Comparison of AngioJet Rheolytic Pharmacomechanical Thrombectomy versus AngioJet Rheolytic Thrombectomy in a Porcine Peripheral Arterial Model

Introduction Rheolytic thrombectomy using the AngioJet catheter for arterial thrombosis has been shown to be effective in restoring blood flow. Additional infusion of thrombolytic agents via the AngioJet catheter results in combined rheolytic pharmacomechanical thrombolysis (PMT), which further enhances thrombectomy efficacy. However, the histologic response to rheolytic PMT therapy remains unclear. This study compares the acute and chronic vessel wall response and hemolysis due to conventional AngioJet rheolytic thrombectomy (RT) and AngioJet PMT in the porcine peripheral arterial model. Methods A total of 19 juvenile pigs were divided into acute and chronic groups. In the acute group (n = 6), bilateral common carotid, femoral, and iliac arteries ranging from 3 to 6 mm in diameter were randomized to the control RT group or to PMT therapy. Vessels were analyzed 4 days following interventions. In the chronic group (n = 5), bilateral common carotid, femoral, and iliac arteries ranging from 3 to 6 mm in diameter were randomized to the control RT group or to PMT therapy. Vessels were analyzed at 30 days following interventions. Hemolytic evaluation was performed in additional eight pigs, which were randomized to either RT or PMT intervention. Results In the acute group, similar histologic injury grades were noted between the RT- and PMT-treated femoral and iliac vessels. Endothelial denudation in the RT and PMT vessels were 43% and 39% (NS), respectively. Vessels with intact internal elastic lamina (IEL) in the RT and PMT groups were 54% and 57% (NS), respectively. In vessels < 4 mm in diameter, fractured IEL in the AT and PMT groups occurred in 23% and 27% (NS), respectively. The degrees of smooth muscle cell (SMC) loss were similar for the RT- and PMT-treated vessels (45% and 40%, respectively; NS). In the chronic group, no differences were seen between the RT and PMT groups with respect to endothelial denudation, IEL fracture rate, or SMC loss. Similar degrees of medial thickening or intimal hyperplasia were noted in the RT and PMT groups (49% and 43%, respectively; NS). No difference in hemolytic effect was noted in the treatment groups. Conclusions AngioJet rheolytic pharmacomechanical thrombectomy treatment incurs an equivalent safety profile in medium-caliber peripheral arteries when compared to rheolytic thrombectomy treatment. No difference in hemolytic reaction occurred in either group. The observed clinical efficacy of rheolytic pharmacomechanical thrombectomy does not result in untoward vessel injury compared to conventional rheolytic thrombectomy therapy. This work was presented at the Molecular Surgeon Symposium on Vascular Injury, Repair and Remodeling at the Baylor College of Medicine, Houston, Texas, May 15 and 16, 2006. The symposium was supported by a grant from the National Institutes of Health (to C. Chen: R13 HL0836500).     

AngioJet机械吸栓与置管溶栓治疗下肢深静脉血栓的成本效益分析

背景与目的：下肢深静脉血栓（DVT）是住院患者常见的并发症,目前对其治疗倾向于快速清除血栓,以减少血栓后遗症的出现。方法主要包括导管接触性溶栓（CDT）及经皮机械性血栓清除术（PMT）,但对CDT和PMT的适应证仍有一定争议,卫生经济学方面也缺少相关研究,无法衡量CDT和PMT治疗方法使患者受益的情况。本研究旨在通过分析接受外科治疗的下肢DVT患者来综合评估比较CDT和AngioJet两种治疗方式对患者的获益情况,为临床医生选择合适的治疗方式提供一些建议,使患者在疗效、生活、经济上能够得到最大的获益。方法：收集苏北人民医院血管外科2018年12月—2020年8月确诊下肢DVT并接受CDT或AngioJet方式治疗的患者临床与随访数据,分析疗效（证候积分）、成本效益,以及随访彩超复查结果、Villalta评分及CIVIQ-2评分。结果：共纳入79例下肢DVT患者,其中AngioJet治疗47例（AngioJet组）,CDT治疗32例（CDT组）。两组患者一般资料与耗材使用情况差异均无统计学意义（均P>0.05）。两组治疗后症状均明显好转,AngioJet组痊愈率高于CDT组（34....     

