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Lispro (LP) and regular human (HR) insulins were compared in Type 1 diabetic (T1DM) patients on either a Mediterranean diet or normal diet. Twelve T1DM patients were recruited and randomized into two groups of 6, groups A and B. They were treated in different sequences (in 3-month intervals for 1 year). Group A: LP insulin and normal diet, LP insulin and Mediterranean diet, regular insulin and Mediterranean diet, regular insulin and normal diet. Group B: regular insulin and normal diet, regular insulin and Mediterranean diet, LP insulin and Mediterranean diet, LP insulin and normal diet. Each patient was treated with rapid acting insulin, either LP insulin or HR insulin, before each main meal and a dose of slow acting insulin at bedtime. Every 15 days the glycemic control, the incidence and frequency of hypoglycemic episodes, and any adverse events were evaluated. Every 3 months, hematology and a chemistry panel, pre- and post-prandial glycemic and insulinemic profiles were evaluated in all patients. HbA1c levels significantly decreased in LP patients on normal diet, post-prandial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards, 15-min post-prandial insulin levels higher in LP- than in HR-treated patients, and hypoglycemic episodes were significantly less in LP- than in HR-treated patients. LP insulin, irrespective of the type of diet, results in more effective glycemic control, significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet.

Wall shear stress contributes to the endothelial production of vasoactive mediators, like nitric oxide (NO). Brachial artery vasodilation that follows increased blood flow is regulated by NO release. Aim of the present study was to investigate whether resting wall shear stress of the brachial artery is related to flow-mediated vasodilation (FMD) induced by forearm ischemia. Wall shear stress was calculated according to the following formula: Wall shear stress=Blood viscosity x Blood velocity/Internal diameter. FMD was calculated as percentage change of brachial artery diameter following forearm ischemia. Twenty-seven healthy male subjects were investigated. Peak wall shear stress and FMD were 37.3+/-12.8 dynes/cm(2) and 110.7+/-5.6%, respectively (mean+/-S.D.). In simple regression analyses, age was inversely associated with wall shear stress (r=48, P<0.01) and, marginally, with FMD (r=0.33, P=0.08). Wall shear stress and FMD were directly related (r=0.60, P<0.001). In multiple regression analysis, including wall shear stress, age, blood pressure, lipids, glucose and Body Mass Index as independent variables, wall shear stress was the only variable independently associated with FMD (standardized beta coefficient=0.690, P

The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.

Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio (WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m2), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 pg x ml(-1) x min(-1)) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)) during saline and vitamin C coinfusion (24 mg/min). The effects of cyclooxygenase activity were evaluated by a dose-response curve to intrabrachial coinfusion of ACh and indomethacin (500 microg/min). Three different groups have been identified according to their BMI: group A (BMI <25), consisting of 10 men and 5 women; group B (BMI between 25 and 29), consisting of 16 men and 8 women; and group C (BMI > or =30), consisting of 24 men and 13 women. Obese subjects had significantly lower forearm blood flow (FBF) during ACh infusions (means +/- SD): 19.8 +/- 2.8, 10.8 +/- 2.7, and 6.5 +/- 1.8 ml x 100 ml(-1) tissue x min(-1) (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity.

We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.

A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63+/-0.09, 0.55+/-0.06, and 0.53+/-0.04 cm [mean+/-SD], P<0.005 by ANOVA; intima-media thickness was 765+/-116, 670+/-116, and 630+/-92 microm [mean+/-SD], P<0.05 by ANOVA). Wall shear stress, calculated as blood velocityxblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4+/-2.9, 13.5+/-3.5, and 12.6+/-1.9 dyne/cm(2) [mean+/-SD], P<0.05 by ANOVA). The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.

