Search

Background Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. Patients/Methods In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n = 85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n = 83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. Results We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment. Conclusions These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis.

Background Non-compaction of ventricular myocardium is a rare congenital cardiomyopathy characterized by the presence of an extremely thickened endocardial layer with prominent trabeculations and deep recesses in communication with ventricular chamber and determining the typical spongeous aspect. The diagnosis of non-compaction of ventricular myocardium is possible through the identification of morphological alterations by echocardiographic evaluation. Ebstein's anomaly is a rare congenital cardiac disease, defined as the significant apical displacement of the part of the tricuspid valve causing significant tricuspid regurgitation and reduction of the functional right ventricle, right atrial and right ventricular dilatation and atrial and ventricular arrhythmias. Case report We present a case of biventricular non-compaction and Ebstein's anomaly in a 29-year-old Italian man that was referred for chest pain. Diagnosis of Ebstein's anomaly was made during a medical control for military service through an echocardiographic evaluation which left the suspicion of myocardium non-compaction. We present the cardiac image of the 2D and 3D eco, RMN, scintigraphy and ventriculaography.

The use of oral contraceptives first became widespread some 40 years ago, and reports of an excess risk of cardiovascular disease among women who used these agents soon followed. Few drugs have been the object of such intensive epidemiological research, the outcome of which has provided clinicians with detailed information about risks not only of specific thrombotic diseases but also important non-contraceptive benefits from the pill. Recently, oral contraceptives have been classified by some according to "generation" (first, second, third, and most recently, fourth generation): first-generation formulations containing lynestrenol or norethindrone, second-generation formulations containing levonorgestrel, third-generation formulations containing desogestrel or gestodene, and oral contraceptives containing an estrogen and other progestagens (cyproterone or norgestimate) or a progestagen alone. The results of several study was that the use of the older high-dose oral contraceptives increased the risk of cardiovascular disease by modifying the Low-density lipoprotein and High-Density lipoprotein cholesterol level, increasing triglyceride serum level, reducing glucose tolerance, raising blood pressure, and promoting clotting mechanisms. In this review we investigate the mechanism of the oral contraceptives and performed a risk assessment of every generation.

The foramen ovale, an atrial septal defect which is essential in the fetal circulation, remains patent through adulthood in approximately 25% of the general population and so it represents the most common persistent abnormality of fetal origin. Patent foramen ovale (PFO) allows interatrial right-to-left blood shunting during those periods of the cardiac cycle in which the right atrial pressure exceeds the left one. An increasing number of pathological manifestations of PFO has been recently identified; among these, paradoxical systemic embolism, refractory hypoxemia in patients with right ventricular myocardium infarction or severe pulmonary disease, orthostatic oxygen desaturation in the rare platypnea-orthodeoxia syndrome, neurological decompression illness in divers, high altitude pilots and astronauts, and finally, migraine headache with aura. Nowadays many techniques allow to detect a PFO. In this study we investigated each of them, assessing their potential diagnostic role even in comparison with the main features of the other methods.

The aim of our study was to evaluate, in patients with proven coronary artery disease (CAD) and treated with elective percutaneous coronary intervention (PCI), whether the coexistence of asymptomatic carotid and femoral atherosclerotic lesions would provide prognostic information in terms of occurrence of restenosis.We studied 104 patients with CAD (M/F=77/27), mean age 60.5+/-9 years. All patients were treated with elective PCI. After PCI the suspicion of restenosis was confirmed by coronary angiography. All patients underwent ultrasound duplex scan of carotid and femoral-popliteal-tibial axis to detect atherosclerotic lesions. According to ultrasound results, patients were classified as normal, with increased intima-media thickness (IMT) or with asymptomatic plaque (AP). If carotid and femoral lesions coexisted (together with coronary ones) patients were considered to have multifocal atherosclerosis.About 90% of the patients had carotid lesions: 40% had carotid IMT and 50% AP. Femoral lesions were found in 72% of the population and in 41% there was an increased IMT and in 21% an increased AP. Prevalence of restenosis after PCI was 12.5%. Patients with restenosis had a significantly higher prevalence of asymptomatic carotid and/or femoral lesions than those without restenosis. The occurrence of restenosis was independently associated with the detection of carotid, femoral and multifocal atherosclerosis.The detection of carotid and/or peripheral atherosclerotic lesions in patients with CAD who underwent PCI may be a marker of increased risk. We believe that investigating these areas, by echo-Doppler duplex scanning, may be a cost-effective strategy in the work-up before elective PCI. It may allow identification of high-risk subgroups of patients, and enable the planning of patient-tailored therapeutic strategies and follow-up.

