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Peter K Henke

Publications and source records attributed to Peter K Henke.

At least 37 records · Page 2Linked to original sources
PubMed2005

Improving quality of care in vascular surgery: the tools are available now.

This overview delineates the current evidence and suggested practice protocols for three areas of vascular disease evaluation and treatment that have shown particular patient benefit. Presented as brief topical reviews are (1) preoperative cardiac evaluation and risk factor modification, (2) use of autologous tissue and graft surveillance for infrainguinal bypass, and (3) deep vein thrombosis risk stratification and prophylaxis. It is this author's hope is that this overview will emphasize currently effective and underused therapies and stimulate further research into best practices for improving the quality of care for vascular surgery patients.

Blood Vessel Prosthesis Implantation↗
PubMed2005

Gender differences in rat aortic smooth muscle cell matrix metalloproteinase-9.

BACKGROUND: A predilection exists for men to develop abdominal aortic aneurysms (AAAs), but the reasons for this gender predisposition are not known. Matrix metalloproteinase-9 (MMP-9) has been implicated in both human and experimental AAAs. This investigation tested the hypothesis that male and female gender differences exist in the production of MMP-9 by rat aortic smooth muscle cells (RASMCs). STUDY DESIGN: In the first set of experiments, cultured male and female RASMCs were stimulated with interleukin-1 beta (IL-1beta) at 2 ng/mL. Messenger RNA was extracted from the RASMCs and gene expression of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1), an MMP-9 inhibitor, was measured by quantitative real-time polymerase chain reaction. Cell culture media were collected for measurement of MMP-9 protein levels and MMP-9 activity by Western blotting and gelatin zymography, respectively. In the second set of experiments, male RASMCs were treated with 17-beta-estradiol (10(-10) to 10(-6) mol/L) and MMP-9 activity was measured. In the third set of experiments, male rats were pretreated with estradiol, and MMP-9 activity was measured in the media from explanted aortas. RESULTS: MMP-9 gene expression was 10-fold higher in male versus female RASMCs (p=0.003). MMP-9 protein levels (p=0.005) and gelatinolytic activities (p=0.01) were also greater in male than female RASMCs. TIMP-1 expression was fourfold higher in male versus female RASMCs (p<0.001). Estradiol-treated male RASMCs did not exhibit a decrease in MMP-9 activity. But aortic explants from male rats pretreated with 17-beta-estradiol had 60% less MMP-9 activity than explants from male controls (p=0.03). CONCLUSIONS: MMP-9 and TIMP-1 are greater in male than in female RASMCs. These findings support the tenet that gender-related differences in MMP-9 may contribute to AAA formation.

Animals↗
PubMed2005

Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic aneurysms.

BACKGROUND: Selective estrogen receptor modulators (SERMs), similar to estrogens, possess vasoprotective effects by reducing release of reactive oxygen species. Little is known about the potential effects of SERMs on the pathogenesis of abdominal aortic aneurysms (AAAs). This study's objective was to investigate the growth of experimental AAAs in the setting of the SERM tamoxifen. METHODS: In the first set of experiments, adult male rats underwent subcutaneous tamoxifen pellet (delivering 10 mg/kg/day) implantation (n = 14) or sham operation (n = 16). Seven days later, all animals underwent pancreatic elastase perfusion of the abdominal aorta. Aortic diameters were determined at that time, and aortas were harvested 7 and 14 days after elastase perfusion for immunohistochemistry, real-time polymerase chain reaction, Western blot analysis, and zymography. In the second set of experiments, a direct irreversible catalase inhibitor, 3-amino-1,2,4-triazole (AT), was administered intraperitoneally (1 mg/kg) daily to tamoxifen-treated (n = 6) and control rats (n = 6), starting on day 7 after elastase perfusion. Aortic diameters were measured on day 14. In a third set of experiments, rats were perfused with catalase (150 mg/kg) after the elastase (n = 5), followed by daily intravenous injections of catalase (150 mg/kg/day) administered for 10 days. A control group of rats (n = 7) received 0.9% NaCl instead of catalase. RESULTS: Mean AAA diameters were approximately 50% smaller in tamoxifen-treated rats compared with sham rats 14 days after elastase perfusion (P = .002). The tamoxifen-treated group's aortas had a five-fold increase in catalase mRNA expression (P = .02) on day 7 and an eight-fold increase in catalase protein on day 14 (P = .04). Matrix metalloprotroteinase-9 activity was 2.4-fold higher (P = .01) on day 7 in the aortas of the controls compared to the tamoxifen-treated group's aortas. Tamoxifen-treated rats had approximately 40% fewer aortic polymorphonuclear neutrophils compared to controls on day 7 (P = .05). Administration of the direct catalase inhibitor AT to tamoxifen-treated rats partially reversed the aneurysm inhibitory effect of tamoxifen by nearly 30% (P = .02). In contrast, catalase administration inhibited AAA formation by 44% (P = .002). CONCLUSIONS: The selective estrogen receptor modulator tamoxifen inhibits the development of AAAs in male rats in association with an up-regulation of catalase and inhibition of aortic wall neutrophil infiltration.

