Arsenic trioxide and neuroblastoma cytotoxicity

The majority of aggressive forms of the childhood tumor neuroblastoma can with current treatment protocols not be cured and possess a major challenge in pediatric oncology. After initial rounds of chemotherapy, surgery and irradiation, which in most cases result in tumor regression, these aggressive neuroblastomas relapse and frequently develop drug resistance. As approximately 50% of the children with neuroblastoma have an aggressive form, there is a compelling demand for new treatment strategies. Arsenic trioxide has the capacity to kill multidrug-resistant neuro-blastoma cells in vitro and in vivo and the drug is currently being evaluated in clinical trials. In this report we discuss the background to the use of arsenic trioxide in cancer therapy and the currently known mechanisms by which arsenic trioxide kills human neuroblastoma cells.     

10-year analysis (1969-1978) of the results of treating children with acute lymphoblastic leukemia--therapeutic implications

The paper deals with the increasing improvement of results obtained in treating acute lymphocytic leukemia in childhood on the basis of own patients (55 children admitted to hospital from 1969 to 1978). The assessment of the results is made by life table analysis according to the method of Cutler and Ederer. In the group of patients with a low risk more than half the children in stable first remission will exceed the 5-year limit after being diagnosed. In the group of patients with a high risk the results are significantly worse and require an intensification of the initial therapy step by step by using an aggressive initial stroke of treatment which is taken into consideration in the last protocol of therapy elaborated by the working committee for paediatric haematology and oncology in the paediatric society of GDR.     

Parent-only treatment for childhood obesity: a randomized controlled trial

Parent-only (PO) treatments for childhood obesity are feasible, more cost-effective and potentially easier to disseminate. The objective of this study was to determine whether a PO treatment is not inferior to a parent + child (PC) treatment for childhood obesity. Eighty parent-child dyads with an 8-12 year old overweight or obese child (>85th BMI-P) were recruited and randomized into PO or PC treatment for childhood obesity. Parents or parent-child dyads attended 5-month treatment groups. Child and parent body size, child caloric intake, and child physical activity were assessed at baseline, post-treatment, and 6-months follow-up. Noninferiority testing using mixed linear models was used to compare PO treatment with PC treatment. Results showed that the PO group was not inferior to the PC group in terms of child weight loss. Results also showed that the PO group was not inferior to the PC group in terms of parent weight loss and child physical activity, but not child caloric intake. This study suggests that a PO treatment could provide similar results to PC in child weight loss and other relevant outcomes, and potentially could be more cost-effective and easier to disseminate. Although further research is needed, this study suggests that PO groups are a viable method for providing childhood obesity treatment.     

Moles,melanomas and epitheliomas in children

The management of moles which occur in childhood is important from the standpoint of clinical diagnosis and treatment. Melanomas of both the malignant and juvenile types are sometimes mistaken for ordinary moles. Malignant epithelial tumors are rare in childhood as are congenital tumors. There is a possible relationship between congenital defects of various types and childhood neoplasms.     

MOLES,MELANOMAS AND EPITHELIOMAS IN CHILDREN

The management of moles which occur in childhood is important from the standpoint of clinical diagnosis and treatment. Melanomas of both the malignant and juvenile types are sometimes mistaken for ordinary moles. Malignant epithelial tumors are rare in childhood as are congenital tumors. There is a possible relationship between congenital defects of various types and childhood neoplasms.     

Modeling Social Transmission Dynamics of Unhealthy Behaviors for Evaluating Prevention and Treatment Interventions on Childhood Obesity

Research evidence indicates that obesity has spread through social networks, but lever points for interventions based on overlapping networks are not well studied. The objective of our research was to construct and parameterize a system dynamics model of the social transmission of behaviors through adult and youth influence in order to explore hypotheses and identify plausible lever points for future childhood obesity intervention research. Our objectives were: (1) to assess the sensitivity of childhood overweight and obesity prevalence to peer and adult social transmission rates, and (2) to test the effect of combinations of prevention and treatment interventions on the prevalence of childhood overweight and obesity. To address the first objective, we conducted two-way sensitivity analyses of adult-to-child and child-to-child social transmission in relation to childhood overweight and obesity prevalence. For the second objective, alternative combinations of prevention and treatment interventions were tested by varying model parameters of social transmission and weight loss behavior rates. Our results indicated child overweight and obesity prevalence might be slightly more sensitive to the same relative change in the adult-to-child compared to the child-to-child social transmission rate. In our simulations, alternatives with treatment alone, compared to prevention alone, reduced the prevalence of childhood overweight and obesity more after 10 years (1.2–1.8% and 0.2–1.0% greater reduction when targeted at children and adults respectively). Also, as the impact of adult interventions on children was increased, the rank of six alternatives that included adults became better (i.e., resulting in lower 10 year childhood overweight and obesity prevalence) than alternatives that only involved children. The findings imply that social transmission dynamics should be considered when designing both prevention and treatment intervention approaches. Finally, targeting adults may be more efficient, and research should strengthen and expand adult-focused interventions that have a high residual impact on children.     

