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Biomedical subjects

Olli Polo

Publications and source records attributed to Olli Polo.

At least 19 recordsLinked to original sources

Family-based association study of the restless legs syndrome loci 2 and 3 in a European population.

Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family-based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846-D9S171 in a subset of South European trios and with a haplotype at D9S156-D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS.

Chromosomes, Human, Pair 12↗

Inspiratory flow shape clustering: an automated method to monitor upper airway performance during sleep.

We describe an automated method for monitoring airflow dynamics in the upper airway of a sleeping subject. Its main task is to determine a set of inspiratory flow shape representatives and their relative incidence in a given respiratory airflow material. The flow shape clustering aims at reducing redundant information in the data, and thereby decreases the time needed to score overnight sleep recordings. Compared with previous computer-assisted systems, built on a pre-defined classification of prototype shapes, we require no a priori assumptions of the flow shape clusters to be discovered. The intrinsic flow shape clustering is performed with a modification of the Isodata algorithm, and the K-means clustering is used as a reference in comparison studies. The operation of the method is demonstrated on clinical sleep recordings both from patients with nocturnal breathing disorders and from non-symptomatic individuals. The feasible results obtained in the practical research design suggest that application of clustering algorithms to respiratory airflow measurements could give important insights into the subtle flow shape abnormalities underlying obstructive sleep-disordered breathing.

Algorithms↗

Sleep deprivation and hormone therapy in postmenopausal women.

BACKGROUND AND PURPOSE: Sleep complaints increase after menopause, but literature on the effect of postmenopausal hormone therapy (HT) on sleep is controversial. The purpose of this study was to determine the effect of ageing and HT on sleep quality, assessed using polysomnography, and on the accuracy of the subjective estimation of sleep quality in women before and after sleep deprivation. PATIENTS AND METHODS: Twenty postmenopausal women (aged 58-72 years) were recruited: 10 HT-users and 10 non-HT-users. Eleven young women (aged 20-26 years) served as controls. Polysomnography and subjective sleep quality were measured on four consecutive nights: adaptation, baseline, 40-h sleep deprivation and recovery. RESULTS: Although the postmenopausal women slept worse than the controls at baseline, and in particular during the recovery night, their recovery response to sleep deprivation was well preserved. At baseline, HT-users had a shorter latency to rapid eye movement (REM) (P=0.043), with fewer awakenings from slow wave sleep (SWS) (P=0.029) but more from REM (P=0.033) than non-HT-users. During recovery, the HT-users had more stage 2 sleep (P=0.048) and less slow wave activity (SWA) in the first non-rapid eye movement (NREM) sleep episode (P=0.021) than the non-HT-users. The poor correlation between subjective and objective sleep quality at baseline became significant during recovery. CONCLUSIONS: Although sleep in postmenopausal women was worse than in young controls, the recovery response following sleep deprivation was relatively well preserved. HT offered no significant advantage to sleep at baseline and slightly weakened the recovery response to prolonged wakefulness.

Adult↗

Menopausal estrogen therapy predicts better nocturnal oxyhemoglobin saturation.

