Osteopontin-deficient progenitor cells display enhanced differentiation to adipocytes.

OBJECTIVE: Osteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation. METHODS: OPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1-/- female mice. Gene expression for hypoxia, inflammation and adipogenesis was checked in WT vs. Spp1-/- mice (n=15). Adipocytes progenitor cells (APC) were isolated by fluorescence cell sorting and role of OPN deficiency in adipogenesis was investigated by cell images and RT-PCR. RESULTS: We show that Spp1-/- maintained normal body and fat-pad weights, although hypoxia and inflammation markers were significantly reduced. In contrast, expression of genes involved in adipogenesis was increased in WAT from Spp1-/- mice. Strikingly, APC from Spp1-/- were diminished but differentiated more efficiently to adipocytes than those from control mice. CONCLUSIONS: APC from SC-WAT of lean OPN-deficient mice display an enhanced capacity for differentiating to adipocytes. These alterations may explain the healthy expansion of WAT in the OPN-deficient model which is associated with reduced inflammation and insulin resistance.

Apoptosis repressor with caspase recruitment domain is regulated by MAPK/PI3K and confers drug resistance and survival advantage to AML.

The apoptosis repressor with caspase recruitment domain (ARC) protein is known to suppress both intrinsic and extrinsic apoptosis. We previously reported that ARC expression is a strong, independent adverse prognostic factor in acute myeloid leukemia (AML). Here, we investigated the regulation and role of ARC in AML. ARC expression is upregulated in AML cells co-cultured with bone marrow-derived mesenchymal stromal cells (MSCs) and suppressed by inhibition of MAPK and PI3K signaling. AML patient samples with RAS mutations (N = 64) expressed significantly higher levels of ARC than samples without RAS mutations (N = 371) (P = 0.016). ARC overexpression protected and ARC knockdown sensitized AML cells to cytarabine and to agents that selectively induce intrinsic (ABT-737) or extrinsic (TNF-related apoptosis inducing ligand) apoptosis. NOD-SCID mice harboring ARC-overexpressing KG-1 cells had significantly shorter survival than mice injected with control cells (median 84 vs 111 days) and significantly fewer leukemia cells were present when NOD/SCID IL2Rγ null mice were injected with ARC knockdown as compared to control Molm13 cells (P = 0.005 and 0.03 at 2 and 3 weeks, respectively). Together, these findings demonstrate that MSCs regulate ARC in AML through activation of MAPK and PI3K signaling pathways. ARC confers drug resistance and survival advantage to AML in vitro and in vivo, suggesting ARC as a novel target in AML therapy.

ISGylation governs the oncogenic function of Ki-Ras in breast cancer.

Aberrant expression of the oncogenic Kirsten-Ras (Ki-Ras) and interferon-stimulated gene 15 (ISG15) pathways is common in breast and other cancers. However, whether these dysregulated pathways cooperate to promote malignancy is not known. This study links Ki-Ras and ISG15 in a previously unidentified regulatory loop that may underlie malignant transformation of mammary cells. We show that oncogenic Ki-Ras regulates the expression of the ISG15 pathway (free ISG15 and ISG15 conjugates), and ISG15, in turn, stabilizes Ki-Ras protein by inhibiting its targeted degradation via lysosomes in breast cancer cells. Disruption of this loop by silencing either Ki-Ras or the ISG15 pathway restored the disrupted cellular architecture, a hallmark feature of most cancer cells. We also demonstrate that ISG15 and UbcH8 (ISG15-specific conjugating enzyme) shRNAs reversed Ki-Ras mutation-associated phenotypes of cancer cells, such as increased cell proliferation, colony formation, anchorage-independent growth in soft agar, cell migration, and epithelial-mesenchymal transition. As UbcH8-silenced breast cancer cells are devoid of ISG15 conjugates but have free ISG15, our results using UbcH8-silenced cells suggest that ISG15 conjugates, and not free ISG15, contributes to oncogenic Ki-Ras transformation. We have thus identified the conjugated form of ISG15 as a critical downstream mediator of oncogenic Ki-Ras, providing a potential mechanistic link between ISG15 and Ki-Ras-mediated breast tumorigenesis. Our findings, which show that inhibition of the ISGylation reverses the malignant phenotypes of breast cancer cells expressing oncogenic Ki-Ras, support the development of ISG15 conjugation inhibitors for treating breast and also other cancers expressing oncogenic Ki-Ras.

