Endovascular stenting of nonmalignant superior vena cava syndrome.

Superior vena cava (SVC) syndrome is associated with advanced malignancy of the chest. Extensive experience is published in the literature regarding the use of endovascular intervention for symptomatic relief in these individuals with limited survival. Symptomatic SVC obstruction may occur from benign conditions that may not alter life expectancy. There are few data regarding endovascular therapy in this setting. We retrospectively analyzed our experience using endovascular intervention for benign SVC obstruction in 19 patients. In our series, the mean age was 46.4 years; 58% were female and 14/19 cases were due to an intravascular device. All patients experienced symptomatic relief. Median follow-up was 28.8 months. Three patients required secondary procedures to maintain patency. Four patients had procedural complications, which did not affect the outcomes. One patient died from complications of anticoagulation at 24 months. Endovascular procedures aimed at relieving SVC stenosis seem to be effective in patients with benign disease.

Chronic mesenteric ischemia: open surgery versus percutaneous angioplasty and stenting.

OBJECTIVE: The aim of the study was to evaluate the safety and efficacy of percutaneous angioplasty and stenting (PAS) in comparison with traditional open surgical (OS) revascularization for the treatment of chronic mesenteric ischemia. METHODS: Over a 3.5-year period, 28 patients (32 vessels) underwent PAS (balloon angioplasty alone, 5 [18%] of 28; angioplasty and stenting, 23 [82%] of 28) for symptoms of chronic mesenteric ischemia. These patients were compared with a previously published series of 85 patients (130 vessels) treated with OS (bypass grafting, 60 [71%] of 85; transaortic endarterectomy, 19 [22%] of 85; or patch angioplasty, 6 [7%] of 85). RESULTS: The PAS and OS groups were similar with respect to baseline comorbidities, duration of symptoms (median: 6.7 vs 10.5 months, P =.52), and the number of vessels involved, but the patients differed in their age at presentation (median: 72 vs 65 years, P =.005). Fewer vessels were revascularized per patient in the PAS group (1.1 +/- 0.4) compared with the OS group (1.5 +/- 0.6, P =.001). Overall, 85.7% (24/28) had one vessel and 14.3% (4/28) had two vessels revascularized in the PAS group versus 48.2% (41/85) with one-vessel and 47.1% (40/85) with two-vessel revascularization in the OS group. No difference was noted in the early in-hospital complications (median: 17.9% [PAS] vs 32.9% [OS], P =.12) or mortality rate (10.7% [PAS] vs 8.2% [OS], P =.71). A reduced length of hospital stay in the PAS patients did not attain statistical significance (median: 5 days [PAS] vs 13 days [OS], P =.08). Although the 3-year cumulative recurrent stenosis (P =.62) and mortality rate (P =.99) did not differ, the PAS treatment group had a higher incidence of recurrent symptoms (P =.001). CONCLUSION: Although the results of PAS and OS were similar with respect to morbidity, death, and recurrent stenosis, PAS was associated with a significantly higher incidence of recurrent symptoms. These findings suggest that OS should be preferentially offered to patients deemed fit for open revascularization.

Endovascular treatment of peripheral arterial disease.

Atherosclerosis is a systemic disease affecting quality and length of life. Endovascular revascularization can be used to improve quality of life. The benefit is greatest in patients with subclavian, renal, or iliac artery symptomatic disease. The advent of stents improves the initial technical success rates of angioplasty to more than 90% in most locations. The development of stent: grafts has altered the treatment of abdominal aortic aneurysms and should be strongly considered as an alternative to open surgery.

Safety-net health plans: a status report.

This paper reports on a national survey of Medicaid managed care plans sponsored by safety-net provider organizations that have a mission of service to low-income populations. We identified ninety-nine safety-net plans and obtained data from eighty of them regarding their sponsorship, age and size, relationships to sponsors, managed care practices, and measures of success. Most plans engage in active managed care and have achieved at least some of their goals. However, 60 percent of plans lost money in 1997, and economic trends have been unfavorable.

