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K Craig Kent

Publications and source records attributed to K Craig Kent.

At least 55 records · Page 3Linked to original sources

Stem cell factor and c-kit are expressed by and may affect vascular SMCs through an autocrine pathway.

INTRODUCTION: Stem cell factor (SCF) is a membrane-bound and soluble growth factor that activates the c-kit tyrosine kinase receptor. Given the similarities between c-kit and platelet-derived growth factor (PDGF) receptors, we hypothesized that similar to PDGF, SCF/c-kit signaling may play a role in smooth muscle cell (SMC) function and thus the development of intimal hyperplasia. MATERIALS AND METHODS: Human saphenous vein SMCs were harvested from veins procured at the time of bypass grafting. Carotid arteries from rats that were balloon injured (n = 12) at variable time points were compared to sham-operated controls (n = 3). Expression of SCF and c-kit was measured by immunohistochemistry (IHC) and Western blotting. RESULTS: Western blotting revealed that human SMCs express membrane-bound SCF. In separate experiments, we found that this growth factor undergoes proteolytic cleavage to its soluble form following exposure to matrix metalloproteinase-9 (MMP-9), a ubiquitous MMP released at the time of arterial injury. We next evaluated in human SMCs, expression of the SCF receptor, c-kit. Western blotting of human SMC lysates revealed minor but consistent expression of c-kit. IHC demonstrated c-kit expression to be localized to the media. To determine if c-kit is up-regulated during the development of intimal hyperplasia, we evaluated expression of this receptor in a rat carotid balloon injury model. Quantification of IHC staining on injured vessels revealed that c-kit expression within the media was significantly increased at 3, 7, 14, and 28 days following injury (28.1, 30.8, 16, and 10.4% increase over sham controls, respectively, P < 0.05). Furthermore, c-kit expression was prominent within the neointima and maximal at 7 days (53.4 +/- 7.8% of area c-kit positive). CONCLUSION: Human vascular SMCs express the growth factor SCF and its receptor, c-kit. SCF is released from its membrane-bound form via MMP-9. This finding and the dramatic increase in c-kit expression observed in the rat carotid artery after balloon injury suggests SCF/c-kit signaling may affect SMC function via an autocrine pathway.

Animals↗

A statewide experience with endovascular abdominal aortic aneurysm repair: rapid diffusion with excellent early results.

OBJECTIVE: The purpose of this study was to compare survival and outcomes of endovascular versus open repair of abdominal aortic aneurysms (AAAs) in New York State (NYS). METHODS: We used the NYS discharge dataset Statewide Planning and Research Cooperative System (SPARCS) to analyze the outcomes of elective admission for nonruptured (International Classification of Diseases-9th revision [ICD-9] 441.4) open aneurysm repair (38.44) and endovascular aneurysm repair (39.71) during the years 2000-2002. The ICD-9 code for endovascular repair was introduced in late 2000, thus capturing 3 months of empiric data for 2000. RESULTS: There has been a significant increase in the number of AAA procedures performed in NYS (comparing before and after 2000: average, 1419 vs 1701; P =.0001), temporally coinciding with the implementation of training programs after US Food and Drug Administration approval of endovascular grafts and the new payment code. From 2000 to 2002 the number of NYS hospitals performing endovascular repairs increased from 24 to 60. By 2002 there were more endovascular repairs being performed than open repairs (871 vs 783). The target population for these surgical interventions showed interesting differences. In 2002, women had a 43% chance of receiving an endograft, whereas men had a 55% probability. The use of endovascular repair over the observation period was relatively constant in patients younger than 65 years. In patients older than 65 years, and especially those older than 75 years, endovascular use increased substantially, so that by 2002 older patients were more likely to undergo endovascular repair than open repair. Patients who underwent endovascular repair had significantly more hypertension, coronary artery disease, diabetes, and hyperlipidemia than did patients who underwent open repair. Yet the mean length of stay for endovascular procedures was approximately 3.6 days, and for open procedures was about 10.3 days, across all 3 years (P = <.0001). Moreover, patients who underwent endovascular repair had statistically fewer postoperative complications and significantly lower mortality. In-hospital mortality in 2001 was 3.55% for open repair and 1.14% for endovascular repair (P =.0018), and in 2002 these rates were 4.21% versus 0.8% (P <.0001), respectively. CONCLUSION: This dataset suggests that endovascular AAA repairs are being performed in a patient population with a higher frequency of comorbidities. However, endovascular repairs still are associated with significantly lower in-hospital mortality, fewer postoperative complications, and a dramatically shorter length of stay. These results suggest that, despite the rapid diffusion of this new technique, early perioperative outcomes may be superior to those with conventional open repair. However, prospective clinical studies are needed to confirm these insights, and such studies may require the infrastructure of consortia of hospitals or society-based registries.

