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Biomedical subjects

P Lavie

Publications and source records attributed to P Lavie.

At least 19 recordsLinked to original sources
PubMed2005

All-cause mortality in males with sleep apnoea syndrome: declining mortality rates with age.

The objective of this study was to assess whether an increasing severity of sleep apnoea is associated with increased all-cause mortality hazards and to assess whether the syndrome is associated with excess mortality, in comparison with the general population. Participants included 14,589 adult males, aged 20-93 yrs, referred to the sleep clinics with suspected sleep apnoea or diagnosed with sleep apnoea. Altogether, 372 deaths were recorded after a median follow-up of 4.6 yrs. The crude all-cause mortality rate was 5.55/1,000 patient yrs, increasing with apnoea severity. Cox proportional analysis revealed that both respiratory disturbance index (RDI) and body mass index significantly influenced all-cause mortality hazard but there was no interaction between them. Males with respiratory disturbance index >30 had a significantly higher mortality hazard rate than the reference group of males with RDI < or =10. Comparing mortality rates of males with moderate/severe sleep apnoea to the general population revealed that only males aged <50 yrs showed an excess mortality rate. The hazard of mortality in sleep apnoea increases with apnoea severity as indexed by respiratory disturbance index. Moderate and severe levels of sleep apnoea are moderately associated with an increased risk of all-cause mortality, in comparison with the general population, particularly in males aged <50 yrs. The lack of information about possible confounders and treatment effects should be taken into consideration in the interpretation of these results.

Adult↗
PubMed2005

Activated CD8+ T-lymphocytes in obstructive sleep apnoea.

T-lymphocytes are implicated in the development of atherosclerosis. The aim of this study was to assess whether the CD8+ T-lymphocytes of obstructive sleep apnoea (OSA) patients undergo phenotypic and functional changes that may exaggerate atherogenic sequelae in OSA. A total of 36 OSA patients, 17 controls and 15 single-night-treated OSA patients were studied. Phenotype and cytotoxicity against K562 target cells were analysed by flow cytometry. Cytotoxicity against human umbilical vein endothelial cells (HUVECs) was assessed by 51Cr release assay. The cytotoxicity of the CD8+ T-lymphocytes of OSA patients against K562 and HUVECs was significantly greater than controls. This increased cytotoxicity directly depended on the presence of perforin and natural killer receptors (CD56, CD16), which were significantly increased in OSA CD8+ T-lymphocytes. Also the percentage of the CD56bright subset, which mediates initial interactions with vascular endothelium, significantly increased in OSA. Nasal continuous positive airway pressure treatment significantly decreased CD8+ T-cell cytotoxicity and CD56 expression, and was positively correlated with natural killer inhibitory NKB1 receptor expression either after a single-night treatment or after a prolonged treatment. In conclusion, the CD8+ T-lymphocytes of obstructive sleep apnoea patients undergo phenotypic and functional changes, rendering them cytotoxic to target cells via increased CD56+/perforin+ expression, which can be ameliorated by nasal continuous positive airway pressure treatment. These results are compatible with the current authors' hypothesis of atherogenic sequelae in obstructive sleep apnoea.

Biomarkers↗
PubMed2002

Incidence of sleep apnea in a presumably healthy working population: a significant relationship with excessive daytime sleepiness.

Seventy-eight workers, drawn from a population of 1502 presumably healthy working men who were interviewed about sleep habits and sleep disorders, underwent polygraphic recordings for at least 1 night. A significant association was found between the complaint of excessive daytime sleepiness and the incidence of sleep apnea. Workers with more than 10 apneas per hour of sleep complained significantly more about loud snoring, hypermotility in sleep, and frequent headaches. They had significantly more ENT findings and hypertension.

Disorders of Excessive Somnolence↗
PubMed2002

Long-term follow-up of untreated patients with sleep apnoea syndrome.

