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Engage with the all the evidence on gulf war syndrome
- Malcolm Hooper (15 September 2002)
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Toss a coin or adjust the facts?
- Gurli Bagnall (15 September 2002)
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Qualitative research may bridge the quantitative Gulf
- Andrew J Ashworth (15 September 2002)
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Gulf War Syndrome ? a Learned Response.
- Robert L Miller, On my own!! (19 September 2002)
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Malcolm Hooper, Emeritus Professor of Medicinal Chemistry University of Sunderland
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This paper1 confirms that Gulf War Veterans, GWVs, are not suffering excessively from post traumatic stress disorder or any formal psychiatric disorder. It then retreats into the psychiatric thicket of somatization as a possible explanation of Gulf War Syndrome/Illness, GWS/I. The enigmatic and oft repeated claim, by Professor Wessely, that GWS/I is “neither psychiatric nor physical but somewhere is between” was scathingly rejected together with somatization and stress theories of GWS/I, by a panel of USA Congressmen, at a Washington Hearing, Jan 24th, 2002 and at a continuation of the hearing in the House of Commons and House of Lords, June 18-19th, 2002. Swathes of evidence have been ignored by Ismail et al. Peer-reviewed research and documents from major hearings in the UK and the USA show that the major biological and chemical toxins to which our troops were exposed cause significant organic illnesses that are consistent with the symptoms described by the Gulf War Veterans, GWVs. Professor Wessely and his group2 have shown that in the UK vaccines (too many, wrongly administered, and experimental) were associated with the symptoms described by GWVs. This was confirmed by Cherry et al3 4 who also showed an association with pesticides. The papers by Cherry et al also suggest that, oil and smoke, and pyridostigmine bromide (used as investigational new drug, IND) have some association with the major symptoms of the GWVs. Steele5 in the States, in an important epidemiological study, has shown that GWS/I is both location and time dependent (some 45% of troops who were furthest forward and stayed longest, until June 1991, have succumbed to GWS/I). The proportion of GWVs with GWS/I reaches 12% in groups that were vaccinated for service in the Gulf but not deployed, compared with 3% of the control group. Haley and his co-workers using a classical epidemiological approach formulated a case definition for GWS6-8 (something lacking from all UK studies) and followed this with intensive and extensive clinical studies. They have shown conclusively that there is extensive neurological damage that can be identified by established clinical tests7 9 and, using magnetic resonance spectroscopy10, that there are biochemical deficits in the deep brain centres, especially, the thalamus, brainstem and basal ganglia. These deficits are consistent with the symptoms experienced by many GWVs and are found in the very early stages of diseases such as Parkinsonism and Huntingdon’s chorea11. Haley et al see this as a result of exposure to low levels of the nerve agent sarin, an irreversible inhibitor of acetylcholinesterase. Until recently the unanimous statement from the military and government in both the UK and the USA was that no nerve agents had been released on the battlefield and that the alarms that had sounded repeatedly (14,000 alarms going off on average 2-3 times per day) were all false12 13. The USA now concedes that some exposure occurred but attributes this mainly to the demolition of storage dumps after the war, such as Khamisiyah12. However, numerous eye witness statements describe alarms sounding from the first day of the air campaign14 15, when suspected storage depots and production units for chemical weapons were bombed in preparation for the ground war. Organophosphate pesticides and pyridostigmine bromide also act on acetylcholinesterase providing a potent ‘triple whammy’ on this key component of the peripheral, central and autonomic nervous systems13. Some of Haley’s work has now been replicated by scientists and clinicians working for the DoD but, strangely, not yet published in the peer-reviewed literature16. A detailed statistical study by Haley et al provides strong evidence of a single GWS17. In this country Jamal18 19 has published clinical studies that agree with