The New England journal of medicine
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Case Reports
Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.
Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.
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Congenital long-QT syndrome is a disorder resulting in ventricular arrhythmias and sudden death. The most common forms of the long-QT syndrome, types 1 and 2, are caused by mutations in the potassium-channel genes KCNQ1 and KCNH2, respectively. Although inheritance of the long-QT syndrome is autosomal dominant, female predominance has often been observed and has been attributed to an increased susceptibility to cardiac arrhythmias in women. We investigated the possibility of an unbalanced transmission of the deleterious trait. ⋯ Positive selection of the mutated alleles that cause the long-QT syndrome leads to transmission distortion, with increased proportions of mutation carriers among the offspring of affected families. Alleles for the long-QT syndrome are more often transmitted to daughters than to sons.
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Randomized Controlled Trial Multicenter Study Comparative Study
A randomized trial of diagnostic techniques for ventilator-associated pneumonia.
Critically ill patients who require mechanical ventilation are at risk for ventilator-associated pneumonia. Current data are conflicting as to the optimal diagnostic approach in patients who have suspected ventilator-associated pneumonia. ⋯ Two diagnostic strategies for ventilator-associated pneumonia--bronchoalveolar lavage with quantitative culture of the bronchoalveolar-lavage fluid and endotracheal aspiration with nonquantitative culture of the aspirate--are associated with similar clinical outcomes and similar overall use of antibiotics. (Current Controlled Trials number, ISRCTN51767272 [controlled-trials.com].).