Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phase.

Pediatric ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is usually associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase is uncommon, but has been associated with an aggressive clinical course and unfavorable prognosis. Overexpression of c-myc has been shown to be a consistent finding in ALK+, but not ALK-negative ALCL (ALK- ALCL), and the c-myc gene is considered a downstream target of deregulated ALK signaling. We describe a pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases described in the literature, it followed an aggressive clinical course despite multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells showed aberrant ALK expression and c-myc overexpression. In addition to the characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation was also present, and c-myc gene rearrangement was confirmed by FISH analysis. The findings in this case demonstrate the association of peripheral blood leukemic involvement and aggressive clinical course, and suggest that other factors, such as c-myc rearrangement, may be responsible for the aggressive clinical behavior in ALK+ ALCL.

A retrospective study of children's perceptions of participation as clinical research subjects in a minimal risk study.

The purpose of the study was to evaluate children's perceptions of their participation as research subjects in a minimal risk research study (a methylphenidate population pharmacokinetic study conducted 8 months earlier). We identified 115 children of an original 189, aged 6 to 19 years, who were responding well to regular methylphenidate for attention-deficit hyperactivity disorder. By using a structured format, telephone interviewers unconnected to the original study questioned the children about what it had been like to be a subject in terms of voluntariness, accuracy of informed consent, reasons for participating, and satisfaction with their experience. Children overwhelmingly perceived their involvement as voluntary (89%) and the information about the study as accurately presented (80%), and they reported a high level of satisfaction with their participation (97%). Self-interest was the most frequently reported reason for participation (47%). In a subsample of 25 children, the percentage of agreement of a 1-week test-retest equaled or exceeded 72% for all answers.

Cytochrome P450-mediated drug interactions.

In this article, the authors have provided child psychiatrists with cytochromal concepts, illustrations of common CYP-based drug interactions, and CYP tables. Clinicians can use these tables to anticipate drug interactions. If two medications are listed on the same CYP, a drug interaction may occur, and depending on whether they are substrates, inducers, or inhibitors, clearance of one or both drugs may be altered. Because new information about CYPs rapidly becomes available, however, CYP tables have a short shelf life. To further predict and reduce the consequences of CYP-based drug interactions, child psychiatrists can limit their own formularies and review PubMed, Ovid, or other literature tracking programs each time they use two or more drugs (including nonpsychiatric ones). The following Internet websites can provide current CYP data: CYP charts http//:@www.dml.georgetown.edu/depts/ph armac ology/clinlist.html http//:@www.accp.com/p450.html CYP drug interaction program http//:@www.mhc.com/Cytochromes/ AIDS drug interactions http//:@www.tthhivclinic.com/interactions.htm http//:@www.fda.gov/oashi/aids/pitabv. htm l http//:@HIV.medscape.com/Medscape/HIV/DrugInteract+ ++ ion s/index.html http//:@www.hopkins-aids.edu/geneva/hilites_f le x_d rug.html.

Case series: clonidine has no systematic effects on PR or QTc intervals in children.

This study retrospectively examined the effects of clonidine, both alone and combined with psychostimulants, on the electrocardiograms (ECGs) of children and adolescents. Two pediatric cardiologists, blinded to treatment condition, examined pre- and posttreatment ECGs in 42 subjects treated with clonidine for attention-deficit/hyperactivity or tic disorder. While ECG variability was found, it did not appear to be related to any systematic effect of clonidine, either alone or in combination with psychostimulants. These data do not rule out the possibility of rare idiosyncratic reactions to clonidine with or without psychostimulants, though none occurred in this sample.

Population pharmacokinetics of methylphenidate in children with attention-deficit hyperactivity disorder.

Sources of individual variation in plasma methylphenidate (MP) concentrations during usual clinical use are not established. This was evaluated in a series of patients receiving clinical treatment with MP. A single plasma MP concentration was determined in each of 273 children and adolescents ages 5 to 18 years (mean: 11.1 years) who were clinically good responders to MP for the treatment of attention-deficit hyperactivity disorder. MP was given on a twice-daily schedule (mean dose: 25 mg/day) in 40% of patients and three times daily (mean dose: 39.3 mg/day) in 60%. A nonlinear regression model was applied to estimate overall population values of MP clearance and elimination half-life (t1/2), assuming a one-component model with first-order absorption and elimination, and further assuming that clearance is linearly related to body weight. The model incorporated each patient's dosage size and schedule, body weight, and time of the plasma sample. Iterated solutions of best fit were: t1/2, 4.5 hours (95% confidence interval [CI]: 3.1-8.1 hours), and apparent clearance, 90.7 ml/min/kg (95% CI: 74.6-106.7 ml/min/kg). The model explained 43% of the overall variance in MP concentrations (r2 = 0.43, p < .001). In a small subsample (N = 16), a second plasma sample was drawn at the same time of day and at the same dose; the correlation between the two concentration values was 0.83. The relatively noninvasive approach used in this study allows the assessment of pharmacokinetic properties of medications under conditions of appropriate clinical use in special populations such as children, adolescents, and the elderly.

