Restless legs syndrome augmentation among Japanese patients receiving pramipexole therapy: Rate and risk factors in a retrospective study.

To investigate the rate of and risk factors for restless legs syndrome (RLS) augmentation in Japanese patients receiving pramipexole (PPX) treatment. Records of 231 consecutive patients with idiopathic RLS who received PPX therapy for more than one month in a single sleep disorder center were analyzed retrospectively. Augmentation was diagnosed based on the Max Planck Institute criteria; associated factors were identified by logistic regression analysis. Mean age at PPX initiation was 60.6 ± 14.9 years and mean treatment duration was 48.5 ± 26.4 months. Augmentation was diagnosed in 21 patients (9.1%). Daily PPX dose and treatment duration were significantly associated with augmentation. By analyzing the receiver operating characteristic curve, a PPX dose of 0.375 mg/day was found to be the optimal cut-off value for predicting augmentation. After stratifying patients according to PPX treatment duration, at median treatment duration of 46 months, optimal cut-off values for daily doses were 0.375 and 0.500 mg/day for <46 months and ≥46 months of treatment, respectively. The RLS augmentation with PPX treatment in Japanese patients was occurred at rate of 9.1%, being quite compatible with previously reported rates in Caucasian patients. The symptom could appear within a relatively short period after starting the treatment in possibly vulnerable cases even with a smaller drug dose. Our results support the importance of keeping doses of PPX low throughout the RLS treatment course to prevent augmentation.

Oropharyngeal Crowding Closely Relates to Aggravation of OSA.

BACKGROUND: Obesity is known to be an important risk factor for OSA; however, OSA can also be seen in nonobese patients with a small maxilla and/or mandible as well as in all obese patients with such features. Thus, we hypothesized that regional factors, oropharyngeal crowding associated with fat deposition, and maxillomandibular enclosure size closely related to the severity of OSA. METHODS: A total of 703 male Japanese subjects were enrolled; theywere classified into obese (BMI ≥ 30 kg/m(2); n = 158) and nonobese (BMI < 30 kg/m(2); n = 545) groups. Using lateral cephalometric analysis, we measured the tongue size (TG), lower face cage (LFC), and TG/LFC ratio (ie, oropharyngeal crowding) to evaluate the state of upper airway crowding. The correlations between these cephalometric measurements and BMI, age, and the apnea-hypopnea index (AHI) were evaluated. RESULTS: In obese subjects, the TG/LFC ratio, BMI, and TG positively correlated with AHI, whereas, in nonobese subjects, age, BMI, and TG/LFC significantly correlated with AHI. Subsequent stepwise multiple linear regression analysis revealed that the variables associated with AHI differed between obese and nonobese OSA subjects, although BMI and TG/LFC were significantly associated with AHI in both groups. In particular, the contribution of TG/LFC to AHI was larger than that of BMI in the obese group. CONCLUSIONS: Oropharyngeal crowding is a local anatomic factor that independently relates to the severity of OSA in both obese and nonobese patients; the more crowded the upper airway, the more severe the OSA.

Progression of obstructive sleep apnoea syndrome in Japanese patients.

PURPOSE: The aggravation of obstructive sleep apnoea syndrome (OSAS) is reportedly associated with weight gain. The present study investigated the factors associated with worsening of respiratory functional parameters in Japanese OSAS patients who showed no body weight change during the follow-up period. METHODS: A follow-up polysomnography (PSG) was performed in 82 patients with a mean of 7.5 years after the diagnostic PSG, and the apnoea-hypopnoea index (AHI), respiratory event duration, minimum percutaneous oxygen saturation (SpO2), baseline SpO2, and 3 % oxygen desaturation index (ODI) during sleep were compared between the two PSGs. Furthermore, factors associated with worsened AHI, respiratory event duration, and minimum SpO2 were investigated using logistic regression analysis. RESULTS: No significant differences were observed in AHI, baseline SpO2, and 3 % ODI between the two PSGs. However, there was a significantly increased respiratory event duration and decreased minimum SpO2 observed. In addition, 17 patients had a ≥25 % AHI increase, and the age of 40-60 years and initial OSAS severity (mild and moderate) were the significantly associated factors. Age of ≥60 years and a baseline body mass index (BMI) of ≥25 kg/m(2) were significantly associated with prolonged respiratory event duration. The age of 40-60 years was significantly associated with decreased minimum SpO2. CONCLUSIONS: Untreated middle-aged patients may be at a high risk for worsened AHI and SpO2 even without weight gain.