There are only a few published studies on the association between subclavian steal syndrome and ischemic heart disease. The objective of this report is to evaluate the efficacy of subclavian stenoocclusion treatment in patients with subclavian steal syndrome (SSS) and previous cor- onary bypass. Over the last 8 years we observed 207 patients who underwent left internal mammary artery–intraventricular artery (LIMA–IVA) bypass graft. Of these, 31 patients were affected by steno-occlusion of the homolateral subclavian artery. Ten patients (group 1) showed latent vertebral-SSS and were pharmacologically treated. Seven patients (group 2) had an intermittent vertebral-SSS; four patients were treated with angioplasty and stent application and three were pharmacologically treated. Fourteen patients (group 3) with complete vertebral-SSS were treated with angioplasty and stent application or carotid-subclavian bypass graft. All pa- tients were followed up every 3 months for a period of 5 years after the diagnosis. The first group of patients showed no angina and no sign of subclavian restenosis. In the second group only two patients, who were affected by angina, showed subclavian restenosis at angiography. In the third group only one patient underwent further angioplasty for restenosis. The results of this study show that the SSS may be an adverse event in patients with a LIMA-IVA bypass graft. Identification of the steal is essential to choose an appropriate therapeutic approac

Venous leg ulcers are common in subjects with chronic venous insufficiency. The increased intraluminal pressure causes alteration of the skin microcirculation, leukocyte activation and release of proteolytic enzymes leading to ulceration. An impaired expression and activity of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) might influence extracellular matrix degradation and deposition in chronic venous ulcers with the failure of the healing process. Our aim was to evaluate plasma concentration of gelatinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in subjects with venous leg ulcers before and after the compression therapy. We enrolled 36 subjects (12 men and 24 women, mean age 67.38 ± 12.7 yrs) with non-infected venous leg ulcers (CEAP C6), which underwent a color Duplex scan examination of the veins and arteries of the inferior limbs and were treated with a multi-layer bandaging system. The ulcer healing was obtained in 23 subjects only (9 men and 14 women). We evaluated, on fasting venous blood, the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 using ELISA kit, before and after the treatment. We observed a significant increase in plasma concentration of gelatinases and their inhibitors and in MMP-2/TIMP-2 ratio in subjects with leg ulcers in comparison with normal controls. In subjects with healed ulcers we found a decrease in MMP-9 and TIMP-1 levels and in MMP-2/TIMP-2 ratio compared to the baseline values, although higher levels of all the examined parameters in comparison with normal controls. In conclusion, plasma MMPs profile is impaired in subjects with venous leg ulcers and it improves after the healing, persisting anyway altered in respect to healthy controls.

Background and Purpose —Several reports have considered the role of systemic leukocytes in acute ischemic stroke (AIS). Initially, greater attention was focused on the leukocyte count and subsequently on their adhesiveness, aggregation, rheology, and activation. The aim of this study was the evaluation of certain polymorphonuclear leukocyte (PMN) parameters, reflecting their rheology and activation, in subjects with AIS. Methods —In a group of 19 subjects with AIS and in a control group of 18 subjects with asymptomatic vascular atherosclerotic disease, we evaluated the PMN membrane fluidity and cytosolic Ca 2+ concentration at baseline and after in vitro chemotactic activation with 4-phorbol 12-myristate 13-acetate (PMA) and N -formyl-methionyl-leucyl-phenylalanine (fMLP). Results —From the obtained data, it is evident that at baseline only PMN membrane fluidity distinguishes control subjects from AIS subjects. After PMN activation with PMA and fMLP, prolonged for 5 and 15 minutes, we found an increase in PMN cytosolic Ca 2+ concentration and a decrease in PMN membrane fluidity only in subjects with AIS. Conclusions —These findings emphasize that in subjects with AIS a functional alteration of systemic PMN cells is clearly expressed during chemotactic activation, although the mechanism of this abnormality is not yet explained.

