Sleep disorders: a risk factor for normal-tension glaucoma?

PURPOSE: To determine the prevalence of sleep-related symptoms and sleep-related breathing disorders by polysomnography in patients with normal-tension glaucoma (NTG). PATIENTS AND METHODS: This comparative case series included 23 patients with NTG, 14 NTG suspects, and 30 comparison patients without NTG. A sleep history was obtained and determined to be positive or negative. Polysomnography was offered for patients with a positive sleep history. Prevalence of a positive sleep history and prevalence of sleep disorders were the main outcome measures. RESULTS: The NTG, NTG suspect, and comparison groups did not differ with respect to age, body mass index, systemic disease, gender, or race. Thirteen (57%) of 23 patients with NTG, 6 (43%) of 14 NTG suspects, and 1 (3%) of 30 comparison patients had a positive sleep history (P = 0.001). Nine of 13 patients with NTG and four of six NTG suspects with a positive sleep history chose to undergo polysomnography. Seven (78%) of nine patients with NTG and all four NTG suspects undergoing polysomnography were diagnosed with a sleep disorder. Five patients with NTG had sleep apnea and two had sleep hypopnea. Two NTG suspects had sleep apnea; one had sleep hypopnea; and one had upper airway resistance syndrome. The one comparison patient with a positive sleep history had upper airway resistance syndrome by polysomnography. CONCLUSIONS: Sleep-disturbed breathing may be a risk factor for NTG. Although we do not provide evidence for a cause-and-effect relationship, various physiologic factors produced by sleep-disturbed breathing may play a significant role in the pathogenesis of this optic neuropathy. We recommend obtaining a sleep history from patients with NTG and performing polysomnography in those patients with sleep disturbance symptoms.

Pleural thickening in mild kaolinosis.

BACKGROUND: Kaolin is found along the "fall line" in Georgia, and parenchymal changes, both simple and complicated pneumoconiosis, have been previously described. This study was done to determine whether pleural thickening occurs in workers with mild kaolin pneumoconiosis. METHODS: We evaluated 350 workers at a kaolin plant in Georgia. Thirty-two workers with abnormal chest radiographs were clinically evaluated. Twelve workers with mild kaolinosis but without any evidence of pleural changes on chest roentgenograms had computed tomography (CT) of the chest to assess the presence of pleural thickening. RESULTS: Nineteen workers had radiographic changes consistent with kaolin pneumoconiosis (prevalence 5.4%), and four workers had evidence of pleural plaques (prevalence 1.1%). Five of the 12 workers had evidence of pleural thickening on CT. CONCLUSIONS: This study shows that pleural thickening may be common on chest tomography in workers with kaolinosis and that the exposure to kaolin dust should be considered in the differential diagnosis of pleural thickening.

Eosinophilic pleural effusion: is it always nondiagnostic?

The presence of eosinophils in the pleural effusion is generally considered nondiagnostic. It usually indicates that the patient has had a previous thoracentesis and that air or blood has come in contact with the effusion. Idiopathic acute eosinophilic pneumonia is characterized by acute onset of pulmonary symptoms with hypoxemia, pulmonary infiltrates, eosinophils in bronchoalveolar lavage fluid, and prompt response to steroid therapy. We report a patient who presented with symptoms of acute pneumonia in which the presence of increased eosinophils in the pleural effusion indicated eosinophilic pneumonia.

Proteinuria in patients with sleep apnea.

BACKGROUND: Proteinuria severe enough to be in the nephrotic range has been noted on occasion in patients with obstructive sleep apnea (OSA), but it is not known what factors are related to the severity of proteinuria in these patients. This study was conducted to determine if the severity of proteinuria is related to the number of apneas. METHODS: The level of proteinuria was determined by the dipstick method in 407 patients in whom OSA had been diagnosed. The apnea-hypopnea index (AHI) was calculated in each patient after all-night polysomnography. Sleep apnea was defined as the presence of at least 30 apneas during a 6- to 8-hour monitoring period and an AHI greater than 15. RESULTS: The apnea-hypopnea index in patients without proteinuria was similar to that of patients with 1+ to 3+ proteinuria. However, the AHI was significantly greater in the 9 patients with 4+ proteinuria. CONCLUSIONS: While severe proteinuria in OSA occurs in patients with a higher rate of sleep apneas, the lesser degree of proteinuria cannot be explained by AHI alone. Other factors that determine the severity of the disease, such as hypoxemia, merit further investigation.

Narcolepsy.

