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Co-Cure Weekly Digest of research and medical posts only - 11 Jun 2007 to 18 Jun 2007

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Date:    Tue, 12 Jun 2007 16:54:55 -0400
From:    "Marcia L. Harmon <MLHarmon cfids.org> via Co-Cure Moderator"
Subject: NOT,RES: CFIDS Association Issues Press Release on New CFS Prevalence Study

The CFIDS Association has issued a press release about the new CFS
prevalence study in Population Health Metrics. The full text of the release
can be read at http://www.cfids.org/sparkcfs/pr060807.pdf

According to the study authors, it is not certain that the prevalence rate
found in Georgia can be extrapolated to the entire United States.  But if
this rate were to be found to be replicable, the prevalence of adults with
CFS in the U.S. would be around 4 million, which is the figure Dr. William
Reeves has frequently cited in presentations based on the Georgia study
data.  The 7.5 million figure in Peter White's commentary appears to
include all Americans, not Americans between the ages of 18-59, which is
the age demographic strictly applicable to the 2.54% prevalence found in

The exact prevalence rate will no doubt continue to be revised as
researchers learn more about CFS, debate the merits of specific methodology
for estimating prevalence, and refine their methodology accordingly in new
studies.  This has happened over the past decade as methods have evolved
and prevalence numbers have been revised especially with regard to large
community-based studies.  And it will continue in the absence of a lab test
or biomarker to more accurately define the number of people who are
suffering from CFS.

There has long been concern in the patient and scientific communities that
earlier prevalence studies may not have reflected the real number of
Americans suffering with CFS.  The new methodology used in the Georgia
study can, and will, be debated over the coming weeks and months in the CFS
research community. That debate is healthy and part of a larger scientific
process that we all hope leads to progressively more accurate estimates of
the number of Americans living with CFS. But in the meantime, we need more
research investigating cause and cure and identifying more effective
treatments for people who are suffering every day with this life-altering

Please look for more information and varying perspectives on the new
prevalence study in the next issues of the CFIDS Chronicle and CFIDSLink.

Marcia Harmon
Director of Communications
CFIDS Association of America

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Date:    Tue, 12 Jun 2007 17:06:40 -0400
From:    "Stephanie Barr <sbarr FMAWARE.ORG> via Co-Cure Moderator"
Subject: NOT,RES: National Fibromyalgia Association Applauds Results of NIH/NIAMS Study on Gabapentin as Effective Treatment for Fibromyalgia

12 June 2007

National Fibromyalgia Association Applauds Results of NIH/NIAMS Study on
Gabapentin as Effective Treatment for Fibromyalgia

ORANGE, Calif----For years, fibromyalgia patients have been anxiously
awaiting the day when there will be a drug approved specifically for
fibromyalgia, the common, often difficult to treat chronic pain illness
many have dismissed as all in the heads of patients.

Now, that day is closer than ever.

New research supported by the National Institutes of Health's National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) shows
that the anticonvulsant medication gabapentin, which is used for certain
types of seizures, can be an effective treatment for the pain and other
symptoms associated with fibromyalgia.

In the NIAMS-sponsored, randomized, double-blind clinical trial of 150
women (90%) and men with the condition, Lesley M. Arnold, M.D., director of
the Women's Health Research Program at the University of Cincinnati College
of Medicine, and her colleagues found that those taking gabapentin at
dosages of 1,200 to 2,400 mg daily for 12 weeks displayed significantly
less pain than those taking placebo. Patients taking gabapentin also
reported significantly better sleep and less fatigue.  For the majority of
participants, the drug was well tolerated. The most common side effects
included dizziness and sedation, which were mild to moderate in severity in
most cases.

Lynne Matallana who founded the National Fibromyalgia Association (NFA) in
1997 after spending 2 years in bed and visiting 37 doctors before being
correctly diagnosed, applauded the study's findings:

"The favorable results of Dr. Lesley Arnold's NIAMS supported clinical
study on the use of Gabapentin as an effective treatment for the pain and
related symptoms of fibromyalgia, gives the fibromyalgia community renewed
hope that science is making inroads into finding effective drugs for the
treatment of this chronic disorder," said Matallana. "As this study and
other new clinical trials prove the safety and efficacy of certain
medications, hope for a future that will include effective treatments is
brighter than ever before."

NIAMS Director Stephen I. Katz. M.D., Ph.D., remarked that "While
gabapentin does not have Food and Drug Administration approval for
fibromyalgia, I believe this study offers additional insight to physicians
considering the drug for their fibromyalgia patients. Fibromyalgia is a
debilitating condition for which current treatments are only modestly
effective, so a study such as this is potentially good news for people with
this common, painful condition."

[The following is reprinted from the NIH/NIAMS announcement released on 6/11]:
Fibromyalgia is a chronic disorder characterized by chronic, widespread
muscle pain and tenderness, and is frequently accompanied by fatigue,
insomnia, depression, and anxiety. It affects three million to six million
Americans, mostly women, and can be disabling.

The precise cause of fibromyalgia in not known, but research suggests it is
related to a problem with the central nervous system's processing of pain.
As with some other chronic pain conditions, people with fibromyalgia often
develop a heightened response to stimuli, experiencing pain that would not
cause problems in other people. Yet, unlike many other pain syndromes,
there is no physical evidence of inflammation or central nervous system damage.

Although gabapentin has little, if any, effect on acute pain, it has shown
a robust effect on pain caused by a heightened response to stimuli related
to inflammation or nerve injury in animal models of chronic pain syndromes.
Researchers have suspected that it might have the same effect in people
with fibromyalgia. The new research, published in the April 2007 edition of
Arthritis & Rheumatism, indicates the suspicions were correct.

Although the researchers cannot say with certainty how gabapentin helps
reduce pain, Dr. Arnold says one possible explanation involves the binding
of gabapentin to a specific subunit of voltage-gated calcium channels on
neurons.  "This binding reduces calcium flow into the nerve cell, which
reduces the release of some signaling molecules involved in pain
processing," she says.

How gabapentin improves sleep and other symptoms is less clear, and there
are probably different mechanisms involved in fibromyalgia
symptoms.  "Gabapentin improved sleep, which is an added benefit to
patients with fibromyalgia who often report unrefreshing or disrupted
sleep," Dr. Arnold says.

What is important is that people with fibromyalgia now have a potential new
treatment option for a condition with few effective treatments.  "Studies
like this give clinicians evidence-based information to guide their
treatment of patients," says Dr. Arnold.

  The mission of the National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS), a part of the Department of Health and Human
Services' National Institutes of Health, is to support research into the
causes, treatment and prevention of arthritis and musculoskeletal and skin
diseases; the training of basic and clinical scientists to carry out this
research; and the dissemination of information on research progress in
these diseases. For more information about NIAMS, call the information
clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the
NIAMS website at http://www.niams.nih.gov

The National Institutes of Health (NIH)  The Nation's Medical Research
Agency  includes 27 Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. It is the primary federal agency
for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit www.nih.gov.

The National Fibromyalgia Association is a non-profit 501(c)(3)
organization whose mission is to develop and execute programs dedicated to
improving the quality of life for people with fibromyalgia by increasing
the awareness of the public, media, government and medical communities. The
NFA publishes a quarterly magazine, Fibromyalgia AWARE and hosts an
award-winning website at www.FMaware.org.


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Date:    Wed, 13 Jun 2007 15:20:25 -0700
From:    "CF-Alliance <cf_alliance yahoo.com>.....................via Co-Cure Moderators
Subject: MED: Gabapentin Shown Effective For Fibromyalgia Pain

Source: NIH/National Institute of Arthritis and Musculoskeletal and Skin
Date: June 12, 2007

Gabapentin Shown Effective For Fibromyalgia Pain

[Return to top]


Date:    Thu, 14 Jun 2007 18:34:38 +0200
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: med: Incline Village & Myalgic Encephalomyelitis


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 >>>>      14 June 2007       <<<<
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Outgoing mail scanned by Norton AV

From: DEnlander aol.com

Reference: *START recognizing ME!!!!* by LK Woodruff;
Help ME Circle, 12 June 2007, who wrote between other

It is important for all reading this article to remember that
the Lake Tahoe outbreak in the '80's appears, in
retrospect, to have actually been yet another ME (Myalgic
Encephalomyelitis) outbreak. And that USA CDC staff then
CHOSE to ignore that illness and it's decades-long
corroborating documentation, and instead decided to say
they were seeing a new, emerging illness...which they
named it 'CFS'.

