Biomedical subjects
Publications and source records attributed to G Ferrari.
We studied POLG1 in 140 UK patients with idiopathic Parkinson disease (PD) and 279 Italian patients with PD and compared them to a UK control group (n = 207) and an Italian control group (n = 285). Our observations do not support a role for common POLG1 genetic variants in PD and indicate that dominant POLG1 mutations are a rare cause of parkinsonism in the general population.
We report on the observation of Bloch oscillations on the unprecedented time scale of several seconds. The experiment is carried out with ultracold bosonic 88Sr atoms loaded into a vertical optical standing wave. The negligible atom-atom elastic cross section and zero angular momentum in the ground state makes 88Sr an almost ideal Bose gas, insensitive to typical mechanisms of decoherence due to thermalization and external stray fields. The small size of the system enables precision measurements of forces at micrometer scale. This is a challenge in physics for studies of surfaces, Casimir effects, and searches for deviations from Newtonian gravity predicted by theories beyond the standard model.
We present a new laser setup designed for high-precision spectroscopy on laser cooled atomic strontium. The system, which is entirely based on semiconductor laser sources, delivers 200 mW at 461 nm for cooling and trapping atomic strontium from a thermal source, 4 mW at 497 nm for optical pumping from the metastable P23 state, 12 mW at 689 nm on linewidth less than 1 kHz for second-stage cooling of the atomic sample down to the recoil limit, 1.2 W at 922 nm for optical trapping close to the "magic wavelength" for the 0-1 intercombination line at 689 nm. The 689 nm laser was already employed to perform a frequency measurement of the 0-1 intercombination line with a relative accuracy of 2.3 x 10(-11), and the ensemble of laser sources allowed the loading in a conservative dipole trap of multi-isotopes strontium mixtures. The simple and compact setup developed represents one of the first steps towards the realization of a transportable optical standards referenced to atomic strontium.
The POLG1 nuclear gene, encoding for the catalytic subunit of the mitochondrial polymerase gamma, has been reported to play a role in male infertility. In fact, genotypes showing alleles different from the common ten repeat CAG allele have been detected in patients with oligozoospermia or in patients with normal spermiograms and unexplained infertility. However, these results have been debated by other studies. To verify these data, we analyzed 625 individuals in three groups of case-controls from three different Italian regions. In these series, the frequency of the different genotypes was not statistically different in oligozoospermic vs normal subjects. Even considering the pooled controls and patients (348 and 277, respectively), no significant difference was shown (p = 0.11). Our findings, in agreement with other studies from Italy and France, suggest that, at least in these countries, the POLG1 CAG-repeat polymorphisms do not contribute to oligozoospermia.
Thymolipoma, a rare benign neoplasm of the anterior mediastinum, is often asymptomatic and as a result it can become quite large before it is diagnosed. CT is the most accurate diagnostic technique to identify the adipose tissue, but it often cannot make a differential diagnosis differentiating it from other anterior mediastinal masses; transthoracic biopsy also reveals the presence of fatty tissue, but a definitive diagnosis can only be achieved by means of surgical excision, which is also curative. We describe the case of a young woman who presented with a fatty neoplasm of the anterior mediastinum. The mass was removed using single-stage bilateral sequential videothoracoscopy. The histopathological diagnosis was thymolipoma.
A vaccine consisting of DNA priming followed by recombinant modified vaccinia Ankara (rMVA) boosting has achieved long-term control of a pathogenic challenge with a chimera of simian and human immunodeficiency viruses (SHIV-89.6P) in rhesus macaques. Based on these results, clade B HIV-1 DNA and rMVA immunogens have been developed for trials in humans. We conducted a first-time in humans phase I safety trial using the pGA2/JS2 (JS2) HIV-1 DNA priming vector expressing Gag, Pol, Env, Tat, Rev, and Vpu. Thirty HIV-uninfected adults were vaccinated with 0.3 or 3 mg of JS2 DNA, or a saline placebo, by intramuscular injection at months 0 and 2. Both doses of DNA were safe and well-tolerated with no differences between the control, 0.3 mg, or 3 mg groups (n = 6, 12, and 12, respectively) through 12 months of postvaccination follow- up. A chromium-release assay using fresh peripheral blood mononuclear cells (PBMCs) and a validated IFN-gamma ELISpot assay with frozen PBMCs failed to detect CD4(+) or CD8(+) HIV-1-specific T cell responses. HIV-specific neutralizing antibodies were also not detected. The vaccine is being further developed as a priming vector for a combined DNA plus rMVA prime/boost HIV vaccination regimen.
