Leg swelling is a common cause for vascular surgical evaluation, and iliocaval obstruction due to May-Thurner syndrome (MTS) can be difficult to diagnose. Physical examination and planar radiographic imaging give anatomic information but may miss the fundamental pathophysiology of MTS. Similarly, duplex ultrasonographic examination of the legs gives little information about central impedance of venous return above the inguinal ligament. We have modified the technique of duplex ultrasonography to evaluate the flow characteristics of the leg after tourniquet-induced venous engorgement, with the objective of revealing iliocaval obstruction characteristic of MTS. Twelve patients with signs and symptoms of MTS were compared with healthy control subjects for duplex-derived maximal venous outflow velocity (MVOV) after tourniquet-induced venous engorgement of the leg. The data for healthy control subjects were obtained from a previous study of asymptomatic volunteers using the same MVOV maneuvers. The tourniquet-induced venous engorgement mimics that caused during vigorous exercise. A right-to-left ratio of MVOV was generated for patient comparisons. Patients with clinical evidence of MTS had a mean right-to-left MVOV ratio of 2.0, asymptomatic control subjects had a mean ratio of 1.3, and MTS patients who had undergone endovascular treatment had a poststent mean ratio of 1.2 (P = 0.011). Interestingly, computed tomography and magnetic resonance imaging results, when available, were interpreted as positive in only 53% of the patients with MTS according to both our MVOV criteria and confirmatory venography. After intervention, the right-to-left MVOV ratio in the MTS patients was found to be reduced similar to asymptomatic control subjects, indicating a relief of central venous obstruction by stenting the compressive MTS anatomy. Duplex-derived MVOV measurements are helpful for detection of iliocaval venous obstruction, such as MTS. Right-to-left MVOV ratios and postengorgement spectral analysis are helpful adjuncts to duplex imaging for leg swelling. The MVOV maneuvers are well tolerated by patients and yields physiological data regarding central venous obstruction that computed tomography and magnetic resonance imaging fail to detect.

Gene therapy shows promise in the treatment of vascular disease, but a formidable challenge has been delivery of genetic material in a safe and non-toxic way. Viral transfection comes with significant clinical implications in terms of safety, and there are still no FDA-approved gene therapy products. This has led to recent interest in developing alternatives to viral transfection that are low risk, predictable, and non-toxic. Biodegradable polymers have shown promise as one of these alternatives, but to date have been exclusively tested in human stem cells. Differentiated cell types would be prime targets for therapeutic gene modulation in the prevention of various disease processes. We aim to establish polymeric transfection as a method of gene therapy in cells of vascular origin. Human aortic smooth muscle cells (HASMC) were transfected with poly(B-amino ester) biodegradable polymers (Stemfect™) conjugated to fluorescently labeled GAPDH or negative control (NC) siRNAs. Increasing polymer and siRNA concentrations were tested for optimal transfection efficiency. Conjugate endocytosis was confirmed by fluorescent microscopy, and gene silencing was assayed by qPCR normalized to 18S. Cellular translocation of the bioconjugates was visible 24 and 48 hours after transfection beginning with a 1.3μl polymer: 200pmol siRNA conjugate. At 48 hours after transfection, efficient gene silencing was achieved in a polymer concentration dependent manner, independent of increasing siRNA concentrations. The highest rate of GAPDH silencing was 84±4% vs. NC (n=5, P<0.05), achieved with a 3.9μl polymer: 200pmol siRNA conjugate. HASMCs were successfully transfected using polymeric bioconjugates. Future studies will expand on this method of gene therapy for transfection of whole vessel segments and in vivo animal models of vascular disease. This may provide new clinical options for genetic therapy in the prevention of peripheral vascular pathologies.

