Faculty Bibliography

Since up to 20% of patients undergoing lower extremity revascularization do not have an adequate venous conduit, some authors have explored the use of prosthetic grafts with adjunctive techniques for lower extremity revascularization. However, the long-term graft patency of those procedures has not been well documented. The purpose of this study was to examine the long-term patency of polytetrafluoroethylene (PTFE) bypass with adjunctive arteriovenous fistula and venous interposition (AVF/VI) for infrapopliteal revascularization. Over a 10-year period, 246 lower extremity reconstructions were performed in 176 (71.5% men) patients with critical ischemia in whom a totally autogenous vein bypass was not feasible. Seventy-six limbs had undergone 1 or more failed ipsilateral infrainguinal bypasses. Indications for surgery were chronic critical limb-threatening ischemia (86%) (rest pain, ischemic ulcer, or gangrene) or acute ischemia (14%). Ages ranged from 46 to 91 years (mean 74 +/-0.6 [SD] years). Risk factors such as diabetes, hypertension, coronary artery disease, end-stage renal disease, and use of tobacco were present in 49%, 49%, 52%, 8%, and 67% of the patients, respectively. During the follow-up, 112 cases (45%) required reinterventions. Twenty-seven patients (15%) required bypass revision twice. During the follow up, 56 limbs (23%) were amputated (above-the-knee amputation 25 (10%); below-the-knee amputation 31 (13%). To date, 150 (85%) patients of a total of 176 are deceased. The primary graft patency rates were as follows: at 1 year, 51%; at 2 years, 41%; 3 years, 35%; and 5 years, 24%. Limb salvage rates were as follows: 1 year, 79%; 2 years, 76%; 3 years 76%; and 5 years, 74%. Patient survival rates were as follows: 1 year, 69%; 2 years, 60%; 3 years, 54%; and 5 years, 40%. Amputation-free patient survival rates were as follows: 1 year, 66%; 2 years, 57%, 3 years, 51%, and 5 years, 30%. This technique appears to offer reasonable patency and limb salvage rates in patients in whom autogenous bypass grafts are not feasible.

The authors have noted a significant incidence of pulmonary embolism and mortality associated with upper extremity deep venous thrombosis (UEDVT). Since there is an association between the site of lower extremity DVT (LEDVT) and pulmonary embolism, they hypothesized that there might also be a correlation between the site of UEDVT and the incidence of pulmonary embolism (PE) and associated mortality. To further elucidate this hypothesis, they analyzed the mortality rate and incidence of PE diagnosed with subclavian/axillary or internal jugular vein thrombosis during a 5-year period at their institution. Two hundred and ten patients were diagnosed with acute internal jugular and/or subclavian/axillary DVT during a 5-year period by duplex scanning. The indications for the duplex examination were upper extremity swelling in 187 (89%) or as part of the work-up for pulmonary embolism in 23 (11%). There were 126 women (60%) and 84, men (40%). The mean age was 67 +/-18 years (range 1-101 years). The patients were divided into 3 groups based on the location of the thrombus: Group I-UEDVT involving the subclavian and/or axillary veins (n = 128); Group II-internal jugular vein thrombosis alone (n = 21); and Group III-concomitant subclavian/axillary and internal jugular vein DVT (n = 61). Risk factors were presence of central venous catheter or pacemaker in 127 patients (60%), malignancy in 78 patients (37%), concomitant lower extremity deep venous thrombosis (LEDVT) in 40 patients (19%), and history of LEDVT in 6 patients (3%). Eighty (38%) patients had more than 1 risk factor. The mean follow-up period was 13 +/-1 months (range 0-49 months). Mortality rates at 1, 3, and 12 months were 13%, 31%, and 40% for Group I; 14%, 33%, and 42% for Group II; and 23%, 44%, and 59% for Group III. The mortality rate in Group I was statistically significantly higher for patients >/=75 years old, patients not treated with anticoagulation, and patients who underwent placement of a central venous line. The same risk factors did not achieve statistical significance in the 2 other groups. The number of patients diagnosed with pulmonary embolism by ventilation/perfusion scans in Groups I, II, and III that could be attributed to the UEDVT solely was 8 (4%), 1 (0.5%), and 3 (2.4%), respectively. Contrary to the initial hypothesis of a relationship between the site of thrombosis and the incidence of pulmonary embolism and mortality, these data showed no statistical differences in mortality rate or incidence of pulmonary embolism among the 3 groups studied. These data also suggest that internal jugular vein thrombosis is a disease process associated with mortality and morbidity rates comparable to those of subclavian/axillary vein thrombosis.

