Nocturia. A rarely recognized symptom of sleep apnea and other occult sleep disorders.

BACKGROUND: Nocturia, awakening from sleep to urinate, is a common symptom in a variety of medical disorders and in the elderly. Awakening from sleep as a result of nocturia is thought to be secondary to a sensation of urinary urgency resulting from an overextended bladder. Nocturia-related awakenings cause significant sleep disruption and fatigue in elderly patients and are correlated with an increased number of falls at night. Sleep disorders such as sleep apnea are also common in the elderly and are frequently the source of awakenings from sleep. The high incidence of both nocturia and sleep disorders in the elderly and other groups of patients suggests that sleep disorders may be the source of some awakenings from sleep usually attributed by patients to nocturia. Nocturia secondary to sleep disorders would be causatively different from nocturia secondary to pressure to urinate in common medical disorders and would require different diagnostic procedures and treatment. OBJECTIVE: To determine the frequency of nocturia as a symptom of primary sleep disorders. METHODS: Eighty consecutive patients, 27 women and 53 men with a mean (+/-SD) age of 58.7+/-14.1 years, undergoing polysomnography (sleep study or PSG) for the evaluation of a suspected sleep disorder and who met the sole criteria of awakening from sleep at least once and urinating voluntarily. Each patient had either a standard PSG recording or a PSG with administration of nasal continuous positive airway pressure. Immediately after each episode of nocturia during the PSG, patients were questioned about the reason they believed they had awakened. The PSG record immediately before awakening from sleep was then reviewed for potential causes of awakening. Patients were also asked on final morning awakening to fill in a questionnaire regarding their awakenings during the prior night. Patient reports were compared with the PSG to determine the accuracy of subjective reports. RESULTS: Patients awakened from sleep and voluntarily urinated a mean (+/- of 1.5+/-0.75 times per night for a total of 121 awakenings for the group. The majority (79.3%) of these awakenings from sleep were found to be directly secondary to sleep apnea, snoring or periodic leg movements in sleep. Patients correctly identified the source of their awakening from sleep on only five(4.9%) occasions and only once was sleep apnea correctly cited by a patient as a source of awakening during the night. CONCLUSION: Most awakenings from sleep attributed by our patients to pressure to urinate were instead a result of sleep disorders, particularly sleep apnea. The fact that patients do urinate once awake likely contributed to faulty post hoc reasoning and might have limited further inquiry by patients and their physicians in clinical settings into the actual sources of awakening from sleep. Even in those patients with well-known medical reasons for noctruria, Sleep disorders were still found to be the source of almost all awakenings from sleep. Patients were extremely poor judges of the reasons they awoke from sleep. The diagnosis of a sleep disorder should be seriously considered whenever a patient reports frequent awakenings from sleep to urinate.

Night terrors in an adult precipitated by sleep apnea.

Parasomnias are generally described as disorders of arousal that arise out of stage 3 and 4 nonrapid eye movement (NREM) sleep without identifiable cause. We present a case of a 35-year-old man who during nasal continuous positive airway pressure (nCPAP) treatment for severe obstructive sleep apnea experienced an intense night terror triggered by a residual obstructive apnea during rebound deep sleep. The role of rebound deep sleep was thought to be essential in creating a state of sleep with a high arousal threshold hypothesized to be important for the occurrence of parasomnias. This case supports the clinical wisdom that identifiable sources of arousal can trigger parasomnias.

A discriminant analysis applied to methacholine bronchoprovocation testing improves classification of patients as normal, asthma, or COPD.

