Familial Sinus Node Disease Caused by a Gain of GIRK (G-Protein Activated Inwardly Rectifying K Channel) Channel Function.

Background: Inherited forms of sinus node dysfunction (SND) clinically include bradycardia, sinus arrest, and chronotropic incompetence and may serve as disease models to understand sinus node physiology and impulse generation. Recently, a gain-of-function mutation in the G-protein gene GNB2 led to enhanced activation of the GIRK (G-protein activated inwardly rectifying K channel). Thus, human cardiac GIRK channels are important for heart rate regulation and subsequently, genes encoding their subunits Kir3.

Aortic elasticity deterioration proves intrinsic abnormality of the ascending aorta in pediatric Turner syndrome unrelated to the aortic valve morphology.

Turner syndrome (TS) is a common genetic disorder in females with high incidence of ascending aortic dilatation and even dissection occurring as early as in the second decade. Known risk factors (RF) are bicuspid aortic valves (BAV), coarctation of the aorta (CoA), and arterial hypertension. Since 10% of dissections occur in patients without RF, an intrinsic aortic wall abnormality has been postulated.

Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease.

Background: In chronic kidney disease (CKD), serum concentrations of fibroblast growth factor 23 (FGF23) increase progressively as glomerular filtration rate declines, while renal expression of the FGF23 coreceptor Klotho decreases. Elevated circulating FGF23 levels are strongly associated with mortality and with left ventricular hypertrophy (LVH), which is a major cause of cardiovascular death in CKD patients. The cardiac FGF23/FGF receptor (FGFR) system and its role in the development of LVH in humans have not been addressed previously.

The addition of tramadol to the standard of i.v. acetaminophen and morphine infusion for postoperative analgesia in neonates offers no clinical benefit: a randomized placebo-controlled trial.

Background: Tramadol is used following neonatal cardiac and general surgery. However, its ability to opioid-spare or facilitate earlier extubation in postoperative neonates is unquantified.

Objective: This randomized placebo-controlled trial aimed to assess whether tramadol's addition to standard analgesia resulted in earlier extubation or reduced analgesic/sedative requirements in postsurgical neonates.

Reference values of aortic flow velocity integral in 1193 healthy infants, children, and adolescents to quickly estimate cardiac stroke volume.

The aortic velocity time integral (VTI) is an echocardiographic tool used to estimate cardiac output (CO) by multiplying it with the aortic valve (AV) area and heart rate (HR). Inaccurate measurement of AV diameter will lead to squared miscalculation of CO. The aortic VTI itself can serve as a left-ventricular (LV) output parameter.

Amplitude-integrated electroencephalography in newborns with inborn errors of metabolism.

Background: The utility of amplitude-integrated electroencephalography (aEEG) monitoring has been established for patients with neonatal hypoxic-ischemic encephalopathy.

Objective: To evaluate the role of aEEG in the diagnostic process and treatment of patients with encephalopathy due to inborn errors of metabolism.

Methods: Cases collected through an international registry were divided into 5 groups of metabolic disorders.

Newborn screening for Pompe disease by measuring acid alpha-glucosidase activity using tandem mass spectrometry.

Background: Pompe disease, caused by the deficiency of acid alpha-glucosidase (GAA), is a lysosomal storage disorder that manifests itself in its most severe form within the first months of life. Early detection by newborn screening is warranted, since prompt initiation of enzyme replacement therapy may improve morbidity and mortality. We evaluated a tandem mass spectrometry (MS/MS) method to measure GAA activity for newborn screening for Pompe disease.

Congenital disorders of glycosylation--a challenging group of IEMs.

Congenital disorders of glycosylation (CDG) are a rapidly growing group of inherited errors of metabolism (IEMs) due to an impairment of one or several glycosylation pathways. During recent years over 30 CDG subtypes have been identified at a molecular and biochemical level. The clinical manifestations in CDG are heterogeneous and may be highly variable within the same subtype and even among affected siblings.

Expanded newborn screening in Europe 2007.

By January 2007 seven European countries had expanded, and more are considering the expansion of their newborn screening programmes by inclusion of ESI tandem mass spectrometry. We present an overview of the current status of expanded newborn screening programmes in Europe. While the first pilot programmes were initiated in 1998 in Germany, most countries started within the last 3 years.

Severe speech delay as the presenting symptom of guanidinoacetate methyltransferase deficiency.

Guanidinoacetate methyltransferase deficiency typically presents with muscular hypotonia, global developmental delay, extrapyramidal signs, and seizures during infancy and childhood. The authors report a 5-year-old child with guanidinoacetate methyltransferase deficiency who presented with severe speech delay, emphasizing the importance of an early screening for disorders of creatine synthesis and transport in every infant or child with isolated speech delay of unknown cause.

Mucopolysaccharidosis type II in females: case report and review of literature.

