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[Return to digest index] --------------------------------------------- This is a special digest of Co-Cure Research & Medical posts only Problems? Write to mailto:firstname.lastname@example.org --------------------------------------------- ---------------------------------------------------------------------- Date: Tue, 13 Feb 2007 13:38:47 -0500 From: Fred Springfield <fredspringfield VERIZON.NET> Subject: RES: Resting muscle pain as the first clinical symptom in children carrying the MTTK A8344G mutation Resting muscle pain as the first clinical symptom in children carrying the MTTK A8344G mutation. Journal: Eur J Paediatr Neurol. 2007 Feb 9; [Epub ahead of print] Authors: van de Glind G, de Vries M, Rodenburg R, Hol F, Smeitink J, Morava E. Affiliation: Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. NLM Citation: PMID: 17293137 The characteristic clinical presentation, especially the appearance of muscle symptoms, is quite unique in children carrying the mtA8344G mutation. The diagnosis of MERRF syndrome is seldom made in the pediatric age. Fatigue is a common finding in children of pubertal age. Fatigue in combination with recurrent resting muscle pain occurs frequently in the initial phase of various hereditary muscle disorders and in several autoimmune, endocrine and metabolic syndromes. In the absence of obvious biochemical/metabolic abnormalities and in the lack of neurological symptoms the complaints are frequently labelled as fibromyalgia or chronic fatigue syndrome. In patients with behavioural or psychiatric abnormalities one might even start to question the organic etiology of the complaints. We describe a family carrying the classic MTTK mutation with a variable degree of heteroplasmy, presenting in childhood as isolated recurrent muscle pain as the first symptom of the disease. [Return to top] ------------------------------ Date: Tue, 13 Feb 2007 15:56:44 -0500 From: Co-Cure Moderator <ray CO-CURE.ORG> Subject: NOT,RES: Report on the 8th International IACFS Conference on CFS, FM, and Related Illnesses by Dr. Charles W. Lapp [Moderator's Note: This report on the 8th International IACFS Conference on CFS, FM, and Related Illnesses was written by Charles W. Lapp, M.D., and is distributed here with his permission.] 8th International IACFS Conference on CFS, FM, and Related Illnesses Fort Lauderdale, Florida January 12-14, 2007 The 2007 meeting of the IACFS (formerly AACFS) has set new records for attendance, including more than 250 professionals and over 300 patients. An effort has been made to expand internationally, and over 21 countries were represented at this meeting! Even before the meeting began, big changes were occurring. The IACFS Board voted to change the name of the organization to the International Association of CFS and ME in recognition of the term ME used by many other English-speaking nations, and thereby tendering an alternate name for this illness. Later in the week, an ad hoc Name Change Committee, put together by ProHealth CEO Rich Carson, also recommended using the term ME (or Mylagic Encephalopathy) in lieu of CFS. CFS will probably remain the scientific term for the illness, but it is hoped that ME will become the common designation. Another key event at this meeting was the introduction of the new Pediatric Case Definition. A working committee of the IACFS has hammered out a proposed manner of diagnosing children and adolescents with this disorder. Research has been hampered in the past by the absence of unifying diagnostic criteria. The committee has provided a summary paper, a questionnaire for clinical use, and a summary "scoring sheet," which should help both clinicians and researchers to understand pediatric CFS/ME better. In reviewing the papers submitted for presentation, it soon became clear that the amount and quality of research in CFS/ME has increased significantly over the past two years, and that many researchers are looking into specific aspects of the illness (such as fatigue, or pain, or sleep disruption) rather than attempting to study the syndrome as a whole. It seems that each year a new aspect of research is introduced, and this year that aspect is "genomics and proteomics." Genomics is defined as the study of function and interactions of genetic material in the genome, while proteomics is the study of proteins made in the cell. Both of these fields are contributing substantially to our understanding of CFS/ME and FM. As Dr. Suzanne Vernon of the CDC pointed out, it is hopeful that these studies will lead to a better understanding of the illness, perhaps a specific marker, and possibly even therapy. Unlike previous conferences, clinical and research papers were inter-mingled this year but organized by general topic such as fatigue, sleep disorders, clinical trials, pain, epidemiology, brain function, behavioral health, pediatrics, gender aspects, and genetics/proteomics. Fatigue Session Seiki Tajima of Osaka, Japan, launched the meeting with a study of activity monitoring and autonomic responses in sleep. Patients wore an activity monitor (similar to a pedometer, but worn on the wrist), which was able to discriminate periods of activity, rest, and sleep during a 24 hour period. Tajima was able to identify at least 5 types of abnormal sleep patterns in PWCs, including a long sleeping type, severe insomnia, hypersomnia, and sleep phase shifting. Autonomic (that is, R-R spectrum) analysis revealed that poor sleep may be due to a lack of parasympathetic activity during attempted sleep periods. Nicole Porter (DePaul University, Chicago) queried PWCs and healthy individuals about their experience of fatigue. She was then able to define at least 5 different fatigue states: Wired fatigue feels over-stimulated but low energy Brain fog fatigue mental or cognitive impairment is associated with fatigue Molasses fatigue heaviness and immobilization, unable to prolong activity Flu-like fatigue weakness with flu-like symptoms Post-exertional fatigue a lack of energy following minor activity Healthy individuals experienced only one type of fatigue (typically flu-like), while PWCs experienced fatigue in diverse ways. Elizabeth Mahoney described a CDC-sponsored study of the effect of allostatic load. One's "allostatic load" is essentially your accumulated stressors. However, the CDC used objective measures (such as heart rate, blood pressure, c-reactive protein levels, waist-to-hip ratio, lipid levels, blood sugar, insulin levels, etc.) as a measure of "load." Based on this premise, women with a high allostatic load were 5 times more likely to develop CFS/ME compared to those with low allostatic loads. This did not hold true for men, however. Mahoney also pointed out that this study demonstrated a high prevalence of metabolic syndrome in PWCs. [Metabolic syndrome is characterized by central obesity, elevated cholesterol and triglycerides, elevated blood sugar; and the presence of metabolic syndrome frequently predicts later diabetes and cardiovascular disorders such as heart attack and stroke.] Margaret Chicorella, both an exercise physiologist and an attorney from University of the Pacific, Stockton, CA, demonstrated how disability could be better defined using a two-part exercise test. When cardio-pulmonary exercise testing is repeated 24+ hours after the first test, oxygen consumption and the maximum achievable heart rate both decrease substantially. This is objective evidence of post-exertional malaise -- a sine qua non of CFS/ME/FM and could be very useful in disability determinations. Paul Nestadt (Mt.Sinai School of Medicine, NYC) used Magnetic Resonance Spectroscopy (1H-MRS) to show that lactate is increased and N-acetyl-aspartate (NAA) is reduced in the brains of PWCs (Persons with CFS/ME). Lactate levels correlated with the level of fatigue, and were not abnormal in persons with depression or anxiety. These findings are further evidence that CFS/ME is not psychiatric in origin, and that mitochondrial function and neuronal density (or metabolism) are reduced in PWCs. Dubbo is small city in the northwest corner of New South Wales, Australia, and has been the site of several epidemiological studies concerning the clinical course of EBV mononucleosis (a DNA virus) and Q-fever (a rickettsial infection). Toni Whistler of the CDC described genetic findings in persons who developed PIFS, or Post-Infectious Fatigue Syndrome, which is very similar to CFS/ME. 30,000 genes were studied, and more than 40% of the pathways were found related to regulatory and metabolic pathways. Cell cycle regulation, gene regulation, and signaling were most commonly involved; and apoptotic, metabolic, and inflammatory (IL 10) pathways were prominent in the sickest patients. Whistler concluded that there is a subset of PIFS in which immune abnormalities play a significant role. Clinical Trials Barry Hurwitz, a colleague of Dr. Nancy Klimas at the University of Miami, presented the findings of their famous "ProCrit Study." 57 PWCs were studied for anemia and low red blood cell volume (RBCV). About 70% of the cohort actually had a low RBC volume. These were given either ProCrit (n=30) or placebo (n=10), while those with normal RBC volume were given placebo injections for 4 months. All were administered iron and dietary salt supplements also. 80% of treated subjects responded to 10,000 units per week of ProCrit, and their RBC volume increased about 26% on average. Orthostatic intolerance (by tilt table testing) improved in treated subjects, but exercise tolerance, fatigue, and other measures did not change. Thus, ProCrit therapy might be modestly helpful for patients with orthostatic intolerance and low RBCV, but not for the general symptoms of CFS/ME. José Montoya (Stanford University School of Medicine) described his recent valgancyclovir (Valcyte™) studies in 12 persons with virally induced fatigue and cognitive dysfunction. Subjects were treated with valgancyclovir for 6 months (one for 3 months only), and 9 had significant improvement in fatigue and cognition. Five of these had elevated EBV titers (VCA-IgG, EBNA, or EBV-EA), 3 had both elevated EBV and HHV6 serologies, one had neither. None had HHV6 elevations alone. Comment: It is not at all clear if any of these patients had CFS/ME. We can only say that a subset of persons with Post-Infectious Viral Syndrome may respond to prolonged therapy with valgancyclovir. Dr. Montoya warned that valgancyclovir is a dangerous drug and must be used with great caution. A study of valgancyclovir specifically in persons with CFS/ME is slated to start this month, and we all anxiously await the outcome! Martin Lerner (Wayne State University, Detroit) described a subset of patients with persistent EBV and/or cytomegalovirus (CMV), electrocardiographic changes, and symptoms of CFS/ME. In addition to having elevated IgM (or EBV-EA) titers, all 37 patients had an elevated heart rate at rest, recurrent T-wave inversions on Holter monitoring, cardiac abnormalities and/or biopsy proven cardiomyopathy. Subjects with EBV positivity were treated with high dose valcyclovir (VCV or Valtrex™) 14mg/kg daily, and subjects with CMV positivity were treated with valgancyclovir (VGCV or Valcyte™) for 3 to 3.5 years with improvement in fatigue, tachycardia, chest pain, syncope, flu-like symptoms, EBV titers, and cardiac wall motion. No serious adverse effects were seen. Pain Dan Clauw (University of Michigan, Ann Arbor) provided his usual elegant and fascinating presentation, this time on "Pain Processing and Therapy in Fibromyalgia." Clauw explained that each of us has a "volume control" for controlling the severity of pain, and that this controller is affected by both genetics and environment (or experience). Studies have shown that persons with FM (PWFs) have a normal "detection threshold" for pain, but a decreased "noxious threshold" to a variety of stimuli, including pressure, heat, noise, and electrical stimulation. Thus, PWFs sense the onset of pain the same as other individuals, but are much more sensitive to pain. This is independent of expectancy or hypervigilance. Such findings can be demonstrated by a functional MRI scan ( fMRI), which senses deoxygenated blood and thereby detects parts of the brain that are activated. Using this technique, Clauw's group has demonstrated that healthy individuals have a minimal response to a modest pain stimulus, while PWFs have a very strong response to the same modest stimulus. This proves, Clauw explains, that "when FM patients say they hurt, they really do hurt!" Studies have also shown that pain is unrelated to co-morbid depression, but persons who catastrophize (negative thoughts, magnification of symptoms, "glass-half-empty") tend to experience more pain. Clauw's management of pain parallels The Stepwise Approach espoused at the Hunter-Hopkins Center: education, pharmacologic therapy, aerobic exercise, alternative therapies (such as hypnotherapy, biofeedback, acupuncture, chiropracty, electrostimulation) and Cognitive Behavioral Therapy (or coaching). He reports good evidence that the following are helpful: Tricyclic antidepressants (amitriptyline, cyclobenzaprine) SNRIs (venlafaxine, duloxetine) and possibly SSRIs Tramadol There is weak evidence for using growth hormone, 5-hydroxy-tryptane, tropisetron, and SAMe; and NO evidence supports the use of NSAIDs (ibuprofen, naproxen, etc.), corticosteroids, or guiafenesin. Clauw is not a fan of opioids, narcotics, or sleep medications in the treatment of FM. Newer possible therapies for fibropain include GHB (Xyrem™), dopamine agonists (roprinolole, pramipexole), and neuromodulators. Lastly, Clauw pointed out that there is a strong familial predisposition to fibromyalgia, with first degree relatives having 8 times the risk of developing FM. Also, Diatchenko has linked abnormalities in the COMT haplotype (which controls serotonin in the body and brain) to TMJ. This means that at least one gene codes for pain, and possibly the tendency to develop FM. Epidemiology Rosemary Underhill of the New Jersey CFS Association studied the prevalence of chronic fatigue and CFS in the offspring of mothers with CFS/ME. A questionnaire to members of the NJCFSA identified 108 mothers with physician-documented CFS/ME. These woman were contacted for details. There were 220 offspring. 24% of mothers had an offspring with documented CFS/ME or chronic fatigue (CF). CFS/ME occurred in 5.5%, and 11.4% had chronic fatigue. Both sons and daughters were affected about equally, and half developed illness after age 18. 42% of the offspring with CFS/ME had already recovered, as had one-third of those with CF. Leonard Jason (DePaul University, Chicago) calculated the economic impact of CFS/ME using both community-based and tertiary sample pools. Indirect costs (that is, loss of production) were estimated to occur in 27%, or an annual loss of $20,000 per person with CFS/ME. Direct costs (drugs, medical tests, office visits, etc.) were ascertained to be $8764 per person in the tertiary sample and $2341 in the community sample. (Patients identified from tertiary care tend to be more ill than those in the community.) Thus, the combined direct and indirect costs were $22,341 per person in the community sample and $28,674 in the tertiary sample, for an annual cost to the US economy of 19.6 to 25.2-billion dollars. Ampligen Dr. William Carter, CEO of Hemispherx Biopharma, reported the Ampligen experience to a crowd of interested providers before sessions began on Saturday, January 13. He stated that since the 1980's about 1000 individuals have been treated with Ampligen, using about 80,000 doses of this experimental drug. Phase III studies have been positive -- showing a 16% increase in exercise ability in treated subjects and preliminary data has been submitted to the FDA toward the New Drug Application for Ampligen. There was no speculation when this process will be complete or when Ampligen might be available to patients. Brain Function The current status of researching brain function in CFS/ME was reviewed by Gudrun Lange (University of Medicine and Dentistry of New Jersey UMDNJ). She described some of the neurocognitive tests used to demonstrate cognitive dysfunction in CFS/ME, and pointed out that testing is much more positive in bedridden subjects (presumably sicker) and after maximal exertion (say on a bicycle or treadmill). Radiological tools that demonstrate positive findings are MRI, CT scanning, SPECT and PET scanning (which measure cerebral blood flow), Proton Magnetic SPECT or Magnetic Resonance Spectroscopy (they measure brain metabolites such as glucose), and blood oxygen level dependent Functional MRI (or fMRI, which measures activation in areas of the brain, say to pain). Studies so far have demonstrated that: PWCs perform as accurately as healthy controls, but require more regions of the brain (that is, PWCs have to work harder to get the same results); The key cognitive deficit in PWC's is their speed of information processing; and, Metabolic findings have been variable, depending on the metabolite and the group studying it. Doctors from Barcelona, Spain, and Santiago, Chile, presented their results of SPECT scanning in PWCs compared to patients with depression. Dr. Garcia-Quintana showed that cerebral blood flow is decreased in the frontal lobes (only) of depressed patients, but reduced in frontal lobes and brainstem in PWCs. PWCs also have an increase of blood flow in the thalamus (a pain control center). Following exercise (or mental strain such as puzzles, short stories, or cubing numbers) the cerebral blood flow was markedly decreased in frontal, pre-frontal, anterior temporal, and cingulated regions in more than 87% of subjects studied. Increased blood levels of the enzymes elastace and RNaseL correlated with more severe loss of cerebral blood flow. Comment: This is old news, but confirms previous studies in the US. We have known for over a decade that frontal, temporal lobe, and brainstem blood flow is reduced in PWCs, which is thought to cause problems with creativity/motivation/memory (frontal lobes), mood and memory (temporal lobes), and the sleep/fatigue/autonomic centers of the brainstem. We also knew that both exercise and mental exertion exacerbate this reduced blood flow for up to 72 hours! The new twist is that elevated elastase and RNaseL levels correlate with reduced blood flow. Fumihara Togo (UMDNJ) presented a short but elegant paper that studied motor tasks and performance time in PWCs. Subjects would focus on a target in this case an arrow pointing left or right and touch one key for left, another for right. Togo demonstrated that motor performance was normal in CFS/ME, but that PWCs were slower to perform. In contrast, depressed patients had difficulty with both motor skills and speed. A similar kind of finger-tapping study was described by Mark Van Ness, Christopher Snell, and Staci Stevens (University of the Pacific). They measured simple reaction time (the response to a simple target) and complex reaction time (response to a target hidden within other information) at rest, and then 30 minutes and 24 hours after an exercise test. They found that PWCs were a bit slower to respond than matched controls even at rest, worst 30 minutes after exercise, and still delayed 24 hours later. This held for simple or complex reaction time. Hiro Kuratsune (Kansai University, Japan) concluded this session with a summary of what is known about brain function in CFS. We know: The MRI is abnormal in the majority of PWCs due to numerous T2 weighted hyperintense spots or foci, and evidence of demyelination PWCs with more brain abnormalities tend to be more physically impaired The volume of gray matter is reduced in proportion to reduced physical activity (that is, the brain shrinks in PWCs who are inactive!) Cerebral blood flow is diminished, especially in the cingulate area (controls attention, autonomic nervous system), temporal lobes (control mood, motivation), and frontal lobes (motivation, creativity, and short term memory) The concentration of acetyl-carnitine is reduced, particularly in the cingulate, and supplementing acetyl-carnitine may increase neurotransmitters such as GABA. glutamine, and aspartate Acetyl-carnitine supplementation may also improve attention 5-HT (serotonin) transporter binding was reduced in the rostral cingulate area in PWCs, which may help explain fatigue and pain Behavioral Health Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) are commonly thought to be the only effective treatments for CFS/ME, mostly due to the influence of two meta-analyses of the treatment literature. (In actuality, these were the only two effective modalities that had been studied extensively, but other treatments may be helpful). Unfortunately, many practitioners concluded erroneously that psychiatric care and vigorous exercise were "the cure" for CFS/ME. Dr. Ellie Stein, a psychiatrist from Calgary, Canada, eloquently addressed this in her introductory remarks. Stein pointed out that CFS/ME and FM are chronic, heterogeneous conditions that are unlikely to respond to any single approach. It is understandable that both have high rates of psychiatric co-morbidity (such as depressed mood and anxiety), yet neither is considered a psychiatric disorder. Since no medication is known to cure CFS/ME or FM, behavioral interventions are a reasonable consideration. The earliest CBT/GET programs were based on the false assumptions that avoidance of activity, illness severity, increased attention to symptoms, and autonomic arousal ("hyper," or hyper-excitable behavior) were causing or perpetuating symptoms, when in actuality they were the result of the illness. Of seven controlled studies using early CBT techniques, only 4 were positive and most were inconclusive or poorly done. Five studies of graded exercise in CFS/ME showed a modest decrease in fatigue, but