Chronic Fatigue Syndrome: US Federal Service

Fostel J, Boneva R, Lloyd A. · National Center for Toxicogenomics, NIEHS MD F1-05, 111 Alexander Drive, PO Box 12233, Research Triangle Park, NC 27709-2233, USA. · Pharmacogenomics. · Pubmed #16610954 No free full text.

Abstract: OBJECTIVE: To identify biomarkers of chronic fatigue syndrome (CFS) and related disorders through analysis of microarray data, pathology test results and self-report symptom profiles. METHOD: To empirically derive the symptom domains of the illnesses, factor analysis was performed on responses to self-report questionnaires (multidimensional fatigue inventory, Centers for Disease Control and Prevention (CDC) symptom inventory and Zung depression scale) before validation with independent datasets. Gene expression patterns that distinguished subjects across each factor dimension were then sought. RESULTS: A four-factor solution was favored, featuring 'fatigue' and 'mood disturbance' factors. Scores on these factors correlated with measures of disability on the Short Form (SF)-36. A total of 57 genes that distinguished subjects along each factor dimension were identified, although the separation was significant only for subjects beyond the extreme (15th and 85th) percentiles of severity. Clustering of laboratory parameters with expression of these genes revealed associations with serum measurements of pH, electrolytes, glucose, urea, creatinine, and liver enzymes (aspartate amino transferase [AST] and alanine amino transferase [AST]); as well as hematocrit and white cell count. CONCLUSION: CFS is a complex syndrome that cannot simply be associated with changes in individual laboratory tests or expression levels of individual genes. No clear association with gene expression and individual symptom domains was found. However, analysis of such multifacetted datasets is likely to be an important means to elucidate the pathogenesis of CFS.

Carmel L, Efroni S, White PD, Aslakson E, Vollmer-Conna U, Rajeevan MS. · National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA. · Pharmacogenomics. · Pubmed #16610948 No free full text.

Abstract: OBJECTIVES: To identify the underlying gene expression profiles of unexplained chronic fatigue subjects classified into five or six class solutions by principal component (PCA) and latent class analyses (LCA). METHODS: Microarray expression data were available for 15,315 genes and 111 female subjects enrolled from a population-based study on chronic fatigue syndrome. Algorithms were developed to assign gene scores and threshold values that signified the contribution of each gene to discriminate the multiclasses in each LCA solution. Unsupervised dimensionality reduction was first used to remove noise or otherwise uninformative gene combinations, followed by supervised dimensionality reduction to isolate gene combinations that best separate the classes. RESULTS: The authors' gene score and threshold algorithms identified 32 and 26 genes capable of discriminating the five and six multiclass solutions, respectively. Pair-wise comparisons suggested that some genes (zinc finger protein 350 [ZNF350], solute carrier family 1, member 6 [SLC1A6], F-box protein 7 [FBX07] and vacuole 14 protein homolog [VAC14]) distinguished most classes of fatigued subjects from healthy subjects, whereas others (patched homolog 2 [PTCH2] and T-cell leukemia/lymphoma [TCL1A]) differentiated specific fatigue classes. CONCLUSION: A computational approach was developed for general use to identify discriminatory genes in any multiclass problem. Using this approach, differences in gene expression were found to discriminate some classes of unexplained chronic fatigue, particularly one termed interoception.

Engel CC. · Department of Psychiatry, F. Edward Hebert School of Medicine of Uniformed Services University of Health Sciences, Bethesda, MD 20814-4799, USA. · CNS Spectr. · Pubmed #16575379 links to  free full text

Abstract: In recent years, research-methods literature mainly addressing controlled clinical trials has arisen regarding explanatory and pragmatic treatment trials. Explanatory trials tend to examine causal mechanisms and questions of efficacy and value internal validity (creating optimal study conditions) over generalizability (using study results to understand treatment effects in real-life patient populations). In contrast, pragmatic trials value "external relevance" (generalizability) of study results over "internal elegance" so that clinicians and health policymakers can better understand how treatments might impact their patients and policies. This review draws inspiration from these contrasting explanatory and pragmatic perspectives and develops them for clinical and research pertaining to idiopathic physical symptoms and related syndromes (eg, somatization disorder, chronic fatigue syndrome, multiple chemical sensitivities, irritable bowel syndrome). Explanatory and pragmatic perspectives are used to examine these idiopathies with regard to causation, case definition, labels, and treatment. It is concluded that idiopathic symptom syndromes are fundamentally pragmatic clinical and research challenges. For epidemiologic and methodologic reasons, the complex explanations for these syndromes remain largely elusive. Even so, scientific and clinical pragmatism offers the opportunity to reduce disagreement between competing medical disciplines and between clinicians and affected patients with regard to irreconcilable etiologic questions and to remain evidence-based in the care of patients.

