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Date:    Tue, 13 Feb 2007 13:38:47 -0500
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Resting muscle pain as the first clinical symptom in  children carrying the MTTK A8344G mutation

Resting muscle pain as the first clinical symptom in children carrying the
MTTK A8344G mutation.

Journal: Eur J Paediatr Neurol. 2007 Feb 9; [Epub ahead of print]

Authors: van de Glind G, de Vries M, Rodenburg R, Hol F, Smeitink J, Morava E.

Affiliation: Department of Pediatrics, Nijmegen Centre for Mitochondrial
Disorders, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500
HB Nijmegen, The Netherlands.

NLM Citation: PMID: 17293137


The characteristic clinical presentation, especially the appearance of
muscle symptoms, is quite unique in children carrying the mtA8344G
mutation. The diagnosis of MERRF syndrome is seldom made in the pediatric
age. Fatigue is a common finding in children of pubertal age. Fatigue in
combination with recurrent resting muscle pain occurs frequently in the
initial phase of various hereditary muscle disorders and in several
autoimmune, endocrine and metabolic syndromes.

In the absence of obvious biochemical/metabolic abnormalities and in the
lack of neurological symptoms the complaints are frequently labelled as
fibromyalgia or chronic fatigue syndrome. In patients with behavioural or
psychiatric abnormalities one might even start to question the organic
etiology of the complaints. We describe a family carrying the classic MTTK
mutation with a variable degree of heteroplasmy, presenting in childhood as
isolated recurrent muscle pain as the first symptom of the disease.

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Date:    Tue, 13 Feb 2007 15:56:44 -0500
From:    Co-Cure Moderator <ray CO-CURE.ORG>
Subject: NOT,RES: Report on the 8th International IACFS Conference on CFS, FM, and Related Illnesses by Dr. Charles W. Lapp

[Moderator's Note: This report on the 8th International IACFS Conference
on CFS, FM, and Related Illnesses was written by Charles W. Lapp, M.D.,
and is distributed here with his permission.]


8th International IACFS Conference on CFS, FM, and Related Illnesses
Fort Lauderdale, Florida
January 12-14, 2007


The 2007 meeting of the IACFS (formerly AACFS) has set new records for
attendance, including more than 250 professionals and over 300
patients.  An effort has been made to expand internationally, and over 21
countries were represented at this meeting!

Even before the meeting began, big changes were occurring.  The IACFS Board
voted to change the name of the organization to the International
Association of CFS and ME  in recognition of the term  ME  used by many
other English-speaking nations, and thereby tendering an alternate name for
this illness.  Later in the week, an ad hoc Name Change Committee, put
together by ProHealth CEO Rich Carson, also recommended using the term ME
(or Mylagic Encephalopathy) in lieu of CFS.  CFS will probably remain the
scientific term for the illness, but it is hoped that ME will become the
common designation.

Another key event at this meeting was the introduction of the new Pediatric
Case Definition.  A working committee of the IACFS has hammered out a
proposed manner of diagnosing children and adolescents with this
disorder.  Research has been hampered in the past by the absence of
unifying diagnostic criteria. The committee has provided a summary paper, a
questionnaire for clinical use, and a summary "scoring sheet," which should
help both clinicians and researchers to understand pediatric CFS/ME better.

In reviewing the papers submitted for presentation, it soon became clear
that the amount and quality of research in CFS/ME has increased
significantly over the past two years, and that many researchers are
looking into specific aspects of the illness (such as fatigue, or pain, or
sleep disruption) rather than attempting to study the syndrome as a whole.

It seems that each year a new aspect of research is introduced, and this
year that aspect is "genomics and proteomics."  Genomics is defined as the
study of function and interactions of genetic material in the genome, while
proteomics is the study of proteins made in the cell. Both of these fields
are contributing substantially to our understanding of CFS/ME and FM. As
Dr. Suzanne Vernon of the CDC pointed out, it is hopeful that these studies
will lead to a better understanding of the illness, perhaps a specific
marker, and possibly even therapy.

Unlike previous conferences, clinical and research papers were
inter-mingled this year but organized by general topic such as fatigue,
sleep disorders, clinical trials, pain, epidemiology, brain function,
behavioral health, pediatrics, gender aspects, and genetics/proteomics.

Fatigue Session

Seiki Tajima of Osaka, Japan, launched the meeting with a study of activity
monitoring and autonomic responses in sleep.  Patients wore an activity
monitor (similar to a pedometer, but worn on the wrist), which was able to
discriminate periods of activity, rest, and sleep during a 24 hour
period.  Tajima was able to identify at least 5 types of abnormal sleep
patterns in PWCs, including a long sleeping type, severe insomnia,
hypersomnia, and sleep phase shifting.   Autonomic (that is, R-R spectrum)
analysis revealed that poor sleep may be due to a lack of parasympathetic
activity during attempted sleep periods.

Nicole Porter (DePaul University, Chicago) queried PWCs and healthy
individuals about their experience of fatigue. She was then able to define
at least 5 different fatigue states:
Wired fatigue  feels over-stimulated but low energy
Brain fog fatigue  mental or cognitive impairment is associated with fatigue
Molasses fatigue  heaviness and immobilization, unable to prolong activity
Flu-like fatigue  weakness with flu-like symptoms
Post-exertional fatigue  a lack of energy following minor activity
Healthy individuals experienced only one type of fatigue (typically
flu-like), while PWCs experienced fatigue in diverse ways.

Elizabeth Mahoney described a CDC-sponsored study of the effect of
allostatic load.  One's "allostatic load" is essentially your accumulated
stressors.  However, the CDC used objective measures (such as heart rate,
blood pressure, c-reactive protein levels, waist-to-hip ratio, lipid
levels, blood sugar, insulin levels, etc.) as a measure of "load."  Based
on this premise, women with a high allostatic load were 5 times more likely
to develop CFS/ME compared to those with low allostatic loads. This did not
hold true for men, however.  Mahoney also pointed out that this study
demonstrated a high prevalence of metabolic syndrome in PWCs.  [Metabolic
syndrome is characterized by central obesity, elevated cholesterol and
triglycerides, elevated blood sugar; and the presence of metabolic syndrome
frequently predicts later diabetes and cardiovascular disorders such as
heart attack and stroke.]

Margaret Chicorella, both an exercise physiologist and an attorney from
University of the Pacific,  Stockton, CA, demonstrated how disability could
be better defined using a two-part exercise test.  When cardio-pulmonary
exercise testing is repeated 24+ hours after the first test, oxygen
consumption and the maximum achievable heart rate both decrease
substantially. This is objective evidence of post-exertional malaise --  a
sine qua non of CFS/ME/FM  and could be very useful in disability
determinations.

Paul Nestadt (Mt.Sinai School of Medicine, NYC) used Magnetic Resonance
Spectroscopy (1H-MRS) to show that lactate is increased and
N-acetyl-aspartate (NAA) is reduced in the brains of PWCs (Persons with
CFS/ME).  Lactate levels correlated with the level of fatigue, and were not
abnormal in persons with depression or anxiety.  These findings are further
evidence that CFS/ME is not psychiatric in origin, and that mitochondrial
function and neuronal density (or metabolism) are reduced in PWCs.

Dubbo is small city in the northwest corner of New South Wales, Australia,
and has been the site of several epidemiological studies concerning the
clinical course of EBV mononucleosis  (a DNA virus) and Q-fever (a
rickettsial infection). Toni Whistler of the CDC described genetic findings
in persons who developed PIFS, or Post-Infectious Fatigue Syndrome, which
is very similar to CFS/ME.   30,000 genes were studied, and more than 40%
of the pathways were found related to regulatory and metabolic
pathways.  Cell cycle regulation, gene regulation, and signaling were most
commonly involved; and apoptotic, metabolic, and inflammatory (IL 10)
pathways were prominent in the sickest patients.  Whistler concluded that
there is a subset of PIFS in which immune abnormalities play a significant
role.


Clinical Trials

Barry Hurwitz, a colleague of Dr. Nancy Klimas at the University of Miami,
presented the findings of their famous "ProCrit Study."   57 PWCs were
studied for anemia and low red blood cell volume (RBCV). About 70% of the
cohort actually had a low RBC volume.  These were given either ProCrit
(n=30) or placebo (n=10), while those with normal RBC volume were given
placebo injections for 4 months. All were administered iron and dietary
salt supplements also.  80% of treated subjects responded to 10,000 units
per week of ProCrit, and their RBC volume increased about 26% on average.
Orthostatic intolerance (by tilt table testing) improved in treated
subjects, but exercise tolerance, fatigue, and other measures did not
change.  Thus, ProCrit therapy might be modestly helpful for patients with
orthostatic intolerance and low RBCV, but not for the general symptoms of
CFS/ME.

José Montoya (Stanford University School of Medicine) described his recent
valgancyclovir (Valcyte™) studies in 12 persons with virally induced
fatigue and cognitive dysfunction.  Subjects were treated with
valgancyclovir for 6 months (one for 3 months only), and 9 had significant
improvement in fatigue and cognition.  Five of these had elevated EBV
titers (VCA-IgG, EBNA, or EBV-EA), 3 had both elevated EBV and HHV6
serologies, one had neither. None had HHV6 elevations alone. Comment:   It
is not at all clear if any of these patients had CFS/ME.  We can only say
that a subset of persons with Post-Infectious Viral Syndrome may respond to
prolonged therapy with valgancyclovir. Dr. Montoya warned that
valgancyclovir is a dangerous drug and must be used with great caution.  A
study of valgancyclovir specifically in persons with CFS/ME is slated to
start this month, and we all anxiously await the outcome!

Martin Lerner (Wayne State University, Detroit) described a subset of
patients with persistent EBV and/or cytomegalovirus (CMV),
electrocardiographic changes, and symptoms of CFS/ME.  In addition to
having elevated IgM (or EBV-EA) titers, all 37 patients had an elevated
heart rate at rest, recurrent T-wave inversions on Holter monitoring,
cardiac abnormalities and/or biopsy proven cardiomyopathy.  Subjects with
EBV positivity were treated with high dose valcyclovir (VCV or Valtrex™)
14mg/kg daily, and subjects with CMV positivity were treated with
valgancyclovir (VGCV or Valcyte™) for 3 to 3.5 years with improvement in
fatigue, tachycardia, chest pain, syncope, flu-like symptoms, EBV titers,
and cardiac wall motion.  No serious adverse effects were seen.


Pain

Dan Clauw (University of Michigan, Ann Arbor) provided his usual elegant
and fascinating presentation, this time on "Pain Processing and Therapy in
Fibromyalgia."   Clauw explained that each of us has a "volume control" for
controlling the severity of pain, and that this controller is affected by
both genetics and environment (or experience).  Studies have shown that
persons with FM (PWFs) have a normal "detection threshold" for pain, but a
decreased "noxious threshold" to a variety of stimuli, including pressure,
heat, noise, and electrical stimulation. Thus, PWFs sense the onset of pain
the same as other individuals, but are much more sensitive to pain. This is
independent of expectancy or hypervigilance.

Such findings can be demonstrated by a functional MRI scan ( fMRI), which
senses deoxygenated blood and thereby detects parts of the brain that are
activated. Using this technique, Clauw's group has demonstrated that
healthy individuals have a minimal response to a modest pain stimulus,
while PWFs have a very strong response to the same modest stimulus.   This
proves, Clauw explains, that "when FM patients say they hurt, they really
do hurt!"

Studies have also shown that pain is unrelated to co-morbid depression, but
persons who catastrophize (negative thoughts, magnification of symptoms,
"glass-half-empty") tend to experience more pain.

Clauw's management of pain parallels The Stepwise Approach espoused at the
Hunter-Hopkins Center:  education, pharmacologic therapy, aerobic exercise,
alternative therapies (such as hypnotherapy, biofeedback, acupuncture,
chiropracty, electrostimulation) and Cognitive Behavioral Therapy (or
coaching).  He reports good evidence that the following are helpful:
Tricyclic antidepressants (amitriptyline, cyclobenzaprine)
SNRIs (venlafaxine, duloxetine) and possibly SSRIs
Tramadol

There is weak evidence for using growth hormone, 5-hydroxy-tryptane,
tropisetron, and SAMe; and NO evidence supports the use of NSAIDs
(ibuprofen, naproxen, etc.), corticosteroids, or guiafenesin. Clauw is not
a fan of opioids, narcotics, or sleep medications in the treatment of
FM.   Newer possible therapies for fibropain include GHB (Xyrem™), dopamine
agonists (roprinolole, pramipexole), and neuromodulators.

Lastly, Clauw pointed out that there is a strong familial predisposition to
fibromyalgia, with first degree relatives having 8 times the risk of
developing FM.  Also, Diatchenko has linked abnormalities in the COMT
haplotype (which controls serotonin in the body and brain) to TMJ. This
means that at least one gene codes for pain, and possibly the tendency to
develop FM.


Epidemiology

Rosemary Underhill of the New Jersey CFS Association studied the prevalence
of chronic fatigue and CFS in the offspring of mothers with CFS/ME.   A
questionnaire to members of the NJCFSA identified 108 mothers with
physician-documented CFS/ME.   These woman were contacted for details.
There were 220 offspring.  24% of mothers had an offspring with documented
CFS/ME or chronic fatigue (CF). CFS/ME occurred in 5.5%, and 11.4% had
chronic fatigue. Both sons and daughters were affected about equally, and
half developed illness after age 18.   42% of the offspring with CFS/ME had
already recovered, as had one-third of those with CF.

Leonard Jason (DePaul University, Chicago) calculated the economic impact
of  CFS/ME using both community-based and tertiary sample pools.   Indirect
costs (that is, loss of production)  were estimated to occur in 27%, or an
annual loss of $20,000 per person with CFS/ME.  Direct costs (drugs,
medical tests, office visits, etc.) were ascertained to be $8764 per person
in the tertiary sample and $2341 in the community sample. (Patients
identified from tertiary care tend to be more ill than those in the
community.)
Thus, the combined direct and indirect costs were $22,341 per person in the
community sample and $28,674 in the tertiary sample, for an annual cost to
the US economy of 19.6 to 25.2-billion dollars.


Ampligen

Dr. William Carter, CEO of Hemispherx Biopharma, reported the Ampligen
experience to a crowd of interested providers before sessions began on
Saturday, January 13.  He stated that since the 1980's about 1000
individuals have been treated with Ampligen, using about 80,000 doses of
this experimental drug. Phase III studies have been positive -- showing a
16% increase in exercise ability in treated subjects  and preliminary data
has been submitted to the FDA toward the New Drug Application for
Ampligen.  There was no speculation when this process will be complete or
when Ampligen might be available to patients.


Brain Function

The current status of researching brain function in CFS/ME was reviewed by
Gudrun Lange (University of Medicine and Dentistry of New
Jersey  UMDNJ).  She described some of the neurocognitive tests used to
demonstrate cognitive dysfunction in CFS/ME, and pointed out that testing
is much more positive in bedridden subjects (presumably sicker) and after
maximal exertion (say on a bicycle or treadmill).

Radiological tools that demonstrate positive findings are MRI, CT scanning,
SPECT and PET scanning (which measure cerebral blood flow), Proton Magnetic
SPECT or Magnetic Resonance Spectroscopy (they measure brain metabolites
such as glucose), and blood oxygen level dependent Functional MRI (or fMRI,
which measures activation in areas of the brain, say to pain).

Studies so far have demonstrated that:
PWCs perform as accurately as healthy controls, but require more regions of
the brain (that is, PWCs have to work harder to get the same results);
The key cognitive deficit in PWC's is their speed of information
processing; and,
Metabolic findings have been variable, depending on the metabolite and the
group studying it.

Doctors from Barcelona, Spain, and Santiago, Chile, presented their results
of SPECT scanning in PWCs compared to patients with depression.  Dr.
Garcia-Quintana showed that cerebral blood flow is decreased in the frontal
lobes (only) of depressed patients, but reduced in frontal lobes and
brainstem in PWCs.  PWCs also have an increase of blood flow in the
thalamus (a pain control center).   Following exercise (or mental strain
such as puzzles, short stories, or cubing numbers) the cerebral blood flow
was markedly decreased in frontal, pre-frontal, anterior temporal, and
cingulated regions in more than 87% of subjects studied.  Increased blood
levels of the enzymes elastace and RNaseL correlated with more severe loss
of cerebral blood flow.  Comment:  This is old news, but confirms previous
studies in the US.  We have known for over a decade that frontal, temporal
lobe, and brainstem blood flow is reduced in PWCs, which is thought to
cause problems with creativity/motivation/memory (frontal lobes), mood and
memory (temporal lobes), and the sleep/fatigue/autonomic centers of the
brainstem. We also knew that both exercise and mental exertion exacerbate
this reduced blood flow for up to 72 hours!  The new twist is that elevated
elastase and RNaseL levels correlate with reduced blood flow.

Fumihara Togo (UMDNJ) presented a short but elegant paper that studied
motor tasks and performance time in PWCs.  Subjects would focus on a
target  in this case an arrow pointing left or right  and touch one key for
left, another for right. Togo demonstrated that motor performance was
normal in CFS/ME, but that PWCs were slower to perform.  In contrast,
depressed patients had difficulty with both motor skills and speed.

A similar kind of finger-tapping study was described by Mark Van Ness,
Christopher Snell, and Staci Stevens (University of the Pacific). They
measured simple reaction time (the response to a simple target) and complex
reaction time (response to a target hidden within other information) at
rest, and then 30 minutes and 24 hours after an exercise test.  They found
that PWCs were a bit slower to respond than matched controls even at rest,
worst 30 minutes after exercise, and still delayed 24 hours later. This
held for simple or complex reaction time.

Hiro Kuratsune (Kansai University, Japan) concluded this session with a
summary of what is known about brain function in CFS. We know:
The MRI is abnormal in the majority of PWCs due to numerous T2 weighted
hyperintense spots or foci, and evidence of demyelination
PWCs with more brain abnormalities tend to be more physically impaired
The volume of gray matter is reduced in proportion to reduced physical
activity (that is, the brain shrinks in PWCs who are inactive!)
Cerebral blood flow is diminished, especially in the cingulate area
(controls attention, autonomic nervous system), temporal lobes (control
mood, motivation), and frontal lobes (motivation, creativity, and short
term memory)
The concentration of acetyl-carnitine is reduced, particularly in the
cingulate, and supplementing acetyl-carnitine may increase
neurotransmitters such as GABA. glutamine, and aspartate
Acetyl-carnitine supplementation may also improve attention
5-HT (serotonin) transporter binding was reduced in the rostral cingulate
area in PWCs, which may help explain fatigue and pain


Behavioral Health

Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) are
commonly thought to be the only effective treatments for CFS/ME, mostly due
to the influence of two meta-analyses of the treatment literature.  (In
actuality, these were the only two effective modalities that had been
studied extensively, but other treatments may be helpful). Unfortunately,
many practitioners concluded erroneously that psychiatric care and vigorous
exercise were "the cure" for CFS/ME.  Dr. Ellie Stein, a psychiatrist from
Calgary, Canada, eloquently addressed this in her introductory remarks.

Stein pointed out that CFS/ME and FM are chronic, heterogeneous conditions
that are unlikely to respond to any single approach. It is understandable
that both have high rates of psychiatric co-morbidity (such as depressed
mood and anxiety), yet neither is considered a psychiatric disorder. Since
no medication is known to cure CFS/ME or FM, behavioral interventions are a
reasonable consideration.

