Tag: Gulf War Illness

Patient activism and the struggle for diagnosis: Gulf War illnesses and other medically unexplained physical symptoms in the US

Abstract:

We examine Gulf War illnesses–which include the fatigue, joint pain, dermatitis, headaches, memory loss, blurred vision, diarrhea, and other symptoms reported by Gulf War veterans–in relation to other medically unexplained physical symptoms such as multiple chemical sensitivity,chronic fatigue syndrome, and fibromyalgia. Our intent is to examine the diagnosis negotiations involved in these mysterious diseases, by showing the different forms of legitimacy involved in such interactions.

Factors involved in diagnostic legitimacy are: diagnostic legitimacy in the medical community, lay acceptance of the diagnosis, uncertainty in looking for causes, and social mobilization. We conclude by noting that research may not be able to find any cause for these diseases/conditions; hence, it may be necessary to embrace medical uncertainty, and also to accept patient experience in order to facilitate diagnosis, treatment, and recovery process.

Such a change can alter patients’ expectations and taken-for-granted assumptions about medicine, and perhaps in turn reduce the frequency with which dissatisfied individuals form illness groups that mobilize to challenge what they see as an unresponsive medical system.

 

Source: Zavestoski S, Brown P, McCormick S, Mayer B, D’Ottavi M, Lucove JC. Patient activism and the struggle for diagnosis: Gulf War illnesses and other medically unexplained physical symptoms in the US. Soc Sci Med. 2004 Jan;58(1):161-75. http://www.ncbi.nlm.nih.gov/pubmed/14572929

 

Aerobic capacity of Gulf War veterans with chronic fatigue syndrome

Abstract:

A large overlap exists between the diagnosis of chronic fatigue syndrome (CFS) and the unexplained symptoms reported by many Gulf War veterans (GV). Previous investigations have reported reduced aerobic capacity in civilians with CFS. The present investigation examined metabolic responses to maximal exercise in GVs with CFS compared with healthy GVs.

Cardiorespiratory and metabolic responses were recorded during a maximal exercise test on a cycle ergometer. The groups were not different in any demographic category (p > 0.05) or self-reported physical activity (p > 0.05). No differences were observed between groups for maximal oxygen uptake (28.9 +/- 6.7 mL/kg/min for CFS vs. 30.8 +/- 7.1 mL/kg/min for controls; p = 0.39), heart rate (155.8 +/- 16.1 bpm for CFS vs. 163.3 +/- 14.9 bpm for controls; p = 0.17), exercise time (9.6 +/- 1.5 minutes for CFS vs. 10.2 +/- 1.4 minutes for controls; p = 0.26), or workload achieved (208 +/- 36.7 W for CFS vs. 224 +/- 42.9 W for controls; p = 0.25). Likewise, no differences were observed at submaximal intensities (p > 0.05).

Compared with healthy controls, GVs who report multiple medically unexplained symptoms and meet criteria for CFS do not show a decreased exercise capacity. Thus, it does not appear that the pathology of the GVs with CFS includes a deficiency with mobilizing the cardiopulmonary system for strenuous physical effort.

 

Source: Nagelkirk PR, Cook DB, Peckerman A, Kesil W, Sakowski T, Natelson BH, LaManca JJ. Aerobic capacity of Gulf War veterans with chronic fatigue syndrome. Mil Med. 2003 Sep;168(9):750-5. http://www.ncbi.nlm.nih.gov/pubmed/14529252

 

Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure

Abstract:

In the present study, we have investigated whether the peripheral cholinergic abnormalities that we have reported previously [Spence, Khan and Belch (2000) Am. J. Med. 108, 736-739] in patients with chronic fatigue syndrome (CFS) are also present in those with Gulf War syndrome (GWS) and agricultural workers exposed to organophosphate pesticides, where cholinesterase inhibition is specifically implicated. We also looked at whether these abnormalities might be due to a reduction in the activity of cholinesterase expressed on the vascular endothelium.

We used laser Doppler imaging to measure the forearm skin blood flow responses to iontophoresis of acetylcholine and of methacholine (which is resistant to breakdown by cholinesterase) in patients with CFS, GWS and those with a history of ill health after definite organophosphate exposure, as well as in matched healthy controls.

The response to acetylcholine was significantly higher in patients with CFS than in controls ( P =0.029, repeated-measures ANOVA), but was normal in those with GWS and those exposed to organophosphates. The methacholine response was higher than the acetylcholine response in all patient groups except for those with CFS, where there was no difference between the responses. Although there are many clinical similarities between these three illnesses, our results indicate peripheral cholinergic abnormalities in the vascular endothelium of only patients with CFS, suggesting that this syndrome has a different aetiology, which might involve inhibition of vascular cholinesterase.