Axillo-subclavian vein thrombosis (AVT) leads to arm swelling, and DUPLEX accuracy is limited by the clavicle. Post-hyperemic brachial vein velocities obtained from DUPLEX may reflect more central obstructive lesions that are not obvious without hyperemia. Patients (11) with prior known AVT were seen for arm swelling. Five of the 11 patients had undergone prior surgery or instrumentation of the subclavian vein. DUPLEX vein imaging of the arm was performed to detect acute or chronic thrombus or absence of flow anatomically. After usual DUPLEX, bilateral arms were compared in each for resting and post-hyperemic velocities using mean ± SD, and t-test to determine significance (p < 0.05). All underwent venography to confirm central vein disease and to treat stenoses related to AVT. Significant diminution in peak velocities occurred in patients with subclavian vein stenoses; resting velocities only tended to decrease in patients with central venous stenoses. Traditional DUPLEX was positive in only two patients, whereby chronic axillary thrombi were seen. These findings suggest that dynamic evaluation of brachial vein flow velocities with DUPLEX can be useful in surgical planning for arm swelling. Compression to create hyperemia seems to augment DUPLEX sensitivity. Prior AVT should prompt evaluation of post-hyperemic flow velocity.Tabled 1Velocities measured at brachial veinResting AsymptomaticResting SymptomaticHyperemia AsymptomaticHyperemia Symptomaticcm/s38.420.974.340.4S. D.18.821.734.034.1p value.08.05 Open table in a new tab

Intimal hyperplasia (IH) occurs more frequently in postmenopausal women taking hormone replacement therapy. Matrix metalloproteinases (MMPs) play an important role in the cellular processes of IH development. We have previously shown estrogen (Est) increases MMP activity in vascular smooth muscle cells (VS MCs). Est has been shown to activate MAPK signaling cascades, and MAPKs are known to regulate MMPs in various cell types. Here we investigated Est-modulated signaling pathways involved in MMP regulation and their downstream effect on the cellular processes of IH. Est receptor antagonist ICI182780 (ICI; 5μM), tamoxifen (Tam; 5μM), or ERK1/2 inhibitor UO126 (UO; 10μM) were added 30min prior to 24h or 5-45min Est exposure (50nM), and cells were subjected to Western blot analyses, and zymography, Boyden chamber migration, and MTT proliferation assays. Est exposure caused activation of ERK1/2 at 30 min in human female VS MCs, with no activation of JNK, p38, or PI3K at any time point (n = 2-3). Est-stimulated MMP enzymatic activity was inhibited by exposure to ICI and Tam. Est increased VS MC migration by 17 ± 2% and proliferation by 12 ± 2% vs control (p < 0.05; n = 8). ICI and Tam inhibited Est-stimulated migration and proliferation to near basal levels. UO inhibited Est-stimulated MMP-2 activity by −8 ± 1% (n = 2), Est-stimulated migration by −34 ± 2% (p < 0.01; n = 4-8), and Est-stimulated proliferation by −9 ± 3% (p < 0.05; n = 3), indicating they occur in an ERK1/2 dependent manner. Estrogen stimulates the cellular processes of IH development via ERK1/2 dependent signaling. Inhibition of ERK1/2 results in downregulation of Est-mediated MMP activity and Est-induced VS MC migration and proliferation. Future studies will include targeted ERK1/2 silencing to assay a possible mechanism for effective IH inhibition. Understanding the signaling mechanisms involved in hormone-mediated IH development could provide a basis for therapeutic strategies of inhibition.

