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Fatigue et Cancer / Rythmicité de l'ARNm dans les neurones circadiens / SAS et cardiopathie coronarienne / saturation de l'hemoglobine en oxygène et disgnostic du SAS

Cœur et sommeil
-La revue Circulation (12 juillet 2010) publie les résultats d’une étude épidémiologique longitudinale ayant porté sur une cohorte de 1927 hommes et 2495 femmes de 40 ans et plus suivis sur 8 ans et 7 mois. Elle explore l’incidence du syndrome d’apnées du sommeil sur la cardiopathie coronaire et l’insuffisance cardiaque. Un « portrait » de l’individu le plus susceptible d’encourir le risque de développer ces comorbidités associées, avec des ronflements.
Pharmacologie
-La fatigue constitue un trouble fréquent chez les malades du cancer. Un essai clinique randomisé de phase 3 en double aveugle contre placébo dont les résultats sont parus dans le Journal of Clinical Oncology(12 uillet 2010) a mis à l’épreuve l’efficacité du méthylphénidate,  phényléthylamine aux propriétés pharmacologiques proches de celles des amphétamines sur ce symptôme. Il apparaît que ces résultats, issus de l’examen de 148 patients ne parviennent pas à démontrer une véritable efficacité de ce traitement sur le long terme.
Chronobiologie
-Une étude parue dans la revue Proceedings of the National Academy of Sciences of the United States of America (12 juillet 2010) a souhaité caractériser l’expression des gènes circadiens de l’adulte drosophile en isolant deux sous-groupes ventraux de neurones latéraux (LNv), contigus mais distincts, composés l’un de 8 petites cellules (s-LNv) et l’autre de 10 grosses cellules (l-LNv), exprimant le neuropeptide PDF (pigment-dispersing factor). Elle met en évidence que le caractère cyclique de l’ARN messager est plus patent dans les neurones circadiens et contribue à son fonctionnement.
Respiration
-La mesure de la saturation de l'hémoglobine en oxygène effectuée par oxymétrie nocturne de pouls est perçue comme une technique de diagnostic pertinente du syndrome d’apnées du sommeil. C’est ce que tend à affirmer une étude parue dans la revue IEEE Transaction of Biomedical Engineering (8 juillet 2010) à partir d’un examen ayant porté sur 148 patients avec suspicion de SAS.
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Journal of Clinical Oncology  2010 Jul 12. [Epub ahead of print]
Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Long-Acting Methylphenidate for Cancer-Related Fatigue: North Central Cancer Treatment Group NCCTG-N05C7 Trial.
Moraska AR, Sood A, Dakhil SR, Sloan JA, Barton D, Atherton PJ, Suh JJ, Griffin PC, Johnson DB, Ali A, Silberstein PT, Duane SF, Loprinzi CL.
Mayo Clinic Rochester, Rochester, MN; Wichita Community Clinical Oncology Program (CCOP), Wichita, KS; Joliet Hematology/Oncology, Joliet, IL; Upstate Carolina CCOP, Spartanburg, SC; Geisinger Clinic and Medical Center CCOP, Danville, PA; Missouri Valley Cancer Consortium, Omaha, NE; and Metro-Minnesota CCOP, St. Louis Park, MN.
Abstract
PURPOSE Fatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities. PATIENTS AND METHODS Adults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change. Results In total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm. CONCLUSION This clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.
PMID: 20625123 [PubMed - as supplied by publisher]
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Circulation. 2010 Jul 12. [Epub ahead of print]
Prospective Study of Obstructive Sleep Apnea and Incident Coronary Heart Disease and Heart Failure. The Sleep Heart Health Study.
Gottlieb DJ, Yenokyan G, Newman AB, O'Connor GT, Punjabi NM, Quan SF, Redline S, Resnick HE, Tong EK, Diener-West M, Shahar E.
VA Boston Healthcare System, Boston, Mass; Boston University School of Medicine, Boston, Mass; Johns Hopkins University, Baltimore, Md; Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa; University of Arizona, Tucson, Ariz; Harvard Medical School, Boston, Mass; Case Western Reserve University, Cleveland, Ohio; American Association of Homes and Services for the Aging and Georgetown University, Washington, DC; University of California, Davis, Calif; and Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Ariz.
