Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks.

N-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2 R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.

Association between health risks and frailty in relation to the degree of housing damage among elderly survivors of the great East Japan earthquake.

BACKGROUND: Many survivors of the Great East Japan Earthquake that occurred in 2011 were at risk of deteriorating health, especially elderly people living in disaster-stricken areas. The objectives of this prospective study were: a) to clarify the different lifestyle and psychosocial factors associated with frailty by sex among the non-disabled elderly survivors, and b) to describe the differences in characteristics stratified by the degree of disaster-related housing damage. METHODS: We followed 2261 Japanese survivors aged ≥65 years (45.3% male; mean age, 71.7 years) without disability or frailty who completed a self-administered questionnaire at baseline. All participants completed a baseline questionnaire in 2011 and at least one identical follow-up questionnaire between 2012 and 2015 regarding lifestyle (smoking status, alcohol intake, physical activity, sedentary lifestyle, and dietary intake) and psychosocial factors (self-rated health, standard of living, psychological distress, and social networks). Frailty was defined as a score of ≥5 on the Kihon Checklist, which is used by the Japanese government to certify the need for long-term care insurance. Adjusted odds ratios and 95% confidence intervals with frailty as the dichotomous dependent variable and health factors as the independent variables were calculated using a multilevel model for repeated measures by sex, followed by stratification analyses by the degree of housing damage. RESULTS: Over the 4-year study period, 510 participants (22.6%) developed frailty. In the post-disaster setting, many of the psychosocial factors remained more prevalent 4 years later among survivors with extensive housing damage. The presence of risk factors regarding the development of frailty differed by the degree of housing damage. Among men, psychological distress, in parallel with a poor social network, was related to frailty among only the participants with extensive housing damage and those living in temporary housing, whereas among women, worsening psychological distress was associated only with no damage and no displaced survivors. Among women with extensive damage and displacement, health outcomes such as overweight and diabetes and poor social networks were strongly related to frailty. CONCLUSIONS: Lifestyle and psychosocial factors associated with the risk of frailty differ by sex and the degree of housing damage.

Living situations associated with poor dietary intake among healthy Japanese elderly: the Ohasama Study.

BACKGROUND: Rapid increases in life expectancy have led to concurrent increases in the number of elderly people living alone or those forced to change living situations. Previous studies have found that poor dietary intake was common in elderly people living alone. However, there have been few studies about the dietary intake in elderly people living in other situations, particularly those living with family other than a spouse (nonspouse family), which is common in Japan. OBJECTIVE: To examine the differences in dietary intake by different living situations in elderly Japanese people. We analyzed the data of 1542 healthy residents in the town of Ohasama aged 60 years and over who had completed self-administered questionnaires. METHODS: The dietary intake was measured using a validated 141-item food frequency questionnaire. Multiple regression models with robust (White-corrected) standard errors were individually fitted for nutrients and foods by living situation. RESULTS: In men, although the presence of other family was correlated with significantly lower intake of protein-related foods, e.g., legumes, fish and shellfish, and dairy products, these declines were more serious in men living with nonspouse family. Conversely, in men living alone the intake of fruits and vegetables was significantly lower. In women, lower intakes of fruit and protein-related foods were significantly more common in participants living with nonspouse family than those living with only a spouse. CONCLUSION: These findings revealed that elderly people living alone as well as those living with family other than a spouse had poor dietary intake, suggesting that strategies to improve food choices and skills for food preparation could promote of healthy eating in elderly Japanese people.

Photonuclear reaction based high-energy x-ray spectrometer to cover from 2 MeV to 20 MeV.

A photonuclear-reaction-based hard x-ray spectrometer is developed to measure the number and energy spectrum of fast electrons generated by interactions between plasma and intense laser light. In this spectrometer, x-rays are converted to neutrons through photonuclear reactions, and the neutrons are counted with a bubble detector that is insensitive to x-rays. The spectrometer consists of a bundle of hard x-ray detectors that respond to different photon-energy ranges. Proof-of-principle experiment was performed on a linear accelerator facility. A quasi-monoenergetic electron bunch (Ne = 1.0 × 10(-6) C, Ee = 16 ± 0.32 MeV) was injected into a 5-mm-thick lead plate. Bremsstrahlung x-rays, which emanate from the lead plate, were measured with the spectrometer. The measured spectral shape and intensity agree fairly well with those computed with a Monte Carlo simulation code. The result shows that high-energy x-rays can be measured absolutely with a photon-counting accuracy of 50%-70% in the energy range from 2 MeV to 20 MeV with a spectral resolution (Δhν/hν) of about 15%. Quantum efficiency of this spectrometer was designed to be 10(-7), 10(-4), 10(-5), respectively, for 2-10, 11-15, and 15-25 MeV of photon energy ranges.

