Rapid Responses to:

LETTERS: Chris Clark Patient organisations in ME and CFS seek only understanding BMJ 2004; 329: 112-b-113-b [Full text]

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Please don't let me be misunderstood

Barrington Johnson   (10 July 2004)

Re: Please don't let me be misunderstood

Jean E Long   (11 July 2004)

Re: Please don't let me be misunderstood

Douglas T Fraser   (11 July 2004)

Save us from the armchair psycho-analysers

Angela P. Kennedy   (11 July 2004)

Re: Save us from the armchair psycho-analysers

Mark Struthers   (12 July 2004)

Re: Please don't let me be misunderstood

Erik R Johnson   (13 July 2004)

Re: Please don't let me be misunderstood

Stephen E Ralph   (13 July 2004)

Re: Please don't let me be misunderstood

Gurli H Bagnall   (13 July 2004)

Re: Save us from the armchair psycho-analysers

Erik R Johnson   (15 July 2004)

CFS is a Th1 Immune Disease, Bacterial in Origin

Trevor G Marshall   (16 July 2004)

Re: CFS is a Th1 Immune Disease, Bacterial in Origin

David W Jameson   (21 July 2004)

Please dont let me be misunderstood

Paul Bissaker   (21 July 2004)

Response to Mr Jameson re: Bacterial Th1 Pathogenesis

Trevor G Marshall   (22 July 2004)

The Power of Placebo

Erik R Johnson   (22 July 2004)

Re: Re: CFS is a Th1 Immune Disease, Bacterial in Origin

Steve Carroll   (22 July 2004)

Re: Response to Mr Jameson re: Bacterial Th1 Pathogenesis

David W Jameson   (24 July 2004)

Re: Re: Response to Mr Jameson re: Bacterial Th1 Pathogenesis

Ellen Goudsmit   (24 July 2004)

Fence Straddling

Erik R Johnson   (25 July 2004)

Re: CFS is a Th1 Immune Disease, Bacterial in Origin

Ellen C G Grant   (25 July 2004)

Dr. De Meirleir's work supports Dr. Marshall's hypothesis - CFS - Th1

Jason L Breckenridge   (26 July 2004)

Chronic Fatigue Syndrome and genital mycoplasmal infections.

Ellen C G Grant   (27 July 2004)

Hormornal Balance Emphasizes Th1 During Pregnancy

Trevor G Marshall   (27 July 2004)

Re: Hormornal Balance switches from Th1 to Th2 during Pregnancy

Ellen C G Grant   (29 July 2004)

A Dichotomy in the Definition of Th1 and Th2 Processes

Trevor G Marshall   (30 July 2004)

Depression - The Sixth Sense

Erik R Johnson   (14 September 2004)

CDC News Release: Psychological Factors played no role in the development of CFS following infection

Erik R Johnson   (10 October 2004)

Are there any randomised controlled trials?!

Cherie L Haack   (27 April 2005)

Patient Experiences with Marshall Protocol: Dangerous

Ken Lassesen   (22 June 2005)