improvement in pain, sleep, autonomic, immune, and cognitive symptoms have not been shown. It has long been suspected that persons with "pure FM" (i.e., less fatigue and cognitive dysfunction) can exert more easily, and several studies have shown temporary improvement in pain and quality of life, but many effects have worn off within a year. CBT has not been proven helpful in "pure FM." No study has measured the effect of CBT or exercise in the severely ill. Stein points out that CBT and GET don't work well because many patients do not have dysfunctional illness beliefs, many are already functioning at maximum activity levels, and the exercise makes some people worse! She recommends "The Stanford Model," a program for persons with chronic illness that is based on education, encouragement, and shared responsibility between patient and professional. The Stanford Model addresses low level exercise, cognitive symptom management, nutrition, energy and sleep management, the use of medication and community resources, managing emotions, and dealing with health care professionals. This program has proven success in MS, rheumatoid arthritis, and other chronic illnesses. Dr. Pat Fennell has also developed a proprietary chronic illness approach, based on her proposed Four Phases of Coping in CFS/ME. This model encourages patients to collect data, take control of symptoms, grieve losses, and search for a new identity. Comment: Dr. Bruce Campbell's CFIDS and FM Self Help Book and his online CFIDS and FM Self Help Course (both available at www.cfidsselfhelp.org) are based on the Stanford Model, and highly recommended! Patricia Fennell's books are available from Barnes & Noble and other booksellers. Stein went on to point out that self-efficacy (that is, the perceived ability to control illness) and acceptance of illness are both associated with positive physical and psychological outcomes. Therefore, CBT and GET are the most studied behavioral interventions, but results are short lived and many do not benefit. Stein urges alternative approaches such as the Stanford Model that are more patient friendly and have a good record of success. Professor Fred Friedberg (Stony Brook University) presented a short course on CFS/ME and FM to his students, and found that even a brief exposure to factual information about these illnesses led to more favorable attitudes by fourth year medical students. Two points that students endorsed strongly were, "It is important for physicians to understand CFS," and "Patients are [NOT] to blame for their illness." Pediatric Session Although CFS/ME is known to occur in children and adolescents, pediatricians have been hampered by the absence of a case definition for children. The adult research definition (Fukuda, et al. Annals of IM, 1994) traditionally has been used, but children have age-specific issues and generally report different symptoms than adults. With this problem in mind, the IACFS developed the Pediatric Case Definition Working Group (Drs. Jason, Bell, DeMeirleir, Gurwitt, Jordan, Lapp, Miike, Torres-Harding and Van Hoof) to study the problem. For more than a year the committee studied various approaches to diagnosis, and developed a new definition, questionnaires, and a scoring sheet for pediatricians. This new definition combines the best aspects of the Fukuda definition with the best aspects of the Canadian Clinical Definition of ME/CFS (Carruthers, et al, JCFS 11(1):7-115, 2003), and has produced two questionnaires with queries that are age-appropriate (for under 11 years old, and 11-18 years old). To establish a diagnosis of pediatric CFS/ME the following five symptom categories must be satisfied: Post-exertional malaise Unrefreshing sleep, or a disturbance of sleep quantity or rhythm Myofascial, joint, abdominal, or headache pain Two or more neurocognitive manifestations; and At least one symptom from two of the following three categories: (1) autonomic manifestations, (2) neuroendocrine manifestations, or (3) immune manifestations. It is hoped that this pediatric case definition will lead to more appropriate identification of children and adolescents with CFS/ME. An article on the development and use of the definition will appear in the Journal of Chronic Fatigue Syndrome shortly. The article, questionnaires, and scoring sheet are available online at www.cfstreatment.info , and will soon be available on www.aacfs.org and www.drlapp.net. Elke Van Hoof (Vrije Universiteit Brussel, Belgium) reported on how adolescents with CFS/ME perceive their social environment. She studied 27 Belgian adolescents (mean age 16 + 3 years), three-quarters of whom were female. Onset of illness was sudden in 48% of cases, and it took about 1½ years to receive a diagnosis. Only 22% were able to attend school full time, and more than half (52%) reported conflicts in school. One third (33%) got help from a teacher or classmate in order to keep up, 82% had to skip classes frequently, and 70% got failing grades. Forty percent were involved in extracurricular activities once in a while, but 48% experienced no activities outside of school. Van Hoof concluded that CFS/ME in adolescence can lead to social isolation, grades that fall below true capability, and poor attendance at school. Thus the adolescent with CFS/ME is vulnerable to a poor self image and low self efficacy. Poster Presentations Each year dozens of prospective papers are submitted to the scientific review committee for consideration. Typically the best papers are presented to the entire assembly, and less solid studies are relegated to "posters" in a side room or along the walls of the auditorium. This year the quality of papers was so good that several poster authors were asked to give a brief summary of their findings to the assembly. C. Lennartsson of the Karolinska Institute (Sweden) confirmed previous reports that low level interval training is well tolerated in CFS/ME. She was followed by Mark Van Ness (University of the Pacific) whose exercise physiology group measured metabolic and immune responses to exercise. They confirmed that maximum aerobic capacity (VO2 peak) was reduced in PWCs compared to sedentary controls (24.3 ml/min/kg compared to 31.4), and the oxygen capacity at the Anaerobic Threshold was also reduced. They introduced a new measure, DVO2 / D workload that is also much lower in PWCs than controls (7.7 in CFS/ME compared to 8.9 in controls, where <8 is clearly abnormal). Serum lactate was elevated in PWCs, suggesting an abnormally early shift to anaerobic metabolism. Pat Fennell (CEO of Albany Health Management) described a paradigm shift that she is seeing in the patient population, namely a shift from acute care to chronic care needs. She briefly discussed her Four Phase Model and the Wagner model of chronic illness management. She urged providers to focus on whether the patient is responding to therapy; whether psychological support is needed; whether disability was inevitable; and whether interventions were appropriately matched to the phase of illness. Garth Nicholson hypothesized that mitochondrial function is reduced in CFS/ME, and that replacement of essential mitochondrial lipids could improve mitochondrial function and reduce reactive oxygen species in the patient. In two studies, patients treated with glycophospholipids and "good" bacteria (NTFactor ™) reportedly achieved up to a 43% reduction in fatigue. Daniel Blockmans (Leuven, Belgium) reported a randomized placebo controlled crossover study of methylphenidate (Ritalin™), 20mg daily, in 60 PWCs. Subjects received either stimulant or placebo for 4 weeks, then treatment was crossed for another 4 weeks. Using the SF-36, the Hospital Depression and Anxiety Scale, and visual analog scales for pain, cognition, fatigue and other symptoms, Blockmans showed that stimulant medication improved fatigue and concentration significantly in 17% of cases. F. Garcia-Fructosa (Clínica CIMA, Barcelona) also provided a poster on the effect of modafanil (Provigil™, another type of stimulant) in PWCs. Modafanil was able to reduce daytime sleepiness by an average of 25% in 31 PWCs. However, 65% of patients reported some adverse effects (mostly anxiety, panic, irritability or palpitations), and 5 had to withdraw from the study. The drug did not interfere with sleep, however. Comment: We have also noted that PWCs with hypersomnolence and/or excessive daytime sleepiness respond very well to stimulant medications. Some report improvement in concentration and focus as well. In our experience adverse effects are usually mild if patients start with a low dose and build up slowly. Staci Stevens (Workwell, University of the Pacific) used the SF-36 survey to monitor post-exertional malaise after 10 minutes of exercise on a bicycle ergometer. Although patients and controls had similar results before exercise and 7 days afterward, it took controls only 1 day to recover, while no PWCs had recovered in 2 days and 50% required 5-6 days to recover. Kenny DeMeirleir (Vrije Universeteit Brussels, Belgium) reported that 20-25% of Belgians typically suffer with lactose and fructose intolerance, respectively, whereas 71% of PWCs have intolerance to fructose (fruit sugars, beans, cauliflower, cabbage, and yes, brussel sprouts). Lactose intolerance was similar (20%) in PWCs and the general population. Jonathan Kerr (St. George's University, London) has done extensive genomic and proteomic studies in PWCs. This time he reports on miRNA short non-coding RNA sequences that are produced in the nucleus, migrate to the cytoplasm, and regulate translation (cellular protein production). Studying 15 PWCs and 30 controls, Kerr found 4 unique miRNAs in PWCs. Paul Cheney reported that PWCs demonstrate evidence of diastolic dysfunction by tilt-echocardiography. This seems to confirm his previous finding of diastolic dysfunction on impedence cardiography, and is consistent with known deficiencies of mitochondrial or cellular energy in patients with CFS/ME and FM. Comment: Our office has obtained impedance cardiograms on at least 8 PWCs, and have seen only trivial diastolic dysfunction, a condition that is reported in even healthy individuals. Confirmatory echocardiography in several subjects (but not tilt-echocardiography) has demonstrated NO significant abnormalities. Genetic / Proteomics Session Suzanne Vernon, Human Genomics Team Leader at the CDC, defines genomics as the study of function and interactions of genetic material in the genome, including interactions with environmental factors. Genetics on the other hand is the study of a single gene. She then described several gene profiling techniques such as microarrays, gene chips, and RT-PCR. Such advanced techniques are used by the CDC and other to unravel the CFS puzzle. One of the most helpful techniques recognizes fine variations in the gene, known as Single Nucleotide Polymorphisms or SNPs (pronounced "snips"). For example, a health gene sequence of nucleotides may look like this to a geneticist: TGCCGAT… An abnormal gene may look like: TTCCGAT… That one small change is referred to as a SNP and can be used: (1) to understand who is predisposed to CFS/ME, (2) as a marker for the illness, or possibly (3) as a clue to a treatment. Certain polymorphisms are associated with specific groups. For example, Vernon and her group have been able to identify normal healthy patients, persons with general fatigue, and PWCs just on the basis of specific polymorphism patterns. PWCs have then been subclassified into several distinct, genetically defined groups. CFS/ME is difficult to study, however, because it does not appear to be controlled by a single gene, and the genes change over time (i.e. they are "epigenetic"). Proteomics is the study of intracellular proteins, particularly their structures and functions. While the genome is a rather constant entity, the proteome differs from cell to cell and is constantly changing through its interactions with the genome and the environment. Genetic Profiles in Severe Forms of FM and CFS was presented by Estibaliz Olano. She and her colleagues at Progenika Biopharma (Barcelona) hypothesized that persons with CFS and FM could be differentiated genetically. From a pool of 2000 subjects they assessed 186 women with FM and 217 women with CFS/ME. These subjects were stratified by special questionnaires into "severe" or "mild-to-moderate" cases. SNP profiling was able to discriminate the severe cases from less severe cases of CFS/ME. These SNPs were related to 6 major genetic areas that fit the clinical understanding of CFS/ME: COMT, THP, DOPA, 5HT (these genes control neurotransmitters) POMC (produces adrenocorticotropin, melanotropes, and melanocyte-stimulating hormone) Glucocorticoid and corticotrophin receptors Interleukins (cytokine production) NOS (nitrous oxide production) TNF (more cytokine production) Also 15 SNPs were identified that separated PWCs from persons with FM with 53% sensitivity and 95% specificity. Comment: This work by a commercial lab in Spain is consistent with findings from the CDC (see below) and other genomic studies. Such corroboration makes it more likely that genomics can help us understand CFS/ME/FM, and perhaps will provide a marker for these illnesses. M.S.Rajeevan reported results from one of the CDC genomic studies. This concluded that SNPs link CFS/ME to HPA axis dysregulation, immune dysfunction, and high levels of allostatic load (that is, chronic stress). 137 subjects were selected from the CDC's Wichita Hospital Study, and these individuals were able to be differentiated into 5 unique classes. Five genomic markers for glucocorticoid receptors were more common in PWCs than in persons with chronic fatigue alone and those who were not fatigued; there were 3 serotonin receptor markers that were associated with CFS as opposed to chronic fatigue or non-fatigued individuals. James Baraniuk (Georgetown University, Washington DC) studied the proteomics of CFS/ME. He defined a proteome as "a set of proteins in one cell, compartment or person." His hypothesis was that Central Nervous System dysfunction was common in CFS, FM, and Gulf War Syndrome, so abnormal proteins would probably appear in cerebrospinal fluid (CSF). He studied the CSF of 52 subjects, most of whom met international criteria for CFS/ME. In his first experiment, 10 proteins were identified as shared between CFS/ME and GWS, but totally absent from healthy individuals. The second experiment demonstrated that keratins (which are rare) and orosomucoids were seen in PWCs, but not in controls. Ten proteins found in the first cohort of PWCs matched the protein abnormalities in the second cohort. Baraniuk estimated that the chance of this occurrence was about one in one million! Baraniuk found proteomic evidence for: protease-anti-protease imbalance, structural injury, oxidant injury, vascular deregulation, leptomeningeal activation, and structural repair. In conclusion, the common "CFS-related proteome" in cerebrospinal fluid suggests shared pathophysiology in CFS, FM, and GWS. This proteome is NOT found in healthy control samples. Lastly, Frederick Albright (University of Utah) used geneology to provide evidence of a heritable contribution in CFS/ME. The Mormon geneology database includes 2.2-million Utah Mormon pioneers and their descendants over 10 generations, and health records have been linked to the geneology since 1994. Thus it is possible to follow the inheritance of CFS over at least 16 years. Albright identified 551 descendents with CFS (65% female, 35% male). He first hypothesized that if CFS is heritable, it should occur at higher frequency in close relatives of CFS cases. In fact, the risk of a first degree relative contracting CFS was 7.68X, while the risk for a second degree relative was 2.54X. This suggests that CFS is indeed heritable. The second hypothesis was that if CFS is familial, CFS cases should be more closely related than controls. Using sophisticated analysis, he demonstrated that case-relatedness was 4.13 units and control relatedness was 2.81, which was statistically significant. Thus CFS/ME appears to be familial as well as heritable. New Methods One of the most fascinating and practical papers was given by Akikazu Sakudo of Osaka University, where he works with H. Karutsune,Y. Watanabe, and others. Sakudo described using visible and near-infrared spectroscopy (which is typically used to examine fruit for ripeness and quality) to discriminate PWCs from normal healthy controls. Both serum scan and a simple scan of the thumb were obtained and then analyzed using "principal component analysis" (PCA) and "soft independent modeling of class analogy" (SIMCA) statistical techniques. The result was a clear separation of normal healthy persons from persons defined by international (Fukuda or CDC) criteria to have CFS/ME. Comment: This is like Star Trek! Using a simple handheld gun-like apparatus, Japanese researchers scanned a test tube of serum or simply scanned the patient's thumb, and immediately the Vis-NIR Spectroscope could predict whether or not the patient had CFS/ME. This technique takes less than one second to perform, and requires no skill on the part of the examiner! Although the spectroscope identified 100% of healthy individuals and 42 of 45 PWCs (93%), it is not known yet if the technique can separate PWCs from persons with other illnesses like MS, rheumatoid arthritis, and depression. If successful, this relatively inexpensive (US $3000-8000) and harmless device could provide rapid definitive diagnosis and finally silence the skeptics. [Thank goodness Vir-NIS spectroscopy can't treat, or I might be put out of a job by a machine!] Viral and Immune Interactions Viral infections have long been suspected as the cause of CFS/ME, but no infectious agent has ever been identified. A related viewpoint is that a virus may trigger CFS/ME, but then an abnormal biochemical change perpetuates the illness. This has been referred to as the "hit-and-run theory." Ron Glaser (Ohio State University) examined another possibility, that latent viruses (or even parts of viruses) could be producing abnormal proteins within the cells of our patients, causing immune dysregulation, cytokine production, and inefficient T-cell or NK-cell function. Viruses (or parts of viruses) can induce cells to manufacture proteins and enzymes, some of which may be injurious to the call. Glaser's group injected into mice an enzyme (dUPTase) that is encoded by the EB virus. Immune function and behavior were then monitored. Lymphocytes in the injected mice were less able to replicate, and the treated animals lost weight, had elevated temperatures, and were slow-moving. Glaser's group also elegantly demonstrated that stress and age affect latent virus activation. Geriatric patients, for example, had much higher titers of antibodies to Epstein-Barr Early Antigen (EA) and Capsid IgG (VCA-IgG) than young adults. And when antibody titers were measured in young students at various times during the school year, titers were noted to rise as much as four-fold during exam periods, and drop to more moderate levels during Summer vacation. Comment: This is no surprise to anybody who has experienced the recurrence of herpetic mouth ulcers or recurrent shingles (zoster) following periods of stress. The point, however, is that latent viruses (like VZV, EBV, and HHV6) can reactivate during periods of stress, causing immune changes and even symptoms of illness. Since EBV is an oncogenic virus, Glaser raises concerns that such reactivation could conceivably cause B-cell lymphomas. To my knowledge the latter has not been confirmed in CFS/ME. One question that arises frequently is, "Which test should we use to detect chronic reactivation of viruses such as HHV6 and EBV?" Dharam Ablashi (HHV6 Foundation, Nevada) pointed out that viral re-activation is more closely associated with CFS/ME than just titers of latent antibodies. He examined several techniques for measuring viral presence. Qualitative PCR on whole blood did not differentiate between active and latent infection, and there was too little virus in serum to make this assay useful. Active infection can be inferred by quantitative PCR, serum nested PCR, and analysis of cytopathic effect, but these techniques are difficult, expensive, and not readily available to clinicians. On the other hand, Ablashi provided evidence that highly elevated titers (>1:320 or 1:640) of commercially available IFA assays for IgG can be used to identify patients suspected of having active infection. Comment: Now we know that high titers of EBV or HHV6 IgG are likely due to reactivation, and possibly amenable for antiviral therapy. Susan Levine (private practice in NY City) and others measured IgG levels to HHV6 and early antigen titers of EBV in persons with CFS/ME. 45% of PWCs had titers of >1:320 to EBV and 35% had titers of >1:320 to HHV6, whereas none of 11 controls had such elevated titers. This suggests that a subset of PWCs suffer from chronic infections with EBV and/or HHV6. Cytokines are immunologically-based chemicals that can cause viral symptoms such as fever, sore throat, swollen glands, achiness, etc. Brian Gurbaxani (CDC, Atlanta) described a simple but helpful study that demonstrated increased levels of one pro-inflammatory cytokine, Interleukin 6 (IL6), in PWCs. His group demonstrated that increased levels of IL6 were proportionate to CFS/ME symptom severity, but also correlated with waist-to-hip ratio (one measure of allosteric load, or "stress") and C-reactive protein (CRP), which is a marker of inflammation. This finding supports the hypothesis that an ongoing inflammatory process could be contributing to CFS symptoms. John Chia (EV Med Research, California) reported on enterovirus infections in PWCs with GI distress. Enteroviruses (a genus of RNA viruses that includes echovirus, coxsackie virus, and poliovirus) have been reported in CFS/ME patients by the British, but have not been explored much in the US. Chia obtained gastric biopsies on 108 PWCs with upper gastrointestinal complaints plus 12 normal healthy subjects and 9 subjects with other GI disorders. 