c_f_s monee Chronic fatigue syndrome researchers offer physical evidence 24 Aug 2004 A University of Alberta study has verified that there is physical evidence for those who suffer from chronic fatigue syndrome (CFS), giving new weight to the often stigmatized and misdiagnosed disorder. Research just published in the "International Journal of Psychophysiology" determined that, using independent criteria, CFS can be distinguished from depression--two disorders that share many of the same symptoms CFS is an often debilitating disorder, characterized by a constellation of symptoms including fever, sore throat, headache, muscle weakness, myalgias, post-external malaise, sleep and cognitive disturbances. The level of disability varies for people with CFS, but some individuals find they are unable to return to work or function normally on a day-to-day basis. Unfortunately, many of these symptoms are subjective in nature and are difficult to quantify or confirm, says Hannah Pazderka-Robinson, the lead author on the study. Not only does the stigma attached with the disorder play an emotional toll on the patient, but it has implications for insurance claims as well. "There are a number of medical professionals who don't believe that CFS exists in the first place," said Pazderka-Robinson. "The problem is, both CFS and depression are characterized by very similar profiles. Imagine a patient who approaches a doctor and tells him they feel depressed and tired all the time. "Since depression shows a high co-morbidity with CFS, some CFS patients are often given antidepressants--that don't work or work poorly, since they do not address the underlying condition. Again, when these medications don't work, physicians sometimes jump to the conclusion that there isn't really anything, physically, wrong. Obviously, both misdiagnosis and the tendency for doctors to treat these patients as if they're not really sick can be extremely distressing. It can also undermine the patient's trust in the doctor and make them less likely to seek treatment if the condition worsens." The most significant part of the research was to provide independent verification for CFS sufferers that these patients are different than normal controls and they're not "just depressed," said Pazderka-Robinson. Numerous psychological investigations have attempted to differentiate these groups, with limited success. The U of A study was the first of its kind to use electrodermal activity--electrodes were placed on each hand--to investigate the differences among CFS, depression patients and healthy controls. Using tone and light stimuli, the results showed that CFS can be discriminated from those with major depression by recordings of skin temperatures and electrodermal activity. Moreover, the profile of CFS patients is clearly different from normal controls, suggesting there is a clear biological basis to the condition. Pazderka-Robinson completed this study with researchers from the University Centre for Neuroscience at the University of Alberta and from Alberta Hospital. http://www.medicalnewstoday.com/medicalnews.php?newsid=12426 . 041222 ... monee CFS or depression - what are the differences Physicians can be very naughty and intellectually lazy when it comes to diagnosing CFS. They are all too willing to label patients as depressed because this leads on to a straightforward and well recognised management protocol- namely, anti-depressants, exercise and, if you are lucky, counselling. Anti-depressants in normal doses will make you worse, as will exercise. Counselling depends on the counsellor - if they do not believe CFS exists then you are well and truly stuffed. There are clear distinctions between the two conditions, including the following- 1- Exercise- this makes CFS patients much worse but can be positively therapeutic in pure depression. 2- Muscle tenderness and pain is common in CFS, and unusual in depression. 3- Response to alcohol and anti-depressants. These almost invariably make CFS patients worse, but depressed patients often get benefits. 4- Sleep disturbance- in CFS, the biological clock is moved on so patients go to sleep late and wake up late in the morning. With depression, one expects to see early morning wakening. 5- Adrenal function. In CFS, this is usually depressed, whereas in depression, there may be associated anxiety, with raised levels of cortisol- see adrenal stress profile. 6- CFS patients often have poor immunity, with recurrent infections. This is not generally a feature of depression. 7- If you can get the tests done, then there will be differences in neuro-psychometric testing, which demonstrate a different type of cognitive disturbance, memory lose and mental agility in both illnesses. Furthermore, SPECT and PET scans demonstrate diminished metabolism in the brain stem, medial and frontal lobes of the cerebral cortex in ME, whilst in depression, diminished metabolism is more widespread and the frontal lobes are chiefly affected. http://www.drmyhill.co.uk/article.cfm?id=210 . 