Quantitative detection of sleep apnea in adults using inertial measurement unit embedded in wristwatch wearable devices.

Sleep apnea (SA) is associated with risk of cardiovascular disease, cognitive decline, and accidents due to sleepiness, yet the majority (over 80%) of patients remain undiagnosed. Inertial measurement units (IMUs) are built into modern wearable devices and are capable of long-term continuous measurement with low power consumption. We examined if SA can be detected by an IMU embedded in a wristwatch device. In 122 adults who underwent polysomnography (PSG) examinations, triaxial acceleration and triaxial gyro signals from the IMU were recorded during the PSG. Subjects were divided into a training group and a test groups (both n = 61). In the training group, an algorithm was developed to extract signals in the respiratory frequency band (0.13-0.70 Hz) and detect respiratory events as transient (10-90 s) decreases in amplitude. The respiratory event frequency estimated by the algorithm correlated with the apnea-hypopnea index (AHI) of the PSG with r = 0.84 in the test group. With the cutoff values determined in the training group, moderate-to-severe SA (AHI ≥ 15) was identified with 85% accuracy and severe SA (AHI ≥ 30) with 89% accuracy in the test group. SA can be quantitatively detected by the IMU embedded in wristwatch wearable devices in adults with suspected SA.

Associations of self-efficacy and outcome expectancy with adherence to continuous positive airway pressure therapy in Japanese patients with obstructive sleep apnea.

Objective: To examine the associations of self-efficacy and outcome expectancy with adherence to continuous positive airway pressure (CPAP) therapy among Japanese men with obstructive sleep apnea (OSA) using objective adherence data for CPAP therapy. Methods: We conducted a retrospective study of 497 Japanese men with OSA who were receiving CPAP therapy. Good adherence was defined as CPAP use of ≥4 hours per night for ≥70% of nights. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of good adherence to CPAP therapy with self-efficacy and outcome expectancy (measured with the CPAP Self-Efficacy Questionnaire for Sleep Apnea in Japanese). The models were adjusted for age, duration of CPAP therapy, body mass index, apnea-hypopnea index, Epworth Sleepiness Scale score, and comorbidities (diabetes mellitus and hypertension). Results: In total, 53.5% of participants had good adherence to CPAP therapy. The mean CPAP use was 5.18±1.53 hours/night. After adjusting for related factors, we found significant associations of good adherence to CPAP therapy with self-efficacy scores (OR, 1.10; 95% CI, 1.05-1.13; p<0.001) and outcome expectancy scores (OR, 1.10; 95% CI, 1.02-1.15; p=0.007). Conclusions: Our results indicate that self-efficacy and outcome expectancy are associated with good adherence to CPAP therapy among Japanese men with OSA.

Associations of diabetes mellitus and hypertension with adherence to continuous positive airway pressure therapy in male patients with obstructive sleep apnea.

Methods: We conducted a retrospective study among 497 male patients with OSA on CPAP therapy. Participants with pretreatment Apnea-Hypopnea Index (AHI) data based on overnight polysomnographic recordings completed a questionnaire. Adherence data for CPAP therapy were collected using a smart card system. We classified CPAP use of ≥4 hours per night and ≥70% of nights as good adherence; other CPAP use was categorized as poor adherence. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for poor adherence to CPAP therapy in the hypertension and diabetes mellitus groups, compared with the no comorbidity group, adjusting for body mass index, duration of CPAP therapy, AHI, and Epworth Sleepiness Scale score. Results: In the no comorbidity, hypertension, and diabetes mellitus groups, 43.4%, 44.7%, and 56.0%, respectively, had poor adherence to CPAP therapy. Being in the diabetes mellitus group was significantly associated with poor adherence to CPAP therapy (OR=1.86, 95% CI: 1.18-2.92, p=0.007); there was no association for the hypertension group. Conclusion: Our results indicate that comorbidity of diabetes mellitus is associated with poor adherence to CPAP therapy in male patients with OSA.

