Effects of systemic administration of mirtazapine on respiratory muscle activity in sleeping rats.

Mirtazapine (MIRT) is an antidepressant with mixed noradrenergic and serotonergic effects in central nervous system. The present study was undertaken to assess whether MIRT can stimulate genioglossus muscle (GG) activity in the conscious, behaving rat. Nine male rats were chronically instrumented with GG and neck muscle EMG electrodes. EEG electrodes were implanted to acquire sleep stage. Results demonstrated a dose-dependent effect of MIRT on GG activity during sleep, although no changes reached statistical significance. Low dose MIRT (0.1 mg/kg) showed a slight increase in GG phasic activity. In contrast, higher doses of MIRT (0.5-1.0 mg/kg) tended to decrease GG activity relative to vehicle, in addition to decreasing total sleep time.

The effect of codeine on the Urge-to-Cough response to inhaled capsaicin.

We have shown previously in normal subjects that a sensory measure, the Urge-to-Cough rating, increases at concentrations of inhaled capsaicin that are lower than those necessary to elicit reflex cough. This finding suggests that the Urge-to-Cough may represent an index of the cough response. Research on cough in the human has most often employed challenge with inhaled capsaicin to induce reflex cough. Current measures of cough sensitivity in the human provide no information regarding the intensity of cough. The influence of codeine on cough perceptual sensitivity and the relationship to cough intensity with capsaicin-induced cough in normal subjects has not been evaluated. This study determined the effect of codeine on capsaicin-induced cough perceptual sensitivity and motor response in normal subjects in a double-blind, placebo-controlled, crossover study. This approach investigated the relevance of cough sensitivity, intensity, and sensory modalities in the assessment of cough suppression in humans. This study consisted of three experimental trials: administration of placebo, 30 mg codeine and 60 mg codeine. The study was double-blinded. The order of the three trials was randomized. Respiratory motor pattern was recorded with EMGs from the rectus abdominis, lateral abdominal muscles and eighth intercostal space. The subjects leaned into a fume hood to inspire deeply for 2 s once through a mouthpiece connected to the nebulizer. A modified Borg scale was used to estimate their Urge-to-Cough. The experimental trial consisted of eight test solutions of 0-200 microM capsaicin. Each solution was presented three times in a randomized block order for a total of 24 presentations. The lowest capsaicin concentration to elicit a cough was determined. The lowest capsaicin concentration to elicit an Urge-to-Cough greater than zero was identified. The Urge-to-Cough sensitivity was determined from the log-log slope. For placebo, the Urge-to-Cough was zero with inhalation of the vehicle and no coughs were observed. The threshold capsaicin concentration for subjects to report an Urge-to-Cough was 15.6 microM (+/-2.6 SEM). The capsaicin concentration threshold for eliciting a cough was significantly greater, 39.3 microM (+/-5.6 SEM). As the capsaicin concentration increased, the magnitude estimation of the Urge to-Cough increased. The slope of the log-log relationship for the Urge-to-Cough was 0.94 (+/-0.07 SEM). As the capsaicin concentration increased, the number and intensity of the coughs increased. The administration of 30 and 60 mg codeine had no significant effect on the threshold capsaicin concentration for the Urge-to-Cough. There was also no significant codeine effect on the slope of the log-log Urge-to-Cough relationship. Thirty and sixty milligram codeine had no significant effect on the relationship between the capsaicin concentration and the number and intensity of the coughs. The results of this study demonstrate that the threshold for a subject to perceive an Urge-to-Cough was less than the capsaicin concentration that elicits the cough motor response. There was a direct relationship between the sensory intensity (magnitude estimation of the Urge-to-Cough) and the cough number and intensity. Thus, as the sense of an Urge-to-Cough increased the cough motor response increased. Neither the 30 nor 60 mg codeine affected the perceptual or motor sensitivity to capsaicin-induced cough. These results showed that the initial threshold for responding to capsaicin-induced cough is the perception of an Urge-to-Cough, followed by a motor cough response if the capsaicin is increased above the perceptual threshold. As the capsaicin concentration increases, both the perceptual need to cough and the cough motor response increase. The response of subjects to inhalation of capsaicin consisted of both a sensory component leading to perception of an Urge-to-Cough and motor cough behavior.

Mucinous adenocarcinoma of the face. A case report.

Cutaneous mucinous adenocarcinoma is a rare neoplasm. It occurs most commonly on the facial skin. We present a case of an apparently recurrent primary mucinous adenocarcinoma of the facial skin and highlight the necessary diagnostic work up and management of this tumour.

