Transcatheter closure of atrial septal defects--is balloon sizing still necessary?

INTRODUCTION: The device closure of atrial septal defects has evolved over the years. In the early days of transcatheter occlusion, balloon sizing was used to choose an appropriate sized device. We postulate that balloon sizing does not value-add to the procedure and is unnecessary. MATERIALS AND METHODS: Patients who had balloon sizing, with (Group 1, n = 38) or without (Group 2, n = 21) atrial septal defect closure, were compared to another group (Group 3, n = 64) who had atrial septal defect closure without balloon sizing. Although the atrial septal defect size (mm) in those without balloon sizing (Group 3) compared to patients who had balloon sizing (Group 1) (18.3 +/- 5.4 vs 14.8 +/- 5.8; P = 0.021) was larger, the Amplatzer septal occluder size chosen (mm) (21.6 +/- 6.3 vs 21.2 +/- 8.1; P = 0.693) was similar. RESULTS: We analysed the degree of absolute sizing, defined as [(Balloon or Amplatzer occluder size) - (transoesophageal echocardiography size)], versus relative sizing, which is defined as [(Balloon or Amplatzer occluder size)--(transoesophageal echocardiography size) / (Balloon or Amplatzer occluder size)]. It was evident that there was greater absolute and relative over-sizing (6.3 +/- 4.4 mm vs 4.2 +/- 2.1 mm; P = 0.009 and 28.3 +/- 15.4% vs 20.0 +/- 7.0%; P = 0.001, respectively) in patients with balloon sizing (Group 1) compared to those who did not (Group 3). Even a greater degree of absolute (5.1 +/- 3.9 mm vs 9.5 +/- 4.7 mm; P <0.001) and relative over-sizing (24.8 +/- 15.6% vs 33.0 +/- 13.6%; P = 0.001) was observed in patients who had balloon sizing but there was no closure (Group 2) compared to those who had balloon sizing and closure of their defects (Group 1). CONCLUSION: Our results showed that balloon sizing tended to over-size the atrial septal defect. This may have an important bearing in selecting a larger device than necessary, or even precluding transcatheter closure of the larger atrial septal defects. It is also associated with increased procedural, fluoroscopy time and cost. We suggest that balloon sizing may no longer be necessary in the protocol of device closure of an atrial septal defect.

Antenatal glucocorticoids reset the level of baseline and hypoxemia-induced pituitary-adrenal activity in the sheep fetus during late gestation.

This study examined the effects of dexamethasone treatment on basal hypothalamo-pituitary-adrenal (HPA) axis function and HPA responses to subsequent acute hypoxemia in the ovine fetus during late gestation. Between 117 and 120 days (term: approximately 145 days), 12 fetal sheep and their mothers were catheterized under halothane anesthesia. From 124 days, 6 fetuses were continuously infused intravenously with dexamethasone (1.80 +/- 0.15 microg.kg(-1).h(-1) in 0.9% saline at 0.5 ml/h) for 48 h, while the remaining 6 fetuses received saline at the same rate. Two days after infusion, when dexamethasone had cleared from the fetal circulation, acute hypoxemia was induced in both groups for 1 h by reducing the maternal fraction of inspired O2. Fetal dexamethasone treatment transiently lowered fetal basal plasma cortisol, but not ACTH, concentrations. However, 2 days after treatment, fetal basal plasma cortisol concentration was elevated without changes in basal ACTH concentration. Despite elevated basal plasma cortisol concentration, the ACTH response to acute hypoxemia was enhanced, and the increment in plasma cortisol levels was maintained, in dexamethasone-treated fetuses. Correlation of fetal plasma ACTH and cortisol concentrations indicated enhanced cortisol output without a change in adrenocortical sensitivity. The enhancements in basal cortisol concentration and the HPA axis responses to acute hypoxemia after dexamethasone treatment were associated with reductions in pituitary and adrenal glucocorticoid receptor mRNA contents, which persisted at 3-4 days after the end of treatment. These data show that prenatal glucocorticoids alter the basal set point of the HPA axis and enhance HPA axis responses to acute stress in the ovine fetus during late gestation.

Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration.

The canine disease, X-linked progressive retinal atrophy (XLPRA), is similar to human RP3, an X-linked form of retinitis pigmentosa, and maps to the same region in the X chromosome. Analysis of the physical map of the XLPRA and RP3 intervals shows a high degree of conservation in terms of genes and their order. We have found different mutations in exon ORF15 of the RPGR gene in two distinct mutant dog strains (XLPRA1, XLPRA2). Microdeletions resulting in a premature stop or a frameshift mutation result in very different retinal phenotypes, which are allele-specific and consistent for each mutation. The phenotype associated with the frameshift mutation in XLPRA2 is very severe and manifests during retinal development; the phenotype resulting from the XLPRA1 nonsense mutation is expressed only after normal photoreceptor morphogenesis. Splicing of RPGR mRNA transcripts in retina is complex, and either exon ORF15 or exon 19 can be a terminal exon. The retina-predominant transcript contains ORF15 as a terminal exon, and is expressed in normal and mutant retinas. The frameshift mutation dramatically alters the deduced amino acid sequence, and the protein aggregates in the endoplasmic reticulum of transfected cells. The cellular and molecular results in the two canine RPGR exon ORF15 mutations have implications for understanding the phenotypic variability found in human RP3 families that carry similar mutations.