Role of Chem/Biol/DU Exp.- GWI (2)

[Henk Vreekamp]

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[CONT.]
> Veterans with transmittable biological exposures could have received these
>through natural contact (soil, water, etc.) or from other types of
>exposures.[15]  Infectious agents have been found in GWI patients' urine [6]
>and blood.[7, 22, 23]  Using a microscopic technique for determining
>bacterial infections in urine, Hyman [25] has found evidence of bacterial
>infections in GWI patients that can be successfully treated with several
>courses of broad spectrum antibiotics.  We found that most of the signs and
>symptoms in subsets of GWI patients can be explained by chronic pathogenic
>bacterial infections, such as mycoplasmal infections.[7, 15, 22, 23]
>Mycoplasmal infections usually produce relatively benign diseases limited to
>particular tissue sites or organs, such as urinary tract or respiratory
>infections.[26]  However, the types of mycoplasmas that we have detected in
>ODS veterans, such as Mycoplasma fermentans, are very pathogenic, colonize a
>variety of organs and tissues, and are difficult to treat.[16, 17]  In
>studies of over 300 patients, including both U.S. and British veterans with
>GWI and their symptomatic family members, evidence of mycoplasmal infections
>has been found in just under one-half of the GWI patients' blood.[22, 23, 27,
>28]  The incidence of mycoplasmal infections in
> nondeployed, healthy subjects was found to be approximately 6-9% (reviewed
>in 28).  The appearance of mycoplasmas in the leukocytes of some controls
>could indicate that these individuals are in a very early stage of the
>illness or that they are nonsymptomatic carriers of the infection.
>
> Since the subgroup of mycoplasma-positive patients may be more symptomatic
>than the average GWI patient, it is likely that the final incidence of
>mycoplasmal infections in GWI will be lower than the incidence rate reported
>above.[28]  Over 80% of mycoplasma-positive GWI patients had Mycoplasma
>fermentans infections, and this has now been confirmed in a large VA study.
>Interestingly, when civilian patients with CSF/ME or FMS were examined for
>systemic mycoplasmal infections, high frequencies of mycoplasmal infections
>were also found (approximately 60%), indicating another link between these
>disorders, but in addition to M. fermentans several other species of
>mycoplasmas were found in CSF/ME and FMS.[27-29]  The types of assays
>performed in these studies were molecular tests of active infections, using
>polymerase chain reaction [26-29], and not antibody tests [11], because the
>latter do not usually detect intracellular mycoplasmas that do not elicit a
>strong antibody response.[7, 26]  The presence of mycoplasmal infections
>could also explain the recent observation of activation of the coagulation
>system in GWI patients [30], since mycoplasmal infections can cause these
>changes.
>
> Other chronic infections have also been found in GWI patients.  For example,
>in contrast to official reports [31], there is some preliminary evidence for
>Brucella infections (Unpublished observations).  Inhalation of Brucella spp.
>(Brucella melitensis strains predominantly) can cause the slow onset of
>brucellosis, a chronic illness that shares many but not all of the signs and
>symptoms of GWI.  Other possible infections include Q Fever [32], caused by
>Coxiella burnetii,
> anthrax caused by Bacillus anthracis, botulism caused by the botulinum toxin
>released from Clostridium botulinum, Yersinia pestis, a gram-negative,
>non-spore forming bacillus obtained from the bite of insects (fleas),
>Malaria, caused by P. falciparum or P. vivax from the bite of infected
>Anopheline mosquitos and other possible infectious agents.  The prevalence of
>these infections has not been determined in GWI patients but it is likely to
>be low.
