Biomedical subjects

Brajesh K Lal

Publications and source records attributed to Brajesh K Lal.

At least 19 recordsLinked to original sources

PubMed2007

Treatment of carotid artery disease: stenting or surgery.

Carotid endarterectomy (CEA) is the only form of cerebral revascularization for which Level 1 evidence of effectiveness has been reported. Recent studies demonstrate the feasibility of carotid artery stenting (CAS) as an alternative to CEA. Its popularity is due to the perceived advantages of a less invasive treatment for carotid occlusive disease. Two randomized trials have reported no difference in the composite stroke, death, and myocardial infarction rate between CAS and CEA. However, these trials were not powered to identify superiority between the two procedures. A trial sponsored by the National Institutes of Health is currently underway to make that determination. The lead-in phase of this trial noted low complication rates with CAS. These results have encouraged the US Food and Drug Administration to approve the use of CAS in patients with neurologic symptoms (ie, ipsilateral stroke, transient ischemic attacks, and amaurosis fugax) in association with severe medical co-morbidities. Patients with carotid restenosis after previous CEA, anatomically inaccessible lesions above C2, and radiation-induced stenoses may also benefit from preferential treatment with CAS. The National Institutes of Health have now expanded the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) to include asymptomatic patients, and resulting data will help to clarify the role of CAS in this subset as well.

Carotid Artery Diseases↗

PubMed2006

Functional significance of differential eNOS translocation.

Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10(-5) M, 10(-4) M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10(-7) M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation.

Acetylcholine↗

PubMed2006

Noninvasive identification of the unstable carotid plaque.

Intraplaque hemorrhage, enlarging lipid cores, and their proximity to the flow lumen are important determinants of carotid plaque rupture and neurological complications. We developed an image-analysis method for B-mode ultrasound, pixel distribution analysis (PDA), for preprocedural identification of these high-risk features in carotid plaques. This technique may improve selection of patients for carotid endarterectomy and carotid artery stenting. Forty-two patients with high-grade carotid stenosis in 45 arteries, 18 symptomatic and 27 asymptomatic, underwent preoperative ultrasound. Intraplaque hemorrhage, lipid, fibromuscular tissue, calcium, lipid core area, and distance from the flow lumen were quantified using pixel intensities of tissues in control subjects. These findings were contrasted between symptomatic and asymptomatic plaques and correlated with histology. Inter- and intraobserver variabilities were determined for this technique. Pixel intensities of control tissues were discrete and significantly different from each other (median: blood 0, lipid 27, muscle 45.5, fibrous tissue 204, and calcium 245). There was more intraplaque hemorrhage (p<0.001) and lipid (p=0.002) but less calcium (p<0.001) within symptomatic plaques. Lipid cores were larger (p=0.005) and their distance from the flow lumen was lower (p=0.01) in symptomatic plaques. Intraplaque hemorrhage, lipid, fibromuscular tissue, calcium, lipid core size, and distance from flow lumen measured by PDA correlated with histology. No significant inter- or intraobserver variabilities were observed in these measurements. PDA accurately identified more intraplaque hemorrhage and lipid, less calcium, and larger lipid cores located closer to the flow lumen in symptomatic patients with carotid stenosis. These data indicate that PDA may be used to identify high-risk carotid atherosclerotic plaques and thereby improve the selection of patients requiring treatment.

Aged↗

PubMed2005

Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell proliferative dysfunction.

Diabetes mellitus is a major risk factor for the development of vascular complications. We hypothesized that hyperglycemia decreases endothelial cell (EC) proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathways. We cultured human umbilical vein ECs (HUVEC) in 5, 20, or 40 mM d-glucose. Cells grown in 5, 20, and 40 mM mannitol served as a control for osmotic effects. We measured EC proliferation for up to 15 days. We assessed apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt by Western blot analysis, and measured Akt kinase activity using a GSK fusion protein. HUVEC proliferation was also tested in the presence of pharmacological inhibitors of PI3k-Akt (wortmannin and LY294002) and after transfection with a constitutively active Akt mutant. ECs in media containing 5 mM d-glucose (control) exhibited log-phase growth on days 7-10. d-Glucose at 20 and 40 mM significantly decreased proliferation versus control (P < 0.05 for both), whereas mannitol did not impair EC proliferation. Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. Pharmacological inhibition of PI3k-Akt resulted in a dose-dependent decrease in EC proliferation. Transfection with a constitutively active Akt mutant protected ECs by enhancing proliferation when grown in 20 and 40 mM d-glucose. We conclude that d-glucose regulates Akt signaling through threonine phosphorylation of Akt and that hyperglycemia-impaired PI3k-Akt signaling may promote EC proliferative dysfunction in diabetes.

