Search PubMed⌕ Search

Biomedical subjects

H L Bush

Publications and source records attributed to H L Bush.

At least 19 recordsLinked to original sources

Thrombolysis for native arterial occlusions of the lower extremities: clinical outcome and cost.

INTRODUCTION: Intra-arterial thrombolysis is commonly used as the initial treatment of acute or subacute lower extremity ischemia. METHODS: To evaluate the efficacy and cost of thrombolysis, we retrospectively analyzed 100 consecutive cases (87 patients) in which intra-arterial lysis (urokinase) was used as the initial treatment for native arterial lower extremity occlusive disease. The mean age of patients was 67 years, 57% of the patients were male, and preexisting peripheral vascular disease was present in 74%. Presenting symptoms were limb-threatening ischemia (53%) and claudication (47%). Acute symptoms (< 2 weeks' duration) were present in 48%. RESULTS: The 30-day morbidity rate was 31%, and four patients died. Complications were significant bleeding (23%), ischemic stroke (1%), and renal failure with (2%) and without (2%) dialysis. Concomitant angioplasty was performed in 63%. Complete or significant lysis as demonstrated with angiography was achieved in 75% of iliac, 58% of femoropopliteal, and 41% of crural vessels (P <.001). Within 30 days of lysis, 9% of patients underwent major amputation and 20% surgical revascularization (in 3 patients the extent of revascularization was lessened by the lytic therapy). Amputation-free survival was 83% and 75% at 6 months and 2 years, respectively. Relief of ischemia (defined as relief of claudication or limb salvage without major surgical intervention) was achieved in only 70% and 43% of patients at 30 days and 2 years, respectively (Kaplan-Meier analysis; mean follow-up, 31 months). Patients with aortoiliac disease had significantly better outcomes than those with infrainguinal disease (P =.03). Duration or type of presenting symptoms did not predict outcome. The cost of the initial hospitalization per patient for thrombolysis was $18,490. CONCLUSION: Thrombolysis can be as or more costly than surgery and is associated with a suboptimal outcome in a significant number of patients. These data lead us to caution against a uniform policy of initial thrombolysis for patients who present with lower extremity ischemia.

Aged↗

Contrast-enhanced peripheral MR angiography from the abdominal aorta to the pedal arteries: combined dynamic two-dimensional and bolus-chase three-dimensional acquisitions.

UNLABELLED: Wang Y, Winchester PA, Khilnani NM, et al. Contrast-enhanced peripheral MR angiography from the abdominal aorta to the pedal arteries: Combined dynamic two-dimensional and bolus-chase three-dimensional acquisitions. Invest Radiol 2001;36:170-177. RATIONALE AND OBJECTIVES: To obtain reliable contrast-enhanced peripheral MR angiography for imaging peripheral vascular disease from the abdominal aorta to the pedal arteries. METHODS: A protocol consisting of contrast-enhanced, dynamic two-dimensional (2D) acquisition at the feet and calf and bolus-chase three-dimensional (3D) acquisition from the abdominal aorta to the calf was developed and applied in patients with peripheral vascular disease. The performance of this integrated protocol was assessed in 89 consecutive patients. RESULTS: The bolus-chase 3D acquisition was of diagnostic quality in 100% of the acquisitions in the abdomen, 96% in the thigh, and 43% in the calf. The poor quality of the calf acquisitions was due to insufficient spatial resolution, poor arterial signal, and venous contamination. Diagnostic-quality images were obtained in 100% of the dynamic 2D acquisitions of the calf and 98% of the feet. CONCLUSIONS: The combined dynamic 2D and bolus-chase 3D contrast-enhanced MR angiography technique provides diagnostic images of the entire lower extremity.

Adult↗

Cross-sectional pattern of collateral vessels in patients with superficial femoral artery occlusion.