Amitrole↗
PubMed2005

Vein wall remodeling after deep vein thrombosis involves matrix metalloproteinases and late fibrosis in a mouse model.

HYPOTHESIS: Deep venous thrombosis (DVT) confers vein wall injury associated with fibrosis and extracellular matrix (ECM) turnover, likely mediated by matrix proteases. This study investigated the expression of proteases and collagen involved in early vein wall remodeling. METHODS: In the mouse, DVT was produced by ligation of the infrarenal inferior vena cava (IVC) or sham operation, and tissue was harvested at 4, 8, and 12 days. The vein wall tissue was processed for real-time reverse transcriptase-polymerase chain reaction (6 to 8 per time point), Western immunoblotting (5 per time point), and gelatin zymography (5 per time point). Analysis of variance was used for multiple comparisons, and a P < .05 was significant. RESULTS: Thrombus resolution was documented by a 38% decrease in the thrombosed IVC weight from day 4 to day 12 (P = .007). Total vein wall collagen increased over time, with a corresponding increase in procollagen I and III, and expression peaked at 12 days (24-fold and 6.1-fold, respectively, P < .02). Matrix metalloproteinase-2 (MMP-2) gene expression was 23-fold greater at 12 days after thrombus formation compared with sham or 4 days after thrombosis (P < .05). Total MMP-2 activity was also significantly elevated at 12 days compared with sham (P < .05). MMP-9 expression was 19-fold and 27-fold higher at days 4 and 8, respectively, relative to sham (P < .05), with no difference in activity. MMP-14 expression was twofold to 3.6-fold greater at day 12 compared with earlier time points and shams (P < .001), but no differences in protein levels were found. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) protein levels were not significantly different from sham over time; however, the ratio of uPA to PAI-1 was decreased through 8 days. CONCLUSIONS: Vein wall remodeling after DVT is similar to wound healing and is associated with increased procollagen gene expression and total collagen. It is also associated with increased early MMP-9 expression, followed by MMP-2 expression and activity after DVT resolution. CLINICAL RELEVANCE: Deep vein thrombosis is an often neglected problem that long term is associated with the postphlebitic syndrome of limb swelling, pain, and often ulceration. The basic mechanisms of the vein wall damage that results have not been delineated. The following study describes the vein wall matrix metalloproteinase gene and activity response induced over time in the vein wall after DVT. Additionally, the corresponding collagen upregulation and proximate plasmin system mediators are determined. With this knowledge, potential therapies to reduce vein wall injury directly might be possible.

Animals↗
PubMed2005

Decreased venous thrombosis with an oral inhibitor of P selectin.