Development of multichannel low-energy neutron spectrometer.

A multichannel low-energy neutron spectrometer for down-scattered neutron (DSN) measurements in inertial confinement fusion (ICF) experiments has been developed. Our compact-size 256-channel lithium-glass-scintillator-based spectrometer has been implemented and tested in ICF experiments with the GEKKO XII laser. We have performed time calibration of the 256-channel analog-to-digital convertor system used for DSN measurements via X-ray pulse signals. We have clearly observed the DD-primary fusion neutron signal and have successfully studied the detector's impulse response. Our detector is soon to be implemented in future ICF experiments.

Intracellular glutathione redox status in human dendritic cells regulates IL-27 production and T-cell polarization.

BACKGROUND: Glutathione redox status, changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione, plays a significant role in various aspects of cellular function. In this study, we examined whether intracellular glutathione redox status in human dendritic cells (DCs) regulates the polarization of Th1/Th2 balance. METHODS: Human monocyte-derived DCs (MD-DCs) treated with glutathione reduced form ethyl ester (GSH-OEt) or L-buthionine-(S,R)-sulfoximine (BSO) were stimulated by lipopolysaccharide (LPS), and the levels of polarization cytokines were measured. Next, DCs matured by LPS or thymic stromal lymphopoietin (TSLP) were cocultured with allogeneic CD4(+) naive T cells and Th1/Th2 balance was evaluated by cytokine production from the primed T cells. RESULTS: Monocyte-derived DCs exposed to GSH-OEt and BSO had increased and decreased intracellular GSH contents, respectively. Lipopolysaccharide-induced interleukin (IL)-27 production was enhanced by GSH-OEt and suppressed by BSO, but neither GSH-OEt nor BSO affected the expression of HLA-DR, CD80, CD83, or CD86. Mature GSH-OEt-treated MD-DCs enhanced interferon (IFN)-γ production from CD4(+) T cells compared with nontreated MD-DCs, and small interfering RNA (siRNA) against IL-27 suppressed the effect of GSH-OEt on IFN-γ production. Additionally, although human myeloid DCs activated by TSLP (TSLP-DCs) prime naïve CD4(+) T cells to differentiate into Th2 cells, treatment of TSLP-DCs with GSH-OEt reduced IL-13 production and enhanced IFN-γ production by CD4(+) T cells. Interleukin-27 siRNA attenuated the inhibitory effect of GSH-OEt on Th2 polarization. CONCLUSION: Our results reveal that Th1 and Th2 responses are controlled by intracellular glutathione redox status in DCs through IL-27 production.

High fruit intake is associated with a lower risk of future hypertension determined by home blood pressure measurement: the OHASAMA study.

We investigate associations of fruit and vegetable intake with the risk of future hypertension using home blood pressure in a general population from Ohasama, Japan. We obtained data from 745 residents aged ≥35 years without home hypertension at baseline. Dietary intake was measured using a validated 141-item food frequency questionnaire, and subjects were then divided into quartiles according to the fruit and vegetable intake. Home hypertension was defined as home systolic/diastolic blood pressure of ≥135/85 mm Hg and/or the use of antihypertensive medication. During a 4-year follow-up period, we identified 222 incident cases of home hypertension. After adjustment for all putative confounding factors, the highest quartile of fruit intake was associated with a significantly lower risk of future home hypertension (odds ratio 0.40, 95% confidence interval 0.22-0.74, P=0.004). In conclusion, this study, based on home blood pressure measurement, suggests that higher intake of fruit is associated with a lower risk of future home hypertension.

Decreased interstitial FOXP3(+) lymphocytes in usual interstitial pneumonia with discrepancy of CXCL12/CXCR4 axis.

