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CO-CURE Medical & Research Posts Only Digest - 25 Sep 2006 to 2 Oct 2006 (#2006-45)

There are 21 messages totalling 3112 lines in this issue. Topics of the week:

[Return to digest index] --------------------------------------------- This is a special digest of Co-Cure Research & Medical posts only Problems? Write to mailto:mods@co-cure.org --------------------------------------------- ---------------------------------------------------------------------- Date: Tue, 26 Sep 2006 12:15:09 +0200 From: "Dr. Marc-Alexander Fluks" <fluks@xxx.xx> Subject: RES,NOT: Omega-3 present at 'Food for the Brain' conference Source: Food for the Brain Date: September 2006 URL: http://www.foodforthebrain.org/FFBconference The Food for the Brain Conference --------------------------------- Saturday 30th September 2006 Brain function is totally dependent on nutrition. What is the best food for the brain? Since we are all genetically unique it's different for each of us. A foundation for mental health is to discover an individual's 'optimum nutrition'. With that foundation the mind becomes clearer and mood brighter, making it easier to learn and resolve psychological conflicts. This conference uniquely brings a wide range of international experts and delegates together - from education, medicine, nutrition, dietetics, psychiatry, psychology and psychotherapy - to explore the rich subject of what is the best food for the brain, and consequently, mental health and behaviour. 'Mental health problems are fast becoming the number one health issue for the 21st century, with one in ten people suffering at any point in time, and one in four people suffering at some point in their life.' World Health Organisation Whether or not you treat patients including nutritional intervention, no-one in the field of mental health can afford to ignore the tell-tale signs of biochemical imbalance that mean a particular individual is likely to respond positively to improved nutrition. If you are relatively new to this field we strongly recommend you attend the Primer 'Nutrition Foundations for Mental Health' by Patrick Holford, founder of the Institute for Optimum Nutrition and director of the Brain Bio Centre, on Saturday afternoon. For more information on the content of each of the days at the conference please click on the links below. Primer - Saturday 30th September http://www.foodforthebrain.org/content.asp?id_Content=1652 Day 1 - Sunday 1st October http://www.foodforthebrain.org/content.asp?id_Content=1653 Day 2 - Monday 2nd October http://www.foodforthebrain.org/content.asp?id_Content=1654 Fund Raising Party, Sunday 1st October http://www.foodforthebrain.org/content.asp?id_Content=1670 Speakers at the conference http://www.foodforthebrain.org/content.asp?id_Content=1649 These 'omega-3' speakers from the CFS-world will attend the conference... - Professor Malcolm Peet - Alex Richardson PhD - Professor Basant Puri Notes... ----------------------------------------------------------------------- * There also is a speaker from 'Vitamin Diagnostics': Tapan Audhya. * This firm is involved in cannibalism and is on the black list of the US government, http://www.cms.hhs.gov/CLIA/downloads/regis03.pdf * 'Vitamin Diagnostics' is also present on the list of pyroluria test laboratories, http://www.nutritional-healing.com.au/content/articles-content.php?heading=Pyroluria * The Dutch firm on this list, 'Klinisch Ecologisch Allergie Centrum' just lost its court case on 'HPU'-quackery (HPU is the disease PWCs in The Netherlands can buy for 500 Euro/450 dollar/330 pounds if they want to proof that CFS is 'all in the mind'). This is the official link to the Amsterdam Court of Justice, http://zoeken.rechtspraak.nl/resultpage.aspx?snelzoeken=true&searchtype=kenmerken&vrije_tekst=AY8209 The court case was on a scientific paper stating that all of this is quackery, http://www.nvkc.nl/publicaties/documents/2006-1-p58-64.pdf The problem, again, is that the text is in Dutch. * On the 'Food for the Brain' address, we also find this firm, Brain Bio Centre Carters Yard London SW18 4JR United Kingdom [Return to top] ------------------------------ Date: Tue, 26 Sep 2006 14:05:53 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Psychometric properties of the Centers for Disease Control and Prevention Health-Related Quality of Life (CDC HRQOL) items in adults with arthritis Psychometric properties of the Centers for Disease Control and Prevention Health-Related Quality of Life (CDC HRQOL) items in adults with arthritis. Health Qual Life Outcomes. 2006 Sep 24;4(1):66 [Epub ahead of print] Mielenz T, Jackson E, Currey S, Devellis R, Callahan LF. PMID: 16995955 ABSTRACT: BACKGROUND: Measuring health-related quality of life (HRQOL) is important in arthritis and the SF-36v2 is the current state-of-the-art. It is only emerging how well the Centers for Disease Control and Prevention (CDC) HRQOL measures HRQOL for people with arthritis. This study's purpose is to assess the psychometric properties of the 9-item CDC HRQOL (4-item Healthy Days Core Module and 5-item Healthy Days Symptoms Module) in an arthritis sample using the SF-36v2 as a comparison. METHODS: In Fall 2002, a cross-sectional study acquired survey data including the CDC HRQOL and SF-36v2 from 2 North Carolina populations of adult patients reporting osteoarthritis, rheumatoid arthritis, and fibromyalgia; 2182 (52%) responded. The first item of both the CDC HRQOL and the SF-36v2 was general health (GEN). All 8 other CDC HRQOL items ask for the number of days in the past 30 days that respondents experienced various aspects of HRQOL. Exploratory principal components analyses (PCA) were conducted on each sample and the combined samples of the CDC HRQOL. The multitrait-multimethod matrix (MTMM) was used to compute correlations between each trait (physical health and mental health) and between each method of measurement (CDC HRQOL and SF36v2). The relative contribution of the CDC HRQOL in predicting the physical component summary (PCS) and the mental component summary (MCS) was determined by regressing the CDC HRQOL items on the PCS and MCS scales. RESULTS: All 9 CDC HRQOL items loaded primarily onto 1 factor (explaining 57% of the item variance) representing a reasonable solution for capturing overall HRQOL. After rotation a 2 factor interpretation for the 9 items was clear, with 4 items capturing physical health (physical, activity, pain, and energy days) and 3 items capturing mental health (mental, depression, and anxiety days). All of the loadings for these two factors were greater than 0.70. The CDC HRQOL physical health factor correlated with PCS (r=-.78, p<0.0001) and the mental health factor correlated with MCS (r=-.71, p<0.0001). The relative contribution of the CDC HRQOL in predicting PCS was 73% (R2= .73) when GEN was included in the CDC HRQOL score and 65% (R2 = .65) when GEN was removed. The relative contribution of the CDC HRQOL in predicting MCS was 56% (R2 = .56) when GEN was included and removed. CONCLUSION: The CDC HRQOL appears to have strong psychometric properties in individuals with arthritis in both community-based and subspecialty clinical settings. The 9 item CDC HRQOL is a reasonable measure for overall HRQOL and the two subscales, representing physical and mental health, are reasonable when the goal is to examine those aspects. [Note: This is an Open Access article. The full text is available in PDF at http://www.hqlo.com/content/pdf/1477-7525-4-66.pdf .] [Return to top] ------------------------------ Date: Wed, 27 Sep 2006 00:26:06 -0700 From: "Jean Harrison...............Via Co-Cure moderator" Subject: MED: One man's meat Something which has troubled me for years is the insistence that a given treatment work for everyone before people think of trying it. The attitude even of the FDA is troubling. Individuals are quite different, and can tolerate different things.."One man's meat is another's poison" is most decidedly true. There are so many things that cannot yet be explained (why do some people die from eating peanuts while others can eat them happily). Yes, I know some are allergic to them but that's just restating the problem. It's the why of the allergy that still remains an unknown. Why can some tolerate ibuprofen while it makes others go into dementia? Why did doctors say that I wasn't "allergic" to certain foods, but when I ate them I broke out in eczema, and if I didn't eat them I didn't break out? Why was I sensitive to foods in the first place? Why are there such broad ranges of "normal" in some tests.. Why is it that something like 90% of adrenal function has to be off before Addisons can be diagnosed? Why is it that some people can smoke all their lives and not get cancer? Had a grandfather who smoked from the time he was 14 till he was 94 when he died of other causes. Yet my mother, his daughter, who smoked lightly, got lung cancer. I have a friend whose husband had stage 4 lung cancer. He was given various trial medications. His wife couldn't understand (nor can I) why it was that he would be taken off if the tumor stopped growing - doctors said that the meds were supposed to make the tumor shrink. Who knows, maybe he'd be alive today - albeit compromised - if they had left him on drugs which simply stopped the growth of his tumor. And by the way, the fellow never smoked, had no family history of lung cancer, but eventually he died of it. And he wasn't diagnosed till it was stage 4. Some day these questions will be answered, but science isn't there yet. Many assumptions are wrong. So I do hope that people with ME/CFS aren't put off by hearing that X drug didn't work for someone - or even by a few people. It might turn out that that drug will be of tremendous benefit to a given patient. The definition of CFS leads to a vastly heterogenous group; it would only make sense if drugs worked for some and not others. So I urge people to try things if they hear that they have helped others with similar medical problems. Obviously I'm not suggesting that you return to graded exercise if you've had problems with exercise; nor am I suggesting taking a medication which you have reason to think won't help. But if you haven't tried something that helps some, just because it doesn't work for some other patients doesn't necessarily mean it won't work for you. Jean Harrison [Return to top] ------------------------------ Date: Tue, 26 Sep 2006 22:24:19 -0400 From: "Lois Ventura <knothome@xxxx.xxx> [via Co-Cure Moderators]" Subject: MED,NOT:ICD-10 INDEX question Recently, there has been some confusion and questions regarding 2006 version of the ICD-10 TABULAR posted to the WHO website. Chronic fatigue syndrome is not listed there, and some may have interpreted that as CFS having been deleted from ICD-10. But there are many listings in the ICD-10 INDEX, which is not posted to the WHO website. (You can buy the INDEX from the WHO website as a download, CD or as a print volume if you can afford the $340 - $1,000.) So, I took the liberty of contacting the North American WHO Collaborating Center and asked if and where CFS was in the ICD-10 INDEX. The communication is below. Also, a few months ago, I asked coder Amy Blum of the CDC's ICD Coordination & Maintenance Committee what the significance of a condition being coded in the ICD TABULAR as opposed to the ICD INDEX. Her response: "The index is the alphabetical list of all terms and conditions that are classified. The tabular is the structured set of codes. There are many terms in the index that are not included in the tabular due to the many codes that are "other" and "unspecified" codes. This is the way a statistical classification is designed." (I'm not a statistician, so I guess this was the short answer, CDC-style:-) She also noted that most doctor's offices and hospitals use the INDEX. (Note: I have already emailed the WHO website contact with the question about posting the 2006 ICD-10 INDEX. I will post a follow-up when/if I receive a response.) Lois Ventura www.name-us.org ----- Original Message ----- From: urcsecretariat To: Lois Ventura Sent: Tuesday, September 26, 2006 8:57 AM Subject: RE: ICD-10 INDEX question Dear Lois, Our apologies for the delay in responding to your email. Chronic fatigue syndrome is indexed in the following manner in ICD-10. Syndrome - fatigue F48.0 - - chronic G93.3 - - postviral G93.3 We suggest you direct your question about whether or not WHO has any plans to publish the index on the website to WHO. The contact there is jakobr@who.int Sincerely, Lori Moskal URC secretariat ------------------------------------------------------------------------- ----- Original Message ----- From: Lois Ventura To: urcsecretariat@cihi.ca Sent: Tuesday, September 05, 2006 12:26 PM Subject: ICD-10 INDEX Dear North American Collaborating Centre Contact: I have noticed in the 2006 revision of the ICD-10 Tabular posted on the WHO website that I cannot find the disease Chronic Fatigue Syndrome. Can you tell me where/if it is listed in the 2006 revision of the ICD-10 INDEX? (I have copies of the ICD-10-CM tabular and index from the U.S. CDC website, but for my research purposes, I am interested in the WHO original ICD-10 2006 revision. I am a patient on disability and cannot afford to purchase a copy of the Index to look this information up. Will the 2006 revised Index be made available also at the WHO website, like the tabular?) Thank you so much for your time! Lois Ventura www.name-us.org [Return to top] ------------------------------ Date: Wed, 27 Sep 2006 13:18:39 -0400 From: Co-Cure Moderator <ray@xxxxx.xxx> Subject: MED: Guidance for Fibromyalgia Patients Who Are Having Elective Surgery If you are having a major surgical procedure there are some issues that you may wish to discuss with your surgeon and anesthesiologist that could reduce the fibro-flare that often occurs after surgery in Fibromyalgia patients. Read this article at http://www.immunesupport.com/library/showarticle.cfm?id=7330 [AOL: <a href="http://www.immunesupport.com/library/showarticle.cfm?id=7330">Here</a>] [Return to top] ------------------------------ Date: Wed, 27 Sep 2006 13:44:12 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: A comprehensive review of 46 exercise treatment studies in fibromyalgia (1988-2005) A comprehensive review of 46 exercise treatment studies in fibromyalgia (1988-2005). Health Qual Life Outcomes. 