The effect of asymptomatic nocturnal hypoglycemia on glycemic control in diabetes mellitus

To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.     

The effect of in-laboratory polysomnography on sleep and objective daytime sleepiness

MSLT guidelines recommend performing MSLTs following polysomnography (PSG) to document the preceding night's sleep. We tested the hypothesis that patients are objectively sleepier after in-laboratory full diagnostic PSG than after a sleep recording at home. Sixteen patients with the sleep apnea/hypopnea syndrome (SAHS; AHI 35+/-SD 28 per hour slept) were recruited into a randomized crossover study. To monitor sleep with minimal disruption at home, only sleep was recorded on 2 consecutive nights, the first for acclimatization. The laboratory limb followed standard PSG. Both study nights were followed next day by MSLT and MWT. There were no differences in MSLT (12.0 SD 5.1 home, 11.6+/-4.7 min laboratory; p=0.7), MWT (32.7+/-8.7, 31.6+/-9.3 min; p=0.6) or total sleep time (362+/-53, 343+/-51 min; p=0.15) between home and laboratory limbs. However, on the home night, fewer microarousals (31+/-14, 54+/-25/hr slept; p<0.0001) and less % wake (15+/-10, 24+/-11; p=0.006) were found. On the home study night, patients had greater % REM sleep, slow-wave sleep and sleep efficiency (all p<0.009). This study does not support the hypothesis that patients are sleepier after laboratory PSG compared to home study night. However, the improved sleep at home raises the question whether laboratory-based polysomnography is always required prior to MSLT/MWT testing or whether less obtrusive monitoring of sleep duration at home would sometimes suffice.     

A mechanism of central sleep apnea in patients with heart failure.

BACKGROUND: Breathing is controlled by a negative-feedback system in which an increase in the partial pressure of arterial carbon dioxide stimulates breathing and a decrease inhibits it. Although enhanced sensitivity to carbon dioxide helps maintain the partial pressure of arterial carbon dioxide within a narrow range during waking hours, in some persons a large hyperventilatory response during sleep may lower the value below the apneic threshold, thereby resulting in central apnea. I tested the hypothesis that enhanced sensitivity to carbon dioxide contributes to the development of central sleep apnea in some patients with heart failure. METHODS: This prospective study included 20 men who had treated, stable heart failure with left ventricular systolic dysfunction. Ten had central sleep apnea, and 10 did not. The patients underwent polysomnography and studies of their ventilatory response to carbon dioxide. RESULTS: Patients who met the criteria for central sleep apnea had significantly more episodes of central apnea per hour than those without central sleep apnea (mean [+/-SD], 35+/-24 vs. 0.5+/-1.0 episodes per hour). Those with sleep apnea also had a significantly larger ventilatory response to carbon dioxide than those without central sleep apnea (5.1+/-3.1 vs. 2.1+/-1.0 liters per minute per millimeter of mercury, P=0.007), and there was a significant positive correlation between ventilatory response and the number of episodes of apnea and hypopnea per hour during sleep (r=0.6, P=0.01). CONCLUSIONS: Enhanced sensitivity to carbon dioxide may predispose some patients with heart failure to the development of central sleep apnea.     

Failure of nocturnal hypoglycemia to cause fasting hyperglycemia in patients with insulin-dependent diabetes mellitus

