Effects of long term octreotide on gall stone formation and gall bladder function.
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Acromegaly↗
Biomedical subjects
C E Sullivan
Publications and source records attributed to C E Sullivan.
Ventilatory response to sustained eucapnic hypoxia in the adult conscious dog.
The ventilatory response to 20 min sustained isocapnic hypoxia (SaO2, 80 +/- 2%) was examined in 5 trained unanesthetized adult dogs breathing through an endotracheal tube. End tidal PCO2 was maintained at the resting levels. The dogs' conscious status was monitored by recording EEG and EOG on a chart recorder. The room temperature was kept between 19 and 21 degrees C. All tests were repeated in each dog on 2 occasions: (1) unloaded tracheal breathing or (2) resistive loaded breathing. During unloaded tracheal breathing, the average ventilation in response to sustained hypoxia rose from a control of 5.1 +/- 0.3 L/min (mean +/- within-dog SE) to 19.2 +/- 1.1 L/min at the initial stage of hypoxia. Ventilation remained at 20.7 +/- 1.3 L/min at 10 min, and then 19.7 +/- 1.4 L/min at the completion of the 20 min hypoxic exposure. There was no ventilatory adaptation observed (P greater than 0.05). After release from hypoxia, the ventilation fell abruptly to 7.6 +/- 0.8 L/min, which was higher than the resting baseline level (P less than 0.05), and then gradually returned to the resting baseline within 10 min. Experiments exposing the dogs to 40 min sustained hypoxia also failed to elicit significant adaptation. During resistive loading, the pattern of average ventilation in response to sustained hypoxia was similar to that observed in unloaded breathing tests. But the ventilatory recovery was longer than unloaded breathing, returning to the resting baseline within 20 min. Again, there was no ventilatory adaptation observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, Physiological↗
Effects of high-frequency pressure waves applied to upper airway on respiration in central apnea.
We examined the effects of high-frequency (30-Hz) low-pressure oscillations on respiration in nine patients with central sleep apnea. All patients were studied during sleep and wore a nasal mask through which the oscillations were applied. All tests were performed during periods of repetitive central apneas. Respiratory efforts were monitored from the airflow and calibrated Respitrace signals. After several cycles of apnea were monitored, the oscillatory pressures were applied for brief periods (less than 5 s) at the midpoint of the central apneas. All trials in which arousal occurred were discarded, leaving a total of 106 trials in the nine patients. High-frequency oscillation of the upper airway stimulated respiratory effort(s) in 68% of all trials (72 of 106). Apnea length was significantly shortened in four of the nine patients. In one patient with a tracheostomy, the stimulus applied to his isolated upper airway evoked respiratory efforts during central apnea in 13 of 15 trials. We conclude that high-frequency oscillatory pressures applied to the upper airway can stimulate respiratory efforts during central apnea. This response may be mediated by upper airway receptors involved in nonrespiratory airway defense reflexes and may have implications in the treatment of patients with central sleep apnea.
Adult↗
Increased normoxic ventilation induced by repetitive hypoxia in conscious dogs.
To determine if a long-lasting increase in normoxic ventilatory drive is induced in conscious animals by repetitive hypoxia, we examined the normoxic [arterial O2 saturation (SaO2) > 93%] ventilatory response following successive episodes of 2-min eucapnic hypoxic challenges (SaO2 = 80%) in awake tracheotomized dogs. End-tidal CO2 was maintained at the resting level during and after repetitive hypoxia. The experimental protocol was performed twice in each of five dogs on separate days. To determine if changes in normoxic ventilation occurred between episodes of repetitive hypoxia, data were compared from six periods (epochs) for all experiments. The mean minute ventilation (VI) during three normoxic periods between episodes of intermittent hypoxia was 135, 154, and 169% of control (P < 0.05). VI during a 30-min recovery period was still higher at 183 and 172% of control (P < 0.05). Normoxic VI between hypoxic and recovery periods was significantly higher than the corresponding values in sham experiments. Our results indicate that a long-lasting increase in normoxic ventilation can be evoked in an awake unanesthetized dog by a short exposure to repetitive hypoxia.