The localization of atherosclerotic lesions is influenced by hemodynamic factors, namely, shear stress and tensive forces. The present study investigated the relationships between shear stress and circumferential wall tension and between these hemodynamic factors and the intima-media thickness (IMT) of the common carotid artery in healthy men. Fifty-eight subjects were studied. Shear stress was calculated as blood viscosityxblood velocity/internal diameter. Circumferential wall tension was calculated as blood pressurexinternal radius. Blood velocity, internal diameter, and IMT were measured by high-resolution echo-Doppler. Mean shear stress was 12.6+/-3.3 dynes/cm(2) (mean+/-SD; range, 4.8 to 20.4) and was inversely related with age, blood pressure, and body mass index (BMI). Mean circumferential wall tension was 3.4+/-0.6x10(4) dynes/cm (range 2.4 to 5.6) and was directly associated with age and BMI. IMT was inversely associated with shear stress (r=0.55, P<0. 0001) and directly associated with circumferential wall tension (r=0. 43, P<0.0001). Shear stress and circumferential wall tension were inversely correlated (r=0.66, P<0.0001). In multiple regression analysis, shear stress and (marginally) cholesterol were independently associated with IMT, whereas circumferential wall tension, age, and BMI were not. These findings confirm that common carotid shear stress varies among healthy individuals and decreases as age, blood pressure, and BMI increase. Our findings also demonstrate that circumferential wall tension is directly associated with wall thickness, age, and BMI and that shear stress is associated with common carotid IMT independent of other hemodynamic, clinical, or biochemical factors.

Objective: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives., Methods: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45., Results: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different., Conclusions: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.

Background: Hypertensive patients are characterized by development of both left ventricular hypertrophy (LVH) and endothelial dysfunction, Methods and Results: We enrolled 65 never-treated hypertensive patients (36 men and 29 women aged 45.6+/-6.0 years) to assess the possible relationship between echocardiographic left ventricular mass (LVM) and endothelium-dependent vasodilation. Left ventricular measurements were performed at end diastole and end systole according to the recommendations of the American Society of Echocardiography and the Penn Convention. LVM was calculated with the Devereux formula and indexed by body surface area and height raised to the 2.7th power. The endothelial function was tested as responses of forearm vasculature to acetylcholine (ACh), an endothelium-dependent vasodilator (7.5, 15, and 30 microg. mL-1. min-1, each for 5 minutes), and sodium nitroprusside (SNP), an endothelium-independent vasodilator (0.8, 1.6, and 3.2 microg. mL-1. min-1, each for 5 minutes). Drugs were infused into the brachial artery, and forearm blood flow (FBF) was measured by strain-gauge plethysmography. A negative significant relationship between indexed LVM and peak of increase in FBF was found during ACh infusions (r=-0. 554; P<0.0001). In addition, hypertrophic patients had a significantly lower responsive to ACh than patients without LVH (the peak increase in FBF was 9.9+/-3.7 versus 16.1+/-8.1 mL per 100 mL of tissue per minute; P<0.0001). No significant correlation was observed between LVM and FBF during SNP infusion., Conclusions: Our data provide the first evidence that echocardiographic LVM in hypertensive patients is inversely related to FBF responses to the endothelium-dependent vasodilating agent ACh, but it is likely that both endothelium and LVM are damaged by hypertension.

Objective: To examine whether middle (two months) and long-term (six months) isradipine sustained-release treatment improves endothelium-dependent vasodilation in never treated hypertensive patients., Methods: The responses of the forearm vasculature to acetylcholine (7.5, 15 and 30 micrograms/min) and sodium nitroprusside (0.8, 1.6, 3.2 micrograms/min) were evaluated in 12 normotensive controls (seven men and five women, aged 25 to 49 years), and in 12 hypertensives (eight men and four women, aged 20 to 47 years) at baseline and after two and six months of isradipine sustained-release treatment. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography., Results: At baseline, the response to acetylcholine was significantly lower in hypertensives vs controls: at the highest dose (30 micrograms/min), forearm blood flow was 28.6 +/- 2.4 ml/100 ml of tissue per min in the controls vs 8.9 +/- 1.0 ml/100 ml of tissue per min in hypertensive (p < 0.0001). Similarly, vascular resistance was significantly (p < 0.0001) higher in hypertensives: 4.8 +/- 0.5 units (controls) vs 15.1 +/- 1.7 units (hypertensives). After isradipine treatment, the forearm blood flow in hypertensive patients changed from 8.9 +/- 1.0 ml/100 ml of tissue per min to 16.0 +/- 1.2 ml/100 ml of tissue per min (two months; p < 0.0001) and 15.2 +/- 1.4 ml/100 ml of tissue per min (six months; p < 0.0001). Isradipine treatment did not modify the vasodilating effect of sodium nitroprusside., Conclusions: Our data demonstrate for the first time that the calcium antagonist isradipine improves acetylcholine-induced vasodilation in hypertensives.