Objective: Intimal hyperplasia (IH) is the most common indicator for secondary intervention in peripheral vascular disease. The major cellular processes contributing to IH development are extracellular matrix (ECM) degradation and vascular smooth muscle cell (VSMC) migration and proliferation. Matrix metalloproteinases (MMPs) are implicated in vascular remodeling due to their ability to selectively degrade components of the ECM. Members of the tetracycline family of antibiotics are potent MMP inhibitors, doxycycline being one of the more potent inhibitors with better absorption and a longer half-life than the parent compound. We have previously shown doxycycline inhibits MMP activity and VSMC migration in vitro. Moreover, doxycycline has been found to inhibit cell proliferation in other cell types. The primary aim of this study was to investigate the therapeutic benefit of using doxycycline in preventing IH. We hypothesized that doxycycline treatment would decrease MMP activity in vivo and inhibit the development of IH in an in vivo model of vascular injury. Methods and Results: Female rats underwent balloon angioplasty (BA) of the left common carotid artery. Doxycycline (doxy; 400 mg/pellet) was delivered via a 90-day slow-release pellet implanted either 3 days prior or at the time of injury. At 14 days post-injury tissue samples were fixed, sectioned, stained with Masson Trichrome elastin for measurement of intima:media (I:M) ratios, and immunostained for isoform-specific MMPs and proliferating cellular nuclear antigen (PCNA). Doxy treatment prior to and at the time of BA lowered I:M ratios to 0.77±0.21 and 1.04±0.32, respectively, compared to 1.25±0.26 in the control group (n=3). However, at 14 days post-BA the tested dose of doxy in either group had no inhibitory effect on MT1-MMP or MMP-2 tissue levels, as measured by immunohistochemistry, or on systemic levels of MMP, as measured by total MMP serum levels using ELISA. In a time course study at 0-21 days post-BA, we have shown I:M ratio increased consistently over time but MT1-MMP protein expression was highest at day 2, then decreased significantly by days 7 and 10 (*P<0.05, n=3). Assays at earlier time points are needed in the doxy treatment groups to examine the role of doxy in the possible inhibition of this early peak in MMP expression. Additionally, at 14 days post-BA, VSMC proliferation in the injured artery is increased by 12.1±3.0% and 15.8±3.5% with doxy treatment prior to and at the time of surgery, respectively, compared to control (n=3), as measured by PCNA immunostaining. Conclusion: We have previously shown doxycycline to be effective in the inhibition of MMP activity and VSMC migration in vitro. In our in vivo model of vascular injury, doxycycline treatment prior to and at the time of vascular injury may hinder or slow the progression of IH development, although the mechanism is unclear based on the present data. Larger study groups are needed in order to delineate the actual role of doxycycline as an inhibitor of IH in vivo. In future studies additional drug delivery systems/doses need to be examined in order to correlate therapeutic serum levels of doxycycline with effective MMP inhibition in serum and arterial tissue and their downstream effect on IH development.

Postmenopausal women taking hormone replacement therapy (HRT) have increased intimal hyperplasia (IH) following vascular intervention. Matrix metalloproteinases (MMPs) play a major role in IH development, and we have shown that hormone exposure results in unbalanced MMP regulation in vascular smooth muscle cells in vitro. Previously we presented data from a small pilot study suggesting a role for HRT in the development of IH via MMP modulation in vivo, using a postmenopausal rodent model of vascular injury. Here we further investigated the role of HRT as a modulator of MMPs and IH in a larger follow-up study. Female rats were aged to 12 months and ovariectomized (OVX). Four weeks later estrogen (E), progesterone (P), estrogen + progesterone (E/P), or placebo (Plac) were delivered via 90-day slow-release pellets. Following 6 weeks of HRT, each rat underwent balloon angioplasty of the left common carotid artery. At 14 days postinjury, tissue samples were collected and stained with Trichrome elastin for intima:media (I:M) measurement and stained for various MMP isoforms. Following vascular injury I:M was decreased in OVX rats compared to non-OVX controls (Fig 1, n = 5-6, P = NS). In OVX animals, HRT exposure did not significantly increase the I:M ratios. (Fig 1, n = 5-6, P = NS). Injury-induced expression of MMP-2 and −9 was significantly decreased in OVX animals compared to non-OVX controls (Table 1; n = 5-6). MMP-2 and −9 levels were subsequently increased by each type of hormone therapy compared to placebo, with a significant increase in MMP-9 in response to estrogen with and without progesterone (Table; n = 5-6). Conversely, TIMP-2 was significantly decreased by estrogen compared to placebo (Table; n = 5-6). There was no effect on intimal MT1-MMP in any group.Table 1% intima stainedNonOVX COVX - PlacOVX - EOVX - POVX - EPMMP-237.8 ± 10.015.4 ± 3.7⁎P < 0.05 vs. NonOVX C26.5 ± 3.738.8 ± 7.638.5 ± 7.6MMP-94.3 ± 0.12.7 ± 0.4⁎P < 0.05 vs. NonOVX C4.7 ± 0.6#P < 0.05 vs. OVX-Plac6.0 ± 1.37.1 ± 1.0#P < 0.05 vs. OVX-PlacTIMP-250.9 ± 8.922.2 ± 3.4⁎P < 0.05 vs. NonOVX C8.7 ± 1.4#P < 0.05 vs. OVX-Plac24.8 ± 10.128.2 ± 9.4 P < 0.05 vs. NonOVX C# P < 0.05 vs. OVX-Plac Open table in a new tab Here we were not able to demonstrate a statistically significant decrease in IH as a result of ovariectomy. Furthermore, HRT at the doses given did not remarkably increase IH. Here we also demonstrate a significant reduction in MMP-2, −9, and TIMP-2 in response to ovariectomy. Subsequent hormone exposure results in the upregulation of MMP-2 and −9 without a counter-regulatory increase in TIMP. We have previously shown elevation in MT1-MMP to occur during the initial phases of IH development; therefore, examination earlier than 14 days postinjury is needed to determine the effect of HRT on this MMP regulatory isoform. Future studies should investigate in vivo manipulation of this unbalanced MMP regulation for prevention of IH in response to HRT exposure.