Although prior studies have implicated nitric oxide (NO), a molecular messenger, in the development and progression of atherosclerosis, most of these studies have centered on atherosclerotic plaques. The current investigation determines whether a correlation exists between the presence of altered levels of NO production by peripheral blood mononuclear cells (PBMCs) and atherosclerotic disease. Venous blood was collected from 8 surgical patients having severe peripheral vascular disease and 8 healthy controls. PBMCs were separated by gradient centrifugation, diluted to 10(5) cells per mL, and cultured. Lipopolysaccharide (LPS), at doses of 10, 25, and 50 ng/mL, was used to stimulate NO production. Total nitric oxide assay was performed to determine the levels of NO produced by PBMCs at 24 and 48 hours. When stimulated by LPS there was an increase in NO production in the PBMCs cultured from control as well as patient samples, as compared to basal NO levels. However, the data demonstrate a significant decrease in the nitric oxide production in the patients with atherosclerosis as compared to that in the control group (p < 0.05). The differential production of nitric oxide by PBMCs of patients with atherosclerotic disease and healthy controls not only suggests that it has a role in the pathogenesis of this disease but also underlines its systemic nature. Blood cells circulating in the body with altered levels of NO production could have profound effects in the microvascular environment mediating molecular pathways and signaling cascades that activate and augment atherosclerosis.

BACKGROUND: Carotid artery balloon angioplasty and stenting (CBAS) is emerging as an acceptable alternative to carotid endarterectomy in selected high-risk patients. Conversely, patients with pre-existing renal impairment, diabetes, or both may be harmed by the nephrotoxic contrast agents required during CBAS. We attempted to limit or eliminate the use of contrast material during CBAS. METHODS: Eighteen patients with severe carotid stenoses (>70%) underwent CBAS at our institution over the last 12 months with duplex scan-assisted CBAS. Of these, 12 were primary procedures, and 6 were performed for carotid re-stenosis. Fourteen patients (78%) were neurologically asymptomatic. The average age of these patients was 75 +/- 11 years (range, 44-92 years). Hypertension, chronic renal insufficiency (serum creatinine level > or =1.5 mg/dL), coronary artery disease, diabetes, and smoking were present in 89%, 67%, 59%, 33%, and 28% of patients, respectively. Preoperative duplex carotid mapping was performed in all cases. All procedures were performed with patients under local anesthesia and light sedation. RESULTS: An ATL HDI 5000 scanner with the SonoCT feature was used. The common femoral artery was cannulated with a single-entry needle under direct ultrasound visualization. Fluoroscopy was used to assist passage of the guidewire into the aorta and the common carotid artery. In only four cases (22%) was an aortic arch angiogram obtained. Selective catheterization of the internal and external carotid arteries was performed under ultrasound guidance. The distal cerebral protection device (17 cases) was placed under fluoroscopic guidance. Balloon width and length were chosen according to ultrasound measurements. Balloon and stent deployment were successfully achieved with ultrasound guidance alone in all cases. Appropriate stent apposition and resolution of the stenosis was confirmed by duplex scanning in all cases. Five patients (28%) were noted to have low (<100 mL/min) internal carotid artery volume flow after stent deployment (range, 20-88 mL/min; mean +/- SD, 50 +/- 25 mL/min). The internal carotid artery volume flow increased immediately after Filterwire retrieval in all cases and ranged from 136 to 400 mL/min (mean, 245 +/- 107 mL/min). This increase was statistically significant ( P < .02). No ipsilateral strokes or deaths occurred during follow-up from 1 to 12 months (mean follow-up, 5 months). CONCLUSIONS: Duplex scan-assisted CBAS is feasible and may reduce the need for intra-arterial contrast injection in selected patients deemed at high risk for renal failure from nephrotoxic contrast material. Additional advantages include direct visualization of the puncture site, precise position of the balloon and stent, and B-mode and hemodynamic confirmation of the adequacy of the technique.

