Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia.

Estimating prognosis in sickle cell anemia (SCA) assumes greater importance as intensive treatments, such as hematopoietic SCT (HSCT), are being tested. Here we estimate the mortality risk from the walk-PHaSST (Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease) trial of homozygous SCA patients with suspected pulmonary hypertension (19/468 deaths; 10 centers in the US and UK). Parallel investigations were also undertaken in the Cooperative Study of Sickle Cell Disease (CSCCD) and a contemporary urban sickle cell disease population (Case Western Reserve University-University Hospitals (CWRU-UH), Cleveland, OH, USA). One- and two-value positive predictive values for 2-year mortality (from study entry) are calculated using factors that include demographics, laboratory values and clinical evaluations. We define high-, intermediate-, and low-risk SCA as > 15%, 10-15% and < 10% 2-year mortality. In walk-PHaSST, no single factor qualifies as high-risk SCA, although several combinations of two factors (that is, both age > 35 years and history of chronic transfusion) do. Either elevated white blood cell count (> 13.5 × 10(3) cells/mcL, 7/70 deaths) or elevated Tricuspid Regurgitant Jet Velocity (⩾ 3.0 m/s, 8/67 deaths) was individually associated with intermediate-risk disease, as were many two-factor combinations. N-terminal pro-brain natriuretic peptide > 160 ng/L, lactate dehydrogenase > 600 IU/L, history of chronic transfusion, sepsis or age > 35 years are individually associated with low-risk SCA, as are many two-factor combinations. SCA risk was integrated with estimated donor type-associated risk from HSCT to form 'Traffic Light' eligibility criteria for clinical trials of HSCT. This method is adaptable to evolutions in clinical care.

A randomized trial of the Vein Viewer versus standard technique for placement of peripherally inserted central catheters (PICCs) in neonates.

OBJECTIVE: Peripherally inserted central catheters are important but can be difficult to place in neonates. Therefore, we compared a near-infrared device, the Vein Viewer, to determine if its use would increase successful line placement, with standard techniques. STUDY DESIGN: Randomized controlled trial in preterm and term neonates in a level 3 Neonatal Intensive Care Unit. RESULT: In all, 115 subjects were enrolled with 59 randomized to the Vein Viewer group and 56 to the control group. Overall, use of the Vein Viewer showed a trend to more successful placement 86 versus 75%; unadjusted odds ratio 2.33 (0.90, 6.04; P=0.08). Infants randomized to the Vein Viewer were more mature (30 ± 2 weeks gestational age (GA) versus 28 ± 2 weeks GA; P=0.08). After adjusting for GA, use of the Vein Viewer was significantly more likely to lead to successful line placement (adjusted odds ratio 3.05 (1.10, 1.82)). CONCLUSION: The Vein Viewer improved successful placement with the most benefit seen in infants of greater GA.

Relationships among depressive symptoms, sexually transmitted infections, and pregnancy in African-American adolescent girls.

STUDY OBJECTIVE: To explore relationships among depressive symptoms, sexually transmitted infections (STI), and pregnancy in African-American adolescent girls. DESIGN: Retrospective chart review. SETTING: A hospital-based outpatient practice serving primarily African-American patients. PARTICIPANTS: A total of 126 female patients ages 13-19 years who had ligase chain reaction (LCR) for N. gonorrhoeae and C. trachomatis. METHODS: Charts were reviewed for history of STI, history of pregnancy, LCR results, and a history of depressive symptoms as indicated by standardized provider notes and patient self-administered questionnaire. Data are compared using Fisher's exact test. RESULTS: Mean age was 16.6 years (+/-1.6 years); 19.8% of participants had a history of depressive symptoms, 40.5% had a history of STI, 8.7% had a prior pregnancy, and 18.2% had a positive LCR. Of patients with a history of depressive symptoms, 64% had a history of STI compared to 34.6% of those without depressive symptoms (P = 0.01). A positive LCR was found in 20% of patients with a history of depressive symptoms and 17.8% of patients without (P = 0.78). Of patients with a history of depressive symptoms, 12% had a prior pregnancy compared to 7.9% without such history (P = 0.45). CONCLUSIONS: African-American adolescent females in our clinic with a history of depressive symptoms were more likely to have a history of STI. A greater percentage of patients with a history of depressive symptoms also had prior pregnancies and/or current STI. Sexually active adolescent girls should be screened for depressive symptoms as part of their evaluation for sexual risk behaviors.

