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ME Research UK Database of Research Publications 1997

Authors Author Address Title Publication Abstract Institut und Poliklinik fur [Chronic fatigue syndrome--a Z Arztl Fortbild Qualitatssich In spite of its nature as an often severe and disabeling disease, it is still unclear, whether the Chronic Albus C. Psychosomatik und disease entity or an 1997 Dec;91(8):717-21 Fatigue Syndrome (CFS) is an entire disease of its own right or not. Moreover, there is a growing evidence Psychotherapie, Universitat unspecified psychosomatic that patients with CFS belong to an inhomogeneous group with different etiologic constellations. Specific zu Koln. disorder]?[article in German] somatic factors, e.g. viruses, seem to be less important for onset than certain personality-traits like depressiveness and workaholism. These traits lead to an increased vulnerability to unspecific psychological or biological stressors that may cause chronic fatigue by complex psychosomatic interferences. Concerning diagnosis, there are no specific methods or results available, the same is true for pharmacological treatment. As a consequence, practitioners should be aware not to miss a somatic disease causing fatigue, and, parallel to this, start right from the beginning talking about the psychosomatic background of CFS. Furthermore, psychotherapy has shown to be effective in CFS. Department of Medicine, Changes in growth hormone, Biol Psychiatry 1997 Mar Chronic fatigue syndrome (CFS) is characterized by severe physical and mental fatigue of central origin. Allain TJ, Bearn JA, Kings College School of insulin, insulinlike growth 1;41(5):567-73 Similar clinical features may occur in disorders of the hypothalamopituitary axis. The aim of the study was Coskeran P, Jones J, Medicine and Dentistry, factors (IGFs), and IGF-to determine whether patients with CFS have abnormalities of the growth hormone/insulinlike growth Checkley A, Butler J, London, United Kingdom. binding protein-1 in chronic factor (GH-IGF) axis basally or following hypothalamic stimulation with insulin-induced hypoglycemia. Wessely S, Miell JP. fatigue syndrome. We compared levels of GH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), insulin, and C-peptide in nondepressed CFS patients and normal controls. We found attenuated basal levels of IGF-I (214 +/- 17 vs. 263.4 +/- 13.4 micrograms/L, p = .036) and IGF-II (420 +/- 19.8 vs. 536 +/- 24.3 micrograms/L, p = .02) in CFS patients and a reduced GH response to hypoglycemia (peak GH; 41.9 +/- 11.5 vs. 106.0 +/- 25.6 mU/L, p = .017). Insulin levels were higher (7.6 +/- 1.0 vs. 4.3 +/- 0.8 mU/L, p = .02) and IGFBP-1 levels were lower (19.7 +/- 4.6 vs. 43.2 +/- 2.7 mg/L, p = .004) in CFS patients compared with controls. This study provides preliminary data abnormalities of the GH-IGF axis in CFS. It is not apparent whether these changes are components of a primary pathological process or are acquired secondary to behavioral aspects of CFS such as reduced physical activity. University of Illinois at The quality of life of persons J Nerv Ment Dis 1997 This descriptive study used a between-methods triangulation design to analyze the multiple dimensions of Anderson JS, Ferrans CE. Chicago Medical Center, with chronic fatigue Jun;185(6):359-67 quality of life in persons with chronic fatigue syndrome (CFS). This method, which refers to the Department of Psychiatry syndrome. combination of both quantitative and qualitative methods in the same study, allowed the authors to obtain 60612, USA. more comprehensive and robust data than could be obtained by either method alone. A convenience sample of 110 persons with CFS completed the quality of life index and CFS questionnaire, and a subset of 22 persons were interviewed regarding their lived experience with CFS. Overall scores on the quality of life index were significantly lower in CFS than for other chronic illness groups. Subjects reported the lowest quality of life scores in health and functioning domain. Indepth interviews provided a more complete understanding of the quality of life in CFS and further explained the low ratings that were found on the quality of life index. The findings suggest that quality of life is particularly and uniquely disrupted in CFS. Birkback College, University Chronic fatigue syndrome: J R Soc Med 1997 In response to reports of negative cooperation between sufferers of chronic fatigue syndrome (CFS) and Ax S, Gregg VH, Jones D. of London, England. sufferers' evaluation of May;90(5):250-4 their doctors, semi-structured interviews were conducted with sufferers from two different patient samples. medical support. Satisfaction with support received and with medical professionals in general was low. Sufferers complained about insufficient informational as well as emotional support from their doctors, and as a consequence most opted for alternative or complementary forms of treatment. In addition, disagreements over illness aetiology and treatment precluded effective cooperation. If satisfaction and compliance are to improve, sufferers will need more information about CFS and more support. Etiology of chronic fatigue Am J Med 1997 Baschetti R. syndrome. Apr;102(4):422-3 Comment on: Am J Med. 1996 May;100(5):548-54 Lung function test findings in Aust N Z J Med 1997 Baschetti R. patients with chronic fatigue Jun;27(3):346 Comment on: syndrome (CFS) Aust N Z J Med. 1996 Aug;26(4):563-4 Similarity of symptoms in Eur J Clin Invest 1997 Baschetti R. chronic fatigue syndrome and Dec;27(12):1061-2 Comment

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Addison's disease. on: Eur J Clin Invest. 1997 Apr;27(4):257-67 Chronic fatigue syndrome. QJM 1997 Nov;90(11):723 Baschetti R. Comment on: QJM. 1997 Mar;90(3):223-33 Afd. Medische Psychologie, [Prevalence of chronic Ned Tijdschr Geneeskd 1997 OBJECTIVE: To determine the prevalence of chronic fatigue syndrome (CFS) and of primary fibromyalgia Bazelmans E, Vercoulen Academisch Ziekenhuis, fatigue syndrome and Aug 2;141(31):1520-3 syndrome (PFS) in the Netherlands. DESIGN: Questionnaire. SETTING: Department of Medical JH, Galama JM, van Weel Nijmegen. primary fibromyalgia Psychology, University Hospital Nijmegen, the Netherlands. METHOD: A questionnaire was mailed to all C, van der Meer JW, syndrome in The the 6657 general practitioners in the Netherlands in order to inform them of the existence of CFS and to ask Bleijenberg G. Netherlands].