OBJECTIVES: The respiratory responses in the few previous studies evaluating the effects of short-term unopposed estrogen therapy on breathing in postmenopausal women have been inconsistent. We performed a study to investigate whether long-term estrogen therapy would prevent age-related decline in nocturnal arterial oxyhemoglobin saturation and whether higher serum estradiol concentration is associated with better arterial oxyhemoglobin saturation. METHODS: Sixty-four healthy postmenopausal women were followed-up for 5 years in a 5-year prospective open follow-up study. The women were users or non-users of estrogen therapy according to their personal preference. RESULTS: Mean overnight arterial oxyhemoglobin saturation was similar at baseline (94.3 +/- 1.1%) and after follow-up (94.5 +/- 1.6%). Present estrogen users had higher mean arterial oxyhemoglobin saturation (95.2 +/- 1.4%) than present non-users (94.0 +/- 1.5%), when adjusted for age and body mass index (p = 0.042). The change in mean arterial oxyhemoglobin saturation during follow-up was not associated with serum estradiol concentration at baseline but associated with estradiol at follow-up (p = 0.042), when adjusted for age and body mass index. At follow-up, women with higher serum estradiol concentration had also higher mean nocturnal arterial oxyhemoglobin saturation (Pearson r = 0.29, p = 0.019) and lower apnea-hypopnea index (Spearman r = -0.28, p = 0.031). The pooled current estrogen users spent proportionally less time with SaO(2) below 90% than non-users (ANCOVA adjusted for age and BMI, p = 0.017). CONCLUSIONS: Estrogen use and especially high serum estradiol concentration predict higher mean overnight arterial oxyhemoglobin saturation. The present data suggest that estrogen therapy has favorable respiratory effects.

Body Mass Index↗

Impact of menopause on the manifestation and severity of sleep-disordered breathing.

BACKGROUND: Decreased production of female hormones might explain the increased prevalence of sleep-disordered breathing in postmenopausal women. OBJECTIVES: We evaluated, whether menopause has an impact on the manifestation of sleep-disordered breathing in terms of signs, symptoms, and breathing pattern. METHODS: The study was a cross-sectional study utilizing a patient database, hospital records, sleep studies, and questionnaires. The hospital records and sleep studies were reviewed in 601 consecutive women studied between 1994 and 1998 in a university hospital pulmonary clinic. The records were completed with questionnaires. RESULTS: Nocturnal breathing abnormalities covered a greater proportion of the night in postmenopausal than in premenopausal women (68.1% versus 35.8% of time in bed, p<0.0001), and the prevalence of sleep-disordered breathing tended to be higher (86.2% versus 79.4% of time in bed, p=0.057). The body mass indices and the major symptoms of sleep-disordered breathing were similar in pre- and postmenopausal women. Postmenopausal women had less nasal congestion (p<0.001) than premenopausal ones. Body mass index was a significant explanatory factor of daytime sleepiness. CONCLUSIONS: Post- and premenopausal women present with similar signs and symptoms when referred to sleep studies. However, sleep-disordered breathing is more severe in postmenopausal than in premenopausal women.

Adult↗

Non-invasive respiratory monitoring during wakefulness and sleep in pre- and postmenopausal women.

Menopause and aging cause hormonal changes with respiratory consequences. The aim of the present study was to investigate the physiological changes in respiration during wakefulness and sleep across menopause in non-patient population using non-invasive measurements of blood and tissue gases. The arterial oxyhemoglobin saturation (SaO2), heart rate, end-tidal partial carbon dioxide tension (EtCO2) and transcutaneous partial carbon dioxide tension (TcCO2) were measured during wakefulness and sleep in thirteen pairs of BMI-matched pre- and postmenopausal women. Postmenopausal women had lower SaO2 during sleep than during wakefulness, whereas premenopausal women maintained their wakefulness SaO2 levels also during sleep. EtCO2 levels did not change either between wakefulness and sleep or between premenopausal and postmenopausal groups. TcCO2 levels increased from wakefulness to sleep in both groups and the increase was greater in the postmenopausal group. The impact of sleep on the non-invasive measurements of blood and tissue gases is stronger in postmenopausal women.

Adult↗

Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease.

BACKGROUND: Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women. METHODS: A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO2 and transcutaneous PCO2 (tcCO2) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA. RESULTS: Thirteen patients completed the trial. At baseline, the average +/- SD of SaO2 mean was 90.6 +/- 3.2 % and the median of SaO2 nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 +/- 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO2 median was 6.0 +/- 0.9 kPa and decreased with MPA by 0.9 +/- 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO2 nadir and tcCO2 median also during REM sleep. Three weeks after cessation of MPA, the SaO2 mean remained 1.4 +/- 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO2 nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO2 mean and SaO2 nadir during sleep with MPA were inversely associated with baseline SaO2 mean (r = -0.70, p = 0.032) and baseline SaO2 nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO2 mean, SaO2 nadir and tcCO2 levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables. CONCLUSION: MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO2 values. Long-term studies in females are warranted.

