Marcello Rossi

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Medical Doctor, specialist in pulmonary medicine, researcher in pulmonary gas exchange.

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A new method to detect crackles in respiratory sounds

Technology and Health Care, Feb 1, 1998

In this paper, an automatic method to detect and analyze crackles in digitised respiratory sounds... more In this paper, an automatic method to detect and analyze crackles in digitised respiratory sounds is presented. The method is based on two steps: (1) a threshold (T) value is applied to the first derivative absolute value (FDAV) of lung sound to locate the "zone of interest" and (2) in this zone a crackle is detected if certain conditions are verified. The first derivative (FD) is evaluated by means of a derivative-smoothing filter, preserving areas under the spectral lines of the signal (moment zero), its mean position in time (first moment) and its spectral line width (second moment). The conditions to verify step 2 concern the following: the number and height of the peaks of FDAV and their distances from the starting point of the crackle, within a temporal window TW. This method shows good performances as an automatic detector (sensitivity 84% and specificity 89%), and is specifically designed to find the starting point of the crackle.

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Placing crackles on the flow-volume plane: a study of the relationship between the time position, the flow and the volume

Technology and Health Care, Feb 1, 1998

The aim of this study was to analyse inspiratory crackles in patients with Pulmonary Fibrosis (PF... more The aim of this study was to analyse inspiratory crackles in patients with Pulmonary Fibrosis (PF) and Bronchiectasis (BE). One case of Chronic Obstructive Pulmonary Disease (COPD) has also been included. The relationships between the time of occurrence of crackles (T) in the breath cycle and the corresponding flow at the mouth (F) and volume (V) have been investigated. The linear correlations between the flow, volume and time have been investigated by Pearson's R-test and the same variables have been analysed by Principal Component Analysis (PCA) in order to verify the effective dimension of these data. The results show a strong correlation between the time of occurrence and the volume in all the examined cases. PCA shows that in all cases F and V account for more than 90% of variation. These results suggest that placing crackles on the flow-volume plane does not cause loss of information.

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Multimedia presentation of lung sounds as a learning aid for medical students

The European respiratory journal, May 1, 1995

New educational technologies might help to compensate for the decrease in time and emphasis dedic... more New educational technologies might help to compensate for the decrease in time and emphasis dedicated to physical examination in medial training. This may, in particular, be applicable for improving the skills in auscultation of the chest. We investigated whether a multimedia presentation of acoustic and graphic characteristics of lung sounds could improve the learning of pulmonary auscultation by medical students, in comparison with conventional teaching methods. We studied 48 medical students without clinical experience, who had received conventional formal teaching on chest examination. Chest auscultation skills were evaluated using an inaccuracy score for the student's auscultation report on three patients, selected according to a standardized procedure. After a baseline evaluation, 27 students in groups of 5-10, participated in a multimedia seminar on lung sounds during which digitized lung sounds were played and the corresponding timeexpanded waveform and frequency spectrum were commented on and displayed on a computer. The remaining 21 students received conventional bedside training, acting as control group. The following week, all the students underwent a second evaluation of chest auscultation skills. No differences in the inaccuracy score were observed between the two groups in the preliminary test. However, in the second postintervention assessment, the inaccuracy score of the students who had followed the seminar (11.2±1.3 points) was significantly lower than that of the controls (16.6±1.6 points). The answers to a feedback questionnaire confirmed that the great majority of the students found the association of the acoustic signals with their visual image to be useful for learning and understanding lung sounds. We conclude that the exposure of inexperienced medical students to a multimedia presentation significantly boosts their learning of lung sounds compared to students receiving only conventional teaching.

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Breathing Abnormalities During Sleep and Wakefulness in Rett Syndrome: Clinical Relevance and Paradoxical Relationship With Circulating Pro-oxidant Markers

Frontiers in Neurology

BackgroundBreathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopment... more BackgroundBreathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers.MethodsFemale patients with a clinical diagnosis of typical RTT (n = 66), MECP2 gene mutation, and apneas were enrolled (mean age: 12.5 years). Baseline clinical severity, arterial blood gas analysis, and red blood cell count were assessed. Breathing was monitored during the wakefulness and sleep states (average recording time: 13 ± 0.5 h) with a portable polygraphic screening device. According to prevalence of breath holdings, the population was categorized into the wakefulness apnea (WA) and sleep apnea (SA) groups, and apnea-hypopnea index (AHI) was calculated. The impact of res...