Cell Division↗

PubMed2005

When is a more proximal amputation needed?

Amputation may be the most appropriate therapy for an ischemic or infected limb, but the level at which to amputate is often difficult to determine. Selecting the appropriate level is crucial when performing an amputation. The goals of surgery are to maintain maximal limb length and ensure successful healing. When more of the foot and limb can be preserved, the chances for rehabilitation are improved. This article reviews how to determine the most appropriate level of amputation.

Amputation, Surgical↗

PubMed2005

Causes of severe chronic venous insufficiency.

A large number of adults in this country have some form of chronic venous insufficiency and a significant percentage of these have venous ulcers. The past decade has refined understanding of leukocyte-mediated injury and has elucidated the role of inflammatory processes in the dermal pathology of chronic venous insufficiency. Understanding of these pathologic cellular functions and molecular regulation of these processes is increasing.

Chronic Disease↗

PubMed2004

Observer variability of iliac artery measurements in endovascular repair of abdominal aortic aneurysms.

Accurate measurement of iliac arteries is essential for successful delivery of aortic endografts without iliac limb endoleak. Although intravascular ultrasound measurements may be reliable, they require an invasive procedure. Therefore, helical computed tomography (hCT) has become the most commonly used modality for obtaining preprocedure arterial diameter measurements. The accuracy of hCT remains ill-defined, however, because an anatomic gold standard with which to compare the measurements is not available. We therefore assessed inter- and intraobserver variability of hCT measurements. We also applied accepted cutoff measurements to determine the clinical impact of observer variability in predicting the need for adjunctive iliac access and iliac limb seal procedures. hCT scans were analyzed in 30 patients who had undergone successful placement of a bifurcated endograft (26 Ancure, 4 Aneurex). Mean age of patients was 75 years, the male/female ratio was 27:3. Three blinded observers measured transverse diameters (maximal aortic aneurysm [Amax], narrowest infrarenal aortic neck [Amin], maximal common iliac [Imax], and narrowest iliac artery [Imin]). Inter- and intraobserver variability was calculated as standard deviation of mean pair differences according to the method of Bland and Altman. The true incidence of adjunctive procedures to facilitate delivery of the device into the aorta and ensure iliac limb seal was compared with that predicted by the observers to obtain sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for the measurements. Interobserver variability of iliac measurements was higher than intraobserver variability (p < 0.05). Interobserver variability of Amax ranged from 4.37 to 10.73% of the mean Amax. Conversely, variability of Amin was 8.91-18.89%, that of Imax was 12.11-22.23%, and that of Imin was 10.51-18.73% (p < 0.05 vs. Amax). Therefore, interobserver variability influenced aortic neck and iliac diameter twice as much as it did aneurysm measurements. To successfully place 30 endografts we performed 8 adjunctive access procedures (4 angioplasties, 4 common iliac artery conduits) and 17 adjunctive procedures in 60 limbs to ensure limb seal (9 unilateral IIA coil embolizations, 8 stents). We used 8.5 (Ancure) and 8.0 (Aneurex) mm as lower limits of acceptability for uncomplicated access, and 13.4 (Ancure) and 16 (Aneurex) mm as the upper limits of acceptability for uncomplicated iliac limb seal. These limits were applied to measurements from the three observers to predict need for adjunctive access or iliac seal procedures in this cohort. Sensitivity, specificity, PPV, and NPV of these observer measurements for a need to perform additional access procedures were 0.67, 0.80, 0.55, and 0.87; the same values for a need to perform additional seal procedures were 0.71, 0.74, 0.52, and 0.86, respectively. Interobserver variability was approximately 20% of measured iliac diameter. This explains why helical CT measurements were noted to have low PPV in predicting the need for an adjunctive access or limb seal procedure. These data establish PPV and NPV for hCT and provide objective evidence for the need to improve iliac artery imaging. Until more accurate imaging becomes available, we recommend oversizing of iliac limbs by 10-20% in patients with wide landing zones and that surgeons be prepared to resolve unexpected iliac artery access or seal problems intraoperatively.

