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Biomedical subjects

G Di Benedetto

Publications and source records attributed to G Di Benedetto.

At least 19 recordsLinked to original sources
PubMed2006

Restricted diffusion of a freely diffusible second messenger: mechanisms underlying compartmentalized cAMP signalling.

It is becoming increasingly evident that the freely diffusible second messenger cAMP can transduce specific responses by localized signalling. The machinery that underpins compartmentalized cAMP signalling is only now becoming appreciated. Adenylate cyclases, the enzymes that synthesize cAMP, are localized at discrete parts of the plasma membrane, and phosphodiesterases, the enzymes that degrade cAMP, can be targeted to selected subcellular compartments. A-kinase-anchoring proteins then serve to anchor PKA (protein kinase A) close to specific targets, resulting in selective activation. The specific activation of such individual subsets of PKA requires that cAMP is made available in discrete compartments. In this presentation, the molecular and structural mechanisms responsible for compartmentalized PKA signalling and restricted diffusion of cAMP will be discussed.

Animals↗
PubMed2005

Imaging the cAMP-dependent signal transduction pathway.

In recent years, the development of new technologies based on the green fluorescent protein and FRET (fluorescence resonance energy transfer) has introduced a new perspective in the study of cAMP signalling. Real-time imaging of fluorescent biosensors is making it possible to visualize cAMP dynamics directly as they happen in intact, living cells, providing important and original insights for our understanding of the spatiotemporal organization of the cAMP/PKA (protein kinase A) signalling pathway.

Animals↗
PubMed2004

Morphological analysis of in vivo velocity field in the alteration of the vasomotor tone.

Vessel wall remodeling is involved in atherogenesis and in several important vascular diseases affecting mainly aged and prosthetic implanted patients. This adaptive response to pathological states in arterial hemodynamics strongly suggests that flow-derived stresses act as mechanical stimuli to the release of endothelium-derived vasoactive factors, leading to vascular alterations. As the correlation of intimal hyperplasia (IH) with blood flow alterations in arteries has been shown to be significant, and as it is well-known that clinical procedures carry a substantial risk of development of vascular disease, the relevance of local hemodynamics must be investigated to describe changes in compliance matching in prosthetic applications. The aim of our research is to investigate the use of principal components analysis, together with varimax rotation, in the individuation process of morphological characteristics of real time ultrasound in in vivo recordings of blood flow velocities, as provided by two different carotid perivascular manipulations. This would be of use in the clinical assessment of atherogenesis, hypertension, prosthetic replacement or more in general in all applications in which vascular tone may be impaired. Data recordings refer to previous animal experiments where the Moncada model was investigated by means of an ultrasound profilometer. The present study confirms the feasibility of the proposed analysis to follow vascular pathology evolution, distiguishing between an in progress and a static situation.

Animals↗
PubMed2002

Computational model of the fluid dynamics of a cannula inserted in a vessel: incidence of the presence of side holes in blood flow.

Vascular access methods, performed by the insertion of cannulae into vessels, may disturb the physiological flow of blood, giving rise to non-physiological pressure variations and shear stresses. To date, the hydrodynamic behaviour of the cannulae has been evaluated comparing their pressure loss-flow rate relationships, as obtained from in vitro experiments using a monodimensional approach; this methodology neither furnish information about the local fluid dynamics nor the established flow field in specific clinical work conditions. Since the shear stress is a critical factor in the design of artificial circulatory devices, more knowledge should be necessary about the local values assumed by the haemodynamic parameters during cannulation. An alternative way to investigate the fluid dynamic as accurately as possible is given by numeric studies. A 3D model of cannula concentrically placed in a rigid wall vessel is presented, with the finite element methodology used to numerically simulate the steady-state flow field in two different venous cannulation case studies, with two cannulae having a central hole and two or four side holes, respectively, with the same boundary conditions. Lower velocity and shear stress peak values have been computed for the model with four side holes upstream of the central hole, in the region of the cannula where the inlet flows meet and towards cannula's outlet, due to the increased flow symmetry and inlet area with respect to the model with two side holes. Starting from the investigation of different cannula designs, numerically assessing the local fluid dynamics, indications can be drawn to support both the design phase and the device optimal clinical use, in order to limit risks of biomechanical origin. Thus the presence of four side holes implied, as a consequence of the greater inlet area and of the increased symmetry, a less disturbed blood flow, together with reduced shear stress values. Furthermore, results show that the numerical simulations furnished useful informations on the interaction between vessel and cannula, e.g. on the fluid dynamics establishing in the free luminal space left, in the vessel, by the inserted cannula.

