Biomedical subjects

O Polo

Publications and source records attributed to O Polo.

At least 19 recordsLinked to original sources

PubMed2006

Parameter estimation of a respiratory control model from noninvasive carbon dioxide measurements during sleep.

A new method for estimating the parameters of a human gas exchange model is presented. Sensitivity analysis is used both to inspect the relative importance of the model parameters and to speed up the par-ameter estimation process. Multistart optimization is used to compensate for the effects of partial and noisy measurements. The validity of the method is first investigated with a test problem for which par-ameter identifiability is shown. The method is then applied to the estimation of sleep-related changes in the respiratory control system from the end-tidal and transcutaneous carbon dioxide measurements on human subjects. The results show that it is possible to gain insight into the behaviour of the rather complex physiological system using only a few noninvasive measurements and tractable computations.

Algorithms↗

PubMed2006

Model-based analysis of mechanisms responsible for sleep-induced carbon dioxide differences.

This work describes a comprehensive mathematical model of the human respiratory control system which incorporates the central mechanisms for predicting sleep-induced changes in chemical regulation of ventilation. The model integrates four individual compartments for gas storage and exchange, namely alveolar air, pulmonary blood, tissue capillary blood, body tissues, and gas transport between them. An essential mechanism in the carbon dioxide transport is its dissociation into bicarbonate and acid, where a buffering mechanism through hemoglobin is used to prevent harmfully low pH levels. In the current model, we assume high oxygen levels and consider intracellular hydrogen ion concentration as the principal respiratory control variable. The resulting system of delayed differential equations is solved numerically. With an appropriate choice of key parameters, such as velocity of blood flow and gain of a non-linear controller function, the model provides steady-state results consistent with our experimental observations measured in subjects across sleep onset. Dynamic predictions from the model give new insights into the behaviour of the system in subjects with different buffering capacities and suggest novel hypotheses for future experimental and clinical studies.

Algorithms↗

PubMed2004

Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study.

OBJECTIVE: To evaluate the short- and long-term safety and efficacy of pergolide therapy for restless legs syndrome (RLS) in a double-blind, placebo-controlled, randomized trial (Pergolide European Australian RLS [PEARLS] study). METHODS: We randomized 100 patients with idiopathic RLS were randomized to pergolide, 0.25 to 0.75 mg, in the evening or placebo for 6 weeks (phase 1); thereafter, patients with response on the Patient Global Impression (PGI) scale continued on double-blind pergolide or placebo, and nonresponders received open-label pergolide up to 1.5 mg/d for 12 months of treatment (phase 2). Sleep efficiency (SE) and periodic limb movements during sleep (PLMS) arousal index were monitored by centrally evaluated polysomnography (PSG). The severity of RLS was assessed using the validated International RLS Scale (IRLS). RESULTS: In phase 1 (change from baseline to week 6), pergolide reduced PLMS arousal index vs placebo (mean +/- SD, -12.6 +/- 10.0 vs -3.6 +/- 15.9; p = 0.004), and SE did not improve (mean +/- SD, +11.3 +/- 11.9% vs +6.1 +/- 18.6%; p = 0.196). Pergolide improved RLS severity score (-12.2 +/- 9.9 vs -1.8 +/- 7.5 placebo; p < 0.001) and was associated with a higher PGI response (68.1% vs 15.1%; p < 0.001) and improvements in periodic limb movements (PLM) index, PGI improvement scale, Clinical Global Impression improvement, and IRLS (all p < 0.001), patient-reported SE (p = 0.019), and quality of sleep (p < 0.001). After 12 months (phase 2), double-blind pergolide maintained improvements in PLMS arousal index and PLM index. Placebo patients switched to open-label pergolide in phase 2 exhibited marked improvements in these measures that were maintained at 12 months. Pooled results from the blinded and open-label pergolide groups demonstrated improvements at 12 months in the PLMS arousal index (p = 0.028) and PLM index (p < 0.0001) compared with placebo. Nausea and headache were more frequent with pergolide than with placebo treatment. CONCLUSIONS: Pergolide substantially improves periodic limb movement measures and subjective sleep disturbance associated with restless legs syndrome. Low-dose pergolide was well tolerated and maintained its efficacy in the long term.

