Biomedical subjects

Thomas W Wakefield

Publications and source records attributed to Thomas W Wakefield.

12 recordsLinked to original sources

PubMed2003

Cellular IL-10 is more effective than viral IL-10 in decreasing venous thrombosis.

BACKGROUND: Systemic administration of cellular interleukin-10 (cIL-10) and gene transfection of viral interleukin-10 (vIL-10) at thrombus induction decreases vein wall inflammation. Only cIL-10, despite sharing an 84% amino acid sequence homology with vIL-10, decreases thrombosis through mechanisms yet to be determined. METHODS: C57BL/6 mice (Mus musculus, n99) were studied. Inferior vena caval thrombosis was created by inferior vena caval ligation and the animals were sacrificed and evaluated at days 2 and 6 after ligation. At thrombus induction groups received intravenous 0.25 microg of cIL-10, 0.25 microg of vIL-10, or saline (untreated controls). Evaluations included thrombus mass and vein wall leukocyte counts, protein levels, and reverse-transcription polymerase chain reaction mRNA levels of P- and E-selectin, monocyte chemotactic protein-1, and IL-10. Groups were compared by analysis of variance and t tests. RESULTS: Less thrombus was noted at both days 2 and 6 in animals treated with cIL-10. At day 2 only, vein wall leukocyte counts revealed a significant decrease in neutrophils in cIL-10 animals versus controls, with no significant differences for vIL-10 animals. In cIL-10-treated animals, P-selectin protein levels were decreased at day 6, along with a decreased thrombus mass, without significant differences in E-selectin, monocyte chemotactic protein-1, or IL-10 protein levels. vIL-10 treated animals showed increased E-selectin mRNA and thrombus mass versus controls on day 6. CONCLUSIONS: cIL-10 is more antithrombotic/anti-inflammatory than vIL-10. This may be the result of cIL-10 decreasing P-selectin protein expression and vIL-10 increasing E-selectin mRNA levels.

Animals↗

PubMed2003

P-selectin inhibition decreases post-thrombotic vein wall fibrosis in a rat model.

BACKGROUND: Post-deep vein thrombosis (DVT) venous insufficiency is a vexing problem despite effective anticoagulation, and is characterized by vein wall fibrosis. This study tested the hypothesis that P-selectin inhibition would decrease post-thrombotic vein wall fibrosis and associated profibrotic mediators. METHODS: A rat stasis model of DVT was used to produce a 2-day-old DVT. Rats then received either intravenous saline (control), rPSGL-Ig (4 mg/kg) once, or daily subcutaneous low molecular weight heparin (LMWH) (0.5 mg/kg). Inferior vena cava wall was harvested 7 days after treatment and processed for thrombus size; leukocyte content; profibrotic mediators by enzyme-linked immunosorbent assay; collagen I and III mRNA expression by semiquantitative real-time polymerase chain reaction; and for collagen protein. RESULTS: Thrombus mass and leukocyte counts were similar between the groups. Treatment with rPSGL-Ig and LMWH resulted in less vein wall collagen (P <.05). rPSGL-Ig treatment (and a similar trend for LMWH) was associated with decreased profibrotic mediators, including less IL-13, MCP-1, bFGH, and transforming growth factor-beta (P <.05). Collagen III gene expression, but not collagen I gene expression, was increased with LMWH treatment (P <.05). CONCLUSIONS: P-selectin inhibition with rPSGL-Ig or LMWH decreases post-DVT vein wall fibrosis, and is associated with decreased vein wall profibrotic mediators. This effect is independent of thrombus mass and vein wall leukocytes.

Animals↗

PubMed2003

Clinical application of sonographic elasticity imaging for aging of deep venous thrombosis: preliminary findings.