Potential pharmacokinetic basis for zolpidem dosing in children with sleep difficulties.

The pharmacokinetics of zolpidem was assessed in this open-label, dose-escalation study in children with insomnia. Twenty-one children, seven per age group (2-6, >6 to 12, >12 to 18 years), received a single dose of zolpidem at one of the three dose levels (0.125, 0.25, or 0.50 mg/kg (20 mg maximum dose)). Multiple pharmacokinetic measures were assessed at nine post-dose intervals and pharmacodynamics was assessed by polysomnography and actigraphy. Significant pharmacokinetic effects by dose were observed only as linear increases in maximum concentration (C(max), P<0.001) and area under the plasma concentration-time curve (AUC, P<0.001). Significant pharmacokinetic effects by age group included an increase in AUC (P=0.02), half-life (P=0.04), and mean residence time (P=0.01), whereas total body clearance decreased (P=0.01) and steady-state volume of distribution was variable. Pharmacodynamic measures were independent of the pharmacokinetic estimates. Overall, zolpidem was well tolerated and a pediatric dose of 0.25 mg/kg is recommended for future efficacy studies.

Identification and quantification of ureaplasmas colonizing the respiratory tract and assessment of their role in the development of chronic lung disease in preterm infants.

BACKGROUND: The role of Ureaplasma urealyticum in the development of chronic lung disease (CLD) in preterm infants continues to be disputed. Recently U. urealyticum has been found to consist of two species, U. urealyticum and Ureaplasma parvum, a finding that has not been considered in previous studies of CLD. This study examined the possible relationships between development of CLD and respiratory colonization by these newly redefined species, their concentrations in lower respiratory secretions and the effect of pulmonary surfactant treatment on these relationships in preterm infants with birth weights < 1500 g. METHODS: Endotracheal aspirates (ETA) were collected from intubated infants when airway suctioning was medically required. ETA were stored at -80 degrees C until quantitative cultures for ureaplasmas and Mycoplasma hominis were performed. Culture results were correlated with development of CLD. RESULTS: Of 475 infants (birth weights < 1500 g) admitted during the 2-year study period, 272 were excluded because they were not intubated or were extubated before ETA could be obtained. An additional 28 infants died, were discharged or were transferred before they could be assessed for CLD. From the remaining 175 infants ureaplasmas were isolated from 66 (38%). No statistically significant associations were identified between development of CLD and the Ureaplasma species isolated, or concentration of ureaplasmas in lower respiratory secretions. These findings were not altered by treatment with pulmonary surfactant (Survanta). CONCLUSION: Lower respiratory colonization by ureaplasmas does not appear to be a contributory cause of CLD in preterm infants.

The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria.

