Severe haemolytic anaemia after valvuloplasty and annuloplasty.

Haemolytic anaemia is a well-recognised but rare complication of heart-valve prostheses. The authors report a case of an 80-year-old woman with severe haemolytic anaemia previously treated with valvuloplasty and annuloplasty without rings. To our knowledge, no cases of haemolysis have been described with this type of surgery.

Association between depressive mood and cigarette smoking in a large Italian sample of smokers intending to quit: implications for treatment.

OBJECTIVE: The aim of the study is to assess the prevalence and degree of depression at baseline of a large cohort of smokers intending to quit. METHODS: A cross-sectional investigation was carried out on a population of 757 smokers attending the Medical Service for Addictive Disorders, at Verona University Hospital. The degree of nicotine addiction was measured by the Fagerstrom Test of Nicotine Dependence (FTND) and current mood tested by the Self-rating Depression Scale (SDS), a commonly used and well validated instrument to assess depressive mood. RESULTS: Two hundred and twenty-two subjects (30.3%) were depressed at baseline (SDS test score > or = 50). Bivariate analysis, using the SDs score dichotomised at the cut-off of 50 as dependent variable, shows that female gender (p=0.01) and widowhood (p<0.001) were correlated to depression. Logistic regression analysis confirms the correlation between depression and female gender (OR=2.03, IC 95%=1.42-2.88, p<0.001) and between depression and widowhood, with the greatest risk of depression among widows and widowers (OR=3.22, IC 95%=1.01-10.27, p<0.048). CONCLUSIONS: The study showed a high degree of pre-treatment depression in smokers intending to quit. Although the association between depression and nicotine dependence has been consistently reported many times, and it is well known that depressed subjects find it more difficult to quit, most guidelines seem not to consider this connection. These findings suggest the need for baseline assessment of depression by screening all smokers seeking assistance in quitting, a priority health objective because smoking is the number one avoidable killer in developed countries.

Insulin and glucose mediate opposite intracellular ionized magnesium variations in human lymphocytes.

Insulin is capable of increasing intracellular magnesium, although very little is known about the effect of insulin on the biologically active fraction of magnesium, i.e. the ionized quota (Mg(i)(2+)), its interactions with glucose, and the cellular mechanisms involved in these processes. We studied the interactions of the effects of insulin and glucose on intracellular ionized magnesium in human lymphocytes. Mg(i)(2+) was measured using a fluorimetric method and the Mg(2+)-sensitive dye, furaptra. We found that insulin significantly increases the Mg(i)(2+)(without insulin 227 +/- 14 microM, with 10 microU/ml, insulin 301 +/- 30 microM, P<0.0001, n = 12) in a dose-dependent manner in all three glucose concentrations tested (5, 7 and 15 mmol/l). The half-maximal effect of insulin was approximately 0.8 microU/ml. Glucose and insulin showed opposite effects in their ability to modify Mg(i)(2+) in lymphocytes. Inhibitors of the membrane Na(+)- Mg(2+) transport system and of phosphatidylinositol (PI) 3-kinase abolish the insulin-mediated increase of Mg(i)(2+), thus suggesting that insulin is capable of increasing Mg(i)(2+) by modulating the activity of this transport system, possibly through the mediation of PI 3-kinase activation. Taking into account the relationship between insulin and glucose plasma levels and their opposing effects on Mg(i)(2+), this mechanism may represent the two limbs of a biphasic regulatory system of Mg(i)(2+) in both physiological and pathological conditions.

Effects of smoking on cardiopulmonary baroreceptor activation and peripheral vascular resistance.

PATIENTS AND METHODS: We studied 16 healthy smokers and 16 nonsmokers acting as controls. We subjected smokers and nonsmokers to cardiopulmonary baroreceptor stimulation by studying forearm and common carotid haemodynamic and sympathovagal balance. Smokers repeated the tests after smoking one cigarette. Smokers and controls were subjected to passive elevation of the legs and the trunk in a horizontal position with pressure monitoring and measurement of the calibre and flow in the brachial and common carotid arteries using a colourDoppler ultrasound. We calculated forearm resistance and carotid wall tension. We also studied R-R variability, calculating the ratio between low frequency (LF) and high frequency (HF) R-R interval variability. RESULTS: During stimulation diastolic blood pressure values decreased in controls and in smokers at rest. After smoking one cigarette, smokers showed an increase in systolic and diastolic blood pressure as well as in the heart rate during stimulation. Humeral artery increased the calibre during stimulation in both groups; after cigarette smoking the calibre declined throughout the study phases. Forearm resistance decreased in both groups during stimulation at rest, but increased after cigarette smoking. The LF/HF ratio decreased during stimulation in both groups, and it increased at rest after smoking. Carotid diameter did not change in either group, and wall tension increased in smokers after smoking one cigarette. CONCLUSIONS: Smoking one cigarette increases resistance, impairs baroreflex and increases carotid wall tension in mild smokers. These findings may explain the higher rate of a cardiovascular event in smokers.