We evaluated leukocyte rheology, expressed as leukocyte filtration, polymorphonuclear (PMN) membrane fluidity and cytosolic Ca2+ concentration in subjects with acute deep venous leg thrombosis (DVT). In 14 subjects with leg DVT we examined the leukocyte filtration [unfractionated, mononuclear cells (MN), PMNs], PMN membrane fluidity and PMN cytosolic Ca2+ concentration. Subsequently, we evaluated the same PMN variables after in vitro chemotactic activation with 4-phorbol-12-myristate-13-acetate. At baseline, we observed a significant difference in the filtration of unfractionated and MNs and in PMN cytosolic Ca2+ concentration. After PMN activation, a significant variation, greater in DVT subjects, was present in PMN filtration at 5 and 15 min. In normals, no variation was present in PMN membrane fluidity or cytosolic Ca2+ concentration after activation, while in subjects with DVT we found a significant variation in both PMN parameters. These results underline that there is a systemic leukocyte functional alteration in DVT.

Objective: To evaluate leucocyte rheology, expressed as leucocyte filtration, polymorphonuclear leucocyte (PMN) membrane fluidity and cytosolic Ca2+ concentration in subjects with post-phlebitic leg syndrome (PPS). Methods: In 22 subjects with PPS we determined leucocyte filtration [unfractionated, mononuclear (MN) and PMN cells], employing the St George Filtrometer, PMN membrane fluidity using the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and PMN cytosolic Ca2+ concentration using the fluorescent probe Fura 2-AM. Subsequently we determined the same PMN parameters after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). Results: At baseline we observed a difference in the filtration parameters of unfractionated and MN cells and an increase in PMN cytosolic Ca2+ concentration. After activation, a significant variation in PMN filtration parameters was evident both in normals and in PPS subjects, although in subjects with PPS this variation, especially with PMA, was significantly greater. We found a decrease in PMN membrane fluidity and an increase in PMN cytosolic Ca2+ concentration only in subjects with PPS. Conclusion: These results suggest that there is a functional alteration of systemic leucocytes in PPS, in which the mechanisms are not yet clear.

Cardiorenal syndrome is a pathophysiological heart and kidney disorder, in which acute or chronic dysfunction of one organ induces a damage in the other. It's a syndrome more and more often encountered in clinical practice and this implies the need to recognize the syndrome through biochemical markers with a good sensitivity and specificity, since its earliest stages in order to optimize therapy. In addition to widely validated biomarkers, such as BNP, pro BNP, creatinine, GFR and cystatin C, other promising molecules are available, like NGAL (neutrophil gelatinase-associated lipocalin, KIM-1 (kidney injury molecule-1), MCP-1 (monocyte chemotactic peptide), Netrin-1, interleuchin 18 and NAG (N-acetyl-β-glucosa-minidase). The role of these emerging biomarkers is still not completely clarified: hence the need of new clinical trials.

The objective of this study was to evaluate whether the presence of a plasminogen activator inhibitor type 1 (PAI-1) promoter polymorphism 4G/5G could significantly influence the proximal extension of vein thrombosis in spite of anticoagulant treatment in patients with calf vein thrombosis (CVT) following orthopaedic, urological and abdominal surgery. We studied 168 patients with CVT, who had undergone orthopaedic, urological and abdominal surgery, subdivided as follows: first, 50 patients with thrombosis progression; second, 118 patients without thrombosis progression. The 4G/5G polymorphism of the plasminogen activator inhibitor 1 was evaluated in all patients and in 70 healthy matched controls. We also studied PAI-1 activity in plasma. The presence of 4G/5G genotype was significantly increased in the group of patients with the extension of thrombotic lesions and was associated with an increase in CVT extension risk (odds ratio adjusted for sex 2.692; 95% confidence interval 1.302-4.702). Moreover, we observed a significant increase of PAI-1 plasma activity in patients with extension of thrombotic lesion vs. patients without extension (P=0.0001). Patients with 4G/5G genotype in the promoter of the plasminogen activator inhibitor - 1 gene present a higher risk of extension of thrombotic lesions. Blood Coagul Fibrinolysis 24:237-242 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

The term metabolic syndrome defines a cluster of risk factors for cardiovascular diseases and diabetes. This syndrome is very frequent in general population. However, despite the efforts to define the diagnostic criteria, nowadays its clinical utility is object of a lively debate.

