The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML).

The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is based upon weighted data on bone marrow (BM) blast percentage, cytopenia, and cytogenetics, separating patients into four prognostic groups. We analyzed the value of the IPSS in 142 children with de novo MDS and 166 children with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in MDS and JMML were analyzed separately. Among the criteria considered by the IPSS score, only BM blasts <5% and platelets >100 x 10(9)/l were significantly associated with a superior survival in MDS. In JMML, better survival was associated with platelets >40 x 10(9)/l, but not with any other IPSS factors including cytogenetics. In conclusion, the IPSS is of limited value in both pediatric MDS and JMML. The results reflect the differences between myelodysplastic and myeloproliferative diseases in children and adults.

Haemophagocytosis in early congenital syphilis.

UNLABELLED: A previously healthy male infant developed hepatosplenomegaly, severe anaemia and thrombocytopenia 5 weeks after birth. Marked haemophagocytosis was present in the bone marrow. A typical maculopapular rash suggested early congenital syphilis. The diagnosis was confirmed by serology and by the presence of untreated syphilis in both parents. CONCLUSION: Syphilis needs to be excluded in infants suspected of haemophagocytic lymphohistiocytosis.

Valproate metabolites in the rat brain--regional distribution in various brain areas.

To investigate the regional distribution of valproic acid (VPA) and 10 of its metabolites in the rat brain, the animals were treated with 300 mg/kg/day VPA i.p. on a 3 times daily dose regimen for 5 days, and the concentrations of the compounds in serum and 15 brain regions were measured. 2-(n-propyl)-(Z)-2-pentenoic acid [(Z)-2-en], a VPA metabolite expected to possess neurotoxic potency in humans, was determined in brain tissue for the first time. The brain/serum concentration ratio of (Z)-2-en was found to be about 14-fold higher than the ratio for its (E)-isomer, thereby demonstrating the influence of the double-bond configuration in the unsaturated metabolites on their ability to penetrate into the central nervous system. The concentrations of VPA and its metabolites in the brain regions were compared to c(hom), the calculated concentration for an assumed homogeneous distribution. The parent drug and its metabolites exhibited individual distribution patterns with varying degrees of inhomogeneity. Elevated metabolite concentrations were found especially in the motorium and the medulla oblongata. Decreased concentrations of VPA and several metabolites were found in the visual cortex.

[Severity of respiratory syncytial virus infection influenced by clinical risk factors and subtype A and B in hospitalized children]. / Rolle der RSV-Subtypen A und B und klinischer Risikofaktoren auf den Schweregrad von RSV-Infektionen bei hospitalisierten Säuglingen und Kleinkindern.

BACKGROUND: Since it is possible to identify the subgroups of RSV, A-subtype and B-subtype, there are findings indicating that the subtype may influence severity of RSV infection. Our study was designed to assess the hypothesis that A-subtype infections were more severe than B-subtype infections among hospitalized children. PATIENTS: All medical records of patients hospitalized with RSV infection between March 1990 and March 1993 were reviewed. A total of 107 children with proven RSV infection were identified. METHODS: Nasal waste specimens for culture were obtained from infants with suspected RSV infection. Subtype determination was done on frozen virus cultures. The following risk factors were defined: age < or = 3 months, weight < 5 kg, prematurity and underlying cardiac or respiratory disease and immune deficiency. To analyse the relationship between risk factors, subtype and severity a multivariate analysis was performed. Severity was measured by clinical observations as following: pH, PCO2, SaO2, oxygen supplementation, history of apnea and length of hospital stay. MAIN RESULTS: Of the enrolled patients 11 had underlying disease and 17 were premature. The age range was 1 week to 4.2 years, median 3.5 months. 46 children were younger than 3 months, 33 had a weight of less than 5 kg. The isolates of 84 children were typeable: 63 isolates were subtype A and 21 subtype B. Underlying disease and prematurity were associated with SaO2 < 87% (p = 0.003) and oxygen supplementation (p = 0.017). A weight of less than 5 kg was correlated with a PCO2 > or = 50 mmHg. The RSV subtype was not significantly correlated with severity. CONCLUSIONS: RSV infection even in very young children is predominantly influenced by underlying disease, prematurity and weight. The RSV subtype was no independent risk factor for an increased morbidity in this retrospective study. Therefore, in our opinion, RSV subtype is less meaningful to predict the severity of RSV infection than known risk factors.

[Oncologic after-care--a patient-oriented concept. Basic diagnostic plan for pediatric oncology patients]. / Onkologische Nachsorge--ein patientenorientiertes Konzept. Ein Basisdiagnostikplan für pädiatrisch-onkologische Patienten.

With intensive treatment many children and young adults with cancer can be cured of their disease. Therefore, the recognition of late effects of therapy will become increasingly important. Future concepts of follow-up care in pediatric oncology will have to serve two purposes: First, to determine the status of the malignant disease with early diagnosis of relapse and second, to recognize relevant side effects of treatment. We present a comprehensive approach of follow-up care which is primarily based on the definition of risk criteria for the development of relevant organ toxicity after different treatment modalities. For each patient a standardized summary of therapy delivered is documented. According to the definition of the risk criteria an individualized schedule for follow-up is decided upon. We hope that this structured concept will result in appropriate patient care while keeping the diagnostic efforts and costs limited.

Restriction and functional changes of dopamine release in rat striatum from young adult and old rats.

In order to investigate the age-related changes in dopaminergic activity in rats, we have utilized the K(+)- and veratridine-stimulated [14C]dopamine release from striatum in vitro as a functional index of responsiveness to these stimuli in aging. We found that the K(+)-stimulated dopamine release from old (12 months) rats decreased by more than 50% compared to that from young adult rats (3 months). Reserpine (5 mg/kg) led to a pronounced decrease of the K(+)-stimulated dopamine release of young adult as well as old rats. Whereas ouabain (10 mumol/l) decreased the K(+)-stimulated dopamine release from young adult rats, in old rats the K(+)-induced dopamine release was increased up to 250%. However, in old rats which were reserpine pretreated, ouabain was unable to stimulate the K(+)-induced dopamine release. In contrast, the veratridine-stimulated dopamine release of old rats was increased up to 200% compared to that of young adult rats and was highly sensitive to reserpine pretreatment but not to ouabain. However, reserpine did not alter this veratridine-stimulated dopamine release from young adult rats. The present data indicate that the age-related reduction of exocytosis-related, Ca(2+)-dependent release mechanisms (K+) are probably compensated via an increase in Ca(2+)-independent, uptake carrier-mediated release processes (veratridine).

Long-term effects of postnatal hypoxia and flunarizine on the dopaminergic system.

Long-term changes of learning behavior and of the striatal dopaminergic system were observed in a rat model of early postnatal hypoxia. Striatal dopamine (DA) concentration, K(+)-stimulated DA release from slices, and DA uptake into crude synaptosomal preparations (S1 fractions) were used as markers of the striatal DAergic system. Active avoidance learning was tested as behavioral criterion. Cyclodextrin and flunarizine were found to produce long-term effects on the DAergic system in control animals. While cyclodextrin normalized hypoxia-induced effects in DA release, flunarizine prevented those in DA uptake and improved avoidance learning.