Synthetic and antimicrobial studies on natural cyclopolypeptide from Caribbean marine-sponge and its analogs

Objective: A natural cyclic peptide, rolloamide, previously isolated from marine-sponge, was synthesized by coupling of tri and tetrapeptide units Boc­Phe-Pro- Val­OMe and Boc­Pro-Leu-Pro-Ile­OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear heptapeptide segment. Design and Methodology: Solution phase technique was adopted for the synthesis of cycloheptapeptide. Required tri and tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc­Phe-Pro­OH and Boc­Pro-Leu­OH with respective amino acid methyl ester hydrochloride Val-OMe.HCl and dipeptide methyl ester Pro-Ile-OMe. Cyclization of linear heptapeptide unit was done by p-nitrophenyl ester method. Similarly, two analogs of rolloamide were prepared by modification of tripeptide unit. The structures of synthesized cyclopeptide and its analogs were elucidated by spectral and elemental analysis. The newly synthesized peptide was subjected to antimicrobial screening and compared with biopotential of analogs. Results: Synthesis of cyclopeptide was accomplished with >84% yield utilizing diisopropylcarbodiimide (DIPC) as coupling agent. Newly synthesized peptide possessed promising activity against C. albicans and P. aeruginosa, K. pneumonia as compared to standard drugs, in addition to moderate activity against dermatophytes. Synthesized peptide analogs showed better antimicrobial potential against C. albicans and dermatophytes. Conclusions: Solution phase technique employing N,Ndiisopropylcarbodiimide (DIPC) and triethylamine (TEA) proved to be effective for the synthesis of natural cycloheptapeptide. N-methyl morpholine (NMM) was found to be a better base for cyclization of linear heptapeptide unit in comparison to TEA and pyridine. Promising antimicrobial potential was seen for newly synthesized cyclic peptide and its analogs.

Outcomes of type 2 endoleaks detected on venous phase CT arteriography.

PURPOSE: The majority of type 2 endoleaks (T2EL) are identified on computed tomography angiography (CTA) both on arterial and venous phase. There is a subset of T2EL that are demonstrated only on venous phase CTA. This study was done to report the outcomes of T2EL detected only on venous phase CTA. MATERIALS AND METHODS: A total of 261 consecutive T2EL treated via embolization were reviewed for the presence of endoleak demonstrated only on venous phase CTA. A group of 16 patients (12 men, 4 women; mean age, 80.1 years) was identified who had pre-embolization venous phase T2EL. Patients were evaluated for presence of T2EL after embolization, change in aneurysm diameter, and need for further intervention. RESULTS: The prevalence of venous phase T2EL was 6.1% (16/261; 95%CI: 3.2%-9.0%). On post-embolization CTA, the rate of successful embolization at 6 months was 2/12 (17%; 95%CI: 0%-38%). At 6-month follow-up, mean change in aneurysm diameter was +2.3mm (n=12; 95%CI: -0.5mm to +5.0mm). In total, 4/16 (25%; 95%CI: 4%-46%) underwent re-embolization and 4/16 (25%, 95%CI: 4%-46%) underwent conversion to open repair. There was one aneurysm rupture, which was successfully treated surgically. CONCLUSION: These results suggest that venous phase T2EL are not as responsive to embolization as standard T2EL and emphasize the need to follow patients with venous phase T2EL closely.

How to manage infected aortic endografts.

Aortic endografts have become the preferred treatment for aneurysms of the descending thoracic aorta and the infrarenal aorta. The prevalence of endograft infections is about 0.6%, and with the growing number of patients with aortic endografts, the number of patients with endograft infections has also increased. It is important for physicians who treat aneurysmal disease with endografting to understand the pathophysiology, work-up, and treatment options available. Currently, the mainstay of treatment is prolonged antibiotic therapy, explant of all prosthetic material, and reconstruction of the vasculature with either an in situ or extra-anatomic bypass. However, there is a growing experience of less invasive treatment strategies that can be used in patients who cannot withstand an operation of this magnitude.

Structural MRI of carotid artery atherosclerotic lesion burden and characterization of hemispheric cerebral blood flow before and after carotid endarterectomy.

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.

Electrifying a medical school course: a case study.

