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Biomedical subjects

F Paleari

Publications and source records attributed to F Paleari.

18 recordsLinked to original sources
PubMed2005

Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome.

AIMS/HYPOTHESIS: Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction. METHODS: In 43 healthy control subjects (age 48.2+/-1.0 years, mean+/-SEM) and in 48 untreated age-matched subjects with metabolic syndrome (National Cholesterol Education Program's Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique). RESULTS: Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1+/-2.6 vs 43.8+/-2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r=0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=-0.44, p<0.001), which was impaired in the metabolic syndrome. CONCLUSIONS/INTERPRETATION: These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.

Adult↗
PubMed2003

Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits.

We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.

Biphasic Insulins↗
PubMed2001

Progression of large artery structural and functional alterations in Type I diabetes.

AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes mellitus is accompanied by reduced arterial distensibility and increased arterial wall thickness even in normotensive subjects with no micro-macrovascular complications. It is not known whether, and how fast, these subclinical markers of vascular damage develop over time. METHODS: We measured arterial wall distensibility in radial, common carotid artery and abdominal aorta in 60 normotensive patients (aged 35.0 +/- 1.2 years, means +/- SE) with Type I diabetes with no microvascular or macrovascular complications and in 20 healthy control subjects matched for age. Arterial distensibility was determined by continuous measurements of arterial diameter through echotracking techniques and by using either the Langewouters (radial artery) or the Reneman formula (carotid artery and aorta). The same echotracking techniques allowed us to ascertain the radial and carotid artery wall thickness. Data were collected before and after 23 +/- 1 months. RESULTS: In the first study, carotid artery distensibility was similar but radial artey and aortic distensibility was less (p < 0.01) in patients with diabetes than in control subjects (-39 % and 25 % respectively). This was accompanied by an increase (p < 0.01) in both radial (42 %) and carotid artery wall thickness (46 %). After 23 +/- 1 months diabetic subjects showed a further reduction in arterial distensibility (radial-12 %, p < 0.05; carotid-8 %, NS; aorta-20% p < 0.05) and an increase in arterial wall thickness (radial + 15 %; carotid 14%, p < 0,05). No change in distensibility and wall thickness values occurred in control subjects. CONCLUSION/INTERPRETATION: The early reduction in arterial distensibility and increase in arterial wall thickness characterizing uncomplicated normotensive Type I diabetes patients shows a measurable worsening over the short term.

Adult↗
PubMed2001

Progression of functional and structural cardiac alterations in young normotensive uncomplicated patients with type 1 diabetes mellitus.

OBJECTIVE: We have recently observed that in young, normotensive patients with a type I diabetes mellitus and no macro or microvascular complications, large artery structure and function are already altered. This study has been done to assess whether this condition is also characterized by early alterations in cardiac structure and function, and whether these alterations progress with time. DESIGN AND METHODS: In 56 insulin-treated, normotensive uncomplicated type I diabetic patients (age 35.0 +/- 2 years, means +/- SE) in good metabolic control, left ventricular wall thickness and diameter were measured by echocardiography together with left ventricular ejection fraction and diastolic function E/A (ratio between early and late ventricular filling), before and after 23 +/- 1 months. The same measurements were made in 20 age and sex-matched subjects who served as controls (C). RESULTS: Compared to C, diabetic patients had a significant increase in left ventricular wall (septal plus posterior wall) thickness (+ 8.4%), left ventricular mass index (+ 11%) and h/r ratio (left ventricular wall thickness/ventricular end diastolic diameter, + 16.0%) whereas they showed a reduction of E/A (-6%). In C, all echocardiographic values were unchanged after 2 years. This was the case also for diabetic patients, except for left ventricular ejection fraction and diastolic diameter which showed a significant reduction (-7.2%) and increase (+ 3.8%), respectively, with a reduction of ratio between LV wall thickness and diameter, h/r (-6.8%). CONCLUSIONS: Uncomplicated type I diabetes mellitus is characterized by early structural and functional cardiac alterations. Some of these alterations show a measurable progression within a relatively short time span.

