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Biomedical subjects

M P d'Ortho

Publications and source records attributed to M P d'Ortho.

At least 19 recordsLinked to original sources
PubMed2005

[Sleep apnoea syndrome and cardiac failure].

Despite recent therapeutic advances, chronic cardiac failure is still associated with a significant morbidity and mortality. Sleep apnoea syndrome is common in this population, affecting almost half of these patients. However, it is rarely diagnosed and treated. There are two types of sleep apnoea syndrome, which can sometimes co-exist: the obstructive apnoea syndrome with collapse of the upper airways, and the central apnoea syndrome with cyclical Cheyne-Stokes respiration, linked with anomalies of central control. Apnoea leads to sympathetic stimulation and an increase in the left ventricular post-charge which can alter cardiac function and the prognosis. Diagnosis of sleep apnoea syndromes is now made with small ambulatory oxymeters which do not disturb sleep and which allow precise detection of episodes of desaturation. Treatment with positive pressure ventilation brings an improvement in daytime symptoms (fatigue, drowsiness) as well as an improvement in cardiac function. Screening for sleep apnoea is thus essential in patients with chronic heart failure, especially in those resistant to optimal drug treatment, in order to improve their management.

Cheyne-Stokes Respiration↗
PubMed2003

Low levels of ventricular CSF orexin/hypocretin in advanced PD.

The origins of excessive daytime sleepiness in Parkinson disease (PD) are unclear. The authors hypothesize that orexin neurons, a recently identified wake promoting system, could contribute to its pathophysiology. They measured orexin-A/hypocretin-1 concentration in ventricular CSF in 19 parkinsonian patients and compared it with neurologic controls. Orexin levels were lower in patients and decreased with the severity of the disease. The authors suggest that orexin neurons contribute to daytime sleepiness in late stage PD.

Antiparkinson Agents↗
PubMed2002

Pathobiology of pulmonary arterial hypertension.

Recent years have witnessed important advances in the understanding of the pathophysiology of primary pulmonary hypertension (PPH). Both genetic and mechanistic studies have succeeded in identifying new molecular pathways relevant to the process of pulmonary vascular remodelling, which underlies PPH. Mutations in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now considered to be the genetic basis for familial PPH and approximately 30% of cases of sporadic PPH. The identification of the relevance of the BMP pathway to the aetiology of PPH now raises many questions about the link between the BMPR-II mutant genotype and the PPH phenotype. As PPH does not develop in all subjects with BMPR-II mutations, environmental or associated genetic factors may play a crucial role. Among these, the finding of an association between PPH and the L-allelic variant of the serotonin transporter (5-HTT) gene indicates that 5-HTT, which controls smooth muscle hyperplasia, probably contributes to susceptibility to PPH or is an important modifier of the PPH phenotype. Recognition of these molecular pathways should provide insight into the pathogenesis not only of primary pulmonary hypertension, but also of secondary forms of pulmonary hypertension. This should soon lead to the development of new and more selective therapeutic approaches to pulmonary hypertension.

Bone Morphogenetic Protein Receptors, Type II↗
PubMed2001

Increased expression of matrix metalloproteinase-9 in nasal polyps.

To investigate the role of gelatinases in nasal polyposis, a common and disabling airway disease characterized by chronic inflammation and tissue remodelling, matrix metalloproteinase-2 (MMP-2) and MMP-9 expression was investigated in the nasal polyps (NP) of 24 patients undergoing ethmoidectomy and compared with 15 control nasal mucosal (CM) samples obtained from snorers during turbinectomy. Tissue samples were either frozen for enzymatic analysis or paraffin wax-embedded for immunohistochemistry. Zymography and quantitative image analysis showed that MMP-9 active forms were significantly increased (p<0.05) in NPs compared to CM (44 +/- 40 versus 13 +/- 19x10(3) AU/10 microg protein), while MMP-2 expression was similar in both tissues. Concomitant studies of gelatinase immunoexpression showed that MMP-9 expression was enhanced (4- to 16-fold) in surface epithelium, glands (p<0.05), and submucosal inflammatory cells (p<0.05). In addition, MMP-9 positivity was markedly increased in endothelial cells (p<0.01). In situ zymography demonstrated marked gelatinolytic activity, consistent with the immunolocalization of MMP-2 and MMP-9. These results suggest up-regulation of active MMP-9 in the glands and vessels characteristic of NPs. It is concluded that MMP-9 may play a role in the upper airway remodelling observed during nasal polyposis.