Ocasio-Tascón ME, Alicea-Colón E, Torres-Palacios A, Rodríguez-Cintrón W. · San Juan VA Medical Center, 10 Casia Street, Pulmonary and Critical Care Section (111E), San Juan, 00927-5800, Puerto Rico. · Sleep Breath. · Pubmed #16496117 No free full text.

Abstract: Sleep complaints are very common among the general population and are usually accompanied by significant medical, psychological and social disturbances (Redline S, Strohl K, Otolaryngol Clin North Am, 132:303, 1999). A higher prevalence of sleep complaints has been described in the elderly (Vgontzas AN, Kales A, Annu Rev Med, 50:387-400, 1999). It is manifested by breathing disturbances during sleep, loud snoring, difficulties maintaining sleep, fatigue, daytime sleepiness, mood effects and impairment of daily activities (Lugaresi E, Cirignotta F, Zucconi M et al., Good and poor sleepers: an epidemiological survey of the San Marino population, Raven, New York, pp 1-12, 1983; Kales A, Soldatos CR, Kales JD, Am Fam Physician, 22:101-108, 1980). It has been associated with cardiovascular, endocrine and neurocognitive manifestations. Growing interest in early diagnosis and treatment has been noted in recent years based on emerging knowledge about the potential health consequences when the disease goes untreated (Nanen AM, Dunagan DP, Fleisher A et al., Chest, 121:1741, 2002). The veteran population in the mainland has a higher tendency for obesity, high blood pressure (HBP), sleep disorders and chronic alcohol consumption (Mustafa M, Erokwu N, Ebose I, Strohl K, Sleep Breath, 9:57-63, 2005). The Hispanic veteran population has never been studied in detail for sleep disorders and related conditions. We used previously validated screening tools for sleep disturbance breathing. Two hundred and forty-five questionnaires were administered. We found a higher prevalence of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in our population compared with data from the mainland (USA). The mean age was 64 years (+/-11). Ninety seven per cent were males. The mean body mass index was 25 kg/cm(2); mean Epworth Sleepiness Scale score was 8. Thirty-four per cent met high-risk criteria for sleep apnea, 53% for insomnia, 13% for symptoms suggestive of narcolepsy and 13% for those suggestive of restless leg syndrome. There were high incidences of alcohol consumption (37.6%), diabetes (32.7%), hypercholesterolemia (31.8%), depression (31.8%), hypertension (39.6%) and post-traumatic stress disorder (PTSD) (9.8%).

Bell IR, Brooks AJ, Baldwin CM, Fernandez M, Figueredo AJ, Witten ML. · Research Service, Southern Arizona VA Health Care System, USA. · Aviat Space Environ Med. · Pubmed #16385767 No free full text.

Abstract: INTRODUCTION: Previous research indicates that a large cohort of veterans from the 1991 Gulf War report polysymptomatic conditions. These syndromes often involve neurocognitive complaints, fatigue, and musculoskeletal symptoms, thus overlapping with civilian illnesses from low levels of environmental chemicals, chronic fatigue syndrome, and fibromyalgia. METHODS: To test for time-dependent changes over repeated intermittent exposures, we evaluated objective performance on a computerized visual divided attention test in chronically unhealthy Gulf War veterans (n = 22 ill with low-level chemical intolerance (CI); n = 24 ill without CI), healthy Gulf War veterans (n = 23), and healthy Gulf War era veterans (n = 20). Testing was done before and after each of three weekly, double blind, low-level JP-8 jet fuel or clean air sham exposure laboratory sessions, including acoustic startle stimuli. RESULTS: Unhealthy veterans receiving jet fuel had faster mean peripheral reaction times over sessions compared with unhealthy veterans receiving sham clean air exposures. Unhealthy Gulf veterans with CI exhibited faster post- vs. pre-session mean central reaction times compared with unhealthy Gulf veterans without CI. Findings were controlled for psychological distress variables. DISCUSSION: These data on unhealthy Gulf veterans show an acceleration of divided attention task performance over the course of repeated low-level JP-8 exposures. The present faster reaction times are consistent with rat neurobehavioral studies on environmental toxicant cross-sensitization and nonlinear dose-response patterns with stimulant drugs, as well as some previous civilian studies using other exposure agents. Together with previous research findings, the data suggest involvement of central nervous system dopaminergic pathways in affected Gulf veterans.