Large artery occlusive disease.

Large artery occlusive disease is a common problem in the United States. It affects both the upper and lower extremities and is associated with significant morbidity and mortality. This article deals with the clinical recognition of this entity in hopes that the general internist and rheumatologist will more easily recognize it. In addition, the latest technology available to diagnose and treat large artery occlusive disease is discussed.

Angioplasty and primary stenting of the subclavian, innominate, and common carotid arteries in 83 patients.

PURPOSE: The initial and long-term results of angioplasty and primary stenting for the treatment of occlusive lesions involving the supra-aortic trunks were studied. METHODS: All patients in whom angioplasty and stenting of the supra-aortic trunks was attempted were included in a prospective registry. Results are, therefore, reported on an intent-to-treat basis. The preprocedural and postprocedural clinical records, arteriograms, and noninvasive vascular laboratory examinations of 83 patients (41 men [49.4%] and 42 women [50.6%]; mean age at intervention, 63 years) in whom endovascular repair of the subclavian (66, 75.9%), left common carotid (14, 16.1%), and innominate (7, 8.0%) arteries was attempted were retrospectively reviewed. RESULTS: Initial technical success was achieved in 82 of 87 procedures (94.3%). The inability to cross 4 complete subclavian occlusions and the iatrogenic dissection of 1 common carotid artery lesion accounted for the 5 initial failures. Complications occurred in 17.8% of 73 subclavian and innominate procedures, including access-site bleeding in 6 and distal embolization in 2. Ischemic strokes occurred in 2 of 14 common carotid interventions (14.3%), both of which were performed in conjunction with ipsilateral carotid bifurcation endarterectomy. The 30-day mortality rate was 4.8% for the entire group. By means of life-table analysis, 84% of the subclavian and innominate interventions, including initial failures, remain patent by objective means at 35 months. No patients have required reintervention or surgical conversion for recurrence of symptoms. Of the 11 patients available for follow-up study who underwent common carotid interventions, 10 remain stroke-free at a mean of 14.3 months. CONCLUSION: Angioplasty and primary stenting of the subclavian and innominate arteries can be performed with relative safety and expectations of satisfactory midterm success. Endovascular repair of common carotid artery lesions can be performed with a high degree of technical success, but should be approached with caution when performed in conjunction with ipsilateral bifurcation endarterectomy.

Vascular claudication: how to individualize treatment.

The development of angioplasty and stenting, along with the improvement of surgical procedures, have given physicians more options for treating claudication. However, most patients with intermittent claudication do not need a revascularization procedure, or even angiography. They do need an assessment of their coronary and carotid arteries. We present a treatment approach based on risk factor modification, symptom severity, and the risks and benefits of various procedures.

Design of a potent novel endotoxin antagonist.

BACKGROUND: Bactericidal permeability increasing protein (BPI) binds to and neutralizes lipopolysaccharide (LPS, endotoxin). Small synthetic peptides based on the amino acid sequence of the LPS binding domain of BPI neutralize LPS, albeit inefficiently. Although the LPS binding domain of native BPI possesses a beta-turn secondary structure, this structure is not present in small derivative peptides. The purpose of this study was to determine whether the addition of a beta-turn to a BPI-derived peptide is associated with more potent endotoxin antagonism. METHODS: We generated a hybrid peptide (BU3) on the basis of (1) a portion of the LPS binding domain from BPI and (2) amino acids known to initiate a beta-turn. BU3 folds with a beta-turn, and we tested its effects on LPS neutralization and LPS-induced tumor necrosis factor-alpha secretion, comparing it with BPI-derived peptide BG22 that lacks a beta-turn and to an irrelevant peptide (BG16). RESULTS: Compared with BG22, BU3 demonstrated enhanced LPS neutralization and inhibition of LPS-induced tumor necrosis factor-alpha secretion in vitro and a similar diminution of endotoxemia and tumor necrosis factor-alpha secretion in a murine model of endotoxemia. CONCLUSIONS: These data demonstrate the potential for enhancing the biologic activity of a BPI-derived peptide endotoxin antagonist via manipulation of its conformational structure.