Development and evaluation of a self-efficacy instrument for Japanese sleep apnea patients receiving continuous positive airway pressure treatment.

The purpose of this study was to develop and evaluate a self-efficacy instrument for Japanese obstructive sleep apnea (OSA) patients treated with continuous positive airway pressure (CPAP). Analyzed subjects were 653 Japanese OSA patients (619 males and 34 females) treated with CPAP at a sleep laboratory in a respiratory clinic in a Japanese city. Based on Bandura's social cognitive theory, the CPAP Self-Efficacy Questionnaire for Sleep Apnea in Japanese (CSESA-J) was developed by a focus group of experts, using a group interview of OSA patients for the items of two previous self-efficacy scales for Western sleep apnea patients receiving CPAP treatment. CSESA-J has two subscales, one for self-efficacy and the other for outcome expectancy, and consists of a total of 15 items. Content validity was confirmed by the focus group. Confirmatory factor analysis showed that the factor loadings of self-efficacy and outcome expectancy were 0.47-0.76 and 0.41-0.92, respectively, for the corresponding items. CSESA-J had a significant but weak positive association with the General Self-Efficacy Scale, and a strong positive association with "Self-efficacy scale on health behavior in patients with chronic disease." Cronbach's alpha coefficient was 0.85 for the self-efficacy subscale and 0.89 for the outcome expectancy subscale. The intraclass correlation coefficient using data from the first and second measurements with CSESA-J for a subset of 130 subjects was 0.93 for the self-efficacy and outcome expectancy subscales. These results support CSESA-J as a reliable and valid instrument for measuring the self-efficacy of Japanese OSA patients treated with CPAP. Further studies are warranted to confirm validity for female OSA patients and generalizability.

Classification of chronic cough by systematic treatment cascade trial starting with beta agonist.

BACKGROUND: Chronic cough is one of the most challenging symptoms to diagnose and treat, not only because of the variety of underlying disorders but also its varying susceptibility to treatments. Etiological studies of chronic cough vary depending on the clinical settings and the particular interests of investigators. OBJECTIVES: The purposes of this study were first to categorize the etiology of chronic cough by its response to systematic diagnostic treatments starting from the ß2 agonist and second to sub-categorize ß2 agonist responsive cough (BRC) by the airway hyperresponsiveness. METHODS: One hundred and eighty-four never-smokers received the maximal dose of procaterol to diagnose BRC. BRC was sub-categorized into two groups with or without airway hyperresponsiveness measured by the methacholine challenge test. Sinobronchial syndrome (SBS) was diagnosed by postnasal drip symptoms and by the response to clarythromycin and carbocysteine. Atopic cough (AC) was diagnosed by the evidence of atopy and the response to cetirizine hydrochloride. Gastroesophageal reflux disease (GERD) was diagnosed by the response to rabeprazole sodium. Since we did not investigate eosinophil counts in the tissue or in the induced sputum, no diagnosis of eosinophilic bronchitis was made. RESULTS: One hundred and nine patients had BRC. Twenty-three of them had bronchial asthma (BA), 53 had cough variant asthma (CVA) and 33 had non-hyperresponsive BRC (NHBRC). Thirty-one patients had GERD, 27 had AC and 14 had SBS. Twenty-five patients had more than one diagnosis in combination, while 6 had other miscellaneous diseases. Twelve patients were undiagnosed and 11 dropped out of the study. CONCLUSIONS: The majority of chronic cough was BRC. NHBRC was a new chronic cough entity. GERD is a common cause of chronic cough in Japan, as in Western countries. AC and SBS are also causes of chronic cough in Japan. TRIAL REGISTRATION: University hospital medical information network (UMIN 000007483).

Accuracy of ECG-based screening for sleep-disordered breathing: a survey of all male workers in a transport company.