Chrousos GP, Kaltsas G. · Athens University, Athens, Greece and National Institutes of Health, Bethesda, MD, USA. · Clin Endocrinol (Oxf). · Pubmed #16181227 No free full text.

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Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, Toomey R, Jackson LW, Alpern R, Parks BJ, Klimas N, Hall C, Pak HS, Hunter J, Karlinsky J, Battistone MJ, Lyons MJ, Anonymous00346. · Veterans Affairs Medical Center, Washington University School of Medicine, St. Louis, Missouri 63106, USA. · Ann Intern Med. · Pubmed #15941694 links to  free full text

Abstract: BACKGROUND: United States military personnel reported various symptoms after deployment to the Persian Gulf during the 1991 Gulf War. However, the symptoms' long-term prevalence and association with deployment remain controversial. OBJECTIVE: To assess and compare the prevalence of selected medical conditions in a national cohort of deployed and nondeployed Gulf War veterans who were evaluated by direct medical and teledermatologic examinations. DESIGN: A cross-sectional prevalence study performed 10 years after the 1991 Gulf War. SETTING: Veterans were examined at 1 of 16 Veterans Affairs medical centers. PARTICIPANTS: Deployed (n = 1061) and nondeployed (n = 1128) veterans of the 1991 Gulf War. MEASUREMENTS: Primary outcome measures included fibromyalgia, the chronic fatigue syndrome, dermatologic conditions, dyspepsia, physical health-related quality of life (Short Form-36 [SF-36]), hypertension, obstructive lung disease, arthralgias, and peripheral neuropathy. RESULTS: Of 12 conditions, only 4 conditions were more prevalent among deployed than nondeployed veterans: fibromyalgia (deployed, 2.0%; nondeployed, 1.2%; odds ratio, 2.32 [95% CI, 1.02 to 5.27]); the chronic fatigue syndrome (deployed, 1.6%; nondeployed 0.1%; odds ratio, 40.6 [CI, 10.2 to 161]); dermatologic conditions (deployed, 34.6%; nondeployed, 26.8%; odds ratio, 1.38 [CI, 1.06 to 1.80]), and dyspepsia (deployed, 9.1%; nondeployed, 6.0%; odds ratio, 1.87 [CI, 1.16 to 2.99]). The mean physical component summary score of the SF-36 for deployed and nondeployed veterans was 49.3 and 50.8, respectively. LIMITATIONS: Relatively low participation rates introduce potential participation bias, and deployment-related illnesses that resolved before the research examination could not, by design, be detected. CONCLUSIONS: Ten years after the Gulf War, the physical health of deployed and nondeployed veterans is similar. However, Gulf War deployment is associated with an increased risk for fibromyalgia, the chronic fatigue syndrome, skin conditions, dyspepsia, and a clinically insignificant decrease in the SF-36 physical component score.

Kop WJ, Lyden A, Berlin AA, Ambrose K, Olsen C, Gracely RH, Williams DA, Clauw DJ. · Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. · Arthritis Rheum. · Pubmed #15641057 links to  free full text

Abstract: OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are associated with substantial physical disability. Determinants of self-reported physical disability are poorly understood. This investigation uses objective ambulatory activity monitoring to compare patients with FM and/or CFS with controls, and examines associations of ambulatory activity levels with both physical function and symptoms during activities of daily life. METHODS: Patients with FM and/or CFS (n = 38, mean +/- SD age 41.5 +/- 8.2 years, 74% women) completed a 5-day program of ambulatory monitoring of physical activity and symptoms (pain, fatigue, and distress) and results were compared with those in age-matched controls (n = 27, mean +/- SD age 38.0 +/- 8.6 years, 44% women). Activity levels were assessed continuously, ambulatory symptoms were determined using electronically time-stamped recordings at 5 time points during each day, and physical function was measured with the 36-item Short Form health survey at the end of the 5-day monitoring period. RESULTS: Patients had significantly lower peak activity levels than controls (mean +/- SEM 8,654 +/- 527 versus 12,913 +/- 1,462 units; P = 0.003) and spent less time in high-level activities when compared with controls (P = 0.001). In contrast, patients had similar average activity levels as those of controls (mean +/- SEM 1,525 +/- 63 versus 1,602 +/- 89; P = 0.47). Among patients, low activity levels were associated with worse self-reported physical function over the preceding month. Activity levels were inversely related to concurrent ambulatory pain (P = 0.031) and fatigue (P < 0.001). Pain and fatigue were associated with reduced subsequent ambulatory activity levels, whereas activity levels were not predictive of subsequent symptoms. CONCLUSION: Patients with FM and/or CFS engaged in less high-intensity physical activities than that recorded for sedentary control subjects. This reduced peak activity was correlated with measures of poor physical function. The observed associations may be relevant to the design of behavioral activation programs, because activity levels appear to be contingent on, rather than predictive of, symptoms.

