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Co-Cure Weekly Digest of research and medical posts only - 28 May 2007 to 4 Jun 2007

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                       This is a special digest of
                  Co-Cure Research & Medical posts only
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Date:    Tue, 29 May 2007 17:11:34 +0000
From:    Gayle Babykin <gbab FRONTIERNET.NET>
Subject: MED: Some pain meds used by patients may cancel out HRT's heart benefits


Chronic Pain Rx News
Managing chronic pain

May 29, 2007


Some pain meds may cancel out HRT's heart benefits
Women who take some painkillers while also taking hormone replacement =20
therapy (HRT) may have higher heart risks than women who do not take =20
the pain meds, researchers say. HRT has long been thought to have a =20
protective effect on women's hearts. But a new study suggests that =20
women who take non-steroidal anti-inflammatory drugs such as Celebrex, =20
ibuprofen, and naproxen along with HRT may lose the therapy's =20
protective effects.
  (HealthDay News) UPDATED 2007-05-28 11:22.
Read this article at: =20

Study: Celebrex+Nexium reduces GI bleeding
Taking the proton pump inhibitor Nexium with Celebrex may reduce the =20
incidence of upper-gastrointestinal bleeding in patients taking the =20
pain med, researchers say. Patients who took Nexium with Celebrex in a =20
recent study had no bleeding events over the course of the study. =20
Patients who took Celebrex and a placebo had an 8.9 percent rate of =20
upper-GI bleeding.
  (MedPage Today) UPDATED 2007-05-24 12:37.
Read this article at: =20

New meds needed for neuropathic pain, researcher says
One researcher says there are not enough meds available to treat the =20
increasingly common disorder known as neuropathic pain. Wyeth's John =20
A. Butera notes that current medications provide only a 30 percent to =20
50 percent reduction in pain in about 50 percent of neuropathic pain =20
patients. New meds must be found, Butera says, so that more people who =20
suffer from this chronic condition can be helped.
  (Medical News Today) UPDATED 2007-05-28 17:12.
Read this article at: =20
MedTrackAlert is not affiliated with any pharmaceutical company. We =20
are dedicated to providing consumers with objective information about =20
prescription-medication discoveries and side effects. You can trust =20
our newsletters to keep you informed.

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Date:    Wed, 30 May 2007 14:32:59 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Responder criteria for operant and cognitive-behavioral treatment of fibromyalgia syndrome

Responder criteria for operant and cognitive-behavioral treatment of
fibromyalgia syndrome.

Arthritis Rheum. 2007 May 25;57(5):830-836 [Epub ahead of print]

Thieme K, Turk DC, Flor H.

University of Heidelberg, Mannheim, Germany.

PMID: 17530683

OBJECTIVE: To predict the effects of cognitive-behavioral therapy (CBT) and
operant-behavioral therapy (OBT) in fibromyalgia syndrome (FMS).

METHODS: A total of 125 patients who fulfilled the American College of
Rheumatology FMS criteria were randomly assigned to CBT (n = 42), OBT (n =
43), or attention placebo (AP; n = 40). The pretreatment to 12-month
followup reliability change index was used to determine clinically
meaningful changes in pain intensity and physical impairment. Multinominal
logistic regression analyses were used to determine the predictors of
improvement in pain intensity and physical impairment for the entire
sample. Analyses of variance were computed to compare the characteristics
of responders and nonresponders in each of the 3 interventions.

RESULTS: At the 12-month followup, 53.5%, 45.2%, and 5% of patients in the
OBT, CBT, and AP groups, respectively, reported clinically meaningful
improvements in pain intensity. Similarly, 58.1%, 38.1%, and 7.5% of
patients treated with OBT, CBT, and AP, respectively, reported clinically
significant improvements in physical impairment. Prior to treatment, the
OBT physical impairment responders displayed significantly more pain
behaviors, physical impairment, physician visits, solicitous spouse
behaviors, and level of catastrophizing compared with nonresponders. The
CBT physical impairment responders, compared with nonresponders, reported
higher levels of affective distress, lower coping, less solicitous spouse
behavior, and lower pain behaviors.