Aged↗

Sleep quality, daytime sleepiness and fasting insulin levels in women with chronic obstructive pulmonary disease.

STUDY OBJECTIVES: To test the clinical observations that patients with chronic obstructive pulmonary disease (COPD) have impaired sleep quality without excessive daytime sleepiness (EDS), and to analyse the aetiological factors. PARTICIPANTS: Fifteen non-diabetic postmenopausal women with moderate to severe COPD and 20 community dwelling age-matched control women. MEASUREMENTS AND RESULTS: Patients completed questionnaires, had a polysomnography and blood tests. Controls filled in the questionnaires. In the Basic Nordic Sleep Questionnaire, the average (+/-sd) scores for sleepiness (9.9+/-3.0 in patients vs. 7.6+/-3.2 in controls, P = 0.025, test range 4-20) and insomnia (18.3+/-3.4 vs. 16.6+/-4.4, P = 123, test range 7-35) were low. Although 53% had a good night's sleep seldom or never and 70% slept restlessly, only 33% felt tired in the mornings. Controls reported better sleep quality, less tiredness and sleepiness. With polysomnography, the total sleep time was 4h 41 min +/-1h 20 min in patients. Sleep was fragmented, the proportion of stage 1 sleep high and rapid eye movement (REM) latency delayed. Sleepiness correlated with fasting serum insulin levels (r = 0.59, P = 0.027) and body movements (r = 0.52, P = 0.047). In stepwise linear regression analyses, sleepiness was positively associated with insulin levels (P = 0.025) but not with body movements. Insulin explained 38.0% of the variance in the sleepiness score, when adjusted for body mass index (BMI). CONCLUSIONS: Despite short and fragmented sleep, non-diabetic patients with COPD did not have marked EDS. An association between fasting insulin and sleepiness suggests that insulin resistance is involved in EDS.

Aged↗

Medroxyprogesterone improves cardiac autonomic control in postmenopausal women with respiratory insufficiency.

OBJECTIVE: To study the effect of medroxyprogesterone acetate (MPA) on autonomic cardiac control in respiratory insufficiency in postmenopausal women. DESIGN: A prospective, single-blind study. SUBJECTS: Eighteen postmenopausal women with respiratory insufficiency and eight asymptomatic postmenopausal women with nocturnal hypoxaemia as controls. METHODS: Oral MPA treatment was given at 30 mg twice daily for 2 weeks. All-night polysomnography including a two-channel electroencephalogram, an electro-oculogram, an electromyogram, an electrocardiogram, arterial oxyhaemoglobin saturation, maximum end-tidal CO2 partial pressure, a ballistocardiogram and breathing movements were recorded at baseline and at the end of MPA treatment. Heart rate variability (HRV) was calculated in time and frequency domains during various sleep stages on and off MPA, and the results were correlated to respiratory variables. RESULTS: At baseline, patients had higher heart rate and lower HRV than controls, suggesting increased cardiac sympathetic output. MPA increased HRV in patients, but not in controls. End-tidal CO2 partial pressure decreased, and respiratory rate increased during treatment in both groups. CONCLUSIONS: HRV is compromised in women with respiratory insufficiency. Peroral MPA increases their HRV to levels comparable with those in controls. This suggests an improvement in vagal cardiac control beneficial to cardiovascular health.

Arrhythmias, Cardiac↗

Long-term progestin therapy for female chronic respiratory insufficiency?

