[Co-Cure ME/CFS & Fibromyalgia Information Exchange Forum Logo]

CO-CURE Weekly Medical and Research Digest Only - 25 Dec 2006 to 1 Jan 2007

There are 14 messages in this issue.

Topics of the week:
[Return to digest index]
              ---------------------------------------------
                       This is a special digest of
                  Co-Cure Research & Medical posts only
               Problems? Write to mailto:mods@co-cure.org
              ---------------------------------------------

----------------------------------------------------------------------

Date:    Tue, 26 Dec 2006 14:35:06 -0500
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
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.

[1] Ben Gurion University, Department of Medicine H, Soroka Medical Center
and Faculty of Health Sciences, Beer Sheva, Israel.

dbuskila@xxxxx.xxx.xx.xx ,
[2] L Sacco University Hospital, Senior Rheumatologist, Rheumatology
Unit,Via GB Grassi 74, 20157 Milano, Italy. 
sarzi@xxxxx.xxx ,
[3] Tel-Aviv University, Departments of Rheumatology, Tel-Aviv Sourasky
Medical Center and Sackler Faculty of Medicine, Tel-Aviv, Israel.

ajacob@post.xxx.xx.xx.

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" <bernicemelsky@xxxxx.xxx>
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" <fluks@xxx.xx>
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: 
wcr1@xxx.xxx; Christine Heim: 
cmheim@xxxxx.xxx; Elizabeth
M Maloney: evm3@xxx.xxx; Laura Solomon Youngblood: 
zfk9@xxx.xxx; Elizabeth
R Unger: eru0@xxx.xxx; Michael J Decker: 
mdecker@xxxxx.xxx; James F
Jones: jaj9@xxx.xxx; David B Rye: 
drye@xxxxx.xxx

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) [1]. 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 [2].

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 [5]. 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 [17]; 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 [4], 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 [19]. 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 [19].
The in-hospital study enrolled people who had participated in the 1997
through 2000 Wichita Population-Based CFS Surveillance Study [4].
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 [20]. 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 [19] of the 1994 CFS case definition [1]. 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 [22], 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 [23].

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
5–10 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 [27]
possibly due to what might be perceived as stressful inter-nap activities
[28], 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 [21]. 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 [29].

Narcolepsy
Narcolepsy was diagnosed if 2 out of 4 MSLTs were positive for REM sleep
and mean sleep onset during MSLT was < 5 minutes [29].


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 [30].
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 [4]; 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" <fluks@xxx.xx>
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: 
wrsmith@u.xxxxx.xxx; Peter D White: 
p.d.white@xxxx.xx.xx;
Dedra Buchwald: 
dedra@u.xxxxx.xxx

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 [1]. Chronic fatigue syndrome (CFS) is a more
narrowly defined illness with prominent fatigue and at least 4 associated
symptoms [2]. Many CFS patients also suffer from fibromyalgia [3], a disabling
condition characterized by chronic widespread pain, fatigue, and sleep
disturbances [4]. Individuals with CFS often perceive physical activity as
more of an effort than healthy people [5], 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 [6], and rate themselves as having been significantly
more active [6] and "action-prone" before they became ill, than do control
subjects [11]; "action-proneness" also increases with treatment [12]. The high
levels of physical activity reported by patients have been corroborated by
their spouses, partners, or parents [13].

The etiology of chronic, unexplained fatigue, CFS, and fibromyalgia remains
unclear [7], but recent work suggests that these disorders may involve
enhanced interoception [14,15]. Interoception is the perception of internal
sensory phenomena, especially visceral perceptions [16]. 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 [17]. 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 [18],
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) [19] 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 [20] and the
American College of Rheumatology [4], respectively. Those who did not meet the
CFS case definition met the criteria for idiopathic chronic fatigue [20].
Fibromyalgia often co-occurred with idiopathic, chronic fatigue and CFS, as
previously described [3].

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 [21]. 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 [22]. 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 [30], 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 [31]. 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 [25]. 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 [34], 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" <bernicemelsky@xxxxx.xxx>
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 <lkw777@xxxxx.xxx..........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 <fredspringfield@xxxxx.xxx>
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 <zen38947@xxx.xx.xx>
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" <bernicemelsky@xxxxx.xxx>
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. 
ejohnson@xx.xxx.xx.

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" <fluks@xxx.xx>
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 <fredspringfield@xxxxxx.xxx>
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.

kataf@xxxxx.xxx.xx.xxx.xx.

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 <fredspringfield@xxxxx.xxx>
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: 
ellengoudsmit@xxxxx.xxx


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 <jillmclaughlin@xxxxx.xxx> 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 <connie.nelson@xxxxxxxxx.xxx>
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]

------------------------------

End of CO-CURE Weekly Medical and Research Digest Only - 25 Dec 2006 to 1 Jan 2007 (#2007-1)

[Return to digest index] 


Copyright © 2006 Co-Cure
Last Revision: January 2, 2007
Please report any problems with this page to the Webmaster.