Cell-surface galectin-3 confers resistance to TRAIL by impeding trafficking of death receptors in metastatic colon adenocarcinoma cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis and preferentially kills tumor cells by engaging specific glycosylated death receptors, resulting in the internalization of ligand/receptor complexes and recruitment of the initiator caspase-8 to an activation platform known as the death-inducing signaling complex (DISC). However, emergence of TRAIL-resistant sub-populations may contribute to therapeutic failure. To investigate resistance mechanisms, we isolated a stable TRAIL-resistant sub-population of the metastatic colon cancer cell line LS-LIM6, designated LIM6-TR. LIM6-TR cells are impaired in endocytosis of TRAIL/death receptors complexes and failed to recruit/activate caspase-8 to the DISC upon TRAIL stimulation. Differential activation of Wnt and JNK pathways is not responsible for acquisition of TRAIL resistance. LIM6-TR cells display a marked increase in cell-surface expression of galectin-3, an endogenous lectin, which co-localizes with and binds death receptors. Silencing of galectin-3 restores TRAIL sensitivity and promotes TRAIL-mediated endocytosis of TRAIL/death receptors complexes. Inhibitors of galectin-3 and glycosylation also re-sensitize LIM6-TR to TRAIL and restore internalization of ligand/receptors complexes. These studies identify a novel TRAIL-resistance mechanism in which galectin-3 impedes trafficking of death receptor by anchoring them in glycan nano-clusters, blocking the execution of the apoptosis signal.

Modulation of alpha-catenin Tyr phosphorylation by SHP2 positively effects cell transformation induced by the constitutively active FGFR3.

The Src homology 2 phosphotyrosyl phosphatase (SHP2) is a nonreceptor-type phosphatase that acts as a positive transducer of receptor Tyr kinase (RTK) signaling, particularly the Ras-REK and PI3K-Akt pathways. Recently, we have demonstrated that SHP2 is required for cell transformation induced by the constitutively active fibroblast growth factor receptor 3 (K/E-FR3) (Oncogene, 22, 6909-6918). In that study, we had detected a phosphotyrosyl protein of approximately 100 KDa (p100) in cells expressing dominant-negative SHP2 (R/E-SHP2), but its identity and relevance in SHP2-meditaed transformation was not known. Here, we report the identification of p100 as alpha-catenin, a vinculin-related protein involved in adherens junction-mediated intercellular adhesion. We show that alpha-catenin becomes Tyr phosphorylated in intercellular adhesion-dependent manner and this event is counteracted by SHP2. Substrate trapping in intact cells and immunocomplex phosphatse assays confirmed that alpha-catenin is in deed an SHP2 substrate. Tyr phosphorylation of alpha-catenin enhances its translocation to the plasma membrane and its interaction with beta-catenin, leading to enhanced actin polymerization and stabilization of adherens junction-mediated intercellular adhesion, a phenomenon commensurate with loss of the transformation phenotype. Site-directed mutagenesis studies also suggested that Tyr phosphorylation of alpha-catenin enhances its inhibitory role on cell transformation. Based on our previous work and the current report, we demonstrate that mediation of cell transformation by SHP2 is a complex process that involves modulation of the Ras-ERK and PI3K-Akt signaling pathways, intercellular adhesion, focal adhesion and actin cytoskeletal reorganization. To our knowledge, this is the first report showing regulation of alpha-catenin function by Tyr phosphorylation and its inhibitory effect on cell transformation.

Changes over time in audiometric thresholds in a group of automobile stamping and assembly workers with a hearing conservation program.

