The role of the vascular surgeon in endovascular procedures.
Explore the source record for details and available documents.
Catheterization↗
Biomedical subjects
K C Kent
Publications and source records attributed to K C Kent.
Thrombolysis for native arterial occlusions of the lower extremities: clinical outcome and cost.
INTRODUCTION: Intra-arterial thrombolysis is commonly used as the initial treatment of acute or subacute lower extremity ischemia. METHODS: To evaluate the efficacy and cost of thrombolysis, we retrospectively analyzed 100 consecutive cases (87 patients) in which intra-arterial lysis (urokinase) was used as the initial treatment for native arterial lower extremity occlusive disease. The mean age of patients was 67 years, 57% of the patients were male, and preexisting peripheral vascular disease was present in 74%. Presenting symptoms were limb-threatening ischemia (53%) and claudication (47%). Acute symptoms (< 2 weeks' duration) were present in 48%. RESULTS: The 30-day morbidity rate was 31%, and four patients died. Complications were significant bleeding (23%), ischemic stroke (1%), and renal failure with (2%) and without (2%) dialysis. Concomitant angioplasty was performed in 63%. Complete or significant lysis as demonstrated with angiography was achieved in 75% of iliac, 58% of femoropopliteal, and 41% of crural vessels (P <.001). Within 30 days of lysis, 9% of patients underwent major amputation and 20% surgical revascularization (in 3 patients the extent of revascularization was lessened by the lytic therapy). Amputation-free survival was 83% and 75% at 6 months and 2 years, respectively. Relief of ischemia (defined as relief of claudication or limb salvage without major surgical intervention) was achieved in only 70% and 43% of patients at 30 days and 2 years, respectively (Kaplan-Meier analysis; mean follow-up, 31 months). Patients with aortoiliac disease had significantly better outcomes than those with infrainguinal disease (P =.03). Duration or type of presenting symptoms did not predict outcome. The cost of the initial hospitalization per patient for thrombolysis was $18,490. CONCLUSION: Thrombolysis can be as or more costly than surgery and is associated with a suboptimal outcome in a significant number of patients. These data lead us to caution against a uniform policy of initial thrombolysis for patients who present with lower extremity ischemia.
Aged↗
Contrast-enhanced peripheral MR angiography from the abdominal aorta to the pedal arteries: combined dynamic two-dimensional and bolus-chase three-dimensional acquisitions.
UNLABELLED: Wang Y, Winchester PA, Khilnani NM, et al. Contrast-enhanced peripheral MR angiography from the abdominal aorta to the pedal arteries: Combined dynamic two-dimensional and bolus-chase three-dimensional acquisitions. Invest Radiol 2001;36:170-177. RATIONALE AND OBJECTIVES: To obtain reliable contrast-enhanced peripheral MR angiography for imaging peripheral vascular disease from the abdominal aorta to the pedal arteries. METHODS: A protocol consisting of contrast-enhanced, dynamic two-dimensional (2D) acquisition at the feet and calf and bolus-chase three-dimensional (3D) acquisition from the abdominal aorta to the calf was developed and applied in patients with peripheral vascular disease. The performance of this integrated protocol was assessed in 89 consecutive patients. RESULTS: The bolus-chase 3D acquisition was of diagnostic quality in 100% of the acquisitions in the abdomen, 96% in the thigh, and 43% in the calf. The poor quality of the calf acquisitions was due to insufficient spatial resolution, poor arterial signal, and venous contamination. Diagnostic-quality images were obtained in 100% of the dynamic 2D acquisitions of the calf and 98% of the feet. CONCLUSIONS: The combined dynamic 2D and bolus-chase 3D contrast-enhanced MR angiography technique provides diagnostic images of the entire lower extremity.
Adult↗
Cross-sectional pattern of collateral vessels in patients with superficial femoral artery occlusion.
RATIONALE AND OBJECTIVES: The purpose of this study was to identify the cross-sectional location of collateral vessels in patients with peripheral vascular disease on three-dimensional magnetic resonance angiograms (3D MRAs) to suggest sites for intravascular or transcutaneous angiogenesis gene delivery in the lower extremity. METHODS: The axial locations were measured and categorized by tissue compartments, as well as by radial coordinates with respect to the femur. RESULTS: Collateral vessels in the thigh were identified in 24 of 93 consecutive patients who underwent peripheral 3D MRA. Ninety-one percent (99/109) of the observed collaterals were located near the adductor canal level of the thigh, with 78% (31/46) of these collaterals located in the fat in or surrounding the posterior muscle. CONCLUSIONS: The majority of collateral vessels in the thigh are located in the fat or muscle within the posterior compartment near the femur at the level of the adductor canal.