CONCLUSION: The results of this study suggest that pretreatment patient
characteristics are important predictors of treatment response and may
serve as a basis for matching treatments to patient characteristics.
Prospective outcome studies are needed to confirm whether the tailoring of
treatment actually leads to better outcomes for patients with FMS.

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Date:    Wed, 30 May 2007 20:25:28 +0100
From:    Ellen Goudsmit <ellengoudsmit HOTMAIL.COM>
Subject: ACT, RES: CBT is not ineffective

I believe that it is important that we do not show bias in our
correspondence with government agencies.

It is difficult to justify comments along the lines of 'CBT and GET are
ineffective' (various posts). Several RCTs have shown that both are helpful
in alleviating fatigue and increasing physical functioning in patients
diagnosed with CFS.  Some studies have reported that a significant number
(70% plus) of patients felt better or much better as a result of these
interventions. This can not be ignored.  However, one can state that the
treatment effects, if measured using the appropriate statistics, tend to be
modest. They are not cures.  Given the disability associated with CFS,
anything which has been tried and tested, and has been shown to alleviate
the symptoms, even moderately, should be welcomed.

What we need is more choice. As noted before, there are
treatments/programmes which are as effective as CBT/GET, and more
appropriate for some patients, and these deserve more attention. That's what
we should be campaigning for. More awareness of those studies, and greater
access to those programmes.

Until we know more about aetiology, doctors have a limited number of
therapeutic options. This means that we need to encourage more research into
the underlying mechanisms, (read, we need to subgroup, to increase both
diagnostic precision and our chances of finding abnormalities), and we need
to promote the therapies which focus on helping those who do not require, or
did not respond to a psychiatric intervention like CBT.

Groups can help by promoting the evidence-based, alternative approaches for
those patients who need a more flexible approach and in particular,  those
with abnormal metabolic and immunological responses to minimal exertion.
If groups show no interest, why should the MRC?

Some patients derive great benefit from CBT. We have to accept that.

Conflict of interest: I assessed an alternative approach to CBT and GET.

Ellen M. Goudsmit  CPsychol CSci AFBPsS

For information on ME and CFS, see:

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Date:    Wed, 30 May 2007 20:00:18 -0700
From:    "Charles Shepherd <charles.c.shepherd btinternet.com> via Co-Cure Moderators"
Subject: Act, RES: The MEA Ramsay Research Fund (UK)



One of the many scandalous aspects of ME/CFS is the fact that research into
the underlying physical cause of this illness has never been given a high
priority by the Medical Research Council (MRC) - the government funded body
that plays a major role in stimulating and funding medical research activity
here in the UK.  Added to this is the fact that pharmaceutical companies don't
generally regard ME/CFS as a useful avenue to pursue. The result is that
almost all research carried out so far into the underlying physical cause has
had to be funded by charities or individuals.

The ME Association has always regarded the promotion and funding of medical
research to be one of our key priorities.  We do this through our Ramsay
Research Fund - named after the late Dr Melvin Ramsay, the consultant in
infectious diseases who brought ME to the attention of the medical profession
following the famous outbreak at London's Royal Free Hospital back in 1955.


The Ramsay Research Fund (RRF)  is there to fund any sort of research activity
that will help to provide:
  a.. a better understanding of the underlying physical cause of ME/CFS
  b.. a diagnostic marker or test
  c.. an effective form of treatment.

Large scale research studies, which may require up to three years funding, now
cost a considerable amount of money as they involve both staff costs and
equipment costs. So this type of funding has to be considered very carefully
as it may mean using up a substantial proportion of the money that we can
raise during the same period of time.

We also have a facility for making small research grants of up to about 2000.
This is money that could be used for a variety of purposes connected to a
research study - for example, the purchase of a specific item of equipment.


