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Biomedical subjects

S Novo

Publications and source records attributed to S Novo.

At least 19 recordsLinked to original sources

Effects of captopril and ticlopidine, alone or in combination, in hypertensive patients with intermittent claudication.

Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were randomly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril (C 50 mg bid) or Ticlopidine (T 250 mg bid) for three months and then with the association C plus T for three months again. After placebo administration for one month, patients were further treated with C plus T at low doses (25 mg bid and respectively 250 mg daily). In the first part of the study, patients of Group II received an inverse sequence of the drugs (before Ticlopidine 250 mg bid and then Captopril 50 bid). In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD, TWD, and WI. T did not modify blood pressure but slightly increased PFWD, TWD, and WI. The improvement was more evident during administration of C plus T, whereas placebo administration induced a trend toward baseline values. Finally, the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters. In conclusion, chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication, improving significantly PFWD and TWD.

Angiotensin-Converting Enzyme Inhibitors

Apo-lipoprotein profile in subjects with extracranial carotid atherosclerosis.

Relationships between plasma lipoproteins and cerebrovascular atherosclerosis are not completely clear. In a group of asymptomatic nondiabetic normolipidemic subjects, plasma lipid and apolipoprotein profiles have been related to extracranial carotid atherosclerotic lesions, as assessed by B-mode ultrasonography and independent relations between lipid and clinical parameters and carotid atherosclerosis have been evaluated. We have found that subjects with atherosclerotic lesions (both intimal thickening or plaque) had TG levels and CHO/HDL-C and LDL-C/HDL-C ratios significantly higher and HDL-C and apo A-I levels significantly lower in comparison with subjects with normal arteries. When patients were divided according to the lesions of carotid arteries subjects with atherosclerotic plaque presented HDL-C and apo A-I levels significantly reduced and TG and apo B levels and CHO/HDL-C and LDL-C/HDL-C ratios significantly increased in comparison with subjects with normal arteries, and HDL-C levels reduced and CHO/HDL-C and LDL-C/HDL-C ratios increased in comparison with subjects with intimal thickening. Patients with intimal thickening and normal subjects differed for HDL-C and TG levels and CHO/HDL-C and LDL-C/HDL-C ratios. At multivariate analysis HDL-C levels (negatively), age, hypertension and cigarette smoking (positively) resulted independently associated with cerebrovascular atherosclerosis. Our data seem to show that, although several lipid and apoprotein abnormalities are able to initiate the atherosclerotic process in extracranial carotid district, probably the presence of low HDL-cholesterol levels is an important condition to determine the further worsening of the lesions.

Adult

[Effects of physical activity on lipids and coagulation].

In order to evaluate the effects of physical activity on seric lipoproteins and coagulation parameters, an 8-week clinical trial was performed. Fifteen healthy young subjects (average age 23 years) with no history of previous agonistic physical activity, entered the study. Each subject underwent a physical programme consisting of three times a week bicycle ergometer exercise with progressive increases in work rate by using stages of 3 min duration until the 85% of the predictive heart rate was reached. Each individual was subjected to four blood drawings according to the following schedule: at the beginning of the study, after 4 weeks, after 8 weeks (at the end of the programme) and 4 weeks after the interruption of training. As far as the seric lipoproteins are concerned, the following parameters were monitored: total cholesterol, HDL-C, LDL-C, VLDL-C, triglycerides, Apo-A1, Apo-B100, NEFA and phospholipids. On the other hand the following coagulation parameters were monitored: fibrinogen PT, aPtt, coagulation factors (II-XII), red cells, leucocytes, platelets, hemoglobin and hematocrit. From the analysis of the data, the following statistically significant results were observed: HDL-C increased by 14%, LDL-C decreased by 13%, Apo-A1 increased by 6%, fibrinogen increased by 31.7%, Ptt decreased by 3.7% and leucocytes increased by 15%. Four weeks after exercise was terminated, all monitored parameters turned into the basal range. Our data seem to demonstrate a positive effect of physical exercise on seric lipoproteins in the short period. Nevertheless they provide evidence of an hypercoagulability condition demonstrated by the important fibrinogen increase and the Ptt decrease.