Associations of Serum Isoflavone, Adiponectin and Insulin Levels with Risk for Epithelial Ovarian Cancer: Results of a Case-control Study.

BACKGROUND: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. MATERIALS AND METHODS: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. RESULTS: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low (Ptrend<0.001). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low (Ptrend=0.005). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low (Ptrend=0.004). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low Ptrend<0.001). CONCLUSIONS: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer.

[The International Classification of Sleep Disorders, third edition. American Academy of Sleep Medicine. Includes bibliographies and index].

The American Academy of Sleep Medicine Board of Directors published the International Classification of Sleep Disorders, 3rd edition (ICSD -3) in 2014. In the 3rd edition, the most drastic change in the content was the unity of secondary insomnia categories into single "chronic insomnia" category. In the central disorders of hypersomnolence section, the nomenclature for narcolepsy was changed to narcolepsy type 1 and type 2. In the sleep related breathing disorder section, several new diagnostic categories were added, and diagnosis of a sleep related hypoventilation disorder was set to require the confirmation of elevated PaCO2. This manuscript overviews the differences and the similarities in the content between the ICSD-3 and the former edition.

The melatonin receptor agonist is effective for free-running type circadian rhythm sleep disorder: case report on two sighted patients.

Along with urbanization of the living environment, the number of patients with circadian rhythm sleep disorder (CRSD) has been increasing. There are several treatment candidates for CRSD, such as light therapy, drugs (melatonin and vitamin B12), and sleep hygiene education. However, successful treatment method has not been established. In free-running type (FRT) CRSD, the endogenous circadian rhythm cannot be entrained to the 24-h light-dark cycle, resulting in free running on a cycle 0.5-2.5 h longer than the 24-h period. This condition is relatively common in blind individuals and is unusual in sighted individuals. Here we report two sighted patients with FRT, successfully treated with a melatonin receptor agonist, ramelteon. Patient 1 (36-year-old female) had suffered from FRT for nearly 4 months after resigning her job. She was given sleep hygiene education together with ramelteon at first and the free-running cycle stopped after treatment day 15. Triazolam was added from the day 25 to promote earlier sleep onset. And the sleep-wake schedule was normalized by the day 34. Patient 2 (33-year-old male) had suffered from FRT for nearly 8 months after starting to take a leave of absence from his job. He was given sleep hygiene education and was treated with ramelteon and methylcobalamin. His sleep-wake schedule was normalized from the first treatment day. By the combined treatment with ramelteon, both patients have maintained favorable sleep-wake schedules. The agonist action of ramelteon at the melatonin 2 receptor may have primarily contributed to the cessation of the free-running cycle in these patients.

Upper airway anatomical balance contributes to optimal continuous positive airway pressure for Japanese patients with obstructive sleep apnea syndrome.

BACKGROUND: The aim of this study was to examine whether the upper airway anatomical balance, as reflected by tongue size relative to maxillomandibular size, is related to optimal nasal continuous positive airway pressure (PnCPAP). METHODS: Sixty-six male Japanese obstructive sleep apnea syndrome (OSAS) patients (median apnea-hypopnea index [AHI] = 33.9 episodes/h [10th/90th percentile = 19.5/59.9], median body mass index [BMI] = 25.1 kg/m(2) [10th/90th percentile = 21.2/30.4]) were recruited. All patients underwent standard polysomnography (PSG), and PnCPAP was determined by nasal continuous positive airway pressure (nCPAP) titration. The anatomical balance was defined as the tongue area (TG) divided by the lower face cage (LFC) measured on cephalometry. A predictive equation of PnCPAP was created using demographic, polysomnographic, and cephalometric variables. RESULTS: Significant correlations were found between PnCPAP and descriptive variables, including BMI, AHI, lowest SpO2, distance from the anterosuperior point of the hyoid bone to the mandibular plane (MP-H), and TG/LFC. Stepwise multiple regression analysis revealed that AHI and TG/LFC were independent predictors of PnCPAP. The predictive equation was: PnCPAP = 1.000 + 0.043 × AHI + 9.699 × TG / LFC, which accounted for 28.0% of the total variance in PnCPAP (R(2) = 0.280, p < 0.01). CONCLUSIONS: Anatomical balance of upper airway in addition to the severity of OSAS is an important contributing factor for PnCPAP in Japanese OSAS patients.