King C, Jason LA. · Spinal Cord Injury Service (128), Hines VA Hospital, P.O. Box 5000, Hines, IL 60141-5128, USA. · Biol Psychol. · Pubmed #15450690 No free full text.

Abstract: Since the publication of the case definition for chronic fatigue syndrome (CFS) in 1988 the diagnostic criteria have been revised twice in the U.S. None of the case definitions were derived empirically. As a result, there is concern regarding the sensitivity, specificity, and reliability of the criteria. The goal of the present study was to identify methods for improving the diagnostic criteria for CFS. Three groups of 15 participants each were recruited: participants with (1) CFS, (2) major depressive disorder (MDD), and (3) healthy controls. Using statistical procedures, three methods for improving the diagnostic criteria were explored: identification of new diagnostic symptoms, the use of severity ratings for symptomatology, and the identification of standardized measures that differentiate cases of CFS from other conditions. Results of the present study suggest that these three methods hold promise for improving the sensitivity, specificity, and reliability of the diagnostic criteria for CFS.

Menon PM, Nasrallah HA, Reeves RR, Ali JA. · Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216, USA. · Brain Res. · Pubmed #15120596 No free full text.

Abstract: The pathogenesis of Gulf War Syndrome (GWS) is not clearly understood. Data exist to suggest that GWS may originate from a combination of chronic fatigue and sensitivity to the exposure of exogenous agents. Since the head region of hippocampus is highly vascularized and thus vulnerable to toxic substances in circulation, we postulated that hippocampal impairment occurs in GWS. To test this, single volume localized in vivo proton MR spectroscopy (MRS) studies of the left and right hippocampi of consenting Gulf War veterans (N=15; 10 with GWS, and 5 without GWS) and control Vietnam veterans (N=6) were conducted in accordance with approved human study protocols. The N-acetyl aspartate (NAA) to creatine and choline to creatine ratios were computed from the spectra. The NAA/creatine ratio of the GWS group (N=10) was found to be significantly lower than that of the entire control group (N=11) or the unaffected GW control group (N=5). No laterality differences were observed among any of the three groups. The choline/creatine ratio of the GWS group was not different from that for either control group. To check the existence of any relationship between age and the NAA/creatine ratios, the entire study population was grouped into those below or above the median age (44.3 years). It was found that the NAA/Cre ratio of the younger group (only Gulf War veterans) was significantly lower than that of the older group. The lower NAA/creatine ratio for the GWS group points to the existence of hippocampal dysfunction.

Peckerman A, Dahl K, Chemitiganti R, LaManca JJ, Ottenweller JE, Natelson BH. · VA Medical Center, East Orange, NJ 07018, USA. · Auton Neurosci. · Pubmed #14614966 No free full text.

Abstract: Abnormal cardiovascular stress responses have been reported in Gulf War veterans with chronic fatigue. However, many of these veterans also suffer from posttraumatic stress disorder (PTSD), which could potentially explain the reported abnormalities. To test this hypothesis, 55 Gulf veterans (GVs) with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) were stratified into groups with (N=16) and without (N=39) comorbid PTSD, and were compared to healthy Gulf veterans (N=47) on cardiovascular responses to a series of stressors. The CFS/ICF with PTSD group had lower blood pressure responses to speech and arithmetic tasks, and more precipitous declines and slower recoveries in blood pressure after standing up than the controls. Similar trends in the CF/ICF group without PTSD were not significant, however. Both CFS/ICF groups had blunted increases in peripheral vascular resistance during mental tasks. However, only the veterans with comorbid PTSD had diminished cardiac output responses to the mental stressors and excessive vasodilatory responses to standing. Symptoms of posttraumatic stress were significant predictors of hypotensive postural responses, but only in veterans reporting a significant exposure to wartime stress. We conclude that comorbid PTSD contributes to dysregulation of cardiovascular responses to mental and postural stressors in Gulf veterans with medically unexplained fatiguing illness, and may provide a physiological basis for increased somatic complaints in Gulf veterans with symptoms of posttraumatic stress.

