Effective three-dimensional evaluation analysis of upper airway form during oral appliance therapy in patients with obstructive sleep apnoea.

The oral appliance (OA) is considered to be an effective treatment modality for obstructive sleep apnoea (OSA). Upper airway enlargement during OA therapy is critical, and lateral cephalometry has been used for the two-dimensional evaluation of upper airway form during this therapy. However, this method cannot provide an accurate three-dimensional (3D) view of upper airway form. To confirm the effects of OA on the upper airway in patients with OSAS, we performed CT in the presence and absence of OA in 15 Japanese patients (12 males, 3 females) who responded to OA therapy. CT in the presence and absence of OA was consecutively performed for each patient, and upper airway cross-sectional area in six arbitrary planes parallel to the palatal plane was measured. Next, 3D image reconstruction was performed; morphological changes in upper airway form were evaluated, and upper airway volume at three levels from the palatal plane to the deepest point of the epiglottis was measured. The cross-sectional area of two planes in the posterior soft palate region significantly increased in the presence of OA compared with that in the absence of OA. In the presence of OA, upper airway cross-sectional area and volume significantly increased in the posterior soft palate region compared with those in the posterior tongue region. 3D CT image reconstruction accurately confirmed morphological changes in the upper airway during OA therapy. Continued use of this 3D evaluation is expected to improve the results of OA therapy in the future.

Narcolepsy and other non-SAS hypersomnia in sleep breathing disorders clinic.

Four of the 708 snorers (0.56%), referred to our sleep breathing disorders clinic for the past 2 years were diagnosed as having narcolepsy-cataplexy. Detecting HLA DRB1*1501/DQB1*0602 positive was informative for differentiating genuine narcolepsy from non-sleep apnea syndrome (non-SAS) hypersomnia in our clinic. A non-SAS obese boy, diagnosed as having essential hypersomnia syndrome, was found to be HLA DRB1*1502/DQB1*0601 positive. His hypocretin concentration was 206 pg/mL in the cerebrospinal fluid.

Effects of physiological cardiac pacing on sleep-disordered breathing in patients with chronic bradydysrhythmias.

In six patients with chronic bradydysrhythmias, polysomnographies were performed before cardiac pacemaker implantation and over the week following implantation. A patient with third-degree atrioventricular block (AVB) and two patients with sinus node dysfunction (SND) were associated with sleep-disordered breathing (SDB). Their cardiac pacemaker therapies, with the increase in the average heart rate, led to a reduction of apnea-hypopnea index and/or an improvement of Cheyne-Stokes breathing. It seems that chronic bradydysrhythmia is one of the causative factors leading to SDB.

In vitro effect of gelatins on murine cell proliferation.

Porcine skin (PS) gelatin suppressed proliferation of a murine hepatic cell carcinoma cell line, MH134, a murine fibrosarcoma cell line, Meth A and a murine T cell lymphoma cell line, RL Male 1. The magnitude of suppression of the proliferation by cold water fish skin (CWFS) or bovine bone (BB) gelatin was lower than that by PS gelatin. On the other hand, BB gelatin stimulated proliferation of murine spleen cells. The magnitude of stimulation of the proliferation by CWFS gelatin was lower than that by BB gelatin. PS gelatin slightly suppressed proliferation of murine spleen cells. PS gelatin induced apoptosis but not necrosis of MH134 tumor cells. CWFS gelatin induced weaker apoptosis of the cells than PS gelatin. DNA histogram indicated that PS and CWFS gelatins acted on MH134 tumor cells to increase ratios of G2 + M-phase.

Primary pulmonary hypertension with central sleep apnea: sudden death after bilevel positive airway pressure therapy.

An obese 23-year-old man with sleep-disordered breathing and primary pulmonary hypertension (PPH) had been administered oral beraprost sodium, anticoagulant warfarin, and home oxygen therapy, at another hospital as treatment for the PPH, but he had not experienced any symptomatic improvement. The patient had a body mass index of 32.4kg/m2, and complained of fatigue, shortness of breath on exertion, excessive daytime sleepiness, and snoring. Arterial blood gas analysis showed a PaO2 and a PaCO2 of 70.9 and 31.2mmHg, respectively. A polysomnographic study revealed central sleep apnea with an apnea-hypopnea index (AHI) of 29.7episodes/h. The patient showed improvement of daytime sleepiness after starting nocturnal nasal bilevel positive airway pressure (BiPAP) therapy for the central sleep apnea, but his pulmonary hypertension, measured in the daytime, worsened. The patient died suddenly while walking to the bathroom in the morning 1 month after initiation of BiPAP therapy. It is necessary to consider the possibility of sudden death when nasal BiPAP therapy is given to a PPH patient with central sleep apnea.

Mitogenic activity of gelatin to murine spleen cells.

We reported previously that gelatin stimulates the growth of spleen cells in vitro. Tritium thymidine (3H-TdR) uptake into phytohemagglutinin (PHA)-stimulated spleen cells as well as intact spleen cells was augmented by gelatin. These findings suggest that gelatin serves as a mitogen for lymphoid cells. In this study, the target of action of gelatin was investigated. Tritium thymidine uptake into T cell-rich fraction was enhanced by incubation with 7.5 mg/ml of gelatin for 48 hours. The level of 3H-TdR uptake into B cell-rich fraction was not definitely increased by gelatin. Flow cytometric analysis confirmed these findings. Namely, it showed that treatment of spleen cells with 7.5 mg/ml gelatin increased a ratio of CD3-positive cells and decreased that of CD19-positive cells. Tritium thymidine uptake into natural killer cell-rich fraction was augmented by gelatin in a similar fashion to T cell-rich fraction. Tritium thymidine uptake into macrophages was very low and not affected by gelatin. Tritium thymidine uptake into macrophage-precursors was very low but was enhanced by gelatin. These findings suggest that gelatin could be used as an agent of cancer biotherapy.

