Purpose To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT). Methods We studied these metabolites in 229 blood samples from 18 children with ALL (N = 16) or NHL (N = 2) on 6MP/Methotrexate maintenance therapy. Results DNA-6TGN levels were signiWcantly correlated to E-6TGN (r p = 0.66, p = 0.003) with a trend to reach a plateau at high E-6TGN levels. To explore the relative DNA incorporation of 6TGN in relation to cytosol 6TGN levels, a DNA-6TGN index was calculated as DNA-6TGN/ E-6TGN. The DNA-6TGN index was inversely correlated to E-6TGN (r p = ¡0.58, p = 0.012), which implies that with increasing levels of E-6TGN relatively less 6TGN are incorporated into DNA. E-MeMP levels were correlated to the DNA-TGN index (r p = 0.60, p = 0.008), indicating that high levels of MeMP result in enhanced DNA-6TGN incorporation, possibly due to inhibition of purine de novo synthesis, mediated by some of the methylated 6MP metabolites. Conclusions DNA-6TGN may prove to be a more relevant pharmacokinetic parameter for monitoring 6MP treatment intensity than the previously used erythrocyte 6MP metabolites levels. Prospective clinical trials are needed to evaluate the usefulness of DNA-6TGN for individual dose adjustments.

Early risk factors for suicide were dissociated relationships with parents, siblings and friends, feeling unheard, self-mutilation and extended suicidal ideation.

Paediatric patients at increased risk of severe hepatotoxicity were identified by early biochemical parameters, prehospital vomiting episodes and latency time before N-acetylcysteine initiation.

A consistently impaired parent-child relationship, 'the feeling of not being heard', and self-mutilation are identifiable early risk factors that require increased concern and attention among professionals who work with children.

Objective. To characterize early risk factors of moderate/severe hepatotoxicity in a pediatric population with acetaminophen overdose, due to suicide attempt, admitted to a general secondary-level pediatric department. Methods. A retrospective case study of 107 patients, 11 to 15 years old. Results. There was a highly significant relationship between the number of episodes of prehospital vomiting and several elevated hepatologically relevant biochemical parameters, for example, maximum aspartate aminotransferase (P = .0001). The duration of the latency time before initiation of N-acetylcysteine treatment was significantly related to the elevation of several hepatologically relevant biochemical parameters (eg, maximum γ-glutamyl transferase; P = .0001). Patients suffering from illness prior to their suicide attempt had significantly greater elevations of their hepatologically relevant biochemical parameters, for example, maximum alanine aminotransferase (P = .01) levels than healthy patients. Conclusion. By use of risk factors, it is possible to identify pediatric patients at increased risk of moderate/severe hepatotoxicity at an early stage of admission.