The earliest CBT/GET programs were based on the false assumptions that
avoidance of activity, illness severity, increased attention to symptoms,
and autonomic arousal ("hyper," or hyper-excitable behavior) were causing
or perpetuating symptoms, when in actuality they were the result of the
illness.  Of seven controlled studies using early CBT techniques,  only 4
were positive and most were inconclusive or poorly done.

Five studies of graded exercise in CFS/ME showed a modest decrease in
fatigue, but improvement in pain, sleep, autonomic, immune, and cognitive
symptoms have not been shown.

It has long been suspected that persons with "pure FM" (i.e., less fatigue
and cognitive dysfunction) can exert more easily, and several studies have
shown temporary improvement in pain and quality of life, but many effects
have worn off within a year. CBT has not been proven helpful in "pure FM."

No study has measured the effect of CBT or exercise in the severely ill.

Stein points out that CBT and GET don't work well because many patients do
not have dysfunctional illness beliefs, many are already functioning at
maximum activity levels, and the exercise makes some people worse!    She
recommends "The Stanford Model," a program for persons with chronic illness
that is based on education, encouragement, and shared responsibility
between patient and professional.  The Stanford Model addresses low level
exercise, cognitive symptom management, nutrition, energy and sleep
management, the use of medication and community resources, managing
emotions, and dealing with health care professionals.  This program has
proven success in MS, rheumatoid arthritis, and other chronic
illnesses.   Dr. Pat Fennell has also developed a proprietary chronic
illness approach, based on her proposed Four Phases of Coping in CFS/ME.
This model encourages patients to collect data, take control of symptoms,
grieve losses, and search for a new identity.  Comment:  Dr. Bruce
Campbell's CFIDS and FM Self Help Book and his online CFIDS and FM Self
Help Course (both available at www.cfidsselfhelp.org) are based on the
Stanford Model, and highly recommended!  Patricia Fennell's books are
available from Barnes & Noble and other booksellers.

Stein went on to point out that self-efficacy (that is, the perceived
ability to control illness) and acceptance of illness are both associated
with positive physical and psychological outcomes.  Therefore, CBT and GET
are the most studied behavioral interventions, but results are short lived
and many do not benefit.  Stein urges alternative approaches such as the
Stanford Model that are more patient friendly and have a good record of
success.

Professor Fred Friedberg (Stony Brook University) presented a short course
on CFS/ME and FM to his students, and found that even a brief exposure to
factual information about these illnesses led to more favorable attitudes
by fourth year medical students. Two points that students endorsed strongly
were, "It is important for physicians to understand CFS," and "Patients are
[NOT] to blame for their illness."


Pediatric Session

Although CFS/ME is known to occur in children and adolescents,
pediatricians have been hampered by the absence of a case definition for
children.  The adult research definition (Fukuda, et al. Annals of IM,
1994)  traditionally has been used, but children have age-specific issues
and generally report different symptoms than adults. With this problem in
mind, the IACFS developed the Pediatric Case Definition Working Group (Drs.
Jason, Bell, DeMeirleir, Gurwitt, Jordan, Lapp, Miike, Torres-Harding and
Van Hoof) to study the problem.  For more than a year the committee studied
various approaches to diagnosis, and developed a new definition,
questionnaires, and a scoring sheet for pediatricians. This new definition
combines the best aspects of the Fukuda definition with the best aspects of
the Canadian Clinical Definition of ME/CFS  (Carruthers, et al, JCFS
11(1):7-115, 2003), and has produced two questionnaires with queries that
are age-appropriate (for under 11 years old, and 11-18 years old).

To establish a diagnosis of pediatric CFS/ME the following five symptom
categories must be satisfied:
Post-exertional malaise
Unrefreshing sleep, or a disturbance of sleep quantity or rhythm
Myofascial, joint, abdominal, or headache pain
Two or more neurocognitive manifestations; and
At least one symptom from two of the following three categories: (1)
autonomic manifestations, (2) neuroendocrine manifestations, or (3) immune
manifestations.

It is hoped that this pediatric case definition will lead to more
appropriate identification of children and adolescents with CFS/ME.  An
article on the development and use of the definition will appear in the
Journal of Chronic Fatigue Syndrome shortly.  The article, questionnaires,
and scoring sheet are available online at www.cfstreatment.info , and will
soon be available on www.aacfs.org   and www.drlapp.net.

Elke Van Hoof (Vrije Universiteit Brussel, Belgium)  reported on how
adolescents with CFS/ME perceive their social environment. She studied 27
Belgian adolescents (mean age 16 + 3 years), three-quarters of whom were
female. Onset of illness was sudden in 48% of cases, and it took about 1½
years to receive a diagnosis.  Only 22% were able to attend school full
time, and more than half (52%) reported conflicts in school. One third
(33%) got help from a teacher or classmate in order to keep up, 82% had to
skip classes frequently, and 70% got failing grades. Forty percent were
involved in extracurricular activities once in a while, but 48% experienced
no activities outside of school.   Van Hoof concluded that CFS/ME in
adolescence can lead to social isolation, grades that fall below true
capability, and poor attendance at school.  Thus the adolescent with CFS/ME
is vulnerable to a poor self image and low self efficacy.


Poster Presentations

Each year dozens of prospective papers are submitted to the scientific
review committee for consideration. Typically the best papers are presented
to the entire assembly, and less solid studies are relegated to "posters"
in a side room or along the walls of the auditorium.  This year the quality
of papers was so good that several poster authors were asked to give a
brief summary of their findings to the assembly.

C. Lennartsson of the Karolinska Institute (Sweden) confirmed previous
reports that low level interval training is well tolerated in CFS/ME.   She
was followed by Mark Van Ness (University of the Pacific) whose exercise
physiology group measured metabolic and immune responses to exercise.  They
confirmed that maximum aerobic capacity (VO2  peak) was reduced in PWCs
compared to sedentary controls (24.3 ml/min/kg compared to 31.4), and the
oxygen capacity at the Anaerobic Threshold was also reduced. They
introduced a new measure, DVO2 / D workload that is also much lower in PWCs
than controls (7.7 in CFS/ME compared to 8.9 in controls, where <8 is
clearly abnormal). Serum lactate was elevated in PWCs, suggesting an
abnormally early shift to anaerobic metabolism.

Pat Fennell (CEO of Albany Health Management) described a paradigm shift
that she is seeing in the patient population, namely a shift from acute
care to chronic care needs. She briefly discussed her Four Phase Model and
the Wagner model of chronic illness management. She urged providers to
focus on whether the patient is responding to therapy; whether
psychological support is needed; whether disability was inevitable; and
whether interventions were appropriately matched to the phase of illness.

Garth Nicholson hypothesized that mitochondrial function is reduced in
CFS/ME, and that replacement of essential mitochondrial lipids could
improve mitochondrial function and reduce reactive oxygen species in the
patient. In two studies, patients treated with glycophospholipids and
"good" bacteria (NTFactor ™) reportedly achieved up to a 43% reduction in
fatigue.

Daniel Blockmans (Leuven, Belgium) reported a randomized placebo controlled
crossover study of methylphenidate (Ritalin™), 20mg daily, in 60 PWCs.
Subjects received either stimulant or placebo for 4 weeks, then treatment
was crossed for another 4 weeks. Using the SF-36, the Hospital Depression
and Anxiety Scale, and visual analog scales for pain, cognition, fatigue
and other symptoms, Blockmans showed that stimulant medication improved
fatigue and concentration significantly in 17% of cases.  F.
Garcia-Fructosa (Clínica CIMA, Barcelona) also provided a poster on the
effect of modafanil (Provigil™, another type of stimulant) in
PWCs.  Modafanil was able to reduce daytime sleepiness by an average of 25%
in 31 PWCs.  However, 65% of patients reported some adverse effects (mostly
anxiety, panic, irritability or palpitations), and 5 had to withdraw from
the study. The drug did not interfere with sleep, however.  Comment:  We
have also noted that PWCs with hypersomnolence and/or excessive daytime
sleepiness respond very well to stimulant medications.  Some report
improvement in concentration and focus as well.  In our experience adverse
effects are usually mild if patients start with a low dose and build up
slowly.

Staci Stevens (Workwell, University of the Pacific) used the SF-36 survey
to monitor post-exertional malaise after 10 minutes of exercise on a
bicycle ergometer. Although patients and controls had similar results
before exercise and 7 days afterward, it took controls only 1 day to
recover, while no PWCs had recovered in 2 days and 50% required 5-6 days to
recover.

Kenny DeMeirleir (Vrije Universeteit Brussels, Belgium) reported that
20-25% of Belgians typically suffer with lactose and fructose intolerance,
respectively, whereas 71% of PWCs have intolerance to fructose (fruit
sugars, beans, cauliflower, cabbage, and yes, brussel sprouts). Lactose
intolerance was similar (20%) in PWCs and the general population.

Jonathan Kerr (St. George's University, London) has done extensive genomic
and proteomic studies in PWCs. This time he reports on miRNA  short
non-coding RNA sequences that are produced in the nucleus, migrate to the
cytoplasm, and regulate translation (cellular protein
production).  Studying 15 PWCs and 30 controls, Kerr found 4 unique miRNAs
in PWCs.

Paul Cheney reported that PWCs demonstrate evidence of diastolic
dysfunction by tilt-echocardiography. This seems to confirm his previous
finding of diastolic dysfunction on impedence cardiography, and is
consistent with known deficiencies of mitochondrial or cellular energy in
patients with CFS/ME and FM.  Comment:   Our office has obtained impedance
cardiograms on at least 8 PWCs, and have seen only trivial diastolic
dysfunction, a condition that is reported in even healthy individuals.
Confirmatory echocardiography in several subjects (but not
tilt-echocardiography) has demonstrated NO significant abnormalities.


Genetic / Proteomics Session

Suzanne Vernon, Human Genomics Team Leader at the CDC, defines genomics as
the study of function and interactions of genetic material in the genome,
including interactions with environmental factors. Genetics on the other
hand is the study of a single gene.  She then described several gene
profiling techniques such as microarrays, gene chips, and RT-PCR.  Such
advanced techniques are used by the CDC and other to unravel the CFS puzzle.

One of the most helpful techniques recognizes fine variations in the gene,
known as Single Nucleotide Polymorphisms or SNPs (pronounced "snips").  For
example, a health gene sequence of nucleotides may look like this to a
geneticist:                              TGCCGAT…
An abnormal gene may look like:                         TTCCGAT…

That one small change is referred to as a SNP and can be used: (1) to
understand who is predisposed to CFS/ME, (2) as a marker for the illness,
or possibly (3) as a clue to a treatment.

Certain polymorphisms are associated with specific groups. For example,
Vernon and her group have been able to identify normal healthy patients,
persons with general fatigue, and PWCs just on the basis of specific
polymorphism patterns.  PWCs have then been subclassified into several
distinct, genetically defined groups.

CFS/ME is difficult to study, however, because it does not appear to be
controlled by a single gene, and the genes change over time (i.e. they are
"epigenetic").

Proteomics is the study of intracellular proteins, particularly their
structures and functions. While the genome is a rather constant entity, the
proteome differs from cell to cell and is constantly changing through its
interactions with the genome and the environment.


Genetic Profiles in Severe Forms of FM and CFS was presented by Estibaliz
Olano.  She and her colleagues at Progenika Biopharma (Barcelona)
hypothesized that persons with CFS and FM could be differentiated
genetically. From a pool of 2000 subjects they assessed 186 women with FM
and 217 women with CFS/ME.  These subjects were stratified by special
questionnaires into "severe" or "mild-to-moderate" cases.   SNP profiling
was able to discriminate the severe cases from less severe cases of
CFS/ME.  These SNPs were related to 6 major genetic areas that fit the
clinical understanding of CFS/ME:

COMT, THP, DOPA, 5HT (these genes control neurotransmitters)
POMC  (produces adrenocorticotropin, melanotropes, and
melanocyte-stimulating hormone)
Glucocorticoid and corticotrophin receptors
Interleukins (cytokine production)
NOS (nitrous oxide production)
TNF (more cytokine production)

Also 15 SNPs were identified that separated PWCs from persons with FM with
53% sensitivity and 95% specificity.

Comment:   This work by a commercial lab in Spain is consistent with
findings from the CDC (see below) and other genomic studies.  Such
corroboration makes it more likely that genomics can help us understand
CFS/ME/FM, and perhaps will provide a marker for these illnesses.

M.S.Rajeevan reported results from one of the CDC genomic studies. This
concluded that SNPs link CFS/ME to HPA axis dysregulation, immune
dysfunction, and high levels of allostatic load (that is, chronic stress).
137 subjects were selected from the CDC's Wichita Hospital Study, and these
individuals were able to be differentiated into 5 unique classes.  Five
genomic markers for glucocorticoid receptors were more common in PWCs than
in persons with chronic fatigue alone and those who were not fatigued;
there were 3 serotonin receptor markers that were associated with CFS as
opposed to chronic fatigue or non-fatigued individuals.

James Baraniuk (Georgetown University, Washington DC) studied the
proteomics of CFS/ME. He defined a proteome as "a set of proteins in one
cell, compartment or person."  His hypothesis was that Central Nervous
System dysfunction was common in CFS, FM, and Gulf War Syndrome, so
abnormal proteins would probably appear in cerebrospinal fluid (CSF). He
studied the CSF of 52 subjects, most of whom met international criteria for
CFS/ME.

In his first experiment, 10 proteins were identified as shared between
CFS/ME and GWS, but totally absent from healthy individuals. The second
experiment demonstrated that keratins (which are rare) and orosomucoids
were seen in PWCs, but not in controls. Ten proteins found in the first
cohort of PWCs matched the protein abnormalities in the second cohort.
Baraniuk estimated that the chance of this occurrence was about one in one
million!

Baraniuk found proteomic evidence for:  protease-anti-protease imbalance,
structural injury, oxidant injury, vascular deregulation, leptomeningeal
activation, and structural repair.  In conclusion, the common "CFS-related
proteome" in cerebrospinal fluid suggests shared pathophysiology in CFS,
FM, and GWS. This proteome is NOT found in healthy control samples.

Lastly, Frederick Albright (University of Utah) used geneology to provide
evidence of a heritable contribution in CFS/ME.  The Mormon geneology
database includes 2.2-million Utah Mormon pioneers and their descendants
over 10 generations, and health records have been linked to the geneology
since 1994. Thus it is possible to follow the inheritance of CFS over at
least 16 years.  Albright identified 551 descendents with CFS (65% female,
35% male).

He first hypothesized that if CFS is heritable, it should occur at higher
frequency in close relatives of CFS cases. In fact, the risk of a first
degree relative contracting CFS was 7.68X, while the risk for a second
degree relative was 2.54X. This suggests that CFS is indeed heritable.

The second hypothesis was that if CFS is familial, CFS cases should be more
closely related than controls. Using sophisticated analysis, he
demonstrated that case-relatedness was 4.13 units and control relatedness
was 2.81, which was statistically significant. Thus CFS/ME appears to be
familial as well as heritable.


New Methods

One of the most fascinating and practical papers was given by Akikazu
Sakudo of Osaka University, where he works with H. Karutsune,Y. Watanabe,
and others.  Sakudo described using visible and near-infrared spectroscopy
(which is typically used to examine fruit for ripeness and quality) to
discriminate PWCs from normal healthy controls. Both serum scan and a
simple scan of the thumb were obtained and then analyzed using "principal
component analysis" (PCA) and "soft independent modeling of class analogy"
(SIMCA) statistical techniques. The result was a clear separation of normal
healthy persons from persons defined by international (Fukuda or CDC)
criteria to have CFS/ME.
Comment:   This is like Star Trek!  Using a simple handheld gun-like
apparatus, Japanese researchers scanned a test tube of serum or simply
scanned the patient's thumb, and immediately the Vis-NIR Spectroscope could
predict whether or not the patient had CFS/ME. This technique takes less
than one second to perform, and requires no skill on the part of the
examiner!  Although the spectroscope identified 100% of healthy individuals
and 42 of 45 PWCs (93%), it is not known yet if the technique can separate
PWCs from persons with other illnesses like MS, rheumatoid arthritis, and
depression.  If successful, this relatively inexpensive (US $3000-8000) and
harmless device could provide rapid definitive diagnosis and finally
silence the skeptics. [Thank goodness Vir-NIS spectroscopy can't treat, or
I might be put out of a job by a machine!]


Viral and Immune Interactions

Viral infections have long been suspected as the cause of  CFS/ME, but no
infectious agent has ever been identified.  A related viewpoint is that a
virus may trigger CFS/ME, but then an abnormal biochemical change
perpetuates the illness.  This has been referred to as the "hit-and-run
theory." Ron Glaser (Ohio State University) examined another possibility,
that latent viruses (or even parts of viruses) could be producing abnormal
proteins within the cells of our patients, causing immune dysregulation,
cytokine production, and inefficient T-cell or NK-cell function.  Viruses
(or parts of viruses) can induce cells to manufacture proteins and enzymes,
some of which may be injurious to the call.  Glaser's group injected into
mice an enzyme (dUPTase) that is encoded by the EB virus. Immune function
and behavior were then monitored.  Lymphocytes in the injected mice were
less able to replicate, and the treated animals lost weight, had elevated
temperatures, and were slow-moving.

Glaser's group also elegantly demonstrated that stress and age affect
latent virus activation. Geriatric patients, for example, had much higher
titers of antibodies to Epstein-Barr Early Antigen (EA) and Capsid IgG
(VCA-IgG) than young adults.  And when antibody titers were measured in
young students at various times during the school year, titers were noted
to rise as much as four-fold during exam periods, and drop to more moderate
levels during Summer vacation.  Comment:   This is no surprise to anybody
who has experienced the recurrence of herpetic mouth ulcers or recurrent
shingles (zoster) following periods of stress. The point, however, is that
latent viruses (like VZV, EBV, and HHV6) can reactivate during periods of
stress, causing immune changes and even symptoms of illness.  Since EBV is
an oncogenic virus, Glaser raises concerns that such reactivation could
conceivably cause B-cell lymphomas. To my knowledge the latter has not been
confirmed in CFS/ME.

One question that arises frequently is, "Which test should we use to detect
chronic reactivation of viruses such as HHV6 and EBV?"    Dharam Ablashi
(HHV6 Foundation, Nevada) pointed out that viral re-activation is  more
closely associated with CFS/ME than just titers of latent antibodies. He
examined several techniques for measuring viral presence.  Qualitative PCR
on whole blood did not differentiate between active and latent infection,
and there was too little virus in serum to make this assay useful. Active
infection can be inferred by quantitative PCR, serum nested PCR, and
analysis of cytopathic effect, but these techniques are difficult,
expensive, and not readily available to clinicians. On the other hand,
Ablashi provided evidence that highly elevated titers (>1:320 or 1:640) of
commercially available IFA assays for IgG can be used to identify patients
suspected of having active infection.  Comment:   Now we know that high
titers of EBV or HHV6 IgG are likely due to reactivation, and possibly
amenable for antiviral therapy.

Susan Levine (private practice in NY City) and others measured IgG levels
to HHV6  and early antigen titers of EBV in persons with CFS/ME.  45% of
PWCs had titers of >1:320 to EBV and 35% had titers of >1:320 to HHV6,
whereas none of 11 controls had such elevated titers.  This suggests that a
subset of PWCs suffer from chronic infections with EBV and/or HHV6.