Abdominal Pain↗

PubMed2003

Sleep-disordered breathing and hormones.

Sleep-disordered breathing (SDB) is not only a problem of the upper airway but is a systemic condition with endocrine and metabolic interactions. The accumulating body of evidence shows that SDB induces changes in the serum levels or secretory patterns of several hormones. Conversely, various endocrine disorders and hormone therapies may induce, exacerbate or alleviate SDB. Much of the understanding of the interactions between hormones and sleep-disordered breathing derive from intervention studies with nasal continuous positive airway pressure therapy. Better understanding of hormones and breathing may open new perspectives in developing strategies to prevent, alleviate or cure sleep-disordered breathing and its systemic consequences.

Female↗

PubMed2002

Adjustment of the human respiratory system to increased upper airway resistance during sleep.

A cardiorespiratory model incorporating control of the human upper airway during sleep is described. Most previous models have not considered the possibility that the upper airway could be a limiting factor for gas exchange. Our model was developed to also predict certain pathophysiological phenomena in the cardiorespiratory system that characterize heavy snoring or sleep apnea. We started by adapting our collapsible upper airway model to include the impact of nasal passage and larynx, and extended the model with equations for gas exchange in the lungs. A feedback loop both to the respiratory pump and the upper airway dilator muscles was included. The model enabled successful breath-by-breath simulations of obstructive events of the upper airway. Although the model incorporates several physiologically relevant components of the system, the simulation results suggest that only few parameters suffice to predict the key adjustments that the cardiorespiratory system is known to make in patients with heavy snoring.

Airway Obstruction↗

PubMed2002

Effect of medroxyprogesterone on pulmonary arterial pressure, exhaled nitric oxide, ECG and arterial blood gases.

OBJECTIVES: To evaluate the effect of medroxyprogesterone acetate (MPA) therapy on pulmonary arterial pressure (PAP), exhaled nitric oxide (NO), electrocardiogram (ECG), and on arterial blood gases (ABG). DESIGN: A double-blind randomized placebo-controlled cross-over trial. SETTING: University hospital in Turku, Finland. SUBJECTS: Fourteen postmenopausal women with respiratory impairment. INTERVENTIONS: A 2-week placebo and a 2-week MPA period (60 mg day -1) followed by 6-week placebo or MPA washout periods. MAIN OUTCOME MEASURES: The systolic PAP was estimated by Doppler echocardiography. PAP, ECG, NO and ABG were monitored at baseline, after 2-week placebo and MPA periods, and after 3- and 6-week placebo and MPA washout periods. RESULTS: The mean PaCO2 at baseline was 5.4 +/- 0.6 kPa (mean +/- SD). The average decrease of PaCO2 on MPA was -0.8 +/- 0.3 kPa (P < 0.001) and 0.3 +/- 1.0 kPa (P = 0.007) at the 3-week washout. The mean systolic PAP at baseline was 44.3 +/- 14.5 mm Hg. MPA did not change PAP until the 6-week washout, when the average increase of + 6.9 +/- 19.8 mm Hg (P = 0.002) was observed. No changes occurred in PaO2, exhaled NO or the ECG axes. The PR interval was shorter only on MPA (15.9 +/- 27.0 ms, P = 0.020) whereas the QRS duration remained shorter up to 3-week washout (3.9 +/0 5.5 ms, P = 0.008 and 4.0 +/- 14.3 ms, P = 0.032). The systolic and diastolic BP and the heart rate did not change. CONCLUSIONS: Despite prolonged decrease in PaCO2, short-term MPA had no effect on exhaled NO and did not decrease systolic PAP in postmenopausal women with respiratory impairment. MPA shortened the PR interval and the QRS duration, the latter effect being sustained at least up to 3 weeks.

Aged↗

PubMed2002

Effect of medroxyprogesterone on arterial blood gases, leptin and neuropeptide Y in postmenopausal females.