Abstract
BACKGROUND: -Clinic-based observational studies in men have reported that obstructive sleep apnea is associated with an increased incidence of coronary heart disease. The objective of this study was to assess the relation of obstructive sleep apnea to incident coronary heart disease and heart failure in a general community sample of adult men and women. Methods and Results-A total of 1927 men and 2495 women >/=40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years in this prospective longitudinal epidemiological study. After adjustment for multiple risk factors, obstructive sleep apnea was a significant predictor of incident coronary heart disease (myocardial infarction, revascularization procedure, or coronary heart disease death) only in men </=70 years of age (adjusted hazard ratio 1.10 [95% confidence interval 1.00 to 1.21] per 10-unit increase in apnea-hypopnea index [AHI]) but not in older men or in women of any age. Among men 40 to 70 years old, those with AHI >/=30 were 68% more likely to develop coronary heart disease than those with AHI <5. Obstructive sleep apnea predicted incident heart failure in men but not in women (adjusted hazard ratio 1.13 [95% confidence interval 1.02 to 1.26] per 10-unit increase in AHI). Men with AHI >/=30 were 58% more likely to develop heart failure than those with AHI <5. Conclusions-Obstructive sleep apnea is associated with an increased risk of incident heart failure in community-dwelling middle-aged and older men; its association with incident coronary heart disease in this sample is equivocal.
PMID: 20625114 [PubMed - as supplied by publisher]
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Proceedings of the National Academy of Sciences of the United States of America. 2010 Jul 12. [Epub ahead of print]
Surprising gene expression patterns within and between PDF-containing circadian neurons in Drosophila.
Kula-Eversole E, Nagoshi E, Shang Y, Rodriguez J, Allada R, Rosbash M.
Howard Hughes Medical Institute, National Center for Behavioral Genomics, Department of Biology, Brandeis University, Waltham, MA 02454.
Abstract
To compare circadian gene expression within highly discrete neuronal populations, we separately purified and characterized two adjacent but distinct groups of Drosophila adult circadian neurons: the 8 small and 10 large PDF-expressing ventral lateral neurons (s-LNvs and l-LNvs, respectively). The s-LNvs are the principal circadian pacemaker cells, whereas recent evidence indicates that the l-LNvs are involved in sleep and light-mediated arousal. Although half of the l-LNv-enriched mRNA population, including core clock mRNAs, is shared between the l-LNvs and s-LNvs, the other half is l-LNv- and s-LNv-specific. The distribution of four specific mRNAs is consistent with prior characterization of the four encoded proteins, and therefore indicates successful purification of the two neuronal types. Moreover, an octopamine receptor mRNA is selectively enriched in l-LNvs, and only these neurons respond to in vitro application of octopamine. Dissection and purification of l-LNvs from flies collected at different times indicate that these neurons contain cycling clock mRNAs with higher circadian amplitudes as well as at least a 10-fold higher fraction of oscillating mRNAs than all previous analyses of head RNA. Many of these cycling l-LNv mRNAs are well expressed but do not cycle or cycle much less well elsewhere in heads. The results suggest that RNA cycling is much more prominent in circadian neurons than elsewhere in heads and may be particularly important for the functioning of these neurons.
PMID: 20624977 [PubMed - as supplied by publisher]
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IEEE Trans Biomed Eng. 2010 Jul 8. [Epub ahead of print]
Multivariate Analysis of Blood Oxygen Saturation Recordings in Obstructive Sleep Apnea Diagnosis.
Alvarez D, Hornero R, Marcos J, Del Campo F.
Abstract
This study focuses on the analysis of blood oxygen saturation (SaO2) from nocturnal pulse oximetry (NPO) to help in the diagnosis of the obstructive sleep apnea (OSA) syndrome. A population of 148 patients suspected of suffering from OSA syndrome was studied. A wide set of 16 features was used to characterize changes in the SaO2 profile during the night. Our feature set included common statistics in the time and frequency domains, conventional spectral characteristics from the power spectral density (PSD) function and nonlinear features. We performed feature selection by means of a step-forward logistic regression (LR) approach with leave-one-out cross-validation. Second and fourth order statistical moments in the time domain (M2t and M4t), the relative power in the 0.014 0.033 Hz frequency band (PR) and the Lempel-Ziv complexity (LZC) were automatically selected. 92.0% sensitivity, 85.4% specificity and 89.7% accuracy were obtained. The optimum feature set significantly improved the diagnostic ability of each feature individually. Furthermore, our results outperformed classic oximetric indexes commonly used by physicians. We conclude that simultaneous analysis in the time and frequency domains by means of statistical moments, spectral and nonlinear features could provide complementary information from NPO to improve OSA diagnosis.
PMID: 20624698 [PubMed - as supplied by publisher]

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Le groupe médical Santé Sommeil a pour vocation de diagnostiquer et traiter les troubles du sommeil et de la veille chez l’adulte et l’enfant.