Adolescent↗

Acute lower extremity ischemia in a 7-year-old boy: an unusual case of popliteal entrapment syndrome.

Popliteal artery entrapment syndrome is a rare cause of acute limb ischemia that most commonly is seen in young adults. The most significant complications associated with popliteal entrapment include aneurysm formation and acute thrombosis. This case presents the youngest patient ever reported with this syndrome and highlights the advantages of multimodal treatment including thrombolysis, popliteal aneurysm resection, and revascularization. Although a significant body of literature exists on popliteal entrapment syndrome in teenagers and young adults, it has not been reported previously in a patient younger than 11 years. Limb salvage was achieved in this patient with a combination of endovascular and surgical techniques.

Acute Disease↗

Understanding trends in inpatient surgical volume: vascular interventions, 1980-2000.

OBJECTIVE: To help understand past and future trends in vascular intervention, we examined changes in the rate of utilization, patient demographics, and length of stay from 1980 to 2000. METHODS: We reviewed the ICD-9 codes for all vascular procedures using the National Hospital Discharge Survey of non-federal United States hospitals (1980-2000). RESULTS: The number of vascular procedures performed in this country increased from 412,557 in 1980 to 801,537 in 2000 (per capita increase of >50%). This increase was most evident in elderly patients (>75 years, 67% per capita increase in discharges). Long hospital stays (> or =7 days) for vascular procedures fell 41%, and short hospital stays (<24 hours) increased 15% over the period of study. The frequency of abdominal aortic aneurysm repairs remained relatively constant. Except for an interval in the late 1980s, and a minor decrease from 1997 to 2000, the frequency of carotid endartarectomy rose dramatically (69%). Lower extremity revascularizations increased steadily until 1990 but then declined 12%. From 1995 to 2000, there was a 27% per capita decrease in the number of renal-mesenteric operations. Correspondingly, over the past 5 years there has been a 979% growth in the number of percutaneous/endovascular interventions. Despite a substantial number of interventions for lower extremity vascular disease, there was a concomitant increase in the number of major and minor amputations. CONCLUSION: Interventions for vascular disease have increased dramatically, with a major shift toward less invasive treatments, particularly for the renal and mesenteric vessels and the lower extremities. These trends in procedural use suggest that vascular surgeons need to embrace catheter-based approaches if they want to remain leaders in the treatment of peripheral vascular diseases.

Adolescent↗

Intracellular calcium transients are necessary for platelet-derived growth factor but not extracellular matrix protein-induced vascular smooth muscle cell migration.

