Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study.

AIMS: Sleep fragmentation is a landmark of sleep disorders, because microarousals are systematically associated with sympathetic surges (i.e., sympathetic arousals). However, the impact of sympathetic sleep fragmentation on blood pressure (BP) remains understudied. We assessed the relationships between 24 h ambulatory BP monitoring, the autonomic arousal index (AAI) derived from pulse transit time, and heart rate variability indices. We hypothesized that repeated sympathetic arousals during sleep are associated with elevated BP in a large population of elderly volunteers. METHODS AND RESULTS: Volunteer subjects (n = 780, 57.4% women) with a mean age of 68.7 years and free of known sleep-disordered breathing, coronary heart diseases, and neurological disorders underwent polygraphy, 24 h ECG Holter monitoring, and 24 h ambulatory BP monitoring. Multivariate regressions showed that sleep fragmentation, expressed by AAI, was associated with elevated diurnal (P = 0.008) and 24 h (P = 0.005) systolic BP and higher risk for 24 h [odds ratio (OR): 1.70 (1.04-2.80), P = 0.036] systolic hypertension, independently of confounders such as sleep-disordered breathing, body mass index, sex, diabetes, hypercholesterolaemia, and self-reported sleep duration and quality. Increased AAI was associated with higher nocturnal and diurnal low-frequency power (P < 0.001) and low-to-high-frequency ratio (P < 0.001), suggesting nocturnal and diurnal sympathetic overactivity. CONCLUSION: In healthy elderly subjects, repetitive sympathetic arousals during sleep are associated with elevated systolic BP and higher risk of hypertension, after controlling for confounders. Sympathetic overactivity is the proposed underlying mechanism. CLINICAL TRIAL REGISTRATION: NCT00766584 and NCT00759304.

The physical activity experience of prostate cancer patients: a multicentre peer motivation monitoring feasibility study. The Acti-Pair study.

BACKGROUND: Although the benefits of physical activity (PA) on health are recognised, prostate cancer patients do not follow PA recommendations. The barriers to PA, whether physical, environmental or organisational, are known. Furthermore, even when such barriers are overcome, this achievement is not systematically accompanied by a change in lifestyle habits. The proposal of a programme enabling the integration of PA in the patient's everyday life represents a new challenge in the personalized management of cancer patients. Peer-mentoring interventions have demonstrated their effectiveness in increasing adherence to PA by patients. This study aimed (1) to assess the feasibility of a peer-mentoring intervention: the Acti-Pair program in a local context and (2) to assess the effectiveness of the intervention in this context. METHODS AND ANALYSIS: A pre-post  design pilot study will be used to evaluate feasibility, potential effectiveness and implementation outcomes overs in prostate cancer patients. We performed a mixed quantitative and qualitative prospective study to assess means and process indicators and the implementation of the Acti-Pair program. This study will be performed in cancer centres of Loire district and will be comprised of three successive stages (1) diagnosis of the target population, (2) recruitment and training of peers, and (3) implementation of this intervention in the Loire department. DISCUSSION: This study will allow us to extend the peer-mentoring intervention to other contexts and assess the effectiveness of this intervention and its generalisability.

Association between C-reactive protein and unrecognised sleep-disordered breathing in the elderly.

Elevated levels of C-reactive protein (CRP) have been reported in patients with sleep-disordered breathing (SDB) and may represent an inflammatory marker of cardiovascular risk. However, the association of CRP with SBD in presumed healthy elderly subjects is unknown. In total, 851 (58.5% females) 68-yr-old subjects, who were free of any known cardiac or sleep disorders, were prospectively examined. Subjects underwent unattended polygraphy, and the apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) were assessed. Elevated levels of CRP were found on the morning after the sleep study in patients with more severe SDB. A significant correlation was found between CRP levels, time spent at night with arterial oxygen saturation <90% and ODI. No association was found between CRP levels and AHI. After adjustments for body mass index, smoking status, hypertension, diabetes and dyslipidaemia, a significant association remained between CRP levels and ODI >10 events.h(-1). CRP levels were frequently increased in a large sample of elderly subjects free of major cardiovascular disease. CRP levels were not correlated with the AHI and the indices of sleep fragmentation; the ODI >10 events.h(-1) was the strongest predictor of raised CRP level. The present results suggest that, in the elderly, intermittent hypoxaemia may underlie inflammatory processes leading to cardiovascular morbidity.

Assessment of a flow cytometry technique for studying signaling pathways in platelets: Monitoring of VASP phosphorylation in clinical samples.

A recently released kit (PerFix EXPOSE) was reported to improve the measurement of the degree of phosphorylation of proteins in leukocytes by flow cytometry. We tested its adaptation for platelets to monitor vasodilator-stimulated phosphoprotein (VASP) phosphorylation, which is the basis of a currently used test for the assessment of the pharmacological response to P2Y12 antagonists (PLT VASP/P2Y12). The PerFix EXPOSE kit was compared to the PLT VASP/P2Y12 kit by using blood samples drawn at 24 h post clopidogrel dose from 19 patients hospitalized for a non-cardio-embolic ischemic stroke and treated with clopidogrel monotherapy for at least five days in an observational study. The platelet PerFix method was based on adaptation of the volume of the sample, the centrifugation speed and the incubation temperature. Poor agreement between prevention by adenosine diphosphate (ADP) of PGE1-induced cAMP-mediated VASP phosphorylation and ADP induced aggregation assessed by Light Transmittance Aggregometry was found. We found a significant correlation between the PLT VASP/P2Y12 kit and the PerFix EXPOSE kit. The PerFix EXPOSE kit may also be helpful to monitor adverse effects of second-generation tyrosine kinase inhibitors on platelets.

