Biomedical subjects

A Redaelli

Publications and source records attributed to A Redaelli.

At least 19 recordsLinked to original sources

PubMed2001

Myosin cross-bridge mechanics: geometrical determinants for continuous sliding.

Advances in experimental techniques have provided new details on the molecular mechanisms governing the cross-bridge kinetics. Nevertheless, the issue of micromechanics of sliding is still debated. In particular, uncertainty exists regarding the myosin filament arrangement and structure and the mechanics of the myosin head with respect to the working stroke distance (WS) and the duty ratio (r), i.e. the fraction of the ATPase cycle time the myosin head is attached to the actin filament. The object of the present work is to provide a theoretical framework to correlate different features of cross-bridge mechanics; the main hypothesis is that the attachment between the actin filament and the surrounding myosin filaments has to be continuous through the sliding (continuous sliding hypothesis) in order to maximise the effect of the myosin head performance. A 3-D model of the sliding mechanism based on a geometrical approach is presented, which is able to identify the architectures that accomplish the continuous sliding under unloaded conditions. About 200 different configurations have been simulated by changing the myosin head binding range, i.e. its ability to reach an actin binding site from its rest position, WS, the myosin head orientation and the actin filament orientation. Only few configurations were consistent with the continuous sliding hypothesis. Depending on the parameter set adopted, the percentage of attached heads (%AH) calculated ranges between 4% and 28%, r between 0.08 and 0.02s(-1), and the sliding velocity between 0.7 and 10.6 microm/s. In all the cases, results were not affected by the WS value.

Actins↗

PubMed2001

Fluid-structure interaction within realistic three-dimensional models of the aneurysmatic aorta as a guidance to assess the risk of rupture of the aneurysm.

Abdominal aortic aneurysm (AAA) disease is a degenerating process whose ultimate event is the rupture of the vessel wall. Rupture occurs when the stresses acting on the wall rise above the strength of the AAA wall tissue. The complex mechanical interaction between blood flow and wall dynamics in a three dimensional custom model of a patient AAA was studied by means of computational coupled fluid-structure interaction analysis. Real 3D AAA geometry is obtained from CT scans image processing. The results provide a quantitative local evaluation of the stresses due to local structural and fluid dynamic conditions. The method accounts for the complex geometry of the aneurysm, the presence of a thrombus and the interaction between solid and fluid. A proven clinical efficacy may promote the method as a tool to determine factual aneurysm risk of rupture and aid the surgeon to refer elective surgery patients.

Aorta, Abdominal↗

PubMed2001

Patterns of regional sympathetic nerve traffic in preascitic and ascitic cirrhosis.

Overactivity of the sympathetic nervous system and portal hypertension are key factors in the development of ascites in cirrhosis. The sympathoexcitation that characterizes the more advanced stages of liver diseases is less clearly defined in preascitic cirrhosis. We measured sympathetic nerve traffic to skeletal muscle (peroneal nerve) and to skin districts by microneurography in (1) 12 Child class A cirrhotic patients with clinically significant portal hypertension (portal pressure gradient > 10 mm Hg, 14.8 +/- 1.2 mm Hg, mean +/- SEM) but without actual or previous ascites, (2) 16 Child class C cirrhotic patients with tense ascites, and (3) 10 patients with mild congestive heart failure, a condition paradigmatic of a marked sympathetic activation. Muscle sympathetic nerve traffic was markedly increased in Child class C subjects as compared with controls (23.9 +/- 1.6 bursts/min, P <.01) and superimposable to that recorded in heart failure patients (52.9 +/- 4.7 vs. 60.3 +/- 2 bursts/min, P = not significant). Muscle sympathetic nerve traffic was also increased in Child class A subjects (41.6 +/- 2 bursts/min, P <.01 vs. controls) although to a lesser extent (P <.05 vs. Child class C patients). Skin sympathetic nerve traffic was within the normal range in all patients. Neurohormones were all markedly increased in Child class C subjects. Only norepinephrine was increased in Child class A patients. Our data show that sympathetic nerve traffic activation (1) is already detectable in Child class A cirrhosis when clinically significant portal hypertension is present but ascites never developed and (2) is not generalized because although muscle traffic is increased, skin traffic is within normal range. The role of drugs modulating sympathoactivation should be investigated in preascitic cirrhosis.

Aged↗

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↗

PubMed2001

A computational study of the hemodynamics after "edge-to-edge" mitral valve repair.

Edge-to-edge mitral valve repair consists in suturing the free edge of the leaflets to re-establish coaptation in prolapsing valves. The leaflets are frequently sutured at the middle and a double orifice valve is created. In order to study the hemodynamic implications, a parametric model of the left heart has been developed. Different valve areas and shapes have been investigated. Results show that the simplified Bernoulli formula provides a good estimation of the pressure drop and that the pressure drop may be predicted on the basis of the pre-operative geometric and hemodynamics data by means of customized models.

Blood Flow Velocity↗

PubMed2001

Primary brain tumours: a review of research and management.

The brain is an incredibly complex organ that contains some 10 billion working cells. Brain tumours can arise from the brain itself, the meninges, the nerves at the base of the brain, or even from outside the brain. The frequency of brain tumours directly reflects the relative proportion of each cell type present at the site of the initial tumour. Symptoms produced by a brain tumour often mimic the symptoms of other diseases and vice versa. Because symptoms can develop gradually, and can be subtle, there may well be a long delay between symptom onset and diagnosis. Treatment of brain tumour depends on the type and stage of the disease, and the patient's age and overall state of health. Treatment options fall into three categories: surgery, radiotherapy and chemotherapy. Biological therapy is also being studied in clinical trials. Primary brain tumours occur in all age groups, but are significantly more frequent in children and adolescents under 15 years old and the elderly. For every person diagnosed with a brain tumour (over 100,000 people annually in the US), an average of 22 years of life expectancy is lost. The estimated annual cost, direct and indirect, of the disease in the US is $104 billion.

Adolescent↗

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↗