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No evidence for altered cellular immune functions in personnel deployed in the Persian Gulf during and after the Gulf War--The Danish Gulf War study.

Veterans who have participated in the Gulf War suffer from a number of symptoms, collectively referred to as the Gulf War Syndrome. It has been hypothesized that a change in the systemic cytokine balance or other changes in immunological parameters could be responsible for some of the symptoms. We analyzed the peripheral blood natural killer (NK) cell activity of 686 Gulf War personnel who had been present in the Persian Gulf area during and immediately after the Gulf War as well as 231 gender and age-matched controls. The test material included individual samples of frozen peripheral blood mononuclear cells kept at -139 degrees C for a period of 50 to 380 days prior to NK cell analysis of freshly thawed cells. Significant differences in NK-cell activity were not observed by direct comparison of the levels of natural cytotoxic activity in the two groups. However, NK-cell cytotoxicity as such decreased due to cryopreservation. Surprisingly, the NK cells obtained from control donors were significantly (p<0.0001) more sensitive to freezing conditions than cells from the Gulf War personnel, leaving the marginal comparison between the two groups untrustworthy, in particular because of the marked difference between the -139 degrees C storage times used for the two groups. Freshly thawed samples of peripheral blood T lymphocytes (CD2+ cells) from 109 randomly selected Gulf War personnel and 68 gender- and age-matched controls were stimulated for 3 days with phytohemagglutinin followed by 4 h activation by phorbol ester and ionomycin, and were stained for intracellular content of interleukin-2, -5, -10 and interferon-gamma. As with natural cytotoxicity, the length of cell storage at -139 degrees C influenced the production of cytokines. No significant differences in the cytokine production between the two groups were observed when the influence of the storage period was taken into consideration. Together, these data suggest that no overall long-term effects on NK-cell function and T-cell cytokine production are present in the Danish Gulf War personnel. Moreover, cryopreservation is a major potential source of bias when studying the physiology of thawed NK and T cells.

Adult↗

[Health status after serving in the Gulf war area. The Danish Gulf War Study].

Increased symptom reporting has been found in American Gulf War Veterans. The symptoms comprise headache, fatigue, impaired short-term memory, sleep disturbances, agitation, respiratory symptoms, muscle and joint pain, diseases of the skin, and intermittent fever. This cross-sectional study was performed to clarify whether a corresponding pattern existed among Danes having served in the Persian Gulf during and mainly after the Gulf War. The investigation took place during the period January 1997 to January 1998 and included 821 subjects who had been deployed in the Persian Gulf within the period August 2, 1990 until December 31, 1997. Of 686 (83.6%) subjects who participated in the study, 95% had been engaged in peace keeping operations after the war. A group consisting of randomly selected age- and gender matched controls, comprised 231 of 400 potential participants (57.7%). All participants underwent clinical and paraclinical examinations, and had an interview based on a previously completed questionnaire. Unspecific symptoms such as repeated fits of headache, fatigue, memory and concentration difficulties, sleep disturbances, agitation, dyspneoa, diseases of the skin, and intermittent fever, were significantly more frequent among Danish Gulf War Veterans (p < 0.05) than among controls; no association was found with respect to muscle and joint pain. The higher symptom prevalence among Gulf War Veterans was observed for conditions which had made their first appearance during or after the Gulf War. The prevalence of diseases and symptoms which had made their first appearance before August 2, 1990 was similar for both groups. This study demonstrated a pattern of diseases and symptoms among Danish Gulf War Veterans consistent with the findings among American Gulf War Veterans. Considering that American Gulf War Veterans were predominantly deployed during the armament phase and the brief war phase, and that Danish Gulf War Veterans were predominantly deployed after the war restoring peace, the results indicate the existence of some common risk factors independent of war action.

Adult↗

Major reproductive health characteristics in male Gulf War Veterans. The Danish Gulf War Study.