PURPOSE: Vascular smooth muscle cell (SMC) migration is a critical component of the hyperplastic response that leads to recurrent stenosis after interventions to treat arterial occlusive disease. We investigated the relationship between intracellular calcium ([Ca(2+)](i)) and migration of vascular SMCs in response to platelet-derived growth factor (PDGF) and extracellular matrix (ECM) proteins. METHODS: Human saphenous vein SMCs were used for all experiments. SMC migration in response to agonists was measured with a microchemotaxis assay. A standard fluorimetric assay was used to assess changes in [Ca(2+)](i) in response to the various combinations of growth factors and ECM proteins. RESULTS: The calcium ionophore A23187 produced a rapid rise in [Ca(2+)](i) and a corresponding 60% increase in SMC migration, whereas chelation of [Ca(2+)](i) with BAPTA (1,2-bis [aminophenoxy] ethane-N,N,N',N'-tetraacetic acid) produced a fivefold decrease in PDGF-induced chemotaxis, suggesting that [Ca(2+)](i) is both sufficient and necessary for SMC migration. Stimulation of SMCs with PDGF produced an early peak followed by a late plateau in [Ca(2+)](i). To establish a relationship between temporal fluctuations in [Ca(2+)](i) and SMC migration, SMCs were pretreated with caffeine and ryanadine, which eliminated the initial peak but not the late plateau in [Ca(2+)](i), and had no effect on chemotaxis in response to PDGF. Incubation of SMCs with nickel chloride eliminated the late plateau, but had no effect on the initial peak in [Ca(2+)](i), and reduced PDGF-stimulated migration by fivefold. We then evaluated the role of calcium in SMC migration induced by ECM proteins such as laminin, fibronectin, and collagen types I and IV. All four matrix proteins stimulated SMC migration, but none produced an elevation in [Ca(2+)](i). Moreover, preincubation of SMCs with caffeine and ryanadine or nickel chloride had no effect on ECM protein-induced chemotaxis. CONCLUSION: [Ca(2+)](i) transients are necessary for PDGF but not ECM protein-induced SMC chemotaxis. Moreover, the ability of PDGF to stimulate vascular SMC migration appears dependent on influx of extracellular calcium through membrane channels. CLINICAL RELEVANCE: Recurrent stenosis after angioplasty or surgical bypass remains a significant challenge in treating vascular occlusive disease. In addition to growth factors, extracellular matrix (ECM) proteins may be potent agonists of this process. In this study we show that the influx of extracellular calcium is an important mechanism for platelet-derived growth factor-induced smooth muscle cell migration but not ECM-induced migration. Of note, in clinical trials calcium channel blockers failed to inhibit recurrent stenosis. Our data provide mechanistic insight to help explain this negative outcome in that therapies designed to inhibit restenosis depend on the effects of both growth factors and ECM proteins.

Calcimycin↗

Abdominal aortic aneurysm causing duodenal obstruction: two case reports and review of the literature.

Obstruction of the upper gastrointestinal tract caused by an abdominal aortic aneurysm (aortoduodenal syndrome) has been rarely reported. The typical presentation includes protracted emesis in a patient with a pulsatile abdominal mass. Clinical features of weight loss, abdominal pain, and distention are present less frequently. The diagnosis is suggested by findings on computed tomography scans, and may be confirmed with upper gastrointestinal contrast material-enhanced studies or upper endoscopy. Aortic aneurysmorrhaphy is curative, and should be undertaken after gastrointestinal decompression and correction of fluid and electrolyte disturbances. We report 2 cases of abdominal aortic aneurysm producing upper gastrointestinal obstruction, and provide a review of the literature relevant to this clinical syndrome.

Aged↗

Resection of an intravenous leiomyoma with intracardiac extension with use of endovascular techniques.

Intravenous leiomyoma with intracardiac extension is a rare entity that necessitates surgical excision to alleviate symptoms and prevent life-threatening complications. These procedures are generally performed under cardiopulmonary bypass, and review of the literature reveals an evolution in management of this disease from 2-stage to single-stage procedures. We report the case of a 45-year-old woman with an intravenous leiomyoma with intracardiac extension after presenting with syncopal symptoms. The intravenous tumor and its supradiaphragmatic extension were ultimately resected via laparotomy without the need for cardiopulmonary bypass. Distal control was achieved by passing an occluding balloon catheter above the tumor through a venotomy with fluoroscopic guidance and echocardiography, thus enabling protected tumor extraction through the intra-abdominal inferior vena cava. In selected patients, we believe use of endovascular techniques combined with proper preoperative imaging can safely permit single-stage resection of these tumors via laparotomy without cardiopulmonary bypass.

Angioplasty, Balloon↗

Characterization of retrograde collateral (type II) endoleak using a new canine model.