100 of the patient biopsies revealed at least mild chronic inflammation, of which 5 demonstrated infection with H.pylori. Eighty-six (86/108=80%) were positive for the VP1 (enteroviral capsid protein), while only 2/21 (10%) of controls were positive. Enteroviral RNA was detected in 5 of the 15 biopsy specimens studied (33%). Thus enteroviral infections may play a role in a subset of PWCs with upper gastrointestinal complaints. While the evidence is not as compelling as with other infectious organisms, Garth Nicholson (Institute for Molecular Medicine, Calfornia) and colleagues continue to report positive PCR results for Mycoplasma species in PWCs and Gulf War Syndrome victims. Additional Posters Tae Park (Seoul, South Korea) reported once again on his remarkable success in treating PWCs with one gram of intravenous gamma globulin weekly for 6 months. In addition Park attends to diet, sufficient salt and water intake, regular exercise, and sleep management. He reported on 50 patients (28M, 22F), all of who were severely ill and disabled with CFS/ME. Twenty-five of the 28 males improved enough to return to work (Karnofsky Performance Score from 40 to 90; Fatigue Impact Scale from 120 to 20-40). Eighteen of 22 females remarkably improved also (KPS 40 to 80; FIS 125 to 40-50). Comment: Four major studies using IVGG for the treatment of CFS/ME have shown variable results two were successful, two were not. Park has abundant and continued success with his regimen, but possibly his adjunctive therapy or regular IV fluid administration contributes to some of his success? Lastly, Jacob Teitelbaum (Annapolis Research Center, Maryland) provided a poster on his most recent vogue, d-ribose. Ribose is a sugar (not at all like table sugar!) that is used by the cell and specifically by the mitochondria in the production of energy. Other studies have suggested that d-ribose supplementation may improve cellular energy in heart and skeletal muscles. Teitelbaum's pilot study included 41 PWCs who took 5 grams of d-ribose thrice daily for about two weeks. Using visual analog scales, 66% of the patients reported significant improvement during the study, with an average increase of 42% in energy and 30% in well-being. Comment: If confirmed, this is great news! I am concerned, however, over the short treatment period, which is well within the placebo effect range. Also, subjective improvement is one thing, but do any objective parameters improve? Teitelbaum states that a randomized controlled trial is underway, so perhaps we will find out soon. Conclusions This was an excellent and exciting meeting, perhaps the best CFS/ME conference yet. Information was so overwhelming that two weeks later I am still trying to sort it out! It is clear from the number and quality of papers submitted that CFS/ME research is beginning to thrive, and that several other nations now rival the US in this field. Particularly productive this year were Japan, Belgium, Spain, Sweden and the United Kingdom. Two salient events during the conference were the IACFS vote to change the name to CFS/ME, and the introduction of the Pediatric Case Definition. I am sure that these recommendations will have both profound and positive consequences. There were several themes that ran through the conference: Researchers are looking more at specific symptoms such as fatigue, pain, and sleep, rather than the syndrome as a whole. Genomics and proteomics are clearly confirming previous theories of pathophysiology, and look hopeful as a means toward a marker for the illness, clues as to causation, and a way of subtyping subjects. As research becomes "deeper" or more molecular the differences between CFS/ME and FM are more distinct. The importance of subtyping is more recognized. At this time many researchers consider such subtypes as male/female, acute/insidious onset, severity, and whether fibromyalgia is present or not. The Center for Disease Control is strongly encouraging specific instruments for documenting symptoms, function, and compliance with the Fukuda Criteria, but these are not yet widely used. As a result, it is not clear what is meant when an author states that his subjects "meet international (or CDC) criteria." And clearly the concept of viruses or latent infections as perpetuators of CFS/ME are back in favor. So what have I learned personally that will aid me in diagnosis and treatment? First of all, I will recommend testing for elastase, RNaseL, C-reactive protein, selected cytokines, and NK Cell Activity, because they are objective markers of pathophysiology and severity, and they can monitor response to therapy. I will recommend a test-retest approach to cardio-pulmonary exercise testing, because it confirms for disability purposes reduced functional capacity as well as post-exertional malaise. I will recommend more overnight sleep studies because a majority of PWCs and PWFs have treatable sleep disorders that can be identified and monitored only by polysomnography. I will encourage a more multi-disciplinary approach, especially supportive counselors for those who are deeply depressed or catastrophizing I will look for lipid abnormalities and evidence of metabolic syndrome in our patients, and address these problems more aggressively. I will recommend exploration of chronic illness models (such as Bruce Campbell's Self Help Course) as a means for group counseling and support. While graded exercise programs may be too aggressive for many patients, interval exercise and heart-rate-limited exercise programs are safe and effective therapies. I will test more for HHV6a and EBV reactivation, and consider cautious administration of valgancyclovir and/or high dose valcyclovir. I will be recommending trials of acetyl carnitine, d-ribose, replacement lipids (such as NTFactor™), and antioxidants based on favorable reports presented at this conference. Charles W. Lapp, MD, Director Hunter-Hopkins Center, P.A., Charlotte, North Carolina January 29, 2007 The above information reflects the personal opinions of the author only, and is not meant to be an exact or exhaustive review of the IACFS conference. This material is copyrighted, but may be reprinted with permission of the author and with appropriate credit. Contact drlapp drlapp.net . (© 2007) [Return to top] ------------------------------ Date: Wed, 14 Feb 2007 14:12:34 +0100 From: "Dr. Marc-Alexander Fluks" <fluks@COMBIDOM.COM> Subject: RES,NOT: IACFS Conference report/Rosamund Vallings Source: Rosamund Vallings Date: February 12, 2007 IACFS Conference report ----------------------- I was privileged to attend the 8th IACFS conference in Fort Lauderdale, Florida from 10-14th January 2007. There was a larger number of presentations and attendees than at any previous CFS conference, and the quality of presentations and research achieved in the past 2 years was indeed exciting. The conference was ably organized and hosted by Dr Nancy Klimas, and thanks must go to her. This conference combined the research and clinical work which thus gave a good overview of all aspects of the illness. The days were long and intensive, but most people (even those with CFS) managed to stay the distance and there was so much to learn. The conference was truly international with participants and presenters from around the globe. FATIGUE SESSION The first session covered various aspects of fatigue. This was overviewed by Prof Y Watanabe from Osaka, Japan. He described about 1/3 of the population in Japan as suffering from fatigue; 42% due to overwork, 19% due to disease and the rest of unknown cause. There are 3 major bioalarm systems: pain, fever and fatigue, the latter being an important bioalarm to order rest. Fatigue is felt in the brain, and maybe acute, subacute or chronic. Various methods were described to study fatigue such as cortical function, behavioural, autonomic nerve function, biochemical markers in plasma and saliva and brain function with scans. The aim of such studies on fatigue is to develop likely therapeutic interventions and anti-fatigue programmes. Not only drug and dietary measures are being studied, but such issues as environment, aromas, animal (pet) intervention, creativity etc. Motivation helps to overcome fatigue particularly with creativity. S.Tajima (Osaka) presented a study using actigraphy showing that quality of sleep was decreased because of increased wake episodes during the sleep period. This leads to lack of para- sympathetic activation during the sleep period, and further deterioration of sleep quality in CFS. Complexity surrounding the word "fatigue" can be reduced by creating new terms to describe fatigue and this was outlined by N.Porter (De Paul Univ, USA). Results using the ME/CFS types questionnaire (MFTQ) showed that there are 5 types of fatigue associated with CFS: 1. Wired (overstimulated, tense, agitated), 2. Brain fog, 3. Molasses fatigue (heaviness) 4. Flu fatigue (immunological) 5. Post-exertional. This new classification of fatigue can help to study fatigue more thoroughly. E.Maloney (Atlanta, Georgia) confirmed the association between CFS and high allostatic load. Allostasis is the maintenance of stability through change. Environment, trauma, stress, behavioural response, genes and developmental experiences all have an effect on the physiological changes leading to allostatic load. 56% of CFS patients were found to have high allostatic load (females>males). Incidentally it was also found that those with CFS in this study in Georgia had a greater prevalence of metabolic syndrome. The greater the allostatic load the greater the prevalence of metabolic syndrome, and females with metabolic syndrome were 4 times more likely to have CFS than females without metabolic syndrome. Claims for disability in the USA in CFS have been limited by lack of a confirmatory test to establish a diagnosis. However an abnormal exercise stress test is an example of a laboratory test that can be used. M.Ciccolella (Stockton,CA) compared tests to show that results from serial exercise tests can be used to assess the effects of post-exertional malaise in CFS. It is concluded that a single exercise test is insufficient to demonstrate the extent of functional impairment in CFS patients. A second test 24 hours later showed that CFS patients had significantly worse performance and this distinguishes CFS from other illnesses. U.Hannestad (Linkoping, Sweden) investigated the possibility of abnormalities in excretion of GABA and -alanine in urine because of the sleep disturbance and fatigue in CFS, GABA being the major neurotransmitter in the CNS, and -alanine exerting inhibitory effects in the CNS. Increased excretion of -alanine was found in a small subgroup of the CFS patients studied. Urine may not be the best body fluid to estimate these chemicals however, and cerebrospinal fluid would be better if practical. P.Nestadt (New York,USA) compared brain metabolite levels between CFS with generalized anxiety disorder and healthy controls and examined the association of derived neurochemicals and psychiatric symptomatology. Previous uncontrolled studies had showed elevated lactate in the brain in CFS. This study showing a significant proportion of CFS patients had elevated ventricular lactate, and marked differences in hippocampal glutamate helped to distinguish between CFS patients with and without depression. Those with CFS also had significantly lower N-acetyl- aspartate in the right hippocampus, indicating reduced neuron density or metabolism. The role of alterations in apoptosis playing a role in post-infection fatigue states (PIFS) was addressed in a study using gene array techniques presented by T.Whistler (Atlanta,Georgia). The severity of an acute infection is related to the likelihood of recovery, and affects the fundamental cellular processes. These resultant altered gene expression profiles are manifest in several persistent symptoms in PIFS. This indicates that many symptoms maybe immunologically mediated. The genes work as a team and there are a number which overlap. An overview of the Fatigue Session was summarized by Fred` Friedberg. He discussed how we can measure fatigue using retrospective questionnaires may not relate to real time. Self report of physical function may not be "actual". In real time measures, subjects may not remember fatigue accurately, so physician visits and behavioural assessments are important. Use of palm pilots can give more accurate real time measures, and practice gives better recall for fatigue. In an actigraphic study over 2 years to assess functional improvement, the better a person's health, the less they reported fatigue having an effect on function, however despite spending less time lying down, they were still not actually better. There was global improvement leading to improved self report functioning which was likely to be due to improved coping ability. It is probable subjects were conducting their activities differently over time. Graded activity was not shown to increase actual activity ability, and there was no confirmation of improved symptoms. Fatigue and pain tended to increase after 30% of increased activity. More sleep time may lead to activity substitution. FATIGUE POSTERS The use of Heart Rate Variability (HRV) software was described by E.Stein (Calgary, Canada) as a useful in office diagnostic tool. HRV has been reported to show significant differences between CFS patients and controls. This software can efficiently distinguish between patients and controls. The severely ill patients were found to be 2SD `below the mean. S. Stevens (Salt Lake City,USA) found that for CFS patients post exertional malaise is an incapacitating feature of the syndrome. There is a delayed recovery response to exercise distinctly different from controls. Patients took on average 4 days to recover from the graded maximal cardiopulmonary test compared with one day for the controls. 50% required more than 5 days to recover. K. de Meirleir (Brussels, Belgium) found that fructose malabsorption is very common in their CFS patients. Lactase deficiency is less common, and equal to the level in the normal population. These conditions can lead to intestinal dysbiosis, and careful diet is therefore required. R. Van Konynenburg (Livermore,USA) claims to have found compelling evidence for glutathione depletion methylation cycle block as part of the pathogenesis of CFS, in a number of patients. He hypothesizes that the higher prevalence of CFS in women is due to genetic polymorphisms in certain enzymes involved in the metabolism of oestrogens. In a pilot study, J.Teilelbaum has treated 41 CFS and FM patients with D-Ribose. This has markedly improved many symptoms such as energy and sleep patterns. A larger RCT is planned. An overview of MCS was presented by P.Gibson (Harrisonburg, USA). She emphasized that there is need for further research in this little understood condition, which has a serious impact on quality of life. She also noted that there is a great lack of understanding of this condition by health professionals, and education is essential. A.Cusco-Segarra (Barcelona,Spain) has found the abbreviated environmental exposure and sensitivity inventory useful to detect MCS. The validity needs some fine tuning. A. Chester (Washington DC, USA) looked at the prevalence of patients with unexplained chronic fatigue and chronic rhinosinusitis. They are more likely to notice a sudden onset of fatigue. The presence of non-frontal headache was also more common than in fatigued patients without sinusitis. Decreased renal function (40-50%) was a frequent finding in a group of 15 CFS patients studied by T.Park (Seoul,Korea). His hypothesis is that CFS is a microvascular disease impacting individual organs. He notes that diabetics with renal vascular disease also complain of profound fatigue. Increased incidence of thyroid malignancy associated with CFS was outlined by B.Hyde (Ottawa,Canada) and he stressed the importance of evaluating for this, if suspected, by thyroid ultrasound and needle biopsy despite normal serum thyroid chemistry. Improvement in symptoms was reported in 6 out of 15 patients after administration of probiotics by A.Sullivan (Stockholm,Sweden). 8 patients were unchanged and one felt worse. Certain strains of lactic acid bacteria help to normalize the cytokine profile and have anti-oxidant effects. SLEEP SESSION An introductory overview of this session was given by J Shaver (Chicago,USA). Generally 1/3 of the population report poor sleep and are unrefreshed on waking. Sleep leads to mind/body recovery. There is no rule of thumb as to the amount of sleep needed, but the aim should be to function efficiently when awake. Sleep measurement was discussed, such as using self-report and polysomnography. Heart rate, leg movement and breathing could thus be monitored. Sleep can be affected by weak sleep drive, excess emotional or physiological arousal, poor synchrony of the light/dark cycle and negative sleep environmental conditioning. Therapy is aimed at: keeping attuned to the light/dark cycle; sleep restriction; behavioural cues, which include bedtime routine and avoiding incompatible cues and dampening of both cognitive arousal and physiological activation. She described various sleep disorders such as restless legs, periodic limb movement and breathing problems and also addressed issues relating to physical illness (such as CFS) and medication effects. Finally she mentioned that both growth hormone and prolactin release are lowered in fibromyalgia (FM), and the sleep disorders aforementioned are superimposed on the sleep deficit associated with FM. C. Lapp (Charlotte NC, USA) followed with a further sleep overview from a physician's point of view. He emphasized that dealing with sleep is one of the most important aspects of the management of CFS. He described a number of problems associated with sleep in CFS: Non- restorative sleep, difficulty in intiating and maintaining sleep, restless legs syndrome (RLS), periodic limb movements (PLMs), nocturnal myoclonus, vivid nightmarish dreams, "tired but wired", phase shift and dysania (foggy,stiff and sore on waking). The sleep may also be affected by primary sleep disorders (apnoea, periodic limb movements, narcolepsy) medication, FM, stress, depression and habituation. Sleep latency may also be increased and there maybe decreased sleep efficiency. In FM the sleep problems encountered include lowering of sleep efficiency and slow wave sleep, increased awakenings and K complexes in stage 2, and increased NREM intrusion. Lapp also described "Upper Airways Resistance Syndrome" (UARS), which is not as severe as apnoea, but leads to frequent arousal with slightly lowered oxygenation, more physical symptoms including low BP and mild eratic breathing. In one study of UARS, use of CPAP decreased physical symptoms by 40%. The approach to treatment should be to rule out primary sleep disorders, deal with patient's preconceptions and denials, emphasise sleep hygiene and consider CBT. Medication to be tried can include: melatonin, antihistamines and tricyclics. Dopamine agonists can be useful for PLMs and clonazepam can reduce restlessness and myoclonus. Reduction of pain is also an important issue. Non-restorative benzodiazepines, such as zopiclone should be avoided. Opiates will reduce short wave sleep and SSRIs may increase RLS. Alcohol should also be avoided. SLEEP POSTERS E. Van Hoof (Brussels,Belgium) found a number of sleep abnormalities as a result of a study in CFS patients. These include, sleep latency problems, -delta intrusion associated with anxiety, but RnaseL-ratio did not correlate with -delta patterns. The results therefore question RnaseL as a biological gradient. It seems that CFS patients may have a heightened perception of sleep dysfunction compared with controls. M.Matthias (Atlanta, USA) found that reports of sleep problems were reported more often in patients than controls experiencing sleep disorders. There was a negative correlation between perceived poor sleep and reduced activity scores in CFS. CLINICAL TRIALS SESSION. This session began with 2 presentations by B Hurwitz (Miami,USA). He covered the previous research showing that those with CFS often have diminished RBC volume due to normochromic, normocytic anaemia (NNA). His team have studied the use of erythropoetin- (EPO-) on RBC volume, fatigue and susceptibility to syncope during head up tilt (HUT) in CFS patients. Patients whose ferritin levels were non responsive to iron supplementation were excluded. Of the 57 patients studied, 66.7% were found to have low blood volume of up to 15% below normal. They looked at the CRP and serum interleukin-6. Pro-inflammatory cytokines have a secondary effect in reducing RBC volume, due to probable suppression of RBC production in the bone marrow. Hurwitz concluded from this study that fatigue in CFS patients with low RBC volume was not improved by EPO treatment, but susceptibility to orthostatic syncope was diminished in those subjects with more substantive EOP-induced RBC volume improvement. A preliminary trial by J Montoya et al (Stanford, USA) showed that Valganciclovir (over 6 months) was associated with positive clinical response in CFS patients with high antibody titres against HHV-6 and EBV. There was marked improvement in fatigue. This warrants a further double- blinded, placebo-controlled trial. This drug is active against all herpes viruses (including EBV and CMV) and is a well absorbed drug. There are potential haematological and renal side effects, and this drug should not be used in pregnancy. M. Lerner (Michigan, USA) had also conducted a Phase 1 clinical trial using valaciclovir or valganciclovir or both for 6 months in CFS patients with positive EBV or CMV titres, who had abnormal ECG T wave flattening or inversion. All 37 patients treated had a positive response with no serious side effects. However patients were encouraged to drink plentifully to avoid renal stone formation, and liver function tests and platelets were monitored. CLINICAL TRIALS POSTERS F. Garcia-Fructuoso (Barcelona,Spain) found modafinil effective in the treatment of daytime sleepiness in CFS. In a study of 31 patients, side effects were experienced by 67% and 5 patients (14%) withdrew from the study because of side effects. D.Blockmans (Leuven,Belgium) found that methylphenindate (2X10mg daily) was significantly better than placebo in reducing fatigue and concentration disturbance in a small % of CFS patients. Lipid replacement and antioxidant therapy for restoration of mitochondrial functioning with a nutritional supplement (NT Factor) was found by G.Nicholson (Huntington Beach,USA) to significantly reduce moderate to severe fatigue. T. Park (Seoul,Korea)used IV gammaglobulin 1gm weekly for 6 months coupled with strict diet (including increased salt), sleep (medicated) and exercise control and showed significant improvement in 50 CFS patients. Advice for dental procedures was outlined by W.Saldana (New York,USA) and she stressed the importance of the dentist being part of the treatment team. Attention must be given to pain management, analgesia, and risks of oral bacteria. R. Shoemaker (Pocomoke, USA) used low dose erythropoietin, in a short clinical trial, safely lowered symptoms and improved levels of C4a in responders. Maintenance of lowered C4a was associated with improved quality of life. Out of 60 patients, 51 noted symptom reduction, however 34 relapsed within 3 months. Another study suggested that the systemic inflammation in CFS caused by elevated C4a may be treated using erythropoietin and that the CNS correlates of cognitive dysfunction in CFS have an inflammatory basis. In a further trial, Tadalafil was used in 30 CFS male patients. This drug has been shown to lower elevated pulmonary artery pressure. This usually falls in response to exercise, improving pulmonary venous return to the atrium. In the trial the drug was found to safely reduce dyspnoea and improved exercise tolerance concomitant with an improvement in pulmonary artery response to exercise. 