|AACFS Summary: Some Gems Shine Through
By Jill McLaughlin
Conference was held in Seattle January 27-29 in conjunction with three sessions sponsored
by DHHS. The conference was
organized as in previous years. Saturday (1/26), was the Research Conference, Sunday
(1/27), was the Clinical Conference and Monday (1/30) was the Patient Conference. Friday
afternoon was the CDC's planning session for optimizing the CFS case definition, Friday
evening the NIH held an overview of the process of grant writing (for investigators only),
and Sunday evening was the name change workgroup open forum.
The Research conference was by far the best. It was broken down
into topics of Epidemiology and Natural History, Physiology,
Microbiology, Immunology, Genetic Studies, the Brain and CFS, and an International
Perspective - Belgium and the Netherlands.
Dr. Lea Steele of the CDC conducted a study of 1548
veterans of the Persian Gulf War and 7% of the Veterans were found to have CFS. Earlier
research has suggested that some Gulf War Veterans actually had CFS and not a new illness.
Gulf War Vets also had other symptoms such as diarrhea, headaches and night sweats that
are not as common in CFS symptomology. In an interview
with Reuter's Health, Steele said, "the chronic fatigue syndrome doctors are the ones
with probably the most expertise in dealing with the symptoms" and that looking into
the similarities and differences between these two illnesses may lead to new treatments
for both conditions.
Dr. Rosane Nisenbaum reported on a study of patients from CDC's
Wichita surveillance to describe the course of CFS during the year following diagnosis.
Fluctuation in illness state reflects the natural history of the disease and suggests the
need for longitudinal studies to re-evaluate CFS over time. They found no association
between illness improvement and illness duration. Approximately 46% improved and 32% did
not. The remainder received other diagnoses which explained their fatigue. [Once again
fatigue and energy levels were being used as an indicator.]
Dr. Pascale DeBecker of Belgium presented a factor analysis study
of symptoms in 1573 patients with CFS and was able to divide the symptom patterns into
four factor groupings - general symptoms, cognitive, musculoskeletal and mood
change/psychiatric. The mood change/psychiatric factor grouping was unrelated to the CFS
definitions. Different factors were associated with changes in acute onset and illness
The focus was on autonomic dysfunction. Dr. Arnold Peckerman of
the CFS Cooperative Research Center presented on baroreflex function in CFS. Several
studies have indicated that the disease process underlying CFS may be involving
baroreceptive reflex control of blood pressure. This study measured barofeflex sensitivity
(BRS) under various conditions involving challenges to blood pressure homeostasis. The
degree of reduction of BRS in CFS during standing correlated with reported severity of
symptoms. A greater suppression of baroreceptor reflex in CFS during orthostatic but
not during mental stress may reflect an impaired ability to maintain cardiac
output. Further research is needed to determine the cardiovascular mechanisms which may be
The objective of a study by Dr. James Baranuik of Georgetown
University was to propose that autonomic dysfunction contributes to CFS pathophysiology.
Isometric handgrip contraction results in a strong sympathetic discharge leading to
an increase in systolis blood pressure and vasoconstriction of tissue vascular beds such
as the nasal sinusoids. Incremental changes between isometric and sham handgrip
contractions were measured and CFS patients had inadequate sympathetic responses. The
preliminary data suggest sympathetic nervous system dysfunction is integral to CFS
pathology. [When asked to comment, he attributes chronic stuffy nose, sinus problems (with
resulting sore throat) to the sympathetic nervous system dysfunction and is very adamantly
opposed to the endoscopic sinus surgery as a treatment.]
Dr. Howard Urnovitz presented for Dr. Cheney who was unable to
attend due to illness. He reported that the RNAs found in the plasma of patients with CFS
may represent a novel mechanism for chronic illness expression . All chronic illnesses
studied thus far including GWS, CFS, AIDS and multiple myeloma show prominent circulating
plasma RNAs not observed in normal controls. The most prominent sequences appear to be
disease specific and vary by less than 1% between individuals with the same or similar
illness. These findings could have both treatment and diagnostic implications.
