Longterm peripheral baroreflex and chemoreflex function after bilateral eversion carotid endarterectomy

Introduction The “eversion” technique for carotid endarterectomy (e-CEA), that involves the transection of the internal carotid artery at the carotid bulb and its eversion over the atherosclerotic plaque, has been associated with an increased risk of postoperative hypertension possibly due to a direct iatrogenic damage to the carotid sinus fibers. The aim of this study is to assess the long-term effect of the e-CEA on arterial baroreflex and peripheral chemoreflex function in humans. Methods A retrospective review was conducted on a prospectively compiled computerized database of 3128 CEAs performed on 2617 patients at our Center between January 2001 and March 2006. During this period, a total of 292 patients who had bilateral carotid stenosis ≥70% at the time of the first admission underwent staged bilateral CEAs. Of these, 93 patients had staged bilateral e-CEAs, 126 staged bilateral s- CEAs and 73 had different procedures on each carotid. CEAs were performed with either the eversion or the standard technique with routine Dacron patching in all cases. The study inclusion criteria were bilateral CEA with the same technique on both sides and an uneventful postoperative course after both procedures. We decided to enroll patients submitted to bilateral e-CEA to eliminate the background noise from contralateral carotid sinus fibers. Exclusion criteria were: age >70 years, diabetes mellitus, chronic pulmonary disease, symptomatic ischemic cardiac disease or medical therapy with b-blockers, cardiac arrhythmia, permanent neurologic deficits or an abnormal preoperative cerebral CT scan, carotid restenosis and previous neck or chest surgery or irradiation. Young and aged-matched healthy subjects were also recruited as controls. Patients were assessed by the 4 standard cardiovascular reflex tests, including Lying-to-standing, Orthostatic hypotension, Deep breathing, and Valsalva Maneuver. Indirect autonomic parameters were assessed with a non-invasive approach based on spectral analysis of EKG RR interval, systolic arterial pressure, and respiration variability, performed with an ad hoc software. From the analysis of these parameters the software provides the estimates of spontaneous baroreflex sensitivity (BRS). The ventilatory response to hypoxia was assessed in patients and controls by means of classic rebreathing tests. Results A total of 29 patients (16 males, age 62.4±8.0 years) were enrolled. Overall, 13 patients had undergone bilateral e-CEA (44.8%) and 16 bilateral s-CEA (55.2%) with a mean interval between the procedures of 62±56 days. No patient showed signs or symptoms of autonomic dysfunction, including labile hypertension, tachycardia, palpitations, headache, inappropriate diaphoresis, pallor or flushing. The results of standard cardiovascular autonomic tests showed no evidence of autonomic dysfunction in any of the enrolled patients. At spectral analysis, a residual baroreflex performance was shown in both patient groups, though reduced, as expected, compared to young controls. Notably, baroreflex function was better maintained in e-CEA, compared to standard CEA. (BRS at rest: young controls 19.93 ± 2.45 msec/mmHg; age-matched controls 7.75 ± 1.24; e-CEA 13.85 ± 5.14; s-CEA 4.93 ± 1.15; ANOVA P=0.001; BRS at stand: young controls 7.83 ± 0.66; age-matched controls 3.71 ± 0.35; e-CEA 7.04 ± 1.99; s-CEA 3.57 ± 1.20; ANOVA P=0.001). In all subjects ventilation (VÝ E) and oximetry data fitted a linear regression model with r values > 0.8. Oneway analysis of variance showed a significantly higher slope both for ΔVE/ΔSaO2 in controls compared with both patient groups which were not different from each other (-1.37 ± 0.33 compared with -0.33±0.08 and -0.29 ±0.13 l/min/%SaO2, p<0.05, Fig.). Similar results were observed for and ΔVE/ΔPetO2 (-0.20 ± 0.1 versus -0.01 ± 0.0 and -0.07 ± 0.02 l/min/mmHg, p<0.05). A regression model using treatment, age, baseline FiCO2 and minimum SaO2 achieved showed only treatment as a significant factor in explaining the variance in minute ventilation (R2= 25%). Conclusions Overall, we demonstrated that bilateral e-CEA does not imply a carotid sinus denervation. As a result of some expected degree of iatrogenic damage, such performance was lower than that of controls. Interestingly though, baroreflex performance appeared better maintained in e-CEA than in s-CEA. This may be related to the changes in the elastic properties of the carotid sinus vascular wall, as the patch is more rigid than the endarterectomized carotid wall that remains in the e-CEA. These data confirmed the safety of CEA irrespective of the surgical technique and have relevant clinical implication in the assessment of the frequent hemodynamic disturbances associated with carotid angioplasty stenting.