Proteinase-free myeloperoxidase increases airway epithelial permeability in a whole trachea model.

In cystic fibrosis the bronchiectatic conducting airways have large numbers of neutrophils in their walls and in their luminal contents. The neutrophil's primary granule enzyme activities of elastase and peroxidase are increased in the sputum of these patients. It has been postulated that these enzymes--together or individually--act to damage the airway epithelium. However, only peroxidase activity has consistently correlated with the degree of structural and functional airway disease in these patients with leakage of plasma protein into the airway lumen (Regelmann et al., Pediatr Pulmonol, 1995; 19:1-9). The present study was designed to test whether human neutrophil-derived myeloperoxidase can independently produce bronchial epithelial damage without the presence of proteases, as measured by increased permeability of the airway epithelium. Human peripheral blood neutrophils were purified, their primary granules isolated, and their peroxidase purified using affinity and ion exchange column chromatography. Activity of the proteinase-free peroxidase was measured using a chromogenic substrate. The effect of this peroxidase on the permeability of excised rat tracheas was measured using radioactive and fluorescent-labeled non-ionic molecules of varying molecular weight. Rat tracheas exposed to 15 minute treatments with either 130 U of peroxidase or hydrogen peroxide (10(-5) M) did not show a significant increase in the permeability of the epithelium to [3H]inulin, [14C]sucrose, and fluorescein isothiocyanate dextran 20 compared with control tracheas. However, those tracheas exposed to 130 U peroxidase followed by 10(-5) M hydrogen peroxide showed an increased permeability to each of the three test solutes. We conclude that proteinase-free myeloperoxidase, in the presence of non-toxic concentrations of its substrates, hydrogen peroxide and halide, produced increases in permeability to non-ionic molecules in the rat trachea within 15 minutes.

Percutaneous transluminal angioplasty and primary stenting of the iliac arteries in 288 patients.

PURPOSE: This study reports the initial and late results of percutaneous transluminal angioplasty (PTA) and intravascular stenting for atherosclerotic occlusive disease of the iliac arteries. METHODS: The preprocedural and postprocedural clinical records, arteriograms, segmental limb pressure measurements (ankle-brachial [ABI] and thigh-brachial [TBI] indexes), and pulse volume recordings of 288 patients who underwent PTA and primary stenting of the common iliac (354, 69.4%) and external iliac (156, 30.6%) arteries were reviewed. Initial and late clinical, hemodynamic, and angiographic success were assessed by objective criteria. Data on patients who underwent unsuccessful attempts at iliac stent placement are unavailable; results are not reported on an intent-to-treat basis. RESULTS: Clinical follow-up data (mean, 11.9 months) are available for 268 of 288 patients (93.1%) and for 394 of 424 limbs (92.9%). The initial success rates, as determined by TBI, ABI, and clinical limb status, were 90.2%, 87.8%, and 74.6%, respectively. The Kaplan-Meier estimates of angiographic patency (101 arteries) were 96%, 81%, and 73% at 6, 12, and 24 months. Cumulative patency rates were 84%, 76%, and 57% on the basis of TBI, ABI, and clinical limb status at 24 months. Factors associated with initial success included the need for multiple stents (p = 0.0001), a higher degree of initial stenosis (p = 0.0001), lower severity of baseline ischemia (p = 0.007), younger age (p = 0.0015), and the preprocedural patency of the ipsilateral superficial femoral artery (p = 0.002). A higher degree of initial stenosis (p < 0.001) and superficial femoral artery patency (p = 0.004) were also associated with late success. CONCLUSIONS: PTA and stenting of the iliac arteries is associated with reasonable angiographic, hemodynamic, and clinical success. The outcome is favorably affected by higher initial severity of stenosis and greater extent of disease, lower severity of baseline ischemia, younger age, and by patency of the ipsilateral superficial femoral artery.

Conversion of HMOs and hospitals: what's at stake?