2006 Sep 25;4(1):67 [Epub ahead of print] Links Jones KD, Adams D, Winters-Stone K, Burckhardt CS. PMID: 16999856 ABSTRACT: The purpose of this review was to: (1) locate all exercise treatment studies of fibromyalgia (FM) patients from 1988 through 2005, (2) present in tabular format the key details of each study and (3) to provide a summary and evaluation of each study for exercise and health outcomes researchers. Exercise intervention studies in FM were retrieved through Cochrane Collaboration Reviews and key word searches of the medical literature, conference proceedings and bibliographies. Studies were reviewed for inclusion using a standardized process. A table summarizing subject characteristics, exercise mode, timing, duration, frequency, intensity, attrition and outcome variables was developed. Results, conclusions and comments were made for each study. Forty-six exercise treatment studies were found with a total of 3035 subjects. The strongest evidence was in support of aerobic exercise a treatment prescription for fitness and symptom and improvement. In general, the greatest effect and lowest attrition occurred in exercise programs that were of lower intensity than those of higher intensity. Exercise is a crucial part of treatment for people with FM. Increased health and fitness, along with symptom reduction, can be expected with exercise that is of appropriate intensity, self-modified, and symptom-limited. Exercise and health outcomes researchers are encouraged to use the extant literature to develop effective health enhancing programs for people with FM and to target research to as yet understudied FM subpopulations, such as children, men, older adults, ethnic minorities and those with common comorbidities of osteoarthritis and obesity. [Note: This is an Open Access article. It can be downloaded in PDF at http://www.hqlo.com/content/pdf/1477-7525-4-67.pdf .] [Return to top] ------------------------------ Date: Wed, 27 Sep 2006 11:39:04 -0700 From: "Marilyn Brandt <msbnurse@xxxxx.xxx>........via Co-Cure moderator" Subject: MED: regarding pre/post-op care for Fibro-mites What a helpful piece of information for those people who are not familiar with how our body works...and how to help your Dr. understand our case and our bodies needs..thanks so much! As a nurse..and also a fibromyalgia patient, I am familiar with these ideas, however, I have one concern...what the Dr.s think when we as patients hand this to them.....I am wondering just what they might tell us to do with this piece of paper ;-)...and it is sad..becasue this could help so many of us feel so much better right away in the post op! Guidance for Fibromyalgia Patients Who Are Having Elective Surgery by The Oregon Fibromyalgia Team ImmuneSupport.com 09-27-2006 If you are having a major surgical procedure there are some issues that you may wish to discuss with your surgeon and anesthesiologist that could reduce the "fibro-flare" that often occurs after surgery in Fibromyalgia patients. 1. Request that you wear a soft neck collar and minimize neck hyperextension (if an endotracheal tube is anticipated). 2. Request that your arm with the intravenous line be kept near your body, not away from your body or over your head. 3. Request that you be given a pre-operative opioid pain medication - about 90 minutes prior to surgery. Opioids are morphine or morphine related drugs. The rationale for the pre-operative use of opioids is to minimize "central sensitization" - as this inevitably worsens the widespread body pain that you are already experiencing. 4. Ask to have a long-acting local anesthetic infiltrated into your incision - even though you will be asleep during the procedure. The rationale for this is to minimize pain impulses reaching the spinal cord and brain, which in turn drive central sensitization. 5. As a Fibromyalgia patient you will need more, a usually longer duration, of post-operative pain medication. In most cases opioids should be regularly administered or self administered with a PCA pump (patient controlled analgesia). 6. Most Fibromyalgia patients require a longer duration of post-operative convalescence, including physical therapy in many cases. This information is reproduced with permission from the Oregon Health & Science Fibromyalgia Research and Treatment Team, headed by Robert Bennett, MD. For information on the team's frequently scheduled speaking engagements in the states of Washington and Oregon and elsewhere, go to their Web site at www.myalgia.com [Return to top] ------------------------------ Date: Thu, 28 Sep 2006 00:25:08 -0700 From: Co-Cure moderator <cocuremoderator@xxxxx.xxx> Subject: Med,Act: Q Fever: soldiers returning from Iraq may be at risk & symptoms from mycoreg@xxxx.xxx Chronic Q Fever is one of the causes of Chronic Fatigue Syndrome/Gulf War Syndrome. The treatment is Doxycycline. * * * * * * * * * * * * * * * * * * * * * * * * * * * MYCOPLASMA REGISTRY REPORTS for gulf war syndrome & chronic fatigue syndrome 2006 Sean Dudley & Leslee Dudley. All rights reserved. <http://groups.yahoo.com/group/MycoplasmaRegistry/> <MycoplasmaRegistry-subscribe@yahoogroups.com> * * * * * * * * * * * * * * * * * * * * * * * * * * * Soldiers Returning From Iraq May Be at Risk for Q Fever By Peggy Peck, Senior Editor, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine. MedPage Today - Little Falls,NJ,USA-September 27, 2006 http://www.medpagetoday.com/Pulmonary/Pneumonia/tb/4183 ELGIN AIR FORCE BASE, Fla., Sept. 27 -- A few troops returning from Iraq are bringing home Q fever, a zoonotic disease caused by the rickettsial pathogen Coxiella burnetii, according to military physicians. During the first Gulf War there only three cases of Q fever occurred among U.S. military forces, but there have been 10 cases among soldiers serving in the current war, the physicians reported in the Oct. 15 issue of Clinical Infectious Diseases. Eight of those cases occurred in patients first diagnosed with pneumonia, wrote Major Patrick J. Danaher, M.D., chief of infectious diseases at the medical center here, and Charmaine Leung-Shea, M.D., of David Grant U.S. Air Force Medical Center at Travis Air Force Base in California. Q fever can range from a subclinical illness to an infection that becomes severe and chronic, or even fatal. It can appear as pneumonia or a cardiovascular or hepatic illness. It can lead to bone infections, or such neurological complications as encephalitis, aseptic meningitis, or dementia. The primary reservoir of Q fever is animals such as sheep, goats, and cattle. One of the patients Drs. Grant and Leung-Shea described subsequently developed chronic fatigue syndrome. The authors concluded that there is a need for further studies, including serosurveys of military units with cases, using stored serum samples obtained before and after deployment. They suggested a case-control study to assess the risk factors for Q fever in U.S. forces in Iraq to allow development of effective prevention strategies, and a longitudinal study to evaluate the occurrence of chronic fatigue syndrome and long-term health sequelae." In their paper, they described two of the 10 cases. The first was a 39-year-old man who served in the U.S. Army in Iraq from April to July 2003. He started weekly Lariam (mefloquine) therapy two weeks before his deployment to Iraq, but he stopped taking the drug two weeks before he returned to the U.S. During his deployment he lived and ate in a house that bordered on an old sheep farm, and at a farewell party before he returned to the U.S. a sheep that was ceremonially slaughtered was served. Two weeks after his return, he developed a sore throat, fever, myalgia, chills, sweats, headache, and anorexia. He made two visits to a primary care clinic and each time was treated with naprosyn. He was also taking AcipHex (rabeprazole) for gastroespohageal reflux disease. A week after onset of symptoms his fever spiked at 104=BA F (40=BAC) and he became listless. He was admitted to a hospital, where the laboratory findings revealed alanine transaminase level more than seven fold higher than the high normal range (465 IU/L), and an alkaline phasphatase level more than twice the normal high range (267 IU/L). Additional lab results included a slightly depressed white blood cell count (4,600 cells/=B5L), a depressed platelet count (64,000 platelets/=B5L), and a slightly elevated fibrinogen level (472 mg/dL). Chest films revealed a right middle lobe infiltrate and CT revealed an enlarged liver. Liver biopsy found numerous nonspecific ganulomas without fibrin rings-a notable finding because the signature liver lesion of C. burnetii is a fibrin-ring granuloma. The patient defervesced with 72 hours of Zosyn (piperacillin-tazobactam). He was discharged after eight days of Zosyn therapy and continued on a six-day outpatient course of Levaquin (levofloxacin). Eight weeks after the onset of illness, he was examined at the infectious diseases clinic. At that time, liver enzymes had returned to normal and the patient was asymptomatic except for mild lethargy. Serological testing done at that time suggested identified C. burnetii as the likely cause of the acute episode and blood work suggested chronic Q fever. He was treated with one month of doxycycline and subsequent serological testing suggested acute, resolved Q fever. Although the patient's symptoms resolved by January 2004, eight months later he developed symptoms of chronic fatigue syndrome. The second patient was a 34-year-old Air Force member who served in Iraq for three months in 2004. He became symptomatic about three weeks after returning to the U.S. and he was admitted to the hospital after four days of fever, headache, myalgia, malaise and anorexia and one day of loose stools. While serving in Iraq he remained within the base compound and reported no suspect food or animal exposure. In the U.S. he had a pet dog and a pet rabbit, both of which were healthy. His wife had a self-limiting febrile illness the week before he became symptomatic. Blood work was unremarkable, but as in the first case he had markedly elevated liver enzymes: asparatate aminotransterase level was more than fourfold higher than normal high range (176 IU/L), and alanine transaminase was almost two and a half times higher (157 IU/L). He received empirical therapy with Rocephin (ceftriaxone) for seven days. A week after discharge, he remained febrile and was started on a month of doxcycline and Rifadin (rifampin). Based on the experience with the first patient, the physicians ordered serological testing for C. burnetii antibodies. Again the first test suggested chronic infection and subsequent tests were consistent with acute Q fever. The authors explained that earlier reports suggested that the risk of Q fever increased with exposure to livestock, as happened with the first case they described, which supported the "theory that Q fever poses an increased threat to nonconventional forces." Primary source: Clinical Infectious Diseases Source reference: Leung-Shea C and Danaher PJ "Q Fever in Members of the United States Armed Forces Returning from Iraq" CID 2006; 43:e77-82 MedPage Today Action Points: Explain to interested patients that this is a preliminary report. The actual risk of Q-fever among soldiers serving in Iraq needs to be confirmed in a larger study. Disclaimer: The information presented in this activity is that of the authors and does not necessarily represent the views of the University of Pennsylvania School of Medicine, MedPage Today, and the commercial supporter. Specific medicines discussed in this activity may not yet be approved by the FDA for the use as indicated by the writer or reviewer. Before prescribing any medication, we advise you to review the complete prescribing information, including indications, contraindications, warnings, precautions, and adverse effects. Specific patient care decisions are the responsibility of the healthcare professional caring for the patient. 9 2004-2006 MedPage Today, LLC. All Rights Reserved. * * * * * * * * * * * * * * * * * * * * * * * * * * * [Return to top] ------------------------------ Date: Fri, 29 Sep 2006 12:45:22 +0200 From: "Dr. Marc-Alexander Fluks" <fluks@xxx.xx> Subject: RES,NOT: Review of 46 exercise treatment studies in fibromyalgia Source: Health and quality of life outcomes Vol. 4, #1, pp 67 Date: September 25, 2006 URL: http://www.hqlo.com/articles/browse.asp http://www.hqlo.com/content/4/1/67 A comprehensive review of 46 exercise treatment studies in fibromyalgia (1988-2005) ----------------------------------------------------------------------- Kim Dupree Jones(1,2), Dianne Adams(1), Kerri Winters-Stone(1), and Carol S Burckhardt(*,1,2) 1 School of Nursing, Oregon Health & Science University, Portland, Oregon, USA; 2 Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, Oregon, USA * Corresponding author Email: Kim Dupree Jones - joneskim@ohsu.edu, Dianne Adams - adamsd@ohsu.edu, Kerri Winters-Stone - wintersk@ohsu.edu Carol S Burckhardt - burckhac@ohsu.edu Abstract The purpose of this review was to: (1) locate all exercise treatment studies of fibromyalgia (FM) patients from 1988 through 2005, (2) present in tabular format the key details of each study and (3) to provide a summary and evaluation of each study for exercise and health outcomes researchers. Exercise intervention studies in FM were retrieved through Cochrane Collaboration Reviews and key word searches of the medical literature, conference proceedings and bibliographies. Studies were reviewed for inclusion using a standardized process. A table summarizing subject characteristics, exercise mode, timing, duration, frequency, intensity, attrition and outcome variables was developed. Results, conclusions and comments were made for each study. Forty-six exercise treatment studies were found with a total of 3035 subjects. The strongest evidence was in support of aerobic exercise a treatment prescription for fitness and symptom and improvement. In general, the greatest effect and lowest attrition occurred in exercise programs that were of lower intensity than those of higher intensity. Exercise is a crucial part of treatment for people with FM. Increased health and fitness, along with symptom reduction, can be expected with exercise that is of appropriate intensity, self-modified, and symptom-limited. Exercise and health outcomes researchers are encouraged to use the extant literature to develop effective health enhancing programs for people with FM and to target research to as yet understudied FM subpopulations, such as children, men, older adults, ethnic minorities and those with common comorbidities of osteoarthritis and obesity. Review Fibromyalgia (FM) is a pain disorder defined by chronic widespread pain and