Giant prolactinoma presented as unilateral exophthalmos in a prepubertal boy: response to cabergoline

We report the case of a giant prolactinoma in a 7-year-old boy, which was complicated by unilateral exophthalmos. The initial levels of prolactin (PRL) were about 80,000 microU/ml. Treatment with cabergoline (CAB) resulted in rapid normalization of serum PRL (6 weeks after initiation of treatment) and reduction of tumor size. In particular, magnetic resonance imaging (MRI), which was done 2.5 months after the patient was put on CAB, revealed tremendous improvement with a decrease in the size of the tumor which now showed no extrasellar extension. Subsequent MRI studies demonstrated further improvement. Exophthalmos, anisocoria and visual fields improved. In summary, this patient represents the first report of the therapeutic use of CAB as the primary mode of treatment in a 7-year-old boy with infiltrative giant prolactinoma complicated by unilateral exophthalmos. It is a noninvasive treatment that can preserve and restore vision, as well as pituitary function, and is preferable to surgery or radiation in the treatment of prolactin-secreting macroadenoma in childhood and adolescence.     

Insecure maternal attachment is associated with depression in ADHD children

The objective of this study was to analyze the possible association between maternal attachment style and comorbidity associated with childhood ADHD. We evaluated a total of 103 children with ADHD treated at a Child and Adolescent Mental Health Centre and their mothers. Comorbidity was evaluated using the MINI-KID interview. Maternal attachment was evaluated using the Adult Attachment Questionnaire. We considered child variables that could be associated with the clinical course of ADHD, such as symptom severity, age, gender, evolution time, academic level, and current pharmacological treatment; parental variables, such as the mother’s psychiatric history, current psychopathology, marital status, academic level, income, and employment, were also considered. We found an association between maternal insecure attachment and comorbid depressive disorder in childhood ADHD. An insecure maternal attachment style must be considered in the assessment and treatment of childhood ADHD with comorbid depression.     

Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting. To examine whether these different phenotypes are due to differences in the VLCAD genotype, we investigated 58 different mutations in 55 unrelated patients representing all known clinical phenotypes and correlated the mutation type with the clinical phenotype. Our results show a clear relationship between the nature of the mutation and the severity of disease. Patients with the severe childhood phenotype have mutations that result in no residual enzyme activity, whereas patients with the milder childhood and adult phenotypes have mutations that may result in residual enzyme activity. This clear genotype-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established.     

Leukemia; duration of life in children treated with corticotropin and cortisone

The average duration of survival of 15 cases of childhood leukemia treated with corticotropin and cortisone was 6.8 months. This survival was the same as observed among 59 children who received no treatment, or treatment with x-ray, or blood transfusion alone. Despite the fact that objective evidence of remission was observed in 7 of 15 children treated with corticotropin and cortisone, the remissions were not reflected by a longer duration of life. Treatment of childhood leukemia with corticotropin and cortisone appears to be a palliative measure, without significant effect on the duration of life.     

LEUKEMIA—Duration of Life in Children Treated with Corticotropin and Cortisone

The average duration of survival of 15 cases of childhood leukemia treated with corticotropin and cortisone was 6.8 months. This survival was the same as observed among 59 children who received no treatment, or treatment with x-ray, or blood transfusion alone.Despite the fact that objective evidence of remission was observed in 7 of 15 children treated with corticotropin and cortisone, the remissions were not reflected by a longer duration of life.Treatment of childhood leukemia with corticotropin and cortisone appears to be a palliative measure, without significant effect on the duration of life.     

Management of childhood illness in Africa. Early evaluations show promising results

This article reports the positive evaluation results of the integrated management of childhood illness (IMCI) strategy for the last 3 years of operation in 28 countries in Africa. The strategy aimed to improve case management skills of health workers through training with locally adapted guidelines such as the use of clinical algorithms to detect the most common causes of childhood illnesses. In addition, the strategy was designed to improve the health system of the region, including the provision of essential drugs. A final component of the program seeks to optimize family and community practices in relation to child health, particularly care seeking behavior. Overall, the benefits include more rational drug use, increased attendance, improved provider morale, and improved perceptions of quality of care by mothers. Although its initial effects are rather small, it should be recognized that the proper implementation of IMCI should contribute to a steady reduction in childhood mortality in Africa.     