Because for-profit conversions of nonprofit organizations are regulated under trust law at the state level, their health policy implications have generally not been part of the process. This paper provides a health policy framework for assessing conversions of hospitals and health maintenance organizations (HMOs). It begins with basic differences in ownership forms and identifies considerations on both sides of the conversion question. The analysis turns on the extent of the social benefits of nonprofits: the regulatory tool provided by tax exemptions, trustworthiness in the presence of informational asymmetries, and community benefit activities. The analysis and the evidence suggest that the nonprofit form continues to hold significant advantages in health care that bear consideration by policymakers faced with conversion proposals.

Limitations of percutaneous transluminal angioplasty with stenting for femoropopliteal arterial occlusive disease.

PURPOSE: To review the results of intravascular stents used to treat superficial femoral artery (SFA) occlusive disease and to assist in patient selection for this procedure. METHODS AND RESULTS: We evaluated 55 patients who underwent balloon angioplasty and stenting of SFA long-segment disease and compared the results with those in the current literature. In our patient group, the SFA mean lesion length was 16.5 cm with the resting ankle-brachial index of 0.48 +/- 0.19. Hemodynamic improvement to an ABI of 0.71 +/- 0.23 (P = .001) and clinical benefit (56%) were maintained at 13.8 months. Primary and secondary patency rates were 22% and 46%, respectively, at 12 months. The literature reports patency rates of 29% to 81% primarily and 43% to 96% secondarily. However, the mean lesion length in these reports varied from 3.7 cm to 13.5 cm, and most of these patients had claudication (50% to 92%). Other variable factors determining long-term success may include the number and type of stent, artery occlusion versus stenoses, presence of diabetes mellitus, and smoking status. CONCLUSIONS: Stenting of short-segment SFA disease remains patent more frequently than for long-segment disease, and may be applicable in patients with disabling claudication or critical limb ischemia. Surgical revascularization is preferred for long-segment disease, with stenting reserved for patients with limb-threatening ischemia and no surgical alternative.

Trust and trustworthy care in the managed care era.

Trust is essential to the doctor/patient relationship, but trust in physicians' fiduciary ethic has become less plausible as a protector of patients' interests. The rise of managed care often is seen as undermining the fiduciary ethic and lessening the trustworthiness of care. But can managed care enhance that trustworthiness? Four possible sources of trustworthiness in managed care are discussed: ethical standards in the managed care industry, nonprofit organizations, physician control, and performance monitoring by purchasers. Limitations on all of these fronts suggest the continuing importance of a strong fiduciary ethic on the part of physicians who make patient care decisions.

Medical professionalism under managed care: the pros and cons of utilization review.

We contend that the full consequences of managed care for American medicine and health care professionals can be more fully understood if strategies for managing care are identified-in particular, strategies for the administrative oversight of professional decision making. In this paper we apply this perspective to the study of third-party utilization review, making use of a national survey of firms contracting to provide prior authorization for hospitalization in 1992. Survey data suggest that (1) existing approaches to utilization review differ greatly among review firms; (2) review practices that might improve agency and accountability seem to be overlooked by most review firms; and (3) a large number of review firms employ practices that undermine professional autonomy in seemingly inappropriate ways.

High incidence of restenosis/reocclusion of stents in the percutaneous treatment of long-segment superficial femoral artery disease after suboptimal angioplasty.