Blood Flow Velocity↗
PubMed2002

Potential mechanical blood trauma in vascular access devices: a comparison of case studies.

Since vascular access devices may cause disturbances in blood flow, possibly damaging red blood cells (RBCs), the correlated risk of lysis must be assessed. The monodimensional approach for the evaluation of cannulae hydrodynamic behaviour (in vitro measured flow curves) does not furnish information on the local flow field occurring in specific clinical conditions. Researchers consider the prediction of blood trauma, induced by mechanical loading, to optimize the design phase, and to furnish indications on their optimal clinical use. In this study, a model of cannula inserted in a non compliant wall vessel was used as a test bench in a Computational Fluid Dynamics (CFD) problem. By means of CFD the flow field was 3D analysed to achieve information on velocity and shear stress local values, when cannula is used for inflow and outflow cannulation. A prediction of potential blood corpuscle damage, based on a power law, quantified the potential blood damage. Several numerical simulations, with different cannula/vessel flow rate ratios were provided, to investigate the incidence of local sites in the design on blood damaging potential during cannulation. Several regions appeared to be sensitive to the flow rate not only inside the cannula but also in the space between cannula and vessel, suggesting new indications for the assessment of a quality factor based on the evaluation of induced blood cells injury.

Blood Flow Velocity↗
PubMed2001

Genetic characterization of the body attributed to the evangelist Luke.

Historical sources indicate that the evangelist Luke was born in Syria, died in Greece, and then his body was transferred to Constantinople, and from there to Padua, Italy. To understand whether there is any biological evidence supporting a Syrian origin of the Padua body traditionally attributed to Luke, or a replacement in Greece or Turkey, the mtDNA was extracted from two teeth and its control region was cloned and typed. The sequence determined in multiple clones is an uncommon variant of a set of alleles that are common in the Mediterranean region. We also collected and typed modern samples from Syria and Greece. By comparison with these population samples, and with samples from Anatolia that were already available in the literature, we could reject the hypothesis that the body belonged to a Greek, rather than a Syrian, individual. However, the probability of an origin in the area of modern Turkey was only insignificantly lower than the probability of a Syrian origin. The genetic evidence is therefore compatible with the possibility that the body comes from Syria, but also with its replacement in Constantinople.

Base Sequence↗
PubMed2001

DNA diversity and population admixture in Anatolia.

The Turkic language was introduced in Anatolia at the start of this millennium, by nomadic Turkmen groups from Central Asia. Whether that cultural transition also had significant population-genetics consequences is not fully understood. Three nuclear microsatellite loci, the hypervariable region I of the mitochondrial genome, six microsatellite loci of the Y chromosome, and one Alu insertion (YAP) were amplified and typed in 118 individuals from four populations of Anatolia. For each locus, the number of chromosomes considered varied between 51-200. Genetic variation was large within samples, and much less so between them. The contribution of Central Asian genes to the current Anatolian gene pool was quantified using three different methods, considering for comparison populations of Mediterranean Europe, and Turkic-speaking populations of Central Asia. The most reliable estimates suggest roughly 30% Central Asian admixture for both mitochondrial and Y-chromosome loci. That (admittedly approximate) figure is compatible both with a substantial immigration accompanying the arrival of the Turkmen armies (which is not historically documented), and with continuous gene flow from Asia into Anatolia, at a rate of 1% for 40 generations. Because a military invasion is expected to more deeply affect the male gene pool, similar estimates of admixture for female- and male-transmitted traits are easier to reconcile with continuous migratory contacts between Anatolia and its Asian neighbors, perhaps facilitated by the disappearance of a linguistic barrier between them.