Haemodynamic effects of AT1 inhibition and Ca2+-channel blockade in hypertensive patients during isometric stress.

To assess the effects of valsartan and amlodipine on the haemodynamics of forearm circulation in hypertensive patients undergoing isometric stress. A total of 24 patients with essential hypertension were subjected to a double blind-cross-over study. The artery left arm flow (strain gauge plethysmography), distensibility of digital arteries (piezoelectric plethysmography) and blood pressure were measured. District resistance was calculated as the ratio between mean arterial pressure and blood flow. The tests were performed at basal conditions (T0) and after 8 days (T8) of therapy with valsartan (160 mg) or amlodipine (10 mg), at rest and during handgrip (HG); treatments were inverted after 15 days of washout. Valsartan and amlodipine reduced blood pressure after 8 days (P<0.05), handgrip increased systolic and diastolic values and heart rate at T0 and only a slight raising in diastolic values at T8. The recovery time of pressure values was longer in hypertensives treated with amlodipine (P<0.05). The forearm flow increased after HG (at T0 an T8) and increased even further after valsartan (P<0.005). Valsartan increased arteriolar distensibility, expressed by the ratio between time to peak and total time (PT/TT) calculated on the sphygmic wave. Amlodipine did not affect PT/TT ratio, whereas it reduced local resistance (T8 vs T0, P<0.05). The reduction effect of valsartan on resistance was detectable also during handgrip, on the contrary amlodipine did not control the increase. Inhibition of AT1 is able to reduce haemodynamic modifications elicited by isometric stress in hypertensive patients.

Catecholamine-induced regulation in vitro and ex vivo of intralymphocyte ionized magnesium.

Despite the importance of the adrenergic activity and of the metabolism of magnesium in some important cardiovascular pathologies, very little is known about how intracellular ionized magnesium (Mgi2+) is regulated by catecholamines. We made an in-vitro study of the variations in the concentration of ionized magnesium in human lymphocytes using the fluorescent probe furaptra in response to different catecholamines. We also made an ex-vivo study of the changes in intracellular ionized magnesium in lymphocytes in 20 subjects with essential arterial hypertension, 10 treated with 120 mg/d of propranolol and 10 with placebo. Norepinephrine and isoproterenol significantly decrease Mgi2+ and this effect is blocked by beta-blockers but not by alpha-blockers. The EC50 of the effect of norepinephrine is within the range of concentrations physiologically present in plasma. The substitution of extracellular sodium with choline blocks the decrease in intracellular ionized magnesium induced by norepinephrine, which leads us to suppose that the magnesium-reducing effect of catecholamines is a result of the activation of a Na+-Mg2+ exchanger. We were not able to demonstrate any change in intracellular ionized magnesium after 1 and 17 days of active treatment in essential hypertensives. The impossibility of demonstrating ex vivo the mechanism of catecholamine-mediated regulation that is evident in vitro is perhaps due to our experimental conditions or to substances which in vivo inhibit the action of the catecholamines on magnesium, such as insulin and/or glucose.

Elevated plasma fibrinogen levels in patients with essential hypertension are related to vascular complications.