Catheter-direct thrombolysis versus pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis

BACKGROUND: Rheolytic mechanical thrombectomy using the AngioJet catheter (Possis Medical, Minneapolis, MN) has been shown to be effective in the treatment of deep venous thrombosis (DVT). Additional infusion of thrombolytic agents via the device creates a novel treatment strategy of pharmacomechanical thrombectomy (PMT), which further enhances thrombectomy efficacy. The purpose of the current study was to compare the treatment outcome in patients with symptomatic DVT who underwent either catheter-directed thrombolysis (CDT) or PMT intervention. METHODS: During a recent 8-year period, clinical records of all patients with symptomatic lower leg DVT undergoing catheter-directed interventions were evaluated. Patients were divided into 2 treatment groups: CDT or PMT. Comparisons were made with regards to the treatment outcome between the 2 groups. RESULTS: A total of 93 patients who underwent 98 catheter-directed interventions for DVT were included in the study. Among them, CDT or PMT was performed in 46 (47%) and 52 (53%) procedures, respectively. In the CDT group, complete or partial thrombus removal was accomplished in 32 (70%) and 14 (30%) cases, respectively. In the PMT cohort, complete or partial thrombus removal was accomplished in 39 (75%) and 13 (25%) cases, respectively. Venous balloon angioplasty and/or stenting in the CDT or PMT groups was necessary in 36 (78%) and 43 (82%), respectively (difference not significant [NS]). Patients in the CDT groups underwent a mean of 2.5 venograms during the hospital course, in contrast to 0.4 venograms per patient in PMT cohorts (P < .001). Immediate (<24 hours) improvement in clinical symptoms in CDT and PMT groups was achieved in 33 (72%) and 42 (81%) cases, respectively (NS). Significant reductions in the intensive care unit (ICU) and hospital lengths of stay was noted in the PMT group (0.6 and 4.6 days) when compared to the CDT group (2.4 and 8.4 days). During follow-up visits, the primary patency rates at 1 year of CDT and PMT groups were 64% and 68%, respectively (NS). Hospital cost analysis showed significant cost reduction in the PMT group compared to the CDT group (P < .01). CONCLUSIONS: PMT with adjunctive thrombolytic therapy is an effective treatment modality in patients with significant DVT. When compared to CDT, this treatment provides similar treatment success with reduced ICU, total hospital length of stay, and hospital costs.     

大腔导管手动抽吸和经皮机械血栓清除术治疗髂静脉闭塞继发髂股静脉血栓形成的比较

背景与目的:急性髂股型深静脉血栓可导致比较严重的并发症,目前治疗方法包括导管接触性溶栓(CDT)、大腔导管手动抽吸(MAT)、经皮机械性血栓清除术(PMT)等技术,本研究比较MAT与PMT术后同期支架置入术治疗髂静脉闭塞继发髂股静脉血栓形成的疗效及安全性,为临床治疗选择提供参考.方法:回顾性分析收治的63例髂静脉闭塞继...     

Aspirex机械清栓治疗创伤后急性下肢深静脉血栓形成的临床疗效

背景与目的 下肢深静脉血栓形成（DVT）行早期血栓清除减容可恢复静脉通畅及缓解症状,目前AngioJet是国内最常用的静脉血栓清除系统,而Aspirex应用较少,本研究探讨Aspirex机械血栓清除治疗在创伤后急性DVT患者中的疗效及安全性。方法 回顾性分析2016年5月—2020年8月在北京积水潭医院血管外科收治的54例创伤后急性DVT患者的病例资料。所有患者行下腔静脉可回收滤器置入术,其中有Dneali 35例（64.8%）、Celect 3例（5.6%）、Cordis 14例（25.9%）、Octoparms及临时滤器（贝朗）各1例（1.9%）。患者创伤经手术及固定治疗后均行彩超检查或造影明确为髂股静脉及下腔静脉血栓形成。其中,22例（40.7%）为髂股静脉血栓、4例（7.4%）为髂及下腔静脉血栓、11例（20.4%）为下腔静脉血栓、17例（31.5%）为股髂静脉及下腔静脉血栓。所有患者在局麻下行经腘静脉或股静途径Straub Aspirex机械血栓清除手术（PMT）,术中联合导管取栓（MAT）、导管接触性溶栓（CDT）、髂静脉球囊扩张及髂静脉支架置入术。统计技术成功率、即刻临床成功率（症状缓解率）、围手术期出血发生率及术后滤器取出率。术后随访1年,超声评价目标静脉通畅率及血栓后综合征（PTS）的发生率。结果 54例患者中,3例（5.6%）行单纯机械血栓清除手术,17例（31.5%）行血栓清除联合导管取栓术,3例（5.6%）行血栓清除联合置管溶栓术,18例（33.3%）行血栓清除联合导管取栓及置管溶栓术,12例（22.2%）行血栓清除联合导管取栓及髂静脉球囊扩张术,1例（1.9%）行血栓清除联合导管取栓及支架置入术。技术成功率及即刻临床成功率均为100%。12例（22.2%）血栓III级清除,33例（61.1%）为II级清除,9例（16.7%）为I级清除,血栓清除成功率为83.3%。围手术期1例（1.9%）出现脑出血,给予停止溶栓及抗凝,2周复查头颅CT见血肿吸收,无后遗症;2例（3.7%）出现鼻出血及穿刺点血肿,给予压迫后缓解,无症状性肺栓塞及死亡等发生。滤器留置时间为（61.4±84.8）d,51例（94.4%）患者尝试行滤器取出,所有患者均成功取出。术后无血栓复发,术后1年PTS的发生率为33.3%,目标静脉通畅率为75.9%。结论 对于创伤后急性髂股及下腔静脉DVT患者,应用Aspirex机械血栓清除疗效显著,较为安全可靠,与导管吸栓、CDT、髂静脉球囊扩张及支架置入结合应用可改善静脉通畅率。     

