Thesis (Ph. D.)--University of California, San Diego, 2000. / Vita. Includes bibliographical references (leaves 117-133).

The diagnosis of obstructive sleep apnea (OSA) syndrome is overnight PSG (mutli-channel system). But it¡¦s hard to be popularized for the general population (about twenty channel signals). In recent decades, several researches were devoted to a replacement system with only one channel signal (oxyhemoglobin saturation). However, it¡¦s hard to match PSG system¡¦s report without EEG wake information. Consequently, two channels (oxyhemoglobin saturation and EEG) were used of this study to enhance the AHI (estimation index for sleep apnea) prediction performance. After surveying the most recent studies, this work proposes a new basleline removal technique for oxygen saturation signal (SpO2) by using median filter. It was proved this technique improves the diagnostic accuracy for OSA. Furthermore, it is also found that by removing the wake periods, diagnostic accuracy can be improved further. By counting the number of times that the desaturation level has dropped more than 2% for at least 3 seconds, the correlation coefficient between AHI and proposed feature is 0.9218. In addition, by removing the wake period, this correlation increases to 0.9425. By using this feature to classify patients with AHI value larger than 5, the proposed approach achieves 93.78% accuracy, 95.94% sensitivity, 78.87% specificity f. Such results demonstrate the feasibility of using single SpO2 channel system for OSA diagnosis.

Solitary extramedullary plasmacytomas are uncommon neoplasms. They occur most frequently in the upper aerodigestive tract and account for 4% of the nonepithelial tumors in this site. The evolution of a plasmacytoma is unsteady and symptoms at presentation have included dystonia, dysphagia, oral pain, cough, and dyspnea on exertion. Plasmaeytoma of the upper aerodigestive tract has not been previously reported as a cause of obstructive sleep apnea.

No description available.

In recent years, sleep medicine has attracted many interests. Among many sleep disorder problems, the sleep apnea syndrome is of great importance. One of its side effects is its negative influences on cardiovascular system whose function can be monitored by ECG. The regulation of the heart rate is extremely important for human body. In general, the heart rate variability is controlled by the balance of the sympathetic and the parasympathetic systems whose functions can be influenced by sleep apnea. This work tries to establish the relation between the heart rate variability and AHI (Apnea & hypopnea index). Through the statistical methods, we analyze how the sleep apnea influences the low frequency (LF) and high frequency components of the RR intervals. With BMI, age and AHI as the independent variables, we set up the regression model to predict LF/HF Our results demonstrate that, for men, the linear relationship between the LF/HF and AHI is statistically significant when AHI is higher than 45. This results may shed some light on developing HRV based diagnosis method for sleep apnea.

The physiological signals of human are very important for the diagnosis of diseases. There are two different applications of physiological signals in this study. One is using oxyhemoglobin saturation to diagnose the obstructive sleep apnea hypopnea syndrome (OSAS); the other is to determine the association between dermatoglyphics and schizophrenia by using fingerprint asymmetry measures. The objective of the first part is to comprehensively evaluate the capablity and reliability of the previously proposed oxyhemoglobin indices derived automatically for predicting the severity of OSAS. Patients with a diagnosis of OSAS by standard polysomnography were recruited from China Medical University Hospital Sleep Center. The result revealed that when AHI cutoff value was set to 30/h, ODI achieves 87.8% sensitivity and 96.6% specificity. Another important finding is that, for both apnea and hypopnea, probability of oxyhemoglobin desaturation increases with increases of body mass index (BMI) and neck circumference (NC). Early detection and intervention strategies for schizophrenia are receiving increasingly more attention. Dermatoglyphic patterns have been hypothesized to be indirect measures for early abnormal developmental processes that can lead to later psychiatric disorders such as schizophrenia. However, previous results have been inconsistent in trying to establish the association between dermatoglyphics and schizophrenia. The goal of second part of this work is to try to resolve this problem by borrowing well developed techniques from the field of fingerprint matching. Fingerprint images were acquired digitally from 40 schizophrenic patients and 51 normal individuals. Based on these images, the sample means of the proposed measures consistently identified the patient group as having a higher degree of asymmetry than the control group.