[article in them if they had any CFS or PFS patients in their practices. RESULTS: Sixty percent (n = 4027) of the Dutch] Erratum in: Ned general practitioners returned the questionnaire. Of all the general practitioners, 27% said they had no CFS Tijdschr Geneeskd 1997 Sep patients, 23% said they had 1 CFS patient, while 21% had 2 CFS patients, and 29% said they had 3 or more 13;141(37):2686 CFS patients in their practice. Concerning PFS the results were 17% (no PFS patients), 18%, 18% and 47%, respectively. With a mean practice of 2486 patients per general practice, the estimated prevalence of CFS was 112 per 100,000 and that of PFS 157 per 100,000 persons. Of the CFS patients 81% were women and 55% were 25-44 years old; for PFS these figures were 87% and 48% respectively. CONCLUSION: Extrapolation of the study results indicates that there are at least 17,000 CFS patients and 24,000 PFS patients in the Netherlands. The found prevalence is probably an under-estimation. Department of Psychology, Effect of noise stress on J Nerv Ment Dis 1997 Beh HC. University of Sydney, New chronic fatigue syndrome Jan;185(1):55-8 South Wales, Australia. patients. Illness Onset Characteristics Journal of Chronic Fatigue Twenty-three children and adolescents with unexplained chronic fatigue were evaluated with emphasis Bell DS in Children with Chronic Syndrome 1997: 3(2): 43 - 51 upon illness-onset characteristics. Ten subjects had an acute, "flu-like" onset, and four of these subjects had Fatigue Syndrome and episodes of mild fatigue in the year prior to onset. The thirteen remaining subjects had a gradual onset of Idiopathic Chronic Fatigue chronic fatigue, the majority describing increasing episodes of apparent infectious illnesses associated with fatigue. In these subjects, the fatigue eventually became constant, causing reduction in overall activity levels. In a comparison of subjects who did and did not meet diagnostic criteria for chronic fatigue syndrome, there were no differences in onset characteristics, but differences were noted in illness severity. The majority of children and adolescents with unexplained chronic fatigue had a gradual onset of debilitating symptoms Cognitive Dysfunction and Journal of Chronic Fatigue The symptom of sensitivity or intolerance to low levels of environmental chemicals (CI) is a characteristic Bell IR, Michele E. Walsh, Disability in Geriatric Syndrome 1997: 3(3): 15 - 42 of several clinical conditions, such as multiple chemical sensitivity (MCS), chronic fatigue syndrome Anita Gross, Jane Veterans with Self-Reported (CFS), fibromyalgia (FM), and the "Persian Gulf Syndrome." Lesser degrees of CI also occur in 15-30% of Gersmeyer, Gary E. Intolerance to Environmental non-clinical populations. The present study examined the prevalence and concomitant health patterns of CI Schwartz, Philip Kanof Chemicals in elderly veterans in a VA primary care medical clinic (N = 160, primarily men). Thirty-seven percent of the sample endorsed the screening question asking whether or not they considered themselves "especially sensitive to certain chemicals." The group with CI reported a significantly higher rate of physical disability and increased susceptibility to becoming sick. The CI group reported significantly decreased rates of current cigarette smoking and alcohol use. Those with and those without CI did not differ in level of depression or in past occupational chemical exposures. However, the CI group scored significantly lower on a screening test for cognitive dysfunction, including a verbal memory performance pattern consistent with early dementia. When the groups were subdivided into individuals high and low in depression, the depressives without CI reported the highest rate of prior occupational exposure to pesticides. The subgroup who had both CI and depression performed most poorly on the attention/concentration screening test. Taken together, the data suggest that CI as a symptom is extremely common in older male veterans and may be a marker for increased risk of further cognitive decline and/or loss of functional independence. However, the role of occupational chemical exposures in initiating CI in these non-MCS patients is unclear and requires additional study. A view of the violence J Anal Psychol 1997 In this paper I ask whether there might be any one particular psychopathology likely to be linked Bennett A. contained in chronic fatigue Apr;42(2):237-51 specifically with the physical illness known as chronic fatigue syndrome (CFS) or myalgic syndrome. encephalomyelitis (ME), and whether CFS/ME aids and abets and "fits' an original mental state. I think the

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question cannot yet be answered. However it is my hypothesis that in some personality structures the onset of CFS/ ME following a physical illness exacerbates negativity and is an aspect of ordinary depression where there is a lowering of energy levels and a loss of zest for life, or it may reveal the pathological aspect of unresolved rage. Depending on the degree of pathological disturbance, working with and through the rage may or may not result in a resolution of the symptoms of ME. In this paper I consider some of the problems in the transference and countertransference relationship, which make it extremely difficult to separate out reality from phantasy. There is then the further problem of the denial of the psyche by the patient as part of the violence inherent in the illness. One case is presented, an example of ME in a borderline male patient in whom resolution could not be achieved. Chronic Fatigue Syndrome Elevation of bioactive J Clin Immunol 1997 The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients Bennett AL, Chao CC, Hu Cooperative Research Center, transforming growth factor-Mar;17(2):160-6 with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression, S, Buchwald D, Fagioli LR, Brigham and Women's beta in serum from patients systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and Schur PH, Peterson PK, Hospital, Boston, with chronic fatigue the chronic progressive (CP) types. Patients with CFS had significantly higher levels of bioactive TGF-beta Komaroff AL. Massachusetts, USA. syndrome. levels compared to the healthy control major depression, SLE, R/R MS, and CP MS groups (P < 0.01). Additionally, no significant differences were found between the healthy control subjects and any of the disease comparison groups. The current finding that TGF-beta is significantly elevated among patients with CFS supports the findings of two previous studies examining smaller numbers of CFS patients. In conclusion, TGF-beta levels were significantly higher in CFS patients compared to patients with various diseases known to be associated with immunologic abnormalities and/or pathologic fatigue. These findings raise interesting questions about the possible role of TGF-beta in the pathogenesis of CFS. Department of Medicine, Somatomedin C (insulin-like J Psychiatr Res 1997 Jan-Chronic fatigue syndrome is a disorder clinically quite similar to fibromyalgia syndrome, and it is of Bennett AL, Mayes DM, Brigham and Women's growth factor I) levels in Feb;31(1):91-6 interest to examine if these two syndromes have pathogenetic as well as clinical features in