Tremulous arytenoid movements predict severity of glottic stenosis in multiple system atrophy.

To determine whether tremulous arytenoid movements predict the severity of glottic stenosis in patients with multiple system atrophy (MSA), 28 MSA patients and 14 age-matched controls underwent fiberoptic laryngoscopy with video monitoring during wakefulness and under anesthesia induced by intravenous injection of propofol. Presence or absence of tremulous arytenoid movements was recorded during wakefulness. The ratio of glottic stenosis (%), which represents the extent of airway narrowing under anesthesia, was obtained by measuring the inspiratory glottic angle during wakefulness and under anesthesia. The median ratio of glottic stenosis was significantly higher in patients with MSA (57.5%) than in control subjects (0.5%). Tremulous arytenoid movements were characterized by shaking movements of the arytenoid region including the vocal folds, which are most apparent in the arytenoid cartilage. In this study, tremulous arytenoid movements were observed in 18 (64.2%) of 28 patients with MSA, who displayed a significantly higher median ratio of glottic stenosis (71.2%) than other patients (34.9%). None of the control subjects exhibited tremulous arytenoid movements. A clear correlation existed between the ratio of glottic stenosis and disease duration. Our observations indicate that tremulous arytenoid movements are a marker of the severity of glottic stenosis, which confers an increased risk of upper airway obstruction in patients with MSA.

Daytime hypoxemia, sleep-disordered breathing, and laryngopharyngeal findings in multiple system atrophy.

BACKGROUND: The mechanism underlying nocturnal sudden death in patients with MSA remains unclear. It may be explained by upper airway obstruction, such as vocal cord abductor paralysis; an impairment of the respiratory center, such as Cheyne-Stokes respiration; or an impaired hypoxemic ventilatory response. OBJECTIVE: To investigate the mechanism of sleep-disordered breathing in multiple system atrophy (MSA). DESIGN: We recruited 21 patients with probable MSA who were admitted sequentially to our hospital, and performed daytime blood gas analysis, pulmonary function tests, polysomnography, and fiberoptic laryngoscopy during wakefulness and with the patient under anesthesia. RESULTS: A decrease in arterial oxygen pressure and an increase in alveolar-arterial oxygen gradient significantly correlated with disease duration (P = .045 and .046, respectively). Polysomnography demonstrated Cheyne-Stokes respiration in 3 (15%) of 20 patients. Fiberoptic laryngoscopy during wakefulness showed that 3 (14%) of the 21 patients exhibited vocal cord abductor paralysis, and laryngoscopy under anesthesia showed that 9 (45%) of 20 patients exhibited vocal cord abductor paralysis. Laryngoscopy under anesthesia also revealed that 11 (55%) of 20 patients showed upper airway obstruction in places other than the vocal cords, including obstruction at the base of the tongue or soft palate. In addition, it demonstrated novel laryngopharyngeal findings, such as floppy epiglottis and airway obstruction at the arytenoid. CONCLUSIONS: We observed daytime hypoxemia with an increased alveolar-arterial oxygen gradient, Cheyne-Stokes respiration, and novel abnormal laryngopharyngeal movements in patients with MSA. We also found that laryngoscopy under anesthesia might be useful for evaluating upper airway obstruction. The significance of these findings to the mechanism of sudden death in those with MSA needs to be examined.

Demographic characteristics of 3,659 Japanese patients with obstructive sleep apnea-hypopnea syndrome diagnosed by full polysomnography: associations with apnea-hypopnea index.

Information on obstructive sleep apnea-hypopnea syndrome (OSAHS) in Japan has been limited. The purposes of this clinical study were to evaluate the demographic characteristics of Japanese OSAHS patients and to assess how demographic factors are associated with OSAHS severity. We analyzed 3,659 OSAHS patients who underwent polysomnographic evaluation between January 2000 and December 2004 at 11 hospitals in Niigata Prefecture, Japan. Data consisted of apnea-hypopnea index (AHI) and demographic characteristics, including sex, age, and body-mass index, for statistical analysis. Levels of obesity were classified according to the WHO criteria. The male-to-female patient ratio for OSAHS was 4.6, and male patients presented more severe OSAHS than female patients. High AHI and a high proportion of moderate to serious OSAHS (AHI > or = 15) were found among the patients in their 30s, as well as female patients in their 70s and male patients in their 80s. The AHI and the proportion of moderate-to-serious OSAHS (AHI > or = 15) were greater in patients classified as underweight than in normal weight patients. In conclusion, there is a higher male predominance in the prevalence of OSAHS, and in both sexes, the results suggest different pathophysiological mechanisms of deteriorating OSAHS between adults under age 55 and adults 55 years or over. In addition, underweight patients exhibit more severe OSAHS than normal weight patients.

Caspase-3, caspase-8, and nuclear factor-kappaB expression in human cholesteatoma.

BACKGROUND: Cholesteatoma is characterized by the accumulation of keratinizing epithelium resulting from the proliferation and differentiation of epithelium. Researchers are presently unraveling the role that apoptosis plays in the disease seen in cholesteatoma epithelium. Caspases play a key role in apoptosis. Caspase-8, which is activated by the induction of tumor necrosis factor-alpha, leads to activation of caspase-3, which activates apoptotic nucleases. Nuclear factor-kappaB is a transcription factor known to inhibit apoptosis induced by tumor necrosis factor-alpha. HYPOTHESIS: In this study, we hypothesized that expression of caspase-3, caspase-8, and nuclear factor-kappaB is uniquely connected to the proliferation, differentiation, and programmed cell death of keratinocytes during the growth and development of cholesteatoma. METHODS: We obtained 41 cholesteatoma specimens for this study. The presence of these proteins in cholesteatoma was examined using immunohistochemistry and a colorimetric assay system. We also examined the patterns of apoptosis by using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. RESULTS: Using the immunoperoxidase staining method, caspase-3 was found to be densely localized in the spinous and granular layers of cholesteatoma epithelium; caspase-8 was also found in the granular layer. Nuclear factor-kappaB was localized densely in the perinuclear region of the epithelium. The results obtained with immunoperoxidase staining agreed with those obtained with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. In addition, the colorimetric assay method was used to measure the activity of caspase-3. CONCLUSION: These findings suggest that caspase-3 and caspase-8 play important roles in programmed cell death, which results in the accumulation of keratin debris during the growth of cholesteatoma. Nuclear factor-kappaB was found in cholesteatoma epithelium, but the transcription factor appeared to be inactivated.