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[Return to digest index] --------------------------------------------- This is a special digest of Co-Cure Research & Medical posts only Problems? Write to mailto:firstname.lastname@example.org --------------------------------------------- ---------------------------------------------------------------------- Date: Tue, 26 Dec 2006 14:35:06 -0500 From: "Bernice A. Melsky" <email@example.com> Subject: RES: The genetics of fibromyalgia syndrome The genetics of fibromyalgia syndrome. Pharmacogenomics. 2007 Jan;8(1):67-74. Buskila D, Sarzi-Puttini P, Ablin JN.  Ben Gurion University, Department of Medicine H, Soroka Medical Center and Faculty of Health Sciences, Beer Sheva, Israel. firstname.lastname@example.org ,  L Sacco University Hospital, Senior Rheumatologist, Rheumatology Unit,Via GB Grassi 74, 20157 Milano, Italy. email@example.com ,  Tel-Aviv University, Departments of Rheumatology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv, Israel. firstname.lastname@example.org. PMID: 17187510 Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. Fibromyalgia overlaps with several related syndromes, collectively compromising the spectrum of the functional somatic disorder. FMS is characterized by a strong familial aggregation. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are not specific for FMS and are similarly associated with additional comorbid conditions. The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS. [Return to top] ------------------------------ Date: Tue, 26 Dec 2006 14:37:59 -0500 From: "Bernice A. Melsky" <email@example.com> Subject: RES: The low-dose dexamethasone suppression test in fibromyalgia The low-dose dexamethasone suppression test in fibromyalgia. J Psychosom Res. 2007 Jan;62(1):85-91. Wingenfeld K, Wagner D, Schmidt I, Meinlschmidt G, Hellhammer DH, Heim C. Department of Psychobiology, University of Trier, Trier, Germany; Department of Psychiatry and Psychotherapy Bethel, Bielefeld, Germany. PMID: 17188125 OBJECTIVE: Fibromyalgia syndrome (FMS) has been associated with decreased cortisol secretion. Patients with posttraumatic stress disorder (PTSD) exhibit similar hypocortisolism in the context of increased negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis. Because trauma and PTSD have been associated with fibromyalgia, we evaluated whether patients with fibromyalgia demonstrate increased HPA feedback sensitivity. METHOD: Baseline blood samples were obtained at 0800 h, and 0.5 mg of dexamethasone was administered to 15 female patients with FMS and 20 normal controls at 2300 h. Adrenocorticotropin (ACTH), cortisol, and dexamethasone levels were measured at 0800 h after dexamethasone intake. RESULTS: There were no group differences in mean ACTH or cortisol levels or in ACTH/cortisol ratio at baseline. After dexamethasone intake, patients with FMS exhibited more pronounced suppression of cortisol but not of ACTH, as well as increased ACTH/cortisol ratios compared with controls. Percent cortisol suppression was associated with pain and fatigue, while ACTH/cortisol ratio and dexamethasone availability were associated with stress and anxiety measures. CONCLUSION: Our results suggest increased sensitivity to glucocorticoid feedback, manifested at the adrenal level, in FMS. [Return to top] ------------------------------ Date: Wed, 27 Dec 2006 12:11:07 +0100 From: "Dr. Marc-Alexander Fluks" <firstname.lastname@example.org> Subject: RES,NOT: Sleep characteristics of CFS Spource: BMC Neurology Vol 6. p 41 Date: November 16, 2006 URL: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17109739 Sleep characteristics of persons with chronic fatigue syndrome and non- fatigued controls: results from a population-based study. ----------------------------------------------------------------------- William C Reeves,(*,1) Christine Heim,(2) Elizabeth M Maloney,(1) Laura Solomon Youngblood,(1) Elizabeth R Unger,(1) Michael J Decker,(3) James F Jones,(1) and David B Rye(3) 1 Viral Exanthems & Herpesvirus Branch, Division of Viral & Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control & Prevention, Atlanta, GA, USA 2 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA 3 Dept. of Neurology, Emory University School of Medicine, Atlanta, GA, USA * Corresponding author. William C Reeves: email@example.com; Christine Heim: firstname.lastname@example.org; Elizabeth M Maloney: email@example.com; Laura Solomon Youngblood: firstname.lastname@example.org; Elizabeth R Unger: email@example.com; Michael J Decker: firstname.lastname@example.org; James F Jones: email@example.com; David B Rye: firstname.lastname@example.org Received July 10, 2006; Accepted November 16, 2006. Abstract Background The etiology and pathophysiology of chronic fatigue syndrome (CFS) remain inchoate. Attempts to elucidate the pathophysiology must consider sleep physiology, as unrefreshing sleep is the most commonly reported of the 8 case-defining symptoms of CFS. Although published studies have consistently reported inefficient sleep and documented a variable occurrence of previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS. Methods This study recruited CFS cases and non-fatigued controls from a population based study of CFS in Wichita, Kansas. Participants spent two nights in the research unit of a local hospital and underwent overnight polysomnographic and daytime multiple sleep latency testing in order to characterize sleep architecture. Results Approximately 18% of persons with CFS and 7% of asymptomatic controls were diagnosed with severe primary sleep disorders and were excluded from further analysis. These rates were not significantly different. Persons with CFS had a significantly higher mean frequency of obstructive apnea per hour (p=.003); however, the difference was not clinically meaningful. Other characteristics of sleep architecture did not differ between persons with CFS and controls. Conclusion Although disordered breathing during sleep may be associated with CFS, this study generally did not provide evidence that altered sleep architecture is a critical factor in CFS. Future studies should further scrutinize the relationship between subjective sleep quality relative to objective polysomnographic measures. Background Chronic fatigue syndrome (CFS) presents a diagnostic and management challenge. A case of CFS is defined by: 1) clinically unexplained, persistent or relapsing fatigue of at least 6 months' duration that is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities, and; 2) concurrent occurrence of at least 4 accompanying symptoms (unusual post-exertional malaise, unrefreshing sleep, significant impairment in memory/concentration, headache, muscle pain, joint pain, sore throat and tender lymph nodes) . No characteristic physical signs or diagnostic laboratory abnormalities herald CFS. Thus, diagnosis depends on evaluation of self-reported symptoms and ruling out medical or psychiatric conditions that could cause the illness. Similarly, the pathophysiology of CFS remains inchoate and as yet there is no definitive treatment; rather, therapy (both pharmacologic and nonpharmacologic) is directed toward relieving symptoms and improving function . Attempts to elucidate the pathophysiology of CFS must consider sleep physiology. Unrefreshing sleep is the most common of the 8 CFS-defining symptoms, reported by 88 to 95% of cases identified in population studies [3,4] and 70 to 80% of patients in clinic-based studies . Most of the postulated etiologies of CFS (e.g., infection, immune and hormone perturbations) affect sleep; and, conversely, primary sleep disorders, sleep deprivation and experimental disruption of sleep produce many of the features of CFS (e.g., fatigue, impaired cognition, joint pain and stiffness) [7-10]. Indeed, untreated primary sleep disorders, such as sleep apnea and narcolepsy, preclude diagnosis of CFS [1,11]. The aforementioned issues raise a central question. Does CFS account for the accompanying sleep disturbances or does an underlying sleep abnormality result in or contribute to CFS? Studies of sleep in persons identified with CFS through tertiary care clinics have not contributed substantially to answering this question [6,12-16]. Although previous studies have consistently reported inefficient sleep and documented a varying occurrence of previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS. As with many studies of CFS, published evaluations of sleep pathology have not uniformly applied the case definition of CFS and often lack appropriate comparison groups. People with CFS use a number of prescription and over the counter medications that affect sleep ; yet most studies do not mention whether or not medications have been considered. Finally, we are aware of no published studies of CFS that have utilized multiple-night polysomnography, nor are we aware of any published studies that address sleep pathology in a population-based sample of persons with CFS. Because an overwhelming majority of persons with CFS remain undiagnosed [4,18], results of studies on CFS patients identified through physician practices may not be generalizable. The objective of this study was to describe clinical and polysomnographic sleep characteristics of persons with CFS identified from the general population of Wichita, Kansas , compared to non-fatigued controls matched for sex, race, age, and body mass index who were randomly selected from the same population. All study participants were admitted to a research ward in Wichita for 2 days . They underwent a complete physical and psychiatric evaluation, their medications were reviewed and they completed 2-overnight polysomnographic studies and a multiple sleep latency (MSLT) evaluation. This report evaluates associations of sleep disorders and variations in sleep architecture with CFS. Methods Participants This study adhered to U.S. Department of Health and Human Services human experimentation guidelines and received Institutional Review Board approval from the CDC and collaborating institutions. All participants gave informed consent. Between January and July 2003, we conducted a 2-day in-hospital study of adults identified with CFS from the general population of Wichita . The in-hospital study enrolled people who had participated in the 1997 through 2000 Wichita Population-Based CFS Surveillance Study . Participants in the in-hospital study were fatigued adults with medically/psychiatrically unexplained chronic fatigue identified during the surveillance study. Fifty-eight had been diagnosed at least once with CFS and 59 had unexplained chronic fatigue that was not CFS. Controls were randomly selected from the cohort who participated throughout surveillance, who did not have medical or psychiatric exclusions, and who had not reported fatigue of at least 1-month duration; they were matched to CFS cases on sex, age, race/ethnicity, and body mass index. Upon admission to this study, subjects were reevaluated for CFS symptoms and exclusionary medical and psychiatric conditions (discussed below). The 43 who, at the time of the in-hospital study, met 1994 criteria for CFS (discussed below) comprise the cases in this report. Controls are 43 individuals who had never reported fatigue during the surveillance study, who were not fatigued at the time of this in-hospital study and who had no exclusionary medical or psychiatric condition identified at the time of study (following section). Because current classification of CFS was not completely in accord with recruitment classification, strict matching was not maintained, though cases and controls were