Endovenous thermal ablation of superficial venous insufficiency of the lower extremity: single-center experience with 3000 limbs treated in a 7-year period.

PURPOSE: To demonstrate that endovenous thermal ablation is not only effective and safe but also a durable treatment in patients with symptomatic varicose veins. METHODS: From February 2002 to February 2009, 2354 patients (1836 women; mean age 53 years, range 15-95) with symptomatic varicose veins in 3000 limbs underwent endovenous laser ablation (EVLA) or radiofrequency ablation (RFA). The majority of treated vessels were the great saphenous veins (GSV; 2619, 87.3%); 269 (8.9%) small saphenous veins (SSV) and 112 (3.8%) accessory saphenous veins (ASV) were also treated, all in outpatient procedures under local intra-compartmental anesthesia. An ultrasound evaluation was performed within 2 weeks of the procedure to evaluate vein occlusion, vein wall thickness, and clot extension into the deep vein. In a long-term evaluation involving the first 165 patients treated from February 2002 to January of 2003, 105 (64%) patients [126 (67%) of the 188 eligible limbs] were followed annually with clinical evaluation, duplex ultrasound, and symptom/satisfaction assessment over a mean 6.7 years. RESULTS: Treatment of 3000 limbs involved the use of EVLA in 2841 (2460 GSVs, 269 SSVs, and 112 ASVs) and RFA in 159 GSVs. Post-procedure duplex ultrasound found 57 (2.0%) veins recanalized or incompletely occluded [51 (2%) treated with EVLA and 6 (3.7%) with RFA] in patients treated for GSV or ASV incompetence. In the 269 SSVs treated (all with EVLA), 18 (6.7%) limbs demonstrated incomplete occlusion. Overall, both EVLA and RFA procedures were well tolerated, with minimal complications. In the longitudinal assessment of the 105 patients (126 limbs) participating in annual follow-up for a mean 6.7 years, the overall rate of satisfaction, symptom relief, and absence of varicosities was 86%. CONCLUSION: Endovenous ablation of saphenous vein has proven to be an effective, safe, and very durable procedure.

HCV NS5B polymerase inhibitors 3: Synthesis and in vitro activity of 3-(1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-4-hydroxy-2H-quinolizin-2-one derivatives.

3-(1,1-Dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-4-hydroxy-2H-quinolizin-2-one derivatives as potential anti-HCV drugs targeting NS5B polymerase have been investigated. Their synthesis, HCV NS5B polymerase inhibition, and replicon activity are discussed.

HCV NS5B polymerase inhibitors 1: Synthesis and in vitro activity of 2-(1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene derivatives.

2-(1,1-Dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene derivatives as potential anti-HCV drugs targeting NS5B polymerase have been investigated. Their synthesis, HCV NS5B polymerase inhibition and replicon activity are discussed.

Endovenous ablation of incompetent saphenous veins: a large single-center experience.

PURPOSE: To evaluate the effectiveness of endovenous treatment of symptomatic varicose veins using the endovenous laser (EVL) or radiofrequency (RF) energy over a >3-year follow-up. METHODS: From February 2002 to August 2005, 981 consecutive patients (770 women; mean age 51 years, range 15-90) with symptomatic varicose veins in 1250 lower limbs underwent endovenous ablation of 1149 great saphenous veins (GSV) and 101 small saphenous veins (SSV) under tumescent anesthesia without intravenous sedation or regional anesthesia. There were 990 GSV and 101 SSV procedures using EVL; 159 GSVs were treated with RF energy. An ultrasound evaluation was performed within 2 weeks of the procedure to evaluate occlusion of the vein, wall thickness, and clot extension into the deep venous system. Follow-up from the first 200 procedures in the series included clinical evaluation and duplex ultrasound scanning at 6 and 12 months and annually thereafter. RESULTS: Of the 1149 GSVs treated, 39 (3.4%) recanalizations were seen in 33 of the EVL and 6 of the RF procedures for inadequate treatment as judged by ultrasound. There were 9 (9.0%) failures among the 101 SSVs treated with EVL. Overall, both EVL and RF procedures were well tolerated, with only minor complications. One obese patient with ulcer developed pulmonary embolus on the fourth postoperative day. There were no differences between EVL and RF in efficacy or complications. Follow-up at a mean 3 years (range 30- 42 months) in 143 treated limbs showed no neovascularization in the groin. CONCLUSION: Outcomes with EVL and RF were good, with low complication rates that may be related to the use of local tumescent anesthesia without intravenous sedation.