Noise induced hearing loss (NIHL) is among the 10 leading occupational diseases, afflicting between 7.4 and 10.2 million people who work in noise above 85 dBA. Although mandatory hearing conservation programs (HCPs) have been in effect since 1972, this problem persists, as hearing protectors are not consistently used by workers, or may not attenuate to manufacturer's estimates in real world conditions. In this study, information from noise and hearing protection use measurements taken at an automobile assembly plant were used to construct average lifetime noise exposure and hearing protection compliance estimates for use in modeling to predict both total hearing loss and onset of two accepted definitions of hearing loss. There were 301 males and females in this cohort; their mean age was 42.6 (7.2) years, and mean tenure was 14.3 (3.5) years. Average length of follow-up was 14.0 years. There were 16 members of this cohort who had hearing loss at the speech frequencies (defined as an average hearing level > or = 25 dB at 500, 1000, and 2000 Hz). In cross-sectional multivariate analyses, years of employment, male gender, and proportion of time wearing hearing protection were the factors most associated with hearing loss at the average of 2000, 3000, and 4000 Hz (p < 0.0001) controlling for age, transfer status (as a surrogate for previous noise exposure), race, and lifetime average noise exposure. The most consistent predictor of hearing loss in both univariate and multivariate analyses was percentage of time having used hearing protection during the workers' tenure.

Risk of spinal cord ischemia after endograft repair of thoracic aortic aneurysms.

BACKGROUND: Surgical repair of thoracoabdominal aneurysms may be associated with a significant risk of perioperative morbidity including spinal cord ischemia, which occurs at a rate of between 5% and 21%. Spinal cord ischemia after endovascular repair of thoracic aortic aneurysms (TAAs) has also been reported. This investigation reviews the occurrence of spinal cord ischemia after endovascular repair of descending TAAs at the Mount Sinai Medical Center. PATIENTS AND METHODS: Between May 1997 and April 2001, 53 patients underwent endovascular exclusion of their TAA. Preprocedure computed tomography scanning and angiography were performed on all patients. All were performed in the operating room using C-arm fluoroscopy. Physical examinations and computed tomography scans were performed at discharge and at 1, 3, 6, and 12 months postoperatively and then annually thereafter. Spinal cord ischemia developed in three of the 53 patients (5.7%) postoperatively. In one patient, cord ischemia developed that manifested as early postoperative left leg weakness occurring after concomitant open infrarenal abdominal and endovascular TAA repair. The neurologic deficit resolved 12 hours after spinal drainage, steroid bolus, and the maintenance of hemodynamic stability. The remaining two patients developed delayed onset paralysis, one patient on the second postoperative day and the other patient 1 month postrepair. Both of these patients had previous abdominal aortic aneurysm repair, and both required long grafts to exclude an extensive area of their thoracic aortas. Irreversible cord ischemia and paralysis occurred in both of these patients. CONCLUSIONS: Endovascular repair of TAA has shown a promising reduction in operative morbidity; however, the risk of spinal cord ischemia remains. Concomitant or previous abdominal aortic aneurysm repair and long segment thoracic aortic exclusion appear to be important risk factors. Spinal cord protective measures (ie, cerebrospinal fluid drainage, steroids, prevention of hypotension) should be used for patients with the aforementioned risk factors undergoing endovascular TAA repair.

Endovascular repair of bleeding aortoenteric fistulas: a 5-year experience.

PURPOSE: Aortoenteric fistula (AEF) is an uncommon but catastrophic complication that can occur either primarily or after aortic reconstruction. Untreated, it is uniformly fatal. Conventional surgical management is associated with a perioperative mortality rate of 25% to 90% and frequent major complications. We reviewed our experience with the endovascular treatment of both primary and secondary AEFs in an effort to determine whether endovascular repair is a less morbid alternative to traditional surgical treatment in select patients. METHODS: In a 5-year period, seven high-risk patients who had bleeding and an AEF documented by means of radiology or endoscopy (2 primary, 5 secondary) were treated with coil embolization (1) or placement of an endovascular aortic stent graft (3 aortouniiliac, 2 tube, 1 bifurcated). One patient underwent computed tomography (CT)-guided percutaneous catheter drainage of an infected perigraft collection. The average follow-up period was 27 months (range, 11-66 months), and follow-up consisted of physical examination, complete blood count, and contrast-enhanced helical CT scanning at 3, 6, and 12 months and yearly thereafter. All patients were treated with intravenous antibiotics perioperatively and were prescribed life-long oral antibiotics on discharge. RESULTS: There was one perioperative death (14%) caused by fungal sepsis. Persistent sepsis after stent-graft placement necessitated laparotomy and bowel resection in one patient. One patient had three bouts of recurrent sepsis that were successfully treated with a change of antibiotic. There were three late deaths (43%) unrelated to the procedure or AEF. Three patients (43%) were alive and well an average of 36 months (range, 23-67 months) after the procedure, with no clinical or radiologic evidence of recurrent bleeding or infection. CONCLUSION: Endovascular management of AEFs is technically feasible and may be the preferred treatment in select patients with bleeding and no signs of sepsis. In the setting of gross infection, it may also be considered in high-risk patients as a bridge to more definitive treatment after hemodynamic stabilization and optimization.