Dr.Christopher Snell did a comparative study of maximal oxygen
consumption and RNAse-L in patients with CFS. Elevated levels of RNAse-L are associated
with reduced VO2-max and exercise duration in patients with CFS. This may demonstrate that
their extremely low tolerance for physical activity may be linked to abnormal oxidative
metabolism perhaps resulting from defective interferon responses. These results have
implications for testing of antiviral therapies for CFS, particularly those directed at
the 2-5A synthetase pathway. (In spite of implications for viral testing, do not see why
this was in the microbiology section)
Dr. Dharam Ablashi's presentation was very comprehensive of HHV-6
testing and clinical manifestations before, during and after antiherpesvirus therapy.
Active infection was determined by culture, IgM and IgG antibody, and PCR on plasma, CFS,
and PBMC's. The HHV-6 isolates obtained were characterized as either variant A or B.
Conclusions: 1. The data presented showed that the majority of CFS patients have HHV-6
infection. 2. It was surprising to find CFS patients exhibiting HHV-6 DNA in the CFS or
plasma as well as in cord blood cells infected with CFS from these patients. These data
suggest the presence of cell free infectious virus in the CSF. It is possible that HHV-6
is invading the CNS and may participate in the neurological manifestations associated with
the disease. 3. Seventy percent of the HHV-6 isolates from CFS patients were variant A,
which is more neurotropic. 4. Potent antiviral agents, such as vancyclovir, foscarnet and
Valciclovir, are useful in suppressing HHV-6, thereby resulting in clinical improvement.
However, longitudinal studies of more patients with CFS using newer antiviral agents which
are less toxic are required to determine what specific role HHV-6 infection plays in the
pathogenesis of the disease. [Dr. Konnie Knox attended the research conference but did not
present as her work is still ongoing and felt she had nothing new to report.]
The immunology portion was very small disproportionate to the
fairly prominent role that immunological abnormalities play in CFS. However, Dr. Kevin
Maher of the University of Miami presented some exciting and significant research on
perforin studies, the first of its kind done in CFS.
Perforin is a protein contained in NK cells that accounts for the
cells cytolytic potential. The most consistent immunological abnormality found in CFS has
been the decrease in NK cell activity (as opposed to a decrease in absolute numbers). In
this study perforin concentrations were measured in an attempt to define the mechanism
underlying the reported cytotoxic defect in CFS. NK intracellular perforin concentration
was significantly correlated with NK cell activity. In addition data has also suggested
that the cytotoxic defect may not be NK cell specific but may encompass the cytotoxic T
cell subset as well.
It appears that the down regulation of the immune response is
perforin dependent; thus perforin is important in homeostasis as well as immune
surveillance. Studies of a rare autosomal recessive genetic perforin deficiency resulted
in immune activation, decreased delayed
hypersensitivity, decreased viral clearance and an increase in pro-inflammatory cytokines.
Those with this defect are healthy until they
were virally infected, i.e.., the viral infection precipitated the illness.
CFS is associated with all the abnormalities of perforin
deficiencies. Perforin deficiency could be proposed as a viable mechanism for the
variable CFS symptomology. The only other immunology study was a multicenter study
of autoimmunity in CFS presented by Dr. E.M. Tan, which was done in conjunction with Drs.
Buchwald, Wesseley and Komaroff. The objective was to determine whether autoantibodies to
a cellular protein expressed primarily by neuronal cells, and whether
microtubule-associated protein-2 (MAP-2) could account for the neurocognitive problems.
Results presented were inconclusive with many disparities in reactivity with MAP-2 in CFS
from different centers and controls.
Genetic studies now involve genetic epidemiology to describe an
array of novel study designs to assess the role of genetic factors in the etiology of CFS.
I cannot do justice to a full review off genetic studies but personally I find the genetic
component to be weak. Most genetic studies seem simplistic and the conclusions poorly
derived. Most jump from the presence of family clustering to the acceptance that it is
hereditary. Too many critical steps have been skipped along the way. Case control studies
have to be carefully controlled and adjusted for all suspected risk factors that might
cluster within families to discern if these risk factors are the explanation for the
familial aggregation (i.e.., clusters may be due to infectious agents or common
environmental exposures). It is also necessary to determine whether the pattern of disease
transmission is what would be expected based on the degree of genetic relatedness. The
epidemiology and natural history do not support the likelihood of genetics as the key.
