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Biomedical subjects

S Fazio

Publications and source records attributed to S Fazio.

At least 109 records · Page 6Linked to original sources
PubMed1993

[The regression of left ventricular hypertrophy and improvement in diastolic filling during antihypertensive therapy with cilazapril].

In order to evaluate the effects of cilazapril on left structure and function in essential hypertension, we evaluated 10 patients (4 females and 6 males) affected with mild-to-moderate systemic hypertension. All patients were treated with cilazapril 5 mg/day over a 6-months period and underwent a 24 hours ambulatory blood pressure monitoring and a complete Doppler echocardiographic examination at study entry, after 3 and 6-months of therapy. After therapy, mean systolic and diastolic arterial pressure decreased significantly from 153 +/- 16/102 +/- 8 mmHg to 135 +/- 13/83 +/- 6 mmHg respectively (p < 0.005/0.001 respectively). Moreover there was a significant decrease of left ventricular mass from 109 +/- 27 to 87 +/- 23 g/m2 (p < 0.005). Ejection phase indices did not change significantly, whereas left ventricular diastolic filling improved after therapy with a significant increase of M1/M2 ratio from 0.9 +/- 0.2 to 1.1 +/- 0.3 (p < 0.02). In conclusion, these data demonstrate that cilazapril 5 mg/day is effective in reducing blood pressure in mild-to-moderate essential hypertension. This normalization of blood pressure measurements is paralleled by a significant decrease of left ventricular mass index and by an improvement of left ventricular diastolic filling.

Adult↗
PubMed1993

Preferential association of apolipoprotein E Leiden with very low density lipoproteins of human plasma.

Apolipoprotein (apo) E Leiden is a rare variant of human apoE characterized by defective receptor binding and associated with dominant transmission of type III hyperlipoproteinemia. In heterozygotes, apoE Leiden is present in higher concentrations in both total plasma and very low density lipoproteins (VLDL) than the other apoE allele product. In the present study we analyzed cell expression and plasma lipoprotein association of apoE Leiden to determine whether the unequal concentration of the two apoE allele products could be explained by differences in secretion rate from the hepatocyte or by preferential association with VLDL. We transfected the rat hepatoma cell line McA-RH7777 with apoE Leiden or normal human apoE3, and studied their secretion and media distribution. In pulse-chase experiments, the secretion of apoE Leiden was comparable to that of both human apoE3 and rat endogenous apoE, approaching 100% in 90 min. In similar transfection experiments, secreted apoE Leiden was significantly less glycosylated than normal apoE3 (21.7% vs. 36.6%, P < 0.005, n = 4), a finding also noted for apoE Leiden in human plasma. In in vitro incubation experiments, apoE Leiden showed a markedly higher preference for VLDL of normolipidemic human plasma when compared to both apoE3 (2.6-fold, P < 0.001) and apoE4 (1.6-fold, P < 0.001). These results suggest that the accumulation of apoE Leiden in VLDL derives from a high affinity of the mutant protein for the VLDL. This enrichment in defective apoE probably exacerbates impairment of VLDL removal from the circulation, thus contributing to the dominant transmission of type III hyperlipoproteinemia.

Animals↗
PubMed1992

Synthesis and secretion of apolipoprotein E occur independently of synthesis and secretion of apolipoprotein B-containing lipoproteins in HepG2 cells.

The synthesis and secretion of apolipoprotein (apo) E, a major protein component of very low density lipoproteins, were examined in the human hepatoma cell line HepG2 under metabolic conditions known to stimulate lipogenesis and the production of apoB-containing lipoproteins. When HepG2 cells were incubated in the presence of fetal bovine serum (5 or 10%) or canine chylomicron remnants (5 or 10 micrograms of protein), the secretion of triglycerides and cholesteryl esters of lipoproteins of d less than 1.063 g/ml increased, as determined by the incorporation of [14C]acetate. Determination of the distribution of apoE among media lipoproteins by agarose column chromatography showed that the majority of secreted apoE was associated with large lipoproteins when cells were incubated with fetal bovine serum. However, immunoblot analysis of total media apoE revealed that incubating cells with or without the lipogenic factors had no effect on the amount of apoE secreted. Pulse-chase and continuous labeling experiments demonstrated that the synthesis and secretion of apoE did not vary under the different metabolic conditions, even though there was a 5-fold increase in apoB secretion in response to increased lipogenesis. Neither apoE nor apoB mRNA levels responded to the lipogenic stimuli. We conclude that the synthesis and secretion of apoE are independent of the production of apoB-containing lipoproteins in HepG2 cells.