 

Source: Khan F, Kennedy G, Spence VA, Newton DJ, Belch JJ. Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure. Clin Sci (Lond). 2004 Feb;106(2):183-9. http://www.ncbi.nlm.nih.gov/pubmed/14503920

 

Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) are characterised by a lack of consistent laboratory and clinical abnormalities. Although they are distinguishable as separate syndromes based on established criteria, a great number of patients are diagnosed with both.

In studies using polymerase chain reaction methods, mycoplasma blood infection has been detected in about 50% of patients with CFS and/or FMS, including patients with Gulf War illnesses and symptoms that overlap with one or both syndromes. Such infection is detected in only about 10% of healthy individuals, significantly less than in patients.

Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery. By means of causation and therapy, mycoplasma blood infection may permit a further subclassification of CFS and FMS.

It is not clear whether mycoplasmas are associated with CFS/FMS as causal agents, cofactors, or opportunistic infections in patients with immune disturbances. Whether mycoplasma infection can be detected in about 50% of all patient populations with CFS and/or FMS is yet to be determined.

 

Source: Endresen GK. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes. Rheumatol Int. 2003 Sep;23(5):211-5. Epub 2003 Jul 16. http://www.ncbi.nlm.nih.gov/pubmed/12879275

 

Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome

Abstract:

PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). We have challenged this notion by examining perceived exertion in civilian females with CFS and expressing the data relative to exercise capacity (%[OV0312]O(2max)). The purpose of the present investigation was to further examine RPE during exercise in a unique population of CFS patients, Gulf veterans (GV).

METHODS: Thirty-four GV (N = 15 CFS, 42 +/- 8 yr; N = 19 healthy, 43 +/- 5 yr) performed a maximal exercise test on a cycle ergometer. After a 3-min warm-up, exercise intensity increased by 30 W every minute until exhaustion. RPE were obtained during the last 15 s of each minute using Borg’s CR-10 scale.

RESULTS: With the exception of peak [OV0312]E, there were no significant differences in any peak exercise variables. Repeated measures ANOVA revealed significantly higher RPE at each power output examined (F(1,32) = 16.4, P < 0.001). Group differences in RPE remained significant when analyzed relative to peak [OV0312]O(2) (F(1,32) = 7.2, P = 0.01). Both group main effects and the interaction were eliminated when self-reported fatigue symptoms were controlled for in the analyses. Power functions for RPE as a function of relative oxygen consumption were not different between groups and were significantly greater than a linear value of 1.0 (1.6 +/- 0.3 for both groups, P < 0.02).

CONCLUSIONS: Our results show that RPE are greater in GV with CFS regardless of whether the data were expressed in terms of absolute or relative exercise intensity. However, self-reported fatigue associated with CFS eliminated the group differences. These results suggest that GV with CFS were unique compared with their civilian counterparts. Future research aimed at determining the influence of preexisting fatigue on RPE during exercise is warranted.

 

Source: Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome. Med Sci Sports Exerc. 2003 Apr;35(4):569-74. http://www.ncbi.nlm.nih.gov/pubmed/12673138

 

Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome

Abstract:

Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001. Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries. The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients.

One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis.

Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy. Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile.

It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome. Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms.

Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome. Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis. Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome.

Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide.

 

Source: Gherardi RK. Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome. Rev Neurol (Paris). 2003 Feb;159(2):162-4. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/12660567

 

Chronic fatigue in a population-based study of Gulf War veterans

Abstract:

Fatigue has been associated with illness in veterans of the Gulf War; however, few studies have confirmed self-reported fatigue by using clinical evaluation, and symptomatic veterans have not been evaluated with established criteria for Chronic Fatigue Syndrome (CFS). The authors describe the frequency and clinical characteristics of CFS in a sample of veterans residing in the northwestern United States. The sample was selected randomly from U.S. Department of Defense databases of troops deployed to southwest Asia during the Gulf War. The selected individuals were invited to participate in a clinical case-control study of unexplained illness.

Of 799 survey respondents eligible for clinical evaluation, 178 had fatigue symptoms. Of the 130 veterans who were evaluated clinically, 103 had unexplained fatigue, and 44 veterans met the 1994 U.S. Centers for Disease Control criteria for CFS. In this population, the authors estimated a minimum prevalence of any unexplained fatigue to be 5.1%, and of CFS to be 2.2%. The estimated prevalence was greater among females than among males. Cases were similar to healthy controls, as determined by laboratory tests and physical findings. In comparison to several clinical studies of CFS patients, the authors of this study found a lower proportion of veterans who reported a sudden onset of symptoms (19%) vs. a gradual onset (50%).

Although it has previously been suggested that veterans of the Gulf War suffer from higher rates of chronic fatigue than the general population, the study results described herein–on the basis of clinical examination of a population-based sample of veterans-actually indicate that an increased rate may indeed exist. Gulf War veterans with unexplained fatigue should be encouraged to seek treatment so that the impact of these symptoms on overall quality of life can be reduced.

