A prospective polysomnographic study on the evolution of complex sleep apnoea.

Complex sleep apnoea (CompSA) may be observed following continuous positive airway pressure (CPAP) treatment. In a prospective study, 675 obstructive sleep apnoea patients (mean age 55.9 yrs; 13.9% female) participated. Full-night polysomnography was performed at diagnosis, during the first night with stable CPAP and after 3 months of CPAP. 12.2% (82 out of 675 patients) had initial CompSA. 28 of those were lost to follow-up. Only 14 out of the remaining 54 patients continued to satisfy criteria for CompSA at follow-up. 16 out of 382 patients not initially diagnosed with CompSA exhibited novel CompSA after 3 months. 30 (6.9%) out of 436 patients had follow-up CompSA. Individuals with CompSA were 5 yrs older and 40% had coronary artery disease. At diagnosis, they had similar sleep quality but more central and mixed apnoeas. On the first CPAP night and at follow-up, sleep quality was impaired (more wakefulness after sleep onset) for patients with CompSA. Sleepiness was improved with CPAP, and was similar for patients with or without CompSA at diagnosis and follow-up. CompSA is not stable over time and is mainly observed in predisposed patients on nights with impaired sleep quality. It remains unclear to what extent sleep impairment is cause or effect of CompSA.

[Measuring sleep duration and sleep quality]. / Messung von Schlafdauer und Schlafqualität.

Restorative functions of sleep are of special interest for sleep medicine. For the assessment of these restorative functions, various parameters are taken into account, among which sleep duration and sleep quality play the most important roles. Both terms are essential for sleep perception, expressing the subjective satisfaction of the individual with the time spent asleep. In recent decades, sleep medicine and sleep research have developed methods for the assessment of both objective and subjective dimensions of sleep. Among subjective methods, taking of the medical history focusing on the patient's sleep is important. Standardized and validated questionnaires play a supportive role. Objective methods are, for example, estimation of the sleep-wake cycle by means of actigraphy and polygraphy. Especially in multimorbid patients, polysomnography is still the gold standard method for diagnostics. An important approach during recent years is shifting from bothering overnight examinations into less disturbing procedures for patients that include performing ambulatory, outpatient examinations in the patients' home rather than inpatient surveillance within sleep centers.

[Perioperative management of patients suffering from sleep-related breathing disorders]. / Perioperatives Management bei Patienten mit schlafbezogenen Atmungsstörungen.

Sleep-related breathing disorders have been associated with increased perioperative morbidity and mortality. The respective patients are at risk during two independent periods. Besides an early period, characterised by the influence of anaesthetics, patients are at risk also during a late period, which is characterised by nocturnal desaturation and disturbances of the cardiovascular system, caused by interference with the sleep architecture, especially of the REM sleep. To assure a safe perioperative management, a close monitoring (O2 saturation and pCO2) and the option for non-invasive ventilation have to be guaranteed.

Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse chromosome 5.

We hypothesized that upper airway obstruction (UAO) leads to a compensatory increase in the duty cycle [ratio of inspiratory time to respiratory cycle length (Ti/Tt)], which is determined by genetic factors. We examined the compensatory Ti/Tt responses to 1). UAO and hypercapnia among normal individuals and 2). hypercapnia in different inbred strains, C3H/HeJ (C3) and C57BL/6J (B6), and their first- and second-generation (F2) offspring. 3). We then used the compensatory Ti/Tt response in the F2 to determine genetic linkage to the mouse genome. First, normal individuals exhibited a similar increase in the Ti/Tt during periods of hypercapnia (0.11 +/- 0.07) and UAO (0.09 +/- 0.06) compared with unobstructed breathing (P < 0.01). Second, the F2 offspring of C3 and B6 progenitors showed an average Ti/Tt response to 3% CO2 (0.42 +/- 0.005%) that was significantly (P < 0.01) greater than that of the two progenitors. Third, with a peak log of the odds ratio score of 4.4, Ti/Tt responses of F2 offspring are genetically linked to an interval between 58 and 64 centimorgans (cM) on mouse chromosome 5. One gene in the interval, Dagk4 at 57 cM, is polymorphic for C3 and B6 mice. Two other genes, Adrbk2 at 60 cM and Nos1 at 65 cM, have biological plausibility in mechanisms of upper airway patency and chemosensitivity, respectively. In summary, Ti/Tt may serve as an intermediate physiological phenotype for compensatory neuromuscular response mechanisms for maintaining ventilation in the face of UAO and hypoventilation and to help target specific candidate genes that may play a role in the expression of sleep-disordered breathing.

