Conditional Gata4 deletion in mice induces bile acid absorption in the proximal small intestine.

BACKGROUND AND AIMS: The transcription factor GATA4 is expressed throughout most of the small intestine except distal ileum, and restricts expression of the apical sodium-dependent bile acid transporter (ASBT), the rate-limiting intestinal bile acid transporter, to distal ileum. The hypothesis was tested that reduction of GATA4 activity in mouse small intestine results in an induction of bile acid transport in proximal small intestine sufficient to restore bile acid absorption and homeostasis after ileocaecal resection (ICR). METHODS: Bile acid homeostasis was characterised in non-surgical, sham or ICR mice using two recombinant Gata4 models in which Asbt expression is induced to different levels. RESULTS: Reduction of intestinal GATA4 activity resulted in an induction of ASBT expression, bile acid absorption and expression of bile acid-responsive genes in proximal small intestine, and a reduction of luminal bile acids in distal small intestine. While faecal bile acid excretion and bile acid pool size remained unchanged, the bile acid pool became more hydrophilic due to a relative increase in tauro-beta-muricholate absorption. Furthermore, proximal induction of Asbt in both Gata4 mutant models corrected ICR-associated bile acid malabsorption, reversing the decrease in bile acid pool size and increase in faecal bile acid excretion and hepatic cholesterol 7alpha-hydroxylase expression. CONCLUSIONS: Reduction of intestinal GATA4 activity induces bile acid absorption in proximal small intestine without inducing major changes in bile acid homeostasis. This induction is sufficient to correct bile acid malabsorption caused by ICR in mice.

Expansion thoracoplasty improves respiratory function in a rabbit model of postnatal pulmonary hypoplasia: a pilot study.

STUDY DESIGN: Using a rabbit model of postnatal pulmonary hypoplasia, we investigated how expansion thoracoplasty affected growth of the spine and lungs. OBJECTIVE: By constricting the hemithorax in a growing rabbit to create postnatal pulmonary hypoplasia, we quantified how expansion thoracoplasty affects lung volume, respiratory function, alveolar morphology, and spine growth. SUMMARY OF BACKGROUND DATA: In children with thoracic insufficiency syndrome, expansion thoracoplasty of the constricted hemithorax improves respiratory function and controls scoliosis. We hypothesize that expansion thoracoplasty of the constricted hemithorax improves pulmonary hypoplasia by allowing the lung to expand, improving respiratory function and stimulating lung growth. METHODS: Postnatal pulmonary hypoplasia and scoliosis were induced in 5-week old rabbits by constricting left ribs 3 to 8. Expansion thoracoplasty through the fused ribs was performed at 10 weeks. These were compared with Disease rabbits allowed to grow with a constricted left hemithorax and Normal rabbits. Spine and thoracic deformity, right and left lung volumes were measured on reconstructed 3-dimensional computed tomography images and functional residual capacity measured by plethysmography. At maturity, lungs were excised and quantitative histology performed to measure alveolar air fraction and surface density. RESULTS: Expansion thoracoplasty of the constricted left hemithorax improved scoliosis but increased left lung volumes only moderately compared with Disease rabbits. For Disease and Thoracoplasty Treated rabbits, a compensatory increase in the volume of the right lung maintained total lung volumes equivalent to Normal. Alveolar air space fraction was greater in Disease rabbits, suggestive of emphysema improved by expansion thoracoplasty. Capillaries adjacent to the alveoli were prominent in Thoracoplasty Treated rabbits. CONCLUSION: Expansion thoracoplasty reduces scoliosis and increases the volume of the constricted hemithorax, but the relative increase in the ipsilateral lung volume is small since compensatory hypertrophy of the contralateral lung also occurred. Expansion thoracoplasty may improve respiratory function by increasing alveolar capillaries and preventing emphysematous changes.

Removal of a sewing needle from an occult esophageal ingestion in a 9-month-old.

A healthy 9-month-old boy presented with a 1-month history of cough. A chest x-ray showed a linear metallic foreign body (FB) lying transversely in the posterior mediastinum. Computed tomographic scan confirmed the location and size of the metallic FB and also revealed a large pericardial effusion that was corroborated by echocardiogram. The patient underwent a right thoracotomy revealing a normal esophagus without mediastinitis and a 12-mm needle in the posterior mediastinum embedded in the pericardium with the sharp end abutting the left atrium. The needle was extracted uneventfully, and his postoperative course was unremarkable. The diagnosis and treatment for this case are discussed along with a review of the literature.