There have been some cell surface markers associated with CFS, but there are some for AIDS
and Lyme disease also. Of course a child has a greater chance of having CFS if the mother
has it, but there is vertical transmission; if a mother has HIV her child may as well.
Enough digression, but some of the genetic studies contradicted
the genetic hypothesis. A poster was presented on a study of cellular immunity in
monozygotic twins discordant for CFS. The nature and extent of immune system abnormalities
was assessed and showed that the perturbations in the immune system in the twin with CFS
had no genetic basis.
The Brain and CFS
Dr. Roderick Mahurin looked at brain correlates of cognitive
effort in CFS. Actual brain imaging shows, in fact, that more areas of the CFS brain are
involved in solving cognitive tasks than non-CFS patients. This proves that in order to
perform a mental task CFS patients do indeed have to "work harder." [This work
was also presented at the State of the Science meeting last fall.]
Dr. R.H.Gracely used brain imaging to show that FM patients' brains respond differently
to stimulus than CFS patients' brains. When FM patients were given the same stimulus that
was given to healthy patients they felt more pain - the previously discovered heightened
sensitivity that has been expressed by patients is seen in this imaging.
Dr. Greta Moorkens from Belgium evaluated the responses to growth
hormone releasing hormone (GHRH) and Hexaralinin CFS and FM in order to characterize the
aberrant behavior of growth hormone secretion. Despite the overlap of signs and symptoms
of both disorders, comparison of HPA revealed specific neuroendocrine characteristics in
patients with CFS and FM, suggesting different etiological mechanisms.
The International Perspective - Belgium and the Netherlands
This session began with some banter about the known competition
and their respective soccer teams, yet this session encompassed the best and the worst.
The Netherlands could be considered the best of psychobabble, of triggers and
precipitating factors and perpetuating factors. The pathogenesis is vague with "no
evidence of pathogens...."The low sense of control of symptoms contributes to
increased levels of fatigue," which can be ameliorated by CBT. I walked out
but, luckily came back to catch most of Dr. Kenny DeMeirleir's presentation.
Dr. DeMeirleir of Belgium was quite the contrast and favors a completely
organic basis. Dr. DeMeirleir gave a comprehensive overview of diagnosis, treatment,
pathogenesis, and pathophysiology. He is the head of a specialist hospital clinic
where all patients were referred and tend to be very severe. These patients all had
thorough and specialized clinical workups. 60% of patients were found to have an infection
at onset. By factor analysis the symptoms fell into 4 main groups: general, cognitive,
musculoskeletal and mood change/psychiatric. He treats mycoplasma and chlamydia infections
fairly aggressively and found that multiple infections correlate with increased low
molecular weight RNase-L. Much was very technical but the pathophysiology was based on the
LMW RNase leading to the channelopathy which causes low body potassium, metabolic
alkalosis, hyperventilation, which can account for the neuromuscular manifestationss
Much of the Belgian research focused on the abnormal enzyme pathways and
88% of patients tested positive to RNase-L, (as discovered by Dr. Robert
Suhadolnik). RNase-L is a likely marker, and correlates with severity. The 37Kda is
produced by calpain cleavage (Mycoplasma can lead to calpain cleavage), which affects the
calcium and potassium balance. When the RNase-L ratio is high the serum calcium is low,
which is consistent with a channelopathy. The channelopathy will lead to low body
potassium, metabolic alkalosis and
hyperventilation syndrome. Symptoms relating to abnormal hormone levels, sodium retention
and abnormal exercise response follow. The CD4/CD8 ratio correlates with VO2 max. A very
complex model was proposed, the mechanism leading to a Th1/Th2 shift with viral
reactivation and intracellular opportunistic infections.
Therapeutic strategies were aimed at restoration of immune
competence with normalization of the Th1/Th2 ratio coupled with antibiotic therapy. These
are completely different approaches, which need to be used together. He stated
emphatically that "all monotherapies fail." Ampligen has been found to be of
great benefit though is still very expensive and is not FDA approved. Antibiotics such as
azithromycin have been found to lead to 50% clinical recovery after a long course. Shorter
courses often lead to relapse after completion. Specialized techniques such as PCR and
gene tracking for mycoplasma have led to better outcomes.