BACKGROUND: At Virginia Commonwealth University School of Medicine, the Dean charged the curriculum office to "electrify the curriculum." An instructional development team chose a 2nd-year course to serve as a model e-course and to provide evaluation data for a 2-year study. DESCRIPTION: The instructional development process used instructional and Web design principles. An evaluation plan included a number of data collection methods: e-mail surveys, a focus group, student diaries, and comprehensive end-of-course student assessments. The e-course allowed students to take advantage of learning opportunities that traditional face-to-face instruction normally does not. EVALUATION: Students found access to multiple images; interactivity; and meaningful, efficient navigation within the site to be useful. Web-based instruction shows promise to aid students in the transition from concept acquisition to complex "doctor thinking." It does not replace the need for human teachers. CONCLUSION: The authors conclude with instructional design suggestions to exploit the power of Web-based teaching for the enhancement of complex learning.

Impact of exclusion criteria on patient selection for endovascular abdominal aortic aneurysm repair.

PURPOSE: Wide-ranging predictions have been made about the usefulness of endovascular repair for patients with abdominal aortic aneurysms (AAAs). The availability of US Food and Drug Administration-approved devices has removed the restrictions on patient selection, which had been controlled by device trials. This study examined the applicability of endovascular AAA repair and identified the anatomic barriers to successful endovascular AAA repair that should guide future device development. METHODS: All patients who came to our institution for infrarenal AAA repair between April 1998 and June 2000 were offered evaluation for endovascular repair. Thin-cut spiral computed tomography scans and arteriograms were obtained on all patients, and their anatomic characteristics were prospectively entered into a database. A wide selection of available devices allowed the treatment of diverse AAA anatomic features. RESULTS: A total of 307 patients were examined (264 men, 43 women). Of these, 204 patients (66%; 185 men, 19 women) underwent endovascular repair, and 103 patients (34%, 79 men, 24 women) were rejected. Reasons for exclusion included short aneurysm neck (56, 54%), inadequate access because of small iliac arteries (48, 47%), wide aneurysm neck (41, 40%), presence of bilateral common iliac aneurysms extending to the hypogastric artery (22, 21%), excessive neck angulation (14, 14%), extensive mural thrombus in the aneurysm neck (10, 10%), extreme tortuosity of the iliac arteries (10, 10%), accessory renal arteries originating from the AAA (6, 6%), malignancy discovered during the examination (5, 5%), and death during the examination interval (2, 2%). Rejected patients had an average of 1.9 exclusion criteria (range, 1 to 4). A disproportionate number of women were excluded because of anatomic findings (P = .0009). Although 80% of patients who were at low risk for surgery qualified for endovascular repair, only 49% of our patients who were at high risk for surgery were acceptable candidates (P < .001). Of the 103 patients who were excluded, 34 (33%) underwent open surgical repair, and the remaining 69 (67%) were deemed to be unfit for open surgery. Three patients (1.4%) failed endograft placement because of inadequate vascular access. CONCLUSION: Most infrarenal AAAs (66%) can be treated with endovascular devices currently available commercially or through US Food and Drug Administration-approved clinical trials. However, patients who are at high risk for surgery and might benefit most from endovascular repair are less likely to qualify for the procedure (49%). Men (70%) are more likely than women (40%) to meet the anatomic criteria for endografting. Difficulties with vascular access and attachment site geometry predominate as reasons for exclusion. Our findings suggest that smaller profile devices, which can negotiate small and tortuous iliac arteries, are needed. Proximal and distal attachment site problems require devices that can accommodate wide and angulated attachment necks and achieve short seal zones.

Endovascular AAA repair in patients with renal insufficiency: strategies for reducing adverse renal events.

