Development of a statistical model for the formation of poly [acryloyl hydroxyethyl starch] microspheres

Approximately 1 in 4 patients with systemic hypertension have a 24-hour blood pressure (BP) profile characterized by a blunted or absent nocturnal decline in pressure. We evaluated the effects of a chronotherapeutic delivery system of controlled-onset extended-release (COER) verapamil hydrochloride and placebo in 257 hypertensive patients according to their circadian BP pattern in an 8-week prospective, multicenter, randomized, and double-blind clinical trial. Patients were stratified into 193 dippers (>10% decline in BP during the period of 10 P.M. to 5 A.M. compared with the hours of 5 A.M. to 10 P.M.) and 64 nondippers (<10% decline in BP during nighttime). During daytime, placebo-subtracted BP was similarly decreased in dippers and nondippers by COER verapamil. During nighttime, the placebo increased nocturnal BP in dippers (baseline nocturnal BP, 133/78 mm Hg) by 3/3 +/- 2/2 mm Hg and reduced BP by -5/-3 +/- 2/2 mm Hg in nondippers (baseline nocturnal BP, 152/94 mm Hg) (p = NS between groups). After controlling for age, gender, ethnicity, and the regression to the mean observed on placebo for all doses, COER verapamil reduced nocturnal BP more in nondippers than dippers -5.8/-2.4 mm Hg, p <0.0001 for systolic BP and p = 0.09 for diastolic BP). Additionally, a significant dose-related reduction in systolic and diastolic nocturnal BP (r = 0.56, p <0.0001 for systolic BP and r = 0.62, p <0.0001 for diastolic BP) was observed with COER verapamil after controlling for baseline covariates. These data demonstrate that nocturnal BP is decreased by a greater extent in nondipper hypertensives than in dipper hypertensives following treatment with COER verapamil HCL.     

An evaluative study of the short-term effects of once-daily, sustained-release theophylline on sleep in nocturnal asthmatics

OBJECTIVE: To examine the effects of once-daily, sustained-release theophylline on sleep patterns in nocturnal asthmatics. DESIGN: Double-blind, randomised, cross-over, placebocontrolled trial over 22 days. Seven-day period to establish therapeutic levels of theophylline (11.8 +/- 3 mg/l); 8-day cross-over period of 4 days' placebo or theophylline; 7-day baseline period. Electrophysiological sleep patterns, overnight bronchoconstriction and arterial O2 saturation monitored on nights 7, 11 and 15. SETTING: Sleep Laboratory, Medical School, University of the Witwatersrand. PATIENTS: Twelve volunteers who met the criteria for asthma, had previously used theophylline, were clinically stable and had a history of nocturnal awakenings caused by asthma were enrolled. OUTCOME MEASURES: Sleep-onset latency (SOL), within-sleep wakefulness (WSW), rapid eye movement sleep (REM), slow-wave sleep (SWS), peak expiratory flow rate (PEFR) and arterial oxygen saturation. RESULTS: SOL increased on theophylline--12 minutes (range 7-9 minutes) compared with placebo--6 minutes (range 3-11 minutes); WSW increased from 33 minutes (range 17-66 minutes) on placebo to 72 minutes (range 35-150 minutes) on theophylline. REM sleep was unaltered. SWS decreased in 10-12 patients, but this difference was not significant. Early morning PEFR was significantly better on theophylline in all study limbs. CONCLUSION: Our findings show that while once-daily, sustained-release theophylline improves bronchodilation in nocturnal asthmatics, it increases nocturnal wakefulness and decreases sleep efficiency during short-term treatment. This may, however, not be a long-term effect.     

Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome: role of recurrent apnoeas

Recent results in animals have suggested that repetition of hypoxaemic stimuli may result in a progressive increase in pulmonary arterial pressure (Ppa). The purpose of the present study was to investigate the effects of recurrent obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five snorers. Mean Ppa was measured before, at the start, at the end and after the selected apnoeas. The analysis was performed for each 1 h period for at least 7 h throughout the night on at least 10 randomly selected apnoeas per hour. In snorers, 100 randomly chosen values were measured during every hour of the night. In the morning after the nocturnal study, the Ppa responses to acute hypoxia and hypercapnia were measured. No Ppa changes throughout the 7 h were found during sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small but significant increase in Ppa throughout the night was noted, affecting the values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in progressive Ppa was also present, irrespective of changes in apnoea duration and apnoea desaturation. The Ppa rise during the night was not affected by diurnal Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery pressure progressively increases during the night, reflecting the cumulative effects of apnoeas and nocturnal hypoxaemia.     

Nocturnal elevation of intraocular pressure in young adults

PURPOSE: To distinguish 24-hour (circadian) and postural effects on intraocular pressure (IOP) in healthy young adults. METHODS: Thirty-three volunteers were housed in a sleep laboratory for 1 day under a strictly controlled 16-hour light and 8-hour dark environment. Sleep was encouraged in the dark period. Intraocular pressure was measured in each eye every 2 hours using a pneumatonometer. Researchers used night-vision goggles to perform IOP measurements in the dark, while the subject's light exposure was minimized. In the first group of 12 subjects, measurements were taken with subjects in the sitting position during the light-wake period and supine during the dark period. In the second group of 21 subjects, all IOP measurements were taken with the subjects supine. RESULTS: Average IOP was significantly higher in the dark period than in the light-wake period in both groups. The lowest IOP occurred in the last light-wake measurement, and the peak IOP occurred in the last dark measurement. The trough-peak difference in IOP was 8.2+/-1.4 mm Hg (mean +/- SEM) in the first group. Intraocular pressure changed sharply at the transitions between light and dark. In the second group, the trough-peak IOP difference was 3.8+/-0.9 mm Hg. Intraocular pressure changed gradually throughout the 24-hour period. In comparison with the sitting IOP in the first group, the supine IOP in the second group was significantly higher during the light-wake period. CONCLUSIONS: Circadian rhythms of IOP were shown in young adults, with the peaks occurring in the late dark period. A nocturnal IOP elevation can appear independent of body position change, but change of posture from upright to recumbent may contribute to the relative nocturnal IOP elevation.     

Effects of amlodipine on 24-hour ambulatory blood pressure profiles, electrocardiographic monitoring, and left ventricular mass and function in black patients with very severe hypertension

In a 3-month, open-label study, 54 consecutive black patients with very severe hypertension were treated with amlodipine. Very severe hypertension was defined as an average sitting diastolic blood pressure (BP) > or = 115 mmHg and < or = 140 mmHg as a mean of 10 readings over a 30-minute period using an automatic BP measuring device and a mean 24-hour diastolic ambulatory blood pressure (ABP) > or = 110 mmHg and < or = 140 mmHg). Serial changes in 24-hour ABP and electrocardiographic monitoring, left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-hour ABP was reduced from 181 +/- 14/119 +/- 6 to 140 +/- 15/92 +/- 9 mmHg at 3 months (P < 0.0001). Target BP (mean 24-hour diastolic ABP < 90 mmHg) was achieved in 35% of the patients. The reduction in BP was sustained for 24 hours after drug administration. Simultaneous BP measurements using the automatic BP measuring device were significantly different from the ABP measurements before and after treatment, suggesting a marked "white coat" pressor effect. At baseline, frequent or complex ventricular arrhythmias (> 30 ventricular extrasystoles per hour, ventricular couplets) were present in 2 (4%) patients, with no significant change after treatment. Left ventricular mass index regressed from 140 +/- 50 to 111 +/- 30 g/m2 at 3 months (P < 0.03); LV performance was not adversely affected. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. In this group of patients, treatment with amlodipine showed a marked and sustained antihypertensive action as demonstrated by 24-hour ABP monitoring, and was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function. Further, a low rate of complex ventricular arrhythmias was documented.     

