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Somatic hypotheses of war syndromes
Abstract
Since the end of the American Civil War, unexplained symptoms in military personnel arising after a war or peace mission have frequently been described. The pattern of symptoms is highly similar for all of the various war syndromes although the conditions of each war or peace mission are widely different. Many somatic hypotheses have been formulated to explain these syndromes; a considerable proportion of them are already outdated. In the last few years much attention has been given to Gulf War Syndrome and to unexplained symptoms of military personnel who were sent to Cambodia, Rwanda, Burundi, Zaire, or the former Yugoslavia. In this review the symptoms of war syndromes will be considered in more detail and the suggested somatic explanations will be discussed. During the last decade the following somatic causes have been suggested as possible explanations for these symptoms: (persistent) infection, abnormal immune response, administration of multiple vaccinations within a short period of time, use of malaria chemoprophylaxis, neurological abnormalities, exposure to toxicological substances and environmental factors. The various investigations performed to study these hypotheses are discussed. The fact that bias regularly occurs in the course of these investigations is pointed out. For the future, a reliable investigation of a war syndrome should be a prospective multidisciplinary study and should distinguish between causative and sustaining factors.
... Because their return, many of these service personnel have complained of a variety of nonspecific symptoms (Amato et al., 1997;Frost, 2000;Gouge et al., 1994;Haley and Kurt, 1997;Wittich, 1996) collectively labeled Gulf War Illness (GWI). Although no specific cause has been identified, it has been suggested that environmental exposures and stressors altered immune function contributing to GWI (Rook and Zumla, 1998;Soetekouw et al., 2000;Voidani and Thrasher, 2004). Several chemical exposures, including DEET, have been identified as potential causative agents due to the prevalence of use. ...
... DEET exposure has been suggested as a causative agent in GWI via mechanisms of immune modulation (Rooke and Zumla, 1998;Soetekouw et al., 2000;Vojdani and Thrasher, 2004). This is the first study designed to establish a NOAEL and LOAEL for DEET based on immunotoxicity testing. ...
... Nevertheless, a full PBPK model is not always required to support a PK risk assessment (Clewell et al., 2002). To determine if DEET exposure during Gulf War deployment may have posed a risk related to suppressed immune function (Rook and Zumla, 1998;Soetekouw et al., 2000;Voidani and Thrasher, 2004), the remainder of the discussion will address these points. ...
N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent used commonly in recreational, occupational and military environments. Due to its widespread use and suggested link to Gulf War Illness, this study examined the immunotoxicity of DEET. Adult female B6C3F1 mice were injected sc for 14 days with DEET at 0, 7.7, 15.5, 31, or 62 mg/kg/day. Due to differences in the dermal absorption of DEET between mice and humans, this study eliminated this confounding factor by utilizing sc injection and measured circulating blood levels of DEET to assess bioavailability from sc administration. Effects on lymphocyte proliferation, natural killer cell activity, thymus and spleen weight and cellularity, the antibody plaque-forming cell (PFC) response, and thymic and splenic CD4/CD8 lymphocyte subpopulations were assessed 24 h after the last dose. No effect was observed in lymphocyte proliferation, natural killer cell activity, thymic weight, splenic weight, thymic cellularity, or splenic cellularity. Significant decreases were observed in the percentage of splenic CD4-/CD8- and CD4+/CD8- lymphocytes but only at the 62 mg DEET/kg/day treatment level and not in absolute numbers of these cells types. Additionally, significant decreases in the antibody PFC response were observed following treatment with 15.5, 31, or 62 mg DEET/kg/day. Pharmacokinetic (PK) data from the current study indicate 95% bioavailability of the administered dose. Therefore, it is likely that DEET exposure ranges applied in this study are comparable to currently reported occupational usage. Together, the evidence for immunosuppression and available PK data suggest a potential human health risk associated with DEET in the occupational or military environments assuming similar sensitivity between human and rodent responses.
... Research has tended to focus on these mechanisms more in relation to established conditions, such as cancer [3], viral recurrence [57], the common cold [15] and physiological mechanisms such as wound healing [59], rather than in conditions where the diagnostic criteria are less well established (cf. [8,105]). The spectrum of symptoms reported in the latter conditions is often referred to as functional or medically unexplained [8,18]. ...
... Finally it has been argued that the spectrum of symptoms documented in GWS is similar to that seen in other wars (e.g., [49,105]). However, Haley [38] argues that: (1) the conditions present in other wars (e.g., the American Civil War) were fundamentally different to those in the Persian Gulf; (2) the diagnostic tests for the physical causes of illness were not as developed as they are today; and (3) for certain wars (i.e., the Vietnam War) assessments took place a long time after the cessation of hostilities. ...
Non-specific illness includes a wide variety of symptoms: behavioural (e.g., reduced food and water intake), cognitive (e.g., memory and concentration problems) and physiological (e.g., fever). This paper reviews evidence suggesting that such symptoms can be explained more parsimoniously as a single symptom cluster than as a set of separate illnesses such as Gulf War Syndrome (GWS) and chronic fatigue syndrome (CFS). This superordinate syndrome could have its biological basis in the activity of pro-inflammatory cytokines (in particular interleukin-1: IL-1), that give rise to what has become known as the 'sickness response'. It is further argued that the persistence of non-specific illness in chronic conditions like GWS may be (in part) attributable to a bio-associative mechanism (Ferguson and Cassaday, 1999). In the case of GWS, physiological challenges could have produced a non-specific sickness response that became associated with smells (e.g., petrol), coincidentally experienced in the Persian Gulf. On returning to the home environment, these same smells would act as associative triggers for the maintenance of (conditioned) sickness responses. Such associative mechanisms could be mediated through the hypothalamus and limbic system via vagal nerve innervation and would provide an explanation for the persistence of a set of symptoms (e.g., fever) that should normally be short lived and self-limiting. We also present evidence that the pattern of symptoms produced by the pro-inflammatory cytokines reflects a shift in immune system functioning towards a (T-helper-1) Th1 profile. This position contrasts with other immunological accounts of GWS that suggest that the immune system demonstrates a shift to a Th2 (allergy) profile. Evidence pertaining to these two contrasting positions is reviewed.
... [9][10][11] A range of hypotheses have been proposed for the mechanisms of persisting health changes after being deployed in war theaters: (persistent) infection, abnormal immune response, administration of multiple vaccinations within a short period of time, use of malaria chemoprophylaxis, exposure to blasts, noise, central sensitization, toxicological substances, and environmental factors. [12][13][14][15] Moreover, changes in sympathetic-parasympathetic balance and the tone of the hypothalamic-pituitary-adrenal axis, stress and behavioral responses are also believed to be important factors in pathogenesis. 16,17 Although understanding of etiology of "War symptoms" is of great interest, a better understanding of their incidence and prevalence rates is of similar importance. ...
Objectives
The impact of deployment and combat on mental health of military personnel is well described. Less evidence is available to demonstrate and summarize the incidence, prevalence, and risks of these exposures on physical health. This study aims to (1) systematically review the available literature to determine the incidence and prevalence of physical health conditions among military personnel during and after deployment and (2) investigate the risks of deployment and combat exposure on physical health.
Methods
A systematic review using the PubMed and EMBASE databases was performed. The literature search was limited to articles written in English, published from 2000 through 2019. The quality of studies was assessed with the Joanna Briggs Institute Appraisal Checklist. The results were grouped per system or condition of physical health and presented by forest plots without a combined effect size estimate.
Results
Thirty-two studies were found eligible for this review. We identified a wide variety of incidence and prevalence rates of numerous physical health conditions and a high heterogeneity across the included studies. Acute respiratory symptoms, diarrhea, musculoskeletal injuries, pain, and tinnitus were found to be the most incident or prevalent conditions. Except for hearing loss, no associations with deployment and physical health problems were observed. An increased risk for asthma, headache, hearing loss, and pain was reported in relation to the combat exposure.
Conclusion
Given the characteristics of included studies and extracted data, the magnitude of the found differences in incidence and prevalence rates is most likely to be due to methodological heterogeneity. The specific exposures (e.g., infrastructure, environmental conditions, and activities during deployment) are suggested to be the determinants of (post) deployment physical health problems and need to be addressed to decrease the impact of deployment. Findings from this systematic review highlight which conditions should be addressed in response to service members’ health and wellness needs in the (post)deployment phase and may be used by clinicians, researchers, and policy-makers. However, knowledge gaps regarding the potential risk factors during deployment and combat still exist. Studies using consistent methods to define and measure the physical health conditions and specific exposures are needed.