Narcolepsy afflicts more than 200,000 Americans. In most cases the first symptom of the disease, excessive daytime sleepiness, develops during childhood or adolescence. This initial presentation is followed by cataplexy or other auxiliary symptoms several years later. Not infrequently, many years pass before the proper diagnosis of narcolepsy is made. Narcolepsy is a chronic lifelong disease without periods of remission. Excessive daytime sleepiness, inappropriate sleep attacks, and the pathognomonic symptom of cataplexy, are diagnostic of narcolepsy. Confirmation of the disease is made by a multiple sleep latency test. Although still not being used for diagnostic purposes, the association between narcolepsy and the human leukocyte group A (HLA) antigen DR2 is the strongest so far described for any disease. With the help of psychosocial support, therapeutic naps, and medications, the patient with narcolepsy may be able to lead a normal life. Methylphenidate and imipramine are the two most widely used drugs for the treatment of daytime somnolence and cataplexy, respectively.

Intracranial hemodynamics in sleep apnea.

Intracranial pressure changes and poor cerebral perfusion have been reported in sleep apnea syndrome (SAS), but such studies have been limited due to lack of a reliable noninvasive study method. We determined the systolic (VS), diastolic (VD), and mean (VM) cerebral blood flow velocities of the middle cerebral artery in 23 individuals (12 severe SAS patients and 11 control subjects) using transcranial Doppler sonography before sleep, during sleep (NREM and REM) and upon awakening. All three velocities (VS = 87.4 cm/s compared to 104.7 cm/s, VD = 41.6 cm/s compared to 47.7 cm/s, and VM = 57.0 cm/s compared to 67.0 cm/s) were decreased in patients with SAS and VS and VM were significantly lower than in control subjects (p = 0.005 and p = 0.033, respectively). The end-tidal CO2 (PETCO2) in the SAS patients (47.3 mm Hg) compared to the control subjects (41.8 mm Hg) was significantly higher (p = 0.003). When the VM was adjusted to normalized CO2 using the Markwalder's equation, the reduction in velocity in patients with SAS (47.5 cm/s) compared to control subjects (63.0 cm/s) became more significant (p = 0.005). This study shows that cerebral blood flow velocities are lower in patients with SAS compared to control subjects and that transcranial Doppler sonography may be useful in such evaluations.

Case report: multiple negative polysomnograms in patients with obstructive sleep apnea.

A single overnight polysomnogram usually is adequate to exclude a diagnosis of obstructive sleep apnea. We report three patients who had multiple negative polysomnograms before a diagnosis of sleep apnea was made. Factors that may cause a false-negative polysomnogram include reduced total or rapid eye movement sleep time, sleeping in the lateral posture, manifestation of the disease predominantly by hypopneas, and recent medical therapy to treat sleep apneas. In patients with a strong clinical suspicion of sleep apnea and a negative polysomnogram, sleep and clinical parameters should be reevaluated and a repeat polysomnogram may be indicated.

Negative polysomnogram in patients with obstructive sleep apnea syndrome.

We evaluated the possibility that in some patients with obstructive sleep apnea, the initial polysomnogram may be negative. We reviewed polysomnograms performed at the Medical College of Georgia from 1984 to 1990 and found nine patients whose initial polysomnogram was negative but whose repeat polysomnogram confirmed obstructive sleep apnea. All nine patients (five women and four men; average age, 44.2 years) had an apnea index of less than 5 (fewer than five apneic episodes per hour) and had a total of fewer than 20 apneic episodes during the initial overnight polysomnogram. The change in average weight was not significant. Three patients had received short-term oxygen therapy, and two of these three received nasal continuous positive airway pressure prior to the initial study. The time that patients spent supine increased from 101 min in the initial study to 180 min in the second, but this was not significant (p = 0.12). Comparison of the initial and diagnostic polysomnograms showed significantly reduced total sleep time (from 3.75 +/- 1.84 h to 5.32 +/- 1.11 h; p = 0.04) and reduced rapid eye movement (REM) sleep time (from 0.27 +/- 0.27 h to 0.75 +/- 0.58 h; p = 0.037) in the initial study. We conclude that in a small subset of patients with obstructive sleep apnea, the initial polysomnogram may be falsely negative, which could be due to previous therapy, a reduction in total sleep time and REM sleep, or other unidentified factors.

Obstructive sleep apnea syndrome.

Over the past 2 decades, we have gained great insight into the sleep apnea syndromes. Though progress in this field continues, many problems, including an incomplete understanding of the disease and its natural history, remain. Future work should clarify these areas as well as provide a better understanding of our available therapeutic options.