Animals↗
Improvement in gas exchange with nasal continuous positive airway pressure in pulmonary alveolar microlithiasis.
A 37-yr-old man with pulmonary alveolar microlithiasis (PAM) presented with respiratory failure and cor pulmonale. The FEV1/FVC was 1.4/1.8 L with total lung capacity of 3.2 L using the helium dilution method (54% predicted) and 6.1 L using body plethysmography (102% predicted), indicating large noncommunicating regions. The KCO (transfer factor per liter lung volume) was 3.05 ml/min/mm Hg/L (47% predicted). Despite home oxygen (3 L/min) and diuretic therapy, the patient remained hypoxic (PaO2, 55 mm Hg) and incapacitated with dyspnea. Nasal continuous positive airway pressure (nCPAP) at 12 cm H2O and oxygen at 1 L/min improved his oxygenation (PaO2, 93 mm Hg), and introduction of this regimen at night resulted in subjective improvement in daytime function. A Grandjean right heart catheter was introduced at the bedside, and the multiple inert gas elimination technique (MIGET) was used to measure ventilation and blood flow distributions at ambient pressure and with the addition of 10 cm H2O nCPAP. The patient had severe pulmonary hypertension (mean Ppa, 57 mm Hg) and severe hypoxemia (PaO2 37 mm Hg), which was mainly due to shunt (16% of cardiac output) and a broadening of the main mode of the ventilation-perfusion (VA/Q) distribution (log SD Q, 0.94). There was a significant reduction in shunt during nCPAP to 6% of cardiac output without increasing Ppa, and this effect appeared to extend past the period of application. We conclude that nCPAP reduces intrapulmonary shunt in this rare condition and allows for correction of hypoxemia with a smaller oxygen flow rate.
Adult↗
A specific and potent pressor effect of hypoxia in patients with sleep apnea.
A hypoxic ramp test (to 75% arterial oxygen saturation) during the awake state was performed in 17 patients with obstructive sleep apnea (OSA). Blood pressure was monitored with an indwelling arterial line (radial artery), and the ventilatory response to eucapnic hypoxia was determined. Eight of the patients were normotensive. The remaining nine hypertensive patients were studied after a 3-wk washout of antihypertensive medication. Compared with a nonmatched group of normotensive nonsnoring control subjects in whom hypoxemia did not affect blood pressure, all OSA patients showed various degrees of pressor responses during hypoxia. The pressor response was of similar magnitude in normotensive and hypertensive patients with OSA. There was a significant relationship between the ventilatory and the pressor responses to hypoxia (p = 0.03) that was similar in both normotensive and hypertensive patients. Although disease severity expressed as apnea index (number of apneas per hour of sleep) or minimum arterial oxygen saturation reached during the overnight recording correlated with the magnitude of the pressor response (p = 0.03 and 0.045, respectively), the ventilatory response to hypoxia was unrelated to disease severity. Hypoxemia induced a similar increase in heart rate in controls and in normotensive patients, but an attenuated heart rate response was seen at the nadir of oxygen saturation in hypertensive subjects (p < 0.05). These data demonstrate that patients with obstructive sleep apneas have a pressor response to hypoxia. This response is likely to be involved in the blood pressure swings seen during apnea in patients with OSA.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Androgen blockade does not affect sleep-disordered breathing or chemosensitivity in men with obstructive sleep apnea.