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MECP2-およびCDKL5-関連Rett症候群におけるサイトカイン調節不全:酸化還元ホメオスタシス異常,炎症およびω-3 PUFAとの関係

Oxidative Medicine and Cellular Longevity (Web), 2015

Anomalia di forma dei globuli rossi e danno ossidativo nella membrana eritrocitaria nella sindrome di Rett

In condizioni fisiologiche, i globuli rossi - cellule dalle dimensioni di 7-8 m (millesimo di mm)... more In condizioni fisiologiche, i globuli rossi - cellule dalle dimensioni di 7-8 m (millesimo di mm) - mostrano una caratteristica forma a disco biconcavo (discociti), di importanza chiave per tutte le loro funzioni, quali la deformabilità (per adattarsi alle sinuosità della rete circolatoria), e lo scambio di ossigeno (O2), ma sono molto suscettibili a cambiamenti morfologici, con conseguente perdita della loro funzionalità. Tra i fattori che causano alterazioni morfologiche ci possono essere i cambiamenti di osmolarità, di pH, condizioni di ipossia e presenza di ossidanti (sostanze o molecole che possono indurre stress ossidativo) [1-5]. I globuli rossi a causa degli alti livelli di ferro cellulare e della proprietà dell’emoglobina ad auto-ossidarsi, sono una costante sorgente di produzione di ossidanti (radicali liberi dell’ossigeno come l’anione superossido) [6,7] e di ferro in forma libera (NPBI), cioè non legato a proteine, redox attivo. Stress ossidativo (SO) e ipossia possono portare ad alterazioni nella forma dei globuli rossi in pazienti adulti con malattia polmonare cronica ostruttiva (COPD) [7,8]. Nella forma tipica della sindrome di Rett (RTT ) il nostro gruppo ha dimostrato la presenza di ipossia cronica, alterati scambi di gas a livello polmonare, aumentato SO e lesioni morfologiche polmonari, simili a quelle evidenziabili nella malattia polmonare interstiziale associata a bronchiolite respiratoria dei fumatori (RB-ILD) [9,10]. Nonostante i globuli rossi svolgano un ruolo fondamentale nel trasporto e scambio di O2 nei mammiferi, finora non esistevano informazioni sulla morfologia dei globuli rossi nelle bimbe e ragazze affette da RTT . In particolare, nei nostri precedenti studi avevamo dimostrato che lo SO è in grado di indurre nei globuli rossi rilascio di NPBI, formazione di metemoglobina (Met-Hb) e alterazioni ossidative dei lipidi (perossidazione lipidica) e delle proteine di membrana [11]. Quindi nel presente studio abbiamo valutato se lo SO possa indurre cambiamenti morfologici e danno ossidativo nei globuli rossi di pazienti Rett con forma classica. La forma dei globuli rossi in pazienti RTT e in soggetti sani è stata correlata ai marker di SO, stato di ossigenazione, scambi gassosi polmonari e vari parametri cardiorespiratori

Oxygen exchange and energy metabolism in erythrocytes of Rett syndrome and their relationships with respiratory alterations

Molecular and Cellular Biochemistry, Jan 7, 2017

Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associat... more Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associated to a mutation on the methyl-CpG-binding protein 2 gene. In the pathogenesis and progression of classic RTT, red blood cell (RBC) morphology has been shown to be an important biosensor for redox imbalance and chronic hypoxemia. Here we have evaluated the impact of oxidation and redox imbalance on several functional properties of RTT erythrocytes. In particular, we report for the first time a stopped-flow measurement of the kinetics of oxygen release by RBCs and the analysis of the intrinsic affinity of the hemoglobin (Hb). According to our experimental approach, RBCs from RTT patients do not show any intrinsic difference with respect to those from healthy controls neither in Hb's oxygen-binding affinity nor in O 2 exchange processes at 37°C. Therefore, these factors do not contribute to the observed alteration of the respiratory function in RTT patients. Moreover, the energy metabolism of RBCs, from both RTT patients and controls, was evaluated by ion-pairing HPLC method and related to the level of malondialdehyde and to the oxidative radical scavenging capacity of red cells. Results have clearly confirmed significant alterations in antioxidant defense capability, adding important informations concerning the high-energy compound levels in RBCs of RTT subjects, underlying possible correlations with inflammatory tissue alterations.