Please don't let me be misunderstood 10 July 2004
Barrington Johnson, Psychiatrist London Send response to journal: Re: Please don't let me be misunderstood	It is disingenuous to suggest that ME pressure groups are only seeking 'understanding' from doctors. What they seek is validation. Doctors cannot give them this because their disease does not fit with a purely medical model of disease. That some forms of the disease may have a medical component is possible, but not proven. Without getting too epistemological about it, the positivist scientific background of doctors is that to prove something exists, we try to prove it doesn't exist. If we cannot, it probably does exist. Doctors try to prove that CF/ME is a medical illness by trying to prove that there is a set of unifying features. We fail. Therefore CF/ME is not proven to be a medically validated illness. QED. What pressure groups such as that represented by Clark are seeking is some sort of back-door validation, in the form of 'understanding' (and of course funding). It is interesting to see the way that Dr Peter White is vilified by the ME pressure groups, because he has examined the evidence thoroughly in the context of a Cochrane Review and has found that graded exercise does seem to be useful. If an HIV or cancer drug was recommended after systematic review of the evidence, do you think the equivalent patient groups would be saying "no, we don't believe that will help us, we're not going to use it"? Sabotage of agreed therapeutic goals is a common feature of CF/ME/Anorexia/Bulimia and the spectrum of personality disorders, which is my basis for grouping these illnesses that psychiatry has inherited because no-one else would touch them. It doesn't mean that we are any better than anyone else at treating them, unfortunately. Unfortunately Dr. White's view of the CF/ME world is markedly different from those on the ground, as the medical filtering mechanism introduces significant selection bias in the group of patients that he, as a consultant in a big teaching hospital is likely to see. This is obviously its purpose, but it is difficult for a man in his position to have the same broad view that the GPs in this study have. I share Clark's interest in semantics. It is interesting to look at the way that ME sufferers describe themselves, as in the BMJ Rapid (?Rabid) Responses to the paper to which Clark responds. Cancer patients, children with chronic disease, and spinal injury patients often classify themselves by anatomical dysfunction e.g. "I'm a T4 para", but more often will define themselves in terms of what they can do "I'm a para basketballer". Reading the self-descriptions of the CF/ME patients, one is struck by how often they label themselves as "x% disabled","disabled patient","unable to work due to ME","unavailable for work due to ill health","unable to work","ex-Violinist","Severe ME sufferer". Has anyone ever heard a cancer patient describe themselves as a "severe cancer sufferer" or "unable to work due to cancer"? There seems to be a definite pattern of labelling themselves by what they can't do, which is interesting, and more than a little dysfunctional. The desperate search for medical validation drives the CF/ME bandwagon to magnify any fragment of pseudo-scientific evidence such as the fact that they have got themselves an ICD-10 classification: G93.3. Bad news here again, I'm afraid: paedophilia is ICD10 classified F65.4, and I don't think there is a shred of scientific evidence for a medical causation of that either. Doctors, along with the rest of humanity, use stereotypes to deal with the complexity of personality. Doctors who are in primary care are probably more adept at using stereotypes than most other people, and particularly other doctors, because they have to deal with a vast array of undifferentiated messy problems (and therefore their use of stereotypes has to be more flexible than say, a consultant orthopaedic surgeon). What I find offensive about the paper is that it denigrates the skills of the experienced General Practitioners involved and suggests that they are somehow at fault because they found that their patients didn't get better. If one is dealing with a patient with a personality disorder, do you allow them to set the agenda? Anyone who deals with PD patients knows that this is a disaster, as goals/ limits/ agreements all go out of the window, and so it is with CF/ME patients. The way they treat the few doctors like Dr White who are trying to help them is a further parallel with the PD spectrum of human behaviour. I saw a headline in the local paper the other day. In 5cm high bold type it said "My wife nearly died from fatigue". But she didn't. B. Johnson. [btw thank you for all the concerns expressed to me as a result of my Rapid Respons "Medical Correctness" to the previous paper. I am called both Fred and Barrington - Fred is a good name, particularly because it cannot be shortened to Barry. My base is in London but I am currently working overseas- my area is acute liaison psychiatry, where I see patients largely unfiltered by the medical system.] Competing interests: None declared
Re: Please don't let me be misunderstood 11 July 2004
Jean E Long, ME survivor PO4 9AA Send response to journal: Re: Re: Please don't let me be misunderstood	I believe Barrington (Fred) Johnson has explained himself very well here, and more than he no doubt intended. He has, for reasons only he can validate, chosen to add to the very same denigration that ME patients, those who represent their interests, and genuine medical experts on ME, understandably challenge. Is it any wonder that these purely subjective, insulting, and questionable opinions are challenged? People with ME want to get well. If any of those who think otherwise had an accurate and informed understanding of how this illness impacts upon our lives, they would be interpreting its aetiology quite differently. If they also took the trouble to read and acknowledge the sound and scientific worldwide research, which has already been published, then they would understand why doctors and patients who accept these findings criticise the very viewpoint you, Barrington (Fred) Johnson, want everyone to believe. We want to work, our culture emphasises the importance of employment, and so not being part of the workforce puts us at yet a further disadvantage. We do not choose to be “unemployable”. To use this inability to work as proof of your beliefs is not only inaccurate, but also adds to the many insults, misguided, and inaccurate judgements upon our collective personalities. Patients with ME cover the full spectrum of personality types and all socio-economic groups. I had a good career, l enjoyed every day I worked because of the satisfaction it gave me. I felt privileged that I was being paid to do something that gave me so much pleasure. I derived equal pleasure from my home life, family, and leisure time; I dealt with any stresses as they came up and then moved on. I had a very balanced life in all those respects. Yet I still became ill with ME. I have nothing to gain financially either, my salary would be many times more than the very modest income I have to live on now. What is more this modest income makes it very difficult to access, and continue, recent treatments or pay for future investigations. These treatments have already made a difference but I still have some way to go. Being able to contribute to this recent debate is proof that treatments of this nature are effective. So are the treatments we need provided through the NHS? No. Why not? Because over the last 15 years the snowballing insistence ME needs to be treated as a somatic (or personality!) disorder has meant precious time and resources have been wasted. In those 15 years many patients have continued to become more disabled, or failed to improve sufficiently to have what most would judge a fulfilling life, whilst medical politics and untenable belief systems have dominated what doctors are told about ME. The claims over the successes of CBT GA/GE programmes have been exaggerated and quite rightly criticised because they frequently do serious harm, in many cases that harm has been very long term. I learned the hard way the damage exercise programmes can do, as have too many others in the UK. If the psychiatric view of ME, and the protocols subsequently recommended, really worked we would have been demanding them years ago, not criticising them. As for the rest of your contribution to this debate, I will leave addressing those issues to others better able and more qualified than I. But what I can tell you Barrington (Fred) Johnson is that you have exposed your own prejudices and a clear ignorance regarding ME, as against idiopathic fatigue states. I have no doubt that some who fall into the latter category also have treatable conditions, but nothing will be learned here because doctors in the UK have been persuaded against carrying out the necessary investigations. Barrington (Fred) Johnson quite unintentionally you have done more to support the ME patient community than you set out to do. You have demonstrated the very attitudes we say exist and which stand in the way of progress. Competing interests: None declared
Re: Please don't let me be misunderstood 11 July 2004
Douglas T Fraser, ex violinist London W6 Send response to journal: Re: Re: Please don't let me be misunderstood	Editor, It may not be the case that Barrington Johnson is experiencing some of the once almost understandable but now inexcusable confusion over ME/CFS as a consequence of the difficulties involved locating and identifying reliable and balanced information on the subject untarnished by the Oxford criteria. However I thought it might be useful to reproduce three fairly lengthy segments from the Canadian "Clinical Working Case Definition- Diagnostic and Treatment Protocols", which may provide a brief introduction to ME/CFS for interested readers. Although the Canadian document obviously requires reading and absorbing in it`s entirety, the sections which might not interest Barrington Johnson are - the "Introduction" p 8-10, the "Differences Between ME/CFS and Psychiatric Disorders" p 27-29 and "Cognitive Behavior Therapy (CBT)and Graded Exercise Therapy (GET)" p 46-49. This covers only about one-tenth of a richly detailed and as I understand very accurate document, which delineates many aspects of the diagnosis, biology and treatment of ME/CFS. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ ABSTRACT. Recent years have brought growing recognition of the need for clinical criteria for myalgic encephalomyelitis (ME), which is also called chronic fatigue syndrome (CFS). An Expert Subcommittee of Health Canada established the Terms of Reference, and selected an Expert Medical Consensus Panel representing treating physicians, teaching faculty and researchers. A Consensus Workshop was held on March 30 to April 1, 2001 to culminate the review process and establish consensus for a clinical working case definition, diagnostic protocols and treatment protocols. We present a systematic clinical working case definition that encourages a diagnosis based on characteristic patterns of symptom clusters, which reflect specific areas of pathogenesis. Diagnostic and treatment protocols, and a short overview of research are given to facilitate a comprehensive and integrated approach to this illness. Throughout this paper, myalgic encephalomyelitis and chronic fatigue syndrome are used interchangeably and this illness is referred to as ME/CFS. INTRODUCTION Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe systemic, acquired illness that can be debilitating. It manifests symptoms predominantly based on neurological, immunological and endocrinological dysfunction. While the pathogenesis is suggested to be multi-factorial, the hypothesis of initiation by a viral infection has been prominent. A wide range of viruses and other infectious agents, such as Epstein- Barr Virus (1,2,3,4,5), Human Herpesvirus-6 and 7 (6,7,8,9,10), Entrovirus (11,12), Cytomegalovirus (13,14,15), Lentivirus (16), Chlamydia (17), and Mycoplasma (18,19), have been investigated but findings are mixed and there is no conclusive support for any one pathogen. As antibody titers in standard laboratory tests usually employ a whole viral preparation or a single viral polypeptide, an incomplete or mutated pathogen replication could go undetected. It is unclear whether the pathogens play a direct causal role, accompany an underlying infection, trigger reactivation/replication of latent pathogens, represent reactivated latent pathogens, activate a neural response or modulate the immune system to induce ME/CFS (20). Possibly a new microbe will be identified. Viral involvement is supported by an infectious initiating trigger in at least half of the patients (21), and by confirmed findings of biochemical dysregulation of the 2-5A synthetase/ribonuclease L (RNase L) antiviral defense