Ricerca, mediante tecniche di proteomica, di biomarcatori proteici utili nella valutazione della qualità degli alimenti di origine animale

In the last decades, the increase of industrial activities and of the request for the world food requirement, the intensification of natural resources exploitation, directly connected to pollution, have aroused an increasing interest of the public opinion towards initiatives linked to the regulation of food production, as well to the institution of a modern legislation for the consumer guardianship. This work was planned taking into account some important thematics related to marine environment, collecting and showing the data obtained from the studies made on different marine species of commercial interest (Chamelea gallina, Mytilus edulis, Ostrea edulis, Crassostrea gigas, Salmo salar, Gadus morhua). These studies have evaluated the effects of important physic and chemical parameters variations (temperature, xenobiotics like drugs, hydrocarbons and pesticides) on cells involved in the immune defence (haemocytes) and on some important enzymatic systems involved in xenobiotic biotransformation processes (cytochrome P450 complex) and in the related antioxidant defence processes (Superoxide dismutase, Catalase, Heat Shock Protein), from a biochemical and bimolecular point of view. Oxygen is essential in the biological answer of a living organism. Its consume in the normal cellular breathing physiological processes and foreign substances biotransformation, leads to reactive oxygen species (ROS) formation, potentially toxic and responsible of biological macromolecules damages with consequent pathologies worsening. Such processes can bring to a qualitative alteration of the derived products, but also to a general state of suffering that in the most serious cases can provoke the death of the organism, with important repercussions in economic field, in the output of the breedings, of fishing and of aquaculture. In this study it seemed interesting to apply also alternative methodologies currently in use in the medical field (cytofluorimetry) and in proteomic studies (bidimensional electrophoresis, mass spectrometry) with the aim of identify new biomarkers to place beside the traditional methods for the control of the animal origin food quality. From the results it’s possible to point out some relevant aspects from each experiment: 1. The cytofluorimetric techniques applied to O. edulis and C. gigas could bring to important developments in the search of alternative methods that quickly allows to identify with precision the origin of a specific sample, contributing to oppose possible alimentary frauds, in this case for example related to presence of a different species, also under a qualitative profile, but morpholgically similar. A concrete perspective for the application in the inspective field of this method has to be confirmed by further laboratory tests that take also in account in vivo experiments to evaluate the effect in the whole organism of the factors evaluated only on haemocytes in vitro. These elements suggest therefore the possibility to suit the cytofluorimetric methods for the study of animal organisms of food interest, still before these enter the phase of industrial working processes, giving useful information about the possible presence of contaminants sources that can induce an increase of the immune defence and an alteration of normal cellular parameter values. 2. C. gallina immune system has shown an interesting answer to benzo[a]pyrene (B[a]P) exposure, dose and time dependent, with a significant decrease of the expression and of the activity of one of the most important enzymes involved in the antioxidant defence in haemocytes and haemolymph. The data obtained are confirmed by several measurements of physiological parameters, that together with the decrease of the activity of 7-etossi-resourifine-O-deetilase (EROD linked to xenobiotic biotransformation processes) during exposure, underline the major effects of B[a]P action. The identification of basal levels of EROD supports the possible presence of CYP1A subfamily in the invertebrates, still today controversial, never identified previously in C. gallina and never isolated in the immune cells, as confirmed instead in this study with the identification of CYP1A-immunopositive protein (CYP1A-IPP). This protein could reveal a good biomarker at the base of a simple and quick method that could give clear information about specific pollutants presence, even at low concentrations in the environment where usually these organisms are fished before being commercialized. 3. In this experiment it has been evaluated the effect of the antibiotic chloramphenicol (CA) in an important species of commercial interest, Chamelea gallina. Chloramphenicol is a drug still used in some developing countries, also in veterinary field. Controls to evaluate its presence in the alimentary products of animal origin, can reveal ineffective whereas the concentration results to be below the limit of sensitivity of the instruments usually used in this type of analysis. Negative effects of CA towards the CYP1A- IPP proteins, underlined in this work, seem to be due to the attack of free radicals resultant from the action of the antibiotic. This brings to a meaningful alteration of the biotransformation mechanisms through the free radicals. It seems particularly interesting to pay attention to the narrow relationships in C. gallina, between SOD/CAT and CYP450 system, actively involved in detoxification mechanism, especially if compared with the few similar works today present about mollusc, a group that is composed by numerous species that enter in the food field and on which constant controls are necessary to evaluate in a rapid and effective way the presence of possible contaminations. 4. The investigations on fishes (Gadus morhua, and Salmo salar) and on a bivalve mollusc (Mytilus edulis) have allowed to evaluate different aspects related to the possibility to identify a biomarker for the evaluation of the health of organisms of food interest and consequently for the quality of the final product through 2DE methodologies. In the seafood field these techniques are currently used with a discreet success only for vertebrates (fishes), while in the study of the invertebrates (molluscs) there are a lot of difficulties. The results obtained in this work have underline several problems in the correct identification of the isolated proteins in animal organisms of which doesn’t currently exist a complete genomic sequence. This brings to attribute some identities on the base of the comparison with similar proteins in other animal groups, incurring in the possibility to obtain inaccurate data and above all discordant with those obtained on the same animals by other authors. Nevertheless the data obtained in this work after MALDI-ToF analysis, result however objective and the spectra collected could be again analyzed in the future after the update of genomic database related to the species studied. 4-A. The investigation about the presence of HSP70 isoforms directly induced by different phenomena of stress like B[a]P presence, has used bidimensional electrophoresis methods in C. gallina, that have allowed to isolate numerous protein on 2DE gels, allowing the collection of several spots currently in phase of analysis with MALDI-ToF-MS. The present preliminary work has allowed therefore to acquire and to improve important methodologies in the study of cellular parameters and in the proteomic field, that is not only revealed of great potentiality in the application in medical and veterinary field, but also in the field of the inspection of the foods with connections to the toxicology and the environmental pollution. Such study contributes therefore to the search of rapid and new methodologies, that can increase the inspective strategies, integrating themselves with those existing, but improving at the same time the general background of information related to the state of health of the considered animal organism, with the possibility, still hypothetical, to replace in particular cases the employment of the traditional techniques in the alimentary field.