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Cytokine Dysregulation inMECP2- andCDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, andω-3 PUFAs

Oxidative Medicine and Cellular Longevity, 2015

An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neur... more An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclindependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2-(MECP2-RTT) (= 16) and CDKL5-Rett syndrome (CDKL5-RTT) (= 8), before and after-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1-and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system. This research is dedicated to all the Rett girls and their families.

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Studio retrospettivo sui ricoveri per tubercolosi nella provincia di Siena Retrospective study on tuberculosis in Siena province

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Sindrome di Rett: effetti degli acidi grassi polinsaturi omega-3 sulle proteine di membrana

Gli acidi grassi polinsaturi ω -3 (ω -3 PUFA) costituiscono una famiglia di acidi grassi biologic... more Gli acidi grassi polinsaturi ω -3 (ω -3 PUFA) costituiscono una famiglia di acidi grassi biologicamente attivi, con potenziale antiossidante ed anti-infiammatorio. In molti casi, i loro effetti si traducono in un miglioramento dei profili di alcuni marcatori associati ad alcune malattie, come nel caso di patologie psichiatriche e neurodegenerative. La sindrome di Rett (RTT) è un raro e grave disordine dello sviluppo neurologico, principalmente causato da mutazioni de novo a carico del gene MECP2 localizzato sul cromosoma X, codificante la proteina methyl-CpG binding protein 2 (MeCP2 ), un importante regolatore epigenetico. Studi pregressi effettuati sui globuli rossi (GR) dei pazienti affetti da RTT, hanno evidenziato alterazioni della forma cellulare, caratterizzate da una predominanza di leptociti nello striscio di sangue periferico. L’associazione dello stress ossidativo (SO) con l’ipossia può essere considerato determinante per l’induzione dell’alterazione della forma eritrocitaria. A causa dell’elevata concentrazione di ferro, ossigeno ed emoglobina, la struttura eritrocitaria è infatti altamente suscettibile al danno ossidativo. Studi pregressi suggeriscono che l’alterazione della forma dei GR nella RTT può essere parzialmente contrastata dalla somministrazione di ω -3 PUFA, ad alte dosi per almeno 12 mesi. In questo studio è stata esaminata, mediante tecniche proteomiche, la componente proteica associata alla membrana eritrocitaria dei pazienti affetti da RTT. I risultati ottenuti hanno fornito nuove informazioni sul ruolo che i cambiamenti proteici hanno, in termini di espressione ed ossidazione, nei leptociti di questi pazienti e hanno indicato che la somministrazione di ω -3 PUFA è in grado di modulare l’espressione e lo stato di ossidazione delle proteine associate alla membrana degli eritrociti dei soggetti affetti da RTT

High-Resolution CT Imaging Study Syndrome : A Physiologic and Unrecognized Lung Disease in Classic Rett

€http://chestjournal.chestpubs.org/content/138/2/386.full.html services can be found online on th... more €http://chestjournal.chestpubs.org/content/138/2/386.full.html services can be found online on the World Wide Web at: The online version of this article, along with updated information and€ISSN:0012-3692(http://chestjournal.chestpubs.org/site/misc/reprints.xhtml)of the copyright holder.may be reproduced or distributed without the prior written permission Northbrook, IL 60062. All rights reserved. No part of this article or PDFby the American College of Chest Physicians, 3300 Dundee Road, Physicians. It has been published monthly since 1935. Copyright 2010CHEST is the official journal of the American College of Chest

Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, andβ-Actin Alterations: An Unrecognized Triad in Classical Autism

Mediators of Inflammation, 2013

Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily risin... more Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6–26 years), nonautistic neurodevelopmental disorders (i.e., “positive controls”), and healthy controls (i.e., “negative controls”). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs al...