Aortic Aneurysm, Abdominal↗

PubMed2004

Carotid artery stenting: is there a need to revise ultrasound velocity criteria?

OBJECTIVES: Ultrasound (US) velocity criteria have not been well-established for patients undergoing carotid artery stenting (CAS). A potential source of error in using US after CAS is that reduced compliance in the stented artery may result in elevated velocity relative to the native artery. We measured arterial compliance in the stented artery, and developed customized velocity criteria for use early after CAS. METHODS: US was performed before and within 3 days after CAS, and after 1 month in a subset of 26 patients. Post-procedural peak systolic velocity (PSV) and end-diastolic velocity (EDV) of the internal carotid artery (ICA), PSV/EDV ratio, and internal carotid artery to common carotid artery ratio (ICA/CCA) were recorded. These were compared with degree of in-stent residual stenosis determined at carotid angiography performed at the completion of CAS. Peterson's elastic modulus (Ep) and compliance (Cp) of the ICA were determined in a subgroup of 20 patients at the distal end of the stent and in the same region in the native ICA before stenting. RESULTS: Ninety CAS procedures were analyzed. Mean (+/-SD) angiographic residual stenosis after CAS was 5.4 +/- 9.1%, whereas corresponding PSV by US was 120.4 +/- 32.4 cm/s; EDV, 41.4 +/- 18.6 cm/s; PSV/EDV ratio, 3.3 +/- 1.2; and ICA/CCA ratio, 1.6 +/- 0.5. PSV was unchanged at 1 month. Post-CAS PSV and ICA/CCA ratio correlated most with degree of stenosis (P <.0001 for both). Only six patients demonstrated in-stent residual stenosis 20% or greater, but the standard US threshold of PSV 130 cm/s or greater (validated for >20% ICA stenosis in our laboratory) categorized 38 of 90 patients as having stenosis 20% or greater. Receiver operator curve analysis demonstrated that a combined threshold of PSV 150 cm/s or greater and ICA/CCA ratio 2.16 or greater were optimal for detecting residual stenosis of 20% or greater, with sensitivity 100%, specificity 98%, positive predictive value 75%, and negative predictive value 100%. After placement of a stent, the ICA demonstrated significantly increased Ep (1.2 vs 4.4 x 10(3) mm Hg; P =.004) and decreased Cp (9.8 vs 3.2 %mm Hg x 10(-2); P =.0004). CONCLUSIONS: Currently accepted US velocity criteria validated in our laboratory for nonstented ICAs falsely classified several stented ICAs with normal diameter on carotid angiograms as having residual in-stent stenosis 20% or greater. We propose a new criterion that defines PSV less than 150 cm/s, with ICA/CCA ratio less than 2.16, as the best correlate to a normal lumen (0%-19% stenosis) in the recently stented ICA. This was associated with increased stiffness of the stented ICA (increased Ep, decreased Cp). These preliminary results suggest that placement of a stent in the carotid artery alters its biomechanical properties, which may cause an increase in US velocity measurements in the absence of a technical error or residual stenotic disease.

Aged↗

PubMed2004

Technical challenges in a program of carotid artery stenting.