See for the whole article:


Unfortunately the Incline Village patients were not reported in the
context that they suffered from a known disease. A disease that
Melvin Ramsay reported previously in 1955. His work at the
Royal Free Hospital in London resulted in the term Myalgic

If the correlation would have been made with this work, the
outbreak may have received more consideration.

However the doctors in this small tucked away ski village, a
remote place called Incline Village, were not in contact with a
medical library and thought, or wished to think, they had
discovered a new disease.

Unfortunately, sadly, they have never even now recognized
Ramsay and his salutary work.

Derek Enlander MD
New York

[Return to top]


Date:    Fri, 15 Jun 2007 05:45:51 +0200
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: med,res: Nitric Oxide Cycle & Therapy


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Martin L. Pall, Professor of Biochemistry and Basic Medical
Washington State University
<martin_pall wsu.edu>

In his new book: *Explaining "Unexplained Illnesses": Disease
Paradigm for Chronic Fatigue Syndrome, Multiple Chemical
Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, Gulf
War Syndrome and Others, Haworth Medical Press*, Prof.
Martin L. Pall mentions a list of agents predicted to
down-regulate NO/ONOO cycle biochemistry




The fifth principle of the NO/ONOO- cycle is that therapy should
focus on down-regulating NO/ONOO- cycle biochemistry. In
other words, lower the cause of illness. Let me state at the outset
that I am a Ph.D., not an M.D. and nothing here should be
viewed as medical advice.

There are several challenges to therapies aimed at lowering
NO/ONOO- cycle biochemistry.

*  The first of these is that we need to stop doing things that
up-regulate this biochemistry and there are various stressors
that up-regulate this biochemistry therefore are of obvious

*  The second is that the complexity of the NO/ONOO- cycle
makes it difficult to down-regulate and makes it likely that we will
need to use multiple agents in order to be effective in such
down-regulation. We don't have a magic bullet to treat these
illnesses and may have to rely, therefore, on complex
combinations of agents each of which may produce an
incremental improvement by lowering aspects of the cycle

*  The third is that peroxynitrite, the most central element in the
NO/ONOO- cycle is difficult to effectively scavenge in vivo and
therefore approaches based solely on scavenging peroxynitrite
may not be expected to be effective.

Let's consider the first of these challenges. Such stressors as
chemical exposure in MCS, excessive exercise in CFS and
psychological stress, especially in PTSD, should be avoided to
have any expectation of effective therapy. Each of these
stressors are expected to up-regulated NO/ONOO- cycle activity
in these individual illnesses. Foods to which individuals have
developed food allergies should be avoided, as antibody-
antigen reactions cause tissues to increase nitric oxide
synthesis. Excitotoxins can stimulate NMDA activity and
up-regulate NO/ONOO- cycle biochemistry and should therefore
be avoided. Excitoxins include monosodium glutamate,
aspartame and possibly certain other flavorings such as
hydrolyzed vegetable proteins.

In Chapter 15 of my book, I consider 30 different agents or
classes of agents that are available today and are predicted to
down-regulate NO/ONOO- cycle biochemistry and are predicted,
therefore, to be potentially useful therapeutic agents. I will add a
31 st such agent that was suggested to me by Dr. Jacob
Teitelbaum. Each of these are listed in the long table that

Table 3 Agents Predicted to Down-Regulate NO/ONOO Cycle

Agent (or class) Mechanism(s) Evidence


Chain breaking antioxidants. Gamma-tocopherol may have
special role in peroxynitrite scavenging and tocotrienols are
reported to have special roles in protecting from excitoxicity

  Chain breaking antioxidant; may also scavenge peroxynitrite;
helps to regenerate other antixoxidants

Coenzyme Q10
  Stimulates mitochondrial function, scavenges peroxynitrite,
lowers NMDA activity

  Antioxidant properties, selenium compounds are peroxynitrite
scavengers, replete deficiencies

  Scavenge peroxynitrite in membranes

  Complex group of phenolic antioxidants with multiple and
variable functions; chain breaking antioxidants, lower NF- kB
activity, scavenge peroxynitrite, superoxide and nitric oxide,
allow regeneration of other antioxidants

TMG, choline, SAMe, others
  Compounds with methyl groups attached to positively charged
nitrogens or sulfurs act to relieve reductive stress

Carnitine/ acetyl carnitine
  Improved transport of fatty acids into mitochondrion for energy
metabolism and regeneration of mitochondrial inner membrane;

  May allow regeneration of oxidized mitochondrial inner
membrane lipids; phosphatidyl choline may act to lower
reductive stress

Hydroxocobalamin (B 12)
  Potent nitric oxide scavenger; limited uptake when taken orally;
other forms of B 12 may act as precursor but with probable
lower efficacy.

Vitamin B 6; pyridoxal phosphate
  Lowers excitoxicity by improving balance between glutamate
and GABA

Riboflavin and also 5'-phosphate
  May increase glutathione reductase activity and thus increase
reduction of oxidized glutathione

Other B vitamins
  Improve energy metabolism, replete deficiencies

Reduced glutathione and precursors
  Reduced glutathione not effective taken orally; precursors
should probably be limited in dosage used. Most important
antioxidant synthesized in body, many functions.

a-lipoic acid
  Helps restore reduced glutathione, antioxidant activity,
regenerate other antioxidants, lowers NF- kB activity ; quality of
supplements seems to be quite variable

Mg 2+
  Magnesium acts to lower NMDA activity, improve energy
metabolism, replete deficiencies

Zn 2+, Mn 2+, Cu 2+
  Precursors of superoxide dismutases, antioxidant activity,
replete deficiencies; doses should be modest

  Lowers glutamate release, excitoxicity

  Lowers excitoxicity, NF- kB activity, iNOS induction, Ca 2+

NMDA antagonists; gabapentin
  Lower excessive NMDA activity, lower response to chemical
exposure in MCS

  Increases uric acid pools which scavenges, in turn, peroxynitrite
breakdown products; may also act to speed recovery of ATP
pools; possible down-side may include increased mast cell

Long chain omega-3 fatty acids
  Lower iNOS induction, lower NF- kB activity, replete

Agents that lower NF- kB activity
  Lower NF- kB activity

  Similar of flavonoids in actions

Algal supplements
  Rich in antioxidants

Hyperbaric O 2 treatment
  May act via hydrogen peroxide to induce synthesis of
tetrahydrobiopterin and therefore decrease NOS uncoupling

Minocycline/ tetracyclines
  Lowers iNOS induction, NMDA activity

  Lowers excitotoxicity

Lowers vanilloid activity, Panax ginseng? Guaifenesin?
  Expected to lower vanilloid activity

  Reported peroxynitrite scavenger, unusual antioxidant

  Lowers NMDA activity

  Increases recovery of ATP pools after energy metabolism
dysfunction; may increase reduction of oxidized glutathione

Evidence is listed as being clinical trial evidence (CT) or clinical
observations/anecdotal evidence (CO/A) or none, based solely
on studies of CFS, MCS, FM or closely related illnesses.

It can be seen from Table 3 that there are many different agents
that are promising candidates for therapy. Most of them are
nutritional supplements. There is some evidence for efficacy of
individual agents based on clinical trials (CT) or from clinical
observations and/or anecdotal evidence (CO/A) but in most
cases, the individual agents where they seem to be effective,
have relatively modest effectiveness. The suggestion is that
combinations of these agents may be much more effective than
individual agents. This combination therapy has been the
approach taken by five different physicians in developing their
treatment protocols and such combination therapy approaches
appear to be the most promising of all therapeutic approaches
for treatment of these illnesses.

Five physicians have developed complex treatment protocols for
these multisystem illnesses. Three of these have focused on the
treatment of chronic fatigue syndrome or closely related fatiguing
illness, one on both chronic fatigue syndrome and fibromyalgia
and one on chemically sensitive patients. Each of these
protocols uses from 14 to 18 different agents or classes of
agents that are predicted to down-regulate NO/ONOO- cycle
biochemistry! While two of these protocols (Teitelbaum's and
Cheney's) contain substantial numbers of agents not obviously
related to the NO/ONOO- cycle, each contains many agents
predicted to down-regulate the cycle. The treatment protocols
are outlined in the lists that follow:

Dr. Paul Cheney has developed his treatment protocol based on
clinical observations and has honed it over the past two
decades of treatment of chronic fatigue syndrome patients. He
advises trying to avoid things that exacerbate the NO/ONOO-
cycle mechanism, some of the same things that I discussed
above. Specifically he suggests attenuating GI tract problems by
such strategies as going on a low food allergen diet, minimizing
environmental chemical exposure and also minimizing
inflammatory diseases, such as around the teeth. The agents
that I list are followed, in some cases, by comments on how they
may act-those comments are mine, not Cheney's.

