3.3 years) was conducted throughout a 14-day hospitalization and again 3 weeks after discharge. Repeated measures analysis of variance was used to examine the change in variables across time. RESULTS: Significant increases were documented from days 1 to 14 in weight (37.1 +/- 13.1 kg to 38.4 +/- 13.5 kg) and pulmonary function (forced expiratory volume in 1 second: 67.6% +/- 19.8% to 78.5% +/- 24.5%). Energy intake was not different between hospitalization and follow-up and averaged 175% of the Recommended Dietary Allowance. REE on day 1 was elevated (122% +/- 11% predicted); however, when expressed with fat free mass as a covariate, no significant changes were noted in REE throughout the eight measurements. CONCLUSIONS: These data suggest that an acute pulmonary exacerbation is not associated with an increase above a subject's baseline REE in children with cystic fibrosis with mild to moderate lung disease. Management of an acute pulmonary exacerbation should be associated with sustained improvement in pulmonary function and nutritional status; in contrast, weight loss or failure to improve pulmonary function should be seen as atypical.

Bone mineral content in children with short bowel syndrome after discontinuation of parental nutrition.

Year 1998
Dellert SF. Farrell MK. Specker BL. Heubi JE.
Division of Pediatric Gastroenterology and Nutrition, Pediatric Bone Research Center, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
To determine whether children with short bowel syndrome had evidence of metabolic bone disease, total body bone mineral content was measured by dual-energy x-ray absorptiometry in 18 patients and 36 age-, sex-, and race-matched control subjects. Children with short bowel syndrome had decreased bone mineral content compared with control subjects; however, it was not significant when adjusted for differences in weight and height. Whether these children will have normal bone accretion throughout puberty is not known.

Pneumatosis intestinale in children with primary combined immunodeficiency.

Year 1998
Tang ML. Williams LW.
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
We report six episodes of pneumatosis intestinale (PI) in children with primary combined immunodeficiency. PI was generally benign and responded to conservative therapy. Increased risk of infection or disruption of gastrointestinal mucosa are probable predisposing factors. A diagnosis of PI should be considered in children with primary combined immunodeficiency who experience otherwise unexplained gastrointestinal symptoms, particularly in the early post-transplant period.

An outbreak of salmonellosis among children attending a reptile exhibit at a zoo.

Year 1998
Friedman CR. Torigian C. Shillam PJ. Hoffman RE. Heltzel D. Beebe JL. Malcolm G. DeWitt WE. Hutwagner L. Griffin PM.
Foodborne and Diarrheal Diseases Branch, Centers for Disease Control and Prevention, Atlanta 30333, USA.
OBJECTIVE: In January 1996, an outbreak of diarrhea caused by Salmonella Enteritidis occurred in children attending a Komodo dragon exhibit at a metropolitan zoo. We sought to determine the extent of the outbreak and mode of transmission. STUDY DESIGN: A case-control study was conducted. Controls were randomly selected from zoo membership lists and matched to patients by age group and date of exhibit visit. RESULTS: Of 65 patients identified, 39 had confirmed and 26 had suspected cases. The median age was 7 years (range, 3 months to 48 years); 55% were enrolled in the case-control study. No patients and two (4%) controls reported touching a dragon; however, 83% of patients but only 52% of controls touched the wooden barrier that surrounded the dragon pen (odds ratio = 4.0, 95% CI 1.2 to 13.9). Washing hands at the zoo after visiting the dragons was highly protective (OR = 0.14, 95% CI 0.03 to 0.7). Cultures from the patients, one dragon, and the exhibit barriers yielded Salmonella Enteritidis, phage type 8. On the basis of an attack rate of 4.3% among exhibit attendees under 13 years old on whom data were collected, we estimate that 315 additional cases of salmonellosis occurred among visitors in this age group. CONCLUSION: This large outbreak demonstrates the importance of environmental contamination in the transmission of Salmonella from reptiles, and the protective value of hand washing. Recommendations regarding reptile exhibits and reptilian pets should emphasize this indirect route.

Methotrexate in patients with Crohns disease after 6-mercaptopurine.

Year 1998
Mack DR. Young R. Kaufman SS. Ramey L. Vanderhoof JA.
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68198-5160, USA.
OBJECTIVE: The objective of this study was to describe the clinical outcome of children with Crohn's disease treated with subcutaneous methotrexate. SUBJECTS/METHODS: Fourteen patients (10 boys) with extensive Crohn's disease diagnosed at a mean age of 10.6 +/- 3.6 years had previously received various medical therapies for 4.3 +/- 4.0 years. Because of the severity of their disease, 6-mercaptopurine had been introduced but discontinued because of the patients' failure to respond (n = 11) or the development of pancreatitis (n = 3). Subsequently, low-dose, weekly, subcutaneous methotrexate was initiated. Pediatric Crohn's Disease Activity Index scores and prednisone requirement were followed as outcome measures. RESULTS: Overall, 9 (64%) of the 14 patients showed improvement, including 6 (55%) of 11 patients who had previously received an adequate trial of 6-mercaptopurine and all three patients who were intolerant of 6-mercaptopurine. Improvement in clinical and laboratory measures occurred by 4 weeks and were similar whether (n = 8) or not (n = 6) the dose of corticosteroids was increased before the start of subcutaneous methotrexate. Three patients were tapered from their initial methotrexate dose after the minimization of corticosteroids and remain well. One patient receiving daily corticosteroids died suddenly after acute onset of illness. Among patients responding, methotrexate was discontinued because of side effects (n = 2) or electively (n = 2). Of the latter two patients, one has resumed methotrexate after disease relapse, whereas the other patient has had a sustained remission. CONCLUSIONS: Low-dose, weekly, subcutaneous methotrexate can induce remission in some pediatric patients with Crohn's disease who fail to adequately respond to other immunomodulator medications.