RATIONALE AND OBJECTIVES: The purpose of this study was to identify the cross-sectional location of collateral vessels in patients with peripheral vascular disease on three-dimensional magnetic resonance angiograms (3D MRAs) to suggest sites for intravascular or transcutaneous angiogenesis gene delivery in the lower extremity. METHODS: The axial locations were measured and categorized by tissue compartments, as well as by radial coordinates with respect to the femur. RESULTS: Collateral vessels in the thigh were identified in 24 of 93 consecutive patients who underwent peripheral 3D MRA. Ninety-one percent (99/109) of the observed collaterals were located near the adductor canal level of the thigh, with 78% (31/46) of these collaterals located in the fat in or surrounding the posterior muscle. CONCLUSIONS: The majority of collateral vessels in the thigh are located in the fat or muscle within the posterior compartment near the femur at the level of the adductor canal.

Adult↗

The cost-effectiveness of repairing ruptured abdominal aortic aneurysms.

BACKGROUND: Although advances in technology have reduced the operative risk of elective abdominal aortic aneurysm (AAA) repair, the surgical repair of ruptured AAAs is associated with a much poorer prognosis and a higher cost. Accordingly, it has been suggested that patients with predictably high rates of morbidity and mortality from ruptured AAA may not benefit from surgical intervention. METHODS AND RESULTS: A cost-effectiveness analysis was performed with the use of a Markov decision-analytic model to compute long-term survival in quality-adjusted life years and lifetime costs for a hypothetical cohort of patients with ruptured AAAs managed with either a strategy of open surgical repair or no intervention. Probability estimates for the various outcomes were based on a review of the literature. Average costs of (1) the immediate hospitalization ($28,356) and (2) complications resulting from the procedure were based on the average use of resources as reported in the literature and from a hospital's cost accounting system. Our measure of outcome was the incremental cost-effectiveness ratio. For our base-case analysis, the repair of ruptured AAAs was cost-effective with an incremental cost-effectiveness ratio of $10,754. (Society is usually willing to pay for interventions with cost-effectiveness ratios of less than $60,000; for example, the costeffectiveness ratios for coronary artery bypass grafting and dialysis are $9500 and $54,400, respectively.) In sensitivity analyses, the cost-effectiveness of repairing ruptured AAAs was influenced only by alterations in the operative mortality. If the operative mortality exceeded 88%, repair of ruptured AAAs was no longer cost-effective. As an independent variable, increasing age had no substantial impact on the cost-effectiveness, although it is reported to be associated with increased operative mortality. It was necessary that the patient's cost of the initial hospitalization for ruptured AAA exceed $195,000 before repairing ruptured AAAs was no longer cost-effective. CONCLUSIONS: Our analysis suggests that despite the high cost and poor outcomes, the surgical repair of ruptured AAAs is still cost-effective when compared with no intervention. The cost of repairing ruptured AAAs falls within society's acceptable limits and therefore should not be a consideration in the management of patients with AAAs.

Age Factors↗

Two decades of abdominal aortic aneurysm repair: have we made any progress?

PURPOSE: Over the past 20 years, there have been numerous advances in our ability to detect and to treat abdominal aortic aneurysms (AAAs). We hypothesized that these advances would lead to (1) an increase in the rate of elective repair and a decrease in the incidence of ruptured AAA (rAAA) and (2) a decrease in operative deaths for both elective AAA (eAAA) and rAAA. METHODS: To test these hypotheses, we investigated the incidence and outcomes of eAAA and rAAA surgery between 1979 and 1997, using the National Hospital Discharge Survey. This data set is a randomized, stratified sample representing discharges from the nation's acute care, nonfederally funded hospitals. Codes from the International Classification of Diseases, Ninth Revision were used to identify our study population. RESULTS: Over the past 19 years, there has been no change in the incidence rate of eAAA repair (range, 44.1-77.9 per 100,000). Moreover, the incidence of rAAAs presenting to the nation's hospitals has not changed (range, 6.6-16.3 per 100,000). There has been no consistent improvement over time in operative deaths associated with either eAAA or rAAA repair (average rates over the study period: eAAA, 5.6%; rAAA, 45.7%). Significant predictors of death from eAAA in patients included an age older than 80 years, African American race, congestive heart failure (CHF), and diabetes (P<.0001 for all). Significant predictors of death from rAAA in patients included age older than 70 years, African American race, female sex, renal failure, and a hospital bed size more than 500 (P<.05 for all). CONCLUSION: On a national level, over the past 19 years, our ability to identify and to treat patients with AAA has not improved. Advances in technology and critical care have not affected outcome. Regionalization of care, screening of high-risk populations, and endovascular repair are strategies that might allow further improvement in the outcome of patients with aneurysmal disease.