041222 ... monee "This web site offers information about chronic fatigue syndrome (CFS) and its diagnosis and treatment." http://www.cdc.gov/ncidod/diseases/cfs/ . 041222 ... monee "The Canadian Expert Consensus Panel has published a medical milestone, the first clinical case definition for the disease known as myalgic encephalomyelitis/chronic fatigue syndrome. This definition is clearly a vast improvement over the CDC's 1994 Fukuda criteria, which led to misunderstanding in both research and treatment modalities by making "fatigue" a compulsory symptom but by downplaying or making optional the disease's hallmark of post-exertional sickness and other cardinal ME/CFS symptoms. In sharp contrast to the Fukuda criteria, this new clinical case definition makes it compulsory that in order to be diagnosed with ME/CFS, a patient must become symptomatically ill after exercise and must also have neurological, neurocognitive, neuroendocrine, dysautonomic, and immune manifestations. In short, symptoms other than fatigue must be present for a patient to meet the criteria. This case definition, which incorporates some of the current research on dysautonomia, cardiac, and immune problems, was published in the Journal of Chronic Fatigue Syndrome, Vol. 11 (1) 2003." http://www.cfids-cab.org/MESA/ccpccd.pdf It is summarized as follows: 1. POST-EXERTIONAL MALAISE AND FATIGUE: There is a loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional fatigue, malaise and/or pain, and a tendency for other symptoms to worsen. A pathologically slow recovery period (it takes more than 24 hours to recover). Symptoms exacerbated by stress of any kind. Patient must have a marked degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level. [Editor’s note: The M.E. Society prefers to use “delayed recovery of muscle function,” weakness, and faintness rather than “fatigue.” Further, we disagree that the muscle dysfunction is “unexplained.” See our M.E. Definitional Framework and researchers’ medical explanations on this website.] 2. SLEEP DISORDER: Unrefreshing sleep or poor sleep quality; rhythm disturbance. 3. PAIN: Arthralgia and/or myalgia without clinical evidence of inflammatory responses of joint swelling or redness. Pain can be experienced in the muscles, joints, or neck and is sometimes migratory in nature. Often, there are significant headaches of new type, pattern, or severity. [Editor’s note: neuropathy pain is a common symptom and should be added here as well.] 4. NEUROLOGICAL/COGNITIVE MANIFESTATIONS: Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, difficulty with information processing, categorizing, and word retrieval, intermittent dyslexia, perceptual/sensory disturbances, disorientation, and ataxia. There may be overload phenomena: informational, cognitive, and sensory overload -- e.g., photophobia and hypersensitivity to noise -- and/or emotional overload which may lead to relapses and/or anxiety. 5. AT LEAST ONE SYMPTOM OUT OF TWO OF THE FOLLOWING CATEGORIES: a. AUTONOMIC MANIFESTATIONS: Orthostatic Intolerance: e.g., neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension, vertigo, light-headedness, extreme pallor, intestinal or bladder disturbances with or without irritable bowel syndrome (IBS) or bladder dysfunction, palpitations with or without cardiac arrhythmia, vasomotor instability, and respiratory irregularities. [Editor’s note: low plasma and/or erythrocyte volume should be added as another explanation for orthostatic intolerance in this disease. We also hold that more cardiac symptoms should be listed such as left-side chest aches and resting tachycardias, which, in addition to low blood volume, have also been documented in the research. The full text of the case definition does suggest 24-hour Holter monitoring, and when tachycardias with T-wave inversions or flattenings are present that they not be labeled as nonspecific since they aid in the diagnosis of ME/CFS. See the above link to access the diagnostic part of the document.] b. NEUROENDOCRINE MANIFESTATIONS: loss of thermostatic stability, heat/cold intolerance, anorexia or abnormal appetite, marked weight change, hypoglycemia, loss of adaptability and tolerance for stress, worsening of symptoms with stress and slow recovery, and emotional lability. c. IMMUNE MANIFESTATIONS: tender lymph nodes, sore throat, flu-like symptoms, general malaise, development of new allergies or changes in status of old ones, and hypersensitivity to medications and/or chemicals. 