Nagelkirk PR, Cook DB, Peckerman A, Kesil W, Sakowski T, Natelson BH, LaManca JJ. · Center for the Study of War-Related Illnesses, Veterans Affairs New Jersey Health Care, East Orange, NJ, USA. · Mil Med. · Pubmed #14529252 No free full text.

Abstract: A large overlap exists between the diagnosis of chronic fatigue syndrome (CFS) and the unexplained symptoms reported by many Gulf War veterans (GV). Previous investigations have reported reduced aerobic capacity in civilians with CFS. The present investigation examined metabolic responses to maximal exercise in GVs with CFS compared with healthy GVs. Cardiorespiratory and metabolic responses were recorded during a maximal exercise test on a cycle ergometer. The groups were not different in any demographic category (p > 0.05) or self-reported physical activity (p > 0.05). No differences were observed between groups for maximal oxygen uptake (28.9 +/- 6.7 mL/kg/min for CFS vs. 30.8 +/- 7.1 mL/kg/min for controls; p = 0.39), heart rate (155.8 +/- 16.1 bpm for CFS vs. 163.3 +/- 14.9 bpm for controls; p = 0.17), exercise time (9.6 +/- 1.5 minutes for CFS vs. 10.2 +/- 1.4 minutes for controls; p = 0.26), or workload achieved (208 +/- 36.7 W for CFS vs. 224 +/- 42.9 W for controls; p = 0.25). Likewise, no differences were observed at submaximal intensities (p > 0.05). Compared with healthy controls, GVs who report multiple medically unexplained symptoms and meet criteria for CFS do not show a decreased exercise capacity. Thus, it does not appear that the pathology of the GVs with CFS includes a deficiency with mobilizing the cardiopulmonary system for strenuous physical effort.

Peckerman A, LaManca JJ, Qureishi B, Dahl KA, Golfetti R, Yamamoto Y, Natelson BH. · VA Medical Center, War-Related Illness and Injury Study Center, East Orange, New Jersey 07018, USA. · Psychosom Med. · Pubmed #14508037 links to  free full text

Abstract: OBJECTIVE: Altered cardiovascular responses to mental and postural stressors have been reported in chronic fatigue syndrome (CFS). This study examined whether those findings may involve changes in baroreceptor reflex functioning. METHODS: Chronotropic baroreceptor reflex (by sequential analysis) and cardiovascular stress responses were recorded during postural (5-minute of active standing) and cognitive (speech task) stress testing in patients with CFS grouped into cases with severe (N = 21) or less severe (N = 22) illness, and in 29 matched control subjects. RESULTS: Patients with CFS had a greater decline in baroreceptor reflex sensitivity (BRS) during standing, although only those with severe CFS were significantly different from the controls. Systolic blood pressure declined during standing in the control group but was maintained in the CFS patients. In contrast, the patients with less severe CFS had blunted increases in blood pressure during the speech task, which could not, however, be explained by inadequate inhibition of the baroreceptor reflex, with all groups showing an appropriate reduction in BRS during the task. CONCLUSIONS: These results indicate that in CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex. This study also suggests that classifying patients with CFS on illness severity may discriminate between patients with abnormalities in peripheral vs. central mechanisms of cardiovascular stress responses.

Hyams KC. · Department of Veterans Affairs, Office of Public Health and Environmental Hazards, Washington, DC, USA. · Med Hypotheses. · Pubmed #12710915 No free full text.

Abstract: Karl Popper's argument that deductive logic and falsifiable hypotheses are necessary for the growth of scientific knowledge has been controversial. One approach to assess the relevance of his ideas to medical science has been to evaluate examples of successful research. Another approach is to analyze an unsuccessful investigation. The inconclusive search for a unique 'chronic fatigue syndrome' offers a well-documented case-study for this analysis. Over the past 130 years, numerous studies have provided clinical and epidemiological data, which have supported competing hypotheses about the etiology of chronic fatigue. However, few hypotheses have been refuted because it has not been possible to establish objective standards of inquiry for a subjective symptom like fatigue. As a result, intensive research efforts have not converged on correct explanations by eliminating erroneous ideas. This unsuccessful investigation illustrates how non-falsifiable hypotheses are insufficient to advance medical knowledge, even when there is an abundance of empirical data.