AIM: We investigated whether or not fibrinogen is related to the cardiovascular risk profile and complications in hypertensive subjects. METHODS: Plasma fibrinogen and laboratory tests including factor VII, homocysteine and microalbuminuria were evaluated in 127 consecutive hypertensive subjects stratified according to cardiovascular risk. Parameters were age, gender, smoking, cholesterol, diabetes, target organ damage: left ventricular hypertrophy (LVH), carotid atherosclerotic complications and retinical vessels. RESULTS: Fibrinogen levels were significantly different between patients according to risk levels (low 290+/-73, n=20, high 342+/-94 mg/dl, n=39, very high risk 350+/-72, n=29, p=0.01), hypertension grade (II-III) and organ damage. Fibrinogen was significantly higher in patients with more severe carotid atherosclerotic lesions and vascular retinal lesions (grades II-III vs 0 and I). Also in patients, matched for age and sex, without and with carotid atherosclerotic lesions, fibrinogen was significantly higher in the latter group. No significant differences were found on the basis of IVS, creatinine and microalbuminuria. In hypertensive patients, fibrinogen directly correlated with age, by multiple linear regression. In hypertensive patients with diabetes, fibrinogen was significantly higher (466+/-176 mg/dL, n=14) than in those hypertensive without diabetes (333+/-87 mg/dL, n=113, p=0.001) and in all patients there was a a significant correlation (r=0.474, p<0.001) between blood glucose and fibrinogen. CONCLUSION: Hyperfibrinogenemia is a marker of vascular damage and could be an important factor contributing to the evolution of the complications.

Causas principales de muerte entre 2.708 heroinómanos del noreste italiano (1985-1998) / Main death causes among 2.708 heroin addicts of Italian northeast (1985-1998)

Objetivos. Establecer las causas de la muerte acaecidas entre 1985 y 1998 en un numeroso grupo de usuarios de droga por vía intravenosa (ADVP) acogidos en 36 Servicios Públicos para Toxicomanías (Ser T) del noroeste italiano. Métodos. Estudio realizado sobre datos recogidos en los archivos de los Ser. T y del Registro Municipal de cada una de las ULSS estudiadas. Individuos implicados. Todos los ADVP que hayan pasado por lo menos una vez por uno de los 36 Ser. T incluidos en el estudio. Resultados. El estudio analizó las causas de la muerte de 2708 individuos. La primera cauda de muerte es la sobredosis (37 por ciento), seguida del SIDA (32,5 por ciento) y de los accidentes de tráfico (9,4 por ciento). El porcentaje de muertes causadas por el SIDA aumentó progresivamente, pasando de un 2.7 por ciento en 1985 a un 42,2 por ciento en 1996, reduciéndose después al 16,9 por ciento en 1998. El porcentaje de fallecimientos por sobredosis se mantuvo prácticamente constante durante todo el tiempo. La edad media de muerte aumentó, pasando de 26 años a mediados de los años 80 a 34 años en 1998. La tasa de mortalidad entre ADVP es 13 veces mayor que en el conjunto de la población (95 por ciento, CI 11.3-14.6). En el conjunto de la población el porcentaje de fallecimientos en edades comprendidas entre los 15 y los 34 años atribuida al uso de opiáceos era en 1991 (año del últimocenso) del 16 por ciento. La prevalencia del VIH no resultó estadísticamente significativa en las causas de muerte por suicidio o sobredosis. Conclusiones. Se comprobó que la tasa de mortalidad era 13 veces superior a la de la población general. Se demostró la importancia del sexo femenino y el drop out de los tratamiento (al margen del tipo de tratamiento en cuestión) como factores de riesgo de sobredosis. La paulatina disminución de muertes por SIDA destaca la importancia de los tratamientos preventivos y terapéuticos adecuados contra la infección de VHC. Las medidas que se adopten en el campo de las drogodependencias, tanto en el ámbito de la política como en la investigación y la formación, deben tener presente el dramáticamente elevado porcentaje de individuos que mueren por consumo de heroína (AU)

Aims: To ascertain the causes of deaths among a very large cohort of heroin injecting drug users (IDUs) who, from 1985 to 1998, attended 36 Public Health Authority Centres for Drug Users (PCDUs) in north-eastern Italy. Design: Retrospective analysis of data, obtained from the Annual Register of each Centre and the Municipal Registry Office of each local health district. Setting: Thirty-six PCDUs in north-eastern Italy and Medical Service for Addictive Disorders of the University of Verona. Participants: All IDUs who had sought medical care at least once in the PCDUs during the study period. Findings: Of 2708 deaths, overdose was found to be the major cause (37%), followed by AIDS (32.5%) and road accidents (9.4%). The percentage of deaths due to AIDS increased steadily from 2.7% in 1985 to 42.2% in 1996, and then decreased to 16.9% in 1998. Deaths due to overdose remained almost constant. The average age of death per year rose from 26 in the mid eighties to 34 in 1998. The mortality rate among IDUs proved much higher compared to the general population of the same age (13-fold, 95% CI 11.3-14.6). The proportion of all deaths attributable to regular use of illegal opiates in the 15-34 age group in the general population in 1991 was 16%. HIV prevalence was not a significant factor in suicides and deaths by overdose. Conclusions: The mortality rate was 13 times greater than in the general population. To be female and to have dropped out of any kind of treatment proved an important risk factor for overdose. The fall in deaths from AIDS enhances the problem to prevent and treat HCV infection. Decisions in drug projects, in research and in training should be influenced by the strikingly high percentage of deaths due to drug use (AU)

