Metabolic and Epigenetic Regulation of SMAD7 by STC1 Ameliorates Lung Fibrosis.

As shown in our previous studies, the intratracheal-administration of STC1 (stanniocalcin-1) ameliorates pulmonary fibrosis by reducing oxidative and endoplasmic reticulum stress through the uncoupling of respiration in a bleomycin-treated mouse model. However, the overall effect of STC1 on metabolism was not examined. Therefore, we first conducted a comprehensive metabolomics analysis to screen the overall metabolic changes induced by STC1 in an alveolar epithelial cell line using capillary electrophoresis time-of-flight mass spectrometry. The results were subsequently validated in multiple alveolar epithelial and fibroblast cell lines by performing precise analyses of each substance. STC1 stimulated glycolysis, acetyl-CoA synthesis, and the methionine and cysteine-glutathione pathways, which are closely related to the uncoupling of respiration, modulation of epigenetics, and reduction in oxidative stress. These results are consistent with our previous study. Subsequently, we focused on the inhibitory factor SMAD7, which exerts an antifibrotic effect and is susceptible to epigenetic regulation. STC1 upregulates SMAD7 in an uncoupling protein 2-dependent manner, induces demethylation of the SMAD7 promoter region and acetylation of the SMAD7 protein in human alveolar epithelial and fibroblast cell lines and a bleomycin-treated mouse model, and subsequently attenuates fibrosis. The antifibrotic effects of STC1 may partially depend on the regulation of SMAD7. In the evaluation using lung tissue from patients with idiopathic pulmonary fibrosis, SMAD7 expression and acetylation were high in the alveolar structure-preserving region and low in the fibrotic region. The intratracheal administration of STC1 may prevent the development of pulmonary fibrosis by regulating the metabolism-mediated epigenetic modification of SMAD7 in patients.

Effect of Respiratory Therapy on the Prognosis of Chronic Heart Failure Patients Complicated With Sleep-Disordered Breathing　- A Pilot Efficacy Trial.

BACKGROUND: Sleep-disordered breathing (SDB) has been reported to influence mortality and occurrence of ventricular tachyarrhythmia in patients with chronic heart failure (CHF). It remains to be elucidated, however, whether respiratory therapy (RT) can affect the occurrence of fatal ventricular tachyarrhythmia in CHF patients with SDB. METHODS AND RESULTS: We prospectively examined whether the severity of SDB was associated with fatal cardiac events in CHF patients and, if so, whether RT for SDB improved prognosis. We enrolled 95 patients with stable CHF, in whom SDB was examined on overnight polygraphy. The severity of SDB was quantified using the apnea-hypopnea index (AHI). All patients with AHI ≥10 (n=42) at initial evaluation were recommended to have RT, such as home oxygen therapy and continuous positive airway pressure, and 24 agreed to this. During the follow-up period of 29±17 months, 8 ventricular tachyarrhythmias occurred and 14 of the 95 patients died. On multivariate proportional hazard analysis AHI ≥5 was a risk factor for fatal arrhythmic events (P=0.026). Although RT significantly reduced AHI, it did not significantly reduce the event rates, but 4 patients with AHI <5 on RT had no fatal arrhythmic events or death. CONCLUSIONS: SDB is an independent prognostic factor and thus an important therapeutic target in CHF patients.

Mesenchymal stem cells correct inappropriate epithelial-mesenchyme relation in pulmonary fibrosis using stanniocalcin-1.

Current hypotheses suggest that aberrant wound healing has a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). In these hypotheses, continuous TGF-ß1 secretion by alveolar epithelial cells (AECs) in abnormal wound healing has a critical role in promoting fibroblast differentiation into myofibroblasts. Mesenchymal stem cells (MSCs) home to the injury site and reduce fibrosis by secreting multifunctional antifibrotic humoral factors in IPF. In this study, we show that MSCs can correct the inadequate-communication between epithelial and mesenchymal cells through STC1 (Stanniocalcin-1) secretion in a bleomycin-induced IPF model. Inhalation of recombinant STC1 shows the same effects as the injection of MSCs. Using STC1 plasmid, it was possible to enhance the ability of MSCs to ameliorate the fibrosis. MSCs secrete large amounts of STC1 in response to TGF-ß1 in comparison to AECs and fibroblasts. The antifibrotic effects of STC1 include reducing oxidative stress, endoplasmic reticulum (ER) stress, and TGF-ß1 production in AECs. The STC1 effects can be controlled by blocking uncoupling protein 2 (UCP2) and the secretion is affected by the PI3/AKT/mTORC1 inhibitors. Our findings suggest that STC1 tends to correct the inappropriate epithelial-mesenchymal relationships and that STC1 plasmid transfected to MSCs or STC1 inhalation could become promising treatments for IPF.