multiple muscle- tendon junction tender points. Like most chronic illnesses, however, the symptoms of FM extend far beyond the defining criteria. Many patients also report fatigue, disrupted or nonrefreshed sleep, mood disturbances, exercise induced symptom flares and multiple other syndromes (e.g., restless legs, irritable bowel and bladder, and chronic headaches) [1,2]. Physical and emotional health as well as quality of life is often seriously impaired [3,4]. Exercise has been suggested as a treatment for FM since Moldofsky first demonstrated that fit people were less likely to develop FM symptoms when their stages 3 and 4 sleep was intentionally disrupted [5]. The first exercise intervention in FM was published in 1988 and since that time a large number of clinical trials have been reported. In 1999, a meta-analysis established that exercise produced higher effect sizes on physical status, FM symptoms and daily functioning than pharmacological treatment [6]. A recent evidence-based review concluded that cardiovascular exercise is as effective in decreasing pain and FM impact as drugs such as amitriptyline [7]. A number of exercise intervention reviews have been published over the years [8-10]. All of them offer valuable synthesis and critiques based on the authors' expertise. However, they are limited somewhat in comprehensiveness and do not provide descriptions and critiques of each individual study that could be helpful to an exercise or health outcomes researcher who wishes to extend the scope of knowledge in the area. The purpose of this review paper is to present a comprehensive evidence table of exercise studies with the anticipation that this individual study tabular format and accompanying comments will be useful to exercise and health outcomes researchers seeking to apply their expertise to FM clinical populations. Methods Article titles with their abstracts were accessed through an English language search of Cochrane Collaboration Reviews, MEDLINE, CINAHL, EMBASE, PubMed, Healthstar, Current Contexts, Web of Science, and PsychInfo & Science Citation Indexes. Keyword MeSH terms for initial inclusion were "fibromyalgia" and "exercise" and resulted in 296 `hits'. A further 37 articles and abstracts were found through hand searching of journals, conference proceedings, bibliographies of selected papers and personal contact with key exercise researchers in the field. The first author (KDJ) reviewed all 333 abstracts using standardized criteria developed to determine what type of design the paper reported [11]. After this preliminary step, those that were found to be reviews, case studies, clinical or theoretical papers, and descriptive or correlational cross-sectional studies were excluded. Those that met minimum criteria for an experiemtnal study (i.e. a sample drawn from an FM population, longitudinal design with pre and post measurement of an outcome variable determined a priori, and an experimental treatment) were included. In a second step, the first and second authors (KDJ and DA) independently extracted the study design, number of subjects, subject characteristics (age, gender), type of exercise, treatment length, frequency, duration and intensity of the exercise, attrition, and outcome variables from the methods section of the full text articles or from the abstract, if only the abstract was available. Any disagreements were discussed and a consensus obtained between the two raters. Both randomized controlled trials (RCTs) and uncontrolled trials were included in order to offer the broadest view of the exercise interventions in FM. Trials had to have enrolled FM subjects who met standardized criteria for FM diagnosis that were acceptable at the time the study was done [12,13]. Study interventions had to meet general criteria for some type of physical movement but did not have to contain a physical fitness outcome measure. Thus, low-intensity modalities such as QiGong and T'ai Chi were included. Studies that educated patients regarding how to exercise but did not have any supervised exercise sessions were excluded. However, some of the studies included in this review table had strong educational and cognitive behavioral components, which may have influenced outcomes. Results of the evidence review Results of the review are described and commented upon in Table 1 (se Additional file 1). Studies are listed in chronological order by year. The following paragraphs summarize the findings by each column in the table. Subjects Through December 2005, 3035 subjects participated in an FM exercise study. Of that number, 2888 (2400 women, 73 men, 415 gender not reported) were patients with FM. Control subjects with various chronic diseases other than FM numbered 135 and there were 12 healthy control subjects. The ages of subjects ranged from 18-80 years, with a mean of 49.5 years. Older adults, men, and minority persons were underrepresented and no exercise interventions with children were found. Modes of training and control interventions Most interventions were comprised of the three major modes of exercise (aerobic training, strength training, flexibility) either singly or in combination. Aerobic training included cycling, walking, calisthenics, pool exercise or dance. Thirty-three were land-based. Seven were exclusively water/pool based while the remainder either progressed from water to land based or mixed water and land throughout the intervention. Five studies used only weight training, either machine weights or free weights (hand weights/elastic bands). Progression was determined by changes in number of repetitions (reps), sets or increasing load (e.g., progressive 8-20 reps, 4-6 sets, and load increased by 40-80%) or progression of elastic band tension. Three studies tested flexibility as either the active intervention or the control intervention. Stretches were described as static and progressed by self-limited tension and discomfort or an increase in time from 10-90 seconds per major muscle group. Three studies tested the independent and combined effect of a drug and exercise (amitriptyline and pyridostigmine). Four used movement therapies (e.g. T'ai Chi, QiGong, balneotherapy, thalassotherapy). We acknowledge that other therapies using balneotherapy in FM exist as a modality for treating symptoms, but are not included in this review as they were not combined with exercise. Intensity of aerobic training Aerobic intensity was reported in 14 studies as target heart rate or percent age-predicted maximum heart rate determined by standard equations. No study set work rate based on initial maximal aerobic capacity determined by graded exercise test. Sustained target heart rate goals ranged from 120-150 beats per minute. Percent maximum heart rates were usually progressive and ranged from 40%-80% of age-predicted maximum. Borg's Rating of Perceived Exertion (RPE) scale or the "ability to talk test" was used in two studies. Measuring heart rate was most often accomplished by self-assessed pulse rate or less frequently by heart rate telemetry. Frequency of exercise sessions and duration of training The number of exercise sessions ranged from 1-5 times per week most commonly 2-3 times weekly. Length of class time ranged from 15-180 minutes per session with the average being 60 minutes. The length of the interventions, excluding follow-up, ranged from 4-24 weeks; the median was 12 weeks. Attrition and compliance Attrition in FM subjects ranged from 0-67% (median 20%, mean 21%) while controls ranged from 0- 48% (median 8%, mean 14%). Compliance was not calculable in the majority of studies. Some studies analyzed data on intent to treat basis and did not report number of sessions subjects attended. Others stated that "the majority" of subjects completed a certain number of classes or that there was a natural break in the data at a certain number of classes. This is problematic in that the "dose" of the intervention was not generally attainable. 0utcome measures The outcome measures in most studies were one or more FM symptoms, measured either on a visual analogue scale, the Fibromyalgia Impact Questionnaire [14] or a health status measure. Fewer also measured fitness markers (strength, flexibility, aerobic capacity). The timing of the measures were pre- vs. post- as compared to multiple time points during the intervention Most failed to explicitly state which outcome was their a priori primary dependent variable. None used real-time symptom monitoring with electronic diaries. Methodological rigor Thirty-nine of the studies were randomized, controlled trials with examiners blinded to treatment allocation. The remaining seven were single group (6 studies), or non-randomly assigned multi- group interventions (1 study). Statistical analyses ranged from questionable paired t-tests, uncorrected for multiple comparisons with no stated a priori hypothesis and within group changes (paired t-tests, change scores and effect sizes) to appropriate statistical methods including independent group t-test, ANOVA and ANCOVA. Abstracts as opposed to full text articles often had inadequate descriptions of methods and analyses making it difficult to confirm the validity of their stated conclusions. Major findings * Most fitness measures improved in people who could tolerate the intervention (e.g., 1- RM or isokinetic dynamometry strength, time on treadmill, V02 max or peak, 6- minute walk, flexibility). * The exercise interventions in most studies did not meet the current exercise recommendation for health as developed by the Centers for Disease Control and Prevention and the American College of Sports Medicine [15,16] (30 minutes of moderate intensity exercise on most days of the week for health related benefits). * Those studies that used a higher heart rate or RPE, higher impact movements (e.g., running, jumping) or those where subjects could not self-adjust exercise intensity (e.g. during a flare) suffered the highest attrition rates. * Subjects attained symptom relief, particularly decreased pain and fatigue as well as improved sleep and mood, with low to moderate intensity exercise of any type. Even very low movement therapies such as QiGong had significant effect sizes for symptom improvement. * Those studies with 50% maximum heart rate had lower attrition and better symptom improvement than those with the higher intensity. * Higher intensity studies resulted in greater fitness gains compared to lower intensity in subjects who could complete the intervention. * Subjects attained symptom relief, particularly decreased pain and fatigue as well as improved sleep and mod, with low to moderate intensity exercise of any type. Even very low movement therapies, such as QiGong, had significant symptom improvement. * Strength and flexibility training are beneficial for symptom control and fitness improvements but there are insufficient data for recommending a uniform, evidence-based prescription for either of these modalities. * Descriptive data as well as exercise intervention studies in men, minorities, children and older adults with FM are lacking. The fitness gains in older subjects were comparable to gains seen in age matched healthy controls and were significant compared to the subject's own baseline scores. * No FM intervention to date has included only overweight or obese persons or individualized the intervention to their unique movement needs (e.g., lower extremity joint protection during weight bearing, awareness of comorbidities such as plantar fasciitis, ankle tendonitis, knee osteoarthritis and a myriad of psychological stigma regarding appearance). * There is a lack of couples or family based exercise studies in FM, though these are common in healthy elderly, heart disease and other chronic illnesses [17-19]. Recommendations for future research * Determine optimal dosing of exercise so that an evidence based exercise prescription that includes mode, intensity, duration and frequency can be recommended. * Determine the dose of exercise that effectively manages symptoms versus the dose that produces a symptom flare. This flare is more pronounced that the well documented delayed onset muscle soreness experienced by health deconditioned persons without FM who engage in unfamiliar muscle activity [20,21]. * Systematically tract the actual amount of exercise performed compared to the prescribed amount of exercise based on study protocol. Summarize and report these deviations in publication to help identify subgroups of FM patients that are unable to achieve a given level of activity. * Select uniform symptom and outcome measures for FM exercise trials. Ideally symptoms could be monitored in "real time" rather than retrospectively. This approach would minimize recall bias and allow tracking of symptom trajectory over time. Calling subjects on some type of routine basis or having subjects carry a preprogrammed electronic device that alarms at set intervals requesting real time symptom data would be two ways to do this [22,23]. Outcome measures should include a patient graded global improvement score as is common in FM medication trials and recommended by the OMERACT 7 workshop [24]. * Examine the combined role of medications and exercise. Many FM subjects take medications and are told to exercise, yet only three studies thus far compare the combined and separate roles of exercise plus specific medications in FM [25-27], although many more acute dosing/cross sectional trials of drug and exercise in FM have been reported. At minimum, medications should be monitored and their use considered in statistical analyses. * Include cost-utility analysis of exercise as a treatment for FM in future trials. * Integrate families or other support systems into lifestyle interventions such as exercise as a way of improving long-term compliance. * Test exercise modalities and movement therapies for a broader array of physical and mental health outcomes, beyond symptoms and physical fitness. For example, descriptive studies have found deficits in balance and increased falls in FM patients [28-30], yet only one intervention study measured balance as an outcome [54]. * Maximize methodological rigor. Randomization should be applied whenever possible to equally distribute variance throughout the groups. Hypotheses should be stated a priori and tested with appropriate correction for multiple comparisons and covaried for baseline differences between groups. CONSORT guidelines for reporting findings should be followed [31]. * Report compliance by calculating the number of classes or minutes attended divided by the number offered. Reporting compliance is critical as it allows reviewers to calculate the "dose" of the intervention that the subject actually received, similar to a pill count in a medication study. * Conduct larger, longer-lasting RCTs that follow the individual from low impact exercise (e.g. pool settings to group based, land laboratory settings to home exercise with weekly booster sessions in community-based venues. This approach would better simulate a real-world application of exercise. * Evaluate methods to increase compliance in longer trials to test techniques such as motivational interviewing. Competing interests All authors declare that they have no competing interests regarding this manuscript. Authors' contributions KDJ conceptualized this paper, analyzed the retrieved literature, and wrote the first draft. DA retrieved and analyzed literature and made the first draft of the table. KW retrieved literature, coauthored the first draft of the table and co-wrote the findings and recommendations sections. CSB critically reviewed and revised the original manuscript and co-wrote the findings and recommendations sections. All authors read and approved the final manuscript. Acknowledgements National Institutes of Health/National Institute of Nursing Research R01 NR008150-01 to the first author. We also acknowledge the work of Joe Flock, RN who retrieved articles and made a preliminary summary table as a part of his masters research independent study with the first author. References 1. Bennett R: Fibromyalgia: present to future. Curr Rheumatol Rep 2005, 7:371-6. 