Adult↗
PubMed2001

Abdominal muscle activity in sleep apnea during continuous positive airway pressure titration.

STUDY OBJECTIVES: The aim of this study was to investigate whether presence of expiratory abdominal muscle activity (EAMA) in obstructive sleep apnea syndrome (OSAS) patients during nasal continuous positive airway pressure (nCPAP) is due to either nCPAP overprescription or nCPAP underprescription. DESIGN: Airflow, esophageal pressure (Pes), and gastric pressure (Pga) were routinely measured during polysomnography aimed at determining the optimal nCPAP level, and the magnitude of EAMA was evaluated in relation to the nCPAP level and to the conventional indexes of upper-airway obstruction used during nCPAP titration. PATIENTS: The study was performed 12 patients with OSAS. RESULTS: Six patients displayed sustained EAMA, ie, EAMA lasting > 3 min, and characterized by a decrease in abdominal diameter and a paradoxical rise in Pga during expiration. In all six patients, EAMA decreased gradually as nCPAP neared optimal levels, and then disappeared when the optimal nCPAP level was achieved. The decrease in EAMA as nCPAP increased was associated with an increase in minute ventilation, decreases in both inspiratory and expiratory resistance, a decrease in Pes swing, and the normalization of the inspiratory flow contour. CONCLUSIONS: We conclude that the EAMA observed in some OSAS patients might be an indirect marker of upper-airway obstruction, and that the presence of EAMA during nCPAP titration might indicate a suboptimal nCPAP level rather than a deleterious effect of nCPAP.

Abdominal Muscles↗
PubMed2001

Combined effects of a nasal dilator and nasal prongs on nasal airflow resistance.

STUDY OBJECTIVES: Nasal prongs (NPs), when used to assess nasal flow, can result in dramatic increases in nasal airflow resistance (NR). The aim of this study was to investigate whether the NP-induced increases in NR could be corrected by the simultaneous use of an internal nasal dilator (ND). DESIGN: NR was estimated by posterior rhinomanometry, in the basal state (NRb), and while breathing with NP (NRp), with ND (NRd), and with both ND and NP (NRd + p). PARTICIPANTS: The study was performed in 15 healthy subjects. MEASUREMENTS AND RESULTS: NR (mean NRb [+/- SEM], 2.5 +/- 0.4 cm H(2)O/L/s) significantly decreased with ND (NRd = 1.4 +/- 0.2 cm H(2)O/L/s; p < 0.001) and significantly increased with NP (NRp = 3.8 +/- 0.8 cm H(2)O/L/s; p < 0.001). A significant logarithmic relationship was found between NRd and NRb (r(2) = 0.95; p < 0.0001), and a significant exponential relationship was found between NRp and NRb (r(2) = 0.99; p < 0.0001). While breathing with both ND and NP, NRd + p was significantly lower than NRb (1.9 +/- 1.4 cm H(2)O/L/s; p < 0.02). CONCLUSIONS: Our results demonstrate that the ND tends to slightly overcorrect the NP-induced increase in NR and suggest that, in view of the possible effects of NPs on upper airway resistance, the combination of both devices might be used for nasal airflow monitoring during nocturnal polysomnography in patients presenting with highly resistive nares.

Adult↗
PubMed2001

Use of glass capillaries avoids the time changes in high blood PO(2) observed with plastic syringes.

STUDY OBJECTIVES: In adults, arterial blood samples are usually drawn using plastic syringes. In contrast to glass syringes, plastic syringes let oxygen diffuse through their wall. This results in PO(2) changes during storage, especially when PO(2) is high. An alternative to glass syringes is the Microsampler (Roche Diagnostics; Schaffhausen, Switzerland), a commercially available device consisting of a heparinized glass capillary fitted with a 26-gauge needle and used to collect arterial blood in the same way as a plastic syringe fitted with a needle. DESIGN: We evaluated the performance of the Roche Microsampler for storing arterial blood in view of PO(2) measurement, comparatively with glass and plastic syringes. Five approximate initial PO(2) levels (650, 400, 200, 130, and 80 mm Hg) and two storage temperatures (ambient temperature and 4 degrees C) were studied. SETTINGS: Bench study. RESULTS: Plastic syringes allowed reliable measurement of PO(2) values when initial PO(2) was too low to ensure complete hemoglobin oxygen saturation, but were associated with time-dependent underestimation of PO(2) at higher initial PO(2) values. No such underestimation occurred with the Roche Microsampler stored at 4 degrees C for up to 1 h for all PO(2) levels studied. CONCLUSION: The Roche Microsamplers appeared to be reliable devices in preventing oxygen diffusion.