The effect of sleep on intracranial hemodynamics: a transcranial Doppler study.

The effect of sleep on intracranial blood flow velocities has not been reported in children or adults, even though blood flow velocities are evaluated for clinical purposes during both sleep and wakefulness. We report the effect of sleep on intracranial blood flow velocities of 11 healthy individuals (five children and six adults) who were monitored by polysomnography and transcranial Doppler sonography (TCD). Thirty-three TCDs were obtained on middle cerebral arteries. Before sleep, during non-rapid-eye-movement sleep, and after sleep, measurements of systolic, end diastolic, and mean flow velocities were obtained by TCD. Pulse oximetry and end tidal carbon dioxide were monitored during each 8-hour polysomnogram. The before-sleep blood flow velocity values were compared to sleep and after-sleep values in children and adults separately using ANOVA. A significant decrease in the blood flow velocities was noted during sleep compared to before-sleep values in both children (P less than .05) and adults (P less than .01). The blood flow velocities after sleep were also decreased compared to before-sleep values. This study shows that sleep reduces blood flow velocities in both children and adults. A decrease in blood flow velocities during normal sleep should be taken into account when interpreting TCDs in patients.

Reduction of peak inspiratory pressure using high frequency jet ventilation and pressure control ventilation following pneumonectomy.

High peak inspiratory pressure (PIP) during mechanical ventilation is associated with increased risk of barotrauma. High frequency jet ventilation (HFJV) and pressure control ventilation (PCV) have been advocated for the reduction of PIP. The Food and Drug Administration has approved HFJV, respiratory frequency as high as 150 breaths per minute (bpm); however, bpm greater than 150 are still considered for experimental use. At less than 40 bpm, the point where HFJV is no longer considered to be high frequency, PCV is substituted which then becomes the mode of choice because of the ability to control ventilating pressures by setting the PIP. We present a case in which we used these two forms of ventilation for reducing the risk of stump blowout and barotrauma following pneumonectomy.

Effects of oral base therapy on serum ionized calcium, phosphorus and parathyroid hormone in chronic hemodialysis patients.

The purpose of this study was to evaluate the effects of oral base therapy on selected chemical parameters in chronic hemodialysis patients. Oral base supplements were administered to 20 acidotic chronic hemodialysis patients for one month. Serum bicarbonate levels rose from 18.6 +/- 2.9 to 22.5 +/- 4.0 mEq/L (p less than 0.0005) and pH rose from 7.35 +/- 0.03 to 7.39 +/- 0.04 (p less than 0.0005). Serum ionized calcium levels fell from 5.03 +/- 0.37 to 4.83 +/- 0.34 mg/dL (1.25 +/- 0.09 to 1.21 +/- 0.08 mmol/L) (p less than 0.01), while intact parathyroid hormone (PTH) levels rose from 547 +/- 697 to 619 +/- 776 pg/mL (p less than 0.05). Base therapy did not result in significant changes in serum levels of total calcium, phosphorus, alkaline phosphatase, urea nitrogen, creatinine, total protein, albumin or potassium. If empiric therapy with exogenous base is given to dialysis patients, ionized calcium levels should be closely monitored since changes in calcium supplement or vitamin D therapy may be required to maintain ionized calcium and parathyroid hormone values at the pre-treatment levels.

Effect of glucocorticoids on the response of airway smooth muscle to catecholamine and resorcinol beta-agonists.

The influence of hydrocortisone (11 beta, 17 alpha, 21-trihydroxy-pregn-4-ene-3,20-dione) or of methylprednisolone (6 alpha-methyl-11 beta, 17 alpha-21-trihydroxy-1,4-pregnadiene-3,20-dione) on the response of airway smooth muscle to a variety of beta-adrenergic bronchodilators was evaluated using incubated guinea pig tracheal rings, preconstricted with histamine. The adrenergic agonists chosen for this study included the nonselective beta 1- and beta 2-catecholamine, isoproterenol, the selective beta 2-catecholamine, rimiterol, and the selective beta 2-resorcinols, fenoterol and terbutaline. When the incubated rings were pretreated with 10-50 micrograms/mL of the steroids, there was a significant enhancement in smooth muscle sensitivity and reactivity to rimiterol and isoproterenol. Tracheal response to fenoterol or terbutaline, on the other hand, was not altered by the glucocorticoids. When used alone, neither steroid exerted an inotropic influence on the tracheal smooth muscle. The results of our study indicate that glucocorticoid enhancement of adrenergic bronchodilators is selective for catecholamines, and not for resorcinols.