Endovenous laser ablation of the saphenous vein for treatment of venous insufficiency and varicose veins: early results from a large single-center experience.

PURPOSE: To report early results of a single-center experience with endovenous laser ablation of the saphenous vein (ELAS). METHODS: From February 2002 to January 2003, 165 eligible patients (116 women; mean age 59.1 years, range 27-90) were treated with ELAS for venous insufficiency in 203 lower limbs. All patients were symptomatic, and the majority (62%) had class 4 or higher clinical disease (CEAP classification). Eighteen (8.9%) patients had ulcers. A 940-nm diode laser was used in an office setting under local tumescent anesthesia to deliver 100 to 140 laser applications along the course of the vein. Two weeks of compression bandages and a 1-week course of ibuprofen were prescribed postoperatively. All patients underwent a duplex scan of the target vein at 2 weeks. RESULTS: The great (154, 76%), short 37 (18%), and accessory 12 (6%) saphenous veins were ablated, achieving a 97% clinical success rate. Postoperative complications were few (mild induration and ecchymosis) and well tolerated (no DVT or nerve injury). Of the 6 (3.0%) recanalized target veins, 4 were only partially open and successfully treated with sclerosis. Of the 18 patients with active ulceration, 15 (83%) demonstrated healing after ELAS. In a satisfaction survey of patients more than 1 year after ELAS treatment, 84% of the 31 responders claimed their symptoms had diminished to none or minimal; 97% were mostly or very satisfied with their treatment results. CONCLUSIONS: ELAS for symptomatic saphenous vein incompetence and varicose veins has excellent short-term subjective and objective outcomes. This technique appears to be very successful in reducing symptoms, resolving varicose veins, and healing ulcers.

Crossing the limbs: a useful adjunct for successful deployment of the AneuRx stent-graft.

PURPOSE: To describe a technique for deploying an AneuRx stent-graft in an abdominal aortic aneurysm (AAA) with an acutely angled aortic neck. TECHNIQUE: In routine cases, the AneuRx stent-graft main body is positioned with the nose cone notch facing the contralateral side. In severely angulated aortic necks, however, the main body of the AneuRx stent-graft can be positioned with the nose cone notch and iliac limb gate facing the ipsilateral side; this dramatically reduces the acuity of the angle at the aortic neck and the iliac gate. This technique of "crossing the limbs" has been successfully used in 7 cases since FDA approval of the AneuRx device. CONCLUSIONS: Proximal neck angulation is an important factor for successful endovascular AAA repair. Crossing the graft limbs reduces the effect of neck angulation on the proximal main body and may decrease the stress upon the contralateral limb gate, which may avoid graft gate disconnection and endoleak.

The AneuRx stent-graft since FDA approval: single-center experience of 230 cases.

PURPOSE: To compare a single-center experience with the AneuRx stent-graft system before and after FDA approval to results from the multicenter phase II clinical trial. METHODS: The medical records of 230 consecutive patients (218 men; mean age 74 years) undergoing AneuRx stent-graft implantation for abdominal aortic aneurysm (AAA) exclusion since September 1999 were reviewed to collect patient characteristics, aneurysm morphology, procedure variables, perioperative morbidity, mortality, and short-term outcome. These data were compared to the 30 patients treated at our institution during the AneuRx phase II clinical trial and to the overall multicenter trial data. Stent-graft difficulty was categorized from 1 (straight neck and access of appropriate size) to 4 (proximal neck <10 mm long or angulated >60 degrees and/or difficult access) based on aneurysm morphology. RESULTS: Data from the 30 patients enrolled in the phase II trial at our institution were comparable in terms of patient characteristics and procedure variables to patients treated after FDA approval and to the multicenter data. However, the proportion of cases involving aneurysms with a more complex morphology (levels 3 and 4) rose 22% after FDA approval, reflecting a change in referral patterns. Our postoperative endoleak and morbidity rates increased nonsignificantly with respect to our own phase II experience (17% versus 6%, 18% versus 11%, respectively); however, they were not significantly different from the multicenter data. Reintervention was performed in 15 of 38 endoleak cases, mostly type I. Only 5 (2.1%) cases had a persistent endoleak at the time of discharge. CONCLUSIONS: Since FDA approval of the AneuRx device, our endovascular practice has changed toward the management of increasingly more complex AAAs. Although we are attempting more challenging cases, we are able to maintain similarly high short-term success rates while offering stent-grafting to an increasing number of patients. These results suggest that more patients may be candidates for endoluminal graft placement than determined by the clinical trial selection criteria, provided that strict surveillance and long-term follow-up is maintained.