NCX4016 (NO-Aspirin) has multiple inhibitory effects in LPS-stimulated human monocytes.

NCX4016 (2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester, NicOx S.A., France) is an anti-thrombotic agent, chemically related to acetylsalicylic acid (ASA) and able to release NO. We tested the effects of NCX4016 and ASA on the release of the thromboxane (TX) A(2) metabolite TXB(2), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), expression and activity of tissue factor (TF) in stimulated, adherent human monocytes. Both ASA and NCX4016 1 - 1000 micromol l(-1) dose-dependently reduced TXB(2) concentration, measured by RIA in the supernatant of 10 microg ml(-1) LPS-stimulated cells. NCX4016 activity was comparable to that of equimolar ASA when incubation lasted 6 h (NCX4016 30 micromol l(-1): -86.0+/-10.1%, NCX4016 300 micromol l(-1): -92.2+/-9.0%, ASA 30 micromol l(-1): -92.3+/-7.5%, ASA 300 micromol l(-1): -97.3+/-1.0%, n=6, M+/-s.d.). Most of the activity of NCX4016 up to 100 micromol l(-1) was prevented by 10 micromol l(-1) ODQ, inhibitor of cyclic GMP. NCX4016 100 - 300 micromol l(-1) reduced TNF-alpha (NCX4016 300 micromol l(-1)=-77.2+/-19.9%, n=6) and IL-6 (NCX4016 300 micromol l(-1): -61.9+/-15.2%, n=6) in LPS stimulated monocytes while ASA had no significant effects. TF activity (NCX4016 300 micromol l(-1): 53.7+/-39.9%, n=4) and immunoreactive TF (NCX4016 300 micromol l(-1): -93.9+/-7.9%, n=7), measured in the supernatant of stimulated cells, were also dose-dependently inhibited by NCX4016 but not by ASA. The present results indicate that NCX4016 inhibits TXA(2) generation as well as cytokine release and TF in human monocytes partly via NO-dependent mechanisms. NCX4016 may have a favourable profile of activities in the clinical setting of athero-thrombosis.

ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans.

The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Delta approximately 26%) of endothelium-dependent vasodilation in the femoral artery (P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirculation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.

Study of 2708 heroin-related deaths in north-eastern Italy 1985-98 to establish the main causes of death.

AIMS: To ascertain the causes of deaths among a very large cohort of heroin injecting drug users (IDUs) who, from 1985 to 1998, attended 36 Public Health Authority Centres for Drug Users (PCDUs) in north-eastern Italy. DESIGN: Retrospective analysis of data, obtained from the Annual Register of each Centre and the Municipal Registry Office of each local health district. SETTING: Thirty-six PCDUs in north-eastern Italy and Medical Service for Addictive Disorders of the University of Verona. PARTICIPANTS: All IDUs who had sought medical care at least once in the PCDUs during the study period. FINDINGS: Of 2708 deaths, overdose was found to be the major cause (37%), followed by AIDS (32.5%) and road accidents (9.4%). The percentage of deaths due to AIDS increased steadily from 2.7% in 1985 to 42.2% in 1996, and then decreased to 16.9% in 1998. Deaths due to overdose remained almost constant. The average age of death per year rose from 26 in the mid eighties to 34 in 1998. The mortality rate among IDUs proved much higher compared to the general population of the same age (13-fold, 95% CI, 11.3-14.6). The proportion of all deaths attributable to regular use of illegal opiates in the 15-34 age group in the general population in 1991 was 16%. HIV prevalence was not a significant factor in suicides and deaths by overdose. CONCLUSIONS: The mortality rate was 13 times greater than in the general population. To be female and to have dropped out of any kind of treatment proved an important risk factor for overdose. The fall in deaths from AIDS enhances the problem to prevent and treat HCV infection. Decisions in drug projects, in research and in training should be influenced by the strikingly high percentage of deaths due to drug use.

