|
Volume 4, number 2 |
ME AND
CFS
|
11th March 2001 |
What follows is a brief summary of the presentations which in my opinion were the most interesting or important either because they showed something new or because they disproved assumptions which have been hindering the acceptance of CFS as a serious disorder worth studying. It is not intended to be complete and many presentations and posters are not mentioned. The summaries are filtered through my personal memory and judgment both of which are liable to error.
After each authors name there may be references other important papers by the author. The bibliography of these papers is at the end of the summary.
This summary is intended for consumers. In addition to summaries of the presentations there are some explanations of medical terminology and the relevance/importance of some technical papers.
- this pre-conference 1/2 day hosted by the CDC was disappointing given the amount of money spent and misspent ($US 13 million misspent and 4 million missing) that the CDC is still at the stage of asking what is fatigue and how can we measure it? No further comment.
Lea Steele, San Franscisco
(Steele et al,
1998)
- studied American Gulf War veterans to discern whether CFS and GWI are related
or the same illness. The incidence
of CFS among GW vets was much greater than in the general population (7% vs.
.4%) however the prevalence of CFS doesnt vary with any of the factors that
predict the severity of GWI eg. branch of service, location of service and
timing of deployment. Also the
symptom pattern was slightly different with GWI having more joint pain,
diarrhea, night sweats and skin rashes than CFS patients. This suggests that GWI
and CFS are not identical.
Rosane Nissenbaum, CDC in
Atlanta Georgia
- described the Wichita Kansas population study funded by the CDC.
Population studies are important because they are free of the self
selection biases which occur when studies are done on patient groups.
ie. patients who go to their doctor are probably not representative of
all patients with a disorder. Through
telephone interviews of 33,000 randomly selected households subjects were
identified who had CFS-like illness and CF not meeting the full CFS criteria.
These people were followed up at one, two and three year intervals.
There was only 30% stability over the first year meaning 30% of the
subjects with CFS-like illness still met full criteria after 1 year.
Interestingly many people said that they were improved but reported no
change in their hours/wk of work and home duties suggesting they were not
entirely well. Never the less,
these data suggest that population derived samples have a higher rate of
spontaneous recovery than clinical samples in which recovery is generally less
than 20% over 4 years.
Leonard Jason, Chicago
(Jason et al,
1999;Jason et al, 1997)
- described subgroups of patients from the Chicago epidemiological study which
was done using similar methodology to the Wichita study.
The overall of prevalence of CFS was found to be 0.4%.
However, women, minorities and unemployed had higher prevalence and more
severe symptoms than men, Caucasians and employed.
Lifetime psychiatric history did not correlate with any severity
measures. Those subjects with
current psychiatric disorder had greater fatigue and social disability than
those without current psychiatric disorder.
This disproved the long held myths that minorities and the poor dont
get CFS and that psychiatric disorder is an important variable in CFS.
Pascale DeBecker, Brussels
Belgium
(De Becker et al,
1998)
- reported on the largest well studied patient group in the world.
Each of 1500 patients seen at Dr. Kenny DeMeileirs CFS clinic at the
Free University of Brussels has been extensively assessed.
Each patient met the 1988 and/or the 1994 diagnostic criteria and
completed a severity checklist of 50 symptoms.
A factor analysis was done to see which symptoms covaried ie. were found
together more often. The
beauty of this model is that it is done by computer without any bias from the
researcher. They found 4 symptom
clusters: general and infective symptoms, neurocognitive, musculoskeletal and
psychiatric. The first three
clusters were strongly associated with whether the patient met the CFS criteria
and with maximum fitness on exercise testing.
The psychiatric cluster didnt seem relevant either to diagnosis or
fitness suggesting it is not a core aspect of CFS. This is a strong argument against CFS being a
psychosomatic or functional somatic disorder.
DeBecker suggested 10 additional symptoms which should be added to the
CFS diagnosis based on this research.
Katherine Rowe, Melbourne
Australia
(Rowe, 1997)
- did a factor analysis similar to De Beckers on 149 PWCs who became ill before
the age of 18. Of the 38 symptoms
used from an adult checklist, 24 were commonly endorsed in the young patients.
She found a 5 factor solution ie. there were 5 clusters of symptoms:
muscle pain/fatigue, neurocognitive, abdominal/head/chest pain,
neurophysiological and immune/infective. Furthermore
she did structural equation modelling to see the direction of effects between
symptom groups. The immune group
seemed to occur first and other symptoms resulted from this.
