Metal excretion and magnesium retention in patients with intermittent claudication treated with intravenous disodium EDTA

Sixty patients with intermittent claudication participated in a double-blind placebo-controlled trial of 20 courses of intravenous chelation therapy with 3 g of disodium EDTA vs placebo during 5-9 weeks. After the first infusion, the 24-h urinary excretion of lead and zinc was approximately 25-fold higher in the EDTA-treated group; relative differences for copper and calcium were smaller. Urinary magnesium excretion in the EDTA-treated group was one-third less than in the control group. After the treatment period, the blood lead concentration had decreased by approximately 73% and the serum zinc concentration by approximately 34%; other changes in blood concentrations were negligible. The loss of essential minerals and the possible redistribution of lead in the body may constitute a disadvantage that should be taken into account in repeated intravenous EDTA treatment.     

The fate of patients with intermittent claudication managed nonoperatively

Of 100 patients with intermittent claudication, followed an average of six years, a surprising 78 per cent either showed improvement or remained stable regarding the presenting complaint. However, 39 per cent showed evidence of further progression of atherosclerosis. In patients with femoropopliteal occlusion in one leg, almost 40 per cent had occlusion in the one leg, almost 40 per cent had occlusion in the other leg after two to six years. The amputation rate was 7 per cent but six of these seven patients had severe diabetes. This study suggests that we are not causing limb loss by adhering to stringent criteria for bypass grafting. It also suggests that the patient with intermittent claudication without associated grave signs has a better than 50 per cent chance of improving and a better than 60 per cent chance that his disease will not show evidence of significant progression during a five to six year period. Such data should be taken into consideration when patients are considered for arterial reconstruction.     

Dissection of the infrarenal aorta treated by stent graft placement

A spontaneous cystic keratinizing epithelioma in the lung of a 704-day-old female Hsd:Sprague-Dawley rat is described. The rat had a white subpleural discoloration on 1 diaphragmatic lobe at necropsy. Microscopically, a central keratin mass, surrounded by a multilayered squamous epithelium of varying thickness, was found. In the periphery of the tumor, epithelial nests projected multifocally into the adjacent alveolar spaces. Immunohistochemical labeling of nuclei by PCNA (proliferating cell nuclear antigen) revealed proliferative activity in 1 or 2 peripheral cell layers in most locations. To the best of the authors' knowledge, this is the first report dealing with the morphological and immunohistochemical features of a spontaneous cystic keratinizing epithelioma in a rat.     

Increased nitric oxide deactivation by polymorphonuclear leukocytes in patients with intermittent claudication

PURPOSE: Local activation of polymorphonuclear leukocytes (PMNLs) is considered an important aspect of the pathogenesis of intermittent claudication, although concrete mechanisms of their effects on circulatory homeostasis in peripheral atherosclerotic disease remain unclear. This study evaluated the ability of PMNLs to deactivate nitric oxide (NO), a key regulator of regional circulation, as a possible factor determining PMNL involvement into ischemic disorders in patients who have intermittent claudication before and after vascular reconstruction. METHODS: A total of 57 patients who had peripheral occlusive disease in an aortofemoral segment before surgical treatment (group 1) and 65 patients who had similar occlusive lesions and other clinical and demographic data 6 to 12 months after undergoing inflow vascular reconstruction (group 2) were examined. All patients from group 2 had anatomically patent grafts; their satisfaction and level of function after surgical treatment were assessed by a five-point questionnaire. The sex- and age-matched control group included 35 subjects. NO activity was bioassayed by measuring its ability to increase cyclic guanosine monophosphate (cGMP) accumulation in rat fetal lung-cultured fibroblasts (RFL-6 cells). The ability of PMNLs to deactivate NO was characterized as the percent decrease in NO-induced cGMP accumulation in RFL-6 cells. RESULTS: Stimulated PMNLs caused inhibition of the activity of authentic NO; accumulation of cGMP induced by sodium nitroprusside was not affected. PMNLs from patients with peripheral atherosclerotic disease either before or after vascular reconstruction had a more marked capacity of NO inactivating than the cells from healthy subjects. For both groups of patients, levels of PMNL-induced NO deactivation were higher for patients with diabetes, and especially both diabetes and arterial hypertension. For both groups of patients, there was no correlation between levels of PMNL-induced NO deactivation and resting ankle-brachial indexes (ABIs). In contrast, close correlation was revealed between levels of PMNL-induced NO deactivation and postexercise ABIs and percent decrease in resting ABIs after exercise in patients evaluated either before or after surgical treatment. CONCLUSIONS: The ability of stimulated PMNLs to deactivate NO is elevated in peripheral occlusive disease and may be implicated in the pathogenesis of intermittent claudication. In patients who underwent successful recanalization of magistral arteries, levels of PMNL-induced NO deactivation remained higher than in control subjects. The increase in the ability of PMNL to deactivate NO positively correlated to ABI decreases after exercise in patients with peripheral occlusive disease either before or after surgical treatment.     