common. Fagioli LR, Guerriero R, Hospital, Boston, MA 02115, patients with chronic fatigue Somatomedin C levels have been found to be lower in patients with fibromyalgia syndrome than in healthy Komaroff AL. USA. syndrome. controls. An attractive hypothesis relating sleep disturbance, altered somatotropic neuroendocrine function and fibromyalgia symptoms has been put forward as a plausible pathogenic mechanism for fibromyalgia syndrome. We therefore sought to investigate the level of somatomedin C in patients with chronic fatigue syndrome. Somatomedin C levels were determined by radioimmunoassay in frozen serum specimens from 49 patients with CFS and 30 healthy blood donor control subjects of similar age and gender. Somatomedin C levels were higher in patients with CFS than in healthy control subjects (255.3 +/- 68.5 vs 211.9 +/- 76.2, P = 0.01). There was no effect of gender, use of nonsteroidal anti-inflammatory drugs or tricyclic drugs on levels of somatomedin C. There was a tendency for somatomedin C levels to fall with age. In contrast to patients with fibromyalgia, in whom levels of somatomedin C have been found to be reduced, levels in patients with CFS were found to be elevated. Thus, despite the clinical similarities between these two conditions, they may be associated with different abnormalities of sleep and/or of the somatotropic neuroendocrine axis. Confronting AIDS in older N J Med 1997 A 57-year-old corporate executive, married with three grown children, began suffering from severe flu-like Berlin B. adults. Nov;94(11):39-41 symptoms and weight loss. Hospitalized for a week, he was tested for chronic fatigue syndrome and mononucleosis. Finally, with no change in his symptoms, his physician recommended an HIV test. The results were positive. [Chronic fatigue syndrome. Med Clin (Barc) 1997 Apr Bertolin JM, Calvo J. To be or not to be]?[article in 19;108(15):577-9 Comment Spanish] on: Med Clin (Barc). 1997 Apr 19;108(15):561-5 Academisch Ziekenhuis, afd. [Attributions and chronic Ned Tijdschr Geneeskd 1997 It was recently suggested that chronic fatigue is merely a question of attribution. Attribution clearly Bleijenberg G. Medische Psychologie, fatigue].[article in Dutch] Aug 2;141(31):1510-contributes to the course of chronic fatigue syndrome (CFS) but is not its sole determinant. The presence of Nijmegen. 2Comment in: Ned Tijdschr strong somatic attributions appears to be one of the perpetuating factors in CFS but not the only one. Many Geneeskd. 1997 Nov CFS patients present a self-diagnosis, e.g. myalgic encephalomyelitis. Communication problems between 29;141(48):2360 Ned patient and doctor easily arise because of different attributions of the complaints. At the start of fatigue Tijdschr Geneeskd. 1997 somatic attributions are of less importance than later on in the course of the complaints. In this process an Nov 29;141(48):2360-1 iatrogenic factor might be involved. On the other hand doctors are able to influence these attributions actively in a favourable direction.

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Use of amantadine for Arch Intern Med 1997 Jun Bowman MA, Kirk JK, chronic fatigue syndrome. 9;157(11):1264-5 Michielutte R, Preisser JS. Controlled Clinical Trial Letter Chronic Fatigue, Fainting Journal of Chronic Fatigue To test the hypothesis that fatigue and fainting occur together, 1,047 polio survivors and 419 non-disabled Bruno RL and Autonomic Dysfunction: Syndrome 1997: 3(3): 109 - control subjects were asked about the frequency and cause of fainting and asked to rate their typical daily Further Similarities Between 116 fatigue severity. Fatigue severity was significantly higher in polio survivors as compared to controls, and in Post-Polio Fatigue and both polio survivors and controls who had fainted, as compared to those who had not. Daily fatigue severity Chronic Fatigue Syndrome? also increased in both groups as the number of lifetime faints increased. Fatigue was significantly higher in controls who fainted one time and three times as compared to controls who had never fainted. Daily fatigue severity was significantly higher in polio survivors who had fainted three, four and five times as compared to those who had never fainted. These findings suggest a physiological relationship between fatigue and fainting, possibly attributable to the close proximity of cardiovascular regulation and brain activation centers within the brain stem. Fatigue and hypotension in patients with chronic fatigue syndrome and in polio Department of Medicine, Screening for psychiatric J Psychosom Res 1997 Psychiatric disorders are common in chronic fatigue (CF) and chronic fatigue syndrome (CFS). To Buchwald D, Pearlman T, University of Washington, disorders in chronic fatigue Jan;42(1):87-94 determine the usefulness of the General Health Questionnaire (GHQ), a self-report measure of Kith P, Katon W, Seattle, USA. and chronic fatigue psychological distress, in identifying those with psychiatric illnesses, a structured psychiatric interview and Schmaling K. syndrome. the GHQ were administered to 120 CF and 161 CFS patients seen in a referral clinic. Overall, 87 (35%) patients had a current and 210 (82%) a lifetime psychiatric disorder. Compared to patients without psychiatric disorders, GHQ scores above the threshold (> or = 12) were more frequent among patients with current (p < 0.001) and lifetime (p < 0.05) diagnoses; scores among patients with CF and CFS were similar. Longer illness duration, greater fatigue severity, and current psychiatric disorders were significant predictors of the GHQ score. In CF and CFS, the best sensitivity (0.69-0.76) and specificity (0.51-0.62) were achieved for current psychiatric diagnoses using a threshold score of > or = 12. Thus, patients scoring < 12 on the GHQ are significantly less likely to have a psychiatric disorder. Department of Medicine, Markers of inflammation and J Rheumatol 1997 OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. Buchwald D, Wener MH, University of Washington, immune activation in chronic Feb;24(2):372-6 We examined the role of serum markers of inflammation and immune activation among patients with CFS Pearlman T, Kith P. Seattle, USA. fatigue and chronic fatigue and in those with chronic fatigue (CF) not meeting the case definition. METHODS: Assays for soluble syndrome. interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on examination. RESULTS: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not observed. The presence of several markers was highly correlated (p < 0.01). CONCLUSION: Our findings that levels of several markers were significantly correlated points to a subset of patients with immune system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall, serum markers of inflammation and immune activation are of limited diagnostic usefulness in the evaluation of patients with CSF and