Acetates↗
PubMed1992

The functional characteristics of a human apolipoprotein E variant (cysteine at residue 142) may explain its association with dominant expression of type III hyperlipoproteinemia.

Type III hyperlipoproteinemia typically is associated with homozygosity for apolipoprotein (apo) E2(Arg158----Cys). Dominant expression of type III hyperlipoproteinemia associated with apoE phenotype E3/3 is caused by heterozygosity for a human apoE variant, apoE3(Cys112----Arg, Arg142----Cys). However, this apoE3 variant was not separable from the normal apoE3 in these patients' plasma because the two proteins have identical amino acid composition, charge, and molecular weight. Therefore, to determine the functional characteristics of this protein, we used recombinant DNA techniques to produce this apoE variant in bacteria. We also produced a non-naturally occurring variant, apoE(Arg142----Cys), that had only the cysteine substituted at residue 142. These two apoE variants were purified from cell lysates of the transfected Escherichia coli by ultracentrifugal flotation in the presence of phospholipid, by gel filtration chromatography, and by heparin-Sepharose chromatography. Both Cys142 apoE variants bound to lipoprotein receptors on human fibroblasts with only about 20% of normal binding activity. Therefore, cysteine at residue 142, not arginine at residue 112, is responsible for the decreased receptor binding activity of the variants. Cysteamine treatment and removal of the carboxyl-terminal domain had little effect on the binding activity, whereas both modulate the receptor binding activity of apoE2(Arg158----Cys). The mutation at residue 142 decreased the binding activity of apoE to both heparin and the monoclonal antibody 1D7 (this antibody inhibits receptor binding of apoE), whereas apoE2(Arg158----Cys), which is associated with recessive expression of type III hyperlipoproteinemia, binds normally to both. The Arg112, Cys142 variant predominantes 3:1 over normal apoE3 in the very low density lipoproteins of plasma from an affected subject, as assessed by differential reactivity with the antibody 1D7. The unique combination of functional properties of the Arg112, Cys142 variant provides a possible explanation for its association with dominant expression of type III hyperlipoproteinemia.

Amino Acid Sequence↗
PubMed1992

Influence of atenolol on the relationship between heart rate and QT interval in patients with exercise-induced myocardial ischemia.

The aim of this study was to analyze the relationship between heart rate and QT interval (HR-QT) during exercise in control subjects (Group A) and in patients with coronary artery disease (CAD) with effort angina and without previous myocardial infarction (MI) (Group B). The diagnosis of CAD was confirmed by coronarographic examination. The correlation HR-QT was significant (p < 0.001) in both groups on effort and at recovery. The analysis of the regression HR-QT was carried out separately, both on effort in upright position and at rest in supine position, to avoid the influence of posture on QT length. During effort, the regression line showed lower slope and intercept values in Group B (p < 0.001) than those for Group A. A similar behavior was also observed at rest. Thus, at the highest heart rate, where ECG signs of ischemia (ST depression > 1 mm) frequently occurred, a longer QT interval was present in Group B. Moreover, in Group B, the QT interval in the presence of ECG signs of ischemia was significantly longer (p < 0.01) than in Group A at comparable heart rates both on effort and at rest, thereby confirming the result obtained by comparing both regression lines. The same effort protocol was repeated in Group B patients after acute administration of atenolol 100 mg per os. After atenolol administration, the analysis of the regression HR-QT in Group B clearly showed a shorter QT interval than that obtained in washout period during the baseline test at the highest heart rates where the ECG frequently showed signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Follow-up of a respiratory rate modulated pacemaker.

The efficacy of 27 respiration sensitive rate modulated pacemakers (Biorate RDP-3 Biotec) implanted in the left pectoral area was evaluated every 3 months during a mean follow-up period of 29 months (range 10-50 months). Rate modulation function was unchanged other than for three patients in whom the auxiliary leads became displaced. Two implants lost ventricular sensing in this nonprogrammable model. In all but the three patients, Holter monitoring demonstrated pacing rate variation corresponding to daily activity. Stress test duration increased from 8.2 +/- 1.5 minutes (in fixed rate VVI rate) to 12.83 +/- 2.0 minutes (in the VVIR mode) (P less than 0.05). Right arm movement increased the pacing rate by 5 +/- 3 beats/min (NS), while the left arm movement increase was 30 +/- 5 beats/min (P less than 0.05). Mental, arithmetic, and nifedipine tests did not change the rate modulated pacing rate. The system responded to a change in respiratory rate by an increase in stimulation rate. A satisfactory response in sensitivity and velocity was present only with medium-high workloads. Interference with rate modulation occurred with movement of the arm ipsilateral to the implanted pulse generator.