The validity of the PAM-RL device for evaluating periodic limb movements in sleep and an investigation on night-to-night variability of periodic limb movements during sleep in patients with restless legs syndrome or periodic limb movement disorder using this system.

BACKGROUND: The status of night-to-night variability for periodic limb movements in sleep (PLMS) has not been clarified. With this in mind, we investigated the validity of PLMS measurement by actigraphy with the PAM-RL device in Japanese patients with suspected restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) and the night-to-night variability of PLMS among the subjects. METHODS: Forty-one subjects (mean age, 52.1±16.1 years) underwent polysomnography (PSG) and PAM-RL measurement simultaneously. Thereafter, subjects used the PAM-RL at home on four more consecutive nights. RESULTS: The correlation between PLMS index on PSG (PLMSI-PSG) and PLM index on PAM-RL (PLMI-PAM) was 0.781 (P<.001). When the PLMSI cutoff value on PSG was set at 15 episodes per hour, the cutoff value for predicting this PLMSI level was 16.0 episodes per hour. When the condition was set to the level in which the mean interclass correlation coefficient reached ≥0.9, the number of required nights for repeated measurements was 26 nights for subjects with PLMI of <15 episodes per hour and three nights for those with PLMI ≥15 episodes per hour on PAM-RL. CONCLUSIONS: PAM-RL is thought to be valuable for assessing PLMS even in Japanese subjects. Recording of PAM-RL for three or more consecutive nights may be required to ensure the screening reliability of a patient with suspected pathologically frequent PLMS.

Oropharyngeal crowding and obesity as predictors of oral appliance treatment response to moderate obstructive sleep apnea.

BACKGROUND: Oral appliances are increasingly prescribed for patients with moderate obstructive sleep apnea (OSA) instead of nasal CPAP. However, the efficacy of oral appliances varies greatly. We hypothesized that oral appliances were not efficacious in patients with moderate OSA who were obese with oropharyngeal crowding. METHODS: Japanese patients with moderate OSA were prospectively and consecutively recruited. The Mallampati score (MS) was used as an estimate of oropharyngeal crowding. Follow-up polysomnography was performed with the adjusted oral appliance in place. Responders were defined as subjects who showed a follow-up apnea-hypopnea index (AHI) of < 5 with > 50% reduction in baseline AHI. RESULTS: The mean baseline AHI was reduced with an oral appliance from 21 ± 4 to 9.8 ± 8 in 95 subjects. Thirty-five patients were regarded as responders. Logistic regression analyses revealed that both MS and BMI could individually predict the treatment outcome. When the cutoff value of BMI was determined to be 24 kg/m2 based on a receiver operating characteristic curve, 53 obese patients (ie, BMI > 24 kg/m2) with an MS of class 4 were indicative of treatment failure with a high negative predictive value (92) and a low negative likelihood ratio (0.28). CONCLUSIONS: We conclude that patients with moderate OSA who are obese with oropharyngeal crowding are unlikely to respond to oral appliance treatment. This simple prediction can be applied without the need for any cumbersome tools immediately after the diagnosis of OSA.

Evaluation of cervical conization as a definitive treatment for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3.

PURPOSE: The aim of the study was to evaluate disease persistence after conization of CIN3 and microinvasive cervical carcinoma. METHODS: Medical records from a total of 231 patients were reviewed. The prevalence of CIN3 and cervical carcinoma diagnosed by means of conization were analyzed. All conizations were performed under lumbar anesthesia using a laser technique. RESULTS: Of the 231 patients, 25 had margin involvement with CIN3 or microinvasive carcinoma. Among these 25 patients, 10 underwent hysterectomy. Two of these 10 patients had CIN3 and eight had microinvasive carcinoma. Residual disease was observed in hysterectomy specimens from 9 of the 10 patients. Of the eight patients diagnosed with microinvasion from post-cone hysterectomy specimens, four had CIN3 and three had microinvasive carcinoma. The three patients with microinvasion were found to have a larger area of residual disease as compared with other patients with margin involvement. CONCLUSIONS: Conization alone seems to be a reasonable treatment for patients with CIN1, 2, 3, and microinvasive carcinoma. For adenocarcinoma, in situ treatment with conization alone is possible but requires careful follow-up. Hysterectomy appears to be a safe treatment option for microinvasive adenocarcinoma, although follow-up by cytology is sometimes possible in cases with negative surgical margins.