CF. Department of Medicine, Interleukin-1 beta, J Clin Immunol 1997 Chronic fatigue syndrome is a condition that affects women in disproportionate numbers, and that is often Cannon JG, Angel JB, Tufts University-New interleukin-1 receptor May;17(3):253-61 exacerbated in the premenstrual period and following physical exertion. The signs and symptoms, which Abad LW, Vannier E, England Medical Center, antagonist, and soluble include fatigue, myalgia, and low-grade fever, are similar to those experienced by patients infused with Mileno MD, Fagioli L, Boston, Massachusetts interleukin-1 receptor type II cytokines such as interleukin-1. The present study was carried out to test the hypotheses that (1) cellular Wolff SM, Komaroff AL. 02111, USA. secretion in chronic fatigue secretion of interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1Ra), and soluble syndrome. interleukin-1 receptor type II (IL-1sRII) is abnormal in female CFS patients compared to age- and activity-matched controls; (2) that these abnormalities may be evident only at certain times in the menstrual cycle; and (3) that physical exertion (stepping up and down on a platform for 15 min) may accentuate differences between these groups. Isolated peripheral blood mononuclear cells from healthy women, but not CFS patients, exhibited significant menstrual cycle-related differences in IL-1 beta secretion that were related to

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estradiol and progesterone levels (R2 = 0.65, P < 0.01). IL-1Ra secretion for CFS patients was twofold higher than controls during the follicular phase (P = 0.023), but luteal-phase levels were similar between groups. In both phases of the menstrual cycle, IL-1sRII release was significantly higher for CFS patients compared to controls (P = 0.002). The only changes that might be attributable to exertion occurred in the control subjects during the follicular phase, who exhibited an increase in IL-1 beta secretion 48 hr after the stress (P = 0.020). These results suggest that an abnormality exists in IL-1 beta secretion in CFS patients that may be related to altered sensitivity to estradiol and progesterone. Furthermore, the increased release of IL-1Ra and sIL-1RII by cells from CFS patients is consistent with the hypothesis that CFS is associated with chronic, low-level activation of the immune system. Intercollege Physiology Gender differences in host J Psychiatr Res 1997 Jan-Extensive studies in both humans and animals have shown that females express enhanced levels of Cannon JG, St Pierre BA. Program, Pennsylvania State defense mechanisms. Feb;31(1):99-113 immunoreactivity compared to males. Whereas this provides females with increased resistance to many University, University Park types of infection, it also makes them more susceptible to autoimmune diseases. This review will focus on 16802-6900, USA. gender-related differences in non-specific host defense mechanisms with a particular emphasis on monocyte/macrophage function and a primary product of monocytes: interleukin-1 (IL-1). Immunomodulatory cytokines such as IL-1 are influenced by gender-sensitive hormones, and reciprocally, these cytokines influence gender-specific hormones and tissues. Patients with chronic fatigue syndrome (CFS) are predominantly women, therefore it may be useful to look toward gender-specific differences in immune function to find a key for this poorly understood syndrome. Chronic Fatigue Syndrome A Journal of Chronic Fatigue No abstract available Chaudhuri A, T. Majeed, Disorder of Central Syndrome 1997: 3(1): 3 - 16 T. Dinan, P. O. Behan Cholinergic Transmission Georgetown University The natural history of J Psychiatr Res 1997 Jan-An outbreak of chronic fatigue syndrome linked with sick building syndrome was recently described as a Chester AC, Levine PH. Medical Center, Washington concurrent sick building Feb;31(1):51-7 new association. Whether chronic fatigue syndrome acquired in this setting tends to remit or, as sporadic DC, USA. syndrome and chronic fatigue cases often do, persist, is unknown. To clarify the natural history of chronic fatigue syndrome in association syndrome. with sick building syndrome the 23 individuals involved in the outbreak were interviewed four years after the onset. In the previous interview one year after the onset of symptoms, 15 (including 5 with chronic fatigue syndrome and 10 with idiopathic chronic fatigue) of the 23 noted fatigue. Three years later 10 of the 15 were "fatigue free" or "much improved". Five were only "some better", "the same", or "worse". Three of the five people previously diagnosed with chronic fatigue syndrome were "much improved" (two) or "fatigue free" (one). The remaining two were seriously impaired, homebound and unable to work. The 10 individuals with substantially improved fatigue (three of the five with chronic fatigue syndrome and seven of the 10 with idiopathic chronic fatigue) were more likely to have noted improvement in nasal and sinus symptoms, sore throats, headaches, and tender cervical lymph nodes when compared to those with a lingering significant fatigue (p < 0.001). Upper respiratory symptoms and headaches improved in those with reduced fatigue but remained problematic in those with persisting significant fatigue. We conclude that the fatigue related to sick building syndrome, including chronic fatigue syndrome, is significantly more likely to improve than fatigue identified in sporadic cases of chronic fatigue syndrome. Georgetown University Chronic fatigue syndrome J Psychiatr Res 1997 Jan-To determine the prevalence of chronic fatigue syndrome (CFS) criteria in other forms of unexplained Chester AC. Medical Center, Washington criteria in patients with other Feb;31(1):45-50 chronic fatigue, 297 consecutive outpatients under the age of 40 from a general medicine practice were D.C., USA. forms of unexplained chronic studied. After excluding the three with chronic fatigue syndrome, the remaining 294 individuals were fatigue. divided into those with unexplained chronic fatigue (64 patients) those without (the remaining 230 patients). Chronic fatigue syndrome criteria noted to be significantly more common in those with unexplained fatigue compared to those without include: fever, painful adenopathy, muscle weakness, myalgia, headache, migratory arthralgia, neuropsychologic symptoms, and sleep disorder. Like chronic fatigue syndrome, unexplained chronic fatigue often started suddenly. I conclude that the CFS criteria are noted more commonly than expected in other forms of unexplained chronic fatigue. Neurally mediated Integr Physiol Behav Sci Chester AC. hypotension, chronic fatigue 1997 Apr-Jun;32(2):160-1 syndrome and upper aerodigestive tract reflexes. Department of Medicine, Chronic pain and fatigue Neuroimmunomodulation Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical Clauw DJ, Chrousos GP.