Adult↗
PubMed2001

A mathematical model of the fetal cardiovascular system based on genetic algorithms as identification technique.

The development of fetal cardiac surgery, considered the ultimate goal in the treatment of congenital cardiac malformations, needs to be supported by detailed knowledge of the blood circulation in the fetal cardiovascular system. The hemodynamic behavior in distal territories is usually inferred from vessel resistance indices, which give limited physiological information. This study presents a mathematical model of the human fetal global cardiovascular system, developed to clarify the relationships and differences existing between upper and lower body circulation. We modelled the heart with two time-varying capacitances, each representing the respective ventricle's pressure-volume relationship. The fetal vascular system was represented using two six-element Windkessel models, for the upper and lower body respectively. We obtained the identification of the set of circuital and elastance function parameters of the model using Genetic Algorithms (GAs), which follow the laws of evolutionary theory. We compared the results of our numerical study on the model identified with data collected from measurements and literature, to validate the proposed global cardiovascular system model of the human fetus. This model is intended as an instrument to investigate the differences in blood distribution between the different vascular districts in the upper and lower fetal body and the role of the aortic isthmus, the small tract of vessel connecting upper and lower fetal vascular beds; it may also represent a useful tool in the assessment of dynamic balance during mechanical assistance of circulation.

Algorithms↗
PubMed2000

Forefoot reconstruction by reversed island flaps in diabetic patients.

Soft-tissue coverage of the foot is often difficult, especially when the distal third of the foot (dorsal or plantar aspects) is involved. The clinical situation can be further complicated when diabetic patients are affected by painful and unstable wounds of this kind because of the familiar phenomenon of vasculopathy. The purpose of this study was to evaluate the possibility of using distally based foot flaps to cover forefoot defects in diabetic patients. Preoperative selection of patients was the key to this study; those who had other major disease, chronic infection, bone involvement, and/or insufficient foot vascularization were excluded from the study. The authors report a series of 12 diabetic patients in whom the reconstruction of medium-sized defects (ranging from 1.5 x 2.0 cm to 3.0 x 7.0 cm) of the forefoot was performed using distally based dorsalis pedis flaps or medial plantar flaps. The transferred flaps survived and adapted well to the defects, except for one flap in a patient who had a slight venous insufficiency at outset. Wearing their own footwear, patients could walk after 20 to 30 days. After the follow-up period (3 months to 3 years), no skin breakdown in the treated areas was observed. Temporary donor-site pain was reported by medial plantar flap patients, and partial skin graft loss at the donor site occurred in some of the dorsalis pedis patients. The authors suggest that in selected cases, medium-sized soft-tissue defects involving the dorsal aspects or the weight-bearing areas of the diabetic foot can be successfully covered with distally based island flaps.

Aged↗
PubMed2000

Primary cardiac rhabdomyosarcoma of the left atrium: an unusual presentation.

Rhabdomyosarcoma accounts for almost 20% of all primary malignant neoplasms of the heart. These tumors usually arise from the ventricular walls. In adult patients, they sometimes arise from the atrial walls and mimic atrioventricular valve stenosis. We describe a case of left atrial rhabdomyosarcoma that presented as severe mitral stenosis and required emergency surgery. The atrial mass was detected by transthoracic and transesophageal echocardiography, but only histopathology confirmed the nature of the lesion. Although rhabdomyosarcomas of the heart are highly lethal, operation is indicated for emergency cases, in order to clarify the diagnosis, relieve symptoms, and improve short-term survival.