BACKGROUND: Prader-Willi syndrome (PWS) is a complex, multisystem disorder. Its major clinical features include neonatal hypotonia, developmental delay, short stature, behavioral abnormalities, childhood-onset obesity, hypothalamic hypogonadism, and characteristic appearance. The genetic basis of PWS is also complex. It is caused by absence of expression of the paternally active genes in the PWS critical region on 15q11-q13. In approximately 70% of cases this is the result of deletion of this region from the paternal chromosome 15. In approximately 28%, it is attributable to maternal uniparental disomy (UPD; inheritance of 2 copies of a chromosome from the mother and no copies from the father, as opposed to the normal 1 copy from each parent) of chromosome 15, and in <2%, it is the result of a mutation, deletion, or other defect in the imprinting center. Clinical diagnostic criteria were established by consensus in 1993. Subsequently, definitive molecular genetic testing became available for laboratory diagnosis of PWS. However, identification of appropriate patients for testing remains a challenge for most practitioners because many features of the disorder are nonspecific and others can be subtle or evolve over time. For example, hypotonic infants who are still in the failure to thrive phase of the disorder often do not have sufficient features for recognition of PWS and often are not tested. Initial screening with these diagnostic criteria can increase the yield of molecular testing for older children and adults with nonspecific obesity and mental retardation. Therefore, the purpose of clinical diagnostic criteria has shifted from assisting in making the definitive diagnosis to raising diagnostic suspicion, thereby prompting testing. We conducted a retrospective review of patients with PWS confirmed with genetic testing to assess the validity and sensitivity of clinical diagnostic criteria published before the widespread availability of testing for all affected patients and recommend revised clinical criteria. METHODS: Charts of all 90 patients with laboratory-confirmed PWS were reviewed. For each patient, the presence or absence of the major, minor, and supportive features listed in the published diagnostic criteria was recorded. The sensitivity of each criterion, mean of the total number of major and minor criteria, and mean total score for each patient were calculated. RESULTS: There were 68 patients with a deletion (del 15q11-q13), 21 with maternal UPD of chromosome 15, and 1 with a presumed imprinting defect. Age range at the time of the most recent evaluation was 5 months to 60 years (median: 14.5 years; del median: 14 years; range: 5 months-60 years; UPD median: 18 years; range: 5-42 years). The sensitivities of the major criteria ranged from 49% (characteristic facial features) to 98% (developmental delay). Global developmental delay and neonatal hypotonia were the 2 most consistently positive major criteria and were positive in >97% of the patients. Feeding problems in infancy, excessive weight gain after 1 year, hypogonadism, and hyperphagia were all present in 93% or more of patients. Sensitivities of the minor criteria ranged form 37% (sleep disturbance and apneas) to 93% (speech and articulation defects). Interestingly, the sensitivities of 8 of the minor criteria were higher than the sensitivity of characteristic facial features, which is a major criterion. Fifteen out of 90 patients with molecular diagnosis did not meet the clinical diagnostic criteria retrospectively. CONCLUSION: When definitive diagnostic testing is not available, as was the case for PWS when the 1993 criteria were developed, diagnostic criteria are important to avoid overdiagnosis and to ensure that diagnostic test development is performed on appropriate samples. When diagnostic testing is available, as is now the case for PWS, diagnostic criteria should serve to raise diagnostic suspicion, ensure that all appropriate people are tested, and avoid the expense of testing unnecessarily. Our results indicate that the sensitivities of most of the published criteria are acceptable. However, 16.7% of patients with molecular diagnosis did not meet the 1993 clinical diagnostic criteria retrospectively, suggesting that the published criteria may be too exclusive. A less strict scoring system may ensure that all appropriate people are tested. Accordingly, we suggest revised clinical criteria to help identify the appropriate patients for DNA testing for PWS. The suggested age groupings are based on characteristic phases of the natural history of PWS. Some of the features (eg, neonatal hypotonia, feeding problems in infancy) serve to diagnose the syndrome in the first few years of life, whereas others (eg, excessive eating) are useful during early childhood. Similarly, hypogonadism is most useful during and after adolescence. Some of the features like neonatal hypotonia and infantile feeding problems are less likely to be missed, whereas others such as characteristic facial features and hypogonadism (especially in prepubertal females) may require more careful and/or expert examination. The issue of who should have diagnostic testing is distinct from the determination of features among confirmed patients. Based on the sensitivities of the published criteria and our experience, we suggest testing all newborns/infants with otherwise unexplained hypotonia with poor suck. For children between 2 and 6 years of age, we consider hypotonia with history of poor suck associated with global developmental delay sufficient criteria to prompt testing. Between 6 and 12 years of age, we suggest testing those with hypotonia (or history of hypotonia with poor suck), global developmental delay, and excessive eating with central obesity (if uncontrolled). At the ages of 13 years and above, we recommend testing patients with cognitive impairment, excessive eating with central obesity (if uncontrolled), and hypogonadotropic hypogonadism and/or typical behavior problems (including temper tantrums and obsessive-compulsive features). Thus, we propose a lower threshold to prompt diagnostic DNA testing, leading to a higher likelihood of diagnosis of this disorder in which anticipatory guidance and intervention can significantly influence outcome.

Perinatal correlates and neonatal outcomes of small for gestational age infants born at term gestation.