6. The illness persists for at least 6 months. It usually has an acute onset, but onset also may be gradual. Preliminary diagnosis may be possible earlier. The disturbances generally form symptom clusters that are often unique to a particular patient. The manifestations may fluctuate and change over time. Symptoms exacerbate with exertion or stress. ---------------------------------------- This summary is paraphrased from Dr. Kenny van DeMeirleir's book Chronic Fatigue Syndrome: A Biological Approach, February 2002, CRC Press, pg. 275. A few edits and suggestions were added by the M.E. Society of America. As we have noted, the M.E. Society of America holds that this is the best case definition so far, although it is not perfect. Listing more cardiac and neurological symptoms (e.g., chest pain, left-side chest aches, tachycardia, and neuropathy pain), and emphasizing muscle weakness and faintness instead of “fatigue,” would have more accurately represented the symptomatology and vastly improved the criteria (please see our M.E. Definitional Framework on this website). Nevertheless, the Canadian Consensus Panel clinical case definition more accurately represents the experience and manifestations of the disease than other current case definitions. http://www.cfids-cab.org/MESA/ccpc.html . 041222 ... monee "There is new research from a New Jersey team, authored by Doctors Arnold Peckerman, Benjamin Natelson et al., which found left-ventricular dysfunction following exertion and orthostatic stress in patients with myalgic encephalomyelitis/chronic fatigue syndrome... Dr. A. Martin Lerner holds U.S. patents for the diagnosis of ME/CFS in the chronic mononucleosis subset of this disease using 24-hour Holter monitoring. He argues that a prominent subset of the disease is a prolonged, chronic mononucleosis following infection with herpesviruses Epstein Barr (EBV), Human Cytomegalovirus (HCMV), or both, and/or possibly Human Herpes Virus 6 (HHV-6). Viral infection persists in the heart, causing left-ventricular dysfunction, producing exercise intolerance. Exercise, in turn, worsens the cardiac dysfunction. He has also postulated that the disease is an early dilated cardiomyopathy that in later stages might result in progressive, end-stage dilated cardiomyopathy, a type of heart failure. Dilated cardiomyopathy is sometimes viewed as "idiopathic," or "Idiopathic Dilated Cardiomyopathy" (IDC). In an editorial response titled "Microbial Persistence and Idiopathic Dilated Cardiomyopathy," Dr. Lerner has postulated that herpesviruses may be the etiological link. The M.E. Society holds that this is a very perceptive thesis..." http://cfids-cab.org/MESA/Lerner.html . - Research Updates - http://www.co-cure.org/infores.htm 041222 ... monee Smiling Through: A memoir of a teenager’s fight with chronic and terminal illness By Anne-Marie Vidal, with special Thanks to Sue Tobias, his mother "...I heard an energetic, warm, smiling voice at the other end of the phone and it surprised me; after all Sue Tobias had been through, I had expected a more tremulous, weak voice betraying the pain of profound loss. While talking to Sue and hearing the story of her courageous son, JR Weber, who had Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) and died of Burkitt’s Lymphoma and Leukemia shortly after his 18th birthday, there was no denying the grief, and the ache of the loss of a child, but it was equally clear that she was more than a survivor-- an amazing woman, mother, and advocate. JR, whose full name was Wayne Allen Weber, Jr., was the last of her five children and the fourth son she would raise, but the only child who had the same chronic illness that held sway over so much of her own life. “JR was about seven when he was diagnosed with CFIDS” Sue told me. “There were many visits to the emergency room,” she continued describing JR’s health prior to his diagnosis. “His throat would be so sore, it would appear to be strep throat, but the test would come back negative. Once his uvula was so swollen it blocked his breathing. He would have dangerously high fevers,” his mother told me... As a chronically ill teen, JR’s life was limited. He knew that he was unlikely to go to college but he remained upbeat. He designed some witty and political websites and played video games, loved movies, not just watching the movie, but could get involved in the technicalities of how a movie is made. He could catch the mistakes in a movie, for instance, a 19th century battle scene where in an actor forgets to remove his digital watch. JR kept his brain sharp by arguing with the talking heads on the news channels and looking for the inconsistencies in their reporting. He had three close friends whose caring sustained him to the end of his life. Yet, the laughter that came easily to the chronically ill JR came less frequently to the seriously ill JR, but he did keep smiling. Sue bought him drums and he drummed his anger and frustration into rhythms that actually were caught up by others who joined him in a band. He showed a great deal of compassion toward wounded animals and was frequently rescuing abandoned and hurt cats and guinea pigs. He enjoyed nursing a seriously ill animal back to health. A mental picture that Sue keeps in her heart is of JR putting a cat under each arm, getting in his recliner, and saying “Now, I am happy,” because at times the chronic fatigue syndrome left him with so little energy, he had to spend most of his day in the recliner. Sue’s incredible inner strength was put to