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Biomedical subjects

A Harf

Publications and source records attributed to A Harf.

At least 73 records · Page 4Linked to original sources

CPAP titration by an auto-CPAP device based on snoring detection: a clinical trial and economic considerations.

This study aimed to assess the ability of an auto-nasal continuous positive airway pressure (nCPAP) device (REM + auto; NPBFD, Nancy, France) to predict the optimal constant nCPAP level. The apnoea/hypopnoea detection facility of the auto-nCPAP device was deliberately disabled and nasal mask pressure vibration detection was the only mode of pressure setting. The auto-nCPAP device was tested on 10 previously untreated patients with obstructive sleep apnoea during a single night, with ambulatory polysomnography performed in a conventional hospital room; the efficacy of the fixed pressure determined by the auto-nCPAP device was assessed by an ambulatory full polysomnography 2 weeks after the initiation of treatment at home. The fixed nCPAP pressure was effective (apnoea/hypopnoea and arousal indices <10 events x h(-1)) in all but two of the 10 patients studied. When the fixed nCPAP pressure was increased by 2 cmH2O in these two patients, sleep and respiration were normalized. Since only 12 ambulatory polysomnographic recordings were used to determine the effective nasal continuous positive airway pressure level, and as the device restored normal breathing and sleep in all 10 patients, it was concluded that this method of nasal continuous positive airway pressure titration may improve cost-effectiveness and reduce waiting lists in sleep laboratories.

Adult↗

Arterial blood pressure response to transient arousals from NREM sleep in nonapneic snorers with sleep fragmentation.

STUDY OBJECTIVES: To assess the hemodynamic effects of graded arousals during nonrapid eye movement (NREM) sleep in patients with partial upper airway obstruction during sleep without obstructive sleep apnea/hypopnea, overnight beat-to-beat BP was recorded in six patients. SETTING: At the end of each nonapneic obstructive event, EEG responses were graded as follows: grade 2, grade 1, and grade 0 were defined as increased high-frequency EEG lasting >15 s, 3 to 15 s, and no EEG arousals according to the American Sleep Disorders Association, respectively. MEASUREMENTS AND RESULTS: The following were observed during grade 0, 1, and 2 EEG patterns (mean+/-SD): systolic pressure increased by 7.1+/-1.5, 11.7+/-1.9, and 14.2+/-3.4 (p<0.005), respectively; diastolic pressure increased by 4.6+/-0.6, 6.7+/-1.7, and 9.4+/-3.0 (p<0.005), respectively; heart rate increased by 2.9+/-0.4, 3.9+/-2.2, and 8.6+/-4.6 (p<0.005), respectively. CONCLUSIONS: We conclude that nonapneic-nonhypopneic obstructive events are followed by arterial systemic pressure increases whose magnitude varies with the grade of the arousal.

Adult↗

Nasal airflow resistance measurement: forced oscillation technique versus posterior rhinomanometry.

This study was designed to determine whether nasal airflow resistance (Rn) which is nonlinear during tidal breathing, can be assessed by the forced oscillation (FO) technique. Rn values obtained by the FO technique and extrapolated to 0 Hz (Rn,FO) were compared to those assessed by posterior rhinomanometry at maximal tidal inspiratory flow (Rn,m), at a 0.5 L x s(-1) flow (Rn,F), and at a 1 hPa transnasal pressure (Rn,P). All Rn estimates were derived from the same inspiratory and expiratory nasal flow and transnasal pressure signals obtained during tidal nasal breathing whilst a forced flow was applied at the nose via a rigid nasal mask in 23 healthy volunteers, of whom 14 had additional measurements after vasoconstrictor treatment. In the basal state, no significant difference, and significant correlations (p<0.0001) were found between Rn,FO and the other Rn estimates. Only the regression line of Rn,FO versus Rn,m was not significantly different from the identity line. After nasal decongestion, Rn,P became significantly higher than the other Rn estimates (p<0.005). The regression line of Rn,FO versus Rn,m remained nonsignificantly different from the identity line. Similar results were observed regarding the percentage values of the different Rn estimates after decongestant treatment. This study shows that, despite its nonlinearity, Rn can be assessed by the FO technique, and that Rn,FO and Rn,m could be indifferently used as physiological indices of nasal patency. As the FO technique is more difficult to implement than the conventional rhinomanometry, its interest in rhinology appears not to be obvious.