To test the hypothesis that nocturnal hypoglycemia causes fasting hyperglycemia (the Somogyi phenomenon) in patients with insulin-dependent diabetes mellitus, we studied 10 patients, who were on their usual therapeutic regimens, from 10 p.m. through 8 a.m. on three nights. On the first night, only a control procedure was performed (blood sampling only); on the second night, hypoglycemia was prevented (by intravenous glucose infusion, if necessary, to keep plasma glucose levels above 100 mg per deciliter [5.6 mmol per liter]); and on the third night, hypoglycemia was induced (by stepped intravenous insulin infusions between midnight and 4 a.m. to keep plasma glucose levels below 50 mg per deciliter [2.8 mmol per liter]). After nocturnal hypoglycemia was induced (36 +/- 2 mg per deciliter [2.0 +/- 0.1 mmol per liter] [mean +/- SE] from 2 to 4:30 a.m.), 8 a.m. plasma glucose concentrations (113 +/- 18 mg per deciliter [6.3 +/- 1.0 mmol per liter]) were not higher than values obtained after hypoglycemia was prevented (182 +/- 14 mg per deciliter [10.1 +/- 0.8 mmol per liter]) or those obtained after blood sampling only (149 +/- 20 mg per deciliter [8.3 +/- 1.1 mmol per liter]). Indeed, regression analysis of data obtained on the control night indicated that the 8 a.m. plasma glucose concentration was directly related to the nocturnal glucose nadir (r = 0.761, P = 0.011). None of the patients was awakened by hypoglycemia. Scores for symptoms of hypoglycemia, which were determined at 8 a.m., did not differ significantly among the three studies. We conclude that asymptomatic nocturnal hypoglycemia does not appear to cause clinically important fasting hyperglycemia in patients with insulin-dependent diabetes mellitus on their usual therapeutic regimens.     

Does nasal decongestion improve obstructive sleep apnea?

Whether nasal congestion promotes obstructive sleep apnea is controversial. Therefore, we performed a randomized placebo-controlled cross-over trial on the effects of topical nasal decongestion in patients with obstructive sleep apnea syndrome (OSA) and nasal congestion. Twelve OSA patients with chronic nasal congestion (mean +/- SD age 49.1 +/- 11.1 years, apnea/hypopnea index 32.6 +/- 24.5/h) were treated with nasal xylometazoline or placebo for 1 week each. At the end of treatment periods, polysomnography including monitoring of nasal conductance by an unobtrusive technique, vigilance by the OSLER test, and symptom scores were assessed. Data from xylometazoline and placebo treatments were compared. Mean nocturnal nasal conductance on xylometazoline was significantly higher than on placebo (8.6 +/- 5.3 versus 6.3 +/- 5.8 mL s(-1)Pa(-1), P < 0.05) but the apnea/hypopnea index was similar (29.3 +/- 32.5/h versus 33.2 +/- 32.8/h, P = NS). However, 30-210 min after application of xylometazoline, at the time of the maximal pharmacologic effect, the apnea/hypopnea index was slightly reduced (27.3 +/- 30.5/h versus 33.2 +/- 33.9/h, P < 0.05). Xylometazoline did not alter sleep quality, sleep resistance time (33.6 +/- 8.8 versus 33.4 +/- 10.1 min, P = NS) and subjective sleepiness (Epworth score 10.5 +/- 3.8 versus 11.8 +/- 4.4, P = NS). The reduced apnea/hypopnea index during maximal nasal decongestion by xylometazoline suggests a pathophysiologic link but the efficacy of nasal decongestion was not sufficient to provide a clinically substantial improvement of OSA.     

Effect of celiprolol treatment in hypertensive patients with sleep apnea.

The effects of a beta-blocker, celiprolol, on sleep and arterial blood pressure (BP) were evaluated during a single-blind study in seven hypertensive patients with sleep apnea. Diurnal ambulatory BP measurements with an automatic cuff-inflation device and polysomnography with simultaneous Finapres BP recording were performed separately on consecutive days at the end of two 21-day treatment periods involving placebo followed by celiprolol (200 mg/day). Age was 59 +/- 2.5 yr (m +/- sem) and body mass index 33.2 +/- 2.3 kg. m-2. Diurnal ambulatory BP was significantly lower with celiprolol than with placebo (systolic 139 +/- 4 vs 152 +/- 5 mmHg, diastolic 86 +/- 2 vs 96 +/- 2 mmHg). The apnea-hypopnea index was similar under celiprolol and placebo (48 +/- 7.4 vs 53 +/- 7.8, respectively), as were the total sleep time and percent of duration of the different sleep stages. Individual average BP values were significantly lower during REM sleep under celiprolol but remained similar under celiprolol and placebo in the other sleep stages. Variability of nocturnal BP (assessed by the SD of distribution of BP variations) was not affected by celiprolol. In conclusion, celiprolol which decreased daytime BP, did not affect sleep pattern or respiratory disturbances, or nocturnal BP variability related to apnea.     