Haley’s work and Mackness et al20 have shown that there is a 50% reduction of paraoxonase in GWVs compared to controls. Paraoxonase is a major detoxifying enzyme for the organophosphates and their analogues used respectively as pesticides and nerve agents and protects against various illnesses, particularly, cardiovascular disease21 and diabetes22. Wessely and his co-workers have also found immunological deficits consistent with the Rook-Zumla hypothesis23. Internal contamination of GWVs by depleted uranium, DU, dust has now been demonstrated some 8-10 years after the Gulf War24. The cumulative radiological dose to tissues where the insoluble and largely immobilised materials reside cannot be accommodated by the present models used to estimate health risks from internal alpha radiation25 26. Radiation damage to blood and the lymphatic system, bone, lungs and the central nervous system are well known27. Motor neurone disease, MND, has been found to occur in USA veterans at twice the prevalence in a control group and clinical and welfare payments authorised before the final paper has been published28. In the UK initial data29 suggests that the rate is four times that in the general population but without any positive response from the MoD. There is growing evidence that lymphatic leukaemia30 and renal cancer rates31 among UK veterans are 10-20 fold higher than in the general population, the only comparison that is available. Not only are the disputed MUPS (multiple unexplained physical symptoms), PUPS (persistent unexplained physical symptoms) and SSIDCs (signs and symptoms of ill-defined conditions) significantly increased in GWVs but also major undisputed illnesses. I find it disturbing that this paper has been peer-reviewed and published without any demand for all this important information to be considered thus allowing a fanciful and insecurely based psychiatric construction with a poor ‘track record’13 to be given the tacit support of the BMJ. References 1 Ismail K, Davies K, Brugha T, David A, Hotopf M, Hull L, Palmer I, Reid S, Unwin C, Wessely S. Do psychiatric disorders explain ill health in United Kingdom Gulf veterans. BMJ 2002;325:576-9. 2 Unwin, C., Blatchley, N., Coker, W., Ferry, S., Hotopf, M., Hull, L., Ismail, K., Palmer, I., David, A., Wessley, S. Health of UK servicemen who served in the Persian Gulf War. Lancet, 1999;353:169-178. 3 Cherry N, Creed F, Silman A, et al. Health and exposures of United Kingdom Gulf war veterans. Pt I: the pattern and extent of ill health. Occup Environ Med 2000;58:291-298. 4 Cherry N, Creed F, Silman A, Dunn et al. Health and exposures of United Kingdom Gulf war veterans. Pt II: The relation of health to exposure. Occup Environ Med 2000;58:299-306. 5 Steele L Prevalence and patterns of Gulf war illness in Kansas veterans: association of symptoms with characteristics of person, place, and time of military service. Am J Epidemiol. 2000;152:992-1002. Ibid idem 2001;154:406-7. 6 Haley RW, Kurt TL, Hom J. Is there a Gulf War syndrome? Searching for syndromes by factor analysis of symptoms. Journal of the American Medical Association 1997;277:215-222. 7 Haley RW, Hom J, Roland PS, Bryan WW, Van Ness PC, Bonte FJ, Devous MD, Mathews D, Fleckenstein JL, Wians FH, Wolfe GI, Kurt TL. Evaluation of neurologic function in Gulf War veterans: a blinded case-control study. Journal of the American Medical Association 1997;277:223-230. 8 Haley RW, Kurt TL. Self-reported exposure to neurotoxic chemical combinations in the Gulf War: a cross-sectional epidemiologic study. Journal of the American Medical Association 1997;277:231-237. 9 Roland PS, Haley RW,Yellin W, Owens K. Vestibular dysfunction in Gulf War syndrome. Otolaryngology--Head and Neck Surgery 2000;122:319-329. 10 Haley RW, Fleckenstein, JL, Bonte FJ, Devous MD, Marshall WW, McDonald, GG, Petty, F. Brain Abnormalities in Gulf War Syndrome: Evaluation with 1H MR Spectroscopy. Radiology 2000;215:807-817 and references cited therein. 11 Haley RW. Gulf War Syndrome:Eight Years of Research on the Nature of the Disease and Its Causes. Testimony given in the House of Lords, June 19th 2002. 12 2nd Report by the Committee on Government Reform and Oversight, Chairman Burton D. Union Calendar No. 228. 105th Congress, 1st Session House Report 105-338, November 1997. 13 Hooper M. The Most Toxic War in Western Military History. Evidence submitted to the House of Commons Select Defence Committee, December 1999. Published in 7th Report of Defence Select Committee. Gulf Veterans' Illnesses. Report and proceedings of the Committee with Minutes of Evidence and Appendices, April 19th 2000. 