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma.

Poor prognosis in ovarian clear cell carcinoma is associated with the expression of a defined set of proteins including osteopontin (OPN) and integrin. Statins, a family of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, are currently being investigated for the treatment and prevention of cancer. In this study, we investigated the effects of simvastatin on ovarian clear cell carcinoma (OCCC) cells in vitro and in vivo and elucidated the mechanism of drug action. Changes in OPN gene expression were determined by real-time RT-PCR, and an MTT assay was performed to determine effects on cell proliferation. Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin on cell proliferation and apoptosis in vivo. According to our experimental results, OPN is an important protein in OCCC. Simvastatin inhibited OCCC cell proliferation, and the inhibition rate was approximately 40% to 50% after treatment with 10 µM simvastatin for 48 h. In the xenograft studies, simvastatin treatment resulted in a significant growth inhibition. Furthermore, the mice treated with simvastatin survived significantly longer compared to the control groups. In conclusion, simvastatin has anticancer effects in vitro and in vivo. Further confirmation of the anticancer effects of statins in future studies will increase the scope for OCCC treatment.

Prediction of histologic type and lymph node metastasis for advanced ovarian cancer on uterine cervical and endometrial cytology.

OBJECTIVE: To evaluate usefulness of uterine cervical and endometrial cytology for detecting ovarian cancer and predicting histologic type. STUDY DESIGN: Retrospective analysis was performed on uterine cervical and endometrial cytology data on 163 patients with ovarian cancer. RESULTS: Cervical and endometrial abnormalities were detected in 10 and 19 of the patients evaluated. Patients whose cervical and endometrial cytology revealed abnormal cells were classified as having ovarian cancer at International Federation of Gynecology and Obstetrics (FIGO) stages III and IV Peritoneal cytology proved positive in many of the patients with abnormal findings on uterine cytologic analysis. Of the 19 patients with positive uterine cytologic findings, 12 had recurrence of ovarian cancer after radical therapies. Lymph node metastases were detected in 9 of 19 patients. Our findings indicated that it is possible to predict histologic type in ovarian cancer in 90% of cases of positive cervical smears and 79% ofabnormal endometrial smears. CONCLUSION: Our study showed that most of the ovarian cancer cases that had abnormalities in uterine cervical and endometrial cytologic tests exhibited progression of disease. As a consequence, our findings indicate that it is possible to predict development of ovarian cancer and its histologic type using cytology screening.

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats.

BACKGROUND: Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. METHODS: In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). RESULTS: Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. CONCLUSIONS: Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

Structure and photoactivity of titania derived from nanotubes and nanofibers.

Photoactivity under UV irradiation for the decomposition of methylene blue in water and for the oxidation of NO gas was studied on titania powders derived from titanate nanotube (TNT) and nanofiber (TNF) by annealing at high temperatures, comparing with granular titania (ST-01). Rate constant for methylene blue decomposition k(MB) increased with increasing annealing temperature above 300 degrees C after the conversion from titanate to tinania. It tended to decrease above 700 degrees C, mainly due to the phase transformation from anatase to rutile. The dependences of k(MB) on full width at half maximum intensity (FWHM) were common for three samples, a sharp maximum at around 0.4 degrees in FWHM, but TNF-derived sample gave much higher maximum than ST-01. Change in fraction of oxidized NO with annealing temperature showed a plateau at around 50% and then decreased abruptly by high temperature annealing. Starting from TNT and TNF has an advantage to form fine particles by annealing above 300 degrees C, giving high photoactivity due to high crystallinity and high adsorptivity particularly for methylene blue.

Analgesic efficacy of controlled-release oxycodone in patients with uterine or ovarian cancer.