Cardiovascular effects of mibefradil in hypertensive patients with obstructive sleep apnea

OBJECTIVE: Hypertension is often seen in obstructive sleep apnea (OSA) and is characterized by increased sympathetic activity, depressed baroreflex and accentuated vascular responsiveness. The objective of this study was to investigate the effects of the new T-selective calcium channel blocker mibefradil on invasively measured blood pressure (BP) and heart rate in hypertensive patients with OSA. METHODS: The present study was a double-blind, randomized and placebo-controlled before and after trial in two parallel groups. Fifty-three men aged 23 69 years with systemic hypertension and OSA were recruited from the Outpatient Department of the Marburg University Sleep Laboratory and hospitalized for 10 days. Mibefradil (50 mg) or placebo were given orally in the morning for 8 days. The main outcome measure was the mean arterial (radial) BP monitored continuously during nocturnal sleep and during standardized daytime physical and psychological performance testing. RESULTS: Mibefradil lowered mean arterial BP and heart rate with (SD) during the entire measurement period compared with placebo: -7.25 (9.59) vs -2.11 (8.43) mmHg (P=0.039) and -4.83 (5.94) vs -1.34 (4.13) bpm (P=0.022), respectively. Both effects were observed during nocturnal sleep and performance testing, including graded exercise. Adverse events did not differ compared with placebo. CONCLUSION: Mibefradil is an effective but well-tolerated antihypertensive that also lowers heart rate over 24 h in OSA, in conditions known to increase BP.     

Agonist regulation of beta-adrenergic receptors: immunoblotting and indirect immunofluorescence reveal agonist-induced lateral sequestration and loss of binding

Sleep and wakefulness were studied polygraphically in two adult male ferrets between the ages of 3 months and 2.5 years. Nine 24-hour recordings were obtained on different light/dark schedules, and one animal was also monitored for 3 days following administration of the serotonin synthesis inhibitor, parachlorophenylalanine. Stage scoring was accomplished utilizing criteria similar to those used in the cat. Certain modifications to the criteria were made to accommodate apparent differences in electrographic indicators of state. Mean daily percentages [+/- standard error of the mean (SEM)] for the major stages were: slow-wave sleep, 36.0 +/- 1.33; rapid eye movement (REM) sleep, 24.4 +/- 0.94; and wake, 39.4 +/- 1.17. Under laboratory conditions, ferrets spend over 60% of the time in sleep and 40.28% +/- 0.93% of total sleep time in REM sleep. The high amount of REM sleep is achieved by having a high number of REM sleep episodes rather than long REM periods. Sleep cycle length was computed in two ways: with long wake episodes removed, 16.7 +/- 0.4 minutes; and with all wake removed, 13.2 +/- 0.3 minutes. Sleep and waking indices in the ferret are compared to those in the cat and discussed with respect to predictions based on several constitutional variables. The high amount of REM sleep and the relative immaturity of the ferret at birth lends additional support for a functional role of REM sleep on ontogenetic development.     

Heavy metals in shrimp culture areas from the Gulf of Fonseca, Central America. II. Cultured shrimps

An increase in magnesium intake has been suggested to lower blood pressure (BP). However, the results of clinical studies are inconsistent. We studied the effects of magnesium supplementation on office, home, and ambulatory BPs in patients with essential hypertension. Sixty untreated or treated patients (34 men and 26 women, aged 33 to 74 years) with office BP >140/90 mm Hg were assigned to an 8-week magnesium supplementation period or an 8-week control period in a randomized crossover design. The subjects were given 20 mmol/d magnesium in the form of magnesium oxide during the intervention period. In the control period, office, home, and average 24-hour BPs (mean+/-SE) were 148.6+/-1.6/90.0+/-0.9, 136.4+/-1.3/86.8+/-0.9, and 133.7+/-1.3/81.0+/-0.8 mmHg, respectively. All of these BPs were significantly lower in the magnesium supplementation period than in the control period, although the differences were small (office, 3.7+/-1.3/1.7+/-0.7 mmHg; home, 2.0+/-0.8/1.4+/-0.6 mmHg; 24-hour, 2.5+/-1.0/1.4+/-0.6 mm Hg). Serum concentration and urinary excretion of magnesium increased significantly with magnesium supplementation. Changes in 24-hour systolic and diastolic BPs were correlated negatively with baseline BP or changes in serum magnesium concentration. These results indicate that magnesium supplementation lowers BP in hypertensive subjects and this effect is greater in subjects with higher BP. Our study supports the usefulness of increasing magnesium intake as a lifestyle modification in the management of hypertension, although its antihypertensive effect may be small.     