Endovascular stent graft placement for patients with aortic aneurysm and end-organ dysfunction

Endovascular stent grafts (ESGs) for the treatment of aortic aneurysm is becoming popular because it is less invasiveness for the patient. This new modality seems to be especially useful for treating high risk patients, such as those with end-organ dysfunction. In this study we retrospectively analyzed the results of ESG placement for patients with renal or hepatic dysfunction. From January 1996 to December 1997, six patients with end-organ dysfunction (two with descending thoracic aneurysm and four with abdominal aneurysm) underwent ESG placement. Five of these patients had renal dysfunction, with serum creatinine levels of 2.0 mg/dl or greater, and the remaining patient had hepatic dysfunction with a prothrombin time less than 60%. One of the patients also had severe atherosclerotic disease with a history of multiple brain infarctions. All the patients received custom made endovascular spiral Z stents covered with a woven Dacron (DuPont Co., Wilmington, DE) graft, which was delivered via a femoral artery under local anesthesia. None of the patients showed significant changes in renal or hepatic function after the procedure. None of the five patients with renal dysfunction needed hemodialysis after ESG placement, although the mean preoperative level of serum creatinine and blood urea nitrogen was 3.4 mg/dl and 42.0 mg/ dl, respectively. All the patients left the recovery room on postoperative day 1. These results indicated that endovascular stent graft placement is extremely useful in the treatment of aortic aneurysm patients with end-organ dysfunction.     

Progressive intermittent claudication is associated with impaired fibrinolysis

OBJECTIVES: Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines. We examined the effect of hydrocortisone on shock reversal, hemodynamics, and survival in this particular setting. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Two intensive care units of a University hospital. PATIENTS: Forty-one patients with septic shock requiring catecholamine for >48 hrs. INTERVENTIONS: Patients were randomly assigned either hydrocortisone (100 mg i.v. three times daily for 5 days) or matching placebo. MEASUREMENTS AND MAIN RESULTS: Reversal of shock was defined by a stable systolic arterial pressure (>90 mm Hg) for > or =24 hrs without catecholamine or fluid infusion. Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients, 15 (68%) and 4 (21%) achieved 7-day shock reversal, respectively, a difference of 47% (95% confidence interval 17% to 77%; p = .007). Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups. At 28-day follow-up, reversal of shock was higher in the hydrocortisone group (p = .005). Crude 28-day mortality was 7 (32%) of 22 treated patients and 12 (63%) of 19 placebo patients, a difference of 31% (95% confidence interval 1% to 61%; p = .091). Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival. There were no significant differences in outcome in responders and nonresponders to a short corticotropin test. The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups. CONCLUSIONS: Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of >96 hrs resulted in a significant improvement in hemodynamics and a beneficial effect on survival. These beneficial effects do not appear related to adrenocortical insufficiency.     