OBJECTIVES: Successful carotid artery stenting (CAS) involves gaining access to the common carotid artery, characterizing and crossing the lesion, deploying an anti-embolic device and stent, and retrieving the anti-embolic device. These steps are critical determinants of the complexity of the procedure. The frequency with which technical challenges are encountered during CAS is ill-defined. The purpose of this investigation was to review the incidence and types of technical challenges encountered during CAS and determine their effect on outcome. METHODS: Data were prospectively collected for 194 consecutive CAS procedures (177 patients) and separated into group 1, standard CAS technique, and group 2, procedures with technical challenges requiring modifications to the technique. Technical challenges were defined as difficult femoral arterial access (aortoiliac occlusive disease), complex aortic arch anatomy (elongated or bovine arch, deep takeoff of the innominate artery, tandem stenoses (CCA, innominate artery), difficult internal carotid artery anatomy (tortuosity, high-grade stenosis), and circumferential internal carotid artery calcification. The incidence of technical challenges, types of technical modifications required, and effect on outcomes were determined. RESULTS: Fifty technically challenging situations (26%) were encountered in 194 CAS procedures (group 2), which required advanced technical skills. Standard methods were used in the other 144 procedures (group 1, 74%). No significant differences in 30-day stroke and death rates were noted between the groups (group 1, 3.1%; group 2, 2.0%; P = .564). CONCLUSIONS: Twenty-six percent of the procedures required a modification in the standard technique for successful CAS. Circumferential calcification and severe tortuosity continue to be relative contraindications to CAS. Recognition of these technical challenges and increasing facility with the methods to manage them will enable expanded use of CAS without increased morbidity and mortality.

Aged↗

PubMed2003

Methicillin-resistant Staphylococcus aureus infection does not adversely affect clinical outcome of lower extremity amputations.

Methicillin-resistant Staphylococcus aureus was first identified in isolation in Europe during the 1960's. Now widespread throughout the world, infection with this organism has emerged as a major problem in surgical practice. However, it remains debatable whether MRSA is more virulent than methicillin-susceptible strains. We have reviewed our most recent 4-year experience of lower extremity amputations to examine the influence of MRSA and non-MRSA infection on clinical outcome. During the past 4 years, 165 patients underwent lower extremity amputation for SVS/ISCVS category III acute limb ischemia and grades II and III chronic limb ischemia. Forty-five had documented MRSA infection, while 57 patients had documented infection with other flora. All patients were treated with appropriate sensitivity-specific antibiotics and aggressive wound care. No significant differences were noted in the level of primary amputation required by the two groups. Similarly, no significant differences were noted in either number of revisions or revision to higher-level amputation, time to heal, hospital length of stay, or 30-day morbidity and mortality rates. Our results demonstrate that MRSA infection does not adversely affect clinical outcome in patients undergoing lower extremity amputations. Appropriate treatment of infections with sensitivity-specific antibiotics, thorough wound debridement, and aggressive wound monitoring should be routine in all patients, regardless of bacterial flora.

Aged↗

PubMed2003

Durability and cumulative functional patency of transposed and nontransposed arteriovenous fistulas.

OBJECTIVES: Preoperative duplex scanning of arm and forearm veins has increased the creation of autogenous arteriovenous (AV) fistulas. However, the cumulative functional patency and durability of transposed AV fistulas (TAVF) compared with nontransposed AV fistulas (AVF) and prosthetic bridging grafts (AVG) remains ill-defined. METHODS: From January 1998 to December 2002, 245 dialysis access procedures were performed at University Hospital and the Veteran Affairs Medical Center in New Jersey. Follow-up data were available for 125 procedures (TAVF, n = 42; AVF, n = 30; AVG, n = 53) performed in 97 patients. All access procedures were planned on the basis of preoperative duplex scans of arm and forearm veins. Functional patency was defined as ability to cannulate and hemodialyze patients successfully. Primary and secondary cumulative functional patency of TAVFs, AVFs, and AVGs was determined with life table analysis, and differences were analyzed with the log-rank test. Differences in revision rates, including thrombolysis, thrombectomies, and operative revisions, were determined with the Fisher exact t test. RESULTS: Mean follow-up was 18 months (range, 4-24 months). For TAVFs, AVFs, and AVGs, primary functional patency rate at 1 year was 76.2%, 53.3%, and 47.2%, respectively, and at 2 years was 67.7%, 34.4%, and 25.5%, respectively. Similarly, secondary functional patency rate at 1 year was 83.2%, 66.7%, and 58.5%, respectively, and at 2 years was 74.6%, 56.2%, and 40.2%, respectively. Primary and secondary functional patency rates for TAVFs were superior to those for AVGs at 1 and 2 years (P <.001). AVFs had superior secondary functional patency rate at 2 years, compared with AVGs (P <.05), and TAVFs had superior primary and secondary patency rates at 2 years, compared with AVFs (P <.05). AVGs required significantly more revisions than did TAVFs (28.5% vs 54.7%; P <.001) or AVFs (36.7% vs 54.7%; P <.05). CONCLUSIONS: Preoperative duplex scanning of upper arm and forearm veins facilitated successful creation of all types of autogenous fistulas at our institution. TAVF cumulative functional patency rates were superior compared with AVGs and AVFs. Furthermore, TAVFs and AVFs were more durable and required fewer revisions than did AVGs. When preoperative duplex criteria indicate that TAVFs can be performed, they should be the initial access of choice, because of their superior long-term patency and durability.