OBJECTIVE: Aging of deep venous thrombosis is an important and difficult clinical problem. Because it is known that thrombi harden as they mature, we have preliminarily tested sonographic elasticity imaging, a technique that estimates tissue hardness, to age venous thrombi. METHODS: Two adult patients with lower extremity thrombi were studied. One had a clinically chronic thrombus (at least 3 years old), whereas the other patient's thrombus was clinically subacute (25 days old). We performed freehand compression sonographic scans using a 5-MHz linear array transducer. Phase-sensitive B-scan frames were processed offline by a two-dimensional complex correlation-based adaptive speckle-tracking technique. The distribution of internal strains in the wall of the vein, thrombus, and surrounding tissue was analyzed. Clot hardness was normalized to the venous wall. RESULTS: The chronic clot was homogeneous, and the strain in the chronic clot was at least 10 times smaller than that in the vessel wall. The subacute clot was much more heterogeneous, and, on average, the strain magnitude in the clot was 3 to 4 times greater than that in the vessel wall. CONCLUSIONS: In this preliminary work, the 2 thrombi appeared very different, and these results suggest that elasticity imaging may be able to age deep venous thrombosis.

Adult↗

PubMed2002

Compression stockings and venous function.

HYPOTHESIS: Surgical compression stockings measurably improve venous physiologic mechanisms, and stocking brands do not differ from one another. METHODS: Eleven patients, (8 men and 3 women [mean age, 53 years]), were included. Six patients had primary venous insufficiency and 5 patients had secondary venous insufficiency; 5 patients were in CEAP class 4 and 6 were in CEAP class 5. Patients were randomly assigned to a sequence of 4 brands of knee-high, open-toe, 30- to 40-mm Hg stockings. Each patient wore a stocking for a 1-month equilibration period, then a different stocking monthly for 4 months in a row. Air plethysmography examinations were performed with and without stockings before and after each month of wear. Patients filled out a daily stocking record log and a monthly satisfaction survey. Stockings underwent compression testing after use. RESULTS: Stockings controlled reflux better than they improved calf muscle pump function. With stockings on, patients in CEAP 4 benefited more than those in CEAP 5 in decreasing reflux, while patients in CEAP 5 benefited more than those in CEAP 4 in improving calf muscle pump function. Changes in residual volume fraction were improved in patients in CEAP 5 wearing stockings but not in patients in CEAP 4. Patients with primary disease had greater volumes of reflux and calf ejection than with secondary disease. There were no hemodynamic differences between stocking brands but there were differences in patient compliance and acceptance. CONCLUSIONS: Surgical support stockings seem to be more effective in controlling reflux than in improving calf muscle pump function. All stocking brands function equally as measured by air plethysmography.

Bandages↗

PubMed2002

Impaired vasoreactivity despite an increase in plasma nitrite in patients with abdominal aortic aneurysms.

OBJECTIVE: This investigation was designed to determine whether differences in vasoreactivity occur in patients with abdominal aortic aneurysms (AAAs) as compared with patients with peripheral arterial occlusive disease (PAOD) or individuals (controls) without known vascular disease. METHODS: Brachial artery vasoreactivity was assessed in a blinded fashion, after endothelium-dependent (ED) and endothelium-independent (EI) flow-mediated vasodilation, in age-matched, male patients with AAAs (n = 11) or PAOD (n = 9) or in controls (n = 10). There were no significant differences in prestudy systolic or diastolic blood pressure, body mass index, or antilipidemic medications among the groups studied. Exclusion criteria included diabetes and tobacco use within 3 months. Quantitative ultrasound scan measurements of brachial artery diameters were performed at rest and after either forearm ischemia (ED) or administration of 0.4 mg sublingual nitroglycerin (EI). Plasma nitric oxide (NO(X) = NO(2) + NO(3)) was measured with the Saville assay. Asymmetric dimethylarginine, an endogenous inhibitor of NO(X) synthase, was measured with liquid chromatography. RESULTS: Initial brachial artery diameters were not significantly different among the groups studied (4.85 +/- 0.18 mm for AAA group, 4.82 +/- 0.17 mm for PAOD group, 4.68 +/- 0.20 mm for controls). ED and EI vasodilation was significantly less (P =.02 and.03, respectively) in the AAA group (-1.71 +/- 1.52 and 8.33 +/- 1.13, respectively) when compared with the controls (2.96 +/- 1.04 and 13.88 +/- 2.16, respectively). However, plasma NO(X) was significantly increased (P =.01) in the AAA group (7.86 +/- 0.85 micromol/L) as compared with both controls (5.13 +/- 0.63 micromol/L) and PAOD (4.85 +/- 0.46 micromol/L). Asymmetric dimethylarginine levels were decreased in the AAA group (0.34 +/- 0.05 micromol/L) as compared with the PAOD group (0.46 +/- 0.09 micromol/L). No correlation existed between aneurysm size and ED or EI vasodilation or plasma NO(X). CONCLUSION: This study is the first to document a divergence between ED and EI vasoreactivity and systemic NO metabolites in patients with AAAs. It is speculated that a dysfunctional vessel wall response, rather than a lack of NO, may be important in the pathogenesis of AAAs.