Cytokines are immunologically-based chemicals that can cause viral symptoms
such as fever, sore throat, swollen glands, achiness, etc.  Brian Gurbaxani
(CDC, Atlanta) described a simple but helpful study that demonstrated
increased levels of one pro-inflammatory cytokine, Interleukin 6 (IL6), in
PWCs.  His group demonstrated that increased levels of IL6 were
proportionate to CFS/ME symptom severity, but also correlated with
waist-to-hip ratio (one measure of allosteric load, or "stress") and
C-reactive protein (CRP), which is a marker of inflammation.   This finding
supports the hypothesis that an ongoing inflammatory process could be
contributing to CFS symptoms.

John Chia (EV Med Research, California) reported on enterovirus infections
in PWCs with GI distress. Enteroviruses (a genus of RNA viruses that
includes echovirus, coxsackie virus, and poliovirus) have been reported in
CFS/ME patients by the British, but have not been explored much in the US.
Chia obtained gastric biopsies on 108 PWCs with upper gastrointestinal
complaints plus 12 normal healthy subjects and 9 subjects with other GI
disorders.  100 of the patient biopsies revealed at least mild chronic
inflammation, of which 5 demonstrated infection with H.pylori.   Eighty-six
(86/108=80%) were positive for the VP1 (enteroviral capsid protein), while
only 2/21 (10%) of controls were positive.  Enteroviral RNA was detected in
5 of the 15 biopsy specimens studied (33%).  Thus enteroviral infections
may play a role in a subset of PWCs with upper gastrointestinal complaints.

While the evidence is not as compelling as with other infectious organisms,
Garth Nicholson (Institute for Molecular Medicine, Calfornia) and
colleagues continue to report positive PCR results for Mycoplasma species
in PWCs and Gulf War Syndrome victims.


Additional Posters

Tae Park (Seoul, South Korea) reported once again on his remarkable success
in treating PWCs with one gram of intravenous gamma globulin weekly for 6
months.   In addition Park attends to diet, sufficient salt and water
intake, regular exercise, and sleep management.  He reported on 50 patients
(28M, 22F), all of who were severely ill and disabled with
CFS/ME.  Twenty-five of the 28 males improved enough to return to work
(Karnofsky Performance Score from 40 to 90; Fatigue Impact Scale from 120
to 20-40). Eighteen of 22 females remarkably improved also (KPS 40 to 80;
FIS 125 to 40-50).   Comment:  Four major studies using IVGG for the
treatment of CFS/ME have shown variable results   two were successful, two
were not. Park has abundant and continued success with his regimen, but
possibly his adjunctive therapy or regular IV fluid administration
contributes to some of his success?

Lastly, Jacob Teitelbaum (Annapolis Research Center, Maryland) provided a
poster on his most recent vogue, d-ribose.  Ribose is a sugar (not at all
like table sugar!) that is used by the cell and specifically by the
mitochondria in the production of energy.  Other studies have suggested
that d-ribose supplementation may improve cellular energy in heart and
skeletal muscles. Teitelbaum's pilot study included 41 PWCs who took 5
grams of d-ribose thrice daily for about two weeks. Using visual analog
scales, 66% of the patients reported significant improvement during the
study, with an average increase of 42% in energy and 30% in
well-being.  Comment:   If confirmed, this is great news!  I am concerned,
however, over the short treatment period, which is well within the placebo
effect range.  Also, subjective improvement is one thing, but do any
objective parameters improve?   Teitelbaum states that a randomized
controlled trial is underway, so perhaps we will find out soon.


Conclusions

This was an excellent and exciting meeting, perhaps the best CFS/ME
conference yet.  Information was so overwhelming that two weeks later I am
still trying to sort it out!

It is clear from the number and quality of papers submitted that CFS/ME
research is beginning to thrive, and that several other nations now rival
the US in this field.  Particularly productive this year were Japan,
Belgium, Spain, Sweden and the United Kingdom.

Two salient events during the conference were the IACFS vote to change the
name to CFS/ME, and the introduction of the Pediatric Case Definition.  I
am sure that these recommendations will have both profound and positive
consequences.

There were several themes that ran through the conference:
Researchers are looking more at specific symptoms such as fatigue, pain,
and sleep, rather than the syndrome as a whole.
Genomics and proteomics are clearly confirming previous theories of
pathophysiology, and look hopeful as a means toward a marker for the
illness, clues as to causation, and a way of subtyping subjects.
As research becomes "deeper" or more molecular the differences between
CFS/ME and FM are more distinct.
The importance of subtyping is more recognized. At this time many
researchers consider such subtypes as male/female, acute/insidious onset,
severity, and whether fibromyalgia is present or not.
The Center for Disease Control is strongly encouraging specific instruments
for documenting symptoms, function, and compliance with the Fukuda
Criteria, but these are not yet widely used. As a result, it is not clear
what is meant when an author states that his subjects "meet international
(or CDC) criteria."
And clearly the concept of viruses or latent infections as perpetuators of
CFS/ME are back in favor.

So what have I learned personally that will aid me in diagnosis and treatment?
First of all, I will recommend testing for elastase, RNaseL, C-reactive
protein, selected cytokines, and NK Cell Activity, because they are
objective markers of pathophysiology and severity, and they can monitor
response to therapy.
I will recommend a test-retest approach to cardio-pulmonary exercise
testing, because it confirms for disability purposes reduced functional
capacity as well as post-exertional malaise.
I will recommend more overnight sleep studies because a majority of PWCs
and PWFs have treatable sleep disorders that can be identified and
monitored only by polysomnography.
I will encourage a more multi-disciplinary approach, especially supportive
counselors for those who are deeply depressed or catastrophizing
I will look for lipid abnormalities and evidence of metabolic syndrome in
our patients, and address these problems more aggressively.
I will recommend exploration of chronic illness models (such as Bruce
Campbell's Self Help Course) as a means for group counseling and support.
While graded exercise programs may be too aggressive for many patients,
interval exercise and heart-rate-limited exercise programs are safe and
effective therapies.
I will test more for HHV6a and EBV reactivation, and consider cautious
administration of valgancyclovir and/or high dose valcyclovir.
I will be recommending trials of acetyl carnitine, d-ribose, replacement
lipids (such as NTFactor™), and antioxidants based on favorable reports
presented at this conference.


Charles W. Lapp, MD, Director
Hunter-Hopkins Center, P.A., Charlotte, North Carolina
January 29, 2007


The above information reflects the personal opinions of the author only,
and is not meant to be an exact or exhaustive review of the IACFS
conference. This material is copyrighted, but may be reprinted with
permission of the author and with appropriate credit.   Contact
drlapp drlapp.net .   (© 2007)

[Return to top]

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

Date:    Wed, 14 Feb 2007 14:12:34 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks@COMBIDOM.COM>
Subject: RES,NOT: IACFS Conference report/Rosamund Vallings

Source:  Rosamund Vallings
Date:    February 12, 2007


IACFS Conference report
-----------------------

I was privileged to attend the 8th IACFS conference in Fort Lauderdale,
Florida from 10-14th January 2007. There was a larger number of
presentations and attendees than at any previous CFS conference, and the
quality of presentations and research achieved in the past 2 years was
indeed exciting. The conference was ably organized and hosted by Dr Nancy
Klimas, and thanks must go to her. This conference combined the research
and clinical work which thus gave a good overview of all aspects of the
illness. The days were long and intensive, but most people (even those
with CFS) managed to stay the distance and there was so much to learn.
The conference was truly international with participants and presenters
from around the globe.


FATIGUE SESSION

The first session covered various aspects of fatigue. This was overviewed
by Prof Y Watanabe from Osaka, Japan. He described about 1/3 of the
population in Japan as suffering from fatigue; 42% due to overwork, 19%
due to disease and the rest of unknown cause. There are 3 major bioalarm
systems: pain, fever and fatigue, the latter being an important bioalarm
to order rest. Fatigue is felt in the brain, and maybe acute, subacute or
chronic. Various methods were described to study fatigue such as cortical
function, behavioural, autonomic nerve function, biochemical markers in
plasma and saliva and brain function with scans. The aim of such studies
on fatigue is to develop likely therapeutic interventions and anti-fatigue
programmes.

Not only drug and dietary measures are being studied, but such issues as
environment, aromas, animal (pet) intervention, creativity etc.
Motivation helps to overcome fatigue particularly with creativity.

S.Tajima (Osaka) presented a study using actigraphy showing that quality
of sleep was decreased because of increased wake episodes during the sleep
period. This leads to lack of para- sympathetic activation during the
sleep period, and further deterioration of sleep quality in CFS.

Complexity surrounding the word "fatigue" can be reduced by creating new
terms to describe fatigue and this was outlined by N.Porter (De Paul Univ,
USA). Results using the ME/CFS types questionnaire (MFTQ) showed that
there are 5 types of fatigue associated with CFS:
1. Wired (overstimulated, tense, agitated),
2. Brain fog,
3. Molasses fatigue (heaviness)
4. Flu fatigue (immunological)
5. Post-exertional.
This new classification of fatigue can help to study fatigue more thoroughly.

E.Maloney (Atlanta, Georgia) confirmed the association between CFS and
high allostatic load. Allostasis is the maintenance of stability through
change. Environment, trauma, stress, behavioural response, genes and
developmental experiences all have an effect on the physiological changes
leading to allostatic load. 56% of CFS patients were found to have high
allostatic load (females>males). Incidentally it was also found that those
with CFS in this study in Georgia had a greater prevalence of metabolic
syndrome. The greater the allostatic load the greater the prevalence of
metabolic syndrome, and females with metabolic syndrome were 4 times more
likely to have CFS than females without metabolic syndrome.

Claims for disability in the USA in CFS have been limited by lack of a
confirmatory test to establish a diagnosis. However an abnormal exercise
stress test is an example of a laboratory test that can be used.
M.Ciccolella (Stockton,CA) compared tests to show that results from serial
exercise tests can be used to assess the effects of post-exertional
malaise in CFS. It is concluded that a single exercise test is
insufficient to demonstrate the extent of functional impairment in CFS
patients. A second test 24 hours later showed that CFS patients had
significantly worse performance and this distinguishes CFS from other
illnesses.

U.Hannestad (Linkoping, Sweden) investigated the possibility of
abnormalities in excretion of GABA and -alanine in urine because of the
sleep disturbance and fatigue in CFS, GABA being the major
neurotransmitter in the CNS, and -alanine exerting inhibitory effects in
the CNS. Increased excretion of -alanine was found in a small subgroup of
the CFS patients studied. Urine may not be the best body fluid to estimate
these chemicals however, and cerebrospinal fluid would be better if
practical.

P.Nestadt (New York,USA) compared brain metabolite levels between CFS with
generalized anxiety disorder and healthy controls and examined the
association of derived neurochemicals and psychiatric symptomatology.
Previous uncontrolled studies had showed elevated lactate in the brain in
CFS. This study showing a significant proportion of CFS patients had
elevated ventricular lactate, and marked differences in hippocampal
glutamate helped to distinguish between CFS patients with and without
depression. Those with CFS also had significantly lower N-acetyl-
aspartate in the right hippocampus, indicating reduced neuron density or
metabolism.

The role of alterations in apoptosis playing a role in post-infection
fatigue states (PIFS) was addressed in a study using gene array techniques
presented by T.Whistler (Atlanta,Georgia). The severity of an acute
infection is related to the likelihood of recovery, and affects the
fundamental cellular processes. These resultant altered gene expression
profiles are manifest in several persistent symptoms in PIFS. This
indicates that many symptoms maybe immunologically mediated. The genes
work as a team and there are a number which overlap.

An overview of the Fatigue Session was summarized by Fred` Friedberg. He
discussed how we can measure fatigue ­ using retrospective questionnaires
may not relate to real time. Self report of physical function may not be
"actual". In real time measures, subjects may not remember fatigue
accurately, so physician visits and behavioural assessments are important.
Use of palm pilots can give more accurate real time measures, and practice
gives better recall for fatigue.

In an actigraphic study over 2 years to assess functional improvement, the
better a person's health, the less they reported fatigue having an effect
on function, however despite spending less time lying down, they were
still not actually better. There was global improvement leading to
improved self report functioning which was likely to be due to improved
coping ability. It is probable subjects were conducting their activities
differently over time. Graded activity was not shown to increase actual
activity ability, and there was no confirmation of improved symptoms.
Fatigue and pain tended to increase after 30% of increased activity. More
sleep time may lead to activity substitution.


FATIGUE POSTERS

The use of Heart Rate Variability (HRV) software was described by E.Stein
(Calgary, Canada) as a useful in office diagnostic tool. HRV has been
reported to show significant differences between CFS patients and
controls. This software can efficiently distinguish between patients and
controls. The severely ill patients were found to be 2SD `below the mean.

S. Stevens (Salt Lake City,USA) found that for CFS patients post
exertional malaise is an incapacitating feature of the syndrome. There is

a delayed recovery response to exercise distinctly different from
controls. Patients took on average 4 days to recover from the graded
maximal cardiopulmonary test compared with one day for the controls. 50%
required more than 5 days to recover.

K. de Meirleir (Brussels, Belgium) found that fructose malabsorption is
very common in their CFS patients. Lactase deficiency is less common, and
equal to the level in the normal population. These conditions can lead to
intestinal dysbiosis, and careful diet is therefore required.

R. Van Konynenburg (Livermore,USA) claims to have found compelling
evidence for glutathione depletion methylation cycle block as part of the
pathogenesis of CFS, in a number of patients. He hypothesizes that the
higher prevalence of CFS in women is due to genetic polymorphisms in
certain enzymes involved in the metabolism of oestrogens.

In a pilot study, J.Teilelbaum has treated 41 CFS and FM patients with
D-Ribose. This has markedly improved many symptoms such as energy and
sleep patterns. A larger RCT is planned. An overview of MCS was presented
by P.Gibson (Harrisonburg, USA). She emphasized that there is need for
further research in this little understood condition, which has a serious
impact on quality of life. She also noted that there is a great lack of
understanding of this condition by health professionals, and education is
essential. A.Cusco-Segarra (Barcelona,Spain) has found the abbreviated
environmental exposure and sensitivity inventory useful to detect MCS. The
validity needs some fine tuning.

A. Chester (Washington DC, USA) looked at the prevalence of patients with
unexplained chronic fatigue and chronic rhinosinusitis. They are more
likely to notice a sudden onset of fatigue. The presence of non-frontal
headache was also more common than in fatigued patients without sinusitis.

Decreased renal function (40-50%) was a frequent finding in a group of 15
CFS patients studied by T.Park (Seoul,Korea). His hypothesis is that CFS
is a microvascular disease impacting individual organs. He notes that
diabetics with renal vascular disease also complain of profound fatigue.

Increased incidence of thyroid malignancy associated with CFS was outlined
by B.Hyde (Ottawa,Canada) and he stressed the importance of evaluating for
this, if suspected, by thyroid ultrasound and needle biopsy despite normal
serum thyroid chemistry.

Improvement in symptoms was reported in 6 out of 15 patients after
administration of probiotics by A.Sullivan (Stockholm,Sweden). 8 patients
were unchanged and one felt worse. Certain strains of lactic acid bacteria
help to normalize the cytokine profile and have anti-oxidant effects.


SLEEP SESSION

An introductory overview of this session was given by J Shaver
(Chicago,USA). Generally 1/3 of the population report poor sleep and are
unrefreshed on waking. Sleep leads to mind/body recovery. There is no
rule of thumb as to the amount of sleep needed, but the aim should be to
function efficiently when awake. Sleep measurement was discussed, such as
using self-report and polysomnography. Heart rate, leg movement and
breathing could thus be monitored. Sleep can be affected by weak sleep
drive, excess emotional or physiological arousal, poor synchrony of the
light/dark cycle and negative sleep environmental conditioning. Therapy
is aimed at: keeping attuned to the light/dark cycle; sleep restriction;
behavioural cues, which include bedtime routine and avoiding incompatible
cues and dampening of both cognitive arousal and physiological activation.
She described various sleep disorders such as restless legs, periodic limb
movement and breathing problems and also addressed issues relating to
physical illness (such as CFS) and medication effects. Finally she
mentioned that both growth hormone and prolactin release are lowered in
fibromyalgia (FM), and the sleep disorders aforementioned are superimposed
on the sleep deficit associated with FM.

C. Lapp (Charlotte NC, USA) followed with a further sleep overview from a
physician's point of view. He emphasized that dealing with sleep is one of
the most important aspects of the management of CFS. He described a
number of problems associated with sleep in CFS: Non- restorative sleep,
difficulty in intiating and maintaining sleep, restless legs syndrome
(RLS), periodic limb movements (PLMs), nocturnal myoclonus, vivid
nightmarish dreams, "tired but wired", phase shift and dysania
(foggy,stiff and sore on waking). The sleep may also be affected by
primary sleep disorders (apnoea, periodic limb movements, narcolepsy)
medication, FM, stress, depression and habituation. Sleep latency may
also be increased and there maybe decreased sleep efficiency. In FM the
sleep problems encountered include lowering of sleep efficiency and slow
wave sleep, increased awakenings and K complexes in stage 2, and increased
NREM intrusion.

Lapp also described "Upper Airways Resistance Syndrome" (UARS), which is
not as severe as apnoea, but leads to frequent arousal with slightly
lowered oxygenation, more physical symptoms including low BP and mild
eratic breathing. In one study of UARS, use of CPAP decreased physical
symptoms by 40%.

The approach to treatment should be to rule out primary sleep disorders,
deal with patient's preconceptions and denials, emphasise sleep hygiene
and consider CBT. Medication to be tried can include: melatonin,
antihistamines and tricyclics. Dopamine agonists can be useful for PLMs
and clonazepam can reduce restlessness and myoclonus. Reduction of pain
is also an important issue. Non-restorative benzodiazepines, such as
zopiclone should be avoided. Opiates will reduce short wave sleep and
SSRIs may increase RLS. Alcohol should also be avoided.


SLEEP POSTERS

E. Van Hoof (Brussels,Belgium) found a number of sleep abnormalities as a
result of a study in CFS patients. These include, sleep latency problems,
-delta intrusion associated with anxiety, but RnaseL-ratio did not
correlate with -delta patterns. The results therefore question RnaseL as
a biological gradient.

It seems that CFS patients may have a heightened perception of sleep
dysfunction compared with controls. M.Matthias (Atlanta, USA) found that
reports of sleep problems were reported more often in patients than
controls experiencing sleep disorders. There was a negative correlation
between perceived poor sleep and reduced activity scores in CFS.


CLINICAL TRIALS SESSION.

This session began with 2 presentations by B Hurwitz (Miami,USA). He
covered the previous research showing that those with CFS often have
diminished RBC volume due to normochromic, normocytic anaemia (NNA). His
team have studied the use of erythropoetin- (EPO-) on RBC volume, fatigue
and susceptibility to syncope during head up tilt (HUT) in CFS patients.
Patients whose ferritin levels were non responsive to iron supplementation
were excluded. Of the 57 patients studied, 66.7% were found to have low
blood volume of up to 15% below normal. They looked at the CRP and serum
interleukin-6. Pro-inflammatory cytokines have a secondary effect in
reducing RBC volume, due to probable suppression of RBC production in the
bone marrow. Hurwitz concluded from this study that fatigue in CFS
patients with low RBC volume was not improved by EPO treatment, but
susceptibility to orthostatic syncope was diminished in those subjects
with more substantive EOP-induced RBC volume improvement.