*  High dose hydroxocobalamin (B12) injections- potent nitric
    oxide scavenger
*  Whey protein-glutathione precursor
*  Guaifenesin-vanilloid antagonist?
*  NMDA blockers
*  Magnesium-lowers NMDA activity
*  Taurine-antioxidant and acts to lower excitotoxicity including
    NMDA activity
*  GABA agonists-GABA acts as an inhibitory neurotransmitter
    to lower NMDA activity-these include the drug neurontin
*  Histamine blockers-mast cells which release histamine are
    activated by both nitric oxide and vanilloid stimulation
    (Chapter 7) and may therefore be part of the cycle mechanism
*  Betaine hydrochloride (HCl)-Betaine lowers reductive
    stress, the hydrochloride form should only be used in those
    with low stomach acid. Betaine (trimethylglycine) is also listed
    separately in the protocol description

Antioxidants listed as follows:

*  Flavonoids, including "bioflavonoids," olive leaf extract,
    organic botanicals, hawthorn extract
*  Vitamin E (forms not listed)
*  Coenzyme Q10-acts both as antioxidant and to stimulate
    mitochondrial function
*  a-lipoic acid
*  Selenium
*  Omega-3 and 6 fatty acids
*  Melatonin-as an antioxidant that may act in the brain
*  Pyridoxal phosphate-improves glutamate/GABA ratio
*  Folic acid-lowers uncoupling of nitric oxide synthases

Cheney prescribes for his patients a total of 18 distinct agents or
classes of agents, each of which can be viewed as
down-regulating aspects of the NO/ONOO- cycle. I would argue
that this in not just coincidental, that it argues in support of the
NO/ONOO- cycle mechanism.

Dr. Jacob Teitelbaum has published placebo-controlled trial
data supporting the efficacy of one version of his protocol
(29,30), something none of these other physicians has done. It
seems to be effective on both chronic fatigue syndrome and
fibromyalgia patients. I am going to describe a recent version of
his complex protocol, focusing on what may be the central parts
of the protocol, the parts described as "nutritional treatments"
and "mitochondrial energy treatments." The last agent in the list,
D-ribose, was added to the protocol recently (personal

*  Daily energy B-complex-B vitamins including high dose B 6,
    riboflavin, thiamine, niacin and also folic acid. These fall into
    four categories that I have listed earlier in the chapter
*  Betaine hydrochloride (HCl)-lowers reductive stress,
    hydrochloride form should only be taken by those deficient in
    stomach acid
*  Magnesium as magnesium glycinate and magnesium
    malate-lowers NMDA activity-often uses magnesium
*  a-Lipoic acid-important antioxidant helps regenerate
    reduced glutathione
*  Vitamin B 12 IM injections, 3 mg injections (does not state
    whether this is hydroxocobalamin)-may act as potent nitric
    oxide scavenger
*  Eskimo fish oil-excellent source of long chain omega-3 fatty
    acids. Lowers iNOS induction, anti-inflammatory
*  Vitamin C
*  Grape seed extract (flavonoid)
*  Vitamin E, natural-does not state whether this includes
    g-tocopherol or tocotrienols
*  Physician's protein formula, used as glutathione precursor
*  Zinc-antioxidant properties and copper/zinc superoxide
    dysmutase precursor
*  Acetyl-L-carnitine-important for restoring mitochondrial
*  Coenzyme Q10-both important antioxidant properties and
    stimulates mitochondrial function
*  D-ribose-acts to increase rate of ATP and reduced
    glutathione regeneration

If you consider that the oral B vitamins fall into four categories
listed earlier in the chapter, Teitelbaum uses a total of 18 agents
or classes of agents that are predicted to down-regulate the
NO/ONOO- cycle, in the core part of his treatment protocol.

Dr. Garth Nicolson started his scientific career developing the
famous Singer/Nicolson, fluid mosaic model of biological
membranes, a model that is described in essentially all of the
standard biochemistry textbooks. He and his colleagues have
published on open label trials of a complex proprietary mixture
known as NT factor TM, apparently designed to improve
mitochondrial and thus energy metabolism function. The trials
have been on a group of older patients with unexplained chronic
fatigue, and consequently there is some question whether these
patients have CFS. Nevertheless, Nicolson and coworkers
(31-33) report statistically significant improvements in fatigue
and in several other changes often found in multisystem disease
patients, affective/meaning, sensory and cognitive/mood. Many
of the NT factor components are predicted to lower much of the
NO/ONOO- cycle biochemistry. Unfortunately, there is no
detailed description of the concentrations of the components of
the NT factor proprietary mixture. The mixture contains the
following components that are predicted to lower NO/ONOO-
cycle biochemistry:

*  Polyunsaturated phosphatidyl choline-predicted to lower
    reductive stress
*  Other phosphatidyl polyunsaturated lipids-this and the
    phosphatidyl choline are predicted to help restore the
    oxidatively damaged mitochondrial inner membrane
*  Magnesium-lowers NMDA activity, may aid in energy
*  Taurine-antioxidant activity and lowers excitoxicity including
     NMDA activity
*  Artichoke extract-as flavonoid source?
*  Spirulina-blue-green alga is a highly concentrated
    antioxidant source
*  Natural vitamin E-does not tell us whether this includes g
    -tocopherol or tocotrienols
*  Calcium ascorbate-vitamin C
*  a -Lipoic acid-important antioxidant, key role in regeneration
    of reduced glutathione, but also has role in energy metabolism
*  Vitamin B 6-balance glutamate and GABA levels, lowers
*  Niacin-role in energy metabolism
*  Riboflavin-important in reduction of oxidized glutathione back
    to reduced glutathione; also has important role in mitochondrial
*  Thiamin-role in energy metabolism
*  Vitamin B 12-as nitric oxide scavenger?
*  Folic acid-lowers nitric oxide synthase uncoupling

The way I have categorized these earlier on this site and in
Chapter 15 of my book, these agents fall into 15 distinct classes
of agents expected to lower NO/ONOO- cycle biochemistry.

Dr. Neboysa (Nash) Petrovic is a South African physician who, I
believe, also has a clinic in England. His CFS treatment protocol
(34) has been described as follows (I am unsure how current this

*  Valine and isoleucine-branched chain amino acids known to
    be involved in energy metabolism in mitochondria, and may be
    expected,therefore, to stimulate energy metabolism; modest
    levels may also lower excitotoxicity
*  Pyridoxine (B 6)-improves balance between glutamate and
*  GABA, lowers excitotoxicity
*  Vitamin B 12 in the form of cyanocobalamin-cyanocobalamin
     is converted to hydroxocobalamin in the human body but the
     latter form will be more active as a nitric oxide scavenger,
    since it does not require such conversion
*  Riboflavin-helps reduce oxidized glutathione back to
    reduced glutathione
*  Carotenoids (alpha-carotene, bixin, zeaxanthin and lutein)-lipid
    (fat) soluble peroxynitrite scavengers
*  Flavonoids (flavones, rutin, hesperetin and others)
*  Ascorbic acid (vitamin C)
*  Tocotrienols-forms of vitamin E reported to have special
    roles in lowering effects of excitotoxicity
*  Thiamine (aneurin)-B vitamin involved in energy metabolism
*  Magnesium
*  Zinc
*  Betaine hydrochloride (HCl)-lowers reductive stress,
    hydrochloride form should only be used by those deficient in
    stomach acid
*  Essential fatty acids including long chain omega-3 fatty acids
*  Phosphatidyl serine-reported to lower iNOS induction

According to the way I have listed these agents, his protocol
contains 14 agents or classes of agents predicted to
down-regulate NO/ONOO- cycle biochemistry.

[Return to top]


Date:    Sat, 16 Jun 2007 16:53:58 -0400
From:    <fredspringfield VERIZON.NET>
Subject: RES: History of chronic fatigue syndrome

[History of chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):975-82

Author: Hashimoto N.

Affiliation: Center for Medical Education and Information.

NLM Citation: PMID: 17561685

Chronic fatigue syndrome (CFS) is not a new disease. Similar morbidities
have been known as different names since past several centuries. For
example, neurasthenia, epidemic neuromyasthenia, myalgic encephalomyelitis,
Akureyri disease, Royal Free disease, chronic EBV disease, post-viral
fatigue syndrome etc.