Obstructive sleep apnoea (OSA) is a common disorder with numerous potential sequelae. Although the majority of these consequences can be reduced with appropriate treatment, only limited data exist regarding the natural progression ofthis disorder in untreated individuals. We hereby report a long-term follow-up of all untreated patients (n = 40) followed-up in the Technion Sleep Clinic, using both subjective and objective measurements. In addition, we report a long-term follow-up of 11 patients who attempted dietary weight loss. The average time interval between the first and second polysomnographies for the untreated group was 5.0 +/- 2.8 yrs, and 2.5 +/- 2.3 yrs for the weight reduction group. There was no significant change in Body Mass Index (BMI) or Respiratory Disturbance Index (RDI) between the two Polysomnographic (PSG) evaluations in the untreated patients. However, eight patients developed hypertension (n=5) or ischaemic heart disease (IHD) (n=3) between the two evaluations. RDI, age and BMI at the time ofthe initial evaluation were not predictive of changes in RDI, snoring intensity or minimal oxygen saturation. However, the patients who developed hypertension/IHD had significantly higher RDI than the patients who did not (46 +/- 27 vs. 23 +/- 17 h(-1), P < 0.005). In the weight-loss group, BMI decreased by a mean of 3.1 kg m(-2), and RDI decreased by 20events h(-1), P<0.05 for both. There was a significant correlation between the weight loss and improvement in RDI (R = 0.75, P = 0.005). We conclude that in untreated obstructive sleep apnoea patients RDI does not necessarily increase over time, but associated hypertension or ischaemic heart disease may develop. When weight loss is successfully achieved, sleep apnoea significantly improves with a high correlation between the extent of weight loss and the improvement in apnoea status.

Adult↗
PubMed2002

Evidence for fractal correlation properties in variations of peripheral arterial tone during REM sleep.

Previous studies utilizing detrended fluctuation analysis (DFA) of heart rate variability during sleep revealed a higher fractal exponent during rapid eye movement (REM) sleep than non-REM sleep. The aim of this study was to determine whether the same difference exists in the variations of peripheral arterial tone (PAT). Finger pulse wave measured by a novel plethysmographic technique was monitored during sleep in 12 chronic heart failure patients, 8 heavy snorers, and 12 healthy volunteers. For each subject, at least two 15-min time series were constructed from the interpulse intervals and from pulse wave amplitudes during REM and non-REM sleep. Fractal scaling exponents of both types of time series were significantly higher for REM than non-REM sleep in all groups. In each of the groups and in both sleep stages, the fractal scaling exponents based on pulse wave amplitude were significantly higher than those based on pulse rate variability. A repeat of the analysis for short-, intermediate-, and long-term intervals revealed that the fractal-like exponents were evident only in the short- and intermediate-term intervals. Because PAT is a surrogate of sympathetic activation, our results indicate that variations in sympathetic activation during REM sleep have a fractal-like behavior.

Adult↗
PubMed2002

The SleepStrip: an apnoea screener for the early detection of sleep apnoea syndrome.

Sleep apnoea svndrome (SAS) is a largely undiagnosed and prevalent disorder. It is associated with cardiovascular morbidity as well as excessive daytime sleepiness and poor quality of life. In the present study the SleepStrip, a novel screening device is introduced, which is low cost and easy to use and is aimed for widespread use. The results of three independent validation studies, which compared the SleepStrip score (Sscore) against "gold standard" polysomnographically-determined apnoea/ hypopnoea index (AHI), are reported both separately and combined. Four hundred and two patients suspected of SAS underwent full polysomnography recordings concomitantly with the use of the SleepStrip. For all samples combined, the correlation between AHI and Sscore was r=0.73, sensitivity and specificity values ranged from 80-86% and 57-86% respectively, and the area under the curve derived from receiver-operating characteristic curves ranged from 0.81-0.92 at varying AHI thresholds. Though not intended as a substitute for polysomnography, the SleepStrip may provide initial screening information, which may be useful in both clinical and experimental settings.

Adolescent↗
PubMed2001

Sleep apnea syndrome: a possible contributing factor to resistant.