Most of the money comes from MEA members in the form of individual or group
donations, or money left in a Will.  We also receive a few anonymous


The MEA is very conscious of the fact that people who give money to research
want to see it spent on research - not on administration.  So in legal terms
the RRF is what is called a restricted fund.  This means that all of the money
donated is used for research activity - it cannot be used for any other
purpose. Unlike many research charities, we do not employ any staff - full
time or even part time - at Head Office to deal with the administration of our
research fund. Staff time and administrative costs at Head Office associated
with running the RRF are all met out of our general funds.  So this is a very
cost effective method of donating money to ME/CFS research.


Over the past twenty years the MEA has funded a considerable number of
important research studies.  Some of the recently funded studies include:

Professor Mina Behan, Dr Fiona Curtis and colleagues at the Department of
Neurology, University of Glasgow.
Study that examined the role of blood brain barrier permeability in ME/CFS.
The blood brain barrier is a cellular barrier that helps to prevent viruses
and toxins that may be in the bloodstream from passing into the brain and
central nervous system.
Professor Mina Behan became seriously ill towards the end of this study and
later died. Preliminary results have been presented at scientific conferences
in London (Physiological Society) and Germany (Third Symposium on 'Signal
Transduction in the blood-brain barrier) and although not published the
results are available to the scientific community.

Professor Ronald Chalmers and colleagues at Saint George's Hospital Medical
School, London.
Study that investigated the role of diagnostic urinary markers, urinary and
plasma organic acids and amino acids, and plasma and urinary carnitine in
chronic fatigue syndrome.
Chalmers RA et al.  CFSUM1 and CFSUM2 in urine from patients with chronic
fatigue syndrome are methodological artefacts.  Clinica Chimica Acta, 2006,
364, 148 - 158.
Jones MG et al.  Urinary and plasma organic acids and amino acids in chronic
fatigue syndrome.  Clinica Chimica Acta, 2005, 361, 150 - 158.
Jones MG et al.  Plasma and urinary carnitine and acylcarnitines in chronic
fatigue syndrome.  Clinica Chimica Acta, 2005, 173 - 177.

Dr Evalina Georgiades and colleagues at the University of Glasgow.
Study that examined the function of various brain chemical transmitters -
serotonin, dopamine - during rest, exercise and recovery, and their possible
role in the production of central fatigue.
Publication: Chronic fatigue syndrome: new evidence for a central fatigue
disorder.  Clinical Science, 2003, 105, 213 - 218.

Professor John Gow and colleagues at the Institute of Neurological Sciences,
University of Glasgow.
Study that investigated the role of antiviral pathways and markers (ie 2-5A
Synthase/Rnase-L) in the assessment of people with ME/CFS.
Publication: Gow JW et al.  Antiviral pathway activation in patients with
chronic fatigue syndrome and acute infection.  Clinical Infectious Diseases,
2001, 23, 2080 - 2081.

Dr Derek Pheby and colleagues a the University of the West of England.
Study that looked at factors that may be involved in the development of severe
Publication:  Dr Pheby presented the key results from this study to a meeting
of the Melvin Ramsay Society in London in April 2007.  The results are now
being prepared for publication in a scientific journal.

Dr Vance Spence and colleagues at the University of Dundee.
Study that investigated the role of peripheral blood vessel dilation in
Publication: Prolonged acetylcholine-induced vasodilation in the peripheral
microcirculation of patients with chronic fatigue syndrome.  Clinical
Physiology and Functional Imaging, 2003, 23, 282 - 285.

Professor Graham Whitehouse and colleagues at the University of Liverpool.
Study using magnetic resonance neuroimaging to investigate the hippocampal
region of the brain.  This study found a significantly reduced concentration
of N-acetylaspartate (NAA) in the right hippocampus.  NAA is an important
marker of neuronal function.
Publication:  Brooks JC et al.  Proton magnetic resonance spectroscopy and
morphometry of the hippocampus in chronic fatigue syndrome.  British Journal
of Radiology, 2000, 73, 1206 - 1208.