Vascular imaging, usually employing nephrotoxic contrast agents is relied upon for all aspects of endovascular AAA repair causing some to consider renal insufficiency a relative contraindication. We sought to determine if endovascular AAA evaluation and repair could be successfully accomplished by minimally or non-nephrotoxic modalities. Records and results for 98 consecutive patients undergoing endovascular AAA repair were reviewed. Patients requiring dialysis preoperatively were excluded (N=3). The average volume of iodinated contrast agent employed for intraoperative imaging was 152 cc (35-420 cc). Twenty patients (20%) had baseline renal insufficiency (serum creatinine > or =1.3 mg/dl). A rise in serum creatinine above baseline was observed in 23 (24%) patients following repair; for 15 (16%) this was permanent. Creatinine rise occurred in patients with both normal (15) and abnormal (8) baseline values (P=0.09). Rise in creatinine was independent of contrast volume employed and of the use of infrarenal vs suprarenal device fixation (P>0.05). Two (2%) patients required permanent dialysis, one of which had a normal baseline creatinine and unclear etiology for renal failure, the other had a baseline creatinine of 2 and required device placement over an accessory renal artery. Strategies to minimize the use of nephrotoxic contrast for patients with renal insufficiency included the use of MRA, rather than contrast-CT for pre and postoperative imaging (7, 35%) and use of Gadolinium rather than iodinated contrast for performance of intraoperative arteriography (5, 25%). Endovascular grafts were successfully designed and implanted based upon MRA as the sole preoperative imaging modality in every case in which it was attempted (7). Mortality was not significantly different between those with and without abnormal baseline renal function (P>0.05). Adverse events (access failures, arterial injuries, blood loss, endoleaks) were not significantly correlated with baseline renal insufficiency, rise in creatinine from baseline, use of MRA or intraoperative Gadolinium angiography (P>0.05).Pre- and postoperative evaluation and performance of endovascular AAA repair can be accomplished in patients with renal insufficiency without increasing the rate of mortality or adverse events employing a strategy which minimizes the use of nephrotoxic contrast agents, relying upon Gadolinium arteriography and MRA. Endovascular grafts can be successfully planned and followed employing MRA as the sole imaging modality.

Quantitative analysis of DNA binding by the Escherichia coli arginine repressor.

Allosteric activation of the hexameric arginine repressor (ArgR) for specific operator DNA binding appears to involve alteration in its quaternary structure. Current models for activation include subunit assembly and/or domain rearrangements in response to binding of the coeffector l-arginine. To investigate the molecular basis for ArgR operator interactions, we have carried out a series of quantitative analyses of ArgR subunit assembly and of the affinity, stoichiometry, cooperativity, and l-arginine- and DNA sequence-dependence of ArgR-DNA binding. The results indicate that subunit assembly plays no role in activation, although communication among subunits of the ArgR hexamer is required for specific DNA binding. The data suggest that DNA is also an allosteric effector of ArgR.

Endovascular repair of aortic aneurysms: critical events and adjunctive procedures.

OBJECTIVE: We sought to define the learning curve relative to the incidence and range of intraoperative problems and to establish guidelines for troubleshooting during the endovascular repair of infrarenal aortic aneurysms. METHODS: We prospectively evaluated our first 75 consecutive cases over a 12-month period and focused on perioperative critical events and adjunctive procedures as categorical outcome measures collected during the operation. Patients were separated into three groups on the basis of the date of their operation, such that group 1 consisted of our first 25 cases, group 2 our next 25 cases, and group 3 our last 25 cases. RESULTS: At least one critical event and adjunctive procedure marked 67 (89%) of 75 cases. In 51%, there were at least two critical events and adjunctive procedures. There were no immediate open conversions or intraoperative deaths. Access problems occurred in 28% of the 75 cases and were addressed by use of brachial-femoral artery access (30%), iliac artery/aortic bifurcation balloon angioplasty (8%), and iliofemoral conduits (4%). Graft foreshortening was the most common deployment event (44%), necessitating distal covered extensions. Iliac graft limb twists and kinks occurred in 12% of cases and were managed with balloon angioplasty and uncovered stents. General incidents included balloon ruptures (10%), arterial dissections (6%), iliac artery rupture (2.6%), and lower extremity ischemia (4%). The two cases of iliac artery rupture were managed with distal covered extensions, and there were no cases of atheroemboli. Intraoperative endoleaks were encountered in 44% of the cases and included proximal attachment sites (15%), distal attachment sites (9%), type 2 sources, and "blushes." Management of intraoperative endoleaks included proximal/distal covered extensions and re-ballooning. Our 30-day endoleak rate was 20%. The incidence of critical events did not decrease in the latter one third compared with the first two thirds of cases. CONCLUSIONS: Critical events occur frequently during endovascular repair of aortic aneurysms. The intraoperative problems range from the common endoleaks, access and deployment issues, and balloon ruptures, to rare but life-threatening complications such as iliac artery rupture. A toolbox of accessories that includes wires, catheters, large balloons, covered proximal and distal extensions, and uncovered stents is essential given the frequency of adjunctive procedures. Successful aortic endografting requires more than mere familiarity with basic endovascular techniques.