Adult

Inhaled platelet-activating factor increases airway sensitivity but not maximal airway narrowing to methacholine in normal subjects.

To examine the effect of inhaled platelet-activating factor (PAF) on airway sensitivity and on maximal airway narrowing, we measured airway response to doubling concentrations of methacholine (MCh) 48 h before and 48 h after inhalation of 10, 50 and 100 micrograms of PAF in six nonatopic, nonasthmatic subjects. The forced expiratory volume in one second (FEV1) and airflow at 30 percent of vital capacity (V30) from partial forced expiration were used to assess changes in airway calibre. Inhalation of PAF caused only minor changes in FEV1. In contrast, inhalation of 100 micrograms of PAF caused a significant fall in V30 from 2.64 +/- 0.35 to 1.35 +/- 0.43 l.min-1 (p < 0.05). Two days after PAF inhalation a leftward shift of the concentration-response curve to MCh was observed. The MCh concentration causing a 20% fall in FEV1 (PC20FEV1) was 11.25 +/- 1.78 and 2.38 +/- 1.29 mg.ml-1 (geometric mean +/- GSEM; p < 0.05) before and after PAF inhalation, respectively. PAF did not affect the maximal airway response to MCh. The maximum percentage fall in FEV1 was 36.2 +/- 1.9% at baseline and 37.6 +/- 1.8% after PAF inhalation. Likewise, maximum percentage change in V30 was 72.8 +/- 3.7% at baseline and 73.6 +/- 3.4% after PAF inhalation. The results of this study show that PAF inhalation increases airway sensitivity without altering the maximal bronchoconstrictive response to MCh in normal subjects.

Administration, Inhalation

Cyclooxygenase products mediate the cutaneous vasodilation induced by endothelin-1 in humans.

Intradermal injection of endothelin-1 (ET-1) causes vasoconstriction (pallor) at the injection site, surrounded by a larger area of vasodilation (flare) in humans. Some of the vasomotor responses to ET-1 are thought to be mediated by prostaglandins. In the present study, we investigated the involvement of cyclooxygenase-derived products of arachidonic acid metabolism on the cutaneous vasomotor responses to ET-1. Ten normal subjects (25-44 years) were studied after treatment with either indomethacin (50 mg t.i.d.) or placebo according to a double blind cross-over design. Five doses of ET-1 (5 x 10(-5) to 5 x 10(-1) pmol) were injected intradermally 2 h after the last dose of indomethacin or placebo. Pallor and flare areas measured by planimetry 15 min after the injection were analyzed to evaluate cutaneous vasomotor responses to ET-1. ET-1 induced dose-dependent pallor and flare responses that were significant at the dose of 5 x 10(-3) pmol or greater. Indomethacin did not affect the ET-1-induced pallor but significantly shifted to the right the flare dose-response curve to ET-1. The inhibition of the flare response to 5 x 10(-1) pmol ET-1 was 58.9 +/- 8.5%. These results indicate that the cutaneous vasodilation induced by intradermal injection of ET-1 is mediated by the release of vasodilating cyclooxygenase products.

Adult

Determination of arterial diameters, length and mass of the plaque, and theoretical volume in the internal carotid artery by quantitative vascular echography.

To study the evolution of atherosclerosis, the consensual changes that occur in the arterial wall, lumen, and atheroma must be evaluated. The authors propose a new, noninvasive method of obtaining arterial diameters, length and mass of plaque, and theoretical volume in the internal carotid artery. The study was performed in 37 patients with different degrees of atherosclerosis (from 20% to 50%). All patients underwent echo examination. Long-axis tomographic planes were recorded with the same angle of incidence by placing a goniometer around the neck. Furthermore, the arterial diameters and the plaque length were measured from photorecordings, and theoretical arterial volume (sum of two bitruncated semiellipsoids), residual volume (Simpson's integral rule), and plaque mass (difference between theoretical vascular volume and residual volume) were calculated. Intraobserver and interobserver variability and reproducibility were tested in all the measurements and calculations. Intraobserver/interobserver variability and reproducibility were found to be less than 8% according to all measurements and calculations. These results indicate that the method is reproducible and allows noninvasive, quantitative assessments of vascular geometry in evolving atherosclerosis.