Adult↗

PubMed2003

In-stent recurrent stenosis after carotid artery stenting: life table analysis and clinical relevance.

OBJECTIVES: Carotid artery stenting has been proposed as an alternative to carotid endarterectomy in cerebral revascularization. Although early results from several centers have been encouraging, concerns remain regarding long-term durability of carotid artery stenting. We report the incidence, characteristics, and management of in-stent recurrent stenosis after long-term follow-up of carotid artery stenting. METHODS: Carotid artery stenting (n = 122) was performed in 118 patients between September 1996 and March 2003. Indications included recurrent stenosis after previous carotid endarterectomy (66%), primary lesions in patients at high-risk (29%), and previous ipsilateral cervical radiation therapy (5%). Fifty-five percent of patients had asymptomatic stenosis; 45% had symptomatic lesions. Each patient was followed up with serial duplex ultrasound scanning. Selective angiography and repeat intervention were performed when duplex ultrasound scans demonstrated 80% or greater in-stent recurrent stenosis. Data were prospectively recorded, and were statistically analyzed with the Kaplan-Meier method and log-rank test. RESULTS: Carotid artery stenting was performed successfully in all cases, with the WallStent or Acculink carotid stent. Thirty-day stroke and death rate was 3.3%, attributable to retinal infarction (n = 1), hemispheric stroke (n = 1), and death (n = 2). Over follow-up of 1 to 74 months (mean, 18.8 months), 22 patients had in-stent recurrent stenosis (40%-59%, n = 11; 60%-79%, n = 6; > or =80%, n = 5), which occurred within 18 months of carotid artery stenting in 13 patients (60%). None of the patients with in-stent recurrent stenosis exhibited neurologic symptoms. Life table analysis and Kaplan-Meier curves predicted cumulative in-stent recurrent stenosis 80% or greater in 6.4% of patients at 60 months. Three of five in-stent recurrent stenoses occurred within 15 months of carotid artery stenting, and one each occurred at 20 and 47 months, respectively. Repeat angioplasty was performed once in 3 patients and three times in 1 patient, and repeat stenting in 1 patient, without complications. One of these patients demonstrated asymptomatic internal carotid artery occlusion 1 year after repeat intervention. CONCLUSIONS: Carotid artery stenting can be performed with a low incidence of periprocedural complications. The cumulative incidence of clinically significant in-stent recurrent stenosis (> or =80%) over 5 years is low (6.4%). In-stent restenosis was not associated with neurologic symptoms in the 5 patients noted in this cohort. Most instances of in-stent recurrent stenosis occur early after carotid artery stenting, and can be managed successfully with endovascular techniques.

Aged↗

PubMed2003

Altered proliferative responses of dermal fibroblasts to TGF-beta1 may contribute to chronic venous stasis ulcer.