Effects of long-term hypoxia on tyrosine hydroxylase protein content in catecholaminergic rat brainstem areas: a quantitative autoradiographic study.

The nucleus tractus solitarius (NTS), the ventrolateral medulla (VLM), the dorsal motor vagus nucleus (DMnX) and the locus coeruleus (LC) are catecholaminergic brainstem areas involved in ventilatory and cardiovascular responses to hypoxia and tyrosine hydroxylation is the rate limiting step of cathecholamine biosynthesis in the central nervous system. The aim of this study was to evaluate the effects of long-term hypoxia on tyrosine hydroxylase (TH) content in these different areas using a quantitative autoradiographic technique. Two experimental groups of rats were studied: Group I (9 males, 8 females) was submitted to normobaric hypoxia (10% O2-90% N2) for 21 days and compared to 12 (6 males, 6 females) normoxic control rats (Group II). Coronal tissue sections from fresh-frozen rat brains, obtained along the caudo-rostral axis, were incubated in the presence of a TH monoclonal antibody, and the reaction was revealed by a 35S-labelled secondary antibody. TH levels were quantified in the NTS, VLM, DMnX and LC by measuring optical density on autoradiographic films using an automatic image analyser system. Regional antigen quantification was assessed by computer-assisted image analysis. Chronic hypoxia led to body weight decrease until day 5, haematocrit increase (65 +/- 2% vs. 44 +/- 2%, P < 0.01) and right ventricle hypertrophy (35 +/- 0.5% vs. 23 +/- 0.1% of the weight of the two ventricles, P < 0.01). TH protein contents expressed as percentage of controls were as follows. In males, in the rostral part of the NTS 132 +/- 9% (P < 0.02), in the caudal part of the NTS, 117 +/- 5% (P < 0.04). In female rats, the TH quantity reached a value of 124 +/- 4% (P < 0.01) in the rostral part and 126 +/- 6% (P < 0.01) in the caudal part of the NTS. In females, TH content was significantly increased in the VLM, 124 +/- 6%, P = 0.01, whereas in males there was only a non-significant trend to increase, 122 +/- 11%. In females, there was a significant increase in the DMnX, 127 +/- 9%, P = 0.05, whereas in males there was only a trend to increase, 120 +/- 5%. This study shows that long-term hypoxia induces a persistent increase in TH protein content both in the caudal and rostral part of the NTS, which are known to receive respectively chemo- and barosensory inputs, and in other catecholaminergic areas involved in baroreflex activity. Our data clearly demonstrate the implication of neurochemical mechanisms in the central relationship between chemo- and baroreflex which are responsible for changes in systemic arterial pressure and oxygen partial pressure as required for maintaining an adequate oxygen supply to the tissues.

[A case of "ventilation difficulty-intubation difficulty" solved with transtracheal jet ventilation]. / Un caso de "dificultad de ventilación-dificultad de intubación" resuelto con ventilación jet transtraqueal.

A 56-year-old man recovering from a glossectomy and radical neck dissection presented severe oral bleeding, tracheal deviation with an asphyxiating hematoma and cyanosis. When 2 attempts at orotracheal intubation with the patient awake failed, transtracheal jet ventilation was used temporarily until a definitive airway could be established. Transtracheal jet ventilation is highly useful for managing an airway and maintaining gas exchange in life-threatening situations in which intubation and ventilation has become impossible, yet it is rarely used for that purpose. An easy, fast procedure that has not been widely used in Spain, this technique provides effective ventilation and oxygen while a definitive resolution of the emergency is sought.

Systematic screening for diabetic retinopathy with a digital fundus camera following pupillary dilatation in a university diabetes department.

AIMS: Screening for diabetic retinopathy (DR) is highly inadequate in France because of insufficient infrastructure and increasing disease prevalence. We describe the results of the first systematic DR screening programme established in a university diabetes department. METHODS: In this cross-sectional study conducted over 1 year, consecutive adult patients underwent three-field retinal photography with the Topcon TRC NW6S digital fundus camera following pupillary dilatation with Tropicamide 1%. A questionnaire provided information on patients' systemic and ocular history. Glycated haemoglobin (HbA1c) was measured at the screening visit. Two ophthalmologists graded the retinal photographs in a masked fashion. RESULTS: Of 1157 patients attending the diabetes department, 1153 (99.7%)underwent photographic screening. Images were gradable in 96% patients. Diabetic retinopathy was detected in 522 (45%) patients and sight-threatening DR in 167 (14%). Of 704 (61%) patients previously believed to have no DR,254 (34%) screened positive. The presence of DR was associated with age,insulin use and non-Caucasian ethnicity in Type 2 patients, and with duration of diabetes and HbA1c in Type 1 and Type 2 patients. Associated ocular pathologies were diagnosed in 612 (53%) patients. CONCLUSIONS: Our photographic screening programme using pharmacological mydriasis provided a high screening coverage feasible in a hospital setting. We obtained information regarding prevalence and associated risk factors of DR inpatients attending a tertiary care centre. Screening was well accepted by patients and met with no protest from city ophthalmologists. It generated considerable interest among endocrinologists and feedback of results is expected to improve optimization of glycaemic control.