Performance of health workers in the management of seriously sick children at a kenyan tertiary hospital: before and after a training intervention

Background

Implementation of WHO case management guidelines for serious common childhood illnesses remains a challenge in hospitals in low-income countries. The impact of locally adapted clinical practice guidelines (CPGs) on the quality-of-care of patients in tertiary hospitals has rarely been evaluated.

Methods and Findings

We conducted, in Kenyatta National Hospital, an uncontrolled before and after study with an attempt to explore intervention dose-effect relationships, as CPGs were disseminated and training was progressively implemented. The emergency triage, assessment and treatment plus admission care (ETAT+) training and locally adapted CPGs targeted common, serious childhood illnesses. We compared performance in the pre-intervention (2005) and post-intervention periods (2009) using quality indicators for three diseases: pneumonia, dehydration and severe malnutrition. The indicators spanned four domains in the continuum of care namely assessment, classification, treatment, and follow-up care in the initial 48 hours of admission. In the pre-intervention period patients'' care was largely inconsistent with the guidelines, with nine of the 15 key indicators having performance of below 10%. The intervention produced a marked improvement in guideline adherence with an absolute effect size of over 20% observed in seven of the 15 key indicators; three of which had an effect size of over 50%. However, for all the five indicators that required sustained team effort performance continued to be poor, at less than 10%, in the post-intervention period. Data from the five-year period (2005–09) suggest some dose dependency though the adoption rate of the best-practices varied across diseases and over time.

Conclusion

Active dissemination of locally adapted clinical guidelines for common serious childhood illnesses can achieve a significant impact on documented clinical practices, particularly for tasks that rely on competence of individual clinicians. However, more attention must be given to broader implementation strategies that also target institutional and organisational aspects of service delivery to further enhance quality-of-care.     

Craniosynostosis: an analysis of the timing, treatment, and complications in 164 consecutive patients

Treatment options for the craniosynostoses vary from conservative observation until completion of growth to radical remodeling in infancy. To further define the timing and type of treatment necessary in these complex disorders, we have retrospectively analyzed all patients operated on for this deformity during the past 12 years. One-hundred and sixty-four patients with craniosynostosis were analyzed and subgrouped into asymmetrical (predominantly unilateral) and symmetrical (bilateral) deformities, in addition to segregation by age and type of procedure performed. This was done recognizing that no deformity, like no normal human face, is truly symmetrical. Results of treatment were categorized on the basis of the need for additional surgery and varied from no refinements necessary (category I) to major reduplication of the initial procedure (category IV). Analysis of the data led us to conclude that excellent results can be expected in the asymmetrical deformities group treated in infancy by a unilateral approach. Similarly, for the mild symmetrical deformities, treatment at this time by bilateral orbital advancement gives satisfactory results in the majority of patients. By contrast, the more severe symmetrical groups treated in childhood have a high incidence of requiring secondary major reconstructions, and consideration should be given to delaying craniofacial surgery until age 7 or older, although earlier cranial surgery may be advisable.     

Invisible impacts but long-term consequences: hypoplasia and contact in central Australia

The dental casts taken of Aboriginal people resident at Yuendumu, Central Australia, between 1950-1970 preserve a unique historical record of defects of the dental enamel (DDEs) among people born from 1890-1960 (n = 377). These data are used, in comparison with precontact data, to trace the chronological changes in childhood development that occurred among Aboriginal people from the point of initial engagement with white settlers to a period of overwhelming government control. The results demonstrate very little change in the frequency of DDE from the precontact period to 1929 but increases after that time, particularly after the forcible settlement of people on a government establishment at Yuendumu in 1946. Apart from the absolute increase in frequency, it is also clear that population variation decreased markedly, with growing numbers of children experiencing multiple defects in early childhood (ca. 0.8-1.5 years of age). The results also indicate that an early onset of DDE constituted a risk for further episodes. These changes in DDE correspond to periods of increasingly intense contact between Aboriginal people and Europeans and with changes to government policy aimed at assimilating the indigenous population. Such policies had marked costs for childhood development. The lack, however, of a visible marker of initial contact demonstrates the importance of the intensity of and motives behind interactions between indigenous and colonial populations in determining the health consequences of colonial encounters.     

Clinical course and seizure outcome of idiopathic childhood epilepsy: determinants of early and long-term prognosis

Background

Idiopathic epilepsies and epileptic syndromes predominate childhood and adolescence epilepsy. The aim of the present study was to investigate the clinical course and outcome of idiopathic childhood epilepsy and identify variables determining both early and long-term prognosis.