Much of the recent interest in CFS was generated by incidence of
infection-like outbreak at Lake Tahoe in Nevada. The Center for Disease
Control (USA) realized that correlation was poor between those patients who
had virologic evidence of EBV infection and those who had the symptoms of
chronic fatigue.

This is a review of the history of CFS.
(1) Historical perspectives in chronic fatigue cases in past old period,
(2) Post-viral infectious fatigue and chronic fatigue (myalgic
(3) Recent trend of CFS studies and its clinical similar situation.

Finally, I would like to state that we intend to draw up a new diagnostic
guideline for CFS in Japan.

[Return to top]


Date:    Sat, 16 Jun 2007 16:57:03 -0400
From:    Fred Springfield <fredspringfield@VERIZON.NET>
Subject: RES: Overview of chronic fatigue syndrome focusing around prevalence and diagnostic criteria

[Overview of chronic fatigue syndrome focusing around prevalence and
diagnostic criteria]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):983-90.

Author: Kuratsune H.

Affiliation: Faculty of Health Science for Welfare, Kansai University of
Welfare Sciences.

NLM Citation: PMID: 17561686

Chronic fatigue syndrome (CFS) is an operational concept proposed by
Centers for Disease Control and Prevention to clarify the unknown etiology
of the syndrome characterized by the sensation of abnormally prolonged
fatigue. Lots of investigators reported various abnormalities such as virus
infection, immune abnormalities, HPA axis abnormalities, metabolic
abnormalities, etc., but there are a few abnormalities common to vast
majority cases of CFS.

Therefore, lots of people as well as medical doctors are still skeptical
about the presence of CFS. However, recent studies reveal that CFS can be
understood to be a special condition based on the abnormality of
neuroendocrine-immunologic system caused by the psycho-social stress and
some genetic components.

Under these conditions, a reactivation of various kinds of herpes virus
infections and/or chronic infections might occur as a result of immune
dysfunction, causing the abnormal production of several cytokines. A
distinctive feature of CFS is thought to be the secondary brain dysfunction
caused by the abnormal production of several cytokines.

In this paper, I show the overview of CFS focusing around prevalence,
economic impact and diagnostic criteria in Japan.

[Return to top]


Date:    Sat, 16 Jun 2007 17:03:42 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Viral infections in chronic fatigue syndrome

[Viral infections in chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):991-6.

Authors: Sairenji T, Nagata K.

Affiliations: Division of Biosignaling, Department of Biomedical Sciences,
School of Life Science, Faculty of Medicine, Tottori University.

PMID: 17561687

Chronic fatigue syndrome (CFS) is a heterogeneous illness in which patients
can have different, overlapping signs and symptoms. No single underlying
cause has been established for all CFS patients. Epidemiological studies
reveal that a flu-like sickness precedes the onset in the majority of cases.

The major hypothesis of the pathogenesis of CFS is that infectious agents
such as viruses, may trigger and lead to chronic activation of the immune
system with abnormal regulation of cytokine production. Many studies have
been performed to identify the possible microbial triggers and to
understand the epidemiological microbial agents.

We have summarized the recent progressive literature of virus, rickettsia,
and mycoplasma implicated in the pathogenesis of CFS.

[Return to top]


Date:    Sat, 16 Jun 2007 17:06:10 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Genetic background of chronic fatigue syndrome

[Genetic background of chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):997-1002.

Authors: Narita M, Narita N.
Affiliation: Graduate School of Medicine, Mie University.

NLM Citation: PMID: 17561688

Although previous twin and family studies have suggested the involvement of
genetic factor(s) in the pathogenesis of chronic fatigue syndrome (CFS),
responsible gene for CFS was not known. We have recently reported the
association of serotonin transporter gene polymorphism in CFS.

A significant increase of longer (L and XL) alleic variants was found in
the CFS patients compared to the controls. Compared to S allele, the L
allele is believed to retain higher transcriptional activity, which causes
decreased concentration of serotonin in the extracellular space, namely,
active serotonin in CFS.

These results thus support the serotonin hypothesis in the pathogenesis of CFS.

[Return to top]


Date:    Sat, 16 Jun 2007 17:23:30 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Clinical features of chronic fatigue syndrome--symptoms

[Clinical features of chronic fatigue syndrome--symptoms]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1011-5.

Authors: Ban N, Saiki T, Ko G, Kuwahata A.

Affiliation: Department of General Medicine, Nagoya University School of

NLM Citation: PMID: 17561690

Chronic fatigue syndrome (CFS) is a clinically defined condition
characterized by long-lasting disabling fatigue, resulting in severe
impairment in daily functioning and associated symptoms such as memory and
concentration difficulties, muscle aches, sleep disturbances, and headache.

Common symptoms encountered in CFS patients were reviewed and top 10 common
symptoms were described in detail with special reference to the particular
features of each symptom helpful to diagnose CFS.

[Return to top]


Date:    Sat, 16 Jun 2007 21:21:34 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Chronic fatigue syndrome and neurotransmitters

[Chronic fatigue syndrome and neurotransmitters]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1005-10.

Authors: Miwa S, Takikawa O.

Affiliation: Department of Cellular Pharmacology, Hokkaido University
Graduate School of Medicine.

NLM Citation: PMID: 17561689

Chronic fatigue syndrome (CFS) is an idiopathic illness characterized by
persistent fatigue, which could be caused by a variety of etiologic factors
including viral infection, abnormal production of cytokines and abnormal
acylcarnitine metabolism.

Recent studies suggest that CFS is closely associated with attenuation of
central synaptic transmission mediated by neurotransmitters such as
serotonin and glutamate. Attenuation of serotonin neurotransmission can be
caused by increased expression of serotonin transporter, which results
either from viral infection and subsequent production of interferon--alpha
or from abnormal promoter for serotonin transporter gene.

Other neurotransmitter systems may be also involved in CFS mediated by
abnormal acylcarnitine metabolism and autoantibodies for neurotransmitter

In this review, we focus recent data on CFS in terms of neurotransmitters.

[Return to top]


Date:    Sat, 16 Jun 2007 21:21:50 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Sleep disturbance

[Sleep disturbance]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1017-22.

Authors: Kumano-go T, Adachi H, Sugita Y.

Affiliation: Osaka University Health Care Center.

NLM Citation: PMID: 17561691

Attempts to elucidate the complex pathophysiology of chronic fatigue
syndrome (CFS) must consider subjective and objective sleep. Several
reports of CFS showed the high rate of sleep disturbance such as insomnia,
hypersomnia, circadian rhythm sleep disorder, sleep apnea/hypopnea syndrome
and so on.

To analyze pulse wave continuously in sleep of CFS patients by laser blood
flowmeter, we set base line component (0.01-0.08 Hz) and pulse wave
component(0.70-1.50 Hz).

Results of FFT analysis indicate that the CFS can have at least three
subtypes of pulse dynamics in sleep.

There probably are different types of illnesses now contained within the
CFS construct, in which identifying subtypes of sleep disturbance can be
one important key.

[Return to top]


Date:    Sat, 16 Jun 2007 21:22:18 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Identification and application of marker genes for  differential diagnosis of chronic fatigue syndrome

[Identification and application of marker genes for differential diagnosis
of chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1029-33.

Author: Kawai T, Rokutan K.

Affiliation: Department of Stress Science, Institute of Health Biosciences,
The University of Tokushima Graduate School.

NLM Citation: PMID: 17561693

Chronic fatigue syndrome (CFS) is a complex disease and has no laboratory
biomarkers, which makes diagnosis of CFS difficult. Several research groups
challenged to identify genes specific for CFS; however, there are no
overlaps between studies.

The U.S. Centers for Disease Control and Prevention reported remarkable
gene expression profiles of a large scale cohort study recruited 227
people. Reported genes were mostly different from the previously reported
genes, again featuring the complexity of CFS.

Separately, we identified 9 genes that were significantly and
differentially expressed between CFS patients and healthy subjects using an
original microarray.

The changes in expression of 9 genes were confirmed by quantitative PCR. We
also demonstrated the usefulness of 9 genes for differential diagnosis of CFS.

[Return to top]


Date:    Sat, 16 Jun 2007 21:22:07 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Psychological symptoms in chronic fatigue syndrome

[Psychological symptoms in chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1023-7.

Author: Yoshiuchi K.

Affiliation: Department of Psychosomatic Medicine, The University of Tokyo.

NLM Citation: PMID: 17561692

Patients with chronic fatigue syndrome (CFS) frequently complain of
psychological symptoms including depression, anxiety, and
neuropsychological impairment.
In addition, patients with CFS have been reported to be more likely to have
psychiatric diseases such as major depressive disorder, panic disorder,
generalized anxiety disorder, and personality disorder.