>
> One possible source for chronic bacterial infections is the multiple
>vaccines that were used in ODS. Unwin et al. [33] found an association of GWI
>with the multiple vaccines received during deployment.  In the U.S., there
>have been GWI signs and symptoms in personnel who recently received the
>anthrax vaccine.  In some cases this has resulted in chronic illnesses in as
>many as 7-10% of personnel receiving the vaccine.[34]  Some of the chronic
>signs and symptoms associated with anthrax vaccination are very similar to
>those found in GWI patients, suggesting that at least some of the chronic
>illnesses suffered by veterans of the 1991 Gulf War may have
> been caused by multiple vaccines in combination with other exposures.[33,
>34]  Relatively minor microorganism contaminants in vaccines could have
>resulted in illness in chemically exposed, immune depressed individuals.  The
>French forces deployed to ODS did not receive multiple vaccines to protect
>against biological warfare agents, and this may turn out to be one of the
>most important reasons why the French reported few if any GWI cases.  The
>other possible reasons were the locations of French forces and the types of
>protective suits used in ODS.
>
> TREATMENT OF GWI
>
> The treatment of chemically exposed patients usually involves removal of
>offending chemicals from the patients' environment, depletion of chemicals
>from the patients' system and treatment of the signs and symptoms caused by
>chemical exposures.[15, 24]  Chemically exposed patients are often extremely
>sensitive to a variety of commonly encountered chemicals, including perfumes
>and air freshners, petrochemical fumes, chlorine, cleaning solutions and
>solvents, among others.  They are also very sensitive to certain foods, and
>special diets are often necessary, and in some cases direct skin contact with
>certain substances can cause strong
> cutaneous reactions.  An important part of treatment for chemical exposures
>requires limiting future exposures to a variety of common chemicals and
>removal of toxic chemicals.[15, 35]
>
> Patients with MCS or OPIDN benefit from procedures that slowly remove
>offending chemicals from their bodies.  We recommend dry saunas for help in
>chemical removal, as well as magnesium sulfate-hydrogen peroxide baths.[35]
>Some GWI patients may have irreversible nerve damage due to organophosphate
>exposure or low level nerve agent exposure potentiated by the effects of the
>antinerve agent pyridostigmine bromide, and it may be difficult to reverse
>their condition.  Chemicals can be reduced through a program of heat
>depuration, physical
> therapy and nutritional supplementation in a special environment.[35]  In
>addition to heat, exercise and diet, a variety of medications may alleviate
>some of the signs and symptoms of chemical exposures in GWI patients.  Many
>patients have benefited from anti-anxiety, anti-depressant and
>anti-inflammatory drugs [5], but
> this may not be beneficial for some GWI patients, especially those with
>biological exposures.
>
> The successful treatment of patients exposed to DU depends on reducing the
>body burden of U-235.  Such particles can remain inert in the lungs for
>extended periods of time, resulting primarily in local tissue alpha
>irradiation and the resulting radiation damage and immune suppression.  In
>time the U-235 moves to the bones where it can be difficult to remove.
>Systemic U-235 can be slowly removed by chelation therapy, usually with
>ethylenediaminetetraacetic acid (EDTA) or penacillamine.[15]
>
> Infectious microorganisms can be treated with the appropriate antibiotics.
>Treatment with antibiotics can result in improvement and even recovery in
>patients exposed to bacteria or mycoplasmas such as M. fermentans.[22, 23]
>The recommended treatments for systemic mycoplasmal infections require
>long-term antibiotic therapy, usually at least 6-12 months of doxycycline,
>ciprofloxacin, azithromycin or clarithromycin.[36]  Long-term treatments are
>required, because few patients recover after only a months treatment [23],
>possibly because of the intracellular locations of mycoplasmas, the
>slow-growing nature of these  microorganisms and their inherent resistance to
>antibiotics.[37]  Once patients recovered and were able to return to active
>duty or normal activity, mycoplasma gene sequences could no longer be
>detected in their blood leukocytes.  These clinical responses were not due to
>placebo effects, because administration of some antibiotics that are not
>effective against mycoplasmal infections, such as penicillins, resulted in
>patients becoming more not less symptomatic, and they are not due to
>immunosuppressive effects that can occur with some of the  recommended
>antibiotics.  Interestingly, CFS/ME, FMS and GWI patients with systemic
>infections that slowly recover on antibiotic therapy are generally less
>environmentally sensitive, suggesting that their immune systems may be
>returning to pre-illness states.  If such patients had illnesses that were
>caused by psychological or psychiatric problems or solely by chemical
>exposures, they should not respond to the recommended antibiotics and slowly
>recover.   In addition, if such treatments were just reducing autoimmune
>responses, then patients should have relapsed after the treatments were
>discontinued.