INTRODUCTION: Transforming growth factor-beta 1 (TGF-beta 1 ) is known to maintain a balance between apoptosis and cellular dysfunction and therefore may have a pivotal role in vessel remodeling during pathogenesis of vascular disorders. We previously demonstrated that inducible nitric oxide synthase (iNOS) mediates signal transduction in vascular wall during the development of varicose veins. Currently, we investigated the expression and correlation of TGF-beta 1 , iNOS, monocyte/macrophage infiltration, and loss of vascular smooth muscle cells (VSMCs), in a series of normal and varicose vein specimens. METHODS: Twenty varicose vein specimens were retrieved from 20 patients undergoing lower-extremity varicose vein excision, and 27 normal greater saphenous vein segments (controls) were obtained from 27 patients undergoing infrainguinal arterial bypass surgery. Principal risk factors (diabetes mellitus, hypertension, tobacco abuse) were also compared. Varicose vein segments were separated into tortuous and nontortuous regions based on their macroscopic and microscopic morphology. VSMC actin, CD68 + monocytes/macrophages, iNOS, and TGF-beta 1 , were examined by immunohistochemistry, immunoblotting, and real-time reverse transcriptase polymerase chain reaction. RESULTS: According to the CEAP classification for chronic lower extremity venous disease, most of the patients were in class 2 for clinical signs of the disease (n = 11). Mean ages were 53.6 +/- 4.7 years for the varicose vein group and 56.5 +/- 4.4 years for the controls. The gender distribution was same in both groups. Immunoreactivity to TGF-beta 1 and iNOS was significantly different in the tortuous regions of the varicose veins compared with nontortuous regions (P < .01). Not only was a significantly higher expression of iNOS noted in the varicose vein group (P < .001), but a differential expression of iNOS was also observed in the tortuous and nontortuous portions of the varicose veins. Significant overexpression of TGF-beta 1 (P < .01) that correlated with overproduction of iNOS and with increased presence of CD68 + monocytes/macrophages was observed in the varicose vein walls compared with normal veins. CONCLUSIONS: This is the first evidence of TGF-beta 1 , as well as iNOS, being differentially upregulated in nontortuous and tortuous segments of varicose veins. The increased expression of TGF-beta 1 and presence of macrophages, correlating with overproduction of iNOS, may be associated with varicosity development and deserves further study. CLINICAL RELEVANCE: The pathogenesis of varicose veins, the most common manifestation of chronic venous disease, is debatable. Elucidation of mechanisms involved in the disease process is the first step to improved therapeutic modulations. Towards this goal, the relationship between NO production and TGF-beta 1 in the molecular pathophysiology of chronic venous disease was investigated. The data identify for the first time, an important role for TGF-b1-iNOS-monocyte/macrophage signaling in the etiology of varicosities. Furthermore, we determine if there are any significant differences within the varicose vein group itself based on regional differences, by classifying the varicose tissues into tortuous and non-tortuous segments.