Adult↗

PubMed2002

Cost of routine screening for carotid and lower extremity occlusive disease in patients with abdominal aortic aneurysms.

OBJECTIVE: The burden of clinically relevant noncoronary atherosclerotic occlusive disease in patients with abdominal aortic aneurysms (AAAs) is poorly defined. Furthermore, the cost-effectiveness of routine versus selective preoperative noninvasive examination of the carotid and lower extremity arterial beds has not been established in patients who undergo elective AAA repair. METHODS: Diagnostic vascular laboratory study results were reviewed in 206 patients who underwent evaluation before AAA repair from 1994 to 1998. The patients underwent routine preoperative carotid duplex scan examinations and lower extremity Doppler scan arterial studies with ankle-brachial index (ABI) determinations. The medical records were reviewed for the identification of clinical evidence consistent with cerebrovascular or lower extremity arterial occlusive disease. The costs of routine screening and selective screening were determined with Medicare reimbursement schedules. RESULTS: The prevalence rate of advanced (80% to 100%) carotid artery stenosis (CAS) was 3.4%, and 18% of the patients had CAS between 60% and 100%. Advanced peripheral vascular occlusive disease (PVOD; ABI, <0.3) was found in 3% of the patients, and 12% of the patients had an ABI of less than 0.6. Most patients with advanced CAS (71%) or advanced PVOD (83%) had clinical indications of their disease. The absence of clinical evidence of disease had a negative predictive value of 99% for both advanced CAS and PVOD. The cost of routine screening for all patients for advanced CAS was $5445 per case. Routine screening for severe PVOD costs were $3732 per case discovered. In contrast, the costs for selective screening for advanced CAS or PVOD in patients with appropriate history or symptoms were $1258 and $785 per case found, respectively. CONCLUSION: Routine noninvasive diagnostic testing for the identification of asymptomatic CAS and PVOD in patients with AAA may not be justified. Preoperative screening is more clearly indicated for patients with AAAs who have clinical evidence suggestive of CAS or PVOD.

Aged↗

PubMed2002

Pediatric splanchnic arterial occlusive disease: clinical relevance and operative treatment.