AIM: Coronary artery bypass graft (CABG) surgery, nowadays, is increasingly performed in patients who are older and have more comorbidities than subjects operated on a decade ago. In this study, we investigated metabolic and hemodynamic features of elderly patients with single vessel coronary artery disease (CAD), undergoing beating heart coronary artery bypass graft (BHCABG) surgery. METHODS: Twenty-five elderly patients, ages 73-78 years, with isolated left anterior descending artery (LAD) disease, were enrolled and compared to a younger similar group of 25 patients, mean age 48+/-1.2 years. A single vessel left internal mammary artery (LIMA) to LAD BHCABG was performed in all patients. Duration of temporary LAD occlusion was 9.8+/-0.5 min in the elderly group, and 10+/-0.4 min in the younger group. Myocardial arterial-venous differences in glucose, lactate, and creatine phosphokinase (CPK) were performed at different time points: preoperatively in the operating room (T0); at the end of the grafting procedure (T1); and before closing the chest (T2). Left ventricular stroke work index (LVSWI), as an indicator of global function of left ventricle, were recorded at T0, T1, T2, 6 (T3) and 48 (T4) hours postoperatively. RESULTS: Preoperative glucose extraction, observed in both groups, did not augment during and after surgery. In addition, neither lactate nor CPK were released in the coronary sinus during temporary LAD occlusion and following reperfusion in either group. Similarly, no significant changes in LVSWI were observed intra- and perioperatively between the two groups. CONCLUSIONS: Cardiac metabolism, hemodynamic parameters and global left ventricular function were not affected in either group by brief LAD occlusion during BHCABG, suggesting that BHCABG is a well-tolerated surgical approach, which can be safely attempted in patients of any age.
OBJECTIVES: Aim of this work is to study the impact of left ventricular rotary blood pump assistance, on energetic variables, when mechanical ventilation (MV) of the lungs is applied. METHODS: Computer simulation was used to perform this study. Lumped parameter models reproduce the circulatory system. Variable elastance models reproduce the Starling's law of the heart for each ventricle. After the reproduction of ischemic heart disease left ventricular assistance was applied using a model of rotary blood pump. The pump speed was changed in steps and was assumed to be constant during each step. The influence of mechanical ventilation was introduced by different values of positive mean thoracic pressure. RESULTS: The increase of the rotational speed has a significant influence on some ventricular energetic variables. In fact it decreased left ventricular external work, left and right ventricular pressure-volume area and the left ventricular efficiency. Finally, it increased the right ventricular efficiency but had no influence on the right ventricular external work. The increase of thoracic pressure from -2 to +5 mmHg caused a significant decrease of external work, pressure-volume area (right ventricular pressure-volume area dropped up to 50%) and an increase of right ventricular efficiency (by 40%) while left ventricular efficiency remained almost stable. CONCLUSIONS: Numerical simulation is a very suitable tool to predict changes of not easily measurable parameters such as energetic ventricular variables when mechanical assistance of heart and/or lungs is applied independently or simultaneously.
The aim of this work is to evaluate in different ventricular conditions the influence of joint mechanical ventilation (MV) and Hemopump assistance. To perform this study, we used a computer simulator of human cardiovascular system where the influence of MV was introduced changing thoracic pressure to positive values. The simulation confirmed that haemodynamic variables are highly sensitive to thoracic pressure changes. On the other hand, Hemopump assistance raises, among the others, mean aortic pressure, total cardiac output (left ventricular output flow plus Hemopump flow) and coronary flow. The simulation showed that the joint action of Hemopump and positive thoracic pressure diminishes these effects.