pathway in monocytes (22,23,24,25,26), a pathway which is activated in viral disorders (27). Before acquiring the illness most patients were healthy, leading full and active lifestyles. ME/CFS most frequently follows an acute pro-dromal infection, varying from upper respiratory infections, bronchitis or sinusitis, or gastroenteritis, or an acute flu-like illness. Other prodromal events that may stress the neuroimmunoendocrine regulatory system include immunization, anesthetics, and exposure to environmental pollutants (28), chemicals, and heavy metals (29). Physical trauma such as a motor vehicle accident, a fall, or surgery may also trigger ME/CFS. In rare occasions, ME/CFS has developed following a blood transfusion. Within days or weeks of the initiating event, patients show a progressive decline in health and develop a cascade of symptoms. The subset of patients that have a gradual onset are less likely to show discrete triggering events. ME/CFS is primarily an endemic disorder (30,31) but occurs in both epidemic (2,32), and sporadic forms. It affects all racial/ethnic groups, is seen in all socioeconomic strata (33,34,25). Epidemiological studies have indicated a wide range of prevalence, from 75 to 2,600 per 100,000 (36,37,38,39,40,41) in different care settings; however, in a large sample of over 28,000 adults, 422 per 100,000 or 0.42% suffered from ME/CFS (36). It is more prevalent in females (522 per 100,000), as is arthritis and rheumatism. When comparing the ME/CFS prevalence figures for women with those for other illnesses, such as AIDS (12 per 100,000), breast cancer (26 per 100,000) (36), lung cancer (33 per 100,000) and diabetes (900 per 100,000), one realizes the need for a clinical definition and research for ME/CFS. In response to cluster outbreaks of this illness, a working case definition for CFS was published under the aegis of the Centers for Disease Control (CDC), U.S.A. in 1988 (42). Their 1994 revised definition (43) has been used as the standard in Canada. These definitions, along with the 1988 and 1990 Australian definitions (30,38), and the 1991 Oxford, U.K. definition (44) have provided a basis for inter-subjective agreement and have played an essential role in orienting clinical research. As the CDC definition was primarily created to standardize research, it may not be appropriate to use for clinical diagnoses, a purpose for which it was never intended. There has been a growing demand within the medical community for a clinical case definition for ME/CFS for the benefit of the family physician and other treating clinicians. The CDC definition, by singling out severe, prolonged fatigue as the sole major (compulsory) criterion, de-emphasized the importance of other cardinal symptoms, including post-exertional malaise, pain, sleep disturbances, and cognitive dysfunction. This makes it more difficult for the clinician to distinguish the pathological fatigue of ME/CFS from ordinary fatigue or other fatiguing illnesses. Based on the consensus panel`s collective extensive clinical experi- ence diagnosing and/or treating more than twenty thousand (20,000) ME/CFS patients, a working clinical case definition, that encompassed the pattern of positive signs and symptoms of ME/CFS, was developed. The objective was to provide a flexible conceptual framework for clinical diagnoses that would be inclusive enough to be useful to clinicians who are dealing with the unique symptomatic expression of individual patients and the unique context within which their illness arises. The panel felt there was a need for the criteria to encompass more symptoms in order to reflect ME/CFS as a distinct entity and distinguish it from other clinical entities that have overlapping symptoms. As fatigue is an integral part of many illnesses, the panel concurred that more of the prominent symptoms should be compulsory. Our strategy was to group symptoms together which share a common region of pathogenesis, thus enhancing clarity and providing a focus to the clinical encounter. The inclusion of more of the potential spectrum of symptomatology in the clinical definition should allow a more adequate expression of the actual symptoms of any given patientęs pathogenesis. We hope that the clinical working case definition will encourage a consideration of the ongoing interrelationships of each patient`s symptoms and their coherence into a syndrome of related symptoms sharing a complex pathogenesis rather than presenting a laundry list of seemingly unrelated symptoms. We believe this will sharpen the distinction between ME/CFS and other medical conditions that may be confused with it in the absence of a definite laboratory test for ME/CFS. Since the development of our clinical criteria, we have had an opportunity to review the analysis of symptoms in over 2,500 patients by De Becker et al. (45). They found that the Holmes definition (42) of fatigue, swollen/tender lymph nodes, sore throat, muscle weakness, recurrent flu- like symptoms, post-exertional fatigue, myalgia, memory disturbance, nonrestorative sleep and replacing low-grade fever with hot flashes; and the addition of ten other symptoms (attention deficit, paralysis, new sensitivities to food/drugs, cold extremities, difficulties with words, urinary frequency, muscle fasciculations, lightheadedness, exertional dyspnea and gastrointestinal disturbance) strengthen the ability to select ME/CFS patients. Based on this study, we added exertional dyspnea and muscle fasciculations to our clinical definition. All the symptoms which the De Becker et al. study (45) recommended adding to strengthen the ability to select ME/CFS patients are in our definition except paralysis, which the panel did not consider prevalent enough for inclusion in a clinical definition. The clinical definition has additional symptoms, such as orthostatic intolerance, which we feel are important in a clinical setting. References 1. Jones JF, Ray CG, Minnich IL, et al. Evidence of active Epstein- Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med 1985;102:1-7. 2. Holmes GP, Kaplan JE, Stewart MD, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein -Barr virus the cause? JAMA May 1 1987;257:17:2297-2302. 3. Lerner AM, Zervos M, Dworkin HJ, Chang CH, OęNeill W. A unified theory of the cause of chronic fatigue syndrome. Infect Dis Clin Pract 1997;6:239 -243. 4. White PD, Thomas JM, Amess J, et al. The existence of a fatigue syndrome after glandular fever. Psychol Med. 1995;25(5):907-916. 5. Lerner AM, Goldstein J, Chang CH, Zervos M, Fitzgerald JT, Dworkin HJ, et al. Cardiac involvement in patients with chronic fatigue syndrome as documented with Holter and biopsy data in Birmingham, Michigan, 1991-1993. Infect Dis Clin Pract 1997;6:327-333. 6. Ablashi DV, Eastman HB, Owen CB, Roman MM, Friedman J, Zabriskie JB, Peterson DL, et al. Frequent HHV-6 antibody and HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. C Clin Virol 2000 May 1;16(3):179-191. 7. Sairenji T, Yamanishi K, Tachibana Y, Bertoni G, Kurata T. Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome. Intervirol 1995;38(5):269-273. 8. Yalcin S, Kuratsune H, Yamaguchi K, Kitani T, Yamanishi K. Prevalence of HHV-6 variantsAand B in patients with CFS. Microbiol Immunol 1994;38:587-590. 9. Di Luca D, Zorzenon M, Mirandola P, Colle R, Botta GA, Cassai E. HHV-6 and HHV-7 in CFS. J Clin Microbiol 1995;33:1660-1661. 10. Wallace HL 2nd, Natelson B, Gause W, Hay J. Human herpesviruses in chronic fatigue syndrome. Clin Diagn Lab Immunol 1999 Mar;6(2):216-223. 11. McGarry F, Gow J, Behan PO. Enterovirus in the chronic fatigue syndrome. Ann Intern Med 1994 Jun 1;120(11):972-973. 12. McArdle A, McArdle F, Jackson MJ, Page SF, Fahal I, Edwards RH. Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. Clin Sci (Lond) 1996 Apr;90(4):295-300. 13. Martin WJ. Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Pathobiol 1997;65:15-18. 14. Martin WJ. Cellular sequences in stealth viruses. Pathobiol 1998;66(2):53-8. 15. Martin WJ. Stealth adaptation of an African green monkey simian cytomegalovirus. Exp Mol Pathol 1999 Apr;66(1):3-7. (Center of Complex Infectious Diseaseshttp:// www.ccid.org/studiesbl.htm) 16. Holmes MJ, Diack DS, Easingwood RA, Cross JP, Carlisle B. Electron microscopic immuno-cytological profiles in chronic fatigue syndrome. J Psychia Res 1997 Jan-Feb;31(1):115-122. 17. Nicolson GL, Nasralla MY, Ranco AR, Nicolson NL, Erwin R, Ngwenya R, Berns PA. Diagnosis and integrative treatment of intracellular bacterial infections in chronic fatigue and fibromyalgia syndromes, Gulf War illness, rheumatoid arthritis and other chronic illnesses. Clin Pract Altern Med 2000;1(2):42-102. 18. Nicolson GL, Nasralla MY, Franco AR, De Meirleir K, Nicolson NL, Ngwenya R, Haier J. Role of mycoplasmal infections in fatigue illnesses: chronic fatigue and fibromyalgia syndromes, Gulf War Illness and rheumatoid arthritis. J CFS 2000; 6(3/4):23-39. http://www.haworthpressinc.com 19. Choppa PC, Vojdani A, Tagle C, Andrin R, Magoto L. Multiplex PCR for the detection of mycoplasma fermentans, M. hominis and M. penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome. Mol Cell Probes 1998 Oct;12(5):301-308. 20. Glaser R, Kiecolt-Glaser J. Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome. Am J Med 1998;105(3A):34S-42S. 21. De Meirleir K, Bisbal C, Campine I, De Becker P, Salehzada T, Demettre E, Lebleu B. A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome. Am J Med 2000;108(2):99-105. 22. Suhadolnik RJ, Peterson DL, Cheney PR, Horvath SF, Reichenbach NL, OęBrien K, et al. Biochemical dysregulation of the 2-5A synthetase/RNase L antiviral defense pathway in chronic fatigue syndrome. J CFS 1999;5(3/4):223-242. 23. Vojdani A, Choppa PC, Lapp CS. Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome. J Clin Lab Immunol 1998;50(1):1-16. 24. Suhadolnik RJ, Reichenbach NL, Hitzges P, Adelson ME, Peterson DL, Cheney PR, Salvato P, Thompson C, Loveless M, Muller WG, Schroder HC, Strayer DR, Carter WA. Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(1)-poly(C12U) in chronic fatigue syndrome. In Vivo 1994; 8:599-604. 25. Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Muller WEG, Schroder HC, Carter WA, Stayer DR. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis 1994;18(Suppl):S96-S104. 26. Suhadolnik RJ, Peterson DL, OęBrien K, Cheney PR, Herst CVT, Reichenbach NL, et al. Biochemical evidence for a novel low molecular weight 2-5A dependent RNase L in Chronic Fatigue Syndrome. J Inteferon Cytokine Res 1997;17:377-385. 27. De Meirleir K, De Becker P, Campine I. Blood transfusion and chronic fatigue syndrome. Abstract. Presented at the CFS Conference, Sydney, Australia, 1999. 28. Bell IR, Baldwin CM, Schwartz GEW. Illness from low levels of environmental chemical: relevance to chronic fatigue syndrome and fibromyalgia. Am J Med 1998 Sept 28;105(3A):74S-82S. 29. Goldberg B, Editors of Alternative Medicine Digest. Chronic Fatigue, Fibromyalgia & Environmental Illness. Future Medicine Publishing, Inc., Tiburon, CA. 1998; pp 190-211. 30. Lloyd AR, Wakefield D, Boughton C, Dwyer J. What is myalgic encephalomyelitis? Lancet 1988 Jun 4;1(8597):1286-1287. 31. Behan PO, Behan WMH, Bell EJ. The post viral fatigue syndromeÖan analysis of findings in 50 cases. J Infect 1985;10:211-222. 32. Hyde BM. Are Myalgic Encephalomyelitis and Chronic Fatigue Syndromes synonymous terms? Paper presented at ME/CFS Conference in New South Wales, Australia. Feb 1998. 33. Centers for Disease Control and Prevention: The Facts about Chronic Fatigue Syndrome. US Dept of Health and Human Services, Public Health Service, Centers for Disease Control Intervention, National Center for Infectious Diseases. Atlanta 1995. 34. Hyde BM, Bastien S, Jain A. Post-Infectious, Acute Onset M.E./CFS (Post-Viral Fatigue Syndrome). In: The Clinical and Scientific Basis of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome; Editors: Hyde BM, Goldstein J, Levine P. The Nightingale Research Foundation, Ottawa 1992;Chp. 4:pp.25-36. 35. Chronic Fatigue Syndrome. U.S. Department of Health and Human Services, Public Health Service, U.S. Centers for Disease Control and Prevention (CDC), National Center for Infectious Disease, Atlanta, GA, 1998 Oct. 36. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W. A community-based study of Chronic Fatigue Syndrome. Arch Intern Med 1999 Oct;159:2129-2137. 37. Bates DW, Schmitt W, Buchwald D, Ware NC, Lee J, Thoyer E, Kornish RJ, Komaroff AL. Prevalence of fatigue and Chronic Fatigue Syndrome in a primary care practice, Arch of Intern Med 1993 Dec;153:2759-2765. 38. Lloyd AR, Hickie I, Boughton CR, Spencer O, Wakefield D. Prevalence of chronic fatigue syndrome in an Australian population. Med. J. Aust. 1990;153:522-528. 39. Buchwald D, et al. Prevalence of chronic fatigue and Chronic Fatigue Syndrome in a large community-based HMO. American Association for CFS. Research Conference Presentation; Fort Lauderdale, Fl., 1994 Oct: pp. 9. 