Kang HK, Natelson BH, Mahan CM, Lee KY, Murphy FM. · Veterans Health Administration, Department of Veterans Affairs, Washington, DC, USA. · Am J Epidemiol. · Pubmed #12522021 links to  free full text

Abstract: The authors estimated the prevalence of post-traumatic stress disorder (PTSD) and illness resembling chronic fatigue syndrome (CFS) in the entire population of Gulf War and non-Gulf-War veterans. They also evaluated the relation between the extent of deployment-related stress and the risk of either PTSD or CFS. In 1995-1997, the authors conducted a health survey in which these two symptom-based medical diagnoses in a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared with those of 15,000 non-Gulf veteran controls. Gulf War veterans, compared with non-Gulf veteran controls, reported significantly higher rates of PTSD (adjusted odds ratio = 3.1, 95% confidence interval: 2.7, 3.4) and CFS (adjusted odds ratio = 4.8, 95% confidence interval: 3.9, 5.9). The prevalence of PTSD increased monotonically across six levels of deployment-related stress intensity (test for trend: p < 0.01), while the prevalence of CFS rose only at the low end of the stress spectrum. While deployment-related stress could account for the higher risks of both PTSD and CFS, additional factor(s) unique to the Gulf environment may have contributed to the risk of CFS among Gulf War veterans.

Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. · Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, NIH, 10 Center Drive, Building 10, Room 9D42, MSC 1583, Bethesda, MD 20892-1583, USA. · Hum Reprod. · Pubmed #12351553 links to  free full text

Abstract: BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.

Arnold MC, Papanicolaou DA, O'Grady JA, Lotsikas A, Dale JK, Straus SE, Grafman J. · National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1440, USA. · Psychol Med. · Pubmed #12214788 No free full text.

Abstract: BACKGROUND: Individuals with acute infections experience a range of symptoms including fatigue, malaise, muscle aches, and difficulties with concentration and memory that are usually self-limited. This cluster of symptoms is otherwise, similar to those that characterize chronic fatigue syndrome (CFS). The goal of the present study was to evaluate the cognitive and psychological functioning of CFS patients and normal controls (NCs) when they both were experiencing acute influenza-like symptoms. To induce influenza-like symptoms, we administered interleukin-6 (IL-6), a cytokine that temporarily activates the acute phase immunological and endocrine responses. METHODS: Nineteen patients who met the 1994 International CFS Study Group Criteria and ten normal controls (NCs) completed routine clinical evaluations, neuropsychological tests of short-term memory, selective attention, and executive control, and self-ratings of somatic symptoms and psychological mood before, shortly following, and 1 day after IL-6 administration. RESULTS: CFS patients consistently reported more somatic symptoms, even when both groups perceived that they were ill. Both groups somatic symptoms increased during the IL-6 challenge, but the CFS patients symptoms increased more rapidly than controls. In general, the CFS patients performed similarly to NCs on the cognitive measures before, during, and after the IL-6. In contrast to predictions, IL-6 provocation did not impair the cognitive performance of either CFS patients or NCs. CONCLUSIONS: The IL-6 provocation exacerbated the patients self-reported symptoms but did not reveal notable cognitive impairments between patients and controls during cytokine-induced acute influenza-like symptoms.

Papp KK, Erokwu B, Decker M, Strohl KP. · Louis B. Stokes Cleveland V.A. Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. · Sleep Breath. · Pubmed #11868151 No free full text.

Abstract: PURPOSE: We report an observational study of medical students' abilities in taking a complex history for which sleep disorders is one of several possible conditions. METHODS: Students are observed taking a focused history from a simulated patient whose chief complaint is "I am tired. I cannot get anything done." Nine groups of students (n = 360) completing the internal medicine core-clerkship were evaluated by one of three examiners. Students received full, partial, or no credit for each item on a uniform behavioral checklist, which included prompts for common medical and psychiatric disorders associated with chronic fatigue. RESULTS: Observed means were lowest for items pertaining to sleep behaviors and head trauma. Fewer than half of the students inquired about whether or not the person had difficulty falling asleep at night, family history of sleep apnea, and frequency and length of naps. In contrast, the majority of students inquired about heart disease, metabolic disorders, the use of illicit drugs, alcohol consumption, and the taking of medications. Examiners accounted for a significant source of variance in scores; yet the station discriminated among top and bottom students as measured by the Objective Structured Clinical Examination (OSCE) overall. No statistically significant differences were observed on the basis of clerkship site, primary care versus traditional-track students, time of year, or gender. CONCLUSION: A majority of students do not adequately cover issues relevant to sleep in contrast to other associated disorders when taking a focused history for chronic fatigue.