Natural progesterone, a potent respiratory stimulant, stimulates leptin production in premenopausal females. Leptin and its counterpart neuropeptide Y (NPY) have recently been linked with respiration. The effect of medroxyprogesterone acetate (MPA) on arterial blood gases, serum leptin and NPY was evaluated in this study. Fourteen postmenopausal females with respiratory impairment, due mostly to chronic obstructive pulmonary disease, were recruited for a randomised, double-blind, placebo-controlled crossover trial. Arterial blood gases, serum leptin and NPY concentrations were measured at baseline and after 14 days of treatment with placebo and MPA, separated by a 6-week washout period. Thirteen patients completed the trial. The mean+/-SD carbon dioxide tension in arterial blood (Pa,CO2) was 5.4+/-0.6 kPa at baseline, and decreased by 0.8+/-0.3 kPa during treatment with MPA. The oxygen tension in arterial blood (Pa,O2) and pH did not change. At baseline, the mean base excess was 0.6+/-1.9 mmol x L(-1) and the mean bicarbonate (HCO3-) concentration was 25.1+/-1.6 mmol x L(-1). With MPA, base excess decreased by 2.2+/-1.2 mmol x L(-1) and HCO3- by 1.9+/-1.0 mmol x L(-1) from baseline. The mean concentrations of serum leptin (19.8+/-9.9 microg x L(-1) at baseline, 19.7+/-9.8 microg x L(-1) with MPA) or NPY (94.0+/-18.3 pmol x L(-1) at baseline, 85.1+/-41.2 pmol x L(-1) with MPA) did not change. However, the reduction in Pa,CO2 correlated with the reduction of serum leptin concentration. Medroxyprogesterone acetate effectively decreased the carbon dioxide tension in postmenopausal females with chronic respiratory impairment. The results suggest that a decrease in the carbon dioxide tension of > or = 0.9 kPa is necessary for a reduction in serum leptin concentration.

Aged↗

PubMed2001

Climacteric vasomotor symptoms do not predict nocturnal breathing abnormalities in postmenopausal women.

OBJECTIVE: To study the association of climacteric vasomotor symptoms and nocturnal breathing abnormalities in a sample of healthy postmenopausal women. METHODS: Out of 71 postmenopausal women who took part in a large sleep study, 65 women were included into the present study. Sleep was monitored with polysomnography and nocturnal breathing with a static-charge sensitive bed and a pulse oximeter. Climacteric vasomotor symptoms were scored daily for 14 days and levels of oestradiol and FSH were measured in the serum. RESULTS: Altogether 21 (32.3%) women had some degree of breathing abnormalities during the study night. The occurrence of clinically significant sleep apnoea was low (1.5%) and of moderate type (OP-2). In contrast, increased respiratory resistance pattern, typical for partial upper airway obstruction, was frequent (16.9%). Seventy-eight per cent of the women had arterial oxyhaemoglobin desaturation events, but only in 4.6% of the women these events occurred more than 5 times/h of time in bed. Older women had more simple periodic breathing (P-1) and lower mean arterial oxyhaemoglobin saturation (SaO(2)). Body mass index (BMI) correlated with the apnoea frequency (OP-2) and inversely with the mean SaO(2). The severity of climacteric vasomotor symptoms or serum oestradiol concentration did not correlate with nocturnal breathing abnormalities. CONCLUSIONS: Nocturnal breathing abnormalities, especially partial upper airway obstruction, are common in postmenopausal women, but climacteric vasomotor symptoms do not predict their occurrence or severity. Increasing age and high BMI are important determinants of nocturnal breathing abnormalities.

Age Factors↗

PubMed2001

A model of a snorer's upper airway.

In snorers, the physiologic decrease of postural muscle tone during sleep results in increased collapsibility of the upper airway. Measurement of nasal pressure changes with prongs is increasingly used to monitor flow kinetics through a collapsing upper airway. This report presents a mathematical model to predict nasal flow profile from three critical components that control upper airway patency during sleep. The model includes the respiratory pump drive, the stiffness of the pharyngeal soft tissues, and the dynamic support of the muscles surrounding the upper airway. Depending on these three components, the proposed model is able to reproduce the characteristic changes in flow profile that are clinically observed in snorers and non-snorers during sleep.