PURPOSE: Sleep-disordered breathing (SDB) is associated with increased risk for cardiovascular morbidity and mortality and for sleepiness-related accidents, but >75 % of the patients remain undiagnosed. We sought to determine the diagnostic accuracy of ECG-based detection of SDB when used for population-based screening. METHODS: All male workers, mostly truck drivers, of a transport company (n = 165; age, 43 ± 12 years) underwent standard attended overnight polysomnography. Cyclic variation of heart rate (CVHR), a characteristic pattern of heart rate associated with SDB, was detected from single-lead ECG signals during the polysomnography by a newly developed automated algorithm of autocorrelated wave detection with adaptive threshold (ACAT). RESULTS: Among 165 subjects, the apnea-hypopnea index (AHI) was ≥5 in 62 (38 %), ≥15 in 26 (16 %), and ≥30 in 16 (10 %). The number of CVHR per hour (CVHR index) closely correlated with AHI [r = 0.868 (95 % CI, 0.825-0.901)]. The areas under the receiver operating characteristic curves for detecting subjects with AHI ≥5, ≥15, and ≥30 were 0.796 (95 % CI, 0.727-0.855), 0.974 (0.937-0.993), and 0.997 (0.971-0.999), respectively. With a predetermined criterion of CVHR index ≥15, subjects with AHI ≥15 were identified with 88 % sensitivity and 97 % specificity (likelihood ratios for positive and negative test, 30.7 and 0.12). The classification performance was retained in subgroups of subjects with obesity, hypertension, diabetes mellitus, dyslipidemia, and decreased autonomic function. CONCLUSIONS: The CVHR obtained by the ACAT algorithm may provide a useful marker for screening for moderate-to-severe SDB among apparently healthy male workers.

Children with severe or moderate obstructive sleep apnoea syndrome show a high incidence of persistence after adenotonsillectomy.

CONCLUSION: Persistent obstructive sleep apnoea syndrome (OSAS) occurs in approximately 20% of normal-weight children after adenotonsillectomy (T&A) and, in nearly 70% of them, it is caused by adenoid regrowth. Patients with severe or moderate OSAS showed a high incidence of persistent disease even after T&A. Allergic disease, severity and large adenoid size are associated with adenoid regrowth and persistent disease. OBJECTIVES: To investigate factors contributing to persistent OSAS and adenoid regrowth after T&A in normal-weight children. METHODS: This was a prospective, observational study at a single institute and involved 49 normal-weight children with severe or moderate OSAS (apnoea-hypopnoea index, AHI, ≥ 5) who underwent T&A. Background information, nasal endoscopic data and pre- and postoperative polysomnographic data were collected. A third polysomnography (PSG) was performed 1.5 year postoperatively in children who subsequently developed symptoms of sleep disturbance. RESULTS: Thirteen children (27%, 13/49) were symptomatic 1.5 years after T&A. Allergic rhinitis (38.5% vs 11.1%, p = 0.03) and allergic disease (69.2% vs 30.6%, p = 0.02) were seen more frequently in these children. A third PSG confirmed persistent disease (AHI ≥ 5) in nine children (18.4%, 9/49). Six children (12.2%, 6/49) were diagnosed as having adenoid regrowth and three (6.1%, 3/49) underwent revision adenoidectomy.

Relationship between adenoid size and severity of obstructive sleep apnea in preschool children.

OBJECTIVE: To investigate the contributions of adenoid and tonsil sizes to obstructive sleep apnea syndrome (OSAS) in normal-weight children in two age categories: preschool and schoolchildren. METHODS: Fifty-eight normal-weight (body mass index z-score<2) symptomatic children with OSAS (apnea-hypopnea index ≥ 2) were evaluated. The patients were divided into two age categories: preschool (age<6; n=33) and schoolchildren (age ≥ 6; n=25). Polysomnographic findings and adenoid and tonsil sizes were compared. The relative contributions of body mass index and adenoid and tonsil sizes were also investigated with a regression analysis. RESULTS: Adenoid grade and apnea index correlated significantly in preschool children (r=0.45, p<0.01). On regression analysis, adenoid grade was a significant predictor of the apnea index in preschool children. The influence of adenoid hypertrophy decreased from preschool to schoolchildren. Tonsil size had little influence on the apnea index in either group. CONCLUSION: Adenoid hypertrophy was a major contributor to OSAS in normal-weight preschool children. The upper airway morphology of younger children with OSAS differed from that of older children with OSAS.

