Specific antibody deficiency in children with chronic wet cough

The prevalence and clinical significance of specific polysaccharide antibody deficiency (SAD) in children are poorly understood. The authors sought to determine the prevalence of SAD in children with chronic wet cough, through a retrospective study of all children with chronic wet cough attending our tertiary respiratory clinic over a 12-month period. Antibody levels to 13 pneumococcal serotypes were measured following vaccination with the unconjugated pneumococcal polysaccharide vaccine, Pneumovax II, and clinical data were reviewed. Twenty-four children over 2 years of age with chronic wet cough were vaccinated. Fourteen (58%) failed to mount an adequate antibody response, consistent with SAD. Children with SAD were more likely than children with normal antibody responses to require intravenous antibiotics (p=0.035) and to have abnormal chest radiographs (p=0.029). The authors conclude that SAD is present in a significant number of children with chronic wet cough. The clinical significance and long-term outcome of SAD warrant further investigation in prospective studies.     

Absence of association between ex vivo susceptibility to doxycycline and pftetQ and pfmdt copy numbers in Plasmodium falciparum isolates from Dakar, Senegal

The objective of this study was to validate the use of pftetQ and pfmdt genes as molecular markers of decreased in vitro susceptibility to doxycycline in 113 Plasmodium falciparum isolates from Dakar, Senegal. The results show that copy numbers of pftetQ and pfmdt, estimated by TaqMan real-time PCR, are not significantly associated with reduced susceptibility to doxycycline in vitro; however, the number of samples with a high doxycycline IC(50) was likely to be too low to derive statistically significant results. Thus, no definitive conclusions could be drawn. The markers should be further tested by analysing more isolates.     

Interval between onset of symptoms and diagnosis of medulloblastoma in children: distribution and determinants in a population-based study

Hospital-based studies have reported long delays in the diagnosis of paediatric brain tumours. Our objective was to describe the duration between onset of symptoms and diagnosis of medulloblastoma in children and study their clinical determinants in a population-based study. This retrospective cohort study included all paediatric medulloblastoma from a region of France from 1990 to 2005. The median interval from symptom onset until diagnosis for these 166 patients was 65?days and did not decrease during the study period. The most frequent manifestations were: vomiting (88%), headaches (79%), psychomotor regression (60% of children under 3?years), psychological symptoms (27%), strabismus (26%), and asthenia (25%). For one third of the children under 3?years, the diagnosis was made only after life-threatening signs of intracranial hypertension appeared. The prediagnosis interval was significantly longer (median 91 vs. 60?days, p?=?0.001) in children with psychological symptoms (27%). Causes for intervals that exceeded the median (65?days) included inconsistent (25%) or late (36%) combination of headaches and vomiting, a period of spontaneous symptom remission (14%?C20%), no (24%) or late (57%) neurological signs, psychological symptoms (35%), and a normal neurological examination (27%). Time to medulloblastoma diagnosis in children remains fairly long, despite advances in imaging. Primary-care physicians must be suspicious not only of suggestive neurological signs, but also of non-specific symptoms that persist or are multiple. A meticulous neurological examination and cerebral imaging for such patients might facilitate earlier diagnosis.     

Lovastatin regulates brain spontaneous low-frequency brain activity in Neurofibromatosis type 1

In the Neurofibromatosis type 1 (NF1) mouse model, lovastatin, used clinically for hypercholesterolemia, improves cognitive dysfunction. While such impairment has been studied in NF1, the neural substrates remain unclear. The aim of this imaging add-on to a Phase 1 open-label trial was to examine the effect of lovastatin on Default Network (DN) resting state functional connectivity (RSFC). Seven children with NF1 (aged 11.9 ± 2.2; 1 female) were treated with lovastatin once daily for 12 weeks. A 7-min 3-T echo-planar-imaging scan was collected one day before beginning treatment (off-drug) and the last day of treatment (on-drug) while performing a flanker task. After regressing-out task-associated variance, we used the residual time series as "continuous resting-state data" for RSFC analyses using 11 DN regions of interest. For qualitative comparisons, we included a group of 19 typically developing children (TDC) collected elsewhere. In the on-drug condition, lovastatin increased long-range positive RSFC within DN core regions (i.e., anterior medial prefrontal cortex and posterior cingulate cortex, PCC). In addition, lovastatin produced less diffuse local RSFC in the dorsomedial prefrontal cortex and PCC. The pattern of RSFC observed in the NF1 participants when on-drug closely resembled the RSFC patterns exhibited by the TDC. Lovastatin administration in this open trial regulated anterior-posterior long-range and local RSFC within the DN. These preliminary results are consistent with a role for lovastatin in normalization of developmental processes and with apparent benefits in a mouse NF1 model.     

