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PAPERS:
Matthew Hotopf, Anthony S David, Lisa Hull, Vasilis Nikalaou, Catherine Unwin, and Simon Wessely
Gulf war illness—better, worse, or just the same? A cohort study
BMJ 2003; 327: 1370 [Abstract] [Full text]
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[Read Rapid Response] Come off it -face the truth!
Malcolm Hooper   (15 December 2003)
[Read Rapid Response] The authors respond to Hooper
Matthew Hotopf, Anthony David, and Simon Wessely   (6 January 2004)

Come off it -face the truth! 15 December 2003
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Malcolm Hooper,
Emeritus Professor of Medicinal Chemistry University of Sunderland, Chief Scientific Advisor GWVs
2,Nursery Close, Sunderland SR3 1PA

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Re: Come off it -face the truth!

Come off it- face the truth! Gulf war illness- better,worse or just the same?[1] is still another unconvincing paper that is both tedious and predictable in its very limited and bland conclusions. This is yet another study funded by the Department of Defence (DOD) in America which involves postal questionnaires followed by statistical analysis – medicine at arm’s length - seeking to justify the, now discredited, attempt to associate Gulf War Syndrome, GWS, with fatigue and common mental disorders. GWS has been acknowledged and substantiated by the work of Haley [2,3] and his analysis confirmed by Khang et al of the Department of Veterans’ Affairs in the States-“there is a cluster of symptoms unique to Gulf War Veterans which could be defined as a new Gulf War syndrome”[4,5]. Steele [6,7] describes, “a unique pattern of symptoms that constitute a GWS”.

Haley identified three sub-syndromes, syndromes 1, fatigue and depression (awakened tired and worn out, concentration and memory problems, excessive fatigue, fatigue more than 24 hours after exertion, feeling anxious, irritable, or upset, feeling depressed “blue”, sleep difficulty, sleepiness during day); syndrome, 2, confusion-ataxia ( blurred vision,concentration and memory problems, irregular heartbeat, loss of balance dizziness and vertigo, speech difficulty, sudden loss of strength, tremor and shaking); syndrome 3 arthro-myo-neuropathy ( back spain and spasms, generalised muscle aches, joint aches, numbness in hands/feet, swelling in hjoints, swelling in extremities). The risks of such syndromes were associated with various exposures, Syndrome 1-(flea collars (pesticides), working in security, younger veterans); Syndrome 2 (reporting a likely chemical weapon attack, adverse reactions to pyridostigmine bromide, being near Khafji on Jan 20th 1991, older veterans); using government issue DEET containing 75% DEET, adverse reactions to PB [2,8,9]. Haley et al went on to demonstrate extensive neurological damage in sick Gulf veterans [8,10,11,12] damage to the basal ganglia (Syndrome 1) or the brain stem (syndrome 3 especially the pons area) or both sites (Syndrome 2). The latter is the most serious and debilitating syndrome. This damage to the central nervous system is consistent with the major symptoms reported by Gulf War Veterans, GWVs, and associated with the early damage and symptoms found in Parkinson’s disease [11,12,13]. Haley’s magnetic resonance study and its conclusions have been replicated by other scientists [14]. The prevalence of motor neurone disease, MND, has been found to be double the expected levels [15] and, in particular, to exceed the expected levels for those under 45 years old suggesting a war-related environmental trigger[16]. This further implicates known neurotoxins such as pesticides, nerve agents, oil and smoke and depleted uranium. Although the American administration has promptly and generously responded to this information the MOD, to its shame, has refused to deal in the same way with UK GWVs where there is a similar incidence according to figures available from the Gulf Veterans organisations [17]. The figures appear to be rising [13].

In his country Mackness and colleagues[18,19] have shown in two studies that there are significant reductions in the levels of serum paraoxonase in all, GWVs, whether classed as sick or well [19]. Such deficits point to an increased susceptibility to atherosclerosis and, diabetes and other diseases and disorders [20]. Similar findings emerged from a study of organophosphate, OP, farmers [21] and are consistent with the widespread and significant exposures of GWVs to both pesticides and nerve agents. Compston et al, have found reduced bone density (osteoporosis) in both GWVs [22] and OP poisoned farmers [23] in the UK yet another link between major chronic poisoning and illness. Osteoporosis may therefore arise from either exposure to multiple vaccines that give rise to an autoimmune induced osteoporosis [24] and/or from OP poisoning [23] which affects the acetylcholinesterase that plays an important role in bone metabolism. Autoimmune responses also include an autoimmune induced atherosclerosis[25]. Two possible mechanisms known to induce atherosclerosis are autoimmune disease and organophosphate poisoning.