Mortality of aerospace workers exposed to trichloroethylene

We assessed the differential effects of a chronotherapeutic agent (controlled-onset extended release [COER] verapamil), administered at bedtime versus a conventional, homeostatic therapy (nifedipine gastrointestinal therapeutic system [GITS]) taken in the morning, on early morning and 24-hour blood pressure (BP), heart rate (HR), and the HR x systolic BP product. The study was a multicenter (n = 51), randomized, double-blind prospective clinical trial with a 10-week treatment period. Dose titration was performed by study investigators based on systolic and diastolic BP values at the doctor's office. Ambulatory BP monitoring was performed at placebo baseline, after 4 weeks of stable double-blind therapy, and at end of the study. Twenty-four-hour BP profiles were studied in 557 hypertensive patients. Changes in BP, HR, slope of the rate of rise of BP and HR, and the HR-systolic BP product during the 4 hours from 1 hour before to 3 hours after awakening were evaluated. The study was powered to show equivalence between the 2 regimens, predefined as a difference between treatment groups in mean change from baseline in early morning BP of +/- 5 mm Hg systolic and +/- 3 mm Hg diastolic. Changes in the early morning BP fell within the definition of equivalence for the 2 treatment strategies (-12.0/-8.2 mm Hg for COER-verapamil and -13.9/-7.3 mm Hg for nifedipine GITS). Changes in both the early morning HR and rate-pressure product were significantly greater following COER-verapamil therapy versus nifedipine GITS (HR, -3.8 beats/minute vs +2.6 beats/minute, p < 0.001 and HR-systolic BP product, -1,437 beats/min x mm Hg vs -703 beats/min x mm Hg, respectively, p < 0.001). Changes in ambulatory BP demonstrated clinically similar reductions for the awake period, but nifedipine GITS lowered systolic BP to a greater extent than COER-verapamil during sleep (-11.0 vs -5.8 mm Hg, p < 0.001). COER-verapamil and nifedipine GITS had equivalent effects (+/- 5/3 mm Hg) on early morning BP. In addition, both extended-release calcium antagonists effectively lowered 24-hour BP. However, COER-verapamil had greater effects than nifedipine GITS on early morning hemodynamics (HR, HR-systolic BP product, rate of rise of BP and HR) and lesser effects during sleep due to its intrinsic pharmacologic properties and chronotherapeutic delivery system.     

CDTect-RIA and CDTect-EIA for determination of serum carbohydrate-deficient transferrin compared

Little is known of the factors that regulate CBF in sleep. We therefore studied 10 lambs to assess the vasodilatory processes that underlie cerebral autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP), were rapidly made hypotensive by inflating a cuff around the brachiocephalic artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3, mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The time (seconds) required for maximal cerebral vasodilation to occur was longer in active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the changes in CPP induced with brachiocephalic occlusion were equal in each state. In conclusion, our studies provide the first evidence that the vasoactive mechanisms that underlie autoregulation of the cerebral circulation function during sleep. Moreover, our data reveal that the speed and the magnitude of the vasodilatory reserves available for autoregulation are significantly less in active sleep than in quiet sleep.     