93% had changes in erectile behaviour. PAIN SESSION Pain was described as a major feature in many aspects of CFS by K.Berkley (Tallahassee, USA) in her overview of pain. It can be extremely disabling, interfering with sleep and causing fatigue. Alleviating sleep disturbances can alleviate pain leading to improved quality of life. Patients conceptualise pain like touch, and better understanding of the mechanisms of pain can make a difference for the individual. There is a pain matrix in the brain and the experience of pain occurs as a result of central processing via a network in the CNS. Multi responses may occur in different organs. Constant integration of information from the body by the CNS leads to planning and reorganizing of body actions. Pain is not a pathway, but a dynamic process. Using endometriosis as an example, symptoms of muscle hyperalgesia, interstitial cystitis and irritable bowel syndrome may become more prominent due to the endometrial growths developing their own nerve supply and sending more input into the CNS leading to cross system interactions. K.Kato (Stockholm, Sweden) looked at associations between chronic widespread pain and its co- morbidities, which included FM, CFS, IBS, etc in the general population. The associations are mediated by genetic and family environmental factors, and the extent of mediation via familial factors is likely to be disorder-specific. In these illnesses there are 2 latent distinct traits that` are common to all, but unique factors specific to each illness. Mechanisms and treatment for fibromyalgia and related conditions was further expanded by D Clauw (Michigan, USA). He described FM as being caused by a combination of genetics, various triggers, and mechanisms such as the relationship between physiological and psychological factors, disordered sensory processing (e.g. increased sensitivity to noise, smell etc) and autonomic/neuroendocrine dysfunction. There is a strong familial disposition. FM patients can be categorized into 3 groups according to psychological factors. Those whose psychological factors worsen symptoms have more tenderness, high depression/anxiety, are high catastrophisisers and have no control over the pain. PET and fMRI have both identified a number of brain regions (thalamus, amygdala and prefrontal cortex) involved in pain processing. There is good evidence to support the treatment of FM through education, aerobic exercise and CBT. Alternative therapies such as balneotherapy, hypnotherapy and biofeedback are moderately useful, but there is only weak evidence for use of other alternative approaches. There is strong evidence supporting the use of pharmacological agents such as tricyclics, SNRIs, and anticonvulsants, but doses should be increased very slowly. Tramadol and SSRIs are modestly helpful and there is only weak evidence to support the use of growth hormone, 5HTP, tropisetron or SAMe. There is no evidence for help from opioids, corticosteroids, NSAIDs, benzodiazepines, non-benzo hypnotics or guaifenesin. PAIN POSTERS A. Bested (Toronto, Canada) and A Logan (Harvard,USA) have written an excellent book "Hope and Help for CFS and FM" providing a useful tool for patients and professionals and covering a wide range of related topics. Sample copies were freely available. EPIDEMIOLOGY and CASE DEFINITION SESSION R. Herrell introduced the session by explaining the history and development of epidemiology and its application to study of disease in the 21st century. Use of modern statistical methods coupled with social and genetic epidemiology has furthered studies, identifying the aetiology of disease and determining interventions. Epidemiological studies by W Reeves et al (Atlanta, USA) compared those meeting the current criteria for CFS, with those with fatigue but insufficient symptoms (ISF) to be diagnosed with CFS and non fatigued controls, in an attempt to subgroup those with CFS according to their level of impairment and symptom severity, and to see if persons with ISF do resemble any of the CFS subgroups. Results suggested that a subset of those with ISF do have a similarly severe illness to CFS, but usually without at least 4 of the case-defining symptoms. A 10 year follow up by H.Kang (Washington, USA) of Gulf war veterans suffering from CFS compared to non-Gulf military peers, showed that the CFS symptoms decreased significantly in the Gulf compared to non-Gulf sufferers. R. Underhill (New Jersey, USA) found that the offspring of mothers with CFS also risk developing CFS or CF in childhood or later life. CFS occurred in 5.5% 0f the offspring. Most of the offspring were born before the mothers developed CFS. 24% of the mothers had an offspring with CFS. Recovery rates were 50% for CFS and almost 1/3 for CF. 1/3 of the mothers also reported they had a parent with CFS or CF. There were however 5 times as many healthy offspring as fatigued. There were no other significant additional risks if the mothers had other blood relatives with CFS. Monozygotic twin studies by A. Jacks (Stockholm, Sweden) using the non-affected twin as a case control, found that gene expression profiles can be explored efficiently. 35 pairs of twins discordant for CFS are being studied. Major co-variates such as depression, life events need to be considered, and full results of this important study should be available in 2008. A follow-up from 9/11 looking at unidentified somatic complaints and coping strategies was undertaken by B. Melamid (New York, USA). This may provide an opportunity to look for early symptoms of unexplained illnesses such as CFS. There was no significant incidence of PTSD reported. Tendency to depression and substance and alcohol abuse were reported depending on proximity to site, loss of loved one etc. Coping with "hope" (less depressed) or "avoidance" (more depressed) were significant predictors of depression. The economic impact of CFS on society in a community based versus tertiary based sample was discussed by L Jason (De Paul University, USA). In the USA there is a 27% reduction in employment attributable to CFS, with 19-27% receiving disability payments and 30% only able to work part-time. These indirect costs amount to about $17½ billion annually. The direct annual health costs for individuals in tertiary care are $8674 and in community care $2300. (This amounts to up to $7 billion annually). For non fatigued controls, annual health care costs $1132. The individual cost per person with CFS is equivalent to $25,000 annually. The rates of CFS throughout the world are variable with an incidence in the USA of 2-4 per thousand. This is equivalent to 800,000 to 1 million people. L.Jason had also studied the rates of CFS in Nigeria, the first community based study in a developing country. Estimate of prevalence was 0.68%, and future research with larger studies is now needed. In Iceland, E.Lindal (Reykjavik) showed different prevalence rates of CFS according to the criteria used. The Fukuda criteria yielded a rate of 2.2%. There was no significant relationship between present day sufferers and those who were in the 1947 epidemic. EPIDEMIOLOGY POSTER SESSION Timed Loaded Standing (TLS) could be a useful measure in the study of populations reporting chronic fatigue. In a study reported by G.Moorkens (Antwerp, Belgium) major differences were shown between patients who were chronically fatigued in Belgium and the Gambia. TLS involves measuring the time a person can stand while holding a 2 pound dumb bell in each hand with the arms at 90 degrees of shoulder flexion. J. Fernandez-Sola (Barcelona,Spain) found that 96% of patients diagnosed with MCS share the criteria for a diagnosis of CFS, and 25% also with that of FM. This suggests a common pathogenic mechanism. T. Osoba (West of England) is working to produce a new case definition of CFS prevalence, to improve the sensitivity, specificity and accuracy of selection of CFS cases. L.Jason (DePaul University,USA) concludes that following use of a broad theoretically driven questionnaire, one can more accurately identify the critical symptoms in CFS. Whether or not to exclude other diseases and the degree of impairment experienced by various groups was the subject of the poster by J.Jones (Atlanta,USA). The contribution of fatiguing illnesses in general needs to be addressed as a public health issue. B. Hyde (Ottawa,Canada) defined the illness in detail, outlining the course of the illness and those abnormalities which can be tested for. He outlined the advantages of the Canadian health system in allowing the physician the ability to order many technological tests at no expense to the patient. He outlined in a further presentation his longstanding historical involvement in CFS with visits to Iceland and Los Angeles. BRAIN FUNCTION SESSION The introductory overview was presented by G Lange (New Jersey,USA). She explained that the worse the results of tests of cognition, the worse the physical ability in CFS. Techniques for measurement included neuropsychological testing, brain imaging and spinal fluid analysis. These could be static e.g. static MRI, showing white/grey abnormailites and brain volume, or dynamic. Examples of dynamic tests are SPECT (cerebral blood flow), CT (absolute and quantatitive blood flow), PET (bloodflow as base and during tasks, cerebral metabolism), MRS (concentration of brain metabolites) Blood O2 Level-fMRI (non-invasive assessment of structure and function). The abnormal findings in CFS were outlined: 1. Neuropsychological - abnormalities in: visual/memory, psychomotor function, attention span, information processing. 2. Static studies - Possible white matter loss, abnormal bright patches. 3. Dynamic studies - Reduced relative and absolute cerebral blood flow in lat frontal, med temporal, brainstem and ant cingulate areas. Reduced relative and cerebral metabolism of glucose and acetylcarnitine. Abnormalities in seratogenic transmitter systems, specifically in hippocampus and ant cingulated. Reduced 5HT and N-acetyl aspartate receptor binding potential. Elevated lactate. These dynamic studies are consistent. Those with CFS appear to perform cognitively as well as healthy controls, but use more brain areas than the healthy to achieve. Speed of information processing seems to be the key deficit. 4. Spinal fluid - Higher protein levels and all results greater in those without psycholoigical diagnoses. Elevated Il-8 and Il-10. The work of the Spanish team headed by AM Garcia Quintana (Barcelona, Spain) was presented confirming abnormalities in cortical uptake, in all patients in the ant temporal and cingulate areas (prefrontal and inf frontal gyrus were also frequently involved), which correlated with elastase and RNaseL abnormalities in 38 patients. Information processing in CFS was shown to be prolonged in highly complex conditions by F.Togo (New Jersey, USA) after controlling for confounding variables. Depression had an additive effect in CFS, but does not explain the cognitive dysfunction in CFS. CFS patients have to work harder than healthy people to achieve same results. J. Mark VanNess (Salt Lake City, USA) showed that CFS patients had slower reaction times compared to sedentary controls. This was compounded by 30 minutes exercise and 24 hours later, the CFS patients had definite persisting significant deficits. Occupational disability assessments need to include an exercise test and neurocognitive testing as validated by E Van Hoof (Brussels, Belgium). The brain function session was summarized by H.Kuratsune (Osaka,Japan) with an overview of Japanese results. CFS has been shown to have an enormous economic impact in Japan costing the nation 10 billion$ annually. Their hypothesis is that neuro-molecular mechanisms lead to chronic fatigue. Brain dysfunction, metabolic abnormalities, reactivation of viruses, immunological abnormalities and HPA abnormalities are being studied. PET is found to be more sensitive than SPECT and have better spatial resolution. Brain acetylcarnitine uptake is abnormal in CFS, there is reduced binding power of 5HT in ant cingulate cortex (correlating with the pain score) and a number of abnormalities with reduced responsiveness on fMRI are an essential feature of CFS. BRAIN FUNCTION POSTERS J. Mark VanNess (Salt Lake City,USA) demonstrated significant metabolic abnormalities in CFS during exercise. There was consistent oxidative dysfunction, lower oxygen consumption and both peak and anaerobic threshold were down. There was no difference in glucose or lactate response. However RNaseL ratio and elastase activity failed to show any differences between the CFS patients and controls. J.Alegre-Martin (Barcelona,Spain) showed there was decreased functional reserve and decreased aerobic power following an exercise test in CFS patients. Neuropsychological study also showed there was considerable cognitive deterioration, and a difference in processing between right and left hemispheres was also observed. There was an association between monocyte RNaseL and elastase suggesting involvement of elastase in the genesis of CFS and elastase inhibitors may have therapeutic implication. That patients with CFS showed slowed cognitive and fine motor processing of visual stimuli leads to the consideration of psychomotor functioning being an interesting variable to consider in further neurobiological research, according to G. Moorkens (Antwerp, Belgium). P. Cheney (Ashville,USA) found an 81% incidence of patent foramen ovale in CFS (normal 10- 15%). The PFOs in CFS ca be modulated up and down supporting a defect in handling of oxygen by products in CFS similar to that seen in fetuses. BEHAVIOURAL HEALTH SESSION E. Stein (Calgary, Canada) gave an excellent overview of the behavioural health interventions in CFS published over the past 10 years. She described ME/CFS and FM as being chronic conditions requiring long term management, and although both have high rates of psychiatric comorbidity, neither is considered to be a psychiatric disorder. Because medications have not been shown to give significant benefit longterm, behavioural interventions have been considered relevant. Early CBT/GET models were based on the assumption that acute illness behaviours were causing or perpetuating CFS. But the only positive CBT study (defined by Fukuda criteria) was in adolescents. Some exercise studies have shown decrease in fatigue, but no studies have shown the effects of exercise or CBT on symptoms other than fatigue or general function. And no study has looked at the effects on the severely ill. In FM, less than half the studies using CBT/GET have resulted in improvements in pain, mood or health and by one year many of the effects have worn off. Interventions in other types of chronic disease have different objectives and the Stanford model for self management is widely used. The aim is to help rather than treat or cure. The programme includes: exercise programme, cognitive symptom management, nutritional change, sleep and energy management, medication, community resources, emotional management, training of health care professionals. In a 2 year follow up for mixed chronic conditions, there was generalized improvement in self-rated health with reduced disability and fatigue. Self efficacy and acceptance of the illness are important. Suicide is the 3rd leading cause of death in CFS (others being cancer and heart disease) and "hope" based interventions for self management should include re- evaluation of life goals and priorities. Medical education was the subject of a presentation by F.Friedberg (Stony Brook, USA). 31 fourth year medical students doing their psychiatry rotation attended a 90 minute seminar on the management of medically unexplained illnesses, exemplifying CFS and fibromyalgia. A modified version of the CFS Attitudes Test was administered before and after the seminar. A significant improvement in attitudes towards CFS was found, particularly in relation to favouring more federal funding for CFS research, employers providing flexible hours for those with CFS and disability issues associated with CFS. Even at initial assessment, the students felt it was important for physicians to understand CFS and that patients are not to blame for getting sick. This brief exposure to factual information about CFS and fibromyalgia was associated with more favourable attitudes towards CFS in fourth year medical students, and the encouraging discussion following presentation of this paper will hopefully lead to more input into medical education. P. Fennell ( New York,USA) discussed behavioural health with a CFS perspective. She noted that there has been a paradigm shift in medicine towards study of chronic illness. 1/3 of doctor visits are for chronic illness, 2/3 deaths are caused by chronic illness and 78% of medical care expenditure is for chronic illness. There are 4 groups of chronically ill: 1. traditional (eg CFS, asthma, lupus) 2. Acute illness survivors (eg post-cancer) 3. Persistent acute illness (eg stroke, HIV) 4. Natural aging. Innovations in chronic care include health care corporations, pharmaceutical companies, federal government and chronic care models such as the Stanford model. The Fennell stage/phase based model is useful in CFS as illness changes over time and the patient needs to cope with change. Medical practice needs to be matched to the phase to improve compliance. BEHAVIOURAL POSTERS The Cog-health test is a short self administered computerized test sensitive to cognitive change and can be a useful tool is assessing cognitive function in CFS and related conditions. A. Cusco- Segarra (Barcelona,Spain) found that using this tool, cognitive function was impaired in CFS and MCS, but not in controls or FM. C. Lennartson (Stockholm,Sweden) showed that low intensity training may be a safe start for physical activity without exacerbating symptoms in CFS. There were social and emotional benefits too. The Four-Phase model was again described by P Fennell (New York, USA) as a tool for clinical case management to help improve coping, alleviate stress, enhance decision making and target interventions in CFS patients and caregivers. This approach can also be useful for victims of disaster. The four-phase model was also shown to be a useful adjunct to the model of human occupation (MOHO) by J.Burke (New York,USA) and can offer an effective treatment option. The team headed by T.Matsui (Osaka, Japan) found that CFS patients are not as severely depressed with perfectionism traits as those with depression alone. But CFS patients were more anxious and showed more maladaptive coping behaviour than the depressed patients. A small pilot study by J.Donalek (Chicago, USA) looking at the impact of CFS on the family with family experiences having to be reshaped, provided food for thought, and it is hoped this study will be enlarged. L.Till (de Paul, USA) describes a buddy system that could prove a useful support system for those with CFS, providing companionship and practical assistance. D.J.Benet (Atlanta, USA) outlined an educational programme for primary care providers as a result of collaboration between government organizations and patient advocacy groups There was a further intervention programme for medical students described by T.Lu (Loyola,USA). The aim is to assist future physicians with diagnosis and treatment of CFS as well as providing encouragement to see more patients with this illness. The trend in publishing of CFS literature over the past decade was reviewed by F.Friedberg (Stony Brook,USA). The output of peer reviewed CFS literature has not increased, but articles on FM and non-CFS fatigue have increased substantially. Exercise intolerance in CFS is evident in a study by C.Ruud (Amsterdam, Netherlands). When CFS patients are subjected to increasing exercise, and compared to controls, there is a lower anaerobic threshold and a state of malaise comparable to overtraining. Physical functioning was also shown to be improved in one woman by the daily IV infusion of 1L of 9% saline over 18 months. Cessation led to reduced function. L.Travis (Salt Lake City, USA) hypothesized that saline increased blood volume and/or augmented autonomic activity. PAEDIATRIC SESSION The paediatric session, introduced by L Jason (Chicago, USA) and D Bell (Lyndonville, USA) focused particularly on the new paediatric case definition, which has been produced by a working group over the past 6 months. For a diagnosis of paediatric CFS, the following 5 classic CFS symptom categories must occur: post-exertional malaise; unrefreshing sleep or sleep disturbance; myofascial pain, joint pain, abdominal pain and or head pain; two or more neurocognitive manifestations; and at least one symptom from two of the following three subcategories: 1. autonomic manifestations or 2. neuro-endocrine manifestations or 3. immune manifestations. The diagnosis can be made after 3 months of persistent or relapsing chronic fatigue that is not a result of exertion, is not substantially relieved by rest and results in substantial reduction in previous levels of educational, social and personal activities. This new paediatric case definition should lead to more appropriate identification of children and adolescents with CFS. A paediatric health questionnaire has been produced with adult and child versions, to be filled out jointly by the child and/or caregiver. Exclusionary criteria include past and present psychotic disorders of any variety, current anorexia or substance abuse. Treated depression is not exclusionary. A panel discussion then followed focusing particularly on paediatric prognosis. D Bell (Lyndonville,USA) had done a 15 year follow up (from 1985) showing that 80% were "well" with 50% of these normal and 50% well but leading limited lives. 