A comparative study of peptide models of the alpha-domain of alpha-lactalbumin, lysozyme, and alpha-lactalbumin/lysozyme chimeras allows the elucidation of critical factors that contribute to the ability to form stable partially folded states.

alpha-Lactalbumin (alpha LA) forms a well-populated equilibrium molten globule state, while the homologous protein hen lysozyme does not. alpha LA is a two-domain protein and the alpha-domain is more structured in the molten globule state than is the beta-domain. Peptide models derived from the alpha-subdomain that contain the A, B, D, and 3(10) helices of alpha LA are capable of forming a molten globule state in the absence of the remainder of the protein. Here we report comparative studies of a peptide model derived from the same region of hen lysozyme and a set of chimeric alpha-lactalbumin--lysozyme constructs. Circular dichroism, dynamic light scattering, sedimentation equilibrium, and fluorescence experiments indicate that the lysozyme construct does not fold. Chimeric constructs were prepared to probe the origins of the difference in the ability of the two isolated subdomains to fold. The first consists of the A and B helices of alpha LA cross-linked to the D and C-terminal 3(10) helices of lysozyme. This construct is highly helical, while a second construct that contains the A and B helices of lysozyme cross-linked to the D and 3(10) helices of alpha LA does not fold. Furthermore, the disulfide cross-linked homodimer of the alpha LA AB peptide is helical, while the homodimer of the lysozyme AB peptide is unstructured. Thus, the AB helix region of alpha LA appears to have an intrinsic ability to form structure as long as some relatively nonspecific interactions can be made with other regions of the protein. Our studies show that the A and B helices plays a key role in the ability of the respective alpha-subdomains to fold.

Balloon embolization of the internal iliac artery before aneurysm endograft deployment.

Six patients, ranging from 69 to 81 years of age, underwent iliac artery embolization with use of Detachable Silicon Balloons (DSB) 11-14 days before stent-graft repair of aneurysms. Balloons of 8.8-mm, 9.4-mm, and 9.9-mm sizes were used with 20-30 g of release force. Deployment difficulty was experienced in three cases. Five of six cases were successful, with the iliac artery remaining occluded at the time of endografting; one case required subsequent coil replacement. The average operative time for balloon embolization (75 min +/- 28) was shorter than that in 18 cases of coil embolization performed within the same time period (111 min +/- 105), but the difference was not significant (P = .21). Postoperatively, one patient (17%) reported buttock claudication after the procedure. Use of the DSB represents an alternative to use of coils for embolization of large and tortuous iliac arteries.

Effects of charged amino acids at b and c heptad positions on specificity and stability of four-chain coiled coils.

An understanding of the balance of chemical forces responsible for protein stability and specificity of structure is essential for the success of efforts in protein design. Specifically, electrostatic interactions between charged amino acids have been explored extensively to understand the contribution of this force to protein stability. Much research on the importance of electrostatic interactions as specificity and stability determinants in two-stranded coiled coils has been done, but there remains significant controversy about the magnitude of the attractive forces using such systems. We have developed a four-stranded coiled-coil system with charged residues incorporated at b and c heptad positions to explore the role of charge interactions. Here, we test quantitatively the effects of varying sidechain length on the magnitude of such electrostatic interactions. We synthesized peptides containing either aspartate or ornithine at both b and c heptad positions and tested their ability to self-associate and to hetero-associate with one another and with peptides containing glutamate or lysine at the same positions. We find that interactions between glutamate and either lysine or ornithine are more favorable than the corresponding interactions involving aspartate. In each case, charged interactions provide additional stability to coiled coils, although helix propensity effects may play a significant role in determining the overall stability of these structures.