She also found three discrete groups based on severity. As an aside, Dr. Rowe reported that young patients were able
to give accurate and discriminating symptom reports, they did not answer yes to
everything or no to everything.
Stanley Schwartz
- followed up a group of CFS patients with and without depression and a group of
depressed patients over 4 years. All
patients received conventional treatment.
He found that in both groups the depressive symptoms were much more
responsive to treatment than the CFS symptoms and that the patients with
CFS+Depression had a better outcome than those with depression alone.
Daniel Cukor/Lana Tiersky, New
Jersey
(Tiersky et al,
1997)
- tested the often proposed hypothesis that CFS is a form of somatization
disorder because patients who complain of more physical symptoms also have more
psychological symptoms. In this
study of 145 PWCs diagnosed using the 1994 criteria there was no correlation
between the number of physical symptoms and the number or presence of
psychiatric diagnosis. In addition
other variable such as age of onset in CFS was different that that typically
seen in somatization disorder. They
conclude CFS has no relation to somatization disorder.
Patricia Soetekouw, Belgium
(Soetekouw et al,
1999)
- confirms the
presence of subtle but important differences between subjects with CFS and
healthy controls. CFS subjects
asked to stand for 5 minutes after lying down had poorer cardiac response to the
stress of standing and had more symptoms during standing.
James Baraniuk
(Baraniuk et al,
1998)
- studied autonomic
function in the nose in an interesting way.
Subjects were asked to do a hand grip exercise.
Normally exercise causes increased lactic acid which activates the blood
vessels in the nose to constrict so that more blood can go to the muscles and
correct the acidity. When the blood
vessels in the nose constrict there is less inflammation and mucous and airflow
increases. This effect was missing
in subjects with CFS but was present in healthy controls.
Baraniuk feels the cause of much nasal congestion and dripping could be
autonomic dysfunction.
Julian Stewart, NY
(Stewart et al,
1999)
- argues that the
term orthostatic intolerance is a misnomer because abnormalities are detectable
even lying down. He is a pediatric
cardiologist who studies Postural Orthostatic Tachycardia Syndrome (POTS).
He hypothesizes and has some research evidence to support that POTS is
due to a pooling of blood in the periphery especially the legs.
This is not generally due to abnormalities of the veins but rather due to
failure of arterial vasoconstriction. Capillary
permeability seems normal but venous emptying may be impaired.
Patrick Englebienne, Brussels
Belgium
(in my personal opinion the most important paper at the conference)
- described an elegant experiment which connects the RNAse-L and channelopathy
hypotheses. Englebienne works with De Meileir, De Becker and colleagues
in Brussels.
Review of RNAse-L this is an enzyme produced by white blood cells which are challenged by certain viruses and possibly also some toxic exposures. The enzyme breaks down the viral RNA and also destroys the infected cell so that the virus has no where to live. Suhadolnik first discovered in 1995 that persons with CFS had elevated levels of an abnormal type of this enzyme (Suhadolnik et al, 1994) . Instead of the normal size 80KDa enzyme subjects with CFS show a 37 KDa enzyme. This finding has been found also by the Belgian group who now commercially tests the ratio of the 37KDa and 80KDa enzymes (De Meileir et al, 2000) . They and an independent group in the US have found that a high ratio is associated with more severe clinical symptoms and decreased exercise fitness. De Meileir et al have recently found that the 37Kda RNAse-L is associated with incomplete cell death. This means that the cell constituents cannot be recycled for use by other cells.
Review of the channelopathy hypothesis of CFS channels are the name given to the thousands of portals which control what enters and leaves a cell. Every cell has specific environmental requirements and controls the environment through channels each of which is exquisitely specific and sensitive. If channels are blocked or leaky the cell will not function optimally and may even die. Poisoning by ciguatera fish toxin is an experimental model for channel dysfunction. It kills cells by incapacitating the channel which controls sodium and potassium concentrations inside and outside of cells. Causes of channelopathy include toxins (eg. ciguatera, DDT), antibodies against the channels, and prolonged stress.