Encapsulated fat necrosis: a case of 'thigh mouse'.

Encapsulated fat necrosis is a rare condition with clinical features that closely resemble a lipoma. The aetiology and pathogenesis are not fully understood but the condition has a distinctive histological appearance. We describe a case of encapsulated fat necrosis that exhibited unusual mobility. The literature is also reviewed.

Cardiac autonomic control in obstructive sleep apnea: effects of long-term CPAP therapy.

To determine how long-term treatment with continuous positive airway pressure (CPAP) affects cardiac autonomic function, we measured R-R interval (RRI), respiration, and blood pressure in 13 awake patients with moderate-to-severe obstructive sleep apnea (OSA) in both supine and standing postures, before and after 3 to 9 mo of home therapy. Using visual feedback, the subjects controlled their respiration to track a randomized breathing pattern. From the RRI spectrum, we computed high-frequency power and the ratio of low-frequency to high-frequency power (LHR). To correct for differences in breathing, the average transfer gain relating respiration to RRI changes (G(RSA)) and the modified low-frequency to high-frequency ratio (MLHR) were also derived. CPAP therapy did not change the conventional spectral indices of heart rate variability (HRV). However, G(RSA) increased with average nightly CPAP use in supine (p < 0.01) and standing (p < 0.03) postures, whereas MLHR decreased with CPAP compliance during standing (p < 0.03). Supine mean heart rate decreased with compliance (p < 0.03). None of the estimated parameters was correlated with duration of therapy when actual CPAP use was not taken into account. These results suggest that CPAP treatment improves vagal heart rate control in patients with OSA and that the degree of improvement varies directly with compliance level.

A small contact burn injury requiring upper limb amputation.

An elderly, demented, man was referred with a fairly small contact burn to the medial side of his left arm and forearm. The thermal injury had caused ischaemia of the forearm and hand. Thrombosis of the underlying brachial artery was suspected, and the only surgical option was amputation. This is an unusual but devastating complication of a contact burn. Those particularly at risk of this injury include the demented, elderly, epileptics and neuropathics, who may lie helpless or unaware of prolonged contact with warm objects.

Reconstruction of the scalp and cranium using multiple free-tissue transfers following recurrent basal cell carcinoma.

It is well-recognised that recurrent disease can occur following surgery for malignancy in the head and neck region. This is particularly true of basal cell carcinoma in which recurrences may occur over many years and despite the use of different treatment modalities. Reconstruction of large defects may become increasingly difficult and can be optimally managed by free tissue transfer. The authors report a case of basal cell carcinoma that has required treatment for over 20 years, unique in that on five different occasions, free flaps have been used for reconstruction.

Spectral indices of cardiac autonomic function in obstructive sleep apnea.

Spectral analysis of heart rate variability (HRV) is useful as a noninvasive means of assessing autonomic function in patients with obstructive sleep apnea (OSA). However, standard spectral measures, such as the ratio of low-frequency to high-frequency power (LHR) and normalized high-frequency power (NHFP), can be confounded by the abnormal breathing patterns that occur during sleep. To circumvent this limitation, we employed an autoregressive modeling approach to partition the RR time-series into a component that is correlated with respiration and a respiration-independent component. From these components, we derived two new spectral indices: the modified LHR (MLHR) and the average gain relating respiration to RR changes (GRSA). Six normals and seven OSA patients were studied in relaxed wakefulness and stage 2 sleep; during sleep, the OSA patients were studied without and with continuous positive airway pressure (CPAP) therapy. All four spectral indices showed significant differences between OSA patients and normals in both wakefulness and sleep, although the changes in MLHR and GRSA were substantially larger and less variable: MLHR (p < 0.0003) and GRSA (p < 0.0001) vs. LHR (p < 0.005) and NHFP (p < 0.004). However, in the OSA subjects, LHR and NHFP were unchanged by CPAP. By contrast, CPAP produced a highly significant increase in GRSA (p < 0.0004), as well as a decrease in MLHR (p < 0.03). Thus, by compensating for the effects of breathing pattern differences, MLHR and GRSA unmasked the effects of CPAP therapy, which has been shown in previous studies to reduce sympathetic activity and increase vagal cardiac modulation.

Acute effects of paroxetine on genioglossus activity in obstructive sleep apnea.