Adolescent↗
PubMed2000

Lacidipine and blood pressure variability in diabetic hypertensive patients.

The aim of our study was to assess the effects of lacidipine, a long-acting calcium antagonist, on 24-hour average blood pressure, blood pressure variability, and baroreflex sensitivity. In 10 mildly to moderately hypertensive patients with type II diabetes mellitus (aged 18 to 65 years), 24-hour ambulatory blood pressure was continuously monitored noninvasively (Portapres device) after a 3-week pretreatment with placebo and a subsequent 4-week once daily lacidipine (4 mg) or placebo treatment (double-blind crossover design). Systolic blood pressure, diastolic blood pressure, and heart rate means were computed each hour for 24 hours (day and night) at the end of each treatment period. Similar assessments were also made for blood pressure and heart rate variability (standard deviation and variation coefficient) and for 24-hour baroreflex sensitivity, which was quantified (1) in the time domain by the slope of the spontaneous sequences characterized by progressive increases or reductions of systolic blood pressure and RR interval and (2) in the frequency domain by the squared ratio of RR interval and systolic blood pressure spectral power approximately 0.1 and 0.3 Hz over the 24 hours. Compared with placebo, lacidipine reduced the 24-hour, daytime, and nighttime systolic and diastolic blood pressure (P<0.05) with no significant change in heart rate. It also reduced 24-hour, daytime, and nighttime standard deviation (-19.6%, -14.4%, and -24.0%, respectively; P<0.05) and their variation coefficient. The 24-hour average slope of all sequences (7.7+/-1.7 ms/mm Hg) seen during placebo was significantly increased by lacidipine (8.7+/-1.8 ms/mm Hg, P<0.01), with a significant increase being obtained also for the 24-hour average alpha coefficient at 0.1 Hz (from 5.7+/-1.5 to 6.4+/-1.3 ms/mm Hg, P<0.01). Thus, in diabetic hypertensive patients, lacidipine reduced not only 24-hour blood pressure means but also blood pressure variability. This reduction was accompanied by an improvement of baroreflex sensitivity. Computer analysis of beat-to-beat 24-hour noninvasive blood pressure monitoring may offer valuable information about the effects of antihypertensive drugs on hemodynamic and autonomic parameters in daily life.

Antihypertensive Agents↗
PubMed1999

Early impairment of large artery structure and function in type I diabetes mellitus.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with an increased incidence of atherosclerosis. How early functional and structural alterations of large arteries that may preceded atherosclerosis occur in the course of this disease has, however, never been conclusively documented. METHODS: We evaluated arterial wall distensibility in the radial artery, common carotid artery and abdominal aorta in 133 patients (aged 35.4 +/- 0.9 years, means +/- SEM) with Type I (insulin-dependent) diabetes mellitus and no macrovascular complications. Arterial distensibility was derived from continuous measurements of arterial diameter through echotracking techniques and use of either the Langewouters (radial artery) or the Reneman (carotid artery and aorta) formula. The same echotracking techniques enabled us to obtain radial artery and carotid artery wall thickness. Data were compared with those from 70 age-matched normotensive control subjects. RESULTS: In diabetic patients arterial distensibility was consistently less (p < 0.01) than in control subjects, the reduction averaging 26%, 14% and 25% for the radial artery, carotid artery and aorta, respectively. This was accompanied by an increase (p < 0.01) in both radial and carotid artery wall thickness. The changes were more pronounced in patients with microalbuminuria, retinopathy or neuropathy or both. They were evident also in those without microvascular complications. This was the case also when subjects in whom diabetes was associated with hypertension (n = 30) were excluded from data analysis. Carotid and aortic wall abnormalities showed a relation with the duration of disease and blood pressure whereas radial artery abnormalities showed a relation with glycated haemoglobin. CONCLUSION/INTERPRETATION: Type I diabetes is characterised by diffuse arterial wall stiffening and thickening which progress with the severity of the disease but can clearly be seen also in the absence of any diabetic-related complication. This suggests that in diabetes stiffening and thickening are an early marker of vascular damage.