Techniques ambulatoires de diagnostic et de monitoring des troubles respiratoires liés au sommeil.Le syndrome d’apnées obstructives du sommeil (SAOS) est un trouble du sommeil très fréquent, fortement lié à l’obésité, ce qui explique sa prévalence en pleine expansion. En parallèle, la demande d’examens polysomnographiques (PSG) en laboratoire du sommeil, méthode diagnostique de référence, est en croissance. Comme l’accès à cette technique est peu aisé, de nombreux appareils simplifiés d’enregistrement de sommeil ont été récemment développés, mais restent imparfaits (mauvaise évaluation du temps de sommeil, sous-estimation de la sévérité du SAOS, faux négatifs, taux d’échec élevé) et sont d’un apport limité pour le diagnostic du SAOS. La PSG au domicile (PSG-d) est une alternative bien plus informative, permettant d’éviter nombre des désavantages rencontrés par l’usage d’appareils simplifiés. Nous l’avons dès lors étudiée pour le diagnostic du SAOS, au travers d’une étude randomisée comparant la PSG-d vs la PSG hospitalière. En termes d’efficacité diagnostique, les résultats sont excellents, avec un faible taux d’échec d’examens à domicile (4.7 vs 1.5%). Les patients préfèrent être enregistrés dans leur propre environnement où la qualité de leur sommeil est d’ailleurs meilleure. Nous avons ensuite voulu faire le point sur la littérature récente au travers d’un article de revue, en analysant les études prospectives randomisées comparant la PSG-d et au labo du sommeil. Les résultats de ces études concordent pour démontrer que la PSG-d constitue une excellente alternative aux tests réalisés à l’hôpital. Outre le SAOS, l’outil permet le diagnostic d’autres troubles du sommeil, comme les mouvements périodiques des jambes durant le sommeil, les troubles du rythme circadien, Une question restée jusqu’ici sans réponse était l’influence de la localisation du branchement des PSG-d, à l’hôpital ou à domicile. Une étude prospective randomisée nous a permis d’établir que la localisation du branchement des PSG-d n’influençait pas la qualité globale de l’examen, ce qui simplifiera l’utilisation de cet outil à l’avenir. Enfin, nous avons utilisé des techniques de télé monitoring (TM) pour contrôler, en temps réel, la qualité des PSG-d. Dans une première étude pilote, la faisabilité a été confirmée, malgré quelques difficultés techniques. Nous avons voulu appliquer la technique à une population de patients souffrant d’un syndrome coronarien aigu, incapables d’être enregistrés au labo du sommeil. Nous avons étudié la qualité du screening du SAOS par PSG vs polygraphie (PG). Les résultats se sont révélés surprenants :82% de cette population présentait des troubles respiratoires liés au sommeil, principalement centraux. La PSG était nettement plus sensible que la PG, et le TM améliorait la qualité des PSG. Chez les patients traités pour SAOS, nous avons ensuite utilisé un outil de monitoring, l’actigraphie (Act), afin d’observer, dans la vie de tous les jours, les changements de schémas de sommeil et d’activité physique engendrés par la pression positive continue (PPC). Dans un premier travail, rétrospectif, nous avons observé ces paramètres chez des SAOS avant traitement, puis au travers d’une étude prospective multicentrique, nous avons suivi 150 patients avant et après PPC, et observé chez eux une augmentation de temps de sommeil, mais pas de l’activité physique. En conclusion, nous avons démontré dans cette thèse l’intérêt clinique de deux excellents outils ambulatoires, la PSG-d et l’Act, pour la prise en charge du SAOS. Les implications potentielles sont une meilleure accessibilité diagnostique pour le SAOS, une initiation thérapeutique plus précoce et un suivi plus précis des SAOS traités, dans des conditions ambulatoires, plus confortables et plus adéquates pour les patients. / Ambulatory diagnostic and monitoring techniques for sleep disordered breathingSleep disordered breathing (SDB), including obstructive sleep apnea syndrome (OSAS), is directly related to obesity. Significant morbi-mortality is associated with OSAS, explaining the increasing demand for in-hospital polysomnography (PSG), the reference diagnostic method. As this technique is complex and time-consuming, many simplified portable monitoring (PM) devices for home sleep testing have been developed. However, the ability of PM devices to detect OSA remains limited: sleep time is not correctly assessed, OSA severity is underestimated, false negative results occur and the failure rate of the tests is high, up to 30%. Home-PSG (H-PSG) is an interesting alternative, avoiding many of these drawbacks. In the first part of this work, we studied the tool in an original study comparing H-PSG and in-lab PSG. Diagnostic efficacy was good and the failure rate low (4.7 vs 1.5%). Patients slept in their own environment and thus sleep quality was better. We were then interested by reviewing recent literature data regarding prospective randomised trials comparing H-PSG and in-lab PSG. We concluded that H-PSG is an excellent alternative for in-lab PSG, allowing not only OSA detection but also diagnosis of a large panel of other sleep disorders (periodic leg movements during sleep, circadian disorders,). As the best place to perform set-up for H-PSG remained unknown, we studied, in another prospective randomised study, the recording’s quality obtained in both settings. As no difference was observed, lab set up was found to be the simpler option for performing H-PSG. We then tested, in a prospective pilot study, real-time telemonitoring (TM) of H-PSG in order to enhance recording quality. Results were encouraging but we faced some technical problems. In a second study, we applied TM coupled with PSG to detect SDB in acute coronary syndrome, in patients too unstable to come in the sleep lab. We compared also PSG results to polygraphy (PG). Surprisingly, 82% of patients suffered from SDB. PSG was much more sensitive than PG to screen SDB in this population and TM improves recording quality. In the second part of this work, we have used actigraphy (Act) to assess sleep and physical activity in OSA patients in real-life conditions. Firstly, in a retrospective study, we documented these parameters before treatment. In a second multicentre study, we evaluated the changes in sleep schemes and physical activity under continuous positive airway pressure (CPAP) in 150 OSA patients. We observed that sleep time was increased under CPAP, but physical activity was not improved, contrarily to sleepiness and quality of life. In conclusion, we have shown through these works the clinical interest of two excellent ambulatory tools, H-PSG and Act, for OSA management. Potential clinical implications include enhanced healthcare accessibility, earlier treatment initiation and a closer follow-up of treated patients, through ambulatory tools, in a comfortable environment for the patients. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Obstructive sleep apnea syndrome (OSAS) is a serious disorder that affects an estimated 24% of middle-age males, and 9% of middle-aged females. In addition, a large portion of individuals with OSAS go undiagnosed. OSAS is associated with several adverse health problems, including the metabolic syndrome. Therefore, there is a clear need to identify new methods for assessing OSAS risk. The exercise test has been used effectively as a diagnostic and prognostic tool for those at high risk for cardiovascular disease and hypertension. Research into the cardiopulmonary responses to exercise testing in young adult men with OSAS has not been examined. Objectives: The objectives of this study were to: 1) evaluate whether OSAS is characterized by exaggerated ventilatory responses to ramp exercise testing, with a secondary aim to evaluate if variations in serum leptin concentration might exert a regulatory in ventilatory responses during exercise; 2) To evaluate whether autonomic control of the cardiovascular response during exercise is distorted by OSAS in young overweight men, as manifested by a blunting of heart rate and exaggeration of blood pressure responses.; 3) To explore whether various simple clinical measures and response patterns from graded exercise testing might serve to discriminate between young men with and without OSAS. Methods: For objectives one and two, 14 obese men with OSAS [age = 22.4 ± 2.8; body mass index (BMI) = 32.0 ± 3.7; apnea-hypopnea index (AHI) = 22.7 ± 18.5], 16 obese men without OSAS (age = 21.4 ± 2.6; BMI = 31.4 ± 3.7), and 14 normal weight subjects (objective 2) (age = 21.4 ± 2.1; BMI = 22.0 ± 1.3) were recruited. For objective three, 91 men (age = 21.6 ± 2.8; AHI range = 0.6 – 60.5; BMI range = 19.0 – 43.9) were recruited. Subjects completed a ramp cycle ergometer exercise test, and a fasting blood sample was obtained to measure plasma leptin and blood lipid levels. Repeated measures ANOVA and stepwise linear regression was used to examine objectives 1 and 2. For objective 3, stepwise linear regression and receiver operator curve (ROC) analysis was utilized. Results: Ventilation (VE), the ventilatory equivalents for oxygen (VE/VO₂) and carbon dioxide (VE/VCO₂) were greater in the OSAS subjects vs. the overweight subjects without OSAS (P = 0.05, P < 0.05 and P < 0.005, respectively) at all exercise intensities. Heart rate (HR) recovery was attenuated in the overweight OSAS subjects compared to the No-OSAS and Control groups throughout 5 minutes of active recovery (P = 0.009). Oxygen uptake, HR, and blood pressure did not differ throughout exercise. Leptin was not associated with ventilatory responses at any exercise intensity. Linear regression analysis revealed hip-to-height ratio (HHR), hip circumference (HC), triglyceride levels, and recovery systolic blood pressure ratio (SBPR) at 2 and 4 minutes were independent predictors of AHI (model fit: R² = 0.68, p <0.0001). ROC analysis determined that percent body fat, HHR, and recovery HR at 2 minutes and 4 minutes were the best single predictors of OSAS risk (AUC = 0.77 for each measure, p = 0.003). Conclusions: Unique ventilatory and hemodynamic characteristics to maximal exercise testing are exhibited in young men with OSAS. These characteristics may be related to alterations in the sympathetic nervous system and chemoreceptor activation, and may be early clinical signs in the progression of OSAS. These exercise characteristics, along with anthropometric and body composition measures may provide useful information in identifying young men at risk for OSAS. / Ph. D.