In the present review article, psychological symptoms and psychiatric
comorbidity in CFS patients were introduced. In addition, differentiation
between CFS and psychiatric disorders were discussed, because there have
been few studies on comorbidity and differentiation between CFS and
undifferentiated somatoform disorder although there has been heated debate
about the existence of CFS itself.

[Return to top]


Date:    Sat, 16 Jun 2007 21:22:31 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: The evaluation of fatigue by using acceleration plethysmography

[The evaluation of fatigue by using acceleration plethysmography]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1034-42.

Author: Yamaguti K.

Affiliation: Department of Physiology, Graduate School of Medicine, Osaka
City University.

NLM Citation: PMID: 17561694

We evaluated the fatigue of patients with chronic fatigue syndrome by using
acceleration plethysmography.

The changes in the acceleration plethysmography were relatively dominant in
the sympathetic nervous system from the viewpoint of the autonomic nervous
system, and the fluctuation in the time-series data of the acceleration
plethysmography was decreased from the viewpoint of chaos or complexity
system. We found the relation between the level of fatigue and the changes
in acceleration plethysmography.

Therefore, the acceleration plethysmography might be useful for the
evaluation of fatigue.

[Return to top]


Date:    Sat, 16 Jun 2007 21:23:08 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Spectroscopic diagnosis of chronic fatigue syndrome by multivariate analysis of visible and near-infrared spectra

[Spectroscopic diagnosis of chronic fatigue syndrome by multivariate
analysis of visible and near-infrared spectra]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1051-6.

Authors: Sakudo A, Kuratsune H, Hakariya Y, Kobayashi T, Ikuta K.

Affiliation: Department of Virology, Research Institute for Microbial
Diseases, Osaka University.

NLM Citation: PMID: 17561696

We have recently evaluated the possibility of visible and near-infrared
(Vis-NIR) spectroscopy for diagnosis of chronic fatigue syndrome(CFS).
Vis-NIR spectra in the 600-1,100 nm region for sera from CFS patients and
healthy donors were subjected to principal component analysis (PCA) and
soft independent modeling of class analogy (SIMCA) to develop multivariate
models to discriminate between CFS patients and healthy donors.

The PCA and SIMCA model predicted successful prediction of the masked
samples. Furthermore, taking advantage of Vis-NIR spectroscopy to enable
noninvasive analysis, our preliminary results have shown that SIMCA model
from Vis-NIR spectra of thumb has achieved 70-80% correct determinations.

In this review, we will introduce the potential of the Vis-NIR spectroscopy
for CFS diagnosis.

[Return to top]


Date:    Sat, 16 Jun 2007 21:22:48 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Chronic fatigue syndrome and herpesvirus reactivation

[Chronic fatigue syndrome and herpesvirus reactivation]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1043-8.

Author: Kondo K.

Affiliation: Department of Virology, The Jikei University School of Medicine.

NLM Citation: PMID: 17561695

Human herpesvirus 6(HHV-6) and human herpesvirus 7(HHV-7) establish
life-long latency, reactivate frequently, and are shed in saliva. To
identify the factor(s) of their reactivation, we have studied the
association with the reactivation and fatigue.

Reactivation was examined for viral DNA by real-time PCR method. As a
result, healthy adults shed the reactivated HHV-6 in the saliva during work
-induced fatigue, and the copy number of HHV-6 DNA was reduced after
holidays. However, no significant HHV-6 DNA increase was observed in
chronic fatigue syndrome (CFS) patients. In contrast, increase of HHV-7
reactivation was observed both in the case of work-induced fatigue and CFS.

These findings suggest that the amount of HHV-6 and HHV-7 reactivation can
be an objective biomarker for fatigue.

[Return to top]


Date:    Sat, 16 Jun 2007 21:23:41 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Antinuclear antibodies

[Antinuclear antibodies]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1067-70.

Author: Nishikai M.

Affiliation: National Hospital Organization Tokyo Medical Center.

NLM Citation: PMID: 17561698

Significance of antinuclear antibodies (ANA) in the patients with chronic
fatigue syndrome (CFS) was reviewed.

When indirect immunofluorescence with the HEp-2 cells as the substrates was
used, prevalence of the positive ANA was reportedly 15-25%. The ANA titers
were low and the immunofluorescent staining patterns were heterogeneous.
One group in the USA reported that 'nuclear envelope staining pattern' was
found in more than 50% of the patients with CFS. This results, however,
have not been confirmed by any other research groups.

Clinical significance of the positive ANA in the CFS patients resides in
differential diagnoses of systemic lupus erythematosus and other diffuse
connective tissue diseases. Recently, several ANAs specific to CFS have
been described. We reported anti-68/48kD protein antibodies utilizing
SDS-PAGE/ immunoblot method. These autoantibodies were found in 13% of 114
CFS patients and 0% in healthy subjects (p < 0.05).

Hypersomnia and difficulty in concentration were found more frequently in
the CFS patients with this specific autoantibody.

[Return to top]


Date:    Sat, 16 Jun 2007 21:23:29 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Estimation of fatigue state in patient with CFS using  actigraph and R-R interval power spectrum analysis

[Estimation of fatigue state in patient with CFS using actigraph and R-R
interval power spectrum analysis]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1057-64.

Authors: Tajima S, Kuratsune H, Yamaguti K, Takahashi A, Takashima S,
Watanabe Y, Nishizawa Y.

Affiliation: Fatigue Clinical Center, Osaka City University Graduate School
of Medicine.

NLM Citation: PMID: 17561697

OBJECTIVES: In this study, we try to estimate the fatigue state using
actigraphy and R-R interval power spectrum analysis.

RESULTS: Actigraphy analysis showed that mean awake activity was decreased
and duration of sleep was prolonged in patients with chronic fatigue
syndrome (CFS), significantly (p < 0.001). Both of sleep episodes in wake
period and wake episodes in sleep period were significantly increased in
CFS patients in comparison with healthy volunteers (p < 0.001) In autonomic
nerve analysis, sleep/awake ratio of high frequency component was
significantly decreased in patients with CFS (p < 0.05).

CONCLUSION: The quality of sleep in patients with CFS was decreased because
of increase of wake episodes in sleep period. Also the lack of
parasympathetic activation during sleep period might be associated with the
deterioration of sleep quality in patients with CFS.

[Return to top]


Date:    Sat, 16 Jun 2007 21:24:13 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Chronic fatigue syndrome: biochemical examination of blood

[Chronic fatigue syndrome: biochemical examination of blood]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1071-6.

Authors: Hakariya Y, Kuratsune H.

Affiliation: Department of Virology, Center for Infectious Disease Control,
Research Institute for Microbial Diseases, Osaka University.

NLM Citation: PMID: 17561699

Though patients with chronic fatigue syndrome (CFS) have lots of
complaints, abnormal findings cannot be detected by biochemical screening
tests. However, some specialized blood tests have revealed neuroendocrine
immune axis abnormalities, which is closely associated with each other.

Recent studies indicate that CFS can be understood as a special condition
based on abnormality of the psycho-neuro-endocrino-immunological system,
with the distinguishing feature of CFS seeming to be the secondary brain
dysfunction caused by several cytokines and/or autoantibodies.

In this paper, we summarize these abnormalities found in CFS and show the
neuro-molecular mechanism leading to chronic fatigue.

[Return to top]


Date:    Sat, 16 Jun 2007 21:24:33 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Overview of medical treatment and management of chronic  fatigue syndrome

[Overview of medical treatment and management of chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1077-81.

Authors: Yoshihara K, Kubo C.

Affiliation: Department of Psychosomatic Medicine, Graduate School of
Medical Sciences, Kyushu University.

NLM Citation: PMID: 17561700

A tailor-made management plan that includes various combinations of
non-pharmacologic and pharmacologic therapy for patients with chronic
fatigue syndrome (CFS) is important.

We present an overview of four aspects of our medical treatment and
management for CFS:
introduction of our medical management system,
summary of our management strategy,
non-pharmacologic therapy,
and pharmacologic therapy; according to foreign guidelines and the latest

The main non-pharmacologic therapies for CFS are rehabilitation and
lifestyle guidance. Using a graded exercise therapy, we have constructed a
broad management strategy for CFS.

Herein we introduce our graded exercise therapy. If the symptoms continue
despite careful management of the program by the physician, consultation
with a psychiatrist or psychosomatic medicine specialist is necessary.

