The pulmonary pathology for which a patient receives ventilatory support may increase the risk of developing barotrauma, because an underlying disease process may weaken the vasculature and render the lung more susceptible to damage by mechanical ventilation. We determined the response of isolated young rabbit lungs to mechanical ventilation after oleic acid (OA) injury. New Zealand White rabbits (0.7-1.3 kg) were anesthetized with pentobarbital sodium (30 mg/kg), tracheotomized, and exsanguinated. The heart and lungs were isolated and perfused with autologous blood at a constant flow. The capillary filtration coefficient (Kf,c, in ml.min-1.cmH2O-1.100 g wet wt-1) and pulmonary arterial (Ppa) and venous pressures were determined before and 30 and 60 min after oleic acid administration (OA group; 0.2 ml into the venous reservoir), ventilation alone (Vent group; peak inspiratory pressure = 25 cmH2O), or oleic acid combined with ventilation (OA + Vent group). Ppa transiently increased by 4.21 +/- 0.822 cmH2O after OA administration but then returned to approximately control values. Baseline Kf,c values for OA (0.288 +/- 0.042), Vent (0.296 +/- 0.035), or OA + Vent (0.276 +/- 0.028) groups were not significantly different from each other. Kf,c after either OA administration (0.45 +/- 0.066) or Vent (0.35 +/- 0.75) were not significantly different from each other or from baseline measurements. In the group ventilated after OA administration (OA + Vent), Kf,c (0.883 +/- 0.148) increased significantly from baseline (P less than 0.001) and was significantly different from all other treatment groups. We conclude that the combination of minimal OA injury and ventilation was more deleterious to the lung than either one alone.

No abstract

The factors that regulate transcription and spatial expression of the adult skeletal muscle Na+ channel, Na(V) 1.4, are poorly understood. Here we tested the role of the transcription factor MRF4, one of four basic helix-loop-helix (bHLH) factors expressed in skeletal muscle, in regulation of the Na(V) 1.4 Na+ channel. Overexpression of MRF4 in C2C12 muscle cells dramatically elevated Na(V) 1.4 reporter gene expression, indicating that MRF4 is more efficacious than the other bHLH factors expressed at high levels endogenously in these cells. In vivo, MRF4 protein was found both in extrajunctional and subsynaptic muscle nuclei. To test the importance of MRF4 in Na(V) 1.4 gene regulation in vivo, we examined Na+ channel expression in MRF4-null mice using several techniques, including Western blotting, immunocytochemistry, and electrophysiological recording. By all methods, we found that expression of the Na(V) 1.4 Na+ channel was substantially reduced in MRF4-null mice, both in the surface membrane and at neuromuscular junctions. In contrast, expression of the acetylcholine receptor, and in particular its alpha subunit, was unchanged, indicating that MRF4 regulation of Na+ channel expression was selective. Expression of the bHLH factors myf-5, MyoD, and myogenin was increased in MRF4-null mice, but these factors were not able to fully maintain Na(V) 1.4 Na+ channel expression either in the extrajunctional membrane or at the synapse. Thus, MRF4 appears to play a novel and selective role in adult muscle.

SummaryWe have previously shown that the basic helix-loop-helix (bHLH) transcription factors coordinate Na V 1.4 Na + channel gene expression in skeletal muscle, but the identity of the co-factors they direct is unknown. Using C2C12 muscle cells as a model system, we test the hypothesis that the bHLH factors counteract negative regulation exerted through a repressor E box (−90/−85) by recruiting positive-acting transcription factors to the nucleotides (−135/−57) surrounding the repressor E box. We used electrophoretic mobility shift assays to identify candidate factors that bound the repressor E box or these adjacent regions. Repressor E box-binding factors included the known transcription factor, ZEB/AREB6, and a novel repressor E box-binding factor designated REB. Mutations of the repressor E box that interfere with the binding of these factors prevented repression. The transcription factor, nuclear factor I (NFI), bound immediately upstream and downstream of the repressor E box. Mutation of the NFI binding sites diminished the ability of myogenin and MRF4 to counteract repression. Based on these observations we suggest that bHLH factors recruit NFI to enhance skeletal muscle Na + channel expression.

Purpose Correction of refractive error in children is important for visual and educational development. The aim of this questionnaire‐based study was to explore paediatric refractive correction by optometrists in England. Methods An online questionnaire was piloted and distributed to optometrists in England. The questionnaire asked about respondents' characteristics (such as type of practice), management of refractive error in 1‐ and 3‐year‐old children and sources of information used as a basis for decisions on prescribing refractive error in children. Results Two hundred and ninety‐three questionnaires were returned, although only 139 (47%) were fully completed. In an average month, about half of respondents examined no children between 0 and 2 years of age, and about half examined no more than five children aged 3–4 years. A significant proportion indicated they would refer children aged 1 or 3 years with refractive error and no other signs or symptoms into the hospital eye service. Almost a quarter would prescribe in full or in part an isometropic refractive correction of +2.00 D for a 3‐year‐old (within the normal range) with no other signs or symptoms, suggesting a degree of unnecessary prescribing. Almost all would act in cases of clinically significant refractive error. Respondents made similar use of their colleagues, optometric or postgraduate/continuing education, professional guidance and peer‐reviewed research as sources of evidence on which to base decisions about prescribing for paediatric refractive errors. Most reported ‘never’ or ‘rarely’ using Cochrane reviews. Conclusions These results suggest optometrists often defer management of paediatric refractive error to the hospital eye service, with implications in terms of underutilisation of community optometric expertise and burden on the National Health Service. In some cases, the results indicate a mismatch between respondents' reported management and existing guidance/guidelines on paediatric prescribing.