demographically comparable. Thirty-six (84%) of the 43 with CFS and 38 (88%) of the 43 controls were women; most (40 CFS and 42 controls) were white; their mean ages were 50.6 and 50.3 years, respectively; and body mass index was 29.4 and 29.3, respectively. Assessment and classification of CFS Subjects who agreed to participate were admitted to a Wichita hospital research unit for 2 days. Subjects brought all their current medications so that clinic staff could record this data and maintain medication profiles throughout the study. To identify medical conditions specified by the case definition as exclusionary for CFS [1,11], participants provided a standardized past medical history, a review of current medications, underwent a standardized physical examination, and provided blood and urine for routine analysis [1,11]. To identify psychiatric conditions exclusionary for CFS, licensed and specifically trained psychiatric interviewers administered the Diagnostic Interview Schedule for current Axis I disorders . Exclusionary psychiatric illnesses specified by the case definition were current melancholic depression, current and lifetime bipolar disorder or psychosis, substance abuse within 2 years and eating disorders within 5 years. A panel of physicians and psychiatrists/ psychologists reviewed this information and identified subjects with disorders exclusionary for the diagnosis of CFS. Subjects with no exclusionary conditions were considered to be CFS if they met empirically measured parameters  of the 1994 CFS case definition . Non-fatigued controls met none of the parameters. Medication use As noted, clinic staff reviewed all current (prescription and over the counter) medications that study participants were taking. Study investigators (DBR, MJD, CH, JFJ, WCR), and other Emory University Department of Psychiatry and Behavioral Sciences collaborators, reviewed all medications and classified them as affecting (inducing sleep, inhibiting sleep or with mixed effects) or not affecting sleep. Those classified as affecting sleep included analgesics (e.g., hydrocodone, Lortab, oxycodone, Propoxyphene), antidepressants (e.g., Celexa(tm), amitriptyline, imipramine, Lexapro(tm), Wellbutrin(tm), Effexor, Prozac(tm), Zoloft(tm), Paxil(tm), fluoxetine), antianxiety (Alprazolam), antihistamines (e.g., diphenhydramine, chlorpheneramine, benadryl, promethazine), decongestants (e.g., pseudoephedrine, guaifenesen), anticonvulsants (e.g., Topamax, Neurotin, clonazepam), anti-sleep phase disorder (melatonin), blood pressure controlling (e.g., Clonidine, Proamatine), antipsychotics (e.g., Seroquel, Zyprexa, Fluvoxamine), stimulants (e.g., methylphenidate, Provigil), peristaltic stimulants (Metoclopramide), and muscle relaxants (cyclobenzaprine). Medications affecting sleep were handled as a binary measure (i.e., they used or did not use one or more of those named above). Analyses took into account use of sleep affecting medications, as noted below. Polysomnographic and Multiple Sleep Latency Techniques Nocturnal polysomnography and daytime multiple sleep latency testing (MSLT) were conducted in a 4-bed laboratory established at Wesley Medical Center, Wichita, KS, and consisted of polysomnography on night #1, MSLT the following day and another polysomnography on night #2. Patients were asked to arrive 3 hours before their typical bedtime on Night 1 to allow adequate time for electrode application and standard biocalibrations. "Lights out" and "lights on" time were 22:00 and 07:00, respectively. The daytime MSLT testing schedule was adjusted for other measures being collected; MSLT began at 11:00 and consisted of three additional naps at 13:00, 15:00, and 17:00. Electrophysiological measures of wakefulness and sleep were acquired and recorded with the Flaga/Medcare N7000 digital polysomnographic system on a Windows XP platform using proprietary software (Flaga/Medcare Somnologica Studio). We employed a sampling rate of 256 Hz to allow for Fast Fourier Transform of EEG signals. Standard gold cup electrodes were employed for recording of EEG, EOG, and EMG for sleep staging and appreciation of sleep architecture. Respiration was measured with inductance plethysmography-like belts placed around the chest and abdomen. A pressure transducer, positioned in close approximation to the nares provided indices of airflow. A pulse oximeter probe was applied to either the right or left index finger, to measure arterial oxygen saturation (Sa02). Electrocardiogram (ECG) was recorded with standard snap electrodes (NeuroSupplies, Waterford, CT). The following signals were recorded: central (C_3-A_2//C_4-A_1) and occipital (O_1-A_1//O_2-A_2) EEG, left and right monopolar EOG, surface mentalis EMG, ECG (modified V3), respiratory airflow and effort and surface EMG from the right and left anterior tibialis. The polysomnographic outcome variables used in our analyses included: total sleep time (TST) (in minutes), sleep efficiency (% of time spent in bed asleep), the percentage of TST spent in non-Rem (NREM) and REM sleep, sleep latency (in minutes) to three consecutive epochs of sleep, and REM Latency, defined as the time between the first epoch of any stage of sleep and the first epoch of REM-sleep. Brief arousals were scored following criteria set forth by the American Academy of Sleep Medicine, and the number of arousals expressed as a rate per hour of sleep adjusted for TST. Periodic leg movements both with and without accompanying arousals, were scored according to conventional criteria , and expressed as an index of the rate of leg movements per hour of sleep, and a separately derived index of those accompanied by an American Academy of Sleep Medicine -defined arousal . Daytime sleepiness was measured with the MSLT, which has demonstrated objective sensitivity to the effects of sleep deprivation, sleep fragmentation, sleep restriction, insufficient sleep, hypersomnia, and in disease states such as sleep apnea and narcolepsy [24-26]. Multiple sleep latency tests were performed and scored according to standard guidelines with the exception that four naps were recorded at 11:00, 13:00, 15:00, and 17:00. The mean sleep latency on the MSLT was defined as the mean time from lights out to the first 30-second epoch scored as sleep. A sleep onset REM was defined as one or more epochs of REM sleep occurring within 15 minutes of the first epoch scored as sleep. Mean MSLT values of 5 or less are considered to represent pathological sleepiness, scores between 5â€“10 are consistent with a degree of daytime sleepiness. Scores of 10 and above are considered normative and believed to denote a lack of daytime sleepiness. Because mean values on the MSLT may adversely be affected by a spurious sleep latency on a single nap opportunity  possibly due to what might be perceived as stressful inter-nap activities , median values were also computed for each subject. Interpretation of polysomnography data Polysomnography data were scored by an Emory University registered polysomnology technologist (blinded as to subjects' fatigue classification). An Emory University Department of Neurology American Board of Sleep Medicine certified physician (DBR), also blinded to the subjects' fatigue classifications, interpreted results. The polysomnology technologist manually scored each recording in 30 second epochs as wake, NREM, Stages 1-4 sleep, or rapid eye movement (REM) sleep. Criteria for scoring respiratory variables were based upon those of the Sleep Heart Health Study . Briefly, apnea was scored if airflow decreased to less than or equal to 25% of the immediately preceding baseline for a period of at least 10 seconds. Hypopnea was scored if either airflow or thoracic-abdominal excursion decreased by at least 30% of baseline, for at least 10 seconds, with a concomitant reduction in SaO2 of 4% or greater. The Respiratory Distress Index (apneas + hypopneas corrected for hour of sleep) was derived from these scored events. To determine the technologist's level of reproducibility, 12 randomly selected studies were scored twice, with at least a six-week interval separating the original scoring and the repeat scoring. Comparison between original and repeat scorings with Kappa analyses yielded a Kappa coefficient of 0.88. Diagnostic criteria for sleep disorders exclusionary for CFS The CFS case definition specifies sleep apnea and narcolepsy as conditions that could explain fatigue and symptoms of CFS and therefore exclude the diagnosis of CFS [1,11]. Obstructive sleep apnea Obstructive sleep apnea was considered clinically significant and therefore exclusionary if an individual's Respiratory Distress Index was =< 30 on either night, or was between 10 and 30 and the individual had an abnormal mean sleep latency of < 5 minutes during MSLT . Narcolepsy Narcolepsy was diagnosed if 2 out of 4 MSLTs were positive for REM sleep and mean sleep onset during MSLT was < 5 minutes . Statistical analysis Data were analyzed by Systat (Systat Software Inc, Richmond, CA) and SAS (SAS Institute Inc, Cary, NC). we used A 2-factor analysis of variance using PROC GLM was to measure the associations between case status and medication use (yes/no) with polysomnographic variables. Log transformed values of polysomnographic variables were used when necessary to satisfy the assumption of normally distributed outcomes. Mean values for each polysomnographic variable were adjusted for medication use using the least square method (LSMEANS). All mean values presented in this paper represent arithmetic means. We also used standard and exact logistic regression models to compute odds ratios as estimates of relative risks and 95% confidence intervals for CFS associated with dichotomous polysomnographic variables (cut-offs based on 25th or 75th percentiles). Measurement of clinical sleep variables included a high number of zero values. Zero-inflated Poisson Regression was used to regress case status and medication use (yes/no) on continuous values of clinical sleep variables. For this final analysis, we used SAS version 9.0 (PROC NLMIXED) and an inflation probability determined by the regressors. Analyses were also performed excluding participants taking medications that affect sleep. Estimates were unchanged when analyses excluded participants taking sleep-affecting medications. For this reason, the results presented in this report do not exclude participants taking such medications, but rather adjust for them in the analysis. We used the chi2 statistic or Fisher's exact test to evaluate associations between CFS and dichotomous variables. Results Primary sleep disorders Eleven study participants had sleep disorders exclusionary for CFS (obstructive apnea n=8, narcolepsy n=3). Persons with CFS had a higher frequency of exclusionary sleep disorders (8 of 43, 18.6%) than non-fatigued controls (3 of 43, 7%), but the difference was not statistically significant (p=.16). The remainder of this presentation considered the remaining 35 individuals with CFS and 40 controls. Sleep architecture and MSLT There were no statistically significant differences in standard polysomnographic measurements between those with CFS and controls on either night 1 or night 2. As expected, total sleep time increased in both groups between nights 1 and 2; latency to sleep onset and to REM onset decreased in both groups; and, waking after sleep onset was less common in both groups on night 2 (data not shown). As night 1 was considered to be an adaptation night, data is shown for night 2 (Table 1). Mean values, adjusted for medication use, did not differ between participants with CFS and non-fatigued