UNLABELLED: Two discriminant functions, incorporating baseline measurements of pulmonary function and measures of airway responsiveness, were developed to improve patient classification into groups of normal, asthma, or COPD. Accuracy of group classification was compared between the usual laboratory method (single discriminating cut-off) and these new mathematically developed functions. Forty-five normal subjects, 27 asthmatic patients, and ten well-defined COPD patients were entered into the analysis. Measurements of airway responsiveness were determined by measurement of both specific airway conductance (SGaw) and spirometry (FEV1) after sequential inhalation of methacholine. RESULTS: A single discriminant cut-off using measures of SGaw (PD35) or FEV1 (PD20) does not sufficiently discriminate asthma from groups that contain normal and COPD subjects (67 to 71 percent predictive value). On the other hand, our discriminant functions demonstrated improved patient classification (positive predictive value, 88 to 89 percent). We conclude that bronchoprovocation tests used to evaluate the diagnosis of asthma should incorporate measures of baseline lung function into the analysis. This, we believe, is especially necessary when baseline lung function demonstrates minimal airflow obstruction and the possibility of other causes of airway disease exist.

A comparison of computer-assisted instruction and small-group teaching of cardiac auscultation to medical students.

Cardiac auscultation is suffering from declining interest, caused by competing diagnostic technology and inadequate training of doctors. Computer-assisted instruction (CAI) supporting graphics and digitized sound could be ideally suited for teaching and sharpening this skill. To evaluate this premise we randomized 35 third-year medical students to 3 hours of seminar teaching plus the use of audiotapes (group 1), the self-use of a MacIntosh-based CAI (group 2), or both (group 3). All students took a pre- and post-test consisting of eight pre-recorded cardiac events and were also assessed for computer anxiety. Although there were no significant differences between pre- and post-tests for each group and among groups, group 1 had a 4.5% deterioration in its diagnostic score compared to the 7.2% and 3.2% improvements of groups 2 and 3 respectively. Group 2 used the CAI significantly more than group 3. We conclude that CAI is at least as effective as seminars in teaching cardiac auscultation to third-year medical students.

Erythrocytes prevent inactivation of alpha 1-antitrypsin by cigarette smoke.

Red blood cells (RBC) possess strong antioxidant activity. We tested whether this activity was sufficient to prevent the oxidative inactivation of alpha 1-antitrypsin (alpha 1-AT) by cigarette smoke. We found that RBC in physiological concentrations completely prevented the inactivation of alpha 1-AT. The major erythrocytic antioxidants, catalase, superoxide dismutase and glutathione were then selectively inhibited and the RBC retested. Only the inhibition of catalase significantly impaired the protective ability of added erythrocytes. We suggest that RBC antioxidants may be an important variable in determining the degree of protection of alpha 1-AT against oxidation.

The effect of aerosolized verapamil on the response to isoproterenol in asthmatics.

Calcium antagonists, like verapamil, may play a beneficial role in the management of airway disease. However, the effect that verapamil plays in modulating the response to beta-adrenergic bronchodilator therapy has not been well characterized. We found that inhaled verapamil, 3 mg, had little effect on the bronchodilator response to sequential inhalations of isoproterenol. Also, verapamil had no significant effect on isoproterenol's protection against methacholine-induced bronchospasm in a group of 8 mild asthmatics. These studies support the safe use of these agents in combination but do not demonstrate any additive or synergistic benefit.

Inhibition of methacholine-induced bronchoconstriction in patients with chronic obstructive pulmonary disease.

Patients with COPD have increased airway responsiveness to pharmacologically induced bronchoconstriction when compared with normal healthy subjects. We questioned whether an inhaled bronchodilator such as isoproterenol would benefit patients with COPD by inhibiting inducible bronchoconstriction. Ten patients with COPD were found to be more sensitive to methacholine by inhalation bronchial challenge testing than were normal control subjects. (PD35 = 58 +/- 110 versus 238 +/- 220 cumulative dose units). Neither group as a whole demonstrated significant inhibition of methacholine-induced bronchoconstriction by prior inhalation of isoproterenol (200 micrograms at mouth). However, within the COPD group, there was a significant negative correlation between both baseline lung function and airway responsiveness (PD35-SGaw) with inhibition of methacholine-induced bronchoconstriction. (r = -0.8, p less than or equal to 0.003). This suggests that those patients with COPD and significantly reduced lung function (%FEV1 less than 50%) demonstrate airway hyperresponsiveness to a degree recorded in asthma and may benefit from therapy that inhibits airway responsiveness.

Factors that contribute to inhibition of methacholine-induced bronchoconstriction.

