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Biomedical subjects

C Marelli

Publications and source records attributed to C Marelli.

At least 19 recordsLinked to original sources

The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal-recessive disorder caused by mutations in the PANK2 gene. The authors report clinical and genetic findings of 16 patients with PKAN. The authors identified 12 mutations in the PANK2 gene, five of which were new. Only nine patients could be classified as classic or atypical PKAN, and intermediate phenotypes are described. Two patients presented with motor tics and obsessive-compulsive behavior suggestive of Tourette syndrome.

Adolescent↗

Preliminary clinical experience in cardiology with sonazoid.

Sonazoid (formerly NC100100) is a new ultrasound contrast agent for intravenous injection developed by Nycomed-Amersham. It consists of perfluorocarbon microbubbles that are stabilized with a surfactant and are within a well-defined size range (median diameter approximately 3 microm). Due to the low diffusibility and blood solubility of the gas, the controlled size distribution of the microbubbles, and the flexibility of the shell, Sonazoid is a free-flowing tracer capable of crossing the pulmonary capillary bed after peripheral intravenous injection. It is stable enough for the duration of the ultrasound examination and provides echo enhancement useful for clinical requirements. The preliminary clinical experience in cardiology indications, including its use in reducing the frequency of inadequate echocardiographic studies in patients with suboptimal echocardiograms, and its use as a myocardial perfusion agent in the setting of acute myocardial ischemia is briefly discussed.

Angioplasty, Balloon, Coronary↗

NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study.

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.

Aged↗

Left ventricular opacification by intravenous contrast echocardiography.

BACKGROUND: The present study was undertaken in order to evaluate the efficacy of the intravenous administration of Albunex in obtaining left ventricular opacification and the relationship between left ventricular opacification and pulmonary pressures and cardiac function. METHODS: Fifty-two adult patients, mostly affected by ischemic heart disease, were enrolled in the study. In 37 of these patients, a complete right heart hemodynamic study was performed after Swan-Ganz catheterization. Albunex was administered in three randomized doses (0.10, 0.15 and 0.20 ml/kg) to all the patients. Left ventricular opacification was assessed both visually and using videodensitometric analysis. RESULTS: Left ventricular opacification was obtained in 93% of all the injections and an intermediate or strong opacification was obtained in 68%, while absent opacification was observed in 6% of the injections, irrespective of the contrast dose. An incremental opacification efficacy trend was observed from the lower to the higher dose, with an intermediate or strong opacification in 58 and in 77% of 0.10 and 0.20 ml/kg injections, respectively. Irrespective of the contrast dose, an enhancement of the endocardial borders was observed in 61% of the wall segments suboptimally visualized in basal conditions. The endocardial borders enhancement was obtained in 39 and in 79% of segments using the 0.10 and the 0.20 ml/kg doses, respectively. No statistically significant differences were observed between the videodensitometric parameters obtained using the three contrast doses. Finally, a significant relationship was observed between left ventricular opacification parameters and pulmonary pressures and left ventricular functional parameters, irrespective of the contrast doses considered. CONCLUSIONS: The results we obtained demonstrate the good overall efficacy of Albunex administered intravenously in order to obtain left ventricular opacification in a clinical population of cardiac patients. Moreover, they suggest that the dosage to be used clinically should preferably be at least 0.20 ml/kg, although no significant influence of contrast dosage on videodensitometric parameters has been observed. Finally, irrespective of the contrast dosage, the magnitude of left ventricular opacification appears to be influenced by the hemodynamic status of the patient.

Adult↗

Assessment of left ventricular systolic function in low-echogenic patients by intravenous Infoson injection during dopamine echocardiography. An open, phase III trial.

This trial evaluated whether the intravenous injection of an ultrasound contrast agent (Infoson) facilitates the assessment of systolic function in 40 low-echogenic patients undergoing low-dose (4 mcg/kg/min) dopamine echocardiography. Interobserver difference in calculated ejection fraction at entry was > 10%. Echocardiographic monitoring was performed in the apical 4-chamber view at four intervals: baseline, no contrast; first Infoson injection; dopamine infusion, no contrast; dopamine infusion+second Infoson injection. The left ventricle was divided into 5 segments and analysis was performed by two blinded observers. Wall motion abnormalities, ejection fraction and the confidence in detecting the endocardial border, were assessed. Infoson provided adequate left ventricular opacification in 90% of the injections, with a significant improvement in endocardial border detection. The interobserver variability of ejection fraction measurements was significantly reduced. The probability of attaining concordance between the investigators on wall motion assessment improved significantly. These results suggest potential applications in stress echocardiography.