Rhona Wilson and colleagues at Saint Bartholomew's Hospital, London.
Study by dieticians into the role of dietary modification - ie a low sugar and
low yeast/ anti-candida diet  - in ME/CFS.
Publication:  Hobday RA et al.  Chronic fatigue syndrome - impact of a low
sugar, low yeast diet on fatigue and quality of life - a randomised
intervention trial.  Submitted for publication.


The RRF is currently funding a very important research study into gene
expression.  This is being carried out by Professor John Gow and Dr Gillian
Gibson at Glasgow Caledonian University.  The aim of this study is to identify
specific genes in people with ME/CFS that have become under expressed or over
expressed - an indication of whether they are activating or suppressing
metabolic pathways and cellular activities under their control.  Preliminary
results suggest that a number of significant abnormalities in gene expression
are occurring in ME/CFS - findings that could eventually lead to specific
diagnostic markers and treatments aimed at the underlying disease process.


Anyone following reports in ME Essential will know that we are keen to set up
a permanent facility here in a UK hospital that will be able to store tissue
(which could be obtained during a routine operation) and post-mortem material
from people with ME/CFS.  We are currently discussing these proposals - which
will involve a hospital building, staff, and the establishment of a database
of willing volunteers - with a group of researchers who are also keen to see
such a facility.  A specific fundraising initiative, involving a walk from the
source of the River Amazon to where it enters the sea, is currently underway.
More information on the MEA website or or page XX of this issue.

We are also keen to fund studies that will help to fill existing gaps in our
knowledge about existing research findings - for example,  the role of immune
system chemicals known as cytokines in the production of fatigue.


We operate a flexible system that encourages researchers to first contact our
medical adviser to informally discuss a proposal.  We also publish an open
invitation in The Lancet to researchers to submit applications on specific
topics.  This is done periodically when we have sufficient funds available to
finance one or more major studies.  We are planning to review our major grant
application form - when this is completed it will be available to download
from the MEA website.  We are currently very willing to consider new
applications for small research grants.


The decision making process is based on guidelines produced by the Association
of Medical Research Charities.  This normally involves a process of both
internal and external peer review.  The internal peer review involves
assessment of the application by trustees and MEA medical advisers.  External
peer review involves the application being sent off to one or more independent
experts in the area of research being proposed.


If you want to help with MEA funded research, cheques should be made out to:
The MEA Ramsay Research Fund' and sent to the ME Association in Buckingham

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Date:    Thu, 31 May 2007 10:15:11 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: A longitudinal study of the relationship between  psychological distress and recurrence of upper respiratory tract  infections in chronic fatigue syndrome

A longitudinal study of the relationship between psychological distress and
recurrence of upper respiratory tract infections in chronic fatigue syndrome.

Journal: Br J Health Psychol. 2006 Dec 18; [Epub ahead of print]

Authors: Faulkner S, Smith A.

NLM Citation: PMID: 17535488

Objectives: Previous research has found that chronic fatigue syndrome (CFS)
patients report increased susceptibility to upper respiratory tract
illnesses (URTIs) when compared with healthy volunteers. This study aimed
to replicate and extend this research by investigating the role of
psychological distress (stress and negative mood) in the recurrence of
URTIs in CFS patients as well as its role in the recurrence of CFS symptoms.

Design: A 15-week diary study.

Methods: Measures of psychological stress, negative mood, recurrence of
URTIs and symptoms were recorded each week for a 15-week period. CFS
patients (N=21), who had been assessed and diagnosed according to the
Oxford criteria, were recruited from the Cardiff Chronic Fatigue Clinic and
compared with a matched group of healthy controls (N=18). Frequency of
occurrence of infectious illness and the relationship between psychological
stress/negative mood and occurrence of illness were assessed.