Aged↗
PubMed1999

Extended vertical transseptal approach versus conventional left atriotomy for mitral valve surgery.

BACKGROUND AND AIM OF THE STUDY: Mitral valve surgery requires optimal exposure of the valvular apparatus, particularly when a conservative procedure is used. Retrospectively, we compared surgical results in patients who underwent mitral valve surgery using the vertical transseptal approach (which has been adopted routinely in our institute) with those in patients undergoing conventional left atriotomy. METHODS: A total of 172 consecutive patients operated on for mitral procedures were allocated to either group A (those operated on through a longitudinal left atriotomy; n = 62), or group B (mitral valve exposure achieved through an extensive vertical transseptal approach; n = 110). RESULTS: In group A, there were 24 valvular reconstructions and 38 valvular replacements. Mean (+/- SD) cardiopulmonary bypass (CPB) time was 65.9 +/- 17 min and mean ischemia time 37.4 +/- 13 min. Total postoperative bleeding was 277 +/- 171 ml. There was no surgical re-exploration for bleeding. One patient in this group died (mortality rate 2%). Among 40 patients in atrial fibrillation preoperatively, four had one episode of temporary junctional rhythm, six had temporary sinus rhythm and two had stable sinus rhythm. Among patients with preoperative sinus rhythm, six (27%) had episodes of atrial fibrillation and two (9%) temporary atrioventricular block. In group B, 46 mitral reconstructions and 64 mitral replacements were performed. Mean CPB time was 67.9 +/- 20 min and mean ischemia time 48.1 +/- 17 min. Total postoperative bleeding was 400 +/- 189 ml. Three patients in this group died (mortality rate 2.7%). Among 60 patients with preoperative atrial fibrillation, six (10%) had one episode of temporary junctional rhythm, 14 (24%) had temporary sinus rhythm and two (3%) had conversion to stable sinus rhythm. Among those in sinus rhythm preoperatively, 16 (32%) had episodes of temporary junctional rhythm, two (4%) had temporary atrial fibrillations, and four (8%) had stable atrial fibrillation. In group B patients, the incidences of ischemia time and total postoperative bleeding (p = 0.004), and postoperative junctional arrhythmia in those with preoperative sinus rhythm (p < 0.001), were greater than in group A patients. CONCLUSIONS: No technique-related deaths occurred; neither were causes of re-exploration for bleeding related to technique, and there was no evidence of residual interatrial shunt. In conclusion, transseptal extended atriotomy provides excellent exposure for mitral valve surgery. Disadvantages of minimally increased ischemia time and surgical bleeding are minor compared with the superior and more complete surgical reconstruction achieved. The advantages of the technique are undermined by the higher incidence of junctional arrhythmia which, even if temporary, requires strict postoperative monitoring.

Cardiopulmonary Bypass↗
PubMed1999

Emergency surgical management of acute aortic dissection: role of transesophageal echocardiography.