BACKGROUND: P-selectin inhibition with protein therapeutics such as antibodies or soluble ligands given intravenously can decrease thrombosis in a mouse ligation model of venous thrombosis. In this study, we hypothesized that oral inhibition of P selectin with a novel oral nonprotein inhibitor (PSI-697) would decrease thrombosis and circulating microparticle populations. This study evaluated the effects on thrombosis and circulating microparticle populations in this murine venous thrombosis model. METHODS: Mice underwent inferior vena cava ligation to induce thrombosis. Mice with high circulating level of P selectin, Delta Cytoplasmic Tail (CT), mice gene-deleted for both E- and P-selectin knockout (EPKO), and wild-type C57BL/6 mice (WT) were studied without and with administration of PSI-697 in food (100 mg/kg daily) from 2 days before thrombosis until the end of the study. Animals were killed 2 and 6 days later. Evaluations included thrombus weight (TW), vein wall morphometrics, microparticle quantification by using fluorescence-activated cell sorter analysis, and vein wall enzyme-linked immunosorbent assays for interleukin (IL)-10, P selectin, and monocyte chemotactic protein 1. RESULTS: PSI-697 significantly decreased TW in WT and CT mice, with a treated vs nontreated TW of 132 +/- 24 vs 228 +/- 29 x 10(-4) g (P = .014) and 166 +/- 19 vs 281 +/- 16 x 10(-4) g (P = .001), respectively. At day 6, the effect was significant only in the CT group (P < .05). Drug therapy at day 2 significantly increased vein wall monocytes in WT mice and increased monocytes and total inflammatory cells in CT animals. A significant decrease in neutrophils and total inflammatory cells was seen in EPKO mice at day 2 with therapy. Therapy significantly increased platelet-derived microparticles and total microparticles in CT mice on day 2. Changes in treated WT and treated EPKO animals were not significant compared with respective vehicle treatments at day 2. On day 6, therapy significantly decreased total microparticles in EPKO animals. Vein wall expression of IL-10 increased in all groups with therapy at day 2 (n = 18) and was significantly increased in WT (2687.5 +/- 903 pg/mL vs 636 +/- 108 pg/mL total protein; P = .038) and CT (2078 +/- 295 pg/mL vs 432 +/- 62 pg/mL total protein; P = .001) mice. Therapy significantly decreased vein wall P selectin, monocyte chemotactic protein 1, and IL-10 levels at day 6. CONCLUSIONS: PSI-697 decreased thrombosis. P-selectin inhibition allowed vein wall inflammatory cell extravasation in this model of complete ligation. Circulating microparticles (platelet-derived microparticles and total microparticles) increased with P-selectin inhibition, possibly because of decreased consumption into the thrombus. In summary, the oral administration of an inhibitor to P selectin provides significant TW reduction. CLINICAL RELEVANCE: Deep venous thrombosis is a significant national health problem in the general population. The average annual incidence of deep venous thrombosis is approximately 250,000 cases per year. The selectin family of adhesion molecules is thought to be largely responsible for the initial attachment and rolling of leukocytes on stimulated vascular endothelium. Recent studies have explored the possible therapeutic implications of P-selectin inhibition to modulate venous thrombosis. For example, prophylactic dosing of a recombinant P-selectin ligand decreases venous thrombosis in a dose-dependent fashion in both feline and nonhuman primate animal models. Additionally, treatment of 2-day iliac thrombi with a recombinant protein, P-selectin inhibitor, significantly improves vein reopening in nonhuman primates. It is interesting to note that P-selectin inhibition decreases thrombosis without adverse anticoagulation. On the basis of the results from these previous studies, the use of P-selectin antagonism is a logical therapeutic approach to treat venous thrombosis. All inhibitors developed to date are either proteins or small molecules with low oral bioavailability that require intravenous or subcutaneous injection. This study evaluates, for the first time, a novel orally bioavailable inhibitor of P-selectin (PSI-697).

Animals↗
PubMed2005

Mitochondrial-dependent apoptosis in experimental rodent abdominal aortic aneurysms.