Arteriosclerosis

[Silent myocardial ischemia: prevalence, prognostic significance, diagnosis].

Silent myocardial ischemia (SMI) has been demonstrated in 2 to 5% of subjects in totally asymptomatic population, in 30% of patients with history of previous myocardial infarction and in 60 to 100% of patients with stable or unstable angina pectoris. In these patients, 60 to 80% of transient episodes of ischemia are silent and SMI is induced by daily activities and so can be registered during continuous ECG monitoring. The finding of SMI during an exercise testing or during ambulatory monitoring has an unfavourable prognostic significance both in apparently asymptomatic subjects and in patients suffering from stable or unstable angina pectoris or survivors to a myocardial infarction. Stress testing and Holter monitoring are the most used non invasive tests to detect SMI. The sensitivity and specificity of ergometer test can be improved by 201-Tl myocardial scintigraphy. Moreover, the ergometer test can be used as a provocative test to induce changes in regional wall kinesis and so these alterations can be evaluated by using echocardiogram and radioisotopic or contrast ventriculography. The echocardiogram allows to evaluate the presence of kinesis changes induced by stress test or by pharmacological stimulation with dipyridamole or dobutamine. SMI can be also detected through the study of metabolic alterations during cardiac catheterism.

Angina Pectoris

[The physiopathology of critical ischemia of the lower limbs].

Peripheral obstructive arterial disease (POAD) of the lower limbs is the third main complication of atherosclerosis, after coronary artery disease and cerebrovascular disease. In 15-20% of cases POAD have an unfavourable evolution toward critical leg ischemia (CLI). This clinical condition is characterized by the onset of rest pain and/or trophic cutaneous lesions until gangrene appears. In some cases amputation is needed. The pathophysiological, clinical and therapeutic aspects of CLI were recently discussed in two Consensus Conferences held in Berlin in 1989 and in Rudesheim in 1991, with the elaboration of a final draft published on circulation. CLI appears when peripheral perfusion critically decreases due to macro and microcirculatory alterations. Atherosclerotic plaque is the primum movens, but often there are more plaques in sequence along the ilio-femoro-popliteal axis. The pathophysiological and clinical consequences are more severe if the stenosis is haemodynamically important, after a rapid progression of plaque growth or when thrombotic complications develop. The reduction in distal perfusion induces troubles in the microcirculation and an embalancement between the microvascular defense system (MDS) and the microvascular flow regulating system (MFRS) with endothelial dysfunction, platelet and leucocytes activation, worsening of blood viscosity due to the increase in fibrinogen levels and to the red cells deformability changes, activation of coagulation and impairment of fibrinolysis. So, a vicious circle appears with further worsening of distal perfusion and onset of trophic lesions. A further worsening of CLI can derive from local recurrent infections particularly frequent in diabetic patients.

Critical Illness

Cholesterol and fibrinogen as predictive factors of progressive carotid atherosclerosis.

In order to detect the presence of determining factors as predictors of progressive carotid atherosclerosis, the incidence of total serum cholesterol and fibrinogen elevation was evaluated in patients affected by coronary artery disease (CAD). 61 subjects with CAD (mean age 62 years) and significative lesions (> 50%) underwent periodic Echo-Doppler (Duplex scanning) of the supra aortic branches. Total serum cholesterol, HDL, LDL and fibrinogen were monitored, as well. A 24 month follow-up period was performed. Indicative of the progression of carotid atherosclerosis has been considered the presence of a stenosis degree over 20% than the initial one. In 14 of the 61 subjects who entered the study, there was evidence of progressive carotid atherosclerosis. The same patients showed higher levels of LDL cholesterol (130 +/- 36.3 vs 96.5 +/- 33.2) and Fibrinogen (398.3 +/- 59.4 vs 328 +/- 36.8) and lower levels of HDL cholesterol (27.2 +/- 4.2 vs 34.4 +/- 10.1). Our results confirm the importance of cholesterol and fibrinogen as determining risk factors, especially in patients with multiple vascular disease (coronary and carotid).

Carotid Artery Diseases

Diabetes, hypertension and atherosclerosis: pathophysiological role of intracellular ions.