Regulatory T cells (Treg) play a critical role in immune homeostasis and expansion of Treg is controlled by chemokine receptors. The chemokine CXCL12 and its G-protein-coupled receptor (CXCR4) are involved in the development of idiopathic pulmonary fibrosis (IPF), but the association of Treg with the CXCL12/CXCR4 axis has not been documented. The aim of this study is to determine the distribution and extent of CXCL12/CXCR4 expression in idiopathic type of pulmonary fibrosis, and the relation of Treg expansion in the interstitium of pulmonary fibrosis patients to CXCL12/CXCR4 expression. CXCL12 expression was examined by immunostaining and ELISA in tissue specimens from patients with usual interstitial pneumonia (UIP, n=15), patients with fibrotic non-specific interstitial pneumonia (f-NSIP, n=4), and controls (n=6). CXCR4 expression was examined by in situ hybridization and immunoblotting. Expression of CD45, CD3, CD20, transcription factor forkhead box P3 (FOXP3), and CD25 was assessed by immunostaining. Fibrosis was evaluated by determining the established fibrosis (EF) score. The CXCL12/CXCR4 axis was upregulated in UIP and f-NSIP, and CXCL12 derived from lung tissue attracted CXCR4(+) cells. CXCR4(+) cells showed a CD3(+) cell distribution pattern. The interstitial FOXP3(+)/CD3(+) and CD25(+)/CD3(+) cell ratios were lower in UIP than f-NSIP, but the CXCR4(+)/CD3(+) cell ratio was not different. The FOXP3(+)/CD3(+) cell ratio and EF score were inversely correlated. These findings suggest that the CXCL12/CXCR4 axis contributes to inflammation in UIP and f-NSIP by promoting the accumulation CXCR4(+) lymphocytes, and a decrease of Treg is correlated with the severity of fibrosis in UIP.

Analysis on the co-localization of asbestos bodies and Fas or CD163 expression in asbestos lung tissue by in-air micro-pixe.

To prevent and control disease caused by exposure to various agents, it is necessary to determine the harmful level of intervention and to establish a method for measuring that level. In-air microparticle-induced X-ray emission (in-air micro-PIXE) analysis is based on irradiation of specimens with a proton ion microbeam, and has been modified for biological application. Two-dimensional analysis and quantitative analysis using the system confirmed that asbestos induced apoptosis by upregulating Fas expression and also revealed the accumulation of CD163-expressing macrophages in the lungs of patients with asbestosis. By quantitative comparison of the area of Fas or CD163 expression and the Fas- or CD163-negative area in asbestos lung tissue, the harmful levels which caused the expression of Fas or CD163 could be estimated on Silica, Ferrous iron, and Magnesium (the components of asbestos) deposition. These results indicate that the system could be useful for investigating the pathogenesis of inhaled particle-induced immune reactions and for determining harmful levels of exogenous agents.

CXCR4+FOXP3+CD25+ lymphocytes accumulate in CXCL12-expressing malignant pleural mesothelioma.

CXCL12 is a chemokine that binds to a G-protein-coupled receptor (CXCR4). CXCL12 is expressed in various tumors and is considered as playing an important role in tumor growth and invasion. The aim of this study is to investigate the expression of CXCL12 in human malignant mesothelioma (MM), the chemotactic effect of CXCL12 derived from MM, and the expression of CXCR4 in MM tissues in relation to regulatory T cells. CXCL12 expression was examined by immunostaining of tissue specimens from malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPEM). The MM group comprised 6 patients (4 men/2 women, MPM=4, MPEM=2, aged 56.0 +/- 12.4 years) and the control (non-mesothelioma) group also had 6 patients (4 men/2 women aged 65.0 +/- 6.7 years). CXCL12 mRNA expression was also examined by RT-PCR in MPM cell lines (H28, H2052, and H2058), while CXCR4 mRNA expression was examined by in situ hybridization in MPM tissue. CXCL12 was expressed in the cytoplasm of MM cells from all patients, but was not expressed in the control group. H2052 and H2058 cells expressed CXCL12 mRNA, but H28 cells did not. CXCL12 in MM tissue homogenate supernatant had a chemotactic effect on CXCR4-expressing THP-1 cells. CXCR4 mRNA was expressed by a part of LCA+CD3+ Foxp3+CD25+ T cells that were located adjacent to the border of CXCL12-expressing epithelioid MPM. These findings suggest that CXCL12 contributed to tumor-related inflammation by inducing the accumulation of CXCR4-expressing cells with regulatory T cell markers around MM.

In-air micro-particle induced X-ray emission analysis of asbestos and metals in lung tissue.