OBJECTIVES: While extrinsic mechanisms of apoptosis in abdominal aortic aneurysms (AAAs) are recognized, this project hypothesizes that an intrinsic, mitochondrial-dependent, mechanism of apoptosis also contributes to experimental AAA formation. METHODS: Rat aortas were perfused with either saline or elastase (N = 5 per group) and harvested 7 days postperfusion. The aortas were placed in gluteraldehyde for subsequent transmission electron microscopy, Bouin's solution for TUNEL, or paraformaldehyde for immunohistochemical staining for caspase-9, caspase-3, and Bid. RESULTS: Abdominal aortic diameters increased 168 +/- 25% (mean +/- SEM) after elastase perfusion. compared with 30 +/- 5% after saline perfusion (P < .001). Apoptosis of aortic smooth muscle cells, macrophages, and neutrophils was evidenced by transmission electron microscopy and TUNEL in the elastase-perfused aneurysmal aortas. Quantitative analysis of the apoptotic cells revealed a significant (P < .01) increase in the number of total apoptotic cells in the elastase-perfused aortas (12 +/- 3 cells per high-power field), compared with that of saline-infused controls (1.3 +/- 0.2). Caspase-9, the key initiator in the mitochondrial-dependent apoptotic pathway, stained positively in only elastase-perfused aortas. Bid staining was not detected in either the elastase-perfused aortas or the saline controls. CONCLUSIONS: Apoptosis is evident in multiple cell lines in elastase-perfused aneurysmal aortas, but rarely observed in control aortas. Caspase-9, the key initiator of intrinsic apoptosis, was documented only in elastase-perfused aortas. These results suggest that mitochondrial-dependent apoptosis is associated with abdominal aortic aneurysm formation.

Animals↗
PubMed2005

The role of inflammation in early and late venous thrombosis: Are there clinical implications?

Venous thrombosis is associated with a significant inflammatory response. Inflammatory cells, adhesion molecules (especially selectins), cytokines, and procoagulant microparticles appear to be associated with the thrombogenic process. Once thrombus forms, inflammatory cells are important to thrombus resolution along with fibrinolytic agents and proinflammatory mediators. Collagen and elastin breakdown by the DVT renders the vein wall stiff and non-compliant. Rapid and complete thrombus resolution should lessen vein wall damage and lessen or prevent the development of chronic venous insufficiency. Understanding the basic biology of thrombogenesis and thrombus resolution is important, as novel therapies to both prevent and treat venous thrombosis and hasten thrombus resolution should result from a better understanding of the basic biological mechanisms.

Cell Adhesion Molecules↗
PubMed2005

Popliteal artery aneurysms: tried, true, and new approaches to therapy.

Popliteal artery aneurysms are the most common peripheral aneurysm. They are associated with concomitant contralateral popliteal aneurysms and abdominal aortic aneurysms. Patients with unrecognized aneurysms may present with acute limb ischemia and potential for limb loss. Use of preoperative lytic therapy to improve distal runoff prior to exclusion and bypass has significantly improved the outcome from acute thrombosis. Long-term follow-up has shown that both proximal and distal ligation of the aneurysm are important because a thrombosed aneurysm may begin to enlarge after a long period of quiescence. Popliteal aneurysms are now being treated with covered stents. This article delineates the current evaluation, preoperative planning, and surgical and endovascular approaches to this disease. With proper diagnosis and repair, excellent limb salvage and postoperative function has become the norm.

Aneurysm↗
PubMed2005

Carotid endarterectomy remains the standard of care, even in high-risk surgical patients.