Methotrexate pneumonitis: a case report and summary of the literature.

Methotrexate is used to treat a growing number of malignancies, severe rheumatoid arthritis, and refractory psoriatic arthritis. Pneumonitis induced by the drug occurs in a small percentage of patients and is usually associated with fever, cough, dyspnea, and restrictive pulmonary disease. Severe reactions may progress to respiratory failure. Early recognition of the toxicity is important, and discontinuation of the drug and therapy with corticosteroids usually lead to dramatic improvement.

Nocturnal urinary protein excretion rates in patients with sleep apnea.

We observed nocturnal urinary protein excretion to be 16.2 +/- 5.5 micrograms/min (mean +/- SE) in 9 healthy control subjects (group I), 29.3 +/- 9.5 micrograms/min in 12 obese patients suspected to have obstructive sleep apnea syndrome (OSAS) but with negative polysomnographic studies (group II), and 94.0 +/- 31.8 micrograms/min in 14 patients with documented OSAS (group III) (II vs. I, NS; III vs. I, p less than 0.05; III vs. II, p less than 0.05). The frequency of abnormal proteinuria, defined as protein excretion greater than the highest rate observed in group I (46 micrograms/min), was 14% in group II and 64% in group III (p less than 0.05). There were no significant differences in age, body weight, body surface area, blood pressure, or indices of sleep apnea between OSAS patients with and without proteinuria. Although the mechanism is unclear, this study shows that nocturnal protein excretion rates are commonly elevated in patients with OSAS.

Sleep apnea and hypothyroidism.

Thyroid deficiency states are now a well recognized cause of the sleep apnea syndrome. The spectrum of disease ranges from mild, asymptomatic hypothyroidism to severe myxedema, and the disorder is associated with both obstructive and central types of sleep apnea. A variety of factors may be involved, including upper airway obstruction with or without obesity, and alterations in ventilatory drive. The definitive therapy is thyroid hormone replacement, which has been shown to diminish or completely eliminate apneic episodes and arterial oxygen desaturation, as well as to effect many improvements in sleep patterns and overall sleep efficiency. The incidence of thyroid deficiency states in patients with sleep apnea syndrome is not known, but it seems reasonable to evaluate thyroid function in all patients. Thyroid replacement therapy seems logical for the treatment of sleep apnea in patients with previously unrecognized subclinical hypothyroidism. Much remains to be learned about the diagnosis and treatment of sleep apnea syndromes associated with thyroid hormone deficiency, and further studies are needed.

Correlates of amylase and lipase levels in chronic dialysis patients.

Serum lipase and amylase isoenzymes were measured in 44 chronic hemodialysis patients, 16 CAPD patients and 22 normal volunteers. The enzyme levels of the two patient groups were similar and were significantly higher than those of the volunteer group. The ratio of pancreatic to salivary amylase was similar in all three groups. Anuric patients in both dialysis groups had higher enzyme levels than those with residual urine output. Linear regression analysis was done to attempt to identify factors which were good predictors of enzyme levels. Although no such factors were found in the hemodialysis group, in the CAPD group there were significant correlations between the degree of azotemia and the magnitude of enzyme elevations. Further studies are needed to determine the relative importance of oversecretion and underexcretion in the genesis of the amylase and lipase elevations found in dialysis patients.

Sleep apnea, proteinuria, and nephrotic syndrome.

Renal abnormalities in patients with obstructive sleep apnea syndrome (OSAS) have not been previously described. Medical records of patients who had been evaluated for possible sleep apnea syndrome and had had complete polysomnograms and urinalyses were reviewed to determine the frequency of proteinuria. High-grade proteinuria (greater than or equal to 3+ on urinalysis) was found in 6 of the 34 patients with obstructive sleep apnea, but in none of 34 patients in a control group matched for sex, age, and weight. In three patients, proteinuria was in the nephrotic range (3.5 g/24 h). The weight (mean +/- SD) of the patients with obstructive sleep apnea (112.7 +/- 35.3 kg) was not significantly different from the control group (109.2 +/- 30.3 kg). Microscopic examination of renal tissue in one patient with OSAS showed minimal changes. In four patients who were followed for 3 years, proteinuria improved after therapy for sleep apnea syndrome. We suggest that proteinuria may not be uncommon in patients with severe obstructive sleep apnea syndrome and may be reversible with correction of the sleep apnea syndrome.