As sleep apnea is more prevalent in men and testosterone has known effects on sleep apnea and chemosensitivity, reduction of androgen activity may influence sleep-disordered breathing and respiratory control. We studied the effect of 1 wk of treatment with flutamide, a nonsteroidal antiandrogen, on sleep, respiration, and ventilatory control in eight men with sleep apnea. Results on flutamide were compared with two baseline studies performed before and after the drug treatment period. Although effective androgen blockade was achieved as evidenced by increased hormone levels, flutamide had no effect on sleep architecture or chemoresponsiveness to hypoxia and hypercapnia. There was a trend towards a reduction in respiratory disturbance index in both NREM and REM sleep (41 +/- 4 baseline versus 34 +/- 3 flutamide, p = 0.09 NREM; 53 +/- 4 baseline versus 48 +/- 3 flutamide, p = 0.16 REM), but this was not significant. Our results indicate that androgen blockade had no clinically significant effect on sleep, sleep-disordered breathing, or chemosensitivity in patients with moderate to severe sleep apnea. More specific blockers such as gonadotrophin-releasing hormone analogs may have more clinical effect or, alternatively, androgen blockade may be more beneficial in patients with milder sleep apnea.
Adult↗
Nocturnal nasal IPPV stabilizes patients with cystic fibrosis and hypercapnic respiratory failure.
Nocturnal nasal intermittent positive pressure ventilation (nIPPV) has been used successfully in the management of patients with respiratory failure due to chest wall deformity and neuromuscular disease. In order to determine if nIPPV is useful in patients with cystic fibrosis (CF) complicated by respiratory failure, we treated four hypercapnic patients for up to 18 months. All patients had failed to respond to intensive conventional therapy, including nocturnal nasal CPAP in three of the patients. Within a few days of commencing nIPPV, all reported improved length and quality of sleep. There was lessening of the degree of hypercapnia and an increase in respiratory muscle strength. After stabilization in the hospital, all patients were able to be discharged home receiving nocturnal assisted ventilation. The improvements seen in these patients have been maintained for up to 18 months. We believe nIPPV offers an effective therapeutic approach for patients with end-stage CF in hypercapnic respiratory failure and may be particularly advantageous for those awaiting heart-lung transplant.
Adult↗
Circadian rhythm of blood pressure in patients with obstructive sleep apnea.
AIMS: The aims of this study were to examine the circadian variation in blood pressure (BP) in obstructive sleep apnea (OSA) and to compare this between normotensive and hypertensive subjects. METHODS: We measured 24-hour ambulatory BP (ABP) in 72 men (mean age 51 +/- 8 years), with OSA diagnosed on overnight sleep study. Measurements of BP were made at 15 min intervals for 24 h using either an Oxford Medilog ABP or Spacelabs 90207 recorder. All recordings were performed after > or = 3 week washout of anti-hypertensive drugs. The day-time monitoring period was defined as 07:00 hrs to 22:00 and night-time 22:00 to 07:00. The ratio of night:day systolic and diastolic BP was calculated. RESULTS: The patients were obese (mean body mass index 33 +/- 5 kg/m2) with a central pattern of obesity (waist:hip ratio 0.99 +/- 0.14, normal < 0.94). The mean 24-h ABP (systolic/diastolic) was 138 +/- 18/88 +/- 12 mmHg. The mean daytime ABP was 143 +/- 18/93 +/- 12 and night-time ABP 128 +/- 20/80 +/- 12 Hg. The night:day BP ratio was 0.90 +/- 0.07 (systolic) and 0.87 +/- 0.09 (diastolic) indicating that average BP was lower during the night. This pattern was similar in normotensive and hypertensive subjects. In contrast there was a significant relationship between increasing BMI and night:day blood pressure ratio (r = 0.56, p < 0.001) independent of the effects of OSA. CONCLUSION: In contrast to previous studies, men with OSA have a normal diurnal pattern of blood pressure levels. These findings suggest that any influence of OSA on BP is manifested throughout the 24-h period.
Adult↗
Sleep apnea in acromegaly.
