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Biomedical subjects

A Redaelli

Publications and source records attributed to A Redaelli.

At least 19 recordsLinked to original sources
PubMed2001

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Adolescent↗
PubMed2001

Hepatocyte proliferation and risk of hepatocellular carcinoma in cirrhotic patients.

OBJECTIVES: High hepatocyte proliferation has been recently proposed as a risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess whether hepatocyte proliferation is an independent risk factor for HCC when considered together with clinical and demographic characteristics. METHODS: We retrospectively evaluated 97 consecutive patients with a histological diagnosis of cirrhosis and preserved liver function, enrolled in a surveillance program for early diagnosis of HCC. Hepatocyte proliferation was evaluated by flow-cytometric analysis in liver samples collected at the time of histological diagnosis of cirrhosis. All patients were followed with abdominal US and serum alpha-fetoprotein (AFP) assays every 6 months. RESULTS: During a mean follow-up of 53 months (range, 12-120 months), 12 patients developed HCC, giving an annual incidence of 2.8%. The mean S-phase fraction was 2.5%+/-1.6 in patients who developed HCC and 0.9%+/-0.6 in those who did not (p < 0.0001). By univariate analysis, S-phase fraction 1.8% or higher and AFP higher than 20 ng/ml were the only two variables significantly correlated with the development of HCC (p < 0.0001, p < 0.0001). Multivariate analysis found that both variables were independently associated with HCC development (p < 0.003 and p < 0.005, respectively), with hazard ratios of 8.0 and 7.3 (confidence intervals, 2.1-31.2 and 1.8-29.2). Among patients with high AFP and/or high S-phase fraction, 11 (39%) developed HCC, compared with only one (1%) with a low S-phase fraction and normal AFP, corresponding to HCC yearly incidences of 9.5% and 0.3% (p < 0.00009). CONCLUSIONS: Patients with high S-phase fraction and/or above-normal serum AFP are at higher risk of developing HCC and should be offered a close surveillance program.

Adult↗
PubMed2000

Depression during interferon therapy for chronic viral hepatitis: early identification of patients at risk by means of a computerized test.

OBJECTIVES: At the doses used for the treatment of chronic viral hepatitis, interferon (IFN)-related side-effects are usually modest, even though in some cases they require the interruption of therapy. Neuropsychiatric disturbances that range from modest depression and irritability to forms of manic-depressive psychosis and attempted or successful suicides are among the most important side-effects. The aim of our study was to determine whether the Minnesota Multiphasic Personality Inventory (MMPI) is a sensitive and reliable test for the early identification of patients at risk of depression before IFN therapy is commenced, and whether it could be useful for the monitoring of these patients during treatment. METHODS: We prospectively studied 67 patients with chronic active liver diseases, consecutively enrolled in open studies and treated with r-IFNalpha2. Before starting therapy and after 3 months of treatment, all patients underwent a clinical neurological evaluation and MMPI. RESULTS: At baseline, the correlation between the clinical evaluation and the score of the depression scale of the MMPI was statistically significant (P< 0.0001). Nine of 14 (64.3%) patients with a baseline score > or = 60/100 showed a depressive mood after 3 months of therapy. Five of 44 patients (11.3%) with a baseline score < 60/100 showed a depression of medium level after 3 months of treatment. This difference was highly significant (P< 0.0001). CONCLUSIONS: According to our results, the MMPI is a reliable and sensitive test for the early identification of patients at risk of depression before and during IFN therapy for chronic viral liver diseases.

Adult↗
PubMed2000

Ventricular motion during the ejection phase: a computational analysis.

In the present paper, the study of the ventricular motion during systole was addressed by means of a computational model of ventricular ejection. In particular, the implications of ventricular motion on blood acceleration and velocity measurements at the valvular plane (VP) were evaluated. An algorithm was developed to assess the force exchange between the ventricle and the surrounding tissue, i.e., the inflow and outflow vessels of the heart. The algorithm, based on the momentum equation for a transitory flowing system, was used in a fluid-structure model of the ventricle that includes the contractile behavior of the fibers and the viscous and inertial forces of the intraventricular fluid. The model calculates the ventricular center of mass motion, the VP motion, and intraventricular pressure gradients. Results indicate that the motion of the ventricle affects the noninvasive estimation of the transvalvular pressure gradient using Doppler ultrasound. The VP motion can lead to an underestimation equal to 12.4 +/- 6.6%.