PURPOSE: Venous ulcer fibroblasts demonstrate decreased proliferative responses to growth factor stimulation, suggesting cellular senescence. However, the role of chronic venous insufficiency (CVI) disease progression and extracellular matrix (ECM) proteins in agonist-induced cellular proliferation is ill-defined. We hypothesize that CVI-induced fibroblast proliferative resistance to growth factors worsens with disease progression and is regulated by the composition of ECM. METHODS: Fibroblast explants were isolated from biopsy specimens from two patients without CVI and 16 patients with CVI of the lower calf (LC) and lower thigh (LT) and stratified according to CEAP disease severity: non-CVI (NC; n = 2), class 2-3 (n = 5), class 4 (n = 5), class 5 (n = 3), and class 6 (n = 3). Proliferation experiments were standardized with a neonatal foreskin fibroblast cell line (HS68). A 10-day course and dose response experiment with 0, 0.5, 1.0, 2.5, 5, 10, and 20 ng/mL of transforming growth factor-beta(1) (TGF-beta(1)) demonstrated maximal cell proliferation at 5 ng/mL of TGF-beta(1) on day 4. Under these conditions, CVI dermal fibroblasts were challenged with and without TGF-beta(1) and evaluated for proliferative responses on plates coated with polystyrene, collagen, and fibronectin. RESULTS: No differences in unstimulated proliferation were observed in LT and LC fibroblasts from patients with class 2-3 disease and LT fibroblasts from patients with class 4 and 5 disease, compared with NC and HS68 cells. LC fibroblasts from patients with class 4 disease (P <.05) and class 5 disease (P <.001), and LC (P <.001), and LT fibroblasts from patients with class 6 disease (P <.001) proliferated to a lesser degree than did NC and HS68 cells. The diminished proliferation observed in class 4 LC cells was reversible with TGF-beta(1) stimulation (P <.004); however, class 5 and class 6 LC and LT fibroblasts did not respond to stimulation with TGF-beta(1). Collagen increased proliferation of HS68 cells with (P <.05) and without (P <.01) TGF-beta(1), compared with cells grown on polystyrene, but did not increase proliferative responses in NC or CVI fibroblasts with and without TGF-beta(1). Similarly, fibronectin increased proliferation of HS68 cells (P <.05) compared with cells grown on polystyrene, but did not alter proliferation in CVI fibroblasts. Fibronectin did seem to inhibit TGF-beta(1)-induced proliferation observed in class 4 LC cells. CONCLUSION: These data indicate that clinical disease progression correlates with cellular dysfunction. Fibroblasts from patients with class 2-3 disease retain their unstimulated and agonist- induced proliferative capacity, compared with NC and HS68 cells. The onset of inflammatory skin changes (class 4 and class 5 disease) diminishes agonist-induced proliferation, and ulcer formation (class 6 disease) severely inhibits it. In addition, the composition of ECM does not affect TGF-beta(1)-induced proliferation of fibroblasts in CVI.

Cell Movement↗

PubMed2003

Carotid artery stenting: analysis of data for 105 patients at high risk.

OBJECTIVES: Carotid artery stenting (CAS) has been recommended as an alternative to carotid endarterectomy (CEA) by some clinicians. However, recently published clinical trials have reported 30-day stroke and death rates of 10% to 12%. This prompted review of our experience with CAS in patients at high risk, to document our results and guide further use of CAS. METHODS: From September 1996 to the present, we performed 114 consecutive CAS procedures in 105 patients. Sixty-three patients were men (60%) and 42 patients were women (40%), with mean age of 70 years (range, 45-93 years). Indications for CAS included recurrent stenosis after previous CEA in 74 patients (65%), primary lesions in 32 patients at high risk (28%), and carotid stenosis with previous ipsilateral radiation therapy in 8 patients (7%). Asymptomatic stenosis (>80%) was managed in 70 patients (61%), and symptomatic lesions (>50%) were treated in 44 patients (39%). RESULTS: CAS was technically successful in all patients. Mean severity of stenosis before CAS was 87% +/- 6%, compared with 9% +/- 4% after CAS. Two patients (1.9%) died, 1 of reperfusion-intracerebral hemorrhage and 1 of myocardial infarction 10 days after discharge; and 1 patient (0.95%) had a stroke (retinal infarction), for a 30-day stroke and death rate of 2.85%. Two patients (1.9%) had transient neurologic events. No cranial nerve deficits were noted. No neurologic complications have been noted in the last 27 patients (26%). CONCLUSIONS: A 30-day stroke and death rate of 2.85% in our experience demonstrates acceptability of CAS as an alternative to repeat operation or primary CEA in patients at high risk or in patients with radiation-induced stenosis. We recommend further clinical investigation of CAS and participation in clinical trials by vascular surgeons.

