Faculty Bibliography

OBJECTIVE: The purposes of this article are to summarize recent developments and concerns in endovascular aneurysm therapy leading to the adjunctive use of endoluminal devices, to review the published literature on stent-supported coil embolization of cerebral aneurysms, and to describe our experience with this technique in a limited subgroup of problematic complex aneurysms over a medium-term follow-up period. METHODS: Between January 2003 and June 2004, 28 individuals among 157 patients with cerebral aneurysms we evaluated were identified as harboring aneurysms with exceptionally broad necks. Out of these 28 patients, 16 were treated with a combination of stents and detachable coils, preserving the parent artery. Recorded data included patient demographics, the clinical presentation, aneurysm location and characteristics, procedural details, and clinical and angiographic outcome. RESULTS: Over an 18-month period, 16 patients with large cerebral aneurysms additionally characterized by neck sizes between 7 and 14 mm were treated, using combined coil embolization of the aneurysm with stent reconstruction of the aneurysm neck. Thirteen out of the 16 aneurysms were occluded at angiographic reevaluation between 11 and 24 months (mean angiographic follow-up, 17.5 mo). There were no treatment-related deaths or clinically evident neurological complications. Thirteen patients experienced excellent clinical outcomes, with good outcomes in two patients and a poor visual outcome in one patient (mean clinical follow-up, 29 mo). A single technical complication occurred, involving transient nonocclusive stent-associated thrombus, which was treated uneventfully with abciximab. CONCLUSION: Stent-supported coil embolization of large, complex-neck cerebral aneurysms seems to provide superior medium-term anatomic reconstruction of the parent artery compared with historic series of aneurysms treated exclusively with endosaccular coils. In the near future, increasingly sophisticated endoluminal devices offering higher coverage of the neck defect will likely enable more definitive endovascular treatment of complex cerebral aneurysms and further expand our ability to manipulate the vascular biology of the parent artery

Some 4- and 2-(nitrobenzyloxycarbonyl)-1, 2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines (4, 6, and 7) were synthesized and evaluated for their ability to exert preferential toxicity to hypoxic EMT6 mammary carcinoma cells using a colony-forming assay. Of these, the 4,5-dimethoxy-2-nitro analogue 6 (50 microM, 1-h exposure) caused greater than 3 logs of kill of hypoxic cells, with relatively minor toxicity to corresponding aerobic cells. The ability of 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues to reach and kill hypoxic cells of solid tumors was also demonstrated using intradermally implanted EMT6 solid tumors in mice. In addition, a possible source of toxicity to normal tissue, i. e., the activation of the 4-nitrobenzyl derivative 4 by glutathione S-transferase-catalyzed thiolysis, was essentially eliminated by replacing one of the benzylic methylene protons by a methyl group. The 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues also appear to be reduced more easily under acidic conditions (pH 6.0) than under neutral conditions, as measured by differential pulse polarography. Since the pH in hypoxic regions is often lower than that in adjacent aerobic regions, this property should aid in the cytotoxic action of these agents against hypoxic cells of solid tumors