Disseminated Strongyloides stercoralis infection. Association with ectopic ACTH syndrome and depressed cell-mediated immunity.

A patient with disseminated Strongyloides stercoralis was evaluated to elucidate host factors that may have led to the development of this infection. The patient was found to have oat cell carcinoma with hypercortisolism produced by tumor adrenocorticotropic hormone. His serum contained a potent inhibitor of lymphocyte blastogenesis. This patient's high level of endogenous cortisol may have impaired lymphocyte function and thereby facilitated infection with S stercoralis.

Pulsatile growth hormone secretion in older persons is enhanced by fasting without relationship to sleep stages.

Spontaneous secretion of GH decreases with aging. To investigate whether fasting increases pulsatile GH secretion in older as it does in younger subjects, we studied six subjects (four postmenopausal women and two men, aged 55-81 yr; body mass indexes, 22-24 kg/ m2). Blood was obtained every 5 min for 24 h on a control (fed) day and on the second day of a fast. Serum GH concentrations, measured by an immunoradiometric assay, were analyzed with a multiple parameter deconvolution method to stimultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 4-fold increase in the 24-h GH production rate (38 +/- 25 vs. 166 +/- 42 micrograms/L distribution volume; P = 0.003) and a 2-fold increase in the amount of GH secreted per pulse (2.4 +/- 1.4 vs. 5.5 +/- 1.2 micrograms/L distribution volume; P = 0.02). The latter was a result of increased secretory burst amplitudes with unchanged secretory burst durations. The number of detectable GH secretory bursts per 24 h was also increased by fasting (13 +/- 1.4 vs. 30 +/- 1.1; P = 0.0004); the GH pulse frequency may have been underestimated in the fed state, as 33 +/- 4.9% of the samples had undetectable ( < 0.2 microgram/L) serum GH concentrations compared to 5.2 +/- 2.6% of the samples on the fasting day (P = 0.004). The t1/2 of endogenous GH was not significantly altered by fasting. The fold increase in GH secretion with fasting was similar to that previously observed in young men, although absolute levels of GH secretion were approximately 50% lower in both fed and fasted conditions. Fasting decreased the proportion of sleep time spent in rapid eye movement sleep (4.7 +/- 1.3 vs. 15 +/- 2.1%; P = 0.005), but did not significantly increase slow wave (stages 3 and 4) sleep. In both fed and fasted conditions, mean GH secretion rates were similar during daytime wakefulness, nocturnal wakefulness, rapid eye movement sleep, and stages 1, 2, and 3 of sleep. We conclude that hyposomatotropism associated with aging is partially reversed by fasting, and the enhancement of GH secretion by fasting is not related to changes in slow wave sleep. These data indicate that GH secretion in older persons can be enhanced by physiological interventions.

Effect of very-low-calorie diets with weight loss on obstructive sleep apnea.

To determine the effect of very-low-calorie diets (VLCDs) with weight loss on obstructive sleep apnea (OSA), we studied eight obese subjects with OSA, five males and three females. Subjects consumed a VLCD of 1760 kJ (420 kcal) (67% protein, 4% fat, 29% carbohydrate) or 3350 kJ (800 cal) (20% protein, 30% fat, 50% carbohydrate) with 100% of the recommended daily allowance of vitamins and minerals. Mean (+/- SD) values of weight and respiration before and after weight loss were, for weight, 153 +/- 37 and 132 +/- 29 kg (P less than 0.05); for BMI (kg/m2), 54 +/- 13 and 46 +/- 10 (P less than 0.05); for desaturations/h sleep, 106 +/- 50 and 52 +/- 45 (P less than 0.05); for apneas + hypopneas/h sleep, 90 +/- 32 and 62 +/- 49; for Pco2, 48 +/- 10 and 42 +/- 4 torr (P less than 0.05). Desaturation episodes/h and apnea + hypopneas/h improved in six patients. The most obese subject (female, BMI 81) who lost the most weight (47 kg) did not improve, nor did the subject who lost the least weight, 7 kg. The number of movements + arousals from sleep decreased in all patients (P less than 0.05). We conclude that VLCD with weight loss can produce improvement in OSA; subjects who lose a small amount of weight or subjects who are extraordinarily obese before and after weight loss may not improve.

Rapidly progressive silicon nephropathy.

Rapidly progressive renal failure developed in four patients with silica exposure. Three presented with manifestations of a connective tissue disorders. All had abnormal proteinuria, hypoalbuminemia and active urinary sediments. Histologically, a distinct constellation of findings was present, consisting of glomerular hypercellularity and sclerosis, crescents, interstitial cellular infiltrates and tubular necrosis with red cell casts as seen on light microscopy. On electron microscopy there was foot process obliteration, characteristic cytoplasmic dense lysosomes, microtubules and dense deposits. Despite vigorous treatment, two patients died of the systemic illness and one is on hemodialysis. The fourth is improved after pulse methylprednisolone therapy. We propose that silica induced this multisystem disease through activation of the immune system and a direct tissue toxic effect.