Aged↗

[An epidemiological survey of cardiovascular disease risk factors in 18-year-old males during their medical check-up at an Army recruiting center in the province of Verona].

Between January and December 1992 an epidemiological survey on the risk factors for cardiovascular disease in eighteen-year old boys during call-up has been performed in Verona. The study involved 3426 subjects: 100% of the boys coming from the metropolitan area and 65% of those coming from the non-metropolitan areas. A family history of hypertension was found in 9.54% of the subjects and a family history of myocardial infarction or sudden death was found in 4.54% of the subjects. 0.18% of the population reported diabetes and 2% hypertension. Prevalence of smoke addiction was 39.1% and in this group 17.54% smoked > or = 20 cigarettes/day. Prevalence of smoke addiction was significantly greater in the boys having one or both smoking parents (p < 0.001), in working people in respect to students (p < 0.001), in boys from metropolitan in respect to those from non-metropolitan areas (p = 0.033), and among those not practising sport activity (p < 0.001). Mean systolic and diastolic blood pressure were 130.16 +/- 13/74.48 +/- 9 mm Hg and 90th percentile was 149/87 mm Hg. Systolic and diastolic blood pressure were significantly lower in boys from metropolitan in respect to those from non-metropolitan areas and in smokers in respect to non smokers. A body mass index > or = 30 was found in 3.04% of the subjects, the body mass index being directly related to systolic and diastolic blood pressure (p < 0.001). Total cholesterol performed on a voluntary basis from capillary blood samples by Reflotron System was determined in 80.06% of the subjects. Mean blood cholesterol was 139.1 +/- 28 mg/dL and 90th percentile's value was 182 mg/dL. Mean blood cholesterol was significantly lower in non-metropolitan in respect to metropolitan areas (p = 0.033). 44.48% of the subjects had one or more risk factors, 5.22% had two risk factors and 0.67% three or more risk factors for cardiovascular disease. This study shows that 1) in this population of young people a significant part is exposed to one or more cardiovascular risk factors; 2) social and environmental factors affect, sometimes deeply, the prevalence of cardiovascular risk factors; 3) The visit for call-up appears to be important in the setting-up of a strategy of primary prevention for cardiovascular disease.

Adolescent↗

Effects of trandolapril on 24-h ambulatory blood pressure in patients with mild-to-moderate essential hypertension.

The effects of trandolapril on 24-h blood pressure in mild-to-moderate hypertensive patients of both sexes were investigated by conventional (clinic) and ambulatory recording in a double-blind study at two dosages, 1 mg (n = 14) and 2 mg (n = 13) once daily for 2 weeks. Both methods of measurement showed significant end-of-treatment decreases (p < 0.01 in all cases) in diastolic and systolic pressure in the 1- and 2-mg groups. Although intergroup differences were not significant, inspection of the mean changes from baseline in the eight 3-h periods constituting the 24-h profile showed that reductions were consistently greater in the 2-mg than in the 1-mg group, by 2 mm Hg diastolic blood pressure and 6 mm Hg systolic blood pressure. Values in the last segment of the placebo washout (46-48 h after the last active dose) showed that these reductions were well maintained, notably in the 2-mg group, with a minimal tendency to drift toward pretreatment levels. No effect was observed on the normal circadian blood pressure rhythm. Both doses were well tolerated. In conclusion, trandolapril is an effective, well-tolerated antihypertensive agent for once-daily dosing at either 1 or 2 mg.

Adult↗

Treatment of intermittent claudication with defibrotide or mesoglycan. A double blind study.

Forty-four patients with intermittent claudication were included and randomised in two groups respectively treated with oral defibrotide (one 400 mg tablet bid) or oral mesoglycan (one 24 mg tablet bid) for 6 months. Twenty-two subjects completed the study in the defibrotide group and 20 in the mesoglycan group. The two treatments were well tolerated and the two drop outs in the mesoglycan group were not due to medical causes. In the defibrotide group, after 1 month the pain-free walking distance (PFWD) increased from 473 +/- 96 m to 586 +/- 84 (p < 0.05). The walking distance (WD) increased from 767 +/- 125 m to 898 +/- 109 (p < 0.05). After 6 months the posterior tibial pressure (PTP) at the end of the treadmill exercise test also increased from 40 +/- 19 to 63 +/- 12 (p < 0.05). No variations in PFWD, WD and PTP were observed in the mesoglycan group. The improvement in walking was possibly due to the action of defibrotide increasing local fibrinolysis and decreasing the distal vasospasm present in subjects with peripheral vascular disease and intermittent claudication.