Nelson JJ, Natelson BH, Peckerman A, Pollet C, Lange G, Tiersky L, Servatius RJ, Policastro T, Fiedler N, Ottenweller JE. · Center for Environmental Hazards Research, Department of Veterans Affairs Medical Center, East Orange, NJ 07018, USA. · Mil Med. · Pubmed #11778414 No free full text.

Abstract: An important question for researchers interested in long-term consequences of military service is the health outcome of symptomatic Persian Gulf War Veterans. From an original group of 76 Gulf War Veterans who received the diagnosis of severe fatiguing illness, we attempted to get 58 veterans to return to our center for a second evaluation. Thirteen returned. Two had recovered by the time of revisit, but the rest remained ill; however, only one was so ill as to be unable to work. The data suggest that the medical consequences of serving in the Persian Gulf are not transient. The difficulty in getting veterans to return to our center suggests potential problems in the proposed nation-wide longitudinal health outcome study of Persian Gulf War Veterans.

Bourdette DN, McCauley LA, Barkhuizen A, Johnston W, Wynn M, Joos SK, Storzbach D, Shuell T, Sticker D. · Portland Veterans Affairs Medical Center, Department of Neurology, Mailcode P-3-NEURO, 3710 SW US Veteran's Hospital Road, Portland, OR 97201, USA. · J Occup Environ Med. · Pubmed #11765674 No free full text.

Abstract: Few epidemiological studies have been conducted that have incorporated clinical evaluations of Gulf War veterans with unexplained health symptoms and healthy controls. We conducted a mail survey of 2022 Gulf War veterans residing in the northwest United States and clinical examinations on a subset of 443 responders who seemed to have unexplained health symptoms or were healthy. Few clinical differences were found between cases and controls. The most frequent unexplained symptoms were cognitive/psychological, but significant overlap existed with musculoskeletal and fatigue symptoms. Over half of the veterans with unexplained musculoskeletal pain met the criteria for fibromyalgia, and a significant portion of the veterans with unexplained fatigue met the criteria for chronic fatigue syndrome. Similarities were found in the clinical interpretation of unexplained illness in this population and statistical factor analysis performed by this study group and others.

Morgen K, Martin R, Stone RD, Grafman J, Kadom N, McFarland HF, Marques A. · Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1400, USA. · Neurology. · Pubmed #11739813 No free full text.

Abstract: OBJECTIVE: To determine patterns of abnormalities on cerebral MRI that may characterize subgroups of patients with post-treatment Lyme disease syndrome (PTLDS) and to help identify pathomechanisms of disease. METHODS: The authors analyzed the distribution of cerebral lesions in a cohort of 27 patients with PTLDS. A subgroup of eight patients with PTLDS was further studied using whole-brain magnetization transfer ratio measures to identify abnormalities not seen on T2-weighted images. RESULTS: Four patients had focal neurologic deficits, relapsing-remitting disease, and lesions in a distribution typical of MS. Twenty-three patients presented with nonfocal symptoms such as fatigue, subjective memory deficits, and mood disturbance. Twelve of these patients had normal MRI, including the more sensitive fluid-attenuated inversion recovery sequence, 10 had primarily punctate and subcortical lesions, and one patient had multiple periventricular lesions. CONCLUSIONS: In a portion of patients with post-treatment Lyme disease syndrome, white-matter hyperintensities tend to occur in subcortical arteriolar watershed areas and are not specific. Magnetization transfer ratio analysis did not provide evidence for structural abnormalities of the brain parenchyma in patients with nonfocal disease.

Curt GA. · National Cancer Institute, National Institutes of Health, Clinical Center, Oncology Program, Building 10, Room 12N214, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. · Recenti Prog Med. · Pubmed #11433722 No free full text.

Abstract: As oncologists have become more effective in alleviating pain, nausea and depression, fatigue has emerged as the most important symptom suffered by cancer patients. Indeed, the current literature suggests that fatigue is currently the most important untreated symptom in cancer medicine. In recent surveys of patients and their caregivers, fatigue is more important for the quality of life than pain, nausea or depression. Yet these same surveys confirm that oncologists underestimate the importance of cancer related fatigue. This may be partly because patients often do not fully share the full nature of their concerns. When patients do raise the issue of fatigue, the physicians' recommendations are often non specific. However, recent research has shown that fatigue is not inevitable and untreatable, but a symptom amenable to differential diagnosis and specific intervention. Like pain, fatigue is intrinsically a subjective problem where the doctor relies on the patient's reporting. Weakness, exhaustion, lethargy and asthenia are all used as functional descriptions of fatigue. While these are descriptive terms, clinical research in the measurement and alleviation of fatigue requires reproducible measurement tools. Several studies already exist and have begun to explore this important area of symptom management.