Adrenergic alpha-Agonists↗

Nasal cavity geometry measured by acoustic rhinometry and computed tomography.

OBJECTIVE: To determine the significance of cross-sectional areas obtained by acoustic rhinometry. DESIGN: Comparison of data obtained by acoustic rhinometry and computed tomography (CT). SETTING: Outpatient clinic. PATIENTS: Nine adults with nasal obstruction due to turbinate hypertrophy. MAIN OUTCOME MEASURES: Acoustic rhinometry and CT were performed after nasal decongestion. The acoustic area-distance curve was analyzed based on 3 notches (A1, A2, and A3) corresponding to 3 local minimal areas. Computed tomographic measurements were made in the coronal plane at 0.5-cm intervals, and the narrowest sections in the anterior (S1), middle (S2), and posterior (S3) parts of the nasal cavity were selected. Mean specific section areas and volumes were computed by integration of the acoustic area-distance curves using the same procedure for the 2 methods. RESULTS: Significant correlations were found between acoustic and CT areas in the anterior nasal cavity (A1 vs S1, P < .001; A2 vs S2, P < .005). Acoustic and CT anterior volumes from A1 to A2 and from S1 to S2 were significantly correlated with each other (P < .005). No correlation was found between acoustic and CT areas measured at the posterior part of the nose (A3 vs S3). A weak correlation was evidenced between acoustic and CT posterior volumes from A2 to A3 and from S2 to S3 (P < .05). CONCLUSIONS: Acoustic rhinometry may be particularly well suited to the evaluation of anterior nasal geometry during clinical studies. At the posterior part of the nose, acoustic measurements may be of limited clinical relevance.

Acoustics↗

Assessment of high-frequency neonatal ventilator performances.

OBJECTIVE: To assess the efficacy and reliability of neonatal high-frequency ventilators. DESIGN: Bench evaluation of neonatal high-frequency ventilators. SETTING: Physiology department and university hospital neonatal intensive care unit. INTERVENTIONS: HFV-Babylog 8000 (Dräger Medical), OHF 1 (Dufour), and SensorMedics 3100A (Sensor-Medics) ventilators were connected to a neonatal test-lung. Tidal volume, peak-to-peak pressure amplitude, and mean airway pressure were measured for several ventilator settings, endotracheal tube sizes, and lung compliances. MEASUREMENTS AND RESULTS: Increasing peak-to-peak pressure resulted in a linear increase in tidal volume delivery in the 0-30% range of maximum amplitude. No significant increase in tidal volume was observed with the HFV-Babylog 8000 when pressure amplitude was above 50%. The maximum tidal volume delivered was substantially smaller with the HFV-Babylog 8000 than with the OHF 1 or SensorMedics 3100A. Tidal volume increased with endotracheal tube size with all three ventilators. Increasing test-lung compliance resulted in lower tidal volumes only with OHF 1. Decreasing mean airway pressure was responsible for a decrease in tidal volume delivery with HFV-Baby-log 8000. CONCLUSION: We found that under our test conditions two of the three ventilators delivered adequate tidal volumes at the usual frequency of 15 Hz, regardless of the size of the endotracheal tube and of the mechanical properties of the respiratory system. When lung compliance increased or mean airway pressure decreased, both of which are common events during the recovery phase of hyaline membrane disease, we found that the intrinsic properties of two of the ventilators tested were responsible for a decrease in tidal volume. This decrease may account for some cases of heretofore unexplained hypercapnia.

Critical Care↗

Sleep apnea-like syndrome induced by nitrous oxide inhalation in normal men.