Screening for obstructive sleep apnea by cyclic variation of heart rate.

BACKGROUND: Despite the adverse cardiovascular consequences of obstructive sleep apnea, the majority of patients remain undiagnosed. To explore an efficient ECG-based screening tool for obstructive sleep apnea, we examined the usefulness of automated detection of cyclic variation of heart rate (CVHR) in a large-scale controlled clinical setting. METHODS AND RESULTS: We developed an algorithm of autocorrelated wave detection with adaptive threshold (ACAT). The algorithm was optimized with 63 sleep studies in a training cohort, and its performance was confirmed with 70 sleep studies of the Physionet Apnea-ECG database. We then applied the algorithm to ECGs extracted from all-night polysomnograms in 862 consecutive subjects referred for diagnostic sleep study. The number of CVHR per hour (the CVHR index) closely correlated (r=0.84) with the apnea-hypopnea index, although the absolute agreement with the apnea-hypopnea index was modest (the upper and lower limits of agreement, 21 per hour and -19 per hour) with periodic leg movement causing most of the disagreement (P<0.001). The CVHR index showed a good performance in identifying the patients with an apnea-hypopnea index ≥15 per hour (area under the receiver-operating characteristic curve, 0.913; 83% sensitivity and 88% specificity, with the predetermined cutoff threshold of CVHR index ≥15 per hour). The classification performance was unaffected by older age (≥65 years) or cardiac autonomic dysfunction (SD of normal-to-normal R-R intervals over the entire length of recording <65 ms; area under the receiver-operating characteristic curve, 0.915 and 0.911, respectively). CONCLUSIONS: The automated detection of CVHR with the ACAT algorithm provides a powerful ECG-based screening tool for moderate-to-severe obstructive sleep apnea, even in older subjects and in those with cardiac autonomic dysfunction.

Diagnosis of sleep apnea by the analysis of heart rate variation: a mini review.

Cyclic variation of heart rate (CVHR) associated with sleep apnea/hypopnea episodes has been suggested as a marker of sleep disordered breathing (SDB). This study examined the utility of ECG-based CVHR detection for diagnosing SDB using simultaneous polysomnography as the reference standard. We used a previously developed automated CVHR detection algorithm (autocorrelated wave detection with adaptive threshold, ACAT) that provides the number of CVHR per hour (CVHR index). The ACAT was refined using a polysomnographic database of 194 subjects with various severities of SDB and then, applied to a single channel ECG obtained during standard overnight polysomnography in 862 consecutive subjects referred for SDB diagnosis. Using multiple thresholds of CVHR index ≥ 38 and <27, positive and negative predictive values of 95.6% and 95.1%, respectively, were achieved for detecting and excluding subjects with apnea-hypopnea index (AHI) ≥ 30, leaving 58 (6.7%) unclassified subjects. Positive and negative likelihood ratios (LRs) were 97.3 and 0.23, respectively. Also, thresholds of CVHR index ≥ 29 and <7 provided 96.1% and 95.1% of positive and negative predictive values, respectively, for subjects with AHI ≥ 15 (LRs, 50.6 and 0.11), leaving 426 (49.4%) unclassified subjects. The CVHR correlated with the AHI (r = 0.86) and showed the limits of agreement with the AHI of 19.6 and -18.6. Automated detection of CVHR by the ACAT algorithm provides useful screening tool for both increasing and decreasing probability of moderate and sever SDB with adequate thresholds.