In recent years, several studies have used the measurement of carotid intima-media thickness (IMT) as a marker of early atherosclerosis: IMT has been shown to correlate significantly with the presence of coronary artery disease (CAD) and to predict fatal and not fatal cerebro- and cardio-vascular events. These findings highlight the importance of recognizing and managing early stages of atherosclerosis for effective cardiovascular prevention. Beyond traditional established cardiovascular risk factors, inflammation has been shown to be crucial throughout atherosclerosis from endothelial dysfunction to plaque rupture and thrombosis. Several studies have shown the existence of a strong relation between CAD and fibrinogen or highly sensitive C-reactive protein (hs-CRP) levels and their predictive role has been examined through stratification or multivariable statistical analyses: levels of these markers of inflammation have been independently associated with the incidence of coronary events after adjusting for traditional cardiovascular risk factors. Recent studies have further addressed the importance of therapeutical modulation of hs-CRP levels in high-risk patients for the prevention of vascular events. The strong relationship between hs-CRP and IMT may potentially account for the complex role of hs-CRP and IMT in the pathogenesis of cardiovascular events. However, beyond the utility of measuring markers of inflammation to assess patients with subclinical carotid atherosclerosis at higher risk of vascular events, further studies are needed to evaluate the therapeutic implications in this category of patients.

Background Isolated ventricular noncompaction (IVNC) is characterized by multiple prominent trabeculations and deep intertrabecular recesses. Some reports prove that the chronic heart failure may occur in approximately half of the patients. In this report we investigate the correlation between the number of non compacted segments and entity of systolic dysfunction from the registry and subregistries of the SIEC. Method To identify the correlation between ventricular dysfunction and number of segments involved in non compaction we evaluated a consecutive series of 238 patients affected by non compaction, from the SIEC (Societa Italiana di Ecografia Cardiovascolare) registry. The average age of patients was 41.5 years (range: 1–92 years), 137 were males and 101 females. In 122 cases we found ventricular systolic dysfunctions with an EF average of 34.6%. The number of affected segments by non-compactation and diastolic dysfunction were found to be non-independent predictors of LV systolic dysfunction. Conclusion From the analyses we carried out, it seems that ventricular dysfunction seems to be completely independent from the segment numbers of non compacted segments.

ASYMPTOMATIC VENTRICULAR PREEXCITATION IN CHILDREN OBJECTIVE: This retrospective study was planned for a good risk assessment of asymptomatic patients affected by ventricular pre-excitation. METHODS: From 1985 to 2007, 124 patients with an atrioventricular pathway (electrocardiographic signs of ventricular pre-excitation) were admitted to our cardiology division. The average age was 7 years (range 1 month to 18 years). The mean follow-up period in the whole population of patients was 4.2 years (range 1-13 years). Four patients were lost during the follow-up. During this period, all patients remained in good health. In all of them, we performed a Holter evaluation every year. An intermittent pathway was detected in 18 patients (15%), and four of them (3.4%) showed a supraventricular tachycardia even though they were asymptomatic patients. An ergometric test was performed in 76 asymptomatic patients; 16 children (21%) showed a total abrupt vanishing of delta wave. A transoesophageal electrophysiological evaluation was performed in 14 patients. CONCLUSION: According to our data, asymptomatic Wolff-Parkinson-White syndrome in children has a good outcome during a short-term (4 years) follow-up. The usefulness of electrophysiological evaluation (in particular its predictive value) is uncertain.

In a recent report about noncompaction Nemes et al. reported that systolic left ventricular (LV) dysfunction assessed using the wall motion score during 2D echocardiography in noncompaction is not confined to noncompacted LV segments. These results confirmed some published reports of our group. Recently we analyzed a population of 238 patients affected by noncompaction, and demonstrated that the number of noncompacted segment is uncorrelated with the degree of systolic dysfunction. It is an attractive hypothesis that the systolic dysfunction could be depend on the fibrosis of the left ventricle, itself a consequence of microcirculatory dysfunction, which has been confirmed by reports that describe microvascular dysfunction using myocardial scintigraphy.