OBJECTIVE: We sought to examine the current perinatal correlates and neonatal morbidity associated with intrauterine growth failure among neonates born at term gestation. STUDY DESIGN: We compared 372 small for gestational age (SGA, birth weight <10th percentile) infants born at term gestation to 372 appropriate for gestational age controls (AGA, birth weight 10th to 90th percentile) matched by sex, race, and gestational age within 2 weeks. RESULTS: Compared with AGA controls, significant (P < .05) maternal risk factors for SGA status included single marital status (59% versus 53%), lower prepregnancy weight (144 +/- 41 lbs versus 153 +/- 40 lbs), lower weight gain during pregnancy (29 +/- 15 lbs versus 33 +/- 15 lbs), smoking (25% versus 17%), hypertension (14% versus 7%), and multiple gestation (9% versus 2%). Mothers of SGA infants were more likely to undergo multiple (>or=3) antenatal ultrasound evaluations (19% versus 7%), biophysical profile monitoring (11% versus 4%), and oxytocin delivery induction (28% versus 16%) (P < .05). Pediatrician attendance was more common among SGA deliveries (50% versus 37%, P < .05). SGA infants had significantly higher rates of hypothermia (18% versus 6%) and symptomatic hypoglycemia (5% versus 1%). These neonatal problems remained significant even when medical or pathologic causes of intrauterine growth failure, including pregnancy hypertension, multiple gestation, and congenital malformations, were excluded. CONCLUSION: Despite higher rates of pregnancy complications among mothers of SGA infants, the rates of neonatal adverse outcomes are low. However, SGA infants remain at risk for hypothermia and hypoglycemia and require careful neonatal surveillance.

Superior visual search in autism.

Children with a diagnosis of autism and normally developing children, matched for age and general ability, were tested on a series of visual search tasks in 2 separate experiments. The children with autism performed better than the normally developing children on difficult visual search tasks. This result occurred regardless of whether the target was uniquely defined by a single feature or a conjunction of features, as long as ceiling effects did not mask the difference. Superior visual search performance in autism can be seen as analogous to other reports of enhanced unique item detection in autism. Unique item detection in autism is discussed in the light of mechanisms proposed to be involved in normal visual search performance.

The pharmacokinetics of colistin in patients with cystic fibrosis.

The safety and pharmacokinetics of colistin were determined after first dose (n = 30) and again under steady-state conditions (n = 27) in 31 patients with cystic fibrosis receiving the drug as a component of their treatment for an acute pulmonary exacerbation of their disease. Patients ranged in age from 14 to 53 years and received colistin for 6 to 35 days. Each patient was started on colistin 5 to 7 mg/kg/day administered intravenously in three equally divided doses. Elimination half-life (t1/2), mean residence time (MRT), steady-state volume of distribution (Vdss), total body clearance (Cl), and renal clearance (Clr) after first-dose administration averaged 3.4 hours, 4.4 hours, 0.09 l/kg, and 0.35 and 0.24 ml/min/kg, respectively. No differences in colistin disposition characteristics between first-dose and steady-state evaluations were observed. Sputum sampling was incomplete and confounded by previous aerosol administration but revealed colistin concentrations that markedly exceeded observed plasma concentrations. Twenty-one patients experienced one or more side effects attributed to colistin administration. The most common reactions involved reversible neurologic manifestations, including oral and perioral paresthesias (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these apparent colistin-induced neurologic adverse effects, though bothersome, were benign and reversible. Intermittent proteinuria was observed on urinalysis in 14 patients, and 1 patient developed reversible, colistin-induced nephrotoxicity. No relationship between the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetic parameter estimate was observed. These data provide no basis for routine monitoring of colistin plasma concentrations to guide dosing for patient safety and suggest slow upward dose titration to minimize the incidence and severity of associated side effects.

Ipratropium bromide plus nebulized albuterol for the treatment of hospitalized children with acute asthma.