INTRODUCTION: The male reproductive system could have been affected by various hazardous agents and exposures during and in the aftermath of the Persian Gulf War scenario. We tested the hypothesis that, compared to controls, male Danish Gulf War Veterans would have adverse sex hormone levels, decreased fertility, and a larger proportion of adverse pregnancy outcomes including spontaneous abortions, congenital diseases and malformations. MATERIAL AND METHODS: A cross-sectional study was performed during the period January 1997 to January 1998 which included 661 male subjects who had been deployed in the Persian Gulf within the period August 2 1990 until December 31 1997. A control group of 215 Danish military men, not deployed in the Gulf region, was selected with random matching by age and type of work. All participants underwent clinical and paraclinical examinations, and had an interview based on a previously completed comprehensive questionnaire. A venous blood sample was drawn to determine serum concentrations of the follicle-stimulating hormone (FSH), the luteinizing hormone (LH), testosterone, serum hormone binding globulin (SHBG), and inhibin B. The free androgen index was calculated from testosterone and SHBG levels. RESULTS: No differences were found between Gulf War Veterans and controls with respect to any of the reproductive hormones measured, nor with respect to fertility or the prevalence of spontaneous abortions, congenital diseases or malformations among the offspring. Also cohabitational characteristics were similar. CONCLUSION: Based on the results of this study we conclude that the biological reproductive health of male Danish Gulf War Veterans seemed to be unaffected by their engagement in the post war peace-keeping mission.

Adult↗

Low paraoxonase in Persian Gulf War Veterans self-reporting Gulf War Syndrome.

Exposure to organophosphate (OP's) insecticides and nerve gases during the Persian Gulf War has been implicated in the development of Gulf War Syndrome. Paraoxonase (PON1) present in human serum detoxifies OP's. We determined the levels of PON1 in the serum of Gulf War Veterans and compared these to those found in a control population. One hundred fifty-two Gulf War Veterans from the UK who self-reported the presence of Gulf War Syndrome via a questionnaire and 152 age and gender matched controls were studied. PON1 activity, concentration, and genotype were determined. In the Gulf War Veterans, paraoxon hydrolysis was less than 50% of that found in the controls (100.3 (14.8-233.8) vs 214.6 (50.3-516.2) nmol/min/ml, P < 0.001). This low activity was independent of the effect of PON1 genotype. The serum PON1 concentration was also lower in the Gulf War Veterans (75.7 (18.1-351.3) vs 88.2 (34.5-527.4) microg/ml, P < 0.00025), which was again independent of PON1 genotype. There was no difference in the rate of diazoxon hydrolysis between the groups (10. 2 +/- 4.1 micromol/min/ml vs 9.86 +/- 4.4, P = NS). A decreased capacity to detoxify OP insecticides resulting from low serum PON1 activity may have contributed to the development of Gulf War Syndrome.

Adult↗

A comparison of the postdeployment hospitalization experience of U.S. military personnel following service in the 1991 Gulf War, Southwest Asia after the Gulf War, and Bosnia.

Much attention has been given to the impact of deployment on the health of veterans from the 1991 Gulf War. Whereas increases in self-reported symptoms have been common, no specific exposures have been implicated. Some have suggested that stress from deployment is the chief cause for multisymptom conditions among Gulf War veterans, but comparisons with the health of other recent deployers have not been made. We sought to examine the impact of several large military deployments on hospitalization experience. Hospitalization records were examined for all active duty personnel deployed exclusively to the Gulf War, Southwest Asia after the Gulf War, or Bosnia. Cox's hazard modeling was used to assess time until first post-deployment hospitalization, separation from active duty, or December 31, 2000, whichever occurred first, while controlling for influential covariates and temporal changes. Personnel deployed to Southwest Asia after the 1991 Gulf War were at a slight increased risk for any-cause hospitalization and for 3 of the 14 major diagnostic categories when compared with veterans of the 1991 Gulf War. Personnel deployed to Bosnia were at a decreased risk for any-cause hospitalization and 12 of the 14 major diagnostic categories when compared with Gulf War veterans. These findings do not fully explain the complexity of postdeployment health experiences. Although the risk for hospitalization may be associated with regional deployment, it is unlikely that Gulf War veterans are at greater risk of hospitalization due to a specific exposure-related disease.

Adolescent↗

Prevalence of Gulf war veterans who believe they have Gulf war syndrome: questionnaire study.