Black or African American↗

Is thrombolysis of lower extremity acute arterial occlusion cost-effective?

BACKGROUND: The TOPAS (thrombolysis or peripheral artery surgery) trial randomized 544 patients with acute lower extremity ischemia to either surgery or thrombolysis. Although statistically equivalent 1-year morbidities and mortalities were demonstrated, the comparative cost-effectiveness of these two interventions has not been explored. MATERIALS AND METHODS: We constructed a Markov decision-analytic model to determine the cost-effectiveness of thrombolysis relative to surgery for a hypothetical cohort of patients with acute lower extremity arterial occlusion. Our measure of outcome was the cost-effectiveness ratio (CER), defined as the incremental lifetime cost per quality-adjusted life year gained. Estimates of 1-year outcomes were based on the TOPAS trial: mortality (lysis, 20%; surgery, 17%), amputation (lysis, 15%; surgery, 13%), the number of additional interventions required following the initial procedure (lysis, 544; surgery, 439). Procedural costs were estimated from the cost accounting system at the New York Presbyterian Hospital as well as from the literature. RESULTS: Operative intervention for acute lower extremity arterial occlusion extended life and was less costly compared to thrombolysis. The projected life expectancy for patients who underwent initial surgery was 5.04 years versus 4.75 years for initial thrombolysis. The lifetime costs were $57,429 for surgery versus $dollar;76,326 for thrombolysis. In performing sensitivity analyses, a threshold CER of $60,000 was considered what society would pay for accepted medical interventions. Thrombolysis became cost-effective if the 1-year mortality rate for lysis was lowered from 20 to 10.7%, if the amputation rate for lysis diminished from 15 to 3.9%, or if the 1-year cost of lysis could be reduced to a level below $13,000. CONCLUSIONS: Initial surgery provides the most efficient and economical utilization of resources for acute lower extremity arterial occlusion. The high cost of thrombolysis is related to the expense of the lytic agents, the need for subsequent interventions in patients treated with initial lysis, and the long-term costs of amputation in patients who fail lytic therapy.

Amputation, Surgical↗

The expression of TGF-beta receptors in human atherosclerosis: evidence for acquired resistance to apoptosis due to receptor imbalance.

The degree of cellularity in vascular lesions is determined by the balance between the migration and proliferation of cells relative to their rate of egress and apoptosis. Transforming growth factor-beta(1) can act as a potent antiproliferative and apoptotic factor for proliferating vascular cells. Our laboratory has previously identified cells cultured from human vascular lesions that are resistant to the antiproliferative effect of TGF-beta(1) due to an acquired mutation in the Type II receptor for TGF-beta(1). In the present studies, the expression of the Type I and II receptors in coronary and carotid atherosclerotic lesions was analysed by immunostaining, RT-PCR, and in situ RT-PCR. Levels of the Type I and Type II receptors varied widely within lesions, with the highest levels in the fibrous cap and at discrete foci within the lesion. Regions of smooth muscle-like cells (SMC) were commonly found that were Type I positive but Type II receptor negative. In 43 cell lines cultured from 126 human lesions, 84% of the lesion-derived cell (LDC) cultures exhibited functional resistance to the antiproliferative effect of TGF-beta(1). This resistance was conferred against TGF-beta(1), TGF-beta(2), and TGF- beta(3), but not interferon-gamma or mimosine. While normal SMC exhibited a four-fold increase in the rate of apoptosis after TGF- beta(1) treatment, most LDC were resistant to apoptosis in response to TGF-beta(1). Resistant cells exhibited selective loss of Type II receptor expression, and retroviral transfection of Type II receptor cDNA partially corrected the functional deficit. Thus, resistance to apoptosis may lead to the slow proliferation of resistant cell subsets, thereby contributing to the progression of atherosclerotic and restenotic lesions.