The mechanisms underlying macrovascular complications in NIDDM are partially understood. In addition to increased prevalence and severity of systemic cardiovascular risk factors, local alterations of arterial wall and hemodynamics may play a role. Atherosclerotic lesions usually lie in regions of low wall shear stress. We therefore investigated the wall shear stress--that is, the frictional force acting tangentially to the endothelial surface--in the common carotid artery of diabetic and control subjects. Enrolled were 18 male NIDDM subjects and 18 age-matched control subjects. None of the participants were hypertensive, hyperlipidemic, or a cigarette smoker. Common carotid wall shear stress was calculated according to the following equation: blood viscosity x blood velocity/internal diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity and internal diameter were measured by high-resolution echo-Doppler. Wall shear stress was significantly lower in NIDDM subjects than in control subjects (mean wall shear stress: 9.7 +/- 2.4 vs. 11.7 +/- 2.6 dynes/cm2, P < or = 0.005). Six diabetic participants had a plaque in one carotid tree and no lesions in the contralateral carotid. Among these subjects, mean wall shear stress was significantly lower in the side with lesion (8.1 +/- 1.6 vs. 10.5 +/- 2.4 dynes/cm2, P < or = 0.02). These findings suggest that diabetes is associated with a more atherosclerosis-prone carotid hemodynamic profile, which might represent an additional factor contributing to the increased prevalence and severity of carotid atherosclerosis in diabetic patients compared with general population.

The impact of molecular genetics in the diagnosis and management of various forms of heritable cardiac or vascular disorders is continuously increasing thanks to the newly available laboratory tools. Familial hypertrophic cardiomyopathy (FHC), an autosomal dominant inherited disease characterized by unexplained left ventricular hypertrophy and a wide range of clinical symptoms, is the first cardiac disorder whose genetic bases have been elucidated. Linkage analysis studies have shown a statistically significant association between the disease status and at least seven genetic loci, all coding for sarcomeric proteins, in unrelated kindreds. A major challenge for physicians is to make an accurate and early diagnosis, not only on the basis of the traditional tools (i.e. physical examination and electro-echocardiography) but also to focus on the impact of genotype on clinical manifestations of FHC. In this review we present the more recent findings on the genetic basis of FHC and analyze the genotype-phenotype correlations of this disorder, whose expression may be modulated by additional factors (modifier genes, genetic background, environmental factors) other than mutations in any of the sarcometric proteins.

The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 microg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive outpatients (17 men and 15 women, aged 43+/-7 years) and in 24 normotensive control subjects (14 men and 10 women, aged 42+/-6 years). Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. In both hypertensive and normotensive groups, a deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was determined by polymerase chain reaction. The response to acetylcholine was significantly reduced in hypertensive patients versus control subjects: at the highest dose (30 microg/min), forearm blood flow was 13.9+/-6.3 mL x 100 mL tissue(-1) x min(-1) in hypertensives versus 27.1+/-9.7 mL x 100 mL tissue(-1) x min(-1) in the controls (P<.001); similarly, vascular resistance was 10.6+/-5.6 U in hypertensive patients and 4.9+/-1.9 U in normotensive subjects. In the hypertensive group, the patients with DD genotype showed significantly less endothelium-dependent vasodilation compared with ID+II genotypes (at the highest dose of acetylcholine, forearm blood flow was 12.1+/-4.2 versus 17.0+/-4.1 mL x 100 mL tissue(-1) x min(-1)) (P<.005). The vasodilator effect of sodium nitroprusside infusions was not statistically different in DD and ID+II hypertensive patients. In conclusion, our data suggest that ACE polymorphism affects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endothelium-dependent agent acetylcholine.

The purpose of the present study was to assess the degree of awareness, treatment and control of hyperlipidaemia compared with hypertension and diabetes mellitus in a selected population of southern Italy. All participants to a cardiovascular disease prevention campaign examined between April 1994 and July 1995 were screened for hyperlipidaemia, hypertension and diabetes mellitus. Subjects received also ECG, echo-Doppler of carotid arteries and filled in a questionnaire concerning personal and familial cardiovascular diseases, smoking habit and drug consumption. Of the 742 participants, 327 were found to have hypertension, 73 to have diabetes mellitus, 287 to have mild hyperlipidaemia and 322 to have moderate-severe hyperlipidaemia. Among hypertensive subjects, 60.2% were aware of their condition, 53.5% were treated and 15.6% had their blood pressure controlled at the recommended level (< 140/90 mmHg). Among diabetic subjects, 76.7% were aware, 64.4% treated and 19.2% reached fasting blood glucose level of less than 7.77 mmol/l (140 mg/dl). Only 24.0% of subjects with mild hyperlipidaemia were aware of their condition. Of the subjects found to have moderate-severe hyperlipidaemia, 64.9% were aware, 32.3% were treated and 9.0% had plasma cholesterol and triglycerides concentration of less than 6.45 and 5.65 mmol/l (250 and 500 mg/dl), respectively (cutoffs chosen to separate mild from moderate-severe hyperlipidaemia). These results show that mild hyperlipidaemia is almost neglected whereas awareness of moderave-severe hyperlipidaemia is quite widespread and comparable to that of hypertension and diabetes mellitus. Prevalence of treatment and control of moderate-severe hyperlipidaemia is, however, much lower than that of hypertension and diabetes.