Adult↗
PubMed1997

Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus.

Diabetic autonomic dysfunction is associated with a high risk of mortality which makes its early identification clinically important. The aim of our study was to compare the detection of autonomic dysfunction provided by classical laboratory autonomic function tests with that obtained through computer assessment of the spontaneous sensitivity of the baroreceptor-heart rate reflex (BRS) by time domain and frequency domain techniques. In 20 normotensive diabetic patients (mean age +/- SD 41.9 +/- 8.1 years) with no evidence of autonomic dysfunction on laboratory autonomic testing (D0) blood pressure (BP) and ECG were continuously monitored over 15 min in the supine position. BRS was assessed as the slope of the regression line between spontaneous increases or reductions in systolic BP and linearly related lengthening or shortening in RR interval over sequences of at least 4 consecutive beats (sequence method), or as the squared ratio between RR interval and systolic BP spectral powers around 0.1 Hz. We compared the results with those of 32 age-matched normotensive diabetic patients with abnormal autonomic function tests (D1) and with those of 24 healthy age-matched control subjects with normal autonomic function tests (C). Compared to C, BRS was markedly less in D1 when assessed by both the slope of the two types of sequences (data pooled) and by the spectral method (-71.3% and -60.2% respectively, both p < 0.01). However, BRS was consistently although somewhat less markedly reduced in D0, the reduction being clearly evident for all the estimates (-57.0% and -43.5%, both p < 0.01). The effects were more evident than those obtained by the simple quantification of the RR interval variability. These data suggest that time and frequency domain estimates of spontaneous BRS allow earlier detection of diabetic autonomic dysfunction than classical laboratory autonomic tests. The estimates can be obtained by short non-invasive recording of the BP and RR interval signals in the supine patient, i.e. under conditions suitable for routine outpatient evaluation.

Adult↗
PubMed1996

Ambulatory blood pressure monitoring.

PREDICTIVE VALUE OF 24-H AMBULATORY BLOOD PRESSURE MONITORING: Average 24-h blood pressure values are more closely related to the target-organ damage of hypertension than are clinic blood pressure readings. Preliminary evidence from longitudinal studies suggests that ambulatory blood pressure is also superior to isolated clinic readings in the prognostic evaluation of hypertensive patients. This is supported by the demonstration that in hypertensive patients with left ventricular hypertrophy, regression of cardiac hypertrophy following treatment was better predicted by the drug-induced reduction in 24-h average blood pressure than clinic blood pressure. BLOOD PRESSURE VARIABILITY: Also, 24-h blood pressure variability seems to be involved in the genesis of hypertension target-organ damage, while the clinical value of specific components of the 24-h blood pressure profile, such the nocturnal blood pressure fall, is still a matter of debate. Similar caution is needed in approaching the clinical significance of white coat hypertension, the definition of which is still affected by important methodological problems.

Blood Pressure↗
PubMed1995

N-3-substituted pyrimidinones as potent, orally active, AT1 selective angiotensin II receptor antagonists.

A novel series of nonpeptide angiotensin II (A II) antagonists containing a pyrimidinone ring which carries a C-linked biphenyltetrazole moiety and a carboxyheteroaryl group on the 3-position have been prepared. Their affinity for the AT1 receptor was determined in a binding assay on rat adrenal cortical membranes. The in vivo antihypertensive properties were tested by evaluating the inhibition of the pressor response to A II followed by iv and id administration. Extensive molecular modeling studies, including comparison of molecular electrostatic potential distributions, conformational analysis, and overlays on a computational pharmacophore model of A II, were used to evaluate structural parameters of the new compounds, in comparison to other known A II antagonists (e.g., DUP-753 and SK&F 108566). According to the modeling studies, the introduction of a (carboxyheteroaryl)methyl moiety at the 3-position of the pyrimidinone ring led to derivatives with increased potency. Methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl ]- 4-yl]methyl]-1-(6H)-pyrimidinyl]methyl]-3-thiophenecarboxylate (3k, LR-B/081), one of the most potent compounds in the series (Ki = 1.4 nM), exhibited a marked antihypertensive activity on oral administration to conscious renal hypertensive rats, with long duration of action. It was selected for clinical evaluation in the treatment of hypertension in man.