BACKGROUND: Noncompaction of left ventricular myocardium is a rare congenital cardiomyopathy resulting from an incomplete myocardial morphogenesis that leads to the persistence of the embryonic myocardium. This condition is characterized by a thin compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep intertrabecular recesses. It is not clear, in noncompaction of myocardium, whether intertrabecular recesses could be responsible for thrombi formation and thromboembolic complications. METHODS: The prevalence of stroke and echocardiographic finding of thrombus was evaluated in a continuous series of 229 patients (men and women) affected by noncompaction of the left ventricular myocardium, who were included in the SIEC registry. We excluded patients affected by atrial fibrillation. RESULTS: The mean age of the patients was 49.5 years. Fifty percent of the patients were affected by a ventricular systolic dysfunction. The mean period of follow-up was 7.3 years. Only four patients had a history of ischemic stroke. A large thrombus into the left ventricular chamber was observed in a 1-year-old child affected by Behcet's disease (high risk of thrombi formation). CONCLUSION: Noncompaction of the left ventricular myocardium, by itself, does not seem to be a risk factor for stroke or embolic results, so there is no indication for oral anticoagulant therapy. © 2008 Italian Federation of Cardiology.

The aim of this study was to evaluate different durations of treatment in patients with calf venous thrombosis (CVT) involving 1 or more deep veins. The authors studied 2 groups of patients with postsurgical CVT diagnosed by echo-color Doppler. The first group consisted of 68 patients with CVT involving a single vein, and the second group consisted of 124 patients with CVT involving 2 or more veins. Immediately after diagnosis, all patients were treated with nadroparin calcium and sodium warfarin. Heparin treatment was withdrawn after 5–6 days of treatment, when the international normalized ratio (INR) was stabilized between 2 and 3. Each group was divided into 2 subgroups receiving anticoagulation treatment for 6 or 12 weeks, respectively. The endpoint was proximal extension of the thrombotic lesion, defined as the extension of the thrombus to the popliteal and/or femoral vein. In patients with single-vessel CVT there was no significant difference between the 2 subgroups, whereas in patients with CVT involving 2 or more vessels, a statistically significant difference was observed, the number of cases showing proximal extension of the thrombus being higher among patients treated for 6 weeks. Twelve weeks of anticoagulation treatment is better than 6 weeks only in patients with postsurgical CVT involving 2 or more veins.

The aim of the study was to verify the association between abdominal aortic aneurysms (AAA) and methylenetetrahydrofolate reductase (MTHFR) mutation, in relation to age. We studied the frequency of the MTHFR 677T allele in two groups of AAA patients, over and under 60 years. The first AAA group included 42 patients (30 men and 12 women) aged between 65 and 75 years; the second AAA group included 46 patients (32 men and 14 women) aged between 49 and 59 years; the control group included 44 healthy controls (29 men and 15 women) aged between 49 and 75 years. We examined MTHFR allele frequency and MTHFR genotype using Nuclear Laser Medicine. MTHFR allele frequency was significantly increased in AAA patients60 compared to healthy controls and in AAA patients60 compared to those60. The genotype study showed a difference between controls and AAA patients and between AAA patients60 and those60. The frequency of MTHFR mutation was more elevated in both AAA groups vs controls, but it was more elevated in younger patients than in the older ones. This mutation might induce an early elastin degradation in the aortic wall.

Background: We conducted a study using an intravenous (i.v.) infusion of iloprost in the treatment of venous ulcers to verify whether the association of i.v. iloprost + local therapy + elastic compression has a favorable effect when compared with traditional treatment with local therapy and elastic compression. Study Design: We evaluated the effects of iloprost in 98 consecutive patients with noncomplicated venous ulcers of lower limbs subdivided into 2 groups: the first group (48 patients) received iloprost in saline solution for 3 weeks and the second group (50 patients) received a venous infusion of a saline solution. The patients were examined at baseline time 0 (first visit) and then after 15, 30, 45, 60, 75 90, 105 120, 135, and 150 days. Results: In the first group, after 90 days, all the ulcers had healed, whereas in the second group only 50% of ulcers had healed after 105 days. At the end of the study, in the second group only 84.09% of ulcers had healed. The statistical analysis showed a significant difference between the first (iloprost group) and the second group (placebo group). Besides, in the first group the cicatrization of the ulcer happened in a shorter period (27.90% after 60 days; 41.86% after 75 days; and 100% after 100 days) whereas in the second group, at the end of the study, in 15.91 % of patients the ulcers had not recovered. Conclusion: Iloprost can significantly reduce healing time for venous leg ulcers through several actions.