Background and Purpose: Little is known about influences of obstructive sleep apnea syndrome (OSAS) on dietary intake and body composition. The purpose of this study was to evaluate dietary status, body fat distribution and leptin in overweight young men with and without OSAS in comparison to published values for normal weight counterparts. Methods: Groups were comprised of 24 sedentary overweight young men with and without OSAS, who had a body mass index (BMI) greater than 25 kg/m². Serum leptin concentration was measured in the 24 subjects using radioimmunoassay, while OSAS assessment was done using nighttime home somnography. Analysis of 4-day diet recalls was performed using Nutritionist Pro (First DataBank, Inc., San Bruno, CA). A Healthy Eating Index (HEI) score was calculated for the 24 overweight subjects. Results: There were no differences between the two overweight groups for total fat mass, central abdominal fat, BMI, waist circumference, leptin, or the HEI. The HEI was not predictive of overall OSAS severity; however, BMI was moderately related to OSAS severity (r = 0.39; p=0.05). The normal weight group did have a 50% higher report of carbohydrate intake, and consumed on average, 500 more kilocalories per day. The normal weight group consumed 50% less sodium, and 50% more Vitamin's C and E including a 13% increase in the HEI. Conclusions: Regulation of eating behavior and related influences on diet composition may be affected by a number of neurohormonal disturbances associated with OSAS and/or obesity, itself. Further research is needed to quantify these possible differences on dietary status and the underlying mechanism involved. / Master of Science