Activin Receptors, Type I↗

Is carotid endarterectomy cost-effective in symptomatic patients with moderate (50% to 69%) stenosis?

OBJECTIVE: Recently published data from the North American Carotid Endarterectomy Trial revealed a benefit for carotid endarterectomy (CEA) in symptomatic patients with moderate (50% to 69%) carotid stenosis. This benefit was significant but small (absolute stroke risk reduction at 5 years, 6.5%; 22.2% vs 15.7%), and thus, the authors of this study were tentative in the recommendation of operation for these patients. To better elucidate whether CEA in symptomatic patients with moderate carotid stenosis is a proper allocation of societal resources, we examined the cost-effectiveness of this intervention. METHODS: A decision-analytic Markov process model was constructed to determine the cost-effectiveness of CEA versus medical treatment for a hypothetical cohort of 66-year-old patients with moderate carotid stenosis. This model allowed the comparison of not only the immediate hospitalization but also the lifetime costs and benefits of these two strategies. Our measure of outcome was the cost-effectiveness ratio (CER), defined as the incremental lifetime cost per quality-adjusted life year saved. We assumed an operative stroke and death rate of 6.6% and a declining risk of ipsilateral stroke after the ischemic event with medical treatment (first year, 9.3%; second year, 4%; subsequent years, 3%). The hospitalization cost of CEA ($6,420) and the annual costs of major stroke ($26,880), minor stroke ($798), and aspirin therapy ($63) were estimated from a hospital cost accounting system and the literature. RESULTS: CEA for moderate carotid stenosis increased the survival rate by 0.13 quality-adjusted life years as compared with medical treatment at an additional lifetime cost of $580. Thus, CEA was cost-effective with a CER of $4,462. Society is usually willing to pay for interventions with CERs of less than $60,000 (eg, CERs for coronary artery bypass grafting at $9,100 and for dialysis at $53,000). CEA was not cost-effective if the perioperative risk was greater than 11.3%, if the ipsilateral stroke rate associated with medical treatment at 1 year was reduced to 4.3%, if the age of the patient exceeded 83 years, or if the cost of CEA exceeded $13,200. CONCLUSION: CEA in patients with symptomatic moderate carotid stenosis of 50% to 69% is cost-effective. Perioperative risk of stroke or death, medical and surgical stroke risk, cost of CEA, and age are important determinants of the cost-effectiveness of this intervention.

Aged↗

Type B aortic dissection and thoracoabdominal aneurysm formation after endoluminal stent repair of abdominal aortic aneurysm.

Endoluminal stent graft repair of abdominal and thoracic aortic aneurysms is being performed in increasing numbers. The long-term benefits of this technology remain to be seen. Reports have begun to appear regarding complications of stent graft application, such as renal failure, intestinal infarction, distal embolization, and rupture. Many of these complications have been associated with a fatal outcome. We describe a case of acute, retrograde, type B aortic dissection after application of an endoluminal stent graft for an asymptomatic infrarenal abdominal aortic aneurysm. An extent I thoracoabdominal aortic aneurysm subsequently developed and was successfully repaired. Aggressive evaluation of new back pain after such a procedure is warranted. Further analysis of the short-term complications and long-term outcome of this new technology is indicated before universal application can be recommended.

Aged↗

The cost-effectiveness of endovascular repair versus open surgical repair of abdominal aortic aneurysms: A decision analysis model.