40. Jason LA, Taylor R, Wagner L, Holden J, Ferrari JR. Estimating rates of chronic fatigue syndrome from a community-based sample: a pilot study. Am J Comm Psychol 1995;23(4):557-568. 41. Wessley S, Chalder T, Hirsch S, Wallace P, Wright D. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. Am J Public Health 1997;87;1449-1455. 42. Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, et al. Chronic Fatigue Syndrome: a working case definition. Ann of Intern Med 1988;108:387-389. 43. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A, and the International Chronic Fatigue Syndrome Study Group. Chronic Fatigue Syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994;121:953-959. 44. Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, et al. A report-chronic fatigue syndrome: guidelines for research. J Roy Soc of Med 1991 Feb;84:118-121. 45. De Becker P, McGregor N, De Meirleir K. A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome. J Intern Med 2001;250:234-240. ~~~~~~~~~~~~~~~~~~~~~~~~~ Differences Between ME/CFS and Psychiatric Disorders ME/CFS is not synonymous with depression or other psychiatric illnesses. The belief by some that they are the same has caused much confusion in the past, and inappropriate treatment. Nonpsychotic depression (major depression and dysthymia), anxiety disorders and somatization disorders are not diagnostically exclusionary, but may cause significant symptom overlap. Careful attention to the timing and correlation of symptoms, and a search for those characteristics of the symptoms that help to differentiate between diagnoses may be informative, e.g., exercise will tend to ameliorate depression whereas excessive exercise tends to have an adverse effect on ME/CFS patients. Response to therapy directed at a presumed psychiatric entity may be a helpful distinguishing feature. 1. Depression may come independent of ME/CFS, or patients may feel sudden waves of depression, which just come and go erratically, and are not tied to any definite external context. These attacks are often a secondary consequence of a chronic illness. Since patients live in a depressing situation with severe social and activity restrictions at work, play and in relationships, it is not surprising that situational depression occurs in a subset of patients in reaction to their illness. These various forms of depression can often be distinguished by careful attention to the dynamics of their progression, their temporal relation to other symptoms, their degree of appropriateness, the effect of exercise, etc. Primary depression may cause a significant symptom overlap with ME/CFS, by resulting in fatigue, sleep disturbances and poor concentration. A comparative study indicated a qualitative difference between the depressive symptoms of ME/CFS and those of depression (53). ME/CFS patients scored higher on items indicating physical complaints and symptoms of fatigue and they scored less frequently for disturbed mood and self-reproach than did depressed patients (53,54). In general, fatigue is not as severe in depression as in ME/CFS. Joint and muscle pains, recurrent sore throats, tender lymph nodes, various cardiopulmonary symptoms (55), pressure headaches, prolonged post- exertional fatigue, chronic orthostatic intolerance, tachycardia, irritable bowel syndrome, bladder dysfunction, sinus and upper respiratory infections, new sensitivities to food, medications and chemicals, and atopy, new premenstrual syndrome, and sudden onset are commonly seen in ME/CFS, but not in depression. ME/CFS patients have a different immunological profile (56), and are more likely to have a downregulation of the pituitary/adrenal axis (57). Anhedonia and selfreproach symptoms are not commonly seen in ME/CFS unless a concomitant depression is also present (58). The poor concentration found in depression is not associated with a cluster of other cognitive impairments, as is common in ME/CFS. EEG brain mapping (59,60) and levels of low molecular weight RNase L (21,26) clearly distinguish ME/CFS from depression. 2. Somatization Disorder may also cause a symptom overlap with ME/CFS. In general, Somatization Disorder patients have a long history of complaints beginning before age 30, and don`t have the sudden, discrete onset so common in ME/CFS. Usually fatigue is not so prominent a symptom, and indeed is not a criterion for the diagnosis of Somatization Disorder (which must include 4 pain symptoms, 2 Gl symptoms, 1 sexual symptom and 1 pseudoneurological symptom that cannot be explained by a general medical disorder) (58). In the DSM IV, the general category of Somatoform Disorder also includes Conversion Disorder, Pain Disorder, Hypochondriasis, Body Dysmorphic Disorder, Undifferentiated Somatoform Disorder, and Somatoform Disorder Not Otherwise Specified. The latter two subtypes have the least stringent criteria for diagnosis. Each type of disorder has special characteristics, but each also shares the general characteristics of all somatoform disorders: the presence of physical symptoms that suggest a general medical condition, but are not fully explained by any demonstrable general medical condition, by the direct effects of a substance, or by another mental disorder. As few as 5% of ME/CFS patients meet the criteria for somatization disorder (61). There are numerous objective findings in patients with myalgic encephalomyelitis/chronic fatigue syndrome, including abnormalities in brain SPECT scans and qEEG brain topography, orthostatic intolerance and dysregulation of the 2-5A synthetase/RNase L antiviral defense pathway and low molecular weight 37kDa RNase L. These can be used to exclude somatization disorder in doubtful cases. References 53. Johnson SK, DeLuca J, Natelson B. Depression in fatiguing illness: comparing patients with chronic fatigue syndrome, multiple sclerosis and depression. J Affect Disord 1995;39:21-30. 54. Natelson BH. Chronic fatigue syndrome. JAMA, May 23/30, 2001;285(20): 2557-2559. 55. Jason LA, Torres-Harding SR, Carrico AW, Taylor RR. Symptom occurrence in persons with chronic fatigue syndrome. Biolog Psychol 2002, Feb.;59(1):15-27. 56. Natelson BH, Denny T, Zhou XD, et al. Is depression associated with immune activation? J Affect Disord 1999;53:179-184. 57. Scott LV, Dinan TG. The neuroendocrinology of chronic fatigue syndrome: focus on the hypothalamic-pituitary adrenal axis. Funct Neurol 1999;14:3-11. 58. Friedberg F. Chronic Fatigue Syndrome: a new clinical application. Profes Psych: Res and Prac, 1996;27:487-494. 59. Flor-Henry P, Lind J, Morrison J, Pazderka-Robinson H, Koles Z. Psychophyiological and EEG findings in chronic fatigue syndrome. (Abstract) Presented at IPEG International Pharmaco-EEG SocietyÖ11th Biennial Congress on Parmaco-EEG, Vienna, Austria 2000 Sept 1-3. Abstract published in Klinische Neurophysiologie 2001;32(1):46-65. 60. van de Sande MI. Myalgic Encephalomyelitis Brain Mapping Research of Dr. Flor-Henry. Quest 1997 Jun/Jul;24:3-5. http://www3.sympatico.ca/me- fm.action/ 61. Johnson SK, DeLuca J, Natelson BH. Assessing somatization disorder in the chronic fatigue syndrome. Psychosom Med 1996;58:50-57. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Cognitive Behavior Therapy (CBT)and Graded Exercise Therapy (GET) Two hypotheses have been presented as underlying the CBT model of chronic fatigue syndrome (105). The first hypothesis assumes that the pathophysiology of CFS is largely irreversible, but considers that a fine- tuning of the patient`s understanding and coping behavior may achieve some improvement in his or her quality of life. The second hypothesis is based on the premise that the patient`s impairments are learned due to wrong thinking, and considers the pathophysiology of CFS to be entirely reversible and perpetuated only by the interaction of cognition, behavior, and emotional processes. According to this model, CBT should not only improve the quality of the patient`s life, but could be potentially curative (105). Some proponents suggest that ideally general practitioners should diagnose CFS and refer patients to a psychotherapist for CBT without detours to medical specialists as in other functional somatic syndromes (106,107). The first hypothesis seems reasonable within the multi- causal biopsychosocial model of disease and illness, however a cure may be found. But there is much that is objectionable in the very value-laden second hypothesis, with its implied primary causal role of cognitive, behavioral and emotional processes in the genesis of ME/CFS. This hypothesis is far from being confirmed, either on the basis of research findings or from its empirical results. Nevertheless, the assumption of its truth by some has been used to influence attitudes and decisions within the medical community and the general cultural and social milieu of ME/CFS. To ignore the demonstrated biological pathology of this illness, to disregard the patient`s autonomy and experience and tell them to ignore their symptoms, all too often leads to blaming patients for their illness and withholding medical support and treatment. It is unlikely that the CBT and GET studies that were included in the recent review of treatments (108) dealt with comparable homogeneous groups since different inclusion and exclusion criteria were used in selecting the test patients and control groups. For example, in the Prins et al. (106) CBT study on ME/CFS, patients had to meet the CDC criteria with the exception of the criterion requiring four of eight additional symptoms to be present. If the sole CDC criterion that patients had to meet was prolonged fatigue, is not this study on chronic fatigue, rather than ME/CFS? In a study by Fulcher and White (109), comparing graded aerobic exercise to flexibility therapy, ME/CFS patients who had an appreciable sleep disturbance were excluded because of the effect that poor sleep has on fatigue. This is puzzling as in a study of symptom prevalence and severity by De Becker et al. (45), 94.8% of 951 patients meeting the Holmes criteria, and 91.9% of 1,578 patients meeting the Fukuda criteria, reported sleep disturbance with an average severity of 2.5 and 2.4, respectively, out of 3. When sleep disturbance is such an integral part of ME/CFS, do the findings in the Fulcher and White study (109) apply to ME/CFS? A systematic review of prognosis studies show that the less stringent the clinical criteria, the better the prognosis (74). In two of the studies reviewed (110,37), 22% and 26% of patients with chronic fatigue reported recovery, respectively, whereas none and 6% of the ME/CFS patients recovered from fatigue. Therefore, care must be taken not to classify patients experiencing chronic fatigue as ME/CFS patients unless they meet all the criteria for ME/CFS, as the outcomes for these two patient groups are substantially different. It is interesting to note that in the treatment review (108), all the CBT and GET studies that indicated improvement used the less restrictive Oxford criteria with the exception of the Prins study (106) that used the CDC criteria for prolonged fatigue but eliminated the other CDC criteria. All studies excluded ME/CFS patients who were too ill to regularly attend treatment sessions. The complexity of CBT studies, their varied inclusion and exclusion criteria, the very limited portions that can be properly blinded, and the subjective means used for most evaluations, puts in question the validity of their results. In addition, the numerous variables between the CBT studies, the CBTs and control programs, the different comparison therapies, and the varied frequency and duration of therapy, make it very challenging to determine which parts are responsible for any perceived improvement. Are any effects due to the shift in cognitive beliefs, the exercise involved, the amount and quality of the attention and counseling, the discontinuance of other medical therapies during the test period, etc.? Thus the Powell et al. study (111) found GET alone to be as effective as CBT, and the Risdale et al. study (112) found CBT to be no more effective than counseling. The GETs included in the review (108) generally involved graded aerobic activities with variable amounts of supervision. These three studies (109,111,113) showed positive effects but the results were modest. Although the more carefully supervised study of Fulcher and White (109) found that 55% of the patients improved over a three month period compared to 27% of patients given flexibility and relaxation exercises, the most common result in both groups was feeling a little better. Since graded aerobic exercises programs can help reduce incapacity and symptoms in many chronic and painful conditions (109), one wonders about the specificity of any effects in ME/CFS patients. Do study results represent a true reflection of the ME/CFS population when there is a high dropout rate? The Prins et al. study (106) on CBT reported significant improvement in fatigue severity in 35% (20 of 58) of the patients. However, these figures do not reflect that 26% (99 of 377) of the patients who were eligible for the study refused to take part, and of the 93 patients who were assigned to CBT, 41% (38) did not complete the trial. In a British study (100), 1,214 of 2,338 patients had tried graded exercise. Of these 417 found it to be helpful, 197 reported no change and 610 (50%) indicated that it made their condition worse. This was the highest negative rating of any of the pharmacological, non-pharmacological and alternate approaches of management covered in the questionnaire and may help explain the high drop out rates noted in some of these programs. The question arises whether a formal CBT or GET program adds anything to what is available in the ordinary medical setting. A well informed physician empowers the patient by respecting their experiences, counsels the patients in coping strategies, and helps them achieve optimal exercise and activity levels within their limits in a common sense, non-ideological manner, which is not tied to deadlines or other hidden agenda. Physicians must take as much care in prescribing appropriate exercise as in prescribing medications to ME/CFS patients (100). Attending physicians should only approve of exercise programs in which the patient`s autonomy is respected, appropriate pacing is encouraged, fluctuations in severity of symptoms are taken into account, and adequate rest periods are incorporated. Patients should be monitored frequently but unobtrusively for signs of relapse. References 105. Sharpe MC, in Demitrak MA, Abbey SE (editors). Chronic Fatigue Syndrome. Guilford Press, NY. 1996, pp. 248. 