Internal iliac artery revascularization as an adjunct to endovascular repair of aortoiliac aneurysms.

PURPOSE: Endovascular repair of aortoiliac aneurysms may be limited by extension of the aneurysm to the iliac bifurcation, necessitating endpoint implantation in the external iliac artery. In such cases the circulation to the internal iliac artery is interrupted. Bilateral internal iliac artery occlusion during endovascular repair may be associated with significant morbidity, including gluteal claudication, erectile dysfunction, and ischemia of the sigmoid colon and perineum. We have employed internal iliac artery revascularization (IIR) to allow endograft implantation in the external iliac artery while preserving flow to the internal iliac artery in patients with aneurysms involving the iliac bifurcation bilaterally. METHODS: A total of 11 IIR procedures were performed in 10 patients undergoing endovascular abdominal aortic aneurysm (AAA) repair (9 men, 1 woman; mean age, 74 years). IIR was accomplished via a retroinguinal incision in 9 cases and a retroperitoneal incision in 2 cases. Six-mm polyester grafts were used for external-to-internal iliac artery bypass in 10 cases and internal iliac artery transposition onto the external iliac artery was used in one case. Endovascular AAA repair was performed using a modular bifurcated device (Talent-LPS, Medtronics, Minneapolis, Minn) after IIR. Bypass graft patency was determined immediately after the surgery, at 1 month, and every 3 months thereafter, using duplex ultrasound scanning and computed-tomography angiography. Mean aneurysm diameters were as follows: AAA, 6.4 +/- 0.7 cm; ipsilateral common iliac, 3.7 +/- 1.0 cm; contralateral common iliac, 3.9 +/- 0.8 cm. RESULTS: Successful IIR and endovascular AAA repair were accomplished in all cases. No proximal, distal, or graft junction endoleaks occurred. Two patients demonstrated retrograde aneurysm side-branch endoleaks originating from the lumbar arteries. One thrombosed spontaneously within 3 months. One perioperative myocardial infarction occurred. Reduction in aneurysm size was documented in 5 aortic, 5 ipsilateral iliac, and 3 contralateral iliac aneurysms. Gluteal claudication, erectile dysfunction, colon and perineal ischemia, and mortality did not occur. All IIRs have remained patent during a follow-up period of 4 to 15 months (mean, 10.1 months). CONCLUSIONS: IIR may be used with good short-term to intermediate-term patency to prevent pelvic ischemia in patients whose aneurysm anatomy requires extension of the endograft into the external iliac artery. This may allow endovascular AAA repair to be performed in patients who might otherwise be at risk for developing complications associated with bilateral internal iliac artery occlusion.

Current use of endovascular grafts for the treatment of abdominal aortic aneurysms.

The development of endovascular techniques for the treatment of abdominal aortic aneurysms has significantly reduced the major morbidity associated with standard surgical repair. The indications for use of endovascular grafts and the limitations of their use have not been fully defined. The effectiveness of the numerous commercially fabricated devices is currently being evaluated. This article describes the general principles of use for endovascular devices and details the features and results for the devices in current use.

Difficult cases in heart failure: familial dilated cardiomyopathy.

While originally thought to be uncommon, familial dilated cardiomyopathy may occur quite often. Aside from symptoms of heart failure, these forms of dilated cardiomyopathy may be associated with arrhythmias and sudden death. The case detailed describes such a patient and emphasizes the importance of a careful family history. Also discussed is the importance of screening of first- and second-degree relatives of these patients. (c)2001 by CHF, Inc.