OBJECTIVE: To provide information on the nature, prevalence, and severity of sleep apnea in patients with acromegaly. DESIGN: Consecutive case series. SETTING: Tertiary referral hospital. PATIENTS: Fifty-three patients with acromegaly were consecutively referred: 33 patients were referred because of clinical suspicion of sleep apnea and 20 patients were referred without suspected apnea. MEASUREMENTS: Sleep studies as well as growth hormone and insulin-like growth factor 1 (IGF-1) measurements were done. MAIN RESULTS: Thirty-one patients (93%; 95% Cl, 85% to 100%) referred because of suspicion of sleep apnea had sleep apnea compared with 12 patients (60%; Cl, 37% to 83%) referred without suspected sleep apnea. Patients with sleep apnea did not have biochemical evidence of increased disease activity (random growth hormone, 12.7 +/- 4.4 micrograms/L; mean growth hormone at 24-hour sampling, 10.8 +/- 8.4 micrograms/L; IGF-1, 90.0 +/- 7.5 nmol/L) compared with patients without sleep apnea (random growth hormone, 14.2 +/- 4.9 micrograms/L, P greater than 0.2; mean growth hormone, 12.4 +/- 3.5 micrograms/L, P greater than 0.2; IGF-1, 90.0 +/- 10.0 nmol/L, P greater than 0.2). Central sleep apnea was the predominant type of apnea in 33% (Cl, 18% to 47%) of patients and was associated with higher random growth hormone and IGF-1 levels than was obstructive apnea (random growth hormone, 23.4 +/- 3.9 compared with 8.8 +/- 3.1 micrograms/L, P less than 0.001; IGF-1, 126 +/- 17.5 compared with 72.5 +/- 7.5 nmol/L, P less than 0.01). CONCLUSIONS: Sleep apnea is common in acromegaly. The rate of central sleep apnea was unexpectedly high in patients with acromegaly, and biochemical evidence of increased disease activity was associated with the presence of central apnea rather than with the degree of sleep apnea. Altered respiratory control is a possible mechanism producing sleep apnea in acromegaly.
Acromegaly↗
Sleep disorders in Marfan's syndrome.
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Adolescent↗
Erythropoietin concentrations in obstructive sleep apnoea.
Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.
Adult↗
Effects of upper airway pressure on abdominal muscle activity in conscious dogs.
We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.
Abdomen↗
Substance P immunoreactive nerves in airways from asthmatics and nonasthmatics.
Substance P has been localized to nerves supplying smooth muscle, blood vessels and glands in the human lung and may play a major role in the pathophysiology of asthma. We performed a morphological study, using the avidin biotin peroxidase immunostaining technique, to examine sections of airway wall from subjects with and without asthma for the presence of substance P immunoreactive nerve fibres. Airways of 200 microns-12 mm were obtained from autopsy, lobectomy and bronchoscopy. Quantitative morphological analysis was performed on 3 mm diameter airways from three asthmatic and three nonasthmatic subjects collected at autopsy, and on biopsies of 10 mm diameter airways from eight asthmatic and thirteen nonasthematic subjects. There was an increase in both the number and the length of substance P immunoreactive nerve fibres, in airways from subjects with asthma when compared with airways from subjects without asthma. Fibres were found in the lamina propria and surrounding vessels and glands. The fibres were commonly seen as bundles rather than as single fibres. There was no difference in the number of substance P nerves between normal subjects and subjects with chronic airflow limitation (CAL). The difference in the number, length and morphological characteristics of the substance P immunoreactive nerves between asthmatic and nonasthmatic subjects were striking.
Adult↗
Abdominal muscle activity in conscious dogs: effect of sleep and route of breathing.