controls. Interestingly, regardless of case status, medication use was independently associated with both REM latency and Stage 1 % total sleep time. Both REM latency and Stage-1 percent of total sleep time were significantly longer in study participants who reported using any sleep medications at the time of the study (P=.02, P=.01, respectively). In addition to comparing polysomnographic measurements as continuous variables between people with CFS and non-fatigued controls, we used regular and exact logistic regression to examine possible associations. We dichotomized measurements based on 25th and 75th percentiles among non-fatigued controls. As with the previous analyses there were no significant differences (data not shown). Virtually identical results were obtained when analysis was restricted to subjects who did not use sleep-altering medications. Finally, evaluation of multiple sleep latency testing studies yielded similar distributions of classifications; (39% normal, 35% borderline and 26% abnormal) between CFS and controls. Disordered breathing and periodic leg movements during sleep Subjects with CFS had significantly more episodes of obstructive apnea and a higher Respiratory Distress Index than did the non-fatigued controls (Table 2). Nonetheless, the difference between the groups in mean obstructive episodes per hour of total sleep was not of a magnitude recognized to have a clinical impact. All other measures of disordered breathing and periodic leg movements were not different between the two groups. Use of medications affecting sleep was independently associated with a higher rate of hypopnea and leg movements episodes per hour, after adjusting for case status (P=.03, P=.05, respectively). However, use of sleep altering medication was associated with a lower rate of obstructive apneic episodes per hour (P <.0001). Discussion To our knowledge, this represents the most comprehensive polysomnographic analyses of a community sample of rigorously evaluated people with CFS and frequency-matched non-fatigued controls. There were no significant differences in rates of primary sleep disorders between CFS cases and NF controls. Thus, in spite of additional attention to methodological issues, our findings are in agreement with prior studies of CFS patients identified through clinical referral [6,12-16]. Similarly, there were no differences in any measured sleep parameters, with the exception of the frequency of obstructive apnea per hour of nighttime sleep and these differences were not clinically meaningful. While subtle breathing problems during sleep might plausibly contribute to CFS, the most striking finding of this study in fact is the absence of readily identifiable differences in objective, polysomnographically defined, sleep parameters between subjects with CFS and non-fatigued controls. Similarly, there were no differences between persons with CFS and non-fatigued controls with respect to daytime multiple sleep latency tests. The lack of differences in overnight sleep parameters and MSLT is in contrast to the participants' self-reported symptoms. For example, 97% of persons with CFS in this study reported unrefreshing sleep compared with 20% of controls. As noted by others, persons with CFS may suffer from an element of sleep-state misperception . Future studies should further scrutinize the association between subjective sleep quality and objective polysomnographic results in persons with CFS. Disorders of sleep were common in both CFS cases and controls in this study. Indeed primary sleep disorders that may respond to therapy were identified in 13% of the overall study population. These findings were unexpected; as the population-based nature of the study eliminated referral bias and potential participants were excluded from the study of they reported diagnosed narcolepsy or sleep apnea disorders during screening interviews. Despite this, sleep apnea and narcolepsy of clinically significant severity were identified in 11 participants, requiring their exclusion from the study. As participants with sleep disorders were not identified until polysomnographic studies were performed, it is arguable that in clinical situations, referral of subjects with unexplained fatigue to a sleep laboratory should be considered in an effort to identify disorders that may respond to intervention. In research settings case ascertainment does not usually include formal sleep studies. Thus, the potential impact of including subjects with primary sleep disorders in the CFS diagnosis should be considered when interpreting results from such studies, and when designing CFS studies. Finally, MSLTs were borderline or abnormal in 60% of subjects. This may be attributed to the occurrence of sleep disorders in our study population, or to environmentally induced sleep disruption occurring during the night preceding the MSLT. The study has several weaknesses that should be considered while evaluating the results. While one of the largest studies identifying CFS cases and NF controls from the general population to date, the small numbers of identified subjects with current CFS may not be sufficient to identify small but biologically significant differences in sleep architecture. Second, our subjects spent two nights in the sleep lab (to allow accommodation) and (although adequate to detect primary sleep disorders) this may not produce an accurate picture of subtle nocturnal sleep behaviors. Moreover, sleep-altering medications were frequently used by both CFS cases and controls and their use was much more common among CFS cases. Some of these medications have opposite effects on sleep and we chose to lump them a sleep-altering. While we employed statistical corrections for their use, may have been inadequate to fully correct for the varied impact of the different formulations. It should nonetheless be noted that stratified analyses restricted to those without sleep-altering medications yielded similar findings compared to the total sample, although the greatly reduced numbers further limited the power of the examination. Finally, the median duration of CFS in the Wichita population was 7.3 years ; thus, findings in this study of prevalent cases may not be applicable to those with shorter illness duration. Conclusion In conclusion, although this study evaluating associations between sleep physiology and CFS addressed the major limitations and methodological issues of previous studies, we could not confirm statistically significant associations between sleep parameters and CFS. Sleep abnormalities therefore are an unlikely contributor to the pathophysiology of CFS and the illness may include sleep-state misperception. However, 18% of persons with CFS had previously unrecognized clinically severe apnea or narcolepsy, demonstrating the importance of evaluating persons with otherwise unexplainable chronic fatigue for sleep disorders. Additional, sufficiently powered, studies with CFS cases identified from the population should be conducted. Abbreviations used CDC - U.S. Centers for Disease Control and Prevention CFS - chronic fatigue syndrome EEG - electroencephalogram EKG - electrocardiogram EMG - electromyography EOG - electrooculogram MSLT - multiple sleep latency testing NREM - non-REM REM - rapid eye movement TST - total sleep time Competing interests The author(s) declare that they have no competing interests. Authors' contributions WCR and CH were principal investigators of the study. WCR, CH, ERU, LSY, JFJ, and MJD designed the study protocol and supervised data collection during the study. MJD designed sleep protocols, trained sleep technicians, and supervised sleep studies. WCR and EMM were responsible for statistical analysis. DBR interpreted polysomnographic data and derived clinical sleep diagnoses. All authors contributed to interpretation of data and writing the manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2377/6/41/prepub Acknowledgements This study was fully funded by the US Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency. Marjorie Morrissey and Sandy Henion, Abt Associates, supervised daily study operations. Daisey Lee, CDC, trained and supervised study staff concerning collection and processing of biologic specimens. J. Max Beck, Emory University School of Medicine, trained and supervised study sleep lab technicians and scored polysomnographic data. Jin-Mann Lin provided statistical review. Tables Table 1. Analysis of Sleep Architecture in CFS and Controls, Measured on Night 2 and Adjusted for Medication Use -------------------------------------------------------------------------------- CFS NF P-Value** n=35 n=40 Adjusted Mean* Adjusted Mean* -------------------------------------------------------------------------------- Total sleep time (min) 400.3 407.9 0.52 Sleep period time (min) 453.8 457.8 0.79 Latency to sleep onset (min) 21.3 17.1 0.47 REM latency (min) 98.4 106.8 0.40 Sleep efficiency (%) 88.3 90.2 0.32 Wake after onset (min) 53.8 44.0 0.69 Wake % Sleep Period 11.7 9.8 0.72 # Arousals 105.7 110.2 0.81 Arousal index 15.9 16.3 0.82 Stage 1 (% TST) 9.6 9.5 0.79 Stage 2 (% TST) 48.2 50.8 0.28 Stage 3/4 (% TST) 19.9 17.4 0.20 REM (% TST) 22.3 23.3 0.98 -------------------------------------------------------------------------------- * Mean values adjusted for medication use (yes/no) ** P-values generated using 2-factor analysis of variance Table 2. Distribution of Breathing and Movement Abnormalities During Sleep -------------------------------------------------------------------------------- Clinical Sleep Variable CFS NF P-Value* n=35 n=40 -------------------------------------------------------------------------------- Hypopnea Mean event/hr 2.66 1.79 0.24 Range (0.00-16.03) (0.00-14.66) Obstructive Apnea Mean event/hr 0.94 0.59 0.003 Range (0.00-12.11) (0.00-10.70) Central Apnea Mean event/hr 0.36 0.15 0.18 Range (0.00-2.44) (0.00-1.89) Mixed Apnea Mean event/hr 0.14 0.15 0.58 Range (0.00-2.28) (0.00-3.15) Snore Index Mean 5.31 4.57 0.95 Range (0.00-27.50) (0.00-34.30) Respiratory Distress Index Mean 4.11 2.69 0.009 Range (0.10-21.21) (0.00-20.35) Periodic Leg Movements Mean events/hr 4.42 4.56 0.35 Range (0.00-25.74) (0.00-39.37) Periodic Leg Movements with Arousals Mean events/hr 1.03 0.87 0.62 Range (0.00-11.57) (0.00=7.09) -------------------------------------------------------------------------------- References 1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994;121:953-9. 2. Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry. 2003;160:221-23 3. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S. A community-based study of chronic fatigue syndrome. Arch Int Med. 1999;18:2129-2137 4. Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Intern Med. 2003;163:1530-6. 5. Morris R, Sharpe M, Sharpley A, Cowen P, Hawton K, Morris J. Abnormalities of sleep in patients with the chronic fatigue syndrome. Br Med J. 1993;306:1161-1164. 6. Buchwald D, Pascualy R, Bombardier C, Kith P. Sleep disorders in patients with chronic fatigue. Clin Infect Dis. 1994;18:S68-72. 7. Cameron C. A theory of fatigue. Ergonomics. 1973;16:633-648. 8. Myles WS. Sleep deprivation, physical fatigue and the perception of exercise intensity. Med Sci Sports Exerc. 1985;17:580-584. 9. Horn JA. Sleep loss and divergent thinking ability. Sleep. 1988;11:528-536. 10. Samkoff JS, Jacques CH. A review of studies concerning effects of sleep deprivation and fatigue on residents' performance. Acad Med. 1991;66:687-693. 11. Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2003;3:25. 12. Krupp LB, Jandorf L, Coyle PK, Mendelson WB. Sleep disturbance in chronic fatigue syndrome. J Psychosom Res. 1993;37:325-331. 