Gene therapy for myocardial angiogenesis

Objectives: We studied the therapeutic potential of ex vivo vascular endothelial growth factor (VEGF) gene-transduced H9c2 cell transplantation for myocardial neovascularization. Methods: The left ventricular free wall of adult Sprague-Dawley rats was cryodamaged. Two weeks after, naked plasmid encoding VEGF (VEGF1: 1μg/100 μl, VEGF5: 5μg/100μl), or VEGF transfected H9c2 myoblasts (0.5× 10⁶ cells/200 μl) were injected into the center of scar tissue. Four weeks after cryoinjury, scar diameters in the each group were measured. Neovascularization in the scar tissue was then quantified histologically. Results: Average scar tissue diameter 4 weeks after cryoinjury was as follows: TE (controls): 6.77±0.31 mm, H9c2: 5.08±0.43 mm; VEGF1: 5.90±0.20 mm; VEGF5: 4.50±0.24 mm. Scar tissue diameter was smaller in the 3 groups than in the control group (p<0.05). Capilary density by histological examination increased in naked plasmid injection groups (VEGF1: 1,209.9±305.3/mm²; VEGF5: 1,072.0±230.8/mm²) versus control (708.2±144.9/mm², p<0.05, p<0.05), and H9c2 cell transplantation group (1,379.4±391.6/mm²) versus controls (p<0.05). Conclusion: VEGF-transfected H9c2 myoblasts can transplantation group was markedly similar to direct myocardial injection in naked plasmid encoding VEGF groups.     

Inhibition of Growth and Metastasis of Tumor in Nude Mice after Intraperitoneal Injection of Bevacizumab

Objective

To explore the inhibitory effect of bevacizumab, a vascular endothelial growth factor antibody, on angiogenesis in human osteosarcoma of nude mice.

Methods

Twenty‐one nude mice were inoculated with red fluorescent protein (RFP)‐labeled human osteosarcoma cell line 143B‐RFP, that is, clones that expressed RFP in the cytoplasm, and randomly assigned to one of three groups: G1 (Control group, injected with saline solution); G2 (intraperitoneal bevacizumab 2 mg/kg twice per week) and G3 (intraperitoneal bevacizumab 5 mg/kg, twice per week). The tumor‐bearing mice were examined in a fluorescence light box that was illuminated periodically. The primary tumors were measured by fluorescence imaging weekly and their volumes calculated.

Results

The mean tumor volumes were significantly smaller in the G3 (186.4 ± 100.8 mm³) than the control group (587.0 ± 406.8 mm³) (P < 0.05) on Day 31, and again significantly smaller in the G3 (677.3 ± 461.9 mm³) than the control group (3162.6 ± 1529.2 mm³) on Day 38 (P < 0.01). The average tumor volume in the G2 group was 493.5 ± 425.4 mm³ on Day 31 and 1870.1 ± 1524.8 mm³ on Day 38. The effect on tumor volume was greater in the G3 than the G2 group. Three mice in the G2 group, four in the G3 group and four in the control group developed lung metastases that were confirmed by pathological examination; these differences were not statistically significant (P < 0.05).

Conclusions

Bevacizumab exhibits strong antiangiogenesis activity in experimental osteosarcoma in a nude mouse model but does not influence the incidence of lung metastasis. Our findings may have considerable potential for the treatment of osteosarcoma.     