End-Tidal CO2 Tension Is Predictive of Effective Nocturnal Oxygen Therapy in Patients with Chronic Heart Failure and Central Sleep Apnea.

Central sleep apnea (CSA) is characterized by recurring cycles of crescendo-decrescendo ventilation during sleep, and enhances sympathetic nerve activity. Thus CSA has a prognostic impact in patients with chronic heart failure (CHF). Although nocturnal oxygen (O2) therapy decreases frequency of CSA and improves functional exercise capacity, it is also known that some non-responders to the therapy exist. We thus aimed to identify predictors of responders to nocturnal O2 therapy in CHF patients with CSA. In 12 CHF patients with CSA hospitalized at our department, sleep study was performed at 2 consecutive nights. Patients nasally inhaled O2 at either the first or second night in a randomized manner. To predict the percentage reduction in apnea-hypopnea index (%ΔAHI) in response to the nocturnal O2 therapy, we performed multiple regression analysis with a stepwise method with variables including age, brain-natriuretic peptide, circulation time, baseline AHI, hypercapnic ventilatory response and end-tidal carbon dioxide tension (PETCO2). Nocturnal O2 therapy significantly decreased AHI (from 32 ± 13 /h to 12 ± 10 /h, P < 0.0001). Among the possible predictors, PETCO2 was the only variable that is predictive of % changes in AHI. Receiver operating characteristics analysis determined 4.25% as the optimal cutoff PETCO2 level to identify responder to nocturnal O2 therapy (> 50% reduction of AHI), with 88.9% of sensitivity and 66.7% of specificity. In conclusion, PETCO2 is useful to predict the efficacy of O2 therapy in CHF patients with CSA, providing important information to the current nocturnal O2 therapy.

Relationship between sleep bruxism and sleep respiratory events in patients with obstructive sleep apnea syndrome.

PURPOSE: Both obstructive sleep apnea syndrome (OSAS) and sleep bruxism (SB) are commonly related to arousal events. In this study, we examined the effect of SB on the sleep architecture and investigated the relationship between SB and sleep respiratory events in patients with OSAS. METHODS: Patients with OSAS (n=67) in whom apnea/hypopnea occurred five or more times per hour were recruited to this study. Healthy volunteers (n=16) were recruited as controls. None of the healthy volunteers had any sleep disorders or medical disorders, nor had they taken any medication or alcohol. Data were collected by standard polysomnography during overnight sleep tests in a dark, quiet room. RESULTS: The frequency of SB was higher in the OSAS than in the control group. The risk of SB was significantly higher in the OSAS than in the control group (odds ratio, 3.96; 95% confidence interval, 1.03-15.20; P<0.05). Apnea/hypopnea and desaturation events occurred significantly more frequently in patients with than without SB. The frequency of the phasic type of SB correlated positively with that of obstructive apnea, micro-arousal, and oxygen desaturation. The frequency of SB events during micro-arousal events consequent on apnea/hypopnea events was significantly higher in the OSAS than in the control group. CONCLUSIONS: We found that patients with OSAS have a high risk of SB. In particular, this is the first report relating phasic-type SB to obstructive apnea events. This relationship suggests that improvement in OSAS might prevent exacerbations of SB.

Phase angle as an indicator of sarcopenia and malnutrition in patients with chronic obstructive pulmonary disease.