Treatment with opioid analgesics often causes adverse reactions that may make continuous use of such drugs difficult. We investigated the efficacy and safety of controlled-release oxycodone in the treatment of gynecologic cancer pain. The patients included 14 with cervical cancer, 6 with corpus cancer, and 17 with ovarian cancer. Treatment with controlled-release oxycodone was started at 5 mg/dose when pain control using nonsteroidal anti-inflammatory drugs became ineffective. The dose was titrated to the optimal level over a mean duration of 2.34 +/- 1.13 days, and the initially optimal dose was 18.92 +/- 5.23 mg/day. Although no patients experienced confusion, vomiting, or respiratory depression, 17 patients experienced adverse events, including constipation in 14 patients and nausea in 9 patients. The incidence of nausea was low in patients receiving oxycodone and prochlorperazine. In the present study, patients with moderate to severe pain caused by gynecologic cancer could successfully be treated with controlled-release oxycodone.

[Pulmonary tumor thrombotic microangiopathy caused by signet ring cell carcinoma in gastric cancer].

This case involved a 38-year-old man who was referred to our hospital with general fatigue, appetite loss, weight loss, cough and exertional dyspnea. Within a couple of days, he was admitted due to advanced dyspnea and general fatigue. Severe hypoxemia was identified and acute right heart failure developed on admission. Treatment was initiated using oxygen, antibiotics and heparin sodium, but the patient died of sudden cardiopulmonary arrest 30 h after admission. Autopsy revealed advanced gastric cancer and widespread tumor embolism together with fibrocellular intimal proliferation and thrombus formation in the small arteries. Pulmonary tumor thrombotic microangiopathy (PTTM) with gastric cancer was diagnosed. PTTM is characterized by widespread fibrocellular intimal proliferation of the small pulmonary arteries and arterioles in patients with metastatic carcinoma. Microscopic pulmonary tumor emboli frequently occur in patients with malignant tumors, but very few cases of PTTM have been reported. PTTM should be considered in the differential diagnosis of acute dyspnea or pulmonary hypertension. In cases of acute cor pulmonal, the existence of malignant cells can be examined using pulmonary arterial wedge aspiration cytology where feasible, in addition to positron emission tomography with F-2-deoxy-2-fluoro-D-glucose, which can be used to investigate certain primary tumors and associated metastatic disease. The suitability of gastroendoscopy to screen for malignancies should be examined.

Cytology of vaginal and uterine sarcomas.

OBJECTIVE: To retrospectively review, based on cytologic and histopathologic findings, the diagnoses of 13 patients with uterine sarcoma and 1 with vaginal sarcoma. STUDY DESIGN: There were 8 cases of uterine carcinosarcoma (CS), 2 of leiomyosarcoma, 2 of endometrial stromal sarcoma (ESS), 1 of endocervical stromal sarcoma (ECSS) and 1 of malignant fibrous histiocytoma (MFH) of the vagina. The presence of sarcomatous components was retrospectively investigated by microscopic observation of preoperative specimens from the endocervical canal and endometrial cells. Characteristic features of sarcomatous cells were then investigated by cytodiagnostic micrometry of malignant cells. RESULTS: Of the 14 patients, 1 with low grade ESS and 1 with homologous CS were diagnosed as negative for sarcomatous components. One case of high grade ESS had been overlooked, as were 4 cases of CS. Thus, 7 cases (50%) were diagnosed as positive for sarcomatous cells by preoperative cytologic observation. Based on these findings, 12 of the 14 cases (85.7%) were positive for sarcomatous elements on retrospective reexamination of the specimens. CONCLUSION: Careful attention should be paid to small sarcomatous cells since cases of ESS or ECSS with such cells show morphologic characteristics similar to those of stromatous cells. Furthermore, careful microscopic observation of an entire specimen is required to avoid misdiagnosis as carcinoma since it is easy to overlook sarcomatous elements in smears with carcinosarcoma if there are only a few sarcomatous cells.

Ultrastructural study of benign, low-malignant potential (LMP), and malignant ovarian tumors.