OBJECTIVE: The clinical significance of retrograde collateral arterial perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) has not been completely characterized. In this study a canine model was used to analyze intra-aneurysmal pressure, thrombus histologic characteristics, endoleak patency, and radiographic appearance of type II endoleaks originating from single and multiple aneurysm side branches. METHODS: Prosthetic aneurysms with an intraluminal solid-state strain-gauge pressure transducer were created in the infrarenal aorta of 14 mongrel dogs. A single collateral side branch was reimplanted in 4 animals, multiple side branches were reimplanted in 6 animals, and no side branches were reimplanted in 4 control animals. Intra-aneurysmal and systemic pressure was measured for 60 to 90 days after creation of the type II endoleak. Endoleak patency and flow were assessed with duplex ultrasound scanning and cine-magnetic resonance angiography. Histologic analysis of the intra-aneurysmal thrombus was also performed. RESULTS: Stent-graft exclusion reduced intra-aneurysmal pressure significantly in all animals, as compared with systemic pressure (P < .001). All intra-aneurysmal pressure values are indexed to the systemic pressure, and are represented as a percentage of the simultaneously obtained systemic pressure, which has a value of 1.0. Type II endoleaks originating from multiple side branches exhibited significantly increased intra-aneurysmal systolic pressure, mean pressure, and pulse pressure, as compared with endoleaks derived from either a single side branch (systolic pressure: multiple, 0.70 +/- 0.28 vs single, 0.50 +/- 0.19; P < .001; mean pressure: multiple, 0.78 +/- 0.23 vs single, 0.59 +/- 0.22, P < .001; pulse pressure: multiple, 0.41 +/- 0.25 vs single, 0.17 +/- 0.15, P < .001) or excluded control aneurysms that had no side branches and no endoleak (systolic pressure, 0.17 +/- 0.09; mean pressure, 0.14 +/- 0.10; pulse pressure, 0.098 +/- 0.08; P < .001). Cine-magnetic resonance angiograms and duplex ultrasound scans documented persistent patency of multiple branch endoleaks up to the time of euthanasia. In contrast, single side branch endoleaks thrombosed within 3 days (P < .001). Thrombus in the aneurysm sac in close proximity to the endoleak contained intact red blood cells and limited fibrin. Thrombus distant from the endoleak demonstrated extensive fibrin deposition and degraded red blood cells. CONCLUSION: The canine model may be used to reliably measure intra-aneurysmal pressure in the presence of patent and thrombosed type II endoleaks. In this model 2 or more side branches are necessary to maintain persistent patency of type II endoleaks. These endoleaks are associated with significantly elevated intra-aneurysmal pressure, that is, 70% to 80% of systemic pressure. These results suggest that persistent type II endoleaks have clinical significance. CLINICAL RELEVANCE: Endoleaks originating from retrograde flow in the side branch vessels of the aneurysm generate significant levels of intra-aneurysmal pressure, that is, 70% to 80% of systemic pressure. At least 2 patent side branch vessels appear to be necessary to cause persistent patency of type II endoleak in the canine model. Further studies will be necessary to enable more complete characterization of retrograde endoleaks and to extend these findings to allow clinical application. However, these results suggest that persistently patent type II endoleaks are clinical significance and may require more intensive follow-up intervention.

Anastomosis, Surgical↗

Computer simulation as a component of catheter-based training.

INTRODUCTION: Computer simulation has been used in a variety of training programs, ranging from airline piloting to general surgery. In this study we evaluate the use of simulation to train novice and advanced interventionalists in catheter-based techniques. METHODS: Twenty-one physicians underwent evaluation in a simulator training program that involved placement of a carotid stent. Five participants were highly experienced in catheter-based techniques (>300 percutaneous cases), including carotid angioplasty and stenting (CAS); the remaining 16 participants were interventional novices (<5 percutaneous cases). The Procedicus VIST simulator, composed of real-time vascular imaging simulation software and a tactile interface coupled to angiographic catheters and guide wires, was used. After didactic instruction regarding CAS and use of the simulator, each participant performed a simulated CAS procedure. The participant's performance was supervised and evaluated by an expert interventionalist on the basis of 50 specific procedural steps with a maximal score of 100. Specific techniques of guide wire and catheter manipulation were subjectively assessed on a scale of 0 to 5 points based on ability. After evaluation of the initial simulated CAS procedure, each participant received a minimum of 2 hours of individualized training by the expert interventionalist, with the VIST simulator. Each participant then performed a second simulated CAS procedure, which was graded with the same scale. After completion, participants assessed the training program and its utility via survey questionnaire. RESULTS: The average simulated score for novice participants after the training program improved significantly from 17.8 +/- 15.6 to 69.8 +/- 9.8 (P < .01), time to complete simulation decreased from 44 +/- 10 minutes to 30 +/- 8 minutes (P < .01), and fluoroscopy time decreased from 31 +/- 7 minutes to 23 +/- 7 minutes ( P < .01). No statistically significant difference in score, total time, or fluoroscopy time was noted for experienced interventionalists. Improvement was noted in guide wire and catheter manipulation skills in novices. Analysis of survey data from experienced interventionalists indicated that the simulated clinical scenarios were realistic and that the simulator could be a valuable tool if clinical and tactile feedback were improved. Novices also thought the simulated training was a valuable experience, and desired further training time. CONCLUSIONS: An endovascular training program using the Procedicus VIST haptic simulator resulted in significant improvement in trainee facility with catheter-based techniques in a simulated clinical setting. Novice participants derived the greatest benefit from simulator training in a mentored program, whereas experienced interventionalists did not seem to derive significant benefit.