He also started to talk about p53 (*see footnote), a tumor
supressor gene that is inactivated in CFS, but was interupted when Dr. Buchwald declared
that time was up and ended the session. He did remark that "You do not use CBT on
someone who has cancer." [Studies have shown that p53 may be a regulator of
apoptosis. Loss of p53 disrupts the normal apoptotic pathways and thus
survival advantage to the cell. This is not good if the cells are undergoing mutations and
rather that being marked for apoptosis, they bypass
this mechanism and are allowed to survive. This forms the fundamental basis for cancer.]
During his presentation, Dr. Howard Urnovitz angrily challenged
him, particularly on mycoplasma testing. He remained calm and defended his position. Dr.
DeMeirleir has written a book that is due out at the end of the year.
I was very disappointed to miss most of Dr. Sidhur Gupta's
talk (no, I did not decide to sleep in!), but Sunday morning's agenda was very
confusing. It was listed as "Business Meeting and Presidential Address" from
7:30 to 8:30, which I took to mean was for AACFS members, so arrived at the very end.
Dr. Leonard Jason's presented three studies to explore the effects
of different diagnostic labels for CFS. All participants filled out a
questionnaire measuring their attributions about various aspects of the illness, including
its cause, nature, severity, contagion, prognosis, and
treatment. Attributions for chronic fatigue syndrome appear to change based upon the
diagnostic label for the syndrome and the type of treatment recommended. Given similar
case presentations with the name myalgic encephalopathy, doctors were more likely to
attribute a physiological cause to the illness and less likely to consider them a
candidate for organ donation. The name clearly makes a difference, and if it were changed
to something more descriptive, patients would receive better medical care.
Dr. Renee Taylor presented a study on the role of interpersonal
violence history and PTST and found no unique relationship linking abuse
to CFS. Other presentations in this section were: The relationship between unexplained
somatic symptoms and psychopathology in CFS, Physiological correlates of CFS-like symptom
development in healthy individuals deprived or routine aerobic exercise, and phases of the
Dr. Katherine Rowe of
Australia concluded that the seven year follow up of the gamma globulin participants in a
former study and she indicated that there was continued improvement in functioning with
75% able to work or attend school full time.
Dr. Kristin Rammohan presented a study investigating the benefit
of modafinil (Provigil), a wake-promoting agent used in the treatment
of narcolepsy in MS patients. Nearly two-thirds of MS patients experience fatigue on
a daily basis. The result was that Modafinil
significantly improves fatigue and daytime sleepiness and is well tolerated by MS
patients. A new study is underway regarding the effectiveness of Modafinil for CFS
patients. A double-blind placebo trial is planned by Dr. David Bell. [This is not a
readily available treatment per se but a potential treatment. It helped patients with one
symptom that both diseases have in common.]
Dr. Nancy Klimas discussed the results of an experimental therapy
to determine the safety and feasibility of immunomodulation using lymph node extraction,
cell culture, followed by autologous cell reinfusion. In many CFS patients, the TH2 immune
system is excessive, while the TH1 immune system response is not strong enough. Klimas'
group extracted lymph nodes from thirteen CFS patients with the goal of turning the TH2
cells into TH1. After these cells were cultured for 10-12 days, they were infused back
into the donors who were then monitored for 24 weeks. [Ed. Note: We spoke to many of the
patients in this study. It seemed the extraction was very painful and the recovery
slow. They had about a year of feeling better than before but then crashed to their
former levels of illness. None we spoke to wanted to repeat the study.]
No adverse effects were noted and patients reported significant
improvement in cognitive function, muscle and lymph pain, fewer sore throats and more
physical stamina. Klimas noted that these studies validate the severity of the biological
underpinnings of this illness and that they are amenable to therapy. Her group hopes to
begin expanded clinical trials within the next 12 months, but the downside of this
procedure is that it is invasive and extremely costly. (This should not have been included
in the treatment section, but under research. It is a Phase 1 clinical trial.