Humans↗

PubMed2001

Estrogen replacement therapy and nocturnal periodic limb movements: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy on nocturnal periodic limb movements in a randomized, double-masked, placebo-controlled, crossover trial. METHODS: Seventy-one healthy postmenopausal women volunteered in answer to a newspaper announcement; 62 women completed the follow-up. Frequency of nocturnal body movements was measured with the static-charge-sensitive bed and all-night polysomnographic recordings. Serum estradiol (E2) and FSH concentrations were also measured at baseline and after each treatment period. The power of the study setup was 94%. RESULTS: Nearly half the women presented with episodes of periodic limb movements (30 of 62 women, or 48%, during placebo and 27, or 44%, during estrogen therapy). In 17 (27%) during placebo and 19 (31%) during estrogen therapy, frequency of periodic limb movements exceeded index level 5 per hour while subjects were in bed. Incidence or intensity of movements, movement durations, and movement intervals did not change with estrogen therapy. The arousal index was similar during the two treatments (medians = 1.7 for placebo and 1.3 for estrogen, P =.758). Variations in serum E2 concentration, age, and body mass index did not explain variations in movement activity. CONCLUSION: Estrogen replacement therapy in doses used to control climacteric symptoms does not alter the incidence or intensity of nocturnal periodic limb movements.

Administration, Cutaneous↗

PubMed2001

Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep.

The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing. Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later. At baseline, the overnight mean+/-SD end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5+/-0.4 kPa the arterial oxygen saturation (Sa,O2) 93.0+/-1.2%, Sa,O2 nadir 80.0+/-6.7%, and frequency of oxygen desaturation > or = 4% (ODI4) per hour 2.2+/-1.3. MPA decreased Pet,CO2 by 0.8 kPa (14.5%, p<0.001). After washout, the mean Pet,CO2 remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline. Sa,O2 did not change. Pet,CO2 was lower on MPA than on nCPAP (4.7+/-0.2 kPa versus 5.0+/-0.3 kPa; p=0.037) but Sa,O2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks posttreatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.

Aged↗

PubMed2001

Analysis of inspiratory flow shapes in patients with partial upper-airway obstruction during sleep.

STUDY OBJECTIVE: To study the spectrum of inspiratory flow signal shapes in patients with partial upper airway obstruction during sleep. DESIGN: We identified seven different inspiratory flow shapes and determined their frequencies in two groups of patients (10 postmenopausal women and 19 men after surgical treatment for sleep apnea) and in 9 control subjects. SETTING: Sleep research unit, Department of Physiology, University of Turku, Finland. MEASUREMENTS AND RESULTS: Nasal flow was recorded with nasal prongs. The shape analyses were performed with an automated attribute grammar recognizer. The inspiratory flow-shape distributions differed significantly between patients and control subjects. The flow shapes were also different between postmenopausal women and men after uvulopalatopharyngoplasty. CONCLUSIONS: The differences in the inspiratory flow-shape distributions between the control subjects and the two patient groups suggest that the upper airways behave differently in the three study groups. Automated inspiratory flow-shape analysis seems to be a promising tool to distinguish patient groups with different upper airway function to be treated with different treatment alternatives. The physiologic correlates of each flow-shape class remain to be elucidated.

Adult↗

PubMed2001

Sleep-related disordered breathing during pregnancy in obese women.