Inhalation of asbestos increases the risk of lung cancer and pulmonary fibrosis. It is difficult to directly assess the distribution and content of inhaled particles in lung tissue sections. The purpose of this study is to employ an in-air micro particle induced X-ray emission (in-air micro-PIXE) system for assessment of the spatial distribution and content of asbestos and other metals in lung tissue. A proton ion-microbeam from this system was applied to irradiate lung tissue of patients with or without asbestosis, tumor tissue from both groups, and asbestos fibers (in vitro). The content of each element composing asbestos and those of other metals were calculated and their distribution was assessed from the characteristic X-ray pattern for each element obtained after irradiation. This in-air micro-PIXE system could identify the location of asbestos bodies composed of Si, Mg, and Fe in lung tissue sections. Macrophage and lymphocytes accumulated in that area. This new system also revealed deposits of titanium, nickel, and cobalt in the lung tissues, in addition to asbestos bodies. The Si and Fe content were higher in lungs with asbestosis than in lungs without asbestosis or in tumor tissue. Analysis of asbestos fibers composed of chrysotile, crocidolite, and amosite showed that the ratios of Si, Fe, and Mg corresponded with those for the chemical structures. In-air micro-PIXE analysis is useful for assessing the distribution and quantities of asbestos bodies and also other metals in lung tissue comparing to immune-related cell localizations, and is also useful for analysis of standard asbestos fibers.

Hypoxemia with high alveolar-arterial oxygen gradient but no lung involvement in a patient with Churg-Strauss syndrome: case report.

Churg-Strauss syndrome (CSS) is characterized by asthma and/or a history of allergy, eosinophilia and an often life-threatening systemic necrotizing vasculitis. We describe a patient with CSS and hypoxemia with a high alveolar-arterial oxygen gradient (AaDO2), but no pulmonary parenchymal involvement. The patient also had a low diffusion capacity with normal lung volume and a high level of serum thrombomodulin, a marker of endothelial cell injury. Treatment for CSS, such as corticosteroid, improved both hypoxemia and AaDO2 consistent with amelioration of diffusion capacity and serum thrombomodulin level, suggesting that this pathosis involves microangiopathy with endothelial cell damage induced by vasculitis in pulmonary blood vessels.

The relationship between oxidative stress and acid stress in adult patients with mild asthma.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of asthma. Interestingly, a low airway pH and a high concentration of 8-isoprostane, a marker of oxidative stress, has been reported to cause inflammatory airway diseases. However, the relationship between these 2 markers and pulmonary function has not been determined in mild asthma patients. METHODS: pH and 8-isoprostane concentration were measured in exhaled breath condensate (EBC) from patients with mild asthma (n = 44) and healthy subjects (n = 20). The relationship between acid stress (pH) and oxidative stress (8-isoprostane) was then analyzed, along with the relationships between these 2 markers and lung function. RESULTS: The median (interquartile range [IQR]) pH of EBC was significantly lower in asthma patients than in control subjects (7.53 [7.41-7.68] vs 7.70 [7.62-7.74], P < .05), while the median (IQR) 8-isoprostane concentration of EBC was significantly higher in asthma patients than control subjects (16.2 [11.7-19.1] vs 3.5 [2.6-7.9] pg/mL, P < .05). There was no correlation between pH and 8-isoprostane concentration. Furthermore, lung function was not correlated with either pH or 8-isoprostane concentrations in EBC. CONCLUSIONS: Acid stress and oxidative stress assessed by pH and 8-isoprostane concentration, respectively, in EBC did not show parallel changes associated with asthma and were not correlated with lung function in asthma patients. These 2 stress factors may have different roles in the pathogenesis of asthma.

Acute impact of volcanic ash on asthma symptoms and treatment.

Information about the impacts of disasters on health is useful for establishing hazard prediction maps and action plans of disaster management. This study aims at learning effective asthma management from the volcano disaster of Mount Asama eruption in Japan on September 1, 2004. We conducted a cross-sectional study to assess the acute impact of volcanic ash on asthma symptoms and their treatment changes by using a questionnaire completed by 236 adult asthmatic patients and their physicians. In the ashfall over 100g/m2 area, 42.9 percent of asthma patients suffered exacerbations, PEF decreased, asthma treatments increased, and inhalation of beta2 stimulants was used most for exacerbated asthma. Compared to severe asthma patients, mild and moderate asthma patients were most at risk. Severe asthma patients were not affected since most of them knew their asthma status was severe, and did not go outside and kept windows closed. Deteriorated asthma symptoms of wheezing, chest tightness and cough appeared in the ashfall over 100g/m2 area. Ash contained inhalable 10microm diameter particles, and included high concentrations of airway toxic substrates of silica. These data suggest that ashfall over 100 g/m2 is harmful, access to these areas by asthma patients needs to be restricted, and these areas need to improve asthma treatment. In addition, the increase in the proportion of asthma patients with wheeze and cough are diagnostic clues for ash-induced asthma in affected areas, and can be used by doctors to tell whether patients are receiving sufficient asthma treatment.