BACKGROUND: Phase angle (PhA), which is measured using bioelectrical impedance analysis, is an indicator of muscle quality and malnutrition. PhA has been shown to be correlated with sarcopenia and malnutrition; however, studies on patients with chronic obstructive pulmonary disease (COPD) are limited. In this study, we investigated the correlation between PhA and sarcopenia and malnutrition and determined the cutoff values of PhA for those in patients with COPD. METHODS: This study included 105 male patients with COPD (mean age 75.7 ± 7.7 years, mean forced expiratory volume in 1s % predicted [%FEV1] 57.0 ± 20.1%) and 12 male controls (mean age 74.1 ± 3.8 years) who were outpatients between December 2019 and March 2024. PhA was measured using the InBody S10, and its correlation with sarcopenia and malnutrition was assessed. The cutoff PhA values for sarcopenia and malnutrition were determined using receiver operating characteristic curves. RESULTS: The prevalence rates of sarcopenia and malnutrition were 31% and 22%, respectively, in patients with COPD. PhA significantly correlated with sarcopenia- and malnutrition-related indicators. Multivariate logistic regression analysis independently correlated PhA with sarcopenia and malnutrition. The cutoff values of the PhA for sarcopenia and malnutrition were 4.75° (AUC = 0.78, 95% CI = 0.68-0.88) and 4.25° (AUC = 0.75, 95% CI = 0.63-0.86), respectively. CONCLUSIONS: PhA was significantly correlated with sarcopenia and malnutrition in Japanese patients with COPD and may be a useful diagnostic indicator.

Utility of the Shortness of Breath in Daily Activities Questionnaire (SOBDA-Q) to Detect Sedentary Behavior in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Sedentary behavior has been shown to be an independent predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). However, physicians have difficulty ascertaining patients' activity levels because they tend to avoid shortness of breath. The reformed shortness of breath (SOB) in the daily activities questionnaire (SOBDA-Q) specifies the degree of SOB by measuring low-intensity activity behavior in everyday living. Therefore, we aimed to explore the utility of the SOBDA-Q in detecting sedentary COPD. We compared the modified Medical Research Council dyspnea scale (mMRC), COPD assessment test (CAT), and SOBDA-Q with physical activity levels (PAL) in 17 healthy patients, 32 non-sedentary COPD patients (PAL ≥ 1.5 METs·h), and 15 sedentary COPD patients (PAL < 1.5 METs·h) in this cross-sectional study. CAT and all domains of the SOBDA-Q in all patients are significantly correlated with PAL, even after adjusting for age. The dietary domain has the highest specificity, and the outdoor activity domain has the highest sensitivity for detecting sedentary COPD. Combining these domains helped determine patients with sedentary COPD (AUC = 0.829, sensitivity = 1.00, specificity = 0.55). The SOBDA-Q is associated with PAL and could be a useful tool for determining patients with sedentary COPD. Moreover, eating and outing inactivity claims reflect sedentary behavior in patients with COPD.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared in order to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Because sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Since sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

A novel EEG index for evaluating the sleep quality in patients with obstructive sleep apnea-hypopnea syndrome.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a highly prevalent sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, decreased sleep quality, and excessive daytime sleepiness. A basic method of evaluating sleep quality is polysomnography (PSG) where sleep stages are identified from the electroencephalogram (EEG), electrooculogram and chin electromyogram. The implementation of PSG is limited to sleep laboratories because this test is rather complicated to perform and quite time-consuming to analysis, requiring skilled technicians. Development of simple alternative methods to PSG could enable sleep tests to be performed at home. Our study aimed to identify simple measures for evaluating the sleep quality. We focused on a simple index, entropy, which is derived from power spectrum of EEG signals throughout the night, and reflects the dynamics of EEG signals, and examined whether the entropy of EEG reflects the sleep quality of OSAHS. The EEG signals for the analysis of EEG entropy were recorded from the temple area. The EEG entropy was compared with the sleep quality by traditional approaches of EEG from PSG in 58 OSAHS patients and 8 healthy volunteers. The EEG entropy in each subject showed the negative values and fluctuated during sleep. There was a significant correlation between the EEG entropy and the sleep quality (r = 0.626, p < 0.001); namely, the amplitude of the fluctuation was increased with the increase in the sleep quality. We therefore propose that the EEG entropy could be useful for evaluating the sleep quality of OSAHS.

Risk prediction for new-onset atrial fibrillation using the Minnesota code electrocardiography classification system.

