New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms

Background: Hyperekplexia mutations have provided much information about glycine receptor structure and function. Results: Weidentified and characterized nine new mutations. Dominant mutations resulted in spontaneous activation, whereas recessive mutations precluded surface expression. Conclusion: These data provide insight into glycine receptor activation mechanisms and surface expression determinants. Significance: The results enhance our understanding of hyperekplexia pathology and glycine receptor structure-function. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A

Long-term Outcome of Children with Newly Diagnosed Pulmonary Arterial Hypertension:Results From the Global TOPP-registry

BACKGROUND AND AIMS: The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global network established to gain insights into the disease course and long-term outcomes of pediatric pulmonary arterial hypertension (PAH). Previously published cohorts in pediatric PAH are obscured by survival bias due to the inclusion of both prevalent (previously diagnosed) and incident (newly diagnosed) patients. The current study aims to describe long-term outcome and its predictors in pediatric PAH, exclusively of newly diagnosed patients.METHODS AND RESULTS: 531 children with confirmed pulmonary hypertension, aged ≥3 months and &lt;18 years were enrolled in the real-world TOPP registry at 33 centers in 20 countries, from 2008 to 2015. Of these, 242 children with newly diagnosed PAH with at least one follow-up visit were included in the current outcome analyses. During long-term follow-up, 42 (17.4%) children died, 9 (3.7%) underwent lung transplantation, 3 (1.2%) atrial septostomy and 9 (3.7%) Potts shunt palliation (event rates: 6.2, 1.3, 0.4, and 1.4 events per 100 person-years, respectively). One, 3-, and 5-year survival free from adverse outcome was 83.9%, 75.2% and 71.8%, respectively. Overall, children with open (unrepaired or residual) cardiac shunts had the best survival rates. Younger age, worse World Health Organization functional class and higher pulmonary vascular resistance index were identified as independent predictors of long-term adverse outcome. Younger age, higher mean right atrial pressure and lower systemic venous oxygen saturation were specifically identified as independent predictors of early adverse outcome (within 12 months after enrolment).CONCLUSIONS: This comprehensive analysis of survival from time of diagnosis in a large exclusive cohort of children newly diagnosed with PAH describes current era outcome and its predictors.</p

Mitral valve prolapse associated with celiac artery stenosis: a new ultrasonographic syndrome?

BACKGROUND: Celiac artery stenosis (CAS) may be caused by atherosclerotic degeneration or compression exerted by the arched ligament of the diaphragm. Mitral valve prolapse (MVP) is the most common valvular disorder. There are no reports on an association between CAS and MVP. METHODS: 1560 (41%) out of 3780 consecutive patients undergoing echocardiographic assessment of MVP, had Doppler sonography of the celiac tract to detect CAS. RESULTS: CAS was found in 57 (3.7%) subjects (23 males and 34 females) none of whom complained of symptoms related to visceral ischemia. MVP was observed in 47 (82.4%) subjects with and 118 (7.9%) without CAS (p < 0.001). The agreement between MVP and CAS was 39% (95% CI 32–49%). PSV (Peak Systolic Velocity) was the only predictor of CAS in MPV patients (OR 0.24, 95% CI 0.08–0.69) as selected in a multivariate logistic model. CONCLUSION: CAS and MVP seem to be significantly associated in patients undergoing consecutive ultrasonographic screening

Clinical features of isolated left ventricular noncompaction in children

Background: Ventricular noncompaction is a rare unclassified cardiomyopathy due to intrauterin arrest of compaction of the loose interwoven meshwork with limited data regarding diagnosis and outcome in children. Methods: In this study we describe clinical features of isolated left ventricular noncompaction (IVNC) in children and compare our findings with those previously reported. A diagnosis of ventricular noncompaction was made according to the characteristic echocardiographic appearance of two-layered myocardial wall consisting of a thin compacted epicardial and a thick noncompacted endocardial layer with numerous, prominent trabeculations and deep intertrabecular recesses communicating with left ventricular cavity. Results: Nine children, eight male and one female, with ages ranging from 10 days to 12 years and follow-up as long as 5 years were included into the study. The primary diagnosis of IVNC had been missed in four of the patients. Clinical manifestations were heart failure in five patients, cardiac murmur in two, dizziness in one, and palpitation in one patient. All patients, except two asymptomatic ones, had electrocardiographic abnormalities. Four patients required hospital admission for decompansated heart failure. Two patients died during follow-up while waiting for heart transplantation. Familial occurrence, ventricular tachycardia and thromboembolic events were not observed in any of the patients. Conclusions: Although IVNC is present at birth, it may become clinically overt at any time from infancy through adolescence. Physicians and echocardiographers should be familiar with the diagnostic pattern of ventricular noncompaction in order to prevent any delay in diagnosis. Since associated morbidity and mortality rates are high, these patients require regular follow-up. (C) 2003 Elsevier Ireland Ltd. All rights reserved

