Background-Lung hypoplasia and persistent pulmonary hypertension of the newborn limit survival in congenital diaphragmatic hernia (CDH). Unlike other diseases resulting in persistent pulmonary hypertension of the newborn, infants with CDH are refractory to inhaled nitric oxide (NO). Nitric oxide mediates pulmonary vasodilatation at birth in part via cyclic GMP production. Phosphodiesterase type 5 (PDE5) limits the effects of NO by inactivation of cyclic GMP. Because of the limited success in postnatal management of CDH, we hypothesized that antenatal PDE5 inhibition would attenuate pulmonary artery remodeling in experimental nitrofen-induced CDH. Methods and Results-Nitrofen administered at embryonic day 9.5 to pregnant rats resulted in a 60% incidence of CDH in the offspring and recapitulated features seen in human CDH, including structural abnormalities (lung hypoplasia, decreased pulmonary vascular density, pulmonary artery remodeling, right ventricular hypertrophy), and functional abnormalities (decreased pulmonary artery relaxation in response to the NO donor 2-(N,N-diethylamino)-diazenolate-2-oxide). Antenatal sildenafil administered to the pregnant rat from embryonic day 11.5 to embryonic day 20.5 crossed the placenta, increased fetal lung cyclic GMP and decreased active PDE5 expression. Antenatal sildenafil improved lung structure, increased pulmonary vessel density, reduced right ventricular hypertrophy, and improved postnatal NO donor 2-(N,N-diethylamino)-diazenolate-2-oxide-induced pulmonary artery relaxation. This was associated with increased lung endothelial NO synthase and vascular endothelial growth factor protein expression. Antenatal sildenafil had no adverse effect on retinal structure/function and brain development. Conclusions-Antenatal sildenafil improves pathological features of persistent pulmonary hypertension of the newborn in experimental CDH and does not alter the development of other PDE5-expressing organs. Given the high mortality/ morbidity of CDH, the potential benefit of prenatal PDE5 inhibition in improving the outcome for infants with CDH warrants further studies. (Circulation. 2011;123:2120-2131.)

Pettibon corrective procedures seemed to be effective at reducing the thoracolumbar scoliosis 15 degrees (43%) after six weeks. The subjective and objective results of this case study warrant further such investigations.

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All diabetics are at risk from the development of the specific and non-specific complications of the disorder. While good control with relative normoglycaemia may be beneficial, most of the emphasis on maintaining stricter blood glucose control has been aimed at the insulin-dependent diabetic. Seventy-four sylphonylurea-treated were observed for a year and their degree of control assessed and compared using simple clinical criteria, plasma glucose levels and haemoglobin A1c concentrations. Control was considered good in 55.4 per cent, 16.2 per cent and 14.9 per cent using each criterion respectively. Simple clinical assessment of control is therefore unlikely to achieve normoglycaemia in the majority of such patients. A more wide ranging assessment and a more aggressive approach to therapy may be desirable if better blood glucose control can be shown to produce a reduction in the significant morbidity and mortality in these patients.