The polymorphonuclear leukocytes (PMN) have a role in the pathophysiology of deep venous thrombosis (DVT). We examined the phenotypical expression of PMN beta2-integrins (CD l l a, CDl l b, CD 11c) in a group of 19 subjects with leg DVT. PMN cells were incubated with fluorescent monoclonal antibodies against CD11a, CD11b, CD11c, and the evaluation was made by flow cytofluorimetry. The same integrins were determined after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) and N-formylmethionyl-leucyl-phenylalanine (fMLP). In DVT subjects, at baseline, the phenotypical expression of CD11b was decreased and that of CD11c increased when compared with normal controls. In normal subjects PMN activation with PMA and fMLP led to a constant increase of all PMN adhesion molecules, while in DVT subjects the CDl l a did not show any change. These data might have therapeutical ap plications, especially with the aim of preventing post-thrombotic deterioration of vein function.

Leukocyte-endothelial interactions could have a pathogenic role in atherogenesis. Adhesion molecules expressed by endothelial cells, such as intercellular adhesion molecule 1 (ICAM-1), interact with leukocyte integrins mediating the firm adhesion of leukocytes to endothelium which is followed by their transendothelial migration. The aim of our research was to evaluate polymorphonuclear leukocyte (PMN) integrin expression, at baseline and after activation, in a group of subjects with chronic vascular atherosclerotic disease (VAD). In 27 subjects with VAD we examined, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA), the PMN integrin pattern (CD11a, CD11b, CD11c, CD18) using indirect immunofluorescence and a flow cytometer. At baseline VAD subjects showed an increase of CD11a and CD18 and a decrease of Cd11b and Cd11c as compared to normal subjects. After activation, in normal subjects, we found an increase in the expression of all integrins, while in VAD subjects we observed an increase of CD11b and Cd11c and a decrease of Cd11a and CD18. In VAD subjects, at baseline, the upregulation of Cd11a and CD18 may reflect PMN in vivo activation; after in vitro activation, the decrease of CD11a may be related to the lack of cytoplasmic deposits of this molecule, while CD18 might be internalized. The integrin behaviour pattern in chronic VAD deserves further investigation, considering that integrins are potential targets of therapeutical strategies, with the aim of preventing the atherosclerotic plaque progression and acute ischaemic events.

In vascular atherosclerotic disease and in diabetes mellitus few studies have evaluated the polymorphonuclear leukocyte (PMN) adhesion molecule pattern. In this study we examined the PMN integrin expression at baseline and after activation in controls and type 2 diabetic subjects with macrovascular complications (MVC). We enrolled 21 subjects with type 2 diabetes mellitus and macrovascular complications, localized in peripheral, coronary and cerebral sites. The patients had peripheral occlusive arterial disease, chronic cerebrovascular disease or coronary heart disease. We evaluated the expression of some PMN integrins (CD11a, CD11b, CD11c, CD18), using flow cytofluorimetry, at baseline and after in vitro activation with 4-phorbol-12-myristate-13 acetate. Type 2 diabetic subjects with MVC showed, compared to normals, an increase of CD11a and CD18 and a decrease of CD11b and CD11c. After activation, in PMN(s) of normal subjects, we found an increase in the expression of all adhesion molecules, while in PMNS of type 2 diabetic subjects with MVC we observed an increase of CD11b and CD11c and a decrease of CD11a. In type 2 diabetic patients with MVC the basal upregulation of CD11a and CD18 may be related to the PMN spontaneous activation, while the behavior of CD11b may depend on its self-consumption. After activation the CD11a modification may be due to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance.