Chaudhuri suggested that CFS is a channelopathy because it shares many similarities with disorders that are known to be associated with abnormal channel function (Strickland et al, 1998) . These similarities include: variability of symptom expression, either excess or loss of function, triggered by environmental stresses eg. smell, food, exercise, infection and neurologic involvement. To date there has only been indirect evidence to support this theory. Chaudhuri and Behan have shown that PWCs use more energy at rest than healthy controls . Burnett in Adelaide has shown that some PWCs have decreased total body potassium and abnormal potassium response to exercise. One of the most important channels is the one that controls sodium and potassium concentrations and this channel alone takes up to 40% of the bodys energy. Therefore even a small anomaly in this channel function could represent a significant energy drain.
In the body every molecule has a regulatory system, usually something that binds to it changing the shape turning it off or on. For RNAse-L the brakes are applied by a protein called RNAse-L inhibitor protein (RLI). Englebienne reports that RLI looks very similar as a family of channels called the ATP binding casette (ABC) family. As a result 37 KDa variety of RNAse-L which is missing some of the usual regulator areas binds by mistake to the ABC channels. These channels include (you guessed it) the sodium/potassium pump that Chaudhuri thinks is involved in CFS. Other members of the family are found in red blood cells, immune function, the uptake of tryptophan (necessary for sleep and mood), can cause sensitivity to toxic chemicals and pain and are known to be involved in neurological disorders all possible mechanisms of CFS symptoms.
Howard Urnovitz (and Paul
Cheney)
- followed up on a finding in Gulf War vets of
RNA fragments found in the blood. It
turns out this RNA is from the gene which makes antibodies.
In order for the body to make antibodies to any infection or foreign
molecule it has to be a very flexible gene, able to recombine and match the
shape of invaders. Perhaps because
of this ability to change, these areas of DNA are also susceptible to being
permanently changed by outside toxins such as infections, vaccines,
radioactivity and pesticides. In
other words a number of different events could cause similar genetic mutations
and thus similar symptoms. This
group is hypothesizing that certain of these RNA molecules may be specific
markers of CFS but more evidence is needed.
- found that PWCs had lower levels of perforin in their natural killer (NK)
cells. NK cells seek out and kill
cells which are infected or cancerous. Perforin
is one of the enzymes which is responsible for cell death.
Mice bred not to produce perforin generally die young of infection and
show increased immune activation similar to subjects with CFS. Low perforin could explain the finding by other groups that
PWCs have low NK cell activity.
Eng Tan
- reports finding high levels of antibodies to tubulin a protein found in cells.
If tubulin is attacked it would have serious effects on cell function.
Kenny De Meileir, Belgium
-informally reported on their labs experience with PCR testing for mycoplasma.
69% of PWCs are positive for mycoplasma compared with 3% of healthy
controls. RNAse-L ratios are
elevated in those PWCs with mycoplasma compared with PWCs who test negative.
Interestingly 67% of a sample of people living in Bijlmer who became ill
after a plane crash occurred in the area are positive for mycoplasma.
They have a CFS like syndrome plus dry skin.
They hypothesize that treating mycoplasma when present will lower the
infective load and help the immune system recover.
However this view was strongly criticized by others who pointed out that
PCR detects DNA sequences and doesnt actually indicate the presence of live
virus. Therefore they caution
against the risks of antibiotic treatment in the absence of evidence of active
infection.
Leslie Aaron, Richard Harrell,
David Lewis
- an amazing twin study was reported with 65 pairs of twins in which one twin
had CFS and the other didnt. By
comparing monozygous (identical) twins and dizygous (fraternal) twins one can
estimate the relative contribution of genetics and environmental causes.
For example if CFS were 100% genetic, 100% of identical twin pairs and
50% of fraternal twins who only share 1/2 of their genes will be the same with
respect to whether they have CFS or not. Things
like life experiences, infections, stress etc wouldnt make any difference.
Conversely if a disorder has no genetic components then there will be no
difference between the rates of concordance in identical and fraternal twins.
In this study the concordance rate for identical twins was 55% and for
fraternal twins was 19%. This
suggests that both genetic and environmental factors contribute to CFS.
Roderick Mahurin, from Dedra
Buchwalds group in Seattle
- did a study to assess whether there is any objective evidence to support
subjective reports from PWCs that mental tasks require more energy than they did
prior to illness. The used SPECT
scans to measure brain blood flow at rest and during a difficult arithmatic/memory
task. The blood flow pattern of the
PWCs was similar to that found in healthy controls doing a more difficult task.