Results: CFS patients reported more URTIs than the controls. Stress scores
(and negative mood) were significantly higher in the week prior to the
occurrence of URTIs than in weeks when no subsequent illness occurred. High
levels of psychological stress also preceded the severity of reported
symptoms of fatigue in the CFS group.

Conclusions: CFS patients reported more frequent URTIs than healthy
controls and these recurrences were preceded by high levels of
psychological stress. High levels of stress were also associated with
greater subsequent fatigue. Possible explanations of these results are

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Date:    Fri, 1 Jun 2007 11:43:54 -0400
From:    Co-Cure Moderator <ray CO-CURE.ORG>
Subject: RES: The Association of Active Trigger Points with Lumbar Disc Lesions

The Association of Active Trigger Points with Lumbar Disc Lesions

Journal of Musculoskeletal Pain, Vol.15(2), pp.11-18 (2007)

Anand S. Samuel PT, Aaron A. Peter PT, K. Ramanathan PT

Objective: To seek indication for an association between trigger points
[TrPs] and lumbar disc lesions as evidenced by the myotomal level of the
disc lesion.

Methods: Sixty subjects, 44 men and 16 women, ranging from 22 to 61
years-old who had lumbar disc prolapse [location confirmed with magnetic
resonance imaging] were recruited to the cross-sectional study from
consecutive sampling. All patients were referred from the Department of
Orthopaedic and Accident Surgery Unit I. Subjects with disc prolapse who
were scheduled for surgery in the following week participated in this
study. They were given a complete physical therapy examination including an
assessment of soft tissue pain and dysfunction. The clinical diagnosis of
TrPs and myofascial pain syndrome were made according to the criteria by
Travell and Simons.

Results: The majority of the patients with LL Vdisc prolapse had active
TrPs in the tibialis anterior. Subjects with LL Vand LS lesions had active
TrPs in the gluteus medius and gastrocnemius. Subjects with LL Vdisc
prolapse had active TrPs in the extensor hallucis longus and tibialis

Conclusions: This study affirms that there is a possibility of a myofascial
pain syndrome component when there is lumbar disc disease, and it also
corresponds to the same myotome level of the lesion.

Keywords: Myofascial pain syndrome, lumbar disc disease, low back pain,
sciatica, trigger points

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Date:    Sat, 2 Jun 2007 12:16:57 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Functioning in individuals with chronic fatigue syndrome: increased impairment with co-occurring multiple chemical sensitivity  and fibromyalgia

Functioning in individuals with chronic fatigue syndrome: increased
impairment with co-occurring multiple chemical sensitivity and fibromyalgia.

Journal: Dyn Med. 2007 May 31;6(1):6 [Epub ahead of print]

Authors: Brown MM, Jason LA.

Affiliation: Department of Psychology, DePaul University, Center for
Community Research, Chicago, IL, USA

NLM Citation: PMID: 17540028

BACKGROUND: Chronic fatigue syndrome (CFS), multiple chemical sensitivity
(MCS), and fibromyalgia (FM) commonly co-occur. Some propose that CFS, MCS,
and FM are manifestations of the same illness based on high rates of
co-occurrence and overlapping diagnostic criteria. This study seeks to
differentiate these diagnoses by comparing individuals with one or more
illness on functioning, psychiatric comorbidity, coping style, and in vivo
physical measures.

METHODS: Participants included 114 men and women who met criteria for CFS.
FM was diagnosed during a physical examination, and MCS was assessed using
a questionnaire. Participants were divided into four groups: CFS alone,
CFS-MCS, CFS-FM, and CFS-MCS-FM. Self-report measures, a psychiatric
interview, and in vivo physical measures were given.

RESULTS: 43.9% met criteria for CFS alone, 23.7% met criteria for CFS-MCS,
15.8% met criteria for CFS-FM, and 16.7% met criteria for CFS-MCS-FM. The
CFS-MCS-FM group was more disabled than the CFS alone group on measures of
physical functioning, general health, and bodily pain. In vivo measures did
not differ, but the CFS-MCS-FM group rated exertion higher than the CFS
alone group.