13. Sharpley A, Clements A, Hawton K, Sharpe M. Do patients with pure chronic fatigue syndrome (neurasthenia) have abnormal sleep? Psychosom Med. 1997; 59:592-596. 14. Le Bon O, Fischler B, Hoffmann G, Murphy JR, De Meirleir K, Cluydts R, Pele I. How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome. Sleep Res Online. 2000;3:43-48. 15. Ball N, Buchwald DS, Schmidt D, Goldberg J, Ashton S, Armitage R. Monozygotic twins discordant for chronic fatigue syndrome objective measures of sleep. J Psychosom Res. 2004;56:207-212. 16. Fossey M, Libman E, Bailes S, Baltzan M, Schondorf R, Amsel R, Fichten CS. Sleep quality and psychological adjustment in chronic fatigue syndrome. J Behav Med. 2004;27:581-605. 17. Jones J, Nisenbaum R, Reeves WC. Medication use by persons with chronic fatigue syndrome. BMC Hlth Quality of Life Outcomes. 2003;1:74. 18. Solomon L, Reeves WC. Factors influencing the diagnosis of chronic fatigue syndrome. Arch Intern Med. 2004;164:2241-2245. 19. Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome - a clinically empirical approach to its definition and study. BMC Medicine. 2005;3:19. 20. Robbins, L.; Cottler, L.; Bucholz, K.; Compton, W. Diagnostic Interview Schedule for DSM-IV (DIS-IV). St. Louis, MO: Washington University; 1995. 21. Whitney CW, Gottlieb DJ, Redline S, Norman RG, Dodge RR, Shahar E, Surovec S, Nieto FJ. Reliability of scoring respiratory disturbance indices and sleep staging. Sleep. 1998;21:749-757. 22. American Sleep Disorders Association Atlas Task Force. Recording and scoring leg movements. Sleep. 1993;16:749-759. 23. American Sleep Disorders Association Atlas Task Force. EEG arousals: scoring rules and examples. Sleep. 1992;15:173-184. 24. Carskadon M. Guidelines for the multiple sleep latency test (MSLT) A standard measure of sleepiness. Sleep. 1986;9:519-524. 25. Carskadon MA, Dement W. The multiple sleep latency test: what does it measure? Sleep. 1982;5:S67-S72. 26. Arand D, Bonnet M, Hurwitz T, Mitler M, Rosa R, Sangal R. The clinical use of the MSLT and MWT. Sleep. 2005;28:123-144. 27. Benbadis SR, Perry M, Wolgamuth BR, Turnbull J, Mendelson WB. Mean versus median for the multiple sleep latency test. Sleep. 1995;18:342-345. 28. Bonnet M, Arand D. Activity, arousal and the MSLT in patients with insomnia. Sleep. 2000;23:205-212. 29. International Classification of Sleep Disorders Diagnostic and Coding Manual, Revised. Rochester, MN: American Sleep Disorders Association; 1997. 30. Watson NF, Kapur V, Arguelles LM, Goldberg J, Schmidt DF, Armitage R, Buchwald D. Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome. Sleep. 2003; 26:324-328. -------- (c) 2006 BMC [Return to top] ------------------------------ Date: Wed, 27 Dec 2006 13:12:05 +0100 From: "Dr. Marc-Alexander Fluks" <email@example.com> Subject: RES,NOT: Premorbid and currently physical activity in CFS Source: BMC Psychiatry Vol 6. p 53 Date: November 13, 2006 URL: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17101056 A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome -------------------------------------------------------------------------- Wayne R Smith,(*,1) Peter D White,(2) and Dedra Buchwald(1) 1 Departments of Psychiatry and Behavioral Sciences (W.S) and Medicine (D.B), University of Washington, Seattle, USA 2 Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Barts and the London, Queen Mary University of London, UK (P.D.W) * Corresponding author. Wayne R Smith: firstname.lastname@example.org; Peter D White: email@example.com; Dedra Buchwald: firstname.lastname@example.org Received June 13, 2006; Accepted November 13, 2006. Abstract Background Patients with chronic fatigue syndrome typically report high levels of physical activity before becoming ill. Few studies have examined premorbid and current activity levels in chronically fatigued patients. Methods In a case-control study, 33 patients with chronic, unexplained, disabling fatigue attending a university-based clinic specializing in fatigue were compared to 33 healthy, age- and sex-matched controls. Patients rated their activity levels before their illness and currently, using scales designed for this purpose. Controls reported their level of activity of 2 years previously and currently. Chi-square analyses, Student's t tests, and Wilcoxon signed rank tests were used in pair matched analyses. Results Compared to healthy controls, patients with chronic, unexplained fatigue rated themselves as more active before their illness (p=<0.001) and less active currently (p=<0.001). The patients also reported they currently stood or walked less than the controls (median [inter-quartile range]=4 [2-5] versus 9 [7.5-12] hours,p=<0.001), and spent more time reclining (median [inter-quartile range]=12 [10-16] versus 8 [8-9.5] hours,p=<0.001) These differences remained significant for the subset of patients who met strict criteria for chronic fatigue syndrome or fibromyalgia. Conclusion Patients with chronic, unexplained, disabling fatigue reported being more active before becoming ill than healthy controls. This finding could be explained by greater premorbid activity levels that could predispose to illness, or by an overestimation of previous activity. Either possibility could influence patients' perceptions of their current activity levels and their judgments of recovery. Perceived activity should be addressed as part of management of the illness. Background Chronic, unexplained, disabling fatigue is reported by up to 2.6 per cent of patients seeking health care . Chronic fatigue syndrome (CFS) is a more narrowly defined illness with prominent fatigue and at least 4 associated symptoms . Many CFS patients also suffer from fibromyalgia , a disabling condition characterized by chronic widespread pain, fatigue, and sleep disturbances . Individuals with CFS often perceive physical activity as more of an effort than healthy people , underestimate their cognitive and physical abilities [5-9], and are more aware of, and focused on, their internal physiological state [7,9,10]. Furthermore, CFS patients aspire to greater activity levels , and rate themselves as having been significantly more active  and "action-prone" before they became ill, than do control subjects ; "action-proneness" also increases with treatment . The high levels of physical activity reported by patients have been corroborated by their spouses, partners, or parents . The etiology of chronic, unexplained fatigue, CFS, and fibromyalgia remains unclear , but recent work suggests that these disorders may involve enhanced interoception [14,15]. Interoception is the perception of internal sensory phenomena, especially visceral perceptions . The biological underpinnings of interoception are only now being explored, but intriguing neuroimaging studies suggest that a discrete interoceptive cortex, the anterior insula, modulates this phenomenon . If interoception were altered in chronically fatigued individuals, this could affect their internal perception and, consequently, their perceived ability and capacity. To replicate previous findings and extend them to well-defined subgroups, we conducted a clinic-based, case-control study of fatigued patients, a large majority of whom suffered from CFS and/or fibromyalgia. We compared self-reported premorbid and current activity levels of the patients and their healthy controls to address the following questions: 1) Do patients with chronic, unexplained, disabling fatigue, including the subsets with CFS and fibromyalgia, perceive their premorbid activity levels as higher than the current activity levels perceived by healthy matched controls? 2) Do patients with chronic, unexplained, disabling fatigue, including the subsets with CFS and fibromyalgia, perceive their current activity levels as lower than those perceived by healthy matched controls? Methods Subjects and Setting Patients were adults evaluated in a university-based referral clinic for chronic fatigue and pain. The clinic accepts both self- and physician-referred patients; individuals were not required to meet case definitions for either CFS or fibromyalgia to be evaluated. Patients underwent an intake evaluation that included a standardized physical examination, medical history, questionnaire on past and current symptoms, screening laboratory tests, and a structured psychiatric interview. A lay interviewer administered the National Institutes of Mental Health Diagnostic Interview Schedule Version III-A , a structured interview that assigns current and lifetime psychiatric diagnoses based on criteria established in the Diagnostic and Statistical Manual of Mental Disorders, 3rded. (Revised)  for somatization disorder, panic disorder, generalized anxiety disorder, major depression, dysthymia, and alcohol abuse/dependence. CFS and fibromyalgia were diagnosed according to the guidelines of the Centers for Disease Control and Prevention  and the American College of Rheumatology , respectively. Those who did not meet the CFS case definition met the criteria for idiopathic chronic fatigue . Fibromyalgia often co-occurred with idiopathic, chronic fatigue and CFS, as previously described . To recruit controls, we asked patients the following: "We would like to compare the activity levels of people with chronic fatigue to healthy people. If you have a healthy friend who would agree to complete [questions about activity] only, please fill out the information below. If possible, pick someone who is similar to you in terms of sex and age." In this way, 33 controls were recruited. The University of Washington Human Subjects Office reviewed and approved all clinic procedures and consent forms. Measures The questionnaire for this study was mailed along with an annual clinic newsletter. Non-responders were mailed the questionnaire a second time, followed by an attempt to gather the information by telephone. The questionnaire contained 4 items specifically asking about levels of activity [see Additional file 1]. Patients were asked to rate their typical levels of activity prior to becoming chronically fatigued and compare it to an average healthy person by using a 10-point scale (1=extremely low to 10=extremely high). Using the same scale, patients were also asked to rate their typical level of activity during the previous 7 days as compared to that of an average healthy person [see Additional file 1]. The other 2 items inquired about activity during the previous 24 hours. One instructed patients to estimate how many hours they had spent standing or walking, sitting, or reclining or lying down. The other asked if this level of activity was higher, lower, or average compared to their recent activity levels. For the healthy controls, the first of the 4 activity questions was revised to ask about their activity as of 2 years ago compared to the average healthy person. The two-year recall period was chosen because the mean fatigue duration reported by patients evaluated in the clinic was nearly 2 years. The remaining 3 questions were identical to those given to patients. No other information was collected from the control subjects. Statistical Analyses Respondents were classified as patients or their friends (i.e., controls). To examine between-group differences, chi-square analyses were used for dichotomous variables and interval variables were compared by using Student's t test when data were normally distributed, and by using Wilcoxon signed rank tests when data were not normally distributed, always using pair-related comparisons. Results Demographic and Clinical Characteristics Overall, 462 of 678 (68%) consecutively evaluated clinic