>
> SUMMARY
>
> Gulf War Illnesses (GWI) can produce complex signs and symptoms, such as
>polyarthralgia, chronic fatigue, short-term memory loss, sleep difficulties,
>headaches, intermittent fevers, skin rashes, diarrhea, vision problems,
>nausea, breathing and heart problems and other signs and symptoms.  Although
>there is not yet a case definition for GWI, the chronic signs and symptoms
>loosely fit the clinical criteria for Chronic Fatigue Syndrome/Myalgic
>Encephalomyelitis and/or
> Fibromyalgia Syndrome.  Some patients have additionally what appears to be
>neurotoxicity and brainstem dysfunction that can result in autonomic, cranial
>and peripheral nerve demyelination, possibly from complex chemical exposures.
> Often these patients have been diagnosed with Multiple Chemical Sensitivity
>Syndrome (MCS) or Organophosphate-Induced Delayed Neurotoxicity (OPIDN).
>Chemically exposed patients can be treated by removal of offending chemicals
>from the patient's environment, depletion of chemicals from the patient's
>system and
> treatment of the neurotoxic signs and symptoms caused by chemical
>exposure(s).  A rather large subset (~40%) of GWI patients have systemic
>infections, including mycoplasmal and other chronic bacterial infections,
>that are probably responsible for the appearance of GWI in immediate family
>members.  These infections can be treated with antibiotics, vitamin and
>nutritional supplementation.  It is likely that GWI patients owe their
>illnesses to a variety of exposures: (a) chemical mixtures, primarily
>organophosphates, anti-nerve agents and possibly nerve agents, (b)
>radiological sources, primarily depleted uranium and possibly fallout from
> destroyed nuclear reactors, and (c) biological sources, primarily bacteria,
>such as M. fermentans, and toxins, before, during and after the conflict.
>The multiple vaccines used in ODS are a prime suspect for chronic infections.
> The multiple, complex exposures during ODS resulted in poorly defined
>chronic illnesses, but subsets of GWI can be treated using appropriate
>procedures.
>
> REFERENCES
>
> 1. NIH Technology Assessment Workshop Panel.  The Persian Gulf Experience
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>
> 2. Nicolson GL, Nicolson NL.  Chronic Fatigue Illness and Operation Desert
>Storm.  J Occup Environ Med  1995; 38:14-17.
>
> 3. Haley RW, Kurt TL, Hom J.  Is there a Gulf War Syndrome?  Searching for
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>
> 4. Murray-Leisure KA, Daniels MO, Sees J, et al.  Mucocutaneous-,
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>
> 5. Baumzweiger WE, Grove R.  Brainstem-Limbic immune dysregulation in 111
>Gulf War veterans: a clinical evaluation of its etiology, diagnosis and
>response to headache treatment. Intern J Med 1998; 1:129-143.
>
> 6. Nicolson GL, Hyman E, Korinyi-Both A, et al.  Progress on Persian Gulf
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>
> 7. Nicolson GL, Nasralla M, Franco AR, et al. Diagnosis and Integrative
>Treatment of Intracellular Bacterial Infections in Chronic Fatigue and
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>Chronic Illnesses. Clin Pract Alt Med 2000; 1:92-102.
>
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>Desert Shield and Desert Storm. JAMA 1996; 275:118-121.