CONCLUSIONS: Individuals with CFS alone were the highest functioning group
across several domains, such as disability, depression, and severity of
symptoms. Participants with three diagnoses experienced the greatest amount
of disability. While substantial co-occurrence of these illnesses was
found, this study provides evidence that having more than one illness
exacerbates one's disability beyond CFS alone.

[Note: This is an Open Access article.  The full text is available in PDF at
http://www.dynamic-med.com/content/pdf/1476-5918-6-6.pdf ]

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Date:    Mon, 4 Jun 2007 00:31:15 -0400
From:    Fred Springfield <fredspringfield@VERIZON.NET>
Subject: RES: Editorial Commentary: What Causes Prolonged Fatigue after Infectious Mononucleosis--and Does It Tell Us Anything about Chronic  Fatigue Syndrome?

What Causes Prolonged Fatigue after Infectious Mononucleosis--and
Does It Tell Us Anything about Chronic Fatigue Syndrome?

Journal: J Infect Dis. 2007 Jul 1;196(1):4-5. Epub 2007 May 24.

Author: White PD.

Affiliations: Wolfson Institute of Preventive Medicine, Barts and
the London, Queen Mary's School of Medicine and Dentistry, University
of London, London, EC1A 7BE, United Kingdom. <p.d.white qmul.ac.uk>.

NLM Citation: PMID: 17538875

Received 20 March 2007;
accepted 21 March 2007;
electronically published 24 May 2007.

Potential conflicts of interest: none reported.

Reprints or correspondence: Dr. Peter D. White, Queen Mary's
School of Medicine and Dentistry, St. Bartholomew's Hospital, London
EC1A 7BE, United Kingdom  <p.d.white qmul.ac.uk>.

Many doctors do not believe that chronic fatigue syndrome (CFS),
sometimes called "myalgic encephalomyelitis," exists [1]. Some believe
that it is no more than an atypical form of depressive illness. Some
believe CFS to be a discrete condition, although recent evidence
suggests that it is heterogeneous [2]. This makes discovering its
pathophysiology extremely complex.

One successful way of sorting fact from fiction has been through
the use of cohort studies of populations at high risk for developing
prolonged fatigue. Perhaps one of the most fruitful areas of research
has involved postinfectious cohorts, particularly following
Epstein-Barr virus (EBV) infections presenting as infectious
mononucleosis (IM) in adults. Five such cohort studies have been
published [3-7]. These studies have demonstrated that a discrete
postinfectious fatigue syndrome exists, one that is not a mood
disorder [8, 9]. In fact, there seems to be not 1 but 2 postinfectious
fatigue syndromes, one characterized by excessive sleep and the other
characterized by insomnia associated with muscle and joint pain [8,
9]. Both syndromes also include poor concentration, irritability, and
psychomotor retardation [8, 9].

The risk of either prolonged fatigue or CFS is 5-6 times that of
other common upper respiratory tract infections, such as Streptococcus
pyogenes infection [3, 7], and there is a 10%-12% risk of CFS 6 months
after infectious onset [3-5]. The risk of CFS is not specific to EBV
alone; CFS has been shown to follow parvovirus infection [10], Q
fever, and Ross River virus infection [5], among others.

It therefore seems that EBV infection, when it presents as IM, is
a significant risk factor for CFS in adults, with the level of risk
consistent with it playing some etiological role. But some 90% of
patients recover from IM without developing CFS, suggesting that EBV
may be a necessary but insufficient cause of CFS in these cases.