... ! ! 4 depression, anxiety, alcohol misuse and PTSD more frequently than non-Vietnam veterans and the general population (CDC, 1989;Kubzansky, Koenen, Spiro, Vokonas, & Sparrow, 2007;NVVRS, 1983;O'Toole, Catts, Outram, & Cockburn, 2009;Schnurr & Spirro, 1999;Schnurr & Green, 2004;Soetekouw et al., 2000). In particular, The National Vietnam Veterans Readjustment Study (NVVRS, 1983) was one of the first and largest investigations into the mental health of Vietnam veterans in the United States. ...
Many Vietnam veterans continue to experience poor mental health and a range of complex, psychosocial difficulties decades after their military service. This qualitative study examined the experience of companion animal ownership for twelve male Vietnam veterans using a phenomenological framework. The men in this study were in the developmental stage of older adulthood and mostly owned dogs as companion animals. In-depth interviews were analysed using thematic content analysis and three main themes emerged. These were: Psychosocial functioning, the human-animal bond and the benefits of the human-animal bond. While these findings are typical of other human-animal research, the companion animal characteristics that facilitated a strong attachment, and therefore beneficial relationship seemed strongly influenced by the men’s military background. This has implications for progressing current knowledge around the effect companion animals can potentially have on an individual’s mental health, as well as clinical relevance for psychology.
... As defined by the CDC, cases of multisymptom GWI must have chronic symptoms from at least two of the following three groups: (1) fatigue; (2) mood/cognition (feeling down or depressed, memory problems, difficulty concentrating, trouble finding words, problems falling or staying asleep); and (3) musculoskeletal (joint pain, muscle pain) [55]. Due to biases that regularly occurred in the course of investigations, there is still uncertainty over the exact causal factors of GWI but, among other factors, multiple vaccinations administered within a short period of time have been repeatedly suspected [56]. ...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial and poorly undersood disabling disease. We present epidemiological, clinical and experimental evidence that ME/CFS constitutes a major type of adverse effect of vaccines, especially those containing poorly degradable particulate aluminum adjuvants. Evidence has emerged very slowly due to the multiplicity, lack of specificity, delayed onset, and frequent medical underestimation of ME/CFS symptoms. It was supported by an epidemiological study comparing vaccinated vs unvaccinated militaries that remained undeployed during Gulf War II. Affected patients suffer from cognitive dysfunction affecting attention, memory and inter-hemispheric connexions, well correlated to brain perfusion defects and associated with a stereotyped and distinctive pattern of cerebral glucose hypometabolism. Deltoid muscle biopsy performed to investigate myalgia typically yields macrophagic myofasciitis (MMF), a histological biomarker assessing longstanding persistency of aluminum agglomerates within innate immune cells at site of previous immunization. MMF is seemingly linked to altered mineral particle detoxification by the xeno/autophagy machinery. Comparing toxicology of different forms of aluminum and different types of exposure is misleading and inadequate and small animal experiments have turned old dogma upside down. Instead of being rapidly solubilized in the extracellular space, injected aluminum particles are quickly captured by immune cells and transported to distant organs and the brain where they elicit an inflammatory response and exert selective low dose long-term neurotoxicity. Clinical observations and experiments in sheep, a large animal like humans, confirmed both systemic diffusion and neurotoxic effects of aluminum adjuvants. Post-immunization ME/CFS represents the core manifestation of “autoimmune/inflammatory syndrome induced by adjuvants” (ASIA).
... The presence of these MUS has also been documented across many other wars, including the Civil War, WWI, WWII, and the Vietnam War. For the latter, dioxin (Agent Orange) exposures have been associated with an array of symptoms including fatigue, shortness of breath, heart palpitations, chronic pain, headaches, muscle and joint pain, diarrhea, perspiration, dizziness, fainting, sleep disturbances, and cognitive complaints (Soetekouw et al., 2000). ...
Unlabelled:
Throughout the history of war, exposure to combat has been associated with clusters of physical and psychological symptoms labeled in various ways, from "hysteria" to "shell shock" in World War I to "polytrauma" in Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF).
Objective:
To describe the historical conceptualizations of combat injury and the ways they are relevant to developing current rehabilitation strategies, discuss the symptom complex presented by OEF/OIF veterans, and describe key elements and principles of holistic, integrated care for post-acute OEF/OIF veterans.
Conclusions:
A conceptualization of rehabilitation recognizing a final common pathway of functional disability and suffering is proposed, and both systematic and treatment-specific aspects at the core of a veteran-centered holistic approach are discussed.
... As occurred after the Gulf War, there have been questions about the causes of debilitating symptoms among veterans of more recent deployments. Unique deployment-related illnesses have been postulated, including a Balkan syndrome [53,54], a Cambodia syndrome [55], and a Chechnya syndrome [56]. In addition, the historical record shows that war veterans have experienced unexplained health problems after every major conflict since the US Civil War [57]. ...
Four weeks after the terrorist attacks on the World Trade Center and the Pentagon, US combat troops began bombing missions
over Afghanistan in Operation Enduring Freedom. Additional Reserve and National Guard personnel were called to active duty
to support the war effort and to ensure security throughout the United States. All of these troops will require health care
and assistance during and after this war on terrorism. They will benefit from recent federal legislation that has increased
access to health care and from the changes implemented by the Departments of Defense and Veterans Affairs since the Gulf War.
An innovative Defense Department “Force Health Protection” strategy places greater emphasis on helping service members and
families stay healthy and fit and on preventing injury and illness. The two agencies also have developed new post-deployment
clinical practice guidelines, established deployment research centers, and made further improvements in preventive medicine,
health surveillance, and risk communication and are thus better prepared for this newest generation of war veterans.
... We found very strong associations between these conditions among Gulf War Seabees (table 6). Since previous research has demonstrated much overlap between these diagnoses (31)(32)(33), since Gulf War veteran groups have reported high prevalences of these conditions (19,21,28,29,(34)(35)(36)(37), since using these diagnoses depends on clinician training (38), since there is a long history of multisymptom sequelae after wars (39,40), and since numerous research teams have tried and failed to identify a specific Gulf War syndrome (6,(41)(42)(43), we aggregated the four diagnoses in a working case definition of Gulf War illness. Realizing that not all very symptomatic Gulf War Seabees seek medical evaluation and thus not all could have received the diagnosis of a multisymptom condition, we also classified Gulf War Seabees who self-reported 12 or more medical problems (table 5) as having evidence of Gulf War illness. ...
US Navy Seabees have been among the most symptomatic Gulf War veterans. Beginning in May 1997, the authors mailed Gulf War-era Seabees a health survey in serial mailings. As of July 1, 1999, 68.6% of 17,559 Seabees contacted had returned the questionnaire. Compared with other Seabees, Gulf War Seabees reported poorer general health, a higher prevalence of all 33 medical problems assessed, more cognition difficulties, and a higher prevalence of four physician-diagnosed multisymptom conditions: chronic fatigue syndrome, posttraumatic stress disorder, multiple chemical sensitivity, and irritable bowel syndrome. Because the four multisymptom conditions were highly associated with one another, the authors aggregated them into a working case definition of Gulf War illness. Among the 3,831 (22% cases) Gulf War Seabee participants, multivariable modeling revealed that female, Reserve, and enlisted personnel and participants belonging to either of two particular Seabee units were most likely to meet the case definition. Twelve of 34 self-reported Gulf War exposures were mildly associated with meeting the definition of Gulf War illness, with exposure to fumes from munitions having the highest odds ratio (odds ratio = 1.9, 95% confidence interval: 1.5, 2.4). While these data do not implicate a specific etiologic exposure, they demonstrate a strong association and a high prevalence of self-reported multisymptom conditions in a large group of symptomatic Gulf War veterans.
... 1,2 Many veterans who returned from Vietnam described having somatic illnesses, such as chronic fatigue, insomnia, headaches, dizziness, shortness of breath, and joint pain, without evidence of physical injury, and were eventually identified as suffering from post-traumatic stress disorder (PTSD). 3,4 Furthermore, many of those veterans suffered long-term mental health consequences; in most instances, those problems were not identified during combat operations but presented many years later. 5 Extensive research demonstrated that Vietnam War-era veterans experienced PTSD at rates far higher than those for other noncombat veteran cohorts or the civilian population, with chronic PTSD rates remaining unusually high 20 years after exposure. ...