Role of nocturnal arterial hypotension in optic nerve head ischemic disorders

OBJECTIVE: To investigate the role of nocturnal arterial hypotension, intraocular pressure (IOP) and heart rate in optic nerve head (ONH) ischemic disorders, and the effects of systemic factors and topical beta-blocker eye-drops on nocturnal arterial hypotension and heart rate. METHODS: We investigated prospectively, by 24-hour ambulatory blood pressure (BP) monitoring and diurnal curve of the IOP, 275 white patients with anterior ischemic optic neuropathy (AION - 114), normal tension glaucoma (NTG - 131) and primary open angle glaucoma (POAG - 30). RESULTS: Hourly average BP data analyses showed a significantly greater drop in mean diastolic BP (p < 0.009) at night in NTG than AION. Cases with visual field deterioration had significantly (p = 0.05) lower minimum nighttime diastolic BP. Arterial hypertensives on oral hypotensive therapy showed a significantly lower mean nighttime systolic BP (p = 0.006) and larger mean percentage drop in systolic (p < 0.0001), diastolic (p = 0.0009) and mean (p < 0.0001) BPs. Normotensives and hypertensives without therapy had no such difference. IOP showed no significant correlation with visual field deterioration in any of these conditions. Patients using beta-blocker eyedrops, compared with those not using them, had greater percentage drop in diastolic BP (p = 0.028), lower minimum nighttime diastolic BP (p = 0.072) and lower minimum nighttime heart rate (p = 0.002). CONCLUSIONS: Findings of our study suggest that nocturnal hypotension, by reducing the ONH blood flow below a crucial level during sleep in a vulnerable ONH, may play a role in the pathogenesis of AION and glaucomatous optic neuropathy (GON) and progression of visual loss in them. Thus, nocturnal hypotension may be the final insult in a multifactorial situation.     

In vitro release of acyclovir from semisolid dosage forms: effect of cyclodextrin and polyethylene glycol

Presynaptic depolarization of trigemino-thalamic (TGT) terminals may contribute to modulation of ascending oro-facial somatosensory information during active (or rapid eye movement) sleep. The relative excitability of TGT terminals was inferred from changes in the current required to maintain an antidromic firing probability of 50% (EC50) during quiet wakefulness as compared to active sleep. Depolarization or hyperpolarization of TGT terminals was defined as a decrease or increase, respectively, in the EC50. Overall, the EC50 of 8 TGT terminals was reduced by a mean 8.8+/-3.6 microA during active sleep relative to quiet wakefulness. This result suggests that depolarization of TGT terminals, which may act to suppress the transfer of sensory information from the trigeminal nucleus to the thalamus, occurs during active sleep.     

Self-awareness, task failure, and disinhibition: how attentional focus affects eating

Prolonged continuous blood pressure (BP) and heart rate (HR) recordings from neonates of 35 to 42 weeks gestation were studied during and after ECMO. Data segments with significant deviation of BP were extracted for further analysis. The simultaneous changes in BP and HR were compared and the slope of the regression determined baroreflex sensitivity (BRS). Of 464 BP deviations, 98% produced curves with a negative slope consistent with the presence of a baroreflex. The average BRS was -1.0 +/- 0.8 bpm/mmHg (mean +/- S.D.) and curves were steeper during rising BP than falling BP (-1.1 +/- 0.9 beats/min per mmHg versus -0.9 +/- 0.6, P = 0.001). The baroreflex was more sensitive during ECMO than after ECMO to both rising BP (-1.0 +/- 0.5 beats/min per mmHg versus -0.7 +/- 0.5, P = 0.004) and falling BP (-1.0 +/- 0.6 beats/min/mmHg versus -0.7 +/- 0.5, P = 0.04). HR response curves obtained during different BP fluctuations on the same recording had varying threshold, consistent with acute resetting. One infant demonstrated chronic baroreceptor resetting over 3 days to a rise in resting BP. The near-term, critically ill neonate has an active baroreflex which is capable of resetting. ECMO was associated with accentuation of the baroreflex response.     