[A case of advanced small cell lung cancer complicated by chronic renal failure treated with amrubicin].

A 64-year old man first visited our clinic approximately 10 years ago because of diabetic nephropathy that had developed into chronic renal failure. He was hospitalized to examine a left S10 tumor shadow. Based on the results of these examinations, a primary left S10 T2N0M1, ED small cell lung cancer, was diagnosed. During his outpatient visits nephropathy was found. Following admission, he began dialysis (HD). During the detailed examinations, chemotherapy with amrubicin (AMR)was performed and the blood concentration of the drug was measured. The results showed no significant variations in blood concentration before and after the dialysis. While PR was achieved in this patient, a reduction in grade 4 eosinophils was observed as an adverse reaction.

[Clinical usefulness and health-economic benefits of a new sheet-like medical device (SD-101) for the diagnosis of sleep apnea syndrome].

The SD-101 (Kenzmedico co. Ltd., Saitama, Japan), a non-invasive medical device capable of measuring respiratory parameters during sleep, has recently been developed. It operates while placed under the body like a bed pad equipped with 162 pressure sensors, with the patient in bed. To evaluate the efficacy and safety of the SD-101 for the diagnosis of sleep apnea syndrome (SAS), we enrolled 52 patients with suspected SAS (45 men and 7 women; mean age, 45.6 +/- 10.9 years) in this study. Each subject underwent measurement using the SD-101 and a polysomnograph simultaneously, and we analyzed and compared them. In addition, health-economic benefits of the SD-101 were estimated based on the results. A significantly strong correlation was obtained between the apnea hypopnea index of PSG and its of SD-101 (r = 0.86, p < 0.0001). No adverse event due to the SD-101 occurred, while use of the SD-101 greatly reduced "feeling of being constrained" and discomfort during examination (Wilcoxon test: p < 0.0001). These findings could indicate that the SD-101 is clinically useful and will make a contribution to health-economic benefits for SAS in Japan.

Age-related changes in growth hormone-immunoreactive cells in the anterior pituitary gland of Jcl: Wistar-TgN (ARGHGEN) 1Nts rats (Mini rats).

Rats of the Jcl: Wistar-TgN (ARGHGEN) 1Nts strain (Mini rats) are transgenic animals carrying an antisense RNA transgene for rat growth hormone (GH); they show poor somatic growth and a low blood GH level compared to age-matched wild-type Wistar (non-Mini) rats. The purpose of the present study was to investigate age-related changes in growth hormone-immunoreactive (GH-IR) cells in the anterior pituitary gland (AP) of Mini rats at four, six, and eight weeks of age. The body weight and size of the GH-IR cells of Mini rats was significantly lower than that of non-Mini rats at six and eight weeks of age; however, this difference was not observed at four weeks of age. The AP volume and the number of GH-IR cells in Mini rats were significantly smaller than those of the age-matched non-Mini rats at the three ages. These results suggest that the abnormal development of GH-IR cells in the AP induced by the GH antisense RNA transgene is responsible for the poor somatic growth and the low blood GH levels in Mini rats.

Hypothalamo-pituitary-adrenal gland axis in mice inhaling toluene prior to low-level long-term exposure to formaldehyde.