Background and Purpose: It is known that atherosclerosis does not involve both carotid arteries to the same extent. Pathological investigations have demonstrated that lesions develop in regions of low wall shear stress. The aims of the present study were to verify the degree of carotid atherosclerosis asymmetry in a population-based study and to evaluate whether wall shear stress is lower in carotids with atherosclerotic lesions than in carotids without lesions., Methods: Participants in a cardiovascular disease prevention campaign (n = 1166) were screened for carotid atherosclerosis by echo-Doppler examination. Of these, 23 subjects who presented plaque in the common carotid or bulb of one side and no plaque in the contralateral carotid tree were enrolled for common carotid wall shear stress measurement. Shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter., Results: Of the 1166 subjects screened, 400 (34%) had plaque and/or stenosis in the carotids. Ninety subjects had lesions exclusively in the right carotid, 111 had lesions exclusively in the left, 70 had lesions in both carotids but with different degrees of severity, and only 129 had similar lesions in both carotids. In the 23 subjects in whom wall shear stress was measured, peak shear stress was 18.7 +/- 4.1 and 15.3 +/- 4.0 dynes.cm-2 (mean +/- SD) (P < .0001) in the side without and the side with plaque, respectively. Mean shear stress yielded similar results., Conclusions: The present results demonstrate that the atherosclerotic involvement of carotid arteries is usually asymmetrical and that wall shear stress is lower in the carotid arteries where plaques are present than in plaque-free arteries. These findings provide in vivo evidence for a strong association between shear stress and atherosclerotic lesions.

We report a clinical case of a patient affected by splenic non-Hodgkin lymphoma and virus C hepatitis. It seems that this kind of association is original because as far as we know the association between non-Hodgkin lymphoma and HCV did not include non-Hodgkin lymphoma involving the spleen. Indeed, in our patient, there was an increase of CD/57 lymphocytes. In our opinion this could be interesting in the disorders of the immune system associated with lymphoma.

Objectives: This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI)., Background: The renin-angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy., Methods: The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/ deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient., Results: Left ventricular mass index values (mean +/- SD) were 137 +/- 28 g/m2 in patients with the DD genotype, 125 +/- 27 g/m2 in those with the ID genotype and 115 +/- 27 g/m2 in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02)., Conclusions: Our data show that the LVMI was significantly enhanced in patients with the DD genotype.

Background: Atherosclerotic lesions lie in regions of low wall shear stress. No relationship between wall shear stress and intima-media thickness in vivo has been reported. Aims of the present study were to verify the reproducibility of wall shear stress measurement in vivo and to evaluate its association with intima-media thickness in the common carotid artery in healthy subjects., Methods and Results: Wall shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity, internal diameter, and intima-media thickness were measured by high-resolution echo Doppler. Twenty-one healthy male subjects were investigated. Peak and mean shear stress values were 29.5 +/- 8.2 and 12.1 +/- 3.1 dynes/cm-2 (mean +/- SD), respectively. Peak shear stress was inversely related to intima-media thickness (r = .62), age (r = .77), systolic blood pressure (r = .61), and body mass index (r = .59) (P < .001 for all coefficients). Mean shear stress yielded similar results. The relationship between shear stress and intima-media thickness was independent of age, blood pressure, and body mass index. The reproducibility, calculated by Kendall's W test, was statistically significant., Conclusions: Our results demonstrate that common carotid artery wall shear stress measurement in vivo is reproducible. It inversely relates to intima-media thickness, age, systolic blood pressure, and body mass index. These findings confirm in vivo the role of shear stress in intima-media thickening.

A previously undescribed de novo insertion-deletion mutation in the beta cardiac myosin heavy chain gene was found in a kindred with familial hypertrophic cardiomyopathy. In the mutated allele there is an inserted-deleted guanine at nucleotides 8823 and 8850 of the beta myosin heavy chain gene, resulting in a dramatic change of the amino acid sequence (AA 395-404). such a mutation, detected in the proband and in his son but not in the proband's parents, is likely to produce major impairment of myosin function.

