A randomized trial of ultrasound-guided peripheral IV catheter placement in difficult access patients using a guidewire approach.

OBJECTIVE: The purpose of this pilot study was to investigate whether use of a guidewire improves successful placement of ultrasound-guided peripheral IVs (PIV) in difficult intravenous access patients in the emergency department (ED). METHODS: This was an unblinded, prospective, randomized trial performed by emergency medicine (EM) clinicians at a single academic ED. Eligible participants were randomized to ultrasound-guided PIV placement with or without the use of a guidewire. PIV access was obtained using the Accucath™ 20 gauge × 5.7 cm catheters by way of deployment or non-deployment of the guidewire. Primary outcome measure was first-pass success rate and secondary outcomes included number of attempts, complication rates, and clinician reported ease of insertion. RESULTS: Seventy patients were enrolled and 69 were included in the final analysis. Thirty-four participants were randomized to use of guidewire and 35 to no guidewire. First-pass success rates were similar with and without guidewire use, 47.1% vs. 45.7%, (p = 0.9). There were no differences found in median number of attempts between the two techniques, 2 (IQR 1-2) vs 2 (IQR 1-2), (p = 0.60). The complication rates were similar, 15% vs. 29% (p = 0.25). Clinicians reported no difference in ease of insertion between methods on a 5-point Likert Scale, mean 2.6 vs 2.7 (p = 0.76). DISCUSSION: In this pilot study comparing ultrasound-guided PIV placement in ED patients using an integrated guidewire versus no guidewire, there was no significant difference in first-pass success, number of attempts, or complication rates. This study provides preliminary data for further investigations.

Analysis of lipid transfer activity between model nascent HDL particles and plasma lipoproteins: implications for current concepts of nascent HDL maturation and genesis.

The specifics of nascent HDL remodeling within the plasma compartment remain poorly understood. We developed an in vitro assay to monitor the lipid transfer between model nascent HDL (LpA-I) and plasma lipoproteins. Incubation of alpha-(125)I-LpA-I with plasma resulted in association of LpA-I with existing plasma HDL, whereas incubation with TD plasma or LDL resulted in conversion of alpha-(125)I-LpA-I to prebeta-HDL. To further investigate the dynamics of lipid transfer, nascent LpA-I were labeled with cell-derived [(3 )H]cholesterol (UC) or [(3)H]phosphatidylcholine (PC) and incubated with plasma at 37 degrees C. The majority of UC and PC were rapidly transferred to apolipoprotein B (apoB). Subsequently, UC was redistributed to HDL for esterification before being returned to apoB. The presence of a phospholipid transfer protein (PLTP) stimulator or purified PLTP promoted PC transfer to apoB. Conversely, PC transfer was abolished in plasma from PLTP(-/-) mice. Injection of (125)I-LpA-I into rabbits resulted in a rapid size redistribution of (125)I-LpA-I. The majority of [(3)H]UC from labeled r(HDL) was esterified in vivo within HDL, whereas a minority was found in LDL. These data suggest that apoB plays a major role in nascent HDL remodeling by accepting their lipids and donating UC to the LCAT reaction. The finding that nascent particles were depleted of their lipids and remodeled in the presence of plasma lipoproteins raises questions about their stability and subsequent interaction with LCAT.

Hypersensitivity to chromium-induced DNA damage correlates with constitutive deregulation of upstream p53 kinases in p21-/- HCT116 colon cancer cells.

The cyclin-dependent kinase inhibitor p21(CIP1/WAF1) is a key component in cell cycle control and apoptosis, directing an anti-apoptotic response following DNA damage. Chromium exposure resulted in a 500-1000 fold increase in apoptosis-induced cell death in p21-/- HCT116 cells compared to wild-type or p53-/- cells. p53 shRNA (or transient p53 siRNA) into p21-/- HCT116 cells reduced Cr(VI) sensitivity, suggesting the enhanced apoptosis in p21-/- cells is p53-dependent. Under non-DNA damage conditions, the p53 level in p21-/- cells was significantly higher than in wild-type cells, due to enhanced p53 phosphorylation and stabilization rather than elevated p53 transcription. Wild-type cells showed significant p53 protein induction upon DNA damage whereas p21-/- cells showed no p53 increase. p21-/- cells display the constitutive activation of upstream p53 kinases (ATM, DNA-PK, ATR, AKT and p38). 2D gel analysis revealed p53 patterns in p21-/- cells were distinct from those in wild-type cells before and after chromium exposure. Our results suggest that p21 has an important role in the cellular response to normal replicative stress and its absence leads to a "chronic DNA damage" state that primes the cell for p53-dependent apoptosis.