Seventy-five patients with hemoptysis were treated with bronchial artery embolization (BAE). The procedure was performed with Hexabrix (sodium methylglucamine ioxaglate), Mikaelson catheters, and Gelfoam particles. Angiographic evaluation of the bronchial artery anatomy revealed ten different configurations, which are described. The embolization attempt failed in three cases (4%); eight additional patients (10.7%) were excluded from the series because of inadequate data. In the remaining 64 patients, 41 underwent BAE alone and 23 underwent either chemotherapy or surgery in addition to embolization. Immediate control of hemoptysis was achieved in 49 of 64 patients (76.6%). Long-term control of hemoptysis was achieved in 46 of the 56 patients included in the long-term follow-up (82.1%). Eight of the 64 patients were lost to follow-up, which ranged from one to 47 months (mean 24.8 months). Hemoptysis recurred in 12 of 56 patients (severe in 10, mild in 2) (21.4%). Twelve patients died (21.4%), five of them due to hemoptysis (8.9%). None of the patients who died of hemoptysis had responded to initial BAE. It is concluded that BAE is an effective treatment for immediate control of life-threatening hemoptysis, allowing long-term control of bleeding in the majority of patients.
This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid monoolein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery.
The thermotropic phase behavior of cationic liposomes in mixtures of two of the most investigated liposome-forming double-chain lipids, dioctadecyldimethylammonium bromide (DODAB) and didodecyldimethylammonium bromide (DDAB), was investigated by differential scanning calorimetry (DSC), turbidity, and Nile Red fluorescence. The dispersions were investigated at 1.0 mM total surfactant concentration and varying DODAB and DDAB concentrations. The gel to liquid-crystalline phase transition temperatures (Tm) of neat DDAB and DODAB in aqueous dispersions are around 16 and 43 degrees C, respectively, and we aim to investigate the Tm behavior for mixtures of these cationic lipids. Overall, DDAB reduces the Tm of DODAB, the transition temperature depending on the DDAB content, but the Tm of DDAB is roughly independent of the DODAB concentration. Both DSC and fluorescence measurements show that, within the mixture, at room temperature (ca. 22 degrees C), the DDAB-rich liposomes are in the liquid-crystalline state, whereas the DODAB-rich liposomes are in the gel state. DSC results point to a higher affinity of DDAB for DODAB liposomes than the reverse, resulting in two populations of mixed DDAB/DODAB liposomes with distinctive phase behavior. Fluorescence measurements also show that the presence of a small amount of DODAB in DDAB-rich liposomes causes a pronounced effect in Nile Red emission, due to the increase in liposome size, as inferred from turbidity results.
As a result of their hydrophobicity, the extended wear silicone-hydrogel lenses (lotrafilcon A and balafilcon A) may carry higher risk of microbial contamination than both the hydrophilic daily wear silicone-hydrogel lens, galyfilcon A and the conventional hydrogel lens, etafilcon A.
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