Algorithms↗
PubMed1999

Poroelastic finite element analysis of a bone specimen under cyclic loading.

It had been suggested that the fluid embodied in bone lacunar-canalicular porosity may play an important role in bone remodelling [Weinbaum et al., 1994. Journal of Biomechanics 27, 339-360]. In this paper a finite element model of a poroelastic prismatic solid of rectangular cross-section is considered to simulate bone behaviour, precisely as in the previous work by Zhang and Cowin [Zhang and Cowin, 1994. Journal of Mechanical Physics of Solids 42, 1575-1599]. This solid is subject to combined cyclic axial and bending loads at its end. The objectives of the study are: (1) to verify the accuracy of the simplifying hypotheses underlying the analytical solutions established by the above authors; (2) to provide further insight into the behaviour of that solid; (3) to test the advantages in generality and versatility and the computing costs of general-purpose finite element codes in poroelastic analysis. The study is parametric with respect to the fluid leakage coefficient, to the ratio of the bending moment and axial load, and to the ratio of the characteristic relaxation time of the pore pressure over the excitation period. Results show that, for all the cases considered, the pore pressure distribution along the section height of the poroelastic beam exhibits a very good matching with previous analytical results. Stresses transversal with respect to the beam axis (assumed as constant or zero in previous analytical solutions) are evaluated. The analysis pointed out that: (1) the effects due to end-loads with zero resultants practically extinguish within a distance from the beam end almost equal to a typical length of the cross-section; (2) cross-sections remain plane above that distance; (3) the transversal total stresses are three orders of magnitude lower than axial stress.

Adaptation, Physiological↗
PubMed1999

The hemodynamic effects of double-orifice valve repair for mitral regurgitation: a 3D computational model.

OBJECTIVES: A 3D computational model has been implemented for the evaluation of the hemodynamics of the double orifice repair. Critical issues for surgical decision making and echo-Doppler evaluation of the results of the procedure are investigated. METHODS: A parametric 3D computational model of the double-orifice mitral valve based on the finite elements model has been constructed from clinical data. Nine different geometries were investigated, corresponding to three total inflow areas (1.5, 2.25 and 3 cm2) and to three orifice configurations (two equal orifices, two orifices of different areas, i.e. one twice as much the other one, and a single orifice). The simulations were performed in transit; the fluid was initially quiescent and was accelerated to the maximum flow rate with a cubic function. For each case, some characteristic values of velocity and pressure were determined: velocities were calculated downstream of each orifice, at the centre of it (Vcen1, Vcen2). The maximum velocity was also determined for each orifice (Vmax1, Vmax2). Maximum pressure drops (deltap(max)) across the valve were compared with the estimations (deltap(Bernoulli)) based on the Bernoulli formula (4 V2). RESULTS: In each simulation, no notable difference was observed between Vcen1 and Vcen2, and between Vmax1 and Vmax2, regardless of the valve configuration. Maximum velocity and deltap(max) were related to the total orifice area and were not influenced by the orifice configuration. Deltap(Bernoulli) calculated with Vmax was well correlated with the deltap(max) obtained throughout the simulations (y = 0.9126x + 0.3464, r = 0.996); on the contrary the pressure drops estimated using Vcen underestimated (y = 0.6757x + 0.3073, r = 0.999) the actual pressure drops. CONCLUSIONS: The hemodynamic behaviour of a double orifice mitral valve does not differ from that of a physiological valve of same total area: pressure drops and flow velocity across the valve are not influenced by the configuration of the valve. Echo Doppler estimation of the maximum velocities is a reliable method for the calculation of pressure gradients across the repaired valve.

Blood Flow Velocity↗
PubMed1999

Correlation of interferon-induced expression of MxA mRNA in peripheral blood mononuclear cells with the response of patients with chronic active hepatitis C to IFN-alpha therapy.