OBJECTIVE: To elucidate the natural history of upper extremity deep venous thrombosis (UEDVT), we examined factors that may contribute to the high mortality associated with UEDVT. METHODS: Five hundred forty-six patients were diagnosed with acute internal jugular/subclavian/axillary deep venous thrombosis from January 1992 to June 2003 by duplex scanning at our institution. There were 329 women (60%). The mean age +/- SD was 68 +/- 17 years (range, 1-101 years). Risk factors for UEDVT were the presence of a central venous catheter or pacemaker in 327 patients (60%) and a history of malignancy in 119 patients (22%). Risk factors for mortality within 2 months of the diagnosis of UEDVT that were analyzed included age, sex, presence of a central venous catheter or pacemaker, history of malignancy, location of UEDVT, concomitant lower extremity deep venous thrombosis, systemic anticoagulation, placement of a superior vena caval filter, and pulmonary embolism. RESULTS: The overall mortality rate at 2 months was 29.6%. The number of patients diagnosed with pulmonary embolism by positive ventilation/perfusion scan or computed tomographic scan was 26 (5%). The presence of a central venous catheter or pacemaker ( P < .001), concomitant lower extremity deep venous thrombosis ( P = .04), not undergoing systemic anticoagulation ( P = .002), and the placement of a superior vena caval filter ( P = .02) were associated with mortality within 2 months of the diagnosis of UEDVT by univariate analysis. Pulmonary embolism ( P = .42), sex ( P = .65), and a history of malignancy ( P = .96) were not. CONCLUSIONS: These data suggest that the high associated mortality of UEDVT may be due to the underlying characteristics of the patients' disease process and may not be a direct consequence of the UEDVT itself.

The traditional approach for patent and exposed and infected infrainguinal bypass grafts in the groin has included wide operative debridement and secondary or delayed primary closure. However, this has been associated with significant risk of further contamination and length of stay. The authors reviewed their experience using the wide debridement, sartorius muscle flap transposition, and primary wound closure as an alternative. During the past 5 years, they have had 50 patients with major wound necrosis or infection in the groin or thigh with the graft or native artery being exposed after debridement. This group included 28 men; 74% of the patients had hypertension, 58% had diabetes, and 20% had renal failure. The grafts were split evenly between native vein and prosthetic material. After wide debridement, closure was performed by the vascular surgeon using the sartorius muscle flap. Postoperatively, there was an 8% major amputation rate and a 12% mortality rate in the first 30 days. One patient developed a pseudoaneurysm 5 weeks after placement of the flap. This patient underwent removal of the infected polytetrafluoroethylene graft with ligation of the common femoral artery. None of the procedures have resulted in further systemic or graft sepsis. None have resulted in arterial or graft blowout. Follow-up was for an average of 18 months. Closure of groin and thigh wounds with exposed bypass graft or native artery can be safely performed with the sartorius muscle flap with excellent results. The length of stay of these patients compared to historical controls is acceptable. Furthermore, the chance of infection of the native artery or bypass may be reduced. Familiarity with this simple technique can be a valuable tool for the vascular surgeon.

BACKGROUND: The published results of carotid endarterectomy (CEA) in chronic renal insufficiency (CRI) patients are contradictory, mostly because of the relatively small number of patients in these studies. To better assess the neurologic complications and mortality, we reviewed a recent and substantially larger series of CRI patients who underwent CEAs. METHODS: From March 2000 to March 2003, 675 consecutive primary CEAs were performed in 609 patients (346 men, 57%) under general anesthesia. Asymptomatic carotid artery stenosis accounted for 71% of cases. CRI (serum creatinine level > or = 1.5 mg/dL) was detected in 166 patients (27%) who underwent 184 CEAs. The remaining 443 patients (73%) had 491 CEAs. RESULTS: Patients with CRI were different in age (76 +/- 8 years vs 72 +/- 9 years, P < .001), male gender (73% vs 51%, P < .001), coronary artery disease (50% vs 28%, P < .001), and diabetes mellitus incidence (38% vs 27%, P < .02). No significant difference in stroke rates was observed between the CRI patients and the control group (1.2% vs 0.5%). The mortality rate for CRI patients was 3%, whereas it was 0% for the control group ( P < .002). The 143 CRI patients with serum creatinine levels from 1.5 to 2.9 mg/dL had a 0.7% mortality rate, whereas it was 17% for 23 patients with serum creatinine levels of 3 mg/dL or more ( P < .001). The stroke rate for the former group was 0.7% and 4.3% for the latter group (NS). Asymptomatic (16) and symptomatic (7) patients with serum creatinine levels of 3 mg/dL or more had mortality rates of 13% and 28%, respectively, with P = .6. CONCLUSION: The high mortality rate observed in patients with serum creatinine levels of 3 mg/dL or more after CEA calls for a nonoperative approach in the management of asymptomatic patients.