Assessment of the nutritional state of dialysis patients

Obstructive sleep apnea syndrome (OSAS) has been associated with a higher than normal cardiovascular morbidity and mortality. Some OSAS patients lack the sleep-related, nocturnal decrease, or "dip," in blood pressure which is seen in normal individuals. These subjects, called "non-dippers," may be at greater risk for cardiovascular problems. We studied 40 OSAS patients (including 3 women) and 6 control subjects, all identified by polysomnography, for nocturnal blood pressure "dipping." We performed a second nocturnal polysomnogram to determine their apnea and hypopnea indices, (A + H)I, and oxygen saturation levels at the beginning of the study and then initiated 48 hours of ambulatory blood pressure monitoring, with data points collected every 30 minutes. Controls, which included one hypertensive subject, were all dippers. Nineteen OSAS subjects (48% of OSAS individuals) were systolic non-dippers and only 9 of them (22.5%) were diastolic non-dippers. We considered the following clinical variables as potential predictors of non-dipping: age, body mass index, respiratory disturbance index, years of reported loud snoring by bed partners, lowest oxygen saturation during nocturnal sleep, and percentage of sleep time spent with oxygen saturation below 90%. Multiple regression analyses indicated respiratory disturbance index as the only significant variable for systolic (p = 0.04) and diastolic (p = 0.03) blood pressure non-dipping. When we forced the following two nonsignificant variables into the model, they showed a very meager impact: number of years with reported loud snoring (p = 0.4 and p = 0.5, respectively for systolic and diastolic blood pressure non-dipping) and age (p = 0.5 and p = 0.6). The calculated model explained only a low percentage of the variance with an r2 of 0.25 and 0.26 for systolic and diastolic blood pressure non-dipping, respectively. Analysis of hypertension/normotension and dipping/non-dipping failed to show a significant relationship in the studied population. Fifty percent of the normotensive OSAS subjects were non-dippers and 43% of the hypertensive OSAS subjects were also non-dippers. We found a relationship between increasing respiratory disturbance index and increasing average 24-hour systolic blood pressure only when OSAS subjects were non-dippers and hypertensive.     

Conserved themes but novel activities in recombinases and topoisomerases

OBJECTIVE: Hypertension is thought to play an important role in the pathogenesis of acromegalic cardiomyopathy. So far, hypertension has been defined by clinical measurement, with considerable variations reported concerning its prevalence in acromegalics. DESIGN: To determine the mean blood pressure (BP) values and the prevalence of hypertension in patients with active acromegaly according to non-invasive 24-hour ambulatory BP monitoring (ABPM) and to compare the data obtained with those provided by clinical measurement. PATIENTS: Forty patients with active acromegaly (22 women, 18 men, mean age 48.6 +/- 12.5 years) were included. Patients were in wash-out for antihypertensive treatment and none had been using any medical treatment for acromegaly for at least 3 months before the study. All were studied as outpatients. MEASUREMENTS: Clinical BP values were calculated as the mean of BP values obtained by standard sphygmomanometric measurement in three separate occasions. Mean 24-hour, daytime and night-time BP values were obtained by ABPM. RESULTS: The mean 24-hour BP values were lower than clinical BP values, the difference being significant for both systolic BP (SBP: 131.1 +/- 21.5 versus 136.1 +/- 16.3 mmHg, P < 0.02) and for diastolic BP (DBP: 74.6 +/- 10.6 versus 88.8 +/- 9.1 mmHg, P < 0.0001). ABPM values recorded during the daytime were 137.8 +/- 20.9 mmHg for SBP and 78.6 +/- 11.5 mmHg for DBP, the latter being significantly lower than the corresponding clinical BP values (P < 0.0001). About 60% of the patients considered hypertensive by clinical measurement were found to be normotensive by ABPM, thereby decreasing the prevalence of hypertension in this series from 42.5% to 17.5% according to ABPM (P < 0.02). In contrast, all patients defined as normotensive by clinical measurement were also normotensive by ABPM. CONCLUSIONS: Ambulatory blood-pressure monitoring indicated a lower prevalence of hypertension in acromegalic patients then usually reported, suggesting that the role of hypertension in the pathogenesis of acromegalic cardiomyopathy is commonly overestimated. We propose that ambulatory blood-pressure monitoring should be routinely proposed in acromegalics with high or borderline clinical blood pressure values although it is not useful in patients defined normotensive according to repeated clinical measurement.     