>
> 9. Leisure KM, Nicolson NL, Nicolson, GL.  Hospitalizations for unexplained
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>
> 10. Kizer KW, Joseph S, Rankin JT. Unexplained illness among Persian Gulf
>War vetrans in an Air National Guard unit: preliminary report -- August
>1990-March 1995.  Morb Mortal Weekly Rep 1995; 44: 443-447.
>
> 11. Sartin JS. Gulf War Illnesses: causes and controversies.  Mayo Clin Proc
>2000; 75:811-819.
>
> 12. Nicolson GL, Nicolson NL.  Gulf War Illnesses: complex medical,
>scientific and political paradox.  Med Confl Surviv  1998; 14: 74-83.
>
> 13. Lange G, Tiersky L, DeLuca J et al. Psychiatric diagnoses in Gulf War
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>
> 14. Haley RW, Fleckenstein JL, Marshall WW, et al.  Effect of basal ganglia
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>Arch Neurol 2000; 280:981-988.
>
> 15. Nicolson GL, Nasralla M, Haier J, et al. Gulf War Illnesses: Role of
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>
> 16. Abou-Donia MB, Wilmarth KR.  Neurotoxicity resulting from coexposure to
>pyridostigmine bromide, DEET and permethrin: Implications of Gulf War
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>
> 17. Haley RW, Kurt TL.  Self-reported exposure to neurotoxic chemical
>combinations in the Gulf War: a cross-sectional epidemiologic study.  JAMA
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>
> 18. Gordon JJ, Inns RH, Johnson MK et al. The delayed neuropathic effects of
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>
> 19. Eddington PG. Gassed in the Gulf. Washington D.C.: Insignia Publishing,
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>
> 20. Korinyi-Both AL, Molnar AC, Korinyi-Both AL, et al. Al Eskan disease:
>Desert Storm pneumonitis. Mil Med 1992;157:452-462.
>
> 21. Magill AJ, Grogl M, Fasser RA, et al.  Viscerotropic leishmaniasis
>caused by Leishmania tropica in soldiers returning from Operation Desert
>Storm.  N Engl J Med 1993; 328:1383-1387.
>
> 22. Nicolson GL, Nicolson NL.  Diagnosis and treatment of mycoplasmal
>infections in Persian Gulf War Illness-CFIDS patients.  Intern  J Occup Med
>Immunol Tox 1996; 5:69-78.
>
> 23. Nicolson GL, Nicolson NL, Nasralla M.  Mycoplasmal infections and
>Chronic Fatigue Illness (Gulf War Illness) associated with deployment to
>Operation Desert Storm.  Intern J Med 1998; 1: 80-92.
>
> 24. U. S. Senate Committee on Banking, Housing and Urban Affairs.  U.S.
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>
> 25. Hyman ES.  A urinary marker for systemic coccal disease.  Nephron  1994;
>68: 314-326.
>
> 26. Nicolson GL, Nasralla M, Haier J, et al.  Diagnosis and treatment of
>chronic mycoplasmal infections in Fibromyalgia and Chronic Fatigue Syndromes:
>relationship to Gulf War Illness. Biomed Ther  1998; 16:266-271.
>
> 27. Vojdani A, Franco AR.  Multiplex PCR for the detection of Mycoplasma
>fermentans, M. hominis and M. penetrans in patients with Chronic Fatigue
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>Fatigue Syndr  1999; 5:187-197.
>
> 28. Nicolson GL, Nasralla M, Franco AR, et al.  Mycoplasmal infections in
>fatigue illnesses: Chronic Fatigue and Fibromyalgia Syndromes, Gulf War
>Illness and Rheumatoid Arthritis.  J Chronic Fatigue Syndr 2000; 6(3/4):23-39.
>
> 29. Nasralla M, Haier J, Nicolson GL.  Multiple mycoplasmal infections
>detected in blood of Chronic Fatigue and Fibromyalgia Syndrome patients. Eur
>J  Clin Microbiol Infect Dis 1999; 18:859-865.
