Evaluating human basal metabolism: the erroneous and misleading use of so-called "prediction equations".

Prediction (regression) equations are widely used, but their reliability as predictive tools is questionable as they provide contradicting results. The key point is that values calculated by regression equations are not precisely defined numbers but lie within a range of possible values in the standard deviation interval, none of which can be considered as the most probable. Ignoring this point leads to illicit/improper calculations, generating wrong results, which may have adverse consequences for human health. To demonstrate this, we applied the equations of Harris and Benedict in a reverse method, i.e. calculating (predicting) the daily energy expenditure in the same subjects used to obtain the equations and comparing values with the original measured data. We used the Bland-Altman and frequency distribution analyses. We found large differences in both individual data and population characteristics, showing that prediction equations are not predictive tools.

Specific anesthesia-induced lung volume changes from induction to emergence: a pilot study.

BACKGROUND: Studies aimed at maintaining intraoperative lung volume to reduce post-operative pulmonary complications have been inconclusive because they mixed up the effect of general anesthesia and the surgical procedure. Our aims were to study: (1) lung volume during the entire course of anesthesia without the confounding effects of surgical procedures; (2) the combination of three interventions to maintain lung volume; and (3) the emergence phase with focus on the restored activation of the respiratory muscles. METHODS: Eighteen ASA I-II patients undergoing ENT surgery under general anesthesia without muscle relaxants were randomized to an intervention group, receiving lung recruitment maneuver (LRM) after induction, 7 cmH2 O positive end-expiratory pressure (PEEP) during anesthesia and continuous positive airway pressure (CPAP) during emergence with 0.4 inspired oxygen fraction (FiO2 ) or a control group, ventilated without LRM, with 0 cmH2 O PEEP, and 1.0 FiO2 during emergence without CPAP application. End-expiratory lung volume (EELV) was continuously estimated by opto-electronic plethysmography. Inspiratory and expiratory ribcage muscles electromyography was measured in a subset of seven patients. RESULTS: End-expiratory lung volume decreased after induction in both groups. It remained low in the control group and further decreased at emergence, because of active expiratory muscle contraction. In the intervention group, EELV increased after LRM and remained high after extubation. CONCLUSION: A combined intervention consisting of LRM, PEEP and CPAP during emergence may effectively maintain EELV during anesthesia and even after extubation. An unexpected finding was that the activation of the expiratory muscles may contribute to EELV reduction during the emergence phase.

Assessment of gas compression and lung volume during air stacking maneuver.

PURPOSE: We reasoned that the application of positive pressure through air stacking (AS) technique could cause gas compression and the absolute lung volumes could be estimated. The aim of this study was to estimate the amount of gas compression (ΔV comp) during AS in healthy subjects positioned at 45° trunk inclination and verify if the simultaneous measurements of chest wall volume changes (ΔV CW), by optoelectronic plethysmography, and changes in lung volume (ΔV ao), by pneumotachograph, combined with pressure variation at the airways opening (ΔP ao) during AS are able to provide reliable data on absolute lung volumes. METHODS: Twenty healthy subjects (mean age 23.5 ± 3.8 years) were studied during a protocol that included slow vital capacity and AS maneuvers. V comp was calculated by subtracting ΔV ao and ΔV CW occurring during AS and total lung capacity (TLC) was estimated by applying Boyle-Mariote's law using V comp and ΔP ao. RESULTS: During AS, 0.140 ± 0.050 L of gas was compressed with an average ΔP ao of 21.78 ± 6.18 cmH2O. No significant differences between the estimated TLC (-0.03 ± 3.0% difference, p = 0.6020), estimated FRC (-2.0 ± 12.4% difference, p = 0.5172), measured IC (1.2 ± 11.2% difference, p = 0.7627) and predicted values were found. CONCLUSION: During AS, a significant gas compression occurs and absolute lung volumes can be estimated by simultaneous measurements of ΔV CW, ΔV ao and ΔP ao.