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Georgetown University syndromes: overlapping 1997 May-Jun;4(3):134-53 literature, although the terms used to describe these symptom complexes have changed frequently. The Medical Center, Washington, clinical and neuroendocrine currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which D.C. 20007, USA. features and potential describe the prominent clinical features of the illness without any attempt to identify the cause. This review pathogenic mechanisms. delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses. Review, Academic Division of Rheumatology, The relationship between J Psychiatr Res 1997 Jan-Interstitial cystitis (IC) is a relatively uncommon and enigmatic disorder characterized by pain in the Clauw DJ, Schmidt M, Immunology and Allergy, fibromyalgia and interstitial Feb;31(1):125-31 bladder and pelvic region, typically accompanied by urinary urgency and frequency. Fibromyalgia is a more Radulovic D, Singer A, Georgetown University cystitis. common disorder, with the prominent symptoms being diffuse musculoskeletal pain and fatigue, and it has Katz P, Bresette J. Medical Center, Washington, been well established that there is substantial clinical overlap between fibromyalgia and chronic fatigue D.C., USA. syndrome (CFS). Although genitourinary and musculoskeletal symptoms predominate in IC and fibromyalgia respectively, both disorders share a number of features, including similar demographics, "allied conditions" (e.g. irritable bowel syndrome, headaches, etc.), natural history, aggravating factors, and efficacious therapy. We hypothesized that there was substantial clinical overlap between fibromyalgia and IC, and examined cohorts of individuals with these two disorders in parallel, to compare the spectrum of symptomatology. Sixty fibromyalgia patients, 30 IC patients, and 30 age-matched healthy controls were questioned regarding current symptomatology. A dolorimeter examination was also performed in the three groups to assess peripheral nociception. We found that the frequency of current symptoms was very similar for the fibromyalgia and IC groups. Both the fibromyalgia and IC patients displayed increased pain sensitivity when compared to healthy individuals, at both tender and control points. These data suggest that IC and fibromyalgia have significant overlap in symptomatology, and that IC patients display diffusely increased peripheral nociception, as is seen in fibromyalgia. Although central mechanisms have been suspected to contribute to the pathogenesis of fibromyalgia for some time, we speculate that these same types of mechanisms may be operative in IC, which has traditionally been felt to be a bladder disorder. Department of Psychiatry, Chronic fatigue syndrome: a J Psychosom Res 1997 The chronic fatigue syndrome is a disabling chronic condition of uncertain cause. Previous studies have Clements A, Sharpe M, University of Oxford, qualitative investigation of Jun;42(6):615-24 found that patients seen in hospital clinics with the syndrome often strongly believe that their illness is Simkin S, Borrill J, Hawton Warneford Hospital, UK. patients' beliefs about the physical in nature and minimize the role of psychological and social factors. There is also evidence that K. alison.clements@psychiatry.illness. patients cope by avoiding activity. However, almost all of these studies have assessed illness beliefs only by ox.ac.uk questionnaire. The aim of this study was to explore the nature and origin of illness beliefs in more detail using in-depth interviews and a qualitative analysis of patient responses. Sixty-six consecutive referrals meeting Oxford criteria for chronic fatigue syndrome were recruited. Analysis of responses indicated that, whereas the most commonly described explanation for the illness was a physical one, more than half the patients also believed "stress" had played a role. Patients believed that they could partially control the symptoms by reducing activity but felt helpless to influence the physical disease process and hence the course of the illness. Patients reported that they had arrived at these beliefs about the illness after prolonged reflection on their own experience combined with the reading of media reports, self help books, and patient group literature. The views of health professionals played a relatively small role. There is potentially a considerable opportunity to help patients arrive at a wider and more enabling explanation of their illness when they first present to primary care. Laboratorio de Biologia [High prevalence without An Med Interna 1997 INTRODUCTION: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology. Some viruses have Cuende JI, Civeira P, Diez Molecular, Hospital reactivation of herpes virus 6 Sep;14(9):441-4 been associated with CFS etiology, specially herpesviruses, enteroviruses and retroviruses. Some studies N, Prieto J. Provincial San Telmo, in subjects with chronic suggest an association between human herpesvirus-6 (HHV-6) and CFS. In order to know if there is an Palencia. fatigue syndrome].[article in active HHV-6 infection in CFS patients we studied the immunologic and virologic status of HHV-6. Spanish] MATERIALS AND METHODS: Twenty patients with CFS were studied. IgG and IgM anti HHV-6 were determined by indirect immunofluorescence assay. DNA from serum and peripheral blood mononuclear cells (PBMC) were studied by dot- and Southern-blotting and nested-PCR to detect HHV-6 DNA. HHV-6 RNA from PBMC were amplified by RT(retrotranscription)-PCR. RESULTS: Ten patients (50%) had IgG anti-HHV-6 in serum but none had IgM anti-HHV-6. Dot-blotting of DNA from 200 microliters of serum

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and Southern-blotting of 10 micrograms of PBMC DNA were negative. Nested-PCR from sera were negative. Nested-PCR with 1 microgram PBMC DNA were positive in 8 out 20 (40%) and with 5 micrograms PBMC DNA were positive in 16 out of 20 (80%). No viral RNA were detected in PBMC. CONCLUSIONS: There is a high proportion of CFS patients infected with HHV-6 but with low viral load. Results do not support HHV-6 reactivation in CFS patients. Afd. Medische Psychologie, [Chronic fatigue syndrome in Ned Tijdschr Geneeskd 1997 The prevalence of chronic fatigue syndrome (CFS) in teenagers is 10-20 per 100,000 inhabitants in the de Jong LW, Prins JB, Academisch Ziekenhuis, young persons].