OBJECTIVE: Splanchnic arterial occlusive disease is rare in childhood. The purpose of this study was to review the clinical relevance and operative treatment of these lesions in a unique experience from a single institution. METHODS: Seventeen children (11 boys and 6 girls) from 2 years to 17 years in age with critical narrowings of the celiac artery (CA) and superior mesenteric artery (SMA) underwent treatment at the University of Michigan from 1974 to 2000. Etiologic factors included embryologic fusion abnormalities of the fetal aortae during formation of the splanchnic arteries (n = 15), inflammatory aortoarteritis (n = 1), and radiation-induced arterial fibrosis (n = 1). Individual lesions included CA occlusions (n = 6) and stenoses (n = 7), SMA occlusions (n = 3) and stenoses (n = 11), and inferior mesenteric artery stenosis (n = 1). Fourteen children had abdominal aortic coarctations, and 15 had renal artery stenoses. Two patients had postprandial abdominal discomfort and food aversion, consistent with intestinal angina. Small stature affected five others, perhaps attributable to severe renovascular hypertension and failure to thrive. Ten children underwent intestinal revascularization, at the time of an aortoplasty or thoracoabdominal bypass for aortic coarctation (n = 7) or at the time of renal artery revascularization (n = 8). Primary splanchnic revascularization procedures included SMA-aortic implantation (n = 3), aorto-SMA and CA bypass with an internal iliac artery graft (n = 3) or a saphenous vein graft (n = 1), CA-aortic implantation at a stenotic SMA origin (n = 2), and CA and SMA intimectomy (n = 1). Secondary operations included SMA-aortic implantation (n = 2). RESULTS: All 10 children who underwent splanchnic revascularization have thrived, gained weight, and are free of abdominal pain, with follow-up periods averaging 9 years. No intestinal ischemic manifestations occurred in the seven children who did not undergo operation. CONCLUSION: Pediatric splanchnic arterial occlusive disease is a rare illness appropriately treated with operation in properly selected children.

Adolescent↗

PubMed2002

Tissue loss, early primary graft occlusion, female gender, and a prohibitive failure rate of secondary infrainguinal arterial reconstruction.

PURPOSE: This study tested the hypothesis that a subset of secondary infrainguinal arterial reconstructions show prohibitive failure rates. METHODS: Records of 79 consecutive patients, 44 men and 35 women, with a mean age of 60 years, who underwent secondary infrainguinal bypass from 1992 to 2000 at the University of Michigan Hospital, were reviewed. Data were analyzed with life-table analysis, logistic regression, and descriptive statistics. RESULTS: Secondary infrainguinal reconstructions were performed in patients who had undergone earlier ipsilateral bypasses once (n = 35) or twice (n = 44). Among the prior procedures, 68% (n = 54) were done at an institution other than the authors'. Comorbidities included coronary artery disease (72%), tobacco use (77%), and diabetes mellitus (34%), but no patient had hemodialysis-dependent renal failure. Disabling claudication, with average ankle brachial index of 0.48, had been the indication for the primary operation in 77% of cases. Femoral-popliteal bypass was the primary procedure in 67%, with a prosthetic graft used in 62%. The mean patency duration of these earlier bypasses was 25 months. The indication for the final bypass was rest pain or tissue loss in 51% of patients, with an average ankle brachial index of 0.37. The most common procedure was a femoral-distal bypass with autologous vein (63%). Mean patency duration of the secondary bypasses was 30 months. Graft failure within 30 days of operation occurred in 22 patients (28%), and amputation was necessitated in 86% of these patients. The presence of rest pain or tissue loss, when accompanied with a history of early prior graft thrombosis in female patients, correlated with worse mean patency rates, recurrent graft failure (P </=.05), and a 94% amputation rate. Men in a similar setting incurred a 57% amputation rate. No association of final patency existed with regard to age, number of prior bypasses, conduit types, tobacco use, or diabetes. CONCLUSION: Secondary infrainguinal bypasses are associated with an increased rate of graft failure and significant limb loss, particularly in those with a history of rest pain or tissue loss, female gender, and early prior graft failure. More appropriate initial operations in carefully selected patients and aggressive postoperative graft surveillance is speculated to improve these outcomes.

Arterial Occlusive Diseases↗

PubMed2002

Southern Association for Vascular Surgery William J. von Leibig Award. Inflammation and intimal hyperplasia associated with experimental pulmonary embolism.