Relationships of C-reactive protein, uric acid, and glomerular filtration rate to arterial stiffness in Japanese subjects.

The relationships between C-reactive protein (CRP), uric acid (UA), glomerular filtration rate (GFR), and arterial stiffness have not been fully investigated. The aim of this study was to clarify whether CRP, UA, and estimated GFR are related to arterial stiffness estimated using brachial-ankle pulse wave velocity (baPWV). The subjects were local government employees (3412 men and 854 women). baPWV, CRP, UA, GFR, and conventional risk factors were evaluated. Multiple linear regression analyses revealed that CRP and UA were significantly related to an elevation of PWV in male and female subjects, and that the estimated GFR was significantly related to an elevation of PWV in male subjects. Significant progressive increases in baPWV were observed across the quartiles of CRP in male subjects and for UA in male and female subjects. In female subjects, the relationship of quartile CRP to baPWV had marginal significance (P = 0.055). But, in male and female subjects, quartile of estimated GFR had no significant association with PWV. These results suggest that CRP and UA are associated with an increase of arterial stiffness in male and female subjects, and that estimated GFR is possibly related to arterial stiffness in male subjects.

[Implementation and evaluation of public relations activity in a community health program].

OBJECTIVE: This study evaluated public relations activity in a community health program in order to develop effective strategies to attract the public attention for the program. METHODS: An intervention study was conducted on public relations for "Nutrition Seminar for Citizens," sponsored by the Health Department of Machida City, Tokyo, in October, 1999. One ward in the city was selected as an intervention area, and another ward which had similar demographic and geographic characteristics was chosen as a control area. Two target populations were defined; one was women in their 20s to 60s (#1) and the other was those who had previously never utilized community health programs sponsored by the city (#2). Handbills were used as the medium for public relations for the seminar. These announced the time, place and content of the nutrition seminar and were designed by authors with special attention to catchphrases, colors and fonts. Handbills were distributed in the intervention area through elementary schools, local voluntary organizations and local health volunteers. In addition, the authors directly handed them out to people in front of two supermarkets in the town. The sources of seminar information were requested from the participants of the Nutrition Seminar with a self-administered questionnaire. RESULTS: 1. The percentage of participants who received the seminar information from handbills was higher than that of those who used monthly newsletters from the city as a source of information. 2. The percentage of participants from the intervention area was higher than that from the control area. 3. Regarding target populations #1 and #2, there were no differences in participation rates between the intervention and control area. 4. Among the four distribution routes, the local voluntary organization route was the most effective for attracting participants. CONCLUSIONS: The results show that handbills can be an effective medium for pubic relations to increase the number of participants in community health programs. Also, local voluntary organizations can play a crucial role in information transfer in the community because of their high credibility. On the other hand, we could not reach specified target populations with the medium. Further surveys are needed to establish optimal media and routes to reach appropriate target populations in health programs.

Regulation of LPS induced IL-12 production by IFN-gamma and IL-4 through intracellular glutathione status in human alveolar macrophages.

Interleukin-12 (IL-12) is secreted from monocytes and macrophages; it exerts pleiotropic effects on T cells and natural killer (NK) cells, and stimulates interferon-gamma (IFN-gamma) secretion. Glutathione tripeptide regulates the intracellular redox status and other aspects of cell physiology. We examined whether IFN-gamma and IL-4 affect the balance between intracellular reduced glutathione (GSH) and oxidized (GSSG) glutathione, as this may affect IL-12 production in human alveolar macrophages (AM). We used both AM from healthy non-smokers obtained by bronchoalveolar lavage and the monocytic THP-1 cell line in this study. Incubation of AM for 2 h with the GSH precursor N-acetylcysteine (NAC) increased the intracellular GSH/GSSG ratio, and enhanced lipopolysaccharide (LPS)-induced IL-12 secretion by AM. In THP-1 cells, NAC increased the GSH/GSSG ratio and the expression of LPS-induced IL-12 mRNA, whereas L-buthionine-[S,R]-sulphoximine (BSO) decreased these. NAC and BSO offset their own effects on the intracellular GSH/GSSG ratio and the expression of LPS-induced IL-12 mRNA. Furthermore, exposure of AM to the helper T cell type 1 (Th1) cytokine IFN-gamma or the helper T cell type 2 (Th2) cytokine IL-4 for 72 h increased and decreased the GSH/GSSG ratio, respectively. Lipopolysaccharide (LPS)-induced secretion of IL-12 in AM was enhanced by IFN-gamma but inhibited by IL-4. These results suggest that IFN-gamma and IL-4 oppositely affect the GSH/GSSG balance, which may regulate IL-12 secretion from AM in response to LPS.

