Efficacy, safety and feasibility of intravenous iloprost in the domiciliary treatment of patients with ischemic disease of the lower limbs.

OBJECTIVE: Intravenous iloprost is an important option in the treatment of ischemic disease of the lower limbs; however, the administration of therapy is frequently compromised because of the need for long cycles of infusion in a hospital setting. The aim of the study is to evaluate the efficacy, safety, feasibility, and the economic impact of infusion therapy in the outpatient setting. PATIENTS AND METHODS: Twenty-four consecutive patients were treated with iloprost at their homes where they were administered a slow rate of infusion for 24 hours a day, during 9.9 ± 2.3 days, with a portable syringe pump (Infonde®). RESULTS: The clinical condition of patients evaluated with the modified SVS/ISCVS scale significantly improved after treatment (+1.29 ± 1.04 points vs. baseline, p<0.001). The drug was well tolerated; neither significant adverse events associated with medication nor problems related to venous access were recorded at home. Ninety-six percent of patients successfully completed the entire treatment cycle, and the evaluation questionnaire showed a high acceptance of the therapy. From the perspective of the hospital authority, lower direct medical costs were estimated for the domiciliary infusion process compared with the inpatient infusion setting. CONCLUSIONS: Treatment with iloprost in the outpatient setting is effective, safe, feasible, and more acceptable to patients than infusion at the hospital. In addition, it has a favorable economic and organizational impact on the medical ward.

Microsomal enzyme inducers raise plasma high-density lipoprotein cholesterol levels in healthy control subjects but not in patients with primary hypoalphalipoproteinemia.

In this study we compared the ability of phenytoin, a microsomal enzyme inducer, to raise plasma high-density lipoprotein (HDL) levels in normolipidemic subjects and patients with primary hypoalphalipoproteinemia. In healthy control subjects, phenytoin caused a dose-dependent increase of plasma HDL, HDL2, and HDL3 cholesterol levels, up to 40% to 50%. Minor changes were recorded in the plasma concentrations of apolipoprotein (apo) A-I and apo A-II; the plasma level of the cholesteryl ester transfer protein (CETP) decreased by 42%. In contrast, none of the patients with hypoalphalipoproteinemia had changes in plasma HDL, HDL2, or HDL3 cholesterol, apo A-I, apo A-II, or CETP levels. These findings indicate that microsomal enzyme inducers are unsuitable to increase plasma HDL levels in high-risk patients with primary hypoalphalipoproteinemia, and they disclose a new mechanism, that is, decreased CETP-mediated transfer of cholesterol out of HDL, for the HDL-raising effect of microsomal enzyme inducers in healthy individuals.

Glycosylation pattern of platelet glycoprotein IIb and IIIa in type IIa hypercholesterolemia.

The microheterogeneity and polymorphism of platelet membrane glycoproteins IIb and IIIa from hypercholesterolemic type IIA patients and from normolipidemic controls were compared by isoelectric focusing followed by immunological detection. Their size and the extent of glycosylation were investigated by polyacrylamide gel electrophoresis and carbohydrate affinity stain. No qualitative or quantitative differences could be detected, either within each test group or between the two groups. This finding rules out the hypothesis that altered molecular forms of the glycoproteins forming the fibrinogen receptor might be involved in the pathogenesis of platelet hyperaggregability in hypercholesterolemic patients.

Lipoprotein changes and increased affinity of LDL for their receptors after acipimox treatment in hypertriglyceridemia.

Modifications in plasma low and high density lipoprotein (LDL and HDL) subfraction distribution, as well as the regulation of cellular LDL metabolism by hypertriglyceridemic LDL were tested before and after treatment with acipimox, a nicotinic acid derivative, in 11 type IV hyperlipidemic patients. Large, less dense LDL particles were found in plasma after acipimox treatment, reflecting compositional changes, characterized by a 25.4% increase in cholesteryl ester content and by a 46.2% reduction of triglycerides in LDL. HDL subfractions were only slightly modified, with an increase of dense, cholesteryl ester-enriched and triglyceride poor HDL3 particles. The LDL (B,E) receptor activity in humans skin fibroblasts of LDL isolated before and after treatment was also evaluated. Hypertriglyceridemic LDL proved rather inefficient in regulating receptor activity with a close to 30% reduction vs. normal LDL in the capacity to inhibit receptor-mediated uptake and degradation of 125I-LDL. Such abnormality was fully corrected after acipimox. The reported findings indicate that acipimox treatment in type IV patients, in spite of a relatively modest plasma triglyceride reduction, can markedly modify LDL distribution and composition, normalizing the defective interaction of hypertriglyceridemic LDL with the LDL (B,E) receptor.