Blood Specimen Collection↗
PubMed2000

Inhibition of matrix metalloproteinases by lung TIMP-1 gene transfer or doxycycline aggravates pulmonary hypertension in rats.

Chronic hypoxic pulmonary hypertension (PH) results from persistent vasoconstriction, excess muscularization, and extracellular matrix remodeling of pulmonary arteries. The matrix metalloproteinases (MMPs) are a family of proteinases implicated in extracellular matrix turnover and hence in smooth muscle and endothelial cell migration and proliferation. Because MMP expression and activity are increased in PH, we designed the present study to investigate whether inhibition of lung MMPs in rats subjected to chronic hypoxia (CH) contributes to or protects against vascular remodeling and PH. To achieve lung MMP inhibition, rats exposed to 10% O(2) for 15 days were treated with either doxycycline (20 mg/kg per day by gavage starting 2 days before and continuing throughout the CH period) or a single dose of recombinant adenovirus (Ad) for the human tissue inhibitors of metalloproteinases-1 (hTIMP-1) gene (Ad.hTIMP-1, 10(8) plaque-forming units given intratracheally 2 days before CH initiation). Control groups either received no treatment or were treated with an adenovirus containing no gene in the expression cassette (Ad.Null). Efficacy of hTIMP-1 gene transfer was assessed both by ELISA on bronchoalveolar lavages and by hTIMP-1 immunofluorescence on lung sections. MMP inhibition in lungs was evaluated by in situ zymography and gelatinolytic activity assessment using [(3)H]gelatin. Rats treated with either doxycycline or Ad.hTIMP-1 had higher pulmonary artery pressure and right heart ventricular hypertrophy more severe than their respective controls. Worsening of PH was associated with increased muscularization and periadventitial collagen accumulation in distal arteries. In conclusion, our study provides compelling evidence that MMPs play a pivotal role in protecting against pulmonary artery remodeling.

Animals↗
PubMed2000

Nasal obstruction as a risk factor for sleep apnoea syndrome.

Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p<0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p<0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.

Airway Resistance↗
PubMed2000

Predictive value of pulmonary function parameters for sleep apnea syndrome.

Nocturnal polysomnography is the standard diagnostic test for sleep apnea syndrome (SAS) but is both expensive and time-consuming. We developed a predictive index for SAS based on pulmonary function data, including respiratory resistance determined by the forced oscillation technique, from 168 obese snorers with suspected SAS. Our model used logistic regression to obtain case-by-case predictions of the probability of SAS, defined as an apnea-hypopnea index (AHI) > or = 15 during overnight polysomnography. We then tested our model in a prospective group of 101 similar patients. Specific respiratory conductance and daytime oxygen saturation contributed significantly to the model. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the index computed from these parameters were 98%, 86%, 90%, and 97%, respectively. In the prospective group, the model proved repeatable, with 100% sensitivity, 84% specificity, 86% PPV, and 100% NPV. The high NPV may help to identify obese snorers with a SAS risk that is so low as to make polysomnography unnecessary. Based on the 50% prevalence of SAS in our study and on the fact that polysomnography is required in all patients with daytime somnolence, we calculated that using our model would have obviated the need for polysomnography in 38% of our patients.

Female↗
PubMed2000

Effects of mandibular advancement on respiratory resistance.