106. Prins JB, Bleijenberg G, Bazelmans E, Elving L, de Boo TM, et al. Cognitive behaviour therapy for chronic fatigue syndrome; a multicentre randomised controlled trial. Lancet Mar 17, 2001;357:841-847. 107. Wessley S, Nimnuan C, Sharpe M. Functional somatic syndromes: one or many? Lancet 1999 Sept 11;354(9182): 936-939. 108. Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Pamirez G. Interventions for the treatment and management of chronic fatigue syndrome. A systematic review. JAMA 2001Sep 19;286(11):1360-1368. 109. Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ June 7, 1997;314:1647- 1662. 110. Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Kormaroff AL. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest Health Care System. Ann Intern Med 1995;123:81-88. 111. Powell P, Bentall RP, Nye FJ, Edwards RH. Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome. BMJ 2001;322:387-392. 112. Ridsdale L, Godfrey E, Chalder T, Seed P, King M, et al. Chronic fatigue in general practice: is counseling as good as cognitive behaviour therapy? A UK randomised trial. Br J Gener Pract, Jan. 2001;51:19-24. 113. Wearden AJ, Morris RK, Mullis R, Strickland PL, Pearson DJ, et al. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiat 1998;172:485-490. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols Bruce M. Carruthers, MD, CM, FRCP(C) Anil Kumar Jain, BSc, MD Kenny L. De Meirleir, MD, PhD Daniel L. Peterson, MD Nancy G. Klimas, MD A. Martin Lerner, MD, PC, MACP Alison C. Bested, MD, FRCP(C) Pierre Flor- Henry, MB, ChB, MD, Acad DPM, FRC, CSPQ Pradip Joshi, BM, MD, FRCP(C) A. C. Peter Powles, MRACP, FRACP, FRCP(C), ABSM Jeffrey A. Sherkey, MD, CCFP(C) Marjorie I. van de Sande, BEd, Grad Dip Ed Journal of Chronic Fatigue Syndrome, Vol. 11(1) 2003 2003 by The Haworth Press, Inc. All rights reserved. 10.1300/J092v11n01_02 [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-HAWORTH. E-mail address: <getinfo@haworthpressinc.com> Website: <http://www.HaworthPress.com> 2003 by The Haworth Press, Inc. All rights reserved.] Address correspondence to: Dr. Bruce M. Carruthers, C58, Site 25, RR 1, Galiano, BC V0N 1P0, Canada (E-mail: carruthers@gulfislands.com). ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ See also: RSE/Wellcome Trust Research Workshop: New developments in the biology of ME/CFS http://www.meresearch.org.uk/melibrary/publications/workshop/spencetalk1.html ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Sincerely, Douglas T Fraser Competing interests: None declared
Save us from the armchair psycho-analysers 11 July 2004
Angela P. Kennedy, Face painter, amateur pianist Essex Send response to journal: Re: Save us from the armchair psycho-analysers	Sir, Barrington Johnson's obvious lack of medical knowledge about ME has already been addressed within this forum. My own concern is Dr Johnson's attempts to speculatively armchair psychoanalyse fellow Rapid Respondents who place their employment status in a compulsory field within the Rapid Response form. Perhaps he is speculatively psychoanalysing everyone who dares respond to the BMJ thus. If I put my usual, that I am the Director of an ME/CFS rights advocacy group, Dr Johnson may accuse me of having delusions of grandeur. If I put that I am a social sciences lecturer and researcher, he may do the same. Maybe if I put that I am a carer, he will accuse me of placing too much importance on this obviously, to him at least, unimportant role in my life. Who knows? The beauty of armchair psychoanalysing by a psychiatrist is that you can make up your own rules of engagement. So, at the risk of being further speculatively armchair psycho- analysed, I have described my occupation in terms of other things that I can do. Wouldn't it be nice if all rapid respondents in the BMJ (including the medics) did this? We could have magicians, S&M fanatics, football hooligans, amateur keyboard players, transvestites, bell-ringers, clowns, oh- and maybe ex- school bullies. the possibilities are endless. But if we may return to serious issues; ME/CFS is often such a devastating illness, that people are placed in the terrible position of having to explain their work identity in past terms, or negative terms. But, from his performance so far, I expect a plea for sympathetic understanding, of the devastating effects on life chances for ME/CFS sufferers, to fall on deaf ears in the case of Dr Johnson. But what I find of grave concern is that a health professional, with an ethical code to uphold, is engaging in armchair speculative psycho- analysing, in a public forum, in Johnson's case, to denigrate seriously ill people. Another psychiatrist was exposed for similar shenanigans some weeks ago: Something to do with something he saw on the telly. Now, isn't it unethical to do that sort of thing? Competing interests: I daren't name any more-in case I'm speculatively psycho-analysed!
Re: Save us from the armchair psycho-analysers 12 July 2004
Mark Struthers, GP Bedfordshire Send response to journal: Re: Re: Save us from the armchair psycho-analysers	Ms Kennedy I agree with all you say. However, could I point out one small error in your penultimate paragraph. I think you may refer to the shenanigans of Professor David Southall. He is a paediatrician and an eminent one at that. He is not a psychiatrist. It was he who dabbled as an amateur psychiatrist and diagnosed double murder off the telly. He finished his amateur dramatic career in front of the GMC. Competing interests: None declared
Re: Please don't let me be misunderstood 13 July 2004
Erik R Johnson, n/a Incline Village NV 89450 Send response to journal: Re: Re: Please don't let me be misunderstood	In response to Barrington Johnsons question; "Has anyone ever heard a cancer patient describe themselves as a "severe cancer sufferer" or "unable to work due to cancer"?" Yes. -Erik Johnson Competing interests: None declared
Re: Please don't let me be misunderstood 13 July 2004
Stephen E Ralph, Retired Diagnostic Radiographer Louth, Lincolnshire, LN11 8BT. Send response to journal: Re: Re: Please don't let me be misunderstood	Margaret Williams – a close watcher of certain psychiatrists --- has observed that psychiatrist “Fred” Barrington Johnson seems equally as obsessed with “validation” of ME as does psychiatrist Simon Wessely, who believes that “Validation is needed from the doctor. Once that is granted, the patient may assume the privileges of the sick role -- sympathy, time off work, benefits etc”. (see Chronic fatigue syndrome: current issues. Wessely S. Reviews in Medical Microbiology 1992:3:211- 216). Barrington Johnson’s latest post brings to mind the item on pseudo- science posted on Co-cure on 11 January 2002 by Alan Gurwitt MD, in which he noted deficits in the work, thinking, terminology and research methods of certain psychiatrists, who often fail to be aware of the mounting neuro -immunological evidence that demonstrates the organic nature of ME/CFS. Gurwitt summed it up in a succinct sentence: “They demonstrate a morbid preoccupation with psychiatric morbidity”. Indeed so. For more quotable quotes on ME/CFS from psychiatrists who seem to desire clinical control over non-psychiatric patients, see “The Mental Health Movement: Persecution of Patients?”, a briefing paper prepared for the House of Commons Select Health Committee by Professor Malcolm Hooper” at... http://www.meactionuk.org.uk/SELECT_CTTEE_FINAL_VERSION.htm Yours sincerely, Stephen Ralph DCR(R) Retired Dx of Ankylosing Spondylitis since 1979 and PVFS/ME/CFS since 1996 Competing interests: None declared
Re: Please don't let me be misunderstood 13 July 2004
Gurli H Bagnall, Independent Patients' Rights Campaigner Marlborough, 7315, New Zealand Send response to journal: Re: Re: Please don't let me be misunderstood	It is quite astonishing how someone with Barrignton Johnson's views routinely ignore the iagtrogenic statistics. They make a nonsense out of his self-righteous indignation over patients who have the temerity to exercise their own intelligence and recognize a load of odorous manure when they see it. Competing interests: None declared
Re: Save us from the armchair psycho-analysers 15 July 2004
Erik R Johnson, n/a Incline Village NV 89450 Send response to journal: Re: Re: Save us from the armchair psycho-analysers	Does it seem reasonable that doctors can restrain, place in detention and forcibly administer drugs to patients who fail to distinguish their mental illness from reality while doctors themselves face no forfeiture of their position, no repercussions or scarcely more than embarrassment after they demonstrate their own incapacity to distinguish reality from mental illness? It is the nature of the limitations and discomfort of disease that inspires patients descriptions of life altering medical conditions. For a doctor to assert that the very expression of these limitations is "dysfunctional" is to disregard the rational basis behind the very function of expressing the condition of illness. What could possibly be more dysfunctional than having a doctor indict illness descriptions as "dysfunctional" simply because they represent limitations? What recourse does a patient have when the doctor makes clear and unequivocal statements that reveal his own dysfunctional behaviors except to point these out and hope that there is some mechanism in the medical system that will recognize the manifestations of mental illness and intervene to police its own mental health? Whose responsibility is it to to prevent the psychiatric abuse and misdiagnosis of patients if it is not those doctors who are sound of mind and can recognize mental illness in their fellow doctors? We have been given repeated and spectacular examples of illnesses whose victims continually pointed out evidence that psychological theorists deliberately disregard or manipulate in an imprudent manner if it jeopardizes their conceptual model of the illness or diminishes their influence in its treatment. These failures to consider exclusionary evidence have harmed every single sufferer who was misdiagnosed, mistreated or whose therapy was delayed until medical intransigence could be finally be overcome by an avalanche of overwhelming proof. If a patient shows a irrational inability to incorporate reality into his actions and his actions have the potential to create harm to others, such behaviors could get him locked in a straitjacket. If a patient points out examples of such denial of reality in doctors to the medical system and there is no response whatsoever, what recourse does he have then and who is to save him from the armchair psycho-analysers? -Erik Johnson Competing interests: None declared
CFS is a Th1 Immune Disease, Bacterial in Origin 16 July 2004