Rendu-Osler-Weber disease is an hereditary disorder characterized by cutaneo-mucous telangiectasis and vascular abnormalities in several organs. Bleeding, especially epistaxis, represents the most important clinical feature. Pulmonary arteriovenous fistulae can cause hypoxaemia, haemoptysis, polycythaemia and clubbing. Diagnosis is based on family and personal history, teleangiectasis, laboratory (haemochrome, fibrinogen, PT, PTT) and instrumental findings (endoscopy and/or roentgen). Therapy depends on symptoms. Embolization of pulmonary arteriovenous fistulae and laser treatment of intestinal vascular abnormalities have been successful. Danazol treatment yielded controversial results. We report the case of a patient admitted for arterial hypertension and recurrent epistaxis. Rendu-Osler-Weber disease diagnosis was made based on positivity at family and personal history, clinical examination, laboratory and instrumental findings. In conclusion we underline the pivotal role of anamnesis and clinical examination in the differential diagnosis of hereditary bleeding disorders and emphasize the importance of early diagnosis for the correct therapeutic approach.

We present a clinical case in which a patient with a brain metastasis had a clinical onset simulating a stroke. Computerized tomography showed a lesion which was diagnosed as ischaemic, whereas magnetic resonance imaging showed an expansive lesion surrounded by an aedematous region of probable neoplastic nature. Indeed histology confirmed the neoplastic origin of the lesion. This kind of presentation is very uncommon but when an hypodense area is detected on CT scan one should always think to this occurrence. Neuroradiology is often necessary for a correct diagnosis. CT scan might usefully be integrated by MRI to distinguish between stroke and brain neoplasty.

There is increasing evidence that arterial intima-media thickness (IMT) might represent an early atherosclerotic lesion. The clinical importance of its measurement is, however, still debated. The aim of the present study was to analyze the effect of coronary heart disease (CHD) risk factors on carotid IMT and to verify whether intima-media thickening is associated with overt atherosclerosis of carotid arteries. Two hundred and seventy-six subjects referred to the Angiology Unit for echo-Doppler examination of carotid arteries during the period January-June 1993 were enrolled. Echo-Doppler was performed with a Multigon Angioview 600. IMT was measured in the common carotid artery, 1 cm proximal to the bulb. CHD risk factors were evaluated by routine methods. In males IMT increased significantly with increasing number of CHD risk factors. In females only the presence of three CHD risk factors was associated with a significant IMT increase. In both sexes IMT was higher in subjects with evidence of atherosclerotic lesions in the carotid arteries. In multiple regression analysis IMT was strongly and significantly associated with the presence of plaques and/or stenosis in the carotid arteries. The present findings suggest that IMT measurement can be useful in clinical practice, giving a comprehensive picture of the damage caused by several CHD risk factors over time on arterial wall.

In order to evaluate the antihypertensive effects of manidipine, at the dosage of 10 or 20 mg once daily, we studied 36 patients (12 males and 24 females, mean age 54.3 years) with mild hypertension. After a wash-out period of 2 weeks and another 2 week run-in period with placebo, all the patients were assigned to a treatment with manidipine 10 mg/ day. After 2 weeks of treatment, the non-normalized (diastolic BP > 90 mmHg) and the non-responders (BP fall < 10 mmHg) received an increase in dosage to 20 mg/day. The drug effects were assessed by casual blood pressure (BP) measurement at baseline and after 4, 8, 12, 24, 36 and 52 weeks. At baseline and after 1 year of treatment a 24-h BP monitoring and a Doppler echocardiogram were performed. Routine laboratory tests were performed at baseline, after 6 months and after 1 year of treatment. At the end of the observation period, both casual systolic (p < 0.01) and diastolic (p < 0.001) BP were significantly reduced; 24-h BP monitoring showed a significant decrease in systolic (p < 0.05) and diastolic (p < 0.01) pressure, systolic and diastolic (p < 0.001) daytime and night-time measurements. The peak to through ratio was 67%. No difference was found in heart rate. Reduced interventricular septum thickness (p < 0.05), increased fractional shortening (p < 0.02), reduced end-systolic stress (p < 0.005) and systemic vascular resistances (p < 0.001), and lower values of atrial filling fraction (AFF) (p < 0.001) after 1 year of treatment have been shown at the Doppler-Echo evaluation. A multilinear regression analysis showed a relation between delta %AFF and delta %24-h systolic BP (R = 0.74; F = 7.5: p < 0.05) and with delta % daytime systolic BP (R = 0.77; F = 9.2; p < 0.02). No abnormal changes were observed in laboratory tests. Three non-responder patients and three patients with adverse effects (1 flushing and 2 ankle oedema) dropped out and were excluded from the final analysis. In conclusion, manidipine at an individualized dose of 10 or 20 mg. was effective and safe in the management of arterial hypertension. Hemodynamic evaluations after 1 year of treatment confirmed an improvement of systolic and diastolic function, with an evident reduction of afterload.