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Batteri patogeni nell'espettorato e grado di ostruzione bronchiale in pazienti con riacutizzazione di broncopneumopatia cronica ostruttiva

Recenti Progressi in Medicina, 2002

Red blood cells in Rett syndrome: oxidative stress, morphological changes and altered membrane organization

Biological Chemistry, 2015

In this review, we summarize the current evidence on the erythrocyte as a previously unrecognized... more

Time-Trend Analysis of Pulmonary and Diaphragmatic Functionality in Patients with Diaphragmatic Palsy or with Chronic Diaphragmatic Hernia after Surgical Treatment

The Thoracic and cardiovascular surgeon, Jan 31, 2015

Background The aim of this study was to assess long-term pulmonary and diaphragmatic function in ... more Background The aim of this study was to assess long-term pulmonary and diaphragmatic function in two cohorts of patients: the first one affected by diaphragmatic palsy (DP) who underwent plication reinforced by rib-fixed mesh and the second one affected by chronic diaphragmatic hernia (TDH) who underwent surgical reduction and direct suture. Materials and Methods From 1996 to 2011, 10 patients with unilateral DP and 6 patients with TDH underwent elective surgery. Preoperative and long-term (12 months) follow-up assessments were completed in all patients, including pulmonary function tests (PFTs) with diffusion of the lung for carbon monoxide (DLCO), measure of maximum inspiratory pressure (MIP) assessed both in standing and in supine positions, blood gas analysis, chest computed tomographic (CT) scan, and dyspnea score. The Pearson chi-square test, Fisher exact test, and Student t-test were applied when indicated. Results At long-term (12 months) postoperative follow-up, patients op...

[Bacterial pathogens in sputum and degree of bronchial obstruction in patients with acute exacerbation of chronic obstructive pulmonary disease]

Recenti progressi in medicina, 2002

In 114 patients with acute exacerbation of chronic obstructive pulmonary disease (AECB) we perfor... more In 114 patients with acute exacerbation of chronic obstructive pulmonary disease (AECB) we performed a microbiological sputum study. In four sub-groups of patients, divided on the basis of the isolated pathogens, we looked for the best forced expiratory volume in one second (FEV1) registered in a previous test (< 12 months), in stable clinical conditions. In 65 samples of sputum (57% of all) the distribution of the isolated pathogens was: H. parainfluenzae 23%, H. influenzae 8%, M. catarrhalis 3%, S. pneumoniae 4%, Enterobacteriaceae (EN) 22%, Pseudomonas and other related germs (BN) 32%, S. aureus 8%. EN and BN showed high sensitivity to various antibiotics. In the patients of the BN sub-group the mean FEV1 showed a significant lower value than in the other sub-groups (from p < 0.01 to p < 0.001). The high percentage of EN and BN seems to be likely explained by the population we studied because there were many subjects with severe clinical and functional conditions, with m...

Oxygen exchange and energy metabolism in erythrocytes of Rett syndrome and their relationships with respiratory alterations

Molecular and Cellular Biochemistry, 2017

Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associat... more Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associated to a mutation on the methyl-CpG-binding protein 2 gene. In the pathogenesis and progression of classic RTT, red blood cell (RBC) morphology has been shown to be an important biosensor for redox imbalance and chronic hypoxemia. Here we have evaluated the impact of oxidation and redox imbalance on several functional properties of RTT erythrocytes. In particular, we report for the first time a stopped-flow measurement of the kinetics of oxygen release by RBCs and the analysis of the intrinsic affinity of the hemoglobin (Hb). According to our experimental approach, RBCs from RTT patients do not show any intrinsic difference with respect to those from healthy controls neither in Hb&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s oxygen-binding affinity nor in O2 exchange processes at 37 °C. Therefore, these factors do not contribute to the observed alteration of the respiratory function in RTT patients. Moreover, the energy metabolism of RBCs, from both RTT patients and controls, was evaluated by ion-pairing HPLC method and related to the level of malondialdehyde and to the oxidative radical scavenging capacity of red cells. Results have clearly confirmed significant alterations in antioxidant defense capability, adding important informations concerning the high-energy compound levels in RBCs of RTT subjects, underlying possible correlations with inflammatory tissue alterations.