AngioJet清除急性下腔静脉血栓的临床效果分析

背景与目的 下腔静脉（IVC）血栓形成常继发于IVC滤器置入术后,急性期主要表现为肢体肿胀和肺栓塞（PE）,慢性期表现为IVC狭窄、闭塞及深静脉血栓后综合征,因此临床上推荐早期清除急性IVC血栓,减少并发症发生。AngioJet目前已广泛应用于清除急性下肢深静脉血栓,但对急性IVC血栓清除的方法及清除效果研究极少。本文旨在探讨AngioJet血栓清除装置治疗急性IVC血栓形成的有效性和安全性。方法 回顾性分析2020年7月—2021年6月北京积水潭医院血管外科行AngioJet治疗的58例急性IVC血栓患者临床资料,评估手术安全性、PE发生率、血栓清除效果、滤器取出率以及住院时间和血栓治疗费用增加。结果 58例患者均放置了可回收型滤器,术后56例（96.6%）成功取出,2例（3.4%）3个月后失访未取出。行AngioJet治疗后,III级清除10例（17.2%）,II级清除34例（58.6%）,I级清除14例（24.1%）;联合使用导管吸栓或导管溶栓后（CDT）血栓III级清除14例（24.1%）,II级清除36例（62.1%）,I级清除8例（13.8%）;2例（3.4%）发生IVC阻塞,3个月随访通畅率96.6%;术前存在PE 16例（27.6%）,术后出现PE或PE加重2例（3.4%）,其余患者无变化或PE减轻,手术前后PE情况前后差异无统计学意义（P>0.05）;患者术后肝肾功能指标升高,但均未达到急性肝损伤和肾损伤诊断标准。单纯应用AngioJet共22例（37.9%）,术后住院时间增加（1.45±0.51）d,增加医疗费用（27 248±78）元;AngioJet联合导管吸栓和（或）CDT共36例（62.1%）,术后住院时间增加（2.22±1.22）d,增加医疗费用（30 607±1 134）元,差异有统计学意义（均P<0.05）。结论 AngioJet清除急性IVC血栓治疗安全有效,未明显增加患者症状性PE风险,使用导管吸栓和CDT导管溶栓等治疗可增加血栓清除效果,但会延长术后住院时间并增加血栓清除相关医疗费用。     

Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis: safety and feasibility study

PURPOSE: The current standard of care for deep venous thromboembolism (DVT) is anticoagulation; however, this treatment method does not rapidly relieve clot burden or clinical symptoms. We describe a rapid and effective method of thrombus removal, with simultaneous percutaneous mechanical thrombectomy (PMT) and thrombolysis. METHODS: Over 26 months 20 patients (22 men, 2 women; mean age, 52 +/- 6 years [range, 38-79 years]) with extensive lower extremity DVT were treated with PMT with the AngioJet thrombectomy device in combination with lytic agent (urokinase, tissue plasminogen activator, or reteplase) added to the infusion. Three patients underwent treatment twice, because of recurrent DVT. The primary end point was angiographic evidence of restoration of venous patency at completion of the procedure. Complications, recurrent ipsilateral DVT, and improvement in clinical symptoms were evaluated. RESULTS: Complete thrombus removal was obtained in 15 procedures (65%), and partial resolution in the remaining 8 procedures (35%). Inciting occlusive lesions responsible for acute DVT were revealed in 14 patients (61%), and angioplasty with or without stenting was performed when necessary. In the 8 procedures with partial resolution additional catheter-directed thrombolysis was carried out on average for 5.7 hours, with further thrombus reduction. Overall, immediate (<24 hours) improvement in clinical symptoms was noted in 17 patients (74%). There were no complications related to either PMT or the short duration of lytic agent infusion. At average follow-up of 10.2 +/- 0.3 months (range, 3-26 months), 3 patients had recurrent ipsilateral DVT, and underwent repeat treatment. CONCLUSIONS: Addition of lytic agent to PMT facilitates thrombus extraction, decreases overall interventional treatment time, and improves patient outcomes. In addition, definitive management of underlying anatomic lesions can be performed in the same setting. Further outcome measures are necessary to study the long-term efficacy of this treatment method on preservation of valve function, reduction of chronic venous insufficiency, and improved quality of life.     