OBJECTIVE: This study tested the hypothesis that high-risk patients can undergo carotid endarterectomy without associated increased risk of stroke, transient ischemic attack (TIA), or death. SUMMARY BACKGROUND DATA: Carotid endarterectomy (CEA) has clearly been shown to be effective in reducing the risk of stroke in selected symptomatic and asymptomatic patients with extracranial carotid stenosis. However, recently, carotid angioplasty with stenting (CAS) has been suggested as an alternative treatment in high-risk surgical patients. METHODS: Medical records for consecutive patients who underwent CEA from 1996 to 2001 were reviewed for demographics, medical history, and hospital course. High-risk patients were defined as those experiencing a myocardial infarction (MI) or an exacerbation of congestive heart failure (CHF) within 4 weeks before CEA; unstable angina; steroid-dependent chronic obstructive pulmonary disease (COPD); prior ipsilateral CEA, neck dissection or irradiation; high carotid bifurcation; and those with combined cardiac-carotid procedures. Poor postoperative outcome was defined as stroke, TIA, or death within 30 days. Univariate, multivariate, and Kaplan-Meier analysis were used as appropriate. RESULTS: Four hundred twenty-nine patients underwent 499 CEAs, of which 84 (17%) were considered high risk. The overall stroke-death rate among all patients was 2.8%. A total of 11 postoperative strokes (2.2%), 7 TIAs (1.4%), and 3 deaths (0.6%) occurred within 30 days after surgery. There was no difference in 30-day poor outcome between high- and low-risk patients (4.8% vs. 4.1%, P = 0.77). When these risk factors were assessed independently, those with recent MI were at higher risk for poor outcome (odds ratio [OR], 13.3; 95% confidence interval [CI], 2.2-82.0; P = 0.03). Multivariate analysis also revealed that a history of contralateral stroke or TIA conferred an increased risk of poor outcome (OR, 3.0; 95% CI, 1.1-8.4; P = 0.02), whereas use of preoperative angiotensin-converting enzyme inhibitors was associated with reduced risk (OR, 0.36; 95% CI, 0.11-1.0; P = 0.05), as was a history of hyperlipidemia (OR, 0.33; 95% CI, 0.13-0.87; P = 0.03). By log-rank analysis, 12-month survival was significantly worse in the high-risk group as compared with the low-risk (96% vs. 91%, P = 0.03). CONCLUSIONS: Patients considered a surgical high risk can undergo CEA without any worse outcome compared with those patients deemed low risk. The benefit of CAS will likely be marginal, and only controlled clinical trials will be able to determine if certain subgroups demonstrate improved outcome with CAS. Carotid endarterectomy remains the standard of care, even in high-risk surgical patients.

Aged↗
PubMed2005

Osteomyelitis of the foot and toe in adults is a surgical disease: conservative management worsens lower extremity salvage.

OBJECTIVE: To characterize the national epidemiology of adult osteomyelitis (OM) and, using a single institutions' experience, test the hypothesis that early surgical therapy as compared with antibiotics alone results in an improved chance of wound healing and limb salvage. BACKGROUND: Foot and digit OM is a very common problem for which management is variable and for which few guidelines exist. METHODS: The Nationwide Inpatient Sample (NIS) and a single institution review from 1993 to 2000 form the basis of this study, using ICD-9CM codes for lower extremity foot and digit OM. Demographics, risk factors, and treatments were analyzed against the outcomes of a healed wound, limb salvage, and death. RESULTS: The NIS included 51,875 patients (incidence = 9/10,000 patients per year) with a mean age of 60 years, and 59% were men. The median length of stay decreased from 9 to 6 days (P < 0.001), but the average admission charge of 19,000 dollars did not significantly decrease over 7 years. Of these patients, 23% underwent a digit amputation and 8.5% suffered proximal limb loss. Single-institution analysis of 237 consecutive patients with OM confirmed a similar mean age (58 years), gender (67% men), and most presented with a foot or digit ulcer (56%). Wound healing was achieved in 56% and overall limb salvage was 80%. Decreased wound healing was associated with peripheral vascular occlusive disease (odds ratio, 0.4; 95% confidence interval, 0.2-0.8, P = 0.006) and preadmission antibiotic use (odds ratio, 0.2; 95% confidence interval, 0.05-1.1, P=0.07), while surgical debridement (odds ratio, 2.2; 95% confidence interval, 1.2-4.2, P = 0.02) was associated with increased healing. Limb salvage was improved with an arterial bypass (odds ratio, 3.9; 95% confidence interval, 1.1-14, P = 0.04), while preadmission solid organ transplant (odds ratio, 0.37; 95% confidence interval, 0.14-0.96, P = 0.04), peripheral vascular occlusive disease (odds ratio, 0.25; 95% confidence interval, 0.12-0.5, P = 0.001), and preadmission antibiotic use (odds ratio, 0.34; 95% confidence interval, 0.15-0.77, P = 0.009) were associated with greater limb loss. CONCLUSION: Digit OM is an expensive and morbid disease. Aggressive surgical debridement/digit amputation and selected use of arterial bypass should improve wound healing and limb salvage, respectively. In contrast, antibiotic therapy alone is associated with decreased wound healing and limb salvage.