Aged↗

PubMed2003

Does severe venous insufficiency have a different etiology in the morbidly obese? Is it venous?

OBJECTIVE: Chronic venous insufficiency (CVI) is the most common cause of leg ulcers. Patients with morbid obesity are remarkable for particularly recalcitrant ulcers. Because obesity is not specifically incorporated in CEAP or other venous scoring systems, we sought to characterize this group of patients more completely. METHODS: Patients with severe CVI (CEAP clinical class, 4, 5, and 6), and class III obesity (body mass index [BMI], >40) were reviewed. Findings from clinical and duplex ultrasound scan (DU) examinations were compared with the CEAP classification, its adjunctive venous clinical severity score, and sensory thresholds. RESULTS: A review of clinic records identified 20 ambulatory patients with a mean age of 62 years, a mean BMI of 52, and a mean weight of 164 kg (361 lbs); all but one had bilateral symptoms. No evidence of venous insufficiency was detected with DU in 24 of the 39 limbs. Although some valvular incompetence was detected with DU in 15 of 39 limbs, these abnormalities were widely dispersed between 28 sites; eight limbs had findings at only one site. Ulceration (mean area, 29 cm(2)) was present in 25 limbs and necessitated 7 months for healing; 13 (52%) recurred at least once during a mean observation period of 36 months. The mean sensory threshold of 5.21 exceeded current risk thresholds used in diabetic screening programs. The distribution of CEAP clinical class was C4 (n = 14), C5 (n = 14), and C6 (n = 11). Increasing CEAP class correlated with an increased mean BMI of 47, 52, and 56, respectively (P <.01). CEAP also correlated with a rising mean venous clinical severity score of 10, 11, and 15, respectively (P <.05). CONCLUSION: Patients with class III obesity had severe limb symptoms, typical of CVI, but approximately two thirds of the limbs had no anatomic evidence of venous disease. The association of increasing limb symptoms with increasing obesity suggested that the obesity itself contributes to the morbidity.

Aged↗

PubMed2002

p42/44MAPK regulates baseline permeability and cGMP-induced hyperpermeability in endothelial cells.

We tested the hypothesis that p42/44MAPK and p38MAPK (mitogen-activated protein kinases; MAPK) signaling pathways regulate endothelial cell permeability to macromolecules. Passage 2-4 human umbilical vein endothelial cells (HUVEC) were grown to confluence on fibronectin-coated Snapwell membranes. The flux of fluorescein isothiocyanate-labeled dextran-70 across the HUVEC monolayers served to determine permeability. Application of 1 mM 8-bromo 3' 5'-cyclic guanosine monophosphate (8-Br-cGMP) increased permeability from 7.0 +/- 1.6 x 10(-6) to 12.5 +/- 2.8 x 10(-6) cm/s (P < 0.05). Pretreatment of HUVEC for 60 min with a selective p42/44MAPK inhibitor (AG126 at 2.7 and 27 microM) blocked 8-Br-cGMP-induced hyperpermeability. However, inhibition of p38MAPK (SB203580 at 0.6 microM) did not influence the cGMP-induced hyperpermeability response. AG126, administered at 27 microM, decreased baseline permeability from 7.9 +/- 0.5 x 10(-6) to 5.9 +/- 0.5 x 10(-6) cm/s (P < 0.05). Our results indicate that the p42/44MAPK signaling pathway is important in the regulation of baseline permeability and cGMP-induced hyperpermeability.

Cells, Cultured↗

PubMed2002

Carotid artery closure for endarterectomy does not influence results of angioplasty-stenting for restenosis.