STUDY OBJECTIVES: This study was designed to evaluate sleep-related disordered breathing in obese women during pregnancy. Obesity is known to predispose to sleep-related breathing disorders. During pregnancy, obese mothers gain additional weight, but other mechanisms may counteract this effect. DESIGN: A case-control study to compare sleep-related breathing in obese pregnant women (mean prepregnancy body mass index [BMI] > 30 kg/m(2)) with pregnant women of normal weight (mean BMI, 20 to 25 kg/m(2)). SETTING: University teaching hospital with a sleep laboratory. PARTICIPANTS: We recruited 11 obese women (BMI, 34 kg/m(2); mean age 31 years) and 11 control women (BMI, 23 kg/m(2); mean age 32 years). INTERVENTIONS: Overnight polysomnography was performed during early (after 12 weeks) and late (after 30 weeks) pregnancy. MEASUREMENTS AND RESULTS: During pregnancy, obese mothers gained 13 kg and control women gained 16 kg. Sleep characteristics did not differ between the groups. During late pregnancy, the women in both groups slept more poorly and slept in supine position less. During early pregnancy, their apnea-hypopnea indexes (1.7 events per hour vs 0.2 events per hour; p < 0.05), 4% oxygen desaturations (5.3 events per hour vs 0.3 events per hour; p < 0.005), and snoring times (32% vs 1%, p < 0.001) differed significantly. These differences between the groups persisted in the second polysomnography, with snoring time further increasing in the obese. Preeclampsia and mild obstructive sleep apnea were diagnosed in one obese mother. One obese mother delivered a baby showing growth retardation (weight - 3 SD). CONCLUSIONS: We have shown significantly more sleep-related disordered breathing occurring in obese mothers than in subjects of normal weight, despite similar sleeping characteristics.

Adult↗

PubMed2001

Aetiology and treatment of sleep disturbances during perimenopause and postmenopause.

The sudden and predictable cessation of ovarian endocrinological function at menopause results in a marked decrease of endogenous estrogen and progestogen secretion. In addition to cessation of menstruation, a wide range of biological functions, including sleep, are affected. Sleep disturbances are more common in women than in men and their incidence increases with age. There are 2 distinct mechanisms by which menopause is known to affect sleep quality. One is menopausal insomnia, which can be considered as part of the symptomatology of the climacterium. Another is sleep-disordered breathing, where impairment of sleep quality is secondary to sleep apnoea or partial upper airway obstruction during sleep. The former is effectively controlled with conventional estrogen replacement therapy, whereas the latter could potentially be improved with progestogens. Many age-related conditions without a direct link with the menopause should also be considered when treating postmenopausal sleep disorders.

Aged↗

PubMed2000

The effect of estrogen replacement therapy on cardiac autonomic regulation.

OBJECTIVE: To study the effects of estrogen replacement therapy (ERT) and sleep stage on autonomic cardiac regulation. SRUDY DESIGN: Seventy-one healthy postmenopausal women received transdermal ERT and placebo separated by a washout in a randomized, placebo-controlled, double-blind, cross-over trial. Polysomnography was conducted at the end of each treatment. Heart rate variability (HRV) was assessed in epochs of the awake state, stage 2, slow wave and REM sleep. The effects of estradiol and sleep stages on HRV were analyzed. RESULTS: ERT decreased heart rate in the awake state and quiet sleep, but not in REM sleep. ERT did not change the heart rate variability. Heart rate decreased and HRV increased during stage 2 and slow wave sleep compared with the awake state with placebo. In REM sleep, similarly, heart rate increased above awake values and the values of HRV parameters fell back to awake levels. CONCLUSIONS: The results suggest that ERT increases vagal tone, but does not change cardiac vagal modulation. Changes in HRV suggest a strong vagal influence in non-REM and a sympathetic influence in REM sleep.

Administration, Cutaneous↗

PubMed2000

Prolonged endocrine responses to medroxyprogesterone in postmenopausal women with respiratory insufficiency.