A preliminary trial by J Montoya et al (Stanford, USA) showed that
Valganciclovir (over 6 months) was associated with positive clinical
response in CFS patients with high antibody titres against HHV-6 and EBV.
There was marked improvement in fatigue. This warrants a further double-
blinded, placebo-controlled trial. This drug is active against all herpes
viruses (including EBV and CMV) and is a well absorbed drug. There are
potential haematological and renal side effects, and this drug should not
be used in pregnancy.

M. Lerner (Michigan, USA) had also conducted a Phase 1 clinical trial
using valaciclovir or valganciclovir or both for 6 months in CFS patients
with positive EBV or CMV titres, who had abnormal ECG T wave flattening or
inversion. All 37 patients treated had a positive response with no
serious side effects. However patients were encouraged to drink
plentifully to avoid renal stone formation, and liver function tests and
platelets were monitored.


CLINICAL TRIALS POSTERS

F. Garcia-Fructuoso (Barcelona,Spain) found modafinil effective in the
treatment of daytime sleepiness in CFS. In a study of 31 patients, side
effects were experienced by 67% and 5 patients (14%) withdrew from the
study because of side effects. D.Blockmans (Leuven,Belgium) found that
methylphenindate (2X10mg daily) was significantly better than placebo in
reducing fatigue and concentration disturbance in a small % of CFS
patients.

Lipid replacement and antioxidant therapy for restoration of mitochondrial
functioning with a nutritional supplement (NT Factor) was found by
G.Nicholson (Huntington Beach,USA) to significantly reduce moderate to
severe fatigue.

T. Park (Seoul,Korea)used IV gammaglobulin 1gm weekly for 6 months coupled
with strict diet (including increased salt), sleep (medicated) and
exercise control and showed significant improvement in 50 CFS patients.

Advice for dental procedures was outlined by W.Saldana (New York,USA) and
she stressed the importance of the dentist being part of the treatment
team. Attention must be given to pain management, analgesia, and risks of
oral bacteria.

R. Shoemaker (Pocomoke, USA) used low dose erythropoietin, in a short
clinical trial, safely lowered symptoms and improved levels of C4a in
responders. Maintenance of lowered C4a was associated with improved
quality of life. Out of 60 patients, 51 noted symptom reduction, however
34 relapsed within 3 months. Another study suggested that the systemic
inflammation in CFS caused by elevated C4a may be treated using
erythropoietin and that the CNS correlates of cognitive dysfunction in CFS
have an inflammatory basis.

In a further trial, Tadalafil was used in 30 CFS male patients. This drug
has been shown to lower elevated pulmonary artery pressure. This usually
falls in response to exercise, improving pulmonary venous return to the
atrium. In the trial the drug was found to safely reduce dyspnoea and
improved exercise tolerance concomitant with an improvement in pulmonary
artery response to exercise. 93% had changes in erectile behaviour.


PAIN SESSION

Pain was described as a major feature in many aspects of CFS by K.Berkley
(Tallahassee, USA) in her overview of pain. It can be extremely
disabling, interfering with sleep and causing fatigue. Alleviating sleep
disturbances can alleviate pain leading to improved quality of life.
Patients conceptualise pain like touch, and better understanding of the
mechanisms of pain can make a difference for the individual. There is a
pain matrix in the brain and the experience of pain occurs as a result of
central processing via a network in the CNS. Multi responses may occur in
different organs. Constant integration of information from the body by the
CNS leads to planning and reorganizing of body actions. Pain is not a
pathway, but a dynamic process. Using endometriosis as an example,
symptoms of muscle hyperalgesia, interstitial cystitis and irritable bowel
syndrome may become more prominent due to the endometrial growths
developing their own nerve supply and sending more input into the CNS
leading to cross system interactions.

K.Kato (Stockholm, Sweden) looked at associations between chronic
widespread pain and its co- morbidities, which included FM, CFS, IBS, etc
in the general population. The associations are mediated by genetic and
family environmental factors, and the extent of mediation via familial
factors is likely to be disorder-specific. In these illnesses there are 2
latent distinct traits that` are common to all, but unique factors
specific to each illness.

Mechanisms and treatment for fibromyalgia and related conditions was
further expanded by D Clauw (Michigan, USA). He described FM as being
caused by a combination of genetics, various triggers, and mechanisms such
as the relationship between physiological and psychological factors,
disordered sensory processing (e.g. increased sensitivity to noise, smell
etc) and autonomic/neuroendocrine dysfunction. There is a strong
familial disposition. FM patients can be categorized into 3 groups
according to psychological factors. Those whose psychological factors
worsen symptoms have more tenderness, high depression/anxiety, are high
catastrophisisers and have no control over the pain. PET and fMRI have
both identified a number of brain regions (thalamus, amygdala and
prefrontal cortex) involved in pain processing.

There is good evidence to support the treatment of FM through education,
aerobic exercise and CBT. Alternative therapies such as balneotherapy,
hypnotherapy and biofeedback are moderately useful, but there is only weak
evidence for use of other alternative approaches. There is strong evidence
supporting the use of pharmacological agents such as tricyclics, SNRIs,
and anticonvulsants, but doses should be increased very slowly. Tramadol
and SSRIs are modestly helpful and there is only weak evidence to support
the use of growth hormone, 5HTP, tropisetron or SAMe. There is no evidence
for help from opioids, corticosteroids, NSAIDs, benzodiazepines, non-benzo
hypnotics or guaifenesin.


PAIN POSTERS

A. Bested (Toronto, Canada) and A Logan (Harvard,USA) have written an
excellent book "Hope and Help for CFS and FM" providing a useful tool for
patients and professionals and covering a wide range of related topics.
Sample copies were freely available.


EPIDEMIOLOGY and CASE DEFINITION SESSION

R. Herrell introduced the session by explaining the history and
development of epidemiology and its application to study of disease in the
21st century. Use of modern statistical methods coupled with social and
genetic epidemiology has furthered studies, identifying the aetiology of
disease and determining interventions.

Epidemiological studies by W Reeves et al (Atlanta, USA) compared those
meeting the current criteria for CFS, with those with fatigue but
insufficient symptoms (ISF) to be diagnosed with CFS and non fatigued
controls, in an attempt to subgroup those with CFS according to their
level of impairment and symptom severity, and to see if persons with ISF
do resemble any of the CFS subgroups. Results suggested that a subset of
those with ISF do have a similarly severe illness to CFS, but usually
without at least 4 of the case-defining symptoms.

A 10 year follow up by H.Kang (Washington, USA) of Gulf war veterans
suffering from CFS compared to non-Gulf military peers, showed that the
CFS symptoms decreased significantly in the Gulf compared to non-Gulf
sufferers.

R. Underhill (New Jersey, USA) found that the offspring of mothers with CFS
also risk developing CFS or CF in childhood or later life. CFS occurred in
5.5% 0f the offspring. Most of the offspring were born before the mothers
developed CFS. 24% of the mothers had an offspring with CFS. Recovery
rates were 50% for CFS and almost 1/3 for CF. 1/3 of the mothers also
reported they had a parent with CFS or CF. There were however 5 times as
many healthy offspring as fatigued. There were no other significant
additional risks if the mothers had other blood relatives with CFS.

Monozygotic twin studies by A. Jacks (Stockholm, Sweden) using the
non-affected twin as a case control, found that gene expression profiles
can be explored efficiently. 35 pairs of twins discordant for CFS are
being studied. Major co-variates such as depression, life events need to
be considered, and full results of this important study should be
available in 2008.

A follow-up from 9/11 looking at unidentified somatic complaints and
coping strategies was undertaken by B. Melamid (New York, USA). This may
provide an opportunity to look for early symptoms of unexplained illnesses
such as CFS. There was no significant incidence of PTSD reported.
Tendency to depression and substance and alcohol abuse were reported
depending on proximity to site, loss of loved one etc. Coping with "hope"
(less depressed) or "avoidance" (more depressed) were significant
predictors of depression.

The economic impact of CFS on society in a community based versus tertiary
based sample was discussed by L Jason (De Paul University, USA). In the
USA there is a 27% reduction in employment attributable to CFS, with
19-27% receiving disability payments and 30% only able to work part-time.
These indirect costs amount to about $17½ billion annually. The direct
annual health costs for individuals in tertiary care are $8674 and in
community care $2300. (This amounts to up to $7 billion annually). For
non fatigued controls, annual health care costs $1132. The individual
cost per person with CFS is equivalent to $25,000 annually.

The rates of CFS throughout the world are variable with an incidence in
the USA of 2-4 per thousand. This is equivalent to 800,000 to 1 million
people. L.Jason had also studied the rates of CFS in Nigeria, the first
community based study in a developing country. Estimate of prevalence was
0.68%, and future research with larger studies is now needed. In Iceland,
E.Lindal (Reykjavik) showed different prevalence rates of CFS according to
the criteria used. The Fukuda criteria yielded a rate of 2.2%. There was
no significant relationship between present day sufferers and those who
were in the 1947 epidemic.


EPIDEMIOLOGY POSTER SESSION

Timed Loaded Standing (TLS) could be a useful measure in the study of
populations reporting chronic fatigue. In a study reported by G.Moorkens
(Antwerp, Belgium) major differences were shown between patients who were
chronically fatigued in Belgium and the Gambia. TLS involves measuring
the time a person can stand while holding a 2 pound dumb bell in each hand
with the arms at 90 degrees of shoulder flexion.

J. Fernandez-Sola (Barcelona,Spain) found that 96% of patients diagnosed
with MCS share the criteria for a diagnosis of CFS, and 25% also with that
of FM. This suggests a common pathogenic mechanism.

T. Osoba (West of England) is working to produce a new case definition of
CFS prevalence, to improve the sensitivity, specificity and accuracy of
selection of CFS cases. L.Jason (DePaul University,USA) concludes that
following use of a broad theoretically driven questionnaire, one can more
accurately identify the critical symptoms in CFS. Whether or not to
exclude other diseases and the degree of impairment experienced by various
groups was the subject of the poster by J.Jones (Atlanta,USA). The
contribution of fatiguing illnesses in general needs to be addressed as a
public health issue.

B. Hyde (Ottawa,Canada) defined the illness in detail, outlining the
course of the illness and those abnormalities which can be tested for. He
outlined the advantages of the Canadian health system in allowing the
physician the ability to order many technological tests at no expense to
the patient. He outlined in a further presentation his longstanding
historical involvement in CFS with visits to Iceland and Los Angeles.


BRAIN FUNCTION SESSION

The introductory overview was presented by G Lange (New Jersey,USA). She
explained that the worse the results of tests of cognition, the worse the
physical ability in CFS. Techniques for measurement included
neuropsychological testing, brain imaging and spinal fluid analysis. These
could be static e.g. static MRI, showing white/grey abnormailites and
brain volume, or dynamic. Examples of dynamic tests are SPECT (cerebral
blood flow), CT (absolute and quantatitive blood flow), PET (bloodflow as
base and during tasks, cerebral metabolism), MRS (concentration of brain
metabolites) Blood O2 Level-fMRI (non-invasive assessment of structure and
function).

The abnormal findings in CFS were outlined:
1. Neuropsychological - abnormalities in: visual/memory, psychomotor
   function, attention span, information processing.
2. Static studies - Possible white matter loss, abnormal bright patches.
3. Dynamic studies - Reduced relative and absolute cerebral blood flow in
   lat frontal, med temporal, brainstem and ant cingulate areas. Reduced
   relative and cerebral metabolism of glucose and acetylcarnitine.
   Abnormalities in seratogenic transmitter systems, specifically in
   hippocampus and ant cingulated. Reduced 5HT and N-acetyl aspartate
   receptor binding potential. Elevated lactate. These dynamic studies
   are consistent. Those with CFS appear to perform cognitively as well
   as healthy controls, but use more brain areas than the healthy to achieve.
   Speed of information processing seems to be the key deficit.
4. Spinal fluid - Higher protein levels and all results greater in those
   without psycholoigical diagnoses. Elevated Il-8 and Il-10.

The work of the Spanish team headed by AM Garcia Quintana (Barcelona,
Spain) was presented confirming abnormalities in cortical uptake, in all
patients in the ant temporal and cingulate areas (prefrontal and inf
frontal gyrus were also frequently involved), which correlated with
elastase and RNaseL abnormalities in 38 patients. Information processing
in CFS was shown to be prolonged in highly complex conditions by F.Togo
(New Jersey, USA) after controlling for confounding variables. Depression
had an additive effect in CFS, but does not explain the cognitive
dysfunction in CFS. CFS patients have to work harder than healthy people
to achieve same results.

J. Mark VanNess (Salt Lake City, USA) showed that CFS patients had slower
reaction times compared to sedentary controls. This was compounded by 30
minutes exercise and 24 hours later, the CFS patients had definite
persisting significant deficits. Occupational disability assessments need
to include an exercise test and neurocognitive testing as validated by E
Van Hoof (Brussels, Belgium).

The brain function session was summarized by H.Kuratsune (Osaka,Japan)
with an overview of Japanese results. CFS has been shown to have an
enormous economic impact in Japan costing the nation 10 billion$ annually.
Their hypothesis is that neuro-molecular mechanisms lead to chronic
fatigue. Brain dysfunction, metabolic abnormalities, reactivation of
viruses, immunological abnormalities and HPA abnormalities are being
studied. PET is found to be more sensitive than SPECT and have better
spatial resolution. Brain acetylcarnitine uptake is abnormal in CFS, there
is reduced binding power of 5HT in ant cingulate cortex (correlating with
the pain score) and a number of abnormalities with reduced responsiveness
on fMRI are an essential feature of CFS.


BRAIN FUNCTION POSTERS

J. Mark VanNess (Salt Lake City,USA) demonstrated significant metabolic
abnormalities in CFS during exercise. There was consistent oxidative
dysfunction, lower oxygen consumption and both peak and anaerobic
threshold were down. There was no difference in glucose or lactate
response. However RNaseL ratio and elastase activity failed to show any
differences between the CFS patients and controls.

J.Alegre-Martin (Barcelona,Spain) showed there was decreased functional
reserve and decreased aerobic power following an exercise test in CFS
patients. Neuropsychological study also showed there was considerable
cognitive deterioration, and a difference in processing between right and
left hemispheres was also observed. There was an association between
monocyte RNaseL and elastase suggesting involvement of elastase in the
genesis of CFS and elastase inhibitors may have therapeutic implication.

That patients with CFS showed slowed cognitive and fine motor processing
of visual stimuli leads to the consideration of psychomotor functioning
being an interesting variable to consider in further neurobiological
research, according to G. Moorkens (Antwerp, Belgium).

P. Cheney (Ashville,USA) found an 81% incidence of patent foramen ovale in
CFS (normal 10- 15%). The PFOs in CFS ca be modulated up and down
supporting a defect in handling of oxygen by products in CFS similar to
that seen in fetuses.


BEHAVIOURAL HEALTH SESSION

E. Stein (Calgary, Canada) gave an excellent overview of the behavioural
health interventions in CFS published over the past 10 years. She
described ME/CFS and FM as being chronic conditions requiring long term
management, and although both have high rates of psychiatric comorbidity,
neither is considered to be a psychiatric disorder. Because medications
have not been shown to give significant benefit longterm, behavioural
interventions have been considered relevant. Early CBT/GET models were
based on the assumption that acute illness behaviours were causing or
perpetuating CFS. But the only positive CBT study (defined by Fukuda
criteria) was in adolescents. Some exercise studies have shown decrease
in fatigue, but no studies have shown the effects of exercise or CBT on
symptoms other than fatigue or general function. And no study has looked
at the effects on the severely ill. In FM, less than half the studies
using CBT/GET have resulted in improvements in pain, mood or health and by
one year many of the effects have worn off.

Interventions in other types of chronic disease have different objectives
and the Stanford model for self management is widely used. The aim is to
help rather than treat or cure. The programme includes: exercise
programme, cognitive symptom management, nutritional change, sleep and
energy management, medication, community resources, emotional management,
training of health care professionals. In a 2 year follow up for mixed
chronic conditions, there was generalized improvement in self-rated health
with reduced disability and fatigue. Self efficacy and acceptance of the
illness are important. Suicide is the 3rd leading cause of death in CFS
(others being cancer and heart disease) and "hope" based interventions for
self management should include re- evaluation of life goals and
priorities.


Medical education was the subject of a presentation by F.Friedberg (Stony
Brook, USA). 31 fourth year medical students doing their psychiatry
rotation attended a 90 minute seminar on the management of medically
unexplained illnesses, exemplifying CFS and fibromyalgia. A modified
version of the CFS Attitudes Test was administered before and after the
seminar. A significant improvement in attitudes towards CFS was found,
particularly in relation to favouring more federal funding for CFS
research, employers providing flexible hours for those with CFS and
disability issues associated with CFS. Even at initial assessment, the
students felt it was important for physicians to understand CFS and that
patients are not to blame for getting sick. This brief exposure to
factual information about CFS and fibromyalgia was associated with more
favourable attitudes towards CFS in fourth year medical students, and the
encouraging discussion following presentation of this paper will hopefully
lead to more input into medical education.

P. Fennell ( New York,USA) discussed behavioural health with a CFS
perspective. She noted that there has been a paradigm shift in medicine
towards study of chronic illness. 1/3 of doctor visits are for chronic
illness, 2/3 deaths are caused by chronic illness and 78% of medical care
expenditure is for chronic illness. There are 4 groups of chronically
ill:
1. traditional (eg CFS, asthma, lupus)
2. Acute illness survivors (eg post-cancer)
3. Persistent acute illness (eg stroke, HIV)
4. Natural aging.

Innovations in chronic care include health care corporations,
pharmaceutical companies, federal government and chronic care models such
as the Stanford model. The Fennell stage/phase based model is useful in
CFS as illness changes over time and the patient needs to cope with
change. Medical practice needs to be matched to the phase to improve
compliance.


BEHAVIOURAL POSTERS

The Cog-health test is a short self administered computerized test
sensitive to cognitive change and can be a useful tool is assessing
cognitive function in CFS and related conditions. A. Cusco- Segarra
(Barcelona,Spain) found that using this tool, cognitive function was
impaired in CFS and MCS, but not in controls or FM.

C. Lennartson (Stockholm,Sweden) showed that low intensity training may be
a safe start for physical activity without exacerbating symptoms in CFS.
There were social and emotional benefits too.

The Four-Phase model was again described by P Fennell (New York, USA) as a
tool for clinical case management to help improve coping, alleviate
stress, enhance decision making and target interventions in CFS patients
and caregivers. This approach can also be useful for victims of disaster.
The four-phase model was also shown to be a useful adjunct to the model of
human occupation (MOHO) by J.Burke (New York,USA) and can offer an
effective treatment option.

The team headed by T.Matsui (Osaka, Japan) found that CFS patients are not
as severely depressed with perfectionism traits as those with depression
alone. But CFS patients were more anxious and showed more maladaptive
coping behaviour than the depressed patients.

A small pilot study by J.Donalek (Chicago, USA) looking at the impact of
CFS on the family with family experiences having to be reshaped, provided
food for thought, and it is hoped this study will be enlarged. L.Till (de
Paul, USA) describes a buddy system that could prove a useful support
system for those with CFS, providing companionship and practical
assistance.