Tarsal tunnel syndrome secondary to an accessory muscle: a case report.

The flexor digitorum accessorius longus is a rare muscular anomaly that has been reported as one of the etiologies of tarsal tunnel syndrome. The authors provide a case report of a patient with tarsal tunnel syndrome that resolved with resection of the flexor digitorum accessorius longus. The patient remains asymptomatic 40 months following surgery.

Endoscopic plantar fasciotomy: a retrospective analysis of results in 53 patients.

This retrospective study analyzes satisfaction of patients who had undergone an isolated endoscopic plantar fasciotomy (EPF) between January 1994 and January 1997. A subjective survey was completed and returned by 53 patients (a total of 69 feet), and a chart review was performed to determine final outcome. Postoperative follow-up averaged 7.2 months (range, 4-42 months). Postoperative pain levels were scored on a 7-point scale at 1 week, 1 month, and 6 months. Forty-three patients (81.1%) were satisfied with the EPF procedure and 10 patients (18.9%) were unsatisfied.

Cultural styles, relational schemas, and prejudice against out-groups.

Two studies provide evidence that Latins (i.e., Mexicans and Mexican Americans) are guided by a concern with socioemotional aspects of workplace relations to a far greater degree than are Anglo-Americans. The focus on socioemotional considerations results in Latins having a relatively greater preference for workgroups having a strong interpersonal orientation. Preferred relational style had a far greater impact on preferences for workgroups and judgments about their likely success than did the ethnic composition of the workgroups for both Latins and Anglo-Americans. Evidence that the two groups differ markedly in relational schemas comes from examination of suggestions about how group performance could be improved, judgments about whether a focus on socioemotional concerns necessarily entails a reduction in task focus, and recall for socioemotional aspects of workgroup interactions. Implications for the dynamics of intercultural contact are discussed.

Invasion of endothelial and epithelial cells by strains of Porphyromonas gingivalis.

Porphyromonas gingivalis is a periodontal pathogen that may also be involved in the pathogenesis of coronary heart disease. This microorganism has the ability to invade several cell lines. In this study, 26 different strains of P. gingivalis were tested for invasion of human umbilical vein endothelial cells and KB cells, a human oral epidermoid cell line. Abilities to invade both cell lines by an individual strain were similar, and their invasion efficiencies could be assembled into four groups: high, moderate, low and non-invasive. Of the 26 strains, only P. gingivalis AJW4 was non-invasive. Since the fimbriae are implicated as having a key role in invasion by this species, the presence of fimbriae on strain AJW4 was investigated. Using polymerase chain reaction (PCR), strain AJW4 was found to contain the fimA gene. Sequence analysis revealed it to be type IV according to the typing scheme developed by Amano et al. Further, fimA is transcribed in this strain as demonstrated by reverse transcription PCR and is expressed on the cell surface as visualized by negative staining and electron microscopy. The adherence+invasion of strain AJW4 was 38.7% of the most invasive strain (strain 381). However, the CFU ml(-1) of strain AJW4 recovered from within cells was 2.9% of strain 381. Even though strains AJW4 and W50 have the same type IV fimbriae, strain AJW4 is 8.9-fold more adhesive yet is internalized 170-fold less. These data indicate that the invasion efficiency of P. gingivalis is variable among the different strains, and that the expression of FimA is not sufficient for invasion.

Expression and immunogenicity of hemagglutinin A from Porphyromonas gingivalis in an avirulent Salmonella enterica serovar typhimurium vaccine strain.