OBJECTIVE: To investigate three families and one sporadic case with a recessively inherited ataxic syndrome. METHODS: Clinical and genetic studies were performed in six individuals. Southern blotting and real time PCR were used to detect deletions of mtDNA and mutations in the POLG gene were identified using a combination of DHPLC and direct DNA sequencing. RESULTS: The patients have a distinctive, progressive disorder that starts with episodic symptoms such as migraine-like headache or epilepsy. Ataxia, which is a combination of central and peripheral disease, develops later as does ophthalmoplegia. The commonest form of epilepsy was focal and involved the occipital lobes. Myoclonus was common and patients have a high risk of status epilepticus. MRI typically shows signal changes in the central cerebellum, olivary nuclei, occipital cortex, and thalami. COX negative muscle fibers were found in four of six; in one patient these were rare and in another absent. Multiple mtDNA deletions were identified in all patients, although in two these were not apparent on Southern blotting and real time PCR was required to demonstrate the defect. Two families were homozygous for a previously described POLG mutation, G1399A (A467T). One family and the sporadic case had the same two new mutations, a G to C at position 1491 (Q497H) and a G to C at 2243 (W748S). CONCLUSIONS: Mutations in POLG cause a recessively inherited syndrome with episodic features and progressive ataxia. Characteristic changes on MRI are seen and although skeletal muscle may appear morphologically normal, multiple mtDNA deletions can be detected using real-time PCR.
In 2001 and 2002, 235 outbreaks of bluetongue were observed in the Lazio and Tuscany regions of central Italy. During entomological surveillance Culicoides imicola, the main vector of bluetongue virus in the Mediterranean region, was detected in only 14 of 28 municipalities affected by outbreaks; Culicoides obsoletus was the most abundant species, contributing 83 per cent of individuals in catches, whereas C. imicola contributed only 2 per cent. In affected municipalities the maximum catch of C. obsoletus was 18,000 specimens, compared with 54 of C. imicola. In October 2002 bluetongue virus serotype 2 was isolated from a single pool of wild-caught, non-blood-engorged parous C. obsoletus inoculated on to BHK-21 cells. Its identity was confirmed by reverse transcriptase-PCR.
Several seroconversions occurring in 2002 among sentinel cattle during the bluetongue-vaccination campaign in Lazio and Tuscany (central Italy) led to the suspicion of vaccine-virus circulation. Therefore in 2003, 17 seroconverting sentinel herds were investigated for the characteristics of the virus involved. From these farms, 91 unvaccinated animals and 57 Culicoides pools were tested for the presence of the bluetongue vaccine virus (serotype-2) or other strains. The presence of vaccine virus serotype-2 was confirmed by PCR followed by restriction analysis in the whole blood of 17 unvaccinated sentinel cattle and 12 pools of Culicoides imicola or C. obsoletus. Of the 17 herds, five were positive only for vaccine virus serotype-2, four were positive for other strains and two for both the vaccine and other strains; the remaining premises were virologicaly negative. The vaccine virus serotype-2 also was detected in areas not included in the vaccination campaign.
This observational prospective multicentre study aims to describe a hospital-based database collecting information about clinical features, management and follow-up of stroke patients. In 18 neurological departments (mostly first-referral) in Piedmont and the Aosta Valley, Italy, between May and July 1999, 604 consecutive patients (97 TIA, 443 ischaemic, and 64 haemorrhagic stroke) were studied. Ischaemic stroke aetiologies were as follows: large-artery atherosclerosis (148), small-artery occlusion (133), cardioembolism (76), other causes (13) and undetermined (73). According to Bamford's classification, 164 were PACI, 126 LACI, 87 TACI and 66 POCI. The diagnostic workup and management of patients is described; only 4% of patients did not receive a CT scan. Four hundred and three patients were discharged to their home, 78 to a rehabilitation unit, 44 to long-term institutional care, 20 to other wards and 59 died while in hospital. After six months, 10 patients were lost to follow-up, 499 were alive and 95 had died. The SINPAC database allows for evaluation of current practice of care in a first-referral stroke population.