OBJECTIVE: We tested the hypothesis that a venous thromboembolism to the pulmonary arterial system (pulmonary embolism [PE]) would cause an inflammatory response within the pulmonary arterial (PA) wall marked by elevated cytokines and chemokines and an influx of inflammatory cells. METHODS: Experimental PE was induced in 70 rats and confirmed with angiography and O(2) saturation depression, and an additional 70 rats underwent sham operations. PA and lung tissue were removed at 3 hours and at 1, 2, 4, 6, 8, and 14 days (n = 10 per time point), were analyzed for proinflammatory cytokines and chemokines, and underwent histologic analysis. Data were analyzed with analysis of variance and the unpaired Student t test. RESULTS: Average gross PE resolution was 40% at 2 days, 90% at 4 days, and 100% at 6 days. Only monocyte chemoattractant protein-1 levels were greater in affected PAs compared with sham PAs at 3 hours, 1 day, and 2 days (137 +/- 13 pg/mg protein, 285 +/- 40 pg/mg protein, and 249 +/- 36 pg/mg protein versus 101 +/- 6 pg/mg protein, 150 +/- 36 pg/mg protein, and 92 +/- 3 pg/mg protein; P <.01 for all). Keratinocyte-derived chemokine, tissue necrosis factor, interleukin-10, nitric oxide, P-selectin, and E-selectin levels were not elevated. Neutrophils infiltrated the PA wall beginning at 3 hours, peaked at 2 days (69.4 +/- 21.7 per five high-power fields; P <.01), and returned to baseline by 8 days after PE. Macrophages peaked at 1 day after PE (29.3 +/- 6.9; P <.01) and returned to baseline by 4 days after PE. PE also was associated with a significantly increased intima to media ratio (P <.05), apparent at 4 days after PE and persisting through 14 days. CONCLUSION: PE is associated with an early influx of polymorphonuclears and macrophages and monocyte chemoattractant protein-1 elevation within the PA wall. These are temporally associated with thrombus resolution and intimal hyperplasia. These factors may mediate these two processes after PE. This offers targets for further study with the hopes of minimizing the pathophysiologic response to PE.

Animals↗

PubMed2002

P-selectin inhibition enhances thrombus resolution and decreases vein wall fibrosis in a rat model.

PURPOSE: The purpose of this study was to compare the efficacy of P-selectin inhibition with standard anticoagulant and thrombolytic therapy in a rodent model of established deep vein thrombosis (DVT). METHODS: Rats underwent temporary inferior vena cava (IVC) ligation for 2 days to create a stasis-induced thrombosis. On day 2, the animals had the IVC ligature removed and received either recombinant P-selectin glycoprotein ligand-Ig (rPSGL-Ig; 4 mg/kg) intravenously, low-molecular weight heparin (LMWH; 450 IU/kg) subcutaneously, tissue plasminogen activator (tPA; 0.5 mg/kg) intravenously, combination rPSGL-Ig plus tPA, or saline vehicle. IVC segments were harvested from rats at 4 (n = 8) and 7 (n = 3) days after treatment. All treatments were given as a single dose except for daily LMWH. Evaluation included contrast venography with computer image analysis, thrombus weight/length (mass), vein wall leukocyte counts, cytokine and tissue factor analysis with enzyme-linked immunosorbent assay, and (ED1) monocyte immunohistochemical staining. Collagen was estimated with a quantitative assay. RESULTS: Contrast venography revealed that rats with both rPSGL-Ig and tPA treatment had significantly smaller thrombi as compared with controls at day 7 (0.34 +/- 0.07 cm(2) and 0.34 +/- 0.05 cm(2) versus 0.68 +/- 0.13 cm(2); P <.05). LMWH and tPA groups had significantly decreased thrombus mass at harvest compared with controls on day 4 (0.06 +/- 0.009 g/cm and 0.08 +/- 0.01 g/cm versus 0.1 +/- 0.005 g/cm; P <.05), and rPSGL-Ig showed a similar trend (P =.072). Vein wall, but not thrombus, monocytes were more numerous in those rats receiving rPSGL-Ig versus controls at day 4 (30 +/- 4 cells/5 high power fields [HPFs] versus 19 +/- 2 cells/5 HPFs; P <.05) and at day 7 (32 +/- 2 cells/5 HPFs versus 20 +/- 3 cells/5 HPFs; P <.05). rPSGL-Ig treatment was associated with significantly reduced vein wall collagen at day 7 versus controls (1.3 +/- 0.6 pg/mg versus 3.7 +/- 0.5 pg/mg; P <.05) and a trend toward lower tissue factor levels. CONCLUSION: rPSGL-Ig, LMWH, and tPA showed equal DVT resolution efficacy over 7 days. However, only rPSGL-Ig was associated with a decrease in vein wall fibrosis, suggesting that purely accelerating DVT resolution may not decrease long-term vein scarring.