Working memory processing of traumatic material in women with posttraumatic stress disorder

Background

Posttraumatic stress disorder (PTSD) is associated with medial frontal and amygdala functional alterations during the processing of traumatic material and frontoparietal dysfunctions during working memory tasks. This functional magnetic resonance imaging (fMRI) study investigated the effects of trauma-related words processing on working memory in patients with PTSD.

Methods

We obtained fMRI scans during a 3-back task and an identity task on both neutral and trauma-related words in women with PTSD who had been sexually abused and in healthy, nonexposed pair-matched controls.

Results

Seventeen women with PTSD and 17 controls participated in the study. We found no behavioural working memory deficit for the PTSD group. In both tasks, deactivation of posterior parietal midline regions was more pronounced in patients than controls. Additionally, patients with PTSD recruited the left dorsolateral frontal sites to a greater extent during the processing of trauma-related material than neutral material.

Limitations

This study included only women and did not include a trauma-exposed non-PTSD control group; the results may, therefore, have been influenced by sex or by effects specific to trauma exposure.

Conclusion

Our results broadly confirm frontal and parietal functional variations in women with PTSD and suggest a compensatory nature of these variations with regard to the retreival of traumatic memories and global attentional deficits, respectively, during cognitively challenging tasks.     

Neurogenesis-independent antidepressant-like effects on behavior and stress axis response of a dual orexin receptor antagonist in a rodent model of depression

Growing evidence indicates that an increase of orexin (or hypocretin) signaling is involved in the pathophysiology of major depression, but little is known regarding the causal link between the orexinergic system and depressive-like states. Here we blocked orexin receptors in mice subjected to unpredictable chronic mild stress (UCMS) to investigate putative antidepressant-like effects of this treatment, as well as the underlying mechanisms. BALB/c mice were exposed to 9 weeks of UCMS and from the third week onward treated daily with fluoxetine (20?mg/kg per day, per os) or with the dual orexin receptor antagonist almorexant (100?mg/kg per day, per os). The effects of UCMS regimen and pharmacological treatments were assessed by physical measures and behavioral testing. The dexamethasone suppression test was performed to examine the integrity of the negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis, and immunohistochemical markers were used to assess cell proliferation (Ki-67), immature newborn neurons (doublecortin), and mature newborn neurons (5-bromo-2'-deoxyuridine/NeuN) in the dorsal and ventral parts of the hippocampus. Our results show that 7 weeks of fluoxetine or almorexant treatments counteract the UCMS-induced physical and behavioral alterations. Both treatments prevented the HPA axis dysregulation caused by UCMS, but only fluoxetine reversed the UCMS-induced decrease of hippocampal cell proliferation and neurogenesis, while chronic almorexant treatment decreased cell proliferation and neurogenesis specifically in the ventral hippocampus. Taken together, this is the first evidence that pharmacological blockade of the orexinergic system induces a robust antidepressant-like effect and the restoration of stress-related HPA axis defect independently from a neurogenic action.     

Shared decision making: improving care for children with autism

Abstract We assessed the extent to which parents of children with autism spectrum disorder report that they are engaged in shared decision making. We measured the association between shared decision making and (a) satisfaction with care, (b) perceived guidance regarding controversial issues in autism spectrum disorder, and (c) perceived assistance navigating the multitude of treatment options. Surveys assessing primary medical care and decision-making processes were developed on the basis of the U.S. Department of Health and Human Service's Consumer Assessment of Healthcare Providers and Systems survey. In May 2009, after pilot testing, we sent surveys to 203 parents of children from ages 3 to 18 with International Classification of Diseases-9 and parent-confirmed autism spectrum disorder diagnoses. The response rate was 64%. Controlling for key demographic variables, parents of children with autism spectrum disorder reporting higher levels of shared decision making reported significantly greater satisfaction with the overall quality of their child's health care (p ≤ .0001). Parents reporting higher levels of shared decision making were also significantly more likely to report receiving guidance on the many treatment options (p = .0002) and controversial issues related to autism spectrum disorder (p = .0322). In this study, shared decision making was associated with higher parent satisfaction and improved guidance regarding treatments and controversial issues within primary care for children with autism spectrum disorder.