Atrial Fibrillation↗
PubMed1992

Evaluation, by noninvasive methods, of the effects of acute loss of thyroid hormones on the heart.

To evaluate the effects of the acute loss of thyroid hormones on the heart the authors studied 11 women with acute hypothyroidism. The cardiac study was performed by means of electrocardiography (ECG), radionuclide ventriculography (RNV) at rest and under effort, and monodimensional echocardiography (MD-echo) and was repeated with ECG and MD-echo after six months of thyroxine suppressive therapy. The ECG showed a significant prolongation of QT interval and flattening and inversion of T wave with normal heart rate. The MD-echo revealed left ventricular function in the normal range and normal left ventricular dimensions. RNV showed the ejection fraction in the lower normal range at rest, which increased to a smaller extent under effort in comparison with a control group. The ECG performed during suppressive therapy with L-thyroxine yielded normal findings with an increase of heart rate and of R wave amplitude, and the MD-echo showed no significant variations of cardiac function due to the increase of heart rate.

Adult↗
PubMed1992

Capillary blood flow to the skin of forearm in cirrhosis.

In liver cirrhosis a hyperkinetic circulatory state is frequently observed as a consequence of an arterial or even a venous peripheral vasodilatation with secondary increase in cardiac output. Indirect evidence suggests that, in liver disease, the manifestation of warm hands, capillary pulsation, or palmar erythema may also relate to such a state by way of an increased skin blood flow. The purpose of the present study has been to directly assess capillary skin blood flow in liver disease through the clearance of a locally injected radioactive substance. The study was performed in 24 patients with different liver diseases, including 14 Child class II cirrhotics, and in 9 control subjects. A small volume of Na 131I solution was injected at the volar surface of the forearm, and radioactive counts were recorded continuously for ten seconds every minute for up to twenty minutes. The best fit line of the disappearance rate was determined by the least square method, and both its T/2 and an estimated blood flow parameter were calculated. The T/2 of isotope disappearance rate was 4.54 +/- 0.71 and 4.38 +/- 0.68 minutes in cirrhotics and controls, respectively. Similarly, estimates of skin blood flow (mL/min/100 g tissue) were 7.82 +/- 1.28 in the cirrhotic patients, not significantly different from those in both patients with mixed liver diseases (7.6 +/- 2.86) and control subjects (8.06 +/- 1.04). Parameters of skin blood flow were also invariant in respect to the various etiologies of liver disease. Thus, the present findings indicate that capillary skin blood flow is not affected by the hyperdynamic circulatory changes occurring in liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Pravastatin in heterozygous familial hypercholesterolemia: low-density lipoprotein (LDL) cholesterol-lowering effect and LDL receptor activity on skin fibroblastS.

The cholesterol-lowering effect of provastatin, a new competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, was studied in 10 patients with heterozygous familial hypercholesterolemia (FH). Residual low-density lipoprotein receptor (LDL-R) activity was also evaluated in cultured skin fibroblasts prior to treatment, and showed a wide range of reduction from 30% to 70% of the normal value. Treatment with pravastatin 40 mg once daily reduced total and LDL cholesterol (LDL-C) after 6 months by 19.7% and 25.4%, respectively (P less than .001). Serum apolipoprotein (apo) B levels decreased significantly by 29.1% (P less than .001). No significant changes were observed in mean serum total triglycerides or high-density lipoprotein cholesterol (HDL-C) levels. A positive correlation between residual LDL-R activity and maximum percent reduction of LDL-C levels was observed (r = .676, P less than .05). No clinically important side effects were recorded and the treatment was well tolerated. Thus, pravastatin effectively reduces LDL in heterozygous FH, and this effect appears to be related to LDL-R status.

Cholesterol, LDL↗
PubMed1991

A form of familial hypobetalipoproteinaemia not due to a mutation in the apolipoprotein B gene.