PURPOSE: To evaluate the efficacy of intravascular stents used to treat long-segment stenoses and occlusions of the superficial femoral artery (SFA) after suboptimal angioplasty. METHODS: Fifty-eight limbs in 55 patients who underwent stenting of the SFA were identified from a vascular registry. Indications for stent placement after suboptimal PTA included flow-limiting dissection, residual pressure gradient (>15 mm Hg) or stenosis (>30%), or failure to establish initial patency. Lesion length ranged from 6 to 35 cm (mean, 16.5 cm). Endpoints for primary patency were: restenosis of >50%, reocclusion, or diminution of the postprocedure ankle-brachial index greater than 0.15. RESULTS: The mean ankle-brachial index improved from 0.48 +/- 0.19 to 0.71 +/- 0.23 (p = 0.001). Primary patency rates by Kaplan-Meier estimates at 1 month, 6 months, and 1 year were 88%, 47%, and 22%, respectively. Secondary patency rates were 94% at 1 month, 59% at 6 months, and 46% at 1 year. The median time to reaching an endpoint of restenosis or reocclusion was 6 months primarily and 9 months secondarily. Clinical improvement at the time of latest follow-up occurred in 56% of patients (mean, 13.8 months). Periprocedural complications occurred in 24.5% of patients with the first intervention. The only factor that favorably influenced outcome was improvement in clinical category after the procedure (p = 0.001). CONCLUSIONS: There was a high incidence of restenosis and reocclusion with long-segment SFA disease that required stents to achieve initial success. Despite close surveillance and reintervention, anatomic patency at 1 year was poor. However, clinical benefit was maintained in the majority of patients. The outcome was similar in the claudication population compared with those who had limb-threatening ischemia. Percutaneous revascularization of long-segment SFA disease requiring stents should be reserved for patients with critical limb ischemia for which no reasonable surgical alternative exists.

Macrophages expressing a fusion protein derived from bactericidal/permeability-increasing protein and IgG are resistant to endotoxin.

OBJECTIVES: To generate a recombinant fusion protein (FP) based on the endotoxin-binding domain of bactericidal/permeability-increasing protein (BPI) and the constant domain of IgG and to test its ability to inhibit lipopolysaccharide (LPS)-induced macrophage tumor necrosis factor alpha (TNF-alpha) secretion. DESIGN: A murine macrophage cell line, RAW 264.7, was transfected with a BPI-IgG FP before incubation with LPS. The amount of LPS-induced TNF-alpha protein secreted was measured and compared with that secreted by cells transfected with a control construct. SETTING: Basic science research laboratory. MAIN OUTCOME MEASURES: Secreted TNF-alpha protein concentration. RESULTS: After transfection, RAW 264.7-cell FP expression was detected in cell lysates and supernatants. At each LPS dose tested, cells transfected with the FP gene secreted less TNF-alpha than did cells transfected with a control construct. CONCLUSIONS: The FP possesses substantial antiendotoxin activity, as delineated by inhibition of LPS-induced TNF-alpha secretion by murine macrophages transfected with the fusion gene construct. In the future, such FP may be used as a clinical reagent to reduce the morbidity and mortality associated with serious gram-negative bacterial infections in surgical patients.

A novel endotoxin antagonist attenuates tumor necrosis factor-alpha secretion.

Twenty-seven amino acid peptides with sequences corresponding to a proposed endotoxin binding region of bactericidal permeability increasing protein (BPI):1) inhibit lipopolysaccharide induced macrophage tumor necrosis factor-alpha (TNF-alpha) secretion, 2) have bactericidal activity against gram-negative bacteria, and 3) protect mice from a lethal lipopolysaccharide (LPS) challenge. Unfortunately, peptides have a short halflife in vivo. Therefore, we have chemically conjugated the BPI based peptide, BG38, to a larger carrier protein, keyhole limpet hemocyanin (KLH), and characterized its ability: 1) to inhibit LPS induced macrophage TNF-alpha secretion and 2) to decrease plasma endotoxin and TNF-alpha levels following an i.v. injection of E. coli 0111:B4 LPS. BG38-KLH inhibited cultured macrophage TNF-alpha secretion in response to LPS derived from four pathogenic strains of gram-negative bacteria in a dose dependent manner (>90% inhibition at 50 microgram/ml, P < 0.05 Student's t test). BG38-KLH also decreased serum endotoxin (>90%, P < 0.05 Student's t test) and peak TNF-alpha levels (>30% inhibition, P < 0.05 Student's t test) following E. coli LPS challenge in a murine gram-negative bacterial sepsis model. Novel endotoxin antagonists based upon a small domain of BPI represent promising reagents for the treatment of serious gram-negative bacterial infections.