Blood Vessel Prosthesis Implantation↗

Stent graft treatment for abdominal aortic aneurysm repair: recent developments in therapy.

PURPOSE OF REVIEW: Minimally invasive endovascular techniques for the treatment of abdominal aortic aneurysms have significantly reduced the morbidity of these procedures compared with standard surgical repair. In addition, patients with extensive comorbid medical illnesses in whom standard operative repair is contraindicated may be successfully treated using endovascular means. RECENT FINDINGS: Recently, several important developments have significantly advanced this area of treatment. The Food and Drug Administration has approved four endovascular stent grafts for the treatment of abdominal aortic aneurysms: the Medtronic AneuRx, the W.L. Gore Excluder, the Cook Zenith, and the Guidant Ancure. The Zenith received approval for marketing in 2003 and has gained relatively wide use, in part because of its ability to treat aneurysms with relatively large-diameter implantations zones. Also in 2003, Guidant Corporation withdrew the Ancure graft from marketing and distribution. The withdrawal was influenced by difficulties encountered using the graft's delivery system and improper reporting to the Food and Drug Administration. Enrollment has also been recently completed for the phase II Food and Drug Administration trials of the Medtronic Talent graft and the Cordis Fortron graft. These devices have been approved for use in the European Union and are awaiting Food and Drug Administration panel meeting in the United States. Several significant advances have also occurred recently in stent graft research and development. Of particular significance has been the initiation of the phase I trial of the Trivascular Enovus graft. Deployment of the Trivascular graft may be accomplished through a delivery system that is considerably reduced in profile. The potential for percutaneous application of the graft may be available in the future. In selecting the specific stent graft to be used for endovascular abdominal aortic aneurysm repair, the specific graft characteristics must be considered, particularly with regard to the individual patient's anatomic and physiologic characteristics. Comparative analysis of the several of the various stent grafts has been performed. Results have varied with regard to the need for secondary interventions, aneurysm sac size reduction, and the occurrence of continued perfusion of the aneurysm sac. In addition, the indications for use of endovascular grafts compared with standard open surgery have not yet been fully defined. SUMMARY: This article describes the general principles of use for endovascular devices for the repair of abdominal aortic aneurysms. It details the features and results for the devices in current use, and highlights the recent developments in stent graft treatment of abdominal aortic aneurysms.

Aortic Aneurysm, Abdominal↗

Decreased venous contamination on 3D gadolinium-enhanced bolus chase peripheral mr angiography using thigh compression.

OBJECTIVE: We evaluated the potential for improving bolus chase peripheral MR angiography in patients with fast arterial flow using thigh compression to prevent venous contamination. SUBJECTS AND METHODS: We performed bolus chase peripheral MR angiography in 32 consecutive patients in whom the travel time for a contrast agent to reach the popliteal artery trifurcation was less than 25 sec. Thigh compression was applied by a tourniquet (n = 13) or blood pressure cuff inflated to 60 mm Hg (n = 19). We compared the results with those of 36 consecutive patients who underwent angiography without thigh compression. The effect of thigh compression on arterial flow and tissue enhancement was assessed in patients with symmetric travel time in both legs by applying compression to one leg during the time-resolved 2D-projection MR angiography with 6 mL of gadolinium. On 3D bolus chase MR angiography, thigh compression was applied bilaterally. Venous contamination on the 3D images of the calf was graded as 0, none; 1, trace; 2, mild; 3, moderate; and 4, severe. Signal-to-noise ratio was measured in the popliteal artery. RESULTS: Thigh compression slowed the arterial travel time by a mean +/- SD of 4.7 +/- 2 sec (p < 0.001) with a blood pressure cuff and 3.1 +/- 1 sec (p < 0.001) with a tourniquet. Blood pressure cuffs reduced the score of venous contamination on the calf station from 1.9 to 0.4 (p < 0.05) for intermediate flow (contrast travel time, 20-25 sec) and from 2.5 to 0.9 (p < 0.05) for fast flow (< 20 sec). Thigh compression increased the popliteal artery signal-to-noise ratio (81 vs 52, p < 0.001). CONCLUSION: Thigh compression with blood pressure cuffs inflated to 60 mm Hg slows down arterial flow, increases arterial signal-to-noise ratio, and reduces venous contamination on 3D gadolinium-enhanced bolus chase peripheral MR angiography.