TNF is a pro-inflammatory cytokine that is thought to play a
mediator role in the pathogenesis of CFS. Etanercept is a recombinant human TNF receptor
that binds TNF and blocks its interaction with cell surface receptors. It has recently
been approved for the treatment of rheumatoid arthritis and is being evaluated in other
Dr. K. Lambrecht of the University of Minnesota Medical School did
a small open label trial of Etanercept for 8 weeks. The results lend support to the to the
concept that pro-inflammatory cytokines such as TNF are involved in the pathogenesis of
CFS and suggest that this inhibitor should be considered for a randomized placebo
controlled trial. [Again this is not a treatment and should have been under research. This
was a pilot study.]
The other two presentations under treatment were on CBT and
Occupational Therapy. These are not treatments. The only real treatment that is readily
available to clinicians was presented by Dr. Katherine Rowe on gamma globulin. Surely the
AACFS knows the difference.
Children and Adolescents
There were two studies of prognosis. Dr. David
S. Bell did a thirteen-year follow up of children and adolescents with CFS. He
found that 80% had a "satisfactory" outcome though the majority still had mild
to moderate symptoms and 20% were still ill. Katherine Rowe of Australia did a 1-9 year
follow up of 200 young people with CFS. When contacted, 30% felt they were well and 60%
were able to study or work full time. However it is not clear how improvement or recovery
should be determined. The results of self reported improvement are often inconsistent;
that is, simply asking people if they are better or worse may not give an accurate
picture. Some of Bell's patients who reported themselves "well" still had
Dr. Julian Stewart presented a vascular perturbations in CFS.
Previous studies have shown that CFS is related to orthostatic intolerance
characterized by upright tachycardia of unclear pathophysiolophysiology. Observing
that edema and acrocyonosis occurred frequently, several vascular parameters were
measured, which showed that resting venous pressure is higher, the threshold for edema is
lower, and filtration is increased. Such findings make CFS patients particularly
vulnerable for dependent pooling and edema. This may imply a redistribution of blood to
the lower extremities even while supine, accounting for tachycardia through vagal
Dr. Stewart also had a poster which showed that vasoconstriction
is defective in children with CFS and POTS. Resting venous pressure is higher related to
peripheral vasodilation while supine. During tilt defective vasoconstriction translates
into enhanced pooling of dependent limbs. This is a new concept - that the consequence of
ANS dysfunction is the pooling of blood in the legs. This phenomena could account for low
blood pressure and low blood volume.
Other presentations in this section were: The Relationship between
unexplained Somatic Symptoms and Psychopathology in CFS, Physiological Correlates of
CFS-like Symptom Development in Healthy Individuals deprived or routine Aerobic Exercise
(this study was funded by the NIH and based on the well known premise of "I feel just
awful when I don't exercise"), and Phases of the Illness (this has been presented
many times by someone who never handled her own illness well in the initial "phase").
There were 155 posters, many of which were much more
interesting and significant than some of the oral presentations: Effective Treatment of
CFS and FM - A randomized, Double-Blind, Placebo-Controlled Intent to Treat Study
Dr. Jacob Teitlebaum should have been included in the treatment
section. Hypothalamic dysfunction has been suggested in CFS and FM, which may result
in disordered sleep, subclinical hormonal deficiencies and immunologic changes. The
current study examines a protocol which treats these abnormalities simultaneously using a
randomized, double blind design with an intent to treat analysis.
Food Intolerance in CFS: This study, done at the University of
Newcastle, NSW, showed that food intolerance, as opposed to food allergy, may represent a
comorbidity in a subgroup of CFS patients with regard to core symptoms and could have
etiological implications for the development of gastrointestinal dysfunction.
Hypercoagulable State Associated with Active HHV-6 viremia in
patients with CFS: The purpose of this study by Dr. Joseph Brewer, MD, Kansas City,
MO and David Berg, Hemex Laboratories, Phoenix AZ, was to analyze the incidence of a
hypercoaguable state and to assess the hereditary hypercoaguable risk factors in a group
of patients with known CFS and HHV-6 viremia. Since HHV-6 is known to infect endothelial
cells, there may be a resultant endothelial cell dysfunction triggering the coagululation
system similar to the procoagulant effect that has been described with cytomegalovirus.