OBJECTIVES: To determine how many veterans in a random sample of British veterans who served in the Gulf war believe they have "Gulf war syndrome," to examine factors associated with the presence of this belief, and to compare the health status of those who believe they have Gulf war syndrome with those who do not. DESIGN: Questionnaire study asking British Gulf war veterans whether they believe they have Gulf war syndrome and about symptoms, fatigue, psychological distress, post-traumatic stress, physical functioning, and their perception of health. PARTICIPANTS: 2961 respondents to questionnaires sent out to a random sample of 4250 Gulf war veterans (69.7%). MAIN OUTCOME MEASURE: The proportion of veterans who believe they have Gulf war syndrome. RESULTS: Overall, 17.3% (95% confidence interval 15.9 to 18.7) of the respondents believed they had Gulf war syndrome. The belief was associated with the veteran having poor health, not serving in the army when responding to the questionnaire, and having received a high number of vaccinations before deployment to the Gulf. The strongest association was knowing another person who also thought they had Gulf war syndrome. CONCLUSIONS: Substantial numbers of British Gulf war veterans believe they have Gulf war syndrome, which is associated with psychological distress, a high number of symptoms, and some reduction in activity levels. A combination of biological, psychological, and sociological factors are associated with the belief, and these factors should be addressed in clinical practice.

Adult↗

Symptoms and medical conditions in Australian veterans of the 1991 Gulf War: relation to immunisations and other Gulf War exposures.

AIMS: To investigate whether Australian Gulf War veterans have a higher than expected prevalence of recent symptoms and medical conditions that were first diagnosed in the period following the 1991 Gulf War; and if so, whether these effects were associated with exposures and experiences that occurred in the Gulf War. METHODS: Cross-sectional study of 1456 Australian Gulf War veterans and a comparison group who were in operational units at the time of the Gulf War, but were not deployed to that conflict (n = 1588). A postal questionnaire was administered and the likelihood of the diagnosis of self-reported medical conditions was assessed and rated by a medical practitioner. RESULTS: Gulf War veterans had a higher prevalence of all self-reported health symptoms than the comparison group, and more of the Gulf War veterans had severe symptoms. Increased symptom reporting was associated with several exposures, including having more than 10 immunisations, pyridostigmine bromide tablets, anti-biological warfare tablets, pesticides, insect repellents, reportedly being in a chemical weapons area, and stressful military service experiences in a strong dose-response relation. Gulf War veterans reported psychological (particularly post-traumatic stress disorder), skin, eye, and sinus conditions first diagnosed in 1991 or later more commonly than the comparison group. Over 90% of medical conditions reported by both study groups were rated by a medical practitioner as having a high likelihood of diagnosis. CONCLUSION: More than 10 years after the 1991 Gulf War, Australian veterans self-report all symptoms and some medical conditions more commonly than the comparison group. Further analysis of the severity of symptoms and likelihood of the diagnosis of medical conditions suggested that these findings are not due to over-reporting or to participation bias.

Adult↗

What was different about exposures reported by male Australian Gulf War veterans for the 1991 Persian Gulf War, compared with exposures reported for other deployments?

This study identified chemical and environmental exposures specifically associated with the 1991 Persian Gulf War. Exposures were self-reported in a postal questionnaire, in the period of 2000-2002, by 1,424 Australian male Persian Gulf War veterans in relation to their 1991 Persian Gulf War deployment and by 625 Persian Gulf War veterans and 514 members of a military comparison group in relation to other active deployments. Six of 28 investigated exposures were experienced more frequently during the Persian Gulf War than during other deployments; these were exposure to smoke (odds ratio [OR], 4.4; 95% confidence interval, 3.0-6.6), exposure to dust (OR, 3.7; 95% confidence interval, 2.6-5.3), exposure to chemical warfare agents (OR, 3.9; 95% confidence interval, 2.1-7.9), use of respiratory protective equipment (OR, 13.6; 95% confidence interval, 7.6-26.8), use of nuclear, chemical, and biological protective suits (OR, 8.9; 95% confidence interval, 5.4-15.4), and entering/inspecting enemy equipment (OR, 3.1; 95% confidence interval, 2.1-4.8). Other chemical and environmental exposures were not specific to the Persian Gulf War deployment but were also reported in relation to other deployments. The number of exposures reported was related to service type and number of deployments but not to age or rank.

