Browsing by Author "Lewis, S."
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- Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trialPublication . Dennis, M.; Lewis, S.; Warlow, C.; FOOD Trial CollaborationSummary Background Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients’ outcomes at 6 months. Methods The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat. Findings Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5·8% (95% CI –0·8 to 12·5, p=0·09) and a reduction in death or poor outcome of 1·2% (–4·2 to 6·6, p=0·7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1·0% (–10·0 to 11·9, p=0·9) and an increased risk of death or poor outcome of 7·8% (0·0 to 15·5, p=0·05). Interpretation Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients
- Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2Publication . Wen, J.; Lopes, F.; Soares, G.; Farrell, S.; Nelson, C.; Qiao, Y.; Martell, S.; Badukke, C.; Bessa, C.; Ylstra, B.; Lewis, S.; Isoherranen, N.; Maciel, P.; Rajcan-Separovic, E.Background Rare, recurrent genomic imbalances facilitate the association of genotype with abnormalities at the “whole body” level. However, at the cellular level, the functional consequences of recurrent genomic abnormalities and how they can be linked to the phenotype are much less investigated. Method and results We report an example of a functional analysis of two genes from a new, overlapping microdeletion of 2p13.2 region (from 72,140,702-72,924,626). The subjects shared intellectual disability (ID), language delay, hyperactivity, facial asymmetry, ear malformations, and vertebral and/or craniofacial abnormalities. The overlapping region included two genes, EXOC6B and CYP26B1, which are involved in exocytosis/Notch signaling and retinoic acid (RA) metabolism, respectively, and are of critical importance for early morphogenesis, symmetry as well as craniofacial, skeleton and brain development. The abnormal function of EXOC6B was documented in patient lymphoblasts by its reduced expression and with perturbed expression of Notch signaling pathway genes HES1 and RBPJ, previously noted to be the consequence of EXOC6B dysfunction in animal and cell line models. Similarly, the function of CYP26B1 was affected by the deletion since the retinoic acid induced expression of this gene in patient lymphoblasts was significantly lower compared to controls (8% of controls). Conclusion Haploinsufficiency of CYP26B1 and EXOC6B genes involved in retinoic acid and exocyst/Notch signaling pathways, respectively, has not been reported previously in humans. The developmental anomalies and phenotypic features of our subjects are in keeping with the dysfunction of these genes, considering their known role. Documenting their dysfunction at the cellular level in patient cells enhanced our understanding of biological processes which contribute to the clinical phenotype.