Leukocytes contain both nicotinic and muscarinic receptors, and while activation of nicotinic receptors suppresses immune/inflammatory responses, the role of muscarinic receptors in immunity is unclear. We examined the effects of a muscarinic receptor antagonist (atropine) and agonist (oxotremorine), administered chronically through miniosmotic pumps, on immune/inflammatory responses in the rat. Results show that while oxotremorine stimulated, atropine inhibited the antibody and T-cell proliferative responses. Moreover, atropine also suppressed the turpentine-induced leukocytic infiltration and tissue injury, and inhibited chemotaxis of leukocytes toward neutrophil and monocyte/lymphocyte chemoattractants. Thus, activation of nicotinic and muscarinic receptors has opposite effects on the immune/inflammatory responses.

Background We investigated the relationship between self-reported sleep characteristics and brachial artery flow-mediated dilation (FMD) in a community-based population. Prior studies document that sleep apnea may be related to endothelial dysfunction but disagree whether subjective reports of sleep may also reflect such associations. Methods In 684 subjects (32% male) between 37 and 60 years enrolled in the Emory-Georgia Tech Predictive Health Institute study, we measured reported sleep characteristics using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) along with cardiovascular risk factors. Endothelial function was assessed using brachial artery FMD. Multivariate analysis of covariance was used to adjust for various cardiovascular risk factors including age, race, gender, smoking, hypertension, diabetes, and body mass index. Results Lower brachial artery FMD values were correlated with higher ESS scores (p = 0.0275), even after adjustment for risk factors (p = 0.03). Total PSQI score was unrelated to brachial artery FMD. However, lower sleep quality (PSQI component 1) was associated with lower brachial artery FMD (multivariate p = 0.038), and participants who coughed or snored during sleep also had lower brachial artery FMD (6.24±3.42%) compared to those who did not (6.92±4.30%) (p = 0.056). This difference remained significant after adjustment for risk factors (p = 0.03). Conclusion In a community-based population, our analysis indicates a significant association between sleepiness and snoring assessed by questionnaires and endothelial function. Simple subjective reports about individuals’ sleep may be highly revealing indicators of endothelial function impairment and thus important indicators of cardiovascular disease risk.

Mortality from various causes is higher in patients on chronic hemodialysis (HD) than in the general population. There is evidence suggesting that some of the deaths in HD patients are preventable. To identify potentially preventable causes of death, we analyzed deaths that occurred in HD patients during hospitalization over a period of 15 years. We performed a retrospective cohort analysis of 410 patients on HD for at least 6 months between 1995 and 2009 (included), who had all their hospitalizations in the same hospital. The patients were classified into 3 groups: Those who died during hospitalization (group A, n=120), those who died away from the hospital (group B, n=135), and those who were alive at the end of the observation period (group C, n=155). Continuous variables were compared between groups by the Kruskall-Wallis statistic. Logistic regression was used to identify predictors of dying during the observation period and predictors of death in the hospital. For the whole HD group of 410 patients, only 9 (2.2%) were women. 59% of the patients had diabetes mellitus. Age at the onset of HD was 65.8 ± 11.5 years and the duration of HD was 34.4 ± 27.9 months. Group A patients had a higher annual rate and duration of hospitalization and a higher Charlson comorbidity index than either of the other 2 groups, and, in comparison with patients in group C, were older at the end of observation and had a shorter duration of HD. Cardiac disease (19.2%), vascular access complications (18.3%), peripheral vascular disease (16.7%), infections (15.8%), trauma (11.7%), central nervous system disease (7.5%), respiratory failure (4.2%), malignancy (3.3%), and gastrointestinal disease (3.3%) were the causes of the last hospitalization in group A. Compared with the patients who died during hospitalization without discontinuing HD, group A patients who discontinued HD had a longer duration of their last hospitalization (52.7 ± 77.7 vs. 14.3 ± 23.8 days, P<0.001). Discontinuation of HD occurred in 80% of the hospitalizations for respiratory failure, 75% of the hospitalizations for malignancy, 57% of the hospitalizations for trauma, and 56% of the hospitalizations for central nervous system disease. Logistic regression identified a high Charlson index, advanced age, and short duration of HD as predictors of death, and an absence of diabetes, high Charlson index, prolonged annual duration of hospitalization, and short distance of the patient's domicile from the dialysis unit as predictors of death in the hospital. A substantial number of hospitalizations leading to the death of HD patients are caused by potentially preventable conditions, including vascular access complications, peripheral vascular disease, and trauma. Implementation of measures preventing these hospitalizations is a worthwhile undertaking.

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