A review of developmental aspects of cytochrome P450.

This article surveys the development of human hepatic P450 cytochromes (CYPs) involved in xenobiotic metabolism from the fetus through the life span and explores possible clinical consequences of developmental issues. These hepatic P450 CYPs come "on line" at different times during fetal and infant development, and each one is discussed in that temporal sequence. CYP3A7. the major fetal hepatic cytochrome, is present during organogenesis, and it is involved in steroid metabolism. Variably expressed in some fetuses, CYP3A5 is also present at significant levels in about half of all children. In adults, CYP3A4 is the major functional member of the CYP3A subfamily. CYP1A1 is also present during organogenesis, and it metabolizes exogenous toxins, some of which are procarcinogens. CYP2E1 may be present in some second-trimester fetuses, and it may be involved in prenatal alcohol metabolism. After birth, hepatic CYP2D6 and CYP2C8/9 and CYP2C18/19 become active. Both CYP2D6 and CYP2C19 have genetic polymorphisms that can bring about differing capacities to metabolize exogenous drugs, including psychotropic drugs. CYP1A2 becomes active in the fourth to fifth postfetal months. It provides the best current examples of the importance of developmental changes in xenobiotic-metabolizing P450 CYPs through its metabolism of caffeine and theophylline in premature infants, neonates, and adolescents.

Effectiveness of methylphenidate in Native American children with fetal alcohol syndrome and attention deficit/hyperactivity disorder: a controlled pilot study.

This pilot study was designed to assess the short-term effectiveness and side effects of methylphenidate in treating symptoms of attention deficit hyperactivity disorder (ADHD) in Native American children (5 to 12 years old) with documented fetal alcohol syndrome (FAS) or partial fetal alcohol syndrome. Using strict criteria for the diagnosis of FAS and ADHD, a randomized double-blind cross-over study of two placebos and a fixed dose of methylphenidate was completed in 4 Native American children in a residential school. Each treatment condition lasted 5 days, and daily observational outcome measures, the Conners Parent Rating Scale (CPRS-48), and the Conners Teacher Rating Scale (CTRS-39), were employed. Methylphenidate significantly improved scores of the Hyperactivity Index Scale on the CPRS-48 and the CTRS-39 but not the Daydreaming-Attention score on the CTRS-39. Side effects were similar to those traditionally found in other populations. The promising preliminary results suggest that a more definitive study of methylphenidate in Native and non-Native children with FAS and ADHD is warranted.

Acceptability of the Conners Parent Rating Scale and Child Behavior Checklist to Dakotan/Lakotan parents.

OBJECTIVE: The objective of this pilot study was to determine how Dakotan/Lakotan parents view the Conners Parent Rating Scale (CPRS) and Child Behavior Checklist (CBCL). METHOD: Using a focus group methodology, four discussion groups were held in different sites across South Dakota where the CPRS and CBCL were in clinical use. RESULTS: Only two questions on each form were incomprehensible to these Dakotan/Lakotan parents. Other questions were hard to answer because certain questions contained implicit dominant cultural values that did not take into account Dakotan/Lakotan cultural values or traditions, or the questions were hard to answer because Dakotan/Lakotan believed their responses could or would be misunderstood by members of the dominant culture who did not understand Dakotan/Lakotan style or customs. CONCLUSIONS: The CPRS and CBCL were generally acceptable to Dakotan/Lakotan parents. Clinicians could make several statements to Native parents that would improve cultural acceptability.

Clonidine: a practical guide for usage in children.

Clonidine, oral and patch, has been used in adults for the treatment of hypertension and Tourette's Syndrome. Recently clinicians have begun to employ it in several oft label usages in children, especially behavioral syndromes. This article is a guide to its usage in children and includes discussion of its indications, contraindications, pre-treatment laboratory studies, dosing and drug interactions.