2. Clauw DJ, Crofford LJ: Chronic widespread pain and fibromyalgia: what we know and what we need to know. Best Pract Res Clin Rheumatol 2003, 17:685-701 3. Burckhardt CS, Clark SR, Bennett RM: Fibromyalgia and quality of life: a comparative analysis. J Rheumatol 1993, 20:475-9. 4. 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Additional file Description: Table 1: Overview of 46 Exercise Intervention Studies for Subjects With Fibromyalgia (FM) (1988--2005) http://www.hqlo.com/imedia/2052908070116155/sup1.DOC -------- (c) 2006 BioMed Central [Return to top] ------------------------------ Date: Fri, 29 Sep 2006 10:13:04 -0400 From: "Rebecca Artman <PANDORARebecca@xxxxx.xxx> via Co-Cure Moderators" Subject: MED: Sleep Loss Affects More than the Brain From Rebecca Artman <PANDORARebecca@aol.com>: Sleep Loss Affects More than the Brain This article is from the September-October issues of The Dana Foundation's Brain Work: The Neuroscience Newsletter. Researchers have known that too little sleep affects mental performance. Now they are finding that sleep loss affects a whole lot more, including the immune system, cardiovascular health, and even hunger regulation. Epidemiologic studies around the world show that time spent in sleep is linked to all causes of death and to conditions that include cardiovascular risk, hypertension, diabetes, and stroke, says David Dinges, a sleep researcher at the University of Pennsylvania School of Medicine in Philadelphia. "The risk goes up when you sleep below seven hours or above eight, especially below seven," he says. Several large studies have been designed to look at the impact of sleep disturbance on physical health, including the Sleep Heart Health Study, a multicenter study implemented by the National Heart, Lung, and Blood Institute at the National Institutes of Health. After compiling the complete health history of more than 1,000 volunteers and obtaining basic information such as weight and blood pressure, the researchers fitted each participant with equipment that enabled the researchers to measure electrical currents in the brain, oxygen saturation in their breath, and chest and body movement. Because different stages of sleep are associated with different electrical patterns as measured by electroencephalogram (EEG), the researchers could see who slept soundly and who had broken sleep. Eyal Shahar of the University of Minnesota, one of the Sleep Heart Health Study leaders, found that people who had severe sleep apnea, in which they stop breathing for a short period of time repeatedly during the night, were 42 percent more likely to have heart problems and 58 percent more likely to suffer a stroke than participants who did not have the disorder. In a separate study, scientists found that patients treated for sleep apnea had a lower risk of heart attack and stroke, and were less likely to require bypass surgery than those who had untreated sleep apnea of a similar severity. Although neither of these studies shows definitively that cardiovascular problems are caused by sleep apnea or disrupted sleep, the data suggest that there is an important interaction between the two processes. Immune System Link To find out what links sleep and cardiovascular problems, scientists are watching what happens to healthy people after sleep deprivation, Dinges says. "In some individuals there is a clear increase in inflammatory markers" after a week of getting only four or five hours of sleep per night, he says. Proinflammatory cytokines, including interleukin-6, become elevated in response to sleep loss. These cytokines likely trigger a chain of other inflammatory proteins, such as C-reactive protein, which is a marker for cardiovascular inflammation and risk. The relationship between sleep, cytokines, and immune system function is not simple, however. In 1994, Dinges found that after sleep deprivation, young adults produced an abnormally high number of white blood cells, as if they were fighting an infection, although no pathogen was present. Such a strong response could lead to an increase in proinflammatory cytokines. On the other hand, Eve van Cauter, a professor of medicine at the University of Chicago, and colleagues found that young men who were sleep-deprived produced a less robust response to an influenza vaccination than did those who were fully rested. Even after ten nights of adequate sleep following the immunization, the effect was still visible, suggesting that some aspect of the immune response was compromised significantly. Metabolic Effects Studies in healthy adults have also shown a strong correlation between sleep and body mass index. In 2004, Shahrad Taheri, Emmanuel Mignot, and colleagues at Stanford University showed that people who slept fewer than eight hours had an increased body mass index in proportion to their decreased sleep, as well as altered levels of hormones that regulate metabolism and hunger. Specifically, volunteers who typically slept five hours per night had a 15 percent reduction in leptin, a hormone that suppresses appetite, and a 15 percent increase in ghrelin, a hormone that stimulates appetite. In other words, people who slept less tended to feel hungrier than those who slept 8 hours. In one experiment, which van Cauter reported in June at the annual sleep research meeting, men consumed 26 percent more calories during periods of extended wakefulness when they got only five hours of sleep per night than they did during recovery periods in which they were allowed to sleep between 10 and 12 hours per night. Researchers calculate that the 15 percent change in leptin could lead to about 500 extra calories per day, significantly more than the body consumes by staying awake. "After several days that could lead to some serious weight gain," says Kristen Knutson, a postdoctoral fellow in van Cauter's group. The research group also reported at the June meeting that sleep quality had an impact on metabolic hormones. They brought nine healthy young adults into the sleep lab for five nights. The first two nights, the volunteers were allowed to sleep normally, but during the following three nights the researchers played intermittent loud noises so that the volunteers experienced "microarousals." With these interruptions, the volunteers never reached the deep sleep stages that are characterized by slow wave activity on an EEG monitor. Sleep fragmentation and suppression of slow-wave sleep reduced insulin sensitivity in these volunteers. Because insulin resistance is considered a prediabetic condition, the work hints at how sleep disorders might increase a person's risk of developing type 2 diabetes, which has been shown previously to correlate with chronic sleep loss in epidemiological studies. Perchance to Think In addition to these physiological changes, scientists find dramatic alterations in cognition after people are either completely deprived of sleep or have several nights with less sleep than normal. When volunteers used a computer task that requires constant attention, Dinges's group saw a steady decline in performance among subjects who slept less. The deficits increased as the number of nights of sleep loss accumulated: people who have short sleep for a couple of weeks can be as impaired cognitively as someone who has been awake for two or three days straight, but they do not know it, Dinges says. In a separate study, the team found that, after 36 hours of complete sleep deprivation, those who were asked to work on the task for a longer period of time performed worse than those similarly sleep-deprived who worked on it for less time. "Even though this is something that people say happens to them in the real world, and is sort of obvious, it has rarely been studied or documented," Dinges says. Remarkably, those who worked harder also spent more time in slow-wave sleep during the recovery period. That observation supports the notion that the brain's requirement for slow-wave sleep is proportional to brain use during waking hours, which researchers refer to as a use-dependent requirement for sleep (see "A Model of Sleep's Role in the Brain"). Scientists used to say that sleep was of, by, and for the brain, but recent findings suggest otherwise. Sleep may have initially evolved to take care of the brain, but many other systems now appear to rely on it for regulation and stabilization. "Sleep is not just one thing," Knutson says. "For a long time people thought that you get sleepy and maybe your brain is not there. But that's not it. It affects the whole body." - Rabiya S. Tuma is a science and medical writer in Berkeley, Calif. For a copy of this article or to subscribe to Brain Work (free) visit www.dana.org; the DANA Foundation prints articles related to the brain. If you are seeing a Neurologist, I highly recommend that you have that doctor subscribe to the DANA Foundations publications. Rebecca Artman Vice President P.A.N.D.O.R.A., Inc. Patient Alliance for Neuroendocrineimmune Disorders Organization for Research & Advocacy http://pandoranet.info/ [Return to top] ------------------------------ Date: Fri, 29 Sep 2006 10:25:12 -0400 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Psychomotor speed: possibly a new marker for overtraining syndrome Psychomotor speed: possibly a new marker for overtraining syndrome. Sports Med. 2006;36(10):817-28. Nederhof E, Lemmink KA, Visscher C, Meeusen R, Mulder T. Center for Human Movement Sciences, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUniversity Center for Sport, Movement and Health, University Medical Center Groningen, Groningen, The Netherlands. NLM Citation: PMID: 17004845 Overtraining syndrome (OTS) is a major threat for performance and health in athletes. OTS is caused by high levels of (sport-specific) stress in combination with too little regeneration, which causes performance decrements, fatigue and possibly other symptoms. Although there is general consensus about the causes and consequences, many different terminologies have been used interchangeably.The consequences of overreaching and overtraining are divided into three categories: (i) functional overreaching (FO); (ii) non-functional overreaching (NFO); and (iii) OTS. In FO, performance decrements and fatigue are reversed within a pre-planned recovery period. FO has no negative consequences for the athlete in the long term; it might even have positive consequences. When performance does not improve and feelings of fatigue do not disappear after the recovery period, overreaching has not been functional and is thus called NFO. OTS only applies to the most severe cases. NFO and OTS could be prevented using early markers, which should be objective, not manipulable, applicable in training practice, not too demanding, affordable and should be based on a sound theoretical framework. No such markers exist up to today. It is proposed that psychomotor speed might be such a marker.OTS shows similarities with chronic fatigue syndrome and with major depression (MD). Through two meta-analyses, it is shown that psychomotor slowness is consistently present in both syndromes. This leads to the hypothesis that psychomotor speed is also reduced in athletes with OTS. Parallels between commonly used models for NFO and OTS and a threshold theory support the idea that psychomotor speed is impaired in athletes with NFO or OTS and could also be used as an early marker to prevent NFO and/or OTS. [Return to top] ------------------------------ Date: Fri, 29 Sep 2006 10:30:49 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Young women with fibromyalgia in the United States and Sweden: Perceived difficulties during the first year after diagnosis Young women with fibromyalgia in the United States and Sweden: Perceived difficulties during the first year after diagnosis. Disabil Rehabil. 