Apnea e reflusso gastroesofageo nel neonato pretermine

Objective: To document the existence of a relationship between apnea of prematurity (AOP) and gastroesophageal reflux (GER) in preterm infants. Setting: One Neonatal Intensive Care Unit Patients: Twenty-six preterm infants (gestational age<32 weeks) with recurrent apneas. Intervention: Simultaneous and synchronized recording of polysomnography and pH-impedance monitoring (pH-MII). Polysomnography detects and characterizes apneas, by recording of breathing movement, nasal airflow, electrocardiogram, pulse oximeter saturation. pH-MII is the state-of-theart methodology for GER detection in preterm newborns. Main outcome measures: Relationship between AOP and GER, which were considered temporally related if both started within 30 seconds of each other. Results: One-hundred-fifty-four apneas out of 1136 were temporally related to GER. The frequency of apnea during the one-minute time around the onset of GER was significantly higher than the one detected in the GER-free period (p=0.03). Furthermore, the frequency of apnea in the 30 seconds after GER (GER-triggered apneas) was greater than that detected in the 30 seconds before (p=0.01). A great inter-individual variability was documented in the proportion of GERtriggered apneas. A strong correlation between total number of apneas and the difference between apneas detected 30 seconds after and before GER was found (p=0.034). Conclusions: Our data show that a variable rate of apneas can be triggered by GER in very preterm infant. Further studies are needed to recognise clinical features which identify those patients who are more susceptible to GER-triggered apneas.