We examined in 19 subjects with acute ischaemic stroke (AIS) the PMN integrin pattern (CD11a, CD11b, CD11c, CD18), using indirect immunofluorescence and adopting a flow cytometer, at baseline and during activation, prolonged for 5 and 15 min, with 4-phorbol 12-myristate 13-acetate (PMA). At baseline, an increase in the expression of CD11c and CD18 and a decrease in the CD11b were evident in AIS subjects compared to normals. After activation, we found in normals a constant and significant increase of all PMN adhesive molecules, while in AIS subjects, we found an increase in CD11b and CD18, a decrease in CD11a and no variation in CD11c. While the basal upregulation of CD11c and CD18 may depend on the PMN spontaneous activation or on the increase of cytokines, the decrease of CD11b may be due to its self-consumption. After activation, the decrease in CD11a noted in AIS may be related to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance.

We evaluated polymorphonuclear (PMN) filtration parameters, membrane fluidity and cytosolic Ca2+ content in 21 normal subjects and in 18 type II diabetics with macrovascular complications (MVC). Evaluations were carried out at baseline and after in vitro activation prolonged for 5 and 15 min. PMA (4-phorbol 12-myristate 13-acetate) and fMLP (N-formyl-methionyl-leucyl-phenylalanine) were used as stimulating agents. TMA-DPH (1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene) was used as fluorescent probe for the membrane fluidity tests and Fura 2-AM for the cytosolic Ca2+ content. A significant variation was evident in PMN filtration parameters at 5 and 15 min. No variation was present in PMN membrane fluidity and cytosolic Ca2+ content in normals. In type II diabetics with MVC, we found an increase solely in PMN cytosolic Ca2+ content after PMA activation and an early decrease in PMN membrane fluidity and a late increase in PMN cytosolic Ca2+ content after fMLP activation. After PMA activation alone (at 15 min), PMN filtration distinguishes normals from type II diabetics with MVC. The PMN filtration parameters behave similarly in the two groups, but PMN membrane fluidity and cytosolic Ca2+ content behave differently.

In 1961 Reivich et al [1] described for the first time a syndrome caused by stenooccluding pathological processes involving the subclavian artery proximal to the emergence of the ipsilateral vertebral artery, and characterized by the activation of specific collateral pathways of the ascending aorta; that same year Fisher et al [2] named it ‘subclavian steal syndrome’. In this case the subclavian artery, stenosed or occluded at the origin, is supplied with blood from the ipsilateral vertebral artery with a reverse flow direction [3]. This allows valid compensation for hemodynamic disorders in the brachial area, at the expense, however, of the encephalic region from which blood diverted to the subclavian artery is subtracted. This phenomenon was first noted in 1886 [4], after a subclavian artery ligation for a traumatic aneurysm: the vertebral artery was ligated and the patient survived ten years. Later contributions on this subject have not only shown that subclavian steal syndrome is a reliable indicator of severe subclavian artery stenosis, though the syndrome itself is relatively benign, but have also provided a more detailed etiological framework showing that alongside arteritic, traumatic, congenital and iatrogenic forms exist others — which occur more frequently — of atherosclerotic origin [5] (Table 17.1).

A double-blind, placebo-controlled study was carried out in 36 patients, aged 30 to 50 years, to evaluate the effectiveness of oral sulodexide in the treatment of chronic venous insufficiency due to idiopathic varices. Patients were allocated at random to receive either oral sulodexide as 2 capsules (each containing 250 lipoproteinolipase releasing units) twice daily or 2 identical placebo capsules twice daily over a period of 45 days. Using strain gauge plethysmographic data, assessments were made of the microcirculatory effects of treatment by calculating the coefficient of capillary filtration from measurements made on both legs of each patient on entry and after 30 and 45 days of treatment. The coefficient is derived from the transmembranous flow values at the occlusive pressures of 60 and 40 mmHg, the difference between the two occlusive pressures examined and a corrective factor to calculate the capillary pressure based on the pressure in the venous circulation. Statistical analysis of the results showed that sulodexide produced a significant mean reduction from baseline values of the coefficient at both the 30 and 45 day examinations whereas the coefficient increased in the placebo group. The difference between the two groups was also statistically significant. These findings suggest that sulodexide has a positive influence on capillary permeability.