[article in Aug 2;141(31):1513-6 Netherlands. The natural course of the disorder is not favourable according to the literature. Proposed Fiselier TJ, Weemaes CM, Nijmegen. Dutch] criteria for the diagnosis 'CFS' in adolescence are: absence of a physical explanation for the complaints, a Meijer-van den Bergh EM, disabling fatigue for at least six months and prolonged school absenteeism or severe motor and social Bleijenberg G. disabilities. Exclusion criterion should be a psychiatric disorder. Factors that attribute to the persistence of fatigue are somatic attributions, illness enhancing cognitions and behaviour of parents as well as physical inactivity. The role of the physician and the role of parents can enhance the problems. The treatment should focus on decreasing the somatic attributions, on reinforcement by the parents of healthy adolescent behaviour, on the gradual increase of physical activity and on decreasing attention (including medical attention) for the somatic complaints. Department of Psychiatry, Chronic fatigue syndrome: Eur J Clin Invest 1997 de Loos WS. Utrecht University Hospital, fatigue of unknown origin. Apr;27(4):268-9 The Netherlands. Thrombosis Research Pathogenesis and Clin Auton Res 1997 The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported De Lorenzo F, Hargreaves Institute, London, UK. management of delayed Aug;7(4):185-90 previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with J, Kakkar VV. orthostatic hypotension in CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with patients with chronic fatigue CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and syndrome. Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment. Academic Department of Cognitive behavior therapy Am J Psychiatry 1997 OBJECTIVE: Cognitive behavior therapy for chronic fatigue syndrome was compared with relaxation in a Deale A, Chalder T, Marks Psychological Medicine, for chronic fatigue syndrome: Mar;154(3):408-14 comment randomized controlled trial. METHODS: Sixty patients with chronic fatigue syndrome were randomly I, Wessely S. King's College Hospital, a randomized controlled trial. in: Am J Psychiatry. 1998 assigned to 13 sessions of either cognitive behavior therapy (graded activity and cognitive restructuring) or London, United Kingdom. Oct;155(10):1461-2 relaxation. Outcome was evaluated by using measures of functional impairment, fatigue, mood, and global improvement. RESULTS: Treatment was completed by 53 patients. Functional impairment and fatigue improved more in the group that received cognitive behavior therapy. At final follow-up, 70% of the completers in the cognitive behavior therapy group achieved good outcomes (substantial improvement in physical functioning) compared with 19% of those in the relaxation group who completed treatment. CONCLUSIONS: Cognitive behavior therapy was more effective than a relaxation control in the management of patients with chronic fatigue syndrome. Improvements were sustained over 6 months of follow-up. Randomized Controlled Trial UMDNJ-New Jersey Medical Sudden vs gradual onset of J Psychiatr Res 1997 Jan-To examine the influence of mode of illness onset on psychiatric status and neuropsychological DeLuca J, Johnson SK, School, Newark, USA. chronic fatigue syndrome Feb;31(1):83-90 performance, 36 patients with CFS were divided into two groups: sudden vs gradual onset of symptoms. Ellis SP, Natelson BH. differentiates individuals on These two CFS subgroups were compared to each other and to sedentary healthy controls on standardized cognitive and psychiatric neuropsychological tests of attention/concentration, information processing efficiency, memory, and higher measures. cortical functions. In addition, the distribution of comorbid Axis I psychiatric disease between the two CFS

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groups was examined. The rate of concurrent psychiatric disease was significantly greater in the CFS-gradual group relative to the CFS-sudden group. While both CFS groups showed a significant reduction in information processing ability relative to controls, impairment in memory was more severe in the CFS-sudden group. Because of the significant heterogeneity of the CFS population, the need for subgroup analysis is discussed. University of Medicine and Cognitive functioning is J Neurol Neurosurg OBJECTIVE: To examine the effect of the presence or absence of psychiatric disease on cognitive DeLuca J, Johnson SK, Dentistry of New Jersey, New impaired in patients with Psychiatry 1997 functioning in chronic fatigue syndrome. METHODS: Thirty six patients with chronic fatigue syndrome Ellis SP, Natelson BH. Jersey Medical School, chronic fatigue syndrome Feb;62(2):151-5 and 31 healthy controls who did not exercise regularly were studied. Subgroups within the chronic fatigue Newark, USA. devoid of psychiatric disease. syndrome sample were formed based on the presence or absence of comorbid axis I psychiatric disorders. Patients with psychiatric disorders preceding the onset chronic fatigue syndrome were excluded. Subjects were administered a battery of standardised neuropsychological tests as well as a structured psychiatric interview. RESULTS: Patients with chronic fatigue syndrome without psychiatric comorbidity were impaired relative to controls and patients with chronic fatigue syndrome with concurrent psychiatric disease on tests of memory, attention, and information processing. CONCLUSION: Impaired cognition in chronic fatigue syndrome cannot be explained solely by the presence of a psychiatric condition. Controlled Clinical Trial Indiana University School of Chronic fatigue syndrome. Curr Ther Endocrinol Metab Demitrack MA, Engleberg Medicine, Indianapolis, 1997;6:152-60 NC. USA. Lilly Research Laboratories, Neuroendocrine correlates of J Psychiatr Res 1997 Jan-Chronic fatigue syndrome remains one of the more perplexing syndromes in contemporary clinical Demitrack MA. Lilly Corporate Center, chronic fatigue syndrome: a Feb;31(1):69-82 medicine. One approach to understanding this condition has been to acknowledge its similarities to other Indianapolis, IN 46285, brief review. disorders of clearer pathophysiology. In this review, a rationale for the study of neuroendocrine correlates of USA. chronic fatigue syndrome is presented, based in part on the clinical observation that asthenic or fatigue states share many of the somatic symptom characteristics seen in recognized endocrine disorders. Of additional interest is the observation that psychological symptoms, particularly disturbances in mood and anxiety, are equally prominent in this condition. At this time, several reports have provided replicated evidence of disruptions in the integrity of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. It is notable that the pattern of the alteration in the stress response apparatus is not reminiscent of the well-understood hypercortisolism of melancholic depression but, rather, suggests a sustained inactivation od central nervous system components of this system. Recent work also implicates alterations in central serotonergic tone in the overall pathophysiology of