MxA, a protein with selective activity against certain viruses, is an accepted specific indicator of type I interferon (IFN) activity. We have developed an internally controlled quantitative-competitive PCR to measure the amounts of MxA mRNA expressed in peripheral blood mononuclear cells (PBMC). This assay is more sensitive, quantitative, and easily applied to serial clinical samples than previously described methods. We have applied this assay retrospectively to 27 patients with chronic active hepatitis C given IFN-alpha2. Most such patients gain no sustained benefit but nevertheless suffer from the side effects, expense, and inconvenience of the treatment. Fourteen of the 27 had been classified on clinical grounds as responders and 13 as nonresponders at the end of a 6 month treatment period. We measured MxA mRNA in PBMC obtained before and after 8 weeks of IFN-alpha2 treatment. All the patients expressed some level of mRNA before treatment began, and after 8 weeks of treatment, the level rose in 19. This increase was significant (p < 0.001) only in patients classified as responders. This strongly suggests that hepatitis C virus (HCV) patients who express increased amounts of MxA mRNA in their PBMC during IFN-alpha treatment are most likely to obtain long-term benefit. If this finding is confirmed in future prospective studies, it will provide an extremely important predictive marker for managing IFN-alpha therapy in patients with HCV.

Adult↗
PubMed1998

Intraventricular pressure drop and aortic blood acceleration as indices of cardiac inotropy: a comparison with the first derivative of aortic pressure based on computer fluid dynamics.

This paper presents a computational approach to ventricular fluid mechanics to evaluate three inotropic indices of early ejection: the intraventricular pressure drop (deltap). the first derivative of aortic flow rate (df/dt) and the first derivative of aortic pressure dp/dt. dp/dt is one of the most frequently used indices for assessing myocardial inotropy. Deltap and df/dt are characteristic of inertia driven flows and reflect the impulsive nature of the flow inside the ventricle during the ejection phase. The study is based on an axisymmetric fluid dynamics model of the left ventricle, developed according to the finite element approach. The fluid cavity is bounded by a shell containing two sets of counter-rotating contractile fibres. Two simulation sets were performed: the former to investigate the sensitivity of deltap and df/dt peaks (deltap(max) and df/dt(max)) with respect to changes in the inotropic state of the fibre. The latter allows the evaluation of the dependency of deltap(max) and df/dt(max) on afterload by means of two supravalvular stenoses of 50% and 70%. The model simulates the inertial features of ventricle behaviour. The calculated values of the indices investigated are in close agreement with those reported in the literature. The sensitivities of deltap(max) df/dt(max) and dp/dt(max) are calculated for the two simulation sets. Data are normalised with respect to the maximum values reached in the simulation set. The comparison indicates that deltap(max) has a greater sensitivity (3.4 vs. 3.1 ) and a more linear pattern than dp/dt(max) for changes in the inotropic state of the fibre. df/dt(max), shows a sensitivity close to dp/dt(max). Results confirm that the afterload does not affect dp/dt(max), in accordance with experimental observations, while deltap(max) and, to a major degree, df/dt(max) decrease when the afterload is increased.

Acceleration↗
PubMed1998

AP endonuclease activity in humans: development of a simple assay and analysis of ten normal individuals.

The human AP endonuclease (APE) activity counteracts the mutagenic and cytotoxic effects of the frequent genomic lesions abasic (AP) sites. In order to investigate the interindividual variability of APE levels, a simple and quantitative assay was developed. Crude lymphocyte extracts were incubated with a depurinated or a control supercoiled plasmid substrate, and the accumulation of nicked circular plasmid forms was monitored by agarose gel electrophoresis. The detected incision activity was AP sites-dependent and EDTA-sensitive. The unit of enzymatic activity was defined as that amount able to incise 1 ng of plasmid DNA carrying 1 AP site/plasmid at 30 degrees C in 10 min. The assay was used to measure the APE activity in 10 healthy individuals ages 25-48 years. Values ranged from 0.38 to 0.94 units/ng protein, with a mean value of 0.62. The use of the assay for screening of people with DNA base excision repair (BER) defects is proposed.

Adult↗
PubMed1998

Optimisation of a stentless valve prosthesis based on an analytic parametric model of the aortic valve.

An analytical mathematical model of a stentless aortic valve has been implemented. The valve is characterised by a trileaflet geometry, cylindrical leaflets; the aortic root is schematised by a conical surface which includes the leaflet attachments. The model is defined through six geometric parameters: the base radius, the valve height, the commissure radius, the leaflet radial, circumferential and attachment line lengths. Five performance indexes have been used to optimise the valve geometry, namely: the systolic area, the leaflet circumferential stress in diastole, the leaflet bending strain in systole and two bending angles related to the rotation of the leaflets from the diastolic to the systolic configuration. The sensitivity analysis is carried out which can identify the influence of each geometric parameter on the performance indexes adopted for the optimum valve design. The analysis of the results provides the geometric configuration which optimises the overall function of the valve throughout the cardiac cycle.