Severity of sleep-disordered breathing improves following parturition

STUDY OBJECTIVE: Changes in sleep-disordered breathing associated with late pregnancy have not previously been systematically investigated; however, a number of case reports indicate exacerbation of obstructive sleep apnea in late pregnancy, often in association with maternal hypertension. We aimed to compare the severity of sleep-disordered breathing and associated maternal blood-pressure responses in late pregnancy with the nonpregnant state. DESIGN: Case-controlled, longitudinal study of sleep-disordered breathing during late pregnancy and postpartum. Study Patients: Ten women referred for suspected sleep-disordered breathing during the third trimester of pregnancy. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Full overnight polysomnography and continuous systemic blood pressure were measured during the third trimester of pregnancy and 3 months following delivery. Parameters of sleep-disordered breathing, including apnea hypopnea index and minimum overnight arterial oxyhemoglobin saturation, were compared between antenatal and postnatal studies. An improvement in both apnea-hypopnea index and minimum arterial oxyhemoglobin saturation occurred consistently in all subjects postnatally. In non-rapid eye movement sleep, mean apnea-hypopnea index was reduced from 63 +/- 15 per hour antenatally to 18 +/- 4 per hour postnatally (P = .03), and in rapid eye movement sleep, from 64 +/- 11 per hour to 22 +/- 4 per hour (P = .002). Minimum arterial oxyhemoglobin saturation was increased from 86% +/- 2% antenatally to 91% +/- 1% postnatally (P = .01). Arterial blood-pressure responses to apnea peaked at 170 to 180 mm Hg antenatally, while they only peaked at 130 to 140 mm Hg postnatally. CONCLUSION: This study indicates that late pregnancy may be associated with increased severity of sleep-disordered breathing and associated blood-pressure responses.     

Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial

STUDY OBJECTIVE: To investigate the short-term effect (4 weeks) of oral appliance therapy for obstructive sleep apnea on blood pressure. DESIGN: Randomized, controlled, crossover trial. SETTING: Multidisciplinary sleep disorders clinic in a university teaching hospital. PATIENTS: Sixty-one patients diagnosed with obstructive sleep apnea on polysomnography (apnea hypopnea index > or = 10 per hour and at least 2 of the following symptoms--daytime sleepiness, snoring, witnessed apneas, fragmented sleep; age > 20 years; and minimum mandibular protrusion of 3 mm). INTERVENTION: A mandibular advancement splint (MAS) and control oral appliance for 4 weeks each. MEASUREMENTS AND RESULTS: Polysomnography and 24-hour ambulatory blood pressure monitoring were carried out at baseline and following each 4-week intervention period. Patients showed a 50% reduction in mean apnea hypopnea index with MAS compared with the control and a significant improvement in both minimum oxygen saturation and arousal index. There was a significant reduction with the MAS in mean (+/- SEM) 24-hour diastolic blood pressure (1.8 +/- 0.5 mmHg) compared with the control (P = .001) but not in 24-hour systolic blood pressure. Awake blood-pressure variables were reduced with the MAS by an estimated mean (+/- SEM) of 3.3 +/- 1.1 mmHg for systolic blood pressure (P = .003) and 3.4 +/- 0.9 mmHg for diastolic blood pressure (P < .0001). There was no significant difference in blood pressure measured asleep. CONCLUSION: Oral appliance therapy for obstructive sleep apnea over 4 weeks results in a reduction in blood pressure, similar to that reported with continuous positive airway pressure therapy.     