To study the relationship between sedation and respiration under N2O, we performed polysomnographic recordings in 15 healthy men with documented normal breathing patterns during sleep. In a first study in five subjects, we found that 50% N2O in O2 compared to 50% O2 increased sleep latency to stage 2 (59 +/- 12 vs. 17 +/- 3 min), total sleep duration (59 +/- 12 vs. 26 +/- 11 min), depth of sleep and respiratory events during sleep (18 +/- 5 vs. 1 +/- 1/h of sleep). In a second study, ten subjects were exposed to N2O (30 and 50%) in O2 during two consecutive experimental periods. Eight subjects had EEG features of physiological sleep, but nevertheless exhibited a total of 181 respiratory events. Respiratory disturbance index (RDI) during sleep was similar under 30 and 50% N2O (25 +/- 7 and 25 +/- 5/h of sleep, respectively). Obstructive events predominated, except in three subjects during N2O 30% and one during N2O 50% exposure. We conclude that N2O can induce central and obstructive sleep apneas.

Administration, Inhalation↗

Carbon dioxide respiratory response during positive inspiratory pressure in COPD patients.

The aim of this study was to compare the effect of inspiratory pressure support (IPS) on the respiratory CO2 response in 13 stable COPD patients and in 13 normal subjects. Without IPS, the slopes of the ventilatory response to CO2 were lower in the patients than in the normal subjects (mean +/- SEM, 0.82 +/- 0.19 vs. 1.69 +/- 0.31 l.min-1.mmHg-1). When IPS was applied, both groups showed, at any level of end-tidal CO2 pressure, an increase in ventilation due to an increase in tidal volume (VT) associated with a decrease in occlusion pressure (P0.1). In addition, respiratory parameters (VE, VT, P0.1, inspiratory flow) were insensitive to CO2 as long as PETCO2 remained below a threshold which was slightly above the eupneic value. However, above this CO2-threshold, no differences in slopes were observed between the IPS and control conditions in either group, except for a decrease in the P0.1 slope during IPS in the COPD patients. In conclusion, IPS induced similar respiratory changes during CO2 response in stable COPD patients and in normal subjects. Above the eupneic value, IPS did not change the slope of the ventilatory response to CO2.

Adult↗

NéoGanesh: a working system for the automated control of assisted ventilation in ICUs.

Automating the control of therapy administered to a patient requires systems which integrate the knowledge of experienced physicians. This paper describes NéoGanesh, a knowledge-based system which controls, in closed-loop, the mechanical assistance provided to patients hospitalized in intensive care units. We report on how new advances in knowledge representation techniques have been used to model medical expertise. The clinical evaluation shows that such a system relieves the medical staff of routine tasks, improves patient care, and efficiently supports medical decisions regarding weaning. To be able to work in closed-loop and to be tested in real medical situations, NéoGanesh deals with a voluntarily limited problem. However, embedded in a powerful distributed environment, it is intended to support future extensions and refinements and to support reuse of knowledge bases.

Artificial Intelligence↗

Physiological effects of selective tibial neurotomy on lower limb spasticity.

OBJECTIVES: To assess by electrophysiology the effect of tibial selective neurotomy on muscle imbalance of the spastic ankle. METHOD: The amplitudes of the H reflexes, M responses (muscle contractions recorded after stimulation of the tibial nerve), and Hmax:Mmax ratio were recorded in 12 patients with chronic lower limb spasticity, before and one month after tibial selective neurotomy. Recordings were done on medial and lateral gastrocnemius and soleus muscles. Clinical evaluation was done with both global (Held's score) and analytical tests (step measurements, gait velocity, and ankle angulation during active and passive movements). RESULTS: After neurotomy, gait improved in all patients. Held's score of spasticity was better in all patients. Active dorsiflexion of the ankle was unchanged in three patients, but the others improved by 5 degrees to 12 degrees. Hmax, Mmax, and Hmax:Mmax ratios were lower. The Hmax on the gastrocnemius muscle, clinical strength, Mmax of all the muscles, and Hmax:Mmax ratio for the soleus and lateral gastrocnemius muscle were significantly lower after surgery. CONCLUSION: There was an improvement of clinical and electrophysiological spastic indices after selective tibial neurotomy. Neurotomy acted not only on motor neurons by decreasing strength, but also the reflex enlargement by decreasing sensory afferents.

