Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia.

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.

Adolescent idiopathic scoliosis treatment using pettibon corrective procedures: a case report.

OBJECTIVE: To investigate the possible benefits of using Pettibon corrective procedures to reduce the curvature associated with idiopathic scoliosis. These procedures were tested to determine potential effectiveness in a single patient. CLINICAL FEATURES: A patient with a 35 degrees left convex thoracolumbar scoliosis was treated using Pettibon corrective procedures. Initial and follow-up outcome measures included a Borg pain scale, a Functional Rating Index, a balance test, and radiographic analysis. INTERVENTION AND OUTCOME: The patient was treated using a combination of manipulative and rehabilitative procedures designed to restore normal sagittal curves and reduce the severity of the coronal curvatures. After six weeks of treatment, the post treatment radiograph revealed a 20 degrees left convex thoracolumbar scoliosis, as well as decreases in the Borg pain scale from six to two, and Functional Rating Index score from 18/40 to 7/40 after the trial period. Her balance time increased from 18 seconds to 56 seconds. CONCLUSION: 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.