2006 Oct 15;28(19):1177-84. Liedberg GM, Burckhardt CS, Henriksson CM. Department of Neuroscience and Locomotion, Section of Occupational Therapy, Faculty of Health Sciences, Linkoping University, Sweden. PMID: 17005479 Purpose. The major symptoms of fibromyalgia (FM) - pain, tiredness, disrupted sleep, and muscle weakness - severely impact everyday activities, including the paid work role of women who have had FM for a long time. There are no prospective studies on young and newly diagnosed women with FM. The aim of the present study was to describe and compare difficulties young and newly diagnosed women in Sweden and the United States experienced during their first year after diagnosis. Method. Three interviews, 6 months apart, were conducted, with 49 Swedish and 45 US women between the ages of 18 and 39. Five open-ended questions were asked concerning physical, psychological and social difficulties and limitations, and factors that increased or decreased their difficulties and limitations. At interviews 2 and 3 the women were also asked about ways of preventing their difficulties. The answers were written down and analysed by a content analysis approach. Results. Consistent categories of difficulties were reported: symptoms, movements, activities, moods, social network, external factors and coping strategies. More US women were working outside their homes than were their Swedish counterparts and they expressed more difficulties compared with the Swedish women. Conclusions. In general, difficulties decreased and coping strategies increased over the 1-year period in both groups of newly diagnosed, young women. [Return to top] ------------------------------ Date: Fri, 29 Sep 2006 19:06:18 -0400 From: "Ellen Goudsmit <ellengoudsmit@xxxxx.xxx> via Co-Cure Moderators" Subject: NOT,RES: Response to article in JRSM >From Ellen Goudsmit <ellengoudsmit@xxxxx.xxx>: The following letter to the editor of the Journal of the Royal Society of Medicine has already been rejected. It's too long. Dear editor, I have just read the review of treatments for chronic fatigue syndrome in the October issue of the JRSM (1). It included my study, but some of the details were inaccurate and the overall judgement was unfair and potentially misleading. The study (reference 102) was a controlled trial which assessed a programme offering among other things, medical care, emotional support, and advice about energy management and sleep. In contrast to cognitive-behaviour therapy (CBT), it does not assume that the symptoms are perpetuated by inactivity and stress, but acknowledges the existing uncertainty about aetiology. It also favours the strategy known as pacing over graded activity and exercise. The consultant and I undertook a pilot study in 1995 to assess its effectiveness over a six month period using the people on the waiting-list as controls. The follow-up assessed the patients still in the programme at 12 months (alas, the NHS did not give me permission to contact those discharged). The participants were selected using strict criteria for post-viral fatigue syndrome and measures assessed somatic symptoms and cognitive functioning, as well as fatigue, self-efficacy and emotional distress. In the original 'York' review of the various treatments for CFS, my study received a validity score of 2. However, after clarification regarding the statistical analysis, this was changed to 3. Chambers et al were clearly not aware of the 'correction' and published the original score. It's a minor issue, but it wasn't the only one. In terms of accuracy, the study should have received a validity score of 4. They refused to acknowledge the follow-up, even though I had sent them details of my findings at 12 months both in an email and on a floppy disc. And the reference was incomplete. The main part of the study formed part of a PhD thesis. I believe that it is common practice to include such details in the reference. Another issue relates to outcome. According to the table (p. 511), the programme had no overall effect but as the authors noted in their recent review for NICE (http://www.nice.org.uk/page.aspx?o=368933, appendix 1, p.423), there were "significant differences between groups for fatigue (F(1,40) = 5.13, p=0.03) and somatic symptoms (F(1,40) = 4.66, p=0.04). In fact, 82% of patients rated themselves as "better" or "much better" and 23% had improved to such a degree that further treatment was no longer deemed necessary. The authors of the review acknowledged that there was also a "significant difference between groups: self-efficacy (F(1,38)=6.79, p=0.13)" That should have read p=.013. You get the drift. To summarise, the patients who were treated felt less fatigue, had fewer somatic symptoms, as well as less depression and anxiety after six months compared to the controls, and this improvement was maintained at follow-up. Admittedly, there was less improvement in cognitive symptoms and functional impairment but surely this did not warrant the judgement of 'no overall effect'? I also noted that a study by a colleague was described as a trial of graded exercise when in fact, it had also assessed the strategy known as pacing. The reviewers didn't need to read the full paper for that information; it was discussed in the first sentence of the abstract (ref 31). My study is one of the few which has assessed an alternative to the CBT-based programmes. It's also one of the few controlled trials to include pacing, a strategy which many patients regard as a particularly helpful way of managing their limited energy. In my view, it deserved an accurate evaluation and a fair summary of the outcome. It didn't get that. 1. Chambers D, Bagnall A-M, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. JRSM 2006; 99: 506-520. ---------------------------------------------------------------------- Ellen M. Goudsmit C. Psychol. AFBPsS The following is an extract from an email from Jos Kleijnen, from the CRD, York. It supports the first argument. VS is validity score. Sent : 08 June 2005 15:08:18 To : "'Ellen Goudsmit'" <ellengoudsmit@xxxxx.xxx> Subject : CFS Report Dear Dr. Goudsmit, I now have received the assessments from the independent reviewers... Regarding the item about baseline comparability, one independent reviewer thought the Anova was ok to deal with this, whereas the second reviewer initially thought it was not but after discussion was happy to change the assessment to "adequate".... In light of this, and emphasising that this is not an acknowledgement that CRD's initial assessment was wrong, I have requested the following amendment to the report which has now been included on the website, and which will also be included in any paper copies of the report that are sold or distributed. -Erratum: p112 'Goudsmit 2000' should read 'Goudsmit 1996'. Baseline comparability of groups should be 'adequate'; VS should be 3. With best wishes, Jos Kleijnen Director of CRD. ---------------------------------------------------------------------- Ellen M. Goudsmit C. Psychol. AFBPsS *** 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: Sat, 30 Sep 2006 13:11:41 +0200 From: "Dr. Marc-Alexander Fluks" <fluks@xxx.xx> Subject: RES,NOT: Ph.D. Thesis of Else Van de Putte in pdf-format The Ph.D. thesis of Else Van de Putte can be downloaded in pdf-format from the archive of the ME-NET list. Title: Exploring Chronic Fatigue Syndrome in Adolescents Author: Elisabeth Machteld van de Putte Date: September 19, 2006 URL: https://listserv.surfnet.nl/scripts/WA.EXE?A3=ind0609E&L=me-net&P=58442&E=2&B=--Boundary_%28ID_J47BNyZ22%2FKTUFozhjtGnQ%29&N=vandeputte.pdf&T=application%2Fpdf [Return to top] ------------------------------ Date: Sat, 30 Sep 2006 11:23:22 -0700 From: Kimberly Hare <kimberly_ohare@xxxxx.xxx> Subject: RES: An experiential mind-body approach to the management of medically unexplained symptoms An experiential mind-body approach to the management of medically unexplained symptoms Medical Hypotheses, Volume 67, Issue 6 , 2006, Pages 1443-1447, doi:10.1016/j.mehy.2006.05.028 D. Bakal, M. Steiert, P. Coll and J. Schaefer Clinic for Mind-Body Medicine, Calgary Health Region and Department of Medicine, University of Calgary, Rockyview General Hospital, 7007 – 14th Street S.W., Calgary, Alta., Canada T2V 1P9 Received 9 May 2006; accepted 16 May 2006. Available online 11 July 2006. Summary This article outlines an experiential mind-body framework for understanding and treating patients with medically unexplained symptoms. The model relies on somatic awareness, a normal part of consciousness, to resolve the mind–body dualism inherent in conventional multidisciplinary approaches. Somatic awareness represents a guiding healing heuristic which allows for a linear treatment application of the biopsychosocial model. The heuristic acknowledges the validity of the patient's physical symptoms and identifies psychological and social factors needed for the healing process. Somatic awareness is used to direct changes in coping styles, illness beliefs, medication dependence and personal dynamics that are necessary to achieve symptom control. The mind–body concept is consistent with and supported by neurobiological models which draw on central nervous system mechanisms to explain medically unexplained symptoms. The concept is also supported by a recent hypothesis concerning the role peripheral connective tissue may play in influencing illness and well-being. Finally, somatic awareness is described as having potential to enhance understanding and conscious use of inner healing mechanisms at the basis of the placebo effect. Introduction Medically unexplained symptoms (MUS) are defined as physical symptoms that prompt the sufferer to seek health care but remain unexplained after an appropriate medical evaluation [1]. Symptoms that are not explained from a medical standpoint are generally assumed to be psychological rather than psychobiological in origin. This assumption is especially troublesome for doctor–patient interactions because doctors come to view the symptoms as “psychiatric” while patients resent the “all in your head” implication. Both parties need a shared or common conceptual framework for understanding and working together in the management of the symptoms. Patients with MUS represent the some of the most frequently occurring conditions seen in primary and specialist care [2]. Common symptoms/syndromes include non-cardiac chest pain, chronic headache, fibromyalgia, dizziness, fatigue, anxiousness, repeated infections, tinnitus, low back pain, insomnia, and depression. The symptoms constitute a significant management issue. Patients with MUS are often extensively investigated, over-referred and treated with symptomatic medication. Although physicians suspect that the patient’s psychological or emotional reactions are behind the symptoms or illness, there is an inner frustration of being unable to identify the real problem. Even after exhaustive investigations and reassurance, patients continue to fear that their symptoms are caused by undiagnosed physical problems. ‘Heartsink’ is a term that has been coined to describe the physician’s frustration with seeing these patients [3]. Patients may further alienate physicians by challenging their investigations and reassurances. Physicians begin to feel that they are being controlled by the patient. Even if psychosocial factors are suspected by both parties, such as job stress or marital dissatisfaction, there are no immediate tools to manage the situation. Some physicians may be tempted to probe defence mechanisms in their patients in order to find underlying psychological causes, such as traumatic life events, abuse or incest. While a high percentage of these patients have experienced trauma and suffer from symptoms of anxiety, depression and insomnia, uncovering evidence of trauma or unconscious dynamics does not generally resolve the symptom. Cognitive behavioural therapy represents the widely adopted non-drug treatment for all medically unexplained symptoms. The successfulness of the approach has been overstated, especially in terms of the providing relief of the actual symptom(s). From a mind-body framework, the cognitive model is limited by a failure to address the pathophysiology of the patients symptom experience. One of the most frequently occurring medically unexplained symptoms is non-cardiac chest pain. More than 50% of patients with chest pain seen in cardiology and primary care settings do not have identifiable ischemic heart disease or another serious medical disorder to account for their physical symptoms [4]. Despite receiving a favourable medical diagnosis, patients with non-cardiac chest pain continue to experience chest pain symptoms as well as distress and interference in their activities of daily living. "There's nothing wrong" does not reassure patients and may result in iatrogenic concern and worry about undiagnosed cardiac problems. The central component of this model is attribution or cognitive appraisal. It is assumed that the patient is interpreting benign or "normal" physical sensations catastrophically as indicative of something dangerous, such as heart attack. The goal of treatment is to correct the misattributions regarding physical symptoms (e.g., chest pain) as being harmful. The attribution model fails to convince the MUS patient that the bodily experiences are normal and that nothing unusual under the skin is taking place. This explanation often does not resonate with patient symptom experiences who find the approach “too psychological” and dismissive of underlying pathophysiology. This paper extends the cognitive approach to include somatic awareness, an experiential body heuristic which assumes a degree of psychobiological veridicality of the patient's presenting symptom. That is, it assumes that there is a central and peripheral physiologic substrate to the patient's condition. Somatic awareness involves the direction of attention to bodily experience and associated feelings for the purpose of achieving health. The heuristic cuts across the biological, psychological and social domains of human functioning. It serves as a powerful clinical tool to facilitate communication and humanistic care between physician and patient. Somatic awareness in a pure sense of the term is the feeling of well-being within the body. Hypothesis The mind-body understanding and management of patients with MUS will advance with the adoption of somatic awareness as an experiential healing heuristic. Somatic awareness involves the direction of attention to bodily experience and associated feelings for the purpose of achieving health. There are conceptual and practical advantages to using an experiential body heuristic in patient care. These include: 1. The utilization of a normal conscious experience that is readily recognized by patients. 2. The experience of a subjective state that is complementary to bodily states associated with healing and wellness. 3. The adoption of a consciousness concept that is consistent with recent theoretical formulations in neurobiology. 