Adult↗

Insanity and war: the Gulf War and a psychiatric institution.

The threat of a chemical war has profound impacts on all layers of society. Hospitalized mental patients, as we have observed them, react in more extreme ways than staff members. They may react overanxiously, totally apathetically, or in context-related flights to partial sanity. Denial and projection were heavily used defense mechanisms together with a tendency of the more acute patients to plunge into their bizarre idiosyncratic world, lending strange meanings to what was happening in the world. Many patients were found to have strong narcissistic traits and to invest most of their libidinal energies in their private world. In times of stress this results in even greater social isolation. Different types of patients in different phases of their illness react differently to such overpowering stress, and the way they react illustrates their cognitive, behavioral, and social deficiencies. WWII literature on the reactions of mentally ill patients to "fly-bombing" seem not to take into consideration the different possible reactions of patients. This may be due to a change in emphasis in the care of mentally disturbed individuals in the last two decades. We propose to use even such an extremely stressful situation as a challenge to the mental health profession to further the well-being of their patients.

Adaptation, Psychological↗

Hospitalizations for unexplained illnesses among U.S. veterans of the Persian Gulf War.

Persian Gulf War veterans have reported a variety of symptoms, many of which have not led to conventional diagnoses. We ascertained all active-duty U.S. military personnel deployed to the Persian Gulf War (552,111) and all Gulf War era military personnel not deployed (1,479,751) and compared their postwar hospitalization records (until 1 April 1996) for one or more of 77 diagnoses under the International Classification of Diseases (ICD-9) system. The diagnoses were assembled by the Emerging Infections Program, Centers for Disease Control and Prevention, and are here termed "unexplained illnesses." Deployed veterans were found to have a slightly higher risk of hospitalization for unexplained illness than the nondeployed. Most of the excess hospitalizations for the deployed were due to the diagnosis "illness of unknown cause" (ICD-9 code 799.9), and most occurred in participants of the Comprehensive Clinical Evaluation Program who were admitted for evaluation only. When the effect of participation in this program was removed, the deployed had a slightly lower risk than the nondeployed. These findings suggest that active-duty Gulf War veterans did not have excess unexplained illnesses resulting in hospitalization in the 4.67-year period following deployment.

Adolescent↗

Pyridostigmine bromide and Gulf War syndrome.

Gulf War Syndrome has become a growing concern of US government, military Gulf war veterans and their families. It is suggested that research on genotype/phenotype of acetylcholinesterase and butyrylcholinesterase may help to discover the role of pyridostigmine bromide in the cause of Gulf War Syndrome.

Acetylcholinesterase↗

Post-combat syndromes from the Boer war to the Gulf war: a cluster analysis of their nature and attribution.

OBJECTIVES: To discover whether post-combat syndromes have existed after modern wars and what relation they bear to each other. DESIGN: Review of medical and military records of servicemen and cluster analysis of symptoms. DATA SOURCES: Records for 1856 veterans randomly selected from war pension files awarded from 1872 and from the Medical Assessment Programme for Gulf war veterans. MAIN OUTCOME MEASURES: Characteristic patterns of symptom clusters and their relation to dependent variables including war, diagnosis, predisposing physical illness, and exposure to combat; and servicemen's changing attributions for post-combat disorders. RESULTS: Three varieties of post-combat disorder were identified-a debility syndrome (associated with the 19th and early 20th centuries), somatic syndrome (related primarily to the first world war), and a neuropsychiatric syndrome (associated with the second world war and the Gulf conflict). The era in which the war occurred was overwhelmingly the best predictor of cluster membership. CONCLUSIONS: All modern wars have been associated with a syndrome characterised by unexplained medical symptoms. The form that these assume, the terms used to describe them, and the explanations offered by servicemen and doctors seem to be influenced by advances in medical science, changes in the nature of warfare, and underlying cultural forces.

Cluster Analysis↗

Is testicular cancer related to Gulf War deployment? Evidence from a pilot population-based study of Gulf War era veterans and cancer registries.