Night-to-night alterations in sleep apnea type in patients with heart failure

In patients with heart failure, apnea type can shift overnight from mainly obstructive to mainly central in association with reductions in PCO(2) and increases in periodic breathing cycle length, indicative of a fall in cardiac output. We hypothesized that the predominant apnea type could also vary from one night to another in association with alterations in PCO(2) and cycle length. We studied 12 men with heart failure in whom the predominant apnea type changed from one night to the next over periods of at least 1 month, and two groups with either predominantly obstructive or central sleep apnea (OSA or CSA) in whom apnea type remained stable over time. In patients with unstable apnea type (n = 12, duration between sleep studies 9.0 +/- 4.4 months), PCO(2) was significantly lower (37.6 +/- 1.6 mmHg versus 41.7 +/- 1.9 mmHg, P < 0.01), and cycle length significantly longer (61.9 +/- 3.4 s versus 51.0 +/- 1.9 s, P < 0.001) during nights with predominantly central than nights with predominantly obstructive apnea. In contrast, in both the stable central (n = 8, duration between sleep studies 11.9 +/- 5.3 months) and the stable obstructive (n = 8, duration between studies 6.9 +/- 5.2 months) sleep apnea groups, neither PCO(2) nor cycle length changed significantly between the baseline and follow-up sleep studies. We conclude that in some patients with heart failure, OSA and CSA are part of a spectrum of periodic breathing that can shift over time in association with alterations in PCO(2), cycle length and probably cardiac function.     

Effect of supplemental nocturnal oxygen on gas exchange in patients with severe obstructive lung disease

We studied the effect of supplemental nocturnal oxygen on blood gases in 15 patients with severe but stable chronic obstructive lung disease (ratio of forced expired volume in one second to forced vital capacity, 37.2 +/- 1.8 [mean +/- S.E.] per cent of predicted; arterial oxygen tension, 50.7 +/- 1.4 mm Hg; and arterial carbon dioxide tension [PCO2], 53.1 +/- 1.5 mm Hg). Sleep variables and measures of gas exchange were determined on two consecutive nights; on the first night the subjects breathed supplemental oxygen, and on the second they breathed room air. Transcutaneous PCO2 was measured with an infrared sensor, and arterial oxygen saturation with an ear oximeter. Breathing of supplemental oxygen sufficient to keep oxygen saturation at or above 90 per cent was associated with only small increases (less than 6 mm Hg) in PCO2 throughout sleep, as compared with values while subjects were breathing room air. The increase in PCO2 occurred early in the night and was not progressive. Only three patients, who were found to have obstructive sleep apnea in addition to obstructive lung disease, had larger increases in PCO2 during sleep and reported morning headaches. We conclude that nocturnal oxygen does not induce clinically important increases in PCO2 during sleep in patients with stable obstructive lung disease and therefore can safely be used to prevent the dangerous consequences of hypoxia.     

Effects of nasal O2 on sleep-related disordered breathing in ambulatory patients with stable heart failure

OBJECTIVE: The purpose of this study was 1) to determine the effects of nasal O2 on periodic breathing, arterial oxyhemoglobin desaturation and nocturnal ventricular arrhythmias in patients with heart failure and 2) determine the characteristics of patients whose periodic breathing will be reversed by O2 administration; our hypothesis was that patients with more severe periodic breathing and desaturation, will respond more favorably to oxygen. DESIGN: Prospective study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs Medical Center. PARTICIPANTS: 36 ambulatory male patients with heart failure whose initial polysomnograms showed periodic breathing with fifteen or more episodes of apnea (A) and hypopnea (H) per hour (AH index, AHI) were treated with nasal O2 during the subsequent full night polysomnography. INTERVENTIONS: Oxygen. MEASUREMENTS AND RESULTS: Arterial blood gases and hydrogen ion concentrations were measured, and cardiac radionuclide ventriculography, Holter monitoring, and polysomnography were done. The studies were scored blindly. Treatment with O2 resulted in a significant reduction in AHI (49+/-19 vs 29+/-29, means+/-SD), central apnea index (28+/-23 vs 13+/-18 per hour), and the percent of total sleep time below an arterial oxyhemoglobin saturation of 90% (23+/-21% vs 0.8+/-2.3%). In spite of virtual normalization of saturation with O2 therapy, the number of ventricular arrhythmias during sleep did not change significantly. In 39% of the patients (14 out of 36), O2 therapy resulted in reversal of central sleep apnea (defined by a reduction in AHI to less than 15/hr). In this group, the AHI decreased by 78% which was significantly (p=0.0001) more than improved (22%) in AHI of the remaining patients (n=22). The main differences between baseline characteristics of the two groups was a significantly higher mean PaCO2 in patients who did respond fully to O2 (39.3+/-5.4 vs 36.1+/-4.2 mm Hg, p=0.03). In both groups, however, O2 administration resulted in significant and similar improvement in arterial oxyhemoglobin saturation (saturation <90%, percent total sleep time 0.1+/-0.3% vs 1+/-3%). CONCLUSION: In patients with stable heart failure, administration of nasal O2 significantly improves periodic breathing and virtually eliminates clinically significant arterial oxyhemoglobin desaturation. The beneficial effects of O2, however, may be modulated by the level of arterial PCO2. Acute O2 therapy has important benefits on sleep apnea and nocturnal arterial oxyhemoglobin desaturation in heart failure patients. Long term benefits of O2 therapy in heart failure and sleep apnea need to be determined.     