[Return to top]


Date:    Sun, 17 Jun 2007 13:02:47 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Overview of psychiatric therapy for chronic fatigue  syndrome

[Overview of psychiatric therapy for chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1082-6.

Authors: Yamadera W, Itoh H.

Affiliation: Department of Psychiatry, Jikei University School of Medicine.

NLM Citation: PMID: 17561701

Chronic fatigue syndrome (CFS) is recognized as a special condition based
on abnormality of psycho-neuro-endocrine-immunological system, which is
caused by several cytokines and autoantibodies. For CFS diagnosis, it is
required to exclude psychiatric diseases which could cause chronic fatigue.

On the other hand, recent studies proved the effectiveness cognitive
behavioral therapy(CBT) for CFS. Distorted cognition relevant to CFS
includes the characteristics such as over adaptation, perfectionism,
avoidance and so on. In the CBT for CFS, it is important to quit seeking
physical causes, to accept the pathological state as it is, to monitor
daily activity and recognize the cognitive and behavioral patterns which
might prolong fatigue, to maintain a constant activity level and to make
planned increases in activity.

[Return to top]


Date:    Sun, 17 Jun 2007 13:06:03 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Attentive consideration for the treatment of chronic  fatigue syndrome

[Attentive consideration for the treatment of chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1089-92.

Author: Murakami M.

Affiliation: Department of Psychosomatic Internal Medicine, Nihon
University Itabashi Hospital.

NLM Citation: PMID: 17561702

The etiology of chronic fatigue syndrome(CFS) is still unknown and under
active discussion, but involvement of psychosocial factors appear to be
essential for the onset and clinical course of CFS. As CFS patients
complain of many stress-related physical and psychological symptom, it is
important to understand the CFS from psychosomatic point of view.

Not only for the pharmaceutical treatment, attentive consideration is
required for treatment of exhaustion of body and mind of CFS patients. Use
of anti-depressants or oriental herb medicine is often effective to relieve
the anxiety and depressive condition. Furthermore to augment the
self-healing potential, psychosomatic approach is important to modify the
life style and behavioral characteristics.

[Return to top]


Date:    Sun, 17 Jun 2007 13:08:41 -0400
From:    Fred Springfield <fredspringfield@VERIZON.NET>
Subject: RES: A new treatment: thermal therapy

[A new treatment: thermal therapy]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1093-8.

Author: Masuda A, Munemoto T, Tei C.

Affiliation: Masuda Clinic.

NLM Citation: PMID: 17561703

Thermal therapy using far-infrared ray dry sauna was performed for patients
with chronic fatigue syndrome (CFS).

Symptoms such as fatigue, pain, and low-grade fever were dramatically
improved on two patients. And prednisolone administration was discontinued
and became socially rehabilitated 6 months after discharge. On other 11
patients with CFS, physical symptoms such as fatigue and pain improved, too.

Furthermore, we reported that repeated thermal therapy had relaxation
effect and diminishes appetite loss and subjective complaints in mildly
depressed patients.

These results suggest that repeated thermal therapy may be a promising
method for the treatment of CFS.

[Return to top]


Date:    Sun, 17 Jun 2007 13:11:17 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Childhood chronic fatigue syndrome

[Childhood chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1099-1104.

Author: Miike T.

Affiliation: Department of Child Development, Faculty of Medical and
Pharmaceutical Sciences, Kumamoto University Graduate School.

NLM Citation: PMID: 17561704

Chronic fatigue syndrome in childhood and adolescents(CCFS) is a complex
and debilitation with severe morbidity and confusion. It is common
condition with up to 3-5% of children and adolescents showing strange
fatigue and confusion for more than 30 days.

In this condition, four major symptoms are important: sleep disorders, easy
fatigability, disturbed learning and memorization and immunological
problems. Routine laboratory studies are similar to adult CFS, although
abnormalities can be seen on serum pyruvic acid level, OGTT pattern, deep
body temperature rhythm, hormonal secretion rhythm, and cerebral blood flow.

For a diagnosis of CCFS, a research group supported by Japanese ministry of
health, labor and welfare developed CCFS case definition on 2004. Treatment
focused to correct disrupted circadian rhythms and supply of energy.

[Return to top]


Date:    Sun, 17 Jun 2007 13:14:37 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: The autonomic function and child chronic fatigue syndrome

[The autonomic function and child chronic fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1105-12.

Author: Tanaka H.

Affiliation: Department of Pediatrics, Osaka Medical College.

NLM Citation: PMID: 17561705

It is postulated that child chronic fatigue syndrome (CFS) involves the
autonomic nervous system, although the precise mechanism has not been
clearly indicated.

This paper reviews recent reports focusing the role of the autonomic
nervous system which plays in CFS. Many of the methods for measuring
autonomic function have appeared in the clinical setting in parallel with
advancing computer technology, but these are limited when applied in
children. In these blood pressure and heart rate changes during orthostatic
stress and these variability are favorably used.

As a result, one third of children with CFS showed abnormal cardiovascular
adjustment during posture change (orthostatic dysregulation: OD) which is
characterized by instantaneous orhthostatic hypotension, postural
tachycardia or neurally-mediated syncope.

Most of the studies using power spectral analysis of heart rate variability
showed sympathetic activation, however no consistent finding has been

In conclusion, autonomic function might be partly involved in CFS such as
OD, but its priority in causing CFS is unclear.

[Return to top]


Date:    Sun, 17 Jun 2007 13:17:54 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Usefulness of growth chart in children and adolescents with chronic fatigue syndrome

[Usefulness of growth chart in children and adolescents with chronic
fatigue syndrome]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1113-9.

Authors: Oki J, Okubo J.

Affiliation: Department of Pediatrics, Asahikawa Kosei Hospital.

NLM Citation: PMID: 17561706

We presented three sheets of growth chart in children with chronic fatigue

The growth chart in 14-year-old boy (patient 1) showed decreased weight
gain because of too much exercise. After that he complained of nausea,
abdominal pain, sleep disturbance and debilitating fatigue.

The growth chart in 12-year-old girl (patient 2) revealed increased weight
gain because of overeating due to the divorce of her parents. She developed
syncope, sleep disturbance, and fatigue during overeating.

The growth chart in 13-year-old girl (patient 3) showed decreased weight
gain after she developed lymph node enlargement. We diagnosed her as
autoimmune fatigue syndrome because of persistent positive antinuclear

Although growth chart will not be able to detect childhood chronic fatigue
syndrome prospectively, the chart may be useful for detecting some life
events in these children.

[Return to top]


Date:    Sun, 17 Jun 2007 13:20:49 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: School phobia and childhood chronic fatigue syndrome (CCFS)

[School phobia and childhood chronic fatigue syndrome (CCFS)]
[Article in Japanese]

Journal: Nippon Rinsho. 2007 Jun;65(6):1121-33.

Author: Tomoda A.

Affiliation: Department of Child Developmental Sociology, Faculty of
Medical and Pharmaceutical Sciences, Kumamoto University.

NLM Citation: PMID: 17561707

Chronic fatigue occurring in previously healthy children and adolescents is
a vexing problem encountered by pediatric practitioners and the impact of
fatigue in youngsters should not be underestimated. In its severe form, it
is often associated with mood disorders. Findings in children and
adolescent cases suggest that severe unexplained fatigue might precede the
development of fatigue-related illness, such as childhood chronic fatigue
syndrome (CCFS).

This is a disabling condition characterized by severe disabling fatigue and
a combination of symptoms, the prominent features being self-reported
impairments in concentration and short-term memory, sleep disturbances and
autonomic symptoms that cannot be explained by medical or psychiatric illness.

We have encountered such patients with these complaints; their major
symptoms include: general fatigue, fever, headache (not migraine), and
memory disturbance. From our clinical experience, we have inferred that
patients with CCFS might experience changes in brain function levels, which
induce an autonomic imbalance and engender symptoms such as general
fatigue, higher-order level cognitive dysfunction, and memory disturbance.

[Return to top]


Date:    Sun, 17 Jun 2007 13:28:49 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue

Sympathetic predominance of cardiovascular regulation during mild
orthostatic stress in adolescents with chronic fatigue.

Journal: Clin Physiol Funct Imaging. 2007 Jul;27(4):231-8

Authors: Wyller VB, Saul JP, Amlie JP, Thaulow E.

Affiliations: Department of Pediatrics, Rikshospitalet-Radiumhospitalet
Medical Centre, Oslo, and Department of Pysiology, Unievrsity of Oslo,
Oslo, Norway.

