TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Outbreaks of influenza A virus infection in neonatal intensive care units.

BACKGROUND: Outbreaks of nosocomial influenza virus infections have been described rarely during childhood and even less so in the neonatal period. METHODS: We report 30 neonates admitted to 2 neonatal intensive care units with nosocomial influenza A virus infection, which occurred in 2 outbreaks during 1999. Risk factors for infection were evaluated, and control measures were adopted. Virus was detected by indirect immunofluorescence antibody screen. Any infant with nasopharyngeal aspirate positive for influenza A virus was considered infected. RESULTS: Of 95 infants screened 30 were positive for influenza A virus (31.5%). Mean birth weight was 1622 g, and mean gestational age was 31 weeks in the infected group. In the noninfected group mean birth weight was 2594 g and mean gestational age was 36.4 weeks. Low birth weight, short gestational age, twin pregnancy and mechanical ventilation were identified as risk factors for infection. Clinical symptoms were seen in 22, and 8 were asymptomatic. Clinical features were predominantly respiratory and digestive. The outcome was favorable in all cases. CONCLUSIONS: Infection by influenza virus has to be considered as a possible cause of nosocomial infection in the neonatal period. Control measures and prevention are important.

Peritoneal drainage as primary management in necrotizing enterocolitis: a prospective study.

BACKGROUND/PURPOSE: The use of peritoneal drainage (PD) in neonates with necrotizing enterocolitis (NEC) is controversial. The authors began to perform it successfully in infants with pneumoperitoneum, and subsequently they extended its use to infants with peritonitis and advanced NEC before radiologic evidence of peritoneal free air. To analyze the efficacy of PD they began a prospective study. METHODS: A prospective study was conducted in 6 neonatal intensive care units (NICU) in Spain: neonates with pneumoperitoneum or peritonitis and advanced NEC were all included, whatever the birth weight and gestational age (GA). RESULTS: PD was performed in 47 infants, but 3 of them were excluded because pneumoperitoneum was caused by pathologies other than NEC. In a cohort of 44 infants, 86% improved after PD, and 64% survived after only PD. After PD, 54% of infants needed delayed surgery. Overall survival rate was 82%; 57% infants with birth weight under 1,000 g, and 95% in infants over 1,000 g at birth. The main cause of mortality was massive NEC in the tiniest babies. Only one infant had a short bowel syndrome. CONCLUSIONS: From the authors' point of view, PD is the first step in treating neonates with pneumoperitoneum or overwhelming NEC, regardless of birth weight and GA. Laparotomy, if it is necessary, always must be performed after clinical stability is achieved. Mortality rates remain higher in the tiniest babies because of massive NEC.