Effect of zolpidem on the efficacy of continuous positive airway pressure as treatment for obstructive sleep apnea

STUDY OBJECTIVE: Assess the effect of the hypnotic zolpidem on the efficacy of nasal continuous positive airway pressure for treatment of Obstructive Sleep Apnea. DESIGN: Randomized double blind placebo controlled, cross-over study. SETTING: Veterans Administration Medical Center. PATIENTS: 16 patients with severe obstructive sleep apnea (apnea+ hypopnea index > 30/hr), on CPAP therapy for at least 6 months. INTERVENTION: Three sleep studies were performed over three consecutive weeks. On night one the pressure level required to prevent apnea, hypopnea, and snoring was determined. On the second and third study nights, either placebo (P) or 10 mg of zolpidem (Z) was given (random order) and subjects slept on the CPAP level determined on the first night. MEASUREMENTS: Sleep architecture, apnea + hypopnea index, arterial oxygen saturation. RESULTS: The sleep architecture was similar on the placebo and zolpidem nights except for a decrease in the sleep latency ( P: 23.5 +/- 4.7; Z: 13.1 +/- 3.3 minutes, P < 0.02) and a small decrease in the arousal index (P < 0.03) on zolpidem nights. The was no significant difference between placebo and zolpidem nights in the apnea + hypopnea index (P: 4.8 +/- 1.4 versus Z : 2.7 +/- 0.47 events/hour), oxygen desaturation index (1.46 +/- 0.53 versus 0.81 +/- 0.29 desaturations/hour), or the lowest SaO2 (91.4 +/- 0.6 versus 91.0 +/- 0.7%). CONCLUSIONS: Acute administration of zolpidem 10 mg does not impair the efficacy of an effective level of CPAP in patients with severe obstructive sleep apnea.     

Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure

Osteitis fibrosa, a frequent complication of chronic renal failure, is characterized by increased rates of bone formation and bone resorption due to increased secretion of parathyroid hormone (PTH). Effective treatment with oral calcitriol is often impossible in patients with osteitis fibrosa, because low doses may cause hypercalcemia. Because short-term infusions of intravenous calcitriol are capable of suppressing the secretion of parathyroid hormone in patients with uremia without causing hypercalcemia, we evaluated the effectiveness of long-term intermittent calcitriol infusions (1.0 to 2.5 micrograms three times weekly, during dialysis) in treating severe osteitis fibrosa in 12 consecutive patients on hemodialysis whose disease was refractory to conventional therapy. After a mean (+/- SE) treatment period of 11.5 +/- 1.4 months, the mean bone-formation rate declined from 1642 +/- 277 to 676 +/- 106 microns 2 per square millimeter per day (P less than 0.01) in the 11 patients who successfully completed the study. Similar reductions occurred in the osteoblastic osteoid (18 +/- 3 to 9 +/- 2 percent; P less than 0.01) and the degree of marrow fibrosis (6.2 +/- 1.7 to 3.5 +/- 1.3 percent; P = 0.01). Concomitant serum biochemical changes included increased calcium levels (2.55 +/- 0.03 to 2.67 +/- 0.05 mmol per liter; P less than 0.01), decreased alkaline phosphatase levels (489 +/- 77 to 184 +/- 32 U per liter; P less than 0.001), and decreased levels of PTH (amino-terminal, 172 +/- 34 to 69 +/- 16 ng per liter in five patients, P less than 0.03; and carboxy-terminal, 1468 +/- 467 to 1083 +/- 402 ml-eq per liter in six patients, P not significant). Although the majority of the patients had transient episodes of asymptomatic hypercalcemia, this complication could be quickly reversed by temporarily halting treatment or decreasing the dose of calcitriol. We conclude that long-term intermittent infusions of intravenous calcitriol are effective in ameliorating osteitis fibrosa in patients on dialysis. Patients whose osteitis fibrosa is refractory to oral calcitriol and who are candidates for parathyroidectomy should be considered first for intravenous calcitriol therapy.     