the ultimate test. At 15 during a checkup, JR mentioned a re-occurring swollen axillary (armpit) gland to the doctor that came and went when his flu like symptoms seemed to peak. Knowing his history, the doctor was anxious to biopsy the area. JR was prescient and said to the doctor “It’s cancer, isn’t it?” The test came back positive for Burkitt’s Lymphoma, a non-Hodgkin’s lymphoma, which although rare, has a strong relationship to the Epstein Barre virus. Burkitt’s Lymphoma occurs clusters and may be one type of cancer in which a transmissible agent plays some role. While only 200 cases of Burkitt’s are diagnosed every year and most are in found in children in South Africa, cases have occurred in places where outbreaks of viruses that led to CFIDS have been noted. These include Incline Village, NV and Denver, CO, where patients being treated for chronic Fatigue Syndrome eventually developed B- cell lymphomas. Additionally, Sue noted that in Grants Pass, Oregon, where she and JR lived, with a population of 22,000, there are not only high rates of Fibromyalgia and CFIDS, but there is also cluster of Burkitt’s lymphoma. For JR, the news was particularly serious, it was a stage 4-cancer meaning his bone marrow and glands were deeply affected and that the cancer was full swing. He required intense chemotherapy over a 5-day period. The side effects were so powerful that 5-7 day hospitalizations and antibiotics and blood transfusions followed them. All of this occurred on a 21-day cycle. JR’s system eventually weakened and he frequently got infections, had mouth sores and eventually lost his hair. Despite these devastating side effects, JR was upbeat. The medications he took were very strong; the chemotherapy was the same as if he was preparing for a bone marrow transplant. The treatment went on for nine months. ...In the next few months, JR was frequently at death’s door, his central lines through which medicine was administered would clog. He vomited blood and had an unexplained seizure. Sue, herself a nurse, found caring for himself as medically complex as emotionally difficult. Within the last months of his life, JR developed Leukemia, because of his already existing critical illness, he was not a candidate for bone marrow treatment... JR died Jan.12, 2003, one month after his 18th birthday, and five months before he would have graduated from high school. Despite her devastating experience, some ill-informed person will occasionally tell Sue “Chronic Fatigue Syndrome is an excuse of being lazy.” Letting them have the full reality of her pain, Sue replied, “That excuse for being lazy took my son to his grave before he could finish high school”. After the shock of her reply, Sue had their attention to explain what CFIDS is and how little it has to do with fatigue. She knows that there are people who are afraid of invisible illnesses like CFS and FMS. When she and JR returned to Grant’s Pass, Oregon, about ten years ago, a Family Nurse practitioner told her: “I wish you and all those like you would leave this valley so we wouldn't have to educate ourselves”. After the anger wore off, she started Rogue Valley CFIDS/ FM Awareness support group. Sue’s courage has been endearing and impressive. As we spoke of JR’s struggle, an emotionally charged topic, her voice would tighten, but she was always professional, compassionate and at times, humorous. “I want to call attention to the link between CFIDS and cancer,” she said, “not enough is known, and what is, receives little attention.” JR Weber lived and died with grace and humor and it is no surprise. His mother also demonstrated the same grace under fire; she argues that her grace, humor and strength, are a gift from JR. One thing is sure; they were an incredible team... Few things in life are certain. But I am positive that Sue is a survivor and an advocate who has kept going through loss, health problems, and negativity. She is an inspiration to me and I hope she is to everyone who reads this..." http://www.ourfm-cfidsworld.org/html/smiling_through.html . 041222 ... monee http://blather.newdream.net/red/t/tired.html http://blather.newdream.net/red/m/m_e.html http://blather.newdream.net/red/t/trauma_and_cfs.html . 041222 ... monee http://blather.newdream.net/red/r/reading_up.html . 041222 ... monee http://blather.newdream.net/red/a/ahhhhhhhhhhhhhhhhhhhhhhhhhhhhh.html http://blather.newdream.net/red/m/my_relentless_heartbeat.html . 041222 ... monee lump twitches strangeness cloud_in_my_eye http://blather.newdream.net/red/h/headaches.html http://blather.newdream.net/red/a/and_i_can_t_sleep.html but_i_should . 