Frequency dependence of lung volume changes during superimposed high-frequency jet ventilation and high-frequency jet ventilation.

BACKGROUND: Superimposed high-frequency jet ventilation (SHFJV) has proved to be safe and effective in clinical practice. However, it is unclear which frequency range optimizes ventilation and gas exchange. The aim of this study was to systematically compare high-frequency jet ventilation (HFJV) with HFJV by assessing chest wall volume variations (ΔEEV(CW)) and gas exchange in relation to variable high frequency. METHODS: SHFJV or HFJV were used alternatively to ventilate the lungs of 10 anaesthetized pigs (21-25 kg). The low-frequency component was kept at 16 min(-1) in SHFJV. In both modes, high frequencies ranging from 100 to 1000 min(-1) were applied in random order and ventilation was maintained for 5 min in all modalities. Chest wall volume variations were obtained using opto-electronic plethysmography. Airway pressures and arterial blood gases were measured repeatedly. RESULTS: SHFJV increased ΔEEV(CW) compared with HFJV; the difference ranged from 43 to 68 ml. Tidal volume (V(T)) was always >240 ml during SHFJV whereas during HFJV ranged from 92 ml at the ventilation frequency of 100 min(-1) to negligible values at frequencies >300 min(-1). We observed similar patterns for Pa(O2) and Pa(CO2). SHFJV provided generally higher, frequency-independent oxygenation (Pa(O2) at least 32.0 kPa) and CO2 removal (Pa(CO2) ∼5.5 kPa), whereas HFJV led to hypoxia and hypercarbia at higher rates (Pa(O2) <10 kPa and Pa(CO2)>10 kPa at f(HF)>300 min(-1)). CONCLUSIONS: In a porcine model, SHFJV was more effective in increasing end-expiratory volume than single-frequency HFJV, but both modes may provide adequate ventilation in the absence of airway obstruction and respiratory disease, except for HFJV at frequencies ≥300 min(-1).

In Vivo Measurement of Tidal Volume During Non-invasive Respiratory Support by Continuous-Flow Helmet CPAP.

Recently, the interest in the Helmet interface during non-invasive respiratory support (NIRS) has increased due to the COVID-19 pandemic. During NIRS, positive end-expiratory pressure (PEEP) can be given as continuous positive airway pressure (CPAP), which maintains a positive airway pressure throughout the whole respiratory cycle with Helmet as an interface (H-CPAP). The main disadvantage of the H-CPAP is the inability to measure tidal volume (VT). Opto-electronic plethysmography (OEP) is a non-invasive technique that is not sensitive to gas compression/expansion inside the helmet. OEP acquisitions were performed on 28 healthy volunteers (14 females and 14 males) at baseline and during Helmet CPAP. The effect of posture (semi-recumbent vs. prone), flow (50 vs. 60 L/min), and PEEP (0 vs. 5 vs. 10 cmH2O) on the ventilatory and thoracic-abdominal pattern and the operational volumes were investigated. Prone position limited vital capacity, abdominal expansion and chest wall recruitment. A constant flow of 60 L/min reduced the need for the subject to ventilate while having a slight recruitment effect (100 mL) in the semi-recumbent position. A progressive increasing recruitment was found with higher PEEP but limited by the prone position. It is possible to accurately measure tidal volume during H-CPAP to deliver non-invasive ventilatory support using opto-electronic plethysmography during different clinical settings.

Comparison of superimposed high-frequency jet ventilation with conventional jet ventilation for laryngeal surgery.