Aortoiliac surgery in chronic hemodialysed patients

Thirty eight patients on chronic hemodialysis were operated on for treatment of complicated aortoiliac atherosclerosis: 31 had aneurysms and 7 had stenotic or obstructive lesions. The 35 male and three female patients ranged in age from 39 to 78 years (mean: 55.3). The duration of hemodialysis treatment before the operation ranged from one month to 22 years but 80% of the patients were operated on during the first five years following the beginning of maintenance hemodialysis. The surgical repairs consisted of long aorta to femoral artery prosthesis in obstructive lesions and of short prostheses in cases of aneurysms so as not to make more difficult subsequent renal transplantation. All patients were operated on from 6 to 18 hours after a dialysis. Hemodialysis was resumed on the day of surgery in few patients or later according to the level of kalemia. Postoperative mortality rate was 10.5% and morbidity 13.5%. Only seven patients underwent secondary renal transplantation. The long-term survival rate was 43% at five years and 11% at ten years. Late deaths were due to coronary artery disease or to worsening of arterial lesions in the lower limbs.     

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.     

Operator volume and outcome of patients undergoing coronary stent placement

OBJECTIVES: The aim of this study was to assess the relation between operator experience in coronary stent placement procedures and the clinical outcome of patients. BACKGROUND: The results of coronary balloon angioplasty are closely related to the experience of the operator performing the procedure. Data on the effect of operator experience on the results after coronary stent placement are missing. METHODS: The study included 3,409 consecutive patients undergoing coronary stent placement for the management of coronary artery disease. A composite end point of cardiac death, myocardial infarction and aortocoronary bypass surgery during the first 30 days after the intervention, was the primary end point and the procedural failure was the secondary end point of the study. RESULTS: Adverse clinical outcome occurred in 2.99% of the 3,409 patients undergoing coronary stent placement. Procedural failure was recorded in 2.08% of the patients. Operator volumes above 483 procedures were associated with a risk-adjusted adverse outcome rate of 1.70%+/-1.28%, which is significantly lower than the overall rate of 2.99%. Operator yearly volumes of under 90 procedures were associated with a risk-adjusted adverse outcome rate of 4.59%+/-1.17%, which is significantly higher than the overall rate of 2.99%. The operator experience was an independent predictor even after adjusting for the effect of other risk factors. The analysis demonstrated that an experience of at least 100 procedures is required to obtain better outcome even in patients with simple coronary lesions and that operators should perform at least 70 procedures annually to expect a better outcome in patients with both simple and complex coronary lesions. CONCLUSIONS: Operator experience is a significant and independent predictor of the outcome of patients undergoing coronary stent placement. An experience of at least 100 procedures and an annual volume of at least 70 procedures are required to ensure a significantly better outcome after coronary stent implantation.     

Aortoiliac stent deployment versus surgical reconstruction: analysis of outcome and cost

PURPOSE: The purpose of this study is to compare complication rate, primary patency, and cost of stent deployment with direct surgical reconstruction for the treatment of severe aortoiliac occlusive disease. METHODS: From March 1, 1992, to May 31, 1996, 119 patients receiving treatment for aortoiliac occlusive disease were analyzed after exclusions. Sixty-five patients had stent deployment and 54 patients had surgical reconstruction. Data were evaluated within and between the groups by univariate and multivariate logistic regression, life-table, t-test, and cross tabulation with chi2 analysis. RESULTS: There was no significant difference between the groups with regard to demographic features or presenting symptoms (all p values > 0.07). Incidence of procedure-related complications was similar (p = 0.30). However, there were more systemic complications in the surgery group (15 versus 2; RR = 5.5, p < 0.01) and more vascular complications in the stent group (16 versus 3; RR = 12, p < 0.002). Incidence and type of late complications were not appreciably different (all p values > 0.05). Cumulative primary patency rate of bypass grafts was significantly better than stented iliac arteries at 18 months (93% versus 77%), 30 months (93% versus 68%) and 42 months (93% versus 68%); p = 0.002, log rank. Multivariate analysis identified female gender (RR = 4.6, p = 0.03), ipsilateral SFA occlusion (RR = 5.6, p = 0.01), procedure-related vascular complication (RR = 9.7, p = 0.002), and hypercholesterolemia (RR = 5.0, p = 0.02) as independent predictors of bypass graft or stent thrombosis. Mean total hospital cost per limb treated did not differ significantly between surgery and stent deployment groups ($9383 versus $8626, respectively; p = 0.66, t-test). CONCLUSIONS: Treatment of severe aortoiliac occlusive disease by surgical reconstruction or stent deployment has a similar complication rate. Mean hospital cost per limb treated is essentially equal. However, cumulative primary patency rate of bypass grafts is superior to stents. Therefore, considering the elements of cost and patency, surgical revascularization has greater value. The benchmark for cost-effective treatment of severe aortoiliac occlusive disease is direct surgical reconstruction.     