Nocturnal overdrive pacing for the treatment of sleep apnea syndrome

STUDY OBJECTIVES: We investigated the effect of 1 week of nocturnal overdrive pacing (NOP) on the apnea-hypopnea index (AHI) in patients with a chronically implanted pacemaker and diagnosed during a screening phase with sleep apnea. DESIGN: Randomized, single-blind, crossover study. SETTING: University medical centers in Zürich, Switzerland, and Berlin, Germany. PATIENTS: Nineteen patients with mild to severe sleep apnea/hypopnea (16 men, mean age = 68.8 +/- 11.4 years) participated. The individuals did not suffer from permanent atrial arrhythmia, did not use continuous positive airway pressure, and had been implanted with atrial or dual-chamber pacemakers. INTERVENTIONS: Nocturnal lower rates were 45 and 75 beats per minute (bpm) at night for the control and NOP arms, respectively, and daytime lower rates were 60 bpm. Subjects were in each arm for 1 week. MEASUREMENTS AND RESULTS: Heart-rate increase from control (61 +/- 9 bpm) to NOP (78 +/- 4 bpm) followed by significant reduction in circulation time (24.6 seconds control, 20.7 seconds NOP; p = .04) resulted in no significant change in AHI (26.8 +/- 17.1/h control, 23.0 +/- 16.7/h NOP; p = .49). Seven subjects characterized by a higher hypopnea index, less stage 1 and 2 sleep, and less slow-wave sleep improved at least 1 AHI severity level with NOP, mainly attributable to reduction of hypopneas. CONCLUSION: NOP over a period of 1 week followed by a reduction in circulation time did not improve AHI in patients with SA. Whether an improvement by 1 AHI severity level in a specific subset of patients reflects a true response remains to be elucidated by further studies.     

Protriptyline in obstructive sleep apnea: a double-blind trial

We evaluated protriptyline, a nonsedating tricyclic antidepressant, as a treatment for obstructive sleep apnea in a double-blind crossover study of five men. After two weeks of treatment, with no change in body weight, daytime somnolence was markedly reduced and nocturnal oxygenation was improved, although apnea duration and frequency were not significantly decreased. Rapid-eye-movement (REM) stage time as a fraction of the total sleep time was reduced during treatment from 0.231 +/- 0.031 to 0.107 +/- 0.013 (mean +/- S.E.M.) (P less than 0.05). REM apnea time as a fraction of total sleep time was reduced from 0.145 +/- 0.022 to 0.054 +/- 0.006 (P less than 0.05). REM reduction during treatment with protriptyline can account for decreased REM apnea time. Similar decreases in REM stage time and REM apnea duration and similar improvement in oxygenation continued after six months of treatment. In addition, body weight, apnea, and arousal frequency were decreased at this time. Although the obstructive sleep apnea was not resolved, it was reduced. Protriptyline can be effective in patients with sleep apnea when the disorder is not life-threatening.     