OBJECTIVE: Carotid angioplasty and stenting (CAS) has been recommended by some authors for the management of postendarterectomy restenosis. However, some authors have expressed concern about the influence of primary closure and patch angioplasty performed during carotid endarterectomy (CEA) on the incidence rate of complications after CAS. METHODS: We analyzed our consecutive series of 54 CAS procedures performed for restenosis after prior CEA. These procedures accounted for 75% of the 72 CAS procedures performed at our institution for all indications during the last 4 years. Of these 54 patients, 28 (52%) were men and 26 (48%) were women, with a mean age of 69 years. The mean clinical follow-up period was 18 months (range, 1 to 48 months). The mean interval between prior CEA and CAS was 16 months (range, 6 to 62 months). Nineteen patients were symptomatic (35%), and 35 were asymptomatic (65%). The mean severity of restenosis was 84% +/- 7% (standard deviation). The mean residual stenosis after CAS was 8% +/- 3% (standard deviation). RESULTS: Among the 54 prior CEAs, eight cases were performed with primary closure (15%), five procedures used patch closure with autologous vein (9%), and 41 operations used Dacron patch closures (76%). All patients were managed successfully with CAS with predeployment angioplasty with low profile balloons, self-expanding stents, and poststent angioplasty to approximate the transverse diameter of the carotid artery. No instances of contrast extravasation, arterial disruption, or subintimal dissection were observed. One stroke (1.8%), a retinal infarction with partial field of vision loss, occurred in a patient with prior CEA and Dacron patch closure, and no deaths were observed in the series. CONCLUSION: Performance of CAS for restenosis after CEA with autologous or synthetic patch angioplasty was technically successful in all 54 procedures. The method of closure of the arteriotomy during CEA, primary closure or patch angioplasty, did not influence the incidence of complications.

Aged↗

PubMed2002

Pixel distribution analysis of B-mode ultrasound scan images predicts histologic features of atherosclerotic carotid plaques.

BACKGROUND: The correlation of B-mode ultrasonographic morphology with histologic characteristics of atherosclerotic carotid plaques remains ill-defined. The classification of plaques with recently reported measures of plaque echogenicity and heterogeneity has been unsatisfactory. We used computer-assisted duplex ultrasound (DU) scan image analysis to determine echogenicity of specific tissues in control subjects. This information was used to quantify each tissue in imaged carotid plaques with pixel distribution analysis (PDA). These objective observations then were quantitatively compared with plaque histology in symptomatic and asymptomatic patients. METHODS: We performed standardized DU scanning of healthy tissues in 10 volunteer subjects and of 20 carotid artery plaques (7 symptomatic and 13 asymptomatic) in 19 patients with carotid stenosis. The plaques underwent histologic analysis after carotid endarterectomy. The grayscale intensity ranges of blood, lipid, fibromuscular tissue, and calcium were calculated in the control subjects. With computer-assisted image analysis, B-mode images of plaques were linearly scaled to normalize data. Pixel distribution within the images then was analyzed. The grayscale ranges of known tissues obtained from control subjects helped define the amount of intraplaque hemorrhage, lipid, fibromuscular tissue, and calcium within carotid plaque images. This analysis was correlated with tissue composition measurements on histologic sections of excised plaques. RESULTS: The median grayscale intensity (range) in control subjects was 2 (0 to 4) for blood, 12 (8 to 26) for lipid, 53 (41 to 76) for muscle, 172 (112 to 196) for fibrous tissue, and 221 (211 to 255) for calcium. PDA-derived predictions for blood, lipid, fibromuscular tissue, and calcium within carotid plaques correlated significantly with the histologic estimates of each tissue respectively (blood: P =.012; lipid: P =.0006; fibromuscular: P =.035; and calcium: P =.0001). A significantly higher amount of blood and lipid was seen within symptomatic plaques compared with asymptomatic ones (P =.0048 and P =.026, respectively). Conversely, a larger amount of calcification was noted within asymptomatic plaques (P =.0002). CONCLUSION: Computer-assisted PDA of DU scan images accurately quantified intraplaque hemorrhage, fibromuscular tissue, calcium, and lipid. Symptomatic plaques had lower calcium content but larger amounts of intraplaque hemorrhage and lipid. Quantitative PDA may be used to determine carotid plaque tissue composition to assist in the identification of symptomatic and potentially unstable asymptomatic plaques.

Aged↗