Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFß) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFß activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms.

Epidemiology of nosocomial infections in selected neonatal intensive care units in Colombia, South America.

OBJECTIVE: The epidemiology of nosocomial infections (NI) in neonatal intensive care units in developing countries has been poorly studied. We conducted a prospective study in selected neonatal units in Colombia, SA, to describe the incidence rate, causative organisms, and interinstitutional differences. STUDY DESIGN: Data were collected prospectively from February 20 to August 30, 2001 from eight neonatal units. NI was defined as culture-proven infection diagnosed after 72 h of hospitalization, resulting in treatment with antibiotics for >3 days. Linear regression models were used to describe associations between institutional variables and NI rates. RESULTS: A total of 1504 infants were hospitalized for more than 72 h, and therefore, at risk for NI. Of all, 127 infections were reported among 80 patients (5.3%). The incidence density rate was 6.2 per 1000 patient-days. Bloodstream infections accounted for 78% of NIs. Gram-negative organisms predominated over gram-positive organisms (55 vs 38%) and were prevalent in infants < or =2000 g (54%). The most common pathogens were Staphylococcus epidermidis (26%) and Klebsiella pneumonia (12%). CONCLUSION: Gram-negative organisms predominate in Colombia among infants <2000 g. The emergence of gram-negative organisms and their associated risk factors requires further study.