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Biomedical subjects

G Binetti

Publications and source records attributed to G Binetti.

At least 73 records · Page 4Linked to original sources

Characterization and distribution of protein kinase C isoforms in human skin fibroblasts.

In the present study we have examined the distribution of several isoforms of protein kinase C, a lipid-regulated serine/threonine kinase essential for signal transduction and cell regulation, in cultured human skin fibroblasts. By Western blot analysis we have detected the presence of at least three of the known protein kinase C isoforms. The calcium-dependent protein kinase C alpha was primarily associated with the cytosolic fraction. Three non-calcium-dependent isoforms, protein kinases C epsilon, C delta, and C zeta, were also detected. Protein kinases C zeta and C delta were present primarily in the cytosol, while protein kinase C epsilon was associated primarily with the membrane fraction. Binding and activity studies were consistent with the pattern of expression and distribution defined by Western blot analysis. These results provide a useful frame of reference for the study of isoform-specific effects of protein kinase C in the regulation of cell growth and metabolism.

Adult↗

Delusions in Alzheimer's disease and multi-infarct dementia.

Neuropsychiatric symptoms such as delusions and misidentifications have been reported in dementia ranging from 10% to 73% in Alzheimer's disease (AD) patients and up to 40% in multi-infarct dementia (MID) patients. The aim of this study was to investigate in 61 AD and 31 MID patients both the frequency and the content of delusions during the course of illness and to evaluate the relationship between these and both functional and mental decline. The results indicated that delusion experiences had occurred in 45% of AD patients and in 38% of MID patients, occurring most frequently during the first year of illness. Patients who experienced psychiatric symptoms showed higher mini mental state examination scores and were less impaired in functional disability measures. With regard to the content, no significant differences were observed between AD and MID patients; 53% of psychotic symptoms were found to be paranoid delusions while 47% were misidentification delusions.

Aged↗

Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease patients.

We attempted to determine whether changes in protein kinase C (PKC) activity in Alzheimer's disease (AD) brains are also present in cultured skin fibroblasts from living patients. Biopsies collected from shoulder skin were transferred to culture plates with an appropriate growth medium, and histone-directed PKC activity as well as phorbol ester binding were individually determined in soluble and particulate fractions prepared from AD and non-AD fibroblast cell lines. Binding experiments indicated that PKC was unevenly distributed between cytosol (78%) and particulate (22%). The Bmax values for phorbol ester binding in soluble and particulate fractions were similar in AD and non-AD patients. Kd values in the cytosol were 94% higher in AD patients, indicating lower affinity of the enzyme for the ligand. Accordingly, the soluble PKC activity was 30% lower in AD patients. The data suggest that the changes in PKC phosphorylating activity represent a diffuse cellular defect in AD and are not confined to the brain. The alterations of the enzyme may participate in the disregulation in processing of beta-amyloid precursor protein in AD.

Aged↗

[A case of oxalosis with heart and lung involvement].

We report the case of a 37-year-old woman with oxalosis, and cardiopulmonary involvement. Two-dimensional and Doppler echocardiography disclosed intracardiac calcifications compatible with deposition of calcium oxalate, and severe chronic pulmonary hypertension. Endomyocardial biopsy showed interstitial deposition of calcium oxalate. The absence of severe cardiac disease strengthened a deposition of calcium oxalate even in the arteries of the lungs, with secondary chronic pulmonary hypertension.

Adult↗

[Heart failure in patients with valve prostheses].

Congestive heart failure in patients with prosthetic valves is a complex syndrome which poses difficult clinical and therapeutical problems. In order to identify etiologic factors, pathophysiologic substrates, clinical pictures and natural history we retrospectively evaluated 124 consecutive patients (mean age 61 +/- 11 years) with prosthetic valves, hospitalized during the 1984-1990 period because of congestive heart failure. The following main etiologies were identified: acute prosthetic valve failure (19%), chronic prosthetic failure (15%), preexisting left ventricular dysfunction (9%), newly acquired left ventricular dysfunction (8%), associated valve diseases (15%), chronic constrictive pericarditis (2%), multiple causes (31%). At a mean follow-up of 8.9 +/- 4.5 years, mortality was 8.8%/patients/year in the whole group, 3% in the subgroup with chronic prosthetic failure and 19% among the cases with preexisting left ventricular dysfunction. Among the patients who underwent reoperation because of prosthetic failure, the following were incremental risk factors: mechanical (vs biological) failing prosthetic valve, mitral prosthesis, emergency operations, mitral and or aortic insufficiency as the initial diagnosis. The preliminary knowledge of the possible etiologies and of the pathophysiologic substrates can help the physician while treating the single patient with heart failure after valve replacement. Many implications derived from this kind of patients are also useful in order to select surgical candidates among patients with valve disease.