Double-Blind Method↗

Acute effects of TTFCA on capillary filtration in severe venous hypertension.

The acute variation in capillary filtration [CF] was evaluated with strain-gauge plethysmography in patients with severe venous hypertension due to deep venous disease. Two groups were selected and randomly treated with a single oral dose or TTFCA (60 mg or 120 mg). CF was assessed again after 5 and 10 hours. Eleven patients were randomised in the 60 mg group and 9 in the 120 mg group. Also 5 normal subjects were studied with the same procedure to act as controls. No variations in CF were observed in normal limbs. In both groups of patients there was a significant decrease in CF after 5 and 10 hours. The percent decrease in CF after 10 hours was higher in the high dose group. These results indicate that TTFCA is acutely effective in reducing CF and oedema in subjects with venous hypertensive microangiopathy. The effects of TTFCA on CF appear to be dose related.

Adult↗

[The microcirculatory activity of Centella asiatica in venous insufficiency. A double-blind study].

In 87 patients with chronic venous hypertensive microangiopathy the efficacy of oral FTTCA (Centella asiatica) administered for 60 days was tested. The microcirculatory effects of two dosages (30 mg bid and 60 mg bid) versus placebo was assessed in a double blind study. The compound was well tolerated and no unwanted effects were observed. Microcirculatory parameters--peri-malleolar skin flux at rest (RF) and transcutaneous PO2 and PCO2--improved as did the abnormally increased RF, PCO2 decreased and PO2 increased in comparison with values measured at inclusion. These results confirm the efficacy of FTTCA in venous hypertensive microangiopathy. Furthermore the effects of FTTCA appear to be dose-related.

Adult↗

[Comparative evaluation of 2 non-ionic contrast media, iopentol (350 mgI/ml) and iopamidol (370 mgI/ml) in coronary angiography].

This randomized double-blind comparative study was designed to investigate the safety and efficacy of a new nonionic monomeric contrast agent, Iopentol 350 mgI/ml, versus a nonionic monomeric contrast agent currently used, Iopamidol 370 mgI/ml, in cardioangiography. Blood pressure, heart rate, end-diastolic left ventricular and mean aortic pressure, ECG, adverse reactions and discomfort were the safety variables recorded; technical adequacy and diagnostic yield were the efficacy variables recorded. A hundred patients entered the trial and were subdivided into two groups of 50 patients each; all of them were included in the safety and efficacy assessments. Demographic data, general and background characteristics and procedural data were comparable in the two treatment groups. No significant difference in efficacy was observed between the two groups: diagnostic yield was optimal in 90% of the patients in the Iopentol group and in 88% of the patients in the Iopamidol group. Systolic blood pressure 30 min. after the examination showed, in both groups, a slight but statistically significant reduction relative to baseline values (-3.48 mmHg and -3.85 mmHg in the Iopentol and in the Iopamidol group, respectively), while no significant reduction was observed in diastolic blood pressure. A statistically but not clinically significant decrease in heart rate was observed in the Iopamidol group 30 min. after the examination (-5.05%), while this variable remained practically the same in the Iopentol group (-0.58%). No difference was found between the two groups relative to the incidence of discomfort following the injection. Other adverse reactions were experienced by 7 patients in the Iopentol group and by 9 patients in the Iopamidol group: they all promptly recovered after medical treatment, with no sequelae. All but one event in the Iopamidol group (chest and abdominal pain with ECG changes) were mild to moderate and mainly related to the procedure and to the underlying disease. In conclusion, both contrast agents are safe and effective for use in cardioangiography.

Contrast Media↗

Reversal of cardiac and large artery structural abnormalities induced by long-term antihypertensive treatment with trandolapril.

