Paediatric stroke: The need for interdisciplinary models of care

Abstract:   Stroke is an important cause of mortality and long-term morbidity in children. The aetiology of stroke in childhood differs from that of adults, with vasculopathies and congenital heart disease being the most commonly identified risk factors. Recognition and diagnosis are often delayed, limiting access to acute medical interventions such as thrombolysis. Optimal management of stroke in children is still not known and existing guidelines are at the level of expert consensus. Interdisciplinary childhood stroke programmes are required to meet the needs of this population and to contribute to the development of evidence-based therapies.     

Pathology of oesophageal tumours

Both epithelial and non-epithelial tumours are seen commonly within the oesophagus. Benign epithelial tumours usually take the form of polypoid squamous lesions; benign non-epithelial tumours tend to be submucosal and smooth muscle in origin. Malignant tumours of the oesophagus are mostly epithelial and divided into squamous cell carcinoma (SCC) and adenocarcinoma. Both tend to develop following epithelial dysplastic changes. Adenocarcinoma mostly arises in the metaplastic columnar lined mucosa seen in Barrett’s oesophagus. Risk factors for SCC include excess alcohol, poor diet and smoking whereas those for adenocarcinoma tend to relate to gastro-oesophageal reflux disease (GORD). Prognosis and management options in both tumours depend primarily on tumour stage.     

Immunoactivating Peptide P4 Augments Alveolar Macrophage Phagocytosis in Two Diverse Human Populations

New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniae ex vivo. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on ex vivo-derived human lung cells.     

β-cell dedifferentiation in diabetes is important,but what is it?

This commentary discusses the concept of β-cell dedifferentiation in diabetes, which is important but not well defined. A broad interpretation is that a state of differentiation has been lost, which means changes in gene expression as well as in structural and functional elements. Thus, a fully mature healthy β cell will have its unique differentiation characteristics, but maturing cells and old β cells will have different patterns of gene expression and might therefore be considered as dedifferentiated. The meaning of dedifferentiation is now being debated because β cells in the diabetic state lose components of their differentiated state, which results in severe dysfunction of insulin secretion. The major cause of this change is thought to be glucose toxicity (glucotoxicity) and that lowering glucose levels with treatment results in some restoration of function. An issue to be discussed is whether dedifferentiated β cells return to a multipotent precursor cell phenotype or whether they follow a different pathway of dedifferentiation.     

Problems & Solutions

Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail immediately. Selected problems and solutions are published each month in this section.     

Trends in and predictors of second‐hand smoke exposure indexed by cotinine in children in England from 1996 to 2006

Aims To explore trends in and predictors of second‐hand smoke (SHS) exposure in children. To identify whether inequalities in SHS exposure are changing over time. Design Repeated cross‐sectional study with data from eight annual surveys conducted over an 11‐year period from 1996 to 2006. Setting England. Participants Nationally representative samples of children aged 4–15 years living in private households. Measurements Saliva cotinine (4–15‐year‐olds), current smoking status (8–15‐year‐olds), smoking status of parents and carers, smoking in the home, socio‐demographic variables. Findings The most important predictors of SHS exposure were modifiable factors—whether people smoke in the house on most days, whether the parents smoke and whether the children are looked after by carers who smoke. Children from more deprived households were more exposed and this remained the case even after parental smoking status has been controlled for. Exposure over time has fallen markedly among children (59% decline over 11 years in geometric mean cotinine), with the most marked decline observed in the period immediately preceding smoke‐free legislation. Declines in exposure have generally been greater in children most exposed at the outset. For example, in children whose parents both smoke, median cotinine declined annually by 0.115 ng/ml compared with 0.019 ng/ml where neither parent smokes (P < 0.05). Conclusions In the 11 years leading up to smoke‐free legislation in England, the overall level of SHS exposure in children as well as absolute inequalities in exposure have been declining. Further efforts to encourage parents and carers to quit and to avoid smoking in the home would benefit child health.