Comparing outcomes of veterans who served in Vietnam and those who served elsewhere, we examined treatment of post-traumatic stress disorder, treatment of other mental health conditions, psychiatric treatment location, and six mental health well-being measures. The analytic sample consisted of nationally representative data from the 2001 National Survey of Veterans. Analyses included multivariate logistic regression that controlled for sociodemographic characteristics. Of Vietnam War-era veterans in the National Survey of Veterans (N = 7,914), 3,937 served in Vietnam and 3,977 served elsewhere. These veterans were stratified into < 60 years of age (N = 6,141) and > or = 60 years of age (N = 1,766). Veterans who served in Vietnam had notably poorer mental health than did those who served elsewhere. There were striking mental health differences between younger and older veterans; younger veterans had substantially worse measures of mental health. These results suggest greater resource needs among younger Vietnam War veterans. Clinicians and the Department of Veterans Affairs should focus on mental health services for younger veterans.
Aim. To evaluate the effectiveness of the color pulse reflexology (CPR) methods and autogenous training (AT) in rehabilitation programs for patients after myocardial infarction (MI) and coronary artery bypass grafting (CABG). Material and methods. The study included 157 male patients with coronary artery disease aged 53.7 + 4.3 years who had undergone myocardial infarction and CABG surgery for 1 to 2 months. The patients were prescribed a standard program of sanatorium-resort treatment using natural factors and necessary medicines. The first – the control group of patients (CG, 63 people) was added to the AT treatment program, and the second – the main group (MG, 52 people) – the CPR method – 10 sessions of each method. The apparatus «Amulet 201» was used to correct the psycho-emotional state of patients with signals of the green and yellow ranges of the optical spectrum through a visual analyzer. Results. In the first group of patients, people with anxiety-depressive and asthenic syndromes experienced “restructuring” of the personal values scale: significantly reduced irritability, mental and physical fatigue, which contributed to the elimination of astenization, the restoration of nervous and physical potential, the behavioral functions and sleep normalization after a course of the treatment. In the second group of patients with cardiophobic and anxiety-sensing syndromes, there was improvement in well-being, sleep, decreased fatigue and phobic experiences, internal tension and anxiety, intensity and frequency of pain in the heart after the treatment. The majority of patients who took CPR and were re-admitted to sanatorium-resort treatment within 12 months after MI showed a significant improvement in their general condition and quality of life. Conclusion. When identifying asthenic, anxiety-depressive and agrypnia syndromes with an average daily non-dipper curve in cardiac surgery patients, the use of AT and CPR against the background of complex sanatorium-resort treatment in most cases gave a good and stable therapeutic effect, helped to correct the psychological and hemodynamic profiles, restore efficiency and improve the quality of life.
Introduction:
After Operation Desert Storm which took place in Iraq from August 1990 to July 1991 involving a coalition of 35 countries and a 700,000 strong contingent of mainly American men, some associations of war veterans, the media and researchers described a new diagnostic entity: the Gulf War Syndrome (GWS).
Literature findings:
GWS seems to be a new disorder which associates a litany of functional symptoms integrating the musculoskeletal, digestive, tegumentary and neurosensory systems. The symptoms presented do not allow a syndrome already known to be considered and the aetiology of the clinical picture remains unexplained, an increasing cause for concern resulting from the extent of the phenomenon and its media coverage. It quickly appears that there is no consensus amongst the scientific community concerning a nosographic description of GWS: where can all these functional complaints arise from? Different aetiopathogenic hypotheses have been studied by the American administration who is attempting to incriminate exposure to multiple risks such as vaccines and their adjuvants, organophosphorous compounds, pyridostigmine (given to the troops for the preventive treatment of the former), impoverished uranium, and the toxic emanations from oil well fires. But despite extremely in-depth scientific investigations, 10 years after the end of the war, no objective marker of physical suffering has been retained to account for the disorders presented. It would appear that the former soldiers are in even better objective health than the civil population whereas their subjective level of health remains low. Within this symptomatic population, some authors have begun to notice that the psychological disorders appear and persist associating: asthenia, fatigability, mood decline, sleep disorders, cognitive disorders and post-traumatic stress disorder (PTSD). Within the nosological framework, does GWS cause functional disorders or somatisation? Finally, 20 years after the end of the fighting, only PTSD has been causally attributed to military deployment.
Clinical findings:
Certain functional symptoms of GWS occur during the latent phase of a future reexperiencing syndrome, latent phase which is the locus of nonspecific symptoms. The psychotraumatised subject does not express himself spontaneously and waits to be invited to do so: if the social context does not allow this expression, the suffering can remain lodged in a few parts of the body. How can the inexpressible part of the trauma be recounted, particularly if the social context does not allow it? For civil society, calling into question "the somatic word" of veterans is difficult: why were they sent to face these hardships? What could we learn from these soldiers we do not wish to listen to: the horror of the war, the aggressive impulse of men, and the confrontation with death? Another obstacle to this reflection is the reference to stress as a prevalent aetiopathogenic model of the psychological trauma. A model like this, considering that PTSD is a normal reaction to an abnormal situation, finally discredits the subject and society and disempowers them by freezing them in a passive status of victim.
Discussion:
However, as GWS affects approximately a quarter of subjects deployed, it is not very likely that all these symptoms are caused by a psychotraumatic reaction. Many veterans suffering from GWS have themselves rejected the diagnosis of PTSD, arguing that they do not suffer repetition nightmares. What the veterans rightly tell us here is that the notions of stress and trauma cannot strictly be superimposed. A subject may have been intensely stressed without ever establishing traumatic flashbacks and likewise; a psychological trauma can be experienced without stress and without fear but in a moment of terror. This clarification is in line with the first criterion of the DSM-IV-TR which necessarily integrates the objective and subjective dimensions as determinants of PTSD. Yet, scientific studies relating to GWS are struggling to establish opposition or continuity links between the objective external exposure (smoke from petrol wells, impoverished uranium, biological agents, chemicals) and the share of inner emotion albeit reactive and characterised by a subjective stress. There were no lack of stress factors for the troops deployed: repeated alerts of chemical attacks, hostility of the environment with its sandstorms and venomous animals, climatic conditions making long hours of backup and static observation difficult, collecting bodies, lack of knowledge of the precise geography of their movements and uncertainty of the duration of the conflict. The military anti-nuclear-bacteriological-chemical uniform admittedly provided protective confinement, shutting out the hostile world from which the threat would come but, at the same time, this isolation increases the fear of a hypothetical risk whilst the internal perceptions are increased and can open the way to future somatisations. In a context like this, the somatic manifestations of anxiety (palpitations, sweating, paresthesia…) are willingly associated with somatised functional disorders to which can also be assigned over-interpretations of bodily feelings according to a hypochondriacal mechanism. The selective attention to somatic perceptions in the absence of mentalisations, the request for reassurance reiterated and the excessive use of the treatment system will be diagnostic indices of these symptoms caused by the stress. Rather than toxic exposure to such and such a substance, the non-specific syndrome called "Gulf War Syndrome" is the result of exposure to the eponymous operational theatre. But if the psychological and psychosomatic suffering occurring in veterans is immutable throughout history, the expression of these difficulties has specificities according to the past cultural, political and scientific context. In the example of GWS, the diffusion of the fear of a pathology resulting from chemical weapons has promoted this phenomenon. In the end, biochemical and biological weapons have not been used on a large scale but the mediatisation of this possibility has led to a deleterious… To spare the bother of a group psychological reflection, the scientific and political authorities chose to investigate the implication of environmental factors in the genesis of the disorder. At individual as well as social level, rather than accept a psychogenic origin, a common defence mechanism is to assign the suffering to an external cause. With the perspective of preventing the risk of diffusion of other unexplained syndromes, which could occur following future armed conflicts, new epidemiological diagnostic models must be defined. The media also has considerable responsibility for the diffusion of epidemic psychological reactions but at the same time, they can inform the population about certain individual or group psychopathological mechanisms.
Conclusion:
The GWS exists: it is not an "imaginary illness" but a serious public health issue which has led to tens of thousands of complaints and swallowed up millions of dollars. To reply to human suffering, a new nosographic entity can spread through society taking the epidemic expression of a somatised disorder via identification, imitation and suggestion mechanisms. This possibility questions not only mental health but also the sociology and politics. It is necessary to inform the leaders and the general population of the possibility of this type of mass reaction, which can take the shape of a highly contagious complex functional syndrome.