Trevor G Marshall, Director Autoimmunity Research Foundation, Thousand Oaks, California Send response to journal: Re: CFS is a Th1 Immune Disease, Bacterial in Origin	We recently established that Sarcoidosis was caused by poorly documented species of antibiotic resistant bacteria which have evolved to infect phagocytes of the immune system. Wirostko, et al, produced TEM photographs of hundreds of these tiny bacteria in the cytoplasm of monocytes, lymphocytes and macrophages in the late 80's. Our recent paper "Sarcoidosis succumbs to antibiotics-implications for autoimmune disease", PMID 15246025, Full text Preprint, explained this phenomenon, and hypothesised that Rheumatoid Arthritis, Lupus and Parkininson's were likely due to a similar Th1 immune pathogenesis. However, during the last several months, an online CFS community, which can be accessed at Yahoo Health Groups (click here), has found that CFS is indeed also associated with elevated levels of the secosteroid hormone 1,25-dihdroxycholecalciferol, a marker of Th1 inflammatory processes. Further, a significant sample (>50) of these CFS patients have found that that the same protocol of innocuous, oral drugs which we developed to treat Sarcoid inflammation has the ability to put CFS into remission. There still is some uncertainty, due to limited sample size, and lack of controls, but, based on the close resemblence between the progess I have seen in our Sarcoidosis cohort and in the CFS patients I will now state that CFS is a Th1 immune disease, bacterial in origin, and that it responds to the same antibacterial therapy as we developed for sarcoidosis. The primary difficulty in treating the disease is, like other diseases with pathogens which cannot be cultured (syphilis), the incidence of Jarisch-Herxheimer during the entire recovery process (12-36 months) must be very carefully managed. Competing interests: None declared
Re: CFS is a Th1 Immune Disease, Bacterial in Origin 21 July 2004
David W Jameson, Recovered CFS/ME patient Belfast, BT4 Send response to journal: Re: Re: CFS is a Th1 Immune Disease, Bacterial in Origin	Trevor Marshall states with certainty that CFS "is" Th1 immune disease caused by bacteria, even though the current results of his research are very far from proving this. It is no surprise that elevated levels of 1,25- dihydroxycholecalciferol are found in some CFS/ME patients, as D-1,25 is produced from vitamin D in the liver and many CFS patients take supplements containing vitamin D. Regarding the "Jarisch-Herxheimer" reactions that occur over 12-36 months, Dr Marshall should know that Jarisch-Herxheimer reactions typically last only for a few hours. It should also be noted that Dr Marshall has not actually studied any patients himself - he relies on symptom reports and vitamin D tests from patients. In no case has he found evidence of actual Th1 bacterial infection. In fact, some of Dr Marshall's advice is likely to be damaging to CFS/ME patients. He advocates using Benicar (which reduces blood pressure) even though hypotension and orthostatic intolerance is a common symptom of CFS/ME. He also advocates avoiding sunlight (to reduce D-1,25), even though a common symptom of CFS/ME is a desynchronised or non-existent circadian cortisol rhythm and sunlight is known to help in restoring abnormal circadian cycles. Given the fact that the placebo effect has resulted in many cases of recovery from CFS/ME, this is probably the best explanation for cases where patients have recovered after following the "Marshall Protocol". Competing interests: None declared
Please dont let me be misunderstood 21 July 2004
Paul Bissaker, Unemployed CFS/ME sufferer Kidderminster Send response to journal: Re: Please dont let me be misunderstood	In response to Barrington Johnson, the sufferers of CFS/Me describe their condition as they do because this debillitating condition makes you incapable of doing what you used to be able to do, in my case I used to ride a mountain bike for pleasure everyday, now it is a rare day when I'm able to even ride it, due to being easily fatigued or muscle pain. I also used to be a national service engineer a brilliant job as far as I was concerned, but due to neck muscle spasms causing me to pass out while at work or play, is no longer one of the things I am able to do. Also I would like to be employed in work, but finding an employer prepared to take me on is like trying to find the holy grail. My home life is now devoid from the hobbies I used to do for the same reasons, in fact it takes me 3 days to mow my very small garden due to fatigue, I have to expell a little energy each day otherwise if I try to complete it in 1 day I end up very ill with flu-like symptoms, aching and sore all over, having difficulty in keeping myself upright. I have always been the type of person who accepts a challenge, a can do person, always getting the job done, always giving 110%, but I now have to accept that this is no longer within my capabilities, although I wish it was not so. My social life is nothing like it was, friends have stopped calling round to see if I would like to go out somewhere, because if you are in pain or fatigued while out, then they do not get the enjoyment that they had planned, so they no longer ask. Yes to other people I look fine, they presume that their is nothing wrong with me and expect me to be able to do the same things they can, but it is not so. This is why the description is always focused on can't because we are grieving for our past capabilities, which were so much more. Competing interests: None declared
Response to Mr Jameson re: Bacterial Th1 Pathogenesis 22 July 2004
Trevor G Marshall, Director Autoimmunity Research Foundation, Thousand Oaks, California 91360 Send response to journal: Re: Response to Mr Jameson re: Bacterial Th1 Pathogenesis	Mr Jameson, the secosteroid hormone 1,25-dihydroxyvitamin-D is not "produced from vitamin D in the liver". The paper I cited in my earlier Rapid Response explains exactly the function of 1,25-D in immune disease. The Pubmed Abstract is at this link, and the full text preprint can be read at this link. Please understand that it does not advance scientific understanding to attack somebody's conclusions without first having read the papers detailing how those conclusions were reached. CFS will remain an enigma until medical science is able to dispel that enigma. Jarisch-Herxheimer shock is a term used to describe the effect on the body of endotoxins released as the treponema causing syphilis are killed. Treponema are eradicated from the bloodstream within days. It is not reasonable to assume that other bacterial pathogens will not take longer to be eradicated from the body. This is especially true when considering those microbes which live in symbiosis within the cytoplasm of cells of the immune system itself. I will repeat the link I gave to the stunning Transmission Electron Micrograph taken by Wirostko, et al, of just such bacteria (click here). Our paper describing the functions of the ARB Olmesartan Medoxomil in Th1 disease is published by JOIMR and can be read at this link (click here). Your comment that I have "not actually studied any patients" myself" would be laughable if this disease was not so tragic. I spend much of my time working closely with the clinical physicians, and I welcome the oportunity to delegate clinical tasks to those with the appropriate expertise. I myself concentrate on the science of unravelling Th1 disease. Finally, the "placebo effect" should only be invoked when it is the most likely explanation for the observed results. In this case, the percentage of patients who are recovering, and the degree of dysfunction they are regaining, are both too high to indicate that any "placebo effect" is in play. Competing interests: None declared
The Power of Placebo 22 July 2004
Erik R Johnson, n/a Incline Village 89450 Send response to journal: Re: The Power of Placebo	Given the fact that Mr. Jameson considers any recovery from CFS likely to be due to the "placebo effect" or by exploiting what some call the "Power of the Mind" to create an illusory belief in a placebo to induce a suggestible attitude of healing, I'd like to point out that this would be exploiting the "Weakness of the Mind" since the placebo effect is predicated upon tricking the mind by the assimilation of false information. It is not my intent to limit the therapies available to people, however the practical application of this concept brings up some further questions and considerations. Might a physician concerned about the toxic effects of unnecessary chemotherapy be ethically compelled to substitute inert placebos to determine the true nature of his patients response to treatment? Of course, in order to maintain the pretense that creates the effect, the placebo would have to be just as unpalatable and expensive as the real treatment lest any suspicion be roused. Should impoverished nations that cannot afford modern medicine freely distribute placebos so that sufferers of various illnesses may at least have the benefits mentioned by Mr Jameson? Is the Placebo Effect limited to certain specific illnesses or would it be a greater public service if Mr. Jamesons emphasis on sharing his therapy were placed in attending to the diseases of greatest need and highest mortality? Does drug testing need to take into account the differential factors induced by the potential of various "medical sounding" names to influence the "belief in efficacy" response necessary for the placebo effect? Has Mr. Jameson informed proponents of CBT/GET that these therapies lack a "believable" rationale for patients who have the conviction that they suffer from a physiological illness and that some impressively named sugar pill is all that is required to construct the complete "Placebo Package"? Will Mr. Jameson make haste in informing the scientific community that the entire concept of double blind randomized trials for drug testing is invalid and unreliable because it is really only testing the subjects belief of whether he is receiving the placebo or the genuine therapy? -Erik Johnson Competing interests: None declared
Re: Re: CFS is a Th1 Immune Disease, Bacterial in Origin 22 July 2004
Steve Carroll, recovering from ReA France 11800 Send response to journal: Re: Re: Re: CFS is a Th1 Immune Disease, Bacterial in Origin	I have been ill with Reactive Arthritis (ReA) for over 5 years. During this time I have used many different antibiotics (abx) with good success. Even though mainstream established medical dogma claims that ReA is an autoimmune disorder, and further that abx have no value in treating ReA or other so called autoimmune disorders, my own findings suggest otherwise. These findings are not unique to me since I have observed others with the same diagnosis recover from ReA with the use of abx. Albeit I am still not yet cured. It would appear that the nano- bacteria that cause these so called auto-immune disorders (which in my experience are nothing more than undiagnosed infections) have been able to establish pockets where they can hideout and survive abx. It just so happens that these pockets are the very same areas where inflammation occurs in me. The Marshall-Protocol (MP) claims that inflammation is the mechanism that bacteria utilize to protect against the immune system and abx. Further that Benicar reduces inflammation, and this action in-itself aids the immune system to clear the nano- bacteria that cause the inflammation. It has been my own findings that after only after a few days of using Benicar (Olmetec) that my own areas of inflammation have been completely reduced to zero. It is suggested by David W Jameson, (above) that the effect of Benicar is most likely a placebo. If David W Jameson is correct that the MP is a nothing more than placebo effect, could David W Jameson, please explain to me why when I don't take the benicar after 7 hours my symptoms return? Competing interests: None declared
Re: Response to Mr Jameson re: Bacterial Th1 Pathogenesis 24 July 2004
David W Jameson, Recovered CFS/ME patient Belfast, BT4 Send response to journal: Re: Re: Response to Mr Jameson re: Bacterial Th1 Pathogenesis	Dr Marshall says "In this case, the percentage of patients who are recovering, and the degree of dysfunction they are regaining, are both too high to indicate that any placebo effect is in play". This is a very dangerous assumption to make with CFS, as the placebo effect has resulted in many severely affected patients recovering. How else to explain people who have recovered due to homeopathy or kinesiology? Also, Reverse Therapy claims to have a 94% success rate at curing CFS using what is essentially psychotherapy. Although their results haven't been published, I have spoken to one severely affected patient who was bed-ridden for 3 months and who has been completely cured using RT after suffering from CFS for 7 years. Using double-blind placebo-controlled trials is the only way to determine whether or not a drug treatment works. This is doubly so for CFS, where psychological or psycho-social treatments appear to cure the illness. Competing interests: None declared
Re: Re: Response to Mr Jameson re: Bacterial Th1 Pathogenesis 24 July 2004