To evaluate the factors that contribute to inhibition of airways reactivity, we compared the effect of inhaled isoproterenol, 125 micrograms, on the response to methacholine-induced bronchoconstriction in 10 normal and 10 asthmatic subjects. We measured in each subject baseline lung function, response to inhaled bronchodilator, dose of bronchodilator causing 50% maximal response, and degree of airways reactivity to inhalation of methacholine before and after isoproterenol. In asthmatics, but not normal subjects, inhalation of isoproterenol led to significant inhibition of methacholine-induced bronchospasm. In asthmatics, the greater the airways reactivity to methacholine the greater the inhibition by isoproterenol (p less than 0.05). In both groups, there was significant correlation between baseline lung function and level of airways reactivity. In neither normal subjects nor asthmatics did the maximal bronchodilator response to isoproterenol inhalation correlate with inhibition of airways reactivity. Studies evaluating inhibition of airways reactivity should take into account the population tested, baseline lung function, and baseline level of airways reactivity.

Purification of Ascaris suum antigen: its allergenic activity in vitro and in vivo.

Crude aqueous extracts of Ascaris suum (CE) have been used widely to study IgE-mediated reactions in various experimental preparations. Because some CE may contain a polypeptide, a mast cell degranulating peptide (MCDP), that degranulates mast cells by nonimmunologic mechanisms, various protocols have been used to ensure that the Ascaris preparation used did not contain MCPD. In general, these protocols have assumed MCDP had been without providing proof. Even protocols designed to isolate the major antigenic determinants from CE have usually been designed to evaluate immunogenic characteristics of the purified Ascaris; thus, few systematic comparisons of CE with purified Ascaris exist concerning mast cell degranulation, and few studies have demonstrated that MCDP has been removed during purification. Since Ascaris has proved to be useful in a variety of studies of IgE-mediated reactions, particularly in large animals (dog and sheep), we have developed a protocol to purify CE and MCDP and characterize their physiochemical and immunologic properties. We compared the allergenic activity of our purified Ascaris to that of CE and MCDP in skin and lung of natively sensitized dogs and in unsensitized rat peritoneal mast cells. Our results indicate that MCDP probably contaminates CE by less than 1.0%. However, the biologic activity of MCDP in dog lung appears insignificant and probably contributes little to CE-induced reactions in doses of CE commonly used (less than or equal to 100 mg injected). If a purified Ascaris preparation is essential, our protocol will yield an Ascaris preparation that has potent IgE-mediated effects in dog preparations with insignificant contamination by MCDP.

Immunologic release of histamine from dog lung: comparison of in vivo and in vitro responses in the same animal.

The purpose of this study was to compare, for the first time, antigen-induced histamine release from the lung in the same natively allergic dogs both in vitro and in vivo. In six dogs, maximal antigen-induced histamine release from the lung correlated closely in vitro and in vivo (r = 0.94), although it varied widely between dogs (0% to 75.5% of total tissue histamine content); similarly, the antigen concentration to produce 50% of maximal histamine release varied sixfold between dogs (40 micrograms/ml to 250 micrograms/ml). In each of five other dogs, terbutaline sulfate administered intravenously caused a dose-dependent inhibition of antigen-induced histamine release from lung fragments in vitro: the maximal inhibition produced by 1 mg/kg was 60 +/- 4.5% (mean +/- SEM). In these same dogs, 10(-5)M terbutaline incubated with lung fragments in vitro caused inhibition of antigen-induced histamine release comparable to 1 mg/kg terbutaline in vivo. Increasing the dose of terbutaline in vitro produced maximal inhibition at 10(-4)M with no greater effect of the drug at 10(-3)M (71.4 +/- 3.8% inhibition). In both experimental situations propranolol caused a dose-dependent inhibition of beta-adrenergic modulation of Ascaris-induced release of histamine. This result supports the conclusion that terbutaline produced its effects by actions mediated by beta-adrenergic receptors on pulmonary mast cells. This experimental approach provides a suitable preparation in which to estimate the effective dose of agonists that modulate antigen-induced mast cell function in vivo.