Endoluminal stent grafting of the thoracic aorta: initial experience with the Gore Excluder.

PURPOSE: The purpose of this study was to describe our experience with endoluminal graft repair of a variety of thoracic aorta pathologies with a commercially developed device currently under investigation. Our patient population included patients eligible for open surgical repair and those with prohibitive surgical risk. METHODS: From February 2000 to February 2001, endovascular stent-graft repair of the thoracic aorta was performed in 46 patients (mean age, 70 years; 29 male and 17 female patients) with the Gore Excluder. Twenty-three patients (50%) had atherosclerotic aneurysms, 14 patients (30%) had dissections, three patients (7%) had aortobronchial fistulas, three patients (7%) had pseudoaneurysms, two patients (4%) had traumatic ruptures, and one patient (2%) had a ruptured aortic ulcer. Patient characteristics, procedural variables, outcome, and complications were recorded. All patients were followed with chest computed tomographic scans at 1, 3, 6, and 12 months. Follow-up period ranged from 1 month to 15 months, with a mean of 8.5 months. RESULTS: All the procedures were technically successful. There were no conversions. Average duration of the procedure was 120 minutes. Average length of stay was 6 days, but most patients (64%) left the hospital within 4 days after endoluminal grafting. The overall morbidity rate was 23%. Two patients (4%) had endoleaks that necessitated a second procedure for successful repair. Two patients (4%) died in the immediate postoperative period. There were no cases of paraplegia. At follow-up examination, one patient had an endoleak found the day after the procedure and another patient had an endoleak 6 months after the procedure. Both cases were treated successfully with additional stent-grafts. There were no cases of migration. One patient died of a myocardial infarction 6 months after graft placement. In patients treated for aneurysm (n = 23), the aneurysm diameter ranged from 5.0 to 9.5 cm (mean, 6.8 cm). Residual sac measurements were obtained at 1, 6, and 12 months, with mean sac reductions of 0.59 cm, 0.77 cm, and 0.85 cm, respectively. In three cases, the sac remained unchanged, without evidence of endoleak. CONCLUSION: Thoracic endoluminal grafting with the Gore Excluder is a safe and feasible alternative to open graft repair and can be performed successfully with good results. Early data suggest an endoluminal approach to these disease entities may be favorable over classical resection and graft replacement.

A direct spectrophotometric assay for peptide deformylase.

A direct UV-VIS spectrophotometric assay has been developed for peptide deformylase. This assay employs a novel class of peptide mimetics as deformylase substrates which, upon enzymatic removal of the N-terminal formyl group, rapidly release free thiols. The released thiols are quantitated using Ellman's reagent. A variety of peptide analogues that contain beta-thiaphenylalanine or beta-thiamethionine as the N-terminal residue were synthesized and found to be excellent substrates of the peptide deformylase from Escherichia coli (k(cat)/K(M) = 6.9 x 10(5) M(-1) s(-1) for the most reactive substrate). The deformylase reaction is conveniently monitored on a UV-VIS spectrophotometer in a continuous fashion. The versatility of the assay has been demonstrated by its application to kinetic characterization of the deformylase, pH profile studies, and enzyme inhibition assays. The assay can also be performed in an end-point fashion. The results demonstrate that this assay is a simple, highly sensitive, and rapid method to study kinetic properties of deformylases without the use of any coupling enzymes.