Ellen Goudsmit, Chartered Health Psychologist Teddington Send response to journal: Re: Re: Re: Response to Mr Jameson re: Bacterial Th1 Pathogenesis	I was interested to read Mr. Jameson's assertion that in relation to CFS, "psychological or psycho-social treatments appear to cure the illness". This elicited the following thoughts. Firstly, no scientist with knowledge of the literature on CFS would claim that there is any treatment at the moment which 'appears to cure CFS'. It makes me wonder how Mr. Jameson defines 'cure'. The fact is that any treatment which increases self-efficacy can lead to temporary improvements in fatigue and emotional distress, hence CBT is as effective as counselling. However, long term follow-ups have been disappointing and there are no reports of any treatment leading to complete remission in a majority of those tested. Secondly, Mr. Jameson is not familiar with the illness itself, because if he were, he'd know that a considerable proportion of patients improve over time regardless of what they do. Has he ever heard of 'effort after meaning'? Thirdly, the term CFS covers a heterogeneous population. Those familiar with the syndrome ceased looking for single cause and a 'one-size fits all' solution years ago. Fourthly, being bedbound with fatigue does not mean that the person has severe CFS. Similarly, the alleged improvements with homeopathy do not support Mr. Jameson's argument that there is a marked placebo effect in this population. Homeopathy is one of the least effective treatments documented in the literature for CFS and there is no evidence from reliable sources relating to kinesiology. Finally, we know that the 1994 diagnostic criteria are open to misinterpretation. Even some researchers seem to ignore the need for a thorough medical examination and have simplified their assessment to the most basic of tests and the counting of symptoms. Fatigue doesn't have to be of new onset anymore, it doesn't have to be profound and any type of headache will do. It is my contention that people who claim to cure over 90% of patients probably don't adhere to the 1994 criteria and can't tell the difference between CFS and disorders like burn-out and somatisation. A lot of the recent correspondence reflects what this field has become. There is a dearth of good science but much 'cheap and cheerful' psychobabble. Doctors write endlessly about the role of deconditioning even though research has shown this is not responsible for the perpetuation of the symptoms. They ignore evidence of ongoing viral infection, preferring a model which reduces CFS to stress, misguided beliefs and avoidance behaviour. No wonder patients have lost trust in orthodox medicine. Who fills the gaping hole? Well-meaning but often untrained individuals, who are not accountable to any professional organisation but who offer the desperate a ray of hope. This area needs more virologists and neurologists. And we need a more balanced discussion of the illness in the mainstream medical journals. New editor, please note! Competing interests: Former ME specialist.
Fence Straddling 25 July 2004
Erik R Johnson, n/a Incline Village 89450 Send response to journal: Re: Fence Straddling	Mr Jameson has made it completely clear that be believes in the Power of Placebo and yet he straddles the fence by maintaining that; "Using double-blind placebo-controlled trials is the only way to determine whether or not a drug treatment works." If the Placebo Effect often manifested in "cures" during double blind controlled trials, the process would fail to identify the difference between Placebo and Therapy. The reason for using Placebos in such trials is because Placebos don't work. The amazing ability of psychotheorists to straddle the fence and argue both sides of a conflicting argument was clearly demonstrated in Professor Wessely and Dr. Whites messages to me in which they claim to recognize physiological abnormalities and signs of unusual inflammation which are not consistent with mental disorders and which caused them to reverse their years of public statements to the contrary. Yet they continue to apply the therapies that were constructed using their old conceptual model: - A model of illness which they contradict with the statement that "CFS is not primarily psychological". And still they fail to look for the primary cause for these admitted abnormalities and abandon their baseless therapies. Professor Wessely and Dr. White have contradicted their former statements without changing their methods, without a retraction, without clarification of their new views, without diverting resources to investigation of the abnormalities and without the basic requirement of correcting such a mistake; An Apology. One cannot argue both sides of conflicting concepts and convey the impression of sanity. The fields of Science and Psychotheories are divided by a growing wall of evidence. It is a fence that can only be straddled for so long until the divisions grow too painfully obvious to ignore. -Erik Johnson Competing interests: None declared
Re: CFS is a Th1 Immune Disease, Bacterial in Origin 25 July 2004
Ellen C G Grant, physician and medical gynaecologist 20 Coome Ridings, Kingston-Upon-Thames, KT2 7JU, Uk Send response to journal: Re: Re: CFS is a Th1 Immune Disease, Bacterial in Origin	The Marshalls’ work on treating sarcoidosis successfully with antibiotics is very interesting. So is their belief that several other unexplained conditions like Chronic Fatigue Syndrome and arthritic conditions are due to infections and immune disturbances.1 It is also thought that ankylosing spondylitis can be due to a genetic increased susceptibility to small bowel infections. Klebsiella pneumoniae was implicated but this has not been substantiated by more recent work.2 Instead, Stone and colleagues have found a higher percentage of affected family members (25.9%) exhibited a predominant response to salmonella typhimurium compared with unaffected family members (5.9%, P < 0.02).3 Having the HLA-B27 gene, on several occasions I have suffered from severe anaemia and abdominal pains, with bleeding from the gut. Both iron and folate deficiencies produced a confusing normochromic anaemia. Each time both the bleeding and pains were stopped by a course of ciprofloxacin. Pathogenic bacteria, aeromonas hydrophila, probably ingested from eating contaminated sea food in Turkey, were isolated during one of these episodes. I now take probiotics and an immunoglobulin gut supplement along with a range of nutritional supplements. As a doctor practising Nutritional Medicine, my experience investigating patients with Chronic Fatigue Syndrome patients is that deficiencies of zinc, copper (low red cell superoxide dismutase activity), magnesium, B vitamins are usually found, as are blocks in both omega- 6 and omega-3 essential fatty acids pathways. As adequate levels of zinc and copper are needed for normally functioning immune systems, such patients are susceptible to infections and they may have had several courses of antibiotics. Antibiotics can cause a leaky gut and fungal or bacterial gut fermentation, which in turn can cause more physical and mental reactions to more foods and chemicals. In many women use of hormones, for contraception or the menopause, has been a major precipitating cause of Chronic Fatigue Syndrome. The disease has been recognised more commonly in young women with the increasing use of sex hormones over the last 50 years. Progesterones upsets copper/zinc balance and is particularly immunosuppressive, thereby increasing the risk of all types of infections. If a range of auto-immune diseases can be treated with antibiotics, my personal experience suggests that it is important to choose an effective one. This can be difficult to find out, which is probably why these diseases have remained mysterious and attracted psychotherapy or homeopathy instead of more scientific treatments. How much auto-immune disease is due to food poisoning? 1 Marshall TG, Marshall FE. Sarcoid succumbs to antibiotics –implications for autoimmune disease. Autoimmunity Reviews 2003; 3: 295- 300. 2 Ebringer A, Wilson C. HLA molecules, bacteria and autoimmunity. J Med Microbiol. 2000;49: 305-11. 3 Stone MA, Payne U, Schentag C, Rahman P, Pacheco-Tena C, Inman RD. Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumonia in the pathogenesis of familial ankylosing spondylitis. Rheumatology (Oxford) 2004 ;43: 148-55. Competing interests: None declared
Dr. De Meirleir's work supports Dr. Marshall's hypothesis - CFS - Th1 26 July 2004
Jason L Breckenridge, CFS Researcher / NCF Volunteer Syracuse New York, 13209 Send response to journal: Re: Dr. De Meirleir's work supports Dr. Marshall's hypothesis - CFS - Th1	It is my opinion that Dr. Marshall's hypothesis has significant merit for chronic fatigue syndrome. The work and research of Dr. Kenny De Meirleir, who is considered an expert in the CFS community, supports Dr. Marshall's theory quite a bit. For example, Dr. De Meirleir proposed that mycoplasma infections are capable of causing the 83 kDa RNase L proteolysis and dysfunction which has been consistently found in CFS patients. Mycoplasma can activate monocytes, neutrofils and T-cells. To bring about their phagocytic activity, monocytes, neutrofils and activated T-cells produce elastase which is one of the primary findings by Dr. De Meirleir and was recently revealed by the National CFIDS Foundation. Dr. De Meirleir holds a worldwide patent on his discovery. Subsequently, in the CFS community, patients tested for human leukocyte elastase (HLE) by R.E.D. Laboratories have consistently shown higher levels of elastase corresponding with the RnaseL proteolysis and dysfunction which clearly could be involved in systematic inflamation and numerous symptoms associated with CFS. Once the 83 kDa RNase L cleavage has occurred, cell apoptosis (programmed cell death) is initiated. Apoptosis in turn enhances the activity of pro-apoptotic and pro-inflammatory proteases including both elastase and calpain, each of which is capable of high molecular weight RNase L proteolysis.. A vicious cycle is initiated by the cell-wall deficient bacteria species (mycoplasma, lyme) and numerous opportunistic infections take advantage of the impaired immune system in CFS patients. Cytokine responses are clearly involved in this process. Dr. De Meirleir's work defintely supports Dr. Marshall's hypothesis that CFS is indeed a Th1 immune disease most likely caused by "stealth" bacteria without cell walls that can evade and disrupt the immune response. In my opinion it is likely there is a genetic or other co-factor in CFS patients. For example, women have considerably higher rates of CFS in the general population (and other autoimmune diseases) than men. It isn't clear why chronic fatigue syndrome and other autoimmune diseases affect women more than men but the answer could likely lead to a greater understanding of the immune system. I highly recommend reading Dr. De Meirleir's work and all the research papers that he has been an investigator in. After reading them, along with Dr. Marshall's research papers, it is fairly clear that there is a common factor that almost every CFS researcher has found - and Dr. Marshall's hypothesis brings it together for a clear understanding of the cause and treatment for chronic fatigue syndrome and possibly other autoimmune conditions. Competing interests: None declared
Chronic Fatigue Syndrome and genital mycoplasmal infections. 27 July 2004
Ellen C G Grant, Physician and medical gynaecologist 20 Coombe Ridings, Kingston-upon-Thames, Surrey, KT2 7JU, UK Send response to journal: Re: Chronic Fatigue Syndrome and genital mycoplasmal infections.	It is interesting that Dr Kenny De Meileir has found evidence of immune dysfunction which he believes is possibly caused by mycoplasmal infections in Chronic Fatigue Syndrome patients. Jason Breckenridge wonders why more women than men have autoimmune diseases than men. Women are able to tolerate the father’s contribution of foreign protein in their child during pregnancy because progesterone is highly immunosuppressive. During pregnancy the immune balance switches from Th1 to Th2 balance. This strengthens humoural immunity but weakens cellular immunity. Immune responses are further compromised considerably when zinc and copper are deficient. The use of contraceptive hormones, which are progesterone dominant, and hormone replacement therapy, which also is progesterone dominant in women with an intact uterus, has resulted in an increase in key nutritional deficiencies and increases in autoimmune diseases in women. Progesterone users had increases in over 60 conditions including more systemic or genital viral, bacterial and fungal infections in the large Royal College of General Practitioners oral contraception study. Many genital infections are undiagnosed and therefore untreated. By 1990 I had screened 114 preconception couples, most with a history of unexplained infertility, failed IVF attempts and recurrent miscarriages and 90% of the women had used hormonal contraceptives. 21% of the females and 5 % of the males had mycoplasmal infections of the endocervix or prostate. These patients were treated with doxycycline for 2 weeks. As progesterone use can also cause cervical erosions, which trap infections and impair antibiotic penetration, erosions were simultaneously treated by cryocautery. Follow-up tests at 6-8 weeks were usually negative. Other types of genital infections were commoner in women than men, with 46% of women and 18% of men having bacterial infections and 45% of the women had raised serum antibodies denoting past infection with chlamydia trachomatis. Mycoplasmal infections are not usually investigated or treated and yet are known to be associated with premenstrual tension, hypertension in pregnancy, infertility and miscarriages. Since the introduction of hormonal contraceptives in the 1960s promiscuity and genital infections have increased. Treatment programmes are not coping in my experience. Successfully treating hidden infections, food allergies and nutritional deficiencies gives excellent pregnancy outcomes. Competing interests: None declared