BACKGROUND:The need for surgeons to exhibit adequate communication skills is paramount to providing exemplary patient care. The manner in which patients are greeted by their surgeon sets the stage for the remainder of the clinical encounter. This study examined patients' expectations for greetings upon meeting a surgeon for the first time. MATERIALS AND METHODS:A convenience sample of 152 English-speaking patients (> or =21 y of age) attending a university-based vascular surgery clinic were recruited to participate in this study. Eligible patients were interviewed prior to their consultation using valid and reliable questionnaires to obtain data about sociodemographic characteristics and expectations for greetings upon meeting a surgeon for the first time. RESULTS:Patients' mean age was 61.4 +/- 14.6 approximately half (n = 81;54.3%) were male, and most were Caucasian (n = 148; 97.4%). Most (n = 132; 86.8%) patients wanted the surgeon to shake their hand, 113 (74.3%) wanted their first name to be used when a surgeon greets them, and 86 (56.6%) wanted a surgeon to introduce him/herself using his/her last name. Patients also desired for surgeons to be attentive/calm and make patient feel like a priority, adjust vocabulary and/or explain better, and be friendly, personable, polite, respectful, and/or courteous. CONCLUSIONS:Surgeons should shake hands, use patients' first names, and introduce themselves using their last names when greeting patients for the first time. They should also be pleasant, personable, and make the patient feel like a priority. Additionally, surgeons should be cognizant of the way in which they present information to patients and verify understanding.

Les buts de cette étude étaient de développer et valider (1) une Evaluation Rapide des Connaissances de la population générale Adulte en Chirurgie Vasculaire (ERCA_CV) pour les chercheurs étudiant l'impact des connaissances des patients sur les résultats en chirurgie vasculaire et (2) une version courte du ERCA_CV (ERCA_CVc) pour permettre à des cliniciens d'évaluer les connaissances de leurs patients en ce qui concerne les termes techniques spécifiques à la chirurgie vasculaire. Un processus en trois phases a été utilisé pour identifier les mots potentiels incluables dans l' ERCA_CV, avec une étude du contenu des sites internets de vulgarisation à la disposition des patients ainsi que d'extraits d'enregistrements d'entretiens chirurgien-patient en consultation. L' ERCA_CV se composait ainsi de 75 mots-clés (par exemple stent, gangrène, invasif, anévrysme) de difficulté variable de prononciation. Cent cinquante-deux patients anglophones (âge ≥ 18 ans) ayant consulté dans un service de chirurgie vasculaire universitaire ont été inclus dans cette étude (âge moyen = 61.4 ± 14.6 ans). Au cours d'entretiens personnalisés, les informations sociodémographiques ont été collectées, et on a demandé aux patients de remplir le très utilisé questionnaire d'évaluation rapide des connaissances en médecine (ERCM) ainsi que l'ERCA_CV. La corrélation entre les scores moyens de l'ERCM (56.9 ± 14.0) et de l'ERCA_CV (63.3 ± 15.6) était très forte (indice de corrélation de Spearman [ρ] = 0.91 ; p < 0.00). L'uniformité interne de l'ERCA_CV était excellente (indice α de Cronbach = 0.98). Le score moyen de l' ERCA_CVc (4.1 ± 2.7) était fortement corrélé avec à la fois l'ERCM (ρ = 0.82 ; p < 0.00) et l'ERCA_CV (ρ = 0.94 ; p < 0.00). L'uniformité interne de l'ERCA_CVc, mesurée en utilisant l'indice α de Cronbach, était de 0.86. Cette étude démontre que les scores ERCA_CV et ERCA_CVc sont des outils prometteurs d'évaluation utilisables pour la recherche et la pratique clinique en chirurgie vasculaire.