20% were still considerably impaired. K.Rowe (Melbourne, Australia) found 60% well at 5 years, 20% nearly better and 20% at about 50% normal. In Japan 75% were described as well at 5 years by T.Miike (Kumamoto,Japan). A paper then presented by K Rowe (Melbourne, Australia) found that of 87 young women at a Melbourne adolescent CFS clinic, 61% had complained of debilitating pain during menstruation, compared to 40% of recovered patients. A 3 month study on 7 young women confirmed significant worsening of CFS symptoms associated with their severe dysmenorrhoea. All responded well to treatment with a combined oral contraceptive pill following an unsatisfactory trial of non steroidal anti-inflammatory medication. Subsequently 56 young women have responded well to oral contraceptives, mostly used continually, with relief of symptoms and improvement in functioning with regard to CFS. This raises the hypothesis that inflammatory cytokines from the uterus may exacerbate CFS symptoms in conjunction with dysmenorrhoea. A study of perception of social environment by adolescents with CFS particularly in relation to school was described by E Van Hoof (Brussels, Belgium). 52% of 27 adolescents with CFS reported conflicts at school, 22% attended school fulltime, 82% had stopped some courses. 48% reported having few friends. She stressed that the diagnosis should be considered as early as 1 month after onset, and this study showed an average of 18 months before a diagnosis was made. C Van der Eb (Lake Bluff, USA) described an adolescent self management protocol, which showed promise as a strategy to help adolescents with CFS to adjust activity/rest and cognition to facilitate symptom management and be more able to participate in normal teenage pursuits. PAEDIATRIC POSTERS No link could be confirmed between the putative symptoms of "hypoglycaemia" and documented blood sugar levels, according to research by F.Cameron (Melbourne,Australia). A number of symptoms maybe attributed to a diagnosis of "hypoglycaemia', but special diets are not likely to be of benefit therefore. E.Van Hoof (Brussels,Belgium) said that as skepticism is often associated with a diagnosis of CFS, parents maybe accused of neglect or abuse. A case study indicating the mistrust and dismissal experienced by some families illustrated this and tragically Munchausen by proxy can be mistakenly diagnosed. GENDER ASPECTS of CFS SESSION B.Evengard (Stockholm,Sweden) gave an overview of gender health. She discussed 3 aspects: Reproductive health (eg breast and prostate cancers); biological differences (eg myocardial infarction) and gender neutral diseases (eg psoriasis) However in gender-neutral diseases treatment can be gender-different. She cited the management of psoriasis in a hospital clinic where treatment was quite different for the sexes with females getting more creams and males more phototherapy. IN CFS more females than males get this illness, and this could be a biological difference or a social (gender) difference. Gender is a social construct. In research men and women should be divided and study design reconsidered. She finished by quoting a Mr Trevis: "It is unethical, unintelligent and uneconomical not to work with gender issues". Gender, sexuality and intimacy are secondary to the clinical encounter in CFS patients according to P Fennell (New York, USA), but should be given equal weight. They can adversely affect assessment and treatment. The illness may affect the mechanics of sex exertion, libido and psychological aspects are all involved. Sexual relationships do change over time and in an illness such as this, patients may need to learn to touch again, to achieve fulfillment. Addressing issues based on gender were further reiterated by L Bateman (Salt Lake City, USA). For women, chronic illness is generally more common and women may not be taken as seriously as men. However thinking of CFS as a "women's" disease may delay men seeking help for CFS. Coping styles may vary between men and women and both male and female spouses carry a heavy burden in many ways. Intimacy issues and issues associated with disability insurance may be different. In the area of research, gender differences may affect test results and disease process, and choice of case definition may affect gender demographics and alter generalizations made about gender. Comorbid mood states, coping behaviours and stress factors may vary by gender as well as subgroup. HPA axis, autonomic nervous system and immune function are affected by gender in complex ways and there is little gender-specific CFS research. By being more aware of gender issues, better clinical care maybe possible together with better understanding of this illness. GENDER POSTERS 2 studies were presented by C.Javierre (Barcelona,Spain) and concluded that in a large group of women compared to healthy female controls, those affected by CFS showed a worse response with lower efficiency to light intensity exercise. Reduced ventilatory efficiency in CFS maybe responsible for a lower PCO2 in blood, associated with weakness and post exertional distress. CARDIOVASCULAR PRESENTATIONS A.Suarez (Barcelona,Spain) looked at cardioventilatory response in a group of 135 CFS women compared to healthy controls. The control group scored 52% higher with workload in maximal test, with O2 uptake 47.5% higher. However in a further supramaximal test after a 5 minute rest, the CFS subjects were able to increase their responses considerably. Diastolic dysfunction in CFS patients is reported at a level well above that for control populations of the same age according to P.Cheney (Ashville, USA). This supports the hypothesis that CFS is a syndrome of cellular energy deficiency. Tilt-echocardiography provides amplification of often masked diastolic dysfunction in patients known to be sensitive to head-up tilt. He cited the possibility of an associated cardiomyopathy as previously described by Natelson and Peckerman. V.Spence (Dundee, Scotland) showed that CFS patients have significantly increased levels of plasma hs-CRP, F2 isoprostanes and oxLDL that correlate positively with arterial stiffness. CRP was a strong predictor of arterial stiffness conferring a significantly increased risk of a future cardiovascular event in CFS patients. GENETICS/PROTEOMICS SESSION A summary of the current state of genomic science relating to CFS was presented by S.Vernon (Atlanta,USA). Genetics is the study of the genes and genomics covers the function and interactions of all the genetic material in the genome. Biologic samples for these studies can be blood, saliva and urine. The analysis includes classical statistics, data mining and pattern recognition, machine learning and multidimensional approaches. Data integration refers to the integration of different types of data and differential analysis techniques. The focus should be on the blood, with 5 litres circulating and blood cells being the sentinels of the disease process. The plasma also has proteins from throughout the whole body. There is dynamic traffic between the blood and the brain. Genomic technology involves profiling by micro-array, gene chips, reverse transcriptase-PCR. Mass spectroscopy is used for protein. Differentially expressed genes are not always the same in various studies, but there is overlapping of pathways and correlation with CFS symptoms. It is possible to subtype CFS genetically. By using gene technology, it is possible to understand who may develop an illness. Genes may also serve as biomarkers, and pharmacogenetics can lead to treatment. F.J.Garcia-Fructuoso (Barcelona, Spain) was unable to present his work in this field owing to illness, but his team emphasise that CFS and FM are 2 genetically distinguishable illnesses, with CFS being an exclusion diagnosis for FM. A fascinating study using the Utah Population Data Base to explore a genetic contribution to CFS and associated disorders was presented by F.Albright (Salt Lake City,USA). They used 3 techniques looking at risks for CFS in relatives, relatedness among CFS patients and identification of high risk CFS pedigrees. First degree relatives share many environmental risks and exposures (relative risk 7.68); but in second degree relatives this is less of a factor (relative risk 2.54). This suggests a genetic component. It is hoped this study will lead to gene identification predisposing to CFS and related conditions. The sex difference observed in CFS indicates a role for oestrogen and oestrogen receptors for disease development and this issue was addressed by B.Evangard (Stockholm, Sweden). Reduced ERbetawt expression is consistent with an immune mediated pathogenesis of CFS. She said that a possible connection between oestrogen, oestrogen receptors and CFS needs to be further evaluated, particularly as estradiol and progestin improve health status in CFS and there is also improvement in pregnancy. J.Baruniuk (Washington DC, USA) obtained genetic samples from the cerebrospinal fluid of 52 patients with CFS, FM and GWI and compared with healthy controls. 5 proteins were predictive of CFS and were absent in the healthy controls. The specific CFS-related proteome suggests a common pathophysiology for these related illnesses, and detection of at least one of the proteins is predictive of CFS. However the research presented by E.Aslakson (Atlanta,USA) showed that a more complete enumeration of altered pathways demonstrated distinct and differing altered biological pathways among CFS subjects, further demonstrating the heterogeneity of CFS. J.Kerr (London,UK) outlined his team's research. The precise gene signature and metabolic pathways need to be identified. The utility of genomics/proteomics can involve inheritance, pathogenesis and diagnosis. Molecules of interest include DNA, RNA and proteins and there is potential for future study of lipids and glycans. Predispositional genes for CFS have been identified associated with Q fever and parvovirus B19. Micro-array techniques are used and immune response, several mitochondrial genes and gene protein signalling are considered important. Studies include: 1.TNF found to be elevated in subgroups of CFS. Etaneacept is a potential treatment. 2. Cerebrospinal fluid proteome. Proton MRS of brain. 3. Urinary excretion of GABA. 4. Serum analysis using new infra-red spectroscopy. This could lead to a diagnostic test. 5. Infection is known to be important, so 28 possible microbes are being studied. Kerr emphasized that this illness is a result of psycho-neuro- endocrine-immune interaction. GENETICS/PROTEOMICS POSTERS S.Mangalathu (Atlanta,USA) described sequence variations in certain genes involved in the regulation of the HPA axis and seratonergic system associated with CFS, allostatic load index and particularly with a CFS subgroup characterized by low HR variability and low urinary free cortisol. These tests need further validation with larger sample size. R.Petty (London,UK) hypothesised that CFS patients may exhibit a miRNA gene signature and tested this by microarray in 15 CFS patients compared to healthy controls. It is hoped that knowledge of the miRNA gene signature of CFS will aid our understanding of the pathogenesis and lead to treatment development. This team, headed by J.Kerr are close to final details. Significantly differentially expressed genes have been identified in a female patient group with gradual illness onset and no previously documented infection. This work presented by H.Grans (Stockholm,Sweden) stressed the importance of subgrouping CFS patients. G.McKeown Eyssen (Toronto,Canada) postulated that impaired metabolism of toxic chemicals maybe the mechanism underlying MCS. A genetic predisposition for MCS may involve altered biotransformation of environmental chemicals. A gene-gene interaction between CYP2D6 and NAT2 (common polymorphisms) suggests that rapid metabolism for both enzymes may confer substantially elevated risk. B.Burke (London,UK) investigated human gene signatures of past persistent microbial infections in unstressed normal blood donors, to consider possible relevance to the pathogenesis of CFS. This work may provide insight into the role of persistent and pre-existent infections in the pathogenesis of subsequent disease development. NEW METHODS FOR EVALUATING FATIGUE SESSION This session was coordinated by the Japanese Association for Fatigue Sciences. The first presentation was given by A.Sakudo (Osaka,Japan) showing that Vis-NIR spectroscopy (a non- invasive technique) for sera combined with chemometric analysis is a promising tool to objectively diagnose CFS. T.Sugino (Wakayama,Japan) discussed the reactivation of HHV-6 and HHV-7 in saliva during fatigue states. Reactivation of HHV-6 relates to extra work load in CFS, while reactivation of HHV- 7 relates to the actual fatigue state in CFS. These viruses have lifelong latency and HHV-6 establishes complete latency in peripheral blood macrophages, and when reactivated is shed directly into the saliva. Reactivated HHV-7 is amplified in peripheral T cells. Virus shedding is influenced by immunological status. Application of DNA chip for fatigue assessment was outlined by K.Rokutan (Tokushima, Japan). Only 2.5ml of blood is required for samples. 9 CFS genes have been identified by PCR and micro- array. The identified genes may be important for subgrouping CFS. Several of the Japanese researchers mentioned an anti-fatigue substance prescribed in Japan. This was D-Ribose. VIRAL & IMMUNE INTERACTIONS and HEALTH SESSION Symptoms observed in CFS are compatible with viral aetiology, and it is possible that CFS is associated with endogenous latent viruses. This was the basis of the talk by R.Glaser (Ohio, USA). Psychological stress is implicated in CFS, which in turn can modulate the expression of several latent herpes viruses including EBV. It has been shown too that the immune and endocrine systems "talk" to each other via receptors. Latent viruses such as EBV and HHV-6 may induce immunopathology by synthesizing viral protein in latently infected cells or in cells in which the virus genome is only partially expressed. These proteins could then induce immune dysregulation with effects on cytokines and chemokynes and/or T cell or NK function. It is difficult to link a specific virus to CFS if the viral reactivation is incomplete, as virus DNA would not be synthesized. Glaser's team have shown that EBV encoded dUTPase is able to induce immune dysregulation and associated symptoms in mice. This suggests that at least one protein of the EBV early antigen complex can induce immune regulation and maybe involved in the pathology of EBV-associated disease. Also from Ohio, M.Wiliams discussed the issue that HHV-6 U45 protein is not a functional dUTPase, but it does induce immune dysregulation similar to EBV-encoded dUTPase. D Ablashi (Santa Barbara, USA) described assays that can now be used to detect chronic reactivation of HHV-6 and EBV. It is vital to be able to distinguish between chronic, active and latent infection with these viruses. Studies have shown that there is a positive association between active HHV-6 and EBV and CFS. Many viruses could be implicated. RNase-L was also found to correlate with HHV-6 infection in CFS (67% concordance). The possibility of antiviral agents being effective was discussed. Cidofovir, foscanet, ganciclovir and valgancoclovir all have potential. Studies with acyclovir have proved negative, but both ampligen and isoprinosine can be useful. Amantadine, red-mauve algae and lamotrigine have all shown promise in vitro. GWI and CFS were compared immunologically by M.Fletcher (Miami, USA). Perforin is a molecule in cytotoxic lymphocytes necessary for killing and is found to be low in both illnesses. NK cell function is low in GWI and moderately low in CFS. CD2 and CD26 activation is high in GWI and moderate in CFS. CD26 cleaves neuropeptide-Y (NPY) and there is significantly reduced NPY in the plasma in GWI but not significantly in CFS. Further studies are underway. B.Gurbaxani (Atlanta,USA) detected elevated Il-6 in the resting state in CFS patients (compared to controls) suggesting that proinflammatory cytokines could be contributing to symptoms and a potential cause or effect of CFS. Il-6 correlates well with CRP and has a negative correlation with cortisol. The incidence of HHV-6 and EBV infection in CFS was further discussed by S.Levine (New York, USA). Their team tried to determine if there were biologic markers of active, chronic viral infection in CFS patients compared to healthy controls. Evidence suggests that there is a subset of CFS patients suffering from these infections. Quantitative PCR in plasma is not useful as there is very little free virus in the plasma, and neither is PCR in PBMCs without a threshold, as it detects both latent and active virus. However serological assays (IgG to HHV-6 and EBV early antigen) are useful as long as a high threshold is used. M.Murovska (Riga,Latvia) presented results of a study in Latvia of CFS and a possible association with HHV-6 and HHV-7 infection. This study also included symptomatology and occupation of patients. She had found that the rate of CFS morbidity is associated with professional activity and amount of intellectual work. Both viruses may be involved in the aetiology of CFS and reactivation may provoke immunodysfunction. Because many CFS patients have persistent or intermittent gastrointestinal symptoms, J.Chia (Lomita, USA) evaluated the presence of viral capsid protein-1 (VP1) and enteroviral RNA in stomach biopsies. These were detected in a number of the biopsies of CFS patients with chronic abdominal complaints, compared to none in controls. G.Nicholson (Huntington Beach, USA) discussed the chronic bacterial co-infections found in CFS. These included evidence of high incidence of systemic mycoplasmal infections of various types and a tendency for those with multiple infections to have more symptoms. Lyme disease, rickettsia and protozoal infections could all be implicated. The ticks causing transmission of Lyme disease may transmit a wide range of infections as well as B.burgdorferi, including mycoplasma, bartonella and ehlicia. This whole session was summarized by A.Komaroff ( Harvard, USA). He reviewed the immune abnormalities which have been demonstrated in CFS. These include activated CD8 (T cells), poorly functioning NK cells, abnormalities in the 2-5A pathway (RNaseL ratio), cytokine abnormalities (proinflammatory dysregulation), increased TGF and 27 times more circulating immune complexes than in controls. Many infectious agents have been cited as implicated such as EBV, Lyme, parvovirus, enteroviruses, Q fever, RRV, mycoplasma, HHV-6 etc. There is evidence for reactivation of HHV-6 and EBV, although the case is not entirely solid as yet. HHV-6 has been shown to infect neural and glial cells and persist in the CNS. It can cause encephalopathy and demyelination and is associated with MS and possibly seizures and cerebral palsy, although these are provocative studies. It is important to distinguish the active from the latent forms. Over the past 10 years there has been increasing evidence that infection is most likely to be a prime cause of CFS. VIRAL/IMMUNE POSTERS A national ME observatory with funding from lottery is being established in the UK. D.Pheby (London,UK) outlined the proposal and they will include various research studies with a vision of advancing science. J.Mikovits (Incline Village, USA) looked at HHV-6 and its intergration into host cells, and this study will contribute to an understanding of whether this virus contributes to CFS, malignancy and immunodeficiency associated with these conditions. Of 40 patients studied, 3 were positive to CIHHV-6. A.Vojdani (Los Angeles,USA) stressed