This validation of subjective effort adds to the evidence against PWCs
being overly sensitive to effort ie. neurotic.
Richard Gracely, from Daniel
Clauws FM research group
- pain like fatigue is a subjective symptom which is hard to validate.
This has led to many skeptics that people with CFS/FM are experiencing
real and significant pain. If
the skeptics read this study they may have to reconsider.
Functional MRI measures neuronal function. f-MRI scans of the brain were done while light and then
intense thumb pressure was being applied. This
allows detection of which brain areas are activated with pressure/pain.
The FM patients showed similar brain activation patterns shown by healthy
controls but at lower pain levels. Like
the previous study, this adds to the objective evidence of lower pain thresholds
in FM.
Gijs Bleijenberg, The
Netherlands
- completed surveys of physicians in 1993 and 1999.
The number of GPs who never make a diagnosis of CFS has decreased
from 27% to 13%. However in
practice when asked what they would do when presented with a potential PWC, 78%
refer to a specialist rather than or before making a diagnosis of CFS.
This is complicated by the patient report that 21% of GPs and 53% of
specialists dont take CFS seriously. Physicians
perceive that PWCs causes problems for physicians including: need for longer
consultations, more communication problems and increased non compliance
compared to other patients.
Anthony Komaroff
(Komaroff, 2000;Komaroff & Buchwald, 1991)
- in his keynote
address, Komaroff reminded physicians of 4 important points
1. the patient will tell you the diagnosis
2. just because it is not written doesnt mean its not true, be willing to seek evidence
3. psychiatric illness is real disease, its not an issue of moral character or strength
4. never succumb to the temptation to blame the patient by saying there is nothing wrong with you when unable to make a diagnosis
Leonard Jason, De Paul
University, Chicago
(Jason et al,
1997;Jason et al, 1995;Jason et al, 1999)
- experimentally
tested effect of CFS label on attitudes of medical students towards PWCs by
giving them an identical case example with three different diagnostic labels
CFS, ME and Florence Nightingale Disease. Students
rated those with CFS as more likely to have a correct diagnosis and more likely
to improve. ME was associated with
being thought to result from a physical cause and to be less suitable candidates
for organ transplantation. Given a
typical CFS history with three different recommended treatments: Ampligen, CBT
and coping skill training, students assumed the subjects treated with ampligen
were more likely to have been correctly diagnosed and to be more severely
affected. Only 20% of medical
students, 40% of family practice residents and 90% of psychiatric residents had
ever read an article about CFS.
Jos Van der Meer, The Netherlands (Bazelmans et al, 1999;Vercoulen et al, 1997)
- did the largest yet
randomized blinded study of CBT in CFS. They
randomly assigned 92 PWCs to receive 16 weekly sessions of CBT, 90 to receive 11
sessions of guided group support and 88 to be untreated.
They also tested each patients with an actometer to measure their actual
activity continuously for 2 weeks. This
device is worn on the ankle and measures all movement.
Using measures of functional impairment, fatigue and overall wellness the
CBT group did significantly better than the other two groups. Yet the rates of improvement were low, 50% in the CBT group
and 35% in the other groups. They
found that the presence of psychiatric diagnosis did not affect outcome.
The least active patients (perhaps the most ill) at the start did the
least well. This study is an
advance over other CBT studies to date as they actually used the 1994 case
definition for CFS which requires physical symptoms to be present.
However it was not reported whether any of those symptoms improved with
treatment.
Pat Fennell, Albany NY
(Fennell, 1995)
- proposed a model
of psychosocial support based on the stage of psychological adjustment to CFS.
In each of four stages: crisis, stabilization, resolution and integration
different psychological tasks are required and different therapeutic approaches
are necessary. She noted that
psychological support for CFS differs from the Kubler Ross model because there
is generally no death or end to the symptoms, rather the PWC and family have to
learn to cope, adjust and find new meaning.
She suggested that chronic illness can be a litmus test like the tablets
which the dentist gives to see where one has missed brushing.
Whereas healthy people can compensate for unresolved emotional issues,
chronic illness tends to diminish this ability and preexisting problems come to
light.
Nancy Klimas
- reports on preliminary results from an extraordinary study probably only
possible at a major institution like the CDC.