NCX4016 (NO-aspirin) inhibits thromboxane biosynthesis and tissue factor expression and activity in human monocytes.

BACKGROUND: NCX4016 (2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester, NicOx S.A., France) is an antithrombotic agent chemically related to acetylsalicylic acid (ASA). We hypothesised that NCX4016, being able to release nitric oxide (NO) and to inhibit cyclo-oxygenase, might inhibit the prothrombotic function in human monocytes. MATERIAL AND METHODS: The effects of NCX4016 and ASA on the release of thromboxane (TX) B2 and tissue factor expression and activity were compared using adherent human monocytes. The tested drugs were added before stimulation with 10 Kg/ml LPS and incubation lasted 6 hours. TXB2 concentration was measured by RIA in the supernatant of cultured cells. Immunoreactive tissue factor (TF) concentration was determined by enzyme-linked immunoassay and TF activity was assayed by measuring the peptidyl activity of the tissue factor/ factor VII complex. RESULTS: Both ASA and NCX4016 10-300 Kmol/L dose-dependently reduced TXB2 release. NCX4016 activity was comparable to that of equimolar ASA. Part of the activity of NCX4016 up to 100 Kmol/L was prevented by 10 Kml/L ODQ, inhibitor of cGMP generation. Immunoreactive TF was dose-dependently inhibited by 300 Kmol/L NCX4016, but not by ASA. Also tissue TF activity was reduced by 300 Kmol/L NCX4016, but not by ASA. CONCLUSIONS: The present results indicate that NCX4016 not only has anti-platelet effects but also inhibits prothrombotic activities in human monocytes, partly via NO-dependent mechanisms. NCX4016 may prove effective in the clinical setting of athero-thrombosis.

Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease.

Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function.

Isolated presence of antibody to hepatitis B core antigen in injection drug users: do they need to be vaccinated?

In a study of 497 injection drug users who had isolated presence of antibody to hepatitis B core antigen (anti-HBc) at the time of enrollment, 404 (81%) retained this condition after a mean of 49 months of follow-up, during which time no new hepatitis B surface antigen marker was detected. These findings support the hypothesis that patients with isolated presence of anti-HBc have strong resistance to reinfection and do not need vaccination.

8-Iso-PGF2 alpha induces beta 2-integrin-mediated rapid adhesion of human polymorphonuclear neutrophils: a link between oxidative stress and ischemia/reperfusion injury.

F(2)-Isoprostanes are generated from a cyclooxygenase-independent oxidative modification of arachidonic acid. They are present in atherosclerotic plaques and are platelet activators as well as potent vasoconstrictors. Polymorphonuclear neutrophils are major players in ischemia/reperfusion injury and in restenosis after PTCA. The effects of 8-isoprostaglandin (PG) F(2alpha) on very rapid beta(2)-integrin-dependent adhesion was evaluated in human neutrophils in vitro by use of purified integrin as ligand. 8-Iso-PGF(2alpha) (1 nmol/L to 20 micromol/L) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen but not to the endothelial ligand intercellular adhesion molecule-1. Pretreatment with anti-ss(2)-integrin subtypes showed activation of CD11b/CD18 and CD11c/CD18. Adhesion triggering was completely prevented by pertussis toxin. SQ29,548, a specific antagonist of thromboxane A2 receptor, also dose-dependently prevented 8-iso-PGF(2alpha)-triggered neutrophil adhesion. 8-Iso-PGF(2alpha) did not trigger adhesion in human monocytes and lymphocytes and did not induce neutrophil chemotaxis or activation of the oxygen free-radical-forming enzyme NADPH-oxidase. These data highlight the role of 8-iso-PGF(2alpha) as a specific activator of rapid neutrophil adhesion and suggest its involvement in the pathogenesis of ischemia/reperfusion injury and in restenosis after PTCA. The effect is transduced via activation of the receptor for thromboxane A2.

Prevalence of carotid artery kinking in 590 consecutive subjects evaluated by Echocolordoppler. Is there a correlation with arterial hypertension?

