Investigation and treatment of a complicated inflammatory aortoiliac aneurysm.

Inflammatory abdominal aortic aneurysms (IAAAs) account for 5% to 10% of all abdominal aortic aneurysms, occurring primarily in males. Their true etiology is unknown. Symptoms and signs of IAAA are so variable that they present to a wide range of specialties. There is debate in the literature whether IAAA is a manifestation of systemic autoimmune disease. We describe the case of a young female patient with complicated inflammatory aortoiliac aneurysmal disease, illustrating diagnostic and treatment challenges that remain. Our patient had a positive autoantibody screen, raised erythrocyte sedimentation rate, positive enzyme-linked immunosorbent spot test, and saccular aneurysms, including infective and inflammatory etiologies in her differential diagnosis. Early diagnosis is crucial to limit disease progression, morbidity, and mortality. Medical management is important to address the underlying disease process, but a combination of endovascular and open surgical intervention is often necessary for definitive treatment. Available evidence offers plausibility for benefit of endovascular intervention over open repair.

The role of doxorubicin in non-viral gene transfer in the lung.

Proteasome inhibitors have been shown to increase adeno-associated virus (AAV)-mediated transduction in vitro and in vivo. To assess if proteasome inhibitors also increase lipid-mediated gene transfer with relevance to cystic fibrosis (CF), we first assessed the effects of doxorubicin and N-acetyl-l-leucinyl-l-leucinal-l-norleucinal in non-CF (A549) and CF (CFTE29o-) airway epithelial cell lines. CFTE29o- cells did not show a response to Dox or LLnL; however, gene transfer in A549 cells increased in a dose-related fashion (p < 0.05), up to approximately 20-fold respectively at the optimal dose (no treatment: 9.3 x 10(4) +/- 1.5 x 10(3), Dox: 1.6 x 10(6)+/-2.6 x 10(5), LLnL: 1.9 x 10(6) +/- 3.2 x 10(5)RLU/mg protein). As Dox is used clinically in cancer chemotherapy we next assessed the effect of this drug on non-viral lung gene transfer in vivo. CF knockout mice were injected intraperitoneally (IP) with Dox (25-100 mg/kg) immediately before nebulisation with plasmid DNA carrying a luciferase reporter gene under the control of a CMV promoter/enhancer (pCIKLux) complexed to the cationic lipid GL67A. Dox also significantly (p < 0.05) increased expression of a plasmid regulated by an elongation factor 1alpha promoter (hCEFI) approximately 8-fold. Although administration of Dox before lung gene transfer may not be a clinically viable option, understanding how Dox increases lung gene expression may help to shed light on intracellular bottle-necks to gene transfer, and may help to identify other adjuncts that may be more appropriate for use in man.