Patients with tender lymph nodes and immune inflammatory shift (Th2) had
their lymph nodes excised, the cells cultured and forced in vitro towards a more
favorable immune profile then reinjected. In
10/11 cases the clinical picture and immune profiles are related tothe procedure
covaried suggesting that immune profiles do have an impact on clinical symptoms.
As a group the patients reported significant improvement in brain fog and
many improved in objective tests of cognitive function.
Kittil Rammohan
- reported on a trial of modafinil (Provigil) a drug approved for use in
narcolepsy in patients with MS who have fatigue similar to that in CFS.
This drug is used for treatment of day time sleepiness not night time
sleep. At 200 mg/day more patients
reported improvement in the Fatigue Severity Scale than those who were untreated
or who were on a higher dose. There
were very few side effects suggesting it may be feasible to try this drug in
PWCs with day time sleepiness.
Katherine Rowe, Melbourne
- reported on a long term followup of children and adolescents treated 7 years
ago with immunoglobulin. About 1/2
were entirely recovered, many reported improvement but continued fatigue and 7%
had a severe course. In a telephone
interview the former PWCs now in their 20s uniformly reported that receiving a
diagnosis was useful and that delay in diagnosis was a problem.
This refutes hypotheses that giving a diagnosis begins a self fulfilling
prophesy of continued illness. It
also suggests that intravenous immunoglobulin may have utility in young
patients.
David Bell, Lyndonville NY
(Bell et al,
1994;Streeten et al, 2000)
- reported on the 15
year follow-up of 47 children who became ill with CFS at the same time in a
small community ie an epidemic outbreak. 37%
were completely well, 43% were functioning well but had to make compensations
for their health, 11% were still ill and 9% were severely ill or worsening.
Those who were most ill initially and missed the most school had the
poorest outcome. Some of the
subjects commented that since they had been ill since childhood they found it
hard to assess if they were completely cured or not.
- if the RNAse theory is
correct and the cascade is started by the enzyme calpain then calcium channel
blockers may help because they inhibit calpain
- tricyclic antidepressants and
flexaril a muscle relaxant which is related help both sleep and pain, other
sleep medications such as zopiclone (Imovane) only address sleep not pain.
There was agreement that serotonin antidepressants (eg. prozac, paxil,
zoloft) are not generally helpful in CFS at least for pain relief.
- there was debate about
whether treating orthostatic intolerance (OI) actually improves the overall CFS
syndrome, some say yes, some say no. Therefore
not all clinicians would treat with fluodrocortisone even in the face of
clinical OI symptoms eg. dizziness, pain, fatigue, nausea upon standing.
- some clinicians felt their
patients could achieve significant improvements by addressing each of the
presenting symptoms. A poster was
presented by Jacob Tietelbaum in which 30/33 of FM patients most of whom also
met criteria for CFS improved using this symptomatic and laboratory testing
approach compared with 12/33 patients in the placebo treatment group.
These patients were given placebo look alikes for all treatments.
Several doctors had a more nihilistic attitude that nothing really works
and as a result offer little symptomatic treatment.
- despite anecdotal reports of
improvement with bovine (from cows) growth hormone (GH) in selected CFS patients
with low GH levels, treatment remains controversial because of side effects.
- there was agreement that
replacement corticosteroid eg. 10 20 mg cortisol daily is not good because
there is limited symptom improvement and potentially serious side effects such
as adrenal suppression.
- there was considerable debate about the usefullness of elimination diets, most alterative treaters advocated it and most conventional physicians disregarded it.
Baraniuk,J.N.,
Clauw,D.J., & Gaumond,E. (1998) Rhinitis symptoms in chronic fatigue
syndrome. Annals of Allergy, Asthma, & Immunology, 81,
359-365.
Bazelmans,E.,
Vercoulen,J.H., Swanink,C.M., Fennis,J.F., Galama, JM, van Weel,C., van der
Meer,J.W., & Bleijenberg,G. (1999) Chronic Fatigue Syndrome and Primary
Fibromyalgia Syndrome as recognized by GPs. Family Practice, 16,
602-604.
Bell,D.S.,
Bell,K.M., & Cheney,P.R. (1994) Primary juvenile fibromyalgia syndrome and
chronic fatigue syndrome in adolescents. Clinical Infectious Diseases, 18
Suppl 1, S21-S23.