Formation of a stable heterodimer between Smad2 and Smad4.

Smad proteins mediate transforming growth factor beta signaling from the cell membrane to the nucleus. Upon phosphorylation by the activated receptor kinases, the receptor-regulated Smad, such as Smad2, forms a heterocomplex with the co-mediator Smad, Smad4. This heterocomplex is then translocated into the nucleus, where it associates with other transcription factors and regulates expression of ligand-responsive genes. The stoichiometry between receptor-regulated Smad and co-mediator Smad is important for understanding the molecular mechanisms of the signaling process. Using purified recombinant proteins, we demonstrate that Smad2 and Smad4 form a stable heterodimer and that the Smad4 activation domain is important for the formation of this complex. Many tumor-derived missense mutations disrupt the formation of this heterocomplex in in vitro interaction assays. Mapping these mutations onto the structures of Smad4 and Smad2 identifies a symmetric interface between these two Smad proteins. Importantly, two previous models on the formation of a heterocomplex are incompatible with our observations and other reported evidence.

The role of magnetic resonance angiography for endoprosthetic design.

OBJECTIVES: Many patients with aortic aneurysms have renal insufficiency and may be at increased risk when conventional imaging modalities (contrast-enhanced computed tomography and arteriography) are used for aortic endograft design. Our objective was to determine if magnetic resonance angiography (MRA) could be used as the sole imaging modality for endoprosthetic design. METHODS: A total of 96 consecutive patients who underwent endovascular repair of thoracic (5) and abdominal (91) aortic aneurysms (April 1998-December 1999) were included in this study. Data were collected prospectively. Gadolinium-enhanced MRA was used preoperatively in place of conventional imaging if renal insufficiency or a history of severe contrast reaction was present. The control group underwent conventional imaging. Endografts used included Ancure, AneuRx, and Talent. RESULTS: Fourteen patients (14.6%) had their endografts designed solely with MRA. Intraoperative access failure; proximal and distal extensions (unplanned); conversion to open, aborted procedures; and endoleaks occurred with equal frequency in both the MRA-designed and control groups (16.7% vs 18.3%, respectively; P =.33). Despite baseline renal insufficiency, there was no significant rise in the creatinine level after endograft implantation in patients with an MRA design (preoperative level, 1.8; postoperative level, 1.9; P =.5). CONCLUSION: MRA may be successfully used as the sole modality for aortic endograft design. The use of MRA for this purpose is noninvasive and minimizes nephrotoxic risk.

Failure of endovascular abdominal aortic aneurysm graft limbs.

OBJECTIVE: Endovascular abdominal aortic aneurysm (AAA) grafts are subject to subsequent failure of endograft limbs. We sought to determine what device-related factors could be identified that might contribute to limb failure. METHODS: We reviewed the records of patients who had undergone endovascular AAA repair and femorofemoral bypass grafting at a single institution. RESULTS: Endovascular AAA repair was performed in 173 patients. There were 137 bifurcated endografts and 36 aortomonoiliac grafts combined with femorofemoral bypass grafts, yielding a total population of 310 aortic graft limbs and 36 femorofemoral grafts. Thirty-nine additional patients underwent femorofemoral bypass grafting for occlusive disease. The cumulative primary patency of all endografts performed for AAA was 92% at 21 months. Secondary patency was achieved for all failed endograft limbs. There were 24 aortic graft limb "failures" that required intervention: seven limbs underwent thrombosis requiring revision; kinked limbs requiring stenting either at the time of graft placement (17) or subsequently (7) were identified. Fully supported endograft limbs had better primary patency (97% at 18 months) than unsupported limbs (69% at 18 months, P <.001). The aortomonoiliac grafts with femorofemoral bypass grafts tended to have better patency (97% at 18 months) than bifurcated endografts (90% at 18 months), but this did not reach statistical significance (P =.28, not significant). Femorofemoral grafts performed for occlusive disease were found to have somewhat lower patency than those performed for AAA (83% vs 92% at 18 months of follow-up, P =.37, not significant). CONCLUSIONS: Fully supported AAA endografts provide superior endograft limb patency compared with unsupported designs. Consideration should be given to routine stenting of all unsupported endograft limbs. Aortomonoiliac grafts and bifurcated grafts provide similar results for endograft limb patency. Femorofemoral bypass grafts performed in conjunction with aortomonoiliac grafts for AAA disease provide excellent short-term patency.