Merging numerical and physical models of the circulation makes it possible to develop a new class of circulatory models defined as hybrid. This solution reduces the costs, enhances the flexibility and opens the way to many applications ranging from research to education and heart assist devices testing. In the prototype described in this paper, a hydraulic model of systemic arterial tree is connected to a lumped parameters numerical model including pulmonary circulation and the remaining parts of systemic circulation. The hydraulic model consists of a characteristic resistance, of a silicon rubber tube to allow the insertion of an Intra-Aortic Balloon Pump (IABP) and of a lumped parameters compliance. Two electro-hydraulic interfaces, realized by means of gear pumps driven by DC motors, connect the numerical section with both terminals of the hydraulic section. The lumped parameters numerical model and the control system (including analog to digital and digital to analog converters)are developed in LabVIEW environment. The behavior of the model is analyzed by means of the ventricular pressure-volume loops and the time courses of arterial and ventricular pressures and flows in different circulatory conditions. A simulated pathological condition was set to test the IABP and verify the response of the system to this type of mechanical circulatory assistance. The results show that the model can represent hemodynamic relationships in different ventricular and circulatory conditions and is able to react to the IABP assistance.
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OBJECTIVES: The analysis of energetic ventricular variable changes during artificial ventilation, obtained by numerical simulation was done. Twenty-one sets of hemodynamic parameters for eight cardiosurgical patients were used to estimate left and right stroke work. The data were collected for three methods of ventilation: conventional, lung-protective (with minute ventilation diminished by half) and high frequency ventilation (with frequency 5, 10, or 15 Hz). METHODS: The computer simulator (CARDIOSIM) of the cardiovascular system, was used as a tool to calculate values of energetic ventricular variables for conditions that corresponded to these during in vivo measurements. Different methods of ventilation caused differences of intrathoracic pressure, haemodynamic and finally energetic ventricular variables. The trends of these variable changes were the same in in vivo and simulation studies, in the whole range of intrathoracic pressure changes (Pt = 1.5-3.5 mmHg). RESULTS: As values of main hemodynamic variables like cardiac output or arterial, systemic and pulmonary pressures were very close in both studies. Cardiac index and left ventricular stroke work also differed less than 10% for all examined patients and computer simulation. In a case of right ventricular stroke work the difference between in vivo data and simulation was a bit greater than 10% for two of eight patients under study. CONCLUSIONS: Our comparative analysis proved that numerical simulation is a very useful tool to predict changes of main hemodynamic and energy-related ventricular variables caused by different levels of positive Pt. It means that it can help an anesthesiologist to choose an appropriate method of artificial ventilation for cardiosurgical patients.
We report on direct experimental evidence of shot noise in a linear macroscopic resistor. The origin of the shot noise comes from the fluctuation of the total number of charge carriers inside the resistor associated with their diffusive motion under the condition that the dielectric relaxation time becomes longer than the dynamic transit time. The present results show that neither potential barriers nor the absence of inelastic scattering are necessary to observe shot noise in electronic devices.
E(max) is an important parameter to evaluate the state of the heart and of its contractile capability. Its determination is not easy and rather inaccurate: However, it can be clinically relevant during mechanical and/or pharmacological heart assistance as it can suggest how to modify pharmacological therapy or the control strategy of the device. Aim of this study is to develop a method based on ventricular energetics to evaluate E(max). If arterial elastance line slope is modified, for example by a slight peripheral resistance increase, E(max) (assuming that it is constant) can be evaluated computing the energy transferred to the arterial elastance before and after the change. The corresponding equation contains known or easily computable variables and the difference delta between end diastolic volume and ventricular rest volume. If the ratio of deltas before and after the disturbance is near to 1, the equation returns a fair estimation of E(max). The method was tested in vitro, in different circulatory conditions, using an open loop numerical model of the circulation built out of a variable elastance model of the ventricle connected to a modified windkessel representing the systemic arterial tree. The results obtained in in vitro experiments suggest clinically testing this method.