STUDY OBJECTIVES: There is evidence supporting an association between sleep apnea and hypertension. However, it is not clear if sleep apnea interteres with the pharmacotherapy of hypertension. To investigate this question, we studied the relationship between the effectiveness of anti-hypertensive treatment in reducing blood pressure, and severity of sleep apnea in a large group of apneic patients referred to a sleep disorders centre at St. Michael's Hospital at the University of Toronto. DESIGN: N/A. SETTING: N/A. PARTICIPANTS: 1,485 adult patients with sleep apnea, as defined by the apnea/hypopnea index (AHI) >10 events/hr, were analyzed. There were 393 who reported using anti-hypertensive medications on a regular basis for more than 6 months. One hundred and eighty-three patients were treated "effectively" (i.e. blood pressure lower than 140/90 mm Hg in the morning and in the evening). Seventy-four patients were treated "ineffectively," defined as blood pressure >140/90 mm Hg in the morning or in the evening. Both groups were compared with respect to clinical and demographic data using analysis of covariance with gender, age, body mass index (BMI), and neck circumference (NC) as covariates. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Ineffectively and effectively treated patients were similar in age (57 +/- 9) vs. 57 +/- 10 years, respectively), and had similar body mass index (33.8 +/- 7.4 vs. 33.4 +/- 7.3 kg/m2, respectively). However, ineffectively treated patients had significantly higher apnea/hypopnea index (44 +/- 29 vs. 33 +/- 25 events/hr, p<.0005), despite having similar nocturnal oxygenation (percent of total sleep time spent with oxygen desaturation lower than 90% was 36 +/- 34 vs. 29 +/- 30% in the ineffective and effective groups, respectively). The difference in AHI persisted even after adjusting for age, gender, and body mass index. CONCLUSIONS: Our results demonstrate that hypertensive patients with sleep apnea whose blood pressure responds beneficially to treatment have less severe sleep apnea than those patients whose blood pressure remains elevated despite anti-hypertensive therapy. Since neither obesity nor nocturnal hypoxemia appear to be important determinants of ineffective treatment, we suggest that resistant hypertension may be caused by frequent intermittent sympathetic stimulation.

Adult↗
PubMed2001

Long-term sleep disturbances in adolescents after minor head injury.

It has been demonstrated that patients in the acute phase after minor head injury (MHI) complain of sleep disturbances. The purpose of the present study was to characterize the long-term effects of MHI on sleep in adolescents. Nineteen adolescents who had suffered MHI 3 years before the study and had complained of sleep disturbances completed a sleep questionnaire and were investigated in the sleep laboratory by whole-night polysomnographic recordings and were actigraphically monitored for 5 days at home. Questionnaire results revealed severe complaints regarding sleep behavior. Polysomnographic recordings revealed that in comparison with controls, MHI was associated with lower sleep efficiency (79.8 +/- [9.8]% vs 87.7 +/- [6.8]%; P < 0.005), with more wake time (10.6 +/- [9.0]% vs 3.4 +/- [4.4]%; P < 0.005), and with more awakenings lasting more than 3 minutes (2.1 +/- [1.5] vs 0.6 +/- [0.8]; P < 0.005). These findings were confirmed by actigraphic monitoring that revealed lower sleep efficiency (90 +/- [5]% vs 94 +/- [3]%; P < 0.05), more minutes of wake time (49 +/- [21] min vs 28 +/- [15] min; P < 0.05), and a trend toward more awakenings longer than 5 minutes (1.8 +/- [0.8] vs 1.2 +/- [0.8]; P = 0.063). Our data demonstrated that 3 years after MHI without any discernible clinical sequel, adolescents still complain of sleep disturbances that could be confirmed by both polysomnographic and actigraphic monitoring.

Adolescent↗
PubMed2001

Clinical and polysomnographic characteristics of 34 patients with Kleine-Levin syndrome.

There is only scant information on sleep characteristics and long-term follow-up in patients with Kleine-Levin syndrome (KLS). This study describes the clinical course, results of polysomnography and long-term follow-up in a relatively large group of patients with KLS. During the years 1982-97, we encountered 34 patients (26 males and eight females) with KLS. We were able to obtain the original polysomnographs from 28 males and four females. In 25 patients, data regarding their present state of health were obtained. Fourteen agreed to be present at a detailed interview and examination while 11 gave the information by phone. The mean age at onset was 15.8 +/- 2.8 years and the mean diagnostic delay, 3.8 +/- 4.2 years. The mean duration of a single hypersomnolent attack was 11.5 +/- 6.6 days. The main abnormal findings extracted out of 35 polysomnographs obtained from 32 patients during and/or in-between attacks included: decreased sleep efficiency, and frequent awakenings from sleep stage 2. All 25 patients reported present perfect health, with no evidence of behavioral or endocrine dysfunction. In adolescents with periodic hypersomnia, the diagnosis of KLS should be explored. Sleep recordings during a hypersomnolent period will often show frequent awakenings from sleep stage 2. The long-term prognosis is excellent.

Adult↗
PubMed2001

Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer's disease.