D.J.Benet (Atlanta, USA) outlined an educational programme for primary
care providers as a result of collaboration between government
organizations and patient advocacy groups

There was a further intervention programme for medical students described
by T.Lu (Loyola,USA). The aim is to assist future physicians with
diagnosis and treatment of CFS as well as providing encouragement to see
more patients with this illness. The trend in publishing of CFS
literature over the past decade was reviewed by F.Friedberg (Stony
Brook,USA). The output of peer reviewed CFS literature has not increased,
but articles on FM and non-CFS fatigue have increased substantially.

Exercise intolerance in CFS is evident in a study by C.Ruud (Amsterdam,
Netherlands). When CFS patients are subjected to increasing exercise, and
compared to controls, there is a lower anaerobic threshold and a state of
malaise comparable to overtraining.

Physical functioning was also shown to be improved in one woman by the
daily IV infusion of 1L of 9% saline over 18 months. Cessation led to
reduced function. L.Travis (Salt Lake City, USA) hypothesized that
saline increased blood volume and/or augmented autonomic activity.


PAEDIATRIC SESSION

The paediatric session, introduced by L Jason (Chicago, USA) and D Bell
(Lyndonville, USA) focused particularly on the new paediatric case
definition, which has been produced by a working group over the past 6
months. For a diagnosis of paediatric CFS, the following 5 classic CFS
symptom categories must occur: post-exertional malaise; unrefreshing sleep
or sleep disturbance; myofascial pain, joint pain, abdominal pain and or
head pain; two or more neurocognitive manifestations; and at least one
symptom from two of the following three subcategories: 1. autonomic
manifestations or 2. neuro-endocrine manifestations or 3. immune
manifestations. The diagnosis can be made after 3 months of persistent or
relapsing chronic fatigue that is not a result of exertion, is not
substantially relieved by rest and results in substantial reduction in
previous levels of educational, social and personal activities.

This new paediatric case definition should lead to more appropriate
identification of children and adolescents with CFS. A paediatric health
questionnaire has been produced with adult and child versions, to be
filled out jointly by the child and/or caregiver.

Exclusionary criteria include past and present psychotic disorders of any
variety, current anorexia or substance abuse. Treated depression is not
exclusionary.

A panel discussion then followed focusing particularly on paediatric
prognosis. D Bell (Lyndonville,USA) had done a 15 year follow up (from
1985) showing that 80% were "well" with 50% of these normal and 50% well
but leading limited lives. 20% were still considerably impaired. K.Rowe
(Melbourne, Australia) found 60% well at 5 years, 20% nearly better and
20% at about 50% normal. In Japan 75% were described as well at 5 years
by T.Miike (Kumamoto,Japan).

A paper then presented by K Rowe (Melbourne, Australia) found that of 87
young women at a Melbourne adolescent CFS clinic, 61% had complained of
debilitating pain during menstruation, compared to 40% of recovered
patients. A 3 month study on 7 young women confirmed significant
worsening of CFS symptoms associated with their severe dysmenorrhoea.
All responded well to treatment with a combined oral contraceptive pill
following an unsatisfactory trial of non steroidal anti-inflammatory
medication. Subsequently 56 young women have responded well to oral
contraceptives, mostly used continually, with relief of symptoms and
improvement in functioning with regard to CFS. This raises the hypothesis
that inflammatory cytokines from the uterus may exacerbate CFS symptoms in
conjunction with dysmenorrhoea.

A study of perception of social environment by adolescents with CFS
particularly in relation to school was described by E Van Hoof (Brussels,
Belgium). 52% of 27 adolescents with CFS reported conflicts at school, 22%
attended school fulltime, 82% had stopped some courses. 48% reported
having few friends. She stressed that the diagnosis should be considered
as early as 1 month after onset, and this study showed an average of 18
months before a diagnosis was made.

C Van der Eb (Lake Bluff, USA) described an adolescent self management
protocol, which showed promise as a strategy to help adolescents with CFS
to adjust activity/rest and cognition to facilitate symptom management and
be more able to participate in normal teenage pursuits.


PAEDIATRIC POSTERS

No link could be confirmed between the putative symptoms of
"hypoglycaemia" and documented blood sugar levels, according to research
by F.Cameron (Melbourne,Australia). A number of symptoms maybe attributed
to a diagnosis of "hypoglycaemia', but special diets are not likely to be
of benefit therefore.

E.Van Hoof (Brussels,Belgium) said that as skepticism is often associated
with a diagnosis of CFS, parents maybe accused of neglect or abuse. A
case study indicating the mistrust and dismissal experienced by some
families illustrated this and tragically Munchausen by proxy can be
mistakenly diagnosed.


GENDER ASPECTS of CFS SESSION

B.Evengard (Stockholm,Sweden) gave an overview of gender health. She
discussed 3 aspects: Reproductive health (eg breast and prostate
cancers); biological differences (eg myocardial infarction) and gender
neutral diseases (eg psoriasis) However in gender-neutral diseases
treatment can be gender-different. She cited the management of psoriasis
in a hospital clinic where treatment was quite different for the sexes
with females getting more creams and males more phototherapy. IN CFS more
females than males get this illness, and this could be a biological
difference or a social (gender) difference. Gender is a social construct.
In research men and women should be divided and study design reconsidered.
She finished by quoting a Mr Trevis: "It is unethical, unintelligent and
uneconomical not to work with gender issues".

Gender, sexuality and intimacy are secondary to the clinical encounter in
CFS patients according to P Fennell (New York, USA), but should be given
equal weight. They can adversely affect assessment and treatment. The
illness may affect the mechanics of sex ­ exertion, libido and
psychological aspects are all involved. Sexual relationships do change
over time and in an illness such as this, patients may need to learn to
touch again, to achieve fulfillment.

Addressing issues based on gender were further reiterated by L Bateman
(Salt Lake City, USA). For women, chronic illness is generally more
common and women may not be taken as seriously as men. However thinking of
CFS as a "women's" disease may delay men seeking help for CFS. Coping
styles may vary between men and women and both male and female spouses
carry a heavy burden in many ways. Intimacy issues and issues associated
with disability insurance may be different.

In the area of research, gender differences may affect test results and
disease process, and choice of case definition may affect gender
demographics and alter generalizations made about gender. Comorbid mood
states, coping behaviours and stress factors may vary by gender as well as
subgroup. HPA axis, autonomic nervous system and immune function are
affected by gender in complex ways and there is little gender-specific CFS
research. By being more aware of gender issues, better clinical care
maybe possible together with better understanding of this illness.


GENDER POSTERS

2 studies were presented by C.Javierre (Barcelona,Spain) and concluded
that in a large group of women compared to healthy female controls, those
affected by CFS showed a worse response with lower efficiency to light
intensity exercise. Reduced ventilatory efficiency in CFS maybe
responsible for a lower PCO2 in blood, associated with weakness and post
exertional distress.


CARDIOVASCULAR PRESENTATIONS

A.Suarez (Barcelona,Spain) looked at cardioventilatory response in a group
of 135 CFS women compared to healthy controls. The control group scored
52% higher with workload in maximal test, with O2 uptake 47.5% higher.
However in a further supramaximal test after a 5 minute rest, the CFS
subjects were able to increase their responses considerably.

Diastolic dysfunction in CFS patients is reported at a level well above
that for control populations of the same age according to P.Cheney
(Ashville, USA). This supports the hypothesis that CFS is a syndrome of
cellular energy deficiency. Tilt-echocardiography provides amplification
of often masked diastolic dysfunction in patients known to be sensitive to
head-up tilt. He cited the possibility of an associated cardiomyopathy as
previously described by Natelson and Peckerman.

V.Spence (Dundee, Scotland) showed that CFS patients have significantly
increased levels of plasma hs-CRP, F2 isoprostanes and oxLDL that
correlate positively with arterial stiffness. CRP was a strong predictor
of arterial stiffness conferring a significantly increased risk of a
future cardiovascular event in CFS patients.


GENETICS/PROTEOMICS SESSION

A summary of the current state of genomic science relating to CFS was
presented by S.Vernon (Atlanta,USA). Genetics is the study of the genes
and genomics covers the function and interactions of all the genetic
material in the genome. Biologic samples for these studies can be blood,
saliva and urine. The analysis includes classical statistics, data mining
and pattern recognition, machine learning and multidimensional approaches.
Data integration refers to the integration of different types of data and
differential analysis techniques. The focus should be on the blood, with
5 litres circulating and blood cells being the sentinels of the disease
process. The plasma also has proteins from throughout the whole body.
There is dynamic traffic between the blood and the brain. Genomic
technology involves profiling by micro-array, gene chips, reverse
transcriptase-PCR. Mass spectroscopy is used for protein. Differentially
expressed genes are not always the same in various studies, but there is
overlapping of pathways and correlation with CFS symptoms. It is possible
to subtype CFS genetically. By using gene technology, it is possible to
understand who may develop an illness. Genes may also serve as biomarkers,
and pharmacogenetics can lead to treatment.

F.J.Garcia-Fructuoso (Barcelona, Spain) was unable to present his work in
this field owing to illness, but his team emphasise that CFS and FM are 2
genetically distinguishable illnesses, with CFS being an exclusion
diagnosis for FM.

A fascinating study using the Utah Population Data Base to explore a
genetic contribution to CFS and associated disorders was presented by
F.Albright (Salt Lake City,USA). They used 3 techniques looking at risks
for CFS in relatives, relatedness among CFS patients and identification of
high risk CFS pedigrees. First degree relatives share many environmental
risks and exposures (relative risk 7.68); but in second degree relatives
this is less of a factor (relative risk 2.54). This suggests a genetic
component. It is hoped this study will lead to gene identification
predisposing to CFS and related conditions.

The sex difference observed in CFS indicates a role for oestrogen and
oestrogen receptors for disease development and this issue was addressed
by B.Evangard (Stockholm, Sweden). Reduced ERbetawt expression is
consistent with an immune mediated pathogenesis of CFS. She said that a
possible connection between oestrogen, oestrogen receptors and CFS needs
to be further evaluated, particularly as estradiol and progestin improve
health status in CFS and there is also improvement in pregnancy.

J.Baruniuk (Washington DC, USA) obtained genetic samples from the
cerebrospinal fluid of 52 patients with CFS, FM and GWI and compared with
healthy controls. 5 proteins were predictive of CFS and were absent in the
healthy controls. The specific CFS-related proteome suggests a common
pathophysiology for these related illnesses, and detection of at least one
of the proteins is predictive of CFS.

However the research presented by E.Aslakson (Atlanta,USA) showed that a
more complete enumeration of altered pathways demonstrated distinct and
differing altered biological pathways among CFS subjects, further
demonstrating the heterogeneity of CFS.

J.Kerr (London,UK) outlined his team's research. The precise gene
signature and metabolic pathways need to be identified. The utility of
genomics/proteomics can involve inheritance, pathogenesis and diagnosis.
Molecules of interest include DNA, RNA and proteins and there is potential
for future study of lipids and glycans. Predispositional genes for CFS
have been identified associated with Q fever and parvovirus B19.
Micro-array techniques are used and immune response, several mitochondrial
genes and gene protein signalling are considered important. Studies
include: 1.TNF found to be elevated in subgroups of CFS. Etaneacept is a
potential treatment. 2. Cerebrospinal fluid proteome. Proton MRS of
brain. 3. Urinary excretion of GABA. 4. Serum analysis using new
infra-red spectroscopy. This could lead to a diagnostic test. 5.
Infection is known to be important, so 28 possible microbes are being
studied. Kerr emphasized that this illness is a result of psycho-neuro-
endocrine-immune interaction.


GENETICS/PROTEOMICS POSTERS

S.Mangalathu (Atlanta,USA) described sequence variations in certain genes
involved in the regulation of the HPA axis and seratonergic system
associated with CFS, allostatic load index and particularly with a CFS
subgroup characterized by low HR variability and low urinary free
cortisol. These tests need further validation with larger sample size.

R.Petty (London,UK) hypothesised that CFS patients may exhibit a miRNA
gene signature and tested this by microarray in 15 CFS patients compared
to healthy controls. It is hoped that knowledge of the miRNA gene
signature of CFS will aid our understanding of the pathogenesis and lead
to treatment development. This team, headed by J.Kerr are close to final
details.

Significantly differentially expressed genes have been identified in a
female patient group with gradual illness onset and no previously
documented infection. This work presented by H.Grans (Stockholm,Sweden)
stressed the importance of subgrouping CFS patients.

G.McKeown Eyssen (Toronto,Canada) postulated that impaired metabolism of
toxic chemicals maybe the mechanism underlying MCS. A genetic
predisposition for MCS may involve altered biotransformation of
environmental chemicals. A gene-gene interaction between CYP2D6 and NAT2
(common polymorphisms) suggests that rapid metabolism for both enzymes may
confer substantially elevated risk.

B.Burke (London,UK) investigated human gene signatures of past persistent
microbial infections in unstressed normal blood donors, to consider
possible relevance to the pathogenesis of CFS. This work may provide
insight into the role of persistent and pre-existent infections in the
pathogenesis of subsequent disease development.


NEW METHODS FOR EVALUATING FATIGUE SESSION

This session was coordinated by the Japanese Association for Fatigue
Sciences. The first presentation was given by A.Sakudo (Osaka,Japan)
showing that Vis-NIR spectroscopy (a non- invasive technique) for sera
combined with chemometric analysis is a promising tool to objectively
diagnose CFS.

T.Sugino (Wakayama,Japan) discussed the reactivation of HHV-6 and HHV-7 in
saliva during fatigue states. Reactivation of HHV-6 relates to extra work
load in CFS, while reactivation of HHV- 7 relates to the actual fatigue
state in CFS. These viruses have lifelong latency and HHV-6 establishes
complete latency in peripheral blood macrophages, and when reactivated is
shed directly into the saliva. Reactivated HHV-7 is amplified in
peripheral T cells. Virus shedding is influenced by immunological status.

Application of DNA chip for fatigue assessment was outlined by K.Rokutan
(Tokushima, Japan). Only 2.5ml of blood is required for samples. 9 CFS
genes have been identified by PCR and micro- array. The identified genes
may be important for subgrouping CFS.

Several of the Japanese researchers mentioned an anti-fatigue substance
prescribed in Japan. This was D-Ribose.


VIRAL & IMMUNE INTERACTIONS and HEALTH SESSION

Symptoms observed in CFS are compatible with viral aetiology, and it is
possible that CFS is associated with endogenous latent viruses. This was
the basis of the talk by R.Glaser (Ohio, USA). Psychological stress is
implicated in CFS, which in turn can modulate the expression of several
latent herpes viruses including EBV. It has been shown too that the
immune and endocrine systems "talk" to each other via receptors. Latent
viruses such as EBV and HHV-6 may induce immunopathology by synthesizing
viral protein in latently infected cells or in cells in which the virus
genome is only partially expressed. These proteins could then induce
immune dysregulation with effects on cytokines and chemokynes and/or T
cell or NK function. It is difficult to link a specific virus to CFS if
the viral reactivation is incomplete, as virus DNA would not be
synthesized. Glaser's team have shown that EBV encoded dUTPase is able to
induce immune dysregulation and associated symptoms in mice. This suggests
that at least one protein of the EBV early antigen complex can induce
immune regulation and maybe involved in the pathology of EBV-associated
disease.

Also from Ohio, M.Wiliams discussed the issue that HHV-6 U45 protein is
not a functional dUTPase, but it does induce immune dysregulation similar
to EBV-encoded dUTPase.

D Ablashi (Santa Barbara, USA) described assays that can now be used to
detect chronic reactivation of HHV-6 and EBV. It is vital to be able to
distinguish between chronic, active and latent infection with these
viruses. Studies have shown that there is a positive association between
active HHV-6 and EBV and CFS. Many viruses could be implicated. RNase-L
was also found to correlate with HHV-6 infection in CFS (67% concordance).
The possibility of antiviral agents being effective was discussed.
Cidofovir, foscanet, ganciclovir and valgancoclovir all have potential.
Studies with acyclovir have proved negative, but both ampligen and
isoprinosine can be useful. Amantadine, red-mauve algae and lamotrigine
have all shown promise in vitro.

GWI and CFS were compared immunologically by M.Fletcher (Miami, USA).
Perforin is a molecule in cytotoxic lymphocytes necessary for killing and
is found to be low in both illnesses. NK cell function is low in GWI and
moderately low in CFS. CD2 and CD26 activation is high in GWI and
moderate in CFS. CD26 cleaves neuropeptide-Y (NPY) and there is
significantly reduced NPY in the plasma in GWI but not significantly in
CFS. Further studies are underway.

B.Gurbaxani (Atlanta,USA) detected elevated Il-6 in the resting state in
CFS patients (compared to controls) suggesting that proinflammatory
cytokines could be contributing to symptoms ­ and a potential cause or
effect of CFS. Il-6 correlates well with CRP and has a negative
correlation with cortisol.

The incidence of HHV-6 and EBV infection in CFS was further discussed by
S.Levine (New York, USA). Their team tried to determine if there were
biologic markers of active, chronic viral infection in CFS patients
compared to healthy controls. Evidence suggests that there is a subset of
CFS patients suffering from these infections. Quantitative PCR in plasma
is not useful as there is very little free virus in the plasma, and
neither is PCR in PBMCs without a threshold, as it detects both latent and
active virus. However serological assays (IgG to HHV-6 and EBV early
antigen) are useful as long as a high threshold is used.

M.Murovska (Riga,Latvia) presented results of a study in Latvia of CFS and
a possible association with HHV-6 and HHV-7 infection. This study also
included symptomatology and occupation of patients. She had found that
the rate of CFS morbidity is associated with professional activity and
amount of intellectual work. Both viruses may be involved in the
aetiology of CFS and reactivation may provoke immunodysfunction.

Because many CFS patients have persistent or intermittent gastrointestinal
symptoms, J.Chia (Lomita, USA) evaluated the presence of viral capsid
protein-1 (VP1) and enteroviral RNA in stomach biopsies. These were
detected in a number of the biopsies of CFS patients with chronic
abdominal complaints, compared to none in controls.

G.Nicholson (Huntington Beach, USA) discussed the chronic bacterial
co-infections found in CFS. These included evidence of high incidence of
systemic mycoplasmal infections of various types and a tendency for those
with multiple infections to have more symptoms. Lyme disease, rickettsia
and protozoal infections could all be implicated. The ticks causing
transmission of Lyme disease may transmit a wide range of infections as
well as B.burgdorferi, including mycoplasma, bartonella and ehlicia.

This whole session was summarized by A.Komaroff ( Harvard, USA). He
reviewed the immune abnormalities which have been demonstrated in CFS.
These include activated CD8 (T cells), poorly functioning NK cells,
abnormalities in the 2-5A pathway (RNaseL ratio), cytokine abnormalities
(proinflammatory dysregulation), increased TGF and 27 times more
circulating immune complexes than in controls. Many infectious agents
have been cited as implicated such as EBV, Lyme, parvovirus,
enteroviruses, Q fever, RRV, mycoplasma, HHV-6 etc. There is evidence for
reactivation of HHV-6 and EBV, although the case is not entirely solid as
yet. HHV-6 has been shown to infect neural and glial cells and persist in
the CNS. It can cause encephalopathy and demyelination and is associated
with MS and possibly seizures and cerebral palsy, although these are
provocative studies. It is important to distinguish the active from the
latent forms. Over the past 10 years there has been increasing evidence
that infection is most likely to be a prime cause of CFS.


VIRAL/IMMUNE POSTERS

A national ME observatory with funding from lottery is being established
in the UK. D.Pheby (London,UK) outlined the proposal and they will
include various research studies with a vision of advancing science.