NLM Citation: PMID: 17564672

Haemodynamic abnormalities have been documented in the chronic fatigue
syndrome (CFS), indicating functional disturbances of the autonomic nervous
system responsible for cardiovascular control.

This study was designed to explore the pathophysiology in adolescent
CFS-patients by analysing RR-interval (RRI) variability and diastolic blood
pressure (DBP) variability during mild orthostatic stress, using an
algorithm which accounts for non-stationary biosignals.

A total of 27 adolescents with CFS and 33 healthy control subjects having
equal age- and sex distribution underwent 15 min of 20 degrees head-up tilt
(HUT). The spectral power densities of RRI and DBP were computed in the
low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band
(0.15-0.4 Hz) using an adaptive autoregressive algorithm to obtain a
time-varying spectrum. RMSSD, a time domain index of RRI variability, was
also computed.

At rest, all indices of variability were similar in the two groups. During
tilt, CFS patients had a larger increase in the LF/HF ratio (P</=0.001) and
normalized LF power of RRI (P</=0.01), and a larger decrease in normalized
HF power (P</=0.01) of RRI than controls. CFS patients also had trends
towards a larger decrease in absolute HF power of RRI and a larger increase
in normalized LF power of DBP.

These findings suggest that adolescents with CFS have sympathetic
predominance of cardiovascular regulation during very mild orthostatic
stress. Possible underlying mechanisms are moderate hypovolemia,
abnormalities of reflex control or physical de-conditioning.

[Return to top]


Date:    Sun, 17 Jun 2007 20:21:20 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Functional somatic syndrome: how it could be relevant to rheumatologists

Functional somatic syndrome: how it could be relevant to rheumatologists.

Mod Rheumatol. 2007;17(3):179-84. Epub 2007 Jun 20.
Masuko K, Nakamura H.

Department of Bioregulation and Proteomics, Institute of Medical Science,
St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku,
Kawasaki, 216-8512, Japan, kmarianna@mac.com.

PMID: 17564771

Functional somatic syndrome (FSS) is defined as a group of related
syndromes characterized more by symptoms, suffering, and disability than by
structural or functional abnormality. The diagnostic criteria and/or
symptoms of FSS often overlap, and co-morbidity is commonly found among the
diseases of FSS. For example, patients with irritable bowel syndrome often
suffer from chronic pain, and a high percentage of co-morbidity can be
found with fibromyalgia.

Accumulating evidence indicates the presence of visceral and somatic
hyperalgesia in FSS as a common feature, and the central sensitization
mechanism has been suggested to play an important role in the
pathophysiology of FSS.

In the present article, the authors introduce the concept of FSS focusing
on its possible relevance to rheumatology in terms of pain perception. A
possible implication of mast cells and proteinase-activated receptor-2
(PAR-2) in FSS is also reviewed.

[Return to top]


Date:    Sun, 17 Jun 2007 20:24:56 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Menopause related sleep disorders

Menopause related sleep disorders.

J Clin Sleep Med. 2005 Jul 15;1(3):291-300.

Eichling PS, Sahni J.

University of Arizona College of Medicine, Sleep Disorders Center, Tucson,
AZ, USA. peichling@canyonranch.com

PMID: 17566192

Sleep difficulty is one of the hallmarks of menopause. Following recent
studies showing no cardiac benefit and increased breast cancer, the
question of indications for hormonal therapy has become even more
pertinent. Three sets of sleep disorders are associated with menopause:
insomnia/depression, sleep disordered breathing and fibromyalgia.

The primary predictor of disturbed sleep architecture is the presence of
vasomotor symptoms. This subset of women has lower sleep efficiency and
more sleep complaints. The same group is at higher risk of insomnia and
depression. The "domino theory" of sleep disruption leading to insomnia
followed by depression has the most scientific support. Estrogen itself may
also have an antidepressant as well as a direct sleep effect. Treatment of
insomnia in responsive individuals may be a major remaining indication for
hormone therapy. Sleep disordered breathing (SDB) increases markedly at
menopause for reasons that include both weight gain and unclear hormonal
mechanisms. Due to the general under-recognition of SDB, health care
providers should not assume sleep complaints are due to vasomotor related
insomnia/depression without considering SDB.

Fibromyalgia has gender, age and probably hormonal associations. Sleep
complaints are almost universal in FM. There are associated polysomnogram
(PSG) findings. FM patients have increased central nervous system levels of
the nociceptive neuropeptide substance P (SP) and lower serotonin levels
resulting in a lower pain threshold to normal stimuli. High SP and low
serotonin have significant potential to affect sleep and mood. Treatment of
sleep itself seems to improve, if not resolve FM. Menopausal sleep
disruption can exacerbate other pre-existing sleep disorders including RLS
and circadian disorders.

[Return to top]


Date:    Mon, 18 Jun 2007 04:26:22 +0200
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: act,med: ME/CFS -Incomprehensible (prevalence)


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Pat Fero is the President of the Wisconsin CFS Association.
She was an ME/CFS patient before her son Casey was born,
who was also diagnosed with ME/CFS at the age of 9.

On July 4, 2005 her son died in his sleep at the age of 23.

The University of Wisconsin forensic pathologist found that
Casey died of myocarditis. His heart was infected with disease.
There was inflammation, and the tissue was full of viral infection.
Casey also had old fibrosis, indicating that the viral infection was
not of a new onset.

Casey Fero died of Chronic Fatigue Syndrome; the pathologist
was shocked about this finding. Although it is well known from
the UK ME literature, that patients die from this disease.

It must be an agony for this sick mother, who's heart is crying for
the bereavement of her dearly loved son, to experience how the
CDC is trying to hide the real nature of this unbearable disease.

They changed ME into the trivial and insulting name *Chronic
FATIGUE Syndrome* and are (with the help of the psychiatric
Wesseley School) redefining this disease every so much years;
and with every change they expand the criteria ad infinitum....

The last manipulations from William C Reeves et all. are
unacceptable. Why are they trying to frustrate research into this
disease? What have they to cover up? What is the closely
guarded secret behind this mysterious, horrible, contagious and
deadly disease?

Jan van Roijen



By Pat Fero

A Madison, Wisconsin woman e mailed me this morning to
say that she read an exchange about the new CDC
prevalence figures. It scared her because it put her in a
HUGE population of invisibles, making the larger
population of "well" people even more uncaring. That
bothers me. We do not need vulnerable people stressed,
so I told her what I thought and decided to send my
thoughts to readers.

I am not a scientist or statistician. With so many people
posting opinions about the CDC new prevalence
estimates, I am unable to keep up with those who have
that kind of education and experience. The fact is, I do not
process numbers all that well.  However, as I work on a
plan, a collaborative effort to set up a national CFS
information co-op with a mission to get information to
those 85% not diagnosed, our work just multiplied to
incomprehensible levels.

So, with a previous estimate of 800,000 people in the US
with CFS ages 18 - 69, I can believe that, let us say 80%
are not diagnosed = 640,000. More than likely, a good
share of these people are misdiagnosed with primary
depression and/or generalized anxiety disorder.  CFS
mythology, lack of clarity of the diagnosis, and WHEN a
patient presents in the course of the illness, might
logically cause an MD to MISS a CFS diagnosis which
could lead to inappropriate treatment options and an
increase in patient symptoms. I know this because I have
seen it for 20 years.

I can not accept the logic that 7 million people in the US
might, MIGHT have CFS = 1,400,000 people ages 18 - 69
diagnosed and the other 5,600,000 people undiagnosed.
That equals the entire population, kids and elderly, of the
state of Wisconsin or the state of Missouri.

Considering that we are working on a project to reach
those people who might possibly have CFS, be sick,
uninformed and possibly alone and broke, we must think
this through. If we believe the CDC figures, then we would
have to be insane to expect to reach so many people with
so few volunteers and so few Founders funding a toll
free number to handle all the callers.

The CDC study says that possibly 2.54% of the Georgia
population might have CFS. Dr. Reeves and colleagues do
not extrapolate this percentile to the entire United States.
After all, scientists tell us not to jump to conclusions
based on preliminary studies. Yet, in scientific
publications that followed the NIH and CDC studies
several years ago, that is exactly what was done which is
how we ended up with the 800,000 figure in the first place.