Ultrasonographic and clinical predictors of intussusception.

Year 1998
Harrington L. Connolly B. Hu X. Wesson DE. Babyn P. Schuh S.
Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, Ontario, Canada.
OBJECTIVE: The objective of this study was to determine the positive and negative clinical predictors of intussusception and the correlation of ultrasonography and air enema in establishing this diagnosis. STUDY DESIGN: This was a prospective descriptive cohort study. SETTING: This study was performed in a tertiary care pediatric emergency department. PARTICIPANTS: Eighty-eight of 245 candidates were assessed for clinical predictors of intussusception. All 245 cases were examined for correlation between ultrasonography and air enema. INTERVENTIONS: A questionnaire, ultrasonography, and air enema were used. RESULTS: Thirty-five of the 88 patients assessed for clinical predictors were positive for intussusception. Significant positive predictors were right upper quadrant abdominal mass (positive predictive value [PPV] 94%), gross blood in stool (PPV 80%), blood on rectal examination (PPV 78%), the triad of intermittent abdominal pain, vomiting, and right upper quadrant abdominal mass (PPV 93%, p = 0.0001), and the triad with occult or gross blood per rectum (PPV 100%, p = not significant). Significant negative predictors were a combination of > or = 3 of 10 clinically significant negative features (negative predictive value 77%, p = 0.035). Of the total 245 cases, intussusception (as confirmed by doughnut, target, or pseudokidney sign) was ruled out by ultrasonography in 97.4%. Alternate ultrasound findings comprised 27% of negative cases. CONCLUSIONS: Excellent positive predictors of intussusception were identified prospectively. Although no reliable negative predictors were found, patients at low risk may be screened by ultrasonography.

Pemoline hepatotoxicity in children.

Year 1998
Marotta PJ. Roberts EA.
Division of Gastroenterology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.
Pemoline hepatotoxicity ranges from asymptomatic elevations in levels of serum aminotransferases to fulminant liver failure. We report five cases of pemoline hepatotoxicity in children (four boys, one girl), including the only reported case resulting in orthotopic liver transplantation. We conclude that pemoline causes toxic liver damage in children. The severity of the damage is highly variable, and its onset may be late in the course of treatment. Pemoline and methylphenidate may act synergistically to cause liver damage. The levels of serum aminotransferases should be monitored throughout treatment with these agents.

Efficacy of milk versus yogurt offered as part of a mixed diet in acute noncholera diarrhea among malnourished children.

Year 1998
Bhatnagar S. Singh KD. Sazawal S. Saxena SK. Bhan MK.
Indian Council of Medical Research Advanced Centre for Diarrheal Disease Research, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
We compared the clinical outcome of acute diarrhea in 96 malnourished boys (aged 4 to 47 months) receiving full-strength milk compared with yogurt offered as part of a mixed diet. All had weight for height less than or equal to 80% of the National Centre for Health Statistics median. They were randomly assigned to receive milk formula (MF; 67 cal/100 ml) or yogurt formula (YF; prepared from the same milk formula) at the rate of 120 ml/kg body weight in seven divided feedings. Stool-reducing substances (> 1%) were detected more frequently in the MF group, and the differences were significant for day 3 of the study (p = 0.04). However, the geometric mean (95% confidence interval) of the total stool weights (gm/kg) during 0 to 72 hours (MF 128.8 [103, 161.4]; YF 110.9 [87, 142.2]) was comparable (p = 0.37) as was the median (range) duration of diarrhea (hours) (MF 45 [4, 183]; YF 52 [7, 173] p = 0.94). The treatment failure rates in the MF (8.2%) and YF (6.3%) groups were also similar (p = 0.67). The children consuming milk had higher median percent weight gain at the end of 72 hours of the study (p = 0.04) and at recovery (p = 0.02). Routine substitution of yogurt as small frequent feedings as an addition for semisolid food to malnourished children with acute diarrhea does not achieve any significant clinical benefit versus milk.

Recurrent abdominal pain: a potential precursor of irritable bowel syndrome in adolescents and young adults.