Background. A primary component in the development of intimal hyperplasia (IH) in response to vascular injury is basement membrane remodeling. Matrix metalloproteinases (MMPs) play a major role in this process by degradation of basement membrane proteins, mainly collagen type IV. Vascular injury initiates an inflammatory cascade with the release of tumor necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1 beta), and C-reactive protein (CRP). We hypothesize serum levels of these elements may serve as biomarkers of the development of IH.Methods and Results. At baseline, 2, 7, 10, and 14 days post-balloon angioplasty of the carotid artery, rat tissue samples were stained with Masson trichrome elastin to examine IH. Intima:media ratios (I:M) increased significantly over time postinjury. Serum samples were collected at the time of tissue sampling, and levels of MMP-2, MMP-9, collagen type IV, TNF alpha, IL-1 beta, and CRP were assayed using sandwich enzyme-linked immunosorbent assay (ELISA). MMP-2 serum levels at 7, 10, and 14 days postinjury were significantly elevated compared with baseline. Other elements were not significantly elevated.Conclusion. Early and persistent elevation in the serum levels of MMP-2 may be a useful biomarker of basement membrane remodeling and the presence of IH. (C) 2010 Elsevier Inc. All rights reserved.

Background: Compression of the left iliac vein by the overlying right iliac artery (May-Thurner Syndrome [MTS]) can cause left leg swelling due to outflow obstruction, increasing the risk for deep vein thrombosis. Discerning pathologic anatomy from normal iliocaval anatomy can be challenging, as planar imaging provides anatomic rather than functional information. Traditional duplex ultrasound (DU) interrogation of the leg provides data limited to only the infrainguinal venous system. Our hypothesis is that DU-derived maximal venous outflow velocity (MVOV) can be a useful screening tool as an adjunct to lower extremity DU to screen for patients with iliocaval obstruction. Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) Methods: MVOV studies of 14 patients with unilateral leg swelling from 2000 to 2009 were compared with a control group of 30 asymptomatic volunteers. Right and left legs of the test group and symptomatic and asymptomatic legs were compared with each other and with controls using the t test. A ratio of symptomatic to asymptomatic extremities was compared to left over right in the controls to generate an index compatible with pathologic venous impedance. The same parameters were also compared after endovenous stenting for positive venographic findings in patients with MTS. Results: Symptomatic extremities had reduced absolute MVOVs (P = .021) compared with the contralateral extremity. In four patients undergoing endovascular stenting for MTS, a significant increase in MVOV of the treated leg was observed (P = .012), and the post-treatment MVOV measurements in the left and right legs were not significantly different (P = .213). On review, we found that a left-to-right MVOV index of <1.06 correlated with positive angiographic findings and success of treatment (P = .0434). In this same group, computed tomography with venous contrast predicted a positive venographic finding in 60% of the patients (3 of 5). Conclusions: Because most patients with unilateral leg swelling undergo routine DU imaging to evaluate for deep vein thrombosis, MVOV studies can be obtained without added risk, exposure, and little technical cost. MVOV and a calculated index of <1.06 seems to be predictive of success of intervention, even when CT interpretation suggested otherwise.