A discussion of anti-Aspergillus niger glucose oxidase monoclonal antibody reactivity to red blood cells of several species.

We observed that mouse spleen cells from rosettes with autologous red blood cells (RBCs) and that rosette-formation was suppressed by anti-Aspergillus niger glucose oxidase monoclonal antibody (mAb). In the present study, we investigated whether RBCs of species besides mice have the structure recognized by anti-A. niger glucose oxidase mAb by using rosette-formation and complement-mediated hemolysis. Lysates of monkey and human RBCs did not suppress rosette-formation whereas autologous (mouse), rat and sheep RBC lysates partially suppressed rosette-formation. Those lysates exerted their suppressive activity after they had been treated at 56 degrees C for 30 min. A. niger glucose oxidase also suppressed rosette-formation with or without treatment at 56 degrees C for 30 min. Alternatively, anti-A. niger glucose oxidase mAb lysed mouse, rat and sheep RBCs but not human RBCs with complement. These findings suggest that the cell surfaces of mouse, rat and sheep RBCs have a structure which can be recognized by anti-A. niger glucose oxidase mAb while the cell surfaces of monkey and human RBCs do not.

Novel rosette formation of murine spleen cells with autologous red blood cells.

Spleen cells of normal BALB/c mice formed rosettes with autologous red blood cells, and the formation was calcium ion dependent. Peritoneal exudate cells, bone marrow cells and thymocytes did not form such rosettes. Spleen cells were passed over a Sephadex G-10 column or incubated on a plastic surface in order to eliminate adherent cells from them. Cells obtained by both these methods were unable to form rosettes. B cell-, T cell- and natural killer cell-enriched fractions in spleen cells were unable to form rosettes either. Some of the mouse IgG subclasses suppressed rosette formation when added to its site. These are monoclonal antibodies whose specificities are directed against Aspergillus niger glucose oxidase. Moreover, Aspergillus niger glucose oxidase suppressed the rosette formation when spleen cells had been treated with it as well as when it had been added to the site of rosette formation. These findings suggest that some murine spleen cells have receptors to a structure on autologous red blood cells, which is recognized by an anti-Aspergillus niger glucose oxidase monoclonal antibody.

Sleep apnea syndrome in patients with pulmonary thromboembolism.

Seven patients (one man and six women) with a diagnosis of pulmonary thromboembolism (PTE) were examined by polysomnography in order to clarify the relationship between sleep-related breathing disorders and PTE. In the chronic stage of PTE, sleep apnea syndrome (SAS) was recognized in two patients (a man and a woman) among the subjects. Four of the five patients without SAS showed nocturnal hypoxemia. The female predominance was different from ordinary SAS without the disease background of PTE even though PTE is accompanied by hypoxemia and pulmonary hypertension like SAS. A pathophysiological relationship between PTE and SAS was not found in this study.

Multiple cardiovascular risk factors in obstructive sleep apnea syndrome patients and an attempt at lifestyle modification using telemedicine-based education.

Severe obstructive sleep apnea syndrome (OSAS) is a typical 'lifestyle-related disease' characterized by a high incidence of cardiovascular risk factors, such as obesity, smoking, hypertriglyceridemia, and diabetes mellitus. Patients with OSAS tend to have eating disorders as a result of efforts to overcome the intolerable sleepiness. Treatment of OSAS should therefore aim to improve the lifestyle through encouraging weight reduction, physical activity increase, and tobacco avoidance, in addition to direct therapy such as continuous positive airway pressure for upper airway obstruction. The telemedicine system we developed was considered to be effective for providing home-based education on nutrition and exercise aimed at correcting multiple risk factors in OSAS patients

Prevalence of ischemic heart disease among patients with sleep apnea syndrome.

We investigated the prevalence of ischemic heart disease (IHD) in sleep apnea syndrome (SAS) and the presence of coronary risk factors involved in the onset of IHD in 386 subjects with suspected SAS due to heavy snoring. The prevalence of IHD among patients with untreated SAS was found to be 23.8%, and the percentage of patients having SAS complicated with IHD was high among those with moderate or severe SAS. Sleep apnea syndrome patients with IHD also showed high prevalences of hypertension and hyperlipidemia. It appears that sleep apnea aggravates the factors that cause coronary vascular disorders, and is involved in the onset of IHD.

Augmented very low frequency component of heart rate variability during obstructive sleep apnea.

After documenting the presence of obstructive sleep apnea syndrome (OSAS) through polysomnographic monitoring, we performed simultaneous ambulatory recordings of electrocardiogram, oronasal airflow, and pulse oximetry on 12 OSAS patients with normal autonomic nervous function for a period of 24 hours. The power spectrum of heart rate variability was investigated before and during treatments using dental appliances. Freuquency domain analysis showed that the very low frequency component of heart rate (0.008-0.04 Hz) was increased in OSAS patients and that a very low frequency peak appeared during episodes of obstructive sleep apnea. The increase in very low frequency identification was synchronized with episodes of absence of air exchange or hypoxemia (decreased arterial oxygen saturation) that occurred repeatedly at a cycle length of 25-120 seconds in our subjects. Frequency domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed that only the very low frequency was significantly decreased during prosthetic mandibular advancement treatment, whereas the other frequencies, i.e. high, low, and ultralow frequency component values, showed no significant changes. Time domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed no significant changes in any of these parameters. Frequency domain analysis of heart rate variability during nocturnal sleep, especially investigation of very low frequency and very low frequency peak, can be a noninvasive low-cost approach to diagnose and even better monitor subjects undergoing treatment at home, particularly considering that R-R intervals can be extracted from pulse oximetry and that analysis software programs are already commercially available.