To gain more insight into the prevention of health problems of military personnel after deployment, the Dutch Ministry of Defense has appointed the Prevention and Health Department of the Netherlands Organization for Applied Scientific Research (TNO) to develop a new Health Monitoring Instrument (HMI). The aim was to draft a compact questionnaire that would provide an indication of the general health condition of the individual soldier after deployment. By using the HMI exactly 6 months after the end of deployment and by asking some questions explicitly about the deployment, researchers should be able to use the questionnaire for monitoring both the general health of soldiers and any possible problems related to the soldiers' deployment. Individual health profiles and derived group tables can be generated automatically by using the SPSS program. It is possible to draw up general health profiles with accessory risk profiles. In case an individual soldier scores a 4 or higher, it is advisable to investigate if special care, or an intensification of present care, is desirable. With this health surveillance instrument it is not only possible to monitor a soldier's individual health status, but also the health status of groups.
In Nederland ontwikkelt een aantal militairen en veteranen na uitzending ernstig invaliderende lichamelijke onbegrepen klachten (LOK), met als consequentie hoge medische consumptie en werkverzuim. De klachten bestaan uit chronische vermoeidheid, chronische pijn (hoofd, rug, spieren en gewrichten), duizeligheid en klachten van de luchtwegen of het maag-darmkanaal. Een medische verklaring voor de klachten ontbreekt, als gevolg waarvan deze patiënten vastlopen in onbevredigende diagnostiek en insufficiënte medische zorg. Over de incidentie bestaan geen harde gegevens en ze worden beschreven met een bandbreedte van 3 tot 20 procent van het uitgezonden personeel. De klachten zijn niet missiespecifiek. Er is geen sprake van een nieuw syndroom; dergelijke klachten komen na veel majeure conflicten van de afgelopen decennia voor en kunnen ook samenhangen met de onderliggende mechanismen die ook bij de posttraumatische stressstoornis (PTSS) een rol spelen. Er bestaat momenteel geen effectief behandelplan voor deze patiënten en er is weinig inzicht in de biologische basis voor de klachten.
Patiënten met onverklaarde lichamelijke klachten behoren niet per definitie bij de psychiater, zij hebben dikwijls multipele complexe problemen en zouden het best behandeld kunnen worden door een team van samenwerkende medisch specialisten en paramedici. In deze bijdrage wordt een traject voor functionele revalidatie met cognitieve gedragstherapie, fysiotherapie, casemanagement en psycho-educatie beschreven. De ontwikkeling van een richtlijn voor de diagnostiek en de behandeling van deze klachten zou ten goede komen aan de kwaliteit van de patiëntenzorg, de invaliditeit als gevolg van de klachten verminderen, de mogelijkheden voor reïntegratie bevorderen en het wetenschappelijk onderzoek stimuleren. In het kader van een poli voor LOK bij militairen heeft Defensie hiermee een begin gemaakt.
In 1992 and 1993, Dutch military personnel were deployed in the peace operation UNTAC in Cambodia. Since returning, Cambodia veterans have reported health complaints which they perceive to be related to their service. Their symptoms strikingly resemble health problems reported by Gulf War veterans. Four years post-return, a cross-sectional survey on health symptoms in Cambodia veterans was initiated. Questionnaires were sent to all Cambodia veterans and four comparison groups. Forgetfulness, difficulty concentrating and fatigue were the symptoms most commonly endorsed. An operational case definition was constructed using a validated fatigue severity questionnaire. Cases were not uniquely found in Cambodia veterans (17%). In Rwanda and Bosnia veterans, respectively, 28% and 11% also met our case definition. Fatigue severity level was predicted by pre-mission, during-mission and post-mission variables, of which retrospective recollection of side-effects of vaccines and causal attributions also have been shown to be relevant in studies on Gulf-related illness.
Dutch (ex-)servicemen were deployed in the 1992-3-peace operation UNTAC in Cambodia. Since their return, they have voiced concerns about the health consequences of their service and they have reported symptoms such as fatigue and cognitive problems. The natural course of symptoms in Dutch Cambodia veterans was evaluated in a prospective study.
At 18-months follow-up, a questionnaire was sent to 354 veterans who met a set case definition for symptoms in Cambodia veterans or who had sub-threshold scores. Initial measurement of fatigue severity, psychological well-being, depression, post-traumatic stress disorder, trait-anxiety, self-efficacy and causal attributions, was used to evaluate predictors for self-reported improvement and low levels of fatigue at follow-up.
At follow-up, 19% of the respondents reported complete recovery, 20% felt much better, 57% had the same complaints and 4% had become worse compared with their initial assessment. Self-reported improvement and less severe fatigue at follow-up were predicted by less severe fatigue at initial assessment and more perceived control over symptoms.
Self-reported improvement was reported in a considerable percentage of Cambodia veterans, whereas another substantial percentage of Cambodia veterans continued to suffer with severe levels of fatigue and related symptoms. Predictors of improvement in Cambodia veterans and patients with chronic fatigue syndrome show similarities and also seem to bear importance for Gulf War veterans.
SPARSE DATA:
The Gulf war syndrome remains a little know entity since its first appearance 10 years ago. The objective of our work was to synthesize the data published on the subject in the scientific literature. We analysed the results of American and English epidemiological surveys, from which it was difficult to distinguish the existence of a univocal syndrome.
IMPRECISE DEFINITION:
It is difficult to give a clear clinical definition of the syndrome, the signs of which fluctuate depending on the studies. Chronic fatigue is frequently associated with the Gulf war syndrome, although some studies have described electrophysiological neurological lesions.
NUMEROUS HYPOTHESES:
The role of stress, vaccinations and their adjuvants, exposition to neurotoxic substances and weak uranium have been incriminated. We propose that multiple factors be integrated in the research for the genesis of this atypic syndrome.
Several recent epidemiological studies have shown that vaccinations against biological warfare using pertussis as an adjuvant were associated with the Gulf war syndrome. If such epidemiological findings are confirmed, we propose that the use of pertussis as an adjuvant could trigger neurodegeneration through induction of interleukin-1beta secretion in the brain. In turn, neuronal lesions may be sustained by stress or neurotoxic chemical combinations. Particular susceptibility for IL-1beta secretion and potential distant neuronal damage could provide an explanation for the diversity of the symptoms observed on veterans.
Post-traumatic stress disorder (PTSD) is sometimes put forward as an explanation for unexplained somatic symptoms in military personnel who have been deployed in war or peace missions. Using a cross-sectional postal survey, we investigated whether PTSD symptoms can account for fatigue in Dutch (ex-)servicemen who returned from the peace operation United Nations Transitional Authority for Cambodia and what features distinguish veterans with and without presumptive PTSD diagnoses. Increased PTSD scores were found in 1.3% of 1,698 veterans. There was no concordance between increased PTSD scores and fatigue, as defined in previous studies. Respondents with presumptive PTSD had more often left service, had more often been exposed to severe and potentially traumatic events, and more often reported a greater impact of the mission. Furthermore, they reported more mental problems that they perceived to be service related and they held a stronger causal attribution to post-traumatic stress. In conclusion, presumptive PTSD cannot offer an explanation for fatigue in Cambodia veterans.
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.
Several articles have suggested that immune dysregulation related to Gulf War deployment may be involved in chronic illnesses with an unclear etiology among Gulf War veterans. To determine whether genetic susceptibility related to the human leukocyte antigen (HLA) system might play a role in development of the veterans' illnesses, we examined the frequency distribution of HLA A, B, DR, and DQ antigens from symptomatic veterans residing in south-central Pennsylvania compared with a local healthy population database. Only HLA-A28 demonstrated statistical significance. A28 was present in 7 (21.9%) of 32 of the veterans and 15 (6.9%) of 217 of the healthy population (p = 0.01, Fisher's exact test). This accounts for a minority of the ill veterans tested and is not statistically significant when corrected for the number of antigens determined. We conclude that specific HLA antigens are not strongly associated with the illnesses of Gulf War veterans.
Both laboratory studies on healthy volunteers and epidemiological evidence from patient samples indicate that odor can act as a trigger for the reporting of medically unexplained symptoms (MUSs).
The relationship between concurrent experiences of odor and MUSs has not been explored in a patient sample.
This study used an 8-day fixed-occasion diary study, in which 17 veterans of the Persian Gulf War completed diary assessments of (a) the intensity and duration of odor and sound and (b) MUS severity.
The results showed that the intensity of odor was positively associated with the severity on the same day and subsequent days' symptoms, whereas the duration of odor was negatively related to the severity of MUS reporting on the same day.