Adult↗
Anatomically tailored k-Space sampling for bolus-chase three-dimensional MR digital subtraction angiography.
The purpose of this study was to evaluate a variable k-space sampling method for bolus-chase three-dimensional magnetic resonance digital subtraction angiography in the arterial system from the abdomen to the calf. Imaging time was minimized by tailoring the acquisition according to the vascular anatomy of the station. For images obtained in 30 patients, results with the modified protocol were compared to those with the previously published protocol. For all stations, significant improvement (P <.001) was found with the modified protocol.
Adult↗
Differential effects of protein kinase C on human vascular smooth muscle cell proliferation and migration.
Vascular smooth muscle cell (SMC) migration and proliferation contribute to intimal hyperplasia, and protein kinase C (PKC) may be required for both events. In this report, we investigated the role of PKC in proliferation and migration of SMC derived from the human saphenous vein. Activation of PKC by phorbol-12,13-dibutyrate (PDBu) or (-)-indolactam [(-)-ILV] increases SMC proliferation. Downregulation of PKC activity by prolonged incubation with phorbol ester or inhibition of PKC with chelerythrine in SMC diminished agonist-stimulated proliferation. In contrast, stimulation of PKC with PDBu or (-)-ILV inhibited basal and agonist-induced SMC chemotaxis. Moreover, downregulation of PKC or inhibition with chelerythrine accentuated migration. We postulated that the inhibitory effect of PKC on SMC chemotaxis was mediated through cAMP-dependent protein kinase (protein kinase A, PKA). In support of this hypothesis, we found that activation of PKC in SMC stimulated PKA activity. The cAMP agonist forskolin significantly inhibited SMC chemotaxis. Furthermore, the inhibitory effect of PKC on SMC chemotaxis was completely reversed by cAMP or PKA inhibitors. In search of the PKC isotype(s) underlying these differential effects of PKC in SMC, we identified eight isotypes expressed in human SMC. Only PKC-alpha, -beta I, -delta, and -epsilon were eliminated by downregulation, suggesting that one or more of these four enzymes facilitate the observed phorbol ester-dependent effects of PKC in SMC. In summary, we found that PKC activation enhances proliferation but inhibits migration of human vascular SMC. These differential effect of PKC on vascular cells appears to be mediated through PKC-alpha, -beta I, -delta, and/or -epsilon.
Cell Division↗
Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-beta type II receptor.
Atherosclerotic lesions may progress due to a "failure to die" by vascular repair cells. Egr-1, a zinc finger transcription factor, is elevated more than 5-fold in human carotid lesions relative to the adjacent tunica media. Lesion cells in vitro also express 2-3-fold higher Egr-1 mRNA and protein levels but express much lower levels of the transforming growth factor-beta (TGF-beta) Type II receptor (TbetaR-2) and are functionally resistant to the antiproliferative effects of TGF-beta. Lesion cells fail to express a TbetaR-2 promoter/chloramphenicol acetyltransferase (CAT) construct but overexpress an Egr-1-inducible platelet-derived growth factor-A promoter/CAT construct. Transfection of Egr-1 cDNA represses TbetaR-2/CAT constructs but induces PDGF-A/CAT. Egr-1 transfection reduces the levels of TbetaR-2 and confers resistance to the antiproliferative effect of TGF-beta1. Egr-1 can interact directly with both the -143 Sp1 site and the positive regulatory element 2 (PRE2) (ERT/ets) region of the TbetaR-2 promoter. Thus, although activating a family of stress-responsive genes, Egr-1 also transcriptionally represses one of the major inhibitory pathways that restrains vascular repair.
Arteries↗
Improving cost efficiency on a vascular surgery service.
BACKGROUND: A vascular task force (VTF) consisting of two vascular surgeons and other key personnel was established to reduce costs and improve efficiency in the management of patients on a vascular surgery service. METHODS: The VTF met monthly beginning in 1994 to study and implement changes in the management of patients with (1) abdominal vascular, (2), carotid endarterectomy (3) distal bypass, and (4) other vascular procedures, including amputations. Length of stay, and fixed and variable costs were assessed for change over time using Pearson correlation coefficients. RESULTS: Improvements in efficiency (length of stay) and decreases in costs (fixed and variable costs) from fiscal year 1993 to fiscal year 1996 were significant for the total group of vascular patients (P </=0.001), with some intergroup differences. The major improvements were in the abdominal vascular and carotid endarterectomy groups, where length of stay and fixed and variable costs were reduced significantly (P </=0.01). Management of distal bypass and other vascular surgery patients showed less striking improvement. CONCLUSION: Vascular surgeons in collaboration with other dedicated personnel involved in the care of vascular patients can improve efficiency and reduce costs. Advances were greatest in patients who required operations for carotid and abdominal vascular disorders and least for patients who required distal bypasses and other vascular procedures.