Ultrastructural characteristics of benign, low-malignant potential (LMP), and malignant ovarian tumors were investigated, considering the aspects of histologic subtypes and histologic grading. In addition, the histogenesis of ovarian cancer was histologically investigated in an attempt to elucidate whether malignant tumor was generated from benign or LMP tumor, or whether it was generated de novo from normal tissues. Although all the benign, LMP, and malignant tumors appeared to be derived from Mullerian duct in serous tumors, the origin of endometrioid or mucinous tumor could not be ultrastructurally clarified. However, there was ultrastructural similarity between benign and malignant tumors among serous, endometrioid, and mucinous tumors, and it was suggested that benign adenoma may be the developmental origin of malignant tumors regardless of the histologic subtype. In addition, the investigation of endometrioid tumors revealed that the differences of histologic grading in malignant tumors reflected the ultrastructural differences, and that G1 tumor had an ultrastructure that was more similar to that of benign and LMP tumors than to that of G2 tumor.

Correlation between responsiveness of neoadjuvant chemotherapy and apoptosis-associated proteins for cervical adenocarcinoma.

OBJECTIVE: Adenocarcinoma of the uterine cervix appears to be increasing in prevalence and it has been suggested that these tumors tend to be less sensitive to radiation therapy and to chemotherapy than squamous carcinomas. In the present study, 29 patients with locally advanced cervical adenocarcinoma (bulky IB-IVB) were treated with neoadjuvant chemotherapy (NAC) using cisplatin, aclacinomycin-A and mitomycin-C, followed by radical surgery or irradiation. METHODS: To predict the prognosis and response to the chemotherapy, the expression of apoptosis associated-proteins, p53, p21WAF1/CIP1, Bcl-2 and activated caspase-3 was evaluated for tumor samples by immunohistochemistry. RESULTS: Of the analyzed clinicopathological factors, the overexpression of p53 was frequently observed in endocervical-type adenocarcinoma, nonresponders to chemotherapy and the grade 0 histologic effect of the chemotherapy. Positive staining of Bcl-2 was frequently observed in the early stage and had a better prognosis than for patients with the negative staining; however, there was no correlation between responders and nonresponders to chemotherapy. The expression of p21WAF1/CIP1 and caspase-3 was not correlated to the clinicopathological factors. CONCLUSION: In this study, the overexpression of p53 was found to be a factor to predict the chemoresistance and positive expression of Bcl-2 indicated as a better prognostic value. For p21WAF1/CIP1 and caspase-3, further analysis is necessary.

[Relationship between sleep disordered breathing and body weight loss in patients with chronic obstructive pulmonary disease].

We evaluated body weight loss and growth hormone secretion in patients with sleep-disordered breathing associated with chronic obstructive pulmonary disease. Of 11 patients hospitalized for pulmonary rehabilitation, five (WL group) had a history of body weight loss within two years before their interviews, while the other 6 patients (NWL group) had no changes in body weight. All patients underwent body index measurements, pulmonary function tests, blood gas analyses, assessments of nutritional status, and full night polysomnography for two consecutive days. Growth hormone levels were measured in the first 3-hour period following falling asleep. There were no significant inter-group differences between the results of pulmonary function tests, blood gas analyses, or nutritional status assessment. The WL group had a significantly higher percentage loss of body weight than the NWL group (mean +/- S.D. 11.5 +/- 4.7% in the WL group versus 2.7 +/- 1.8% in the NWL group, p < 0.01). The WL group had a significantly higher sleep apnea/hypopnea index than the NWL group (42.4 +/- 9.5/hr in the WL group versus 7.8 +/- 2.9/hr in the NWL group, p < 0.01). The WL group showed a higher rate of stage I + II sleep than the NWL group (84.9 +/- 7.0% versus 64.5 +/- 8.7%), with lower rates of slow wave sleep (2.2 +/- 2.1% versus 15.0 +/- 8.7%) and rapid eye movement sleep (12.9 +/- 6.3% versus 20.6 +/- 1.0%). The WL group showed a low level of growth hormone secretion with no peak in the sequential curve, but had a higher level of insulin growth factor-1 than the NWL group (148 +/- 36 ng/ml versus 90 +/- 22 ng/ml, p < 0.01). These results suggest that chronic obstructive pulmonary disease patients undergoing weight loss are likely to have an increase of growth hormone secretions in the daytime, possibly induced by underlying psychiatric disorders such as depression. Patients with chronic obstructive pulmonary disease may lose weight regardless of nutritional status because of a disturbance of growth hormone secretion resulting of sleep-disordered breathing.