The hypercoagulable state associated with active HHV-6 infection may be a
significant contributing factor to the symptoms seen in CFS. Treatment of the active HHV-6
infection and management of the hypercoaguable state may be important. [Ed. Note:
Berg had submitted a much larger study on his work with 500 patients, a highly significant
number, but was turned down. One should remember that most who selected the studies
presented are highly biased themselves]
. Possible Triggers and Mode of Onset in CFS: This retrospective
study done in Belgium showed that infectious agents play an important role in the onset of
CFS. There were ten distinct groupings of factors involved in the onset and most involved
CFS: Quantitative Assessment of Cerebral Volumes: This
quantitative volumetric study done by the NJ CFS Research Center suggests that some CFS
patients show lateral ventricular enlargement, specifically in the body of the lateral
ventricle. Enlargement of the body
of the lateral ventricle is associated with white matter loss in the frontal as well as
parietal lobes. [Enlargement of the entire ventricular system or one of its sub-components
is generally regarded as an indirect measure of white matter loss, since much of the
ventricular system is surrounded by white matter structures. A previous study by Natelson
reported that compared to healthy sedentary controls some CFS patients showed evidence of
A Definition based Analysis of Symptoms in a Large Cohort of
Patients with CFS: The purpose of this study, done by Drs. Pascale DeBecker and Kenny
DeMeirleir of Belgium, was to determine the homogeneity of a large CFS population using
multivariate analysis to assess the symptom presentation and the differences between the
Holmes and Fukada definitions. CFS patients fulfilling the Holmes criteria have increased
prevalence and severity of symptoms that determine the difference between CFS and CF
patients. This study shows that
patients fulfilling the Fukada criteria were less severely affected, leading to increased
heterogeneity and that the addition of certain symptoms and removal of others would
strengthen the ability to select patients. (That is, the 1994 definition is too broad and
should be revised.)
Chronic Infections as a Source of CFS: This study by Dr. Cecile
Jadin of South Africa was to show the prevalence of pathogenic microorganisms in CFS.
(They have also confirmed the link between Rickettsial-like organisms and autoimmune
diseases, heart disease, MS and other neurological and psychological disorders.) After
testing and antibiotic treatment, patients showed significant improvement. Conclusion:
"Even if chemistry is an impressive way to explain the symptoms, microbiology is the
start of successful treatment."
Material by her is offered under our Materials section.
Analysis of Oxidative Changes Associated with the Different CFS
Factor Analysis Symptom Clusters: Another one from Belgium!!! This study was to determine
if the different factor analysis symptom groupings determined in a large epidemiological
study were associated with changes in blood cell parameters indicative of oxidative
stress, and concluded that different factor symptom groupings are associated with changes
in red cell oxidative marker parameters, suggesting that each measure represents a
distinct change in chemistry.
Social Isolation and Cognitive Deficits in Danish CFS Patients at Diagnosis and 5 Year
Follow Up: This study by Frank Albrecht and Dr. Mette Marie Anderson showed that CFS
patients exhibit long term functional impairment and that substantial improvement is
uncommon. The illness tends to fluctuate without really changing and that emotional
adjustment often improves independently of the course of the illness - i.e.., there is no
connection between these problems and CFS.
Measuring Exercise Capacity in Female
CFS Patients: This study showed that compared to healthy sedentary females CFS
patients show a significant decreased exercise capacity which could significantly
influence their physical capacities. Reaching the age-predicted target heart seemed to be
a limiting factor in CFS patients, which could be due to autonomic disturbances.
RNase-L Posters: Most of the work from Belgium centers around
RNase-L and cellular activation and the immune system and there were several posters. One
indicated that the 37kDa LMW RNase-L fragment is produced by proteolytic cleavage of the
native 80kDa monomeric protein. Calpain has been identified as one of the proteolytic
enzymes involved in the cleavage. The 37kDa fragment could retain both the 2-5a binding
and catalytic activities.
A poster by Dr. S. Roelens concluded that there is a correlation
between the presence of 37kDa binding RNase-L protein and a 26kDa actin fragment in
peripheral blood mononuclear cells (PBMC) in CFS. Some of the actin fragments seen in CFS
patients are likely to be generated by apoptotic proteases. Also the amount of native
actin in the serum correlates with the amount of RnaseL in the PBMC extracts of CFS
patients. (Measurement of actin may be a more readily available potential diagnostic test
as it is found in serum rather than the more difficult direct measure of RNase-L.)