[Diaphragmatic hernia with omental vessels delineated by computed tomography].

A 50-year-old man was admitted to our hospital for the evaluation of a blunted left costophrenic angle on chest roentgenograms. Chest non-enhanced computed tomographic (CT) scans demonstrated the omentum as a crescent-shaped, fat-dense, mass-like shadow on the left dorsal thoracic wall, contiguous with the abdominal cavity and floating. Omental vessels were recognized as funicular water densities running in the superior-to-inferior direction. Magnetic resonance imaging disclosed that the omental vessels ran continuously from the abdominal cavity into the thoracic cavity through a defect in the diaphragm. Diaphragmatic hernia was diagnosed, and corrective surgery performed. We reported this case because the CT-based delineation of omental vessels protruding into the thoracic cavity is rare.

Efficacy of endoscopic static pressure/area assessment of the passive pharynx in predicting uvulopalatopharyngoplasty outcomes.

OBJECTIVES/HYPOTHESIS: Although uvulopalatopharyngoplasty (UPPP) is an attractive surgical treatment for obstructive sleep apnea (OSA), the unpredictable outcome limits application of the procedure. Since UPPP corrects only retropalatal airway (RP) patency, we hypothesized that response to UPPP is determined by collapsibility of the retroglossal airway (RG), where UPPP does not correct. METHODS: We estimated closing pressure (Pclose) for each pharyngeal segment by endoscopically obtaining the static pressure/area relationship of the passive pharynx in completely paralyzed and anesthetized patients with sleep-disordered breathing (n = 41) before UPPP. Preferable response to UPPP was defined as the number of oxygen dips (ODI), obtained by nocturnal oximetry, less than 10 h(-1) after UPPP. RESULTS: Patients with negative Pclose at RG responded to UPPP significantly better than those with positive Pclose at RG (22/30 [73%] vs. 3/11 [27%], P<.05). ODI after UPPP was significantly correlated with age, Pclose at RP, and Pclose at RG. CONCLUSIONS: Endoscopic assessment of anatomic abnormality of the pharynx in paralyzed patients with sleep-disordered breathing under general anesthesia has clinical value for the improvement of UPPP outcome.

Comparison of static mechanical properties of the passive pharynx between normal children and children with sleep-disordered breathing.

Collapsibility of the active pharynx, where active contraction of the upper airway muscles is evident, was previously reported to be higher in children with obstructive sleep apnea (OSA) than in those with primary snoring during sleep. Contribution of neuromuscular and anatomic factors to the increased collapsibility, however, was not estimated. We therefore evaluated collapsibility of the passive pharynx, in which upper airway muscle activities were eliminated. Our aim in the present study was to test the hypothesis that children with sleep-disordered breathing (SDB) have a structurally narrowed and a more collapsible pharynx compared with normal children. The static pressure/area relationship of the passive pharynx was endoscopically quantified in 14 children with SDB and in 13 normal children under general anesthesia with complete paralysis. The majority of children with SDB primarily closed their airways at levels of enlarged adenoids and tonsils with positive closing pressure (Pclose) (3.5+/-4.3 cm H2O), whereas half of the normal children closed their airways at the soft palate edges and the other half at the tongue bases with subatmospheric Pclose (-7.4+/-4.9 cm H2O). Cross-sectional area of the narrowest segment was significantly smaller in SDB children than in normal children. Interestingly, collapsibility of the retropalatal and retroglossal segments significantly increased in SDB children, compared with the normal subjects. We conclude that anatomic factors play a significant role in the pathogenesis of pediatric OSA and that predisposing structural abnormalities of the entire pharynx are likely to contribute to manifestation of OSA in addition to enlarged adenoids and tonsils.