Background: Intimal thickening is an adaptive process of the arterial wall, presumably related to atherogenesis. Sex and interethnic differences in intimal thickening, as demonstrated histologically on autoptic material, would indicate a strong genetic control on this process. An insertion/deletion (ID) polymorphism in the angiotensin-converting enzyme (ACE) gene has been shown to be an independent risk factor for cardiovascular disease, especially in subjects otherwise at low risk for coronary heart disease. The aim of the present study was to evaluate the relationship between intimal plus medial thickness (IMT) and ACE-I/D genotype., Methods: 132 healthy male subjects from Southern Italy were enrolled. IMT has been evaluated from high resolution B-mode echo-Doppler images. Blood lipids and glucose were measured using standard methods. Cigarette consumption was recorded by questionnaire. ACE genotypes were analysed by polymerase chain reaction., Results: Blood lipids, blood pressure and percentage of smokers were similar in the three groups. IMT was greatest in DD subjects, lowest in II subjects and intermediate in heterozygotes. The association between the presence of the D allele and IMT values was statistically significant. Significance was maintained after the elimination of subjects with carotid atherosclerotic plaques., Conclusions: The present data suggest that the ACE gene seems to be a candidate gene that strongly influences the IMT of the arterial wall and might therefore be involved in the individual's predisposition to the development of atherosclerosis.

A case of occult bleeding of the upper intestinal tract in a patient with secondary polycythaemia and aortic valve stenosis is described. Routine tests failed to disclose the origin of the bleeding and the patient's condition continued to deteriorate. On the 23rd day after admission, laparotomy was performed, and an ulcerated diverticulum diagnosed. Resection of the diverticulum was done immediately. The patient had an uneventful post-operative recovery and was dismissed from the hospital 15 days later. Our experience underscores the necessity for early laparotomy in cases of gastrointestinal bleeding of obscure origin.

We compared the efficacy and tolerability of isradipine (ISR) and fosinopril (FOS) once-a-day administration in 17 outpatients, 9 men and 8 women, aged 35-65 years (mean +/- SD = 58 +/- 10 years), affected by mild to moderate primary systemic hypertension. The patients were given single-blind placebo for 2 weeks and thereafter, in double-blind, randomized, crossover sequence, ISR (5 mg) and FOS (20 mg), both for 4 weeks. At the end of each period, patients underwent 24-h noninvasive blood pressure (BP) monitoring by means of an A&D TM 2420 Monitor Model 7, with readings taken very 10 min during the day (from 7 A.M. to 11 P.M.), and every 20 min during the night (from 11 P.M. to 7 A.M.) Similarly, BP load (BPL) as percentage of systolic and diastolic BP reading > 140 and > 90 mmHg was investigated. Both ISR and FOS induced a highly significant (p < 0.0001) decrease in BP from 158/96 +/- 7/6 mmHg to 133/86 +/- 6/6 and to 132/83 +/- 10/7 mmHg, respectively. Mean BP decreased from 117 +/- 6 mmHg to 102 +/- 6 mmHg (ISR) (p < 0.0001) and to 99 +/- 8 mmHg (FOS) (p < 0.0001). Both ISR and FOS significantly (p < 0.0001) reduced systolic BPL from 78 +/- 16% to 44 +/- 13% and 28 +/- 12%, respectively, and diastolic BPL from 70 +/- 15% to 40 +/- 13% (p < 0.0001) and 35 +/- 13% (p < 0.0001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Intima-media thickness has been reported to be increased in several patients with disorders such as diabetes mellitus, systolic hypertension and familial hypercholesterolemia. No data are available for the less severe but more frequent forms of hyperlipidemia. The aim of the present study was to compare the intima-media thickness in men with mild to moderate hyperlipidemia with that in age- and sex-matched normolipidemic controls., Methods: Fifty hyperlipidemic patients and 50 controls were enrolled in this study. Intima-media thickness was evaluated from high-resolution B-mode echo-Doppler images. Blood lipids and glucose were measured using standard methods. Cigarette consumption was recorded by questionnaire., Results: Intima-media thickness was significantly higher in hyperlipidemic patients than in controls. Smokers, both hyperlipidemic and controls, had higher values of intima-media thickness, although not significantly so, than non-smokers. The distribution of intima-media thickness values ranged from 0.52 to 1.24 mm in hyperlipidemic patients and from 0.46 to 0.82 mm in controls. Eighteen patients with hyperlipidemia had an intima-media thickness larger than 0.82 mm and, of these, 14 had atherosclerotic plaques in the carotid arteries. Furthermore, 11 hyperlipidemic patients showed signs of cardiovascular disease and had significantly enlarged intima-media thickness compared with participants without cardiovascular disease., Conclusions: Intima-media thickness in the common carotid artery is enlarged in patients with mild to moderate forms of hyperlipidemia and the highest values of intima-media thickness are frequently associated with atherosclerotic plaques in the carotid arteries and signs of cardiovascular disease.