Obstructive sleep apnea in Costello syndrome

Costello syndrome (CS) was initially described by Costello in 1971; it is caused by a germline mutation in HRAS proto-oncogene. The aim of the present study was to evaluate the respiratory activity during sleep in a group of subjects with CS. We studied 10 consecutive patients, 4 males and 6 females, aged 3-29 years, affected by CS. All patients underwent clinical, neurological, otholaryngologic and radiologic evaluation, and a full-night polysomnography in the sleep laboratory. Polysomnography showed that seven patients presented a relevant number of respiratory events of obstructive type during sleep. The apnea-hypopnea index (AHI) ranged from 0 to 19.2 events per hour (mean index = 7.5 +/- 6.9 events/hr). In one patient AHI was not evaluable because of tracheostomy. Apnea induced mild or moderate hemoglobin desaturations (mean of lowest SpO2 values = 85.4 +/- 5.5%). Only sporadic respiratory pauses of central type were observed (mean number of central apnea per study: 7.2 +/- 6.8 events/hr). Sleep structure was fragmented, with a high number of awakenings (mean number of awakenings was 13.2 +/- 8.1; of these, 4.8 +/- 2.5 lasted longer than 2 min). In all patients, otolaryngologic and radiologic observations revealed one or more sites of narrowing in the upper airways. Our results suggest that Costello patients have a high prevalence of obstructive sleep-related respiratory disorders, which need to be assessed by means of polysomnography.     

Nocturnal myocardial ischemia and cardiac arrhythmia in patients with sleep apnea with and without coronary heart disease

Summary To study the effect of apnea and hypoventilation-induced hypoxemia on the heart, we carried out polysomnographic recordings over; 4 nights with electrocardiographic tracings in 30 patients with and without coronary heart disease. Evaluations of the data were based on the 2nd and 4th nights. In six subjects, five with coronary heart disease, we found 85 episodes of nocturnal ischemia, mainly during REM sleep (83.5%), high apnea activity, and sustained and progressive hypoxemia. Complex ventricular ectopy was observed in 14/13 patients (nights 2/4) and repetitive ventricular ectopy in 5/3. There was no significant difference in the quality and quantity of ventricular ectopy during wake and sleep states between the CHD group and the control group. In one patient ventricular bigeminy was observed only at a threshold of SaO₂ below 60%. Bradyarrhythmia was made evident in four subjects from the CHD group and correlated mainly with apnea activity. We suppose that patients with sleep apnea and CHD are at cardiac risk because coronary heart disease can be aggravated by insufficient arterial oxygen supply due to cumulative phases of apnea and hypoventilation. The reduced hypoxic tolerance of the heart may lead to myocardial ischemia: and increased electrical instability.Abbreviations AI apnea index (apnea episodes per hour) - bpm beats per minute (heart rate) - CHD coronary heart disease - NREM non-rapid eye movement - PVC premature ventricular contraction - REM rapid eye movement - SRBD sleep-related breathing disorders     

Effect of strict glycemic control on renal hemodynamic response to amino acids and renal enlargement in insulin-dependent diabetes mellitus

BACKGROUND. Many patients with insulin-dependent diabetes mellitus have an increase in the glomerular filtration rate and renal enlargement early in the course of their disease. Both these changes may be risk factors for the later development of diabetic nephropathy. Their cause is not known, but they could be due to augmented renal responses to the increase in plasma amino acid concentrations that occurs when dietary protein intake is high, a factor known to increase glomerular filtration and renal blood flow in normal subjects. METHODS. We measured the glomerular filtration rate and renal plasma flow after an overnight fast and during an infusion of amino acids in 12 patients with insulin-dependent diabetes mellitus and 9 normal subjects. The diabetic patients were studied when they were hyperglycemic, when they were euglycemic after an insulin infusion for 36 hours, and after intensive insulin therapy for 3 weeks. Kidney volume was measured by ultrasonography before and after the period of intensive insulin therapy. RESULTS. The glomerular filtration rate and renal plasma flow were normal after fasting when the patients were hyperglycemic (mean [+/- SE] fasting plasma glucose level, 11.5 +/- 0.7 mmol per liter). After the amino acid infusion, these values increased more in the patients (glomerular filtration rate, 2.65 +/- 0.07 ml per second per 1.73 m2 of body-surface area; renal plasma flow, 13.30 +/- 0.68 ml per second per 1.73 m2; P less than 0.05 for both) than in the normal subjects (2.25 +/- 0.08 and 11.20 +/- 0.65 ml per second per 1.73 m2, respectively). The 36-hour infusion of insulin in the diabetic patients did not alter the glomerular filtration rate or renal plasma flow either before or during the amino acid infusion. After three weeks of intensive insulin therapy (fasting plasma glucose level, 5.3 +/- 0.2 mmol per liter), the glomerular filtration rate and renal plasma flow after the amino acid infusion (2.33 +/- 0.03 and 11.30 +/- 0.43 ml per second per 1.73 m2, respectively) were similar to those in the normal subjects. The kidney volumes in the normal subjects and the patients with diabetes were 219 +/- 14 and 312 +/- 14 ml per 1.73 m2, respectively (P less than 0.01); the volume decreased to 267 +/- 22 ml per 1.73 m2 (P less than 0.001) in the diabetic patients after three weeks of intensive insulin therapy, which was not significantly different from the volume in the normal subjects (P = 0.1). CONCLUSIONS. Conventionally treated diabetic patients who have normal renal function while fasting have augmented renal hemodynamic responses to increased plasma amino acid concentrations. The concomitant decrease in these hemodynamic responses and in kidney size with strict glycemic control suggests that these phenomena are related and influenced by the metabolic state.     

