This prospective study extending for more than 3 years had two objectives: (a) to use Doppler ultrasonography (US) to estimate the incidence of asymptomatic catheter-related upper extremity deep venous thrombosis (DVT) in a large population and (b) to study the effect of the catheter position as an individual risk factor for catheter-related DVT. Between October 1995 and June 1998, a total of 145 patients who had oropharyngeal tract cancer and who were fitted with the same totally implantable central venous catheters (CVCs) were included in the study. Follow-up included (a) estimation of the position of each catheter tip on a chest radiograph obtained immediately after surgery and (b) regular monthly Doppler US screening for catheter-related DVT. Seventeen patients developed catheter-related DVT; 13 of them were asymptomatic. The mean interval between CVC implantation and detection of thrombosis was 42.2 days. Correct positioning of the distal catheter tip was associated with a significantly lower rate of catheter-related DVT. Only five of 87 patients with a correctly positioned distal catheter tip (ie, either in the superior vena cava or at the junction between the right atrium and the superior vena cava) developed thrombosis, compared with 12 of 26 patients with a misplaced catheter (P <.001). The side on which the CVC was implanted did not influence the catheter-related DVT rate. The rate of asymptomatic catheter-related DVT is high and could be lowered with correct initial CVC positioning.

The mechanotransducer channels of auditory hair cells are gated by tip-links, oblique filaments that interconnect the stereocilia of the hair bundle. Tip-links stretch from the tips of stereocilia in the short and middle rows to the sides of neighboring, taller stereocilia. They are made of cadherin-23 and protocadherin-15, products of the Usher syndrome type 1 genes USH1D and USH1F, respectively. In this study we address the role of sans, a putative scaffold protein and product of the USH1G gene. In Ush1g ^−/− mice, the cohesion of stereocilia is disrupted, and both the amplitude and the sensitivity of the transduction currents are reduced. In Ush1g ^fl/fl Myo15-cre ^+/− mice, the loss of sans occurs postnatally and the stereocilia remain cohesive. In these mice, there is a decrease in the amplitude of the total transducer current with no loss in sensitivity, and the tips of the stereocilia in the short and middle rows lose their prolate shape, features that can be attributed to the loss of tip-links. Furthermore, stereocilia from these rows undergo a dramatic reduction in length, suggesting that the mechanotransduction machinery has a positive effect on F-actin polymerization. Sans interacts with the cytoplasmic domains of cadherin-23 and protocadherin-15 in vitro and is absent from the hair bundle in mice defective for either of the two cadherins. Because sans localizes mainly to the tips of short- and middle-row stereocilia in vivo, we conclude that it belongs to a molecular complex at the lower end of the tip-link and plays a critical role in the maintenance of this link.