14 Johnson A. Gulf War Syndrome:Legacy of a Perfect War. MCS Information Exchange, Brunswick, Maine, USA, 2001. 15 Thomas W. Bringing the War Home, Earthpulse Press, Anchorage, 1998. 16 Feussner JR, written testimony to US House of Representatives Committee on Government Reform. Subcommittee on National Security, Veterans Affairs and International Relations, Chairman Christopher Shay, Rayburn House, January 24th 2002. 17 Haley RW, Luk GD, Petty F. Use of structural equation modeling to test the construct validity of a case definition of Gulf War syndrome: Invariance over developmental and validation samples, service branches and publicity. Psychiatry Research 2001;102:175-200. 18 Jamal GA, Hansen S, Apartopoulos F, Peden A. The "Gulf War syndrome". Is there evidence of dysfunction in the nervous system. J Neurology Neurosurgery and Psychiatry 1996;60:449-450. 19 Jamal, G.A. Gulf War Syndrome-a model for the complexity of biological and environmental interaction with human health. Adverse Drug React. Toxicol. Rev. 1998;17:1-17. 20 Mackness B, Durrington PN, Mackness MI. Low paraoxonase in Persian Gulf War Veterans Self-Reporting Gulf War Syndrome. Biochem Biophys Res Comm 2000, 276, 729-733. 21 Mackness MI, Mackness B, Durrington PN, Fogelman AM, Berliner J, Lusis AJ, Navab M, Shih D, Fonarow GC. Paraoxonase and Coronary Heart Disease. Current Opinion in Lipidology 1998,9, 319-3234. 22 Mackness B, Mackness MI, Arrol S, Turkie W, Julier K, Abuasha B, Miller JE, Boulton AJM, Durrington PN. Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus. Atherosclerosis 1998, 139, 341-349. 23 Rook, G. and Zumla, A. Gulf War Syndrome: is it due to a systemic shift in cytokine balance towards a Th2 Profile? Lancet 1997;349:1831-33. 24 Durakovic A, Horan P, Dietz L. The Quantitative Analysis of Depleted Uranium Isotopes in British, Canadian and U.S. Gulf War Veterans. Military Medicine 2002;167:620-627. 25 Busby C. Science on Trial: On the Biological Effects and Health Risks following Exposure to Aerosols produced by the use of Depleted Uranium Weapons. Submisison to the Royal Society Working Group, 2000- available at www.llrc.org/ 26 Busby C. Wings of Death, Green Audit Books, Aberystwyth, 1995. 27 Durakoviae A. Medical effects of internal contamination with uranium. Croatian Med J 1999;40:49-66. 28 Charatan F. US links motor neurone disease with Gulf war service. BMJ 2002;324:65. 29 Nine cases are known to the Gulf Veterans Association of which four have died. 30 Five cases have been identified among the 2,500 members of the National Gulf Veterans and Families Association. 31 Lee H. reported to meeting between Ministry of Defence, MAP and NGV&FA St Christopher’s House, Southwark Street, London, 9th January 2002. |
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Gurli Bagnall, Patients' Rights Campaigner
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Phase 1 of this 2 part study, was published in the BMJ, 1 September, 2001. I quote from the subsequent and unsolicited e/mail correspondence that I had with Professor Wessely in November of that year. S.W. “honestly, how can I tackle….. ‘the fact that his theory revolves around attacking the character, integrity and intelligence of people’…., other than saying, “oh no it doesn’t.” G.B. “….This study required the co-operation and good faith of a large number of GW veterans who filled out your questionnaire. What a shock it would be for them if they knew that your considered opinion was that ‘Those who believed they had Gulf War Syndrome were more likely to be of lower rank…. and were less well educated…” and then (by golly!) ‘We adjusted for confounding factors that had the potential to distort the results - such as education, rank….’ Does this not come under the heading of manipulating the facts to fit a pre-determined outcome? “And you tell me that you don’t make diagnoses of psychiatric disturbance by attacking character, integrity and intelligence?” In Phase 2, I note that Professor Wessely et al have again been busy with their little mallets, hammering the persistent square pegs into the desired round hole. In this section, education was not raised, but the authors adjusted for “potential confounding by age, sex, rank and marital status”. Despite a great deal of criticism, the point has still not been taken. A broken leg is a broken leg, irrespective of age, sex, rank, marital status, income or education. Disabled Gulf War veterans are sometimes diagnosed with ME -or as Wessely prefers, CFS. As in other aspects of poorly understood neurological conditions, Wessely’s subjective opinion waxes and wanes. In 1998, he said this of ME: “Ten years ago, the illness was seen as a…. mysterious virus that remained hidden in the body, with a preference for infecting active, middle class professionals.” 