OBJECTIVE: To evaluate the endocrinologic changes associated with, and possibly responsible for, prolonged ventilatory improvement after short-term medroxyprogesterone acetate (MPA) in chronic respiratory failure. METHODS: Fourteen postmenopausal women with permanent or previous episodic hypercapnic or hypoxemic respiratory failure were enrolled in a placebo-controlled, 12-week, single-mask trial including 14-day treatment periods with placebo and MPA (60 mg daily) and a 6-week follow-up. We evaluated the duration of MPA-induced alterations on serum concentrations of progesterone, estradiol, testosterone, FSH, LH, sex hormone-binding globulin (SHBG), and prolactin. Hormones were measured four times: at baseline, after 14 days with MPA, and during the washout on days 21 and 42. RESULTS: With MPA, FSH decreased 42.7% (P <.001, 95% confidence interval [CI] -54.2, -31.6), LH 62.1% (P <.01; 95% CI -81. 0, -32.6), and SHBG 58.1% (P <.001; 95% CI -63.0, -43.9). Luteinizing hormone remained decreased (-28.7%; P <.01; 95% CI -42.0, -14.2) at the 3-week washout, whereas FSH and SHBG were back to pretreatment levels. Prolactin had a borderline initial increase of 23.5% (P =.097; 95% CI -3.5, 50.5) with MPA and a significant increase at the 3-week (31.9%; P <.05; 95% CI 1.0, 62.9) and 6-week (26.4%; P <.05; 95% CI 4.4, 48.3) washouts. CONCLUSION: Medroxyprogesterone acetate 60 mg daily for 2 weeks has both immediate (FSH, LH, and SHBG), prolonged (LH), and rebound endocrinologic (prolactin) effects up to 6 weeks after treatment. The MPA-induced widespread endocrine aftereffects could explain the earlier reported prolonged ventilatory improvement.

Chronic Disease↗

PubMed2000

Detection of high-frequency respiratory movements during sleep.

Sleep-related breathing disorders are common in adults and they have a significant impact on vigilance and quality of life. Previous studies have shown the validity of the static-charge-sensitive bed (SCSB) in monitoring breathing abnormalities during sleep. A whole nights sleep study produces a signal with considerable length, and therefore an automated analysis system would be of great need. In this work we focus on detection of high-frequency respiratory movement (HFRM) patterns which are related to increased respiratory efforts. The paper documents four methods to automatically detect these patterns. The first two are based on classical statistical tests applied to the SCSB signal, and the other two use spectral characteristics in order to adaptively segment the SCSB signal. Finally we adjust each method to detect patterns that coincide with the HFRMs determined by an expert, and evaluate the performance of the methods using independent test data.

Algorithms↗

PubMed2000

IGF-I and ventilation after short-term progestin in postmenopausal women with chronic respiratory insufficiency.

Progestins stimulate respiration. We have previously shown prolonged ventilatory improvement in chronic respiratory failure with short-term medroxyprogesterone acetate (MPA). The mechanism of the sustained respiratory effect is unknown. Insulin-like growth factor-I (IGF-I) and insulin have anabolic effects which could also improve ventilation in the long-term. To better understand the interactions between hormones and control of breathing, we evaluated the degree and duration of changes in IGF-I, insulin and cortisol after short-term MPA therapy in chronic respiratory insufficiency. Fourteen postmenopausal women with permanent or episodic hypercapnic or hypoxaemic respiratory failure were recruited for a placebo-controlled single-blind trial. After 14 days of placebo treatment and 7 days of washout, a daily dose of 60 mg MPA was administered for 14 days. Serum IGF-I, insulin and cortisol were measured five times at 3-week intervals: at baseline, after 14 days on placebo, after 14 days on MPA, and during the washout, on days 21 and 42. Serum IGF-I levels were 15.2 (SD 4.6), 20.8 (SD 6.8) and 17.2 (SD 6.4) at baseline, on MPA and after a 3-week washout. Serum insulin levels did not change [12.5 mU l(-1) (SD 4.1), 12.2 mU l(-1) (SD 4.8) and 14.5 mU l(-1) (SD 3.6), respectively]. Serum cortisol did not change. On MPA, IGF-I increased on average by 5.6 nmol l(-1) [95% confidence interval (95% CI) 1.4 to 9.9] or 42.0% (95% CI 6.3 to 77.8) from baseline. The IGF-I response coincided with the previously reported ventilatory improvement. MPA 60 mg daily for 2 weeks increases serum IGF-I in postmenopausal women with chronic respiratory insufficiency. During follow-up after MPA, there was a trend towards increased IGF-I and insulin levels. The role of these two hormones to induce prolonged ventilatory stimulation could not be excluded and further studies in larger populations are warranted.

Age Factors↗