Aortic Valve↗

Usefulness of nicorandil in congestive heart failure.

Rest and exercise hemodynamic and hormonal effects of nicorandil, a nicotinamide-nitrate vasodilator, were assessed in 9 patients with New York Heart Association class II or III congestive heart failure (CHF) and left ventricular ejection fraction less than or equal to 40%. Single oral doses of placebo and 40 and 60 mg of nicorandil were given in a double-blind, randomized trial. Hemodynamic measurements were assessed at rest, up to 8 hours after dose and at peak exercise performed on an upright cycloergometer 1 hour after the dose. Forearm blood flow and venous capacitance were measured by plethysmography 45 minutes after dose. Plasma noradrenaline and plasma renin activity were assessed 1 hour and 2 hours after dose, respectively. Data were analyzed by analysis of variance. Peak effects were observed between 30 and 60 minutes after dose. Mean blood pressure decreased from 86 +/- 7 mm Hg after placebo to 78 +/- 7 mm Hg after 40 mg (p less than 0.05) and to 78 +/- 7 mm Hg after 60 mg (p less than 0.05) of nicorandil. Mean pulmonary artery pressure decreased from 24 +/- 11 to 15 +/- 17 mm Hg (p less than 0.05) and to 17 +/- 7 mm Hg (p less than 0.05) and mean pulmonary wedge pressure decreased from 15 +/- 8 to 9 +/- 4 mm Hg (p less than 0.05) and to 10 +/- 5 mm Hg (p less than 0.05). The changes were significant up to 6 to 8 hours after both doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Idiopathic restrictive cardiomyopathy in the young: report of two cases.

Two cases of idiopathic restrictive cardiomyopathy in young age are reported. This rare kind of restrictive cardiomyopathy is characterized by the absence of specific histologic features of myocardial abnormalities. In both cases (aged 12 and 9 years at diagnosis), the clinical picture was characterized by severe and slowly progressive congestive heart failure. The electrocardiogram showed biventricular hypertrophy, right bundle branch block and pseudoinfarctional Q waves. Echocardiography revealed moderate pericardial effusion, biatrial enlargement, and normal or nearly normal biventricular dimensions and systolic function. Cardiac catheterization disclosed the typically restrictive filling pattern. Right ventricular endomyocardial biopsy demonstrated moderate interstitial fibrosis and cellular hypertrophy without any evidence of infiltrative or storage myocardial disease or endocardial pathology. One patient underwent cardiac transplantation, whereas in the other, transplantation was contraindicated because of longstanding pulmonary hypertension and liver cirrhosis. The knowledge of this rare entity may correctly orient the diagnostic process in children suspected of having restrictive myocardial disease. Heart, or even heart-lung, transplantation must be considered in cases with congestive heart failure before irreversible damage occurs in many organs.

Adult↗

[Cardiac involvement in HIV infection: a prospective, multicenter clinical and echocardiographic study].

Cardiac abnormalities are frequently reported in patients with acquired immunodeficiency syndrome (AIDS). Much less is known about the true prevalence of cardiac involvement in patients with human immunodeficiency virus (HIV) infection. We prospectively examined 138 consecutive patients with HIV infection including 41 with AIDS, 49 with AIDS-related complex (ARC), 32 with chronic lymphoadenopathy syndrome (LAS) and 16 with asymptomatic HIV infection. Sixty-one patients had opportunistic infection. The prevalence of cardiac involvement progressively increased from patients with HIV infections or LAS (4%) to ARC (14%) to AIDS (37%). "Major" echocardiographic abnormalities (dilated cardiomyopathy and/or infective endocarditis and/or severe pericardial effusion) were identified in 3 patients (2%), "minor" abnormalities (mild pericardial effusion, hypokinesis of the interventricular septum, mild dilatation of the left ventricle in 21 (15%). Electrocardiographic abnormalities unassociated with echo abnormalities or clinical problems were seen in other 11 patients. End diastolic left ventricular dimension (normalized for body surface area) was higher among AIDS respect to pre-AIDS patients (30.1 +/- 7.1 vs 27.6 +/- 7.5; p less than 0.01) and among patients with respect to patients without opportunistic infections (29.5 +/- 6.5 vs 27.5 +/- 2.4; p less than 0.05). Left ventricular shortening fraction was lower in the subgroup with and absolute CD4 lymphocyte count less than 100/mm3 (31 +/- 7 vs 34 +/- 5; p less than 0.055). In conclusion, in a large, unselected group of patients with HIV infection, echocardiogram discloses cardiac abnormalities in 17% of the cases; their clinical relevance is generally low but in selected patients cardiac tamponade and/or dilated cardiomyopathy (secondary to viral myocarditis) may cause death.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

Felodipine in severe chronic congestive heart failure: acute effects on central hemodynamics and regional blood flow distribution.