Aged↗
PubMed2005

D-dimer, P-selectin, and microparticles: novel markers to predict deep venous thrombosis. A pilot study.

Current plasma markers for diagnosis of deep venous thrombosis (DVT) allow for exclusion of the diagnosis, but lack adequate specificity to establish the diagnosis. Thus, a prospective study was performed to determine the sensitivity and specificity of plasma assays for D-dimer, soluble P-selectin (P-selectin), and total microparticles in patients with documented DVT by duplex ultrasound. Three groups of individuals were examined: 30 normals; 22 positive for DVT on duplex ultrasound (Group 2); and 21 symptomatic, but negative on duplex ultrasound for DVT (Group 3). Group 1 individuals had D-dimer values of 1.53 +/- 0.12 mg/l and P-selectin values of 0.34 +/- 0.05 ng/mg total protein. Group 2 vs. Group 3 individuals had D-dimer values of 7.57 +/- 2.03 vs. 3.19 +/- 0.79 mg/l, p = 0.02; P-selectin values of 0.98 +/- 0.11 vs. 0.55 +/- 0.08 ng/mg total protein, p < 0.01; and micro-particle values of 129 +/- 17% vs. 99 +/- 12% of control, p = ns. Using a logistic regression model with dichotomous variables, we determined a sensitivity of 73%, specificity of 81%, and accuracy of 77% when combining D-dimer, soluble P-selectin, and total microparticles to differentiate Group 2 from Group 3 patients. Logistic regression using continuous variables yielded similar results (p = 0.05). This study demonstrates that plasma markers for DVT can be developed and achieve moderate sensitivity and specificity in diagnosing DVT. However for clinical applicability, the sensitivity/specificity will need to be improved. These studies also suggest the importance of soluble P-selectin in assessing DVT in humans.

Female↗
PubMed2004

Gender differences in experimental aortic aneurysm formation.

OBJECTIVE: It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs). METHODS AND RESULTS: Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase. CONCLUSIONS: These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.

Animals↗
PubMed2004

Effect of increasing patient age on complication rates following intact abdominal aortic aneurysm repair in the United States.

INTRODUCTION: Advanced age is generally acknowledged as a risk factor for adverse surgical outcomes, but little information exists to define the magnitude of this association from a population-based perspective. This study was undertaken to determine the relation of patient age to complications following abdominal aortic aneurysm (AAA) repair in a population-based experience. METHODS: This study was based upon data from 6397 patients with a primary diagnosis of intact AAA and a procedure code for repair of AAA from the Nationwide Inpatient Sample (NIS) in 2000. The NIS is a 20% stratified random sample representative of all United States hospitals. Primary outcome variables were postoperative complications determined from secondary diagnostic codes. Adjustment for confounding variables was performed using multiple logistic regression. RESULTS: At least one complication affected 29% of patients. Increasing age correlated with a higher risk of having one or more complications (51-60 years, 18.8%; 61-70 years, 27.3%; 71-80 years, 31.2%; >80 years, 34.3%; P < 0.01). Comparison of the oldest to the youngest age group revealed an increased incidence of pulmonary insufficiency (13.9% versus 6.4%), pneumonia (7.7% versus 3.0%), reintubation (9.5% versus 3.9%), acute renal failure (8.8% versus 2.5%), myocardial infarction (4.3% versus 1.6%), and mortality (7.9% versus 1.1%). The association of increasing age to complications and mortality persisted after adjusting for patient case-mix. CONCLUSIONS: Older patient age is independently associated with an increased risk of major postoperative complications after AAA repair. The increasing age of the United States population will compound this healthcare problem. Quality improvement efforts must focus on minimizing complication rates in elderly patients undergoing common vascular surgical procedures including AAA repair.

Age Distribution↗
PubMed2004

Deep vein thrombosis resolution is modulated by monocyte CXCR2-mediated activity in a mouse model.