End-stage chronic obstructive pulmonary disease often leads to hypercapnic respiratory failure. Oxygen supplementation therapy may further aggravate hypercapnia and not all patients are compliant with non-invasive ventilation. This case documents successful control of chronic respiratory failure with medroxyprogesterone in a postmenopausal woman during 1-year follow-up.

Aged↗

Does leptin link sleep loss and breathing disturbances with major public diseases?

Leptin is best known as a regulator of energy homeostasis, but it also interacts with sleep and breathing. Leptin secretion increases at night and decreases during the day. The circadian secretory profile of leptin is determined both by the hypothalamic circadian pacemaker and sleep-wake cycle. Leptin is also a powerful respiratory stimulant. Serum leptin levels are higher in obstructive sleep apnoea syndrome but lower during extended sleep deprivation in healthy subjects or in narcolepsy. Abnormalities in serum leptin concentrations have recently been linked with deleterious effects on weight control, cardiovascular health and glucose regulation. Since sleep curtailment and sleep-disordered breathing are epidemics of the modern society, better understanding of leptin pathophysiology could open new perspectives to pathophysiology of major public diseases, including obesity and metabolic syndrome.

Humans↗

Prediction of inspiratory flow shapes during sleep with a mathematic model of upper airway forces.

STUDY OBJECTIVES: To predict the airflow dynamics during sleep using a mathematic model that incorporates a number of static and dynamic upper airway forces, and to compare the numerical results to clinical flow data recorded from patients with sleep-disordered breathing on and off various treatment options. DESIGN: Upper airway performance was modeled in virtual subjects characterized by parameter settings that describe common combinations of risk factors predisposing to upper airway collapse during sleep. The treatments effect were induced by relevant changes of the initial parameter values. SETTING: Computer simulations at our website (http://www.utu.fi/ml/sovmat/bio/). PARTICIPANTS: Risk factors considered in the simulation settings were sex, obesity, pharyngeal collapsibility, and decreased phasic activity of pharyngeal muscles. INTERVENTIONS: The effects of weight loss, pharyngeal surgery, nasal continuous positive airway pressure, and respiratory stimulation on the inspiratory flow characteristics were tested with the model. MEASUREMENTS AND RESULTS: Numerical predictions were investigated by means of 3 measurable inspiratory airflow characteristics: initial slope, total volume, and flow shape. The model was able to reproduce the inspiratory flow shape characteristics that have previously been described in the literature. Simulation results also supported the observations that a multitude of factors underlie the pharyngeal collapse and, therefore, certain medical therapies that are effective in some conditions may prove ineffective in others. CONCLUSIONS: A mathematic model integrating the current knowledge of upper airway physiology is able to predict individual treatment responses. The model provides a framework for designing novel and potentially feasible treatment alternatives for sleep-disordered breathing.

Arousal↗

Effect of medroxyprogesterone on inspiratory flow shapes during sleep in postmenopausal women.

We previously showed that medroxyprogesterone acetate (MPA) effectively decreases the arterial CO(2) levels in postmenopausal women with partial upper airway obstruction. The aim of the present study was to analyze the effects of MPA on the inspiratory flow shapes during sleep. Eight postmenopausal women with hypoxemia and partial upper airway obstruction during sleep (patients) received MPA 60 mg daily for 14 days. Four matched postmenopausal women without MPA treatment served as controls. Sleep and nasal pressure were recorded on each visit. Each breath was analyzed for duration, volume and inspiratory flow shape class. MPA shortened inspiration and prolonged expiration. The inspiratory volumes increased consistently in all flow shape classes. The inspiratory shapes with single late peak were transformed to those with double peak. MPA also decreased shapes with mid-peak or mid-plateau. MPA did not have an effect on sleep. Sleep modified the flow shape distribution only in patients but in a similar fashion in stages S2, SWS and REM. The results suggest that postmenopausal women present with a significant proportion breaths with poor initial inspiratory flow, which is reversed with MPA-induced respiratory stimulation.