PURPOSE: Endovascular repair (EVR) is a less-invasive method for the treatment of abdominal aortic aneurysms (AAAs) as compared with open surgical repair (OSR). The potential benefits of EVR include increased patient acceptance, less resource utilization, and cost savings. This study was designed to determine whether the EVR of AAAs is a cost-effective alternative to OSR. METHODS: A cost-effectiveness analysis was performed using a Markov decision analysis model to compute long-term survival rates in quality-adjusted life years and lifetime costs for a hypothetical cohort of patients who underwent either OSR or EVR. Probability estimates of the different outcomes of the two alternative strategies were made on the basis of a review of the literature. The average costs of (1) the immediate hospitalization ($16,016 for OSR, $20,083 for EVR), (2) the complications that resulted from each procedure, (3) the subsequent interventions, and (4) the surveillance protocol were determined on the basis of average resource utilization as reported in the literature and from our hospital's cost accounting system. Our measure of outcome was the cost-effectiveness ratio. RESULTS: For our base-case analysis (70-year-old men with 5-cm AAAs), EVR was cost-effective with a cost-effectiveness ratio of $22,826-society usually is willing to pay for interventions with cost-effectiveness ratios of less than $60,000 (eg, cost-effectiveness ratios for coronary artery bypass grafting and dialysis are $9500 and $54,400, respectively). This conclusion did not vary significantly with increases in procedural costs for EVR (ie, if the cost of the endograft increased from $8000 to $12,000, EVR remained cost-effective with a cost-effectiveness ratio of $32,881). The cost-effectiveness of EVR was critically dependent on EVR producing a large reduction in the combined mortality and long-term morbidity rate (stroke, dialysis-dependent renal failure, major amputation, myocardial infarction) as compared with OSR (ie, a reduction in the combined mortality and long-term morbidity rate of OSR from 9.1% to 4.7% made EVR no longer cost-effective). CONCLUSION: Despite the high cost of new technology and the need for close postoperative surveillance, EVR is a cost-effective alternative for the repair of AAAs. However, the cost-effectiveness of this new technology is critically dependent on its potential to reduce morbidity and mortality rates as compared with OSR. EVR may not be cost-effective in medical centers where OSR can be performed with low risk.

Aged↗

Bolus-chase MR digital subtraction angiography in the lower extremity.

A bolus-chase magnetic resonance (MR) angiographic technique performed with a prototypic stepping table and coil holder and a 15-20-mL injection of contrast material was developed to depict the entire lower extremity. Image acquisition was synchronized with passage of the contrast medium bolus through the lower extremity. Ten subjects underwent the examination, which was performed in less than 1 minute. All major arteries were well demonstrated in all cases.

Adult↗

Distal lower extremity arteries: evaluation with two-dimensional MR digital subtraction angiography.

PURPOSE: To test the hypothesis that magnetic resonance (MR) digital subtraction angiography is superior to two-dimensional time-of-flight (TOF) MR angiography for demonstration of patent arteries in the distal lower extremity. MATERIALS AND METHODS: Thirty-seven lower extremities in 23 consecutive patients were imaged with two-dimensional TOF MR angiography and two-dimensional MR digital subtraction angiography. Images were interpreted in a randomized and blinded manner. Each lower extremity was subdivided into seven potential arterial segments. The number of digital arteries visualized was also determined. Overall image quality of MR digital subtraction and TOF angiograms was compared. The relative ability of MR digital subtraction angiography and TOF MR angiography to demonstrate patent arterial segments was assessed. RESULTS: MR digital subtraction angiography was significantly superior to TOF MR angiography for demonstration of patent arterial segments and digital arteries (P < .001). MR digital subtraction angiographic images were qualitatively superior to TOF images (P < .001). CONCLUSION: Two-dimensional MR digital subtraction angiography is superior to two-dimensional TOF MR angiography for help in identifying patent segments in the distal lower extremity.

Adult↗

Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells.

Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF-beta1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF-beta1 (TbetaR-II), causing acquired resistance to TGF-beta1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A10 microsatellite within TbetaR-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in TbetaR-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF-beta1. We propose that microsatellite instability in TbetaR-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions.

Arteriosclerosis↗

Hypothermia during elective abdominal aortic aneurysm repair: the high price of avoidable morbidity.

PURPOSE: Adverse outcomes apparently associated with hypothermia led us to examine patients undergoing elective abdominal aortic aneurysm (AAA) repairs to test the hypothesis that hypothermia (temperature less than 34.5 degrees C) is associated with increased morbidity and excess mortality rates. METHODS: Two hundred sixty-two elective AAA repairs were retrospectively reviewed for preoperative and intraoperative risk factors. Core temperature, age, Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores (raw and temperature-adjusted), fluid resuscitation, and perioperative organ dysfunction were recorded prospectively. Outcome measures included lengths of stay in the intensive care unit and in the hospital, and hospital mortality rates. RESULTS: Except for a higher risk of hypothermia in women (p < 0.05), by univariate analysis, preoperative risk factors were similar in patients in the hypothermic and normothermic groups. After operation, patients with hypothermia had significantly greater APACHE scores (p < 0.0001), and patients in the hypothermic nonsurvivor group took significantly longer to rewarm (p < 0.05), suggesting marked hypoperfusion. Patients with hypothermia had significantly greater fluid (p < 0.05), transfusion (p < 0.01), vasopressor (p < 0.05), and inotrope (p < 0.05) requirements, resulting in significantly higher incidences of organ dysfunction (53.0% vs 28.7%, p < 0.01) and death (12.1% vs 1.5%, p < 0.01) and markedly prolonged lengths of stay in the unit (9.2 +/- 2.0 vs 5.3 +/- 0.6, p < 0.05) and in the hospital (24.3 +/- 2.9 vs 15.0 +/- 0.08, p < 0.01). By multivariate analysis, female gender (p = 0.004) was the only predictor of intraoperative hypothermia, whereas initial hypothermia was significantly predictive of both prolonged hypothermia and development of organ failure (p < 0.05). Organ failure (p < 0.05) and acute myocardial infarction (p < 0.01) were independent predictors of death. CONCLUSIONS: After AAA repair, patients with hypothermia have multiple physiologic derangements associated with adverse outcomes. Although multiple etiologic factors are interacting, body temperature is one variable that should be controlled during aortic surgery.

APACHE↗

Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1.

Atherosclerosis and postangioplasty restenosis may result from abnormal wound healing. The present studies report that normal human smooth muscle cells are growth inhibited by TGF-beta1, a potent wound healing agent, and show little induction of collagen synthesis to TGF-beta1, yet cells grown from human vascular lesions are growth stimulated by TGF-beta1 and markedly increase collagen synthesis. Both cell types increase plasminogen activator inhibitor-1 production, switch actin phenotypes in response to TGF-beta1, and produce similar levels of TGF-beta activity. Membrane cross-linking of 125I-TGF-beta1 indicates that normal human smooth muscle cells express type I, II, and III receptors. The type II receptor is strikingly decreased in lesion cells, with little change in the type I or III receptors. RT-PCR confirmed that the type II TGF-beta1 receptor mRNA is reduced in lesion cells. Transfection of the type II receptor into lesion cells restores the growth inhibitory response to TGF-beta1, implying that signaling remains responsive. Because TGF-beta1 is overexpressed in fibroproliferative vascular lesions, receptor-variant cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components. This TGF-beta1 receptor dysfunction may be relevant for atherosclerosis, restenosis and related fibroproliferative diseases.

Actins↗

Recurrent systemic embolization caused by aortic thrombi.

The aorta is a commonly unrecognized source of systemic embolization. Transesophageal echocardiography is a reliable method for visualization of the intima of the thoracic aorta and identification of aortic thrombi. Balloon embolectomy of the aorta can be used to remove thrombi and prevent further embolic events.

Aged↗