Animals↗

PubMed2002

Endovascular treatment of abdominal aortic aneurysm is associated with a low incidence of deep venous thrombosis.

OBJECTIVE: This study was performed to define the incidence of acute deep venous thrombosis (DVT) after endovascular treatment of abdominal aortic aneurysms (AAAs). Because aortic endograft placement requires prolonged femoral vessel instrumentation, it may be hypothesized that these patients are at increased risk for development of an acute DVT. PATIENTS AND METHODS: Fifty consecutive patients (42 men, eight women) ranging in age from 48 to 85 years (mean, 72 years) underwent endovascular treatment of an AAA from January 2000 to August 2001. Clinical examination and bilateral lower extremity duplex ultrasonography for DVT were performed on the first postoperative day and at the 1-month follow-up visit. No patient had a prior DVT or identifiable hypercoagulable state. Seven patients (14%) had concurrent malignant disease. Preoperative antiplatelet agents were administered in 26 patients (52%), and nine (18%) were on warfarin sodium therapy before surgery. No new DVT prophylaxis was initiated perioperatively. Epidural anesthesia was used in 60% of the patients, with general endotracheal anesthesia used in the remainder. Risk factors for DVT were evaluated with univariate statistical analysis. RESULTS: Three patients (6%) had an acute postoperative DVT develop. Two occurred in the femoral veins, and one occurred in the popliteal vein. Of these patients, one had been continued on perioperative anticoagulation therapy, and the remaining two were started on low-molecular weight heparin and warfarin sodium therapy on recognition of the DVT. One patient had an intraoperative injury of the affected common femoral vein, and this individual was the only one to have clinical signs of a DVT. The mean follow-up period was 8 +/- 0.8 months. In this experience, factors that may have placed patients at increased risk for an acute DVT were not identified. CONCLUSION: Six percent of patients undergoing endovascular repair of AAAs had postoperative DVT develop. These patients had a number of risk factors for the development of a DVT; however, no specific factor was identified that predisposed to DVT.

Aged↗

PubMed2002

Variation in death rate after abdominal aortic aneurysmectomy in the United States: impact of hospital volume, gender, and age.

OBJECTIVE: To determine whether high-volume hospitals (HVHs) have lower in-hospital death rates after abdominal aortic aneurysm (AAA) repair compared with low-volume hospitals (LVHs). SUMMARY BACKGROUND DATA: Select statewide studies have shown that HVHs have superior outcomes compared with LVHs for AAA repair, but they may not be representative of the true volume-outcome relationship for the entire United States. METHODS: Patients undergoing repair of intact or ruptured AAAs in the Nationwide Inpatient Sample (NIS) for 1996 and 1997 were included (n = 13,887) for study. The NIS represents a 20% stratified random sample representative of all U.S. hospitals. Unadjusted and case mix-adjusted analyses were performed. RESULTS: The overall death rate was 3.8% for intact AAA repair and 47% for ruptured AAA repair. For repair of intact AAAs, HVHs had a lower death rate than LVHs. The death rate after repair of ruptured AAA was also slightly lower at HVHs. In a multivariate analysis adjusting for case mix, having surgery at an LVH was associated with a 56% increased risk of in-hospital death. Other independent risk factors for in-hospital death included female gender, age older than 65 years, aneurysm rupture, urgent or emergent admission, and comorbid disease. CONCLUSIONS: This study from a representative national database documents that HVHs have a significantly lower death rate than LVHs for repair of both intact and ruptured AAA. These data support the regionalization of patients to HVHs for AAA repair.

Adult↗