What cofactors make CFS happen after IM? A systematic review of
all studies of prolonged fatigue found that physical inactivity was
the most replicated predictor [11]. Of particular interest, the first
reported cohort study showed that neither premorbid mood disorder nor
recent stressful life events predicted post-IM CFS, once comorbid mood
disorder had been controlled for [12]. By contrast, these same factors
did predict depressive illness after IM, reinforcing the contrast with
mood disorders. Predictiors of prolonged fatigue 6 months after onset
were early positivity for heterophil antibody and evidence of physical
deconditioning 4 months earlier. There were no significant
associations with any other immune response to EBV [11, 12]. No other
cohort has shown convincing associations with the immune response to
EBV [5, 13].

Lloyd and colleagues in Australia have collaborated with Reeves
and colleagues at the Centers for Disease Control and Prevention, and
this has led to a cohort study of not 1 but 3 high-risk infections:
IM, Q fever, and Ross River virus infection. The population was based
around Dubbo, a rural area in Australia. This work has already shown
that the risk of CFS is about the same in all 3 cohorts, with some 1
in 10 going on to develop CFS [5]. The group has also shown no
association between CFS and EBV load in mouth washings [13]. The only
significant predictor of CFS was the initial severity of acute IM at
onset [5]. The to-date limited evidence base for significant
predictors and associations is unlikely to be related to the apparent
heterogeneity of CFS, because at most there are only 2 apparent
phenotypic illnesses of prolonged fatigue after IM [8, 9]. It is more
likely related to looking for the wrong risk factor over the wrong
time scale. These problems may be overcome by the method used by
Cameron et al. in their study of the same cohort presented in this
issue of the Journal [14].

Cameron and colleagues used a nested case-control study from the
Dubbo cohort of EBV-infected people to examine gene expression over
time, seeking associations and predictions in those patients with
prolonged fatigue. The study was innovative and may provide a means of
understanding the pathophysiology of complex syndromes such as
postinfectious fatigue syndrome.

The authors found 35 genes that were abnormally expressed over
time in those with prolonged disabling fatigue. More genes were found
to be associated with fatigue and separately with musculoskeletal
pain. The genes identified had no obviously coherent pattern of
functions, but some genes were related to signal transduction
pathways, metal ion binding, and ion channel activity. No consistent
target tissue was identified. Although cluster analysis was reasonably
accurate in differentiating case from control subjects soon after
infectious onset, no differentiation was possible 6 months after onset.

The strengths of the study include its longitudinal cohort design
and repeated measures. Although none of the identified genes had
previously been found in gene expression studies of CFS, this may be
because of the heterogeneity of CFS [15]. The authors acknowledge this
but point out that there was a pattern in the genes found in that they
are important in immune response and neuronal function.

The weaknesses of the study include the small number of subjects
(with type I errors likely), the lack of matching by sex, and the lack
of validation by real-time polymerase chain reaction analysis of
messenger RNA. We cannot be sure that gene expression in lymphocytes
reflects gene expression in other tissues, such as the brain. Because
gene expression changes rapidly and in response to behavioral changes,
the lack of replication of the results of previous studies is no surprise.

What can we conclude from this study? Gene expression may perhaps
help us identify pathways involved in the pathophysiology of complex
syndromes such as CFS. Examining more homogeneous populations, such as
individuals from high-risk infectious cohorts, is more likely to
identify underlying pathology, but large cohorts are needed to make
progress. This will require large, multicenter cohort studies with
longitudinal measures of gene expression. The alternative is either to
seek correlations with less changeable genetic variables, such as
single-nucleotide polymorphisms, or to test hypotheses by directly
measuring biological processes that are related to previously observed
abnormalities, such as sleep architecture, interoception (visceral
perception), inactivity, and the functional immune system.