Gralnek IM, Hays RD, Kilbourne A, Naliboff B, Mayer EA. · Greater Los Angeles VA Health Care System, Los Angeles, California 90073, USA. · Gastroenterology. · Pubmed #10982758 No free full text.

Abstract: BACKGROUND & AIMS: Few data are available to evaluate health-related quality of life (HRQOL) of people with irritable bowel syndrome (IBS). We evaluated and compared the impact of IBS on HRQOL using previously reported HRQOL data for the U.S. general population and for people with selected chronic diseases. METHODS: Using the SF-36 Health Survey, we compared the HRQOL of IBS patients (n = 877) with previously reported SF-36 data for the general U.S. population and for patients with gastroesophageal reflux disease (GERD), diabetes mellitus, depression, and dialysis-dependent end-stage renal disease (ESRD). RESULTS: On all 8 SF-36 scales, IBS patients had significantly worse HRQOL than the U.S. general population (P < 0. 001). Compared with GERD patients, IBS patients scored significantly lower on all SF-36 scales (P < 0.001) except physical functioning. Similarly, IBS patients had significantly worse HRQOL on selected SF-36 scales than patients with diabetes mellitus and ESRD. IBS patients had significantly better mental health SF-36 scale scores than patients with depression (P < 0.001). CONCLUSIONS: IBS patients experience significant impairment in HRQOL. Decrements in HRQOL are most pronounced in energy/fatigue, role limitations caused by physical health problems, bodily pain, and general health perceptions. These data offer further insight into the impact of IBS on patient functional status and well-being.

Nawab SS, Miller CS, Dale JK, Greenberg BD, Friedman TC, Chrousos GP, Straus SE, Rosenthal NE. · Section on Biological Rhythms, National Institute of Mental Health, Bethesda, MD 20892-1390, USA. · Psychiatry Res. · Pubmed #10904124 No free full text.

Abstract: Two hundred and twenty-five subjects, including normal volunteers and patients with previously documented seasonal affective disorder (SAD), chronic fatigue syndrome (CFS), Cushing's syndrome, Addison's disease and obsessive-compulsive disorder (OCD), completed a self-rated inventory of reported sensitivity to various chemical exposures. Patients with CFS, Addison's disease and SAD self-reported more sensitivity to chemical exposures than normal controls. In addition, women reported more sensitivity than men. This report suggests that chemical sensitivity may be a relevant area to explore in certain medical and psychiatric populations. A possible relationship between reported chemical sensitivity and hypothalamic-pituitary-adrenal (HPA)-axis functioning is discussed.

Davis SD, Kator SF, Wonnett JA, Pappas BL, Sall JL. · Preventive Medicine, Evans US Army Community Hospital, Fort Carson, Colorado, USA. · Am J Med Sci. · Pubmed #10698092 No free full text.

Abstract: BACKGROUND: Many patients with chronic fatigue syndrome (CFS) have neurally mediated hypotension when subjected to head-up tilt, suggesting autonomic nervous system dysfunction. Some Gulf War veterans have symptoms similar to CFS. Whether they also tend to have neurally mediated hypotension is unknown. METHODS: We performed 3-stage tilt-table testing on 14 Gulf War veterans with chronic fatigue, 13 unfatigued control Gulf War veterans, and 14 unfatigued control subjects who did not serve in the Gulf War. Isoproterenol was used in stages 2 and 3 of the tilt protocol. RESULTS: More fatigued Gulf War veterans than unfatigued control subjects had hypotensive responses to tilt (P < 0.036). A positive response to the drug-free stage 1 of the tilt was observed in 4 of 14 fatigued Gulf War veterans versus 1 of 27 unfatigued control subjects (P < 0.012). Heart rate and heart rate variation during stage 1 was significantly greater in the fatigued group (P < 0.05). CONCLUSION: We conclude that more fatigued Gulf War veterans have neurally mediated hypotension than unfatigued control subjects, similar to observations in CFS. Autonomic nervous system dysfunction may be present in some fatigued Gulf War veterans.