Plasma triglycerides and lipoprotein(a): inverse relationship in a hyperlipidemic Italian population.

The relationship between plasma lipoprotein(a) (Lp(a)) levels and other clinical/biochemical variables was investigated in 1200 consecutive hyperlipidemic patients. Plasma Lp(a) concentrations were measured by a sandwich-ELISA method, while the patients were either on diet or diet plus lipid-lowering drugs; 38% of them had a plasma Lp(a) level > 30 mg/dl. The median plasma Lp(a) concentration and the frequency of Lp(a) > 30 mg/dl were significantly lower in individuals with severe hypertriglyceridemia vs. hypercholesterolemics (HC) or mixed hyperlipidemics (M-HLP), but similar to normolipidemic healthy controls. Patients with isolated moderate hypertriglyceridemia had Lp(a) levels intermediate between HC and M-HLP subjects. The in vitro addition of triglyceride-rich lipoproteins to normotriglyceridemic plasma did not affect the Lp(a) measurement. Plasma Lp(a) concentrations in the whole hyperlipidemic population correlated negatively with triglycerides and positively with total cholesterol, HDL-cholesterol and age, being unrelated to either body mass index or lipid-lowering treatment. In HC patients, the presence of tendon xanthomas was associated with twofold higher Lp(a) levels. These findings argue for a regulatory role of triglycerides on plasma Lp(a) levels in hyperlipidemic patients.

Cholesterol efflux from Fu5AH hepatoma cells induced by plasma of subjects with or without coronary artery disease and non-insulin-dependent diabetes: importance of LpA-I:A-II particles and phospholipid transfer protein.

We measured the capacity of human plasma to induce cholesterol efflux from Fu5AH rat hepatoma cells in four groups of men with or without non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD). Plasma from men with both NIDDM and CAD (n = 47) had the lowest efflux capacity (17.3 +/- 3.6%) whereas healthy control subjects with neither diabetes nor CAD (n = 25) had the highest capacity (19.8 +/- 3.4%). The groups with CAD but no diabetes (n = 44) and with NIDDM but no CAD (n = 35) had intermediate efflux values (18.5 +/- 3.8 and 18.5 +/- 3.9%, respectively). In a 2 x 2 factorial ANOVA, the differences were significant with respect to the presence of CAD (P = 0.038) and NIDDM (P = 0.041), with no interaction between the factors. The concentration of HDL particles containing apolipoprotein (apo) A-I but no apo A-II (LpA-I) was not related to efflux capacity in univariate or multivariate analyses. A multivariate regression analysis showed that when controlled for the presence of NIDDM and CAD, the concentration of particles containing both apo A-I and apo A-II (LpA-I:A-II) and plasma phospholipid transfer protein activity were both positively, independently, and significantly (P < 0.001) related to cholesterol efflux capacity.

Elevated triglycerides and low HDL cholesterol in transgenic mice expressing human apolipoprotein A-I(Milano).

In general, plasma concentrations of high density lipoproteins (HDL) are inversely related to the incidence of coronary artery disease. One exception to this trend is individuals with apolipoprotein A-I(Milano) (apo A-IM), a molecular variant of apo A-I, which results in very low plasma apo A-I and HDL-cholesterol levels. Despite these low levels, and other lipoprotein defects, individuals with this mutation have no increased risk for cardiovascular disease. As a first step in proving why apo A-IM carriers appear to be protected from the pro-atherogenic effect of a low HDL, transgenic mice expressing apo A-IM were generated. Mice expressing either wild-type human apo A-I or apo A-IM, together with human apo A-II, were crossed into mice lacking murine apo A-I. Apo A-IM/A-II mice had lower cholesterol and HDL plasma levels compared to apo A-I/A-II mice. Moreover, as in human carriers, apo A-IM mice were characterized by elevated triglyceride plasma levels and by the presence of a population of very small HDL particles. These results indicate that the expression of apo A-IM in a mouse model reproduces the major lipid/lipoprotein abnormalities observed in human carriers. Thus, apo A-IM transgenic mice appear to be a suitable model in which to assess whether the mutation has an anti-atherogenic effect.