Effectiveness of pigtail catheter crushing combined with AngioJet mechanical aspiration for treatment of acute left iliofemoral vein thrombosis

Background/objectiveWe investigated the efficacy of combined pigtail catheter crushing and AngioJet mechanical aspiration of thrombi in the treatment of acute iliofemoral deep venous thrombosis (DVT).MethodsEighty-two patients with acute iliofemoral DVT were retrospectively divided into a pigtail catheter + AngioJet group (group A, 42 cases) and an AngioJet-only group (group B, 40 cases). The difference in the circumference of the healthy limbs before and after treatment, immediate thrombus clearance rate in the lower limbs, recannalization percentage of venous lumen, and duration of postoperative hematuria were compared to evaluate the safety and effectiveness of the combination method.ResultsThe technical success rate was 100%, no serious bleeding complications occurred, lower extremity symptoms were effectively alleviated, and post-treatment recannalization percentage of venous lumen were similarly high in both groups. Group A fared significantly better than group B in immediate thrombus clearance (P < 0.05), intraoperative aspiration time (199.38 ± 68.55 vs. 295.30 ± 76.02 s), postoperative CDT urokinase dosage (2.10 ± 0.94 vs. 3.07 ± 0.94 million units), and duration of postoperative hematuria (13.23 ± 2.96 vs. 16.75 ± 3.11 h) (all P < 0.001). At 6 months, the recannalization percentage of venous lumen of group A and group B was 89.71 ± 16.02% and 88.64 ± 16.68%, respectively.ConclusionThe combination of pigtail catheter crushing and AngioJet mechanical aspiration of thrombi for acute left iliofemoral vein thrombosis is safe, easy, and effective, with a satisfactory short-term outcome.     

AngioJet血栓清除术治疗存在溶栓禁忌证的急性下肢深静脉血栓

目的观察AngioJet血栓清除术对存在溶栓禁忌证的急性下肢深静脉血栓形成(LEDVT)的治疗效果。方法对18例存在溶栓禁忌证的急性LEDVT患者先行下腔静脉滤器置入术,而后行AngioJet血栓清除术;对合并髂静脉闭塞患者行髂静脉成形术。术后随访,观察治疗效果及安全性。结果18例均一次性治疗成功,血栓均完全清除;12例合并左髂静脉闭塞,均成功行血管成形术;18例患侧下肢静脉血流均恢复通畅。术后16例出现血红蛋白尿,无出血、肺栓塞等并发症。对16例随访3~37个月,13例下肢静脉血流通畅,3例血栓复发。结论采用AngioJet血栓清除术治疗存在溶栓禁忌证的LEDVT患者临床疗效较好。     

Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic syndrome

Although much of the interest in pulse methylprednisolone therapy (PMT) has centered around its use in children with focal segmental glomerulosclerosis, PMT has also been shown to be effective in the treatment of other proteinuric renal diseases. We hypothesized that a PMT-based treatment protocol, derived from the Tune-Mendoza protocol, would effectively induce a more rapid remission in young children with idiopathic steroid-resistant nephrotic syndrome (SRNS). A retrospective analysis was conducted of 11 consecutive SRNS patients (mean age 3.6±1.5 years) that received PMT between 1 August 1992 and 1 May 1998. The initial mean urinary protein/urinary creatinine ratio (UP/UC, mg/mg) was 8.3±9.7 and mean estimated creatinine clearance (C _Cr) 137.7±47.0 ml/min per 1.73 m². An average of 24.8±10.5 PMT doses were given. The mean duration of PMT therapy until remission was 23.4±29.9 days (median 12 days). Cyclosporine and cyclophosphamide were used to maintain and extend remissions in 5 and 4 patients, respectively. At the conclusion of the study, the mean UP/UC was 0.12±0.22 and mean C _Cr 151.8± 39.8 ml/min per 1.73 m² (no C _Cr≤100 ml/min per 1.73 m²). Of the 11 patients, 9 attained complete remission. Adverse effects were mild and infrequent. This PMT protocol appears to safely and effectively induce remission in young children with SRNS. A future prospective trial that evaluates the efficacy of PMT in young children with SRNS is warranted. Received: 15 March 2000 / Revised: 14 August 2000 / Accepted: 18 August 2000     

L-arginine improves endothelial vasoreactivity and reduces thrombogenicity after thrombolysis in experimental deep venous thrombosis