Aged↗

Increased recognition of type II endoleaks using a modified intraoperative angiographic protocol: implications for intermittent endoleak and aneurysm expansion.

Retrograde arterial perfusion of the aneurysm sac (type II endoleak) may complicate endovascular abdominal aortic aneurysm (AAA) repair and may lead to AAA expansion and rupture. Aneurysm expansion may also occur in the absence of a demonstrable endoleak. Current intraoperative assessment techniques may underrepresent the incidence of type II endoleaks. This study evaluated the incidence and impact of previously unrecognized type II endoleaks using a modified intraoperative angiographic protocol. A total of 391 patients undergoing endovascular AAA repair were evaluated. In 264 patients standard completion angiograms were performed. In 127 patients a modified angiographic protocol was used to visualize collateral lumbar and inferior mesenteric arteries as well as the aneurysm sac. The modified protocol uses digital subtraction fluoroscopy continuously for 60 sec after injections of 20 mL iodinated contrast both in the pararenal aorta and within the endovascular graft. Postoperative CT scans were performed at 1, 6, and 12 months and annually thereafter. The average age was 73.3 years; 324 patients were men and 67 were women. Mean follow-up was 11.4 months (range, 1-60 months). Type II endoleaks were documented intraoperatively in a significantly increased proportion of patients in whom the modified angiographic protocol was used: modified, 53/127 = 41% vs. standard, 17/264 = 6%; p < 0.001. No significant difference in the incidence of type II endoleaks was present on CT scan at 6 or 12 months after surgery (6 months: modified, 6/72 = 8% vs. standard, 10/159 = 6%, p = NS; 12 months: modified, 2/36 = 5% vs. standard, 6/138 = 4%, p = NS). Forty-six type II endoleaks resolved spontaneously (10 in the standard cohort, 36 in the modified cohort). One patient had a 10-mm increase in AAA diameter after spontaneous thrombosis of a type II endoleak 18 months postoperatively. One patient had a type II endoleak intraoperatively and at 12 months after surgery but the endoleak was absent at 1 and 6 months. Thirteen patients from the standard protocol cohort and 1 from the modified protocol cohort developed newly visualized type II endoleaks during follow-up. These findings may imply intermittent patency of the artery supplying the type II endoleak. The overall morbidity rate was 14% and the perioperative mortality rate was 1.8%. Retrograde (type II) endoleaks originating from AAA side branches occur intraoperatively more frequently than is currently recognized. Intermittent patency and thrombosis of these vessels may also occur and may contribute to AAA expansion. The full significance of these previously unrecognized endoleaks with respect to risk of aneurysm rupture remains to be definitively determined.

Aged↗

Atherosclerotic disease distribution in carotid and vertebrobasilar arteries: clinical experience in 100 patients undergoing fluoro-triggered 3D Gd-MRA.

PURPOSE: To determine how often three-dimensional gadolinium-enhanced magnetic resonance angiography (3D Gd-MRA) shows disease outside of the standard two-dimensional time-of-flight magnetic resonance angiography (2D TOF-MRA) imaging volume. MATERIALS AND METHODS: One hundred consecutive patients with known or suspected cerebrovascular disease were examined using fluoro-triggered 3D Gd-MRA with a 1.5 Tesla scanner. All vessel segments from the aortic arch to the circle of Willis were independently evaluated for the presence of occlusive disease, ulceration, aneurysm, and anatomic variations by two radiologists blinded to clinical information. Branch vessel and circle of Willis visibility were also assessed. Kappa statistics were calculated to determine interobserver agreement. RESULTS: Interobserver agreement for the degree of stenosis was good to excellent (kappa = 0.83-1.0). Disagreement was more frequent in the cases of mild stenoses and was less frequent for stenoses > or = 50%. In 38% of the patients, 3D Gd-MRA demonstrated either ulcerated plaques in carotid arteries (N = 14) or stenosis > or = 50% in great vessel (N = 20) and/or vertebral artery (N = 38) origins, none of which can be readily evaluated on standard TOF-MRA. CONCLUSION: Fluoro-triggered 3D Gd-MRA provides a comprehensive evaluation of the carotid arteries including all vessel segments from the aortic arch to the circle of Willis.