Obstructive sleep apnea syndrome (OSAS) is a complex disorder characterized by repetitive bouts of upper airway collapse during sleep, causing subsequent intermittent hypoxia, hypercapnia, and fragmented sleep and is also associated with significant morbidity including daytime sleepiness, hypertension, and elevated cardiovascular risk. OSAS affects at least 4% of men and 2% of women; unfortunately, it is estimated that 80% to 90% of adults with OSAS remain undiagnosed. Both clinical characteristics and complex genetic and environmental interactions have made it difficult to understand OSAS disease etiology and identifying patients at risk is still elusive. A pattern of gene expression in cells or tissues related to a disease state for OSAS would provide beneficial information to be most effective in screening or diagnosing this disease. Objectives: The objectives of this study were to: 1) map out the study design and bench assay strategies by which to investigate this issue; 2) find out if there are specific differences in the global gene expression profiles of adult females with OSAS compared to those without OSAS, under conditions in which subjects were clinically similar (BMI, diabetes, cardiovascular disease, etc.); and 3) assess the protein expression differences that could potentially be linked via well-established molecular pathways associated with any differences found in global gene expression profiles in the presence and absence of OSAS. Methods: Subjects were overweight premenopausal Caucasian women with untreated OSAS (n=6; age = 40.7 ± 3.4; BMI = 49.04 ± 6.97; apnea-hypopnea index = 27.3 ± 16.02), and control subjects (n=10) (age = 38.2 ± 7.6; BMI = 47.94 ± 6.15; apnea-hypopnea index < 5), and matched for other clinical characteristics (diabetes, cardiovascular disease status, medications, etc.) recruited from either Carilion Clinic Pulmonary/Sleep Medicine or Carilion Clinic Bariatric Surgery practices. Subjects provided a fasting blood sample in which the monocytes were isolated from whole blood. The RNA was extracted from the monocytes, assessed for purity and quantity, frozen and shipped to collaborators at Dana-Farber Cancer Institute and hybridized to Affymetrix whole human genome chips on a gene chip. The initial computational evaluation and interpretation generated the hypothesis. Two-step quantitative real time polymerase chain reaction (qPCR) was performed to verify the results from the microarray analysis. The laminin enzyme immunoassay (EIA), and cellular adhesion assays were performed to determine if genomic changes resulted in proteomic and phenotypic assessments. Results: OSAS subjects had nine aberrantly regulated genes, of which three genes (LAMC-1, CDC42, and TACSTD2) showed a pattern in segregation between OSAS and controls subjects based on expression patterns. In addition, qPCR indicated a 2.1 fold increase in LAMC-1 and a 1.1 fold increase CDC42 expression unique to the tissue samples of patients with OSAS. Though the serum laminin EIA did not differ between groups, a statistically significant increase in peripheral blood mononuclear cells (PBMC) cellular adhesion in OSAS patients versus control subjects was found. The OSAS subjects had a well cell count of 9.27 ± 1.54 cells vs. controls 5.75 ± 0.78 cells (p Ë‚ 0.05), which is relative to the 103 cells/field that were plated. Conclusions: Cells isolated from women with moderate-severe OSAS show an abnormality in cellular adhesion, a process driven in part by the gene LAMC-1, which was also aberrantly expressed in these subjects. This suggests that inflammation may be linked to the pathogenesis of OSAS. This pilot study has provided the framework and preliminary data needed to propose a larger study with extramural research funding. / Ph. D.