patients completed the questionnaire. Of these 462, 44 patients had a friend who completed the 4 activity items; these 44 patients and their friends constituted the study sample. The 44 patients tended to be older than the larger clinic population (43.6 vs. 39.6 years, p=0.02), but did not differ in gender (84% vs. 74% female), marital status (50% vs. 50% married), duration of fatigue (5.9 vs. 5.2 years), or proportion diagnosed with CFS (57% vs. 56%) or fibromyalgia (21% vs. 23%). Likewise, our study sample had rates similar to those of all clinic patients for lifetime diagnoses of alcohol abuse (14% vs. 16%), major depression (69% vs. 65%), dysthymic disorder (26% vs. 22%), generalized anxiety disorder (17% vs. 24%), panic disorder (26% vs. 19%), and somatization disorder (29% vs. 21%). However, they tended to be diagnosed more often with melancholic depression (11% vs. 5%, p=0.02). Of the 44 fatigued clinic patients, we limited our analysis to the 33 who met criteria for CFS, idiopathic chronic fatigue, and/or fibromyalgia. The other 11 patients were excluded for medical or psychiatric conditions that could explain their fatigue . The demographic and clinical characteristics of the 33 patients and their 33 matched controls are presented in Table 1. Patients and controls did not differ in age (p=0.22) or sex (p=0.50). Of the 33 patients with chronic, unexplained, debilitating fatigue, 25 (76%) met the criteria for CFS, 7 (21%) met the criteria for idiopathic chronic fatigue, and 9 (27%) met criteria for fibromyalgia. Only 1 had fibromyalgia alone, without CFS or idiopathic chronic fatigue. Table 2 illustrates that, compared with their matched controls, the 33 patients rated themselves as more active before the onset of illness (Z score -3.05, p=0.002) and less active currently (Z score -4.72, p<0.001). More specifically, in the previous 24 hours, patients reported standing or walking 5 hours less than their healthy friends (Z score -4.39, p<0.001) and lying or reclining 4 hours more (Z score -4.29, p<0.001), with no differences in the time spent sitting (Z score -0.86, p=0.39). For both patients and controls, the activity reported during the previous 24 hours represented a typical day (Z score -1.12, p=0.26). Lastly, we considered premorbid and current activity levels in the CFS and fibromyalgia subgroups. These results are not displayed in the table. The median rating (and interquartile range) for premorbid activity level was 9 (8-9.5) among the 25 CFS patients versus 8 (7-9) among controls (Z=-2.18, p=0.03). Among CFS patients, the median rating (and interquartile range) for current activity was 3 (2-5) versus 8 (6.5-8.5) among controls (Z=-4.23, p<=0.001). In the 9 patients with fibromyalgia, the median rating (and interquartile range) for premorbid activity was 9 (8-9.5) versus 8 (7-8.5) among controls (Z=-2.46, p=0.01), and the current activity was lower: 4 (1.5-4.5) versus 7 (6-8) (Z=-2.53, p=0.01). Discussions and Conclusion We have confirmed the previous finding that patients with CFS report higher levels of premorbid activity than do healthy control subjects, and we have extended this finding to include patients with chronic, unexplained fatigue and fibromyalgia. As expected, both CFS and fibromyalgia patients reported less current activity than healthy controls, but small sample sizes and Bonferroni's corrections resulted in borderline significance for some of the sub-group comparisons. Our findings are congruent with those of 3 retrospective studies reporting that CFS patients perceived themselves as more active before their illness began than healthy controls [6,11,21]. In contrast, the only prospective cohort study of risk factors for CFS found that sedentary behavior at 10 years of age doubled the risk of self-reported CFS in adulthood . Since no prospective data exist on the actual pre-morbid activity levels of individuals who later suffer a fatiguing illness, it is unclear whether our data reflect pre-morbid excessive activity, or alternatively, illness-related alterations in the perception or recall of premorbid activity. One of the "altered-perception" hypotheses involves sensitized interoception. CFS and fibromyalgia have been postulated to be central nervous system hypersensitivity disorders, characterized by enhanced or sensitized interoception [15,23,24]. A central nervous system hypersensitivity disorder would be consistent with patients' reports of disturbed cognition and concentration and sensitivity to exercise, chemicals, and odors [5,7-9,25]. Support for this explanation comes from investigations that have described discrepancies between subjectively reported impairments and objective measures of activity [26,27], effort with exercise [5,28,29], sleep quantity and quality , and cognitive symptoms and cognitive abilities [8,9,25,29]. Of interest, humans appear to have a distinct cortical image of homeostatic afferent activity that reflects all aspects of the physiological condition of all tissues of the body. This interoceptive system is linked to the autonomic nervous system, but is distinct from the exteroceptive system that reflects somatic motor activity. The primary interoceptive representation in the anterior insula cortex engenders distinct bodily sensations, including pain, temperature, itch, sensual touch, muscular and visceral sensations, and vasomotor activity . Neuroimaging studies relevant to interoception and the feeling of self are rapidly accumulating and underscore the biological underpinnings of this phenomenon [16,17]. Lastly, perception and consequent ability, as well as external agents, may influence patients' beliefs. For example, when benign chemicals were given blindly to people with CFS and multiple chemical sensitivities, individuals who believed they were getting the chemical performed poorly on cognitive tests, whereas cognitive function did not differ between those who received the chemicals and those who did not . In another investigation, fatigued people and CFS patients had greater doubts about actions and more concerns over mistakes than controls [32,33]. Such self-critical personality traits might diminish judgments of current abilities and exaggerate previous abilities. This study has several limitations. First, our sample was drawn from consecutive patients evaluated at a referral clinic. Because patients who present to specialty clinics probably differ from community samples or those drawn from primary care clinics on important variables , our results may not be generalizable to other settings or other fatigued patients. Second, because our measures were obtained at only one time point, we do not know if these activity levels represent sustained or transitory levels. Similarly, to minimize the burden on the control subjects, we did not ask them to provide detailed demographic information. Third, our measures of activity were brief and not validated against actigraphy or even the report of the friends, and therefore are subject to the usual biases associated with self-reported health-related behavior, including the propensity to over-value pre-illness functioning. Fourth, we could not verify objectively that the selected friend was actually healthy, yet the presence of chronic conditions would decrease the differences between groups and thus render our findings less significant. Lastly, only a small fraction of the total clinic population obtained data from a friend. The small sample that we examined, however, was similar in most respects to the larger clinic population. In conclusion, we have replicated previous work showing that CFS patients report greater premorbid activity levels than healthy controls, and we have extended these observations to more rigorously defined fatiguing conditions. These findings suggest that at this point clinical management should address both perceptions of symptoms as well as actual activity levels. Cognitive behavior therapy and graded exercise programs are designed to change both dimensions, and have been shown to be efficacious treatments for the majority of adult, ambulant CFS patients [35,36]. Other innovative interventions that can be easily implemented and are acceptable to patients are also needed. List of Abbreviations CFS = chronic fatigue syndrome SD = standard deviation Competing interests The author(s) declare that they have no competing interests. Authors' contributions DB designed and implemented the intervention, and edited the manuscript. WRS managed data flow, undertook preliminary analyses, and edited and revised the manuscript. PDW undertook final analyses and wrote majority of the manuscript. All authors read and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-244X/6/53/prepub Supplementary Material Additional File 1 Chronic Fatigue Activity Questionnaires. Fours questions completed by patients followed by the corresponding four questions completed by the matched controls. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1647270&blobname=1471-244X-6-53-S1.doc Acknowledgements Supported in part by grant U19 AI38429 from the National Institute of Allergy and Infectious Diseases (Dr. Buchwald). Tables Table 1. Demographic and clinical characteristics of patients and healthy control subjects -------------------------------------------------------------------------------- Characteristic Patients Controls -------------------------------------------------------------------------------- Demographic Number 33 33 Age, mean years (SD) 45.6 (11.8) 44.1 (13.1) Female, n (%) 26 (79) 28 (85) Clinical CFS criteria met, n (%) 25 (76) - Idiopathic chronic fatigue 7 (21) criteria met n (%) Fibromyalgia criteria met1 9 (27) - n (%) -------------------------------------------------------------------------------- ^1 1 patient had fibromyalgia, but neither CFS nor idiopathic chronic fatigue. Table 2. Previous and current activity levels of patients and healthy control subjects -------------------------------------------------------------------------------- Characteristic Patients Controls -------------------------------------------------------------------------------- Previous activity level1,2, 9 (8-9.5) 8 (6.5-8.5)* median (IQR)3 Previous activity level, n (%) Level 1 0 0 Level 2 0 0 Level 3 0 1 (3) Level 4 1 (3) 1 (3) Level 5 0 2 (6) Level 6 1 (3) 4 (12) Level 7 3 (9) 5 (15) Level 8 8 (24) 12 (36) Level 9 12 (36) 5 (15) Level 10 8 (24) 3 (9) Last week's activity2, 3 (2-5) 8 (6-8)^+ median (IQR)3 Last week's activity, n (%) Level 1 5 (15) 0 Level 2 6 (18) 0 Level 3 7 (21) 1 (3) Level 4 4 (12) 2 (6) Level 5 5 (15) 3 (9) Level 6 3 (9) 4 (12) Level 7 1 (3) 5 (15) Level 8 2 (6) 11 (33) Level 9 0 4 (12) Level 10 0 3 (9) Last 24 hours' activities, median hours (IQR)3 Standing or walking 4 (2-5) 9 (7.5-12)^+ Sitting 6 (5-9) 6 (4-8) Reclining or lying down 12 (10-16) 8 (8-9.5)^+ Activity Level in Last 24 Hours, %^4 Higher than recently 6 24 Lower than recently 45 27 Average 49 48 -------------------------------------------------------------------------------- ^1 premorbid activity level for patients, activity level 2 years ago for friends; ^2 rated from 1 (extremely low) to 10 (extremely high); 3 interquartile range; 4 compared to recent levels. ^* p=<0.01 ^+ p=< 0.001 References 1. Wessely S, Chalder T, Hirsch S, Wallace P, Wright D. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. Am J Public Health. 1997;87:1449-55. 2. Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER, International Chronic Fatigue Syndrome Study Group. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Research. 2003;3:25. 3. Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med. 2001;134:868-81. 4. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lichtbroun AS, Masi AT, McCain GA, Reynolds WJ, Romano TJ, Russell IJ, Sheon RP. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: Report of the multicenter criteria committee. Arthritis Rheum. 1990;33:160-72. 5. Fulcher KY, White PD. Strength and physiological response to exercise in patients with the chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2000;69:302-7. 6. Riley MS, O'Brien CJ, McCluskey DR, Bell NP, Nicholls DP. Aerobic work capacity in patients with chronic fatigue syndrome. BMJ. 1990;301:953-6. 7. Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry. 2003;160:221-36. 8. Metzger FA, Denney DR. Perception of cognitive performance in patients with chronic fatigue syndrome. Ann Behav Med. 2002;24:106-12. 9. Vercoulen JH, Bazelmans E, Swanink CM, Galama JM, Fennis JF, van der Meer JW, Bleijenberg G. Evaluating neuropsychological impairment in chronic fatigue syndrome. J Clin Exp Neuropsychol. 1998;20:144-56. 10. Moss-Morris R, Chalder T. Illness perceptions and levels of disability in patients with chronic fatigue syndrome and rheumatoid arthritis. J Psychosom Res. 2003;55:305-8. 11. Van Houdenhove B, Onghena P, Neerinckx E, Hellin J. Does high "action- proneness" make people more vulnerable to chronic fatigue syndrome? A controlled psychometric study. J Psychosom Res. 1995;39:633-40. 12. Van Houdenhove B, Bruyninckx K, Luyten P. In search of a new balance. Can high "action-proneness" in patients with chronic fatigue syndrome be changed by a multidisciplinary group treatment? J Psychosom Res. 2006;60:623-5. 13. Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommnen H. Premorbid "overactive" lifestyle in chronic fatigue syndrome and fibromyalgia: an etiological relationship or proof of good citizenship? J Psychosom Res. 2001;51:571-6. 14. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002;46:1333-43. 15. White PD. What causes chronic fatigue syndrome? BMJ. 2004;329:928-9. 16. Craig AD. Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol. 2003;13:500-5. 17. Craig AD. Human feelings: why are some more aware than others? Trends Cog Sci. 2004;8:239-41. 18. Robins, LN.; Helzer, JE. Diagnostic Interview Schedule (DIS): version III-A. St. Louis: Department of Psychiatry, Washington University School of Medicine; 1985. 19. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (Revised). Washington DC: American Psychiatric Association; 1987. 20. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994;121:953-9. 21. MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK. A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med. 1996;100:548-54. 22. Viner R, Hotopf M. Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. BMJ. 2004;329:941. 23. Cameron OG, Minoshima S. Regional brain activation due to pharmacologically induced adrenergic interoceptive stimulation in humans. Psychosom Med. 2002;64:851-61. 24. Eriksen HR, Ursin H. Subjective health complaints, sensitization, and sustained cognitive activation (stress). J Psychosom Res. 2004;56:445-8. 25. Smith S, Sullivan K. Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled, crossover study. Int J Behav Med. 2003;10:162-73. 26. Vercoulen JH, Bazelmans E, Swanink CM, Fennis JF, Galama JM, Jongen PJ, Hommes O, Van der Meer JW, Bleijenberg G. Physical activity in chronic fatigue syndrome: assessment and its role in fatigue. J Psychiatric Res. 1997;31:661-73. 27. Van der Werf SP, van den Broek HL, Anten HW, Bleijenberg G. Experience of severe fatigue long after stroke and its relation to depressive symptoms and disease characteristics. Eur Neurol. 2001;45:28-33. 28. Gibson J, Carroll N, Clague JE, Edwards RHT. Exercise performance and fatigability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1993;56:993-8. 29. Lawrie S, MacHale SM, Power MJ, Goodwin GM. Is the chronic fatigue syndrome best understood as a primary disturbance of the sense of effort? Psychol Med. 1997;27:995-9. 30. Watson NF, Kapur V, Arguelles LM, Goldberg J, Schmidt DF, Armitage R, Buchwald D. Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome. Sleep. 2003;26:324-8. 31. Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ. Neural systems supporting interoceptive awareness. Nature Neurosci. 2004;7:189-95. 32. Magnusson AE, Nias DK, White PD. Is perfectionism associated with fatigue? J Psychosom Res. 1996;41:377-83. 33. White C, Schweitzer R. The role of personality in the development and perpetuation of chronic fatigue syndrome. J Psychosom Res. 2000;48:515-24. 34. Euba R, Chalder T, Deale A, Wessely S. A comparison of the characteristics of chronic fatigue syndrome in primary and tertiary care. Br J Psychiatry. 1996;168:121-6. 35. Whiting P, Bagnall A, Sowden A, Cornell J, Mulrow C, Ramirez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA. 2001;286:1360-8. 36. Wallman KE, Morton AR, Goodman C, Grove R, Guilfoyle AM. Randomised controlled trial of graded exercise in chronic fatigue syndrome. Medical Journal of Australia. 2004;180:444-448. -------- (c) 2006 BioMed Central Ltd. [Return to top] ------------------------------ Date: Wed, 27 Dec 2006 13:11:59 -0500 From: "Bernice A. Melsky" <email@example.com> Subject: RES: Illness perceptions and related outcomes among women with fibromyalgia syndrome Illness perceptions and related outcomes among women with fibromyalgia syndrome. Womens Health Issues. 2006 Nov-Dec;16(6):353-60. Stuifbergen AK, Phillips L, Voelmeck W, Browder R. The University of Texas at Austin School of Nursing, Austin, Texas. PMID: 17188218 PURPOSE: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain, multiple tender points, and fatigue, and affects 3-6 million Americans, 75% of whom are female. The purpose of the present study was to examine the illness perceptions of women with FMS using Leventhal's common sense self-regulation model. DESIGN: Ninety-one women with FMS took part in this study. Pearson correlations and stepwise multiple regressions were used to assess relationships among variables and explanation of variance in the outcomes of health behaviors, FMS impact, and subjective physical and mental health. RESULTS: Participants viewed their FMS as chronic with a somewhat fluctuating course, having serious consequences in their lives, and difficult to understand in a coherent fashion. The women tended to find their FMS emotionally distressing and unamenable to personal control or efficacious treatment. Emotional representations explained 41% of the variance in mental health scores and 17% in reported health behaviors. CONCLUSIONS: Overall, this sample of women with FMS had fairly negative perceptions of their illness. As suggested by Leventhal's model, cognitive and emotional representations predicted different outcomes. Interventions that address psychological as well as the physical components of the illness experience may offer benefits for women with FMS. [Return to top] ------------------------------ Date: Wed, 27 Dec 2006 13:58:51 -0800 From: "LK Woodruff <firstname.lastname@example.org..........via Co-Cure moderators" Subject: MED: Biomarker for Sleepiness Identified Not sure how, or even if, this correlates to the sub-cortical sleep dysfunction found in M.E., but it's an interesting finding. LKW Biomarker for Sleepiness Identified NEW YORK (Reuters Health) Dec 15 Salivary levels of amylase appear to provide a "simple and quantifiable biomarker of sleepiness," according to a report in the December 11th Early Edition of the Proceedings of the National Academy of Sciences. "We demonstrate here that 28 hours of waking in human subjects significantly increased Amylase activity and mRNA levels compared with untreated, circadian-matched controls," senior author Dr. Paul J. Shaw, from Washington University School of Medicine in St. Louis, and colleagues write. The authors note that at present there are no quantifiable markers for gauging an individual's sleepiness before untoward outcomes occur. For example, inadequate sleep can produce cognitive impairments and attention deficits, increasing the risk of occupational injuries and motor vehicle accidents. In the present study, the researchers used genetic and pharmacologic tools to dissociate sleep drive from wake time in Drosophila melanogaster. The results showed a high correlation between Amylase levels and sleep drive. Further testing in humans confirmed that salivary amylase is a useful biomarker for sleep drive. These findings represent the first step in developing a means of identifying sleepiness in vulnerable groups, Dr. Shaw's team concludes. Proc Natl Acad Sci USA 2006. http://www.medscape.com/viewarticle/549476?src=mp Related Links Resource Centers Insomnia and Sleep Health [Return to top] ------------------------------ Date: Thu, 28 Dec 2006 13:13:17 -0500 From: Fred Springfield <email@example.com> Subject: RES: Chronic Fatigue Syndrome Answers Sought Medical News & Perspectives: Chronic Fatigue Syndrome Answers Sought Journal: JAMA. 2006;296:2915, December 27, 2006 Author: Tracy Hampton, PhD NLM Citation: PMID: 17190885 Nearly 20 years after being named as a clinical entity, chronic fatigue syndrome (CFS) remains a puzzling disease. Bolstered by recent findings providing clues to factors that play a role in the disorder, health officials have launched an effort to alert patients and physicians to the syndrome's potential seriousness. They discussed the endeavor during a recent telebriefing. "Sometimes people question if [CFS is] real or not real," said Julie Gerberding, MD, MPH, director of the Centers for Disease Control and Prevention (CDC), in Atlanta. In addition to demonstrating that this illness is real, researchers are uncovering potential triggers and treatments. Recent research efforts and awareness campaigns are shedding light on chronic fatigue syndrome. A GOOD START Some information has emerged from the Wichita CFS Surveillance Study, launched by CDC researchers in 1997. Collecting information on 90 000 individuals in Wichita, Kan, and conducting extensive clinical assessments of about 7000, the group found that the age group most affected includes individuals between 40 and 59 years, that 373 per 100 000 women are affected (about 4 times the rate found in men), and that nonwhite women are affected more than white women, at a rate of 495 per 100 000 compared with 352 per 100 000 (Reyes M et al. Arch Intern Med. 2003;163:1530-1536). Monitoring patients with CFS in Wichita over time revealed that the disease may be associated with genetic and environmental determinants. "We're a long way from having the answers, but I think we have a very good start," said William Reeves, MD, of the CDC. Recent efforts to decipher the causes of CFS have found that some cases may be linked to stress and childhood trauma. In a case-control study of 43 adults with CFS and 60 nonfatigued controls (mean age of 50.5 years) from Wichita, Reeves and colleagues found that exposure to childhood trauma was associated with a 3- to 8-fold increased risk for CFS across different trauma types -- emotional, physical, and sexual abuse, and emotional and physical neglect (Heim C et al. Arch Gen Psychiatry. 2006;63:1258-1266). The authors suggest that studies analyzing the psychological and neurobiological mechanisms that link childhood adversity to CFS risk may provide targets for prevention. Recently published results from a prospective case-control study found that higher emotional instability and self-reported stress were associated with an increased risk for CFS (Kato K et al. Arch Gen Psychiatry. 