Objectives: To evaluate the effects of isradipine (ISR) and diltiazem (DIL) on exercise tolerance and ischemic ST depression in patients with stable effort angina., Methods: Fourteen out-patients, 9 males and 5 females, aged 46-65 years (mean +/- SD = 57 +/- 8), with ischemic heart disease and reproducible ST-segment depression on two consecutive exercise stress tests in baseline conditions, underwent a study consisting of 4 periods: 1 and 3 placebo, 2 and 4 at random ISR (5 mg b.i.d.) and DIL (120 mg b.i.d.). At the end of each period a multistage treadmill exercise stress test (Bruce protocol) was performed., Results: Both drugs significantly (p < 0.001) increased ischemia time (IT) (0.1 mV ST depression) as compared to placebo, from 438 +/- 132 s. to 620 +/- 164 s. (ISR) and 583 +/- 147 s. (DIL) without statistical difference between two drugs (p = 0.2), and significantly reduced (p < 0.002) the maximal ST depression, from -0.20 +/- 0.11 mV to -0.07 +/- 0.07 mV (ISR) and -0.09 +/- 0.11 mV (DIL). At the IT, systolic blood pressure increased (p = 0.02), from 180 +/- 19 mm Hg to 187 +/- 15 mm Hg (ISR) and 191 +/- 15 mm Hg (DIL); similarly, heart rate increased from 133 +/- 24 bpm to 144 +/- 18 bpm (ISR: p = 0.002) and 140 +/- 17 bpm (DIL: p = NS)., Conclusions: ISR and DIL, at the above dosage have showed an important and significant anti-ischemic effect (IT = +41.5% during ISR and +33.1% during DIL).

Objective: To verify whether carotid arterial intimal plus media thickness (IMT) is greater in non-insulin-dependent diabetes mellitus (NIDDM) subjects, known to be at high risk for atherosclerosis. Evidence is growing that IMT is increased in subjects with coronary heart disease (CHD) risk factors like hypercholesterolemia and cigarette smoking., Research Design and Methods: Fifty-four NIDDM subjects and 54 sex- and age-matched control subjects underwent CHD risk factors assessment and echo-Doppler examination of carotid arteries. IMT was measured by computer technique in the common carotid artery (CCA). Presence of plaques and/or stenosis (carotid atherosclerosis [CA]) was also evaluated by a single-blinded reader., Results: NIDDM subjects had larger IMT, higher levels of triglycerides, and lower concentrations of high-density lipoprotein (HDL) cholesterol compared with control subjects. IMT was positively correlated to age and systolic blood pressure and inversely to HDL cholesterol in both groups. The prevalence of CA was 46% in NIDDM subjects and 18% in control subjects. In multiple regression analysis, IMT was the only variable significantly associated to CA., Conclusions: IMT of CCA is enlarged in NIDDM subjects compared with control subjects. Its association with carotid plaques and/or stenosis might be of importance to detect early atherosclerotic lesions in the carotid arteries.

We report a case of elbow fracture associated with brachial artery stenosis. Several authors reported that elbow fractures are associated with brachial artery injury. In the present case we detected brachial artery stenosis in a patient with a history of elbow fracture. Therefore we suggest that every patient with elbow trauma should undergo an assessment for brachial artery stenosis.