Background It is generally accepted that a significant portion of our population harbors asymptomatic compression of the left iliac vein by the right iliac artery. This was demonstrated originally in autopsy studies by McMurrich in 1908 (33% of 107 cadavers) and more recently by the analysis of Contrast CT scans 1 (66% of 50 patients). Authors have found that Venography may lack the sensitivity to be considered a true “gold standard” (66% sensitive) while IVUS is over 90% sensitive 2. No studies have addressed the physiologic difference in flow hemodynamics between the left and right lower extremities in normal individuals. We use Doppler ultrasound to demonstrate asymmetric flow in the lower extremities of normal individuals. Methods Maximum venous outflow velocity (MVOV) in the Common femoral veins were recorded using Doppler ultrasound on 30 volunteers. Inclusion criteria included age 18–30, BMI <30, female sex and no history of venous disease or leg swelling. All studies were preformed by the same experienced vascular technologist. Volunteers were instructed to lay supine while a blood pressure cuff was inflated to 100 mmhg around the mid-thigh. Presence of arterial flow was confirmed with color duplex after cuff inflation. Prior to rapid cuff release at 1 minute patients were instructed to exhale and hold their breath to augment venous outflow. Flow velocities in the left and right common femoral veins were recorded. Results The average age was 20.9 years (range 19–28 years) and the average BMI was 21.9 (range, 18–25). MVOV was slower on the left side in 22, slower on the right in 7 and equal in one volunteer. The mean right MVOV was 117.23 cm/sec, SD 46.95 and the mean left MVOV was 95.44 cm/sec, SD 32.94 ( P = 0.0095). There was no correlation between left and right MVOV with respect to age, BMI or height. Conclusions Significant differences in lower extremity venous flow are present in normal individuals at rest. This finding correlates with anatomic studies demonstrating a predilection towards narrowing of the left iliac vein in normal subjects. This simple, non-invasive method of quantifying venous hemodynamics may aid in selecting patients for further diagnostic testing or intervention.

Los objetivos del presente estudio fueron desarrollar y evaluar el cuestionario REAL_VS (1) (Rapid Estimate of Adult Literacy in Vascular Surgery) para los investigadores que estudian la influencia del nivel cultural en lo que respecta al conocimiento y desarrollo de la cirugía vascular, y una versión breve, el REAL_VSs (2), que permita a los médicos evaluar la familiaridad de los pacientes con los términos relacionados con la cirugía vascular. Se usó un proceso de tres fases para identificar los términos potenciales a incluir en el REAL_VS, incluida una revisión del contenido del material educativo para pacientes existente en internet y la audición de una muestra aleatoria de 50 grabaciones archivadas de encuentros cirujano vascular-paciente. El REAL_VS estuvo formado por 75 términos (p. ej., stent, gangrena, cruento, aneurisma) de dificultad variable. Para participar en el presente estudio se incluyeron a 152 pacientes que hablaban inglés (≥ 18 años de edad) que asistían a una clínica de cirugía vascular universitaria (media de edad = 61,4 ± 14,6 años). Durante las entrevistas personales, se obtuvo la información sociodemográfica de los pacientes, y se les administró la Rapid Estimate of Adult Literacy in Medicine (REALM), una encuesta de amplia utilización, al igual que el REAL_VS. Las puntuaciones medias obtenidas en la primera (56,9 ± 14,0) y en la segunda (63,3 ± 15,6) se correlacionaron de manera significativa (correlación de rango de Spearman [ρ] = 0,91; p < 0,00). La congruencia interna del REAL_VS (alfa de Cronbach = 0,98) fue excelente. Las puntuaciones medias obtenidas en el REAL_VSs (4,1 ± 2,7) se correlacionaron tanto con la encuesta REALM (ρ = 0,82; p < 0,00) como con la REAL_VS (ρ = 0,94; p < 0,00). La congruencia interna, determinada utilizando el valor alfa de Cronbach, del REAL_VSs fue de 0,86. El presente estudio demuestra que tanto el REAL_VS como el REAL_VSs son instrumentos válidos para usar en la investigación sobre cirugía vascular y la práctica clínica.