Familial hypobetalipoproteinaemia (FHBL) is a dominant disorder of lipoprotein metabolism characterized by levels of apolipoprotein B-carrying lipoproteins (VLDL, IDL and LDL) which are 50% of the normal levels in the heterozygotes and almost absent in the homozygotes. Several reports have recently shown that the underlying defect in FHBL involves different mutations in the apo B gene which lead to reduced levels of apo B mRNA or to the production of truncated forms of apo B having either a lower synthetic rate or a higher catabolic rate than normal apo B. We here present a three-generation family with several FHBL members in which the linkage analysis shows absence of co-segregation between apo B gene alleles and the hypocholesterolaemic phenotype. We conclude that a dominantly transmitted mutation in a gene other than that for apo B is responsible for the low plasma cholesterol levels.

Adult↗
PubMed1991

Fourier analysis in patients with different pacing modes.

The purpose of this study was to evaluate the usefulness of phase analysis in detecting the altered activation sequence induced by different pacing modes. Radionuclide ventriculography and planar gated blood pool scintigraphy were performed at rest in 56 patients with different pacemakers. This method permitted us to localize the pacemaker impulse site in the right ventricle and its diffusion in the heart. In patients with VVI pacemaker, this technique showed an evident asynchronism of contraction and relaxation of each ventricle and the standard deviation of phase angle (sigma), calculated by computer, is greater during pacing than sinus rhythm for left (LV) and right (RV) ventricles (LV sigma: 17 degrees +/- 4 vs 11 degrees +/- 3, less than 0.001; RV sigma: 31 degrees +/- 7 vs 14 degrees +/- 4, P less than 0.001). In the patients with VVI rate responsive pacemakers, the LV sigma changed from 18.5 +/- 3 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.001, while the RV sigma changed from 30 degrees +/- 8 to 14 degrees +/- 4, P less than 0.001. Instead in the patients with DDD pacemakers, the LV sigma changed from 15.5 degrees +/- 2 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.05, while the RV sigma changed from 29.1 degrees +/- 6 to 14 degrees +/- 4, P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1991

Efficacy of ticlopidine in the prevention of thromboembolic events in patients with VVI pacemakers.

This study was designed to evaluate whether long-term treatment with ticlopidine reduces the incidence of thromboembolic episodes in patients with a VVI pacemaker. One hundred eleven patients with a VVI pacemaker were randomly assigned to two groups: group A (52 patients) was treated with ticlopidine at the dose of 250 mg a day; and group B (59 patients) was not treated and served as a control group. The primary analysis of efficacy of ticlopidine was based on the occurrence of thromboembolic episodes and of cardiovascular and cerebrovascular deaths. The mean follow-up period was 66 months. In group A, there was a significant reduction in the incidence of thromboembolic episodes (P less than 0.05) with a smaller incidence of total cardiovascular and cerebrovascular deaths (8 in group A and 18 in group B; P = 0.05) as compared with group B. Twelve percent of patients had moderate side effects with 1 dropout (epistaxis). Our data confirm the high incidence of thromboembolic events in patients with a VVI pacemaker and demonstrate the efficacy of ticlopidine in preventing them.

Aged↗
PubMed1991

[Anaerobic threshold in the evaluation of heart function in patients with rate-responsive pacemaker].

It is very difficult to evaluate the ability of carrying out physical exercise in patients with rate responsive (RR) pacemaker (PM). However, the anaerobic threshold (AT) proved to be a useful parameter in the evaluation of cardiac function. The AT can be easily reproduced and not influenced from emotional aspects of both the patient and the physician, moreover being under maximum and then easy to achieve. Aims of our study were: to evaluate if the cardiopulmonary stress test can represent a method to be used for a more correct rate responsive pacemaker programming; to compare the data obtained of 3 rate responsive pacemakers steered by different sensors. We have studied 24 patients, of whom 10 with Activitrax (A), 8 with Meta (M), and 6 with Phymos MPT (P) pacemakers. Patients were submitted to symptoms limited cycloergometer stress test at 2 different settings: fixed rate at 70 b/min; increasing rate at until 85% of maximum heart rate for each patient, with range 0 + 10 W/min. Gas exchange data were continuously collected using an automated system (Medical Graphic System 2001) based on Whipp and Wasserman's method.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold↗
PubMed1991

[Pancreatoduodenectomy with preservation of the stomach and pylorus: technical and functional aspects].