OBJECTIVE: To determine whether the addition of repeated doses of nebulized ipratropium bromide (IB) to a standardized inpatient asthma care algorithm (ACA) for children with status asthmaticus improves clinical outcome. STUDY DESIGN: Children with acute asthma (N = 210) age 1 to 18 years admitted to the ACA were assigned to the intervention or placebo group in randomized double-blind fashion. Both groups received nebulized albuterol, systemic corticosteroids, and oxygen according to the ACA. The intervention group received 250 microg IB combined with 2.5 mg albuterol by jet nebulization in a dosing schedule determined by the ACA phase. The placebo group received isotonic saline solution substituted for IB. Progression through each ACA phase occurred based on assessments of oxygenation, air exchange, wheezing, accessory muscle use, and respiratory rate performed at prescribed intervals. RESULTS: No significant differences were observed between treatment groups in hospital length of stay (P =.46), asthma carepath progression (P =.37), requirement for additional therapy, or adverse effects. Children >6 years (N = 70) treated with IB had shorter mean hospital length of stay (P =.03) and more rapid mean asthma carepath progression (P =.02) than children in the placebo group. However, after adjustment was done for baseline group differences, the observed benefit of IB therapy in older children no longer reached statistical significance. CONCLUSION: The routine addition of repeated doses of nebulized IB to a standardized regimen of systemic corticosteroids and frequently administered beta-2 agonists confers no significant enhancement of clinical outcome for the treatment of hospitalized children with status asthmaticus.

Placental lesions associated with cerebral palsy and neurologic impairment following term birth.

OBJECTIVE: The aim of this study was to determine the association of placental findings with cerebral palsy and related forms of neurologic impairment (NI) following birth at > or =37 weeks gestation (term). DESIGN: In a retrospective comparison, placentas from 40 term infants with NI ascertained on the basis of clinicopathologic review for medicolegal consultation were compared with placentas from 176 consecutive meconium-stained term infants at low risk for NI. RESULTS: After stratification for severity, 9 lesions were significantly increased in placentas from infants with NI: 5 lesions generally considered to occur within days of the time of labor and delivery (meconium-associated vascular necrosis, severe fetal chorioamnionitis, chorionic vessel thrombi, increased nucleated red blood cells, and findings consistent with abruptio placenta) and 4 lesions generally believed to have their onset long before labor and delivery (diffuse chronic villitis, extensive avascular villi, diffuse chorioamnionic hemosiderosis, and perivillous fibrin). Findings independently associated with NI by logistic regression in this descriptive study were severe fetal chorioamnionitis (odds ratio [OR], 13.2; 95% confidence interval [CI], 1.2-144); extensive avascular villi (OR, 9.0; 95% CI, 1.6-51); and diffuse chorioamnionic hemosiderosis (OR, 74.8; 95% CI, 6.3-894). The risk of NI increased as a function of the number of lesions present (OR, 10.1; 95% CI, 5.1-20 for each additional lesion), particularly when lesions generally considered to occur near the time of labor and those believed to occur well before labor were found in the same placenta (OR, 94.2; 95% CI, 11.9-747). CONCLUSIONS: These findings suggest that placental pathology can contribute to an understanding of the mechanisms that contribute to NI at term.

Lead exposure from blood transfusion to premature infants.

OBJECTIVE: The objective of this study was to determine the exposure of premature infants to lead from blood transfusions. STUDY DESIGN: Blood lead concentrations were determined for 19 very premature infants at the time of admission, at 4 weeks of life, and before and after transfusions and in the donor packed red blood cells of 79 transfusions. RESULTS: The number of transfusions per patient was 4. 2 +/- 2.8 (mean +/- SD) with 15.7 +/- 1.9 mL/kg packed red blood cells for a lead dose of 1.56 +/- 1.77 microg/dL. The total dose of lead from these transfusions over the 4-week period was 4.0 +/- 2.8 microg/kg (range, 0.9-10.6 microg/kg). Increases in post-transfusion blood lead concentration were linear with doses higher than 1.5 microg/dL. Packed red blood cells with a blood lead concentration of > or = 5 microg/dL resulted in an elevated post-transfusion blood lead concentration in some infants. CONCLUSIONS: The lead exposure to these infants through blood transfusion exceeds the acceptable daily intake values for lead and may result in unacceptably high post-transfusion blood lead concentrations. Use of packed red blood cells with lead concentrations <3.3 microg/dL is one cost-effective means to reduce exposure.

Serum alpha-fetoprotein levels in Beckwith-Wiedemann syndrome.