>
> 30. Hannan KL, Berg DE, Baumzweiger W, et al.  Activation of the coagulation
>system in Gulf War Illnesses: a potential pathophysiologic link with chronic
>fatigue syndrome, a laboratory approach to diagnosis.  Blood Coagulat
>Fibrinol 2000; 7:673-678.
>
> 31. DeFraites RF, Wanat ER, Norwood AE, et al.  Report: Investigation of a
>suspected outbreak of an unknown disease among veterans of Operation Desert
>Shield/Storm, 123d  Army Reserve Command, Fort Benjamin Harrison, Indiana,
>April, 1992. Epidemiology Consultant Service (EPICON), Division of Preventive
>Medicine, Walter Reed Army Institute of Research, Washington, D.C.
>
> 32. Ferrante MA, Dolan MJ. Q fever meningoencephalitis in a soldier
>returning from the Persian Gulf war.  Clin Infect Dis 1993; 16:489-496.
>
> 33. Unwin C, Blatchley N, CokerW, et al. Health of UK servicemen who served
>in the Persian Gulf War.  Lancet  1999; 353:169-178.
>
> 34. Nicolson GL, Nass M, Nicolson NL. The anthrax vaccine controversy.
>Questions about its efficacy, safety and strategy.  Med  Sentinel 2000;
>5:97-101.
>
> 35. Rea WJ, Pan Y, Johnson AR, et al.  Reduction of chemical sensitivity by
>means of heat depuration, physical therapy and nutritional supplementation in
>a controlled environment.  J Nutrit Environ Med 1996; 6: 141-148.
>
> 36. Nicolson GL.  Considerations when undergoing treatment for chronic
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>War Illnesses. (Part 1). Antibiotics Recommended when indicated for treatment
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>123-128.
>
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>
> FIGURE LEGENDS
>
> Figure 1. Figure 1A and 1B.  Incidence of increase in severity of signs and
>symptoms in 300 chronic illness patients.  Severity of illness was scored
>using 118 signs and symptoms on a 10-point scale (0, none; 10 extreme) prior
>to and after the onset of illness.  Scores were placed into 29 categories
>containing 3-9 signs/symptoms and were recorded as the sum of differences
>between values before and after onset of illness divided by the number of
>questions in the category.  Changes in score values of 2 or more points were
>considered relevant.  Patient groups were: CFS/ME, FMS, GWI and chronic
>illness patients without evidence of bacterial infection.  The patients
>groups had the following incidence of Mycoplasma species infections: CFS/ME,
>56.1%; FMS, 64%; GWI, 44.5%; Other chronic illness patients, 0%. Asterisk (*)
>indicates score = 0.
>
> Figure 2. Multiple exposures (chemical, radiological, biological) or
>multifactorial causes may have resulted in GWI in susceptible individuals
>(modified from reference 15).
>
> ABOUT THE AUTHOR
>
> Prof. Garth L. Nicolson is the President and Chief Scientific Officer of the
>Institute for Molecular Medicine in Huntington Beach, California.  He was
>formally the David Bruton Jr. Chair in Cancer Research and Professor and
>Chairman at the University of Texas M. D. Anderson Cancer Center in Houston
>and he was Professor of Internal Medicine and Professor of Pathology and
>Laboratory Medicine at the University of Texas Medical School at Houston.  He
>was also Professor of Comparative Pathology at Texas A & M University.  Among
>the most cited scientists in the world, having published over 515 medical and
>scientific papers (including 3 Current Contents Citation Classics), edited 14
>books, and has served on the Editorial Boards of 12 medical and scientific
>journals and currently serving as Editor of two (Clinical & Experimental
>Metastasis and the Journal of Cellular Biochemistry).  Dr. Nicolson has won
>many awards, such as the Burroughs Wellcome Medal of the Royal Society of
>Medicine, Stephen Paget Award of the Metastasis Research Society and the
>National Cancer Institute Outstanding Investigator Award.
>

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