Adolescent↗

Gelatinases in epithelial lining fluid of patients with adult respiratory distress syndrome.

Gelatinases A and B are matrix metalloproteinases secreted as inactive pro forms and are capable of degrading basement membrane components after activation in the extracellular environment. To determine whether the presence of gelatinases A (noninflammatory cells) and B (inflammatory cells) in epithelial lining fluid (ELF) is associated with the adult respiratory distress syndrome (ARDS), we studied 28 patients divided into four groups based on the presence of ARDS and/or multiple organ failure (MOF). Gelatinase activities were quantified in ELF using zymography. ARDS patients had larger ELF volumes than non-ARDS patients: 9.2 +/- 8.5 ml/100 ml recovered lavage fluid (n = 18) vs. 1.9 +/- 1.7 ml/100 ml (n = 11), respectively (P < 0.001). The presence of activated gelatinase A in ELF was a sensitive (16 out of 18 ARDS patients, 89%) and specific (0 out of 11 non-ARDS patients with or without MOF) marker for ARDS. Activated gelatinase (A + B) activities per microliter ELF were correlated with albumin concentrations in ELF (P < 0.01), and activated gelatinase activities in ELF were correlated with the volume of ELF (P < 0.0005). This could suggest an involvement of these gelatinases in alveolar-capillary permeability increase.

Adult↗

Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury in rats.

Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4 and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial partial pressure of O2 (PaO2)/fraction of inspired O2 (FIO2) during mechanical ventilation. The severity of lung injury in the two models was clearly different, since PaO2/FIO2 were approximately 400 mmHg in PYO- and LPS-induced injuries, respectively. Both contrast, alveolar neutrophil influx, unstimulated oxygen metabolite production, and proteinase (elastase, gelatinase B) secretions of ex vivo alveolar PMNs were not larger in the PYO model. Thus the difference in severity was not associated with variations in alveolar neutrophil recruitment or activation. Moreover, gelatinase and leukocyte elastase activities were absent in bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar spaces. We conclude that alveolar neutrophils are not sufficient to create severe respiratory failure.

Animals↗

Alveolar epithelial cells in vitro produce gelatinases and tissue inhibitor of matrix metalloproteinase-2.

Type II pneumocytes are key cells of the alveolar epithelium. They lie on the alveolar basement membrane, which influences their phenotype and functions. We hypothesized that type II pneumocytes degrade basement membrane components by producing gelatinases, members of the matrix metalloproteinase family. To investigate this hypothesis, we used primary cultures of rat type II pneumocytes and cultures of the human A549 cell line. We found by zymography that 70-kDa gelatinase was present in media conditioned by these cells. This 70-kDa gelatinase was identified as gelatinase A by a Western blot, and the presence of its mRNA was demonstrated by reverse transcription-polymerase chain reaction. A 95-kDa gelatinase could be induced under certain conditions. Production of gelatinases may take place during the turnover of basement membranes, in physiological and in pathophysiological processes. This was suggested by the increase in production of both gelatinases that we observed after in vitro exposure to LPS or interleukin-1. The presence of tissue inhibitors of matrix metalloproteinase-1 and -2 was also demonstrated, suggesting that degradation of extracellular matrix by type II pneumocytes is tightly regulated.

Animals↗

Divergent regulation of 92-kDa gelatinase and TIMP-1 by HBECs in response to IL-1beta and TNF-alpha.