Antithrombotic therapy after coronary stent placement

Subacute stent thrombosis and hemorrhagic complications due to intensive anticoagulant therapy limit the clinical benefit of coronary stenting. Antithrombotic therapy after coronary stent placement has not been standardized yet. From January 1994 to December 1995 a total of 338 Palmaz-Schatz stents were implanted in 285 patients. Procedural success rate was 98.8%. In the initial period, after stent placement, patients were treated with acetylsalicylic acid (ASA) and warfarin (135 patients, Group A), while subsequently, according to the results of other studies, patients were treated with ASA plus ticlopidine (146 patients, Group B). Two hours after sheath removal, Group A patients were treated with intravenous heparin until therapeutic INR (2.5-3.5) was reached; warfarin was stopped 3 months later. In Group B patients 2 hours after sheath removal a treatment with subcutaneous heparin 25,000 IU/die plus ticlopidine 500 mg/die was started. Subcutaneous heparin was maintained until hospital discharge, ticlopidine was stopped after 1 month and ASA was maintained indefinitely. There were no significant differences in baseline characteristics between the two groups. Most patients had unstable angina and in the majority of cases the stent was implanted due to intimal dissection after balloon dilation. Eleven patients had subacute thrombosis of the stent (3.9%): 9 patients were in Group A (6%) and 2 patients were in Group B (1.3%; p = 0.04). Seven patients (6 in Group A, 1 in Group B) were treated with emergency coronary angioplasty and 3 (2 in Group A, 1 in Group B) with coronary bypass; nevertheless 7 patients (6 in Group A, 1 in Group B) had an acute myocardial infarction. Eight patients (6 in Group A, 2 in Group B) had major bleeding due to a large groin hematoma requiring blood transfusion or vascular surgery. In conclusion, after coronary stenting antithrombotic therapy with ASA plus ticlopidine, as compared with anticoagulant therapy, reduces the incidence of both cardiac events and hemorrhagic complications.     

The white blood cell adhesion molecule E-selectin predicts restenosis in patients with intermittent claudication undergoing percutaneous transluminal angioplasty

BACKGROUND: Experimental studies have shown that endothelial dysfunction is an early event preceding restenosis. Monocytes and neutrophils have been shown to bind to damaged endothelium via the cell adhesion molecules (CAMs). The selectins are involved in capturing the leukocytes and tethering them to the endothelium. E-selectin is a CAM that is only expressed on activated endothelial cells. Its ligands are expressed on monocytes and neutrophils and it has been found to exist in a soluble form. This soluble form may represent a marker for endothelial damage and may be a precursor of smooth muscle proliferation. METHODS AND RESULTS: Fifty-four patients who were undergoing peripheral arterial balloon angioplasty had blood sampled before angioplasty. E-selectin was measured in plasma with the use of an ELISA. At follow-up angiogram, 30% (n=14) of the patients had restenosed at 1 year. There was a significant difference in baseline E-selectin levels in patients who restenosed compared with those who did not (65.3 ng/mL [58.25 to 78.05] versus 52.3 [34.2 to 62.1], Mann-Whitney U, P<.007). Endothelial activation with subsequent adherence of white blood cells is an important step in restenosis. CONCLUSIONS: We have shown an increased level of shed E-selectin in patients destined for restenosis and suggest that this work further supports a role for white blood cell/endothelial interaction in restenosis after angioplasty.     