Objective To report a case of ovarian hyperstimulation syndrome with methylenetetrahydrofolate reductase (MTHFR) gene 677T homozygosis mutation and A1298C gene heterozygosis mutation. Design Case report. Setting A pregnant woman in an academic hospital. Patient(s) A woman with ovarian hyperstimulation syndrome. Intervention(s) Nadroparin was administered for 2 weeks at a dosage of 200 IU/kg twice per day and then once per day; also administered once per day were folates, 5 mg; B6 vitamin, 15 mg; and B12 vitamin, 1 mg. Main Outcome Measure(s) Clinical follow-up. Result(s) Delivery was regular within the set time limits, and the fetus was born alive and in good health. Conclusion(s) We believe that MTHFR mutation research could be executed in women before ovarian stimulation treatment, but other observations are necessary to support this recommendation.

The effect of ticlopidine was compared with flunarizine in patients with iliac–femoral and / or femoral–popliteal arteriosclerotic arteriopathy accompanied by lesions of the cervical arteries of no haemodynamic significance. In the lower limbs, plethysmography (strain gauge measurements) and Döppler ultrasonography integrated by spectral analysis of the cervical arteries showed qualitative and quantitative improvements of the regional haematic flow. Side-effects were negligible which suggests that ticlopidine is useful in the treatment of multiple arteriosclerotic arteriopathy.

Objective: to evaluate leukocyte rheology, polymorphonuclear leukocyte (PMN) membrane fluidity and cytosolic Ca2+ concentration in subjects with post-phlebitic leg syndrome (PPS) and acute deep-venous leg thrombosis (DVT). Subjects: twenty-two subjects with leg PPS and 14 subjects with leg DVT. Methods: we evaluated the leukocyte filtration (unfractionated, mononuclear cells (MN) and PMN), the PMN membrane fluidity and the PMN cytosolic Ca2+ concentration. Subsequently, we evaluated the same PMN variables after in vitro chemotactic activation with 4-phorbol 12-myristate 13-acetate (PMA) and N -formyl-methionyl-leucyl-phenylalanine (fMLP). Results: at baseline we observed a significant difference in the filtration variables of unfractionated and MN cells and in PMN cytosolic Ca2+ concentration. After activation, in normal subjects and subjects with PPS and DVT, a significant variation in PMN filtration at 5 and 15 minutes was evident. In normal subjects, no variation was present in PMN membrane fluidity or cytosolic Ca2+ concentration after activation. In subjects with PPS and DVT, we found a decrease in PMN membrane fluidity and an increase in PMN cytosolic Ca2+ concentration. After PMN activation (at 5 and 15 min) Δ% of IRFR distinguished normal subjects from subjects with PPS and DVT, while no difference was found in Δ% of membrane fluidity or cytosolic Ca2+ concentration. Conclusions: there is a functional alteration of leukocytes in these patients whose mechanisms are not yet clear.

The aim of this research was the evaluation of white blood cell (WBC) filtration, reflecting WBC flow properties, polymorphonuclear cell membrane fluidity, and cytosolic Ca 2+ content in subjects with vascular atherosclerotic disease (VAD) and in VAD subjects with noninsulin-dependent diabetes mellitus (NIDDM), in good hemodynamic balance. The authors examined WBC filtration (unfractionated, mononuclear [MN], polymorphonu clear [PMN] cells), using the St. George Filtrometer and considering, respectively, the initial relative flow rate (IRFR) and the clogging rate (CR); the PMN membrane fluidity, employing the fluorescent probe TMA-DPH and calculating the fluorescence polarization degree; and the PMN cytosolic Ca2+ content, adopting the fluorescent probe Fura 2-AM and considering the ratio between the Fura 2-Ca2+ complex and the unchelated Fura 2 fluorescence intensity. The obtained data showed that only the filtration parameters (IRFR, CR) of unfrac tionated WBCs discriminated normal subjects from VAD groups, whereas the filtration parameters of MN and PMN cells did not demonstrate any distinction. PMN membrane fluidity did not distinguish normal subjects from VAD groups, whereas PMN cytosolic Ca2+ content was significantly increased in VAD groups in comparison with normal subjects. No relationship was evident between WBC filtration and plasma metabolic para meters ; the correlations obtained between PMN filtration and other PMN parameters need further investigation.