Massive proteinuria and acute renal failure in a patient with acute silicoproteinosis.

Acute pulmonary silicoproteinosis, massive proteinuria and fatal renal failure developed in a 23 year old male sandblaster. Examination of the kidney by immunofluorescence revealed granular deposits of immunoglobulin M (IgM) and the third component of complement (C3) along the glomerular basement membrane. Light microscopy disclosed mild proliferative glomerulonephritis with loss of colloidal iron staining for sialoprotein, and electron microscopy disclosed an increased density of epithelial cytoplasm, altered lysosomes and endothelial cell microtubular structures. The silicon content of the kidney was 264 parts per million (ppm), but particles of silicon were not demonstrated by electron microscopy. No primary or systemic causes of renal diseases were elucidated. The renal dysfunction apparently resulted from acute renal silicon toxicity, a new complication of acute pulmonary silicoproteinosis.

Adipose tissue deposition in sleep apnea.

To determine whether adipose tissue is deposited in the neck adjacent to the upper airway in patients with obstructive sleep apnea (OSA), we studied 21 subjects with OSA and nine without OSA using magnetic resonance imaging with a T-1 weighted spin echo sequence and polysomnography. We observed that patients with OSA had a larger volume of adipose tissue adjacent to their upper airway than did subjects without OSA.

Lateral pharyngeal fat pad pressure during breathing.

The purpose of this study was to test whether pressure in tissue lateral to the upper airway, the lateral pharyngeal fat pad, differs from atmospheric and pharyngeal pressure and whether it changes with breathing. We studied five male pigs by inserting a transducer-tipped catheter into their fat pad space using computed tomography (CT) scan guidance. We measured airflow with a pneumotachograph attached to a face mask and pharyngeal pressure with a balloon catheter. Fat pad pressure correlated positively with airflow and with pharyngeal pressure, decreasing during inspiration and increasing during expiration. Pressure in the fat pad differed from atmospheric pressure, generally exceeding it, and from pharyngeal pressure. We conclude that lateral pharyngeal fat pad pressure differs from atmospheric and pharyngeal pressure and that it changes with breathing.

Time-on-task decrements in "steer clear" performance of patients with sleep apnea and narcolepsy.

Loss of attention with time-on-task reflects the increasing instability of the waking state during performance in experimentally induced sleepiness. To determine whether patients with disorders of excessive sleepiness also displayed time-on-task decrements indicative of wake state instability, visual sustained attention performance on "Steer Clear," a computerized simple RT driving simulation task, was compared among 31 patients with untreated sleep apnea, 16 patients with narcolepsy, and 14 healthy control subjects. Vigilance decrement functions were generated by analyzing the number of collisions in each of six four-minute periods of Steer Clear task performance in a mixed-model analysis of variance and linear regression equations. As expected, patients had more Steer Clear collisions than control subjects (p=0.006). However, the inter-subject variability in errors among the narcoleptic patients was four-fold that of the apnea patients, and 100-fold that of the controls volunteers; the variance in errors among untreated apnea patients was 27-times that of controls. The results of transformed collision data revealed main effects for group (p=0.006), time-on-task (p=0.001), and a significant interaction (p=0.022). Control subjects showed no clear evidence of increasing collision errors with time-on-task (adjusted R2=0.22), while apnea patients showed a trend toward vigilance decrement (adjusted R2=0.42, p=0.097), and narcolepsy patients evidenced a robust linear vigilance decrement (adjusted R2=0.87, p=0.004). The association of disorders of excessive somnolence with escalating time-on-task decrements makes it imperative that when assessment of neurobehavioral performance is conducted in patients, it involves task durations and analyses that will evaluate the underlying vulnerability of potentially sleepy patients to decrements over time in tasks that require sustained attention and timely responses, both of which are key components in safe driving performance.

Colonic motor activity in women during sleep.

The relationship between colonic motility, sleep, and arousals from sleep has never been studied in women and only once in men. The purpose of this study was to determine how sleep and arousals from sleep affected colonic motility in women during the follicular phase of their menstrual cycle. We monitored sleep and segmental colonic motility in six healthy women during the follicular phase of the menstrual cycle. We observed no colonic motility during sleep; during awake periods or during arousals, we observed isolated low-amplitude bursts of colonic motility. This colonic motility occurred during 25% of the arousal and awakening time. In contrast, morning awakening was associated with high-amplitude independent and related colonic motility in all colonic segments. We conclude that in women in the follicular phase of their menstrual cycle, colonic motility is inhibited during sleep; colonic motility at night only occurs during arousals or awakenings from sleep.