Mandibular advancing devices are proposed as nonsurgical treatment for certain patients with an obstructive sleep apnoea syndrome. Since they act by increasing the upper airway calibre, the aim of the present study was to investigate the changes in respiratory resistance (Rrs) resulting from mandibular advancement. Rrs was measured at the nose by the forced oscillation technique (4-32 Hz). Ten normal subjects were studied under three conditions: resting mandibular position, passive mandibular advancement steadied by a wax bite, and voluntary advancement, in random order. Respiratory resistance was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression analysis of respiratory resistive impedance versus frequency. R0 (mean+/-SEM=3.5+/-0.2 cmH2O x L(-1) x s in the resting position) decreased significantly with passive advancement (2.9+/-0.2 cmH2O x L(-1) x s, p<0.001), but remained unchanged with voluntary mandibular advancement (3.6+/-0.2 cmH2O x L(-1) s). Similar results were obtained for R16. The results of this study demonstrate that the effects of mandibular advancement on upper airway resistance differ, depending on whether advancement is passive or active, and suggest that in order to simulate the actual effects of therapeutic devices, mandibular advancement should be passive.

Adult↗
PubMed2000

Effects of nasal prongs on nasal airflow resistance.

STUDY OBJECTIVES: The aim of this study was to investigate whether nasal prongs, which have been proposed to assess nasal flow during sleep, affect nasal airflow resistance (NR). DESIGN: NR was estimated by posterior rhinomanometry at a 0.5 L/s flow, under eight conditions: in the basal state, and with seven different nasal prongs. PARTICIPANTS: The study was performed in 17 healthy supine subjects, 8 of whom had basal NR values within the normal range (< or = 2 cm H(2)O.L(-1).s, group 1), and 9 had increased basal NR values (> 2.5 cm H(2)O.L(-1).s, group 2), because of nare narrowness and/or deviated nasal septum. MEASUREMENTS AND RESULTS: NR increased significantly while breathing with nasal prongs (p < 0.0001 in both groups). The changes in NR (DeltaNR) induced by the different nasal prongs were characterized by large intersubject and intrasubject variability, with a maximum DeltaNR of 24.2 cm H(2)O.L(-1).s. Significant differences were found between the DeltaNR induced by the different nasal prongs (p < 0.001 in group 1, and p < 0.0003 in group 2), and for six of them, DeltaNR was significantly higher in group 1 than in group 2 (p < 0.02). CONCLUSIONS: This study demonstrates that nasal prongs can markedly increase NR in subjects presenting with nare narrowness and/or deviated nasal septum. Further investigations that would include nocturnal polysomnography are still required to evaluate the possible influence of nasal prongs on the diagnosis of obstructive sleep apnea syndrome and its severity.

Adult↗
PubMed2000

Constant vs. automatic continuous positive airway pressure therapy: home evaluation.

STUDY OBJECTIVES: To compare the efficacy and patient tolerance, compliance, and preference between auto-continuous positive airway pressure (CPAP) and constant CPAP. DESIGN: Single-blinded, crossover, cohort study of consecutive patients with obstructive sleep apnea syndrome, with two treatment periods of 2 months each. PATIENTS: Twenty-five patients (22 men, 3 women) with sleep apnea syndrome confirmed by ambulatory polysomnography. MEASUREMENTS AND INTERVENTIONS: After baseline polysomnography, patients underwent in-laboratory polysomnography for titration of constant CPAP. The order of treatment was randomly allocated, either auto-CPAP and then constant CPAP, or vice versa. The auto-CPAP pressure range was 6 to 16 cm H(2)O. At the end of each 2-month period, patients underwent a control ambulatory polysomnography and received a questionnaire on subjective well-being and device evaluation. Duration of use was checked through CPAP device monitoring. RESULTS: No differences were found in apnea/hypopnea index (constant CPAP, 9.7+/-1.9 events/h vs auto-CPAP, 10.6+/-9.3 events/h), awakening/arousal index (constant CPAP, 13.7 +/- 8.0 events/h vs auto-CPAP, 15.5 +/- 8.9 events/h), slow-wave sleep duration, nocturnal saturation, or complaint of daytime sleepiness. The mean pressure required was significantly lower during auto-CPAP than during constant CPAP (8.8+/-1.8 cm H(2)O vs. 9.7+/-2.6 cm H(2)O, respectively). Patient tolerance, compliance, and duration of use were similar with both treatments. CONCLUSIONS: Auto-CPAP is as effective as constant CPAP. A wide pressure range for auto-CPAP can be used in all patients, suggesting that, in the future, use of a broad pressure range in the auto-CPAP mode could obviate the need for the titration night.

Circadian Rhythm↗
PubMed1999

Accuracy of the i-STAT bedside blood gas analyser.