PKA phosphorylation redirects ERα to promoters of a unique gene set to induce tamoxifen resistance.

Protein kinase A (PKA)-induced estrogen receptor alpha (ERα) phosphorylation at serine residue 305 (ERαS305-P) can induce tamoxifen (TAM) resistance in breast cancer. How this phospho-modification affects ERα specificity and translates into TAM resistance is unclear. Here, we show that S305-P modification of ERα reprograms the receptor, redirecting it to new transcriptional start sites, thus modulating the transcriptome. By altering the chromatin-binding pattern, Ser305 phosphorylation of ERα translates into a 26-gene expression classifier that identifies breast cancer patients with a poor disease outcome after TAM treatment. MYC-target genes and networks were significantly enriched in this gene classifier that includes a number of selective targets for ERαS305-P. The enhanced expression of MYC increased cell proliferation in the presence of TAM. We demonstrate that activation of the PKA signaling pathway alters the transcriptome by redirecting ERα to new transcriptional start sites, resulting in altered transcription and TAM resistance.

ECG signal analysis for the assessment of sleep-disordered breathing and sleep pattern.

The diagnosis of sleep-disordered breathing (SDB) usually relies on the analysis of complex polysomnographic measurements performed in specialized sleep centers. Automatic signal analysis is a promising approach to reduce the diagnostic effort. This paper addresses SDB and sleep assessment solely based on the analysis of a single-channel ECG recorded overnight by a set of signal analysis modules. The methodology of QRS detection, SDB analysis, calculation of ECG-derived respiration curves, and estimation of a sleep pattern is described in detail. SDB analysis detects specific cyclical variations of the heart rate by correlation analysis of a signal pattern and the heart rate curve. It was tested with 35 SDB-annotated ECGs from the Apnea-ECG Database, and achieved a diagnostic accuracy of 80.5%. To estimate sleep pattern, spectral parameters of the heart rate are used as stage classifiers. The reliability of the algorithm was tested with 18 ECGs extracted from visually scored polysomnographies of the SIESTA database; 57.7% of all 30 s epochs were correctly assigned by the algorithm. Although promising, these results underline the need for further testing in larger patient groups with different underlying diseases.

Comparison of the effects of nebivolol and valsartan on BP reduction and sleep apnoea activity in patients with essential hypertension and OSA.

OBJECTIVES: To investigate the effect of nebivolol, a third generation beta-blocker, on blood pressure (BP) reduction and polysomnographic parameters in hypertensive patients with mild-to-moderate obstructive sleep apnoea (OSA). METHODS: In this double-blind, parallel group study, patients were randomized to nebivolol 5 mg or valsartan 80 mg once daily following a 14-day, placebo run-in period during which any antihypertensive medication were discontinued. BP and heart rate measurements and overnight polysomnography were performed at baseline and after 6 weeks of treatment. Safety and tolerability were assessed. RESULTS: Thirty-one patients were randomized to nebivolol (n = 16) or valsartan (n = 15). After six weeks both systolic and diastolic BP were effectively reduced by both treatments. Reductions in BP were not statistically significant different between agents, but mean heart rate was significantly decreased with nebivolol (compared with valsartan (p < 0.001). There was no statistically significant difference between both treatments for the change from baseline to treatment end for mean (+/-SD) Apnoea Hypopnoea Index (AHI) (nebivolol: 23.0 +/- 9.2 to 27.9 +/- 21.2 events/h; valsartan: 23.8 +/- 6.6 to 22.5 +/- 18.0 events/h; p = 0.48) or for any other sleep-related parameters. Both agents were well tolerated. CONCLUSION: Nebivolol has a significant BP reduction effect in patients with OSA that is similar to valsartan and reduces heart rate to a greater extent which may prove beneficial in selected patients.

SENSATION remote monitoring system for enabling the "anytime, anywhere" monitoring of patients with selected sleep disorders.

The SENSATION Integrated Project aims at promoting the health, safety and quality of life of people and protect the environment by reducing relevant accidents and thus the impact on environment through the application of novel micro and nano sensors and related technologies, of low-cost and high-efficiency, for physiological state monitoring. The focus of the work will be the brain activity, including the sleep and wakefulness states and their boundaries, stress, inattention and hypovigilance states, for hypovigilance detection, prediction and management as well as diagnosis, treatment and remote monitoring of sleep disorders. In this paper, a presentation of the application scenarios of the integrated medical system will be made.