IACFS Conference Summary from Rosamund Vallings

Discussion in 'Fibromyalgia Main Forum' started by mezombie, Feb 15, 2007.

  1. mezombie

    mezombie Member

    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.