Pancreatoduodenectomy is the most used resective operation in the treatment of cephalopancreatic pathology; nevertheless it is a severely demolitive operation, especially if performed according to the traditional technique. It can induce early as well as late complications in a high percentage of cases. A number of technical improvements have been proposed so far in order to reduce or avoid such complications; duodenopancreatectomy with gastric and pyloric preservation (PPDP) is the most representative one. The Authors analyze technical and functional features of PPDP in 22 patients operated on; results are compared with the traditional technique. In conclusion, among all the techniques proposed, PPDP assures the best improvement in the quality of life of these patients.

Ampulla of Vater↗
PubMed1991

Subclinical cardiotoxicity by doxorubicin: a pulsed Doppler echocardiographic study.

In order to detect subclinical levels of Doxorubicin (D) cardiotoxicity, 21 patients aged 42 +/- 8 years with malignancies and treated with D as a part of a multiple regimen, were evaluated. The mean cumulative dose of D was 242 +/- 112 mg.m-2 (150 to 520 mg.m-2). Patients with systemic hypertension, valvular diseases, suspected coronary artery disease, ejection fraction less than 55% as assessed by radionuclide angiography, and aged more than 50 years were excluded from the study. A Doppler echocardiographic examination was performed before and after the course of D therapy with a mean interval of 142 days. The following variables were assessed: fractional shortening (FS), ejection fraction (EF), stroke volume (SV), isovolumic relaxation time (IVRT), maximal early diastolic flow velocity (Emax), maximal late diastolic flow velocity (Amax), and mitral deceleration time (Mdt). Indices derived from 19 aged-matched normal subjects were compared to those of the patients before the course of therapy. Doppler echocardiographic measurements did not differ significantly between the control group and patients before the course of therapy. While there were no significant changes in FS, EF, and SV in the study group before and after therapy, indices of diastolic filling showed striking differences: IVRT changed from 72 +/- 11 to 87 +/- 19 ms (P less than 0.001), Emax from 81 +/- 12 to 65 +/- 17 cm.s-1 (P less than 0.001), Mdt from 174 +/- 25 to 183 +/- 34 ms (P less than 0.05), Amax from 44 +/- 17 to 52 +/- 16 cm.s-1 (P less than 0.01). These data demonstrate impaired diastolic filling after doxorubicin therapy at conventional dosages.

Adult↗
PubMed1991

Phase image analysis in Wolff-Parkinson-White syndrome. Role of transesophageal pacing.

Phase image analysis (first Fourier harmonic transformation) has been performed in 5 men with WPW syndrome to define the abnormal patterns of ventricular emptying during sinus rhythm and transesophageal pacing at different rates. All patients but one showed basal ventricular preexcitation. Of the 4 patients with basal ventricular preexcitation the earliest ventricular emptying occurred in the left ventricular free-wall in 1 patient and in the right ventricular free-wall in 3 patients. In the patient without ventricular preexcitation at rest transesophageal pacing at a rate of 100 bpm induced first ventricular activation in the left lateral ventricular free-wall while at a rate of 120 bpm it returned to normal. In the patients with ventricular preexcitation at rest, the basal image abnormalities become more evident as preexcitation was augmented. Of interest, in 1 patient with basal type B ventricular preexcitation the sequential phase image analysis, at a rate of 100 bpm confirmed the earliest ventricular activation in the right ventricular free-wall while at a rate of 120 bpm showed the earliest emptying in left ventricular free-wall suggesting the presence of 2 accessory connections. We conclude that phase mapping combined with transesophageal pacing may be a useful and reliable method to localize single as well as multiple accessory pathways in patients with ventricular preexcitation.

Adolescent↗
PubMed1990

Cardiac function and sympathetic activity in young diabetics.

This study was aimed at evaluating cardiac function, both systolic and diastolic, in young type 1 diabetics with a mean duration of the disease of 10.9 +/- 6 years and without evidence of cardiac autonomic neuropathy and micro- or macroangiopathy. Thirteen diabetics, with good metabolic control, and 10 normal matched subjects were studied by echocardiography at rest and by radionuclide ventriculography both at rest and during effort. The level of plasma catecholamines was also determined. The echocardiographic data were comparable in the two groups. Scintigraphic data showed an increased peak ejection and peak filling rate (P less than 0.001) in diabetics while the other indices of cardiac function were comparable. Norepinephrine (P less than 0.01) and epinephrine (P less than 0.001) were higher in diabetics. A hypothesis is formulated that the higher indices of flow velocities in type 1 diabetics are supported by a sympathetic overactivity.

Adult↗