The ACE gene has recently been shown to be associated with myocardial infarction, especially in subjects considered at low risk for coronary heart disease (CHD) according to common classification criteria. The possible relationship between deletion polymorphism in this gene and CHD risk factors, as well as asymptomatic extracoronary atherosclerosis, has been investigated in the present study. One hundred and seventy-four subjects, enrolled in a cardiovascular disease prevention study, underwent clinical and biochemical examination and ACE-I/D polymorphism determination. Subjects > 45 years of age (n = 107) also received echo-Doppler examination of the carotid arteries. Based on the results of ACE-I/D polymorphism, subjects were divided into three groups: homozygous for deletion (D/D), homozygous for insertion (I/I) and heterozygous (I/D). The prevalence of CHD risk factors as well as of extracoronary atherosclerosis was similar in the three genotype groups. Similarly, there was no association between the presence of atherosclerotic lesions and genotype in subjects at low and high CHD risk. Ten subjects with diabetes mellitus had ACE-D/D genotype. Among these subjects seven had hypertension. Eight subjects with diabetes mellitus had ACE-I/D genotype and only one of these was hypertensive. None of the ACE-I/I subjects was diabetic. ACE-I/D polymorphism seems to play a role in the development of hypertension, at least in diabetic subjects. Its determination may help to identify and monitor diabetic subjects prone to hypertension.

The present study was designed to investigate on possible association between SstI polymorphism in the ApoAI-CIII-AIV gene cluster, classical coronary heart disease risk factors and extracoronary atherosclerosis. One hundred and twenty six male subjects were enrolled and underwent echo-Doppler examination of carotid and femoral arteries, coronary heart disease risk factors assessment and SstI genotyping. The frequency of the rare SsI allele was 12.1% and 6.7% in subjects with or without extracoronary lesions respectively and was not associated with differences in the distribution of coronary heart disease risk factors. Forty subjects had hypertension, 34 homozygous for the frequent allele and 6 with presence of the rare allele. Among these, 10 subjects (29%) and 5 subjects (83%), respectively, had extracoronary atherosclerosis. Furthermore, subjects homozygous for the rare allele exhibited lipid abnormalities and a family history positive for hypertension and/or hyperlipidemia. These findings suggest a possible role for the ApoAI-CIII-AIV gene complex in both lipid metabolism and blood pressure regulation and could be of help to identify, within hypertensives, those subjects prone to extracoronary atherosclerosis.

This study was designed to compare the efficacy and tolerability of amlodipine (AML) and ramipril (RAM) administered once a day in patients affected by mild to moderate primary systemic hypertension. Twenty outpatients, 12 men and 8 women (age range 35-64 years), were enrolled. The patients received single-blind placebo for 2 weeks and thereafter in a double-blind, randomized crossover sequence AML (10 mg) and RAM (5 mg), both for 4 weeks. At the end of each period, the patients underwent 24-hour noninvasive blood pressure monitoring with readings taken every 10 min during daytime (from 07.00 to 23.00 h) and 20 min during nighttime (from 23.00 to 07.00 h). Both AML and RAM induced a highly significant (p < 0.0001) decrease in blood pressure from 162/103 +/- 7/3 to 132/82 +/- 6/6 and 135/83 +/- 6/5 mm Hg, respectively. The mean blood pressure decreased from 122 +/- 5 to 99 +/- 6 (AML; p < 0.0001) and 100 +/- 5 mm Hg (RAM; p < 0.0001). No significant differences in heart rate were noted during drug administrations. Treatment did not have to be discontinued in any patient because of adverse reactions. In conclusion, both AML and RAM reduced the blood pressure markedly, even if AML proved to be significantly more effective than RAM.

Intimal plus media thickening has been described to be associated with several cardiovascular risk factors. Aim of the present study was to evaluate the intimal plus media thickness in male subjects with hypertension compared to age matched males normotensive controls. Twenty subjects with hypertension, defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg and/or use of antihypertensive drugs, and forty age matched controls have been enrolled. Intimal plus media thickness has been measured from B-mode echography images by a computer. Plasma lipids have been measured by routine methods. A zero random sphygmomanometer has been used to detect blood pressure. Intima plus media thickness resulted enlarged in subjects with hypertension compared to normotensive controls. The thickening of intima-media complex seems related to atherosclerotic lesions, therefore its early detection by noninvasive techniques might improve the identification and the monitoring of high risk hypertensive subjects.