BACKGROUND: New ventilators have simplified the use of supraglottic superimposed high-frequency jet ventilation (SHFJV(SG)), but it has not been systematically compared with other modes of jet ventilation (JV) in humans. We sought to investigate whether SHFJV(SG) would provide more effective ventilation compared with single-frequency JV techniques. METHODS: A total of 16 patients undergoing minor laryngeal surgery under general anaesthesia were included. In each patient, four different JV techniques were applied in random order for 10-min periods: SHFJV(SG), supraglottic normal frequency (NFJV(SG)), supraglottic high frequency (HFJV(SG)), and infraglottic high-frequency jet ventilation (HFJV(IG)). Chest wall volume variations were continuously measured with opto-electronic plethysmography (OEP), intratracheal pressure was recorded and blood gases were measured. RESULTS: Chest wall volumes were normalized to NFJV(SG) end-expiratory level. The increase in end-expiratory chest wall volume (EEV(CW)) was 239 (196) ml during SHFJV(SG) (P<0.05 compared with NFJV(SG)). EEV(CW) was 148 (145) and 44 (106) ml during HFJV(SG) and HFJV(IG), respectively (P<0.05 compared with SHFJV(SG)). Tidal volume (V(T)) during SHFJV(SG) was 269 (149) ml. V(T) was 229 (169) ml (P=1.00 compared with SHFJV(SG)), 145 (50) ml (P<0.05), and 110 (33) ml (P<0.01) during NFJV(SG), HFJV(SG), and HFJV(IG), respectively. Intratracheal pressures corresponded well to changes in both EEV(CW) and V(T). All JV modes resulted in adequate oxygenation. However, was lowest during HFJV(SG) [4.3 (1.3) kPa; P<0.01 compared with SHFJV(SG)]. CONCLUSION: SHFJV(SG) was associated with increased EEV(CW) and V(T) compared with the three other investigated JV modes. All four modes provided adequate ventilation and oxygenation, and thus can be used for uncomplicated laryngeal surgery in healthy patients with limited airway obstruction.

Breathing patterns recognition: A functional data analysis approach.

BACKGROUND AND OBJECTIVE: The ongoing pandemic proved fundamental is to assess a subject's respiratory functionality and breathing pattern measurement during quiet breathing is feasible in almost all patients, even those uncooperative. Breathing pattern consists of tidal volume and respiratory rate in an individual assessed by data tracks of lung or chest wall volume over time. State-of-art analysis of these data requires operator-dependent choices such as individuation of local minima in the track, elimination of anomalous breaths and individuation of breath clusters corresponding to different breathing patterns. METHODS: A semi-automatic, robust and reproducible procedure was proposed to pre-process and analyse respiratory tracks, based on Functional Data Analysis (FDA) techniques, to identify representative breath curve and the corresponding breathing patterns. This was achieved through three steps: 1) breath separation through precise localization of the minima of the volume trace; 2) functional outlier breaths detection according to time-duration, magnitude and shape; 3) breath clustering to identify different pattern of interest, through K-medoids with Alignment. The method was firstly validated on simulated tracks and then applied to real data in conditions of clinical interest: operational volume change, exercise, mechanical ventilation, paradoxical breathing and age. RESULTS: The total error in the accuracy of minima detection and in was less than 5%; with the artificial outliers being almost completely removed with an accuracy of 99%. During incremental exercise and independently on the bike resistance level, five clusters were identified (quiet breathing; recovery phase; onset of exercise; maximal and intermediate levels of exercise). During mechanical ventilation, the procedure was able to separate the non-ventilated from the ventilatory-supported breathing and to identify the worsening of paradoxical breathing due to the disease progression and the breathing pattern changes in healthy subjects due to age. CONCLUSIONS: We proposed a robust validated automatic breathing patterns identification algorithm that extracted representative curves that could be implemented in clinical practice for objective comparison of the breathing patterns within and between subjects. In all case studies the identified patterns proved to be coherent with the clinical conditions and the physiopathology of the subjects, therefore enforcing the potential clinical translational value of the method.

Virtual reality for COPD rehabilitation: a technological perspective.

Virtual Reality (VR) is a promising technology for implementing personalized, motivating and controlled rehabilitation scenarios. Although its clear potential benefits, VR has been poorly investigated in pulmonary rehabilitation. This review analyses the state of the art, by searching the scientific and grey literature, regarding the use of VR for the rehabilitation of patients with chronic obstructive pulmonary disease, providing a technological perspective. First, the main characteristics of the included systems are presented in terms of visualization devices, way of interaction and type of feedback they provide. Then, results of the selected studies are reported considering feasibility, safety, usability and user experience as outcomes. Finally, the main findings are discussed and future directions for research are outlined.