OBJECTIVE: To assess a possible correlation between high blood pressure and prevalence of kinking in carotid arteries. DESIGN: Between July 1, 1997 and December 31, 1998, we evaluated the subjects submitted to Echocolordoppler examination of carotid arteries. SETTING: Patients were examined at the Laboratory for Noninvasive Vascular Diagnostics of the University Hospital in Verona. SUBJECTS: 590 consecutive subjects (M/F ratio, 1/1.2; mean age, 67 years; range, 36-86 years). MAIN OUTCOME MEASURES: An Echocolordoppler ultrasonograph to evaluate by means of the standard longitudinal and transverse scans the usual parameters of both intima-to-lumen interface and flow. Moreover, particular attention was paid to the analysis of the conformational characteristic of the vessels. Kinking has been classified in three classes according to the degree of bending. All the subjects were asked to compile a questionnaire that provided us with the clinical history. RESULTS: The prevalence of hypertension in the subjects with kinking appeared higher than in subjects without this abnormality (chi2 = 6.44, P < 0. 02). We found also a significant association between kinking and transitory ischaemic attacks (chi2 = 6.987, P < 0.01). CONCLUSIONS: The high prevalence of kinking in the hypertensives agrees with the pathogenetical hypothesis ascribing a role to the high endoluminal pressure. The presence of hypertension and kinking of the internal carotid artery suggests that they could be additive risk factors in the pathophysiology of a transitory ischaemic attack.

Activity of cardiopulmonary baroreceptors, peripheral resistance and cutaneous microcirculation in patients with peripheral obstructive arterial disease.

OBJECTIVES: To assess the effects of cardiopulmonary baroreceptors on the haemodynamics of the humeral and common carotid arteries in patients suffering from peripheral artery disease (PAD) and to discover whether the stimulation of these receptors modifies the cutaneous microcirculation in the forearm. DESIGN: We studied a group of patients suffering from peripheral artery disease and two groups as controls. SETTING: Patients were examined at the ambulatory for Vascular Research, Division of Vascular Medicine and Rehabilitation, University of Verona. PATIENTS: We studied 15 patients with peripheral artery disease of the lower limbs at Fontaine stage II (group C), 10 free of arterial pathologies (group B) and 10 young people (group A). MAIN OUTCOME MEASURES: We subjected the patients to passive elevation of the legs and the trunk in a horizontal position with pressure monitoring and measurement of the calibre and flow in the brachial and common carotid arteries using a colourDoppler ultrasound. We also studied the cutaneous microcirculation with laserDoppler flowmetry. RESULTS: During the test, arterial pressure and cardiac frequency remained constant in group A, systolic pressure values showed a slight, but statistically significant increase in group B, whilst the increase in systolic pressure values at this stage was marked in group C. Diastolic pressure values and cardiac frequency remained unchanged in all groups. The calibre of the humeral artery increased in the control groups. Carotid resistance was unchanged in the three groups. Humeral resistance during the test decreased in the two control groups whilst it increased in group C. The number of perfusion units felt in the control groups; no variations in group C. CONCLUSIONS: Our study demonstrates, in patients with peripheral artery disease, a reduction in the activity of the cardiopulmonary baroreceptors with an increase in the humeral resistance during the test and impairment of the mechanisms of cutaneous microcirculatory vasoregulation in the forearm.

Intralymphocyte free magnesium in patients with primary aldosteronism: aldosterone and lymphocyte magnesium homeostasis.

It is known that hyperaldosteronism has been associated with magnesium deficiency, yet there are no data on the intracellular concentration of ionized magnesium ([Mg(2+)(i)]) in subjects with primary aldosteronism (PA). We measured intralymphocyte free magnesium ([Mg(2+)(i)]) and intralymphocyte free calcium ([Ca(2+)(i)]) in 16 patients with PA and 26 normotensive control subjects (NCs). [Mg(2+)(i)] and [Ca(2+)(i)] were also measured in blood lymphocytes incubated in vitro with aldosterone, according to a fluorimetric method. In subjects with PA, [Mg(2+)(i)] was significantly lower than that in NCs (mean+/-SD; PA 203+/-56 micromol/L, NCs 291+/-43 micromol/L, 95% confidence interval 57 to 119, P=0.001). In the patients, [Ca(2+)(i)] did not prove to be statistically different from that of NCs (mean+/-SD; PA 47.2+/-10.6 nmol/L, NCs 53.2+/-11 nmol/L). The lymphocytes exposed to the action of aldosterone showed a significant reduction in [Mg(2+)(i)] (n=15, NCs 271+/-28 micromol/L, aldosterone treatment 188+/-39 micromol/L, P=0.001, 95% confidence interval 57 to 108). The dose-effect curve of aldosterone on [Mg(2+)(i)] showed an EC(50) value of approximately 0.5 to 1 nmol/L aldosterone. The reduction in [Mg(2+)(i)] mediated by aldosterone is antagonized by the receptor inhibitor of aldosterone; it is inhibited by inhibitors of protein synthesis and is not measurable when the lymphocytes are incubated in an Na(+)-free medium. The data are consistent with the hypothesis that aldosterone affects the cellular homeostasis of magnesium, probably through modification of the activity of the Na(+)-Mg(2+) antiporter.

Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity.

OBJECTIVE: To ascertain in obesity the role of body fat distribution (the strongest predictor of morbility and mortality in obese subjects) in determining the degree of endothelial dysfunction, an early marker of atherosclerotic disease. SUBJECTS: 18 premenopausal women with uncomplicated obesity excluding other cardiovascular risk factors and 12 age-matched slim healthy women. MEASUREMENTS: Endothelium-dependent vasodilation, studied as diameter variation in response to an increase in shear-stress, was evaluated in the right common femoral artery of obese and slim subjects by a non invasive approach and compared to glyceril-trinitrate vasodilation. To characterize better the vascular functional and/or structural properties, we studied the arterial wall distensibility by an echo-tracking system. Adipose tissue regional distribution was determined by computerised axial tomography. RESULTS: The endothelium-dependent vasodilation was significantly impaired in obese subjects (P<0.005 versus non-obese subjects) while glyceril-trinitrate vasodilation and arterial distensibility were similar in the two groups. In our obese subjects endothelial-dependent vasodilation was inversely correlated to body fat distribution (visceral/subcutaneous adipose tissue ratio: r=- 0. 624, P=0.0058). In contrast, metabolic parameters (except C-peptide response during oral glucose tolerance test (OGTT): r=-0.587, P=0. 01), blood pressure values and body weight did not correlate with the endothelial function. CONCLUSION: Uncomplicated obesity per se is characterised by an alteration of the endothelial function; the degree of this vascular damage is predicted by body fat distribution independently of body weight and metabolic and other haemodynamic parameters, and correlates with an index of insulin secretion.

ACE inhibitors improve endothelial function in type 1 diabetic patients with normal arterial pressure and microalbuminuria.

OBJECTIVE: The purpose of this study was to test whether a short-course treatment with ACE inhibitors may restore endothelium-dependent and/or -independent vasodilation in the femoral artery of microalbuminuric patients with type 1 diabetes and normal arterial pressure. RESEARCH DESIGN AND METHODS: We studied nine normotensive microalbuminuric type 1 diabetic patients and two groups of control subjects matched for femoral artery diameter to type 1 diabetic patients after placebo (control group A, n = 17) and ACE inhibitor (control group B, n = 18) treatment, respectively. The patients were enrolled in a double-blind cross-over study with a 1-week trial of either placebo, captopril (25 mg t.i.d.), or enalapril (10 mg/day) in randomized order to ascertain whether short-term ACE inhibition obtained with (captopril) or without (enalapril) a sulfhydryl donor molecule ameliorates vessel wall function. Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation were evaluated in the right common femoral artery by echo Doppler. RESULTS: Both captopril and enalapril normalized (control group B 22.9+/-3.2% per 8 min) endothelium-dependent response (19.6+/-7.5 and 18.0+/-5.3 vs. -10.4+/-4.1% per 8 min, P < 0.01, for both captopril and enalapril versus placebo, respectively) in the type 1 diabetic patients. Captopril (28.4+/-3.5 vs. 17.1+/-3.5% per 5 min during placebo, P < 0.05) but not enalapril (20.1+/-3.0 vs. 31.7+/-2.8% per 5 min, P < 0.05 for enalapril versus control group B, and NS for captopril vs. control group B) ameliorated endothelium-independent vasodilation in type 1 diabetic patients. CONCLUSIONS: ACE inhibition improves endothelium-dependent vasodilation in the femoral artery of normotensive microalbuminuric type 1 diabetic patients. Captopril also ameliorates endothelium-independent vasodilation, possibly through its sulfhydryl donor properties. These results may be of pathophysiological relevance to prevent cardiovascular complications in these patients.