BACKGROUND: Few risk models are available to predict future onset of atrial fibrillation (AF) in workers. We aimed to develop risk prediction models for new-onset AF, using annual health checkup (HC) data with electrocardiogram findings. METHODS AND RESULTS: We retrospectively included 56,288 factory or office workers (mean age = 51.5 years, 33.0% women) who underwent a HC at a medical center and fulfilled the following criteria; age ≥ 40 years, no history of AF, and greater than 1 annual follow-up HC in 2013-2016. Using Cox models with the Akaike information criterion, we developed and compared prediction models for new-onset AF with and without the Minnesota code information. We externally validated the discrimination accuracy of the models in a general Japanese population cohort, the Hisayama cohort. During the median 3.0-year follow-up, 209 (0.37%) workers developed AF. Age, sex, waist circumference, blood pressure, LDL cholesterol, and γ-GTP were associated with new-onset of AF. Using the Minnesota code information, the AUC significantly improved from 0.82 to 0.84 in the derivation cohort and numerically improved from 0.78 to 0.79 in the validation cohort, and from 0.77 to 0.79 in the Hisayama cohort. The NRI and IDI significantly improved in all and male subjects in both the derivation and validation cohorts, and in female subjects in both the validation and the Hisayama cohorts. CONCLUSIONS: We developed useful risk model with Minnesota code information for predicting new-onset AF from large worker population validated in the original and external cohorts, although study interpretation is limited by small improvement of AUC.

[Evaluation of a simplified index (spectral entropy) about sleep state of electrocardiogram recorded by a simplified polygraph, MemCalc-Makin2].

BACKGROUND: Polysomnography (PSG) is the gold standard for the diagnosis of sleep apnea hypopnea syndrome (SAHS), but it takes time to analyze the PSG and PSG cannot be performed repeatedly because of efforts and costs. Therefore, simplified sleep respiratory disorder indices in which are reflected the PSG results are needed. The Memcalc method, which is a combination of the maximum entropy method for spectral analysis and the non-linear least squares method for fitting analysis (Makin2, Suwa Trust, Tokyo, Japan) has recently been developed. Spectral entropy which is derived by the Memcalc method might be useful to expressing the trend of time-series behavior. AIM: Spectral entropy of ECG which is calculated with the Memcalc method was evaluated by comparing to the PSG results. SUBJECTS: Obstructive SAS patients (n = 79) and control volanteer (n = 7) METHODS: ECG was recorded using MemCalc-Makin2 (GMS) with PSG recording using Alice IV (Respironics) from 20:00 to 6:00. Spectral entropy of ECG, which was calculated every 2 seconds using the Memcalc method, was compared to sleep stages which were analyzed manually from PSG recordings. RESULTS: Spectral entropy value (-0.473 vs. -0.418, p < 0.05) were significantly increased in the OSAHS compared to the control. For the entropy cutoff level of -0.423, sensitivity and specificity for OSAHS were 86.1% and 71.4%, respectively, resulting in a receiver operating characteristic with an area under the curve of 0.837. The absolute value of entropy had inverse correlation with stage 3. CONCLUSIONS: Spectral entropy, which was calculated with Memcalc method, might be a possible index evaluating the quality of sleep.

[Effect of age on electrocardiogram entropy value of parameters by sleep respiratory disturbance].

BACKGROUND: Spectral entropy of electrocardiogram (ECG), which was calculated using the MemCalc method with a portable bio-signal measurement instrument (PBSM), might be a possible parameter for evaluating the quality of sleep. AIM: This study assessed the effects of ECG spectral entropy on obstructive sleep apnea/hypopnea syndrome (OSAHS) depending on age. STUDY DESIGN: ECG was recorded using a PBSM, and the maximum entropy of ECG every 9 RR intervals was calculated. These entropies were compared with the age and sleeping indices obtained with a conventional polysomnography (PSG) system. SETTING AND PARTICIPANTS: Seventy-six patients suspected of OSAHS were recorded from 20:00 to 06:00 using a conventional PSG system (Alice III) and a PBSM (MemCalc-Makin2) simultaneously. RESULTS: ECG entropy showed correlations to high frequency (HF, 0.15-0.40 Hz) heart rate variability in the cardiac parasympathetic activity index, as did the ECG entropy value, and a negative correlation was found with the age (r = 0.538, p < 0.0001), and positive correlation with the HF value (r = 0.810, p < 0.0001). The ECG entropy value in subjects aged > or = 40 with no different sleep respiratory disturbance index by PSG data (AHI, Arousal Index, DSI, and sleep efficiency, etc.) to 60 years old was compared with those aged > or = 60. The ECG entropy value and HF value decreased at > or = 60 years old with statistically significant. CONCLUSION: The value of ECG entropy corresponds to cardiac parasympathetic function, and it decreases according to age (increase by the absolute value).