Effect of gemfibrozil treatment in hypercholesterolemia on low density lipoprotein (LDL) subclass distribution and LDL-cell interaction.

Gemfibrozil, a widely used fibric acid derivative, corrects hypercholesterolemia in a non-negligible fraction of patients. To investigate the mechanism of the cholesterol-lowering activity of fibric acids, a study was performed in 12 type IIa hyperlipidemic patients treated with gemfibrozil for 12 weeks. Changes in low density lipoprotein (LDL) structure and composition, agonist capacity of LDL against the LDL-receptor in human skin fibroblasts, LDL-receptor activity in mononuclear cells, lecithin:cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, were evaluated. Plasma total and LDL cholesterol levels decreased by 17% and 20% after 12 weeks of treatment, the reduction being directly correlated with the baseline levels (r = 0.75 and 0.78, respectively). The mean LDL diameter increased significantly, from 25.5 to 26.1 nm, while the relative content of small LDL particles (< 25.1 nm) increased from 23.4% to 32.8% of total LDL. Neither the apolipoprotein (apo) B secondary structure nor the affinity of LDL for the LDL-receptor of fibroblasts were affected. The LDL-receptor activity in patients' mononuclear cells increased 3-fold, the rise being unrelated to the plasma cholesterol reduction. LCAT activity did not change, while CETP activity was reduced by 25% (P = 0.13) after treatment. These findings indicate that gemfibrozil causes significant changes in LDL structure that do not, however, affect the LDL interaction with peripheral cells.

Mechanisms of high-density lipoprotein reduction after probucol treatment: changes in plasma cholesterol esterification/transfer and lipase activities.

Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo)A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma.

New devices for carotid reconstruction.

An analysis of the reason for re-exploration of the carotid bifurcation immediately after surgery has demonstrated that in the majority of cases it is a question of defects of the distal part of the seat of CEA. The aim of this paper is to illustrate the use of an originally planned catheter and shunt during carotid surgery that may obviate some of the problems faced daily by surgeons during carotid reconstruction.

Routine ultrasound surveillance after carotid endarterectomy.

Ultrasounds (US) are employed in preoperative carotid disease diagnosis and in carotid endarterectomy (CEA) follow-up. The authors present their experience about postoperative modifications in CEA site with US evaluation with particular interest in restenosis. Clinical and instrumental examinations were performed at intervals 1, 3, 6, 12, and 24 months following surgery. Follow-up data were available on 189 CEAs. In 58 cases a primary closure was performed, whereas in the other 131 cases, a patch was applied. 15 restenosis (7.9%) were seen during the follow-up control period with 2 cases of haemodynamic restenosis (1%). Good results were recorded with PTFE patch angioplasty (restenosis 4.4%), instead of vein (restenosis 14.2%) and a biosynthetic material called Omniflow (restenosis 9.5%). A vein patch dilatation was encountered in 13 applications (30.9%). In conclusion the routine application of US after carotid endarterectomy allowed us to monitor the evolution of the repair processes and of the stenotic lesions from the very beginning.

Rapid improvement of symptomatology with pantoprazole, amoxycillin and metronidazole in Helicobacter pylori-positive duodenal ulcer patients.