4. The use of an experiential guide that networks the biological, psychological and social variables unique to each patient. A number of writers have emphasized the need to study and treat medically unexplained symptoms within a biopsychosocial framework [4]. However, the biopsychosocial model has proved to be a better philosophy of care than a practical clinical guide. A suggestion to make the model more practical involves adopting a treatment framework based on structural causality rather than circularity [5]. Structural causality recognizes the multifaceted nature of a symptom or illness but proposes a linear treatment plan reflecting the intervention that is likely to give the greatest chance of success. Somatic awareness is ideally suited to serve in this capacity. Somatic awareness attracted brief curiosity from 19th century philosophers, such as Bain and Weber, as a possible sixth sense, but was eventually ignored in favour of study of the traditional external senses. This view has changed with interest from neurobiologists in interoception – defined as the sense of physiological condition of the whole body. Brain structures have been identified which have direct involvement in the awareness of inner bodily processes. Craig proposed that anterior insula (AI) of the forebrain is involved with interoception and hypothesized that the insular cortex maintains a form a peripheral autonomic asymmetry, with the right AI contributing to aroused (sympathetic) feelings and the left AI contributing to affiliative (parasympathetic) feelings [6] and [7]. These formulations support Damasio’s neurobiological ‘somatic marker’ hypothesis of consciousness which states that subjective process of feeling emotions requires the participation of brain regions that are involved in mapping of internal bodily states [8]. The mind, according to Damasio, is not only ‘embrained’ but also ‘embodied’. Another significant theoretical development has been the shift from the search for disease-specific mechanisms to etiologic models based on mechanisms, processes and networks that occur across illness conditions. Central nervous system concepts involving sensitization, wind-up and plasticity are being used to describe depression [9], fibromyalgia [10], chronic headache [11] and irritable bowel syndrome [12]. The network plasticity hypothesis of depression, for example proposes that depression represents disturbances in the activity-dependent information processing of the brain rather than a chemical imbalance of signalling molecules [9]. Several writers have proposed that MUS may be the final common manifestation of multiple etiological pathways [1]. The musculoskeletal system is hypothesized to represent a pathway that is at the basis of all MUS conditions. Langevin [13] hypothesized that unspecified “loose” connective tissue, which is part of the musculoskeletal system, distributed throughout the body may serve as a body-wide mechanosensitive signalling network. Connective tissue may also serve as a major component of physiological feedback from the whole body that contributes to interoception and emotions and feelings. Connective tissue involvement might explain the communality and co-occurrence of symptoms within and across patients with MUS. Symptoms involving diffuse pain, fatigue, headache, insomnia, and anxiety and depression tend to occur across all patients with MUS [1]. Somatic awareness constitutes an experiential bridge of the elements of the biopsychosocial domain. It provides a parsimonious and linear framework for dealing with the multitude of variables that contribute to MUS within a patient. Patient symptom experiences are validated at the biological level and are seen as indicative of real, rather than imagined, physiologic events – even if the events have yet to be objectively identified. Non-cardiac chest pain, for example, is likely determined in part by heightened chest wall muscle activity that can be controlled through somatic awareness strategies. The approach does not attempt to ‘psychologize’ the patient’s symptom experiences. Psychological influences are seen as psychobiological in nature rather than mental phenomena. It is much easier for the patient to accept, experience and alter the impact of previous trauma, personality, stress and emotions if he/she views the body as the mediator of these experiences. To illustrate, many patients with MUS have experienced childhood trauma and insecure attachment [14]. The majority also believe that they have dealt with the trauma and “moved on.” Through somatic awareness, they are dismayed to discover that their body remains hypervigilant and continues to influence and be influenced by current feelings and interpersonal interactions. The body is indeed the “unconscious mind.” A patient with non-cardiac chest pain reported an emotionally abusive childhood with an alcoholic father. Some 50 years later, she continued to experience chest tightness and/or pain in the presence of a controlling husband as well as in other uncomfortable social situations. Instructions in autogenic relaxation, breathing awareness, and suggestions to improve spousal communications were required to control the tightness and pain. Normally, bodily changes accompanying thought and feeling take place outside of awareness, making the use of somatic awareness less than self-evident. Patients may intellectually grasp the role that psychosocial stress plays in contributing to their symptom, yet they have difficulty experiencing the mind–body connection. Although able to describe with great detail and precision the location and nature of a bodily symptom, they are unaware of the thoughts, feelings, and bodily sensations which contribute to symptom onset. They are even less aware of potential healing sensations and feelings. For example, a 59-year-old semi-retired rancher presented with persistent abdominal pain and fatigue – wondering if he was “going to die.” Medical investigations including an MRI on the abdomen were negative. Twenty years earlier, his wife was involved in an extra-marital affair while taking a college course away from home. He admitted to still being angry over the affair but he did not connect this feeling to his abdominal pain and fatigue. He also suffered from existential issues surrounding retirement and a life-long need for accomplishment. He exhibited a number of illness behaviours tied to fatigue, believing that he could not perform most activities. Somatic awareness is used, session by session, to increase the patient’s experiential understanding of the connection between bodily symptoms and accompanying thoughts and feelings, and to guide symptom management and wellness through "letting go" and patient-centered self-soothing strategies. Consequences A practical consequence of the somatic awareness heuristic is that physicians have a clinical framework for understanding and managing their MUS patients. Experientially, “heartfelt” replaces heartsink in the interpersonal approach to these patients. The concept also provides common conceptual ground for integrating practices of different health professionals. Physicians adopting the framework will need to make a shift in their theoretical perspectives and approach to MUS patients and their symptoms. The shift is from a purely objective disease framework to a subjective psychobiological understanding of the symptom. Symptomatic medication use and alternative treatments are antagonistic with somatic awareness and self-regulation. We have observed that patients who are using antidepressant, anxiolytic, and opioid medications generally do not benefit from somatic awareness therapy. Patients who smoke cigarettes do not benefit as well. These patients have an overwhelming “fear of not having medication” or “something” to take. Patients who have been relying on medications have very strong fears that they will relapse or worsen without medication, even if the medication is ineffective. The chemical imbalance theory of depression when given to patients is notorious for exacerbating this fear. There is growing recognition that medications which are used to control MUS contribute to drug dependence, withdrawal and further central sensitization. The drugs exacerbate the very pain and mood symptoms that they are designed to control [15]. Adoption of somatic awareness patient care provides a more sophisticated mind–body model than exists within multidisciplinary stepped care models. The stepped care framework usually involves the treatment of MUS patients with psychotropic medication, complementary treatments, and/or cognitive behavioural therapy. Mind–body treatments, when delivered in an “add-on” or isolated fashion have very little impact. Patients treated in a menu-driven manner do not develop an experiential understanding of their somatic selves and tend to continue seeking external treatments in the form of conventional or alternative medicine. Interventions consistent with somatic awareness, especially in the form of self-soothing, are useful (relaxation instructions, biofeedback, massage, yoga) but not when offered in isolation. The phenomenological and physiological aspects of somatic awareness need empirical study. We need to know if somatic awareness operates in the background of consciousness or is better utilized as a self-reflective state. Given that patients are generally unaware of their interoceptive body-self, we need to assess whether other cognitive, perceptual, and emotional states block its awareness in consciousness. For example, are patients who are emotionally unaware also somatically unaware? Goldberg, Harel and Malach examined whether sensory involvement of the brain results in the disengagement of self-related brain processes – a condition described as the brain “losing its self.” They demonstrated, using fMRI, that areas of brain activity involved in self-representation are inhibited during tasks requiring the processing of visual and auditory sensory stimuli, suggesting that the mind can “lose itself” under stimulation [16]. The blocking did not occur under an introspective condition in which subjects had to indicate if the various sensory stimuli created an emotional feeling. Malach (personal communication) speculated that somatic awareness is analogous to other sensory perceptions and may be in an antagonistic relationship with prefrontal self-related areas. Their research paradigm, however, cannot rule out a cortical structure that is “running in the background” – i.e. active continuously, regardless of the cognitive task involved. This is an important issue for the future of somatic awareness – a fully integrated self requires ‘finding’ rather than losing the body in consciousness. The experiential concepts of somatic awareness and associated psychobiological processes have relevance for understanding the placebo effect in medicine. It is hypothesized that somatic awareness is the conscious mind’s equivalent of the response. A vast body of placebo research has taught us that the mindful intentionality to effect therapeutic change is possible in every medically unexplained symptom. Yet psychological explanations of the placebo based on expectancy are usually in the minds of others, not in the minds of patients. Once the patient recognizes that the source of healing is some inner self-regulatory process, it will become possible to shift placebo power to the individual [17]. With somatic awareness, we have the means to gain a better understanding and utilization of inner healing processes within an evidence-based framework. In summary, somatic awareness represents a dimension of normal consciousness with enormous healing and wellness potential. Health professionals are provided with a non-confrontational experiential framework that acknowledges both the validity of the patient’s physical symptoms and the identification of psychological and social factors needed for the healing process. Somatic awareness is supported by modern theory in neurobiology and serves as an experiential probe into the critical aspects of MUS development and maintenance. In addition, it recognizes the existence of inner mind–body healing processes and serves to direct physician and patient in the collaborative discovery of these resources. “Unexplained” symptoms are no longer mysterious medical events and are investigated and treated within a holistic paradigm. References [1] R.D. Richardson and C.C. Engel Jr., Evaluation and management of medically unexplained physical symptoms, Neurologist 10 (2004), pp. 18–30. [2] P. Fink, M. Steen Hansen and L. Sondergaard, Somatoform disorders among first-time referrals to a neurology service, Psychosomatics 46 (2005), pp. 540–548. [3] C.C. Butler, M. Evans and and the Welsh Philosophy and General Practice Discussion Group, The ‘heartsink’ patient revisited, Br J Gen Prac 49 (1999), pp. 230–233. [4] J.L. Esler and B.C. Bock, Psychological treatments for noncardiac chest pain. Recommendations for a new approach, J Psychosom Res 56 (2004), pp. 263–269. Abstract | Full Text + Links | PDF (164 K) [5] F. Borrell-Carrio, A.L. Suchman and R.M. Epstein, The biopsychosocial model 25 years later: principles, practice, and scientific inquiry, Ann Fam Med 2 (2004), pp. 576–582. [6] A.D. Craig, How do you feel? Interoception: the sense of the physiological condition of the body, Nat Rev Neurosci 3 (2002), pp. 655–666. [7] A.D. Craig, Forebrain emotional asymmetry: a neuroanatomical basis?, Trends Cogn Sci 9 (2005), pp. 566–571. Abstract | Full Text + Links | PDF (122 K) [8] A. Damasio, The person within, Nature 423 (2003), p. 227. [9] E. Castren, Is mood chemistry?, Nat Rev Neurosci 6 (2005), pp. 241–246. [10] D.D. Price and R. Staud, Neurobiology of fibromyalgia syndrome, J Rheumatol Suppl 12 (2005), pp. 22–28. [11] L. Buchgreitz, A.C. Lyngberg, L. Bendtsen and R. Jensen, Frequency of headache is related to sensitization: a population study, Pain 123 (2006), pp. 19–27. Abstract | Full Text + Links | PDF (346 K) [12] M.P. Jones, J.B. Dilley, D. Drossman and M.D. Crowell, Brain–gut connections in functional GI disorders: anatomic and physiologic relationships, Neurogastroenterol Motil 18 (2006), pp. 91–103. [13] H.M. Langevin, Connective tissue: a body-wide signaling network?, Med Hypotheses 66 (2006), pp. 1074–1077. Abstract | Full Text + Links | PDF (73 K) [14] R.J. Waldinger, M.S. Schulz, A.J. Barsky and D.K. Ahern, Mapping the road from childhood trauma to adult somatization: the role of attachment, Psychosom Med 68 (2006), pp. 129–135. [15] J. Moncrieff, Why is it so difficult to stop psychiatric drug treatment? It may be nothing to do with the original problem, Med Hypotheses 67 (2006), pp. 517–523. Abstract | Full Text + Links | PDF (99 K) [16] I.I. Goldberg, M. Harel and R. Malach, When the brain loses its self: prefrontal inactivation during sensorimotor processing, Neuron 50 (2006), pp. 329–339. Abstract | Full Text + Links | PDF (719 K) [17] R. Kradin, The placebo response. Its putative role as a functional salutogenic mechanism of the central nervous system, Perspect Biol Med 49 (2004), pp. 617–634. Copyright 2006 Elsevier Ltd All rights reserved. [Return to top] ------------------------------ Date: Sat, 30 Sep 2006 15:45:58 -0400 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability Brief report Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. Journal: J Affect Disord. 