These results are consistent with an associative mechanism underlying symptom reporting in veterans. By contrast, the duration, but not the intensity, of sound was related to the severity of MUS reporting on the same day.
Using the strength-of-conclusion scheme enumerated in Box 2, based on two class II studies, there is probably a causal link between deployment to the Persian Gulf theater of operation and the development of the poorly defined multisymptom illness known as GWS (level B). Based on class IV studies, there is insufficient evidence to determine if exposure to toxins encountered during the Persian Gulf war caused GWS (level U). A major limitation of the literature regarding the GWS is the reliance on self-reporting to measure exposure to putative causal toxins. Although objective measures of toxin exposure in GWV generally is unavailable, modeling techniques to estimate exposure levels to low-level nerve agents and smoke from oil well fires have been developed. It would be useful to determine if exposure levels determined by these techniques are associated with GWS. The lack of a clear case definition GWS also hampers research. Some go even further, claiming that the absence of such a definition renders the condition illegitimate. Although an objective marker to GWS would be useful for studies, the absence of such a marker does not make the syndrome any less legitimate. in essence, GWS merely is a convenient descriptive term that describes a phenomenon: GWV reporting suffering from medically unexplained health-related symptoms. In this sense, it shares much with the other medically unexplained syndromes encountered in practice. The real debate surrounding medically unexplained conditions is not whether or not they exist, but defining their cause. In this regard, investigators fall into two camps. One camp insists that the conditions are caused by a yet-to-be-discovered medical problem, rejecting out of hand the possibility of a psychologic origin. The other camp insists the conditions are fundamentally psychogenic rejecting the possibility of an undiscovered medical condition. The evidence shows, however, that the conditions exists, the suffering is real, and the causes are unknown.
Following their participation in a United Nations peacekeeping operation in Cambodia (1992-1993), Dutch veterans complained of symptoms similar to those reported by Gulf War veterans. The authors conducted a matched case-control study to evaluate 76 symptomatic and 32 matched asymptomatic Cambodia veterans on the basis of data collected by postal questionnaire. The number of symptomatic veterans who reported having used insect repellants that contained N,N,-diethyl-meta-toluamide (DEET) during the mission in Cambodia was significantly higher, compared with asymptomatic veterans. The percentage of veterans who reported feeling ill following brief exposures to chemicals such as paint or pesticides was equal in both groups, but the percentage was low compared with the results of other studies of Multiple Chemical Sensitivity Syndrome. The current study was limited by self-report and time delay (potential recall bias) between deployment to Cambodia and the time of survey. Nevertheless, the study results did not support the hypothesis that symptoms in the total group of Cambodia veterans could be related to Multiple Chemical Sensitivity Syndrome.
Reverse transcriptase PCR (RT-PCR) was used for polyribonucleotide assays with sera from deployed Persian Gulf War veterans with the Gulf War Syndrome and a cohort of nonmilitary controls. Sera from veterans contained polyribonucleotides (amplicons) that were obtained by RT-PCR and that ranged in size from 200 to ca, 2,000 bp. Sera from controls did not contain amplicons larger than 450 bp, DNA sequences were derived from two amplicons unique to veterans. These amplicons, which were 414 and 759 nucleotides, were unrelated to each other or to any sequence in gene bank databases. The amplicons contained short segments that were homologous to regions of chromosome 22q11.2, an antigen-responsive hot spot for genetic rearrangements. Many of these short amplicon segments occurred near, between, or in chromosome 22q11.2 Alu sequences. These results suggest that genetic alterations in the 22q11.2 region, possibly induced by exposures to environmental genotoxins during the Persian Gulf War, may have played a role in the pathogenesis of the Gulf War Syndrome. However, the data did not exclude the possibility that other chromosomes also may have been involved. Nonetheless, the detection of polyribonucleotides such as those reported here may have application to the laboratory diagnosis of chronic diseases that have a multifactorial etiology.
Objective:
To provide a multidimensional characterization of fatigue in patients with multiple sclerosis (MS).
Design:
Cross-sectional design. Fifty patients with clinically definite MS were compared on the dimensions of fatigue with 51 patients with chronic fatigue syndrome (CFS) and 53 healthy subjects.
Results:
Fourty-six percent of the patients with MS reported fatigue to be present at least once a week. Patients with MS and patients with CFS had significantly higher subjective fatigue severity scores than healthy subjects. Patients with MS and patients with CFS had significantly higher scores on measures of psychological well-being than healthy subjects. Patients with MS had scores similar to those of patients with CFS, except that patients with CFS had significantly higher somatization scores. High somatization scores reflect strong focusing on bodily sensations. Both groups of patients were significantly less active than the healthy subjects. The Kurtzke Expanded Disability Status Scale (EDSS) and the Beck Depression Inventory scores were not related to subjective fatigue severity. In patients with MS and in patients with CFS, subjective fatigue severity was related to impairment in daily life, low sense of control over symptoms, and strong focusing on bodily sensations. In CFS, but not in MS, evidence was found for a relationship between low levels of physical activity and attributing symptoms to a physical cause and between subjective fatigue severity and physical activity.
Conclusions:
Patients with MS experienced significant fatigue, which had a significant impact on daily functioning and was not related to depression or Expanded Disability Status Scale score. Psychological factors, such as focusing on bodily sensations and low sense of control, play a role in the experience of fatigue in MS and CFS.
This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.
Despite inherent difficulties in defining and measuring stress, a scientific framework has been provided in recent years for
understanding how disruptive life experiences might be translated into altered susceptibility to infectious diseases. Studies
of the effects of stress on pathogenesis of infectious disease are highly relevant to assessment of the biological importance
of the immune impairments that have been associated with stress. With a few notable exceptions, investigations of viral infections
in humans and in animal models support the hypothesis that stress promotes the pathogenesis of such infections. Similar conclusions
can be drawn from studies of bacterial infections in humans and animals and from a small number of studies of parasitic infections
in rodent models. While many of these studies have substantial limitations, the data nonetheless suggest that stress is a
potential cofactor in the pathogenesis of infectious disease. Given recent unprecedented advances in the neurosciences, in
immunology, and in the field of microbial pathogenesis, the relationship between stress and infection should be a fruitful
topic for interdisciplinary research.
The etiology of chronic fatigue syndrome (CFS) is unknown. Some patients have high antibody titers to viral capsid antigen
(VCA) and early antigen (EA) of Epstein-Barr virus (EBV), suggesting that reactivation of EBV is involved. We investigated
virus load (spontaneous transformation) and immunologic regression of EBV-induced transformation in peripheral blood mononuclear
cells (PBMCs) from 10 selected patients with CFS who had high antibody titers to VCA and EA. The outcome was compared with
that for nine healthy controls and one patient with severe chronic active EBV infection (SCAEBV). There were no significant
differences in viral load between patients and healthy controls. Immunologic regression of in vitro-transformed PBMCs was
also equally efficient in patients and controls. The SCAEBV-infected patient and two controls, who were all seronegative for
EBV, showed impaired regression. In conclusion, we were unable to demonstrate a role for reactivation of EBV in CFS, even
in selected patients with high titers of antibody to VCA and EA of EBV.
Because no information exists on the prevalence of chemical sensitivity syndromes such as multiple chemical sensitivities, a questionnaire for use in population studies was developed and tested to assess the presence or absence of chemical sensitivity. Seven hundred five individuals attending clinics answered a questionnaire asking whether each of 122 common substances caused symptoms. Results showed that patients with multiple chemical sensitivities and asthma had average total scores that were significantly different from each other and from those of each of the other diagnostic categories. Higher total scores were also reported by female patients. The instrument described here may facilitate meaningful prevalence studies of multiple chemical sensitivities. It will also allow study of chemically induced symptoms in other conditions such as asthma.
The possible role of enteroviral persistence in the etiology of the chronic fatigue syndrome (CFS) was investigated by serological
testing, VP-1 antigen testing, and polymerase chain reaction (PCR) analysis of stool specimens as well as by viral cultures
of stool—both direct and after acid treatment. No differences between 76 patients with disabling unexplained fatigue and 76
matched controls were found by serological or antigen testing. Furthermore, no enteroviruses were isolated from any stool
culture. Enterovirus was detected by PCR in one stool specimen from a patient with CFS but was not detectable in a second
sample obtained from the same patient 3 months later. All stool specimens from controls were PCR-negative. These results argue
against the hypothesis that enteroviruses persist in patients with CFS and that their persistence plays a role in the pathogenesis
of this syndrome.