1 The previous year, he stated: “CFS patients seen in specialist clinics commonly show characteristic type A personality traits, such as perfectionism and over- achievement.” 2 In the aforementioned correspondence, the following was Wessely’s response to my challenge that those in the lower ranks with minimal education, were predisposed to GWS. “You are twice as likely to develop cancer or heart attack if you are in a lower social class compared to an upper - each year of education reduces your risk of either outcome. We have already shown that CFS, yes, CFS, is commoner in lower socio economic groups…..and that is not surprising, indeed the only disease I know that is not commoner in lower social class is breast cancer, because of the confounding effect of childbirth.” Apart from the contradictory mental image I had of busy, stressed- out CEOs dropping dead with heart attacks, whatever happened to the Type A over-achievers, and the active middle class professionals? It is interesting, however, that he compares ME/CFS - which he persistently categorizes as a psychiatric disorder - with cancer and heart disease. A Freudian slip, perhaps? Professor Wessely might like to toss a coin so that we can have definite answers to these vexing issues. “Sickness is no longer a personal matter: it has become social, political, bureaucratic” said Ziauddin Sardar. He went on to say, “All the actors involved in this drama have their own perspectives….[such as] the government with avoiding paying compensation at all costs. So one would expect the Ministry of Defence to deny the existence of Gulf War Syndrome and it does, operating on the simple basis of ‘no bug, no dosh”. 3 Two years before this, Matthew Norman wrote: “We are intrigued to note that the Ministry of Defence has endorsed the Gulf War Syndrome research programme….of Dr. Simon Wessely. “Dr. Wessely’s last foray into the public eye came last year, when he was associated with the controversial report dismissing ME as having no physical basis. He has since been forced to change his mind on that one.” [And has since then, changed his mind back again!] “Let us hope he makes no similar mistake about Gulf War Syndrome being a malingerer’s charter.” 4 These references to the MoD are interesting because both studies were funded by the US Department of Defence, and in both cases, no competing interests were declared. I guess the eagle eye of the BMJ missed that. Twice. Gurli Bagnall, Patients’ Rights Campaigner, New Zealand. References 1 Simon Wessely: New Statesman 30 January, 1998. pp 32-33 2 Anthony J. Cleare, Simon C. Wessely: Update 20 May 1998: 1016-1026 3 New Statesman, 5 February, 1999. 4 The Guardian, 6 March 1997, page 15. |
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Andrew J Ashworth, Hospital Practioner Community Alcohol & Drug Service, Forth Valley Primary Care NHS Trust, Stirling FK7 8AH
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Just as quantitative conclusions cannot be drawn from qualitative studies, the reverse is also true. Ismail et al’s quantitative approach (1) claims to tell us what Gulf War Syndrome isn’t, based on the current method of classifying illnesses, but it takes us no further towards developing an understanding of what it is that causes Gulf War veterans to report sick more often than controls. If we miss the diagnosis, we may miss the cure. A qualitative study might start by exploring some of the symptoms reported in the study (eg low mood, sleep disorder) and exploring other symptoms that might be present and have not previously been associated with Gulf War service. I have, by this simple qualitative “listening” approach already described (2) a mild Parkinsonian syndrome in opiate misusers, the putative mechanism for addiction being a behavioural change to increase dopamine secretion by opiate mu stimulation in patients whose dopamine system is compromised by increased endogenous Dynorphin (an opiate kappa agonist) secretion that acts as a presynaptic inhibitor of dopamine release (3) (4). Since Dynorphin appears to be an endogenous chronic “painkiller” released in association with prolonged mu stimulation (5), it is possible that prolonged stress (such as that experienced by combatants) may lead to