The effects of OPs are known to be amplified by synergism between OPs and pyrethroids, DEET and other pesticides [26]. The immune system suffers extensive damage from OP exposure [27] and autoantibodies to neuronal filament proteins have been identified in OP poisoned individuals [28]

A recent inquest on a GWV concluded with the coroner’s verdict that although death was due to natural causes (heart attack) in which atherosclerosis played a major part exposures in the Gulf War 1991 had contributed to the cause of death. The testimony given at the inquest included a description of the veteran’s medical condition as global illness syndrome- every major system in the body had been damaged [29] and contributed to his death. Somewhat earlier an inquest on an organophosphate poisoned farmer [30] resulted in an open verdict in which her medical condition was described as multiple system atrophy, a condition linked to Parkinsonism [31].

The real question on GWS is how long will the Department of Defence in American and the MOD in the UK persist in obfuscation, deception and denial before admitting that the toxic exposures in the Gulf are responsible for GWS and compensate and support all those veterans and their families who have become so ill simply for laying down their lives for their country and its citizens. The attempt to label GWVs as mentally ill and fatigued and the derisory offer of graded exercise therapy and cognitive behavioural therapy as an effective treatment for their illnesses is no longer sustainable- a fact increasingly recognised in the USA but belligerently resisted by the MOD and UK Government with its “tin ear, cold heart, and closed mind”, Burton 1997 [32]- a charge acknowledged in the letter from Leo S Mackay the Deputy Secretary Department of Veterans’ Affairs when responding to the research report [7], October 28th 2002. .

References

1. Hotopf M, David AS, Hull L, Nikalaou V, Unwin C, Wessely S. Gulf wat illness- better, worse, or jjust the same? Acohort study. BMJ 2003;327:1370-2.

2. Haley, R.W., Thomas, L.K., Horn, J. Is there a Gulf War Syndrome: Searching for Syndromes by Factor Analysis of Symptoms. JAMA 1997, 277, 215-222.

3. 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.

4. Kang H, Mahan C, Lee KY, Murphy FM, Simmens S, Young H, Levine P. Unique Cluster of Symptoms Among Gulf War Veterans which could be defined as a new Gulf War Syndrome. Poster presentation at a Conference on Federally Sponsored Gulf War Veterans’ Illnesses Research, June 23-25, 1999. Pentagon City.

5. Kang HK, Mahan CM, Murphy FM, Simmens SJ, Young HA , Levine PH. Evidence for a deployment–related Gulf War syndrome by factor analysis. Arch Environ Health 2002;57:61-8. The time elapsing between the appearance of the final paper and the initial conference presentation is indicative of the unwillingness of the DOD NA D Deparatment of Veterans’ Affairs to let go of the attemtpto deny any unique GWS.

6. 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.

7. Steele L. Research Advisory Committee Interim Report 2002 June 25th 2002 submitted to Anthony Principi , Secretary of Veterans’ Affairs. This report contains useful summaries of the work of Lea Steele (epidemiology), Robert Haley (clinical and advanced studies) and Beatrice Golomb (pyrdostigmine bromide).

8. Haley, R.W., Kurt, T.L. Self-reported Exposure to Neurotoxic chemical Combinations in the gulf War: A Cross-sectional Epidemiologic Study. JAMA 1997;277:231-237.

9. A useful summary is available at the Southwestern Medical Site. Gulf War Syndromes. http://www.swmed.edu/newsgwschart.htm downloaded 11 September 19998.

10. Haley, R.W., Horn, J., Roland, P.S., Wilson, W.B., Van ness, P.C., Bonte, F.J., Devous, M.D., Matthews, D., Fleckenstein, J.L., Wians, F.H., Wolfe, G.I., Kurt, T.L. Evaluation of Neurologic Function in Gulf War Veterans. JAMA 1997;277:223-230.

11. Haley RW, Fleckenstein JL, Marshall WW, McDonald GG, Kramer GL, Petty F. Effect of basal ganglia injury on central dopamine activity in Gulf war syndrome. Arch Neurol. 2000;57:1281-5.

12. 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

13. Haley RW. Gulf War Syndrome. A lecture given in the House of Lords, 19th June 2002.

14. Meyerhoff DJ, Lindgren J, Hardin D, Griffis JM, Weiner MW. Reduced N- acetylaspartate in the right basal ganglia of ill Gulf War veterans by magnetic resonance spectroscopy. Proceedings of the International Society of Magnetic Resonance Medicine 2001;9:994.

15. Horner RD, Kamin KG, Feusssner JR, Grambow SC, Hoff-Lindquist J, Harati Y et al. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neeurology 2003;61:42-9.

16. Haley RW. Excess incidence of ALS in young Gulf War veterans. Neurology 2003;61:750-6.

17. Cammock L. Gulf Veterans Association reports 9 cases of ALS. The 4 who have died have been recorded by the MOD but not the living ones. The USA study identified 40 cases in 700,000. The 9 in the 53,000 UK GWVs would equate to a higher incidence. No study has been commissioned to my knowledge.

18. 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.

19. Hotopf M, Mackness IM, Nikolaou V, Collier D, Curtis C, David A, Durrington P, Hull L, Ismail K, Peakman M, Unwin C, Wessely S, Mackness B. Paraoxonase in Persian Gulf War Veterans. J Occup Environ Med 2003;45:668- 675.