Morphological changes and oxidative damage in Rett Syndrome erythrocytes

Biochimica et Biophysica Acta (BBA) - General Subjects, 2012

Background: Hypoxemia and increased oxidative stress (OS) have been reported in Rett Syndrome (RT... more Background: Hypoxemia and increased oxidative stress (OS) have been reported in Rett Syndrome (RTT), a genetical neurodevelopmental disorder. Although OS and hypoxemia can lead to red blood cells (RBCs) shape abnormalities, no information on RBCs morphology in RTT exists. Here, RBCs shape was evaluated in RTT patients and healthy subjects as a function of OS markers, blood oxygenation, pulmonary gas exchange, and cardio-respiratory parameters. Methods: RBCs morphology was evaluated by Scanning Electron Microscopy. Intraerythrocyte and plasma non protein-bound iron (NPBI), esterified F 2 -Isoprostanes (F 2 -IsoPs), 4-HNE protein adducts (4-HNE PAs) were measured. Pulmonary oxygen gradients and PaO 2 were evaluated by gas analyzers and cardiopulmonary variables by pulse oximetry. In RTT patients these parameters were assessed before and after ω-3 polyunsaturated fatty acids (ω-3 PUFAs) administration. Results: Altered RBCs shapes (leptocytes) and increased NPBI were present in RTT, together with increased erythrocyte membrane esterified F 2 -IsoPs and 4-HNE PAs. Abnormal erythrocyte shapes were related to OS markers levels, pulmonary gas exchange, PaO 2 and cardio-respiratory variables. After ω-3 PUFAs, a decrease of leptocytes was accompanied by a progressive increase in reversible forms of RBCs. This partial RBCs morphology rescue was related to decreased OS damage markers, improved pulmonary oxygen exchange, and cardiopulmonary physiology. Conclusions: These findings indicate that in RTT 1) RBCs shape is altered; 2) the OS-hypoxia diad is critical in generating altered RBCs shape and membrane damage; 3) ω-3 PUFAs are able to partially rescue RBCs morphology and the OS-derived damage. General significance: RBCs morphology is an important biosensor for OS imbalance and chronic hypoxemia.

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Altered erythrocyte membrane fatty acid profile in typical Rett syndrome: Effects of omega-3 polyunsaturated fatty acid supplementation

by Carla Caffarelli and Marcello Rossi

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2014

This study mainly aims at examining the erythrocyte membrane fatty acid (FAs) profile in Rett syn... more This study mainly aims at examining the erythrocyte membrane fatty acid (FAs) profile in Rett syndrome (RTT), a genetically determined neurodevelopmental disease. Early reports suggest a beneficial effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on disease severity in RTT. A total of 24 RTT patients were assigned to ω-3 PUFAs-containing fish oil for 12 months in a randomized controlled study (average DHA and EPA doses of 72.9, and 117.1mg/kgb.w./day, respectively). A distinctly altered FAs profile was detectable in RTT, with deficient ω-6 PUFAs, increased saturated FAs and reduced trans 20:4 FAs. FAs changes were found to be related to redox imbalance, subclinical inflammation, and decreased bone density. Supplementation with ω-3 PUFAs led to improved ω-6/ω-3 ratio and serum plasma lipid profile, decreased PUFAs peroxidation end-products, normalization of biochemical markers of inflammation, and reduction of bone hypodensity as compared to the untreated RTT group. Our data indicate that a significant FAs abnormality is detectable in the RTT erythrocyte membranes and is partially rescued by ω-3 PUFAs.

Inflammatory Lung Disease in Rett Syndrome

by Marcello Rossi, Ingrid Iacona, and Alessandro Ginori

Mediators of Inflammation, 2014

Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the ... more Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n= 228) and to examine lung histology in aMecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with “high” (39.8%) and “low” (34.8%) patterns dominating over “mixed” (19.6%) and “simple mismatch” (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively corr...

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