this finding. The implications of these observations are far from clear, but they highlight the fact that, though chronic fatigue syndrome overlaps with the well-described illness category of major depression, these are not identical clinical conditions. MRC/UCT Bioenergetics of The 'worn-out athlete': a J Sports Sci 1997 Chronic fatigue in the athletic population is a common but difficult diagnostic challenge for the sports Derman W, Schwellnus Exercise Research Unit, clinical approach to chronic Jun;15(3):341-51 physician. While a degree of fatigue may be normal for any athlete during periods of high-volume training, MP, Lambert MI, Emms University of Cape Town fatigue in athletes. the clinician must be able to differentiate between this physiological fatigue and more prolonged, severe M, Sinclair-Smith C, Kirby Medical School, Sports fatigue which may be due to a pathological condition. As chronic fatigue can be the presenting symptom of P, Noakes TD. Science Institute of South many curable and harmful diseases, medical conditions which cause chronic fatigue have to be excluded. Africa, Newlands, South The clinician must then be able to differentiate between chronic fatigue associated with training or chronic Africa. fatigue from other medical causes, and also between the chronic fatigue syndrome and the overtraining syndrome. Once the clinician has excluded all of the above medical conditions which cause chronic fatigue in athletes, a significant proportion of fatigued athletes remain without a diagnosis. Novel data indicate that skeletal muscle disorders may play a role in the development of symptoms experienced by the athlete with chronic fatigue. The histological findings from muscle biopsies of athletes suffering from the 'fatigued athlete myopathic syndrome' are presented. We have designed a clinical approach to the diagnosis and work-up of the athlete presenting with chronic fatigue. The strength of this approach is that it hinges on the participation of a multidisciplinary team in the diagnosis and management of the athlete with chronic fatigue. The athlete, coach, dietician, exercise physiologist and sport psychologist all play an important role in enabling the physician to make the correct diagnosis. Wolfson Institute of Chronic fatigue syndrome--Eur J Clin Invest 1997 The chronic fatigue syndrome (CFS) has been intensively studied over the last 40 years, but no conclusions Dickinson CJ. Preventive Medicine, St. aetiological aspects. Apr;27(4):257-67Comment have yet been agreed as to its cause. Most cases nowadays are sporadic. In the established chronic condition

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Bartholomew's & Royal in: Eur J Clin Invest. 1997 there are no consistently abnormal physical signs or abnormalities on laboratory investigation. Many London School of Medicine Apr;27(4):255-6 Eur J Clin physicians remain convinced that the symptoms are psychological rather than physical in origin. This view & Dentistry, London, UK. Invest. 1997 is reinforced by the emotional way in which many patients present themselves. The overlap of symptoms Dec;27(12):1061-2 between CFS and depression remains a source of confusion and difficulty. But even if all CFS patients were rediagnosed as depressives, this would not negate the possibility of an underlying organic cause for the condition, in view of the growing evidence that depression itself has a physical cause and responds best to physical treatments. There is some evidence both for active viral infection and for an immunological disorder in the CFS. Many observations suggest that the syndrome could derive from residual damage to the reticular activating system (RAS) of the upper brain stem and/or to its cortical projections. Such damage could be produced by a previous viral infection, leaving functional defects unaccompanied by any gross histological changes. In animal experiments activation of the RAS can change sleep state and activate or stimulate cortical functions. RAS lesions can produce somnolence and apathy. Studies by modern imaging techniques have not been entirely consistent, but many magnetic resonance imaging (MRI) studies already suggest that small discrete patchy brain stem and subcortical lesions can often be seen in CFS. Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis--in both of which conditions chronic fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in the RAS of the brain stem. If similar underlying lesions in the RAS can eventually be identified in CFS, the therapeutic target for CFS would be better defined than it is at present. A number of logical approaches to treatment can already be envisaged. Neuropsychological Journal of Chronic Fatigue Dimitrov M , Jordan Assessment of Chronic Syndrome 1997: 3(4): 31 - 42 Grafman Fatigue Syndrome Department of Psychological Blunted serotonin-mediated Psychoneuroendocrinology We examined 5HT1a-mediated ACTH release in patients with chronic fatigue syndrome (CFS) using a Dinan TG, Majeed T, Medicine, St Bartholomew's activation of the 1997 May;22(4):261-7 between-subjects design. Patients attending a specialist outpatient clinic for CFS, who fulfilled CDC Lavelle E, Scott LV, Berti Hospital, London, UK. hypothalamic-pituitary-criteria, together with age- and sex-matched healthy comparison subjects, were recruited. Subjects had a C, Behan P. T.G.Dinan@mds.qmw.ac.uk adrenal axis in chronic cannula inserted in a forearm vein at 0830 h and were allowed to relax until 0900 h, when baseline bloods fatigue syndrome. for ACTH and cortisol were drawn. They were then given ipsapirone 20 mg PO and further blood for hormone estimation was taken at +30, +60, +90, +120 and +180 min. Baseline ACTH and cortisol levels did not differ between the two groups. Release of ACTH (but not cortisol) in response to ipsapirone challenge was significantly blunted in patients with CFS. We conclude that serotonergic activation of the hypothalamic-pituitary-adrenal axis is defective in CFS. This defect may be of pathophysiological significance. The Prevalence of Chronic Journal of Chronic Fatigue Objective. To compare the prevalence of unexplained chronic fatigue (CF) and chronic fatigue syndrome Dobbins JG, Bonnie Fatiguing Illnesses Among Syndrome 1997: 3(2): 15 - 27 (CFS) among adolescents in three studies conducted by the Centers for Disease Control and Prevention and Randall, Michele Reyes , Adolescents in the United to compare these estimates with those for adults in two of the studies. Design. Thc studies used the Lea Steele, Elizabeth A. States following three designs: (i) a physicianbased CFS surveillance system, (ii) a random, cross-sectional Livens BA, William C. community telephone survey and (iii) a cross-sectional survey of school nurses. Setting. Surveillance Reeves