OBJECTIVE: To determine the role of CXCR2, the receptor for cysteine-X-cysteine (CXC) chemokines, and its primary effector cell, the neutrophil (PMN), on deep venous thrombosis (DVT) resolution. METHODS AND RESULTS: DVT in BALB/c, anti-CXCR2 antibody-treated, and BALB/c CXCR2(-/-) mice were created by infrarenal inferior vena cava (IVC) ligation and the thrombus harvested at various time points over 21 days. The CXCR2(-/-) mice had significantly larger thrombi at early time points (days 2 to 8), and significantly decreased intrathrombus PMNs, monocytes, and neovascularization as compared with controls. Thrombus KC/CXCL1 was significantly higher at 2 days in CXCR2-/- thrombi as measured by enzyme-linked immunosorbent assay. Fibrin content was significantly higher, with less uPA gene expression at 4 days in CXCR2-/- thrombi. Late fibrotic maturation of the thrombus was delayed in the CXCR2-/- mice, with significantly decreased 8 day MMP-2 activity, whereas MMP-9 activity was elevated as compared with controls. Similar impairment in DVT resolution was found at 8 days with anti-CXCR2 inhibition. However, systemic neutropenia, unlike CXCR2 deletion, did not increase the thrombus size as compared with controls. CONCLUSIONS: Normal DVT resolution involves CXCR2-mediated neovascularization, collagen turnover, and fibrinolysis, and it is probably primarily monocyte-dependent.

Animals↗
PubMed2004

Attending, house officer, and medical student perceptions about teaching in the third-year medical school general surgery clerkship.

BACKGROUND: There has been declining interest in surgery among medical students and one reason might be the third-year clerkship experience. The aim of this study was to clarify the perceptions and expectations of attendings, residents, and medical students on the clerkship experience. STUDY DESIGN: A survey was distributed to all general surgery attendings, the entire general surgery house staff, and an entire third year medical school class inclusive of the 2001-2002 academic year at a single institution. Statistic analysis consisted of chi-square and Kruskal-Wallis-ANOVA on ranks with Dunn's test for multiple comparisons. A p < 0.05 was significant. RESULTS: Responses were obtained from 59 attending surgeons (50%), 38 surgical residents (32%), and 107 medical students (66%). Of this student cohort, 35% were planning to choose a surgical specialty as a career. Agreement was high among faculty, students, and residents about factors considered important in evaluation, expectations of skills, and level of skills needed before the clerkship. Medical students desired more hours of instruction, believed they performed fewer procedures per week, and thought that feedback was poor compared with the opinions of faculty and residents (p < 0.002). Nearly 50% of medical students believed they were an inconvenience to the service; 30% of house officers and 27% of faculty (p < 0.001) believed this also. Almost all faculty and residents, however, wanted medical students on the service (> 95%). Faculty believed residents did a better job teaching than either the students or residents themselves did (p < 0.001), and students thought that residents were the primary source of education in patient care. CONCLUSIONS: Considerable differences exist between faculty, surgical resident, and medical student perceptions and expectations of medical student education. Structured direct faculty contact, definition of medical student roles on the surgical team, and more consistent feedback can be rapidly improved.

Attitude of Health Personnel↗
PubMed2004

Risk for stroke after elective noncarotid vascular surgery.