Adult↗

TGF-beta stimulates collagen (I) in vascular smooth muscle cells via a short element in the proximal collagen promoter.

BACKGROUND: Accumulation of extracellular matrix contributes to the development of intimal hyperplasia. Transforming growth factor beta (TGF-beta) stimulates the production of several matrix proteins in vascular smooth muscle cells (SMC) including type I collagen, but the underlying mechanisms of TGF-beta's effects are not well understood. MATERIALS AND METHODS: The effect of TGF-beta on type I collagen biosynthesis was determined by a [3H]proline incorporation assay and Northern blotting. The promoter of human alpha2(I) procollagen (COL1A2) gene was analyzed by transient transfection analysis and gel mobility shift assay. RESULTS: Treatment of human vascular SMC with TGF-beta stimulated collagen synthesis and increased the level of alpha2(I) collagen mRNA. A collagen-luciferase reporter gene, constructed by linking the human COL1A2 promoter with the firefly luciferase gene, was transiently expressed in human SMC. Treatment with TGF-beta significantly stimulated the activity of this collagen-luciferase reporter. Using deletion analysis, we identified a 150 bp DNA fragment (-334 to -184) in the human COL1A2 promoter as the site through which TGF-beta mediates collagen gene expression in human SMC. Gel mobility shift assays demonstrated that this 150 bp DNA fragment formed conjugates with multiple nuclear factors derived from SMC, a process that was further enhanced by TGF-beta. CONCLUSIONS: TGF-beta stimulates the human type I collagen gene via a DNA element located in the proximal region of its promoter. Interventions that disrupt interaction between this DNA element and nuclear factors may block the production of collagen in response to TGF-beta and consequently may have a significant effect on the development of intimal hyperplasia.

Binding Sites↗

Management of endoleak after endovascular aneurysm repair: cuffs, coils, and conversion.

OBJECTIVE: The effectiveness of endovascular treatment of abdominal aortic aneurysm (AAA) may be limited by persistent perfusion of the aneurysm sac (endoleak). Endoleak that results in persistent systemic pressurization of the aneurysm or in continued AAA expansion is believed to require treatment to prevent rupture. This report describes the results of three techniques used to treat endoleak. METHODS: Endovascular repair of AAA was performed in 597 patients between January 1996 and September 2002. Seventy-three endoleaks that required treatment developed in 70 patients (11.7%). These involved the graft attachment site (type I) or the graft junction site (type III) or originated from collateral side-branch vessels (type II) and were associated with an increase in aneurysm size. Endoleak type was confirmed at angiography in all cases. Average time between the initial endovascular procedure and endoleak treatment was 14.5 +/- 5.7 months. The techniques used for endoleak treatment were deployment of an endovascular extension graft or cuff (n = 44), coil embolization (n = 24,) and conversion to conventional open repair (n = 5). Configurations of endovascular grafts in which endoleak developed were bifurcated (n = 44), aortouniiliac (n = 15), and aortoaortic-tube (n = 11). Mean follow-up after endoleak treatment was 24.5 +/- 12.2 months (range, 1-60 months). RESULTS: Endovascular extension grafts or cuffs were used to treat 41 attachment site endoleaks and 3 graft junction endoleaks, with overall technical success rate of 97%. Embolic coils were used to treat 16 retrograde side-branch endoleaks and 8 attachment site endoleaks, with overall technical success rate of 87%. Conversion to open surgery was performed in 4 patients with attachment site endoleaks and 1 patient with a graft junction site endoleak, and was successful in all cases. After endoleak treatment, aneurysm size decreased (>5 mm) in 38% of patients, stabilized in 58% of patients, and increased (>5 mm) in 4% of patients. Major morbidity occurred in 7.0%, with no perioperative deaths. CONCLUSIONS: Endovascular extension grafts, coil embolization, and conversion to open surgery each may be used to effectively repair endoleak. Selection of the treatment method used is determined by the anatomic characteristics of the endoleak and the patient's ability to tolerate conventional repair. Conversion to open repair was uniformly successful. Deployment of an extension cuff was successful when complete closure of the endoleak was achieved. Embolic coils were effective for retrograde endoleaks and provided stabilization of AAA size in selected patients with attachment site endoleaks in limited follow-up.

Aged↗