increased Dynorphin activity at a level that creates low mood & insomnia (as described by Ismail et al)as well as ammoniacal perspiration, anorexia, reduced libido and physical weakness and is associated with abnormal glabellar tap test, cogwheel rigidity, tremor and reduced grip strength. On the basis that reducing mu stimulation would lead to increased efficacy of presynaptic inhibition of dopamine release, these symptoms would be expected to occur when the individual’s lifestyle had become less exciting (for example after leaving the theatre of combat). It is becoming clear that modern armies are not best suited to modern wars such as those on drugs and terrorism; modern science, with its quantitative bias is similarly leading to impasse in the field of discovery. It is all very well for quantitative scientists to ensure we civilise new lands of knowledge, but it first takes qualitative “explorers” to discover those new lands to civilise. 1 Khalida Ismail, Kate Kent, Traolach Brugha, Matthew Hotopf, Lisa Hull, Paul Seed, Ian Palmer, Steve Reid, Catherine Unwin, Anthony S David, and Simon Wessely; The mental health of UK Gulf war veterans: phase 2 of a two phase cohort study BMJ 2002; 325: 576 2 Ashworth AJ. Suicidal risk may also have physical signs bmj.com/cgi/eletters/ 3 Smith JA. Loughlin SE. Leslie FM. Kappa-Opioid inhibition of [3H]dopamine release from rat ventral mesencephalic dissociated cell cultures. Molecular Pharmacology. 42(4):575-83, 1992 Oct. 4 Gauchy C. Desban M. Krebs MO. Glowinski J. Kemel ML. Role of dynorphin-containing neurons in the presynaptic inhibitory control of the acetylcholine-evoked release of dopamine in the striosomes and the matrix of the cat caudate nucleus.Neuroscience. 41(2-3):449-58, 1991. 5 Wan XW. Li WH. Huang M. You ZD. Tan YX. Lu CL. Gong ZH. Levels of immunoreactive dynorphin A1-13 during development of morphine dependence in rats. |
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Robert L Miller, GP Principal 222 Woodstock Road, Belfast BT6 9DL, On my own!!
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Dear Sir, The tone of the response to this article on "Gulf War Syndrome" is quite striking. It is clear from the tone of the letters and the quantity of citations quoted that this is a topic which arouses intense interest and emotion in some people such as the correspondants involved. Like most GPs who have to spread themselves thinly across all of the ills which can afflict mankind, I have some personal contact with sufferers of GWS but not to an extent which would encourage me to believe that I had learnt all about it. And yet. There is no general agreement, despite many "false dawns" that any infective or toxic agent has been discovered to cause GWS or indeed CFS or ME. (Some of your correspondants seem to lump them together). I have heard Simon Wessley deliver papers on CFS and was impressed by the fact that he did not claim to know the cause. I was also impressed to find that he felt threatened by those who claimed to know what the cause was, toxic or infective. He was able to show that the media was involved in some way in the development of outbreaks of this condition (CFS or ME). Perhaps your correspondants are correct in lumping all of these conditions together. Many clinicians (and patients) would claim that fibromyalgia might also be included in the group. Apart from the lack of agreed external causation, these conditions are characterised by belief or unbelief. New patients have never asked me if I believed in cancer or diabetes. However some have asked me if I believed in ME and I suspect other doctors have had similar experiences. While listening to Simon Wessely it occurred to me that the syndrome(s) he was describing could be explained if catching these conditions was a learned response such as experienced in religious conversion. It/they are certainly coherent systems of thinking, feeling and behaving akin to becoming a communist or a buddhist. This would imply that cure might involve elements of treatment found helpful in producing re-conversion though this is not always felt to be appropriate or desirable. Many with ME and their supporters wish to claim scientific respectability for the condition. A scientific hypothesis should by definition, according to Karl Popper, be capable of disproof. I wite only to suggest that my hypothesis might well be capable of disproof in some ingenious scientific experiment. But I wont be the one to do it. I'm only a GP! Lewis Miller. |
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