Mucopolysaccharidosis type II (Hunter disease, iduronate-2-sulfatase deficiency) was diagnosed in a 4-year-old female by demonstrating low iduronate-2-sulfatase activity both in leukocytes and fibroblasts and by the presence of a novel, complex rearrangement of the iduronate-2-sulfatase gene in heterozygous form. Mucopolysaccharidosis type II is inherited in an X-linked recessive manner and consequently females are rare. The disease phenotype in this case is due to complete unilateral inactivation of the nonmutant paternal X chromosome of the patient.

Nuclear magnetic resonance spectroscopy in glutaryl-CoA dehydrogenase deficiency.

Nuclear magnetic resonance (NMR) spectroscopy is a safe, noninvasive method that is the preferred technique for in vivo analysis of specific chemical compounds in localized brain regions. Besides quantification of compounds, NMR spectroscopy allows the detailed analysis of neurotransmitter, glucose and lactate metabolism following peripheral infusions of stable isotopically labelled precursors. The latter has been successfully applied to patients with different neurological disease states not including glutaryl-CoA dehydrogenase (GCDH) deficiency.

Low-volume peritoneal dialysis in 116 neonatal and paediatric critical care patients.

Unlabelled: Acute renal insufficiency accounts for high mortality in paediatric intensive care patients, particularly in infants. Peritoneal dialysis, usually carried out with dialysate volumes of >20 ml/kg body weight, increases pulmonary artery pressure, which may compromise myocardial function in critical illness. In this paper we report our experiences with the use of lower dialysate volumes in the treatment of critically ill children with renal impairments.

Coeliac disease in children and adolescents with type 1 diabetes mellitus: to screen or not, to treat or not?

Coeliac disease is more prevalent in individuals with type 1 diabetes mellitus than in the normal population. It often presents in an atypical or silent form. Specific autoantibodies are found in almost all cases.

Treatment of toxoplasmosis in pregnancy: concentrations of spiramycin and neospiramycin in maternal serum and amniotic fluid.

Toxoplasma infection during pregnancy is widely treated with oral spiramycin to reduce the risk of congenital toxoplasmosis in the infant. Failures of therapy have been observed, however. In this study, a sensitive high-performance liquid chromatography technique was used to measure concentrations of spiramycin and neospiramycin, one of the major metabolites of spiramycin, in maternal serum and amniotic fluid.

Severe respiratory failure following charcoal application in a toddler.

Charcoal has been commonly used for enteral detoxication with few adverse effects. In toddlers charcoal can often be simply applied via a gastric tube. Regurgitation and aspiration is considered a rare event.

Ambient ozone exposure is associated with eosinophil activation in healthy children.

Background: Eosinophil activation is characteristic for allergic airways disease. However, eosinophilic airways inflammation has also been observed subsequent to ambient ozone exposure.

Methods: For a population sample of 877 children living at nine sites with different ozone exposure we measured urinary eosinophil protein X (U-EPX) as a marker of eosinophil activation.

Sleep-wake cycles in preterm infants below 30 weeks of gestational age. Preliminary results of a prospective amplitude-integrated EEG study.

In the newborn, presence of sleep-wake cycles indicates integrity and maturity of the central nervous system. By spectral EEG analysis and polygraphic recordings subtle variations of EEG background activity and behavioural patterns corresponding to early sleep-wake cycles have been found in preterm infants as young as 27 weeks of gestation. The emergence of sleep-wake cycles at early gestational ages may have a positive predictive value for long-term neurological outcome.

Survival after intrauterine myocardial infarction: noninvasive assessment of myocardial perfusion with 99mTc-Sestamibi scintigraphy.

Survival after severe intrauterine myocardial infarction has not been reported previously. We describe the course of a neonate with a structurally normal heart, who presented with cardiogenic shock at birth due to intrauterine myocardial infarction with a huge ventricular aneurysm. Myocardial perfusion was assessed noninvasively by means of 99mTc-Sestamibi, a radiopharmaceutical agent recently introduced in nuclear cardiology to avoid repeated coronary angiography.

SIDS related anxiety--a risk factor analysis.

Background: The growing public interest in the Sudden Infant Death Syndrome (SIDS) has led to a new psychological problem--SIDS related anxiety (SRA). General public awareness, unfavourable experience in the past, present problems with the infant or insufficient support from the family may lead or contribute to SRA.

Objective: The study was conducted to explore which of these factors contribute most to the development of SRA.

Long-term experience with subcutaneously tunneled external ventricular drainage in preterm infants.

We previously reported on a series of 27 newborn infants treated for posthemorrhagic hydrocephalus with external ventricular drainage during 1984 to 1989. In the present study we continued to evaluate this technique during the subsequent 8 years (37 patients; mean birthweight 1251+/-478 g; mean gestational age 29+/-2.9 weeks; 51 drains), and we now report on the long-term experience with this method, complications, and neurodevelopmental outcome of the survivors.