In order to assess the effect of felodipine, a new calcium antagonist with vascular selectivity, on regional blood flow distribution at rest in chronic congestive heart failure, ten patients were studied during an acute test. Right heart catheterization allowed the evaluation of hemodynamic parameters; renal blood flow was calculated using paraamino-hippuric acid clearance; hepatic blood flow measurement was based on indocyanine green clearance; and limb blood flow was assessed with venous occlusion plethysmography. Blood samples were collected for the analysis of plasma catecholamines, renin, and aldosterone. All parameters were recorded in duplicate under basal conditions and after felodipine infusion. The infusion of felodipine induced a significant increase in cardiac index, stroke work index, and limb blood flow. Systemic and pulmonary arterial blood pressure, pulmonary wedge pressure, and systemic resistance underwent a significant decrease. The heart rate, pulmonary resistance, renal blood flow, and hepatic blood flow were not changed. In conclusion, felodipine was of benefit in congestive heart failure at rest in an acute test, acting through a marked decrease in vascular resistance and a consequent improvement in cardiac output and limb blood flow. No changes in renal and hepatic blood flow were observed.

Adult↗

Myocardial, coronary, and peripheral effects of xamoterol (ICI 118,587) in open-chest pigs.

The hemodynamic and coronary effects of increasing doses of xamoterol, a beta-adrenoceptor partial agonist, were assessed in an anesthetized pig preparation in which cardiovascular reflexes were abolished and sympathetic tone was modified by infusion of noradrenaline (NA). Xamoterol, in basal conditions, increased heart rate (HR) from 104 +/- 12 to 120 +/- 13 beats/min (p less than .001); systolic, diastolic, and mean blood pressure, respectively, from 77 +/- 8 to 103 +/- 17 mmHg (p less than .01), from 48 +/- 7 to 70 +/- 12 mmHg (p less than .01), and from 58 +/- 7 to 84 +/- 14 mmHg (p less than .01); left ventricular dP/dT max from 2098 +/- 564 to 4205 +/- 937 mmHg/sec (p less than .001); and systemic vascular resistance (SVR) from 1745 +/- 564 to 2270 +/- 739 dynes sec cm-5 (p less than .01). The increase in HR and dP/dT max brought about by xamoterol was about 37% and 56%, respectively, of the maximum increase produced by NA. At the highest level of sympathetic tone, xamoterol reduced HR from 148 +/- 11 to 122 +/- 11 beats/min (p less than .001) and no significant change was observed in dP/dT max. The increase in blood pressure and SVR induced by xamoterol was maintained at each level of sympathetic tone. On the contrary, SVR did not change after NA, as expected, since receptors were fully blocked. For a given inotropic effect, xamoterol and NA produced a similar increase in coronary blood flow and myocardial O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

[Analysis of the diastolic function of the left ventricle by Doppler echocardiography in athletes engaged in competitive sports activities].

In order to assess left ventricular diastolic function in elite athletes we studied 24 athletes (mean age 21 +/- 5 years) with the echo-Doppler technique. The control group consisted of 14 healthy males (mean age 24 +/- 6 years) and 99 patients (mean age 50 +/- 14 years) with primary or secondary left ventricular hypertrophy. The following variables were calculated: age, systolic and diastolic blood pressure, septal and posterior wall thickness, left ventricular volume and dimensions, myocardial mass index and mass/volume ratio, left ventricular end-systolic and peak systolic stress, RR interval, isovolumic relaxation time (IVRT), early (E) and late (A) peak flow velocity, E/A ratio, time and rate of deceleration of early diastolic flow. Compared with the normal subjects significant differences were observed with regard to systolic blood pressure, left ventricular wall thickness, myocardial mass, mass/volume ratio and peak systolic stress in the athlete group. In spite of a noticeable increase in myocardial mass indexes, all the diastolic function parameters were normal in the athletes. In this group a linear positive correlation between rapid filling indexes, ventricular mass and mass/volume ratio exists. These correlations are not present in the patients group. Moreover a linear negative correlation between RR interval and late diastolic flow velocity was found. In conclusion, the global diastolic ventricular function, evaluated with the echo-Doppler technique, is normal in athletes in spite of an increase in ventricular mass. Th early diastolic flow velocity is in direct proportion with mass increase and may represent one of the physiological mechanisms of the athlete heart adaptations.