Abdomen↗
Activation of integrin receptors is required for growth factor-induced smooth muscle cell dysfunction.
PURPOSE: Growth factors and cytokines such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-beta) stimulate smooth muscle cell (SMC) proliferation and extracellular matrix (ECM) protein production by binding and activating their respective receptors. Recent investigations suggest that simultaneous activation of integrins, which are heterodimeric receptors for ECM, may also be required for growth factor and cytokine function. In this study, we tested the hypothesis that activation of two integrins, alpha v beta 3 and alpha 2 beta 1, both previously identified in vascular SMCs, is necessary for growth factor- and cytokine-induced vascular SMC dysfunction. METHODS: DNA synthesis was measured after stimulation of SMCs derived from human saphenous vein with the growth factors PDGF-BB, EGF, and bFGF. SMC fibronectin (Fn) production was measured (by means of Western blotting) in SMCs stimulated for 72 hours with TGF-beta1 or EGF. Both endpoints were measured in the presence and absence of antibodies that block the function of the alpha v beta 3 and alpha 2 beta 1 integrins as well as the alpha2 and beta1 subunits. RESULTS: The alpha v beta 3 integrin blocking antibody significantly inhibited PDGF-BB-, EGF-, and bFGF-induced SMC proliferation. The alpha v beta 3 integrin antibody also markedly inhibited TGF-1- and EGF-induced SMC Fn production. Neither the alpha 2 beta 1 integrin nor the alpha2 or the beta1 subunits inhibited either proliferation or matrix protein production in response to any of these agonists. CONCLUSION: The alpha v beta 3 integrin is required for growth factor- and cytokine-induced SMC proliferation and FN production, whereas alpha 2 beta 1 is not. Since activation of alpha v beta 3 is required for the activity of at least four distinct growth factors and cytokines, inhibition of this integrin might be used as a therapeutic tool for the prevention of intimal hyperplasia.
Antibodies, Blocking↗
Gene therapy to prevent vein graft stenosis--ready for prime time?
Explore the source record for details and available documents.
Genetic Therapy↗
Is lower extremity revascularization worthwhile in patients with end-stage renal disease?
BACKGROUND: The purpose of this study was to review the results of lower extremity revascularization in patients with end-stage renal disease and to determine in these patients the functional benefit and cost of an aggressive approach to limb preservation. METHODS: During a 5-year period at our institution, 33 bypass operations were performed on 31 limbs of 23 dialysis-dependent patients. Indications for revascularization were limited (18) or extensive (12) tissue loss or ischemia without tissue loss (3). Procedures included aortobifemoral bypass (1), femoropopliteal bypass (10), and femorotibial/pedal bypass (22). A digital or transmetatarsal amputation was performed in 57% of limbs. RESULTS: The 30-day primary patency was 100%. Cumulative primary and secondary patency rates at 2 years were 65% and 79%, respectively. Limb salvage was 67% and 59% at 1 and 2 years, respectively. Patient survival was poor (47% at 2 years). Peritoneal dialysis was predictive of poor survival (P <.001). Four of 5 patients on peritoneal dialysis died within 3 months of intervention. Extensive tissue loss was predictive of a diminished rate of limb salvage (P =.027). Only 39% of limbs with extensive tissue loss were salvaged at 1 year compared with 78% and 100% of limbs with limited and no tissue loss, respectively. The average hospital cost was $44,308 per year of limb salvage. CONCLUSIONS: Although revascularization of ischemic limbs in dialysis patients can be achieved with an excellent initial graft patency and reasonable limb salvage, patient survival is poor and costs are high. A selective approach to revascularization in these complicated patients may be indicated. For patients treated with peritoneal dialysis and for those with extensive tissue loss, primary amputation may be the preferred approach.
Adult↗
The effect of protein kinase C and its alpha subtype on human vascular smooth muscle cell proliferation, migration and fibronectin production.