Effects of propofol anaesthesia on thoraco-abdominal volume variations during spontaneous breathing and mechanical ventilation.

BACKGROUND: Anaesthesia based on inhalational agents has profound effects on chest wall configuration and breathing pattern. The effects of propofol are less well characterised. The aim of the current study was to evaluate the effects of propofol anaesthesia on chest wall motion during spontaneous breathing and positive pressure ventilation. METHODS: We studied 16 subjects undergoing elective surgery requiring general anaesthesia. Chest wall volumes were continuously monitored by opto-electronic plethysmography during quiet breathing (QB) in the conscious state, induction of anaesthesia, spontaneous breathing during anaesthesia (SB), pressure support ventilation (PSV) and pressure control ventilation (PCV) after muscle paralysis. RESULTS: The total chest wall volume decreased by 0.41 ± 0.08 l immediately after induction by equal reductions in the rib cage and abdominal volumes. An increase in the rib cage volume was then seen, resulting in total chest wall volumes 0.26 ± 0.09, 0.24 ± 0.10, 0.22 ± 0.10 l lower than baseline, during SB, PSV and PCV, respectively. During QB, rib cage volume displacement corresponded to 34.2 ± 5.3% of the tidal volume. During SB, PSV and PCV, this increased to 42.2 ± 4.9%, 48.2 ± 3.6% and 46.3 ± 3.2%, respectively, with a corresponding decrease in the abdominal contribution. Breathing was initiated by the rib cage muscles during SB. CONCLUSION: Propofol anaesthesia decreases end-expiratory chest wall volume, with a more pronounced effect on the diaphragm than on the rib cage muscles, which initiate breathing after apnoea.

Computational Fluid Dynamics (CFD) Analysis of Subject-specific Bronchial Tree Models in Lung Cancer Patients.

Lung resection is the only potentially curative treatment for lung cancer. The inevitable partial removal of functional lung tissue along with the tumoral mass requires a careful and structured pre-operative condition of patients. In particular, the postoperative residual functionality of the lung needs to be predicted. Clinically, this is assessed through algorithms based on pulmonary function tests (PFTs). However, these approaches neglect the local airway segment's functionality and provide a globally averaged evaluation. CFD was demonstrated to provide patient-specific, quantitative, and local information on flow dynamics and regional ventilation in the bronchial tree. This study aims to apply CFD to characterize the flow dynamics in 12 patients affected by lung cancer and evaluate the effects of the tumoral masses on flow parameters and lobar flow distribution. Patient-specific airway models were reconstructed from CT images, and the tumoral masses were manually segmented. Measurements of lungs and tumor volumes were collected. A peripherality index was defined to describe tumor distance from the parenchyma. CFD simulations were performed in Fluent®, and the results were analyzed in terms of flow parameters and lobar volume flow rate (VFR). The predicted postoperative forced expiratory volume in 1s (ppoFEV1) was estimated and compared to the current clinical algorithm. The patients under analysis showed relatively small tumoral masses located close to the lung parenchyma. CFD results did not highlight lobar alterations of flow parameters, whereas the flow to the lung affected by the tumor was found to be significantly lower (p=0.026) than the contralateral lung. The estimation ppoFEV1 obtained through the results of the simulations showed a high correlation (ρ=0.993, p<0.001) with the clinical formula.Clinical Relevance- The proposed study establishes the efficacy and applicability of CFD for the pre-operative characterization of patients undergoing lobectomy surgery. This technique can provide additional information on local functionality and flow dynamics to support patients' operability.

A Multidisciplinary Evaluation of Patients with DMD in An Italian Tertiary Care Center.