Adolescent↗

[Idiopathic restrictive cardiomyopathy: clinical, hemodynamic, histologic and prognostic profile].

Idiopathic restrictive cardiomyopathy is a rare myocardial disease characterized by restrictive physiology without a specific histologic basis. To assess its clinical, hemodynamic, morphologic and prognostic details we retrospectively evaluated all the patients hospitalized in our Institute from 1974 to 1988. Nine patients, aged 42 +/- 16 years, M/F ratio = 0.29, who represent 64% of all the restrictive myocardial diseases biopsied were identified. Severe cardiac heart failure (3-4 NYHA) and arrhythmias (ventricular and supraventricular) were extremely common. The electrocardiogram showed several non specific signs: low voltage of QRS in peripheral leads (4/7), pseudo-infarctional aspects (3/7), mono or biventricular hypertrophy (3/7) disturbance of ventricular conduction (3/7), aspecific abnormalities of ventricular repolarization (3/7). All patients showed a prolonged QTc. M-mode and 2-dimensional echocardiography demonstrated in 6 cases biatrial enlargement, normal or slightly enlarged ventricles, normal or moderately depressed fractional shortening; biventricular concentric hypertrophy was detected in 3 cases, asymmetrical septal hypertrophy in 1. Five patients showed pericardial effusion. Cardiac catheterization disclosed an increase of left and right ventricular end-diastolic pressures (8/8) with a dip-plateau pattern and/or characteristic W waveform in the atrial pressure tracing (9/9). Passive pulmonary hypertension was detected in 6/9 cases. The cardiac index was decreased in 4/8 cases. Left ventricular angiography showed mitral regurgitation in 5/8 patients, tricuspidal in 5/8. Ejection fraction was decreased in 3/8 cases. Endomyocardial biopsy showed interstitial fibrosis (8/9), cellular hypertrophy and/or nuclear alterations (7/9), slight endocardial thickening (2/9). At a mean follow-up of 22 +/- 15 months 3 patients died and 2 underwent heart transplantation. In conclusion idiopathic restrictive cardiomyopathy is one of the most frequent forms of restrictive myocardial diseases in our geographic area. Severe congestive heart failure and arrhythmias are extremely common. The disease can be suspected by clinical, electrocardiographic and echocardiographic features, but the final diagnosis requires cardiac catheterization and endomyocardial biopsy. Prognosis is severe and heart transplantation must be considered in the cases with severe heart failure.

Adolescent↗

[Cerebral and renal aspergillosis in a patient with orthotopic heart transplant: diagnosis, treatment and follow-up].

A cardiac transplant recipient developed systemic aspergillosis with abscesses from aspergillus fumigatus in the brain and the right kidney. Surgical resections were performed (lobectomy for the brain abscess, partial resection for the renal abscess followed, after extension of the infection, by right nephrectomy) combined with therapy with itraconazole, a new antimycotic agent. Recovery from the infection was obtained and at 18 months of follow-up the patient feels well without signs of recurrences of the infection.

Aspergillosis↗

Haemodynamic effects of short term intravenous amiodarone for hypertrophic cardiomyopathy.

The haemodynamic effects of an intravenous amiodarone infusion (5 mg/kg for 10 minutes) were measured in ten patients with hypertrophic cardiomyopathy (two with a left ventricular outflow gradient at rest) five, 15, and 30 minutes after drug administration. Mean (SD) pulmonary capillary wedge pressure rose significantly at five and 15 minutes (from 12.3 (6.2) mm Hg to 17.6 (9.2) and to 16.2 (8.6] with a subsequent tendency to fall to control values at 30 minutes. Mean right atrial and right ventricular end diastolic pressures increased from 3.6 (1.8) mm Hg to 7.3 (3.1) and from 6.3 (2.4) to 9.8 (3.2) mm Hg respectively at 30 minutes. The increase in filling pressures was paralleled by a decrease of left ventricular max dP/dt from 1522 (414) to 1372 (327) to 1316 (338) and to 1326 (379) five, 15, and 30 minutes after infusion. Despite this slight negative inotropic effect, cardiac index and stroke volume index were unchanged or slightly increased, possibly because of the decrease in systemic vascular resistance (from 1326 (330) dyn s cm-5/m2 to 1152 (285]. In both patients with outflow gradient the pressure gradient at rest decreased (from 110 to 65 and from 85 to 65 mm Hg) through a reduction of left ventricular systolic pressure. Thus short term intravenous infusion of amiodarone is safe in patients with hypertrophic cardiomyopathy. The main changes were a mild depression of ventricular contractility, which was well tolerated and adequately compensated for by a decrease in afterload.

Adult↗