BACKGROUND/AIMS: To evaluate the efficacy and tolerability of a new 1-week triple therapy regimen consisting of pantoprazole, amoxycillin and metronidazole. METHODOLOGY: The study involved 51 Helicobacter pylori (H. pylori) positive patients (M:30, F:21, mean age: 52.5 years, range: 24-75) affected with duodenal ulcer in active phase. At baseline and 6 weeks after the completion of treatment, clinical assessment, endoscopy with gastric biopsies, rapid urease test, 13C urea breath test, and serum laboratory analyses were performed. All patients were treated with pantoprazole 40 mg once daily, plus amoxycillin 1 gram tid and metronidazole 250 mg tid for 1 week, and pantoprazole 40 mg once daily for a second week. A clinical diary for daily assessment of symptoms and side effects was completed by patients during the treatment period. RESULTS: Three patients were discontinued from the study. Six weeks after therapy, the ulcer was healed in 47 of 48 patients (97.9%, 95% CI = 93.9-100). The cure rates of H. pylori infection, expressed using both the intention-to-treat and per protocol analyses, were 80.4% (95% CI = 69.5-91.3) and 85.4% (95% CI = 75.4-95.4), respectively. The therapy led to a significant, rapid disappearance or reduction in daytime epigastric pain, from 68.8% on day 1 to 82.2% on day 3 (p < 0.001) and in nocturnal epigastric pain, from 80.6% on day 1 to 93.3% on day 3 (p < 0.001). After 2 weeks of treatment, the percentage of patients completely free of pain was 82.2% for daytime pain and 90.3% for nocturnal pain. A rapid improvement in acid regurgitation, heartburn, nausea and vomiting was also observed with a median value of symptom disappearance of 2 days. The percentages of patients completely symptom-free were 37.5% after 1 day, 54.1% after 3 days, 75% after 2 weeks, and 83.3% after 2 months. H. pylori-cured patients showed a significant decrease in the histological activity of both antral (p = 0.0001) and body (p < 0.008) gastritis. Mild to moderate adverse events were reported by 15 patients. CONCLUSIONS: One week triple therapy with pantoprazole in combination with amoxycillin and metronidazole, followed by a second week of pantoprazole, was well tolerated and highly effective for the 1) rapid improvement or resolution of symptoms; 2) healing of the DU; 3) eradication of H. pylori infection; and, 4) reduction of histological signs of chronic gastritis activity.

Early and late results of biosynthetic ovine carotid angioplasty.

Recent major technical improvements in the field of carotid surgery have been related to anesthesiology and cerebral monitoring. However early embolic events and recurrent stenosis are, after intraoperative ischaemia, the main problems of carotid endarterectomy (CEA) and therefore technical improvements that reduce the incidence of these complications are required. The choice between primary closure and angioplasty is still debated. In the case of angioplasty, the choice of patching material seems to be important in preventing these complications. The Authors present their experience with a biosynthetic ovine patch in carotid surgery. In the period from January 1982 to November 1991, 1013 carotid endarterectomies were performed on 866 patients (659 men, 207 women) with atherosclerotic disease at the carotid bifurcation. In 147 cases a bilateral CEA was performed. Recently, in 37 cases of patch angioplasty, the Authors used the biosynthetic ovine patch. No deaths and no permanent neurological deficit were registered in this series either during awakening or the immediate postoperative period. Of these 37 patients, all except 4, had a minimum follow-up of 24 months. Two cases of non-hemodynamic restenosis were detected, one at 6 and one at 12 months; both were asymptomatic. In this series the total restenosis ratio was 5.5% (2/36), and the cumulative mortality rate 10.8% (4/37) (IMA 2, hepatic insufficiency 1, cerebral hemorrhage 1). The Authors' preliminary experience with this biosynthetic graft as a patching material has been satisfactory. They believe that this biosynthetic graft (Omniflow) on account of its handling and particularly its healing characteristics can be considered as a graft material for patching at the carotid level.

Transrenal E-XL stenting prior to EVAR in the case of abdominal aortic aneurysm associated to proximal aortic neck dissection.

Chronic dissection of proximal aortic neck is a rare occurrence in patients with abdominal aortic aneurysm (AAA) and a gold standard therapy has not been defined so far. Herein we report two successful cases of an original adjunctive procedure involving the transrenal placement of a self-expanding nitinol stent (E-XL aortic stent, Jotec GmbH, Germany) in order to fix a dissection flap in the aortic neck wall prior to the deployment of the bifurcated endograft. Primary technical success and midterm clinical success was achieved in both cases with freedom from any early or late reintervention. Scheduled follow-up angio-CT scans did not show any Type I endoleak, graft migration or renal/visceral arteries complications. According to these findings, patients with an AAA, presenting with a proximal neck with chronic dissection, can be safely and effectively treated by pre-emptive transrenal E-XL stenting and endovascular aneurysm repair.

An original technique for the treatment of symptomatic common carotid artery occlusion and concomitant ipsilateral internal carotid artery stenosis.

Successful hybrid treatment of the total symptomatic acute occlusion of a common carotid artery (CCA) concomitant to ipsilateral internal carotid artery (ICA) stenosis has only been described once in the literature to date. The management of this anatomic distribution of disease can be a challenge both to plan and perform. The aim of this paper is to report an original hybrid revascularization technique for the treatment of two patients with symptomatic CCA acute occlusion and ipsilateral ICA stenosis. Details of the surgical technique and mid-term follow-up are provided.