Hormornal Balance Emphasizes Th1 During Pregnancy 27 July 2004
Trevor G Marshall, Director Autoimmunity Research Foundation, Thousand Oaks California 91360 Send response to journal: Re: Hormornal Balance Emphasizes Th1 During Pregnancy	Ellen C G Grant proposed "during pregnancy the immune balance switches from Th1 to Th2 balance." This is not correct. Th1 inflammation is mediated by the secosteroid hormone 1,25-dihydroxcholecalciferol. During pregnancy, excess quantities of this hormone are manufactured in the placenta. See, for example, "Vitamin D and placental-decidual function" However, as described in our paper "Sarcoidosis Succumbs to Antibiotics, implications for autoimmune disease" the excess 1,25-D actually stimulates the production of monocytes and their differentiation into macrophages, making an ideal environment for the proliferation of the Th1 intracellular bacterial pathogens. In the U.S.A. the body's Th1 and Th2 balance can now be evaluated from a simple blood draw for 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and InterLeukin 2 Receptor (IL2R) assays. All of the U.S. labs perform these tests routinely. My understanding is that in the UK the 1,25-D test has to be run through the SAS, as Manchester Infirmary is still the only testing lab. As a result there is a danger of the UK falling behind in immunology, making rapid diagnosis of the immune diseases extremely difficult. Competing interests: None declared
Re: Hormornal Balance switches from Th1 to Th2 during Pregnancy 29 July 2004
Ellen C G Grant, physician and medical gynaecologist 20 Coombe Ridings, Kingston-upon-Thames, KT2 7JU, UK Send response to journal: Re: Re: Hormornal Balance switches from Th1 to Th2 during Pregnancy	I am surprised that Trevor Marshall disagrees that cell mediated immunity is usually down regulated during pregnancy, as recent publications confirm.1,2 Elenkovi reviewed the evidence for raised levels of glucocorticoids selectively suppressing the Th1-cellular immunity axis, and inducing a shift toward Th2-mediated humoural immunity, rather than generalized immunosuppression in pregnancy. He concluded that this may affect the susceptibility to or the course of infections as well as autoimmune and atopic/allergic diseases.1 Al-Shammri and colleagues found that the immune balance in six of the eight multiple sclerosis patients studied showed a distinct shift from a Th2 cytokine bias during pregnancy towards a Th1 cytokine bias after delivery.2 Vitamin D can be measured in laboratories in London and deficiencies are common. The enzyme 1 alpha hydroxylase is a magnesium dependent enzyme and the synthesis of 1, 25-dihydroxyvitamin D may be impaired when magnesium is deficient. Zinc, copper, magnesium and selenium are important and correctable causes of unexplained infertility, failed implantation or recurrent miscarriages. Normal physiological immune responses to pregnancy can be impaired by deficiencies of essential nutrients or by infections. 1 Elenkov IJ. Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci. 2004; 1024: 138-46. 2 Al-Shammri S, Rawoot P, Azizieh F, AbuQoora A, Hanna M, Saminathan TR, Raghupathy R. Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis. J Neurol Sci. 2004; 222: 21-7. Competing interests: None declared
A Dichotomy in the Definition of Th1 and Th2 Processes 30 July 2004
Trevor G Marshall, Director Autoimmunity Research Foundation, Thousand Oaks, California 91360 Send response to journal: Re: A Dichotomy in the Definition of Th1 and Th2 Processes	If indeed " Vitamin D can be measured in laboratories in London" then why do we not have published data to confirm the statement "deficiencies are common". Please note that I am talking about the active metabolite, the secosteroid hormone 1,25-dihydroxyvitamin-D (1,25-D), and not the inactive precursors, to which I think Dr Grant is referring as "Vitamin D". Al-Shammri and colleagues measured interferon-gamma, IL-4 and IL-10 in response to stimulation by a mitogen. Since the excess 1,25-D from the placenta down-regulates interferon-gamma, I would indeed expect that cytokine to be released in smaller quantities. My observation of what happens in the Th1 diseases (Lupus and Sarcoidosis) during pregnancy is that the patients' symptoms disappear as the elevated level of 1,25-D conditions the immune system to ignore the intra-cellular pathogens. The pathogens therefore proliferate unchecked. Post partum, the patient relapses to a condition worse than that before the pregnancy, under the increased load of bacterial pathogens. So I guess it comes to a definition of what the Th1/Th2 balance really is. Dr Grant brings up a fundamental dichotomy which needs further definition and elucidation. Is a Th1 immune reaction characterized by a proliferation of phagocytic monocytes, macrophages and dendritic cells, or is it solely defined by cytokine profile? The high level of 1,25-D during pregnancy conditions the cellular proliferation, but swings the cytokine profile towards Th2. I have always accepted the former definition (that cellular proliferation, and the resulting inflammatory proliferation, is key), yet convention mandates measurement of the cytokine profile. Normally the two move in unison, but there is stark dichotomy during pregnancy and post-partum. Hmmm, an excellent point, Dr Grant... Competing interests: None declared
Depression - The Sixth Sense 14 September 2004
Erik R Johnson, n/a Incline Village 89450 Send response to journal: Re: Depression - The Sixth Sense	The Era of blaming Depression on disordered thinking is at an end. Depression is the Sixth Sense - it is a perceptual construct of relevant information about immunological dysregulation. Robert Dantzer and Keith Kelley, professors in the department of animal sciences at the University of Illinois report in Medical News Today 28 Jul 2004; "Scientists build on case connecting inflammatory disease and depression" http://www.medicalnewstoday.com/medicalnews.php?newsid=11307&nfid=rssfeeds "For the first time, we have evidence of a strong relationship between a molecular event and the development of psychopathology," Dantzer and Kelley have demonstrated that mice develope fever and display sickness related behaviors when cytokines are administered directly to the brain and that when neuronal pathways from the body to the brain are severed, cytokines do not cause "sickness behavior". People suffering from Depression have sent a clear and consistent message to psychotheorists that their "sickness behaviors" are actually due to sickness instead of the sickness arising from mental attitudes or behavioral traits. Now there is proof. Perhaps the psychotheorists can now turn their attention to analyzing their own dysfunctional behaviors and determine how people who demonstrate an obsessive preoccupation with theories of psychological causality can fail to understand these clear and simple words: "We are Depressed because we are SICK - Not sick because we are Depressed!" -Erik Johnson Competing interests: None declared
CDC News Release: Psychological Factors played no role in the development of CFS following infection 10 October 2004
Erik R Johnson, n/a Incline Village 89450 Send response to journal: Re: CDC News Release: Psychological Factors played no role in the development of CFS following infection	This press release may interest readers: October 7, 2004 American Association for Chronic Fatigue Syndrome (AACFS) Seventh International Conference on Chronic Fatigue Syndrome, Fibromyalgia and Related Disorders October 8-10,2004 Madison, Wisconsin, USA Cosponsored by the Centres for Disease Control and Prevention (CDC) and the National Centre for Infectious Diseases . CDC researcher Dr. VVilliam Reeves, Chief of the CFS research program, reported that $US 9.1 billion of earnings and wages are lost amually in the US alone due to disability caused by CFS. . CFS patients are more sick and have greater consequent disability than patients with chronic obstructive lung disease, cardiac disease, osteoarthritis and depression yet fewer than 16% of CFS sufferers in the general population are diagnosed and treated for CFS. . A CDC collaborative study with Australian researchers found that the strongest predictor of the development of post-infectious (chronic) fatigue syndrome is the severity of the acute illness at onset. Psychological factors played no role in the development of CFS following infection. . The CDC and NIH have proposed the formation of an international collaborative network cal1ed the Chronic Fatigue Syndrome Research Network (CRN) to foster collaborative, innovative and incisive research. Such a network will assist in the establishment of diagnosis and therapeutic interventions and bring help to the hundreds of thousands of CFS sufferers and their families world wide. Competing interests: None declared
Are there any randomised controlled trials?! 27 April 2005
Cherie L Haack, Junior Medical Practitioner and Chronic Fatigue Sufferer Queensland, Australia Send response to journal: Re: Are there any randomised controlled trials?!	I have begun reading Dr Marshall's work with interest. It appears that there aren't many clinical trials at this stage. Are there any large randomised, placebo controlled, double-blinded studies on the Marshall Protocol in sarcoidosis? Equally there need to be formal clinical trials for CFS (Chronic Fatigue Syndrome). I think it is correct to be concerned that an unconfirmed treatment may do harm rather than good. In particular, there is the impact of trying multiple treatments with all sorts of costs (financial, lifestyle, etc) and getting few results. I know from experience that this is wearying. It appears that Dr Marshall's work points to an exciting new method of therapy for sarcoidosis, at least. And it is a pity that the practice of medicine is always slow to realise the value of new research. However, I imagine the underlying pathophysiology of CFS is a little different to that of sarcoidosis and needs to be elucidated further. (For example, people with CFS do not develop clinically obvious granulomas, as in sarcoidosis). Compare, for example, the underlying pathophysiolgy of toxity due to excess vitamin D ingestion (I mean the precursor) in an otherwise healthy person, with the pathophysiology of sarcoidosis as elucidated by Dr Marshall. The treatment is very different. In Dr Marshall's paper (A Review - Vitamin D and Calcium in Sarcoidosis, Trevor G Marshall, PhD, 5 July 2003,http://www.sarcinfo.com/calcium.htm), he demonstrates the importance of guiding therapy by a correct (and complete) understanding of the pathophysiology. However, in the absence of this understanding, correctly conducted clinical trials often appear to suffice. What further steps are being taken to understand how this new understanding of immune function applies to CFS? This line of research may be very fruitful. Competing interests: None declared
Patient Experiences with Marshall Protocol: Dangerous 22 June 2005
Ken Lassesen, Consultant Kingston, WA 98346 Send response to journal: Re: Patient Experiences with Marshall Protocol: Dangerous	A recent internet survey of people[36] with CFIDS and FM who has tried the Marshall Protocol found: 31% with any improvement (lowest of all protocols) 14% no change 56% with loss (highest of all protocols) The numbers are statistically significant. Summary Raw Numbers This volunter survey of the popular treatment protocols was conducted on the largest CFIDS group on Yahoo (thus one patient, one vote). The two protocols that had the best chances of improvement and the least chance of adverse effects are protocols that used minerals and supplements (including vitamin D -- up to 4000 IU/day). Interestingly, those supplementing with Vitamin D frequently report a significant increase of body temperature (normally CFIDS patients are below normal, as low as 96F in rare cases). Note: I am a moderator of the CFSFMExperimental and a fully recovered former CFIDS patient. I working more than usual hours in my profession for one of the world's premiere companies. Competing interests: None declared