Year 1998
Walker LS. Guite JW. Duke M. Barnard JA. Greene JW.
Division of Adolescent Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-3571, USA.
OBJECTIVES: To assess symptoms of irritable bowel syndrome (IBS) in patients with recurrent abdominal pain (RAP) 5 years after their initial evaluation, to identify the relation of IBS symptoms to functional disability and health service use, and to determine the extent to which IBS symptoms are associated with life stress and poor psychosocial adjustment. METHODS: Patients with RAP (n = 76) and control subjects (n = 49) completed a telephone interview; measures included the Bowel Disease Questionnaire, the Functional Disability Inventory, the Life Events Questionnaire, the Family Inventory of Life Events, the Center for Epidemiological Studies Depression Scale, the Self-Perception Profile for Adolescents, and the Health Resources Inventory. RESULTS: Five years after the initial evaluation, patients with RAP reported significantly more episodes of abdominal pain than did control subjects, as well as significantly higher levels of functional disability, school absence, and clinic visits for abdominal distress. Female patients with RAP were more likely than female control subjects to meet the Manning criteria for IBS. Among patients with RAP, higher levels of IBS symptoms were associated with significantly greater functional disability, more clinic visits, more life stress, higher levels of depression, and lower academic and social competence. CONCLUSION: Female patients with a history of RAP may be at increased risk of IBS during adolescence and young adulthood. Among adolescents and young adults with a history of RAP, IBS symptoms are likely to be associated with high levels of disability and health service use.

Antibody-negative chronic hepatitis C virus infection in immunocompetent children.

Year 1998
Maggiore G. Caprai S. Cerino A. Silini E. Mondelli MU.
Dipartimento di Medicina della Procreazione della Eta Evolutiva, Universita degli Studi La Sapienza, Pisa, Italy.
Antibody-negative hepatitis C virus (HCV) infection, defined by the presence of HCV viremia in the absence of a serologic response to HCV, was detected in two immunocompetent and symptom-free children; each had a history of exposure to blood products. HCV infection may occasionally explain cryptogenic elevation of aminotransferases, even in the absence of serum anti-HCV. HCV-RNA should be investigated in these cases, particularly in the presence of previous exposure to blood products.

Perianal granuloma caused by Enterobius vermicularis: report of a new observation and review of the literature.

Year 1998
Avolio L. Avoltini V. Ceffa F. Bragheri R.
Divisione di Chirurgia Pediatrica, IRCCS Policlinico San Matteo, Pavia, Italy.
The literature reports 12 cases of enterobiasis presenting as perianal abscess or granuloma. We describe an additional case of a perianal granuloma containing Enterobius vermicularis eggs in a 5-year-old boy. We suggest routine parasite screening for all children presenting with this condition.

Chylothorax and chylopericardium: a complication of a central venous catheter.

Year 1998
Kurekci E. Kaye R. Koehler M.
Children's Hospital Pittsburgh, Pediatric Hematology/Oncology, Philadelphia, PA 19134-1095, USA.
This article describes a rare and severe complication of central venous catheterization, namely extensive thrombosis within the venous system of the chest resulting in bilateral chylothorax and chylopericardium. The complication resolved with drainage, catheter removal, and low molecular weight heparin therapy.

The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel.

Year 1998
Rosenstein BJ. Cutting GR.
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
The diagnostic criteria proposed here are not likely to cover every possible clinical scenario, and there will be clinical dilemmas. For the vast majority of patients with CF, the diagnosis will be suggested by the presence of one or more characteristic clinical features, a history of CF in a sibling, or a positive newborn screening test result and will then be confirmed by laboratory evidence of CFTR dysfunction (Table V). Abnormal CFTR function will usually be documented by two elevated sweat chloride concentrations obtained on separate days or identification of two CF mutations. For patients in whom sweat chloride concentrations are normal or borderline and in whom two CF mutations are not identified, an abnormal nasal PD measurement recorded on 2 separate days can be used as evidence of CFTR dysfunction. Clinical judgment will continue to be essential in patients who have typical or "atypical" clinical features but who lack conclusive evidence of CFTR dysfunction. Such patients will require close clinical follow-up along with laboratory reevaluation as appropriate.

Uncertainty in the diagnosis of cystic fibrosis: possible role of in vivo nasal potential difference measurements.

Year 1998
Wilson DC. Ellis L. Zielenski J. Corey M. Ip WF. Tsui LC. Tullis E. Knowles MR. Durie PR.
Department of Paediatrics, University of Toronto, Ontario, Canada.
The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive clinical evaluation, multiple sweat chloride tests, and genotype analysis. We hypothesized that nasal transepithelial potential difference measurements have a useful role in this situation. In 11 patients without an established diagnosis of CF, results of simultaneous nasal potential difference (PD) and sweat chloride measurements were compared with those from control subjects, obligate CF heterozygotes, and patients with a confirmed diagnosis of CF. Two patients conformed to the PD profile for CF patients, whereas nine had values corresponding to those of the healthy control subjects. Subsequently the 5-thymidine (IVS8-5T) CF gene variant was identified in the two patients with abnormal PD measurements.