We studied the change in the hypothalamo-pituitary-adrenal gland (HPA) axis upon adding prior toluene inhalation to our previous formaldehyde inhalation experiments to determine whether short term exposure to relatively high levels of toluene triggers multiple chemical sensitivity (MCS). Data come from immunocytochemical, morphometrical and RT-PCR measurements. Four groups of adult female mice were exposed to differing concentrations (0, 80, 400, and 2,000 ppb) of formaldehyde for 16 hr/day, 5 days/week for twelve weeks, after the mice were exposed intranasally to 500 ppm toluene per mouse for 6 hr/day, for 3 days. We found that the number of corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons was up-regulated according to the amount of formaldehyde as well as inhalation of formaldehyde alone in our previous experiment. The proportion of adrenocorticotropin hormone (ACTH)-ir cells increased according to the formaldehyde concentration, though there was no significant difference between the 400 and 2,000 groups. The number of ACTH-ir cells was higher in the 400 group than in the other groups (0, 80, and 2,000). Expression of ACTH-mRNA was also up-regulated according to the quantity of formaldehyde. The sinusoid in the anterior pituitary showed more dilatation in the 400 and 2,000 groups than in the control group, especially in the 2,000 group. We propose that exposure to toluene prior to inhalation of formaldehyde has no effect on the HPA axis and as a trigger of MCS, although greater sinusoid dilatation was found in the anterior pituitary gland at higher concentrations of formaldehyde.

[Clinical characterization of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia pattern].

OBJECTIVE AND METHODS: To assess the clinical significance of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia (NSIP) pattern (IP/NSIP groups), we measured the levels of serum (n = 14) and bronchoalveolar lavage fluid (BALF, n = 10) CA19-9 in IP/NSIP groups. RESULT: The serum levels of CA19-9 did not correlate with the serum levels of LDH, of KL-6, or of SP-D or with the intensity of chest Ga-67 scintigraphy. There were no significant differences between the serum CA19-9 levels before therapy and those after therapy in improving patients. The levels of CA19-9 in fibrotic NSIP groups (serum:n = 7, 138.3 + /- 79.6 U/ml BALF: n = 5, 845.8 + /- 334.2 U/ml) were significantly higher than those in cellular NSIP groups (serum: n = 7, 12.8 +/-2.1 U/ml, BALF: n = 5, 40.8 +/- 16.2 U/ml). Immunohistochemical stains of CA19-9 showed the strong positivity in the bronchiolar epitheliums located in severe fibrotic lesions and the mucus within the lumens of microscopic honeycomb. The serum levels of CA19-9 were increased in both worsening patients. CONCLUSION: We speculated that the serum levels of CA19-9 may reflect the progression of lung fibrosis but not the disease activity in IP-NSIP groups.

Age-related changes in growth hormone (GH)-releasing hormone and somatostatin neurons in the hypothalamus and in GH cells in the anterior pituitary of female mice.

We have observed growth hormone-releasing hormone (GHRH)-immunoreactive (ir) neurons in the arcuate nucleus (ARC), somatostatin (SS)-ir neurons in the periventricular nucleus (PeN), and pituitary growth hormone (GH)-ir cells in female C57BL/6J mice at 2 months old (2 M), 4, 12 and 23 M, using immunocytochemical and morphometric methods. The number of GHRH-ir neurons decreased with age. The number of SS-ir neurons increased from 2 to 4 M, but decreased after 4 M. The volume of the anterior pituitary and the number of adenohypophysial parenchymal cells fell from 12 to 23 M. The proportion of GH-ir cells decreased significantly from 2 to 4 M and decreased in number from 12 to 23 M as well as in size from 2 to 4 M and from 12 to 23 M. Our results show that both GHRH-ir neurons and SS-ir neurons are fewer in old female mice, but the ratio of the number of SS-ir neurons to GHRH-ir neurons increases in old females. We suggest that the fall in the number and size of GH-ir cells in the pituitary gland with age may be involved in the increase in the ratio of the number of SS-ir neurons to GHRH-ir neurons in the hypothalamus in female mice, as well as in males.

[Clinical evaluation of portable overnight sleep respiration graph for diagnosis of sleep apnea syndrome].