Aortic Valve↗
PubMed1997

The assignment of velocity profiles in finite element simulations of pulsatile flow in arteries.

In this paper we present a new method for the assignment of pulsatile velocity profiles as input boundary conditions in finite element models of arteries. The method is based on the implementation of the analytical solution for developed pulsatile flow in a rigid straight tube. The analytical solution provides the fluid dynamics of the region upstream from the fluid domain to be investigated by means of the finite element approach. In standard fluid dynamics finite element applications, the inlet developed velocity profiles are achieved assuming velocity boundary conditions to be easily implementable-such as flat or parabolic velocity profiles-applied to a straight tube of appropriate length. The tube is attached to the inflow section of the original fluid domain so that the flow can develop fully. The comparison between the analytical solution and the traditional numerical approach indicates that the analytical solution has some advantages over the numerical one. Moreover, the results suggest that subroutine employment allows a consistent reduction in solving time especially for complex fluid dynamic model, and significantly decreases the storage and memory requirements for computations.

Algorithms↗
PubMed1997

Assessment of the influence of the compliant aortic root on aortic valve mechanics by means of a geometrical model.

In recent years several researchers have suggested that the changes in the geometry and angular dimensions of the aortic root which occur during the cardiac cycle are functional to the optimisation of aortic valve function, both in terms of diminishing leaflet stresses and of fluid-dynamic behaviour. The paper presents an analytical parametric model of the aortic valve which includes the aortic root movement. The indexes used to evaluate the valve behaviour are the circumferential membrane stress and the stress at the free edge of the leaflet, the index of bending strain, the bending of the leaflet at the line attachment in the radial and circumferential directions and the shape of the conduit formed by the leaflets during systole. In order to evaluate the role of geometric changes in valve performance, two control cases were considered, with different reference geometric configuration, where the movement of the aortic root was ignored. The results obtained appear consistent with physiological data, especially with regard to the late diastolic phase and the early ejection phase, and put in evidence the role of the aortic root movement in the improvement of valve behaviour.

Aorta↗
PubMed1996

Computational analysis of the ductus venosus fluid dynamics based on Doppler measurements.

The simplified Bernoulli equation is currently used to evaluate pressure gradients on the basis of Doppler velocity measurements when direct pressure data require highly invasive procedures. Recently, this method was applied to the ductus venosus (DV) in order to estimate the fetal central venous pressure. The complex geometry- and consequently hemodynamics-of this fetal region suggests caution in automatically converting Doppler velocity measurements to pressure data. To investigate the reliability of the Bernoulli equation for this practice, we simulated the hemodynamics of the branching between the umbilical vein (UV) and the DV on the basis of ultrasonographic data from a normal fetus, using a simplified parametric 3D numerical model of a bent tube with varying cross section (UV) and a smaller trumpet-shaped branch (DV). A finite element formulation has been adopted to solve the governing Navier-Stokes equations. The results show that the simplified Bernoulli equation, despite of its simplicity, provides a good estimation of the pressure drop between the UV and the DV outlet section (with an error of about 0.25 mmHg, equal to 15%, compared with the model results). Nevertheless, attention must be paid to the velocity measurement sites, as discussed in this paper. In turn, the error becomes notable (2.8 mmHg, i.e., 34%) for high velocity values, thus suggesting that the error in evaluating the pressure drop with the simplified Bernoulli equation during fetal inspiratory movements may be substantial.

Blood Flow Velocity↗
PubMed1996

Computational evaluation of intraventricular pressure gradients based on a fluid-structure approach.