the importance of screening for Lyme disease and other related disorders due to overlapping symptoms. In vivo-Induced Antigen Technology is a new technique described which identifies pathogen antigens that are immunogenic and expressed in vivo during human infection. Cryptostrongylus Pulmoni is a worm found in the sputum of 63% of CFS patients in a study by L.Klapow (Santa Rosa, USA). Retention of infected larvae leading to chronic auto-infection is a possibility in CFS. Larvae could also migrate from the intestines and back into the lungs. If this is occurring, inhaled anti-roundworm medications would seem logical. N.Klimas (Miami, USA) reported a dramatic significant increase in the number of NK cells (X4) in peripheral blood following an exercise challenge in GWI. T cells also increased (X1.5), and both sets of cells had returned to baseline at 4 hour follow up. There was no significant effect of the exercise on the actual percentage of activated T cells and NK cells or in the number of molecules per NK cells. Visible and near-infrared spectroscopy was used by Y.Hakariyal (Osaka, Japan) for diagnosis of SLE with fatigue similar to CFS. SLE was detected in 85.7% SLE patients, and differentiated between anti-phospholipid (aPL) positive and negative patients. CFS can be discriminated from SLE and aPL. B.Evangard (Stockholm, Sweden) compared the composition of intestinal microflora in CFS patients when in the acute phase of the illness. Increased levels of c.albicans were found and may prove a useful marker for ecological disturbance and contribute to symptoms. Future research is thus warranted. Chronic enteroviral infection may be implicated in the cause of CFS. J.Chia (Lomita, USA) postulated that further viral studies could lead to the use of antiviral agents directed against viral RNA polymerase. Their team showed there was improvement in symptoms in EV positive CFS patients treated with -interferon and ribavirin or combined - and -interferon. D.Strayer (Philadelphia, USA) did a meta-analysis of 2 trials of ampligen and found it was generally well tolerated in CFS and provided significant improvement in exercise duration and concomitant medication usage when compared to placebo. Active infection with CMV maybe detected in patients with life-altering fatigue and this maybe useful guidance in making a diagnosis and use of antiviral treatment. M.Lerner (Detroit, USA) described use of IgM serum antibodies to CMV nonstructural gene products p52 and CM2. Data produced in one study to check cytokine patterns in CFS did not support a Th2 cytokine bias. S.Repka-Ramirez (Utah,USA) did a study using nasal lavage to check mucosal immunity and eosinophilia to test their hypothesis. Comparing CFS patients, FM patients and controls by L.Bazzichi (Pisa, Italy) looking at antipolymer antibody seroreactivity, it was shown that seroreactivity was higher in CFS than FM or controls. Cytokine levels were not significantly different between CFS and FM. The whole conference was finally summarized by Prof Anthony Komaroff and he is encouraged by the wealth of new research presented and the exciting developments we have seen in the understanding of this illness over the past decade. The future certainly bodes well for CFS. Dr Klimas was thanked for her hard work in bringing such an excellent conference together, and members of the IACFS were encouraged to vote towards a name change for the organization to the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyopathy quite a mouthful, but a true reflection of the organisation's international status and more acceptable options for the name of the illness. I must thank the ANZMES for their help in enabling me to attend this very worthwhile event. -------- (c) 2007 Rosamund Vallings [Return to top] ------------------------------ Date: Wed, 14 Feb 2007 14:33:22 +0100 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: IACFS Conference report/Anthony Komaroff The IACFS Conference report of Anthony Komaroff can be found at, http://www.instatapes.com/IACFS/06/player.HTM See also, http://www.instatapes.com/IACFS/ [Return to top] ------------------------------ Date: Sat, 14 Apr 2007 09:35:55 -0700 From: "Dr. Marc-Alexander Fluks.............via Co-Cure moderators" Subject: RES,NOT: IACFS Conference report/Virginia Teague Source: IACFS Date: February 12, 2007 Author: Virginia Teague URL: http://iacfs.net/p/1,522.html A Retrospective on the 8th IACFS Conference ------------------------------------------- This year's IACFS conference in Fort Lauderdale at the Bahia Mar Resort offered attendees an innovative format focused on the theme of interdisciplinary research and integrative care. The conference began with a two-day session focused on the needs of patients. Patient advocates from international advocacy organizations on CFS, FM, and related illnesses met for the first time to share their ideas in workshops on fundraising fundamentals, empowerment, and media training. Co-hosted by P.A.N.D.O.R.A (Patient Alliance for Neuroendcocrineimmune Disorders Organization for Research and Advocacy, Inc.), these sessions, attended by 350 patients and 222 professionals, provided a unique opportunity for patients to meet and talk with leading international researchers and clinicians. Tom Sheridan opened the session with insight on how patients and advocates can come together on policy, politics, and press to further understanding and funding for the essential research that will provide long sought answers on causation, markers, and treatment. Quoting Dr. Tony Komaroff, Mr. Sheridan said the debate over whether CFS is actually a disease is over-welcome words for patients, researchers, and clinicians. Other topics for these sessions include presentations by national and international experts on mold and environmental illness, Lyme Disease, and the role of HHV-6 virus on CFS and fibromyalgia (FM), as well as pediatric CFS, family issues, ergonomics and natural pain relief, sleep disorders, social security concerns, and employment-related legal issues for the disabled and chronically ill. Of special interest was Montoya's groundbreaking study on antiviral therapy for CFS patients with elevated antibodies to HHV-6 and EBV, in which 25 CFS patients were treated with the drug valganciclovir, an antiviral often used in treating diseases caused by human herpes viruses. During the past three years, 21 of the patients responded with significant improvement that was sustained even after going off the medication at the end of the treatment regimen, which usually lasted six months. Later this year, with a $1.3 million grant from Roche Pharmaceuticals, Dr. Montoya will replicate his preliminary study among a specific subset of CFS patients who have viral-induced dysfunction of the central nervous system. This and other research summarized in the first two days of the conference was further expanded on during the three-day professional session, which 169 patients also attended. Each session was introduced by an expert who reviewed methodology and new findings that may hold relevance, followed by presentations on original research, and concluding with a summary by an expert in CFS or FM that emphasized practical clinical applications and priorities for future research. Eliminating separate tracks for clinical and research presentations made it possible for attendees to gain a broader perspective without being forced to choose which presentations they would attend, especially important now when so much new information is changing the way the disease will be diagnosed, evaluated, and treated. In informal sessions, clinicians also had an opportunity to exchange ideas and share information on what works and what doesn't with their patients. On Friday, the professional conference began with a session on various aspects of fatigue, introduced by Watanabe (Osaka, Japan). Tajima's study using Actigraphy and R-R power spectrum analysis revealed quality of sleep for CFS patients was decreased because of increased wake episodes during the sleep period, leading to a lack of parasympathetic activation during the sleep period and further deterioration of sleep quality. Porter (De Paul University, USA) presented new terms to differentiate five types of fatigue that will help to clarify the amorphous term: wired (over stimulated, tense, agitated), brain fog, molasses fatigue (heaviness), flu fatigue (immunological), and post-exertional. Maloney (Atlanta, Georgia) confirmed the association between CFS and high allostatic load: 56% of CFS patients were found to have high allostatic load (females > males). Moreover, the greater the allostatic load, the greater the prevalence of metabolic syndrome: females with metabolic syndrome were 4 times more likely to have CFS than females without metabolic syndrome. Ciccolella (Stockton, CA) compared serial exercise test results to assess the effects of post-exertional malaise in CFS, and concluded that a single exercise test is insufficient to determine the extent of functional impairment in CFS patients. A second test 24 hours later revealed CFS patients had significantly worse performance than controls, significant support for claims of disability. Nestadt (New York, USA) compared brain metabolites in patients with CFS, those with Generalized Anxiety Disorder, and healthy controls, and discovered a significant proportion of CFS patients had elevated brain ventricular lactate. Marked differences in hippocampal glutamate helped differentiate between CFS patients with and without depression. Those with CFS also had significantly lower N-acetyl-aspartate in the right hippocampus, indicating reduced neuron density or metabolism. These findings support literature suggesting neurobiological distinctions between "pure" CFS and CFS with psychiatric comorbidity. Whistler (Atlanta, Georgia) addressed alterations in apoptosis in post-infection fatigue, and noted the severity of acute infection is related to the likelihood of recovery and affects the fundamental cellular processes. These altered gene expression profiles are manifest in several persistent symptoms of PIFS, indicating many symptoms may be immunologically mediated. Sessions on sleep, clinical trials, and pain followed. Of special interest was Clauw's (Michigan, USA) study on pain processing and treatments in FM and related conditions, in which functional MRI studies revealed a lower threshold of pain and all sensory signals for FM patients. In a session on epidemiology and case definition, the use of modern statistical information coupled with social and genetic epidemiology is providing new ways to evaluate the disease and determine intervention. Epidemiological studies by Reeves et al. (Atlanta, USA) compared those meeting the current criteria for CFS with those having fatigue but insufficient symptoms (ISF) to be diagnosed with CFS and non-fatigued controls in an attempt to subgroup those with CFS according to their level of impairment and symptom severity. Results suggested that a subset of those with ISF do have a similarly severe illness to CFS, but without at least 4 of the case-defining symptoms. A ten-year follow-up by Kang (Washington, DC) of Gulf War veterans suffering from CFS compared to non-Gulf military peers showed that CFS symptoms decreased significantly in the Gulf veterans compared to non-Gulf sufferers. Jason (DePaul, USA) discussed the economic impact of CFS on society in a community-based versus tertiary-based sample, estimating that the direct and indirect costs of CFS in the United States are between 22 and 28.6 billion dollars annually. Kuratsune estimates an annual economic impact in Japan of 10 billion. The incidence of CFS throughout the world is variable, with estimates in the USA of 2-4 per thousand (c. 800,000 to 1 million people). Jason has also studied the rates of CFS in Nigeria, the first community-based study in a developing country, estimating a prevalence of 0.68%, higher than the United States. In Ireland, Lindal found no positive correlation between the prevalence of CFS today, which is similar to findings in U.S. studies, and the 1947 Iceland Disease. Saturday's agenda opened with the brain session, introduced by Lange (New Jersey, USA), who pointed out the strong correlation between low tests of cognition and low physical ability in CFS patients. Tests for measurement include neuropsychological testing, brain imaging, and spinal fluid analysis. Quintana et al. (Barcelona, Spain), in a study using Brain SPET quantification, found a congruent pattern in basal conditions: changes after a stress test suggest inhibitory ways in frontal and especially in anterior temporal lobes. A study by Togo (New Jersey, USA) found that CFS patients have a similar response accuracy compared with controls, but have to work longer and harder in high complexity conditions. Depression had an additive effect in CFS, but does not explain the cognitive dysfunction in CFS. Van Ness (Salt Lake City, USA) showed that CFS patients had slower reaction times compared to sedentary controls. This was compounded by 30 minutes exercise; 24 hours later the CFS patients had definite persisting significant deficits (reinforcing the importance of follow-up testing revealed in Ciccolella's observations in Friday's fatigue session). Kuratsune summarized the brain function session, emphasizing that brain dysfunction is a key abnormality in understanding the state of chronic fatigue. Osaka studies have hypothesized that neuro-molecular mechanisms lead to chronic fatigue. Brain dysfunction, metabolic abnormalities, reactivation of viruses, immunological abnormalities and HPS abnormalities are being studied. PET is found to be more sensitive than SPECT and has better spatial resolution. Brain acetylcarnitine uptake is abnormal in CFS, and there is reduced binding power of 5HT in the anterior cingulate cortex (correlating with the pain score). A number of abnormalities with reduced responsiveness on fMRI is an essential feature of CFS. After a session on behavioral health, focusing on ways to help patients cope with their illness and ways to train healthcare providers to respond to their patients, Jason opened the pediatric session, presenting a new pediatric case definition that should allow for more appropriate identification of children and adolescents with CFS. Jason and his international team of researchers have produced two sliding-scale questionnaires designed for children over the age of twelve and parents/guardians of younger children. A special session devoted to selected oral presentations of poster, another new format at this conference. Saturday's agenda concluded with the gender session. Evengard (Stockholm, Sweden) gave an overview, noting that the perception that CFS is a "women's thing" has severely impacted both research and treatment of the disease. The implications of gender were further explored after the evening awards banquet with a panel discussion on politics and women's health. Sunday's agenda opened with a session on genetics/proteomics where considerable strides are being made that may lead to providing biomarkers and creating personalized therapy for those afflicted. Vernon (Atlanta, USA) introduced the session, noting the challenge of CFS is that it is not a single gene disease, and the gene effect may be epigenetic. The Garcia-Fructuoso research group (Barcelona, Spain) emphasized that CFS and FM are two genetically distinguishable illnesses with extremely high specificity in women, suggesting CFS can be as an exclusion diagnosis for FM. Albright (Salt Lake City, USA) used the Utah Population Data Base to explore a genetic contribution to CFS and associated disorders. Using three techniques to look at risks for CFS in relatives, relatedness among CFS patients, and identification of high risk CFS pedigrees, the study found a relative risk of 7.68 in first degree relatives who share many environmental risks and exposures; in second degree relatives this was less of a factor (relative risk 2.54), suggesting a genetic component which might lead to gene identification predisposing to CFS and related conditions. Evengard noted the sex difference observed in CFS indicates a role for estrogen and estrogen receptors for disease development. Baruniuk (Washington, DC) obtained genetic samples from the cerebrospinal fluid of 52 patients with CFS< FM, and GWI and compared with healthy controls. He found 5 proteins predictive of CFS that were absent in the healthy controls. The specific CFS-related proteome suggests a common pathophysiology for these related illnesses, and detection of at least one of the proteins is predictive of CFS. However, the research presented by Aslakson (Atlanta, USA) showed that a more complete enumeration of altered pathways demonstrated distinct and differing altered biological pathways among CFS subjects, further demonstrating the heterogeneity of CFS. Kerr (London, UK) outlined his team's research. The precise gene signature and metabolic pathways need to be identified. The utility of genomics/proteomics can involve inheritance, pathogenesis, and diagnosis. Molecules of interest include DNA, RNA, and proteins, and there is potential for future study of lipids and glycans. Kerr emphasized that this illness is a result of psycho-neuro-endocrine-immune interaction. Predispositional genes for CFS have been identified that are associated with Q fever and parvovirus B19. The Japanese Association for Fatigue Sciences coordinated the session that followed on new methods for evaluating fatigue. Sakudo's study (Osaka, Japan) of Near-Infrared Spectroscopy as a tool for diagnosing CFS showed near perfect dissemination between healthy controls and CFS patients, suggesting that Vis-NIR spectroscopy for sera combined with chemometrics analysis could provide a promising tool to objectively diagnose CFS. Noninvasive approaches to CFS diagnosis using Vis-NIR spectroscopy are now ongoing. Rokutan (Tokushima, Japan) outlined application of DNA chip for fatigue assessment. Only 2.5 ml of blood is required for samples. Nine CFS genes have been identified by PCR and microarray, and the identified genes may be important for subgrouping CFS. He noted stress assessment was particularly important, and may be a powerful tool to differentiate between stress disorder and CFS. Several of the Japanese researchers mentioned D-Ribose, an anti-fatigue substance prescribed in Japan. Introducing the viral and immune interactions and health session, Glaser (Ohio, USA) focused on symptoms in CFS that are compatible with a viral etiology, suggesting CFS is associated with endogenous latent viruses such as EBV and HHV-6 that may induce immunopathology by synthesizing viral protein in latently infected cells in which the virus genome is only partially expressed. These proteins could then induce immune dysregulation with effects on cytokines and chemokines and/or T cell or NK function. It is difficult to link a specific virus to CFS if the reactivation is incomplete since virus DNA would not be synthesized. Glaser's team has shown that EBV encoded dUTPase is able to induce immune dysregulation and associated symptoms in mice, suggesting that at least one protein of the EBV early antigen complex can induce immune regulation and may be involved in the pathology of EBV-associated disease. He noted that stress changes cellular immunity. The cellular immune system in older people is also less effective and thus more prone to another virus or stress. Ablashi (Santa Barbara, USA) described assays that can now be used to detect chronic reactivation of HHV-6 and EBV. Studies have shown there is a positive association between HHV-6 and EBV and CFS, and many viruses could be implicated. Rnase-L was also found to correlate with HHV-6 infection in CFS (65% concordance). Antiviral agents may be effective in treating CFS, as Montoya's initial study using valganciclovir suggests. Fletcher (Miami, USA) compared GWI and CFS immunologically, and found perforin to be low in both illnesses. NK cell function is low in GWI and moderately low in CFS. CD2 and CD26 activation is high in GWI and moderate in CFS. CD26 cleaves neuropeptide-Y (NPY), and there is significantly reduced NPY in plasma in GWI, but not significantly in CFS. Further studies are underway. Gubaxani (Atlanta, USA) detected elevated IL-6 in the resting state in CFS patients, suggesting that proinflammatory cytokines could be contributing to symptoms and thus be a potential cause or effect of CFS. Levine's research team (New York, USA) tried to determine if there are biologic markers of active, chronic viral infection in CFS patents, and evidence suggests there is a subset of CFS patients suffering from these infections. Serological assays are useful as long as a high threshold is used. Tony Komaroff provided an overview of summarized the conference's findings, noting that great strides are being made to find objective biologic evidence for a disease that has been officially defined by a group of symptoms. Specifically, Komaroff highlighted four areas: the importance of the role of the brain, mitochondrial dysfunction and oxidative stress, new molecular markers, and new methods for epidemiology. In studies on the role of the brain, Komaroff made special note of functional MRI studies done by Clauw on FM patients, and the new available neuroimaging tools discussed by Lange. He also mentioned Nestadt's study on increased lactic acid in ventricles of the brain and the many studies done by Watanabe and Kuratsune on diminished blood flow, uptake of acetylcarnitine, and diminished serotonin transceptors in special areas of the brain associated with short-term memory, pain recognition, and autonomic function. Komaroff mentioned another study by Nestadt on mitochondrial dysfunction and oxidative stress, as well as studies by Ciccolella and Van Ness on impaired oxygen and lowered anaerobic threshold, especially in follow-up tests, which he linked to Kuratsune's study on impaired brain function; at baseline in either exercise or cognitive testing, function attenuates with repeated testing. He noted Whistler's study on impaired mitochondrial pathways, Baruniuk's study on proteins in spinal fluid, Kerr's and Rokutan's studies on mitochondrial gene expression, as well as studies by Spence and Belch and Cheney and Lerner. Of special interest was Sakudo's near perfect results using near-infrared spectroscopy to differentiate between CFS patients and controls, which Komaroff described as "more beautiful than Elizabeth Taylor when she was young on a good day." Although this study must replicated, Komaroff considers it most promising. Certain findings from different studies coalesce in a meaningful way, such as Baruniuk's study on proteins found in the spinal fluid of Gulf War, FM, and CFS patients. Baruniuk's proteomic study also is significant in revealing how the immune system reacts to stress. Komaroff also mentioned Kerr's poster presentation on miRNA control expression of genes, suggesting a possible fingerprint that is potentially very impressive. New approaches to epidemiology are also providing more insight into subgroups. Statistical methods to collect meticulous data on patients without imposing a bias on it reveal subgroups that are also being defined in laboratories. Of particular note, Komaroff believes, is Maloney's study on allostatic load, which could tell us a lot about CFS. Presentations by Reeves, Jason, and Kuratsune revealed startling figures on the number of people afflicted with CFS and the cost of the illness to society. Quoting Evengard, Komaroff observed, "The invisible has been made visible." Komaroff concluded by saying converging evidence from different investigators using different technologies on different patients is telling us where to look to make scientific advances to understand this illness and, ultimately, to fix it. Virginia Teague is media liason for the 8th IACFS Conference. A freelance editor and writer, she is an adjunct professor, Liberal Arts, Nova Southeastern University, and former managing editor, Journal of Chronic Fatigue Syndrome. -------- (c) 2007 IACFS [Return to top] ------------------------------ Date: Wed, 14 Feb 2007 14:11:21 -0500 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: The PedsQL as a patient-reported outcome in children and adolescents with fibromyalgia: An analysis of OMERACT domains The PedsQL as a patient-reported outcome in children and adolescents with fibromyalgia: An analysis of OMERACT domains. Health Qual Life Outcomes. 