Algorithms for UAS insertion in civil air space

One of the most interesting challenge of the next years will be the Air Space Systems automation. This process will involve different aspects as the Air Traffic Management, the Aircrafts and Airport Operations and the Guidance and Navigation Systems. The use of UAS (Uninhabited Aerial System) for civil mission will be one of the most important steps in this automation process. In civil air space, Air Traffic Controllers (ATC) manage the air traffic ensuring that a minimum separation between the controlled aircrafts is always provided. For this purpose ATCs use several operative avoidance techniques like holding patterns or rerouting. The use of UAS in these context will require the definition of strategies for a common management of piloted and piloted air traffic that allow the UAS to self separate. As a first employment in civil air space we consider a UAS surveillance mission that consists in departing from a ground base, taking pictures over a set of mission targets and coming back to the same ground base. During all mission a set of piloted aircrafts fly in the same airspace and thus the UAS has to self separate using the ATC avoidance as anticipated. We consider two objective, the first consists in the minimization of the air traffic impact over the mission, the second consists in the minimization of the impact of the mission over the air traffic. A particular version of the well known Travelling Salesman Problem (TSP) called Time-Dependant-TSP has been studied to deal with traffic problems in big urban areas. Its basic idea consists in a cost of the route between two clients depending on the period of the day in which it is crossed. Our thesis supports that such idea can be applied to the air traffic too using a convenient time horizon compatible with aircrafts operations. The cost of a UAS sub-route will depend on the air traffic that it will meet starting such route in a specific moment and consequently on the avoidance maneuver that it will use to avoid that conflict. The conflict avoidance is a topic that has been hardly developed in past years using different approaches. In this thesis we purpose a new approach based on the use of ATC operative techniques that makes it possible both to model the UAS problem using a TDTSP framework both to use an Air Traffic Management perspective. Starting from this kind of mission, the problem of the UAS insertion in civil air space is formalized as the UAS Routing Problem (URP). For this reason we introduce a new structure called Conflict Graph that makes it possible to model the avoidance maneuvers and to define the arc cost function of the departing time. Two Integer Linear Programming formulations of the problem are proposed. The first is based on a TDTSP formulation that, unfortunately, is weaker then the TSP formulation. Thus a new formulation based on a TSP variation that uses specific penalty to model the holdings is proposed. Different algorithms are presented: exact algorithms, simple heuristics used as Upper Bounds on the number of time steps used, and metaheuristic algorithms as Genetic Algorithm and Simulated Annealing. Finally an air traffic scenario has been simulated using real air traffic data in order to test our algorithms. Graphic Tools have been used to represent the Milano Linate air space and its air traffic during different days. Such data have been provided by ENAV S.p.A (Italian Agency for Air Navigation Services).

Dynamic analysis of the motorcycle chattering behaviour by means of symbolic multibody modelling

Aim of this research is the development and validation of a comprehensive multibody motorcycle model featuring rigid-ring tires, taking into account both slope and roughness of road surfaces. A novel parametrization for the general kinematics of the motorcycle is proposed, using a mixed reference-point and relative-coordinates approach. The resulting description, developed in terms of dependent coordinates, makes it possible to efficiently include rigid-ring kinematics as well as road elevation and slope. The equations of motion for the multibody system are derived symbolically and the constraint equations arising from the dependent-coordinate formulation are handled using a projection technique. Therefore the resulting system of equations can be integrated in time domain using a standard ODE algorithm. The model is validated with respect to maneuvers experimentally measured on the race track, showing consistent results and excellent computational efficiency. More in detail, it is also capable of reproducing the chatter vibration of racing motorcycles. The chatter phenomenon, appearing during high speed cornering maneuvers, consists of a self-excited vertical oscillation of both the front and rear unsprung masses in the range of frequency between 17 and 22 Hz. A critical maneuver is numerically simulated, and a self-excited vibration appears, consistent with the experimentally measured chatter vibration. Finally, the driving mechanism for the self-excitation is highlighted and a physical interpretation is proposed.

Dynamics and control issues of multi-rotor platforms

This thesis deals with the analytic study of dynamics of Multi--Rotor Unmanned Aerial Vehicles. It is conceived to give a set of mathematical instruments apt to the theoretical study and design of these flying machines. The entire work is organized in analogy with classical academic texts about airplane flight dynamics. First, the non--linear equations of motion are defined and all the external actions are modeled, with particular attention to rotors aerodynamics. All the equations are provided in a form, and with personal expedients, to be directly exploitable in a simulation environment. This has requited an answer to questions like the trim of such mathematical systems. All the treatment is developed aiming at the description of different multi--rotor configurations. Then, the linearized equations of motion are derived. The computation of the stability and control derivatives of the linear model is carried out. The study of static and dynamic stability characteristics is, thus, addressed, showing the influence of the various geometric and aerodynamic parameters of the machine and in particular of the rotors. All the theoretic results are finally utilized in two interesting cases. One concerns the design of control systems for attitude stabilization. The linear model permits the tuning of linear controllers gains and the non--linear model allows the numerical testing. The other case is the study of the performances of an innovative configuration of quad--rotor aircraft. With the non--linear model the feasibility of maneuvers impossible for a traditional quad--rotor is assessed. The linear model is applied to the controllability analysis of such an aircraft in case of actuator block.