Porphyromonas gingivalis is a major etiologic agent of periodontitis, a chronic inflammatory disease that ultimately results in the loss of the supporting tissues of the teeth. Previous work has demonstrated the usefulness of avirulent Salmonella enterica serovar Typhimurium strains as antigen delivery systems for protective antigens of pathogens that colonize or cross mucosal surfaces. In this study, we constructed and characterized a recombinant S. enterica serovar Typhimurium avirulent vaccine strain which expresses hemagglutinin A and carries no antibiotic resistance markers. HagA, a major virulence-associated surface protein, is a potentially useful immunogen that contains an antigenic epitope which, in humans, elicits an immune response that is protective against subsequent colonization by P. gingivalis. The hagA gene, including its promoter, was cloned into a balanced-lethal Salmonella vector and transferred to the vaccine strain. Heterologous expression of HagA was demonstrated in both Escherichia coli JM109 and S. enterica serovar Typhimurium vaccine strain chi4072. The HagA epitope was present in its native configuration as determined by immunochemistry and immunoelectron microscopy. Purified recombinant HagA was recognized by sera from mice immunized with the S. enterica serovar Typhimurium vaccine strain. The HagA-specific antigen of the vaccine was also found to be recognized by serum from a periodontal patient. This vaccine strain, which expresses the functional hemagglutinin protein, induces a humoral immune response against HagA and may be useful for developing a protective vaccine against periodontal diseases associated with P. gingivalis.

Physiologic and thermal responses of male and female patients with multiple sclerosis to head and neck cooling.

Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. The objective of this study was to determine the thermal and physiologic responses of patients with multiple sclerosis to short-term maximal head and neck cooling. A Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used to cool the head and neck regions of 24 female and 26 male patients with multiple sclerosis in this study. The subjects, seated in an upright position at normal room temperature (approximately 22 degrees C), were cooled for 30 min by the liquid cooling garment, which was operated at its maximum cooling capacity. Oral, right, and left ear temperatures and cooling system parameters were logged manually every 5 min. Forearm, calf, chest, and rectal temperatures, heart rate, and respiration rate were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. This protocol was performed during the winter and summer to investigate the seasonal differences in the way patients with multiple sclerosis respond to head and neck cooling. No significant differences were found between the male and female subject group's mean rectal or oral temperature responses during any phase of the experiment. The mean oral temperature decreased significantly (P < 0.05) for both groups approximately 0.3 degrees C after 30 min of cooling and continued to decrease further (approximately 0.1-0.2 degrees C) for a period of approximately 15 min after removal of the cooling helmet. The mean rectal temperatures decreased significantly (P < 0.05) in both male and female subjects in the winter studies (approximately 0.2-0.3 degrees C) and for the male subjects during the summer test (approximately 0.2 degrees C). However, the rectal temperature of the female subjects did not change significantly during any phase of the summer test. These data indicate that head and neck cooling may, in general, be used to reduce the oral and body temperatures of both male and female patients with multiple sclerosis by the approximate amount needed for symptomatic relief as shown by other researchers. However, thermal response of patients with multiple sclerosis may be affected by gender and seasonal factors, which should be considered in the use of liquid cooling therapy.

Comparison of treatment plans for lower extremity arterial occlusive disease made with electrocardiography-triggered two-dimensional time-of-flight magnetic resonance angiography and digital subtraction angiography.

BACKGROUND: The purpose of the study was to determine whether preoperative treatment plans for patients with lower extremity ischemia can be made with electrocardiography (EKG)-triggered two-dimensional (2D) time-of-flight (TOF) magnetic resonance angiography (MRA) as accurately as digital subtraction angiography (DSA). METHODS: Forty patients were prospectively evaluated with the combination of EKG-triggered 2D TOF MRA, DSA, and pulse volume recordings. Blinded reviewers graded arterial segments for disease severity. Accuracy of separate MRA- and DSA-based treatment plans was compared with the procedures performed based on all available information. RESULTS: There was an 86% exact match between MRA- and DSA-based plans (92% MRA and 94% DSA accuracy). The MRA-based plan accurately predicted 90% of suprainguinal and 95% of infrainguinal procedures, whereas the DSA-based plan accurately predicted 100% of suprainguinal and 85% of infrainguinal procedures. Two-year primary patency was 83% for all procedures. Radiologists' review of disease severity resulted in a mean exact correlation between studies of 81% (kappa = 0.64). The agreement between radiologists interpreting the MRA was 84% (kappa = 0.7) compared with 82% (kappa = 0.66) for the DSA. CONCLUSIONS: MRA- and DSA-based preoperative management plans were of comparable efficacy. Significant interobserver variability was seen with the interpretations of both preoperative studies. EKG-triggered 2D TOF MRA can be used to plan arterial reconstructions; however, all patients require arterial pressure measurements prior to suprainguinal repair and confirmatory intraoperative angiography during infrainguinal revascularization.