Administration, Oral↗
PubMed1994

Nonpeptide angiotensin II receptor antagonists. Synthesis, in vitro activity, and molecular modeling studies of N-[(heterobiaryl)methyl] imidazoles.

With the aim of explaining the influence of the structural changes on the biphenylic moiety on the activity, a series of N-[(heterobiaryl)methyl]imidazoles (I), constructed on the model of DuPont compounds by replacing either the central or terminal phenyl ring with a heteroaromatic one, such as furan, thiophene, thiazole, and pyridine, was synthesized. Compared to the reference DuPont compound (EXP-7711), all the heterobiaryl derivatives showed a reduced potency both in receptor binding (rat adrenal capsular membranes) and in the functional assay (angiotensin II-induced contraction of rabbit aorta strips). The lower activity was justified by the extensive molecular modeling studies, which took into consideration the conformational and electrostatic features of several heterobiaryl derivatives. On the basis of the results obtained, it was hypothesized that the central aromatic ring of the biarylic portion works as a spacer, orienting in the right way the terminal phenyl ring, whose electronic distribution is, instead, crucial to its fitting well with a lipophilic pocket at the receptor site.

Adrenal Glands↗
PubMed1989

Hypothyroidism and polyneuropathy.

The prevalence and characteristics of polyneuropathy were assessed using standard clinical and electrophysiological criteria in 39 consecutive outpatients with primary hypothyroidism, 15 of whom were previously untreated. Subjective complaints, mainly paraesthesiae, were recorded from 25 cases (64%) and objective findings supporting a clinical diagnosis of polyneuropathy were present in 13 (33%). Using standard electrophysiological criteria, a definite diagnosis of polyneuropathy was made in 28 cases (72%). The commonest sites of abnormal nerve conduction were the sensory nerves, especially the sural nerve. Polyneuropathy was generally mild. None of the clinical and biochemical indicators of hypothyroidism were significantly correlated with the electrophysiological signs of peripheral nerve impairment or the diagnosis of polyneuropathy.

Adolescent↗
PubMed1984

[Function of the pituitary-thyroid axis after partial resection of the thyroid].

The TSH, T4 and T3 responses to TRH were measured in 48 patients who underwent selective goitre resection (hemithyroidectomy, ablation of single nodule); moreover 3 groups of healthy, hypothyroid and hyperthyroid persons served as reference groups. The main object was to detect eventual onset of preclinical hypothyroidism. This condition was observed after hemithyroidectomy only in 12.5%, and never after ablation of single nodule. Were detected too, among operated patients, 2 subjects with light and 1 with clear hyperthyroidism. Therapeutic implications of such a finding were taken into consideration.

Adult↗
PubMed1982

[The TRH test in simple goiter].

The TSH response to TRH and the increase in serum T3 after TRH infusion were measured in 25 euthyroid patients with non toxic goiter. On the ground of anatomic characters we divided the goitrous patients into 3 groups: subjects with diffuse goiter, with multinodular and with uninodular goiter; delta TSH and delta T3 did not differ significantly in the three groups. On the contrary, either absent hormonal increase (preclinic hyperthyroidism), or exceeding response (preclinic hypothyroidism), or normal response (real euthyroidism) were found in the different patients of a same group. Therapeutic implications of such a finding were taken into consideration.

Female↗