Recently, a noninvasive medical device (SD-101) capable of detecting breathing pattern changes in a subject lying supine or on the side has been developed. We therefore tested whether the SD-101 would be useful for diagnosing sleep apnea syndrome (SAS). Seventy patients who had been suspicious of SAS were enrolled (M/F = 61/9, mean age +/- SD = 46.6 +/- 14.7 y/o). They took 2 distinct screening tests for SAS (using the SD-101 and one of the most popular screeners for SAS in Japan (Apnomonitor III: AP, Chest Co., Tokyo)) and a simultaneously performed standard polysomnography (PSG). All patients were then asked to respond to a questionnaire on awareness of invasiveness experienced during each study (both from the screeners and from the standard PSG). The data were then compared with those from PSG mainly using correlation coefficients and the x2 test for analysis of subjective invasiveness. Statistical significance was defined as a p value of less than 0.05. As a result, the apnea-hypopnea index (AHI) from SD-101 (r=0.947, p<0.0001) had a significantly higher correlation coefficient (p<0.0001) than that from the AP (r=0.601, p<0.0001) in relation to that from PSG. The SD-101 had a significantly lower invasiveness than either AP or PSG (p<0.0001). In conclusion, SD-101 could be much more useful for checking AHI than other conventional screeners, such as AP, which suggests that SD-101 is more useful for defining SAS.

Effect of prolonged exposure to low concentrations of formaldehyde on the corticotropin releasing hormone neurons in the hypothalamus and adrenocorticotropic hormone cells in the pituitary gland in female mice.

We examine the effect on the hypothalamus-pituitary-adrenal gland (HPA) axis of prolonged exposure to low levels of formaldehyde in female C3H/He mice, using immunocytochemical and RT-PCR methods. Two groups of female mice were exposed to differing concentrations (0, 80, 400, 2000 ppb) of formaldehyde inhalation for 16 h/day, 5 days/week, for 12 weeks. The corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons in the hypothalamus were then examined, together with the adrenocorticotropin hormone (ACTH)-ir cells and ACTH mRNA in the pituitary. One group comprised sham control mice. The other group was made allergic by injection of ovalbumin (OVA) and alum prior to exposure to formaldehyde, since most sick building syndrome (SBS) sufferers are women with allergic disease. These animals were further exposed to aerosolized OVA as a booster four times during the exposure period. Our results showed a dose-dependent increase in the number of CRH-ir neurons in the non-allergy (NAG) group. A similar pattern was found in ACTH-ir cells and ACTH mRNA. The allergy (AG) model group showed an increase in basal levels of all markers of HPA activity. Moreover, the AG mice appeared to respond to the lowest concentration of formaldehyde, and all indices of HPA activity were reduced at the highest concentrations of formaldehyde. These results relate to an important clinical issue and also have implications in the broader area of HPA regulation. We conclude that our experimental system may be a suitable animal model for SBS and/or multiple chemical sensitivity (MCS).

Reversible formation of giant and normal-sized mitochondria in gastric parietal cells of guinea pigs.

Mitochondria occasionally increase in size in response to metabolic injury. Numerous studies have reported giant mitochondria in patients with various diseases and animals with metabolic injuries, and there are few reports on giant mitochondria in normal cells under physiological conditions. Here, we report a reversible formation of giant and normal-sized mitochondria in gastric parietal cells of guinea pigs. We morphometrically analyzed the frequency distribution of mitochondrial area on ultrathin sections of parietal cells in guinea pigs fed freely (control group), starved for 60-72 hr (starvation group), and starved and then injected with histamine (histamine group). The distribution was significantly different between the control and starvation group and between the starvation and histamine group: the histogram of the starvation group significantly shifted toward large mitochondria compared with that of the control or histamine group; the frequency of mitochondria more than 2 microm2 in size was significantly higher in the starvation group than that in the control or histamine group. This is the first report that clearly demonstrated the presence of giant mitochondria in gastric parietal cells under the starved condition and a mitochondrial recovery in a normal size after the administration of histamine. Because gastric parietal cells change their membrane system according to the state of gastric acid secretion, the present data may offer new insight into the morphological changes in gastric parietal cells.