We conducted a retrospective study that compared serial alpha-fetoprotein (AFP) concentrations obtained from 22 children with Beckwith-Wiedemann syndrome (BWS) with levels established for healthy children. The AFP concentration is greater in patients with BWS and declines during the postnatal period at a significantly slower rate than what is reported in healthy children. AFP levels obtained in the course of routine tumor screening in children with BWS should be interpreted with a normal curve established specifically for BWS rather than with previously published data for healthy infants and children.

Acute hemoperitoneum in children: prevalence of low-attenuation fluid.

BACKGROUND: Recent evidence indicates that acute hemoperitoneum may have lower than expected attenuation values at CT. OBJECTIVE: To characterize the attenuation of acute hemoperitoneum at CT in children following blunt abdominal trauma and to assess the prevalence of low-attenuation fluid. MATERIALS AND METHODS: The CT scans of 19 consecutive children with isolated hepatic or splenic injury and associated peritoneal fluid were retrospectively analyzed. The attenuation value of peritoneal fluid was assessed in all peritoneal spaces. RESULTS: Fluid was noted in 53 peritoneal spaces (27 abdominal, 26 pelvic). Fluid attenuation ranged from 20 to 64 HU. The mean fluid attenuation in pelvic spaces (37.5 +/- 9.4 HU) was significantly lower than in abdominal spaces (444.9 +/- 10.2 HU) (P = 0.008). Fluid in 8/26 (31 %) pelvic spaces and 2/27 (7 %) abdominal spaces had attenuation values < or = 30 HU. Fluid surrounding the site of injury (perihepatic or perisplenic space) was significantly higher in attenuation than fluid at other sites (P < 0.001). There was no correlation between the mean attenuation value of peritoneal fluid in each patient and the admission hematocrit (r = -0.14, P = 0.55). CONCLUSIONS: There is great variability in the attenuation of acute hemoperitoneum. Blood in pelvic spaces has significantly lower attenuation than blood in abdominal spaces. Hemoperitoneum in the pelvis has values of < or = 30 HU in approximately one-third of spaces. The attenuation of acute hemoperitoneum does not correlate with hematocrit.

Infections in children with cancer: a continued need for the comprehensive physical examination.

Few studies have addressed the influence of profound myelosuppressive therapy in contemporary protocols on infectious morbidity in pediatric oncology patients. This study evaluates the types of infections and the methods used to diagnose infection in patients enrolled in current Children's Cancer Group (CCG) protocols. Data were collected on patients enrolled in CCG protocols from January 1, 1992, through December 31, 1995. Of the 155 protocol patients, 102 were completely evaluated and had data collected through August 1, 1996. Patients were divided into two diagnosis groups: leukemia/lymphoma (N = 51) and solid tumor (N = 51). Eighty-five (83%) patients had documented infections and 17 (17%) did not. Overall, 96 (94%) patients had in-dwelling central venous catheters. Twelve categories of infection were identified. Data were analyzed for age, gender, diagnosis, neutropenia, organism, and disease state (primary active, recurrent active, primary remission, and secondary remission). Statistical comparisons were made only on rates, whereas descriptive comparisons were given for numbers of infections and organisms. The infection rates for patients with active disease were 1.01 and 1.15 per 100 patient days (primary versus recurrent) and 0.59 and 0.38 per 100 patient days for patients with disease in remission (primary versus secondary). Diagnosis-group infection rates were 0.66 and 0.68 per 100 patient days for patients with solid tumors and leukemia/lymphoma, respectively. Three hundred thirty infections, including 19 polymicrobial infections, were recorded. The three most common types of infection were otitis media, septicemia, and urinary tract infection. More infections were associated with an age at diagnosis of less than 3 years, a leukemia/lymphoma diagnosis in remission, and an absolute neutrophil count >500 cells/microL. One hundred ninety-four organisms were isolated from 330 infections. Gram-positive organisms (n = 74) such as coagulase-negative Staphylococci (n = 38) predominated over gram-negative organisms (n = 63) for all infectious categories. Specifically, gram-positive organisms (n = 39) were isolated more often from blood cultures than were gram-negative organisms (n = 27). The overall mortality for patients was 36%. Seven of the 37 (19%) patient deaths were attributed to infection. These patients predominantly were girls with neutropenia and leukemia/ lymphoma in active disease who died of gram-negative sepsis. Infections with gram-positive organisms continue to be major causes of morbidity in pediatric oncology patients receiving contemporary CCG protocols. However, infection-related mortality, especially with gram-negative organisms, occurs less frequently than does malignancy-related mortality. Common childhood infections (such as otitis media) seem equally as prevalent as bacteremia in pediatric oncology patients. Thus, a comprehensive physical examination is as imperative as the microbiologic evaluation in diagnosing infection in this patient population.