Recent studies have indicated postmenopausal women receiving hormone replacement therapy (HRT) have more adverse outcomes of peripheral arterial disease after vascular reconstruction, including increased intimal hyperplasia (IH) and restenosis. The major cellular processes contributing to IH pathogenesis are extracellular matrix (ECM) degradation and vascular smooth muscle cell (VSMC) proliferation, migration, and invasion of the ECM. We have previously shown hormone exposure results in unbalanced matrix metalloproteinase (MMP) regulation in VSMCs, a family of ECM degradative enzymes known to play a role in vascular remodeling. Here we examine the role of hormonally-stimulated MMP activity in the regulation of the cellular processes contributing to IH development. Data from the type of analyses presented here could be used to develop a computational model of vascular restenosis focusing on the importance of hormone-modulated VSMC function.

Background. Postmenopausal women receiving hormone replacement therapy have more adverse outcomes after vascular reconstructions. Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key group of enzymes involved in vascular remodeling are matrix metalloproteinases (MMPs). Here we studied the effect of estrogen (Est) and progesterone (Prog) on AV W gene expression in human VSMCs.Methods and results. VSMCs were incubated with Est (5 ng/mL), Prog (50 ng/mL), Est+Prog combination (Est/Prog), and interleukin-1 beta (100 U/mL; IL-1 beta). Gene array analysis indicated Est+IL-1 beta increased the expression of MMP-3. Reverse transcriptase-polymer chain reaction (RT-PCR) analyses revealed MMP-3 m-RNA levels were significantly increased by Est/ Prog+IL-1 beta treatment. However, Western blot and further RT-PCR analyses indicated no change in MMP-3 in response to hormones alone. RT-PCR analyses revealed membrane type 1 (MT1)-MMP mRNA levels, not MMP-2 or tissue inhibitor of AMP (TIMP), were significantly increased by Est/Prog+IL-1 beta, and Western blot analyses confirmed a significant increase in MT1-MMP protein in response to Est alone.Conclusion. Estrogen and progesterone affect the MMP pathway of VSMCs via isoform specific mechanisms and may lead to unbalanced MMP regulation. Estrogen up-regulates MT1-MMP without a corresponding increase in TIMP-2, known activator and inhibitor of MMP-2, respectively. Additionally, estrogen up-regulates MMP-3 only in the presence of IL-1 beta. This differential regulation, combined with case-specific variations in degree of inflammatory response, may explain why some women receiving exogenous hormone therapy at the time of vascular interventions are more susceptible to complications. (C) 2008 Elsevier Inc. All rights reserved.

The purposes of this study were to develop and validate the (1) Rapid Estimate of Adult Literacy in Vascular Surgery (REAL_VS) for researchers studying the impact of literacy skills as related to vascular surgery-related knowledge and outcomes and (2) short version of the REAL_VS (REAL_VSs) to allow clinicians to gauge their patients' familiarity with vascular surgery-related terms. A three-phase process was used to identify potential words for inclusion in the REAL_VS, including reviewing Internet-based patient education material content and listening to a random sample of 50 archived audiorecordings of vascular surgeon-patient encounters. The REAL_VS was composed of 75 terms (e.g., stent, gangrene, invasive, aneurysm) of varying pronunciation difficulty. One hundred fifty-two English-speaking patients (>or=18 years of age) attending a university-based vascular surgery clinic were recruited to participate in this study (mean age = 61.4 +/- 14.6 years). During face-to-face interviews, patients' sociodemographic information was collected, and patients were administered the widely used Rapid Estimate of Adult Literacy in Medicine (REALM) and REAL_VS. Mean scores on the REALM (56.9 +/- 14.0) and REAL_VS (63.3 +/- 15.6) were highly correlated (Spearmans rank correlation [rho] = 0.91; p < 0.00). Internal consistency of the REAL_VS (Cronbachs alpha = 0.98) was excellent. Mean scores on the REAL_VSs (4.1 +/- 2.7) were highly correlated with both the REALM (rho = 0.82; p < 0.00) and REAL_VS (rho = 0.94; p < 0.00). Internal consistency, measured using Cronbachs alpha, of the REAL_VSs was 0.86. This study demonstrates that both the REAL_VS and REAL_VSs are both promising tools for use in vascular surgery research and clinical practice, respectively.