The possible relationship between military deployment and the subsequent increase in cancer rates has been prominent since the Vietnam War. The objective of this study was to investigate whether any form of cancer was increased among veterans deployed to the Persian Gulf in the 1991 conflict. This study matched data from central cancer registries in the District of Columbia and New Jersey with the records for 1.4 million Gulf War era veterans, i.e., 621,902 veterans who arrived in the Persian Gulf before March 1, 1991, and 746,248 non-Gulf veterans. Using a proportional incidence ratio, testicular cancer was found to be the only significantly increased malignancy among deployed Persian Gulf War veterans. The increase became apparent 2 to 3 years after the Persian Gulf War and peaked 4 to 5 years afterward. Our data and those of investigators studying Vietnam veterans suggest that testicular cancer may be related to military deployment.

Adult↗

Antibodies to squalene in Gulf War syndrome.

Gulf War Syndrome (GWS) is a multisystemic illness afflicting many Gulf War-era veterans. The molecular pathological basis for GWS has not been established. We sought to determine whether the presence of antibodies to squalene correlates with the presence of signs and symptoms of GWS. Participants in this blinded cohort study were individuals immunized for service in Desert Shield/Desert Storm during 1990-1991. They included 144 Gulf War-era veterans or military employees (58 in the blinded study), 48 blood donors, 40 systemic lupus erythematosus patients, 34 silicone breast implant recipients, and 30 chronic fatigue syndrome patients. Serum antibodies to squalene were measured. In our small cohort, the substantial majority (95%) of overtly ill deployed GWS patients had antibodies to squalene. All (100%) GWS patients immunized for service in Desert Shield/Desert Storm who did not deploy, but had the same signs and symptoms as those who did deploy, had antibodies to squalene. In contrast, none (0%) of the deployed Persian Gulf veterans not showing signs and symptoms of GWS have antibodies to squalene. Neither patients with idiopathic autoimmune disease nor healthy controls had detectable serum antibodies to squalene. The majority of symptomatic GWS patients had serum antibodies to squalene.

Autoantibodies↗

Increased psychological distress among Danish Gulf War veterans--without evidence for a neurotoxic background. The Danish Gulf War Study.

INTRODUCTION: Compared with controls, up to six years after their return, Danish Gulf War veterans have a significantly higher prevalence of self-reported neuropsychological symptoms, potentially as a result of neurotoxic exposure during deployment. We tested the hypotheses that: 1) GW veterans would perform less well than controls using a computerized neuromotor test battery; and that 2) GW veterans have a psychological profile different from that of controls. MATERIAL AND METHODS: A cross-sectional study of 686 subjects who had been deployed in the Persian Gulf within the period August 2, 1990 until December 31, 1997; the control group comprised 231 subjects matched according to age, gender and profession. All participants underwent clinical and paraclinical examinations, along with a neuromotor test battery (CATSYS Test System) and a psychological health status questionnaire, the SCL-90-R rating scale. RESULTS: No differences were found between GW veterans and controls with respect to lifestyle and cohabitational characteristics. Differences between the two groups with respect to neuromotor function were very small. Within the GW veteran group, stratified according to clustering of neuropsychological symptoms, and stratified according to SCL-90-R score, no trends were found suggesting reduced motor function with increasing symptoms. Of nine dimensions constructed on the basis of the SCL-90-R items, six were significantly associated with being a Gulf War veteran. Statistically, the strongest associations were found for ratings of the obsessive-compulsive dimension and of the depression dimension. No associations were found with respect to phobic anxiety, paranoid ideation, and psychoticism. INTERPRETATION: The increased psychological distress found among Danish GW veterans seemed rather due to a mentally distressing environment than to neurotoxic exposure.

Adult↗

Anniversary reactions in Gulf War veterans: a naturalistic inquiry 2 years after the Gulf War.

The goal of this study was to assess the occurrence of anniversary reactions in Gulf War veterans 2 years after the conclusion of Operation Desert Storm. Subjects were administered questionnaires and asked to identify specific months of best and worst functioning, and months of least or most symptoms of posttraumatic stress disorder (PTSD). Negatively experienced months were compared to documented dates of exposure to traumatic events during the war. Anniversary reactions occurred with a frequency greater than chance and were seen most in individuals exposed to a greater number, and to more severe types, of traumatic events. This suggests that anniversary reactions are etiologically linked to traumatic events and may be a part of the syndrome of PTSD.

Chi-Square Distribution↗