Evaluation of the upper airway in patients with obstructive sleep apnea.

Multiple methods have been used to study the structure and physiological behavior of the upper airway (UA) in patients with obstructive sleep apnea (OSA). Valuable information may be obtained from the physiologic measurement of pressure and resistance along the UA, as well as from imaging techniques that include: direct or fiberoptic visualization, cephalometric roentgenograms, fluoroscopy, acoustic reflection, computerized tomography, and magnetic resonance imaging. This review summarizes the information that each of these methods has contributed to our understanding of the UA. The results obtained with these different methodologies have generally been complementary with structural narrowing being identified in the majority of patients with OSA. This narrowing is usually focal and located in the velopharyngeal or retropalatal segment of the UA. This is also the predominant site of initial UA collapse. Although obesity with enlargement of soft tissue structures is considered the predominant mechanism leading to UA narrowing, abnormal craniofacial development on a genetic or developmental basis plays an important contributory role.

Effect of nasal obstruction on upper airway muscle activation in normal subjects.

It is not known whether nasal occlusion produces obstructive sleep apnea (OSA) by decreasing upper airway muscle activation via nasal reflexes or by increasing upper airway resistance and hence lowering the pressure in the pharnyx. The purpose of this study was to determine the effect of nasal occlusion on upper airway muscle activation. We studied seven men and measured alae nasi (AN) and genioglossal (GG) electromyograms (EMGs) during two nights of sleep, one with their nose open and the other with their nose occluded. Nasal occlusion produced OSA in all subjects and also increased the percentage of time during sleep in which phasic AN and GG EMG activity was present. Apneas tended to occur at the nadirs of EMG activity. This suggests that nasal occlusion generally increases respiratory drive to upper airway muscles during sleep and that it does not cause OSA by merely decreasing respiratory drive to these muscles.

Obstructive sleep apnea in premenopausal women. A comparison with men and with postmenopausal women.

Because obstructive sleep apnea (OSA) is unusual in premenopausal women, we describe ten women with this syndrome and compare them to 13 postmenopausal women and with 32 men with OSA. Two premenopausal women had structural abnormalities of their pharynx, and the remaining eight were significantly more obese than men with OSA. In these eight patients, there was no relationship between pulse flow resistance and the degree of OSA in contrast to significant relationships in postmenopausal women, and men. Hypercapnia occurred in three premenopausal women, no postmenopausal women and in two men. We conclude that premenopausal women with OSA are more likely than men and postmenopausal women to have structural abnormalities of their upper airway, to be extremely obese, and to be hypercapneic, and that OSA occurs in them independent of their upper airway dimensions.

A pulse method of measuring respiratory system compliance in ventilated patients.

We describe a method of measuring total static respiratory system compliance (Crs) in ventilated patients during inflation, which appears to detect relaxation of respiratory muscles and does not require an end-inspiratory pause or disconnection of a constant-flow intermittent mandatory ventilation (IMV) circuit. Flow is measured with a pneumotachometer attached to the endotracheal tube. Transthoracic pressure is taken as the difference between mouth pressure measured at the proximal pneumotachometer port and body surface (atmospheric) pressure. Flow and transthoracic pressure are displayed on separate channels of a strip chart recorder. The ventilator is adjusted to deliver a constant rule of air flow. When inflation begins, the pressure tracing shows an initial step rise related to the flow resistance of the subject followed by a section with a slower rise and a constant slope. Respiratory system compliance is calculated by dividing the flow rate in L/sec by the slope of the pressure tracing in cm H2O/sec. Pulse Crs was compared with static Crs measured with an end-inspiratory pause in nine subjects receiving mechanical ventilation. Correlation between pulse Crs and static Crs in nine ventilated patients was highly significant (4 = .997, pulse Crs = 1.00 static Crs + 0.001). We conclude that with the pulse method, one can measure static Crs during inflation without an inspiratory pause and without disconnecting an IMV circuit.

Deaths and complications associated with fiberoptic bronchoscopy.

A questionnaire was sent to 1,041 owners of fiberoptic bronchoscopes requesting data about complications of bronchoscopic examination; 323 (31 percent) of the questionnaires were returned. From approximately 48,000 procedures, ten deaths were reported and are described. Information about two additional deaths not obtained from data on the questionnaires is also included. All patients who died had either myocardial disease, severe chronic pulmonary disease, serious pneumonia, or cancer. Two deaths were associated with evidence on necropsy of fresh myocardial infarctions that had been unsuspected prior to the procedure. Two deaths occurred after administration of local anesthesia prior to bronchoscopic examination. Two were patients who previously had slowly hemorrhaging tumors that hemorrhaged massively following, respectively, forceps biopsy and saline lavage. Four brushes broke off in bronchi. Ten cardiac arrests and 41 life-threatening reactions to anesthesia also occurred.