J.Mikovits (Incline Village, USA) looked at HHV-6 and its intergration
into host cells, and this study will contribute to an understanding of
whether this virus contributes to CFS, malignancy and immunodeficiency
associated with these conditions. Of 40 patients studied, 3 were positive
to CIHHV-6.

A.Vojdani (Los Angeles,USA) stressed the importance of screening for Lyme
disease and other related disorders due to overlapping symptoms. In
vivo-Induced Antigen Technology is a new technique described which
identifies pathogen antigens that are immunogenic and expressed in vivo
during human infection.

Cryptostrongylus Pulmoni is a worm found in the sputum of 63% of CFS
patients in a study by L.Klapow (Santa Rosa, USA). Retention of infected
larvae leading to chronic auto-infection is a possibility in CFS. Larvae
could also migrate from the intestines and back into the lungs. If this is
occurring, inhaled anti-roundworm medications would seem logical.

N.Klimas (Miami, USA) reported a dramatic significant increase in the
number of NK cells (X4) in peripheral blood following an exercise
challenge in GWI. T cells also increased (X1.5), and both sets of cells
had returned to baseline at 4 hour follow up. There was no significant
effect of the exercise on the actual percentage of activated T cells and
NK cells or in the number of molecules per NK cells.

Visible and near-infrared spectroscopy was used by Y.Hakariyal (Osaka,
Japan) for diagnosis of SLE with fatigue similar to CFS. SLE was detected
in 85.7% SLE patients, and differentiated between anti-phospholipid (aPL)
positive and negative patients. CFS can be discriminated from SLE and
aPL.

B.Evangard (Stockholm, Sweden) compared the composition of intestinal
microflora in CFS patients when in the acute phase of the illness.
Increased levels of c.albicans were found and may prove a useful marker
for ecological disturbance and contribute to symptoms. Future research is
thus warranted.

Chronic enteroviral infection may be implicated in the cause of CFS.
J.Chia (Lomita, USA) postulated that further viral studies could lead to
the use of antiviral agents directed against viral RNA polymerase. Their
team showed there was improvement in symptoms in EV positive CFS patients
treated with -interferon and ribavirin or combined - and -interferon.

D.Strayer (Philadelphia, USA) did a meta-analysis of 2 trials of ampligen
and found it was generally well tolerated in CFS and provided significant
improvement in exercise duration and concomitant medication usage when
compared to placebo.

Active infection with CMV maybe detected in patients with life-altering
fatigue and this maybe useful guidance in making a diagnosis and use of
antiviral treatment. M.Lerner (Detroit, USA) described use of IgM serum
antibodies to CMV nonstructural gene products p52 and CM2.

Data produced in one study to check cytokine patterns in CFS did not
support a Th2 cytokine bias. S.Repka-Ramirez (Utah,USA) did a study using
nasal lavage to check mucosal immunity and eosinophilia to test their
hypothesis.

Comparing CFS patients, FM patients and controls by L.Bazzichi (Pisa,
Italy) looking at antipolymer antibody seroreactivity, it was shown that
seroreactivity was higher in CFS than FM or controls. Cytokine levels were
not significantly different between CFS and FM.


The whole conference was finally summarized by Prof Anthony Komaroff and
he is encouraged by the wealth of new research presented and the exciting
developments we have seen in the understanding of this illness over the
past decade. The future certainly bodes well for CFS. Dr Klimas was
thanked for her hard work in bringing such an excellent conference
together, and members of the IACFS were encouraged to vote towards a name
change for the organization to the International Association for Chronic
Fatigue Syndrome/Myalgic Encephalomyopathy ­ quite a mouthful, but a true
reflection of the organisation's international status and more acceptable
options for the name of the illness.

I must thank the ANZMES for their help in enabling me to attend this very
worthwhile event.

--------
(c) 2007 Rosamund Vallings

[Return to top]

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

Date:    Wed, 14 Feb 2007 14:33:22 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: IACFS Conference report/Anthony Komaroff

The IACFS Conference report of Anthony Komaroff can be found at,
  

  

   http://www.instatapes.com/IACFS/06/player.HTM

See also,

  
  
   http://www.instatapes.com/IACFS/

[Return to top]

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

Date:    Sat, 14 Apr 2007 09:35:55 -0700
From:    "Dr. Marc-Alexander Fluks.............via Co-Cure moderators"
Subject: RES,NOT: IACFS Conference report/Virginia Teague

Source: IACFS
Date:   February 12, 2007
Author: Virginia Teague
URL:                      http://iacfs.net/p/1,522.html


A Retrospective on the 8th IACFS Conference
-------------------------------------------

This year's IACFS conference in Fort Lauderdale at the Bahia Mar Resort
offered attendees an innovative format focused on the theme of
interdisciplinary research and integrative care. The conference began with a
two-day session focused on the needs of patients. Patient advocates from
international advocacy organizations on CFS, FM, and related illnesses met
for the first time to share their ideas in workshops on fundraising
fundamentals, empowerment, and media training. Co-hosted by P.A.N.D.O.R.A
(Patient Alliance for Neuroendcocrineimmune Disorders Organization for
Research and Advocacy, Inc.), these sessions, attended by 350 patients and
222 professionals, provided a unique opportunity for patients to meet and
talk with leading international researchers and clinicians.

Tom Sheridan opened the session with insight on how patients and advocates
can come together on policy, politics, and press to further understanding and
funding for the essential research that will provide long sought answers on
causation, markers, and treatment. Quoting Dr. Tony Komaroff, Mr. Sheridan
said the debate over whether CFS is actually a disease is over-welcome
words for patients, researchers, and clinicians.

Other topics for these sessions include presentations by national and
international experts on mold and environmental illness, Lyme Disease, and
the role of HHV-6 virus on CFS and fibromyalgia (FM), as well as pediatric
CFS, family issues, ergonomics and natural pain relief, sleep disorders,
social security concerns, and employment-related legal issues for the
disabled and chronically ill.

Of special interest was Montoya's groundbreaking study on antiviral therapy
for CFS patients with elevated antibodies to HHV-6 and EBV, in which 25 CFS
patients were treated with the drug valganciclovir, an antiviral often used
in treating diseases caused by human herpes viruses. During the past three
years, 21 of the patients responded with significant improvement that was
sustained even after going off the medication at the end of the treatment
regimen, which usually lasted six months. Later this year, with a $1.3
million grant from Roche Pharmaceuticals, Dr. Montoya will replicate his
preliminary study among a specific subset of CFS patients who have
viral-induced dysfunction of the central nervous system.

This and other research summarized in the first two days of the conference
was further expanded on during the three-day professional session, which 169
patients also attended. Each session was introduced by an expert who reviewed
methodology and new findings that may hold relevance, followed by
presentations on original research, and concluding with a summary by an
expert in CFS or FM that emphasized practical clinical applications and
priorities for future research. Eliminating separate tracks for clinical and
research presentations made it possible for attendees to gain a broader
perspective without being forced to choose which presentations they would
attend, especially important now when so much new information is changing the
way the disease will be diagnosed, evaluated, and treated.

In informal sessions, clinicians also had an opportunity to exchange ideas
and share information on what works and what doesn't with their patients.

On Friday, the professional conference began with a session on various
aspects of fatigue, introduced by Watanabe (Osaka, Japan). Tajima's study
using Actigraphy and R-R power spectrum analysis revealed quality of sleep
for CFS patients was decreased because of increased wake episodes during the
sleep period, leading to a lack of parasympathetic activation during the
sleep period and further deterioration of sleep quality. Porter (De Paul
University, USA) presented new terms to differentiate five types of fatigue
that will help to clarify the amorphous term: wired (over stimulated, tense,
agitated), brain fog, molasses fatigue (heaviness), flu fatigue
(immunological), and post-exertional. Maloney (Atlanta, Georgia) confirmed
the association between CFS and high allostatic load: 56% of CFS patients
were found to have high allostatic load (females > males). Moreover, the
greater the allostatic load, the greater the prevalence of metabolic
syndrome: females with metabolic syndrome were 4 times more likely to have
CFS than females without metabolic syndrome. Ciccolella (Stockton, CA)
compared serial exercise test results to assess the effects of
post-exertional malaise in CFS, and concluded that a single exercise test is
insufficient to determine the extent of functional impairment in CFS
patients. A second test 24 hours later revealed CFS patients had
significantly worse performance than controls, significant support for claims
of disability. Nestadt (New York, USA) compared brain metabolites in patients
with CFS, those with Generalized Anxiety Disorder, and healthy controls, and
discovered a significant proportion of CFS patients had elevated brain
ventricular lactate. Marked differences in hippocampal glutamate helped
differentiate between CFS patients with and without depression. Those with
CFS also had significantly lower N-acetyl-aspartate in the right hippocampus,
indicating reduced neuron density or metabolism. These findings support
literature suggesting neurobiological distinctions between "pure" CFS and
CFS with psychiatric comorbidity. Whistler (Atlanta, Georgia) addressed
alterations in apoptosis in post-infection fatigue, and noted the severity of
acute infection is related to the likelihood of recovery and affects the
fundamental cellular processes. These altered gene expression profiles are
manifest in several persistent symptoms of PIFS, indicating many symptoms may
be immunologically mediated.

Sessions on sleep, clinical trials, and pain followed. Of special interest
was Clauw's (Michigan, USA) study on pain processing and treatments in FM
and related conditions, in which functional MRI studies revealed a lower
threshold of pain and all sensory signals for FM patients.

In a session on epidemiology and case definition, the use of modern
statistical information coupled with social and genetic epidemiology is
providing new ways to evaluate the disease and determine intervention.
Epidemiological studies by Reeves et al. (Atlanta, USA) compared those
meeting the current criteria for CFS with those having fatigue but
insufficient symptoms (ISF) to be diagnosed with CFS and non-fatigued
controls in an attempt to subgroup those with CFS according to their level of
impairment and symptom severity. Results suggested that a subset of those
with ISF do have a similarly severe illness to CFS, but without at least 4 of
the case-defining symptoms. A ten-year follow-up by Kang (Washington, DC) of
Gulf War veterans suffering from CFS compared to non-Gulf military peers
showed that CFS symptoms decreased significantly in the Gulf veterans
compared to non-Gulf sufferers. Jason (DePaul, USA) discussed the economic
impact of CFS on society in a community-based versus tertiary-based sample,
estimating that the direct and indirect costs of CFS in the United States are
between 22 and 28.6 billion dollars annually. Kuratsune estimates an annual
economic impact in Japan of 10 billion. The incidence of CFS throughout the
world is variable, with estimates in the USA of 2-4 per thousand (c. 800,000
to 1 million people). Jason has also studied the rates of CFS in Nigeria, the
first community-based study in a developing country, estimating a prevalence
of 0.68%, higher than the United States. In Ireland, Lindal found no positive
correlation between the prevalence of CFS today, which is similar to findings
in U.S. studies, and the 1947 Iceland Disease.

Saturday's agenda opened with the brain session, introduced by Lange (New
Jersey, USA), who pointed out the strong correlation between low tests of
cognition and low physical ability in CFS patients. Tests for measurement
include neuropsychological testing, brain imaging, and spinal fluid analysis.
Quintana et al. (Barcelona, Spain), in a study using Brain SPET
quantification, found a congruent pattern in basal conditions: changes after
a stress test suggest inhibitory ways in frontal and especially in anterior
temporal lobes. A study by Togo (New Jersey, USA) found that CFS patients
have a similar response accuracy compared with controls, but have to work
longer and harder in high complexity conditions. Depression had an additive
effect in CFS, but does not explain the cognitive dysfunction in CFS. Van
Ness (Salt Lake City, USA) showed that CFS patients had slower reaction times
compared to sedentary controls. This was compounded by 30 minutes exercise;
24 hours later the CFS patients had definite persisting significant deficits
(reinforcing the importance of follow-up testing revealed in Ciccolella's
observations in Friday's fatigue session). Kuratsune summarized the brain
function session, emphasizing that brain dysfunction is a key abnormality in
understanding the state of chronic fatigue. Osaka studies have hypothesized
that neuro-molecular mechanisms lead to chronic fatigue. Brain dysfunction,
metabolic abnormalities, reactivation of viruses, immunological abnormalities
and HPS abnormalities are being studied. PET is found to be more sensitive
than SPECT and has better spatial resolution. Brain acetylcarnitine uptake is
abnormal in CFS, and there is reduced binding power of 5HT in the anterior
cingulate cortex (correlating with the pain score). A number of abnormalities
with reduced responsiveness on fMRI is an essential feature of CFS.

After a session on behavioral health, focusing on ways to help patients cope
with their illness and ways to train healthcare providers to respond to their
patients, Jason opened the pediatric session, presenting a new pediatric case
definition that should allow for more appropriate identification of children
and adolescents with CFS. Jason and his international team of researchers
have produced two sliding-scale questionnaires designed for children over the
age of twelve and parents/guardians of younger children. A special session
devoted to selected oral presentations of poster, another new format at this
conference.

Saturday's agenda concluded with the gender session. Evengard (Stockholm,
Sweden) gave an overview, noting that the perception that CFS is a
"women's thing" has severely impacted both research and treatment of
the disease. The implications of gender were further explored after the
evening awards banquet with a panel discussion on politics and women's
health.

Sunday's agenda opened with a session on genetics/proteomics where
considerable strides are being made that may lead to providing biomarkers and
creating personalized therapy for those afflicted. Vernon (Atlanta, USA)
introduced the session, noting the challenge of CFS is that it is not a
single gene disease, and the gene effect may be epigenetic. The
Garcia-Fructuoso research group (Barcelona, Spain) emphasized that CFS and FM
are two genetically distinguishable illnesses with extremely high specificity
in women, suggesting CFS can be as an exclusion diagnosis for FM. Albright
(Salt Lake City, USA) used the Utah Population Data Base to explore a genetic
contribution to CFS and associated disorders. Using three techniques to look
at risks for CFS in relatives, relatedness among CFS patients, and
identification of high risk CFS pedigrees, the study found a relative risk of
7.68 in first degree relatives who share many environmental risks and
exposures; in second degree relatives this was less of a factor (relative
risk 2.54), suggesting a genetic component which might lead to gene
identification predisposing to CFS and related conditions. Evengard noted the
sex difference observed in CFS indicates a role for estrogen and estrogen
receptors for disease development. Baruniuk (Washington, DC) obtained genetic
samples from the cerebrospinal fluid of 52 patients with CFS< FM, and GWI and
compared with healthy controls. He found 5 proteins predictive of CFS that
were absent in the healthy controls. The specific CFS-related proteome
suggests a common pathophysiology for these related illnesses, and detection
of at least one of the proteins is predictive of CFS. However, the research
presented by Aslakson (Atlanta, USA) showed that a more complete enumeration
of altered pathways demonstrated distinct and differing altered biological
pathways among CFS subjects, further demonstrating the heterogeneity of CFS.
Kerr (London, UK) outlined his team's research. The precise gene signature
and metabolic pathways need to be identified. The utility of
genomics/proteomics can involve inheritance, pathogenesis, and diagnosis.
Molecules of interest include DNA, RNA, and proteins, and there is potential
for future study of lipids and glycans. Kerr emphasized that this illness is
a result of psycho-neuro-endocrine-immune interaction. Predispositional genes
for CFS have been identified that are associated with Q fever and parvovirus
B19.

The Japanese Association for Fatigue Sciences coordinated the session that
followed on new methods for evaluating fatigue. Sakudo's study (Osaka,
Japan) of Near-Infrared Spectroscopy as a tool for diagnosing CFS showed near
perfect dissemination between healthy controls and CFS patients, suggesting
that Vis-NIR spectroscopy for sera combined with chemometrics analysis could
provide a promising tool to objectively diagnose CFS. Noninvasive approaches
to CFS diagnosis using Vis-NIR spectroscopy are now ongoing. Rokutan
(Tokushima, Japan) outlined application of DNA chip for fatigue assessment.
Only 2.5 ml of blood is required for samples. Nine CFS genes have been
identified by PCR and microarray, and the identified genes may be important
for subgrouping CFS. He noted stress assessment was particularly important,
and may be a powerful tool to differentiate between stress disorder and CFS.
Several of the Japanese researchers mentioned D-Ribose, an anti-fatigue
substance prescribed in Japan.

Introducing the viral and immune interactions and health session, Glaser
(Ohio, USA) focused on symptoms in CFS that are compatible with a viral
etiology, suggesting CFS is associated with endogenous latent viruses such as
EBV and HHV-6 that may induce immunopathology by synthesizing viral protein
in latently infected cells in which the virus genome is only partially
expressed. These proteins could then induce immune dysregulation with effects
on cytokines and chemokines and/or T cell or NK function. It is difficult to
link a specific virus to CFS if the reactivation is incomplete since virus
DNA would not be synthesized. Glaser's team has shown that EBV encoded
dUTPase is able to induce immune dysregulation and associated symptoms in
mice, suggesting that at least one protein of the EBV early antigen complex
can induce immune regulation and may be involved in the pathology of
EBV-associated disease. He noted that stress changes cellular immunity. The
cellular immune system in older people is also less effective and thus more
prone to another virus or stress. Ablashi (Santa Barbara, USA) described
assays that can now be used to detect chronic reactivation of HHV-6 and EBV.
Studies have shown there is a positive association between HHV-6 and EBV and
CFS, and many viruses could be implicated. Rnase-L was also found to
correlate with HHV-6 infection in CFS (65% concordance). Antiviral agents may
be effective in treating CFS, as Montoya's initial study using
valganciclovir suggests. Fletcher (Miami, USA) compared GWI and CFS
immunologically, and found perforin to be low in both illnesses. NK cell
function is low in GWI and moderately low in CFS. CD2 and CD26 activation is
high in GWI and moderate in CFS. CD26 cleaves neuropeptide-Y (NPY), and there
is significantly reduced NPY in plasma in GWI, but not significantly in CFS.
Further studies are underway. Gubaxani (Atlanta, USA) detected elevated IL-6
in the resting state in CFS patients, suggesting that proinflammatory
cytokines could be contributing to symptoms and thus be a potential cause or
effect of CFS. Levine's research team (New York, USA) tried to determine if
there are biologic markers of active, chronic viral infection in CFS patents,
and evidence suggests there is a subset of CFS patients suffering from these
infections. Serological assays are useful as long as a high threshold is
used.

Tony Komaroff provided an overview of summarized the conference's findings,
noting that great strides are being made to find objective biologic evidence
for a disease that has been officially defined by a group of symptoms.
Specifically, Komaroff highlighted four areas: the importance of the role of
the brain, mitochondrial dysfunction and oxidative stress, new molecular
markers, and new methods for epidemiology.

In studies on the role of the brain, Komaroff made special note of functional
MRI studies done by Clauw on FM patients, and the new available neuroimaging
tools discussed by Lange. He also mentioned Nestadt's study on increased
lactic acid in ventricles of the brain and the many studies done by Watanabe
and Kuratsune on diminished blood flow, uptake of acetylcarnitine, and
diminished serotonin transceptors in special areas of the brain associated
with short-term memory, pain recognition, and autonomic function.

Komaroff mentioned another study by Nestadt on mitochondrial dysfunction and
oxidative stress, as well as studies by Ciccolella and Van Ness on impaired
oxygen and lowered anaerobic threshold, especially in follow-up tests, which
he linked to Kuratsune's study on impaired brain function; at baseline in
either exercise or cognitive testing, function attenuates with repeated
testing. He noted Whistler's study on impaired mitochondrial pathways,
Baruniuk's study on proteins in spinal fluid, Kerr's and Rokutan's
studies on mitochondrial gene expression, as well as studies by Spence and
Belch and Cheney and Lerner.