STUDY OBJECTIVE: To determine the acute effects of paroxetine on genioglossus activity during NREM sleep. DESIGN: A single dose of Paroxetine (40 mg) or placebo was administered four hours before bedtime on nights separated by one week in a double blind randomized crossover manner. The moving time average of genioglossus muscle activity (EMGgg) expressed as a percentage of maximum was measured using a mouthpiece electrode customized for each subject. The peak inspiratory and tonic values of EMGgg and the corresponding esophageal pressure deflections (DP) during the last three occluded breaths of obstructive apneas during NREM sleep were analyzed. SETTING: NA. PARTICIPANTS: 8 adult men with severe obstructive sleep apnea (OSA). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Paroxetine increased the peak inspiratory EMGgg (29.8+/-2.4 (SE) versus 24.4+/-2.7 % max, p<0.05) and peak EMGgg/DP ratio (0.78+/-0.12 versus 0.65+/-0.11 % max/cm H2O, p<0.01) but not the tonic EMGgg (11.6+/-0.9 versus 9.8+/-0.7 % max) nor the DP (39.4+/-2.2 versus 38.2+/-2.8 cm H2O). Linear regression analysis of the peak inspiratory EMGgg versus DP relationship showed that paroxetine increased the slope (0.62+/-0.11 versus 0.49+/-0.09 % max/cm H2O, p<0.01). However, the apnea + hypopnea index (paroxetine: 75.2+/-5.5 versus placebo: 73.7+/-6.9 events/hour) did not differ. CONCLUSIONS: Paroxetine augmented peak inspiratory genioglossus activity during NREM sleep but this effect was not sufficient to decrease the frequency of obstructive apnea in this group with severe OSA.

Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea.

We studied the within-night variability of the maximum esophageal pressure deflection before apnea termination (DPmax) in nine patients with severe obstructive sleep apnea as an index of the arousal threshold and the mean electroencephalogram (EEG) delta power for each 30 s as an index of the timing of sleep cycles. Periodicity in the time variation of delta power and DPmax was analyzed by determining their power spectral density and their relationship determined by cross correlation. DPmax and delta power varied cyclically and in phase with a major periodicity (major peak in power spectral density) of 117.6 +/- 8.8 (SE) min. The correlation between the values of DPmax and delta power was significant (P < 0.001) in each subject (mean r = 0.47 +/- 0.03), and the coherence between DPmax and delta power at their dominant frequency was high. Within cycles of non-rapid-eye-movement sleep, DPmax and delta power increased, reaching peak values on average at or after midcycle. These findings suggest that the arousal threshold to airway occlusion in patients with obstructive sleep apnea varies cyclically during the night synchronous to the underlying cycles of sleep.

Ventilatory dynamics of transient arousal in patients with obstructive sleep apnea.

The hyperpnea that accompanies arousal at the end of obstructive apnea is believed to be due to the progressive build-up in chemical drive during the apnea and a state-related decrease in upper airway resistance. We postulated the existence of a third component: a state-related transient increase in neural drive to the ventilatory pump muscles. To quantify this contribution, we measured the ventilatory response to arousal (VRA) in eight patients with obstructive sleep apnea (OSA) during continuous positive airway pressure (CPAP) therapy, applied at individually titrated levels. CPAP application reduced total pulmonary resistance (RL) to approximately normal levels, stabilizing ventilation and sleep state. Transient arousal from stage 2 sleep was induced using 5-sec tones (60-90 dB). Mean inspiratory flow increased above control on the second and third post-arousal breaths (P < 0.05), with a peak increase of 7.8 +/- 2.9 L/min while the accompanying changes in RL were significant. The time-course of VRA measured in three normal subjects under CPAP was similar to that observed in the OSA patients. However, elimination of CPAP prolonged the VRA time-course. Taken together, these findings demonstrate that: (1) during arousal, the increase in state-related neural respiratory drive is short-lived but not substantial; and (2) the resulting VRA time-course is shaped by the dynamics of the upper airway response to arousal.

Nasal dermoid cysts in siblings.

Nasal dermoid cysts are congenital malformations which result from anomalous embryological development. Two cases occurring in siblings are presented. There have been several previous reports that the condition may be familial but in this report the initial suspicion of the milder anomaly in the younger child was raised primarily because of his older brother's history. This further report suggests that the incidence of familial occurrence of this anomaly may be greater than current literature suggests, and the possibility that other family members may be affected should be remembered by clinicians treating patients with this condition.