In 15 patients with untreated mild to moderate essential hypertension and left ventricular hypertrophy, we assessed blood pressure, echocardiographic left ventricular mass index, brachial artery compliance (pulsed doppler flowmetry), and calculated forearm vascular resistance (strain gauge plethysmography) before, during (6 and 12 months) and after (1 month washout period) 1 year of satisfactory (blood pressure < or = 140/90 mm Hg) antihypertensive therapy with the angiotensin-converting enzyme inhibitor trandolapril (2.0 mg orally once daily). During the antihypertensive effective treatment, we observed a significant reduction of systolic and diastolic blood pressures, left ventricular mass index, and forearm vascular resistance at both 6 and 12 months. In addition, brachial artery compliance was significantly increased. After washout, systolic (156 +/- 3 mm Hg) and diastolic (102 +/- 1 mm Hg) blood pressures returned to levels comparable to baseline. However, left ventricular mass index (132 +/- 4; p < 0.01) and brachial artery compliance (1.53 +/- 0.01; p < 0.01) were still different from baseline. These results demonstrate that chronic antihypertensive treatment with trandolapril is associated with a stable regression of cardiac and vascular abnormalities, which is partially unrelated to the blood pressure lowering effect.

Angiotensin-Converting Enzyme Inhibitors↗

Fibrinolytic enhancement in diabetic microangiopathy with defibrotide.

Skin microcirculation was evaluated in 117 patients with diabetic microangiopathy over a period of six months. They were divided into two groups. Group 1 (64 patients) was treated with oral defibrotide, a new profibrinolytic drug, in association with diet and oral antidiabetic drugs. Group 2 (53 patients) was treated only with diet and antidiabetic agents. The microcirculation was studied by means of laser-Doppler flowmetry transcutaneous partial pressure of oxygen and carbon dioxide pressure measurements, and evaluation of capillary filtration. After six months, patients in group 1 improved their microcirculatory parameters in association with an improvement in signs and symptoms. Moreover, 30 patients in group 1 and 36 in group 2 were followed up for eighteen months, and the authors observed that the deterioration of the microcirculatory parameters was significantly slowed in diabetics treated with defibrotide. A decrease in plasma fibrinogen during defibrotide treatment was observed in all treated patients in association with an increased fibrinolytic activity. In conclusion, it appears that defibrotide, enhancing fibrinolysis, improved the microcirculation in diabetics, preventing further, progressive deterioration.

Adult↗

[Skin blood flow and veno-arteriolar response in essential hypertension].

High arteriolar resistance and vasoconstriction are considered an important factor in essential hypertension. In 98 patients with essential hypertension and 60 normals we evaluated skin flow at rest (RF) and the veno-arteriolar response (VAR = the vasoconstriction due to leg dependency) using laser-Doppler flowmetry. Measurements were repeated after four weeks in normals and after treatment with nifedipine (10 mg tid) in hypertensives. At the beginning of the study in hypertensives RF and VAR were lower than in normals. After nifedipine treatment a decrease in blood pressure was associated with an increase in RF and VAR. A difference was also observed between responders and non responders (16.3%). RF and VAR at the beginning of the study were both higher in non responders and did not change after treatment indicating that the degree of vasoconstriction in these patients was lower. In conclusion microcirculation changes in hypertension may be quantified by laser-Doppler flowmetry and used to evaluate vasoconstriction and the effects of drugs.

Adult↗

Pharmacological activity and safety of trandolapril (RU 44570) in healthy volunteers.

The pharmacological activity and safety of the new angiotensin converting enzyme (ACE) inhibitor trandolapril (RU 44570) has been evaluated in ten healthy male volunteers given 2 mg once daily for seven days. Assessment criteria included evaluation of plasma ACE and renin activity and aldosterone levels in the supine and standing positions, monitoring of blood pressure, heart rate and electrocardiogram, routine blood and urine laboratory tests, and evaluation of adverse effects. Plasma ACE activity (both in the supine and standing positions) was significantly lower after the first dose and was almost completely suppressed after 7 days of treatment. Plasma renin activity with the subjects in both positions was significantly increased at the end of treatment. Plasma aldosterone did not vary significantly, except for an increase in the standing position after 7 days of wash-out. No significant changes occurred in blood pressure, heart rate, electrocardiogram, blood or urine laboratory tests. No adverse effects were reported, in particular, no orthostatic hypotension, cough or episodes of bronchospasm occurred. It is concluded that oral trandolapril 2 mg o.d. is an effective and long-lasting ACE inhibitor with a good safety profile on repeated dosing. Further studies are warranted to investigate its therapeutic application as well as its safety profile after long-term administration.

Adult↗