Gender-related differences in infrarenal aortic aneurysm morphologic features: issues relevant to Ancure and Talent endografts.

PURPOSE: The purpose of this study was to determine whether gender-related anatomic variables may reduce applicability of aortic endografting in women. METHODS: Data on all patients evaluated at our institution for endovascular repair of their abdominal aortic aneurysm were collected prospectively. Ancure (Endovascular Technologies (EVT)/Guidant Corporation, Menlo Park, Calif) and Talent (World Medical/Medtronic Corporation, Sunrise, Fla) endografts were used. Preoperative imaging included contrast-enhanced computed tomography and arteriography or magnetic resonance angiography. RESULTS: One hundred forty-one patients were evaluated (April 1998-December 1999), 19 women (13.5%) and 122 men (86.5%). Unsuitable anatomy resulted in rejection of 63.2% of the women versus only 33.6% of the men (P = .026). Maximum aneurysm diameter in women and men were similar (women, 56.94 +/- 8.23 mm; men, 59.29 +/- 13.22 mm; P = .5). The incidence of iliac artery tortuosity was similar across gender (women, 36.8%; men, 54.9%; P = .2). The narrowest diameter of the larger external iliac artery in women was significantly smaller (7.29 +/- 2.37 mm) than in men (8.62 +/- 2.07 mm; P = .02). The proximal neck length was significantly shorter in women (10.79 +/- 12.5 mm) than in men (20.47 +/- 19.5 mm; P = .02). The proximal neck width was significantly wider in women (30.5 +/- 2.4 mm) than in men (27.5 +/- 2.5 mm; P = .013). Proximal neck angulation (>60 degrees) was seen in a significantly higher proportion of women (21%) than men (3.3%; P = .012). Of the patients accepted for endografting, a significantly higher proportion of women required an iliofemoral conduit for access (women, 28.6%; men, 1.2%; P = .016). CONCLUSION: Gender-related differences in infrarenal aortic aneurysm morphologic features may preclude widespread applicability of aortic endografting in women, as seen by our experience with the Ancure and Talent devices. In addition to a significantly reduced iliac artery size, women are more likely to have a shorter, more dilated, more angulated proximal aortic neck.

Update on the Talent aortic stent-graft: a preliminary report from United States phase I and II trials.

PURPOSE: Phase I and phase II trials were conducted to determine the safety and efficacy of the Talent aortic stent-graft (Medtronic World Medical, Sunrise, Fla) in the treatment of infrarenal abdominal aortic aneurysms (AAA). This is a preliminary report of the technical results and 30-day clinical outcome of these trials. METHODS: Multicenter prospective trials were conducted to test the Talent stent-graft in high-risk and low-risk patient populations with AAA, including phase I feasibility and phase II clinical trials. The low-risk study included concurrent surgical controls. RESULTS: In the phase I trial, deployment success was achieved in 92% (23/25 patients), and initial technical success was 78% (18/23 implants without endoleak). The 30-day technical success rate was 96%, with six endoleaks that resolved spontaneously (without need for further intervention); and the 30-day mortality rate was 12% (3/25 patients). The phase II high-risk trial demonstrated a deployment success of 94% (119/127 patients) and an initial technical success of 86% (102/119 implants). The 30-day technical success rate was 96%, and the 30-day mortality rate was 1.5% (2/127 patients). The phase II low-risk trial included a first-generation and a second-generation Talent stent-graft. Deployment success rates were 97% and 99%, respectively, and technical success rates at 30 days were 97% and 96%, respectively. The 30-day mortality rate was 2% in the phase II low-risk first-generation device trial, and the adverse-event rate was 20%. Corresponding figures for the second-generation device were 0% and 1.8%, respectively. CONCLUSION: The Talent stent-graft can be deployed successfully and achieves endovascular exclusion in a large proportion of patients with AAA. Morbidity and mortality rates are acceptable. One-year clinical results and the comparison with concurrent surgical control subjects remain to be evaluated.