20. Mackness B, Durrington P, Mackness MJ. Human Serum Paraoxonase. Gen Pharmac 1998;31:3329-336.

21. Paraoxonase and the susceptibility to organophosphate poisoning in farmers dipping sheep. Mackness B, Durrington P, Povey A, Thomson S, Dippnall M, Mackness M, Smith T, Cherry N. Pharacogenetics 2003;13:81-8.

22. Compston JE, Vedi S, Stephen AB, Bord S, Lyons AR, Hodges SJ, Scammell BE. Reduced bone formation in UK Glf War veterans: a bone histomorphometric study. J Clin Pathol 2002;56:897 -9.

23. Compston JE, Vedi S, Stephen AB, Bord S, Lyons AR, Hodges SJ, Scammell BE. Reduced bone formation after exposure to organophosphates. Lancet 1999;354:1791-2.

24. Report on Alex Izet –a vaccine damaged GWV who was not deployed to the Gulf.

25. Harats JG, Shoenfeld Y. Autoimmunity as an additional risk factor for atherosclerosis- a report. American Autoimmune Related Disease Association, AARDA, available at http://www.aarda.org/research/research_display.php?ID=11.

Autoimmune diseases and vaccination. An impressive list of the extensive effects of vaccines by this mechanism with summaries of some useful references is available at http://www.whale.to/vaccines/autoimmune1.htm

26. Abou-Donia, M.B., Wilmarth, K.R., Jensen, K.F., Oehme, F.W., Kurt, T.L. Neurotoxicity Resulting from coexposure to pyridostigmine Bromide, DEET, and Permethrin: Implications of Gulf War Chemical Exposures. J. Toxicol. environ.Health 1996, 48, 35-56.and numerous papers since.

27. Repetto R, Baliga S. Pesticides and immunosuppression: The risks to public health. Health Policy and Planning 1997;12:97-106.

28. Abou-Donia MB, Garretson LK. Detection of neurofilament autoantibodies in human serum following chemically induced neurologic disorder. Environ Epidemiol Toxicol 2000;2:37-41.

29. Inquest on Major Ian Hill, Coroner’s Court, Warrington, November 24th 2003.

30. Inquest on Mrs K Sunderland, Coroner’s Court, Honiton, Devon, November 7th 2003.

31. Wenning GK, Quinn NP. Parkinsonism.. Multiple system atrophy. Baillieres Clin Neurol 1997;6:187-204.

32. Burton, D. 2nd Report by the Committee on Government Reform and Oversight, Union Calendar No. 228. 105th Congress, 1st Session House Report 105-338, November 1997.

Competing interests: None declared
The authors respond to Hooper 6 January 2004
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Matthew Hotopf,
reader
Gulf War Illnesses Research Unit, Department of Psychological Medicine, Guy's, King's, and St Thomas,
Anthony David, and Simon Wessely

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Re: The authors respond to Hooper

Ours is the first paper on the natural history of Gulf War illness, and it is difficult to understand why an academic of Hooper’s stature should not see the importance of describing the continued effect of service in the 1990-91 Gulf War on the health of veterans. It is hard to see how our findings could have been more helpful to the cause of Gulf War veterans seeking recognition for their plight.

Hooper’s wider analysis is contradictory. He refers to our research, based on questionnaires, as “medicine at arms length”, before citing Dr Haley’s work favourably, much of which is also based on questionnaires (albeit with smaller sample sizes, lower response rates and no control groups) (1). He suggests we have attempted “to associate Gulf War Syndrome, with fatigue and common mental disorders”, when we have demonstrated in the BMJ that common mental disorders, whilst increased in Gulf war veterans, cannot be an explanation for Gulf War illness (2). One of the papers on paraoxonase cited favourably by Hooper is by our group in collaboration with Mackness and colleagues (3). Hooper mentions multiple vaccination – but fails to mention that ours was the first study to demonstrate a link between mulitple vaccines and illness (4).

If one truth has to be faced, it is that Gulf War illness is complex, and sufferers are not helped by simplistic solutions or selective citation of the literature.

Reference List

1. Haley RW, Kurt TL, Hom J. Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of symptoms.[comment][erratum appears in JAMA 1997 Aug 6;278(5):388]. JAMA 1997;277(3):215-22.

2. Ismail K, Kent K, Brugha T, Hotopf M, Hull L, Seed P et al. The mental health of UK Gulf war veterans: phase 2 of a two phase cohort study. Br.Med.J. 2002;325(7364):576.

3. Hotopf M, Mackness MI, Nikalaou V, Collier DA, Curtis C, David A et al. Paraoxonase in Persian Gulf War Veterans. Journal of Occupational and Environmental Medicine 2003;45:668-75.

4. Unwin C, Blatchley N, Coker W, Ferry S, Hotopf M, Hull L et al. Health of UK servicemen who served in the Persian Gulf War. Lancet 1999;353:169-78.

Competing interests: None declared