PURPOSE: Nitric oxide (NO) is important in regulation of platelet aggregation, endothelial function, and intravascular thrombosis. The purposes of this study were to assess the effect of thrombolysis on endothelial function in a porcine model of deep venous thrombosis (DVT) and to evaluate the effect of NO precursor l-arginine on endothelial function after thrombolytic therapy. METHODS: DVT was created in bilateral iliac veins by deploying a self-expanding stent-graft that incorporated an intraluminal stenosis, from a groin approach. Five pigs underwent sham operation. After 7 days of DVT, animals were randomized to three groups: saline pulse-spray (saline group, n = 5), thrombolytic pulse-spray with tissue plasminogen activator (alteplase, 8 mg; t-PA group, n = 5), and thrombolytic pulse-spray plus intravenous l-arginine (20 mmol/L; arginine group, n = 5). At 2 weeks iliac vein patency was evaluated at venography and intravascular ultrasound scanning. NO level was determined with a chemiluminescent assay of the nitrite and nitrate metabolites (NO(x)). Thrombogenicity was evaluated with radiolabeled platelet and fibrin deposition. Veins were harvested and evaluated with light microscopy and scanning electron microscopy. Endothelial function was evaluated with organ chamber analysis. RESULTS: All iliac veins remained patent at 2 weeks. The luminal areas in the sham, saline, t-PA, and arginine groups were 53 +/- 23 mm(2), 14 +/- 11 mm(2), 34 +/- 19 mm(2), and 42 +/- 21 mm(2), respectively. No difference in endothelial cell structure was observed between the three treatment groups at light microscopy or scanning electron microscopy. Although no difference in fibrin deposition was noted among the three treatment groups, decreased platelet deposition occurred in the arginine group compared with the saline or t-PA groups (P <.05). The arginine group showed greater endothelial-dependent relaxation compared with the t-PA or saline groups (73% +/- 23% vs 49% +/- 18% and 32% +/- 21%; P <.05). Local NO(x) level in the arginine group was correspondingly higher compared with the saline or t-PA groups (1.8 +/- 0.3 micromol/L vs 0.3 +/- 0.05 micromol/L and 0.2 +/- 0.04 micromol/L; P <.05). CONCLUSIONS: NO precursor l-arginine supplementation enhances NO production at sites of venous thrombosis. Moreover, l-arginine preserves endothelial vasoreactivity and reduces platelet deposition after thrombolysis in iliac DVT. These data suggest that l-arginine may preserve endothelial function after thrombolysis and may reduce the likelihood of postthrombotic syndrome.     

Regulation of amino acid arginine transport by lipopolysaccharide and nitric oxide in intestinal epithelial IEC-6 cells

As a precursor for nitric oxide (NO) synthesis and an immune-enhancing nutrient, amino acid L-arginine plays a critical role in maintaining intestine mucosal integrity and immune functions in sepsis. However, the relationship between intestinal arginine transport and NO synthesis in sepsis remains unclear. In the present study, we investigated the effects of lipopolysaccharide (LPS) and NO on the arginine transport in cultured rat intestinal epithelial IEC-6 cell. Near-confluent IEC-6 cells were incubated with LPS (0-50 μg/ml) in serum-free Dulbecco’s modified Eagles’s medium, in the presence and absence of the NO donor sodium nitroprusside (SNP, 0–500 μmol/L) and the inducible nitric oxide synthase (iNOS) inhibitor N-ω-nitro-L-arginine (NNA, 0–1000 μmol/L) for various periods of time (0-48 hours). Arginine transport activity, arginine transporter CAT1 mRNA and protein levels were measured with transport assay, Northern blot analysis, and Western blot analysis, respectfully. LPS increased arginine transport activity in a time- and dose-dependent fashion. Prolonged incubation of LPS (24 hours, 25 μg/ml) resulted in a 3-fold increase of arginine transport activity (control: 28 ±5; LPS: 92 ±20 pmol/mg/ min, P < 0.05), with the System y⁺ as the predominant arginine transport system, and a 2-fold increase of System y⁺ CAT1 mRNA and transporter protein levels (P < 0.05). LPS increased the arginine transport System y⁺ maximal velocity (V_max, control: 1484 ±180; LPS: 2800 ±230 pmol/mg/min, P<0.05) without affecting the transport affinity (K_m, control: 76 ±8; LPS: 84 ±14 μmol/L, p = NS). The LPSinduced arginine transport activity was blocked by sodium nitroprusside (SNP) (control: 25 ±6; LPS: 97 ±26*; SNP: 22 ±0.4⁺; LPS+SNP: 33 ±10.3⁺ pmole/mg/min, *P < 0.01 and ⁺p = NS, compared with control). In contrary, the LPS-induced arginine transport activity was further augmented by NNA (control: 18 ±3.2; LPS: 59 ±2.7*; NNA: 26.3 ±5.8; LPS + NNA: 127 ±18⁺ pmol/mg/min; *P < 0.01 compared with control and ⁺P < 0.01 compared with control or LPS). LPS-stimulates arginine transport activity in IEC-6 cells via a mechanism that involves increase of transport System y⁺ mRNA levels and transporter protein levels. The LPS-stimulated arginine transport activity is regulated by the availability of nitric oxide. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). This work was supported in part by The Society for Surgery of Alimentary Tract Career Development Award (M.P.) and National Institute of Diabetes and Digestive and Kidney Disease Grant DK-62165 (M.P.).     