The clinical coincidence of hypertension, obesity and non insulin diabetes mellitus (NIDDM) has long been recognized. Increasing interest has also been recently focused on the possible role of insulin and insulin resistance in mediating this association. There is also evidence that hyperglycemia per se may have a role in the pathogenesis of hypertension and atherosclerosis in NIDDM patients. Glucose is a determinant to cellular ion homeostasis, promoting an increase of intracellular calcium and suppressing intracellular free magnesium and pH. Moreover, hyperglycemia promotes glycosilation of proteins and the consequent accumulation of advanced glycosilation end products in tissues. It has recently been suggested that iter is a cellular ionic basis for the clinical and epidemiological linkage of hypertension, left ventricular hypertrophy (LVH), obesity and non insulin dependent diabetes mellitus (NIDDM). These clinical conditions may be different expressions of a common underlying defect in ion handling, displayed by elevated cytosolic free calcium and suppressed free magnesium levels. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion specific agents, such as calcium channel blocker drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent cardiac, vascular and metabolic aspects of the hypertensive states.

Arteriosclerosis

The incidence of asymptomatic extracoronary atherosclerosis in patients with coronary atherosclerosis.

Atherosclerosis is a systemic vascular disease that can produce pathologies in any organ. The aim of this study was to evaluate the incidence of asymptomatic peripheral atherosclerosis (PA) in patients symptomatic for angina and myocardial infarction affected by coronary atherosclerosis (CAD). 315 patients (268 male and 47 female) aged between 36 and 69 years, asymptomatic for claudicatio and cerebral ischaemic disease, underwent selective coronary angiography to detect coronary stenosis > or = 50% and Echo-Color-Doppler examination of the epiaortic trunks and upper and lower limb arteries to detect peripheral stenosis > or = 30%. In the total population the incidence of PA in patients with CAD was 23% but in patients with trivascular CAD it was 32%. These data suggest that in patients with trivascular CAD it is necessary to investigate peripheral circulation as, also in asymptomatic patients, polydistrictual atherosclerosis was frequent.

Adult

Hypertension and other risk factors in peripheral arterial disease.

Aim of this study has been to evaluate the prevalence of arterial hypertension and other risk factors in patients suffering with PAD in two clinical samples (1.: 102 patients with PAD, 69 M, 33 F, studied in our angiology laboratory, matched for sex and age with 102 healthy volunteers; 2.: 184 hospitalized patients, 80 M, 104 F, mean age 57.2 +/- 10.8, with PAD) and in two epidemiological studies (1.: Trabia Study, 835 subjects; and 2.: Casteldaccia Study, 723 subjects). All patients performed a full clinical and laboratory examination, including the determination of the ankle/arm pressure ratio (Winsor index, positive for PAD when lower than 0.95). In the first clinical study we observed a significantly (p < 0.01) greater prevalence of arterial hypertension (51.9 vs 9.8%), hypercholesterolemia (48.2 vs 21.6%), hypertriglyceridemia (53.7 vs 26.1%), smoking habit (64.3 vs 44.2%), and hyperglycemia (26 vs 7.9%) in PAD patients than in controls. In the second clinical study, considering separately the patients under and over 65 years, all risk factors resulted more prevalent in younger people than in the aged, except diabetes and hypertension.

Adult

Regression of structural vascular changes in hypertensives after captopril treatment.

In order to investigate whether hypertension-related structural vascular changes may be influenced by antihypertensive treatment, 10 patients were studied suffering from essential arterial hypertension, five males and five females, aged between 34 and 61 years (mean age: 46.9 +/- 8.13 years). All patients received a placebo for 1 week and then captopril, 75 mg b.i.d. for 3 months. After placebo and captopril treatments, the following parameters were evaluated: SBP, DBP, mean blood pressure (MBP), by the formula 1/3 (SBP + 2 x DBP) and basal and minimal vascular resistances, respectively obtained by the ratios MBP/rest flow and MBP/peak flow. Blood flows have been obtained by strain gauge plethysmography. A significant decrease in systolic (P less than 0.025), diastolic (P less than 0.01) and mean blood pressure (P less than 0.01), basal vascular resistances (52 +/- 19 vs 28 +/- 12 A.U., P less than 0.01) and minimal vascular resistances (6.3 +/- 2.2 vs 3.9 +/- 2.8 A.U., P less than 0.025) has been observed after captopril treatment in comparison to placebo, whereas rest (2.9 +/- 0.7 vs 4.1 +/- 0.9 ml.min-1.100 g-1, P less than 0.01) and peak blood flows (21.3 +/- 5.8 vs 29.7 +/- 9.4 ml.min-1.100 g-1) significantly increased. These data seem to indicate that antihypertensive treatment with the angiotensin-converting enzyme inhibitor, captopril, is not only efficacious in inducing a significant blood pressure decrease, consequent to the reduction of basal vascular resistance (due to the vasodilating effects of the drug), but is also able to reduce minimal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Lipids and serum apoproteins in subjects with slight or mild coronary atherosclerosis evaluated with angiography].