Another poster showed that the activation of RNase-L in the PBMC
of CFS patients upregulates apoptotic activity in these cells, which is likely to be
further downregulated by the large accumulation of its proteolytic cleavage products. This
suggests that accumulation of LMW RNase-L fragments in the PBMC could exert a blockade in
the apoptotic cascade, impairing the elimination of already damaged cells. RnaseL and
G-actin fragments were found in CD14+cells, which suggests that the abnormal apoptotic
process may lead to the altered immunologic functioning in CFS.
Dr. Kenny DeMeirleir found that the presence of an increased
amount of LMW RnaseL correlates with higher levels of IFN gamma,
which has antiviral properties. Normal NK cell numbers and high LMW/HMW RnaseL ratio
correlate with higher IL-2 levels in CFS
patients compared to controls.
Dr. Patrick Englebienne demonstrated how the interaction of RnaseL
ankyrin domain with ABC transporters might explain pain and many of the physiological
disorders of CFS. The study suggests that the possible dysregulations in ABC transporter
function find an origin in
their abnormal interaction with the small fragments of RNase-L containing ankyrin repeat
motifs, released from a proteolytic
cleavage of pathological origin. [Dr. Ablashi's presentation also demonstrated the
correlation between active HHV-6 infection and LMW RNase-L levels.]
[Ed. Note: The fact that Dr. DeMeirleir has seen a reduction in p53 is in agreement
with what has already been published on HHV-6A, for example:
Oncogene 1990 Sep;5(9):1365-70, "Oncogenic potential of human
Razzaque A, Division of Virology, CBER, FDA, Bethesda,
The ability of human herpesvirus-6 (HHV-6, GS strain) DNA to neoplastically transform
established NIH3T3 cells was examined. Transfection of NIH3T3 cells with the intact
genomic DNA (170 Kb) or the subgenomic clone pZVH14 containing an 8.7 Kb insert followed
by focal or G418 selection resulted in the formation of morphologically transformed cells.
When injected subcutaneously into nude mice, these cell lines gave rise to rapidly growing
tumors while cells transfected with control vector DNA did not grow in agarose and did not
produce tumors in mice. By Southern blot analysis, HHV-6 DNA was detected in the G418
selected primary transfectants and tumor cell
lines, but not in the focus derived transformed and tumor cell lines. The data suggest
that HHV-6 DNA contains sequences which may contribute to neoplastic transformation, but
are not likely to be required for maintenance of transformation.
Please note!: This was published before the Tahoe publication on the presence of HHV-6A/GS
(same strain and variant) in patients with CFS. To say that this virus is ubiquitous is in
fact, not true. This is why HHV-6A differs in its destructive capacity from HHV-6B.
These are cancer viruses that are have the capability of causing cancer and are most
destructive to the host! This is why ME/CFIDS destroys the very lives of its
victims. It is no wonder that Dr. DeMeirleir commented, "You do not use CBT on
someone who has cancer!" after Dr. Buchwald cut his presentation short claiming they
were running behind schedule.]
Case Definition Session (1/26)
Unfortunately my plane was late so arrived toward the end.
Most of what I heard was "the same" - agreement of the need for a
clinical definition, that self reported data is inadequate, fatigue as a problematic
concept, the need to look at severity of symptoms rather than the presence or absence
thereof, lack of operational definitions, criteria variance accounting for unreliability.
Dr. William Reeves of the CDC spent time to consider how to define
the severity of "chronic unwellness," how to identify the role of chronic
fatigue in chronic unwellness and how to determine if fatigue is the driving force of the
symptoms and to consider if the concept of CFS is adequate to define people who are
chronically unwell. Many in the audience offered suggestions, such as indirect sampling to
identify markers, identify molecular profiles, need for case control studies. There were
many who, as time went on, seriously challenged the concepts and angrily pushed for better
answers. Finally, Dr. Nancy Klimas got quite upset and angrily lashed out at the audience
telling them to let the
investigators use the time .. and to use the definition to do good science! She stated
that there will be a forum at the next meeting (presumably referring to the next case
definition committee meeting) and concluded that, with all the ambiguities, the current
definition is a good tool, they just need to determine how to better use it..... That
session adjourned after her fierce defense.