2007 Feb 12;5(1):9 [Epub ahead of print] Varni JW, Burwinkle TM, Limbers CA, Szer IS. PMID: 17295915 ABSTRACT: BACKGROUND: Fibromyalgia is a chronic health condition characterized by widespread musculoskeletal pain, multiple tender points on physical examination, generalized muscular aching, stiffness, fatigue, nonrestorative sleep pattern, cognitive dysfunction, and mood disturbance. Recently, the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Fibromyalgia Syndrome Workshop ranked and prioritized the domains that should be consistently measured in fibromyalgia clinical trials, specifically, pain, generic health-related quality of life, fatigue, sleep quality, and physical function. The focus of these deliberations was exclusively on adult patients, and to our knowledge, these domains have not been previously tested within a multidimensional framework in children and adolescents with fibromyalgia. METHODS: An analysis to determine the feasibility, reliability, and validity of the PedsQL 4.0 (Pediatric Quality of Life Inventory) Generic Core Scales, PedsQL Multidimensional Fatigue Scale, and PedsQL Rheumatology Module Pain and Hurt Scale as patient-reported outcome (PRO) measures for pediatric patients with fibromyalgia. The PedsQL Scales were completed by 59 families in a pediatric rheumatology clinic in a large childrens hospital. RESULTS: The PedsQL evidenced minimal missing responses (0.53% patient self-report, 0.70% parent proxy-report), achieved excellent reliability for the Generic Core Scales Total Scale Score (alpha = 0.88 patient self-report, 0.87 parent proxy-report), the Multidimensional Fatigue Scale Total Scale Score (alpha = 0.94 patient self-report, 0.94 parent proxy-report), and acceptable reliability for the 4-item Rheumatology Module Pain and Hurt Scale (alpha = 0.68 patient self-report, 0.75 parent proxy-report). The PedsQL Generic Core Scales and Multidimensional Fatigue Scale significantly distinguished between pediatric patients with fibromyalgia and healthy children. Pediatric patients with fibromyalgia self-reported severely impaired physical and psychosocial functioning, significantly lower on most dimensions when compared to pediatric cancer patients receiving cancer treatment, and significantly lower on all dimensions than pediatric patients with other rheumatologic diseases. Patients with fibromyalgia self-reported significantly greater pain and fatigue than pediatric patients with other rheumatologic conditions, and generally more fatigue than pediatric patients receiving treatment for cancer. CONCLUSIONS: The results demonstrate the excellent measurement properties of the PedsQL Scales in fibromyalgia. These PedsQL Scales measure constructs consistent with the recommended OMERACT Fibromyalgia Syndrome Workshop domains. The findings highlight the severely impaired HRQOL of pediatric patients with fibromyalgia. Regular monitoring of pediatric patients with fibromyalgia will help identify children and adolescents at risk for severely impaired HRQOL. These PedsQL Scales are appropriate outcome measures for clinical trials and health services research for pediatric patients with fibromyalgia. [Return to top] ------------------------------ Date: Thu, 15 Feb 2007 10:54:29 -0500 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Widespread Pain and Fibromyalgia in a Biracial Cohort of Young Women Widespread Pain and Fibromyalgia in a Biracial Cohort of Young Women. J Rheumatol. 2007 Feb 1; [Epub ahead of print] Gansky SA, Plesh O. From Preventive and Restorative Dental Sciences, Center for Health and Community, University of California, San Francisco, San Francisco, California, USA. PMID: 17299839 OBJECTIVE: To assess the distribution of widespread pain, tenderpoints (TP), and fibromyalgia (FM) in young African American (AA) and Caucasian (C) women. METHODS: A community population of 1334 young (21-26 yrs old) women (684 AA and 650 C) was surveyed and classified for body pain spread [chronic widespread pain (CWP), axial regional chronic pain (RCP), nonaxial RCP, or no pain]. Of these women, 553 were examined for TP based on American College of Rheumatology criteria. RESULTS: Overall, 5.6% reported CWP, while 22% reported axial RCP, and 16% reported nonaxial RCP. From the CWP group, 57% were confirmed as FM cases. C women had significantly more TP and greater TP pain score than AA women (p </= 0.005). Overall FM prevalence was 2.4% (95% confidence interval: 1.7-3.5%), with 3.0% in AA and 2.0% in C women. Increase in body pain and tenderness was significantly associated with decreased subjective socioeconomic status (SSS), worse self-reported health, greater impact of premenstrual symptoms on activities, and greater depressive symptoms. The effect of depressive symptoms on pain differed by race. CONCLUSION: Widespread pain and tenderness is highly prevalent in these young women. Racial differences seem to exist; C women had significantly increased tenderness while AA women had more widespread pain. The association of depressive symptoms and pain was stronger in AA women. Racial differences emerged relatively early in these young women. [Return to top] ------------------------------ Date: Thu, 15 Feb 2007 17:32:04 +0100 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: CDC television spot on CFS Source: Associated Press Date: February 14, 2007 URL: http://www.ftimes.com/main.asp?SectionID=1&SubSectionID=1&ArticleID=38785&TM=50793.27 Study Focuses on Chronic Fatigue -------------------------------- ATLANTA (AP) - The television spot shows a 40-year-old woman, in slow motion, as her family and co-workers rush by over the course of a day. It ends with her sitting alone, amid the remnants of a birthday party. 'The worst part isn't even that everyone thinks the problem's in my head,' a female voice intones. 'The worst part of chronic fatigue syndrome is missing my life.' The spot is the centerpiece of a remarkable $4.5 million public awareness campaign bankrolled by the U.S. Centers for Disease Control and Prevention. It's remarkable, in part, because of the role advocacy and politics played in creating it. Chronic fatigue syndrome is not contagious or life-threatening, and medical skeptics continue to question its merits as a focus for public health. But the money is being spent, in part, thanks to strategic lobbying and congressional interest. It is not the only example, or the most successful. In 2000, the March of Dimes lobbied Congress to create a center on birth defects within the CDC. In December, advocates - including Autism Speaks, an effective fundraising organization founded by General Electric Co. Vice Chairman Bob Wright - were credited with passage of a bill that targeted nearly $1 billion over five years to research that condition. But chronic fatigue syndrome paved the way, said Shelley Hearne, former executive director of Trust for America's Health, a public health advocacy group. She is now a visiting scholar at Johns Hopkins University's Bloomberg School of Public Health. In the 1990s, Congress authorized money for CDC to study the cause of chronic fatigue syndrome. In 1998, advocates caught the CDC diverting nearly $13 million of that funding and spending it in other areas. There was a federal probe, and CDC eventually replaced the money. It proved to be a turning point in how the agency interacts with - and is influenced by - advocates and the lawmakers who support them, Hearne said. 'I think it was really the first wake-up call to the agency that it needed to understand and respond to the needs of the public,' she said. Clearly, most researchers believe chronic fatigue is real and that there is strong justification for the CDC to be working on it. But some are skeptical, and feel the agency has leaned too far, at times putting lesser ailments ahead of the public good because advocates and politicians demand it. 'I personally believe the CDC's emphasis on this has been wrong from day one. They have responded to pressure,' said Dr. Peter Manu, a New York-based researcher who does not believe chronic fatigue is a real disease. Chronic fatigue syndrome is characterized by at least six months of severe fatigue not helped by bed rest. Patients also report muscle pain and impaired memory. The CDC estimates more than 1 million Americans have the condition, with the rate four times higher among women. It became a national health issue in 1984, when clusters of cases were reported in Incline Village, Nev., and in Lyndonville, N.Y. Similar reports came in from around the country, although scientists believe the illness probably existed before then but wasn't recognized. One challenge is that chronic fatigue syndrome doesn't have observable symptoms, said Laura Hillenbrand, a journalist who wrote the best-selling book 'Seabiscuit' and who has been diagnosed with the illness. 'I have definitely gotten a raised eyebrow and a 'You look fine!' said Hillenbrand, 39. Chronic fatigue syndrome came to be known as 'yuppie flu,' because many of the sufferers were white, educated and relatively affluent. Several key members of Congress took it seriously, though, including Harry Reid, the Democratic Senate majority leader, who was a Nevada congressman when the Incline Village cluster was reported. Another was John Porter, an Illinois Republican on the House Appropriations subcommittee that oversees public health programs and agencies. Porter became involved when a constituent, Chicago-area philanthropist Ted Van Zelst, visited and told Porter about his daughter's mystery illness. In 1987, Van Zelst became the first person to testify before Congress requesting research money for chronic fatigue. At about the same time, a small organization formed in Charlotte, N.C., that became the nation's most influential chronic fatigue advocacy group - the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America. The group was influenced by AIDS activists, who in the 1980s eschewed gentle advocacy for hard-nosed politicking and government watchdogging. But the CFIDS Association had a tougher challenge: Their syndrome doesn't shorten lives, there's no proof it's infectious, and many doctors refused to take it seriously. It was unexplained, yes, but not fatal - more like a Nancy Drew mystery than an Agatha Christie. At the CDC, the investigation was placed in the division responsible for deadly infections like influenza and rabies. The response there to chronic fatigue was tepid, said Dr. William Reeves, who now heads the CDC's chronic fatigue syndrome research. 'They deal with acute infectious agents that make people dead. That was the mind-set,' he said. The CFIDS Association, led by Kim McCleary, applied pressure by becoming a part of the government apparatus. Heeding congressional requests, federal officials in 1995 gave advocates a place on a U.S. advisory committee on chronic fatigue syndrome. It was a turning point, because the 5-year-old panel previously was populated only by scientists and government officials. It was at one of the panel's meetings in 1998 that CDC's misuse of chronic fatigue funding was exposed. McCleary pressed a CDC official on how the chronic fatigue money was being spent, and Reeves emerged as a whistleblower who refused to back up his boss, Dr. Brian Mahy. Mahy contended $6 million had been spent on the disease in the prior year as Congress requested. But Reeves had complained to Mahy that chronic fatigue efforts were not getting the money Congress intended. 'It was basically, 'Go out there and lie for me,' Reeves said in a recent interview. 'I just basically said 'No.' Mahy, who still works at CDC, declined to comment for this article. An investigation found that nearly $13 million of $22.7 million meant for chronic fatigue work was spent on other programs. Lawmakers grilled the CDC director at the time, Dr. Jeffrey Koplan. Porter, the Illinois congressman, was upset but there wasn't much he could do, since Congress usually doesn't mandate how the CDC should divvy its money among programs. Congress puts spending recommendations in appropriations reports, but they're not binding, said Porter, who now works for a Washington law firm. That's an important point: There are authorization bills that often get a lot of press, such as the recent autism bill, but they don't come with actual money. Advocates say it's a bit like parents giving their teen permission to go to the movies, but not the allowance money to buy the ticket. 'Almost never do we substitute political judgment for scientific judgment in the actual appropriations' for the CDC, Porter said. Some current and former CDC officials said that shifting funds to other disease-fighting efforts was not a crime. 'This wasn't a case of someone taking money for a holiday on the French Riviera,' Koplan said, in a recent interview. But the agency clearly bungled how it communicated with Congress, said Koplan, now an administrator at Emory University. 'We had not done procedurally what the CDC should do, which is inform Congress and ask their permission when funds for one health problem are used for another health problem,' he said. In the 2006 budget year, the CDC spent about $6 million on chronic fatigue research. That doesn't include the $4.5 million for the slick new ad campaign unveiled in Washington last fall; and the NIH spent another $5.5 million on the disorder. CDC funding for the condition has been steady in recent years, and chronic fatigue syndrome is only a minor budget line at the agency. Dental health programs get twice as much, and birth defects and disabilities efforts get more than seven times as much, according to agency budget figures. Domestic HIV/AIDS research and programs typically get more than 130 times the chronic fatigue allocation. The public awareness campaign money is considered reparations for the diversion of funds in the mid-1990s, said McCleary, who was master of ceremonies at the CDC press conference on the new ad campaign. 'It's sort of considered their good faith for any of that ever happening,' she said. CDC officials say science is driving the public awareness campaign, not guilt. Scientists at the press conference noted the CDC's chronic fatigue research group generated about 80 peer-reviewed papers since 2000 that provided new information about the cost and genetics of the condition. 'The science is there and we need to respect and make that science more visible,' CDC chief Julie Gerberding said at the event. At the same time, officials recognized that they still don't know for certain what causes the illness. There still is no medical test for it, nor a cure. It may be a collection of illnesses, with different mechanisms. Reeves co-authored a 2004 article that found a decline in chronic fatigue in the first few months after the Sept. 11, 2001, terrorist attacks. A study published last year found that childhood abuse and neglect increased the likelihood of chronic fatigue in some patients. Such findings may suggest a complex interaction between stress, genetics and other factors in why some people develop chronic fatigue. Or, according to Manu, it may suggest something else entirely - an absence of real physical illness. 'I don't think there is much to it,' said Manu, a professor at Yeshiva University's Albert Einstein College of Medicine. He believes many of the skeptical researchers have moved on to other topics and have stopped talking about chronic fatigue. Manu is one of only a few scientists still making such arguments. Others say scientific consensus has shifted away from Manu, and most doctors no longer doubt chronic fatigue is a real medical condition. The new ad campaign is playing a pivotal role in finally moving American society past skepticism, CFIDS Association officials said. As of the end of January, the spot has aired 4,425 times in 122 markets on 180 TV stations, McCleary said. Advocates are also working with Hillenbrand, who is considered the highest-profile celebrity to speak often and openly about the condition. Celebrities make a big impression on many members of Congress, McCleary noted. She recalled watching a hearing several years ago when the actor Anthony Edwards appeared before Congress to talk about autism. At the time, he was starring in the television hit 'ER' as Dr. Mark Greene. 'They treated him like he was a doctor,' she said. Hillenbrand said it's gratifying that most doctors and government officials are finally taking the condition seriously, and she appreciates how warmly she's been treated by leaders such as President Bush. 'The first thing the president said to me when I first met him was, 'Don't get up!' said Hillenbrand, who has been to the White House four times, including for a screening of the 'Seabiscuit' movie. 'It's nice to know that there is understanding and compassion in high places.' -------- (c) 2007 Associated Press [Return to top] ------------------------------ Date: Thu, 15 Feb 2007 22:10:24 -0500 From: "Dr. Marc-Alexander Fluks <fluks dds.nl> (via Co Cure Moderators) Subject: RES,NOT: IACFS Conference report/Rosamund Vallings - CORRECTION There is a mistake in the session: BEHAVIOURAL POSTERS ---- "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> wrote: > Source: Rosamund Vallings > Date: February 12, 2007 > IACFS Conference report > ----------------------- > BEHAVIOURAL POSTERS > Exercise intolerance in CFS is evident in a study by C.Ruud (Amsterdam, > Netherlands). When CFS patients are subjected to increasing exercise, and > compared to controls, there is a lower anaerobic threshold and a state of > malaise comparable to overtraining. This study is done by: Ruud. C. W. Vermeulen (Amsterdam, Netherlands) Jan van Roijen [Return to top] ------------------------------ Date: Fri, 16 Feb 2007 14:05:35 -0500 From: Fred Springfield <fredspringfield VERIZON.NET> Subject: RES: Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability. Journal: Theor Biol Med Model. 