下肢深静脉血栓清除临床关注焦点

下肢深静脉血栓形成（DVT）是血管外科常见的疾病之一，越来越多的证据表明早期进行血栓清除安全有效，并能降低以肢体炎性肿胀、皮肤溃疡等为主要临床表现的血栓后综合征（PTS）的发生风险，同时提高患者的生活质量。血栓清除的方式主要包括手术切开取栓、导管接触性溶栓（CDT）和经皮机械性血栓清除术（PMT）。血栓清除方法的多样化及其设备快速更新为临床医生带来了福音，此外，下腔静脉可回收滤器的合理应用大大提高了血栓清除手术的安全性，血栓清除后髂静脉球囊及支架的应用可避免血栓的复发。尽管临床上还有许多问题存在争议，并缺少高质量、高级别的研究证据，但下肢DVT血栓清除的必要性、有效性及安全性逐渐形成共识。笔者就临床实践中相关的焦点问题进行阐述和总结。     

Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice

The aim of this study was to examine the mechanism of interferon alpha (IFN-α) on inhibition of metastasis and recurrence of hepatocellular carcinoma (HCC). Nude mice bearing human HCC xenografts with high metastatic potential (LCI-D20) underwent curative resection of tumors on postimplant day 11. IFN-α was begun the next day at different dosages given subcutaneously for 35 consecutive days; normal saline solution was injected into the control mice. The mice were killed 48 hours after the final treatment, and the parameters were evaluated. The HCC intrahepatic recurrence rate, the size of the recurrent lesions, the rate of lung metastasis, the serum vascular endothelial growth factor level, and the microvessel density (immunohistochemistry) were as follows: 100%, 2136 ± 794 mm³ (mean ± standard deviation), 100%, 265.7 ± 154.7 pg/ml, and 144 ± 37/HP, respectively, in the control mice, whereas these same values were 62.5%, 89 ± 45 mm³, 12.5%, 53.3 ± 9.9 pg/ml, and 86 ± 25/HP, respectively, in the IFN-α 1.5 × 10⁷ U/kg treatment group (P < 0.05) and 26.7%, 46 ± 21 mm³, 0%, 65.2 ± 17.9 pg/ml, and 39 ± 14/HP in the IFN-α 3 × 10⁷ U/kg treatment group, respectively (P < 0.05). However, a significant difference was not found in the serum levels of basic fibroblast growth factor among the control and IFN-α treatment groups. IFN-α inhibits metastasis and recurrence of human HCC after curative resection in nude mice mediated by antiangiogenesis through downregulating expression of vascular endothelial growth factor but not basic fibroblast growth factor. Winner of the 2002 Grassi Prize, International Society of Digestive Surgery, Hong Kong, China, December 11, 2002. Supported in part by State Key Basic Research Program Grant G1998051211, National Natural Scientific Foundation of China 30100077, and Fudan Scientific Foundation.     

THE EFFECT OF ARTERIAL CLAMP DURATION ON ENDOTHELIAL INJURY: AN EXPERIMENTAL STUDY

Background : Arterial clamp-related endothelial damage was investigated in an animal model to quantify the surface area of endothelial disruption. The influence of the duration of clamp application on this damage was evaluated. Methods : Four identical angled DeBakey vascular clamps were applied on each of eight carotid arteries in four heparinized adult sheep for durations of 15, 30, 45 and 60 min. The applied clamping forces were measured and kept constant. After the last clamp was removed, the areas of endothelial loss were identified by in vivo staining with Evan's blue dye. The vessels were excised and the blue stained areas measured by computer-assisted analysis. The morphological appearance of the specimens was assessed by scanning electron microscopy. Results : Endothelial damage following clamping for 15 min (10.6 ± 4.3 mm²) was significantly less than for 30 min (19.0 ± 4.7 mm²), 45 min (19.8 ± 4.6 mm²) and 60 min (20.7 ± 4.9 mm²; P= 0.005), but there were no significant differences between the areas of endothelial loss observed for 30, 45, and 60 min. These results corresponded to the damage seen using scanning electron microscopy, which showed partial disruption of endothelium at 15 min compared to more complete destruction at longer durations. Conclusion : Evan's blue staining combined with computer-assisted surface area measurement is an accurate method for quantifying endothelial damage. The extent of damage caused by vascular clamps is partly time-dependent, being less for 15 min than for 30 min of clamping, but not significantly increasing for durations greater than 30 min.     