2006 Sep 26; [Epub ahead of print] doi:10.1016/j.jad.2006.08.021 Authors: Michael Maes [a, b, *], Ivana Mihaylova [a] and Jean-Claude Leunis [c] Affiliations: [a] MCare4U Outpatient Clinics, Belgium [b] Department of Psychiatry, Vanderbilt University Nashville, TN, USA [c] Laboratory Ategis, Waver, Belgium Received 18 December 2005; revised 14 August 2006; accepted 16 August 2006. Available online 27 September 2006. NLM Citation: PMID: 17007934 Abstract There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls. We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory. The results show that enterobacteria are involved in the etiology of CFS and that an increased gutintestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability. Keywords: Chronic fatigue syndrome; Inflammation; Immunity; Autoimmune; IgA; Enterobacteria; Gut permeability; Oxidative stress; Leaky gut Copyright 2006 Published by Elsevier B.V. [Return to top] ------------------------------ Date: Sat, 30 Sep 2006 16:18:51 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Migraine, fibromyalgia, and depression among people with IBS: a prevalence study Migraine, fibromyalgia, and depression among people with IBS: a prevalence study. BMC Gastroenterol. 2006 Sep 28;6(1):26 [Epub ahead of print] Cole JA, Rothman KJ, Cabral HJ, Zhang Y, Farraye FA. PMID: 17007634 ABSTRACT: BACKGROUND: Case descriptions suggest IBS patients are more likely to have other disorders, including migraine, fibromyalgia, and depression. We sought to examine the prevalence of these conditions in cohorts of people with and without IBS. METHODS: The source of data was a large U.S. health plan from January 1, 1996 though June 30, 2002. We identified all people with a medical claim associated with an ICD-9 code for IBS. A non-IBS cohort was a random sample of people with an ICD-9 code for routine medical care. In the cohorts, we identified all claims for migraine, depression, and fibromyalgia. We estimated the prevalence odds ratios (PORs) of each of the three conditions using the Mantel-Haenszel method. We conducted quantitative sensitivity analyses to quantify the impact of residual confounding and in differential outcome identification. RESULTS: We identified 97,593 people in the IBS cohort, and a random sample of 27,402 people to compose the non-IBS comparison cohort. With adjustment, there was a 60% higher odds in the IBS cohort of having any one of the three disorders relative to the comparison cohort (POR 1.6, 95% CI 1.5 - 1.7). There was a 40% higher odds of depression in the IBS cohort (POR 1.4, 95% CI 1.3 - 1.4). The PORs for fibromyalgia and migraine were similar (POR for fibromyalgia 1.8, 95% CI 1.7 - 1.9; POR for migraine 1.6, 95% CI 1.4 - 1.7). Differential prevalence of an unmeasured confounder, or imperfect sensitivity or specificity of outcome detection would have impacted the observed results. DISCUSSION: People in the IBS cohort had a 40% to 80% higher prevalence odds of migraine, fibromyalgia, and depression. [Return to top] ------------------------------ Date: Sat, 30 Sep 2006 16:29:05 -0400 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome Journal: Arthritis Rheum. 2006 Sep 28;54(10):3351-3362 [Epub ahead of print] Authors: Dane B. Cook [1 *], Paul R. Nagelkirk [2], Ashok Poluri [3], John Mores [3], Benjamin H. Natelson [3] [1] University of Wisconsin, Madison [2] University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark [3] Ball State University, Muncie, Indiana [*] Correspondence to Dane B. Cook, University of Wisconsin, Madison, Department of Kinesiology, Room 2033-Unit II Gym, 2000 Observatory Drive, Madison, WI 53706 email: Dane B. Cook <dcook@education.wisc.edu> Funded by: NIH; Grant Number: AI-32247 NLM Citation: PMID: 17009309 OBJECTIVE: To investigate cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome (CFS), accounting for comorbid fibromyalgia (FM) and controlling for aerobic fitness. METHODS: Twenty-nine patients with CFS only, 23 patients with CFS plus FM, and 32 controls completed an incremental bicycle test to exhaustion. Cardiorespiratory and perceptual responses were measured. Results were determined for the entire sample and for 18 subjects from each group matched for peak oxygen consumption. RESULTS: In the overall sample, there were no significant differences in cardiorespiratory parameters between the CFS only group and the controls. However, the CFS plus FM group exhibited lower ventilation, lower end-tidal CO(2), and higher ventilatory equivalent of carbon dioxide compared with controls, and slower increases in heart rate compared with both patients with CFS only and controls. Peak oxygen consumption, ventilation, and workload were lower in the CFS plus FM group. Subjects in both the CFS only group and the CFS plus FM group rated exercise as more effortful than did controls. Patients with CFS plus FM rated exercise as significantly more painful than did patients with CFS only or controls. In the subgroups matched for aerobic fitness, there were no significant differences among the groups for any measured cardiorespiratory response, but perceptual differences in the CFS plus FM group remained. CONCLUSION: With matching for aerobic fitness, cardiorespiratory responses to exercise in patients with CFS only and CFS plus FM are not different from those in sedentary healthy subjects. While CFS patients with comorbid FM perceive exercise as more effortful and painful than do controls, those with CFS alone do not. These results suggest that aerobic fitness and a concurrent diagnosis of FM are likely explanations for currently conflicting data and challenge ideas implicating metabolic disease in the pathogenesis of CFS. [Return to top] ------------------------------ Date: Sun, 1 Oct 2006 00:11:31 +0200 From: Jan van Roijen <j.van.roijen@xxxxx.xx> Subject: res: ME/CFS -enterobacteria involved in etiology ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 1 oktober 2006 <<<< Editorship : j.van.roijen@chello.nl Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ 30 Sep 2006 Fred Springfield 19 Sep 2006 Fred Springfield posted the abstract on Co-Cure of: *Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability* - Journal: J Affect Disord. 2006 Sep 26; Authors: Michael Maes, Ivana Mihaylova and Jean-Claude Leunis: http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0609e&L=co-cure&T=0&P=2842 `````````````````````````````````````````````````````````````````````````````` ~jvr: as 'fair use' I add the *discussion * section from this study ````````````````````````````````````````````````````````````````````````````````` 6. Discussion The findings of the present study show that CFS is accompanied by increased serum levels of IgA and, to a lesser extent, IgM against the LPS of gram-negative enterobacteria. Increments in serum IgM levels can be seen in mucosal immunity and immune activation, e.g. in the B1 lymphocytes. The latter are a significant source of natural serum IgM, thereby serving as a first line of defence against systemic bacterial and viral infections (Thurnheer et al., 2003). B1 cells can migrate to the intestinal lamina propria and differentiate into IgA-producing serum cells, playing a role in mucosal immunity (Thurnheer et al., 2003). The results of our study suggest that there is a chronic immune response raised to the LPS of enterobacteria. Many conditions can cause the mucosal barrier to become more permeable, whereby enlarged spaces between the cells of the gut wall cause a loss of the protective barrier. This may induce an increased bacterial translocation and thus increased serum endotoxin concentrations which, in turn, may trigger an immune response (Wu et al., 2004). Thus, the increased serum IgA and IgM levels against the LPS of gram-negative enterobacteria in CFS indicate the presence of an increased gut permeability and an immune response mounted against LPS of the enterobacteria. The relationship established between irritable bowel and the serum IgA to enterobacteria suggests that irritable bowel in CFS reflects in part disorders in gutintestinal permeability rather than psychological stress as most psychiatrists tend to confirm. Interestingly, the intestinal barrier may be compromised by factors which are known to trigger CFS, e.g. psychological stress (Meddings and Swain, 2000); sustained strenuous exercise (Davis et al., 2005); food allergies (Andre et al., 1987), surgery and trauma (Pape et al., 1994), but also inflammation. The latter through an increased production of interferon-gamma and interleukin-6 is an essential factor in the loss of the epithelial barrier function (Yang et al., 2003). Normally poorly invasive enterobacteria may, in situations of inflammatory stress, exploit lipid raft-mediated transcytotic pathways to cross the intestinal epithelium, and these effects may precede cytokine-induced disruption of tight junctions (Clark and Diehl, 2002). The increased gut permeability may also explain the occurrence of autoimmunity in many patients with CFS, such as against neurofilaments, gangliosides, and serotonin (Maes, 2005; Maes et al., in preparation). Thus, enterobacteria may have caused the autoimmunity in CFS, for example, by acting as superantigens for T lymphocytes or by a mechanism called molecular mimicry (Levin et al., 2002). Indeed, those enterobacteria have antigenic sites very similar to those of neuronal tissue and its lipid structures. These antigens in turn will go into various tissues and trigger inflammation and once autoantibodies are formed the inflammation may become chronic. Thus, various trigger factors, such as viral and bacterial infections, psychological stress, physical exhaustion, food allergies, increased gut permeability or other sources of inflammation, e.g. injury, may induce immune activation, oxidative stress and inflammation and thus the symptoms of chronic fatigue (Maes, 2005). Inflammation may in turn induce an increased gastro-intestinal permeability, which may aggravate the inflammation in a preexisting fatigue syndrome or cause autoimmunity (Maes, 2005). The results of the present study show that patients with CFS and other forms of chronic fatigue with a known etiology should be checked for the presence of increased gut permeability by the measurements of IgA/ IgM against the LPS of gram-negative bacteria. In addition, we suggest that patients with CFS who suffer from an increased gut permeability should be treated with specific antioxidants. Copyright 2006 Published by Elsevier B.V. [Return to top] ------------------------------ Date: Sun, 1 Oct 2006 13:48:01 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Community patient education and exercise for people with fibromyalgia: a parallel group randomized controlled trial Community patient education and exercise for people with fibromyalgia: a parallel group randomized controlled trial. Clin Rehabil. 2006 Oct;20(10):835-46. Hammond A, Freeman K. Rheumatology Department, Derbyshire Royal Infirmary, Derby, UK. a-hammond@btconnect.com. PMID: 17008336 OBJECTIVE: To evaluate the effects of a community patient education -exercise programme, using a cognitive-behavioural approach, for people with fibromyalgia. DESIGN: A randomized, parallel group trial with assessments at 0, 4 and 8 months. SETTING: Community leisure centres. SUBJECTS: People with fibromyalgia (n=183) attending a rheumatology outpatient department at a large district general hospital. INTERVENTIONS: Participants were randomized to a patient education-exercise group (n=97) or relaxation (attention control) group (n=86). MAIN MEASURES: The Fibromyalgia Impact Questionnaire (0-80; lower score means better health). Secondary outcomes included: the Arthritis Self-Efficacy Scale(pain and other symptoms subscales: 1 -10 scale; higher scores mean greater self-efficacy) and self-reported improvement. RESULTS: Fifty participants withdrew or were unable to attend and 133 completed and returned baseline questionnaires: patient education group (n=71); relaxation group (n=62); 120/133 participants were women. Average age was 48. 53 (SD 10.89) years. Follow-up ranged between 73 and 82% of questionnaires returned. At four months, there was a difference in average changes in total Fibromyalgia ImpactQuestionnaire scores between the two groups: patient education group -3.38 (SD 9.35); relaxation group 0.3 (SD 8.85); P=0.02. Arthritis Self-Efficacy Scale scores were significantly higher in the patient education group: pain 0.59 (SD 1.45)compared to the relaxation group's -0.12 (SD 1.22); P=0.003; other symptoms (patient education group 0.72 (SD 1.33); relaxation group 0.03 (SD 1.16); P=0.002). At eight months these differences were no longer apparent. Forty-seven per cent in the patient education group self-reported improvement compared with 13% in the relaxation group (varkappa=13.65; P=0.0001). CONCLUSION: Short-term improvements resulted from the education -exercise programme but were not sustained. Appropriate selection may improve efficacy. [Return to top] ------------------------------ Date: Mon, 2 Oct 2006 11:27:13 +0200 From: "Dr. Marc-Alexander Fluks" <fluks@xxx.xx> Subject: RES,NOT: Enterobacteria in CFS Source: Journal of Affective Disorders Preprint Date: September 26, 2006 URL: http://www.sciencedirect.com/science/journal/01650327 [Brief report] Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability ------------------------------------------------------------------------------ Michael Maes(a,b,*), Ivana Mihaylova(a), Jean-Claude Leunis(c) a MCare4U Outpatient Clinics, Belgium b Department of Psychiatry, Vanderbilt University Nashville, TN, USA c Laboratory Ategis, Waver, Belgium * Corresponding author. M-Care4U Outpatient Clinics, Olmenlaan 9, 2610 Antwerp, Belgium. Tel.: +32 3 4809282; fax: +32 3 2889185. E-mail address: crc.mh@telenet.be (M. Maes). URL's: http://www.nfb.be, http://www.ediver.be, http://www.mcare4u.com, http://www.marquiswhoswho.net/MMAES/, http://hcr3.isiknowledge.com/author.cgi?