The survival of human skin stored by refrigeration at 4 degrees C in McCoy's 5A medium: does oxygenation of the medium improve storage time?

To establish the viable storage time of human skin stored by refrigeration at 4 degrees C in McCoy's 5A medium and to establish whether oxygenating the medium improves the viable storage time, the following experiment was conducted. Eighty discs of human split-thickness skin graft, each 3 mm in diameter, were stored in 40 sterile sealable containers under four different conditions: in 0.9% saline, in McCoy's 5A medium, in oxygenated McCoy's 5A medium, and in carbon dioxide supplemented McCoy's 5A medium. Skin graft viability was assessed using tissue culture. Skin stored in saline was viable for only 1 week, whereas skin stored in McCoy's 5A medium and in oxygenated McCoy's 5A medium was viable for 4 weeks. Skin stored in carbon dioxide supplemented McCoy's 5A solution did not even survive the first week. These findings show that McCoy's 5A medium allows at least 4 weeks of viable human skin storage by refrigeration at 4 degrees C. Furthermore, oxygenating the medium does not seem to improve the viable storage time, and carbon dioxide supplementation is detrimental. The advantages of skin storage by refrigeration and the implications of the above findings are discussed. A clinical case in which split-thickness skin was stored for approximately 5 weeks and still resulted in good graft take is quoted as an example of our experience with the use of McCoy's 5A medium.

Fuzzy assessment of sleep-disordered breathing during continuous positive airway pressure therapy.

We propose a new method of quantifying sleep-disordered breathing (SDB) for the purpose of automating continuous positive airway pressure (CPAP) titration. Our algorithm, based on fuzzy logic, emulates the less-than-crisp kind of decision-making generally employed at the human level. Three input variables were first derived on a breath-by-breath basis from respiratory airflow measurements. These were: (1) the relative duration of inspiratory flow limitation in each breath; (2) the degree of hypopnea relative to the past 15 breaths; and (3) the intensity of snoring. Using these descriptors as inputs, our fuzzy inference algorithm produced a "severity index" (SI) quantifying the degree of SDB. Severity index was determined in CPAP titration procedures conducted on one normal snorer and 12 patients with moderate-to-severe obstructive sleep apnea. SI computed over the last 6 minutes of each CPAP level was compared against other more-conventional indices of SDB, such as total pulmonary resistance (RL), the number of apneas and hypopneas (NAH), and the number of arousals (NAr). In all but one of the subjects, the correlation coefficients for SI vs each of RL, NAH, and NAr were significantly different from zero, but not different from each other. The group correlation coefficients for SI vs RL, NAH, and NAr were 0.89, 0.86, and 0.87, respectively, demonstrating that SI accurately quantifies SDB. SI collapses multiple features of the airflow pattern into a single index and, therefore, may be useful as a "feedback" variable for the automatic control of CPAP therapy.

Respiratory arousal from sleep: mechanisms and significance.

The mechanisms by which respiratory stimuli induce arousal from sleep and the clinical significance of these arousals have been explored by numerous studies in the last two decades. Evidence to date suggests that the arousal stimulus in nonrapid eye movement sleep (NREM) is related to the level of inspiratory effort rather than the individual stimuli that contribute to ventilatory drive. A component of the arousal stimulus proportional to the level of inspiratory effort may originate in mechanoreceptors either in the upper airway or respiratory pump. Medullary centers responsible for ventilatory drive may also send a signal proportionate to the level of drive to higher centers in the brain which are responsible for arousal. Thus, the arousal stimulus may consist of multiple components, each increasing as inspiratory effort increases. The level of effort triggering arousal is an index of the arousability of the brain (arousal threshold). A deeper stage of sleep, central nervous system depressants, prior sleep fragmentation, and the presence of obstructive sleep apnea (OSA) have been observed to increase the arousal threshold to airway occlusion. Less information is available concerning the mechanisms of arousal from rapid eye movement (REM) sleep. While REM sleep is associated with the longest obstructive apneas in patients with OSA, normal human subjects appear to have a similar or lower arousal threshold to respiratory stimuli in REM compared to NREM sleep. Recent studies have challenged the assumption that the termination of all obstructive apnea is dependent on arousal from sleep. Improvements in methods to detect and quantitate changes in the cortical electroencephalogram (EEG) may better define the relationship between arousal and apnea termination. This may result in improved criteria for identifying EEG changes of clinical significance. While little is known concerning the mechanisms of arousal in central sleep apnea, arousal may play an important role in inducing this type of apnea in some patients.