041222 ... monee http://blather.newdream.net/t/the_pain.html http://blather.newdream.net/red/n/neck.html http://blather.newdream.net/red/s/shoulder.html http://blather.newdream.net/red/t/ten_years.html 041222 ... . the_pain 041222 ... monee Research Kills Theory That Chronic Fatigue Syndrome/ME is Psychosomatic ImmuneSupport.com 12-06-2002 High Profile Sufferer: Up to 6,000 ME sufferers in Northern Ireland, like round-the-world yachtswoman and author Clare Francis, are now being recognised as suffering with the debilitating illness Source: the Irish News (Belfast, Northern Ireland) via Co-Cure By Anne Madden Health Correspondent "...A light flashed at the end of a tunnel of ignorance and enigma for thousands of ME sufferers at a conference in Belfast on Saturday, November 2, 2002. World-renowned clinician Professor Kenny De Meirleir from Belgium discussed the findings of his research which demolishes the long-held theory that ME is psychosomatic. The debilitating condition, which affects around 6,000 people in Northern Ireland and 240,000 across the UK, has a range of symptoms chiefly characterised by chronic tiredness. For years ME (Myalgic Encephalomyelitis) or Chronic Fatigue Syndrome (CFS) has been mocked as the 'yuppie flu' suggesting that sufferers are all middle class neurotics. However, the results of Professor De Meirleir's £3 million research offer a powerful case for ME being a biological, not a psychological problem. The professor, who is an advisor to the US and Canadian governments on ME, told the conference at Queen's University, Belfast that the difficulty of the disease is that it is not one but several conditions. He described how there are three main sub-groups of the disease, from mild to severe, with a variety of symptoms. But the factor that is common to them all is a disordered immune system. "Innate immunity dysfunction would be a more accurate name for CFS," he said. Professor De Meirleir described how there are a number of different mechanisms which trigger the condition, but he has no doubt that CFS is an immune disorder. "No two people have the same disorder," he said. "In some people it is stress plus exposure to heavy metals. In other cases people may have had a long-standing stress plus a viral infection which wasn't treated properly." The professor offered hope to many sufferers that if CFS is diagnosed in its early stages it can be treated with the right combination of therapies. However, the most severe cases who suffer for more than 10 years can suffer permanent damage to their immune system which greatly enhances their risk of cancer. "The pathology of the disease is not a mystery anymore," he said. "The Americans have now worked out the entire genome of CFS. Unsurprisingly, all the genes are related to the immune system. We can say for certain that CFS is an immune disorder. However, he argued that genetic predisposition is a weak factor in the disease, although it is about twice as common in women as men. Exposure to heavy metals or organophosphates , contracting a lymphotropic virus such as Dengue fever or EBV and long-standing mental or physical stress can all be trigger factors. His research also reveals that 6.4 per cent of ME patients began suffering symptoms 40 to 72 hours after a blood transfusion..." "It is time people with ME had their condition investigated just like people who present with other diseases such as cancer" http://www.immunesupport.com/library/showarticle.cfm/ID/4099/e/1/T/CFIDS_FM/ . 041222 ... monee "...According to a large American study by Dr. Leonard Jason, approximately 422 per 100,000 people (approximately 150,000 Canadians) suffer from ME/CFS compared to 26 per 100,000 women who have breast cancer. ME/CFS is a severe illness that can be debilitating. There is no known cure. It often begins with a viral type infection such as an acute respiratory or flu-like illness. But instead of recovering, the person's health deteriorates and many other symptoms appear. A number of viruses have been studied but so far there is no conclusive support for any one pathogen causing the illness. Numerous studies have confirmed that there is a biochemical breakdown of one of the body s defense pathways used to fight viruses, which supports the theory that ME/CFS is triggered by an infection. Other triggers and mechanisms are also being investigated..." http://pages.ivillage.com/cfidspgh/id83.html . 041222 ... monee chronic_fatigue_syndrome myalgic_encephalomyelitis . 041222 ... monee Novel Chronic Fatigue Syndrome (CFS) Theory Finally Produces Detailed Explanations for Many CFS Observations 03-12-2003 By Dr. Martin L. Pall Professor of Biochemistry and Basic Medical Sciences Washington State University Source: http://molecular.biosciences.wsu.edu/Faculty/pall.html A novel theory of the cause of Chronic Fatigue Syndrome (CFS) has been published which is supported by diverse biochemical and physiological observations of CFS, while providing explanations for five of most difficult puzzles about this medical condition. The theory has been published by Dr. Martin L. Pall (Professor of Biochemistry and Basic Medical Sciences, Washington State University) in several publications (1-4,9). The theory starts with the observation that infections that precede and may therefore induce CFS and related conditions act to induce excessive production of inflammatory cytokines that induce, in turn, the inducible