2007 Feb 14;4(1):8 [Epub ahead of print] Authors: Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. NLM Citation: PMID: 17300722 ABSTRACT: BACKGROUND: The bodys primary stress management system is the hypothalamic pituitary adrenal (HPA) axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the bodys cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. RESULTS: We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states (low and high) and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model, low GR concentration represents the normal steady state, and high GR concentration represents a dysregulated steady state. A short stress in the normal steady state produces a small perturbation in the GR concentration that quickly returns to normal levels. Long, repeated stress produces persistent and high GR concentration that does not return to baseline forcing the HPA axis to an alternate steady state. One consequence of increased steady state GR is reduced steady state cortisol, which has been observed in some stress related disorders such as Chronic Fatigue Syndrome (CFS). CONCLUSIONS: Inclusion of pituitary GR expression resulted in a biologically plausible model of HPA axis bistability and hypocortisolism. High GR concentration enhanced cortisol negative feedback on the hypothalamus and forced the HPA axis into an alternative, low cortisol state. This model can be used to explore mechanisms underlying disorders of the HPA axis. [Note: This is an Open Access article. The PDF version is available at http://www.tbiomed.com/content/4/1/8/abstract .] [Note: Something that is bistable can be stable in two states.] [Return to top] ------------------------------ Date: Fri, 16 Feb 2007 15:08:24 -0500 From: Fred Springfield <fredspringfield VERIZON.NET> Subject: RES: Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome. Journal: Am J Med Sci. 2007 Feb;333(2):78-84. Van Hoof E, De Becker P, Lapp C, Cluydts R, De Meirleir K. From the Department of Human Physiology (evh, pdb, kdm) and the Department of Psychology (evh, rc), Vrije Universiteit, Brussels, Belgium; and from the Hunter-Hopkins Center, Charlotte, North Carolina (cl). NLM Citation: PMID: 17301585 BACKGROUND: Patients with chronic fatigue syndrome (CFS) present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances. METHODS: Forty-eight patients who fulfilled 1994 Centers for Disease Control and Prevention criteria for CFS underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2',5'-oligoadenylate trimer. Basic descriptive statistical parameters were calculated. RESULTS:: Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L. CONCLUSIONS:: The main findings are 1) validation of sleep latency problems and other sleep disturbances as already suggested by several authors; 2) alpha-delta intrusion seems associated with anxiety; and 3) elevated RNase L did not correlate with alpha-delta sleep. [Return to top] ------------------------------ Date: Sat, 17 Feb 2007 00:30:56 +0100 From: Jan van Roijen <j.van.roijen CHELLO.NL> Subject: res: Defining occurrence & influence of alpha-delta sleep in CFS ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 16 February 2007 <<<< Editorship : j.van.roijen chello.nl Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ Fri, 16 Feb 2007 Fred Springfield posted the abstract of *Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome* - Van Hoof E et al. - Co-Cure: http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0702c&L=co-cure&T=0&P=2654 -------------------------------------------------------------- ~jvr: as fair use I add the discussion section of this article -------------------------------------------------------------- Discussion Sleep architecture variables demonstrated significantly different sleep onset latency and sleep disturbances in CFS patients (Table 4). Because of the resemblance between the CFS patients used by Fischler et al13 and Fossey et al15 and our CFS population, their results may apply to our sample, although no healthy control group was used. Similar results were already reported by several other authors, such as Whelton et al10 and Stough and Withers.14 CFS patients present less sleep continuity. Patients experience problems falling asleep, represented by the large sleep latency. The low sleep efficiency index and the high number of micro-awakenings objectify the subjectively presented complaints of a distorted sleep pattern and a nonrestorative sleep.5–7 The patients slept about 5.5 hours. They spent almost 30% of the time awake in bed. Interestingly, a lot of shifts between stages are apparent. Again, the results of the sleep architecture underscore the distorted sleep pattern and an unrefreshing sleep. Alpha-delta intrusion is present although a wide range of the percentage of this intrusion indicates its nonspecific nature. This sleep anomaly is thought to be accompanied by indications of vigilance during sleep and the subjective experience of unrefreshing sleep. The latter seems not solely associated with alpha-delta intrusion because no differences in feelings of fatigue and unrefreshing sleep could be found between CFS patients with low or high alpha-delta intrusion. Our results emphasize the nonspecific nature of alpha-delta sleep in CFS patients, a suggestion made by several authors.19–23 For instance, Manu and associates found no correlation between alpha-delta sleep and CFS, fibromyalgia, major depression, primary sleep disorders, or Lyme disease but did find that alpha-delta sleep was more common among chronic fatigue patients without major depressive disorders.23 Although the sample showed high RNase L, no differences were apparent between patients with low and high alpha-delta intrusion. Furthermore, no correlations appeared between alpha-delta sleep and immunologic parameters, including RNase L. So far, it has been thought that a potential acquired channelopathy, a consequence of immune deregulation through RNase L, leads to sleep disturbances including alpha-delta sleep.25,26 Our results suggests that RNase L and the subsequent channelopathy are not associated with alpha-delta intrusion. Moreover, none of the self-reported sleep problems, nor the objective sleep parameters, are associated with RNase L. This result questions at least a part of the suggested hypothesis proposed by Englebienne and De Meirleir.25 The suggested acquired channelopathy with loss of intracellular potassium should lead to metabolic and intracellular abnormalities, including central fatigue and sleep disturbances such as alpha-delta intrusion. Our results do not support the inclusion of sleep disturbances in- cluding alpha-delta intrusion in the list of potential consequences of the suggested channelopathy. The results the deregulation of the 2–5A synthetase/ RNase L pathway are similar to those of previous studies.27,28 It is still unclear, however, whether the 37 kDa RNase L ratio is representative of the CFS population in general, and whether the 37 kDa RNase L ratio is characteristic of a particular stage in the course of the illness or if it fluctuates over time (as is the case with symptom severity in the majority of CFS patients). Recent research suggest the ratio could be associated with (the severity) of the experienced complaints and its associated clinical causes.25 For instance, the deregulation of the 2-5A synthetase/RNase L pathway appears to accompany different aspects of immune dysfunction in CFS patients. A reduced number and activity (cytotoxicity) of NK-cells have been reported in patients with CFS.29–31 In addition, a negative correlation between the RNase L ratio and both the number and percentage of NK-cells was observed in CFS patients. In our study, no deviant NK-cells percentages were found. Moreover, no correlations were found between the RNase L ratio and the NK-cells. To be a biological gradient, a correlation between the biological parameter of interest (i.e., impairment of the RNase L pathway) and the clinical severity of the disorder of interest (i.e., CFS) is required. No significant correlations regarding self-reported complaints, objective sleep parameters, and immune parameters were found in this study. For interpreting a correlation analysis, however, one should focus on the correlation coefficient rather than interpreting the P-value. Correlation coefficients as low as 0.2, regardless of the P-value, suggest no association is present. Although no significant associations were found, some correlation coefficients suggested possible relationships. The Bonferroni-corrections and the small sample size could prevent any significant results. Further research is necessary to clarify possible associations. Using our present results, no significant findings appeared, casting into question the biological gradient of the RNase L ratio regarding the NK-cells and sleep disturbances. Anxiety differed between low and high alphadelta sleep. People suffering from high alpha-delta intrusion experience more anxiety. Anxiety could be the result of the higher vigilance in slow wave sleep. The major clinical importance of this study is that because of alpha wave intrusion in phase 3 and 4 of the non-REM sleep, full benefit is not taken from the recuperative function of slow wave sleep. This study had several limitations. First, the study was done retrospectively and therefore strong causal relations were difficult to make. Second, a limited number of CFS patients were enrolled and there was no healthy control group, although the results were similar to those of Fischler et al13 and Fossey et al,15 who did include a healthy control group. Therefore, more research is needed, not only with a increased number of CFS patients that would give more accurate results, but also with the same polysomnographic protocol and adequate control subjects, including patients with non-CFS-induced fatigue. The relatively small number of CFS patients in this study was due to recent changes in polysomnographic protocols; only 41 CFS patients were found to have completed a similar 2-night polysomnographic protocol. Moreover, 1-night polysomnographic protocols should be avoided due to the first-night effect.32 In summary, one obvious limitation of the present study is the lack of power due to a small sample size. However, the well-documented expense related to laboratory sleep research,33 as well as the difficulties regularly encountered with subject attrition in such extensive, demanding, and lengthy investigations make small sample size an unfortunate but common consequence. Nevertheless, the comprehensive data collected make an important contribution to CFS research and should form the basis for future investigations. Summarizing, the main findings of this study are as follows: 1) The existence of sleep latency problems and other sleep disturbances are validated, as already suggested by several authors. 2) Alpha-delta intrusion seems associated with anxiety. 3) An elevated RNase L-ratio did not correlate with alphadelta sleep. 4) The results from the correlation analysis questions RNase L as a biological gradient. To our knowledge, this is the first study in which immune parameters were correlated to polysomnographic variables in CFS patients. More research is undoubtedly necessary to state causal relationships, although some interesting suggestions have been made. [Return to top] ------------------------------ Date: Sat, 17 Feb 2007 01:04:19 +0100 From: Jan van Roijen <j.van.roijen CHELLO.NL> Subject: not,res: Science: The ME/CFS Dragon Slayer ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 16 February 2007 <<<< Editorship : j.van.roijen chello.nl Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ Quote from below: *....In a nutshell, the science behind all the remarkable reports we heard at this conference is freeing us from any doubt that ME/CFS is a very real disease with an etiology not rooted in the psyche....* ~jvr ```````` http://www.immunesupport.com/library/showarticle.cfm?id=7729&T=CFIDS_FM Science: The ME/CFS Dragon Slayer ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ A Patient Advocate's Perspective on the 2007 IACFS Conference by John Herd ImmuneSupport.com 02-14-2007 John Herd has been called a "founding father" of CFS patient advocacy. He has attended almost every ME/CFS conference since the late '80s. But at the 2007 IACFS conference, he reports, he saw something entirely new: "The ME/CFS community is no longer confined by national borders. We are all in this together." Little by little, patient advocates are beginning to produce their summaries of reports from the 2007 IACFS professional and patient conference in Florida. It's a gradual process because five days of conferencing would be hard on anyone…and it's far harder on ME/CFS patients. And there's an immense amount to talk about pertaining to what transpired at the conference. The scientific reports were absolutely breathtaking, though so technically rooted in science that many are hard to get your head around without interpretation. The Conference 'Stress Test' Truth be told, the conference is as tough a stress test as doctors could devise for ME/CFS patients. Advocates who attend the IACFS conference deserve a lot of credit and recognition for exhibiting such a level of commitment that they'd be willing to put themselves through such a grueling exercise in order to represent the patient community. The Science, Once So Scattered, Is Converging In a nutshell, the science behind all the remarkable reports we heard at this conference is freeing us from any doubt that ME/CFS is a very real disease with an etiology not rooted in the psyche. This science is a dragon slayer, and the dragon is the bygone 'all in the head' dogma that no one - not doctors, not governments, not the public - is going to be able to hold onto much longer. That said, I'll let others begin to report in lay terms on all the scientific headway presented at the conference. What I will say now is that the conference had a very different feel to it than the past five IACFS conferences I've attended. On my way home I realized why: It was convergence. In the past, conference sessions reported on many kinds of interesting but seemingly unrelated small pieces of the biologic ME/CFS puzzle. These pieces represented scientists reaching out in many directions to grasp little pieces of the puzzle, but there was little sense of connectedness. The science reported at this year's conference felt very different. It seemed like much of it was different kinds of science coming together - each building on the other with associations. It felt like finally the many small pieces of the puzzle were finally beginning to reveal a cohesive picture, the picture of what ME/CFS really is. The Experts are Acting Like a Global Team Instead of the doctors and researchers seeming to be scientific athletes, each playing his or her solitary sport, they and their work seemed to be a team sport. The players and their activities (their scientific findings) harmonized in a fashion that gave confidence we're closing in on answers we've long sought. In addition to the convergence of ideas, the conference embodied a remarkable physical convergence. Nancy Klimas, MD, president of the IACFS, announced that there were doctors present from some 28 different counties. That's 28 countries where clinical and research experts will be carrying back and sharing the latest knowledge to help patients and ignite more research. For example, I met one marvelous doctor from South America who realized not only that her country was offering almost nothing for ME/CFS patients - but that she herself knew very little about the illness. She wasn't just attending the conference…she's been doing an extended medical fellowship here. And now she can return to her country with knowledge that will benefit many. There were too many doctors from too many countries to mention them all. But just for example: * Vance A. Spence, PhD, attended to share the work that ME Research UK has been conducting, and to bring back to the UK knowledge that may help to change things there. His organization http://www.meresearch.org.uk/ is a charity dedicated to funding ME/CFS research and publishing the results. * Jonathan Kerr, MD, PhD, was also at the conference, sharing his stunning genetic work. Dr. Kerr, a professor of microbiology at Imperial College, London, is studying the mechanisms of gene expression in ME/CFS. * Doctors from Japan reported on many kinds of work they're conducting, which sound as though they'll make tremendous contributions to our understanding of the illness. Patient Advocates Connecting Globally Too Just as there was a strong sense that the experts are cooperating to build on each other's findings and work in unison, the same was true of the international patient advocate gathering. In the context of the IACFS dual conference, advocates from across the U.S. and different countries had an unparalleled opportunity to meet and share their knowledge, talk shop amongst each other, and lay plans for the future. This Organization is Very Definitely International Let no one doubt that the IACFS has gone international. It is very much a global organization with global reach. In keeping with that international mission, and because the illness is known as ME throughout much of the world, the organization is changing its name to the IACFS/ME. The take-away message? The ME/CFS community is no longer confined by national borders. We are all in this together. Special Thanks to Special Volunteers Finally, on behalf of all who will benefit from this international sharing, we owe special thanks and recognition to PANDORA – the conference's host and co-sponsor. Kudos to President Marla McKibben Silverman, Vice President Rebecca Artman, and the other PANDORA volunteers for their enormous contributions to the conference. Their work, along with the IACFS/ME leadership's work, made this 2007 conference the most profoundly important conference and meeting of minds we've ever seen in the history of ME/CFS. [Return to top] ------------------------------ Date: Sun, 18 Feb 2007 21:06:43 +0100 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Ayurveda for CFS causes heavy metal poisoning Source: U.K. Medicines and Healthcare products Regulatory Agency (MHRA) Date: February 16, 2007 URL: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary=true&ssDocName=CON2030310&ssTargetNodeId=663 Ayurvedic medicines containing heavy metals ------------------------------------------- he MHRA have been made aware of at least six cases of heavy metal poisoning in the last 3-4 years associated with the use of Ayurvedic medicines. In most of these cases, the Ayurvedic medicines contained lead. There has also been a case of arsenic poisoning. The Ayurvedic medicines in question were obtained from the Indian sub-continent and brought back to the UK for self use. Patients were treating diabetes, chronic fatigue syndrome and hypertension. The MHRA would strongly advise caution on the part of consumers and that they consult their GPs before use. Previous concerns about the heavy metal content of some Ayurvedic Medicines were highlighted in a press release dated 17 August 2005 'Ayurvedic Medicines may contain Heavy Metals' from the Current Safety Issues on the MHRA website, http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&ssDocName=CON2014944&ssSourceNodeId=663&ssTargetNodeId=389 -------- (c) 2007 MHRA [Return to top] ------------------------------ Date: Sun, 18 Feb 2007 21:00:25 +0000 From: Ellen Goudsmit <ellengoudsmit HOTMAIL.COM> Subject: RES: Effect sizes (Cohen's d) for various interventions to treat CFS/ME Taking a different perspective. The assessment of treatments for CFS/ME using Cohen's d. Ellen Goudsmit PhD C.Psychol. Objective: To compare different treatments for CFS/ME using one recognised measure of effect size. Method. Cohen's d (delta) was computed using the mean fatigue scores (and SD) obtained from published trials or studies reported in the CRD reviews. In one case, Cohen's d was calculated using the F statistic and checked for reliability using an additional formula plus second measure of effect size. Results. There were few differences between the various programmes for CFS/ME. Effect sizes were generally moderate. TREATMENT D Reference CBT/GET .78 Deale et al 1997 CBT/GET .64 Prins et al, 2001 GET .57 Fulcher and White 1997 Multi-dimensional* .71 Goudsmit 1996 Discussion. The results suggest that a larger study may be of interest. They also give an indication of the modest effects of the various treatments when using fatigue as the outcome measure. Further research should include effect size statistics computed for other symptoms and quality-of-life. For example, a study of a client-centered, multi-dimensional programme which provided data for these variables reported d values between .66 and .71 (Taylor, 2004). Similarly, in the GET trial(Fulcher and White), d calculated from the data for the MOS-SF physical functioning subscale was .69, but d for the MOS-SF as a whole was .499. One is higher than that for fatigue, the other is lower. The inclusion of different outcome measures may give a more realistic view of the effect of a given treatment than data for fatigue and emotional distress. Caveats. This analysis was limited by the lack of statistical information in some papers. Moreover, a number of studies did not provide data for fatigue (e.g. Marlin et al, 1998). Conclusion. Based on effect sizes, there appears little evidence to recommend one treatment above another. Moreover, the generally modest values for Cohen's d support claims that certain intervention are helpful, rather than "effective". Postscript. Values of .2 or less are considered small, .50 or above are moderate and .8 or above are considered as indicative of a large effect. * This programme did not incude CBT. ---------------------------------------------------------------------- Ellen M. Goudsmit C. Psychol. AFBPsS For information on ME and CFS, see: http://freespace.virgin.net/david.axford/melist.htm *** This e-mail and any attachments are confidential and solely for the information of the addressee. Any copying or disclosure to a third party is unauthorised and the sender is not responsible for any matter resulting from changes to the text made by a third party. [Return to top] ------------------------------ Date: Mon, 19 Feb 2007 16:57:50 -0500 From: "Cort Johnson <phoenixcfs yahoo.com> via Co-Cure Moderator Subject: NOT,RES: IACFS Conference III: Immune, Gut, Sleep and Pain Presentations Welcome to Part III of our overview of the IACFS conference in Florida. This part deals with immune, gut, pain and sleep issues. We hear an exciting breakthrough in the Dubbo's studies attempts to unravel post-infective fatigue, more news of natural killer cell dysfunction in CFS, a study suggesting a viral infection is commonly present in the gastrointestinal system of CFS patients, two Lyme studies, plus much more. ot You can find this session at the URL below http://phoenix-cfs.org/IACFS%202007%20Conference%20III%20Immune,%20Gut,%20Pain%20and%20Sleep.htm The next section on the Clinical Trials will be coming up shortly. Please subscribe to Phoenix Rising Happy reading, Cort [Return to top] ------------------------------
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