The accuracy of transesophageal echocardiography in the diagnosis and surgical management of acute aortic dissection was determined in 54 patients who underwent surgery for acute aortic dissection. Results of the investigations were compared to the surgical assessment. From April 1993 to November 1997, we operated 54 patients (44 male and 10 female) for acute aortic dissection. Mean age was 60 +/- 9 years. At surgery, a De Bakey type I aortic dissection was diagnosed in 30 patients, type II in 23 and type III retrograde in 1. Operating procedures were: replacement of ascending aorta (24 cases), replacement of ascending aorta and aortic arch (17 cases), replacement of ascending aorta and aortic valve replacement (2 cases), Bentall procedure (6 cases) and end-to-end anastomosis of the ascending aorta (4 cases). Initial diagnosis, performed in emergency wards, was done on a clinical basis in 6 patients, on CT scan in 19, on transthoracic echocardiography in 14, and on TEE basis in 12. Three patients underwent angiography before our evaluation. As per our protocol, all patients underwent confirmation of the diagnosis by TEE. Seven patients needed additional instrumental investigations, 2 with CT scan and 5 with angiography. TEE confirmed the diagnosis of aortic dissection in all cases but one. Moreover, it described the site of the intimal tear, the extension of the dissecting process and accessory findings, such as pericardial effusion, aortic incompetence and left ventricular function. The interval between patient presentation and skin incision was a maximum of 70 minutes. At surgery, diagnosis of De Bakey classification was confirmed in 98% of cases; in 90.7% of cases exact location of the entry site was confirmed. In one case, an entry site in the arch diagnosed by TEE but not recognized at surgery, was observed at necropsy. Intraoperatively, we routinely used TEE to monitor retrograde systemic perfusion and correct implant of the vascular prosthesis. One case of malperfusion of the thoracic aorta through the false lumen was observed and managed. In one case we diagnosed acute obstruction of the prosthesis by bleeding in the wrapped aorta, which required reoperation. Assessment of ventricular function was obtained in all patients: in two cases, observation of low right ventricular function led us to perform aortocoronary by-pass to the right coronary artery. In conclusion, the high level of correspondence between TEE diagnosis and surgical anatomy prompted us to perform transesophageal echocardiography as the primary and often sole diagnostic procedure in acute aortic dissection. TEE, in experienced hands, has proven to be a highly reliable, safe and low-cost diagnostic tool. It can be performed at the patient's bedside within just a few minutes of the suspected diagnosis, thereby lowering the mortality rate of the natural history. Again, it can also be used in the operating theatre as an "on-line examination" as well as for assessment of correct surgical repair. Other diagnostic procedures do not yield more information and can cause dangerous delays in intervention.

Adult↗
PubMed1998

A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease.

The aim of this randomized, open, parallel group study was to compare the clinical efficacy of formoterol dry powder capsule 12 micrograms b.i.d. and salmeterol dry powder 50 micrograms b.i.d. in the treatment of patients with reversible obstructive airways disease. The 6-month treatment was preceded by a 2 week run-in period. Morning pre-dose peak expiratory flow (PEF) during the last 7 days of treatment was the primary variable. Throughout the study, patients recorded morning and evening pre-dose PEF, use of rescue medication, respiratory symptoms and adverse events. Clinic visits were scheduled at monthly intervals. Of the 482 patients randomized (equal numbers in the two treatment groups), 428 completed the study. Four hundred and twenty-five patients were included in the efficacy analysis for the primary variable. For mean morning pre-dose PEF during the last 7 days of treatment, the 95% confidence interval (CI) for the treatment contrast formoterol minus salmeterol was included entirely in the pre-defined range of equivalence (CI limits = -8.69, +9.841 min-1). This was also the case for the morning PEF during the last week before each clinic visit. For mean evening pre-dose PEF, the estimated treatment contrasts showed a trend towards superiority of formoterol over salmeterol, which became statistically significant at 2, 3 and 4 months (P < 0.05; estimated contrasts 7.27, 10.45 and 10.511 min-1, respectively). No treatment group differences were found in use of rescue medication and respiratory symptom scores. The incidence of adverse events was similar in the two groups. These findings demonstrate that formoterol 12 micrograms b.i.d. and salmeterol 50 micrograms b.i.d., both formulated as dry powders, have similar long-term efficacy and safety profiles in patients with reversible obstructive airways disease.

Administration, Inhalation↗
PubMed1998

Carcinoma of the male breast: an underestimated killer.

Male breast carcinoma represents only 1 percent of all breast cancers. Despite the rarity of this neoplasia, the malignancy is often very aggressive, mostly because of delayed diagnosis. Consequently, large excisions are usually needed, and subsequent reconstruction is performed by means of fasciocutaneous or myocutaneous local or distant flaps, depending on the stage of the neoplasia. The signs, symptoms, prognosis, and reconstructive methods of such an unusual form of breast cancer are discussed in this article.

Adult↗