With more widespread prolonged survival, Duchenne muscular dystrophy patients progressively experience multisystem complications. We retrospectively reviewed the charts of 132 Duchenne patients (112 alive/20 dead, age 3.5÷32.3 years) with the aims: 1) to provide a comprehensive description of the clinical status considering different aspects of the disease; 2) to propose a new scoring tool able to consider and pool together heterogeneous different functional. Five functions were analyzed: cardiac, respiratory, nutritional, ambulation and scoliosis. For each function, different items were considered and classified according to clinical severity (as indicated by international guidelines) and an incremental scoring was assigned. In addition, a global score incorporating all functions was defined. The scoring system confirmed that despite the significant protective role of steroids, all functions deteriorated with age. The severity of the global score became significantly higher since the age of 13 years. The severity of cardiac, respiratory and nutritional dysfunction was higher since 18 years. Deceased patients were characterized by significantly worse cardiac function, absence of steroid therapy and later use of respiratory assistive devices. The index proposed in this pilot study is a promising tool able to aggregate and correlate heterogeneous functions. It could become either an individual prognostic indicator of decline or a global score to evaluate changes in clinical trials therefore allowing multicenter studies, optimizing the management of both the primary and the secondary complications of the disease and understanding their relative impact.

Texture-based classification of lung disease patterns in chronic hypersensitivity pneumonitis and comparison to clinical outcomes.

Computer-aided detection algorithms applied to CT lung imaging have the potential to objectively quantify pulmonary pathology. We aim to develop an automatic classification method based on textural features able to classify healthy and pathological patterns on CT lung images and to quantify the extent of each disease pattern in a group of patients with chronic hypersensitivity pneumonitis (cHP), in comparison to pulmonary function tests (PFTs).27 cHP patients were scanned via high resolution CT (HRCT) at full-inspiration. Regions of interest (ROIs) were extracted and labeled as normal (NOR), ground glass opacity (GGO), reticulation (RET), consolidation (C), honeycombing (HB) and air trapping (AT). For each ROI, statistical, morphological and fractal parameters were computed. For automatic classification, we compared two classification methods (Bayesian and Support Vector Machine) and three ROI sizes. The classifier was therefore applied to the overall CT images and the extent of each class was calculated and compared to PFTs. Better classification accuracy was found for the Bayesian classifier and the 16x16 ROI size: 92.1±2.7%. The extent of GGO, HB and NOR significantly correlated with forced vital capacity (FVC) and the extent of NOR with carbon monoxide diffusing capacity (DLCO).Clinical Relevance- Texture analysis can differentiate and objectively quantify pathological classes in the lung parenchyma and may represent a quantitative diagnostic tool in cHP.

Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

BACKGROUND: Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). METHODS: In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. RESULTS: Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, p<0.001), while patients with PF and CF showed an increased breathing frequency (49+/-6 and 34+/-2/min, respectively) and decreased tidal volume (0.75+/-0.10 and 0.79+/-0.07 litres) (p<0.05). During exercise, end-expiratory chest wall and rib cage volumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. CONCLUSIONS: There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

Abdominal volume contribution to tidal volume as an early indicator of respiratory impairment in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterised by progressive loss of muscular strength that leads to an increasingly restrictive pulmonary syndrome. However, it is still not clear whether this determines alterations in the breathing pattern. We studied: 66 DMD patients at different stages of the disease (mean+/- sem age 12.6+/-0.6 yrs, range 5-22 yrs of age), subdivided into four groups according to age; and 21 age-matched healthy male controls. Spirometry, lung volumes and nocturnal oxygen saturation were measured in all DMD patients. Ventilatory pattern and chest wall volume variations were assessed by optoelectronic plethysmography during spontaneous breathing both in seated and supine positions. Whilst in a seated position, no significant differences were found between patients and controls or between different age groups. In the supine position, the average contribution of abdominal volume change (DeltaV(AB)) to tidal volume progressively decreased with age (p<0.001). The patients who showed nocturnal hypoxaemia showed significantly lower Delta V(AB). In conclusion, chest wall motion during spontaneous breathing in awake conditions and in supine position is an important indicator of the degree of respiratory muscle impairment in DMD. DeltaV(AB) is not only an important marker of the progression of the disease but is also an early indicator of nocturnal hypoxaemia.