Recent studies suggest melatonin, due to its antioxidant and free-radical-scavenging actions, may play a role in the neuroprotection against amyloid, which is implicated in the pathogenesis of Alzheimer's disease (AD). In this study, we determined urinary 6-sulfatoxymelatonin (aMT6s) excretion together with actigraphic sleep-wake patterns of untreated male patients with AD who lived at home. Results were compared with those obtained from normal age-matched elderly and normal young male subjects. Similar measurements were also performed in another group of patients with AD who were treated with a cholinesterase inhibitor (Donepezil, Aricept). Total 24h aMT6s values were significantly reduced in elderly controls (19.9h +/- 5.2 microg/ 24h), in those with untreated AD (12.7 +/- 4.4 microg/24h), and in patients treated for AD (12.4 +/- 4.4 microg/24h) compared with normal young men (32.8 +/- 3.1 microg/24h). A day-night difference in aMT6s was evident in all young controls, in 50% of elderly controls, in only 20% of patients with untreated AD, and in 67% of those with AD receiving Aricept. Sleep quality (expressed as sleep efficiency, wake time, and long undisturbed sleep duration) was better in young and elderly controls compared with the two groups of patients with AD. There was no significant correlation between aMT6s values or sleep patterns and the severity of cognitive impairment in patients with AD. Taken together, these data suggest that disrupted sleep, decreased melatonin production, and partial lack of day-night difference in melatonin secretion were observed equally in normal elderly and in patients with AD. Our results do not permit drawing any conclusion as to whether changes in urinary aMT6s excretion is correlated with disturbed sleep in patients with AD.

Adult↗
PubMed2001

Sleep-wake as a biological rhythm.

Evidence that the sleep-wake rhythm is generated endogenously has been provided by studies employing a variety of experimental paradigms such as sleep deprivation, sleep displacement, isolating subjects in environments free of time cues, or imposing on subjects sleep-wake schedules widely deviating from 24 hours. The initial observations obtained in isolated subjects revealed that the period of the endogenous circadian pacemaker regulating sleep is of approximately 25 hours. More recent studies, however, in which a more rigorous control of subjects' behavior was exerted, particularly over lighting conditions, have shown that the true periodicity of the endogenous pacemaker deviates from 24 hours by a few minutes only. Besides sleep propensity, the circadian pacemaker has been shown to regulate sleep consolidation, sleep stage structure, and electroencephalographic activities. The pattern of light exposure throughout the 24 hours appears to participate in the entrainment of the circadian pacemaker to the geophysical day-night cycle. Melatonin, the pineal hormone produced during the dark hours, participates in communicating both between the environmental light-dark cycle and the circadian pacemaker, and between the circadian pacemaker and the sleep-wake-generating mechanism. In contrast to prevailing views that have placed great emphasis on homeostatic sleep drive, recent data have revealed a potent circadian cycle in the drive for wakefulness, which is generated by the suprachiasmatic nucleus. This drive reaches a peak during the evening hours just before habitual bedtime.

Circadian Rhythm↗
PubMed2001

Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men.

Recently, we have demonstrated that in normal men the nocturnal testosterone rise antedated the first rapid eye movement (REM) sleep episode by about 90 min and was correlated with REM latency. To further elucidate whether the diurnal testosterone rhythm is a sleep-related phenomenon or controlled by the circadian clock, we determined serum testosterone levels in 10 men during the ultrashort 7/13 sleep-wake cycle paradigm. Using this schedule, subjects experienced partial sleep deprivation and fragmented sleep for a 24-h period. Serum testosterone levels were determined every 20 min between 1900-0700 h with simultaneous sleep recordings during the 7-min sleep attempts. The results were compared with those obtained in men during continuous sleep. Although mean levels and area under the curve of testosterone were similar in both groups, fragmented sleep resulted in a significant delay in testosterone rise (03:24 h +/- 1:13 vs. 22:35 h +/- 0:22). During fragmented sleep, nocturnal testosterone rise was observed only in subjects who showed REM episodes (4/10). Our findings indicate that the sleep-related rise in serum testosterone levels is linked with the appearance of first REM sleep. Fragmented sleep disrupted the testosterone rhythm with a considerable attenuation of the nocturnal rise only in subjects who did not show REM sleep.