Obstructive sleep apnea treatment: peripheral and central effects on plasma renin activity and aldosterone

To assess the effect of obstructive sleep apnea treatment on plasma renin activity (PRA) and plasma aldosterone seven male patients were studied under two conditions: untreated and treated with nasal continuous positive airways pressure (CPAP). PRA and plasma aldosterone were measured at 10-min intervals for both nights. CPAP treatment diminished the urinary and Na+ excretion, whereas plasma volume increased. The mean levels of PRA and aldosterone were significantly enhanced by the treatment, increasing respectively from 1.5 +/- 0.3 to 3.0 +/- 0.7 ngAI ml-1.hr-1 (p less than 0.05) and from 8.0 +/- 1.0 to 12.0 +/- 1.7 ng.100 ml-1 (p less than 0.05). PRA curves reflected the overall sleep structure as similarly described in normal subjects. The apnea-induced sleep disturbance led to flat PRA profiles and the restoration of a normal sleep pattern by treatment restored the PRA oscillations related to the sleep cycles and consequently restored aldosterone oscillations. The mean amplitude of these oscillations increased respectively from 1.0 +/- 0.1 to 1.8 +/- 0.4 ngAI ml-1.hr-1 and from 5.4 +/- 1.2 to 10.9 +/- 1.9 ng.100 ml-1. These results suggest that CPAP treatment modifies the nocturnal patterns of PRA and aldosterone by increasing their mean levels and their oscillation amplitude. This indicates increased secretion, which contributes to the normalization of urine and Na output.     

Effects of nocturnal wearing of dentures on the quality of sleep and oral-health-related quality in edentate elders with untreated sleep apnea: a randomized cross-over trial

Study ObjectivesThis study aims to assess whether the nocturnal wear of dentures has an effect on the quality of sleep and oral-health-related quality of life of the edentulous elderly with untreated sleep apnea.MethodsA single-blind randomized cross-over design with two sequences and two periods was used. Participants (n = 77) were randomly assigned either to sequence 1 (nocturnal wear followed by nocturnal nonwear of the denture for 30–30 days) or sequence 2 (nocturnal nonwear followed by nocturnal wear of denture for 30–30 days). The primary sleep outcome was the quality of sleep, assessed through sleep fragmentation measured as Apnea–Hypopnea Index (AHI) and respiratory arousal from portable polysomnography. Secondary outcomes were daytime sleepiness, sleep quality (Pittsburgh Sleep Quality Index, PSQI) and oral-health-related quality of life measured by validated questionnaires.ResultsThe mean paired difference in AHI scores for the period of wearing versus not wearing dentures at night was small 1.0 event per hour (p = 0.50; 95% confidence interval (CI) = −2.0 to 4.1). The mean respiratory arousal index was higher when wearing dentures at night than when not wearing dentures at night, with a mean paired difference of 2.3 events per hour (p = 0.05; 95% CI = 0.0 to 4.6). No difference in sleepiness and PSQI were noted. Wearing dentures at night resulted in a statistically significantly higher mean score of psychological discomfort when compared to not wearing dentures at night.ConclusionsThe results provide some support to usual practice guidelines to remove dentures at night in edentulous elders suffering from sleep apnea.Clinical trial registrationNCT01868295.