Paroxetine pharmacokinetics in depressed children and adolescents.

OBJECTIVE: To describe the pharmacokinetics and safety of paroxetine in children and adolescents and to explore the role of genetic polymorphisms in paroxetine pharmacokinetics. METHOD: Thirty depressed youths were enrolled. Samples for phenotyping with respect to cytochrome P450 2D6 (CYP2D6) and catechol-O-methyltransferase were collected. A single 10-mg dose of paroxetine was then administered followed by 5 days of blood and urine collection for pharmacokinetic analyses. Subjects subsequently received open treatment for 8 weeks, and weekly blood samples were obtained for plasma concentration measurements. RESULTS: There was tremendous interindividual variability in paroxetine disposition. The mean half-life of paroxetine was 11.1 +/- 5.2 (SD) hours. The average clearance was 88.7 +/- 66.4 mL/min/kg. The mean area under the plasma drug concentration curve was 0.09 +/- 0.10 microgram/mL.hr. Within-subject variability of plasma paroxetine concentrations was generally not significant. Clearance and fractional urinary excretion of paroxetine were found to correlate with CYP2D6 activity. Two subjects developed hypomania necessitating drug discontinuation. No clinically significant changes in any safety assessments were noted. CONCLUSIONS: Paroxetine is more rapidly cleared in youths than adults and may be given once daily in this population. Short-term treatment with paroxetine appears safe and well tolerated in this relatively small sample of pediatric patients.

Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells.

The neuropathology of the effects of ethanol on the developing central nervous system are similar to those of patients with mutations in L1, a neural cell adhesion molecule. This observation suggests that inhibition of L1 plays a role in the pathogenesis of alcohol-related neurodevelopmental disorders. Here we examine the effects of ethanol on L1 homophilic binding and on L1-mediated neurite outgrowth. Ethanol had no effect on cell adhesion or aggregation in a myeloma cell line expressing full-length human L1. In contrast, the rate of L1-mediated neurite outgrowth of rat postnatal day 6 cerebellar granule cells grown on a substratum of NgCAM, the chick homologue of L1, was inhibited by 48.6% in the presence of ethanol with a half-maximal concentration of 4.7 mM. The same effect was found with soluble L1-Fc, thus showing that the inhibitory effect is not dependent on cell adhesion. In contrast, neither laminin nor N-cadherin-mediated neurite outgrowth was inhibited by physiologic concentrations of ethanol. We conclude that one mechanism of ethanol's toxicity to the developing central nervous system may be the inhibition of L1-mediated neurite outgrowth.

Effectiveness of influenza vaccine in health care professionals: a randomized trial.