 

Source: McCauley LA, Joos SK, Barkhuizen A, Shuell T, Tyree WA, Bourdette DN. Chronic fatigue in a population-based study of Gulf War veterans. Arch Environ Health. 2002 Jul-Aug;57(4):340-8. http://www.ncbi.nlm.nih.gov/pubmed/12530602

 

Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome

Abstract:

We explored the relationship between a set of immunological variables and a set of cognitive and functional status measures and a diagnosis of chronic fatigue syndrome (CFS) in civilians and veterans using various regression and factor analytic methods.

Our approach emphasized the extraction of a few distinct factors in order to limit statistical problems associated with doing large numbers of multiple comparisons. This approach led to our finding cytokine data grouping into type 1 and type 2 clusters. A type 2 cluster plus a T and B cell factor predicted CFS caseness for Gulf War veterans but not for civilians with CFS. When a cognitive variable, reaction time, was added into the model, both immunological factors lost statistical significance; this indicates that the cognitive variable reaction time moderated the effects of the immunological factors in predicting patient status.

We did a similar analysis on the roles of the immunological and cognitive variables in functional status using SF-36 data. Higher levels of these same two immunological factors predicted poorer general health as well as poorer physical and social functioning in Gulf War veterans but not in civilians with CFS. When the reaction time factor was added, only the lymphocyte factor remained significant. This implies that lymphocytes are directly related to functional status in Gulf War veterans with CFS, but the Th2 factor produces its effect on functional status via changes in cognitive abilities.

Copyright 2002 S. Karger AG, Basel

 

Source: Brimacombe M, Zhang Q, Lange G, Natelson B. Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome. Neuroimmunomodulation. 2002-2003;10(2):93-100. http://www.ncbi.nlm.nih.gov/pubmed/12372983

 

The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations

Abstract:

This monograph of peer-reviewed articles is based on presentations at the conference “Environmental Factors in Medically Unexplained Physical Symptoms and Related Syndromes” held 10-12 January 2001 in Piscataway, New Jersey, USA. The purpose of the conference was to determine research priorities for elucidating the role of environmental factors in medically unexplained symptoms and symptom syndromes. These include conditions such as chronic fatigue syndrome, multiple chemical sensitivities, sick building syndrome, Gulf War illness, and the like. Approximately 1 1/2 days were devoted to plenary talks and 1 day was devoted to break-out sessions to discuss epidemiologic, psychosocial, and experimental research. Recommendations were made for a series of epidemiologic, psychosocial, and experimental research approaches, with acknowledgment that nosology issues are clearly fundamental to advancing understanding of these conditions.

 

Source: Kipen HM, Fiedler N. The role of environmental factors in medically unexplained symptoms and related syndromes: conference summary and recommendations. Environ Health Perspect. 2002 Aug;110 Suppl 4:591-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241210/ (Full article)

 

Controlled exposures to volatile organic compounds in sensitive groups

Abstract:

Sensitivities to chemicals are characterized by symptoms in multiple organ systems in response to low-level chemical exposures. This paper reviews studies of controlled exposures to odorants and to mixtures of volatile organic compounds. Sensitive subgroups include subjects who met Cullen’s 1987 criteria for multiple chemical sensitivity (MCS), Gulf War veterans with chronic fatigue syndrome and chemical sensitivity (CFS/CS), and subjects with specific self-reported sensitivities to methyl terbutyl ether (MTBE) in gasoline (MTBE-sensitive). All studies include comparison of age- and sex-matched healthy controls.

Studies of olfaction did not support unusual sensitivity, defined as lower odor thresholds, among MCS subjects; however, a dose-response pattern of symptoms was observed in response to suprathreshold concentrations of phenyl ethyl alcohol. In blinded, controlled exposures to clean air, gasoline, gasoline/11% MTBE, and gasoline/15% MTBE, a threshold effect was observed with MTBE-sensitive subjects reporting significantly increased symptoms to gasoline/15% MTBE exposure. Autonomic arousal (heart and respiration rate; end-tidal CO2) in response to odor of chemical mixtures may mediate symptoms for subjects with generalized chemical sensitivities, but not for those whose sensitivities are confined to specific chemicals.

For example, Gulf War veterans with CFS/CS experienced reduced end-tidal CO2 when exposed to diesel fumes, while exposure to MTBE did not produce any psychophysiologic changes in MTBE-sensitive subjects. Controlled olfactory and exposure studies reveal that significant responses can be observed in chemically sensitive subjects even when de-adaptation has not occurred. However, these studies suggest that symptoms are not necessarily accompanied by changes in physiologic arousal. Subject characteristics play a critical role in outcomes.

 

Source: Fiedler N, Kipen HM. Controlled exposures to volatile organic compounds in sensitive groups. Ann N Y Acad Sci. 2001 Mar;933:24-37. http://www.ncbi.nlm.nih.gov/pubmed/12000025