Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders?A successful strategy for clinical research of rare diseases

BACKGROUND: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. AIMS: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. METHODS: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. RESULTS: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (</= 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. CONCLUSIONS: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies

Spontaneous Septum Pellucidum Fenestration Complicating Posthemorrhagic Hydrocephalus in an Extremely Low Birth Weight Infant

A 25 weeks' gestation infant developed posthemorrhagic hydrocephalus. On postnatal Day 29 an ultrasound of the brain showed a fenestration between the septum pellucidum and the left lateral ventricle which continued to enlarge as the clinical course deteriorated. Color Doppler showed low flow between the septum pellucidum leaflets suggesting a persistence of erythrocytes. However, color Doppler artifacts could have resulted in this interpretation. The infant died on day 34 from multiple organ failure. Despite spontaneous fenestration of the septum pellucidum being previously described, it has not been associated with hemorrhagic hydrocephalus. Serial scanning of intracranial structures by high frequency probes can allow better understanding of the pathophysiology of neurologic complications in preterm infants. © 2013

Widening the horizon of neonatal neurophysiology.

In this Editorial we discussed the work by Myers et al. (2012) on spectral analysis of background EEG activity in a large cohort of newborns born either at term or preterm. Their results show that most of the decrease in high frequency activity prior to term-equivalent age is due to a reduction in bursts of rapid oscillations. These results are in accord with previous spectral analyses of transients, leading to postulate a link between GABA neurons and bursting activity until the physiological disappearance of cortical subplate generators is completed. This EEG feature, peculiar to newborn EEG maturation, is then suggested to be a potential marker of GABA involvement in membrane potential generation

No kinetic interaction between levetiracetam and cyclosporine: a case report.

Levetiracetam is a new antiepileptic drug reported to be effective and well-tolerated in adults and children affected by epilepsy. Its lack of hepatic cytochrome metabolism is the theoretic basis for the absence of interactions with other drugs that follow this pathway. We present a 14-year-old girl who underwent orthotopic heart transplantation, followed by antirejection therapy including cyclosporine. Symptomatic occipital lobe epilepsy developed that was successfully treated with oxcarbazepine, but cyclosporine plasma levels decreased to below the antirejection threshold. Oxcarbazepine was replaced by levetiracetam. Levetiracetam did not affect the metabolism of cyclosporine, and cyclosporine plasma levels have remained in the therapeutic range up to now. The patient is still seizure-free and does not complain of any side effects after a 1-year follow-up. Further studies are necessary to confirm the lack of interactions between these drugs, which would make levetiracetam a useful therapeutic option in managing seizure control during antirejection therapy with cyclosporine

I disturbi del comportamento alimentare in et\ue0 evolutiva

none5noneFranzoni E; Garone C; Sarajlija J; Tzolas V; Cecconi IFranzoni E; Garone C; Sarajlija J; Tzolas V; Cecconi