nitric oxide synthase (iNOS). This enzyme, in turn, synthesizes excessive amounts of nitric oxide which reacts with another compound (superoxide) to produce the potent oxidant peroxynitrite. Peroxynitrite acts via six known biochemical mechanisms to increase the levels of both nitric oxide and superoxide which react to produce more peroxynitrite. In this way, once peroxynitrite levels are elevated, they may act to continue the elevation, thus producing a self-sustaining vicious cycle (ref.1). It is this cycle, according to the theory, that maintains the chronic symptoms of CFS and it is this cycle, therefore, that must be interrupted to effectively treat this condition. Twelve different observations on chronic fatigue syndrome and its symptoms provide support for this theory: 1. The levels of neopterin, a marker for the induction of the inducible nitric oxide synthase are reported to be elevated in CFS (1). 2. Mitochondria are reported to be dysfunctional in CFS and mitochondria are known to be attacked by peroxynitrite and also by nitric oxide (1). 3. Both cis-aconitate and succinate levels are reported to be elevated in CFS and the enzymes that metabolize these two compounds are known to be inactivated by peroxynitrite (1). 4. The four inflammatory cytokines implicated have been reported to be elevated in 10 different studies of CFS (1,2). 5. These same inflammatory cytokines have been reported to induce fatigue when injected into humans (1). 6. An animal (mouse) model of CFS has "fatigue" induced by a bacterial extract that can induce both the inflammatory cytokines and also the inducible nitric oxide synthase. 7. Polyunsaturated fatty acid pools are reported to be depleted in CFS and such polyunsaturated fatty acids are known to be oxidized by oxidants such as peroxynitrite. 8. Anecdotal evidence has suggested that antioxidants such as coenzyme Q10, flavonoids and glutathione precursors may be useful in CFS treatment, consistent with a role for an oxidant such as peroxynitrite. 9. Women are reported to produce more nitric oxide than men, possibly explaining the gender bias seen in CFS. A similar gender bias is seen in autoimmune diseases characterized by excessive peroxynitrite (e.g., lupus, rheumatoid arthritis). 10. Cases of CFS are associated with high levels of deleted mitochondria DNA, suggesting but not proving that mitochondrial dysfunction can produce the symptoms of CFS (1). 11. Biochemical similarities - depletion of glutamine and cystine pools - have been reported in CFS and several diseases characterized by elevated peroxynitrite levels, suggesting a similar biochemical basis for all of these conditions (1). 12. Because peroxynitrite is a potent oxidant, this theory predicts that oxidative stress will be elevated in CFS. There was no direct evidence for this when the theory was published, but three subsequent papers have reported substantial evidence for such oxidative stress in CFS (5-7A). These results, may therefore, be considered to confirm important predictions of the theory, although the authors were unaware of this theory when they initiated these studies. CFS puzzles explained by the elevated nitric oxide/peroxynitrite theory: There are five different puzzles of CFS that are explained by this theory. The first of these, the chronic nature of CFS, is explained by the self-sustaining vicious cycle that is central to this theory. The second is how infection and other stress which often precede CFS may produce CFS. This theory predicts that each of these can lead into this mechanism by inducing excessive nitric oxide. Infection is not the only stress that may be involved in this way - both physical trauma and severe psychological trauma can produce excessive nitric oxide synthesis (2). In addition, tissue hypoxia may induce this cycle by increasing levels of superoxide (the other precursor of peroxynitrite) (2). A third puzzle about CFS is how it leads to the many biochemical/physiological correlates reported to occur in CFS. This is discussed with the list of 12 such correlates described above. A fourth puzzle about CFS is how the diverse symptoms of this condition may be generated. It turns out that a variety of factors, including nitric oxide, superoxide, oxidative stress and mitochondrial/energy metabolism dysfunction may have important roles (2). For example, nitric oxide is known to stimulate the nociceptors that initiate the perception of pain, and therefore excessive nitric oxide may cause the multi-organ pain associated with CFS (2). Nitric oxide has a central role in learning and memory and so its elevation may also provide a partial explanation for the cognitive dysfunction characteristic of CFS (2). Other symptoms explained by this theory include orthostatic intolerance, immune dysfunction, fatigue and post-exertional malaise (2). The immune dysfunction reported in CFS may allow for opportunistic infections to develop, such as mycoplasma or HHV6 infections, which may exacerbate the basic CFS mechanism by increasing