CONTEXT: Data are limited and conflicting regarding the effectiveness of influenza vaccine in health care professionals. OBJECTIVE: To determine the effectiveness of trivalent influenza vaccine in reducing infection, illness, and absence from work in young, healthy health care professionals. DESIGN: Randomized, prospective, double-blind, controlled trial over 3 consecutive years, from 1992-1993 to 1994-1995. SETTING: Two large teaching hospitals in Baltimore, Md. PARTICIPANTS: Two hundred sixty-four hospital-based health care professionals without chronic medical problems were recruited; 49 participated for 2 seasons; 24 participated for 3 seasons. The mean age was 28.4 years, 75% were resident physicians, and 57% were women. INTERVENTION: Participants were randomly assigned to receive either an influenza vaccine or a control (meningococcal vaccine, pneumococcal vaccine, or placebo). Serum samples for antibody assays were collected at the time of vaccination, 1 month after vaccination, and at the end of the influenza season. Active weekly surveillance for illness was conducted during each influenza epidemic period. MAIN OUTCOME MEASURES: Serologically defined influenza infection (4-fold increase in hemagglutination-inhibiting antibodies), days of febrile respiratory illness, and days absent from work. RESULTS: We conducted 359 person-winters of serologic surveillance (99.4% follow-up) and 4746 person-weeks of illness surveillance (100% follow-up). Twenty-four(13.4%) of 179 control subjects and 3 (1.7%) of 180 influenza vaccine recipients had serologic evidence of influenza type A or B infection during the study period. Vaccine efficacy against serologically defined infection was 88% for influenza A (95% confidence interval [CI], 47%-97%; P=.001) and 89% for influenza B (95% CI, 14%-99%; P=.03). Among influenza vaccinees, cumulative days of reported febrile respiratory illness were 28.7 per 100 subjects compared with 40.6 per 100 subjects in controls (P=.57) and days of absence were 9.9 per 100 subjects vs 21.1 per 100 subjects in controls (P=.41). CONCLUSIONS: Influenza vaccine is effective in preventing infection by influenza A and B in health care professionals and may reduce reported days of work absence and febrile respiratory illness. These data support a policy of annual influenza vaccination of health care professionals.

Low yield of bacterial stool culture in children with nosocomial diarrhea.

OBJECTIVE: To determine whether bacterial stool cultures (BSC) are useful in initial evaluation of children with symptoms of nosocomial diarrhea. To answer this question we performed a retrospective record review to determine the yield of BSC in children who developed diarrhea after the third hospital day (HD-3). METHODS: The hospital computer record keeping system was utilized to compile the result of BSC collected from children and adolescents ages 0 to 20 years between January 1, 1988, and October 31, 1996. All specimens were analyzed for Salmonella, Shigella, Yersinia and Campylobacter. We reviewed hospital charts of all children who developed a positive BSC beyond HD-3 to determine the time of onset of diarrhea and clinical circumstances. RESULTS: A total of 11 516 BSCs were submitted from 9262 children during the 8 1/2-year period. Five hundred sixty-eight (6.6%) of 9262 children had at least 1 positive BSC. Two thousand five hundred seventy-two children had the first BSC submitted after HD-3 and 13 (0.5%) of these children had a positive result. Chart review of these 13 children demonstrated that 6 had onset of diarrhea during the first 3 hospital days. Therefore only 7 children met our criteria for having nosocomially acquired diarrhea caused by a bacterial pathogen. Children whose first BSC was submitted after HD-3 accounted for 3767 (46%) of the total 8126 inpatient BSCs and in excess of $21000 annually in patient billing charges. CONCLUSION: In the absence of a known exposure the isolation of a bacterial pathogen from the stool of children with onset of diarrhea beyond HD-3 is a rare event. Under most circumstances BSC should not be part of the initial evaluation of children with symptoms of nosocomial diarrhea.

Intrinsic hyperreactivity of mucosal T cells to interleukin-2 in pediatric Crohn's disease.

OBJECTIVES: To cells play a crucial role in many chronic inflammatory diseases. Mucosal T cells are particularly important in the pathogenesis of Crohn's disease (CD). We investigated the response of T cells in CD and other intestinal inflammatory conditions to interleukin-2 (IL-2), a cytokine essential for T-cell activation, growth, and function. STUDY DESIGN: T-cell reactivity was assessed by measuring growth induced by IL-2 in mucosal endoscopic biopsy specimens obtained from children with CD, ulcerative colitis, indeterminate colitis, and chronic nonspecific colitis and from children without gastrointestinal inflammation. RESULTS: CD mucosal T cells grew remarkably and significantly more than T cells from normal, ulcerative colitis, and chronic nonspecific colitis mucosa. T cells from indeterminate colitis mucosa grew similarly to those of CD mucosa. The enhanced growth response in CD was independent of disease location, presence or absence of intestinal inflammation, treatment, disease duration, or clinical activity. CONCLUSION: Mucosal T cells from children with CD exhibit an intrinsic hyperreactivity to IL-2. This may represent a primary pathogenic abnormality in this condition.