Female↗

Breathing during sleep in menopause: a randomized, controlled, crossover trial with estrogen therapy.

OBJECTIVE: To evaluate the prevalence of different types of nocturnal breathing abnormalities in postmenopausal women and the effect of estrogen replacement therapy (ERT) on nocturnal breathing. METHODS: A prospective, randomized, placebo-controlled, double-blind, crossover study was completed by 62 of 71 recruited healthy women. The first 3-month treatment period with either estrogen or placebo was followed by placebo washout for a month and then by a second treatment period with crossover to either estrogen or placebo. On a night after each treatment period, sleep was monitored with polysomnography, and breathing was assessed with a static-charge-sensitive bed and oximeter. For the respiratory variables, a sample size of 48 subjects was sufficient to give statistical power of 85% with a significance level of P <.05. RESULTS: The occurrence of obstructive sleep apnea in all women was low (1.6%), but partial upper airway obstruction, manifesting as an increased respiratory resistance pattern, was more common (17.7%). Estrogen replacement therapy decreased the occurrence (P =.047) and frequency (P =.049) of sleep apnea but had no effect on partial upper airway obstruction or arterial oxyhemoglobin saturation. CONCLUSION: Partial upper airway obstruction is the most prevalent form of sleep-disordered breathing, occurring ten times more frequently than sleep apnea in postmenopausal women. Unopposed estrogen replacement therapy has only a minor effect on sleep apnea and has no effect on partial airway obstruction.

Cross-Over Studies↗

State of vigilance, oestrogen replacement therapy, and lipid profile as modifiers of nocturnal movement-induced heart rate responses.

STUDY OBJECTIVES: To investigate the body movement-associated heart rate responses during sleep in postmenopausal women and to evaluate the possible effect of transdermal oestrogen replacement therapy and metabolic factors on these responses. DESIGN: A prospective double-blind cross-over placebo-controlled trial. SETTING: A university sleep research unit. PATIENTS: Seventy-one healthy postmenopausal women. METHODS: The subjects underwent a whole-night polysomnography including an electrocardiogram (ECG) and a sensitive whole-body movement sensor channel. Body movements of 2-15 s duration with an artefact-free ECG were identified and heart rate was automatically analysed for 30 s before and 60 s after movement. The movement-induced reflex tachycardia and the following rebound bradycardia were measured for the awake state, non-rapid eye movement (REM) sleep and REM sleep. Indices of the heart rate response correlated with age, body mass index (BMI) and high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol ratio. RESULTS: The tachycardia response to a body movement was stronger during sleep than in the awake state, being strongest in REM sleep. The rebound bradycardia following a tachycardia response was relatively similar in REM and in the awake states, but attenuated in non-REM sleep. Oestrogen did not influence the heart rate response. Increasing age and BMI attenuated the response, while an increase in the HDL/LDL cholesterol ratio enhanced the rebound bradycardia response. CONCLUSIONS: Sleep powerfully modulates the rapid cardiac autonomic responses to internal stressors. Postmenopausal hormone replacement therapy does not influence these responses, but they are strongly modulated by lipid metabolism and closely correlated with age and BMI.

Aging↗

Hormones and breathing.

A number of hormones, including hypothalamic neuropeptides acting as neurotransmitters and neuromodulators in the CNS, are involved in the physiologic regulation of breathing and participate in adjustment of breathing in disease. In addition to central effects, some hormones also control breathing at peripheral chemoreceptors or have local effects on the lungs and airways. Estrogen and progesterone seem to protect from sleep-disordered breathing, whereas testosterone may predispose to it. Progesterone and thyroxine have long been known to stimulate respiration. More recently, several hormones such as corticotropin-releasing hormone and leptin have been suggested to act as respiratory stimulants. Somatostatin, dopamine, and neuropeptide Y have a depressing effect on breathing. Animal models and experimental human studies suggest that also many other hormones may be involved in respiratory control.

Animals↗