inflammatory cytokine synthesis. What about multiple chemical sensitivity, posttraumatic stress disorder and fibromyalgia? A fifth puzzle regarding CFS is its variable symptoms and, most importantly, its association with three other conditions of equally puzzling etiology, multiple chemical sensitivity (MCS), posttraumatic stress disorder (PTSD) and fibromylagia (FM). The theory explains the variable symptoms, from one case to another, in part, by a somewhat variable tissue distribution of the elevated nitric oxide/peroxynitrite. A common etiology (cause) for CFS with MCS, PTSD and FM has been suggested by others (discussed in refs 4,9). A common causal mechanism for these four conditions is suggested not only by the association among these different conditions (many people are afflicted by more than one) but also by the overlapping symptoms typically found in these four conditions (see refs. 4 and 9 for discussion). These overlaps raise the question about whether MCS, FM and PTSD may be caused by excessive nitric oxide and peroxynitrite. Each of these four conditions is reported to be often preceded by and possibly induced by exposure to a relatively short-term stress that can induce excessive nitric oxide synthesis. Pall and Satterlee (4) present a substantial case for an excessive nitric oxide/peroxynitrite cause for multiple chemical sensitivity (MCS), including the following: - Organic solvents and pesticides whose exposure is reported to precede and presumably induce multiple chemical sensitivity, are also reported to induce excessive nitric oxide synthesis. Such chemicals are also reported to induce increased synthesis of inflammatory cytokines which induce, in turn, the inducible nitric oxide synthase (leading to increased synthesis of nitric oxide). - Neopterin, a marker of induction of the inducible nitric oxide synthase, is reported to be elevated in MCS. - Markers of oxidative stress are reported to be elevated in MCS, as predicted if excessive peroxynitrite is involved. - In animal models of MCS, there is convincing evidence for an essential role for both excessive NMDA activity (where such activity is known to induce excessive nitric oxide) and for excessive nitric oxide synthesis itself. If one blocks the excessive nitric oxide synthesis in these animal models, the characteristic biological response is also blocked. This and other evidence shows that nitric oxide has an essential role (4). Somewhat similar evidence is available suggesting an elevated nitric oxide/peroxynitrite mechanism for both PTSD and FM (9). PTSD is thought to be induced by excessive NMDA stimulation, which, as discussed above, is known to produce excessive nitric oxide and peroxynitrite (9). Two inflammatory cytokines known to induce increased synthesis of nitric oxide have been reported to be elevated in PTSD. PTSD animal model studies have reported an essential role for both excessive NMDA stimulation and nitric oxide synthesis in producing the characteristic biological response. Interestingly, a recent study of FM implicates elevated nitric oxide and also elevated NMDA stimulation (8), and such NMDA stimulation is known to increase nitric oxide synthesis. As in the other conditions discussed here, there is a pattern of evidence from studies of FM patients, consistent with the proposed nitric oxide/peroxynitrite mechanism (9). The theory that elevated nitric oxide/peroxynitrite is responsible for the etiology of CFS, MCS, PTSD and FM appears to be the only mechanism to be proposed that explains the multiple overlaps among these four conditions. While the pattern of evidence supporting it cannot be considered definitive, the many types of evidence providing support for this view must be considered to be highly suggestive. What does this proposed mechanism suggest about CFS treatment? As discussed in ref 1, there are a number of agents that may be useful in the treatment of CFS, based primarily on anecdotal evidence, that are expected to lower the consequences of the proposed nitric oxide/peroxynitrite mechanism. Possibly the most intriguing such mechanism relates to the widespread use of vitamin B12 injections in treatment of CFS (3). Two forms of vitamin B12 are being used here, hydroxocobalamin, which is a nitric oxide scavenger and cyanocobalamin, which is converted to hydroxocobalamin by Pall human cells (3). These observations suggest that the nitric oxide/peroxynitrite proposed mechanism for CFS makes useful predictions for effective treatment. It is hoped that this proposed mechanism may allow us to optimize the use of these and other agents for treatment of CFS and related conditions. Other sites with thoughtful presentations that you may wish to access are as follows: http://www.cfsresearch.org/cfs/ http://www.square-sun.co.uk/cfs-nim/ http://www3.sympatico.ca/me-fm.action/ from: http://www.chronicfatiguesupport.com/library/showarticle.cfm/ID/4393/ . 041222 ... monee in_memory_of_those_who_have_died . 041223 what's it to you? who go blather from