1. Thomas MA, Smith AP. Primary healthcare provision and Chronic
Fatigue Syndrome: a survey of patients' and General Practitioners'
beliefs. BMC Fam Pract 2005; 6:49.
2. Vollmer-Conna U, Aslakson E, White PD. An empirical delineation of
the heterogeneity of chronic unexplained fatigue. Pharmacogenomics
2006; 7:355-64.
3. White PD, Thomas JM, Amess J, et al. Incidence, risk and prognosis
of acute and chronic fatigue syndromes and psychiatric disorders after
glandular fever. Br J Psychiatry 1998; 173:475-81.
4. Buchwald D, Rea T, Katon W, Russo J, Ashley R. Acute infectious
mononucleosis: characteristics of patients who report failure to
recover. Am J Med 2000; 109:531-7.
5. Hickie I, Davenport TA, Wakefield D, et al. Viral and non-viral
pathogens precipitate post-infective and chronic fatigue syndromes: a
prospective cohort study. BMJ 2006; 333:575-8.
6. Candy B, Chalder T, Cleare AJ, et al. Predictors of fatigue
following the onset of infectious mononucleosis. Psychol Med 2003;
7. Petersen I, Thomas JM, Hamilton WT, White PD. Risk and predictors
of fatigue after infectious mononucleosis in a large primary care
cohort. QJM 2006; 99:49-55.
8. White PD, Grover SA, Kangro HO, Thomas JM, Amess J, Clare AW. The
validity and reliability of the fatigue syndrome that follows
glandular fever. Psychol Med 1995; 25:917-24.
9. White PD, Thomas JM, Sullivan PF, Buchwald D. The nosology of
sub-acute and chronic fatigue syndromes that follow infectious
mononucleosis. Psychol Med 2004; 34:499-507.
10. Kerr JR, Bracewell J, Laing I, et al. Chronic fatigue syndrome
and arthralgia following parvovirus B19 infection. J Rheumatol 2002;
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14. Cameron B, Galbraith S, Zhang Y, et al. Gene expression
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 2007 by the Infectious Diseases Society of America. All rights reserved.

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Date:    Mon, 4 Jun 2007 00:35:31 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis

Gene expression correlates of postinfective fatigue syndrome after
infectious mononucleosis.

Journal: J Infect Dis. 2007 Jul 1;196(1):56-66. Epub 2007 May 24.

Authors: Cameron B, Galbraith S, Zhang Y, Davenport T, Vollmer-Conna U,
Wakefield D, Hickie I, Dunsmuir W, Whistler T, Vernon S, Reeves WC, Lloyd
AR; Dubbo Infection Outcomes Study.

Affiliation: School of Medical Sciences, University of New South Wales,
Sydney, 2052, Australia. <A.Lloyd unsw.edu.au>.

NLM Citation: PMID: 17538884

Background. Infectious mononucleosis (IM) commonly triggers a protracted
postinfective fatigue syndrome (PIFS) of unknown pathogenesis.

Methods. Seven subjects with PIFS with 6 or more months of disabling
symptoms and 8 matched control subjects who had recovered promptly from
documented IM were studied. The expression of 30,000 genes was examined in
the peripheral blood by microarray analysis in 65 longitudinally collected
samples. Gene expression patterns associated with PIFS were sought by
correlation with symptom factor scores.

Results. Differential expression of 733 genes was identified when samples
collected early during the illness and at the late (recovered) time point
were compared. Of these genes, 234 were found to be significantly
correlated with the reported severity of the fatigue symptom factor, and
180 were found to be correlated with the musculoskeletal pain symptom
factor. Validation by analysis of the longitudinal expression pattern
revealed 35 genes for which changes in expression were consistent with the
illness course. These genes included several that are involved in signal
transduction pathways, metal ion binding, and ion channel activity.

Conclusions. Gene expression correlates of the cardinal symptoms of PIFS
after IM have been identified. Further studies of these gene products may
help to elucidate the pathogenesis of PIFS.

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Date:    Mon, 4 Jun 2007 14:36:23 -0400
From:    "David Axford <axford worldonline.co.uk> via Co-Cure Moderator"
Subject: RES: Latest version of the academic review on pacing

The latest version of the academic review on pacing is now available at:

You may also find the article using the SEARCH tool which is on the home page.

It is possible that your browser won't log on first time due to the large
number of people who are accessing the web-site. Please be patient and try
again at different times when it's less busy.

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