Methods

We followed 303 children with newly diagnosed idiopathic epilepsy aged 1–14 years old, both prospectively and retrospectively. Outcome was defined at one, 2 and 4 years of follow-up, as well as at the end of the study period for all patients. Based on the data collected, patients were classified in four patterns of clinical course: “excellent”, “improving”, “relapsing” and “poor”. Variables defined at intake and after the initial year of treatment were analyzed for their prognostic relevance towards the clinical course and outcome of the patients.

Results

The mean age at seizure onset was 6,7 years and the mean duration of follow-up was 8,3 years (range 2,0-22,0,SD 4,24). During the initial year of treatment, 70,3% of patients were seizure-free. The course of epilepsy was “excellent” in 53,1% of the subjects, “improving” in 22,8%, “relapsing” in 22,1% whereas only 6 children with idiopathic epilepsy (2%) had a “poor” clinical course exhibiting drug-resistance. After multivariate analysis, variables predictive of a poor initial response to therapy were early seizure onset, multiple seizure types and history of status epilepticus. At the end of follow-up, early response to treatment was of significant positive predictive value, while the presence of multiple seizure types and the history of migraine had a negative impact on prognosis.

Conclusions

In the vast majority of children, the long-term prognosis of idiopathic epilepsy is favorable. More than half of the patients attain seizure freedom immediately and their clinical course is considered “excellent”. About one fifth exhibit either an improving or a fluctuating course. Early seizure onset, multiple seizure types and status epilepticus are predictive of an initial poor response to treatment in children with idiopathic epilepsy. Initial non-response to treatment, multiple seizure types and history of migraine are determinants of a less favorable final outcome after long-term follow-up.

     

Cryoconservation des tissus testiculaires: Quel avenir?

Over the last twenty years, an increased incidence of cancer has been observed in the population of adolescents and young adults. With the progress in cancer diagnosis and therapy, childhood cancer has become a curable disease. The efficacy of treatment is associated with a high degree of toxicity and gonadal function is particularly sensitive to this toxicity. Prevention of sterility in childhood cancer survivors will become a major challenge in reproductive medicine. Cryopreservation of ovarian tissue is performed in girls and women before cancer treatment. Cryopreservation of ejaculated spermatozoa is possible in sexually mature boys. However, for prepubertal boys or after failure of ejaculated sperm collection, mature or immature testicular tissue banking should be proposed. However, an optimal cryopreservation protocol is a prerequisite for clinical applications. Furthermore, the future applications of immature testicular tissue banking should be developed, not solely autologous testicular tissue grafting, but also in vitro maturation of germ cells. Cryopreservation protocols, transplantation and in vitro maturation techniques should be improved in animal models and in humans.     

IgA deficiency in one of identical twins.

A disease resembling childhood coeliac disease occurred in one of identical twins. When the twins were investigated at the age of 23 the initial diagnosis could not be substantiated but the twin who had been ill had selective IgA deficiency. Differences dating from early infancy may have been a result of the discordance for IgA deficiency. Thus in some patients environmental influences may be important in either the initiation or the perpetuation of the deficiency.     

Feasibility of guided cognitive behaviour therapy (CBT) self-help for childhood anxiety disorders in primary care

Anxiety disorders in childhood are common, disabling and run a chronic course. Cognitive behaviour therapy (CBT) is effective but expensive and trained therapists are scarce. Guided self-help treatments may be a means of widening access to treatment. This study aimed to examine the feasibility of guided CBT self-help in primary care for childhood anxiety disorders, specifically in terms of therapist adherence, patient and therapist satisfaction and clinical gain.Participants were children aged between five and 12 years referred to two primary child and adolescent mental health services (PCAMHSs) in Oxfordshire, UK, who met diagnostic criteria for a primary anxiety disorder. Of the 52 eligible children, 41 anxious children were assessed for anxiety severity and interference before and after receiving CBT self-help delivered via a parent (total therapy time = five hours) by primary mental health workers (PMHWs). Therapy sessions were rated for treatment adherence and parents and PMHWs completed satisfaction questionnaires after treatment completion. Over 80% of therapy sessions were rated at a high level of treatment adherence. Parents and PMHWs reported high satisfaction with the treatment. Sixty-one percent of the children assessed no longer met the criteria for their primary anxiety disorder diagnosis following treatment, and 76% were rated as 'much'/'very much' improved on the Clinical Global Impression-Improvement (CGI-I) scale. There were significant reductions on parent and child report measures of anxiety symptoms, interference and depression. Preliminary exploration indicated that parental anxiety was associated with child treatment outcome. The findings suggest that guided CBT self-help represents a promising treatment for childhood anxiety in primary care.