INTRODUCTION: Patients undergoing operations to treat peripheral vascular disease have systemic atherosclerosis and are at risk for stroke. However, the incidence and effect of cerebrovascular events on noncarotid vascular surgical outcomes are not well-defined. METHODS: Patients undergoing common operations for vascular disease from 1997 to 2000 were examined with data from the Veterans Affairs (VA) National Surgery Quality Improvement Project and the VA patient treatment files. Operations studied included abdominal aortic aneurysmectomy (n = 2551), aortobifemoral bypass (n = 2616), lower extremity bypass (n = 6866), and major lower extremity amputation (n = 7442). The incidence of perioperative stroke was determined, and logistic regression analysis was used to identify independent risk factors for stroke. Logistic and linear regression analyses were used to quantify the effect of postoperative stroke on adjusted mortality and length of stay. Odds ratio (OR) and 95% confidence interval (CI) were defined. P <.05 was considered significant. RESULTS: Stroke was uncommon after noncarotid vascular procedures, occurring in only 0.4% to 0.6% of patients. Independent risk factors for stroke include preoperative ventilation (OR, 11; 95% CI, 5.0-22.3; P <.001), previous stroke or transient ischemic attack (OR, 4.2; 95% CI, 2.7-6.4; P <.001), postoperative myocardial infarction (OR, 3.3; 95% CI, 1.3-8.7; P =.009), and need to return to the operating room (OR, 2.2; 95% CI, 1.4-3.5; P =.001). Factors that did not appear to be associated with stroke risk included procedure type, diabetes, renal failure, dialysis dependence, number of transfused units of blood, and hypertension. After controlling for other postoperative complications and comorbid conditions, postoperative stroke significantly increased the risk for perioperative mortality (OR, 6.3; 95% CI, 3.4-11.4; P <.001), with similar magnitude as postoperative myocardial infarction (OR, 6.3; 95% CI, 3.9-10.1; P <.001). Stroke was also associated with a 48% increase in overall length of stay. CONCLUSIONS: Stroke after noncarotid peripheral vascular surgery is uncommon, but results in markedly increased mortality and length of stay. Stroke risk is most strongly associated with previous stroke history and greater degree of illness. Patients with these associated conditions deserve particular attention to assessing and medically managing modifiable risk factors.

Aged↗
PubMed2004

Patients undergoing infrainguinal bypass to treat atherosclerotic vascular disease are underprescribed cardioprotective medications: effect on graft patency, limb salvage, and mortality.

INTRODUCTION: Established American Heart Association guidelines recommend the use of statin drugs, angiotensin converting enzyme (ACE) inhibitors, and antiplatelet agents in patients with systemic atherosclerosis, such as those undergoing operative intervention to treat peripheral atherosclerotic disease. Many of these patients have not received treatment of coronary heart disease and have not been prescribed these medications. Whether statin drugs and ACE inhibitors confer an improvement in graft patency, limb salvage, and operative mortality is unknown. METHODS: Consecutive patients who underwent infrainguinal bypass between 1997 and 2002 were evaluated for demographic data, comorbid disease, medication use, as well as cumulative graft patency, limb salvage, and mortality. Univariate, multivariate logistical regression, and Kaplan-Meier analyses were performed. P <.05 was considered significant. RESULTS: Two hundred ninety-three patients (mean age, 64 years; 67% men) underwent 338 infrainguinal bypass procedures with autologous vein (n = 218), prosthetic grafts (n = 88), or composite prosthetic-vein grafts (n = 32). Limb salvage was the operative indication in 75% of procedures. Coexisting diseases included hypertension (70%), diabetes (52%), hyperlipidemia (37%), coronary heart disease (51%), congestive heart failure (14%), and active tobacco use (30%). Statin drugs were taken by 56% of patients, ACE inhibitors by 54% of patients, and antiplatelet agents or warfarin sodium (Coumadin) by 93% of patients. Postoperative graft surveillance was done in 39% of patients. Cumulative graft patency was 73%, limb salvage was 85%, and mortality was 9%, with a mean follow-up of 17 months. Factors independently associated with increased graft patency included statin drug use (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.1-6.4), male sex (OR, 2.8; 95% CI, 1.6-5.0), and graft surveillance (OR, 2.4; 95% CI, 1.3-4.5). Factors associated with decreased amputation rate were statin drug use (OR, 0.34; 95% CI, 6.15-0.77) and graft surveillance (OR, 0.23; 95% CI, 6.1-0.63). Factors associated with decreased mortality included graft surveillance (OR, 0.18; 95% CI, 0.1-0.56), whereas congestive heart failure (OR, 6.5; 95% CI, 2.5-17) and hemodialysis-dependent renal failure (OR, 29; 95% CI, 6.1-140) were associated with increased mortality. Kaplan-Meier analysis showed that only ACE inhibitors were associated with lower mortality (P =.05) CONCLUSIONS: Patients undergoing infrainguinal bypass are undertreated with respect to cardioprotective medications. ACE inhibitor use is associated with lower mortality, and statin drug use is associated with improved graft patency and limb salvage. Institution of consensus guidelines concerning these medications should be considered by all vascular specialists, including vascular surgeons.

Angiotensin-Converting Enzyme Inhibitors↗