[Examination of spirometry techniques on instruction by medical technologists for screening purposes].

BACKGROUND: The burden of chronic obstructive pulmonary disease (COPD) remains very high. Current consensus guidelines emphasize the importance of the early detection of COPD, but its underdiagnosis is common in general practice. Spirometry is the "gold standard" in the diagnosis of COPD. However, it remains underused in general practice because the application of spirometry is viewed as difficult to obtain accurate results. AIMS: To clarify the accuracy of spirometry techniques for screening purposes. METHOD: Subjects (n = 142) were told about the spirometry procedure using pre-determined descriptions, followed by the first spirometry test. Special medical technologists gave instructions on the detailed spirometry procedure on reference to the first test of results, and the second spirometry test was performed. The second spirometric indices, SVC, FVC, FEV1, FEV1%, and PEF, were compared with the first ones. RESULTS: The instruction by special medical technologists significantly improved all spirometric indices except for FEV1%. For a diagnosis of restrictive disorder (VC<80%), the impact of intervention by the special medical technologists was highly significant (p<0.001). In contrast, for the diagnosis of obstructive disorder (FEV1%<70%), the impact was small. CONCLUSION: To detect obstructive disorder, the high-level accuracy of special spirometry techniques is not always necessary.

[Chronic obstructive pulmonary disease (COPD)].

Insomnia is common in many patients with chronic obstructive pulmonary disease (COPD). The causes of insomnia are sleep induced pathophysiological effect of COPD itself, COPD comorbidities and the presence of coexisted obstructive sleep apnea. Sleep has profound adverse effects on respiration and gas exchange in patients with COPD. There are several mechanisms underlying oxygen desaturation during sleep. They include decreased functional residual capacity, decreased ventilatory responses to hypoxia and hypercapnia, impaired respiratory mechanical effectiveness, respiratory muscle fatigue, decreased respiratory drive, and increased upper airway resistance. COPD comorbidities include DM, cardiovascular diseases, osteoporosis, depression, and GERD. The coexistence of COPD and sleep apnea-hypopnea syndrome has been denominated "overlap syndrome".

Combination of assist use of short-acting beta-2 agonists inhalation and guidance based on patient-specific restrictions in daily behavior: Impact on physical activity of Japanese patients with chronic obstructive pulmonary disease.

BACKGROUND: Assist use of inhaled short-acting beta 2 agonists (SABAs) is reportedly effective for preventing shortness of breath on exertion in chronic obstructive pulmonary disease (COPD) patients. However, it is unclear what strategy would be useful for improving physical activity in such patients. The aim is to investigate the effects of assisted use of SABA (procaterol) on physical activity in Japanese COPD patients targeting patient-specific restrictions in daily behavior. METHODS: Fourteen patients with stable COPD (age: 72.1±1.5, %FEV1: 55.6±4.5%) were asked to inhale 20 µg of procaterol 15 minutes before patient-specific daily physical activity that had been identified as limited by a questionnaire and document their usage in a diary. Physical activity was measured using a triaxial accelerometer and the results were collected every month for 2 months. In the first month, a clinician assessed whether inhalation of SABA was appropriate based on a usage diary and coached patients to conduct adequate assist use of SABA for limited physical activity. RESULTS: The strategy significantly improved the physical activity level, assessed using the values of the metabolic equivalents (METs) multiplied by physical activity endurance, at ≥3.0 METs (p<0.05), and physical activity endurance at ≥2.5 and ≥3.0 METs, (p<0.05, p<0.05, respectively). The degree of improvement of physical activity level was significantly positively correlated with the baseline %FVC and %FEV1 (p<0.05, p<0.05, respectively). CONCLUSIONS: Assist use of SABA targeting patient-specific restrictions, particularly when better lung function is still preserved, could be a useful approach for improving physical activity in patients with COPD.