BACKGROUND: Vascular smooth muscle cell (SMC) migration, proliferation and extracellular matrix protein production are key steps in the formation of intimal hyperplasia, a process that leads to failure of vascular reconstructions. Protein kinase C (PKC) may be involved in all 3 cellular events. PKC consists of a family of 11 isotypes, 8 of which we have identified in human vascular SMCs. In this study we evaluate the role of PKCalpha as a second messenger for proliferation, migration and fibronectin production induced by human saphenous vein SMCs. METHODS: DNA synthesis was evaluated by using (3)H-thymidine incorporation. Mitogen-activated protein kinase (MAP-K) activation was quantified by Western blotting with an antibody to its phosphorylated substrate, Elk-1. Chemotaxis was evaluated by using a microchemotaxis chamber. SMC fibronectin was measured by Western blotting. For all experiments, PKCalpha was blocked with a selective inhibitor, Gö6976. RESULTS: Gö6976, at concentrations that allow selective inhibition of PKCalpha, inhibited platelet-derived growth factor-stimulated SMC proliferation and MAP-K activation by 30% to 40% and 30% to 60%, respectively. SMC chemotaxis was stimulated approximately 2-fold by the PKCalpha inhibitor. Neither basal nor transforming growth factor-betaI induced fibronectin production was affected by Gö6976. CONCLUSIONS: Our data suggest that PKCalpha is a positive mediator of SMC proliferation and MAP-K activity, a negative regulator of migration and has no effect on SMC fibronectin production. These data suggest that modulating activities of specific PKC isotypes might be useful in both the study and control of intimal hyperplasia.
Carbazoles↗
The cost-effectiveness of repairing ruptured abdominal aortic aneurysms.
BACKGROUND: Although advances in technology have reduced the operative risk of elective abdominal aortic aneurysm (AAA) repair, the surgical repair of ruptured AAAs is associated with a much poorer prognosis and a higher cost. Accordingly, it has been suggested that patients with predictably high rates of morbidity and mortality from ruptured AAA may not benefit from surgical intervention. METHODS AND RESULTS: A cost-effectiveness analysis was performed with the use of a Markov decision-analytic model to compute long-term survival in quality-adjusted life years and lifetime costs for a hypothetical cohort of patients with ruptured AAAs managed with either a strategy of open surgical repair or no intervention. Probability estimates for the various outcomes were based on a review of the literature. Average costs of (1) the immediate hospitalization ($28,356) and (2) complications resulting from the procedure were based on the average use of resources as reported in the literature and from a hospital's cost accounting system. Our measure of outcome was the incremental cost-effectiveness ratio. For our base-case analysis, the repair of ruptured AAAs was cost-effective with an incremental cost-effectiveness ratio of $10,754. (Society is usually willing to pay for interventions with cost-effectiveness ratios of less than $60,000; for example, the costeffectiveness ratios for coronary artery bypass grafting and dialysis are $9500 and $54,400, respectively.) In sensitivity analyses, the cost-effectiveness of repairing ruptured AAAs was influenced only by alterations in the operative mortality. If the operative mortality exceeded 88%, repair of ruptured AAAs was no longer cost-effective. As an independent variable, increasing age had no substantial impact on the cost-effectiveness, although it is reported to be associated with increased operative mortality. It was necessary that the patient's cost of the initial hospitalization for ruptured AAA exceed $195,000 before repairing ruptured AAAs was no longer cost-effective. CONCLUSIONS: Our analysis suggests that despite the high cost and poor outcomes, the surgical repair of ruptured AAAs is still cost-effective when compared with no intervention. The cost of repairing ruptured AAAs falls within society's acceptable limits and therefore should not be a consideration in the management of patients with AAAs.
Age Factors↗
Two decades of abdominal aortic aneurysm repair: have we made any progress?