In this study 126 subjects (91 males and 35 females, range of age 43-65 years) were studied by coronary angiography. We considered positive for coronary atherosclerosis also patients showing mild or moderate stenosis (> or = 25%). In all subjects we have evaluated serum lipid and apoprotein A-I, B, C-II, C-III and E levels; therefore also cholesterol concentrations in all lipoprotein fractions, separated by sequential ultracentrifugation (VLDL d < 1.006, LDL d 1.006-1.063, HDL d > 1.063 g/ml) and apoprotein B in LDL have been measured. Subjects with coronary atherosclerosis have shown significantly higher levels of total cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios than controls. Therefore, a lower apo A-I/apo B ratio in males and a higher LDL-apo B levels in females has been found in subjects with coronary atherosclerosis in comparison with controls. The stepwise multiple analysis has demonstrated that LDL-cholesterol levels is the parameter that best correlates with the presence of coronary atherosclerosis. These data confirm the importance of the reduction of LDL-cholesterol levels in primary and secondary prevention of coronary heart disease.

Apolipoproteins

[Acute effects of transdermal administration of nitroglycerin on effort tolerance and myocardial perfusion, evaluated by Tl-201 scintigraphy, in patients with stable effort angina].

The aim of this study was to evaluate the effects of the transdermal application of nitroglycerin (NGT) on exercise tolerated and regional myocardial perfusion, as evaluated by 201 thallium stress scintigraphy, in patients with stable effort angina. We studied 20 patients, 15 men and 5 women, aged between 43 and 68 years, with average age of 55 +/- 8 years, suffering from effort angina, whose angina threshold was stable in 3 stress testing performed in the week before the study started. The patients, after a pharmacological washout of 1 week, underwent 2 exercise testing 20 hours after the application of a patch containing placebo or 10 mg NGT, with an interval of 7 days. 60-90 s before stress testing was interrupted, 2 mCi of thallium 201 were injected in an antecubital vein of the arm. The scintigraphic images were obtained soon in the 0, 45 and 90 degree views and after 4 hours reperfusion. Under placebo patch all patients interrupted ergometer test for angina, while under the patch containing active NGT angina was present in 11/20 patients and 9 patients stopped the test because of muscular exhaustion. NGT induced an increase of the ergometer test duration (+26%); this difference was statistically significant. The ST segment downsloping decreased significantly both at maximal common work and at exercise peak after NGT application in comparison with placebo. The perfusional defects observed on the scintigraphic images obtained soon after the exercise (and reversible after 4 hours of reperfusion) on placebo patch, diminished significantly after NGT and the captation index lung/heart decreased also significantly (from 49 to 41%), showing so an improvement of cardiac performance. In conclusion the transdermal application of NGT, in patients with effort angina, demonstrated to have antianginal and antiischemic effect, reducing the number of patients interrupting the stress testing for angina, increasing the exercise tolerated and diminishing the ST segment downsloping, objective demonstration of myocardial ischemia. This antianginal and antiischemic effect might follow to the reduction of the preload induced by nitrates, in part also the reduction of the afterload, factors determining a decrease of the wall tension and so of MVO2, but also to a redistribution of the subendocardial flow as demonstrated by 201-Tl scintigraphic images. These effects induce also a global improvement of the left ventricular function as demonstrated by the reduction of the lung/heart index of thallium captation.

Administration, Cutaneous