Twenty-four-hour ambulatory oxygen desaturation and electrocardiographic recording in obstructive sleep apnea syndrome

BACKGROUND: Although nocturnal pulseoximetry is routinely performed in obstructive sleep apnea syndrome (OSAS), pulseoximetry over a 24-h period has not been studied. HYPOTHESIS: The purpose of the study was to determine whether simultaneous 24-h oxygen desaturation and electrocardiographic (ECG) recording might be used to screen for daytime sleep sequelae in patients with OSAS. METHODS: Simultaneous recording of arterial oxygen saturation (SpO2) and ECG was conducted over a 24-h period in 18 male patients with OSAS (mean age 51.3 years) who were diagnosed by standard polysomnography (PSG), and in 15 age-matched healthy subjects (mean age 52.7 years) as controls to evaluate circadian variation of these parameters. The measures of heart rate variability (HRV) were calculated from 24-h ambulatory ECGs. Seventeen patients with OSAS showed excessive daytime sleepiness (EDS). We calculated the duration in which SpO2 decreased to < 90% (duration of SpO2 < 90%). The number of apnea/hypopneas per hour (AHI) during sleep was investigated with Apnomonitors (Chest MI, Co., Tokyo) on the same day as the SpO2 recordings. RESULTS: Controls showed no episodes of oxygen desaturation. In patients with OSAS, driving (33.3% of patients with OSAS) was the most common activity in which SpO2 decreased to < 90%, followed by daytime napping (27.8%) and resting after meals (22.2%). The duration of SpO2 < 90% over a 24-h period correlated significantly with the duration levels recorded during sleep (r = 0.99, p < 0.05) and in the afternoon (r = 0.62, p < 0.05), and with the AHI (r = 0.55, p < 0.05), but not with the duration of SpO2 < 90% in the morning. The number of ventricular premature beats correlated significantly with the duration of SpO2 < 90% for a 24-h period, but not with measures of HRV. Ventricular tachycardia was found in two (11.1%) and ST-T depression in three patients (16.6%) with underlying cardiac diseases. CONCLUSION: Our results suggest that daytime sleep attacks accompanied by oxygen desaturation in patients with moderate to severe OSAS may contribute to the occurrence of traffic or cardiovascular accidents. We conclude that 24-h ambulatory recordings of SpO2 and ECG are useful for screening for daytime sleep sequelae associated with the potential risk of this pathology in OSAS during social activities.     

Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation

The goal of this work is to study the consequences of the last on variations of the blood pressure (BP) in the course of 24 hours. From 1994 to 1997 we have selected 99 hypertensive patients and studied their BP profile. This study included 72 women and 27 men. Their age varies from 22 to 72 years (average 56.7 +/- 9 years). All these patients has an ambulatory blood pressure measurement (ABPM) before the fast and during Ramadan. Before Ramadan the period of the sleep goes from 10 pm +/- 1 h to 8 am +/- 1 h. During the month of Ramadan, the sleep lasts from 0 h +/- 1 to 9 am +/- 1 h. [table: see text] No statistically significant difference is noted between these 2 periods neither for the systolic BP (SBP) nor for the diastolic BP (DBP), for the BP of 24 hours, and the diurnal and nocturnal periods. We have then the compared the hourly average on 24 hours of the 99 patients. We observed that during the month of Ramadan the peak of the awakening is delayed by 2 hours and the nocturnal through is delayed by 1 hour. After this study, which is the first one to deal with variations of blood pressure during the fast of Ramadan we can confirm that in patients with essential hypertension without complications, the fast is well supported. The variations of BP are minimal and are related to the variations of the sleep, activity and eating pattern.     