PURPOSE: Over the past 20 years, there have been numerous advances in our ability to detect and to treat abdominal aortic aneurysms (AAAs). We hypothesized that these advances would lead to (1) an increase in the rate of elective repair and a decrease in the incidence of ruptured AAA (rAAA) and (2) a decrease in operative deaths for both elective AAA (eAAA) and rAAA. METHODS: To test these hypotheses, we investigated the incidence and outcomes of eAAA and rAAA surgery between 1979 and 1997, using the National Hospital Discharge Survey. This data set is a randomized, stratified sample representing discharges from the nation's acute care, nonfederally funded hospitals. Codes from the International Classification of Diseases, Ninth Revision were used to identify our study population. RESULTS: Over the past 19 years, there has been no change in the incidence rate of eAAA repair (range, 44.1-77.9 per 100,000). Moreover, the incidence of rAAAs presenting to the nation's hospitals has not changed (range, 6.6-16.3 per 100,000). There has been no consistent improvement over time in operative deaths associated with either eAAA or rAAA repair (average rates over the study period: eAAA, 5.6%; rAAA, 45.7%). Significant predictors of death from eAAA in patients included an age older than 80 years, African American race, congestive heart failure (CHF), and diabetes (P<.0001 for all). Significant predictors of death from rAAA in patients included age older than 70 years, African American race, female sex, renal failure, and a hospital bed size more than 500 (P<.05 for all). CONCLUSION: On a national level, over the past 19 years, our ability to identify and to treat patients with AAA has not improved. Advances in technology and critical care have not affected outcome. Regionalization of care, screening of high-risk populations, and endovascular repair are strategies that might allow further improvement in the outcome of patients with aneurysmal disease.
Black or African American↗
High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis.
To understand the mRNA transcript profile in the human atherosclerotic lesion, RNA was prepared from the fibrous cap versus adjacent media of 13 patients undergoing carotid endarterectomy. cDNA expression arrays bearing 588 known genes indicated that lesions express unexpectedly high levels of the early growth response gene, Egr-1 (NGFI-A), a zinc-finger transcription factor that modulates a cluster of stress-responsive genes including PDGF and TGF-beta. Expression of Egr-1 was an average of 5-fold higher in the lesion than in the adjacent media, a result confirmed by RT-PCR, and many Egr-1-inducible genes were also strongly elevated in the lesion. Time-course analyses revealed that Egr-1 was not induced ex vivo. Immunocytochemistry indicated that Egr-1 was expressed prominently in the smooth muscle-actin positive cells, particularly in areas of macrophage infiltration, and in other cell types, including endothelial cells. Induction of atherosclerosis in LDL receptor-null mice by feeding them a high-fat diet resulted in a progressive increase in Egr-1 expression in the aorta. Thus, induction of Egr-1 by atherogenic factors may be a key step in coordinating the cellular events that result in vascular lesions.
Animals↗
The effect of growth factors, cytokines, and extracellular matrix proteins on fibronectin production in human vascular smooth muscle cells.
PURPOSE: Although 60% to 80% of the mature intimal hyperplastic plaque is composed of extracellular matrix (ECM) proteins, little is known about the factors that stimulate smooth muscle cells (SMCs) to produce these proteins. A major component of the ECM protein is fibronectin. Thus we studied fibronectin production and its response to various growth factors, cytokines, and other ECM proteins that are released at the time of vascular injury. METHODS: Quiescent cultured human SMCs were stimulated for varying intervals with increasing concentrations of agonist. Fibronectin in the cell medium was assayed by immunoblotting with a fibronectin-specific antibody. RESULTS: After 72 hours of stimulation, transforming growth factor-beta (10 ng/mL) had the most profound effect on fibronectin production (9.6- +/- 2.1-fold; P <.05), followed by epidermal growth factor (100 ng/mL; 5.0- +/- 0.1-fold; P <.05, for both). Surprisingly, the platelet-derived growth factors (AA, AB, and BB) and fibroblast growth factor did not stimulate fibronectin production. Among the matrix proteins studied, only collagen type I (20 microg/mL) stimulated fibronectin production (1.9- +/- 0.1-fold; P <.05), whereas collagen type IV and laminin had no effect. The contractile protein angiotensin II (100 ng/mL) was a weak stimulant of fibronectin (1.6- +/- 0.2-fold; P <.05). Time course studies of fibronectin production up to 72 hours revealed kinetics that varied with each agonist. Transforming growth factor-beta stimulated significant early production of fibronectin, whereas fibronectin production in response to epidermal growth factor and collagen type I was initially modest but increased with time. The effect of angiotensin II did not become evident until 72 hours. CONCLUSION: Cytokines, growth factors, and matrix proteins have varying quantitative effects on ECM protein production by human vascular SMCs. Knowledge of the factors that influence ECM protein production may allow for the design of specific inhibitors that can prevent intimal hyperplasia.
Cells, Cultured↗
Inferior vena cava filter placement. American College of Radiology. ACR Appropriateness Criteria.
Explore the source record for details and available documents.
Angiography↗
Iliac angioplasty. American College of Radiology. ACR Appropriateness Criteria.
Explore the source record for details and available documents.
Angiography↗