Paradoxical movement of the lower ribcage at rest and during exercise in COPD patients.

Paradoxical inward displacement of the costal margin during inspiration is observed in many chronic obstructive pulmonary disease patients at rest but its importance is unclear. The current authors studied 20 patients (forced expiratory volume in one second 32.6+/-11.7, functional residual capacity 186+/-32% predicted) and 10 healthy controls at rest and during symptom-limited incremental exercise. With optoelectronic plethysmography, the phase shift between pulmonary and abdominal ribcage volumes and the percentage of inspiratory time the ribcage compartments moved in opposite directions were quantified, using control data to define the normal range of movement. Eight patients showed lower ribcage inspiratory paradox at rest (P+), while 12 patients did not (P-). This was unrelated to resting lung function or exercise tolerance. Total end-expiratory chest wall volume (EEV(cw)) increased immediately when exercise began in P+ patients, but later in exercise in P- patients. This difference in EEV(cw) was mainly due to a greater increase of end-expiratory pulmonary ribcage volume in P+ patients. During exercise, dyspnoea increased similarly in the two groups, while leg effort increased more markedly in the patients without paradox. In conclusion, lower ribcage paradox at rest is reproducible and associated with early-onset hyperinflation of the chest wall and predominant dyspnoea at end-exercise. When paradox is absent, the sense of leg effort becomes a more important symptom limiting exercise.

Efficacy of lung volume optimization maneuver monitored by optoelectronic pletismography in the management of congenital diaphragmatic hernia.

Newborns affected by congenital diaphragmatic hernia (CDH) need cardio-respiratory stabilization before undergoing surgical repair. Open lung strategy is a well-established approach to optimize lung volume in preterm infants with Respiratory Distress Syndrome (RDS), using both High Frequency Oscillatory Ventilation (HFOV) and Conventional Mechanical Ventilation (CMV). We report a case of left CDH with severe lung hypoplasia, managed applying open lung strategy in HFOV (pre-surgery period) and in Assist-Control with Volume Guarantee (post-surgery period), guided by SpO2 changes, TcPO2 and TcPCO2 monitoring. Opto-electronic plethysmography was used to measure end-expiratory chest wall volume changes (ΔEEcw) related to lung volume variations occurring during pressure changes. OEP confirmed the efficacy of using SpO2 and transcutaneous gas monitoring during this recruitment maneuver.

Effect of lung resection on pleuro-pulmonary mechanics and fluid balance.

The aim of the study was to determine in human patients the effect of lung resection on lung compliance and on pleuro-pulmonary fluid balance. Pre and post-operative values of compliance were measured in anesthetized patients undergoing resection for lung cancer (N=11) through double-lumen bronchial intubation. Lung compliance was measured for 10-12 cm H2O increase in alveolar pressure from 5 cm H2O PEEP in control and repeated after resection. No air leak was assessed and pleural fluid was collected during hospital stay. A significant negative correlation (r(2)=0.68) was found between compliance at 10 min and resected mass. Based on the pre-operative estimated lung weight, the decrease in compliance following lung resection exceeded by 10-15% that expected from resected mass. Significant negative relationships were found by relating pleural fluid drainage flow to the remaining lung mass and to post-operative lung compliance. Following lung re-expansion, data suggest a causative relationship between the decrease in compliance and the perturbation in pleuro-pulmonary fluid balance.

Spontaneous Breathing Pattern as Respiratory Functional Outcome in Children with Spinal Muscular Atrophy (SMA).