Effects of Respiration on Left Ventricular Diastolic Function in Healthy Children

Pulsed Doppler echocardiographic indices of mitral valve filling were measured in 20 healthy children, between 3 and 125 years old, in order to evaluate the effects of spontaneous respiration on left ventricular diastolic filling patterns. There were significant respiratory variations in four parameters of left ventricular diastolic function: The peak early filling velocity, the ratio of early to late peak filling velocity, and the ratio of early to late diastolic velocity-time integral decreased significantly during inspiration (mean decrease 7%, P<0·05; 16%, P<0·01; and 12%, P<0·05, respectively). On the other hand there was a significant increase in late peak filling velocity with inspiration (10% increase, P<0·05). Other variables of left ventricular diastolic filling were unchanged with inspiration. These results suggest that assessment of left ventricular diastolic function in children should be standardized with regard to respiratory phases in any clinical application. (Eur Heart J 1996; 17: 453%456)Scopu

A rare case: Celiac artery compression syndrome in an asymptomatic child

Celiac artery compression syndrome is a rare disorder and charecterized by postprandial intestinal angina caused by insufficient blood supply to the gastrointestinal organs in symptomatic patients. This pathology is also known as median arcuate syndrome. The authors report a case of 12-year-old boy with severe celiac artery compression by the median arcuate ligament that was diagnosed by Magnetic Resonance Angiography (MRA) and color dupplex ultrasonography (US). There was only a bruit in the upper midepigastrium, and there were no gastrointestinal symptoms despite severe compression of celiac trunk. This clinicopathologic entity is very rare but represents severe complaints and clinical results caused by a decreased rate of the intestinal blood flow. In this report the authors suggest that the diagnosis of celiac artery compression should be considered in asymptomatic pediatric patients representing abdominal bruit or with palpated thrill in the upper epigastrium. In comparison with case reports present in the English-language literature, the patient reported on here is the youngest diagnosed

Cardiac troponin T and myocardial injury during routine cardiac catheterisation in children

Background: This study aims to investigate whether intracardiac catheterization produces myocardial damage on pediatric heart. Methods: Five blood samples were collected (basal, immediate post procedure, at 4, 12 and 24 h after the procedure) for troponin T and creatine kinase NIB (CKMB) from 48 consecutive patients (age: 5.34+/-6.03 years). The effect of age, duration of procedure, pulmonary hypertension, cyanosis, and medication taken for congestive heart failure on the levels of troponin T and CKMB were sought. Results: The increase in CKMB (basal CKMB: 3.93+/-3.70 ng/ml; peak CKMB: 8.68+/-10.89 ng/ml; P25 mmHg), longer procedure time (>30 min), and patients taking anti-congestive heart failure therapy had significantly higher levels of CKMB and troponin (P>0.05). Conclusion: All patients undergoing cardiac catheterization are under risk of myocardial injury, and younger patients with pulmonary hypertension and especially with compensated cardiac failure have increased risk of myocardial damage, and need to be handled carefully. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

Non-invasive evaluation of aortic regurgitation by Doppler echocardiography in children: comparison with contrast angiography

Doppler indexes have been used successfully to determine the severity of aortic regurgitation (AR) in adults but have not been evaluated in children. To determine the accuracy of pulsed, color, and continuous-wave (CW) Doppler echocardiographic indexes in assessing the degree of AR in children, the correlation between the non-invasive measurements and angiographic grading of the regurgitant flow (1+ to 4+) was examined in 14 children (mean age 11+/-3 years) with chronic AR