DNA copy number variants: A potentially useful predictor of early onset renal failure in boys with posterior urethral valves.

INTRODUCTION: Posterior urethral valves (PUV) are among the most common urological causes of chronic kidney disease (CKD) in childhood. Recently, genomic imbalances have been cited as potential risk factors for altered kidney function and have been associated with CKD. The phenotypic effects of a copy number variant (CNV) in boys with PUV are unknown. Here, it was hypothesised that the progression to early renal failure in PUV patients may be influenced by genetic aberrations. OBJECTIVE: To assess the relationship between CNVs and renal outcomes. PATIENTS AND METHODS: Between September 2012 and July 2015, 45 children with PUV were recruited to evaluate the presence of CNVs in their DNA. The patients' medical records were retrospectively reviewed. The criteria for outcomes of renal function included: assessments of the nadir serum creatinine in the first year of life, the estimated glomerular filtration rate at 1 and 5 years, and the requirement for renal replacement. RESULTS: Thirteen CNVs were identified in 12 boys (29% of the cohort). Microarray analysis revealed two pathogenic CNVs (well-established CNVs known to be associated with genetic disease) and 11 of unknown significance (CNVs with insufficient current available evidence for unequivocal determination of clinical significance), including genes that have been previously implicated in kidney diseases and urogenital disorders. The median follow-up was 10.2 years (range 3-17.5) in the group of patients with CNV compared with 5.8 years (range 1-16.6) in those CNV-. The nadir creatinine values were significantly higher in boys with CNVs than in those without CNVs (57.5 µmol/L (range 23-215) and 28 µmol/L (range 18-155), respectively (P = 0.05) (Figure). Boys CNV+ had a worse prognosis, with a higher incidence of Stage-V CKD compared with the control group (33% with CNVs vs. 9% in CNV-, P = 0.06) at a median age of 22 months (range 8 months-16 years). Four (33%) patients CNV+ underwent renal transplantation. DISCUSSION: The role of CNVs in the deterioration of renal function remains unknown. It can be hypothesised that CNVs could be a contributing factor or may serve as an accelerant for the progression to renal failure. CONCLUSION: The CNVs >100 Kb were significantly associated with early onset renal failure in children with PUV. Prenatal detection of CNV could help to identify foetuses at high risk of severe renal impairment in cases of suspected PUV, especially in cases without oligohydramnios or severe pulmonary hypoplasia. These preliminary results should be confirmed in a larger cohort of patients.

Emergency stenting of vertical vein in a neonate with obstructed supracardiac total anomalous pulmonary venous drainage.

A late preterm newborn baby presented with respiratory distress and increasing cyanosis within 2 hours of birth. Bedside transthroracic echocardiography showed a critically obstructed vertical vein in a supracardiac total anomalous pulmonary venous drainage (TAPVd). Emergency stenting of the vertical vein was successfully performed at 24 hours of life.

Late presentation of Nipah virus encephalitis and kinetics of the humoral immune response.

Nipah virus is a newly discovered paramyxovirus transmitted directly from pigs to humans. During a large encephalitis outbreak in Malaysia and Singapore in 1998-9, most patients presented acutely. A 12 year old child is described who developed encephalitis 4 months after exposure to the virus. She was diagnosed by a new indirect IgG enzyme linked immunosorbent assay (ELISA), which is also described. The late presentation and IgG subclass responses had similarities to subacute sclerosing panencephalitis. Nipah virus should be considered in patients with encephalitis even months after their possible exposure.

Radiofrequency catheter ablation in the treatment of supraventricular tachycardia in the elderly.

OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of radiofrequency catheter ablation for the treatment of supraventricular tachycardias in an elderly (> or = 70 years of age) group of patients. BACKGROUND: Supraventricular tachycardias are the most common form of cardiac arrhythmia and affect all age groups. Although usually well tolerated in youth, supraventricular tachycardias may be associated with disabling symptoms and have life-threatening potential in the elderly. In addition, antiarrhythmic agents are less well tolerated and may be associated with a higher incidence of toxicity in the elderly. METHODS: From May 1989 to March 1993, 454 patients underwent a radiofrequency catheter ablation procedure at the University of California, San Francisco, for the treatment of symptomatic supraventricular tachycardia. Sixty-seven of these patients were > or = 70 years of age and constituted the study group. Patients underwent one of the following catheter ablation procedures: complete atrioventricular (AV) junctional ablation for ventricular rate control in patients with atrial fibrillation (37 patients), AV node modification for the treatment of AV node reentrant tachycardia (17 patients), accessory pathway ablation (9 patients), ablation of the "slow zone" to cure atrial flutter (4 patients) and atrial tachycardia ablation (1 patient). One patient underwent ablation for both AV node reentrant tachycardia and atrial flutter. RESULTS: Success was achieved in 67 (98.5%) of 68 ablation procedures. There were no procedural or early deaths. The overall complication rate was 7.4%, and only one patient (1.5%) had long-term sequelae (permanent cardiac pacing for complete heart block). At a mean (+/- SD) follow-up of 22.1 +/- 12.9 months, 63 (94%) of 67 patients were alive, with no antiarrhythmic agents for the treatment of their presenting arrhythmia. CONCLUSIONS: In this series radiofrequency catheter ablation appears to be an effective and safe treatment option for elderly patients (> or = 70 years of age) with a variety of symptomatic, drug-resistant supraventricular tachycardias. Because of the high incidence of severe symptoms associated with tachycardic episodes, the expense and the possible severe proarrhythmic problems associated with antiarrhythmic medications in this age group, catheter ablation may be considered an early rather than a "last resort" treatment option.

The effect of protein deficiency on some rat liver lipid metabolic enzymes and CoA.

Two groups of male Wistar rats were fed normal (i.e., 18%) and protein-free diets, respectively, for 7 weeks. In vivo incorporation of [1-14C] acetate into palmitic, stearic, oleic, and arachidonic acids by the liver was reduced in the protein-deficient rats. In vitro incubation of liver microsomes with labeled palmitate or linoleate revealed no change in the specific activities of chain elongating or desaturating enzymes. Protein deficiency resulted in a decrease in specific activity of short chain acyl-CoA synthetase and in total CoA, accompanied by the virtual disappearance of acyl-CoA and an increase in free CoA. Furthermore, there was less microsomal fatty acid synthetase and mitochondrial beta-hydroxybutyrate dehydrogenase activity. These results are discussed in relation to fatty acid synthesis and the changes in liver fatty acid composition.