An accidental subclavian artery cannulation: successful catheter removal by percutaneous vascular stenting.

Central venous catheterisation may sometimes be associated with life-threatening complications. Of these, subclavian artery puncture (infraclavicular approach), though seldom, (incidence 1-2%) following accidental arterial cannulation, may lead to arterial occlusion, embolism, pseudoaneurysms, vessel laceration or dissection or fatal hemorrhaging. Such complications may be even more severe in critically ill patients requiring systemic anticoagulation therapy or those with acute coagulation dysfunction. The authors report a case of an accidental cannulation of the subclavian artery with a central catheter and its successful removal using an endovascular cover stent positioned via a percutaneous approach. The cover stent can be employed to occlude arterial lacerations. This device was preferred because of the patient's severe clinical condition (a 77-year-old woman with acute right heart thrombosis, atrial hyperkinetic arrhythmia, and cardiogenic shock requiring hemodynamic invasive monitoring and systemic thrombolysis) and because of the presenting anatomical and vascular characteristics (lack of space between introduction site and left ventricle, retroclavicular medial location) that did not permit a safe conventional surgical approach (thoracotomy). Echocolor Doppler sonography was a valuable aid in preoperative assessment, measurement of arterial diameter and cover stent sizing. The procedure was performed under general anesthesia 6 days after admission to the intensive care unit without sequelae. In conclusion, the endovascular procedure permitted safe removal of the arterial catheter without complications. A possible alternative to conventional procedures, the endovascular technique may offer an adequate choice for treating acutely ill patients ineligible for invasive interventions.

Isoelectric focusing and immunoblotting of the platelet membrane glycoprotein complex IIb. IIIA following urea solubilization.

Effective solubilization of the major platelet membrane component, the glycoprotein IIb.IIIa complex, can be achieved with 8 M urea. By avoiding nonionic detergents in the separation medium it is possible to obtain clear immunoblot patterns without interference from the isoelectric focusing matrix. Upon running on a pH 4.25-5.25 immobilized pH gradient, immunoreactive bands corresponding to the nonreduced IIb.IIIa complex stain between pH 4.5 and 5.0. The method appears of significant potential utility in evaluating glycoprotein IIb.IIIa polymorphisms under different clinical conditions.

Plasma lipoprotein(a) is an independent factor associated with carotid wall thickening in severely but not moderately hypercholesterolemic patients.

BACKGROUND AND PURPOSE: To evaluate whether high levels of low-density lipoprotein cholesterol (LDL-C) may promote the atherogenic effect of lipoprotein(a) [Lp(a)], we investigated the association between elevated Lp(a) levels and thickening of intima plus media in the common carotid artery (CC-IMT) in patients with different degrees of hypercholesterolemia. METHODS: One hundred type II hypercholesterolemic patients and 25 normolipidemic subjects were selected for the study. Plasma lipid and lipoprotein levels were determined enzymatically; Lp(a) levels were determined by enzyme-linked immunosorbent assay. An Lp(a) concentration > 30 mg/dL was arbitrarily considered a risk factor. For each patient mean CC-IMT was determined by B-mode ultrasound; in 60 patients and in the 25 control subjects, the maximal IMT in the entire carotid tree was also determined. RESULTS: CC-IMT values were higher in hypercholesterolemic patients with plasma Lp(a) levels > 30 mg/dL than in those with lower levels (P < .01). CC-IMT and maximal IMT directly and independently correlated with plasma levels of Lp(a) (r = .33 and r = .25, respectively; both P < .05). The effect of LDL-C concentrations on the relationship between IMT and Lp(a) was investigated by dividing the patients into quartiles of plasma LDL-C levels. After stratification, CC-IMT significantly correlated with plasma Lp(a) levels in the patients with severe hypercholesterolemia (LDL-C > 5.2 mmol/L) but not in patients in the lowest quartile, ie, those with moderate hypercholesterolemia. No correlation between CC-IMT and Lp(a) was found in normolipidemic control subjects. CONCLUSIONS: Elevated plasma levels of Lp(a) can be considered an additional independent factor associated with thickening of the common carotid arteries in patients with severe hypercholesterolemia but not in those with moderate hypercholesterolemia or in normocholesterolemic subjects.