Of special interest was Sakudo's near perfect results using near-infrared
spectroscopy to differentiate between CFS patients and controls, which
Komaroff described as "more beautiful than Elizabeth Taylor when she was
young on a good day." Although this study must replicated, Komaroff
considers it most promising.

Certain findings from different studies coalesce in a meaningful way, such as
Baruniuk's study on proteins found in the spinal fluid of Gulf War, FM, and
CFS patients. Baruniuk's proteomic study also is significant in revealing
how the immune system reacts to stress. Komaroff also mentioned Kerr's
poster presentation on miRNA control expression of genes, suggesting a
possible fingerprint that is potentially very impressive.

New approaches to epidemiology are also providing more insight into
subgroups. Statistical methods to collect meticulous data on patients without
imposing a bias on it reveal subgroups that are also being defined in
laboratories. Of particular note, Komaroff believes, is Maloney's study on
allostatic load, which could tell us a lot about CFS. Presentations by
Reeves, Jason, and Kuratsune revealed startling figures on the number of
people afflicted with CFS and the cost of the illness to society. Quoting
Evengard, Komaroff observed, "The invisible has been made visible."

Komaroff concluded by saying converging evidence from different investigators
using different technologies on different patients is telling us where to
look to make scientific advances to understand this illness and, ultimately,
to fix it.

Virginia Teague is media liason for the 8th IACFS Conference. A freelance
editor and writer, she is an adjunct professor, Liberal Arts, Nova
Southeastern University, and former managing editor, Journal of Chronic
Fatigue Syndrome.

--------
(c) 2007 IACFS

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

Date:    Wed, 14 Feb 2007 14:11:21 -0500
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: The PedsQL as a patient-reported outcome in children and adolescents with fibromyalgia: An analysis of OMERACT domains

The PedsQL as a patient-reported outcome in children and adolescents with
fibromyalgia: An analysis of OMERACT domains.

Health Qual Life Outcomes. 2007 Feb 12;5(1):9 [Epub ahead of print]

Varni JW, Burwinkle TM, Limbers CA, Szer IS.

PMID: 17295915


ABSTRACT:
BACKGROUND: Fibromyalgia is a chronic health condition characterized by
widespread musculoskeletal pain, multiple tender points on physical
examination, generalized muscular aching, stiffness, fatigue,
nonrestorative sleep pattern, cognitive dysfunction, and mood disturbance.
Recently, the Outcome Measures in Rheumatoid Arthritis Clinical Trials
(OMERACT) Fibromyalgia Syndrome Workshop ranked and prioritized the domains
that should be consistently measured in fibromyalgia clinical trials,
specifically, pain, generic health-related quality of life, fatigue, sleep
quality, and physical function. The focus of these deliberations was
exclusively on adult patients, and to our knowledge, these domains have not
been previously tested within a multidimensional framework in children and
adolescents with fibromyalgia.

METHODS: An analysis to determine the feasibility, reliability, and
validity of the PedsQL 4.0 (Pediatric Quality of Life Inventory) Generic
Core Scales, PedsQL Multidimensional Fatigue Scale, and PedsQL Rheumatology
Module Pain and Hurt Scale as patient-reported outcome (PRO) measures for
pediatric patients with fibromyalgia. The PedsQL Scales were completed by
59 families in a pediatric rheumatology clinic in a large childrens hospital.

RESULTS: The PedsQL evidenced minimal missing responses (0.53% patient
self-report, 0.70% parent proxy-report), achieved excellent reliability for
the Generic Core Scales Total Scale Score (alpha = 0.88 patient
self-report, 0.87 parent proxy-report), the Multidimensional Fatigue Scale
Total Scale Score (alpha = 0.94 patient self-report, 0.94 parent
proxy-report), and acceptable reliability for the 4-item Rheumatology
Module Pain and Hurt Scale (alpha = 0.68 patient self-report, 0.75 parent
proxy-report). The PedsQL Generic Core Scales and Multidimensional Fatigue
Scale significantly distinguished between pediatric patients with
fibromyalgia and healthy children. Pediatric patients with fibromyalgia
self-reported severely impaired physical and psychosocial functioning,
significantly lower on most dimensions when compared to pediatric cancer
patients receiving cancer treatment, and significantly lower on all
dimensions than pediatric patients with other rheumatologic diseases.
Patients with fibromyalgia self-reported significantly greater pain and
fatigue than pediatric patients with other rheumatologic conditions, and
generally more fatigue than pediatric patients receiving treatment for cancer.

CONCLUSIONS: The results demonstrate the excellent measurement properties
of the PedsQL Scales in fibromyalgia. These PedsQL Scales measure
constructs consistent with the recommended OMERACT Fibromyalgia Syndrome
Workshop domains. The findings highlight the severely impaired HRQOL of
pediatric patients with fibromyalgia. Regular monitoring of pediatric
patients with fibromyalgia will help identify children and adolescents at
risk for severely impaired HRQOL. These PedsQL Scales are appropriate
outcome measures for clinical trials and health services research for
pediatric patients with fibromyalgia.

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

Date:    Thu, 15 Feb 2007 10:54:29 -0500
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Widespread Pain and Fibromyalgia in a Biracial Cohort of  Young Women

Widespread Pain and Fibromyalgia in a Biracial Cohort of Young Women.

J Rheumatol. 2007 Feb 1; [Epub ahead of print]

Gansky SA, Plesh O.

 From Preventive and Restorative Dental Sciences, Center for Health and
Community, University of California, San Francisco, San Francisco,
California, USA.

PMID: 17299839


OBJECTIVE: To assess the distribution of widespread pain, tenderpoints
(TP), and fibromyalgia (FM) in young African American (AA) and Caucasian
(C) women.

METHODS: A community population of 1334 young (21-26 yrs old) women (684 AA
and 650 C) was surveyed and classified for body pain spread [chronic
widespread pain (CWP), axial regional chronic pain (RCP), nonaxial RCP, or
no pain]. Of these women, 553 were examined for TP based on American
College of Rheumatology criteria.

RESULTS: Overall, 5.6% reported CWP, while 22% reported axial RCP, and 16%
reported nonaxial RCP. From the CWP group, 57% were confirmed as FM cases.
C women had significantly more TP and greater TP pain score than AA women
(p </= 0.005). Overall FM prevalence was 2.4% (95% confidence interval:
1.7-3.5%), with 3.0% in AA and 2.0% in C women. Increase in body pain and
tenderness was significantly associated with decreased subjective
socioeconomic status (SSS), worse self-reported health, greater impact of
premenstrual symptoms on activities, and greater depressive symptoms. The
effect of depressive symptoms on pain differed by race.

CONCLUSION: Widespread pain and tenderness is highly prevalent in these
young women. Racial differences seem to exist; C women had significantly
increased tenderness while AA women had more widespread pain. The
association of depressive symptoms and pain was stronger in AA women.
Racial differences emerged relatively early in these young women.

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

Date:    Thu, 15 Feb 2007 17:32:04 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: CDC television spot on CFS

Source: Associated Press
Date:   February 14, 2007
URL:                      http://www.ftimes.com/main.asp?SectionID=1&SubSectionID=1&ArticleID=38785&TM=50793.27


Study Focuses on Chronic Fatigue
--------------------------------

ATLANTA (AP) - The television spot shows a 40-year-old woman, in slow
motion, as her family and co-workers rush by over the course of a day. It
ends with her sitting alone, amid the remnants of a birthday party.

'The worst part isn't even that everyone thinks the problem's in my head,'
a female voice intones. 'The worst part of chronic fatigue syndrome is
missing my life.'

The spot is the centerpiece of a remarkable $4.5 million public awareness
campaign bankrolled by the U.S. Centers for Disease Control and Prevention.
It's remarkable, in part, because of the role advocacy and politics played
in creating it.

Chronic fatigue syndrome is not contagious or life-threatening, and medical
skeptics continue to question its merits as a focus for public health. But
the money is being spent, in part, thanks to strategic lobbying and
congressional interest.

It is not the only example, or the most successful. In 2000, the March of
Dimes lobbied Congress to create a center on birth defects within the CDC.
In December, advocates - including Autism Speaks, an effective fundraising
organization founded by General Electric Co. Vice Chairman Bob Wright -
were credited with passage of a bill that targeted nearly $1 billion over
five years to research that condition.

But chronic fatigue syndrome paved the way, said Shelley Hearne, former
executive director of Trust for America's Health, a public health advocacy
group. She is now a visiting scholar at Johns Hopkins University's
Bloomberg School of Public Health.

In the 1990s, Congress authorized money for CDC to study the cause of
chronic fatigue syndrome. In 1998, advocates caught the CDC diverting
nearly $13 million of that funding and spending it in other areas. There
was a federal probe, and CDC eventually replaced the money.

It proved to be a turning point in how the agency interacts with - and is
influenced by - advocates and the lawmakers who support them, Hearne said.
'I think it was really the first wake-up call to the agency that it needed
to understand and respond to the needs of the public,' she said.

Clearly, most researchers believe chronic fatigue is real and that there is
strong justification for the CDC to be working on it. But some are
skeptical, and feel the agency has leaned too far, at times putting lesser
ailments ahead of the public good because advocates and politicians demand
it.

'I personally believe the CDC's emphasis on this has been wrong from day one.
They have responded to pressure,' said Dr. Peter Manu, a New York-based
researcher who does not believe chronic fatigue is a real disease.

Chronic fatigue syndrome is characterized by at least six months of severe
fatigue not helped by bed rest. Patients also report muscle pain and
impaired memory. The CDC estimates more than 1 million Americans have the
condition, with the rate four times higher among women.

It became a national health issue in 1984, when clusters of cases were
reported in Incline Village, Nev., and in Lyndonville, N.Y. Similar reports
came in from around the country, although scientists believe the illness
probably existed before then but wasn't recognized.

One challenge is that chronic fatigue syndrome doesn't have observable
symptoms, said Laura Hillenbrand, a journalist who wrote the best-selling
book 'Seabiscuit' and who has been diagnosed with the illness. 'I have
definitely gotten a raised eyebrow and a 'You look fine!' said Hillenbrand,
39.

Chronic fatigue syndrome came to be known as 'yuppie flu,' because many of
the sufferers were white, educated and relatively affluent.

Several key members of Congress took it seriously, though, including Harry
Reid, the Democratic Senate majority leader, who was a Nevada congressman
when the Incline Village cluster was reported.

Another was John Porter, an Illinois Republican on the House Appropriations
subcommittee that oversees public health programs and agencies. Porter
became involved when a constituent, Chicago-area philanthropist Ted Van
Zelst, visited and told Porter about his daughter's mystery illness. In
1987, Van Zelst became the first person to testify before Congress
requesting research money for chronic fatigue.

At about the same time, a small organization formed in Charlotte, N.C.,
that became the nation's most influential chronic fatigue advocacy group -
the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of
America.

The group was influenced by AIDS activists, who in the 1980s eschewed
gentle advocacy for hard-nosed politicking and government watchdogging. But
the CFIDS Association had a tougher challenge: Their syndrome doesn't
shorten lives, there's no proof it's infectious, and many doctors refused
to take it seriously. It was unexplained, yes, but not fatal - more like a
Nancy Drew mystery than an Agatha Christie.

At the CDC, the investigation was placed in the division responsible for
deadly infections like influenza and rabies. The response there to chronic
fatigue was tepid, said Dr. William Reeves, who now heads the CDC's chronic
fatigue syndrome research. 'They deal with acute infectious agents that
make people dead. That was the mind-set,' he said.

The CFIDS Association, led by Kim McCleary, applied pressure by becoming a
part of the government apparatus. Heeding congressional requests, federal
officials in 1995 gave advocates a place on a U.S. advisory committee on
chronic fatigue syndrome. It was a turning point, because the 5-year-old
panel previously was populated only by scientists and government officials.

It was at one of the panel's meetings in 1998 that CDC's misuse of chronic
fatigue funding was exposed.

McCleary pressed a CDC official on how the chronic fatigue money was being
spent, and Reeves emerged as a whistleblower who refused to back up his
boss, Dr. Brian Mahy. Mahy contended $6 million had been spent on the
disease in the prior year as Congress requested.

But Reeves had complained to Mahy that chronic fatigue efforts were not
getting the money Congress intended. 'It was basically, 'Go out there and
lie for me,' Reeves said in a recent interview. 'I just basically said 'No.'

Mahy, who still works at CDC, declined to comment for this article.

An investigation found that nearly $13 million of $22.7 million meant for
chronic fatigue work was spent on other programs. Lawmakers grilled the CDC
director at the time, Dr. Jeffrey Koplan.

Porter, the Illinois congressman, was upset but there wasn't much he could
do, since Congress usually doesn't mandate how the CDC should divvy its
money among programs. Congress puts spending recommendations in
appropriations reports, but they're not binding, said Porter, who now works
for a Washington law firm.

That's an important point: There are authorization bills that often get a
lot of press, such as the recent autism bill, but they don't come with
actual money. Advocates say it's a bit like parents giving their teen
permission to go to the movies, but not the allowance money to buy the
ticket.

'Almost never do we substitute political judgment for scientific judgment
in the actual appropriations' for the CDC, Porter said.

Some current and former CDC officials said that shifting funds to other
disease-fighting efforts was not a crime. 'This wasn't a case of someone
taking money for a holiday on the French Riviera,' Koplan said, in a recent
interview.

But the agency clearly bungled how it communicated with Congress, said
Koplan, now an administrator at Emory University. 'We had not done
procedurally what the CDC should do, which is inform Congress and ask their
permission when funds for one health problem are used for another health
problem,' he said.

In the 2006 budget year, the CDC spent about $6 million on chronic fatigue
research. That doesn't include the $4.5 million for the slick new ad
campaign unveiled in Washington last fall; and the NIH spent another $5.5
million on the disorder.

CDC funding for the condition has been steady in recent years, and chronic
fatigue syndrome is only a minor budget line at the agency. Dental health
programs get twice as much, and birth defects and disabilities efforts get
more than seven times as much, according to agency budget figures. Domestic
HIV/AIDS research and programs typically get more than 130 times the
chronic fatigue allocation.

The public awareness campaign money is considered reparations for the
diversion of funds in the mid-1990s, said McCleary, who was master of
ceremonies at the CDC press conference on the new ad campaign.

'It's sort of considered their good faith for any of that ever happening,'
she said.

CDC officials say science is driving the public awareness campaign, not
guilt. Scientists at the press conference noted the CDC's chronic fatigue
research group generated about 80 peer-reviewed papers since 2000 that
provided new information about the cost and genetics of the condition.

'The science is there and we need to respect and make that science more
visible,' CDC chief Julie Gerberding said at the event.

At the same time, officials recognized that they still don't know for
certain what causes the illness. There still is no medical test for it, nor
a cure. It may be a collection of illnesses, with different mechanisms.

Reeves co-authored a 2004 article that found a decline in chronic fatigue
in the first few months after the Sept. 11, 2001, terrorist attacks. A
study published last year found that childhood abuse and neglect increased
the likelihood of chronic fatigue in some patients.

Such findings may suggest a complex interaction between stress, genetics
and other factors in why some people develop chronic fatigue. Or, according
to Manu, it may suggest something else entirely - an absence of real
physical illness.

'I don't think there is much to it,' said Manu, a professor at Yeshiva
University's Albert Einstein College of Medicine. He believes many of the
skeptical researchers have moved on to other topics and have stopped
talking about chronic fatigue. Manu is one of only a few scientists still
making such arguments. Others say scientific consensus has shifted away
from Manu, and most doctors no longer doubt chronic fatigue is a real
medical condition.

The new ad campaign is playing a pivotal role in finally moving American
society past skepticism, CFIDS Association officials said. As of the end of
January, the spot has aired 4,425 times in 122 markets on 180 TV stations,
McCleary said.

Advocates are also working with Hillenbrand, who is considered the
highest-profile celebrity to speak often and openly about the condition.
Celebrities make a big impression on many members of Congress, McCleary
noted.

She recalled watching a hearing several years ago when the actor Anthony
Edwards appeared before Congress to talk about autism. At the time, he was
starring in the television hit 'ER' as Dr. Mark Greene. 'They treated him
like he was a doctor,' she said.

Hillenbrand said it's gratifying that most doctors and government officials
are finally taking the condition seriously, and she appreciates how warmly
she's been treated by leaders such as President Bush.

'The first thing the president said to me when I first met him was, 'Don't
get up!' said Hillenbrand, who has been to the White House four times,
including for a screening of the 'Seabiscuit' movie. 'It's nice to know
that there is understanding and compassion in high places.'

--------
(c) 2007 Associated Press

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

Date:    Thu, 15 Feb 2007 22:10:24 -0500
From:    "Dr. Marc-Alexander Fluks <fluks dds.nl> (via Co Cure Moderators)
Subject: RES,NOT: IACFS Conference report/Rosamund Vallings - CORRECTION

There is a mistake in the session:

BEHAVIOURAL POSTERS


---- "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> wrote:
 > Source: Rosamund Vallings
 > Date: February 12, 2007

 > IACFS Conference report
 > -----------------------


 > BEHAVIOURAL POSTERS

 > Exercise intolerance in CFS is evident in a study by C.Ruud (Amsterdam,
 > Netherlands). When CFS patients are subjected to increasing exercise, and
 > compared to controls, there is a lower anaerobic threshold and a state of
 > malaise comparable to overtraining.

This study is done by: Ruud. C. W. Vermeulen (Amsterdam, Netherlands)

Jan van Roijen

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Date:    Fri, 16 Feb 2007 14:05:35 -0500
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Inclusion of the glucocorticoid receptor in a  hypothalamic pituitary adrenal axis model reveals bistability

Inclusion of the glucocorticoid receptor in a hypothalamic pituitary
adrenal axis model reveals bistability.

Journal: Theor Biol Med Model. 2007 Feb 14;4(1):8 [Epub ahead of print]

Authors: Gupta S, Aslakson E, Gurbaxani BM, Vernon SD.

NLM Citation: PMID: 17300722

ABSTRACT:
BACKGROUND: The bodys primary stress management system is the hypothalamic
pituitary adrenal (HPA) axis. The HPA axis responds to physical and mental
challenge to maintain homeostasis in part by controlling the bodys cortisol
level. Dysregulation of the HPA axis is implicated in numerous
stress-related diseases.

RESULTS: We developed a structured model of the HPA axis that includes the
glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of
pituitary GR synthesis. The nonlinear effect arises from the fact that GR
homodimerizes after cortisol activation and induces its own synthesis in
the pituitary. This homodimerization makes possible two stable steady
states (low and high) and one unstable state of cortisol production
resulting in bistability of the HPA axis. In this model, low GR
concentration represents the normal steady state, and high GR concentration
represents a dysregulated steady state. A short stress in the normal steady
state produces a small perturbation in the GR concentration that quickly
returns to normal levels. Long, repeated stress produces persistent and
high GR concentration that does not return to baseline forcing the HPA axis
to an alternate steady state. One consequence of increased steady state GR
is reduced steady state cortisol, which has been observed in some stress
related disorders such as Chronic Fatigue Syndrome (CFS).