Randomised comparison of primary stent placement versus primary angioplasty followed by selective stent placement in patients with iliac-artery occlusive disease. Dutch Iliac Stent Trial Study Group

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is a safe, simple, and successful treatment for intermittent claudication caused by iliac-artery occlusive disease. Primary stent placement has been proposed as more effective than PTA. We compared the technical results and clinical outcomes of two treatment strategies-primary placement of a stent across the stenotic segment of the iliac artery, or primary PTA followed by selective stent placement when haemodynamic results were inadequate. METHODS: We randomly assigned 279 patients with intermittent claudication, recruited from departments of vascular surgery, either to direct stent placement (group I, n=143) or primary angioplasty (group II, n=136), with subsequent stent placement in case of a residual mean pressure gradient greater than 10 mm Hg across the treated site. The main inclusion criterion was intermittent claudication on the basis of iliac-artery stenosis of more than 50%, proven by angiography. All patients had a clinical assessment before intervention and at 3, 12, and 24 months. Clinical success was defined as improvement of at least one clinical category. Secondary endpoints were initial technical results, procedural complications, cumulative patency as assessed by duplex ultrasonography, and quality of life. FINDINGS: In group II, selective stent placement was done in 59 (43%) of the 136 patients. The mean follow-up was 9.3 months (range 3-24). Initial haemodynamic success and complication rates were 119 (81%) of 149 limbs and 6 (4%) of 143 limbs (group I) versus 103 (82%) of 126 limbs and 10 (7%) of 136 limbs (group II), respectively. Clinical success rates at 2 years were 29 (78%) of 37 patients and 26 (77%) of 34 patients in groups I and II, respectively (p=0.6); however, 43% and 35% of the patients, respectively, still had symptoms. Quality of life improved significantly after intervention (p<0.05) but we found no difference between the groups during follow-up. 2-year cumulative patency rates were similar at 71% versus 70% (p=0.2), respectively, as were reintervention rates at 7% versus 4%, respectively (95% CI -2% to 9%). INTERPRETATION: There were no substantial differences in technical results and clinical outcomes of the two treatment strategies both at short-term and long-term follow-up. Since angioplasty followed by selective stent placement is less expensive than direct placement of a stent, the former seems to be the treatment of choice for lifestyle-limiting intermittent claudication caused by iliac artery occlusive disease.     

Renal artery stent placement for the management of ischemic nephropathy

The aim of this work was to determine the oesophageal transit time (OTT) of a bolus using the biomagnetic technique and compare the results to those obtained by means of scintigraphy. For the biomagnetic evaluation, a test meal (yoghurt) uniformly labelled with 5 g of powder ferrite was swallowed in a single gulp by 19 normal volunteers in the upright position. One sensor (first order gradiometer) was placed at the furcula and a second one at the xiphoid process to detect the passage of the test meal and the magnetic signal output was recorded in a computer. The OTT was determined by plotting the voltage signal against time. The scintigraphic technique was used in the same volunteers: the test meal was labelled with less than 350 MBq of 99mTc-phytate and swallowed in the same way. The bolus transit was recorded at 4 frames s(-1) (100-120 frames acquisition) and the OTT was determined by drawing two regions of interest in the same areas as the sensors. The results were determined by plotting counts against time. The averages for OTTs were 3.8 +/- 0.8 s for the scintigraphic technique and 4.6 +/- 0.9 s for the biomagnetic technique. Although scintigraphic OTT was significantly shorter than magnetic OTT, there was a significant correlation between them. We conclude that the biomagnetic study may be used to evaluate OTT.