The Department of Veterans' Affairs, Jackson, Mississippi, and the Mississippi State Department of Health conducted a collaborative investigation of an apparent increase in the numbers of birth defects and other health problems among children born to veterans of two Mississippi National Guard units who had served in the Persian Gulf War. The medical records of all children conceived by and born to veterans of the two units after deployment were reviewed; observed numbers of birth defects and other health problems were compared with expected numbers using rates from birth defect surveillance systems and previous surveys. The total number of all types of birth defects was not greater than expected, but whether the number of specific birth defects was greater than expected could not be determined. The frequency of premature birth, low birth weight, and other health problems appeared similar to that in the general population.
The Vietnam Experience Study was a multidimensional assessment of the health of Vietnam veterans. From a random sample of enlisted men who entered the US Army from 1965 through 1971, 7924 Vietnam and 7364 non-Vietnam veterans participated in a telephone interview; a random subsample of 2490 Vietnam and 1972 non-Vietnam veterans also underwent a comprehensive medical examination. During the telephone interview, Vietnam veterans reported current and past health problems more frequently than did non-Vietnam veterans, although results of medical examinations showed few current objective differences in physical health between the two groups. The Vietnam veterans had more hearing loss. Also, among a subsample of 571 participants who had semen samples evaluated, Vietnam veterans had lower sperm concentrations and lower mean proportions of morphologically “normal” sperm cells. Despite differences in sperm characteristics, Vietnam and non-Vietnam veterans have fathered similar numbers of children.
Consensus criteria for the definition of multiple chemical sensitivity (MCS) were first identified in a 1989 multidisciplinary survey of 89 clinicians and researchers with extensive experience in, but widely differing views of, MCS. A decade later, their top 5 consensus criteria (i.e., defining MCS as [1] a chronic condition [2] with symptoms that recur reproducibly [3] in response to low levels of exposure [4] to multiple unrelated chemicals and [5] improve or resolve when incitants are removed) are still unrefuted in published literature. Along with a 6th criterion that we now propose adding (i.e., requiring that symptoms occur in multiple organ systems), these criteria are all commonly encompassed by research definitions of MCS. Nonetheless, their standardized use in clinical settings is still lacking, long overdue, and greatly needede-specially in light of government studies in the United States, United Kingdom, and Canada that revealed 2-4 times as many cases of chemical sensitivity among Gulf War veterans than undeployed controls. In addition, state health department surveys of civilians in New Mexico and California showed that 2-6%, respectively, already had been diagnosed with MCS and that 16% of the civilians reported an 'unusual sensitivity' to common everyday chemicals. Given this high prevalence, as well as the 1994 consensus of the American Lung Association, American Medical Association, U.S. Environmental Protection Agency, and the U.S. Consumer Product Safety Commission that 'complaints [of MCS] should not be dismissed as psychogenic, and a thorough workup is essential', we recommend that MCS be formally diagnosed-in addition to any other disorders that may be present-in all cases in which the 6 aforementioned consensus criteria are met and no single other organic disorder (e.g., mastocytosis) can account for all the signs and symptoms associated with chemical exposure. The millions of civilians and tens of thousands of Gulf War veterans who suffer from chemical sensitivity should not be kept waiting any longer for a standardized diagnosis while medical research continues to investigate the etiology of their signs and symptoms.
To the Editor.
—If the National Institutes of Health (NIH) Technology Assessment Workshop report on Operation Desert Storm syndrome/illnesses was meant to address fears that these illnesses are not being taken seriously and to establish practical working case definitions for the chronic illnesses associated with Operations Desert Shield and Desert Storm, it was not an auspicious start. After listening to the health complaints of numerous veterans of Operations Desert Shield and Desert Storm, including our stepdaughter and her colleagues who served in the US Army's 101st Airborne Division, and complaints about their inability to convince military hospitals and Veterans Affairs medical centers that they are suffering from a possible syndrome with the same major symptoms listed in the workshop report, we attempted to suggest that many of these symptoms can be explained by aggressive pathogenic mycoplasma infections, such as Mycoplasma incognitus or Mycoplasma penetrans,2 and they should be treatable
FOLLOWING the return of US and coalition forces from the complex environment of the Persian Gulf region during Operations Desert Shield and Desert Storm and the operational conditions of the military deployment, a variety of health effects have been reported. Many troops were exposed to potentially adverse substances and experiences present in this wartime environment, fumes and smoke from military operations, oil well fires, diesel exhaust, toxic paints, pesticides, sand, depleted uranium, infectious agents, chemoprophylactic agents, and multiple immunizations; some troops are convinced they were exposed to chemical or biological weapons. Few combat casualties occurred, but substantial transient gastrointestinal and respiratory symptoms were seen during the troop buildup and immediately after the short conflict. Since then, there have been increasing reports of illness from troops who were participants in these operations, and many attribute their health problems to these experiences. Many of the cases include combinations of nonspecific symptoms of
Between August 1990 and March 1991, the United States deployed 697 000 troops to the Persian Gulf to liberate Kuwait from Iraqi occupation. Since the Gulf War, most veterans seeking medical care at Departments of Veterans Affairs and Defense medical facilities have had diagnosable conditions, but the symptoms of several thousand veterans have not been readily explained. The most commonly reported, unexplained complaints have been chronic fatigue, rash, headache, arthralgias/myalgias, difficulty concentrating, forgetfulness, and irritability. These symptoms have not been localized to any one organ system, and there has been no consistent physical sign or laboratory abnormality that indicates a single specific disease. Because of the unexplained illnesses being experienced by some Gulf War troops, a comprehensive clinical and research effort has been organized by the Departments of Veterans Affairs, Defense, and Health and Human Services to provide care for veterans and to evaluate their medical problems. To determine the causes and most effective treatments of illnesses among Gulf War veterans, a thorough understanding of all potential health risks associated with service in the Persian Gulf is necessary. These risks are reviewed in this article and include possible reactions to prophylactic drugs and vaccines, infectious diseases, and exposures to chemicals, radiation, and smoke from oil fires.(Arch Intern Med. 1995;155:262-268)
The absence of laboratory tests and clear criteria to identify homogeneous (sub)groups in patients presenting with unexplained fatigue, and to assess clinical status and disability in these patients, calls for further assessment methods. In the present study, a multi-dimensional approach to the assessment of chronic fatigue syndrome (CFS) is evaluated. Two-hundred and ninety-eight patients with CFS completed a set of postal questionnaires that assessed the behavioural, emotional, social, and cognitive aspects of CFS. By means of statistical analyses nine relatively independent dimensions of CFS were identified along which CFS-assessment and CFS-research can be directed. These dimensions were named: psychological well-being, functional impairment in daily life, sleep disturbances, avoidance of physical activity, neuropsychological impairment, causal attributions related to the complaints, social functioning, self-efficacy expectations, and subjective experience of the personal situation. A description of the study sample on these dimensions is presented.
Stress modulates a variety of immune responses. We investigated the effects of immobilization stress on the pathogenesis of acute murine toxoplasmosis, an infection in which cell-mediated immunity is of major importance in host defense. Repetitive over-night immobilization beginning 3 days prior to infection enhanced (p < 0.05) the mortality of mice infected with a virulent strain (C56) of Toxoplasma gondii (77% vs 15% mortality in restrained and control mice, respectively). Daily immobilization for 14 days prior to infection abrogated (p < 0.05) the lethal effect of immobilization, suggesting an adaptive mechanism. To explore the effect of immobilization with a less virulent strain, the Me49 strain of T. gondii was studied. Acute infection with T. gondii Me49 resulted in anorexia and weight loss, while spleen size and respiratory burst activity of peritoneal exudate cells were enhanced (p < 0.01). Immobilization (twice daily for 2 h) did not significantly alter survival or other clinical features of acute T. gondii infection. In addition, immobilization suppressed (p < 0.05) phorbol myristate acetate-stimulated release of superoxide anion by peritoneal exudate cells in healthy naive mice, but not in infected mice. These findings indicate that immobilization stress can alter the pathogenesis of acute T. gondii infection in healthy mice, but the effect of this stress paradigm will be influenced, in part, by the timing of the immobilization and the virulence of the strain of T. gondii.