Bronchial coarctation.

A 38-year-old white woman with chronic bronchitis was found to have proximal coarctation of several third and fourth order bronchi. These lesions persisted despite treatment with prednisone, 40 mg a day for eight weeks. We think these lesions are congenital in origin and were exacerbated by chronic bronchitis.

Apnea duration and hypoxemia during REM sleep in patients with obstructive sleep apnea.

Nocturnal sleep studies of 12 patients with obstructive sleep apnea and a matched control group of 12 subjects without the sleep apnea syndrome were analyzed to compare arterial oxyhemoglobin saturation (SaO2) during REM and non-REM sleep. Mean percentage of total sleep time spent in REM sleep was not significantly different in patients with obstructive sleep apnea and in subjects without significant apnea (14.2 +/- SEM 2.2 percent in patients vs 12.0 +/- 2.2 percent in nonapnea subjects). Apneas were longer during REM than non-REM sleep in all 12 patients (p less than 0.01). Oxyhemoglobin desaturations were more frequent during REM than non-REM sleep in both apnea patients and the control subjects. In addition, there was a greater mean fall in SaO2 per desaturation episode in both the apnea patients and non-apnea subjects. We conclude: 1) sleep apneas are longer during REM sleep than non-REM sleep in patients with obstructive sleep apnea; 2) hypoxemia is greater during REM sleep than non-REM sleep in subjects with and without the sleep apnea syndrome.

Effect of intranasal obstruction on breathing during sleep.

While nasal mucosal stimulation in animals has been reported to produce central apneas and while nasal packing in humans is known to produce sleep-disordered breathing, it is controversial whether intranasal obstruction in humans produces predominantly central or obstructive apnea. To answer this question, we studied eight normal men by having them sleep in random order with their nose open or occluded with petrolatum gauze. Esophageal pressure was measured to detect respiratory effort, and standard techniques were used to monitor and score the stages of sleep. Intranasal occlusion increased both the number of apneas plus hypopneas per hour of sleep and the minutes of obstructive events per hour of sleep (p less than 0.05). The minutes of central events per hour of sleep also increased significantly but not to the degree that occurred with obstructive events. Nasal obstruction produced no immediate changes in pulmonary function. The subject with the highest resistance measured through the mouth with the pulse flow method had the most apneas following nasal occlusion. We conclude that intranasal obstruction produces predominantly obstructive apneas and hypopneas during sleep.

Absence of clinical pneumonia following bronchoscopy with contaminated and clean bronchofiberscopes.

Two hundred forty-nine fiberoptic bronchoscopy procedures were surveyed for the presence of bronchoscopy-related pneumonia. The first 103 procedures were performed during a period when the fiberscope was presemably contaminated with Pseudomonas aeruginosa. Chart review of these 103 procedures and prospective epidemiologic surveillance of the remaining 146 procedures revealed no cases of bronchoscopy-related pneumonia.

Treatment of obstructive sleep apnea with continuous nasal airflow delivered through nasal prongs.

We describe a new device for treating obstructive sleep apnea (OSA) which is similar to nasal CPAP, but less cumbersome. The device consists of a 7 mm diameter flexible tube terminating at one end in nasal prongs covered with foam cylinders. The foam cylinders are compressed, inserted into the nostrils and released, forming a tight seal. The other end of the catheter is attached to a compressor delivering between 7 and 15 L/min of air. We studied four men and two women with OSA, the first night without treatment and the following night with continuous nasal airflow. A desaturation index was calculated by multiplying the average number of desaturation episodes per hour of sleep times the average maximum desaturation per episode. With continuous nasal airflow there was a significant decrease in all parameters (p less than .025). We conclude that continuous nasal airflow decreased oxyhemoglobin desaturation in patients with OSA and may be useful in patients with mild-to-moderate OSA and in patients who do not tolerate nasal CPAP.

Prolonged effect of inhaled glycopyrrolate in asthma.

Glycopyrrolate, a quaternary ammonium anticholinergic compound is a potentially useful bronchodilator. To determine the efficacy, optimal dose, and duration of action of inhaled glycopyrrolate, we gave the drug to 11 asthmatic patients. Each subject received placebo or glycopyrrolate (100, 200, 600, or 1,200 micrograms) by inhalation in a double-blind, randomized, crossover design. Measurements included FEV1, FVC, heart rate, and blood pressure before administration of the drug and periodically for 12 hours. For eight hours following all doses of glycopyrrolate, both FEV1 and FVC (both as percent of predicted) were significantly greater for drug than for placebo. Glycopyrrolate may be a useful long-acting drug for the treatment of asthma.