Well here we are and I accept, extrapolation be damned,
that close to one million people in the United States may
have CFS. If I accept the NEW data and extrapolate, then I
would also have to believe that:

1. We have and epidemic. OOPS...never supposed to use
     the word epidemic.
2. Uninformed, uncaring MD's ignoring the masses have
     enabled this epidemic.
3. The WI CFS Assn as well as other organizations are so
     sheltered that millions of people have never found us in
     all these years.
4. There is collusion with the media and government to
     keep this quiet so as not to alarm the masses.
5. Despite the  7 million sick and disabled people, there is
     no scientific interest.
6. Adding a few million people to the disability rolls is
7. We need to work harder to campaign for funding, build
     community and increase awareness  for a potential 7
     million CFS patients..


Nope.   I do not accept the new data. It must reflect the
population of people with some generalized fatigue state
which might tell us how stressed humans are in 2007. This
may be real and terribly unfortunate, but it has nothing to
do with CFS as I know it. It has nothing to do with Myalgic
encephalomyelitis as I know it.  I hope that patients online
prepare to talk about this in a calm, reasonable way as
inquiries might bring them someone close by who is
frightened, unaware of funding and politics and just needs
to hear that these new studies do not state the facts.

As for me, someone will have to hit me over the head with
proof, proof, proof that the methods used in the CDC
studies are valid. Until that happens, I will ignore anything
that comes from further investigations of CFS by the CDC.
It feels like I need to get off thin ice and head to safe

[Return to top]


Date:    Mon, 18 Jun 2007 16:00:36 +0200
From:    Jan van Roijen <j.van.roijen@CHELLO.NL>
Subject: med: Myocarditis & viruses associated with CFS


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Reference: *myocarditis* in the introduction to *ME/CFS
-Incomprehensible (prevalence)* by Pat Fero; see Co-Cure:



From: Kristin Loomis <kristin_loomis@hhv-6foundation.org>

Myocarditis and viruses associated with CFS

Several viruses associated with CFS also cause myocarditis.
Stanford infectious disease specialist Jose Montoya believes
that  a co-infection of two herpesviruses, HHV-6 & EBV is the
root cause for a significant subset of patients diagnosed with
chronic fatigue syndrome, based on his success with treating a
number of theses patients who had elevated antibodies to
HHV-6 & EBV. (Kogelnik 2006) He has also successfully treated
a number of patients who had been diagnosed with CFS but in
fact had parvovirus B-19.

Researchers at the Robert Bosch Medical Center in Stuttgart,
Germany recently demonstrated that both HHV-6 and parvovirus
B-19 are far more common in myocarditis than was previously
believed. The common wisdom among cardiologists has always
been that the viruses invlolved were adenovirus or coxsackie

Not only did the German group find 35% or 31 out of 87 biopsies
positive for HHV-6 at pathogenic levels, they determined that
patients with HHV-6 involvement progressed more frequently
toward chronic heart failure. Furthermore, unlike patients with
parvovirus B-19 (the most common virus found), patients with
HHV-6 had no chest pain and often did not seek treatment until
the late stages of disease (Mahroldt, 2006)

Kuhl et al found in 2005 found HHV-6 in 23% of 172 myocarditis
patient biopsies, and also found that when the virus cleared
(which happened spontaneously in 44% of the cases) there was
patient improvement in left ventricular ejection fraction, while in
patients where the virus did not clear, there was progressive
impairment. (Kuhl, 2005)

Infectious disease specialist Martin Lerner has found 24-hour
Holter monitor abnormalities in Chronic Fatigue Syndrome
patients with elevated antibody titers to EBV, CMV or HHV-6.
Furthermore, he has demonstrated improvement in both fatigue
levels and cardiac function in several small trials of antiviral
therapy with ganciclovir and valacyclovir.  (Lerner 1993, Lerner
2001, Lerner 2002) Another group of CFS researchers found
reduced cardiac output as measured by impedance
cardiography in patients with chronic fatigue syndrome.
(Peckerman 2003)

Although the Stanford group believes that the most important
site of persistent viral infection is in the CNS tissue, they are
studying the possibility that one or more of these viruses could
also be causing subclinical myocarditis in a subset of CFS

Montoya is currently conducting a placebo controlled trial of the
antiviral drug Valcyte for patients with elevated antibodies to
HHV-6 and EBV. He treats parvovirus B-19 patients with high
dose IVIG.

Kristin Loomis
Executive Director
HHV-6 Foundation
Santa Barbara, CA
805-695-8465 Fax

[Return to top]


Date:    Mon, 18 Jun 2007 13:57:27 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Hypothesis: Bipolar Illness with Complaints of Chronic Musculoskeletal Pain Is a Form of Pseudofibromyalgia

Hypothesis: Bipolar Illness with Complaints of Chronic Musculoskeletal Pain
Is a Form of Pseudofibromyalgia.

Semin Arthritis Rheum. 2007 Jun 13; [Epub ahead of print]

Wallace DJ, Gotto J.

Clinical Professor of Medicine, Cedars-Sinai Medical Center, David Geffen
School of Medicine at UCLA, Los Angeles, California.

PMID: 17570468

OBJECTIVE: To present a hypothesis accounting for the differential response
of bipolar patients diagnosed with fibromyalgia (FM) to standard therapies,
taking into account the markedly statistically significant increase of its
prevalence in the syndrome.

METHODS: All articles relating to the heading bipolar illness AND
fibromyalgia as well as bipolar illness AND pain were searched using PubMed
and Medline since 1966. The prevalence of bipolar illness in our last 100
FM consultations was reviewed.

RESULTS: Ten percent of our 100 most recent FM consultations included
patients with an established diagnosis of bipolar illness. They had little
if no response to traditional FM interventions and appeared to have vague
and uncertain tender point examinations.

CONCLUSIONS: Bipolar illness may be associated with a form of chronic
musculoskeletal pain complaints that is not FM. Studies into the role that
neurotransmitters play in bipolar patients with complaints of
musculoskeletal discomfort deserve further exploration.

[Return to top]


Date:    Mon, 18 Jun 2007 14:01:23 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Hypothesis: The Chaos and Complexity Theory May Help our Understanding of Fibromyalgia and Similar Maladies

Hypothesis: The Chaos and Complexity Theory May Help our Understanding of
Fibromyalgia and Similar Maladies.

Semin Arthritis Rheum. 2007 Jun 13; [Epub ahead of print]

Martinez-Lavin M, Infante O, Lerma C.

National Institute of Cardiology, Mexico City, Mexico.

PMID: 17570473

BACKGROUND: Modern clinicians are often frustrated by their inability to
understand fibromyalgia and similar maladies since these illnesses cannot
be explained by the prevailing linear-reductionist medical paradigm.

OBJECTIVE: This article proposes that new concepts derived from the
Complexity Theory may help understand the pathogenesis of fibromyalgia,
chronic fatigue syndrome, and Gulf War syndrome.

METHODS: This hypothesis is based on the recent recognition of chaos
fractals and complex systems in human physiology. RESULTS: These nonlinear
dynamics concepts offer a different perspective to the notion of
homeostasis and disease. They propose that the essence of disease is
dysfunction and not structural damage. Studies using novel nonlinear
instruments have shown that fibromyalgia and similar maladies may be caused
by the degraded performance of our main complex adaptive system. This
dysfunction explains the multifaceted manifestations of these entities.

CONCLUSIONS: To understand and alleviate the suffering associated with
these complex illnesses, a paradigm shift from reductionism to holism based
on the Complexity Theory is suggested. This shift perceives health as
resilient adaptation and some chronic illnesses as rigid dysfunction.

[Return to top]


Date:    Mon, 18 Jun 2007 17:12:40 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Reflections on Relevance: The Fields of Psychosomatics  and Psychotherapy in 2006

Reflections on Relevance: The Fields of Psychosomatics and Psychotherapy in

Journal: Psychother Psychosom. 2007;76(4):203-212.

Author: Balon R.

Affiliation: Department of Psychiatry and Behavioral Neurosciences Wayne
State University School of Medicine, Detroit, Mich., USA.

NLM Citation: PMID: 17570958

This article reviews several areas of new and interesting development in
the fields of psychosomatics and psychotherapy published in the literature
during 2006.

These areas are:
(1) cardiovascular illness and its interplay with depression;

(2) risks and predisposing factors in the areas of mental illness and
physical illness;

(3) new developments in chronic fatigue syndrome, and

(4) new or newly explored/modified (psycho)therapies, especially
cognitive-behavioral therapy.

In addition, an important area of conflict of interest in psychiatry in
particular and in biomedical science in general is discussed, as this issue
has reached prominence in the biomedical literature.

Copyright (c) 2007 S. Karger AG, Basel.

[Return to top]


End of Co-Cure Weekly Digest of research and medical posts only - 11 Jun 2007 to 18 Jun 2007

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