CONCLUSIONS: Inclusion of pituitary GR expression resulted in a
biologically plausible model of HPA axis bistability and hypocortisolism.
High GR concentration enhanced cortisol negative feedback on the
hypothalamus and forced the HPA axis into an alternative, low cortisol
state. This model can be used to explore mechanisms underlying disorders of
the HPA axis.


[Note: This is an Open Access article.  The PDF version is available at
http://www.tbiomed.com/content/4/1/8/abstract .]

[Note:  Something that is bistable can be stable in two states.]

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

Date:    Fri, 16 Feb 2007 15:08:24 -0500
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Defining the occurrence and influence of alpha-delta  sleep in chronic fatigue syndrome

Defining the occurrence and influence of alpha-delta sleep in chronic
fatigue syndrome.

Journal: Am J Med Sci. 2007 Feb;333(2):78-84.

Van Hoof E, De Becker P, Lapp C, Cluydts R, De Meirleir K.

 From the Department of Human Physiology (evh, pdb, kdm) and the Department
of Psychology (evh, rc), Vrije Universiteit, Brussels, Belgium; and from
the Hunter-Hopkins Center, Charlotte, North Carolina (cl).

NLM Citation: PMID: 17301585


BACKGROUND: Patients with chronic fatigue syndrome (CFS) present a
disordered sleep pattern and frequently undergo polysomnography to exclude
a primary sleep disorder. Such studies have shown reduced sleep efficiency,
a reduction of deep sleep, prolonged sleep initiation, and alpha-wave
intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L
antiviral pathway and a potential acquired channelopathy are also found in
a subset of CFS patients and could lead to sleep disturbances. This article
compiles a large sleep study database on CFS patients and correlates these
data with a limited number of immune parameters as it has been thought that
RNase L could be associated with these sleep disturbances.

METHODS: Forty-eight patients who fulfilled 1994 Centers for Disease
Control and Prevention criteria for CFS underwent extensive medical
evaluation, routine laboratory testing, and a structured psychiatric
interview. Subjects then completed a complaint checklist and a two-night
polysomnographic investigation. RNase L analysis was performed by gel
electrophoresis using a radiolabeled 2',5'-oligoadenylate trimer. Basic
descriptive statistical parameters were calculated.

RESULTS:: Patients experienced a prolonged sleep latency, showed a low
sleep efficiency index, and had a low percentage of slow wave sleep. The
present alpha-delta intrusion correlated with anxiety; no correlations
appeared, however, between alpha-delta sleep and immunologic parameters,
including RNase L.

CONCLUSIONS:: The main findings are

1) validation of sleep latency problems and other sleep disturbances as
already suggested by several authors;

2) alpha-delta intrusion seems associated with anxiety; and

3) elevated RNase L did not correlate with alpha-delta sleep.

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

Date:    Sat, 17 Feb 2007 00:30:56 +0100
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: res: Defining occurrence & influence of alpha-delta sleep in CFS

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>>   16 February 2007  <<<<
Editorship : j.van.roijen chello.nl
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

Fri, 16 Feb 2007 Fred Springfield posted the abstract of
*Defining the occurrence and influence of alpha-delta  sleep
in chronic fatigue syndrome* - Van Hoof E et al. -
Co-Cure:
http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0702c&L=co-cure&T=0&P=2654



--------------------------------------------------------------
~jvr: as fair use I add the discussion section of this article
--------------------------------------------------------------



Discussion

Sleep architecture variables demonstrated significantly different
sleep onset latency and sleep disturbances in CFS patients (Table
4). Because of the resemblance between the CFS patients used by
Fischler et al13 and Fossey et al15 and our CFS population, their
results may apply to our sample, although no healthy control group
was used. Similar results were already reported by several other
authors, such as Whelton et al10 and Stough and Withers.14 CFS
patients present less sleep continuity. Patients experience problems
falling asleep, represented by the large sleep latency. The low sleep
efficiency index and the high number of micro-awakenings objectify
the subjectively presented complaints of a distorted sleep pattern
and a nonrestorative sleep.5–7 The patients slept about 5.5 hours.
They spent almost 30% of the time awake in bed. Interestingly, a lot
of shifts between stages are apparent. Again, the results of the sleep
architecture underscore the distorted sleep pattern and an
unrefreshing sleep.

Alpha-delta intrusion is present although a wide range of the
percentage of this intrusion indicates its nonspecific nature. This
sleep anomaly is thought to be accompanied by indications of
vigilance during sleep and the subjective experience of unrefreshing
sleep. The latter seems not solely associated with alpha-delta
intrusion because no differences in feelings of fatigue and
unrefreshing sleep could be found between CFS patients with low or
high alpha-delta intrusion. Our results emphasize the nonspecific
nature of alpha-delta sleep in CFS patients, a suggestion made by
several authors.19–23 For instance, Manu and associates found no
correlation between alpha-delta sleep and CFS, fibromyalgia, major
depression, primary sleep disorders, or Lyme disease but did find
that alpha-delta sleep was more common among chronic fatigue
patients without major depressive disorders.23


Although the sample showed high RNase L, no differences were
apparent between patients with low and high alpha-delta intrusion.
Furthermore, no correlations appeared between alpha-delta sleep
and immunologic parameters, including RNase L. So far, it has been
thought that a potential acquired channelopathy, a consequence of
immune deregulation through RNase L, leads to sleep disturbances
including alpha-delta sleep.25,26 Our results suggests that RNase L
and the subsequent channelopathy are not associated with
alpha-delta intrusion. Moreover, none of the self-reported sleep
problems, nor the objective sleep parameters, are associated with
RNase L. This result questions at least a part of the suggested
hypothesis proposed by Englebienne and De Meirleir.25 The
suggested acquired channelopathy with loss of intracellular
potassium should lead to metabolic and intracellular abnormalities,
including central fatigue and sleep disturbances such as alpha-delta
intrusion. Our results do not support the inclusion of sleep
disturbances in- cluding alpha-delta intrusion in the list of potential
consequences of the suggested channelopathy.


The results the deregulation of the 2–5A synthetase/ RNase L
pathway are similar to those of previous studies.27,28 It is still
unclear, however, whether the 37 kDa RNase L ratio is
representative of the CFS population in general, and whether the 37
kDa RNase L ratio is characteristic of a particular stage in the
course of the illness or if it fluctuates over time (as is the case with
symptom severity in the majority of CFS patients). Recent research
suggest the ratio could be associated with (the severity) of the
experienced complaints and its associated clinical causes.25 For
instance, the deregulation of the 2-5A synthetase/RNase L pathway
appears to accompany different aspects of immune dysfunction in
CFS patients. A reduced number and activity (cytotoxicity) of
NK-cells have been reported in patients with CFS.29–31 In addition,
a negative correlation between the RNase L ratio and both the
number and percentage of NK-cells was observed in CFS patients.
In our study, no deviant NK-cells percentages were found. Moreover,
no correlations were found between the RNase L ratio and the
NK-cells.


To be a biological gradient, a correlation between the biological
parameter of interest (i.e., impairment of the RNase L pathway) and
the clinical severity of the disorder of interest (i.e., CFS) is required.
No significant correlations regarding self-reported complaints,
objective sleep parameters, and immune parameters were found in
this study. For interpreting a correlation analysis, however, one
should focus on the correlation coefficient rather than interpreting the
P-value. Correlation coefficients as low as 0.2, regardless of the
P-value, suggest no association is present. Although no significant
associations were found, some correlation coefficients suggested
possible relationships. The Bonferroni-corrections and the small
sample size could prevent any significant results. Further research
is necessary to clarify possible associations. Using our present
results, no significant findings appeared, casting into question the
biological gradient of the RNase L ratio regarding the NK-cells and
sleep disturbances.


Anxiety differed between low and high alphadelta sleep. People
suffering from high alpha-delta intrusion experience more anxiety.
Anxiety could be the result of the higher vigilance in slow wave sleep.
The major clinical importance of this study is that because of alpha
wave intrusion in phase 3 and 4 of the non-REM sleep, full benefit is
not taken from the recuperative function of slow wave sleep.

This study had several limitations. First, the study was done
retrospectively and therefore strong causal relations were difficult to
make. Second, a limited number of CFS patients were enrolled and
there was no healthy control group, although the results were similar
to those of Fischler et al13   and Fossey et al,15 who did include a
healthy control group. Therefore, more research is needed, not only
with a increased number of CFS patients that would give more
accurate results, but also with the same polysomnographic protocol
and adequate control subjects, including patients with
non-CFS-induced fatigue. The relatively small number of CFS
patients in this study was due to recent changes in
polysomnographic protocols; only 41 CFS patients were found to
have completed a similar 2-night polysomnographic protocol.
Moreover, 1-night polysomnographic protocols should be avoided
due to the first-night effect.32 In summary, one obvious limitation of
the present study is the lack of power due to a small sample size.
However, the well-documented expense related to laboratory sleep
research,33 as well as the difficulties regularly encountered with
subject attrition in such extensive, demanding, and lengthy
investigations make small sample size an unfortunate but common
consequence. Nevertheless, the comprehensive data collected
make an important contribution to CFS research and should form
the basis for future investigations.

Summarizing, the main findings of this study are as follows:

1) The existence of sleep latency problems and other sleep
disturbances are validated, as already suggested by several
authors.

2) Alpha-delta intrusion seems associated with anxiety.

3) An elevated RNase L-ratio did not correlate with alphadelta sleep.

4) The results from the correlation analysis questions RNase L as a
biological gradient. To our knowledge, this is the first study in which
immune parameters were correlated to polysomnographic variables
in CFS patients. More research is undoubtedly necessary to state
causal relationships, although some interesting suggestions have
been made.


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Date:    Sat, 17 Feb 2007 01:04:19 +0100
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: not,res: Science: The ME/CFS Dragon Slayer

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


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Quote from below:

*....In a nutshell, the science behind all the
remarkable reports we heard at this conference is
freeing us from any doubt that ME/CFS is a very
real disease with an etiology not rooted in the
psyche....*


~jvr


````````


http://www.immunesupport.com/library/showarticle.cfm?id=7729&T=CFIDS_FM




Science: The ME/CFS Dragon Slayer
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
A Patient Advocate's Perspective on the 2007 IACFS Conference



by John Herd


ImmuneSupport.com

02-14-2007



John Herd has been called a "founding father" of CFS patient
advocacy. He has attended almost every ME/CFS conference since
the late '80s. But at the 2007 IACFS conference, he reports, he saw
something entirely new: "The ME/CFS community is no longer
confined by national borders. We are all in this together."

Little by little, patient advocates are beginning to produce their
summaries of reports from the 2007 IACFS professional and patient
conference in Florida. It's a gradual process because five days of
conferencing would be hard on anyone…and it's far harder on
ME/CFS patients. And there's an immense amount to talk about
pertaining to what transpired at the conference. The scientific
reports were absolutely breathtaking, though so technically rooted in
science that many are hard to get your head around without
interpretation.


The Conference 'Stress Test'

Truth be told, the conference is as tough a stress test as doctors
could devise for ME/CFS patients. Advocates who attend the IACFS
conference deserve a lot of credit and recognition for exhibiting such
a level of commitment that they'd be willing to put themselves
through such a grueling exercise in order to represent the patient
community.


The Science, Once So Scattered, Is Converging

In a nutshell, the science behind all the remarkable reports we heard
at this conference is freeing us from any doubt that ME/CFS is a
very real disease with an etiology not rooted in the psyche.


This science is a dragon slayer, and the dragon is the bygone 'all in
the head' dogma that no one - not doctors, not governments, not the
public - is going to be able to hold onto much longer. That said, I'll let
others begin to report in lay terms on all the scientific headway
presented at the conference.


What I will say now is that the conference had a very different feel to
it than the past five IACFS conferences I've attended. On my way
home I realized why: It was convergence.


In the past, conference sessions reported on many kinds of
interesting but seemingly unrelated small pieces of the biologic
ME/CFS puzzle. These pieces represented scientists reaching out
in many directions to grasp little pieces of the puzzle, but there was
little sense of connectedness.

The science reported at this year's conference felt very different. It
seemed like much of it was different kinds of science coming
together - each building on the other with associations. It felt like
finally the many small pieces of the puzzle were finally beginning to
reveal a cohesive picture, the picture of what ME/CFS really is.


The Experts are Acting Like a Global Team

Instead of the doctors and researchers seeming to be scientific
athletes, each playing his or her solitary sport, they and their work
seemed to be a team sport. The players and their activities (their
scientific findings) harmonized in a fashion that gave confidence
we're closing in on answers we've long sought.


In addition to the convergence of ideas, the conference embodied a
remarkable physical convergence. Nancy Klimas, MD, president of
the IACFS, announced that there were doctors present from some
28 different counties. That's 28 countries where clinical and
research experts will be carrying back and sharing the latest
knowledge to help patients and ignite more research.


For example, I met one marvelous doctor from South America who
realized not only that her country was offering almost nothing for
ME/CFS patients - but that she herself knew very little about the
illness. She wasn't just attending the conference…she's been doing
an extended medical fellowship here. And now she can return to her
country with knowledge that will benefit many.


There were too many doctors from too many countries to mention
them all. But just for example:

* Vance A. Spence, PhD, attended to share the work that ME
Research UK has been conducting, and to bring back to the UK
knowledge that may help to change things there. His organization
http://www.meresearch.org.uk/ is a charity dedicated to funding
ME/CFS research and publishing the results.

* Jonathan Kerr, MD, PhD, was also at the conference, sharing his
stunning genetic work. Dr. Kerr, a professor of microbiology at
Imperial College, London, is studying the mechanisms of gene
expression in ME/CFS.

* Doctors from Japan reported on many kinds of work they're
conducting, which sound as though they'll make tremendous
contributions to our understanding of the illness.


Patient Advocates Connecting Globally Too

Just as there was a strong sense that the experts are cooperating to
build on each other's findings and work in unison, the same was true
of the international patient advocate gathering.


In the context of the IACFS dual conference, advocates from across
the U.S. and different countries had an unparalleled opportunity to
meet and share their knowledge, talk shop amongst each other, and
lay plans for the future.


This Organization is Very Definitely International

Let no one doubt that the IACFS has gone international. It is very
much a global organization with global reach. In keeping with that
international mission, and because the illness is known as ME
throughout much of the world, the organization is changing its name
to the IACFS/ME.


The take-away message? The ME/CFS community is no longer
confined by national borders. We are all in this together.


Special Thanks to Special Volunteers

Finally, on behalf of all who will benefit from this international sharing,
we owe special thanks and recognition to PANDORA – the
conference's host and co-sponsor. Kudos to President Marla
McKibben Silverman, Vice President Rebecca Artman, and the other
PANDORA volunteers for their enormous contributions to the
conference.


Their work, along with the IACFS/ME leadership's work, made this
2007 conference the most profoundly important conference and
meeting of minds we've ever seen in the history of ME/CFS.

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Date:    Sun, 18 Feb 2007 21:06:43 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: Ayurveda for CFS causes heavy metal poisoning

Source: U.K. Medicines and Healthcare products Regulatory Agency (MHRA)
Date:   February 16, 2007
URL:                      http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2030310&ssTargetNodeId=663


Ayurvedic medicines containing heavy metals
-------------------------------------------

he MHRA have been made aware of at least six cases of heavy metal
poisoning in the last 3-4 years associated with the use of Ayurvedic
medicines. In most of these cases, the Ayurvedic medicines contained
lead. There has also been a case of arsenic poisoning.

The Ayurvedic medicines in question were obtained from the Indian
sub-continent and brought back to the UK for self use. Patients were
treating diabetes, chronic fatigue syndrome and hypertension.

The MHRA would strongly advise caution on the part of consumers and that
they consult their GPs before use. Previous concerns about the heavy
metal content of some Ayurvedic Medicines were highlighted in a press
release dated 17 August 2005 'Ayurvedic Medicines may contain Heavy
Metals' from the Current Safety Issues on the MHRA website,
  

  

   http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&ssDocName=CON2014944&ssSourceNodeId=663&ssTargetNodeId=389

--------
(c) 2007 MHRA

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

Date:    Sun, 18 Feb 2007 21:00:25 +0000
From:    Ellen Goudsmit <ellengoudsmit HOTMAIL.COM>
Subject: RES: Effect sizes (Cohen's d) for various interventions to treat CFS/ME

Taking a different perspective. The assessment of treatments for CFS/ME
using Cohen's d.

Ellen Goudsmit PhD C.Psychol.

Objective: To compare different treatments for CFS/ME using one recognised
measure of effect size.

Method. Cohen's d (delta) was computed using the mean fatigue scores (and
SD) obtained from published trials or studies reported in the CRD reviews.
In one case, Cohen's d was calculated using the F statistic and checked for
reliability using an additional formula plus second measure of effect size.

Results. There were few differences between the various programmes for
CFS/ME. Effect sizes were generally moderate.

TREATMENT                   D     Reference

CBT/GET                       .78   Deale et al 1997
CBT/GET                       .64   Prins et al, 2001
GET                              .57   Fulcher and White 1997
Multi-dimensional*           .71   Goudsmit 1996

Discussion. The results suggest that a larger study may be of interest. They
also give an indication of the modest effects of  the various treatments
when using fatigue as the outcome measure.

Further research should include effect size statistics computed for other
symptoms and quality-of-life.  For example, a study of a client-centered,
multi-dimensional programme which provided data for these variables reported
d values between .66 and .71 (Taylor, 2004).  Similarly, in the GET
trial(Fulcher and White), d calculated from the data for the MOS-SF physical
functioning subscale was .69, but d for the MOS-SF as a whole was .499. One
is higher than that for fatigue, the other is lower.  The inclusion of
different outcome measures may give a more realistic view of the effect of a
given treatment than data for fatigue and emotional distress.

Caveats. This analysis was limited by the lack of statistical information in
some papers. Moreover, a number of studies did not provide data for fatigue
(e.g. Marlin et al, 1998).

Conclusion. Based on effect sizes, there appears little evidence to
recommend one treatment above another. Moreover, the generally modest values
for Cohen's d  support claims that certain intervention are helpful, rather
than "effective".

Postscript. Values of .2 or less are considered small, .50 or above are
moderate and .8 or above are considered as indicative of a large effect.
* This programme did not incude CBT.


----------------------------------------------------------------------
Ellen M. Goudsmit C. Psychol. AFBPsS


For information on ME and CFS, see:
http://freespace.virgin.net/david.axford/melist.htm


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

Date:    Mon, 19 Feb 2007 16:57:50 -0500
From:    "Cort Johnson <phoenixcfs yahoo.com> via Co-Cure Moderator
Subject: NOT,RES: IACFS Conference III: Immune, Gut, Sleep and Pain  Presentations


Welcome to Part III of our overview of the IACFS conference in Florida.
This part deals with  immune, gut, pain and sleep issues. We hear an
exciting breakthrough in the Dubbo's studies attempts to unravel
post-infective fatigue, more news of natural killer cell dysfunction in
CFS, a study suggesting a viral infection is commonly present in the
gastrointestinal system of CFS patients, two Lyme studies, plus much more. ot

You can find this session at the URL below
http://phoenix-cfs.org/IACFS%202007%20Conference%20III%20Immune,%20Gut,%20Pain%20and%20Sleep.htm

The next section on the Clinical Trials will be coming up shortly.

Please subscribe to Phoenix Rising

Happy reading,

Cort

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

End of Co-Cure Weekly Digest of research and medical posts only - 12 Feb 2007 to 19 Feb 2007

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