2006;63:1267-1272). Included in the study were 19 192 Swedish twins born between 1935 and 1958. In the early 1970s, participants who were in their 20s and 30s at the time were asked questions about their personalities and their level of daily stress. Information about current CFS was obtained from telephone interviews conducted between 1998 and 2002; 1570 were categorized as having chronic fatigue (fatigue lasting at least 6 months). Several analyses were performed among unrelated individuals and monozygotic and dizygotic twins. Emotional instability and stress were associated with CFS, while extraversion was not. Individuals who reported that their lives were stressful were 64% to 65% more likely to develop CFS than individuals who did not see their lives as stressful. Genetic factors seemed to interact with the impact of stress: risk increased to more than 5-fold after accounting for genetic factors in the twin analyses. EFFECTIVE MANAGEMENT Current therapy for CFS includes symptom management, coping strategies, cognitive behavioral therapies, and exercise in addition to standardized treatments that help manage pain, sleep problems, and severe fatigue. However, researchers are working to develop newer therapies that target the root causes of CFS. "There are now over 4000 published studies that show underlying biological abnormalities in patients with this illness," said Anthony Komaroff, MD, of the Harvard Medical School, in Boston. Among some of the suspects are impairments in metabolism and dysfunction of the immune and nervous systems. To help in the effective management of CFS, the CDC has joined the Chronic Fatigue and Immune Dysfunction Syndrome Association of America to launch a new public awareness campaign, advocating for effective management of CFS through partnerships between patients and physicians. Included in this effort is a CFS "toolkit" that provides fact sheets for clinicians who wish to review the best practices related to diagnosing and managing CFS (http://www.cdc.gov/cfs/toolkit.htm). [Return to top] ------------------------------ Date: Fri, 29 Dec 2006 08:55:08 +0000 From: Maggie Wallace <firstname.lastname@example.org> Subject: MED: Acupuncture for fibromyalgia--a systematic review of randomized clinical trials. http://highwire.stanford.edu/cgi/medline/pmid;17189243 Acupuncture for fibromyalgia--a systematic review of randomized clinical trials. E Mayhew and E Ernst Rheumatology, December 19, 2006; . Complementary Medicine, Peninsula Medical School, Universities of Exeter & Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, UK. Objective. Acupuncture is often used and frequently advocated for the symptomatic treatment of fibromyalgia. A systematic review has previously demonstrated encouraging findings. As it is now outdated, we wanted to update it. Methods. We searched seven electronic databases for relevant randomized clinical trials (RCTs). The data were extracted and validated independently by both authors. As no meta-analysis seemed possible, the results were evaluated in narrative form. Results. Five RCTs met our inclusion criteria, all of which used acupuncture as an adjunct to conventional treatments. Their methodological quality was mixed and frequently low. Three RCTs suggested positive but mostly short-lived effects and two yielded negative results. There was no significant difference between the quality of the negative and the positive RCTs. All positive RCTs used electro-acupunture. Conclusion. The notion that acupuncture is an effective symptomatic treatment for fibromyaligia is not supported by the results from rigorous clinical trials. On the basis of this evidence, acupuncture cannot be recommended for fibromyalgia. PMID: 17189243 [Return to top] ------------------------------ Date: Fri, 29 Dec 2006 10:18:57 -0500 From: "Bernice A. Melsky" <email@example.com> Subject: RES: Hypothalamic-Pituitary-Adrenal Axis Function in Sjogren's Syndrome: Mechanisms of Neuroendocrine and Immune System Homeostasis Hypothalamic-Pituitary-Adrenal Axis Function in Sjogren's Syndrome: Mechanisms of Neuroendocrine and Immune System Homeostasis. Ann N Y Acad Sci. 2006 Nov;1088:41-51. Johnson EO, Kostandi M, Moutsopoulos HM. Department of Anatomy-Histology-Embryology, University of Ioannina, School of Medicine, Ioannina 45-110, Greece. firstname.lastname@example.org. PMID: 17192555 To date, evidence suggests that rheumatic diseases are associated with hypofunctioning of the hypothalamic-pituitary-adrenal (HPA) axis. Sjogren's syndrome (SS), the second most common autoimmune disorder, is characterized by diminished lacrimal and salivary gland secretion. To examine HPA axis activity in SS patients, the adrenocorticotropin (ACTH) response to ovine corticotropin-releasing factor (oCRH) was used as a direct measure of corticotrophic function, and the plasma cortisol response to the ACTH released during oCRH stimulation as an indirect measure of adrenal function. Significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to oCRH compared to normal controls. Fibromyalgia (FM) patients demonstrated elevated evening basal ACTH and cortisol levels and a somewhat exaggerated peak, delta, and net integrated ACTH response to oCRH. A subgroup of SS patients also met the diagnostic criteria for FM and demonstrated a pituitary-adrenal response that was intermediate to SS and FM. These findings suggest not only adrenal axis hypoactivity in SS and FM patients, but also that varying patterns of adrenal and thyroid axes dysfunction may exist in patients with different rheumatic diseases. [Return to top] ------------------------------ Date: Sat, 30 Dec 2006 16:27:41 +0100 From: "Dr. Marc-Alexander Fluks" <email@example.com> Subject: RES,NOT: Call for proposals: CFS research NIH Source: NIH Date: December 22, 2006 URL: http://grants.nih.gov/grants/guide/pa-files/PA-07-263.html Title: Chronic Fatigue Syndrome: Pathophysiology and Treatment (R03) -------------------------------------------------------------------- Announcement Type This is a reissue of PA-05-030, which was previously released December 21, 2004. NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide. APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT. This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply). A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV. Program Announcement (PA) Number: PA-07-263 (...) Release/Posted Date: December 22, 2006 Opening Date: January 5, 2007 (Earliest date an application may be submitted to Grants.gov) (...) ------------------------------------------------------------------------------ Additional Overview Content Executive Summary * Purpose. This Funding Opportunity Announcement (FOA) issued by the Office of Research on Women's Health (ORWH) and co-sponsoring Institutes and Centers (ICs) of the National Institutes of Health (NIH) solicits grant applications from organizations/institutions that propose to examine the etiology, diagnosis, pathophysiology, and treatment of chronic fatigue syndrome (CFS) in diverse groups and across the lifespan. Applications that address gaps in the understanding of the environmental and biological risk factors, the determinants of heterogeneity among patient populations, and the common mechanisms influencing the multiple body systems that are affected in CFS are encouraged. The NIH is interested in funding interdisciplinary research that will enhance our knowledge of the disease process and improve the diagnosis, treatment, and quality of life of all persons with CFS. * Mechanism of Support. This FOA will use the NIH Small Research Grant (R03) award mechanism and runs in parallel with FOAs of identical scientific scope, PA-07-265 and PA-07-264, which solicit applications under the Research Project Grant (R01) and the Exploratory/Developmental Grant (R21) award mechanisms respectively. * The R03 grant mechanism supports different types of projects including pilot and feasibility studies; secondary analysis of existing data; small, self-contained research projects; development of research methodology; and development of new research technology. * The R03 is intended to support small research projects that can be carried out in a short period of time with limited resources. * The R03 is not renewable. * Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received. * Budget and Project Period. Budgets for direct costs of up to $50,000 per year and a project duration of up to two years may be requested for a maximum of $100,000 direct costs over a two-year project period. * Eligible Institutions/Organizations. Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity (Foreign Organization); Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations. * Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. * Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct. * Application Materials. See Section IV.1 for application materials. * General Information. For general information on SF424 (R&R) Application and Electronic Submission, see the following Web sites: o SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm o General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/ * Hearing Impaired. Telecommunications for the hearing impaired is available at: TTY 301-451-0088. (...) [Surf to the above URL for more info] [Return to top] ------------------------------ Date: Sat, 30 Dec 2006 13:12:11 -0500 From: Fred Springfield <firstname.lastname@example.org> Subject: RES: Brain Cytokines and the 5-HT System during Poly I:C-Induced Fatigue Brain Cytokines and the 5-HT System during Poly I:C-Induced Fatigue. Journal: Ann N Y Acad Sci. 2006 Nov;1088:230-7. Authors: Katafuchi T, Kondo T, Take S, Yoshimura M. Affiliation: Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. email@example.com. NLM Citation: PMID: 17192569 Fatigue is evoked not only by peripheral factors, such as muscle fatigue, but also by the central nervous system (CNS). For example, it is generally known that the feeling of fatigue is greatly influenced by psychological aspects, such as motivation. However, little is known about the central mechanisms of fatigue. The clinical symptoms of chronic fatigue syndrome (CFS) are shown to include disorders in neuroendocrine, autonomic, and immune systems. On the other hand, it has been demonstrated that cytokines produced in the brain play significant roles in neural-immune interactions through their various central actions, including hypothalamo-pituitary and sympathetic activation, as well as immunosuppression. In this article, using the immunologically induced fatigue model, which was achieved by intraperitoneal (i.p.) injection of synthetic double-stranded RNAs, polyriboinosinic: polyribocytidylic acid (poly I:C) in rats, we show an involvement of brain interferon-alpha (IFN-alpha) and serotonin (5-HT) transporter (5-HTT) in the central mechanisms of fatigue. In the poly I:C-induced fatigue rats, expression of IFN-alpha and 5-HTT increased, while extracellular concentration of 5-HT in the medial prefrontal cortex decreased, probably on account of the enhanced expression of 5-HTT. Since the poly I:C-induced reduction of the running wheel activity was attenuated by a 5-HT(1A) receptor agonist, but not by 5-HT(2), 5-HT(3), or dopamine D(3) receptor agonists, it is suggested that the decrease in 5-HT actions on 5-HT(1A) receptors may at least partly contribute to the poly I:C-induced fatigue. [Return to top] ------------------------------ Date: Sat, 30 Dec 2006 13:26:48 -0500 From: Fred Springfield <firstname.lastname@example.org> Subject: RES: The Language of Health Care: Chronic Fatigue Syndrome Letters THE LANGUAGE OF HEALTH CARE Chronic fatigue syndrome Journal: J R Soc Med 2007;100:7 Author: Ellen M Goudsmit, Ph.D. E-mail: email@example.com I have just read the review of treatments for chronic fatigue syndrome (CFS) in the October issue of the JRSM.1 It included my study, but some of the details were inaccurate and the overall judgement was unfair and potentially misleading. In the original 'York' review of the various treatments for CFS, my study received a validity score of two. However, after clarification regarding the statistical analysis, this was changed to three (Kleijnen, personal communication). Chambers et al. were clearly not aware of the 'correction' and published the original score. It's a minor issue, but it wasn't the only one. Another example relates to the assessment of the results. According to the table (p. 511), the programme had no overall effect but as the authors noted in their recent review for NICE (http://www.nice.org.uk/page.aspx?o=368933, appendix 1, p. 423), there were 'significant differences between groups for fatigue... and somatic symptoms'. They would also have been aware that 82% of the patients rated themselves as 'better' or 'much better' and that 23% had improved to such a degree that they were discharged. To summarize, patients reported less fatigue, fewer somatic symptoms, less anxiety and depression after six months compared to the controls, and the improvements were maintained at follow-up. Yet the authors judged the treatment had 'no overall effect'. My study is one of the few which has assessed an alternative to the CBT-based programmes. It's also one of the few controlled trials to include pacing, a strategy which many patients regard as a particularly helpful way of managing their limited energy. In my opinion, it deserved an accurate evaluation and a fair summary of the outcome. It didn't get that. Footnotes Competing interests None declared. REFERENCES Chambers D, Bagnall A-M, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med 2006;99:506 -20 © 2007 The Royal Society of Medicine [Return to top] ------------------------------ Date: Sat, 30 Dec 2006 22:51:51 -0500 From: "Jill McLaughlin <firstname.lastname@example.org> via Co-Cure Moderators" Subject: NOT,MED: IACFS Patient Conference Agenda http://www.aacfs.org/p/224.html The Patient Conference Agenda Wednesday, January 10th 8:30 -9:00 am Commodore Ballroom Welcome & Opening Remarks Nancy Klimas, MD President, IACFS Faculty, Dept. of Medicine, University of Miami School of Medicine Marly C. Silverman Founder, Patient Alliance for Neuroendocrineimmune Disorders Organization for Research and Advocacy (P.A.N.D.O.R.A.) ________________________________________________________ 9:00-10:00am Commodore Ballroom Legislatively Speaking Tom Sheridan _______________________________________________________ 10:00am Exhibit Hall Opens 10:00 10:15 am Break - See Exhibitors ________________________________________________________ 10:15-11:00 am - Commodore Ballroom Advocacy Workshop Fundraising Fundamentals Joanne Nowlin Davis, CFRE 10:15-11 a.m Seafarer Advocacy Workshop Empowerment within the CFS Community Kim McCleary 10:15-11:45 Mariner Room Workshop: Understanding and Living with CFS/FM Lyme Disease Garth Nicholson, PhD 10:15-11:00 Clipper Room Understanding and Living with CFS/FM Ergonomics, Posture and Natural Pain Relief Bernard Burton, DOC _______________________________________________________ 11:00-12:00 pm - Commodore Ballroom Advocacy Workshop Media Panel: How to Convey your Advocacy Message to the Media Slide Presentation by Sheila Hershow, Dezenhall Resources Moderator: Marly C. Silverman Panel: Martin Kramer, Ron St. John, Marla Schwartz & Diane Mohoreanu 11:00-12:00 pm Mariner Room Workshop: Understanding and Living with CFS/FM Social Security Disability Issues Lyle Lieberman, JD & Robert Gutierrez, JD 11:00-12:00 pm Seafarer Room Workshop: Understanding and Living with CFS/FM Effective Treatment of CFS & Fibromyalgia-including new research on D-Ribose Jacob Teitelbaum, MD 11:00-12:00 - Clipper Workshop: Understanding and Living with CFS/FM SPANISH SPEAKING ONLY Fibromyalgia and Chronic Fatigue Syndrome en Espanola Maria Gutierez, MD & Jackie Junco-Valderes, MD ________________________________________________________ 12:00-1:15 pm Lunch ________________________________________________________ 1:15-2:15 pm Commodore Ball Room Understanding and Living with CFS/FM SPANISH SPEAKING ONLY Social Security Disability en Espanola Robert Gutierrez, JD 1:15-2:15 pm Mariner Room Understanding and Living with CFS/FM Private Disability Issues and ERISA Steve Krafchick, JD 1:15-2:15 pm Seafarer Room Advocacy Workshop Media Training 101 - (You need to sign up ahead of the conference for this presentation if you are not part of the 2007 Advocates Extraordinaire! Leadership and Advocacy Training Program Diane Mohoreanu 1:15-2:15 pm Clipper Room Advocacy Workshop Media Training 201 - (You need to sign up ahead of the conference for this presentation if you are not part of the 2007 Advocates Extraordinaire! Leadership and Advocacy Training Program space limited) Sheila Hershow ________________________________________________________ 2:15 - 3:15 pm Commodore Ballroom Understanding and Living with CFS/FM Legal and Medical Issues Affecting Employment for the Disabled and Chronically Ill Moderator: Jason Newfield, JD Panel: Steve Krafchick, Alicia Paulino-Grishman, Lyle Lieberman, JD, Robert Gutierrez, JD, Rosa Berrocal & Ken Friedman, MD 2:15-3:15 pm Mariner Room Understanding and Living with CFS/FM Technology and the CFS Patient Rebecca Palmberg 2:15 - 3:15 pm - Seafarer Room Advocacy Workshop Media Training #101 - (You need to sign up ahead of the conference for this presentation if you are not part of the 2007 Advocates Extraordinaire! © Leadership and Advocacy Training Program. Space is limited) Diane Mohoreanu 2:15 - 3:15 pm - Clipper Room Advocacy Workshop Media Training #201 - (You need to sign up ahead of the conference for this presentation if you are not part of the 2007 Advocates Extraordinaire! © Leadership and Advocacy Training Program. Space is limited) Martin Kramer __________________________________________________ 3:15-3:30 pm Break - Visit Exhibits __________________________________________________ 3:30-4:45 pm - Commodore Ballroom Moving our Agenda Forward: Brainstorming Session for All Advocacy Groups Co-Moderator: Jason Newfield, JD Co-Moderator: Janet Canterbury, PhD Group Leaders: Alexander Kushch, PhD , Beth Wheeling, PhD, Alicia Paulino-Grishman, JD, Justin Frankel, JD, Connie Borschel, Steve Krafchick, JD & Barry Gregory, PhD _______________________________________________________ 4:45-6:00pm Commodore Ballroom Strategy Meeting: Finalize Consensus and Develop Preliminary Patient Issues For Future Presentation to the IACFS Executive Board Co-Moderator: Jason Newfield, JD Co-Moderator: Janet Canterbury, PhD Group Leaders: Alexander Kushch, PhD , Beth Wheeling, PhD, Alicia Paulino-Grishman, JD, Justin Frankel, JD, Connie Borschel, Steve Krafchick, JD, &Barry Gregory, PhD ______________________________________________________ 6:00-7:00pm Gardens if weather permits and Seafarer Room Attendee Networking Reception and PANDORA Box Art Auction Start 6:30 7:00-7:45pm - Seafarer Room Cocktail Speaker Effective Pain Management in CFS and Fibromyalgia Jacob Teitelbaum, MD Thursday, January 11th 9:00-10:15am Commodore Ballroom What's New in CFS & FM Science, Treatment and Demographics Introduction: Nancy Klimas, MD President, IACFS Faculty, Dept. of Medicine University of Miami, Miller School of Medicine, Miami, FL Moderator: Eleanor Hanna Associate Director, Special Projects and Centers, Office of The Director, National Institute of Health Panel: Members of the IACFS Board of Directors: Dharam V. Ablashi, DVM, MS, Dip. Bact., Kenny De Meirleir, MD, PhD, Birgitta Evengård, MD, PhD, Leonard A. Jason, PhD, Hirohiko Kuratsune, MD, D. Med. Sci. & Gudrun Lange, PhD ________________________________________________________ 10:15-11:00am Break - Visit Exhibits ________________________________________________________ 11:00-12:00pm Commodore Ballroom Workshop: Medical Research and Treatment Updates I Integrative & Complimentary Medicine Kenny De Meirleir, MD, PhD 11:00-12:00pm Clipper Room Workshop: Medical and Research Updates II Pain Dr. Steven Croft 11:00-12:00pm Mariner Room Workshop: Managing Your Quality of Life Track The Art and Science Behind coping and Empowerment Patricia A. Fennell, MSW, LCSW-R, Gudrun Lange, PhD, Fred Friedberg, PhD & Marla Silverman 11:00-12:00pm Seafarer Room Workshop: Family Issues and Pediatrics Finding Medical, School and Community Resources to Treat a Child with CFS Leonard A. Jason, PhD, David Bell, MD & Charles Lapp, MD ________________________________________________________ 12:00-1:30pm Lunch Break-Visit Exhibits ________________________________________________________ 1:30-2:30pm - Commodore Ballroom Workshop: Managing Your Quality of Life Making the Most of Your Doctor's Appointments Lucinda Bateman, MD 1:30-2:30pm Clipper Room Workshop: Medical Research and Treatment Updates I Multiple Chemical Sensitivities Alex Delgado, PhD 1:30-2:30pm Mariner Room Workshop: Family Issues and Pediatrics-New Pediatric Case Definition for CFS Leonard A. Jason, PhD & David Bell, MD 1:30-2:30pm - Seafarer Room Workshop: Medical Research and Treatment Updates II Exercise Challenges for the CFS Patient Kenny De Meirleir, MD & Chuck Lapp, MD ________________________________________________________ 2:30-3:30pm Commodore Ballroom Workshop: Family Issues and Pediatrics- Couples, Sex & Family Patricia A. Fennell, MSW, LCSW-R 2:30-3:30pm- Clipper Room Workshop: Medical and Research Updates III HHV 6 Update Jose Montoya 2:30-3:30pm Mariner Room Workshop: Medical and Research Updates I Sleep Disorders are they the Cause or the side effect of CFS David Bell, MD 2:30-3:30pm- Seafarer Room Workshop: Medical Research and Treatment Updates II Risk Factors for people with CFS Leonard A. Jason, PhD ________________________________________________________ 3:30-4:00pm Break - Visit Exhibits ________________________________________________________ 4:00-5:30pm Commodore Ballroom Ask the Experts Moderator: Nancy Klimas, MD President, IACFS Faculty, Dept. of Medicine, University of Miami School of Medicine Panel: IACFS Board of Directors: David S. Bell, MD, Lucinda Bateman, MD, Kenny De Meirleir, MD, PhD, Patricia Fennell, MSW, CSW-R, Fred Friedberg, PhD & Charles W. Lapp, MD ________________________________________________________ 6:00-8:30pm Seabreeze Attendee Banquet and P.A.N.D.O.R.A. Sand Castle Awards Keynote Address: Paul R. Cheney, MD, PhD The State of the Art of CFS ######## [Return to top] ------------------------------ Date: Sun, 31 Dec 2006 09:21:11 +0100 From: connie <email@example.com> Subject: NOT,ACT,MED:PACE Trial [UK} The first PACE Trial Participants' Newsletter, Issue 1. June 2006, can be read here: http://www.pacetrial.org/partsletter.pdf See extract below: "The National Institute for Clinical Excellence is due to publish its first draft guidance on the management of CFS/ME later this year. This guidance will be used by the NHS to decide on which treatments to offer patients. To help this process, York University is about to publish a systematic review of all treatments for CFS/ME. This review is likely to conclude that the PACE study is vital to understand which treatments are most effective and whether certain treatments best suit different individuals." You can also read The PACE Trial patient clinic leaflet at the following link: http://www.pacetrial.org/PCL%20version%2009.pdf TC Connie [Return to top] ------------------------------
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