included all patients with unexplained fatigue seen by participating physicians in four communities over a 2-year period; the community survey was conducted in a defined, urban population; and the survey of nurses included all middle, junior, and high school nurses in two communities. Patients or other participants. Twenty-three adolescent cases of unexplained chronic fatiguing illness were reported to the surveillance system, 7 of whom were classified with CFS. The community survey screened 2,249 persons between the ages of 2 and 17 years and identified 5 with unexplained chronic fatiguing illness, only one of whom might have had CFS. The school nurses identified 22 students with unexplained fatiguing illness, 10 of whom had received a diagnosis of CFS. Main outcome measures. The prevalence of unexplained chronic fatiguing illness was estimated in all three studies. The prevalence of CFS was estimated in one study, the prevalence of CFS-like illness was estimated in another, and the prevalence of a reported diagnosis of CFS was estimated in the third. Results. In general, the prevalence estimates of CF, CFS-like illness, and CFS for adolescents were lower than those for adults. One study also included children ages 2 to 11 years and found very little CF and no CFS. Cases of CFS among adolescents were evenly distributed across

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individual years of age. Conclusions. CFS was clearly present among adolescents, although the prevalence for this group was lower than for most adult age groups: Differences in prevalence estimates among the three studies were consistent with differences in study designs. The validity of adolescent/adult comparisons within each study should not be affected by the study design. Further study of the applicability of the current CFS case definition to adolescents is warranted. Chronic fatigue syndrome in BMJ 1997 Oct Dowsett EG, Colby J. children. Journal was wrong 11;315(7113):949 Comment to critizise study in on: BMJ. 1997 Jun schoolchildren. 7;314(7095):1635-6 Long-Term Sickness Journal of Chronic Fatigue A study was made to determine whether the recognition of multiple cases of myalgic Dowsett EG, Jane Colby Absence Due to ME/CFS in Syndrome 1997: 3(2): 29 - 42 encephalomyelitis/chronic fatigue syndrome (ME/CFS) in one school is a unique experience. A five-year UK Schools An retrospective period prevalence survey (1991-1995) was collated from sequential reports made in six Epidemiological Study with English Local Education Authority (LEA) areas. By means of a confidential questionnaire circulated to Medical and Educational 2,942 school principals via internal mail, 1,098 schools, comprising 27,327 staff and 333,024 pupils, were Implications investigated. Details were obtained on age, gender, location in school sector, work pattern and morbidity. Forty-two percent of all medically certified long-term sickness absence was ascribed to ME/CFS, this figure being well in excess of all other causes. This diagnosis was significantly associated with case clustering, variable geographical prevalence, a marked increase in the female:male case ratio at puberty and prolonged disturbance of educational potential. We conclude that ME/CFS in schools leads to serious economic and career problems. Redirection of research to special educational needs and to early diagnosis of infectious agents which can trigger ME/CFS in schools might prevent, at low cost, much chronic illness and education deficit. Division of Role of cysteine and FASEB J 1997 The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell Droge W, Holm E. Immunochemistry, Deutsches glutathione in HIV infection Nov;11(13):1077-89 activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a Krebsforschungszentrum, and other diseases associated complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in Heidelberg, Germany. with muscle wasting and patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic immunological dysfunction. fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these symptoms in diseases of different etiological origin suggests a causal relationship. The low NK cell activity in most cases is not life-threatening, but may be disastrous in HIV infection because it may compromise the initially stable balance between the immune system and virus, and trigger disease progression. This hypothesis is supported by the coincidence observed between the decrease of CD4+ T cells and a decrease in the plasma cystine level. In addition, recent studies revealed important clues about the role of cysteine and glutathione in the development of skeletal muscle wasting. Evidence suggests that 1) the cystine level is regulated primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is a physiological regulator of nitrogen balance and body cell mass, 3) the cyst(e)ine-mediated regulatory circuit is compromised in various catabolic conditions, including old age, and 4) cysteine supplementation may be a useful therapy if combined with disease-specific treatments such as antiviral therapy in HIV infection. Review, Academic SDRM, Hopital Saint-Neurotic, neuromuscular and Magnes Res 1997 The nervous form of magnesium imbalance represents the best documented experimental and clinical Durlach J, Bac P, Durlach Vincent-de-Paul, Paris. autonomic nervous form of Jun;10(2):169-95 aspects of magnesium disorders. The nervous form of primary magnesium deficit (MD) in the adult appears V, Bara M, Guiet-Bara A. magnesium imbalance. as the best descriptive model for analysis of the symptomatology, aetiology, physiopathology, diagnosis and therapy of the most frequent form of MD. Nervous hyperexcitability due to chronic MD in the adult results in a non-specific clinical pattern with associated central and peripheral neuromuscular symptoms, analogous to the symptomatology previously described in medical literature as latent tetany, hyperventilation syndrome, spasmophilia, chronic fatigue syndrome, neurocirculatory asthenia and idiopathic Barlow's disease. On encountering this non-specific pattern, the signs of neuromuscular hyperexcitability are of much greater importance. Trousseau's sign is less sensitive than Chvostek's sign, but their sensitivities are increased by hyperventilation (Von Bondsdorff's test). Examination of the precordial area will be conducted in order to search clinical stigmata of mitral valve prolapse (MVP) which is a frequent dyskinesia due to chronic MD (about a quarter to one-third of cases). The electromyogram (EMG) shows one (or several) trains of autorhythmic activities beating for more than 2 min of one of the three tetanic activities (uniplets, multiplets or 'complex tonicoclonic tracings') during one of the three

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