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure

BACKGROUND: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep. METHODS AND RESULTS: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate. CONCLUSIONS: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.     

Autonomic nervous system dysfunction in elderly hypertensive patients with abnormal diurnal blood pressure variation: relation to silent cerebrovascular disease

To investigate the relationships among diurnal blood pressure (BP) variations and autonomic nervous system dysfunction, we assessed heart rate variability (HRV) using power spectral analysis of the 24-hour RR interval in 51 asymptomatic elderly hypertensive patients with various patterns of nocturnal BP fall. The extreme-dippers with marked nocturnal BP fall (n=16) had lower asleep low-frequency power (LF)/high-frequency power (HF) ratios (a relative index of sympathetic nervous system activity), while the nondippers without nocturnal BP fall (n=18) had lower awake LF/HF ratios and asleep/awake ratio for HF (an index of parasympathetic nervous activity), when compared with dippers with appropriate nocturnal BP fall (n=17). The incidence of multiple lacunar infarction detected by brain magnetic resonance imaging was 56% in the extreme-dippers and 38% in the nondippers, and both were markedly higher than that (6.3%) in the dippers (both P<.01). There was no significant relationship between the BP level and any HRV parameter for either the daytime or nighttime period. The asleep/awake ratio for systolic BP was significantly correlated with the asleep/awake ratio for HF (r= -.363, P<.01) and with the asleep/awake ratio for the LF/HF ratio (r=.540, P<.001), regardless of whether multiple lacunar infarction was present. In conclusion, the autonomic nervous system activity is not related to high BP level per se, rather its diurnal variation is more important as a determinant of the diurnal BP patterns, regardless of the presence or absence of cerebrovascular disease.     

Twenty-four hour time and frequency domain variability of systolic blood pressure and heart rate in an experimental model of arterial hypertension plus obesity]

Modifications of heart rate (HR) and systolic blood pressure (SBP) variabilities (V) have been reported in the human syndrome arterial hypertension plus insulin-resistance. The aim of this study was to characterize the 24 h SBPV and HRV in both time and frequency domains during weight increase in dogs fed ad libitum with a high fat diet. Implantable transmitter units for measurement of blood pressure and heart rate were surgically implanted in five beagle male dogs. BP and HR were continuously recorded using telemetric measurements during 24 hours, before and after 6 and 9 weeks of hypercaloric diet in quiet animals submitted to a 12h light-dark cycle. To study nychtemeral cycle of SBP and HR, two periods were chosen: day (from 6.00 h to 19.00 h) and night (from 23.00 h to 6.00 h). Spontaneous baroreflex efficiency was measured using the sequence method. Spectral variability of HR and SBP was analyzed using a fast Fourier transformation on 512 consecutive values and normalized units of low (LF: 50-150 mHz, reflecting sympathetic activity) and high (HF: respiratory rate +/- 50 mHz, reflecting parasympathetic activity) frequency bands were calculated. The energy of total spectrum (from 0.004 to 1 Hz) was also studied. Body weight (12.4 +/- 0.9 vs 14.9 +/- 0.9 kg, p < 0.05). SBP (132 +/- 1 vs 147 +/- 1 mmHg, p < 0.05) significantly increased after 9 weeks of hypercaloric diet. A nycthemeral HR rhythm was present at baseline (day: 79 +/- 1 vs night: 71 +/- 1 bpm) but not after 9 weeks (day: 91 +/- 4 bpm ; night: 86 +/- 2 bpm). Concomitantly, the efficiency of spontaneous baroreflex decreased at 6 weeks (36 +/- 1 vs 42 +/- 2 mmHg/ms, p < 0.05). A significant decrease in HF energy of HRV was found after 6 but not after 9 weeks. LF energy of SBPV was increased at 6 but not at 9 weeks (table). [table: see text] In conclusion, this study shows that an hyperlipidic and hypercaloric diet induces transient variations in autonomic nervous system activity which could be the physiopathological link between obesity, insulin-resistance and arterial hypertension.