Transcatheter Atrial Septal Defect Closure in Children with and without Fluoroscopy: A Comparison.

OBJECTIVE: The aim of this study was to compare feasibility, effectiveness, safety, and outcome of atrial septal defect (ASD) device closure in children with and without fluoroscopy guidance. METHODS AND RESULTS: Children undergoing transcatheter ASD closure between 2002 and 2016 were included into this single center, retrospective study. Patients were analysed in two groups [1: intraprocedural fluoroscopy ± transoesophageal echocardiography (TOE) guidance; 2: TOE guidance alone]. Three-hundred-ninety-seven children were included, 238 (97 male) in group 1 and 159 (56 male) in group 2. Two-hundred-twenty-nine of 238 (96%) patients underwent successful fluoroscopy guided ASD closures versus 154/159 (97%) successful procedures with TOE guidance alone. Median weight (IQR) at intervention was 20kg (16.0-35.0) in group 1 versus 19.3kg (16.0-31.2) in group 2. Mean (SD) preinterventional ASD diameter was 12.4mm (4.4) in group 1 versus 12.2mm (3.9) in group 2. There was no significant difference in number of defects or characteristics of ASD rims. Median procedure time was shorter in group 2 [60min (47-86) versus 34min (28-44)]. Device-size-to-defect-ratio was similar in both groups [group 1: 1.07 versus group 2: 1.09]. There were less technical intraprocedural events in group 2 [10 (6.3%) versus 47 (20%)]. Intraprocedural complications were less frequent in group 2 [1 (0.6%) versus 8 (3.3%)]. CONCLUSION: Transcatheter ASD device closure with TOE guidance alone (i.e., without fluoroscopy) is as effective and safe as ASD closure with fluoroscopy guidance. As fluoroscopy remains an important adjunct to transoesophageal echocardiography, especially in complex defects and complications, procedures are always performed in a fully equipped cardiac catheterization laboratory.

Startle and prepulse inhibition as a function of background noise: a computational and experimental analysis.

Schmajuk and Larrauri [Schmajuk NA, Larrauri JA. Neural network model of prepulse inhibition. Behav Neurosci 2005;119:1546-62.] introduced a real-time model of acoustic startle, prepulse inhibition (PPI) and facilitation (PPF) in animals and humans. The model assumes that (1) positive values of changes in noise level activate an excitatory and a facilitatory pathway, and (2) absolute values of changes in noise level activate an inhibitory pathway. The model describes many known properties of the phenomena and the effect of brain lesions on startle, PPI, and PPF. The purpose of the present study is to (a) establish the magnitude of startle and PPI as a function of pulse, prepulse, and background intensity, and (b) test the model predictions regarding an inverted-U function that relates startle to the intensity of the background noise.

A schizophrenia-related sensorimotor deficit links alpha 3-containing GABAA receptors to a dopamine hyperfunction.

Overactivity of the dopaminergic system in the brain is considered to be a contributing factor to the development and symptomatology of schizophrenia. Therefore, the GABAergic control of dopamine functions was assessed by disrupting the gene encoding the alpha3 subunit of the GABA(A) receptor. alpha3 knockout (alpha3KO) mice exhibited neither an obvious developmental defect nor apparent morphological brain abnormalities, and there was no evidence for compensatory up-regulation of other major GABA(A)-receptor subunits. Anxiety-related behavior in the elevated-plus-maze test was undisturbed, and the anxiolytic-like effect of diazepam, which is mediated by alpha2-containing GABA(A) receptors, was preserved. As a result of the loss of alpha3 GABA(A) receptors, the GABA-induced whole-cell current recorded from midbrain dopamine neurons was significantly reduced. Spontaneous locomotor activity was slightly elevated in alpha3KO mice. Most notably, prepulse inhibition of the acoustic startle reflex was markedly attenuated in the alpha3KO mice, pointing to a deficit in sensorimotor information processing. This deficit was completely normalized by treatment with the antipsychotic D2-receptor antagonist haloperidol. The amphetamine-induced hyperlocomotion was not altered in alpha3KO mice compared with WT mice. These results suggest that the absence of alpha3-subunit-containing GABA(A) receptors induces a hyperdopaminergic phenotype, including a severe deficit in sensorimotor gating, a common feature among psychiatric conditions, including schizophrenia. Hence, agonists acting at alpha3-containing GABA(A) receptors may constitute an avenue for an effective treatment of sensorimotor-gating deficits in various psychiatric conditions.

Cardiac arrest in an infant with congenital adrenal hyperplasia.

We report a 3-month-old boy who suffered an out-of-hospital cardiac arrest. During resuscitation, the medical team was informed that he was receiving hydrocortisone treatment. The possibility of adrenal insufficiency with hyperkalemic cardiac arrest prompted the administration of calcium, which resulted in the return of spontaneous circulation. The infant's diagnosis of congenital adrenal hyperplasia was not spontaneously mentioned by the parents. This case illustrates the importance of obtaining adequate parental information and considering hyperkalemia as a possible cause of cardiac arrest.

Effect of phenobarbital on the expression of bile salt and organic anion transporters of rat liver.

BACKGROUND/AIMS: The hepatic clearance of drugs and cholephilic organic anions is stimulated by phenobarbital (PB). Our aim was to analyze the effects of PB on the expression of hepatocellular bile salt and organic anion transporters. METHODS: Male Sprague-Dawley rats were treated intraperitoneally with PB (80 mg/kg/d) or saline for 5 days. Transporter expression was quantified by northern and western blot analysis and initial uptake rates of bromosulphophthalein (BSP) and digoxin were measured in isolated hepatocytes. RESULTS: Compared to control rats, PB treatment increased expression of the organic anion transporting polypeptide 2 (Oatp2; Slc21aS) more than 2-fold on the RNA (P < 0.05) and protein (P < 0.001) levels. Expression of Oatpl (Slc21al), Oatp4 (Slc21a6) and the Na+-taurocholate cotransporting polypeptide (Ntcp; Slc10a1) was unaltered. At the canalicular pole, expression of the bile salt export pump (Bsep; ABCB11) and of the multidrug resistance proteins 2 (Mrp2; ABCC2) and 6 (Mrp6; ABCC6) was not significantly changed. Whereas hepatocellular BSP uptake was unaffected by PB, digoxin uptake was stimulated 4-fold. CONCLUSIONS: The induction of digoxin uptake by PB correlates with Oatp2 expression. In contrast, the lack of increase of Oatpl and Oatp4 expression is in accordance with unchanged BSP uptake. These data challenge the previously held view that PB induces hepatocellular BSP uptake systems.

Identification of organic anion transporting polypeptide 4 (Oatp4) as a major full-length isoform of the liver-specific transporter-1 (rlst-1) in rat liver.

A novel organic anion transporting polypeptide (Oatp)4(1) was isolated from rat liver that is 35 amino acids longer than the reported rat liver specific organic anion transporter (rlst)-1 and exhibits a 64% amino acid sequence identity with the human OATP-C (LST-1/OATP2; gene symbol SLC21A6). When expressed in Xenopus laevis oocytes, Oatp4 (Slc21a10) mediated polyspecific uptake of a variety of organic anions including taurocholate (K(m) approximately 27 microM), bromosulfophthalein (K(m) approximately 1.1 microM) and steroid conjugates. Based on nuclease protection analysis Oatp4 appears to be the predominant transcript in rat liver indicating that rlst-1 plays a minor role in overall hepatic organic anion uptake.