INTRODUCTION: SMA is characterised by progressive motor and respiratory muscle weakness. We aimed to verify if in SMA children 1)each form is characterized by specific ventilatory and thoraco-abdominal pattern(VTAp) during quiet breathing(QB); 2)VTAp is affected by salbutamol therapy, currently suggested as standard treatment, or by the natural history(NH) of SMA; 3)the severity of global motor impairment linearly correlates with VTAp. MATERIALS AND METHODS: VTAp was analysed on 32 SMA type I (SMA1,the most severe form), 51 type II (SMA2,the moderate), 8 type III (SMA3,the mildest) and 20 healthy (HC) using opto-electronic plethysmography. Spirometry, cough and motor function were measured in a subgroup of patients. RESULTS: In SMA1, a normal ventilation is obtained in supine position by rapid and shallow breathing with paradoxical ribcage motion. In SMA2, ventilation is within a normal range in seated position due to an increased respiratory rate(p<0.05) with reduced tidal volume(p<0.05) secondary to a poor contribution of pulmonary ribcage(%ΔVRC,P, p<0.001). Salbutamol therapy had no effect on VTAp during QB(p>0.05) while tachypnea occurred in type I NH. A linear correlation(p<0.001) was found between motor function scales and VTAp. CONCLUSION: A negative or reduced %ΔVRC,P, indicative of ribcage muscle weakness, is a distinctive feature of SMA1 and SMA2 since infancy. Its quantitative assessment represents a non-invasive, non-volitional index that can be obtained in all children, even uncollaborative, and provides useful information on the action of ribcage muscles that are known to be affected by the disease.Low values of motor function scales indicate impairment of motor but also of respiratory function.

Healthy and tumoral tissue resistivity in wild-type and sparc-/- animal models.

Despite the technological improvement of radiologic, endoscopic and nuclear imaging, the accuracy of diagnostic procedures for tumors can be limited whenever a mass-forming lesion is identified. This is true also because bioptical sampling cannot be properly guided into the lesions so as to puncture neoplastic tissue and to avoid necrotic areas. Under these circumstances, invasive and expensive procedures are still required to obtain diagnosis which is mandatory to plan the most appropriate therapeutic strategy. In order to test if electrical impedance spectroscopy may be helpful in providing further evidence for cancer detection, resistivity measurements were taken on 22 mice, 11 wild-type and 11 sparc-/- (knock out for the protein SPARC: secreted protein acidic and rich in cysteine), bearing mammary carcinomas, by placing a needle-probe into tumor, peritumoral and contralateral healthy fat areas. Tumor resistivity was significantly lower than both peritumoral fat and contralateral fat tissues. Resistivity in sparc-/- mice was lower than wild-type animals. A significant frequency dependence of resistivity was present in tissues analyzed. We conclude that accurate measurements of resistivity may allow to discriminate between tissues with different pathological and/or structural characteristics. Therefore, resistivity measurements could be considered for in vivo detection and differential diagnosis of tumor masses.

On the role of the acidic cluster Glu 92-94 of spinach ferredoxin I.

The role of the acidic cluster Glu 92-94 of spinach ferredoxin I in the interaction both with the photosystem I multisubunit complex and the ferredoxin-NADP+ reductase, either membrane-bound or purified, was studied by kinetic characterization of site-directed mutants. Three mutants of ferredoxin have been produced to evaluate the effects of elimination of one or two negative charges in the three specific positions of the acidic cluster. Kinetic characterization of the ferredoxin mutants E92A/E93A, E93A and E93A/E94A as electron carriers in the photosynthetic electron transport chain, allowed to establish that the two latter mutants were nearly indistinguishable from the wild-type protein in their ability to be photoreduced by photosystem I and as electron donor to the reductase in the NADP+ photoreduction with thylakoid membranes. The E92A/E93A ferredoxin mutant behaved very similarly to E92 mutants previously characterized. Thus, the elimination of the carboxyl groups adjacent to residue 92 did not further impaired ferredoxin I main function, i.e., as an electron carrier in NADP+ photoreduction. The two double mutants showed a reduced rate in the cross-linking of ferredoxin to the reductase promoted by a soluble carbodiimide, indicating an involvement of the acidic cluster in the formation of the active covalent complex between the two proteins.