Adult↗
PubMed2001

Plasma homocysteine levels in obstructive sleep apnea: association with cardiovascular morbidity.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality. Plasma levels of homocysteine are also associated with cardiovascular morbidity and mortality. We therefore investigated homocysteine and conventional cardiovascular risk factors in OSA patients with and without cardiovascular morbidity in comparison with normal control subjects and ischemic heart disease (IHD) patients without OSA. SETTING: Technion Sleep Medicine Center, Haifa, Israel. METHODS AND PARTICIPANTS: Levels of homocysteine, cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, creatinine, vitamins B(12) and B(6), and folic acid were determined in 345 participants after overnight fasting. These included OSA patients with IHD (n = 49), with hypertension (n = 61), or without any cardiovascular disease (n = 127). Two control groups were employed: IHD patients without or with low likelihood for sleep apnea (n = 35), and healthy control subjects (n = 73). RESULTS: After adjustment for age, body mass index, creatinine, and existence of diabetes mellitus, OSA patients with IHD had significantly higher homocysteine levels (14.6 +/- 6.77 micromol/L) than all other groups including the IHD-only patients. Hypertensive OSA patients had comparable homocysteine levels to IHD patients (11.80 +/- 5.28 micromol/L and 11.92 +/- 5.7 micromol/L, respectively), while patients with OSA only had comparable levels to normal control subjects (9.85 +/- 2.99 micromol/L and 9.78 +/- 3.49 micromol/L, respectively). No differences in conventional cardiovascular risk factors or in vitamin levels were found between groups. CONCLUSIONS: Patients with the combination of IHD and OSA have elevated homocysteine levels. We hypothesize that these results may be explained by endothelial dysfunction combined with excess free-radical formation in OSA patients.

Adult↗
PubMed2001

Daily and yearly burnout symptoms in Israeli shift work residents.

Burnout is a syndrome of physical and emotional exhaustion that develops among individuals who are open to public demands. In view of their heavy work load and sleep deprivation, we decided to evaluate the impact of long working hours on burnout and psychological status among a sample of residents during the first 2 years of their residency. Seventy-eight residents participated in the study, all residents completed self-administered questionnaires, and their sleep-wake cycle was monitored by a wrist-worn actigraph for a period of 5-7 days. The questionnaires included a short form suitable for Experience Sampling Method (ESM), and a longer background Questionnaire. The results revealed that sleep duration, Work Load and the interaction between them, explain the Negative Mood the day after the night shift. However, positive mood, and fatigue were not affected by sleep duration or workload. In general, after one year of residency, residents become more stressed, less involved in the job, and had a high level of burnout and psychosomatic symptoms. However, after the second year, the burnout symptoms were almost the same as at the beginning except for the level of stress that remained high. Sleep duration was unrelated to the burnout symptoms.

Adult↗
PubMed2001

Can we consider medical residents as shift workers?

Although medical residents are characterized by long working hours, night shifts and high levels of work load, it is unclear if their work schedule can be classified as shift work, or if it has a similar impact on residents' well-being. The present paper compared the profile of complaints about sleep or daytime functioning of medical residents to that of rotating shift workers and day workers, of similar ages. Sixty-one residents (aged: 32.2 +/- 2.2 years), after 2 years of residency, participated in the study. The two control groups with a similar age range (26-40 years) were chosen, and included 94 rotating shift workers and 146 day workers. All subjects completed self-administered questionnaires on their sleep habits, and their sleep-wake cycle was monitored by a wrist-worn actigraph. Ten percent of the residents complained about difficulties falling asleep, 34% complained about morning tiredness, 14% complained about mid-sleep awakening, and 20% about prolonged fatigue. The residents slept significantly less than the day workers, and their sleep efficiency was significantly higher. When examining their subjective complaints profile, residents complained more than day workers and their answers were more similar to those of rotating shift workers, therefore they can be considered to be characterized as shift workers.

Activities of Daily Living↗
PubMed2000

Kleine Levin syndrome (KLS) in young females.

During the years 1982-1998, we encountered 7 adolescents and one young woman suffering from KLS. In 4 patients, hypersomnolence was accompanied by hyperphagia and hypersexuality, while in the remaining 4, recurrent hypersomnia was the only symptom. Mean age at onset of hypersomnolent attacks was 15.1+/-3.5 yrs. The mean duration of a hypersomnolent attack was 9.9+/-5.4 days, and the number of attacks per patient was 6.2+/-3.4. Polysomnographic recordings from 3 patients inbetween attacks, and from one patient during an attack, showed relatively normal sleep structure with decreased sleep efficiency due to numerous awakenings from sleep stage 2. Besides the recurrent hypersomnia, all patients enjoyed good health, with no evidence of behavioral or endocrine dysfunction. Similarly aged males with KLS from our clinic and previously reported females, had similar clinical features.

Adolescent↗