To the Editor.—
Agent Orange is an herbicide containing equal parts of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. It was used extensively in Vietnam as a defoliant. A toxic contaminant is dioxin, 2,3,7,8 tetrachlorodibenzo-p-dioxin.A ten-month study of 78 Vietnam veterans who claimed exposure to Agent Orange yielded many findings: 85% of the men experienced a rash that was resistant to treatment. Using immunofluorescence in one patient, a skin biopsy specimen showed intraepithelial and intercellular IgA, IgG, and IgM. In 53% of the patients, the rash was aggravated by sunlight.Joint pain occurred in 71%, stiffness in 59%, and swelling in 45%. Hypersomnolence occurred in 44% of the men and extreme fatigue in 80%. Sinus bradycardia and premature ventricular contractions were not infrequent.Persistent neurological complaints were tingling (55%), numbness (60%), dizziness (69%), headache (35%), and autonomic dyscontrol (18%). Severe psychiatric manifestations were depression (73%), suicidal attempts (8%), and
Tritiated arginine-vasopressin (AVP), desglycinamide-vasopressin (DGAVP), chicken gonadotropin releasing hormone (GnRH) or carbetocin were injected intracarotidally into rats exposed to a restraint stress for 60 min. The peptide accumulations were determined in 9-13 brain regions and anterior pituitary. In separate experiments the cerebral blood flow was measured. The blood supply to the brain was decreased in stressed animals as indicated by: 1. significant decrease (17-50%) of cerebral blood flow; 2. diminished accumulation of tritiated AVP in the regions lacking a blood-brain barrier (BBB). Consequently, the values of peptide accumulation were corrected for the changed blood supply. Compared with control animals, restraint stress induced a higher accumulation of AVP (+41%), DGAVP (+60%), carbetocin (+81%) and GnRH (+104%).
The authors examined how the self-reported health of 7,924 US Army Vietnam veterans in 1985-1986 related to the men's perceived exposure to herbicides and combat in Vietnam. The results showed strong, positive associations between the extent of reported herbicide exposure (classified as a four-level ordinal index) and all 21 health outcomes studied, with clear "dose-response" relations in most instances. In contrast, only chloracne and psychological symptoms, including a symptom pattern consistent with posttraumatic stress disorder, were found to be strongly related to the amount of reported combat exposure (classified as a four-level ordinal index). The multiple herbicide/outcome associations seem implausible because of their nonspecificity and because of collateral biologic evidence suggesting the absence of widespread exposure to dioxin-containing herbicides among US Army combat units. These associations may have resulted from long-term stress reactions that produced somatization, hypochondriasis, and increased utilization of medical care among some Vietnam veterans. The available data suggest, however, that the association between reported combat exposure and psychological symptoms consistent with posttraumatic stress disorder may be causal.
Chronic fatigue syndrome (CFS) is an idiopathic disorder in which the chief symptoms is profound fatigue. To explore the relationship between immune stimulation and fatigue, we developed a murine model for quantifying fatigue: reduction in voluntary running and delayed initiation of grooming after swimming. Inoculation of female BALB/c mice with Corynebacterium parvum antigen or the relatively avirulent Me49 strain of Toxoplasma gondii induced fatigue: baseline running reduced to less than 50 and 30% for 8 and 14 days, respectively, and delayed initiation of grooming after swimming in both immunologically stimulated groups. A threefold evaluation of serum transforming growth factor-beta levels, a cytokine increased in CFS patients, was found in fatigued C. parvum- and T. gondii-inoculated mice. This murine model appears promising for investigation of the pathogenesis of immunologically mediated fatigue.
The status of the blood-brain barrier (BBB) was examined following short-term forced swimming (FS) exercise in younger rats (age 8-9 wks, 80-90 g). Subjection of animals to continuous FS for 30 min duration increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in 5 and 8 brain regions, respectively. Extravasation of the tracers was markedly pronounced in the cerebellum followed by the cerebral cortex. EBA staining was confined mainly to the posterior cingulate cortex, parietal and occipital cortices, whole cerebellar vermis and the mediolateral cerebellar cortices as well as the dorsal surface of the hippocampus. In addition to the above brain regions. BBB permeability to 131I-sodium extended to the caudate nucleus, thalamus and hypothalamus. At this time period, the serotonin (5-hydroxytryptamine, 5-HT) content showed a profound increase in plasma and brain of about 150% and 250% respectively from the control value. Pretreatment with p-CPA (p-chlorophenylalanine, a serotonin synthesis inhibitor) prevented both the increased permeability of the BBB and the rise in plasma and brain 5-HT level. However, prior treatment with cyproheptadine (a 5-HT2 receptor antagonist) prevented the increased permeability alone. The 5-HT level continued to remain high. These results suggest that short-term FS increases BBB permeability in specific brain regions. This increased permeability appears to be mediated through serotonin via 5-HT2 receptors.
The effects of swimming exercise on the pathogenesis of acute murine toxoplasma infection were studied. Swimming (45 min/day) initiated on the day of inoculation with the avirulent Me49 strain of Toxoplasma gondii did not alter survival of infected mice. At a later stage of infection, daily swimming appeared to promote the recovery of appetite and weight gain. Immune activation was apparent in toxoplasma-infected mice, and swimming blunted splenic enlargement but not the respiratory burst activity of peritoneal exudate cells. Infection caused a significant elevation of serum tumor necrosis factor (TNF) levels which was attenuated by a daily swimming program. These data show that swimming exercise is not deleterious to mice acutely infected with T. gondii Me49 and that the more rapid recovery in exercised mice is associated with reduced serum TNF levels.
Pyridostigmine bromide, a reversible inhibitor of acetylcholinesterase (AChE), is effectively used as a pre-treatment to organophosphate intoxication. Previous studies have shown that an oral dose of 30 mg twice a day produces a sufficient inhibition of the enzyme activity (20-40%) without causing any significant adverse effect. During the Persian Gulf war pyridostigmine was taken for the first time under a chemical warfare threat. We searched for symptoms and complaints that may be related to the medication. Our survey included 213 soldiers who completed a questionnaire regarding possible symptoms and their severity. AChE inhibition level was compared between groups of soldiers with and without complaints. The most frequent symptoms were nonspecific and included dry mouth, general malaise, fatigue and weakness. Typical effects, such as nausea, abdominal pain, frequent urination and rhinorrhea, were infrequent. The severity of the symptoms was generally mild. The symptoms appeared around 1.6 h after taking the medication and recurred after each intake. No correlation was found between levels of cholinesterase and type or severity of complaints. Anxiety, which accompanies wartime, may have contributed to the appearance of significant symptoms. Further investigations concerning the effects of pyridostigmine ingestion under stressful conditions are warranted.
Effects of cold or isolation stress on brain penetration by the neurovirulent noninvasive Sindbis virus strain (SVN) were studied in mice. SVN injected intracerebrally (i.c.) causes acute encephalitis and kills adult mice but is unable to invade the brain and kill when injected intraperitoneally (i.p.). Mice inoculated i.p. with SVN were exposed to cold stress or were singly housed. Both stress patterns induced SVN encephalitis and death in 42% (cold) and 37% (isolation) of the tested mice. No death was observed in the control injected mice. Brain virus levels were found to be more than 10(6) PFU in all dying mice. No virus was detected in the control group brains. The virus that was isolated from the brains of moribund mice demonstrated no changes in neuroinvasive and neurovirulent properties. We suggest a stress induced blood-brain-barrier opening with subsequent virus entrance as the mechanism of stress induced SVN encephalitis.
A double blind study of daily doxycycline (100 mg) vs. weekly mefloquine (250 mg) was performed on United States soldiers training in Thailand to assess the effect of doxycycline malaria prophylaxis on the incidence of gastrointestinal infections. During a 5 week period, 49% (58/119) of soldiers receiving doxycycline and 48% (64/134) of soldiers receiving mefloquine reported an episode of diarrhea. Infection with bacterial enteric pathogens was identified in 39% (47/119) of soldiers taking doxycycline and 46% (62/134) of soldiers taking mefloquine. Forty-four percent (59/134) of soldiers receiving mefloquine and 36% (43/119) of soldiers receiving doxycycline were infected with enterotoxigenic Escherichia coli (ETEC), while 9% (12/134) of soldiers receiving mefloquine and 4% of soldiers receiving doxycycline were infected with Campylobacter. Side effects from either medication were minimal. After 5 weeks in Thailand, the percent of non-ETEC strains resistant to greater than or equal to 2 antibiotics increased from 65% (77/119) to 86% (95/111) in soldiers on mefloquine and from 79% (84/106) to 93% (88/95) in soldiers on doxycycline. Doxycycline prophylaxis did not prevent or increase diarrheal disease in soldiers deployed to Thailand where ETEC and other bacterial pathogens are often resistant to tetracyclines.
