ABSTRACT
Regional right ventricular dysfunction with akinesia of the mid-free wall with normal apical motion known as McConnell's sign is an under-reported echocardiographic finding in the setting of pulmonary embolism. We conducted a literature review and systematic analysis, while describing 2 cases of pulmonary embolism with findings of reverse McConnell's sign.
ABSTRACT
BACKGROUND: DNase (Pulmozyme) effectiveness in cystic fibrosis treatment is in some cases limited by its inability to access DNA trapped within bundles in highly viscous fluids that also contain actin. Dissociating DNA-containing bundles using actin depolymerizing agents and polyanions has potential to increase DNase efficacy. METHODS: Fluorescence measurements of YOYO-1 and a rheological creep-recovery test quantified DNA content and viscoelasticity in 150 sputum samples from adult CF patients and their susceptibility to fluidization by DNase1, alone and in combination with gelsolin and poly-aspartate (p-Asp). Fluidization of sputum by these agents is compared to their capacity to increase antibacterial activity in sputum, measured using a luminescent Pseudomonas aeruginosa strain and a bacterial killing assay. RESULTS: The polyanion p-Asp (1-50 µg/g of sputum), the actin severing protein gelsolin (10-90 µg/g) and their combination enhance the ability of DNase 1 to increase the abnormally low mechanical compliance of CF sputum and to promote bacterial killing in sputum by colistin and tobramycin, two antibiotics commonly used to treat CF. CONCLUSIONS: Addition of low concentrations of p-ASP or gelsolin can increase the therapeutic value of Pulmozyme (DNase 1).
Subject(s)
Cystic Fibrosis/metabolism , Deoxyribonuclease I/pharmacology , Gelsolin/pharmacology , Peptides/pharmacology , Pseudomonas Infections/metabolism , Pseudomonas aeruginosa/drug effects , Sputum/chemistry , Adolescent , Adult , Child , Compliance , Cystic Fibrosis/drug therapy , Cystic Fibrosis/microbiology , Deoxyribonuclease I/metabolism , Female , Humans , Male , Middle Aged , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/isolation & purification , Recombinant Proteins/pharmacology , Suppuration/microbiology , Young AdultABSTRACT
Lung cancer is difficult to treat with a poor prognosis and a five year survival of 15%. Current molecularly targeted therapies are initially effective in non-small cell lung cancer (NSCLC) patients; however, they are plagued with difficulties including induced resistance and small therapeutically responsive populations. This mini review describes the mechanism of resistance to several molecularly targeted therapies which are currently being used to treat NSCLC. The major targets discussed are c-Met, EGFR, HER2, ALK, VEGFR, and BRAF. The first generation tyrosine kinase inhibitors (TKIs) resulted in resistance; however, second and third generation TKIs are being developed, which are generally more efficacious and have potential to treat NSCLC patients with resistance to first generation TKIs. Combination therapies could also be effective in preventing TKI resistance in NSCLC patients.