De
Becker,P., Dendale,P., De Meirleir,K., Campine,I., Vandenborne,K., &
Hagers,Y. (1998) Autonomic testing in patients with chronic fatigue syndrome. American
Journal of Medicine, 105, 22S-26S.
De
Meileir,K., Bisbal,C., Campine,I., De Becker,P., Salehzada,T., Demettre E.,
& Lebleu,B. (2000) A 37kDa 2-5A
binding protein as a potential biochemical marker for chronic fatigue syndrome. American
Journal of Medicine, 108, 99-105.
Fennell,P.A.
(1995) The four progressive stages of the CFS experience: a coping tool for
patients. Journal of Chronic Fatigue Syndrome, 1, 69-79.
Jason,L.A.,
King,C.P., Richman,J.A., Taylor,R., Torres,S.R., & Song,S. (1999) U.S. case
definition of chronic fatigue syndrome: diagnostic and theoretical issues. Journal
of Chronic Fatigue Syndrome, 5, 3-33.
Jason,L.A.,
Richman,J.A., Friedberg,F., Wagner,L., Taylor,R., & Jordan,K.M. (1997)
Politics, science, and the emergence of a new disease. The case of chronic
fatigue syndrome. American Psychologist, 52, 973-983.
Jason,L.A.,
Taylor,R., Wagner,L., Holden,J., Ferrari,J.R., Plioplys,A.V., Plioplys,S.,
Lipkin,D., & Papernik,M. (1995) Estimating rates of chronic fatigue syndrome
from a community-based sample: a pilot study. American Journal of Community
Psychology, 23, 557-568.
Komaroff,A.L.
(2000) The biology of chronic fatigue syndrome. American Journal of Medicine,
108, 169-171.
Komaroff,A.L.
& Buchwald,D. (1991) Symptoms and Signs of Chronic Fatigue Syndrome. Reviews
of Infectious Diseases, 13(Suppl 1), S8-S11.
Rowe,K.S.
(1997) Double-blind randomized controlled trial to assess the efficacy of
intravenous gammaglobulin for the management of chronic fatigue syndrome in
adolescents. Journal of Psychiatric Research , 31, 133-147.
Soetekouw,P.M.,
Lenders,J.W., Bleijenberg,G., Thien,T., & van der Meer,J.W. (1999) Autonomic
function in patients with chronic fatigue syndrome. Clinical Autonomic
Research, 9, 334-340.
Steele,L.,
Dobbins,J.G., Fukuda,K., Reyes,M., Randall,B., Koppelman,M., Reeves, & WC.
(1998) The epidemiology of chronic fatigue in San Francisco. American Journal
of Medicine, 105, 83S-90S.
Stewart,J.M.,
Gewitz,M.H., Weldon,A., Arlievsky,N., Li,K., & Munoz,J. (1999) Orthostatic
intolerance in adolescent chronic fatigue syndrome. Pediatrics, 103,
116-121.
Streeten,D.H.,
Thomas,D., & Bell,D.S. (2000) The roles of orthostatic hypotension,
orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of
the chronic fatigue syndrome. American Journal of the Medical Sciences, 320,
1-8.
Strickland,P.,
Morriss,R., Wearden,A., & Deakin,B. (1998) A comparison of salivary cortisol
in chronic fatigue syndrome, community depression and healthy controls. Journal
of Affective Disorders, 47, 191-194.
Suhadolnik,R.J.,
Reichenbach,N.L., Hitzges,P., Sobol,R.W., Peterson,D.L., Henry, B, Ablashi,D.V.,
Muller,W.E., Schroder,H.C., & Carter,W.A. (1994) Upregulation of the 2-5A
synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clinical
Infectious Diseases, 18 Suppl 1, S96-104.
Tiersky,L.A.,
Johnson,S.K., Lange,G., Natelson,B.H., & DeLuca,J. (1997) Neuropsychology of
chronic fatigue syndrome: a critical review. Journal of Clinical & Experimental Neuropsychology, 19,
560-586.
Vercoulen,J.H.,
Bazelmans,E., Swanink,C.M., Fennis,J.F., Galama,J.M., Jongen,P.J., Hommes,O.,
van der Meer,J.W., & Bleijenberg,G. (1997) Physical activity in chronic
fatigue syndrome: assessment and its role in fatigue. Journal of Psychiatric
Research, 31 , 661-673.
Copyright Ellie
Stein MD FRCP(C) March 2001.
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