A health survey of 2,039 persons in 606 households located near the Stringfellow Hazardous Waste Disposal site, Riverside County, California, and in a reference community was conducted to assess whether rates of adverse health outcomes were elevated among persons living near the site. Data included a household questionnaire, medical records of reported cancers and pregnancies, and birth and death certificates. The study areas appeared similar with respect to mortality, cancer incidence, and pregnancy outcomes. In contrast, rate ratios were greater than 1.5 for 5 of 19 reported diseases, i.e., ear infections, bronchitis, asthma, angina pectoris, and skin rashes. Prevalence odds ratios for 23 symptoms were uniformly greater than 1.0, and 8 symptoms had odds ratios greater than 1.5: blurred vision, pain in ears, daily cough for more than a month, nausea, frequent diarrhea, unsteady when walking, and frequent urination. The apparent broad-based elevation in reported diseases and symptoms may reflect increased perception or recall of conditions by respondents living near the site. These results indicate that future community-based health studies should include medical and psychosocial assessment instruments sufficient to distinguish between changes in health status and effects of resident reporting tendency.
The syndrome variously called Da Costa's syndrome, effort syndrome, neurocirculatory asthenia, etc has been studied for more than 100 years by many distinguished physicians. Originally identified in men in wartime, it has been widely recognised as a common chronic condition in both sexes in civilian life. Although the symptoms may seem to appear after infections and various physical and psychological stresses, neurocirculatory asthenia is most often encountered as a familial disorder that is unrelated to these factors, although they may aggravate an existing tendency. Respiratory complaints (including breathlessness, with and without effort, and smothering sensations) are almost universal, and palpitation, chest discomfort, dizziness and faintness, and fatigue are common. The physical examination is normal. The aetiology is obscure but patients usually have a normal life span. Reassurance and measures to improve physical fitness are helpful.
A household health survey of residents living near two hazardous waste disposal sites in Calcasieu Parish, Louisiana was conducted in 1981-1982 as part of a comprehensive study of the effects of those sites on the environment and on the health of nearby residents. An unexposed community was included in the health survey for comparison. Due to media coverage and public concern about the sites, two potential indices of reporting bias, hypochondriasis and respondent's opinion about the environmental effects of waste sites, were included in the survey. Because air and water quality data showed little evidence that hazardous concentrations of chemicals were being released from the sites, questions were raised about the interpretation of the health survey data. The data were analyzed, therefore, for the association between symptom reports and the potential indices of reporting bias. Hypochondriasis scores were associated with symptom reports regardless of location of residence while an individual's opinion showed a different pattern by area of residence. Respondents living near one of the waste disposal sites who answered "yes" to the opinion question were 2-3 times more likely to report some types of symptoms than residents of the comparison community. In contrast, there was little difference in symptom reports between the exposed and comparison communities for those answering "no" to the opinion question. The usefulness of self-reported symptom data in studies of communities near hazardous waste disposal sites is discussed, and attention is called to the need to develop measures sensitive to reporting bias in epidemiologic studies.
Synopsis
A review is presented of literature describing cardiovascular manifestations of anxiety until the end of the second World War. Clear observations of this important group of somatic anxiety symptoms have been made throughout history, although then, as now, the interpretation of these observations has varied according to the point of view and orientation of the writer. An understanding of the interrelationships between somatic and psychic symptoms of anxiety is particularly necessary now that certain specific symptomatic treatments are available.
The regional capacity of the blood-brain barrier (BBB) has been investigated in rat brain during normal conditions and after acute immobilization (IMO). The BBB function was monitored by fluorescence microscopical localization of systemically administered vital dye (trypan blue) and by studying the ability of the brain capillaries to decarboxylate and trap injected L-DOPA. The results demonstrated clear signs of dye penetration into the parenchyma of certain brain regions (area preoptica, some hypothalamic nuclei, area ventralis tegmenti and ventral part of the pons and medulla oblongata) in addition to the areas known to be 'outside the BBB' (the circumventricular organ). There was an an apparent increase in dye penetration in these regions after IMO, most pronounced in the reticular formation of the brain stem. In the mesencephalic reticular formation ruptures of a substantial number of vessels occurred after IMO leading to massive leakage of dye into surrounding brain parenchyma. The main finding after L-DOPA administration was indications of a more efficient decarboxylation and trapping of L-DOPA in most brain regions after IMO. The findings of dye penetration in certain brain regions, which are known to be involved in autonomic regulation, may reflect possible ways of chemical communication between the circulation and neuronal structures in these regions and/or possibly constitute the basis for inactivation processes for transport of substances outwards from the brain as well as potential loci for adverse effects and development of pathological conditions.
An assessment was conducted of the impact of infectious diseases on the 697,000 U.S. troops deployed to the Persian Gulf during
1990–1991 in Operations Desert Shield and Desert Storm. The incidence of nonbattle injuries, including infectious diseases,
during this conflict was lower than during previous wars involving U.S. military personnel. The major reported causes of morbidity
were generally mild cases of acute diarrheal and upper respiratory disease. The most unexpected outcome was the lack of arboviral
infections, particularly sandfly fever, and the occurrence among U.S. troops of 12 cases of visceral leishmaniasis due to
Leishmania tropica. The fact that infectious diseases were not a major cause of lost manpower, in sharp contrast to the experience among military
personnel in World War II, can be attributed to a combination of factors: the presence of a comprehensive infrastructure of
medical care, extensive preventive medicine efforts, and several fortuitous circumstances. Beneficial conditions that may
not be present in future conflicts in this region include isolation of most combat troops to barren desert locations during
the cooler, winter months, which provided the least favorable conditions for transmission of arthropod-borne diseases.
EDITOR,—Since my predecessor last wrote to the BMJ1 the number of patients concerned about their health in relation to service during the Gulf war in 1990-1 who have undergone systematic assessment by the defence medical services has risen to 200. Our assessment programme is being subjected to clinical audit by the Royal College of Physicians. When the programme is complete a detailed report will be published; meanwhile, I offer this summary of our findings.
Some 45000 British personnel were involved …
To investigate the relation between severity of complaints, laboratory data and psychological parameters in patients with chronic fatigue syndrome (CFS).
Eighty-eight patients with CFS and 77 healthy controls matched for age, sex and geographical area.
Patients and controls visited our outpatient clinic for a detailed medical history, physical examination and psychological tests: Checklist Individual Strength (CIS). Beck Depression Inventory (BDI) and Sickness Impact Profile (SIP). Venous blood was drawn for a complete blood cell count, serum chemistry panel, C-reactive protein and serological tests on a panel of infectious agents.
All patients fulfilled the criteria for CFS as described by Sharpe et al. (J R Soc Med 1991; 84: 118-21), only 18 patients (20.5%) fulfilled the CDC criteria. The outcome of serum chemistry tests and haematological tests were within the normal range. No significant differences were found in the outcome of serological tests. Compared to controls, significant differences were found in the results on the CIS, the BDI, and the SIP. These results varied with the number of complaints (CDC criteria). When the number of complaints was included as the covariate in the analysis, there were no significant differences on fatigue severity, depression, and functional impairment between patients who fulfilled the CDC criteria and patients who did not.
It is concluded that the psychological parameters of fatigue severity, depression and functional impairment are related to the clinical severity of the illness. Because the extensive panel of laboratory tests applied in this study did not discriminate between patients and controls, it was not possible to investigate a possible relation between the outcomes of psychological and laboratory testing.
EDITOR,—Tony Revell's letter concerning the 200 personnel now assessed by the Ministry of Defence raises more questions than it answers.1 Not the least is why it has taken over four years for the Ministry of Defence to start assessing these men and women when so many complaints were made soon after their return from the Gulf in 1991. Since 98% are (by the Ministry of Defence's own submission) …
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Mefloquine hydrochloride is now one of the major antimalarial drugs used both in prophylactic and therapeutic regimens. Large-scale studies have shown that it is efficacious and relatively well tolerated. However, some severe side effects, particularly neuropsychiatric reactions, have been described. We describe two young men with no previous medical history who experienced severe psychiatric reactions during prophylactic and curative mefloquine therapy. In both cases, full recovery was rapid after cessation of the therapy. There is no explanation for these reactions. Serum levels of mefloquine were within the normal range. The absence of contraindications and minor side effects during an initial course of mefloquine should be confirmed before another course is prescribed.
The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.