Although ultrasonography (US) advantageously portrays lumen and wall thickness, velocity criteria have been used primarily to interpret carotid artery stenosis. The relationship of US and velocity measurements was investigated. Peak-systolic and end-diastolic velocities (PSV, EDV) increase exponentially as the lumen of the internal carotid artery narrows and the percent stenosis (%S) increases. We tested the consistency of the, relationship between carotid velocities and US %S in two distinct data sets. One data set was used to obtain regression equations relating velocity parameters and %S based on US. Validation of these equations was conducted using a separate, independent data set. US measurements were classified in 12 %S intervals, PSV, EDV, the ratio of the internal carotid artery to the common carotid artery PSV, and %S were entered consecutively until 10 records for each %S interval were obtained. Regression equations obtained in the first data set were used to predict %S in the second data set. Predicted %S was then compared with actual US %S. The highest correlation in the first data set (r = .89) was between %S and the natural logarithm (In) of PSV. This In PSV -%S equation was then applied to a second data set of an additional 120 carotid duplex images. In the second data set, actual %S and PSV-predicted %S differed by >10% in 38 cases (32%). When all velocity-%S regression equations were used for comparison, differences between actual and at least one velocity-predicted %S were >10% in 19% of the arteries. Conversely, actual %S matched at least one prediction of %S based on velocity data in 81% of the cases. US %S differed significantly from single velocity-based estimates of %S in at least one-third of the cases. On the other hand, four of five US measurements were confirmed by at least one velocity parameter. Emphasis on US, in addition to velocity data, is recommended for the interpretation of duplex US carotid examinations.

Von Hippel-Lindau (VHL) gene is a tumor suppressor gene that plays a genome "gatekeeper'' role and controls several downstream effector genes. We have previously demonstrated that both in vivo and in vitro adenovirus-mediated gene transfer of tumor suppressor genes into the vascular endothelium is effective in decreasing neointimal hyperplasia and abnormal cell proliferation. The degree of apoptosis induced by these genes is critical in mediating the in vivo responses to gene therapy and the maintenance of the crucial balance between cell death and viability. Since VHL gene is known to regulate vascular endothelial growth factor (VEGF) as well as other angiogenic factors, it may exhibit a greater potential in the attenuation of vascular disorders in comparison to other tumor suppressor genes. This study focused on whether adenovirus-mediated VHL gene transfer into human vascular smooth muscle cells has an effect on cell proliferation and induction of apoptosis. Human aortic smooth muscle cells (HASMC) were grown as monolayers and transfected with varying titers of adenovirus containing the VHL cDNA (AdVHL). The negative controls were adenovirus containing green fluorescent protein (AdGFP), vector alone (AdNull), and virus-free infection medium. Adenovirus encoding wild-type p53 (Adp53) was used as positive control. Cell viability and proliferation were determined by using trypan blue exclusion and MTS-based CellTiter 96 AQ Proliferation Assay. Apoptosis was evaluated by TUNEL assay, morphologic changes, and nucleosomal DNA degradation. Following AdVHL transfection HASMCs demonstrated a dose-dependent decrease in viability as compared to negative controls (p < 0.05). AdVHL-transfected cells exhibited a decrease in their proliferative ability by 40.21 +/-1.66 (SEM)%. In cultures transfected with the positive control, Adp53, the cell viability as well as proliferation was highly reduced (p < 0.001). AdGFP and AdNull did not increase HASMC apoptosis above baseline levels. The cells exposed to adenoviruses expressing tumor suppressor genes underwent apoptosis, with Adp53 demonstrating a very high magnitude of cell death (75.27 +/-3.52 [SEM]%). AdVHL expression caused 45.36 +/-2.55 (SEM)% apoptosis in HASMC. Recombinant adenovirus-mediated VHL expression is efficacious in limiting vascular smooth muscle cell growth in vitro. Overexpression of VHL suppresses HASMC proliferation and regulates apoptosis. Further experiments are indicated to examine whether VHL may be a useful adjunct in limiting myointimal hyperplasia.