Abdominal muscle activity (EMGabd) was studied in 4 adult dogs during wakefulness and sleep. The dogs were previously prepared with a permanent side-hole tracheal stoma, and were trained to sleep with a tightly-fitted snout mask, hermetically sealed in place. They breathed either through a cuffed endotracheal tube inserted distally into the tracheal stoma (tracheal), or through the upper airway, with the tracheal stoma plugged (nasal). Sleep state was determined by behavioural, electroencephalographic and electromyographic criteria. EMGabd activity was measured using fine bipolar needles inserted into the abdominal muscle layers. Expiratory EMGabd augmented progressively from sleep onset to SWS regardless of route of breathing, and without major changes in the animal's ventilation. Maximal EMGabd occurred in SWS during nasal breathing; EMGabd increased from a mean of 16.6 +/- 0.3 mV awake, to 23.8 +/- 0.3 mV in SWS, representing an overall increase of 55.0 +/- 7.5% from the awake level. EMGabd increased similarly during tracheal breathing, with an overall increase of 62.0 +/- 15.4% in SWS. We conclude that the consistent augmentation of expiratory EMGabd activity in sleep indicates that expiration in the dog is an active process, which is enhanced during nasal breathing and NREM sleep.
Abdomen↗
Respiratory failure and sleep in neuromuscular disease.
Sleep hypoxaemia in non-rapid eye movement (non-REM) and rapid eye movement (REM) sleep was examined in 20 patients with various neuromuscular disorders with reference to the relation between oxygen desaturation during sleep and daytime lung and respiratory muscle function. All the patients had all night sleep studies performed and maximum inspiratory and expiratory mouth pressures (PI and Pemax), lung volumes, single breath transfer coefficient for carbon monoxide (KCO), and daytime arterial oxygen (PaO2) and carbon dioxide tensions (PaCO2) determined. Vital capacity in the erect and supine posture was measured in 14 patients. Mean (SD) PI max at RV was low at 33 (19) cm H2O (32% predicted). Mean PE max at TLC was also low at 53 (24) cm H2O (28% predicted). Mean daytime PaO2 was 67 (16) mm Hg and PaCO2 52 (13) mm Hg (8.9 (2.1) and 6.9 (1.7) kPa). The mean lowest arterial oxygen saturation (SaO2) was 83% (12%) during non-REM and 60% (23%) during REM sleep. Detailed electromyographic evidence in one patient with poliomyelitis showed that SaO2% during non-REM sleep was maintained by accessory respiratory muscle activity. There was a direct relation between the lowest SaO2 value during REM sleep and vital capacity, daytime PaO2, PaCO2, and percentage fall in vital capacity from the erect to the supine position (an index of diaphragm weakness). The simple measurement of vital capacity in the erect and supine positions and arterial blood gas tensions when the patient is awake provide a useful initial guide to the degree of respiratory failure occurring during sleep in patients with neuromuscular disorders. A sleep study is required to assess the extent of sleep induced respiratory failure accurately.
Adult↗
Tracheal smooth muscle responses to upper airway pressure in conscious dogs.
We studied the influence of changes in pressure applied to the isolated upper airway of four conscious dogs on tracheal smooth muscle tone and breathing pattern. The dogs were prepared with a permanent side-hole tracheal stoma and were trained to sleep with a snout mask hermetically sealed in place while breathing through a cuffed endotracheal tube inserted distally into the tracheal stoma. Changes in tracheal smooth muscle tone were continuously monitored by measuring the pressure in the water-filled cuff that distended the tracheal airway while pressure changes were introduced in the upper airway independently of breathing. Increases or decreases of upper airway pressure (+/- 10 cmH2O) had little effect on tracheal airway smooth muscle tone. In contrast, an oscillating pressure wave at 30 Hz and +/- 3 cmH2O amplitude (or -3 to -7 cmH2O amplitude) caused a marked increase in tracheal airway smooth muscle tone. An elevated tracheal airway tone could be maintained over many minutes when the oscillating pressure stimulus was pulsed so that there was a cycle of 0.5 s on, 0.5 s off. This stimulus did not change the functional residual capacity but resulted in coughing, swallowing, or sighing in 54% of the tests. In the remaining tests, the pressure stimulus produced a rapid, shallow, and erratic breathing pattern. The tracheal airway constrictor response (but not the ventilatory response) was completely abolished by intravenous atropine. We suggest that upper airway vibration is a potentially powerful mechanism of reflex airway smooth muscle constriction.
Animals↗
Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs.
We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.
Anesthesia↗