The performance of the i-STAT portable clinical analyser for measuring blood gases and pH was evaluated with reference to a conventional blood gas analyser (ABL520 Radiometer). Ninety-two samples from the routine blood gas analysis laboratory were chosen according to a wide distribution of partial pressure of carbon dioxide (Pa,CO2), partial pressure oxygen (Pa,O2) and pH and then analysed. All measurements were performed in duplicate by trained technicians from the central hospital laboratory. Differences between duplicate measurements were computed for Pa,CO2: (1.2 versus 0.4%), Pa,O2 (1.7 versus 1.1%) and pH (0.06 versus 0.02%), for the i-STAT and ABL520, respectively. pH and Pa,CO2 values measured with the i-STAT were very close to those obtained with the ABL520, the difference (mean+/-SD) being 0.006+/-0.018 and -0.13+/-0.17 kPa, respectively. Statistical analysis showed that the differences between analysers did not depend on values of pH or Pa,CO2. The performance of the analysers depended on the level of PO2. Below 15 kPa (n=48), the two systems gave nearly identical values, the mean difference was 0.01+/-0.37 kPa. Between 16 and 55 kPa (n=44), there was a systematic but small (-0.69+/-0.67 kPa) underestimation of Pa,O2 measured with the i-STAT (p<10(-8)). In conclusion, this study shows that blood gas analysis using the i-STAT portable device is comparable with that performed by a conventional laboratory blood gas analyser.

Blood Gas Analysis↗
PubMed1999

Protruding the tongue improves posterior rhinomanometry in obstructive sleep apnoea syndrome.

In posterior rhinomanometry (PRM), oropharyngeal pressure is measured using a tube placed between the tongue and the hard palate. For valid results the patient must position the tongue and soft palate so that both the oropharynx and nasopharynx remain open. A high rate of failure of conventional PRM has been reported in normal individuals. In patients with obstructive sleep apnoea syndrome (OSAS), upper airway abnormalities may further increase the failure rate. This study proposes a modification of the technique in which protrusion of the tongue enhances pressure transmission between the nasopharynx and the mouth. In eight normal subjects, resistance was similar when measured by both methods. Of 24 OSAS patients, conventional PRM was unsuccessful in 11. In the remaining 13 patients, a significant correlation between the two methods was found, but resistance was lower by "tongue-out" than by conventional PRM, consistent with a decrease, during tongue protrusion, in retropalatal resistance, which is a component of the "nasal" resistance measured by PRM. In 26 OSAS patients, unilateral nasal resistance values measured by "tongue-out" PRM were similar to those measured by anterior rhinomanometry. When the "tongue-out" method was used routinely in 541 snorers, failure rates were 1.1% in the 272 non-OSAS patients and 3.7% in the 269 OSAS patients. These results indicate that posterior rhinomanometry with tongue protrusion is a highly effective tool for measuring nasal resistance in snorers.

Adolescent↗
PubMed1999

Role of collagenase in mediating in vitro alveolar epithelial wound repair.

Type II pneumocytes are essential for repair of the injured alveolar epithelium. The effect of two MMP collagenases, MMP-1 and MMP-13 on alveolar epithelial repair was studied in vitro. The A549 alveolar epithelial cell line and primary rat alveolar epithelial cell cultures were used. Cell adhesion and cell migration were measured with and without exogenous MMP-1. Wound healing of a cell monolayer of rat alveolar epithelial cell after a mechanical injury was evaluated by time lapse video analysis. Cell adhesion on type I collagen, as well as cytoskeleton stiffness, was decreased in the presence of exogenous collagenases. A similar decrease was observed when cell adhesion was tested on collagen that was first incubated with MMP-1 (versus control on intact collagen). Cell migration on type I collagen was promoted by collagenases. Wound healing of an alveolar epithelial cell monolayer was enhanced in the presence of exogenous collagenases. Our results suggest that collagenases could modulate the repair process by decreasing cell adhesion and cell stiffness, and by increasing cell migration on type I collagen. Collagen degradation could modify cell adhesion sites and collagen degradation peptides could induce alveolar type II pneumocyte migration. New insights regarding alveolar epithelial cell migration are particularly relevant to investigate early events during alveolar epithelial repair following lung injury.

Animals↗