Increased risk of renal dysfunction with percutaneous mechanical thrombectomy compared with catheter-directed thrombolysis

Objective

Percutaneous mechanical thrombectomy (PMT) is regularly used in the treatment of both venous and arterial thrombosis. Although there has been no formal report, PMT has been linked to cases of reversible postoperative acute kidney injury (AKI). The purpose of this study is to evaluate the risk of renal dysfunction in patients undergoing PMT vs catheter-directed thrombolysis (CDT) for treatment of an acute thrombus.

Combination of anorganic bovine‐derived hydroxyapatite with binding peptide does not enhance bone healing in a critical‐size defect in a rabbit model

Anorganic bovine‐derived hydroxyapatite (ABM) in combination with binding peptid (P‐15) has demonstrated the capacity to improve the healing of periodontal defects. This study evaluated the benefit of ABM/P‐15 to promote healing of cortical long bone defects in a rabbit model. A 5‐mm segmental bone defect was created in the femur and fixed with a plate. There were two treatment groups: no implant (n = 12) and ABM/P‐15 (n = 12). At 4, 8, and 12 weeks, healing of the defect was evaluated with radiographs and histomorphometric examination of the treated femora. After 4 weeks, radiographs showed bone formation without signs of complete consolidation in three of four animals in the control group and two of four ABM/P‐15 treated animals. At the later course of the treatment, no radiologic difference was evident between the treatment groups. Histomorphometric evaluation revealed an area of 1.29 ± 0.11 mm² and 0.97 ± 0.21 mm² of newly produced bone in animals of the control group and ABM/P‐15 group after 4 weeks. After 8 and 12 weeks, animals in the control group had an area of 2.44 ± 0.62 mm² and 2.5 ± 0.2 mm² of newly produced bone within the osteotomy gap compared to 1.6 ± 0.65 mm² and 1.56 ± 0.27 mm² in the ABM/P‐15 group (p = 0.0004). An enhanced or accelerated ingrowth of bone, as reported in previous studies, was not observed. Our results imply that the ABM/P‐15 is not a suitable graft for the treatment of critical‐sized segmental defects in long bones. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:759–763, 2008     

Guided Bone Regeneration of Femoral Segmental Defects using Equine Bone Graft: An In-Vivo Micro-Computed Tomographic Study in Rats

ABSTRACT

Background and objectives: Guided bone regeneration (GBR) is commonly used for osseous defect reconstruction. The objective of this study was to evaluate in real-time (in-vivo) the efficacy of equine bone graft for GBR in segmental critical-size defects (CSD) of the femur in a rat model. Materials and methods: Following ethical approval, 30 male Wistar-Albino rats (age 12–14 months/weight 450–500 grams) were included. Under general-anesthesia, a mid-diaphyseal segmental CSD (5 mm) was created in the femur and stabilized using titanium Miniplate(4 holes,1.0 mm thickness). Depending upon material used for GBR, animals were randomly divided into three groups(n = 10/per group). Negative control-Defect covered with resorbable collagen membrane(RCM); Positive control-Defect filled with autologous bone and covered by RCM; Equine bone-Defect filled with equine bone and covered by RCM. Real-time in-vivo Micro-CT was performed at baseline, 2, 4, 6 and 8 weeks to determine volume and mineral density of newly formed bone (NFB) and remaining bone graft particles (BGP). Results: In-vivo micro-CT revealed increase in volume and mineral density of NFB within defects from baseline to 8-weeks in all groups. At 8-weeks NFB-volume in the equine bone group(53.24 ± 13.83 mm³; p < 0.01) was significantly higher than the negative control(5.6 ± 1.06 mm³) and positive control(26.07 ± 5.44 mm³) groups. Similarly, NFB-mineral density in the equine bone group(3.33 ± 0.48 g/mm³; p < 0.01) was higher than the other (negative control–0.27 ± 0.02 g/mm³; positive control–2.55 ± 0.6 g/mm³). A gradual decrease in the BGP-volume and BGP-mineral density was observed. Conclusion: The use of equine bone for GBR in femoral segmental defects in rats, results in predictable new bone formation as early as 2-weeks after bone graft placement.