&link1=Browse&link2=Results&id=5139 (M. Maes). Received 18 December 2005; received in revised form 14 August 2006; accepted 16 August 2006 Abstract There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls. We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory. The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability. Keywords: Chronic fatigue syndrome; Inflammation; Immunity; Autoimmune; IgA; Enterobacteria; Gut permeability; Oxidative stress; Leaky gut 1. Introduction There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. Immune activation is suggested by an increased expression of T lymphocyte activation markers, such as CD26 and CD38 and alterations in cytokine production. Poor cellular immunity is suggested by lowered natural killer cell cytotoxity, decreased mitogen-induced lymphocyte responses and defects in early T cell activation. Inflammatory reactions are indicated by decreased serum zinc levels and increased serum concentrations of the alpha2 globulin fraction (review: Maes et al., 2005, 2006). Increased oxidative stress in CFS is suggested by increased levels of isoprostanes and oxidized low density lipoproteins (Kennedy et al., 2005), higher LDL thiobarbituric acid reactive substances (TBARS) and decreased anti-oxidative defences, such as lower serum zinc and dehydroepiandrosterone-sulphate (Vecchiet et al., 2003; Maes et al., 2005, 2006). The occurrence of CFS may not only be triggered by viral and bacterial infections, stressful life events and physical stress, type IIIIV allergies for food and heavy metals, but also by an increased permeability of the gut barrier (Maes, 2005). The present study has been carried out in order to examine whether CFS is accompanied by an increased permeability of the gut barrier whereby an immune response is mounted to endotoxins secreted by gram-negative enterobacteria. 2. Subjects and methods 2.1. Subjects Forty subjects participated in the present study, 11 unrelated controls (staff or their family members), and 29 patients admitted to the M-Care4U Outpatient Clinics, Belgium. We made the diagnosis of CFS by means of the Centers for Disease Control and Prevention (CDC) criteria (Fukuda et al., 1994). Patients with chronic fatigue but not fulfilling all diagnostic CFS criteria were classified as suffering from partial CFS. The severity of CFS was measured by means of the FibroFatigue scale, i.e. the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (Zachrisson et al., 2002). The inclusion and exclusion criteria have been presented elsewhere (Maes et al., 2005, 2006). Patients and controls gave written informed consent after the study protocol was fully explained. The study has been approved by the local ethical committee. 3. Methods Fasting blood was sampled during the morning hours for the determination of the IgM and IgA against the LPS of 7 different enterobacteria (see Table 1). The analyses were performed by means of an indirect ELISA method according to the methods outlined by the manufacturer (Gemacbio, The Ultimate Biopharmaceuticals, France) and described previously (Geffard et al., 2002). Each serum sample was measured in duplicate and tested simultaneously with three standard solutions. The optical densities (OD) of the three standards are expressed as Z values. The biological interassay CV values are b10%. 4. Statistics Relationships between variables were assessed by means of Pearson's product moment correlation coefficients, canonical correlation analysis and Spear- man's rank order correlations. Group mean differences were examined by means of analysis of variance (ANOVA) or covariance (ANCOVA) and by means of linear discriminant analysis. Post-hoc contrasts between multiple group means were ascertained by means of the Dunn test. The independence of classification systems was ascertained by means of analysis of contingence tables (chi2-test) and Fisher's exact probability test. 5. Results Table 1 shows that there were no significant differences in age or in sex distribution between the study groups. At the p = 0.01 level, no significant relationships were found between age or gender and the serum IgM and IgA levels. Patients with CFS had significantly greater scores on the FibroFatigue scale than patients with partial CFS (50.9 p/m 5.5 versus 32.6 p/m 5.3, F=84.7, df=1/24, p<10^-5). Table 1 shows that the serum IgM levels against LPS of Proteus mirabilis were significantly greater in patients with partial CFS and CFS than in the normal controls. The IgM levels against LPS of Pseudomonas putida and Klebsiella pneumoniae were significantly higher in CFS patients than in normal controls. We found a significantly greater number of CFS patients (40%) with abnormally increased IgM levels (i.e. anyone of the 7 IgM values >3 Z values) (psi=0.47, p=0.02) as compared to partial CFS patients (16.7%) and controls (0%). Serum IgA levels to LPS of all enterobacteria were significantly higher in CFS patients versus normal controls and patients with partial CFS. The prevalence of CFS patients with abnormally increased IgA levels (i.e. anyone of the 7 IgA>3 Z values) was significantly higher in CFS patients (66.7%) than in normal controls (0%, psi=-0.68, p=0.0006) and in partial CFS patients (7.1%,psi=-0.61, p=0.001). The severity of the FibroFatigue scale was significantly related to the first principal component (PC) of the IgA (r=0.55, p=0.002) data, which explained 71.7% of its variance. There were significant correlations between this first PC and muscular tension (r=0.38, p=0.04), fatigue (r=0.41, p=0.03), concentration difficulties (r=0.39, p=0.03), failing memory (r=0.36, p=0.048), and irritable bowel (r=0.69, p=0.0001). 6. Discussion The findings of the present study show that CFS is accompanied by increased serum levels of IgA and, to a lesser extent, IgM against the LPS of gram-negative enterobacteria. Increments in serum IgM levels can be seen in mucosal immunity and immune activation, e.g. in the B1 lymphocytes. The latter are a significant source of natural serum IgM, thereby serving as a first line of defence against systemic bacterial and viral infections (Thurnheer et al., 2003). B1 cells can migrate to the intestinal lamina propria and differentiate into IgA-producing serum cells, playing a role in mucosal immunity (Thurnheer et al., 2003). The results of our study suggest that there is a chronic immune response raised to the LPS of enterobacteria. Many conditions can cause the mucosal barrier to become more permeable, whereby enlarged spaces between the cells of the gut wall cause a loss of the protective barrier. This may induce an increased bacterial translocation and thus increased serum endotoxin concentrations which, in turn, may trigger an immune response (Wu et al., 2004). Thus, the increased serum IgA and IgM levels against the LPS of gram-negative enterobacteria in CFS indicate the presence of an increased gut permeability and an immune response mounted against LPS of the enterobacteria. The relationship established between irritable bowel and the serum IgA to enterobacteria suggests that irritable bowel in CFS reflects in part disorders in gut-intestinal permeability rather than psychological stress as most psychiatrists tend to confirm. Interestingly, the intestinal barrier may be compromised by factors which are known to trigger CFS, e.g. psychological stress (Meddings and Swain, 2000); sustained strenuous exercise (Davis et al., 2005); food allergies (Andre et al., 1987), surgery and trauma (Pape et al., 1994), but also inflammation. The latter through an increased production of interferon-gamma and interleukin-6 is an essential factor in the loss of the epithelial barrier function (Yang et al., 2003). Normally poorly invasive enterobacteria may, in situations of inflammatory stress, exploit lipid raft-mediated transcytotic pathways to cross the intestinal epithelium, and these effects may precede cytokine-induced disruption of tight junctions (Clark and Diehl, 2002). The increased gut permeability may also explain the occurrence of autoimmunity in many patients with CFS, such as against neurofilaments, gangliosides, and serotonin (Maes, 2005; Maes et al., in preparation). Thus, enterobacteria may have caused the autoimmunity in CFS, for example, by acting as superantigens for T lymphocytes or by a mechanism called molecular mimicry (Levin et al., 2002). Indeed, those enterobacteria have antigenic sites very similar to those of neuronal tissue and its lipid structures. These antigens in turn will go into various tissues and trigger inflammation and once autoantibodies are formed the inflammation may become chronic. Thus, various trigger factors, such as viral and bacterial infections, psychological stress, physical exhaustion, food allergies, increased gut permeability or other sources of inflammation, e.g. injury, may induce immune activation, oxidative stress and inflammation and thus the symptoms of chronic fatigue (Maes, 2005). Inflammation may in turn induce an increased gastro-intestinal permeability, which may aggravate the inflammation in a preexisting fatigue syndrome or cause autoimmunity (Maes, 2005). The results of the present study show that patients with CFS and other forms of chronic fatigue with a known etiology should be checked for the presence of increased gut permeability by the measurements of IgA/IgM against the LPS of gram-negative bacteria. In addition, we suggest that patients with CFS who suffer from an increased gut permeability should be treated with specific antioxidants. Acknowledgments The research reported was supported by a NARSAD Distinguished researcher award to M.Maes and by M-CARE4U and CRC-MH, Antwerp, Belgium. The secre- tarial assistance of Indra Corten is greatly appreciated. Table Table 1. Age and gender distribution and the measurements of serum IgM and IgA levels against the LPS of Hafnia alvei, Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri and Klebsiella pneumoniae in normal controls, patients with partial CFS and patients with CFS ----------------------------------------------------------------------------------------------------- Variables Normal controls Partial CFS CFS F or chi p value (df=2/37) ----------------------------------------------------------------------------------------------------- Age sex 41.5 (10.4) 41.4 (11.0) 44.5 (10.4) F = 0.4 0.7 3/8 4/10 5/10 chi=0.13 0.9 (df=2) Hafnia alvei IgM -0.46 (1.12) -0.19 (1.24) 0.20 (1.32) F = 0.9 0.6 IgA -0.84 (0.61) -0.40 (0.55) 0.43 (1.59) F = 4.7 0.01 Pseudomonas aeruginosa IgM -0.45 (1.23) -0.10 (0.96) 0.75 (1.53) F = 3.1 0.054 IgA -0.02 (1.20) 0.45 (1.69) 2.66 (3.33) F = 5.0 0.01 Morganella morganii IgM -0.25 (0.96) -0.03 (1.07) 0.76 (1.80) F = 1.6 0.2 IgA -0.78 (0.51) -0.08 (1.13) 2.03 (3.65) F = 5.2 0.01 Proteus mirabilis IgM -1.18 (1.52) 0.22 (1.27) 0.90 (1.49) F = 6.9 0.003 IgA -0.94 (0.82) 0.19 (1.20) 2.95 (4.33) F = 6.9 0.003 Pseudomonas putida IgM -0.19 (0.92) 0.50 (1.60) 1.44 (1.68) F = 3.9 0.02 IgA -0.45 (0.58) 0.31 (1.21) 3.82 (4.53) F = 8.5 0.001 Citrobacter koseri IgM -0.14 (1.09) 0.39 (1.82) 0.94 (2.10) F = 1.2 0.3 IgA -0.44 (0.54) 0.04 (1.11) 3.54 (4.11) F = 9.5 0.0007 Klebsiella pneumoniae IgM -0.69 (0.74) 0.71 (1.76) 1.58 (3.15) F = 3.3 0.047 IgA -0.92 (1.99) 0.28 (1.10) 1.89 (2.61) F = 6.3 0.004 ----------------------------------------------------------------------------------------------------- All results are shown as mean (p/m SD). Significantly different from normal controls at pb0.01; significantly different from normal controls at p<0.05; significantly different from normal controls and partial CFS at p<0.05 (all results of Dunn tests). References Andre, C., Andre, F., Colin, L., Cavagna, S., 1987. Measurement of intestinal permeability to mannitol and lactulose as a means of diagnosing food allergy and evaluating therapeutic effectiveness of disodium cromoglycate. Ann. Allergy 59, 127-130. Clark, J.M., Diehl, A.M., 2002. Hepatic steatosis and type 2 diabetes mellitus. Curr. Diabet. Rep. 2 (3), 210-215. Davis, M.S., Willard, M.D., Williamson, K.K., Steiner, J.M., Williams, D.A., 2005. Sustained strenuous exercise increases intestinal permeability in racing Alaskan sled dogs. J. Vet. Intern. Med. 19 (1), 34-39. Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G., Komaroff, A., 1994. The chronic fatigue syndrome: a comprehen- sive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann. Intern. Med. 121 (12), 953-959. Geffard, M., Bodet, D., Martinet, Y., Dabadie, M.-P., 2002. Detection of the specific IgM and IgA circulating in sera of multiple sclerosis patients: interest and perspectives. Immuno-Analyse Biol. Spec. 17, 302-310. Kennedy, G., Spence, V.A., McLaren, M., Hill, A., Underwood, C., Belch, J.J., 2005. Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic. Biol. Med. 39 (5), 584-589. Levin, M.C., Lee, S.M., Kalume, F., Morcos, Y., Dohan Jr., F.C., Hasty, K.A., Callaway, J.C., Zunt, J., Desiderio, D., Stuart, J.M., 2002. Autoimmunity due to molecular mimicry as a cause of neurological disease. Nat. Med. 8 (5), 509-513. Maes, M., 2005. Van Freud tot Omega-3. Standaard Boekhandel, Brussels. Maes, M., Mihaylova, I., De Ruyter, M., 2005. Decreased dehydroe- piandrosterone sulfate but normal insulin-like growth factor in Chronic Fatigue Syndrome (CFS): relevance for the inflammatory response in CFS. Neuro-endocrinol Lett. 26 (5), 487-492. Maes, M., Mihaylova, I., De Ruyter, M., 2006. Lower serum zinc in Chronic Fatigue Syndrome: relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. J. Affect Disord. 90 (23), 141-147. Meddings, J.B., Swain, M.G., 2000. Environmental stress-induced gastrointestinal permeability is mediated by endogenous gluco- corticoids in the rat. Gastroenterology 119 (4), 1019-1028. Pape, H.C., Dwenger, A., Regel, G., et al., 1994. Increased gut per- meability after multiple trauma. Br. J. Surg. 81, 850-852. Thurnheer, M.C., Zuercher, A.W., Cebra, J.J., Bos, N.A., 2003. B1 cells contribute to serum IgM, but not to intestinal IgA, production in gnotobiotic Ig allotype chimeric mice. J. Immunol. 170 (9), 4564-4571. Vecchiet, J., Cipollone, F., Falasca, K., Mezzetti, A., Pizzigallo, E., Bucciarelli, T., De Laurentis, S., Affaitati, G., De Cesare, D., Giamberardino, M.A., 2003. Relationship between musculoskel- etal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci. Lett. 335 (3), 151-154. Wu, G.H., Wang, H., Zhang, Y.W., Wu, Z.H., Wu, Z.G., 2004. Glutamine supplemented parenteral nutrition prevents intestinal ischemia- reperfusion injury in rats. World J. Gastroenterol. 10 (17), 2592-2594. Yang, R., Han, X., Uchiyama, T., Watkins, S.K., Yaguchi, A., Delude, R.L., 2003. IL-6 is essential for development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice. Am. J. Physiol.: Gastrointest. Liver Physiol. 285 (3), G621-G629. Zachrisson, O., Regland, B., Jahreskog, M., Kron, M., Gottfries, C.G., 2002. A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale). J. Psychosom. Res. 52, 501-509. -------- (c) 2006 Elsevier/ScienceDirect B.V. [Return to top] ------------------------------

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