Mutations of a putative cyclic-nucleotide-binding domain (CNBD) can disrupt the function of the hyperpolarization-activated cyclic-nucleotide-gated channel (HCN2) and the human ether-a-go-go-related gene potassium channel (HERG). Loss of function caused by C-terminal truncation, which includes all or part of the CNBD in HCN and HERG, has been related to abnormal channel trafficking. Similar defects have been reported for several of the missense mutations of HERG associated with long QT syndrome type 2 (LQT2). Thus, we postulate that normal processing of these channels depends upon the presence of the CNBD. Here, we show that removal of the entire CNBD prevents Golgi transit, surface localization and function of HERG channel tetramers. This is also true when any of the structural motifs of the CNBD is deleted, suggesting that deletion of any highly conserved region along the entire length of the CNBD can disrupt channel trafficking. Furthermore, we demonstrate that defective trafficking is a consequence of all LQT2 mutations in the CNBD, including two mutations not previously assessed and two others for which there are conflicting results in the literature. The trafficking sensitivity of the CNBD might be of general significance for other ion channels because complete deletion of the CNBD or mutations at highly conserved residues within the CNBD of the related ERG3 channel and HCN2 also prevent Golgi transit. These results broadly implicate the CNBD in ion-channel trafficking that accounts for the commonly observed loss of function associated with CNBD mutants and provides a rationale for distinct genetic disorders.
Background: Periprosthetic femoral fracture after total hip arthroplasty (THA) is an increasing clinical problem and a challenging complication to treat surgically. The aim of this retrospective study was to review the treatment of periprosthetic fractures and the complication rate associated with treatment at our institution. Methods:We reviewed the cases of patients with periprosthetic femoral fractures treated between January 2004 and June 2009. We used the Vancouver classification to assess fracture types, and we identified the surgical interventions used for these fracture types and the associated complications. Results:We treated 45 patients with periprosthetic femoral fractures during the study period (15 men, 30 women, mean age 78 yr). Based on Vancouver classification, 2 patients had AL fractures, 9 had AG, 15 had B1, 24 had B2, 2 had B3 and 4 had C fractures. Overall, 82% of fractures united with a mean time to union of 15 (range 2-64) months. Fourteen patients (31%) had complications; 11 of them had a reoperation: 6 to treat an infection, 6 for nonunion and 2 for aseptic femoral component loosening.
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