In this study, we addressed the question of whether human bronchial epithelial cells (HBECs) contribute to the regulation of 92-kDa gelatinase activity by secreting tissue inhibitor of metalloproteinase (TIMP)-1. We investigated expression of 92-kDa gelatinase and TIMP-1 in response to lipopolysaccharide (LPS) and to the proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Confluent HBECs from explants were cultured in plastic dishes coated with type I and III collagen. We demonstrated that TIMP-1 was expressed at both the protein and mRNA levels by primary cultures of HBECs. Gelatin zymography of HBEC-conditioned media showed that exposure of HBECs to LPS, IL-1beta, or TNF-alpha induced a twofold increase in the latent form of 92-kDa gelatinase production, as well as its activation. Also, quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) demonstrated a twofold increase in the 92-kDa mRNA level in response to both cytokines. In contrast, TIMP-1 production evaluated by immunoblotting was unchanged in the presence of LPS and IL-1beta and was clearly decreased in the presence of TNF-alpha. Quantitative RT-PCR demonstrated that TIMP-1 mRNA levels remained unchanged in response to LPS or IL-1beta but decreased by 70% in the presence of TNF-alpha. All of these results strongly suggest that the control mechanisms regulating the expression of 92-kDa gelatinase and TIMP-1 by HBECs in response to inflammatory stimuli are divergent and result in an imbalance between 92-kDa gelatinase and TIMP-1 in favor of the metalloproteinase. Such an imbalance may contribute significantly to acute airway inflammation.

Breast↗

Modulatory effects of PKC activity on increased 92-kDa gelatinase secretion by neonatal alveolar macrophages.

We previously demonstrated that alveolar macrophages (AMs) from neonatal rats can secrete more 92-kDa gelatinase than AMs from adult rats. In this study, we investigated the role of the protein kinase C (PKC) pathway in the transductional regulation of 92-kDa gelatinase secretion by rat AMs, and we also evaluated maturational changes in this role with increasing postnatal age. After AM stimulation by phorbol 12-myristate 13-acetate (PMA), we observed a dose-dependent increase in gelatinase secretion that was significantly more marked in AMs from 6-day-old rats than in AMs from adult rats and that was inhibited by the PKC inhibitor calphostin C. Adenosine 3',5'-cyclic monophosphate mimetics or concanavalin A failed to induce an increase in gelatinase secretion by AMs. Time-dependent variations in PKC activity after PMA stimulation differed significantly between 6-day-old rats and adult rats; PKC activity decreased in adult AMs (50%) but remained stable in 6-day-old AMs. We therefore investigated age-related differences in the intracellular proteolytic degradation of PKC, which is thought to be mediated by calpains. Leupeptin, used as a calpain inhibitor, inhibited the decrease in PKC activity after exposure of adult AMs to PMA and induced a greater than threefold increase in PMA-induced gelatinase secretion. Calpain activity was significantly lower in AM extracts from 6-day-old than from adult rats. The physiological implication of these developmental changes in 92-kDa gelatinase regulation was demonstrated by investigation of AMs from 1-day-old rats that showed a high level of spontaneous PKC-dependent gelatinase secretion coexisting with very low calpain activity. We conclude that sustained PKC activity is a key factor in the increased gelatinase secretion by AMs seen during the postnatal period and is due, at least in part, to reduced PKC degradation.

Aging↗

Effects of chest wall counterpressures on lung mechanics under high levels of CPAP in humans.