The dynamics of intraventricular blood flow, i.e. its rapid evolution, implies the rise of intraventricular pressure gradients (IPGs) characteristic of the inertia-driven events as experimentally observed by Pasipoularides (1987, 1990) and by Falsetti et al. (1986). The IPG time course is determined by the wall contraction which, in turn, depends on the load applied, namely the intraventricular pressure which is the sum of the aortic pressure (i.e., the systemic net response) and the IPG. Hence the IPGs account, at least in part, for the wall movement. These considerations suggest the necessity of a comprehensive analysis of the ventricular mechanics involving both ventricular wall mechanics and intraventricular fluid dynamics as each domain determines the boundary conditions of the other. This paper presents a computational approach to ventricular ejection mechanics based on a fluid-structure interaction calculation for the evaluation of the IPG time course. An axisymmetric model of the left ventricle is utilized. The intraventricular fluid is assumed to be Newtonian. The ventricle wall is thin and is composed of two sets of counter-rotating fibres which behave according to the modified version of Wong's sarcomere model proposed by Montevecchi and Pietrabissa and Pietrabissa et al. (1987, 1991). The full Navier-Stokes equations describing the fluid domain are solved using Galerkin's weighted residual approach in conjunction with finite element approximation (FIDAP). The wall displacement is solved using the multiplane quasi-Newton method proposed by Buzzi Ferraris and Tronconi (1985). The interaction procedure is performed by means of an external macro which compares the flow fields and the wall displacement and appropriately modifies the boundary conditions to reach the simultaneous and congruous convergence of the two problems. The results refer to a simulation of the ventricular ejection with a heart rate of 72 bpm. In this phase the ventricle ejects 61 cm3 (ejection fraction equal to 54 percent) and the ventricular pressure varies from 78 mmHg to 140 mmHg. The IPG show an oscillating behaviour with two major peaks at the beginning (11.09 mmHg) and at the end (4.32 mmHg) of the ejection phase, when the flow rate hardly changes, according to the experimental data. Furthermore the wall displacement, the wall stress and strain, the pressure and velocity fields are calculated and reported.

Blood Flow Velocity↗
PubMed1996

A new pulsatile blood pump for adult cardiopulmonary bypass: design criteria and preliminary fluid dynamic evaluation.

A new pulsatile pumping device for adult cardiopulmonary bypass has been designed. Its main characteristic consists in having a fully disposable pumping head, since polymeric materials have been adopted for the housing as well as for the built-in inlet and outlet valves. Furthermore, the valves show an innovative design, as they are ring-shaped and accomplish their task by virtue of their elastic deformability. The design phase of the pumping head and the first fluid dynamic evaluations have been performed by numerical methods. Particularly, a three-dimensional CAD model of the pumping head (in the current configuration) is presented in this paper. On the basis of this model, computational fluid dynamic analysis of the hydraulic behaviour has been performed for some components. The obtained results show complex velocity patterns in the pumping chamber during the filling phase as well as limited pressure gradients across the inlet valve.

Biocompatible Materials↗
PubMed1995

Repair of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-induced damage by mammalian cell extracts.

The repair of damage induced by the alkylating antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated using an in vitro excision repair system. Hamster cell extracts prepared from the parental CHO-9 cell line and the ERCC1 mutant 43-3B were both proficient in the repair of CCNU-induced damage. The in vitro repair of CCNU damage was faster than the repair of UV damage and plasmid substrates were rapidly and efficiently incised after incubation with either CHO-9 or 43-3B extracts. 7-Methylguanine (7-meG) and 3-methyladenine (3-meA) glycosylases were active to a similar extent in the CHO-9 and 43-3B extracts. The data indicate that most damage induced by CCNU is repaired via the ERCC1-independent base excision repair pathway, initiating with removal of chloroethylated and hydroxyethylated bases by N-glycosylases. Yet, the sensitive phenotype of 43-3B cells suggests that the ERCC1 gene product is required for the removal of a small subset of CCNU-induced lesions that are important for drug cytotoxicity.

Animals↗
PubMed1995

Preliminary design and optimization of an ECC blood pump by means of a parametric approach.

This study concerns the development of an analytical parametric model of a centrifugal disk pump. The advantage of this kind of approach is to have an adaptable tool as a first step for the design of a pump device. The method allows the evaluation of the velocity profiles and the shear stresses within the impeller disks in the flow domain along with the performance of the device in terms of torque, mechanical power, power loss, head-flow performance, pump efficiency, and hemolytic index. Some simplifying hypotheses are assumed: steady state condition, laminar flow, Newtonian and incompressible fluid. The radial velocity profiles are assumed to be uniform and the flow cross-sectional area is assumed to be constant along the radius. The influence of the housing and secondary flows caused by recirculation are neglected. To test the approach reliability, the model was used to simulate a pump with the following characteristics: an external and internal radius of 50 mm and 5 mm, respectively, and a channel height of 2.5-0.25 mm (h) from inlet to outlet section. The angular velocity omega was varied in the range 500-3,000 rpm. The flow rate has been varied from 1 to 5 L/min. The results show that when the flow rate is increased, head performances obtained using this pump model vary from 411 to 100 mm Hg, and its efficiency varies from 48 to 15%. A parallel simulation has been carried out by means of a Finite Element Method model with an angular velocity equal to 2,000 rpm.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