Respiratory resistance among adults in a population-based cohort study in Northern Japan.

BACKGROUND: Forced oscillation technique (FOT) is a noninvasive method used to measure respiratory system resistance (Rrs) and reactance (Xrs) during quiet breathing, which has been extensively studied in clinical settings. The distribution of measured FOT values was previously assessed in a community-based cohort study. In this study, we aimed to confirm the distribution of measured FOT values in a different cohort in order to investigate the relationship between these values and patient clinical and biological data. METHODS: We reviewed FOT data and relevant patient clinical and biological information collected from the Community-Based Cohort Study (CommCohort Study), carried out between 2013 to 2016 as a part of the Tohoku Medical Megabank project (TMM). In total, 16,231 adults were enrolled in the study (Male/Female: 4886/11,345). RESULTS: Significant gender differences were observed in distributions of Rrs and Xrs values at 5 Hz (termed R5 and X5, respectively). R5 values in males were lower than those in females, while X5 values in males were slightly less negative. High R5 values were strongly associated with high BMI, short height, smoking status in males, high serum IgE level, and high peripheral blood eosinophil count. CONCLUSION: The present distribution values and their relation to clinical and biological data should provide useful insights for clinical settings and serve as a helpful guide in implementing FOT. Forced oscillation technique, respiratory system resistance, respiratory system reactance, gender difference, obesity.

[Staging of sleep based on electroencephalograms and mental electromyograms recorded by a simplified polygraph, MemCalc-Malkin2].

OBJECTIVE: To examine the feasibility of MemCalc-Malkin2, a simplified polygraph, for staging of sleep. DESIGN: Electroencephalograms and mentalelectromyograms were recorded in 33 patients with possible obstructive sleep apnea-hypopnea syndrome by a simplified polygraph, MemCalc-Malkin2, and their frequencies were analyzed according to the sleep stage that were determined by a simultaneous conventional polysomnography. RESULTS: Sleep was divided into four stages, i.e., awake(SWake), rapid eye movement phase(SREM), shallow non-REM sleep {S(1+2)}, and deep non-REM sleep {S(3+4)}. The ratio of the amount of beta waves to that of delta waves was significantly different between the four sleep stages (p < 0.05), being highest in SWake and lowest in S(3+4). Mental electromyographic discharges were significantly more active in SWake and S(1+2) than in S(3+4) and SREM. CONCLUSION: A MemCalc-Malkin2 appears promising for staging of sleep.

The relationship between increased oxidative stress and visual field defect progression in glaucoma patients with sleep apnoea syndrome.

PURPOSE: Sleep apnoea syndrome (SAS) is often associated with glaucoma, and intermittent hypoxia, present in SAS, can contribute to glaucoma pathogenesis. However, the relationships between SAS, high systemic oxidative stress and the speed of glaucoma progression are unclear. Thus, we investigated these relationships in glaucoma patients with and without SAS. METHODS: Peripheral blood samples were collected from 166 eyes of 166 Japanese patients: 42 controls, 109 open-angle glaucoma (OAG) patients without SAS and 15 OAG patients with SAS. Prognostic factors for visual field defect progression were determined with logistic regression. Diacron reactive oxygen metabolites (dROM) and biological antioxidant potential (BAP) were measured with a free radical analyser. Clinical parameters were also recorded. Intergroup comparisons used the Mann-Whitney U test. RESULTS: Multiple regression analysis showed that SAS was a statistically significant contributing factor to fast visual field defect progression, defined as mean deviation (MD) slope ≤-2.0 dB/Y (SAS: odds ratio (OR) = 14.48; p = 0.002). The non-SAS and SAS groups had similar age, sex, intraocular pressure (IOP), axial length and antiglaucoma drug use. The SAS group had a significantly higher dROM level (p = 0.001), BAP level (p = 0.038) and steeper MD slope (p = 0.001) than the non-SAS group. CONCLUSION: Glaucoma patients with SAS have higher dROM, as well as steeper MD slope, than patients without SAS, suggesting that SAS may induce systemic oxidative stress and promote glaucomatous visual field defect progression.