We assessed the respective effects of thoracic (TCP) and abdominal/lower limb (ACP) counterpressures on end-expiratory volume (EEV) and respiratory muscle activity in humans breathing at 40 cmH2O of continuous positive airway pressure (CPAP). Expiratory activity was evaluated on the basis of the inspiratory drop in gastric pressure (DeltaPga) from its maximal end-expiratory level, whereas inspiratory activity was evaluated on the basis of the transdiaphragmatic pressure-time product (PTPdi). CPAP induced hyperventilation (+320%) and only a 28% increase in EEV because of a high level of expiratory activity (DeltaPga = 24 +/- 5 cmH2O), contrasting with a reduction in PTPdi from 17 +/- 2 to 9 +/- 7 cmH2O . s-1 . cycle-1 during 0 and 40 cmH2O of CPAP, respectively. When ACP, TCP, or both were added, hyperventilation decreased and PTPdi increased (19 +/- 5, 21 +/- 5, and 35 +/- 7 cmH2O . s-1 . cycle-1, respectively), whereas DeltaPga decreased (19 +/- 6, 9 +/- 4, and 2 +/- 2 cmH2O, respectively). We concluded that during high-level CPAP, TCP and ACP limit lung hyperinflation and expiratory muscle activity and restore diaphragmatic activity.

Adult↗

Ventilatory and hemodynamic effects of continuous positive airway pressure in left heart failure.

The ventilatory and hemodynamic effects of continuous positive airway pressure (CPAP) delivered via a face mask (at 0, 5, and 10 cm H2O, and after a return to 0 cm H2O) were studied in nine patients with acute left heart failure (pulmonary artery occlusion pressure [PAOP] > or = 18 mm Hg, and cardiac index [CI] < or = 2.8 L/min/m2). CPAP at 10 cm H2O induced an improvement in lung compliance (60 +/- 10 ml/cm H2O to 87 +/- 20 ml/cm H2O, p < 0.05) and in lung and airway resistance (5.7 +/- 1.0 cm H2O/L/s to 3.4 +/- 1.0 cm H2O/L/s, p < 0.05), a reduction in work of breathing (18 +/- 3 J/min to 12 +/- 2 J/min, p < 0.05), and in the pressure-time index of the respiratory muscles (279 +/- 22 cm H2O/s/min to 174 +/- 25 cm H2O/s/min, p < 0.05), without significant changes in breathing pattern. Despite a significant reduction in the negative swings in intrathoracic pressure (15.2 +/- 1.9 cm H2O to 10.8 +/- 1.8 cm H2O, p < 0.001), no significant change was observed in CI or stroke volume during CPAP. However, mean transmural filling pressures decreased significantly with CPAP, suggesting a better cardiac performance. Neither the level of stroke volume nor of PAOP, was predictive of changes in CI or in stroke volume. In patients with respiratory insufficiency caused by congestive heart failure (CHF), CPAP reduces respiratory muscle effort without altering cardiac output. The slight decrease in mean transmural left and right atrial pressures suggests an improvement in cardiac performance.

Adult↗

Pulmonary function in obese snorers with or without sleep apnea syndrome.

We evaluated pulmonary function abnormalities associated with the sleep apnea syndrome (SAS) in 170 habitual snorers without SAS (n = 62, apnea-hypopnea index [AHI] < 10 per hour of sleep), with moderately severe SAS (n = 56, 10 < or = AHI < 30) or with severe SAS (n = 52, AHI > or = 30). The three groups were similar regarding obesity (BMI approximately 30 kg.m-2) and smoking history (approximately 20 pack-years). Pulmonary function was assessed by spirometry, forced oscillation mechanics, and gas exchange studies. Forced expiratory flows decreased as the SAS severity increased (p < 0.001, p < 0.02, and p < 0.05 for FEF50, FEV1, and FEV1/VC, respectively). Multiple regression analysis showed that the correlation between FEV50 and the AHI persisted when smoking history was taken into account (p < 0.05), suggesting that SAS may be an independent risk factor for small airway disease. A highly significant correlation was found between specific respiratory conductance (sGrs) and the AHI (p < 0.0001). In a multiple regression analysis (p < 0.0001), variables that influenced sGrs were distal airway obstruction as assessed by FEV50 (p < 0.05), morphological upper airway abnormalities as assessed by cephalometric parameters (p < 0.02), and the AHI (p < 0.0005). SAS appears to be highly correlated to lower and upper airway obstruction, as demonstrated by a reduction in specific respiratory conductance, which adds to the increase in breathing load due to obesity.

Analysis of Variance↗